Several FDA-approved anti-cancer drugs induce stem cell tumors, perhaps thwarting therapy

Several FDA-approved anti-cancer drugs induce stem cell tumors, perhaps thwarting therapy
Drosophila intestines provide ‘ready-made stem cell microenvironments’ that are ‘difficult-to-impossible’ to create in petri dishes, offering an unconventional screen that allows researchers to test drugs in vivo. Credit: University of Massachusetts Amherst        

                                

Using a new approach to systematically test chemotherapy drugs in an unusual animal model, a research team led by University of Massachusetts Amherst molecular biologist Michele Markstein, with Norbert Perrimon at Harvard Medical School, report that several have a serious side effect: Inducing hyper proliferation in stem cells that could lead to tumor recurrence.

Markstein says, “We discovered that several chemotherapeutics that stop fast growing tumors have the opposite effect on stem cells in the same animal, causing them to divide too rapidly. This was a surprise, because it showed that the same drug could have opposite actions on cells in the same animal: Suppressing tumor growth on one cell population while initiating growth in another. Not only is the finding of clinical interest, but with this study we used an emerging new non-traditional tool for assessing drugs using stem cells in the fruit fly gut.” Continue reading “Several FDA-approved anti-cancer drugs induce stem cell tumors, perhaps thwarting therapy”

Ancient humans ‘rampantly interbred’ with Neanderthals and a mystery species in Lord Of The Rings-style world of different creatures

  • Genome  analysis of Neanderthal and human-like group called  Denisovans
  • It reveals  ancient bedfellows may have included  ‘mystery human ancestor’
  • Has been  likened to Lord Of The Rings world of creatures which  interbred

By  Daily Mail Reporter

PUBLISHED: 17:13 EST, 19  November 2013 |  UPDATED: 09:55 EST, 20 November 2013

Ancient humans rampantly indulged in  interspecies sex in a Lord Of The Rings-type world of different  human  groups, new DNA analysis has revealed.

And our ancient bedfellows appear to have  included a ‘mystery human ancestor’, which has not yet been identified.

Genome analysis from a Neanderthal and  another group of ancient humans, the Denisovans, was presented to a meeting of  the Royal Society in London, and it included ‘snippets’ of  the mystery  DNA  – neither human nor Neanderthal.

It suggests that interbreeding was rampant  and more widespread between the human-like groups living in Europe and Asia more  than 30,000 years ago than previously thought, scientists say.

Researchers compared DNA from Neanderthals (skull, pictured) and another group of ancient humans called Denisovans 

Researchers compared DNA from Neanderthals (skull,  pictured) and another group of ancient humans called Denisovans

Continue reading “Ancient humans ‘rampantly interbred’ with Neanderthals and a mystery species in Lord Of The Rings-style world of different creatures”

Researchers advance toward engineering ‘wildly new genome’

Contact: David Cameron david_cameron@hms.harvard.edu 617-432-0441 Harvard Medical School

In two parallel projects, researchers have created new genomes inside the bacterium E. coli in ways that test the limits of genetic reprogramming and open new possibilities for increasing flexibility, productivity and safety in biotechnology.

In one project, researchers created a novel genome—the first-ever entirely genomically recoded organism—by replacing all 321 instances of a specific “genetic three-letter word,” called a codon, throughout the organism’s entire genome with a word of supposedly identical meaning. The researchers then reintroduced a reprogramed version of the original word (with a new meaning, a new amino acid) into the bacteria, expanding the bacterium’s vocabulary and allowing it to produce proteins that do not normally occur in nature.

In the second project, the researchers removed every occurrence of 13 different codons across 42 separate E. coli genes, using a different organism for each gene, and replaced them with other codons of the same function. When they were done, 24 percent of the DNA across the 42 targeted genes had been changed, yet the proteins the genes produced remained identical to those produced by the original genes.

“The first project is saying that we can take one codon, completely remove it from the genome, then successfully reassign its function,” said Marc Lajoie, a Harvard Medical School graduate student in the lab of George Church.  “For the second project we asked, ‘OK, we’ve changed this one codon, how many others can we change?'”

Of the 13 codons chosen for the project, all could be changed.

“That leaves open the possibility that we could potentially replace any or all of those 13 codons throughout the entire genome,” Lajoie said.

The results of these two projects appear today in Science. The work was led by Church, Robert Winthrop Professor of Genetics at Harvard Medical School and founding core faculty member at the Wyss Institute for Biologically Inspired Engineering. Farren Isaacs, assistant professor of molecular, cellular, and developmental biology at Yale School of Medicine, is co-senior author on the first study.

Toward safer, more productive, more versatile biotech

Recoded genomes can confer protection against viruses—which limit productivity in the biotech industry—and help prevent the spread of potentially dangerous genetically engineered traits to wild organisms.

“In science we talk a lot about the ‘what’ and the ‘how’ of things, but in this case, the ‘why’ is very important,” Church said, explaining how this project is part of an ongoing effort to improve the safety, productivity and flexibility of biotechnology.

“These results might also open a whole new chemical toolbox for biotech production,” said Isaacs. “For example, adding durable polymers to a therapeutic molecule could allow it to function longer in the human bloodstream.”

But to have such an impact, the researchers said, large swaths of the genome need to be changed all at once.

“If we make a few changes that make the microbe a little more resistant to a virus, the virus is going to compensate. It becomes a back and forth battle,” Church said. “But if we take the microbe offline and make a whole bunch of changes, when we bring it back and show it to the virus, the virus is going to say ‘I give up.’ No amount of diversity in any reasonable natural virus population is going to be enough to compensate for this wildly new genome.”

In the first study, with just a single codon removed, the genomically recoded organism showed increased resistance to viral infection. The same potential “wildly new genome” would make it impossible for engineered genes to escape into wild populations, Church said, because they would be incompatible with natural genomes. This could be of considerable benefit with strains engineered for drug or pesticide resistance, for example. What’s more, incorporating rare, non-standard amino acids could ensure strains only survive in a laboratory environment.

Engineering and evolution

Since a single genetic flaw can spell death for an organism, the challenge of managing a series of hundreds of specific changes was daunting, the researchers said. In both projects, the researchers paid particular attention to developing a methodical approach to planning and implementing changes and troubleshooting the results.

“We wanted to develop the ability to efficiently build the desired genome and to very quickly identify any problems—from design flaws or from undesired mutations — and develop workarounds,” Lajoie said.

The team relied on number oftechnologies developed in the Church lab and the Wyss Institute and with partners in academia and industry, including next-generation sequencing tools, DNA synthesis on a chip, and MAGE and CAGE genome editing tools. But one of the most important tools they used was the power of natural selection, the researchers added.

“When an engineering team designs a new cellphone, it’s a huge investment of time and money. They really want that cell phone to work,” Church said. “With E. coli we can make a few billion prototypes with many different genomes, and let the best strain win. That’s the awesome power of evolution.”

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Funding was from Department of Energy [DE-FG02-02ER63445], NSF [SA5283-11210], NIH [NIDDK-K01DK089006], DARPA [N66001-12-C-4040, N66001-12-C-4020, N66001-12-C-4211], Arnold and Mabel Beckman Foundation, Department of Defense NDSEG Fellowship, NIH-MSTP-TG-T32GM07205, NSF graduate fellowship, NIH Director’s EarlyIndependence Award [Grant 1DP5OD009172-01], U.S. Office of Naval Research [N000141010144], Agilent Technologies, Wyss Institute, and Department of Defense NDSEG Fellowship, and Air Force Contract #FA8721-05-C-0002.

Written by JAKE MILLER

Harvard Medical School has more than 7,500 full-time faculty working in 11 academic departments located at the School’s Boston campus or in one of 47 hospital-based clinical departments at 16 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Cambridge Health Alliance, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Pilgrim Health Care, Hebrew SeniorLife, Joslin Diabetes Center, Judge Baker Children’s Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital and VA Boston Healthcare System.

The Wyss Institute for Biologically Inspired Engineering at Harvard University uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Boston Children’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, andCharité – Universitätsmedizin Berlin, the Institute crosses disciplinary andinstitutional barriers to engage in high-risk research that leads to transformative technological breakthroughs. By emulating Nature’s principles, Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and new start-ups. The Wyss Institute recently won the prestigious World TechnologyNetwork award for innovation in biotechnology.

Study finds evidence of nerve damage in around half of fibromyalgia patients

Contact: Mike Morrison mdmorrison@partners.org 617-724-6425 Massachusetts General Hospital

Small study could lead to identification of treatable diseases for some with chronic pain syndrome

About half of a small group of patients with fibromyalgia – a common syndrome that causes chronic pain and other symptoms – was found to have damage to nerve fibers in their skin and other evidence of a disease called small-fiber polyneuropathy (SFPN). Unlike fibromyalgia, which has had no known causes and few effective treatments, SFPN has a clear pathology and is known to be caused by specific medical conditions, some of which can be treated and sometimes cured. The study from Massachusetts General Hospital (MGH) researchers will appear in the journal Pain and has been released online.

“This provides some of the first objective evidence of a mechanism behind some cases of fibromyalgia, and identifying an underlying cause is the first step towards finding better treatments,” says Anne Louise Oaklander, MD, PhD, director of the Nerve Injury Unit in the MGH Department of Neurology and corresponding author of the Pain paper.

The term fibromyalgia describes a set of symptoms – including chronic widespread pain, increased sensitivity to pressure, and fatigue – that is believed to affect 1 to 5 percent of individuals in Western countries, more frequently women.  While a diagnosis of fibromyalgia has been recognized by the National Institutes of Health and the American College of Rheumatology, its biologic basis has remained unknown.  Fibromyalgia shares many symptoms with SFPN, a recognized cause of chronic widespread pain for which there are accepted, objective tests.

Designed to investigate possible connections between the two conditions, the current study enrolled 27 adult patients with fibromyalgia diagnoses and 30 healthy volunteers.  Participants went through a battery of tests used to diagnose SFPN, including assessments of neuropathy based on a physical examination and responses to a questionnaire, skin biopsies to evaluate the number of nerve fibers in their lower legs, and tests of autonomic functions such as heart rate, blood pressure and sweating.

The questionnaires, exam assessments, and skin biopsies all found significant levels of neuropathy in the fibromyalgia patients but not in the control group.  Of the 27 fibromyalgia patients, 13 had a marked reduction in nerve fiber density, abnormal autonomic function tests or both, indicating the presence of SFPN.  Participants who met criteria for SFPN also underwent blood tests for known causes of the disorder, and while none of them had results suggestive of diabetes, a common cause of SFPN, two were found to have hepatitis C virus infection, which can be successfully treated, and more than half had evidence of some type of immune system dysfunction.

“Until now, there has been no good idea about what causes fibromyalgia, but now we have evidence for some but not all patients.  Fibromyalgia is too complex for a ‘one size fits all’ explanation,” says Oaklander, an associate professor of Neurology at Harvard Medical School.  “The next step of independent confirmation of our findings from other laboratories is already happening, and we also need to follow those patients who didn’t meet SFPN criteria to see if we can find other causes.  Helping any of these people receive definitive diagnoses and better treatment would be a great accomplishment.”

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Other authors of the Pain report are Zeva Daniela Herzog, Heather Downs and Max Klein, PhD, all of MGH Neurology.  Preliminary results of the study were presented at the 2012 American Neurological Association meeting, and it was supported by Public Health Service grants NINDS K24NS059892 and UIL RR025758, Department of Defense grant GW093049, and a donation from Jane Cheever Powell.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $775 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

83 percent of radiologists did not report seeing the LARGE gorilla in a lung nodule detection task

Contact: Jessica Maki jmaki3@partners.org 617-534-1603 Brigham and Women’s Hospital

If you’re not looking for it, you probably won’t see it

Brigham and Women’s Hospital study examines sustained inattentional blindness in expert observers

Boston—If you were working on something at your computer and a gorilla floated across your computer screen, would you notice it? You would like to think yes, however, research shows that people often miss such events when engaged in a difficult task. This is a phenomenon known as inattentional blindness (IB). In a new study from Brigham and Women’s Hospital (BWH) in Boston, researchers have found that even expert searchers, operating in their domain of expertise, are vulnerable to inattentional blindness. This study published this week Psychological Science.

“When engaged in a demanding task, attention can act like a set of blinders, making it possible for stimuli to pass, undetected, right in front of our eyes,” explained Trafton Drew, PhD, post-doctoral researcher at BWH and lead author on this study. “We found that even experts are vulnerable to this phenomenon.”

The researchers asked 24 radiologists to perform a familiar lung nodule detection task. They examined five scans; each scan contained an average of 10 nodules. A gorilla, 48 times larger than the average nodule, was inserted in the last scan. The researchers found that 83 percent of radiologists did not report seeing the gorilla. With the help of Melissa Le-Hoa Vo, post-doctoral researcher at BWH, the researchers tracked the eye-movements of the radiologists and found that that the majority of those who missed the gorilla looked directly at it.

“The radiologists missed the gorillas not because they could not see them, but because the way their brains had framed what they were doing. They were looking for cancer nodules, not gorillas,” explained Jeremy Wolfe, senior psychologist and director of the Visual Attention Laboratory at BWH. “This study helps illustrate that what we become focused on becomes the center of our world, and it shapes what we can and cannot see.”

The researchers note that it would be a mistake to regard these results as an indictment of radiologists and stress that even this high level of expertise does not immunize against inherent attentional limitations of what we perceive. The results suggest that even expert searchers typically only see what they are looking for, and are often unaware of the unexpected. The researchers hope that the results will lead more expert searchers to recognize the important role of attention in determining what the searcher will find and what they may miss.

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This work was funded by a NRSR post-doctoral fellowship from the NIBIB to TD.

Brigham and Women’s Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member ofPartners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs more than 15,000 people. The Brigham’s medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at itsBiomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by nearly $625 million in funding. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses’ and Physicians’Health Studies, OurGenes and the Women’s Health Initiative.  For more information and resources, please visit BWH’s online newsroom.

Twelve minutes’ exercise per week ‘enough to stay fit’: Just 4 minutes 3 times a week

*EEV Note: Hmmm, I think we have a different opinion on what is meant by Fit.

Just 12 minutes of intensive exercise per week is enough to improve your health if you are overweight, a study has found.

Just 12 minutes of intensive exercise per week is enough to improve your health if you are overweight, a study has found.

12 minutes of high-intensity exercise across three sessions could be enough to keep us fit and healthy Photo: Alamy

 

Nick Collins

By , Science Correspondent

5:38PM BST 30 May 2013

Four-minute bursts of high-intensity exercise such as running on a treadmill, three times a week are enough to increase fitness, researchers found.

Overweight volunteers who undertook the regime for 10 weeks increased their body’s oxygen uptake – a measure of fitness – by 10 per cent and saw small decreases in their blood pressure and glucose levels.

Health guidelines generally state that we should undertake at least 150 minutes of moderate exercise or 20 minutes of vigorous exercise per week in order to stay healthy.

But the new study suggests that just 12 minutes of high-intensity exercise, spread out across three sessions, could be enough to keep us fit and healthy, researchers said.

The team from the Norwegian University of Science and Technology in Trondheim studied the effects of different exercise regimes on 24 men who were overweight but otherwise healthy.

Three times a week for 10 weeks, the men undertook bouts of “vigorous” exercise, which involved running on a treadmill at a speed which raised their heart rate to 90 per cent of its maximum capacity.

For half of the men the regime involved simple four-minute sessions, three times a week, while the other half completed three sixteen-minute sessions, each of which was divided into four-minute segments.

Despite carrying out different amounts of exercise, the results for the two groups were strikingly similar.

Oxygen uptake – the amount of oxygen the body can use during exercise – increased by 10 per cent in the four-minute group, and by 13 per cent in the sixteen-minute group.

Blood pressure and glucose levels lowered by similar amounts in both groups, but the more intensive sixteen-minute sessions was more effective at lowering cholesterol and body fat.

Writing in the Public Library of Science ONE journal, the researchers said that such improvements could lower the risk of death from conditions like heart disease and stroke.

“These data suggest that it may be possible to reduce cardiovascular mortality with substantially less exercise than is generally recommended, provided it is performed in a vigorous manner,” they wrote.

The researchers said the exercises could easily be incorporated into a daily regime, for example by walking quickly up six to ten flights of stairs or by walking up a hill with an eight to 10 per cent gradient.

Some doctors have raised concerns that carrying out intensive exercise could pose a health risk to unfit people. Andrew Marr, the BBC presenter, was told that his stroke earlier this year was caused by a work-out on a rowing machine.

Speaking at the time Dr Thomas Lee, Professor of Medicine at Harvard Medical School, said: “Short episodes of very intense exercise can raise one’s risk for a stroke or heart attack or fatal arrhythmia during or right after the burst of exertion.

“I think this approach, which used to be known as “intervals”, is very reasonable and accepted among young athletes…I don’t encourage it among most of my older patients.”

But the researchers said their previous work had showed that “most individuals can engage in this type of exercise training as it has been performed without any adverse events”.

Dr Arnt Erik Tjønna said the programme of brief but intensive exercise sessions could be a “time-efficient” method of staying fit.

Previous studies have found that a lack of free time is one of the most frequently mentioned issues when people are asked what prevents them from exercising.

“Since we know that more and more people are inactive and overweight, the kind of improvement in physical fitness that we saw in this study may provide a real boost for inactive people who are struggling to find the motivation to exercise,” he said.

http://www.telegraph.co.uk/health/healthnews/10089411/Twelve-minutes-exercise-per-week-enough-to-stay-fit.html

Young people who undergo CT scans are 24 percent more likely to develop cancer compared with those who do not, a study published today on bmj.com suggests

Contact: Emma Dickinson edickinson@bmj.com 44-020-738-36529 BMJ-British Medical Journal

Small cancer risk following CT scans in childhood and adolescence confirmed

But the absolute excess for all cancers combined is low

The researchers say that in a group of 10,000 young people, they would expect 39 cancers to occur during the next 10 years, but if they all had one CT scan, up to six extra cancers would occur.

CT (computed tomography) scans have great medical benefits, but their increasing use since the 1980s has raised some concerns about possible cancer risks, particularly following exposures in childhood. Most previous studies have estimated risks indirectly, and some radiation experts have questioned the validity of these estimates.

There is currently much uncertainty and as such, researchers from Australia and Europe carried out a study comparing cancer rates in patients exposed to CT scans at ages 0-19 years compared with unexposed persons of a similar age. All participants were born between 1985 and 2005 with total follow-up ending at the end of 2007. This is the largest ever population-based study of medical radiation exposure.

Data were taken from Australian Medicare records and from national cancer records. The main outcome of the research was to identify cancer rates in individuals exposed to a CT scan more than one year before any cancer diagnosis. Mean length of follow-up was 9.5 years for the exposed group and 17.3 for the unexposed group.

The cohort included 10.9 million people, 680,211 of whom were CT-exposed at least 12 months before any cancer diagnosis. 18% of these had more than one scan.

By the end of 2007, 3150 of the exposed group and 57,524 of the unexposed group had been diagnosed with cancer. The incidence rate was 24% greater in the exposed group after adjusting for age, sex and year of birth. Risk increased by 16% for each additional CT scan.

For brain cancer, although the incidence in the exposed group declined with time since first CT-exposure, brain cancer incidence was still significantly increased more than 15 years after first exposure. For other solid cancers (tumours as opposed to cancers of the blood or bone marrow) the absolute excess cancer incidence increased significantly with time since first exposure.

For all cancers combined, although the proportional increase declined with years since first CT scan, it was still increased at 15+ years after first exposure.

For brain cancer, the highest risk was seen in children exposed before the age of five years and this risk decreased with increasing age at first exposure. However, despite this decrease, risk for all cancers combined remained significantly increased in the oldest age at exposure group (15-19 years).

For solid cancers other than brain cancer, the proportional increase in risk was somewhat greater in females: 23% compared with 14% in males.

The researchers say that almost 60% of CT scans were of the brain and recognise that “in some cases the brain cancer may have led to the scan rather than vice versa”. They add that they “cannot assume that all the excess cancers […] were caused by CT scans” and they “cannot rule out the possibility of some reverse causation, particularly for some cases of brain cancer”.

Nevertheless, they conclude that the “increased incidence of many different types of cancer […] is mostly due to irradiation”. They point out that because the cancer excess was still continuing at the end of follow-up, the “eventual lifetime risk from CT scans cannot yet be determined”. They recommend that practitioners will need to weigh the benefits against the potential risks to justify each CT scan decision.

In an accompanying editorial, Dr Sodickson from Harvard Medical School says it is important to recognise that the incidence of cancer in children is extremely small and so “a 24% increase makes this risk just slightly less small”. He says that there are many methods to manage radiation dose and with further validation of risk models, “more accurate risk assessment “can be performed to “better inform imaging decisions”.

Folate and vitamin B12 reduce disabling schizophrenia symptoms in some patients

Contact: Kristen Stanton kstanton3@partners.org 617-643-3907 Massachusetts General Hospital

Adding supplements to antipsychotic medication alleviated negative symptoms in patients with specific gene variants

Adding the dietary supplements folate and vitamin B12 to treatment with antipsychotic medication improved a core symptom component of schizophrenia in a study of more than 100 patients. The study focused on negative symptoms of schizophrenia – which include apathy, social withdrawal, and a lack of emotional expressiveness. While the level of improvement across all participants was modest, results were more significant in individuals carrying specific variants in genes involved with folate metabolism. The report from a team based at Massachusetts General Hospital (MGH) will appear in the journal JAMA Psychiatry (formerly Archives of General Psychiatry) and has been issued online.

“The symptoms of schizophrenia are complex, and antipsychotic medications provide no relief for some of the most disabling parts of the illness. These include negative symptoms, which can be particularly devastating,” says Joshua Roffman, MD, MMSc, of the MGH Department of Psychiatry, corresponding author of the JAMA Psychiatry paper. “Our finding that folate plus vitamin B12 supplementation can improve negative symptoms opens a new potential avenue for treatment of schizophrenia. Because treatment effects differed based on which genetic variants were present in each participant, the results also support a personalized medical approach to treating schizophrenia.”

An essential nutrient, folate (or folic acid) is required for the synthesis of DNA and neurotransmitters and plays a role in the control of gene expression. Adequate folate intake during pregnancy can reduce the risk of birth defects – in particular neural tube defects – and studies have suggested that folate deficiency during pregnancy significantly increases the risk of schizophrenia among offspring. Earlier research by members of the MGH-based team associated low blood folate levels with more severe negative symptoms among patients with schizophrenia.

The current study was designed specifically to investigate whether supplementation with folate and B12 – which can magnify the effects of folate – reduced negative symptoms of schizophrenia. A 2011 pilot study found symptom improvement only among patients carrying a variant in a folate-pathway gene called MTHFR that reduced the gene’s activity. To get a clearer picture of folate’s effect on negative symptoms, the current study enrolled 140 patients with schizophrenia at community mental health centers in Boston, Rochester, N.Y., and Grand Rapids, Mich.

Participants were all taking antipsychotic medications – which have been shown to alleviate positive symptoms, such as hallucinations and delusions, but not negative symptoms – and were randomized to receive daily doses of either folate and vitamin B12 or a placebo for 16 weeks. Every two weeks their medical and psychiatric status was evaluated, using standard symptom assessment tools along with measurements of blood levels of folate and homocysteine, an amino acid that tends to rise when folate levels drop. Nutritional information was compiled to account for differences in dietary intake of the nutrients. Participants’ blood samples were analyzed to determine the variants they carried of MTHFR and three other folate-pathway genes previously associated with the severity of negative symptoms of schizophrenia.

Among all 140 participants in the study protocol, those receiving folate and vitamin B12 showed improvement in negative symptoms, but the degree of improvement was not statistically significant compared with the placebo group. But when the analysis accounted for the variants in the genes of interest, intake of the two nutrients did provide significant improvement in negative symptoms, chiefly reflecting the effects of specific variants in MTHFR and in a gene called FOLH1. Variants in the other two genes studied did not appear to have an effect on treatment outcome.

While a low-functioning variant in FOLH1 had been associated with more severe negative symptoms in previous research, in this study it was the high-functioning FOLH1 variant that predicted a better treatment outcome. Measurement of participants’ blood folate levels throughout the study provided an explanation for this unexpected finding. Those with the low-functioning FOLH1 variant started the trial with substantially lower folate levels, suggesting a problem with folate absorption. Although supplementation enabled their blood folate levels to eventually catch up with those of participants with the high-functioning variant, it was probably too late to produce symptom improvement during the 16-week trial period.

“For participants who did show a benefit, it took the full 16 weeks of treatment for that benefit to appear,” Roffman explains. “While we don’t know why this is the case, changes in gene expression – which take time – are a likely explanation. Folate plays a critical role in DNA methylation, which regulates gene expression, so it’s plausible that its effects on negative symptoms act through gene expression changes. Participants with the low-functioning FOLH1 variant might eventually show a benefit of folate supplementation if treated for a longer period of time, but that needs to be investigated in future studies.”

He adds that, while the benefits of supplementation for the overall group were modest, the lack of effective treatment for negative symptoms and the safety of folate and vitamin B12 supplementation support the need for larger-scale trials. In addition, the impact of genotype on this study’s results suggests the need to investigate the role of folate pathway variants in conditions such as dementia and cardiovascular disease, in which low folate appears to increase risk but supplementation trials have had inconclusive results.

“We are now conducting a clinical trial of 1-methylfolate, which bypasses some of these folate-pathway enzymes and might have greater efficiency among individuals with low-functioning variants,” explains Roffman, an assistant professor of Psychiatry at Harvard Medical School. “Understanding more about the basic neural mechanisms of folate in patients with schizophrenia could help us generate more targeted and effective interventions to reduce and possibly even prevent symptoms.”

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The senior author of the JAMA Psychiatry report is Donald Goff, MD, formerly of MGH Psychiatry and now at the Nathan Kline Institute and New York University School of Medicine. Additional co-authors are Gail Galendez, Lisa Raeke, Noah Silverstein, Jordan Smoller, MD, ScD, and Michelle Hill, MD, MGH Psychiatry; Eric Macklin, PhD, MGH Biostatistics Center; Steven Lamberti, MD, University of Rochester Medical Center; and Eric Achtyes, MD, MS, Michigan State University College of Human Medicine. The study was supported primarily by National Institute of Mental Health grant R01MH070831.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $775 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2012, MGH moved into the number one spot on the 2012-13 U.S. News & World Report list of “America’s Best Hospitals.”

Salt identified as autoimmune trigger

Contact: Bill Hathaway 203-432-1322 Yale University

For the past few decades, health officials have been reporting increases in the incidence of autoimmune diseases such as multiple sclerosis (MS). Now researchers at Yale School of Medicine, Harvard Medical School and the Broad Institute have identified a prime suspect in the mystery — dietary salt.

In the March 6 issue of the journal Nature, Yale researchers showed that salt can induce and worsen pathogenic immune system responses in mice and that the response is regulated by genes already implicated in a variety of autoimmune diseases.

In accompanying papers in the same issue of Nature, researchers from Brigham and Women’s Hospital and Harvard identified the key molecular pathway involved in the response to salt, and the Broad Institute sketched out the regulatory network of genes that governs this autoimmune response.

“These are not diseases of bad genes alone or diseases caused by the environment, but diseases of a bad interaction between genes and the environment,” said David Hafler, the Gilbert H. Glaser Professor of Neurology, professor of immunobiology, chair of the Department of Neurology, and senior author of the Yale paper.

The research was inspired, in part, by an observation that eating at fast-food restaurants tended to trigger an increase in production of inflammatory cells, which are mobilized by the immune system to respond to injury or pathogens but which, in autoimmune diseases, attack healthy tissue. Researchers at Yale and colleagues in Germany led by Dominik Mueller wanted to know whether high salt content in diet might induce the destructive immune system response that is the hallmark of autoimmunity.

They found that adding salt to the diet of mice induced production of a type of T cells previously associated with autoimmune diseases and that mice on salt diets developed a more severe form of an MS animal model, experimental autoimmune encephalomyelitis.

The research at the Broad Institute, Brigham and Women’s Hospital, Harvard University, and Yale University expands the understanding of how one type of immune cell — known as a T helper 17 or Th17 cell — develops, and how its growth influences the development of other kinds of cells involved in the immune system. Reconstruction of this molecular circuitry confirmed the surprising role of salt, said the researchers.

“The question we wanted to pursue was: How does this highly pathogenic, pro-inflammatory T cell develop?” said Vijay Kuchroo, a senior scientist at Brigham and Women’s Hospital and a Broad Institute associate member. Kuchroo is also the Wasserstrom Professor of Neurology at Harvard Medical School and co-director of the Center for Infection and Immunity at Biomedical Research Institutes. “Once we have a more nuanced understanding of the development of the pathogenic Th17 cells, we may be able to pursue ways to regulate them or their function.”

“Humans were genetically selected for conditions in sub-Saharan Africa, where there was no salt,” Hafler said. “Today, Western diets all have high salt content and that has led to increase in hypertension and perhaps autoimmune disease as well.”

Hafler noted that all test-tube cell biology is performed based on the salt levels found in blood and not in the tissues where immune cell ultimately travel to fight infections. That may have been a reason salt’s role in autoimmunity has gone undetected.

“We may have been using the wrong concentrations of salt in our experiments for the past half-century,” Hafler said. “Nature did not want immune cells to become turned on in the pipeline, so perhaps blood salt levels are inhibitory.”

Patient trials to assess affects of salt on autoimmune diseases are being planned.

“The value in doing an unbiased analysis is that we’re able to understand a lot more about the molecular biology at play and put forth a completely novel process,” said Aviv Regev, a Broad Institute core member and an associate professor of biology at MIT. Regev is also an Early Career Scientist at Howard Hughes Medical Institute and the director of the Klarman Cell Observatory at the Broad.

Hafler is not waiting with his own patients.

“I already recommend that my patients use a low-salt, low-fat diet,” he said

Markus Kleinewietfeld was lead author of the Yale-led study.

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Work was funded by: This work was supported by a National MS Society Collaborative Research Center Award CA1061-A-18, National Institutes of Health Grants P01 AI045757, U19 AI046130, U19 AI070352, and P01 AI039671, and by a Jacob Javits Merit award (NS2427) from the National Institute of Neurological Disorders and Stroke and the Nancy Taylor Foundation for Chronic Diseases, Inc.

OMEGA-3s Inhibit Breast Cancer Tumour Growth, U of G Study Finds

February 21, 2013 – News Release

A lifelong diet rich in omega-3 fatty acids can inhibit growth of breast cancer tumours by 30 per cent, according to new research from the University of Guelph.

The study, published recently in the Journal of Nutritional Biochemistry, is believed to be the first to provide unequivocal evidence that omega-3s reduce cancer risk.

“It’s a significant finding,” said David Ma, a professor in Guelph’s Department of Human Health and Nutritional Sciences, and one of the study’s authors.

“We show that lifelong exposure to omega-3s has a beneficial role in disease prevention – in this case, breast cancer prevention. What’s important is that we have proven that omega-3s are the driving force and not something else.”

Breast cancer remains the most common form of cancer in women worldwide and is the second leading cause of female cancer deaths.

Advocates have long believed diet may significantly help in preventing cancer. But epidemiological and experimental studies to back up such claims have been lacking, and human studies have been inconsistent, Ma said.

“There are inherent challenges in conducting and measuring diet in such studies, and it has hindered our ability to firmly establish linkages between dietary nutrients and cancer risk,” he said.

“So we’ve used modern genetic tools to address a classic nutritional question.”

For their study, the researchers created a novel transgenic mouse that both produces omega-3 fatty acids and develops aggressive mammary tumours. The team compared those animals to mice genetically engineered only to develop the same tumours.

“This model provides a purely genetic approach to investigate the effects of lifelong omega-3s exposure on breast cancer development,” Ma said.

“To our knowledge, no such approach has been used previously to investigate the role of omega-3s and breast cancer.”

Mice producing omega-3s developed only two-thirds as many tumours – and tumours were also 30-per-cent smaller – as compared to the control mice.

“The difference can be solely attributed to the presence of omega-3s in the transgenic mice – that’s significant,” Ma said.

“The fact that a food nutrient can have a significant effect on tumour development and growth is remarkable and has considerable implications in breast cancer prevention.”

Known as an expert in how fats influence health and disease, Ma hopes the study leads to more research on using diet to reduce cancer risk and on the benefits of healthy living.

“Prevention is an area of growing importance. We are working to build a better planet, and that includes better lifestyle and diet,” he said.

“The long-term consequences of reducing disease incidence can have a tremendous effect on the health-care system.”

The study also involved lead author Mira MacLennan, a former U of G graduate student who is now studying medicine at Dalhousie University; U of G pathobiology professor Geoffrey Wood; former Guelph graduate students Shannon Clarke and Kate Perez; William Muller from McGill University; and Jing Kang from Harvard Medical School.

Funding for this research came from the Canadian Breast Cancer Research Alliance/Canadian Institutes of Health Research, the Canada Foundation for Innovation and the Ontario Research Fund.

Contact: Prof. David Ma Department of Human Health and Nutritional Sciences davidma@uoguelph.ca 519 824-4120, Ext: 52272/53906

For media questions, contact Communications and Public Affairs: Lori Bona Hunt, 519-824-4120, Ext. 53338, or lhunt@uoguelph.ca; or Kevin Gonsalves, Ext. 56982, or kgonsalves@uoguelph.ca.

Almost one-third of chemotherapy used “off-label”

Photo
4:44pm EST

By Andrew M. Seaman

NEW YORK (Reuters Health) – About one-third of chemotherapies are used to fight cancers that drug regulators never approved them to treat, says a new study.

Chemotherapies – drugs that kill rapidly dividing cells – are approved by the Food and Drug Administration (FDA) to fight specific cancers, but there’s nothing stopping doctors from prescribing the drugs “off-label” to treat other types of tumors.

Some researchers have questioned whether doctors were prescribing the expensive and toxic drugs outside of their intended use, according to the study’s researchers, led by Rena Conti, an assistant professor of health policy and economics at the University of Chicago.

“The main criticism of off-label prescribing has been the concern that it jeopardizes patient safety because the full risk-benefit ratio is often not completely understood,” wrote the University of Toronto’s Dr. Monika Krzyzanowska, who published an editorial accompanying the study in the Journal of Clinical Oncology on Tuesday.

But that doesn’t mean the billions of dollars spent on off-label chemotherapies are wasted, according to Conti.

“We don’t know what the outcomes are. We can’t make a judgment of whether the off-label use we document… is appropriate or inappropriate,” said Conti.

For the new study, the researchers used a national prescription database from U.S. cancer doctors to estimate how the most common intravenous or injected chemotherapies were used in 2010.

They found ten chemotherapies that were still protected from competition by patents. They ranged from almost 500,000 doses of Genentech’s Avastin or bevacizumab – approved to treat brain, colorectal, lung and kidney cancers – to about 53,000 doses of Celegene’s Vidaza or azacitidine – used to treat certain blood disorders.

Overall, about 70 percent of the doses of the ten chemotherapies were used “on-label,” which means the doses were used in line with FDA approval. The other 30 percent was used to treat cancers the drug regulators never approved.

The researchers also looked at whether the off-label use of chemotherapies was supported by the National Comprehensive Care Network (NCCN), a group that publishes its own guidelines on cancer care.

They found that 14 percent of chemotherapies were prescribed off label but were supported by the NCCN’s expert opinion, and 10 percent were prescribed without NCCN or FDA support.

Conti told Reuters Health that doctors follow guidelines from expert organizations when there is not enough data for the FDA to make a decision, such as when rare diseases make it too difficult to conduct a clinical trial.

Conti and her colleagues point out, however, that some researchers have criticized NCCN recommendations, because of possible delays in guidelines based on the latest data, and possible conflicts of interests.

The total cost of chemotherapies for 2010 was $12 billion. Of that, $4.5 billion went toward off-label chemotherapies – $2.5 billion for non-NCCN supported uses.

‘A LITTLE TROUBLING’

“To me it’s a little troubling that so many drugs are given in areas where there is not a lot of data to back it up,” said Dr. Nancy Keating, a cancer researcher who was not involved with the new study.

“The tricky thing is patients with cancer and their doctors are looking for anything with a benefit. So I think they’re sometimes willing to try things where there isn’t as much data as you would like,” said Keating, from Boston’s Harvard Medical School and Brigham and Women’s Hospital.

But Conti said they can’t tell from their data whether patients prescribed on-label chemotherapy did better than patients receiving off-label chemotherapy.

“What our study basically does is highlight this proportion of use that is off-label and endorsed by expert opinion, or off-label and not endorsed by expert opinion,” Conti said.

She added that their study shows chemotherapy use is driven by FDA approval and expert opinion. The other chunk that’s prescribed without expert or FDA backing may be in response to a lack of available treatments, she said.

http://www.reuters.com/article/2013/02/19/us-chemotherapy-idUSBRE91I18T20130219

 

Yale study links common chemicals to osteoarthritis : perfluorinated chemicals

Contact: Michelle Bell michelle.bell@yale.edu 203-432-9869 Yale School of Forestry & Environmental Studies

New Haven, Conn. – A new study has linked exposure to two common perfluorinated chemicals (PFCs) with osteoarthritis. PFCs are used in more than 200 industrial processes and consumer products including certain stain- and water-resistant fabrics, grease-proof paper food containers, personal care products, and other items. Because of their persistence, PFCs have become ubiquitous contaminants of humans and wildlife. The study, published in Environmental Health Perspectives, is the first to look at the associations between perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), and osteoarthritis, in a study population representative of the United States.

“We found that PFOA and PFOS exposures are associated with higher prevalence of osteoarthritis, particularly in women, a group that is disproportionately impacted by this chronic disease,” said Sarah Uhl, who authored the study along with Yale Professor Michelle L. Bell and Tamarra James-Todd, an epidemiologist at the Harvard Medical School and Brigham and Women’s Hospital. The research was the focus of Uhl’s Master’s of Environmental Science Program at the Yale School of Forestry and Environmental Studies.

The authors analyzed data from six years of the National Health and Nutrition Examination Survey (NHANES, 2003-2008), which enabled them to account for factors such as age, income, and race/ethnicity. When the researchers looked at men and women separately, they found clear, strong associations for women, but not men. Women in the highest 25% of exposure to PFOA had about two times the odds of having osteoarthritis compared to those in the lowest 25% of exposure.

Although production and usage of PFOA and PFOS have declined due to safety concerns, human and environmental exposure to these chemicals remains widespread. Future studies are needed to establish temporality and shed light on possible biological mechanisms. Reasons for differences in these associations between men and women, if confirmed, also need further exploration. Better understanding the health effects of these chemicals and identifying any susceptible subpopulations could help to inform public health policies aimed at reducing exposures or associated health impacts.

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New study finds neither HFCS nor table sugar increases liver fat under ‘real world’ conditions !!! STUDY designed to FAIL !!!

EEV: This study must be faulted in two area’s immediately:

1. Length of Study 10 Weeks, like Huh?

2. “Not only is it safe to consume caloric sweeteners at recommended levels, it is important for consumers to understand that high fructose corn syrup and table sugar have the same amount of calories and studies like this indicate your body metabolizes them about the same.” Huh, Huh?

3. Study Participants had to be disease free between 25 and 35 kg yet consume no more than more than 14 alcoholic beverages per week.

4. HFCS was based upon percentage of calories required for weight maintenance, not real world caloric intake.

5. Even though all caloric intake equal, the 30% sweetener group gained weight, but no fat?

6. Lots of holes in this partial blind study, but the researches did report honestly. Even though the study sucked and open to experimenter bias in its reporting and design.

7. Oh and the COI’s

Steve Bravo: Has received consulting fees and equipment support from Siemens Inc.

James M. Rippe: Dr. Rippe’s research organization has received funding and Dr. Rippe has received consulting fees from ConAgra Foods, PepsiCo International,

Kraft Foods, the Corn Refiners Association and Weight Watchers Internationals

Contact: Carol Moreau cmoreau@rippelifestyle.com 508-756-1228 Rippe Lifestyle Institute

Adds to scientific evidence that the sweeteners are metabolically equivalent

SHREWSBURY, MA — A study published today in the Journal of Applied Physiology, Nutrition, and Metabolism presented compelling data showing the consumption of both high fructose corn syrup (HFCS) and sucrose (table sugar) at levels consistent with average daily consumption do not increase liver fat in humans, a leading cause of non-alcoholic fatty liver disease (NAFLD). The findings also add to an already well-established body of science that high fructose corn syrup and table sugar are metabolically equivalent.

Increased fat levels in the liver and muscle tissue have also shown to contribute to insulin resistance, a key factor in the development of type 2 diabetes.

The study, conducted by James Rippe, MD, Founder and Director of the Rippe Lifestyle Institute and Professor of Biomedical Sciences at the University of Central Florida, examined sixty-four individuals who consumed low-fat milk sweetened with either HFCS or sucrose with the added sugar matching the 25th, 50th and 90th percentile population consumption levels of fructose for ten weeks.

The results showed fat content of the liver remained unchanged when the six HFCS and sucrose groups were averaged. Fat content in muscle tissue was also unchanged over the 10 weeks when the six HFCS and sucrose groups were averaged.

“The study’s results are compelling because this is the first study of its kind to test the effects of HFCS and sucrose on liver fat levels in humans using real world conditions,” said Dr. Rippe, who received a grant from the Corn Refiners Association (CRA) to conduct the study. “Previous studies that sought to find a link between caloric sweeteners and diseases such as type 2 diabetes and liver disease often subjected individuals to unrealistically high levels of fructose or had subjects consume fructose independent of glucose, which is just not how fructose is consumed in our daily diet.  Using real world conditions, we find that HFCS and other caloric sweeteners do not appear to increase liver fat or contribute to insulin resistance.”

The two largest sources of fructose in the human diet are sucrose (containing 50% fructose and 50% glucose) and HFCS which is present in the human diet in two forms:  HFCS-55 (which consists of 55% fructose, 42% glucose and 3% other carbohydrates) and HFCS-42 (which consists of 42% fructose and 58% glucose).

“This study seems to confirm what physicians, registered dietitians and healthcare associations such as the American Medical Association have been saying for decades,” said Dr. Mark Haub, Associate Professor in the Department of Nutrition at Kansas State University. “Not only is it safe to consume caloric sweeteners at recommended levels, it is important for consumers to understand that high fructose corn syrup and table sugar have the same amount of calories and studies like this indicate your body metabolizes them about the same.”

For further information or to obtain a copy of this study, please visit www.nrcresearchpress.com/journal/apnm

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Dr. Rippe is a cardiologist and graduate of Harvard College and Harvard Medical School. His research laboratory has conducted numerous studies and published widely in the areas of nutrition and weight management. He is an advisor to the food and beverage industry and has received unrestricted educational grants from the Corn Refiners Association. He is the Founder and Director of the Rippe Lifestyle Institute, and Professor of Biomedical Sciences at the University of Central Florida.

Skin, soft tissue infections succumb to blue light : 100% Survival of Infections Vs. 18%

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

Blue light can selectively eradicate Pseudomonas aeruginosa infections of the skin and soft tissues, while preserving the outermost layer of skin, according to a proof-of-principle study led by Michael R. Hamblin of the Massachusetts General Hospital, and the Harvard Medical School, Boston. The research is published online ahead of print in the journal Antimicrobial Agents and Chemotherapy

“Blue light is a potential non-toxic, non-antibiotic approach for treating skin and soft tissue infections, especially those caused by antibiotic resistant pathogens,” says Hamblin.

In the study, animal models were infected with P. aeruginosa. All of the animals in the group treated with blue light survived, while in the control, 82 percent (9 out of 11) of the animals died.

Skin and soft tissue infections are the second most common bacterial infections encountered in clinical practice, and represent the most common infection presentation—more than 3 percent—in patients visiting emergency departments, says Hamblin. The prevalence of skin and soft tissue infections among hospitalized patients is 10 percent, with approximately 14.2 million ambulatory care visits every year and an annual associated medical cost of almost $24 billion (equivalent to $76 for every American), says Hamblin.

Treatment of skin and soft tissue infections has been significantly complicated by the explosion of antibiotic resistance, which may bring an end to what medical scientists refer to as the antibiotic era, says Hamblin. “Microbes replicate very rapidly, and a mutation that helps a microbe survive in the presence of an antibiotic drug will quickly predominate throughout the microbial population. Recently, a dangerous new enzyme, NDM-1, that makes some bacteria resistant to almost all antibiotics available has been found in the United States. Many physicians are concerned that several infections soon may be untreatable.”

Besides harming public health, antibiotic resistance boosts health care costs. “Treating resistant skin and soft tissue infections often requires the use of more expensive, or more toxic drugs, and can result in longer hospital stays for infected patients,” says Hamblin.

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A copy of the manuscript can be found online at http://bit.ly/asmtip0113b. Formal publication of the paper is scheduled for the March 2013 issue of Antimicrobial Agents and Chemotherapy.

(T. Dai, A. Gupta, Y.-Y. Huang, R. Yin, C.K. Murray, M.S. Vrahas, M. Sherwood, G.P. Tegos, and M.R. Hamblin, 2013. Blue light rescues mice from potentially fatal Pseudomonas aeruginosa burn infection: efficacy, safety, and mechanism of action. Antim. Agents Chemother. Published ahead of print 21 December 2012 ,doi:10.1128/AAC.01652-12)

Antimicrobial Agents and Chemotherapy is a publication of the American Society for Microbiology (ASM).  The ASM is the largest single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide

Physicians’ brain scans indicate doctors can feel their patients’ pain — and their relief

Contact: Bonnie Prescott bprescot@bidmc.harvard.edu 617-667-7306 Beth Israel Deaconess Medical Center

Novel experiment illuminates the importance of the doctor-patient relationship

BOSTON – A patient’s relationship with his or her doctor has long been considered an important component of healing. Now, in a novel investigation in which physicians underwent brain scans while they believed they were actually treating patients, researchers have provided the first scientific evidence indicating that doctors truly can feel their patients’ pain – and can also experience their relief following treatment.

Led by researchers at Massachusetts General Hospital (MGH) and the Program in Placebo Studies and Therapeutic Encounter (PiPS) at Beth Israel Deaconess Medical Center/Harvard Medical School, the new findings, which appear on-line today in Molecular Psychiatry, help to illuminate one of the more intangible aspects of health care – the doctor/patient relationship.

“Our findings showed that the same brain regions that have previously been shown to be activated when patients receive placebo therapies are similarly activated in the brains of doctors when they administer what they think are effective treatments,” explains first author Karin Jensen, PhD, an investigator in the Department of Psychiatry and Martinos Center for Biomedical Imaging at MGH and member of the PiPS. Notably, she adds, the findings also showed that the physicians who reported greater ability to take things from the patients’ perspective, that is, to empathize with patients’ feelings, experienced higher satisfaction during  patients’ treatments, as reflected in the brain scans.

“By demonstrating that caring for patients involves a complex set of brain events, including deep understanding of the patient’s facial and body expressions, possibly in combination with the physician’s own expectations of relief and feelings of reward, we have been able to elucidate the neurobiology underlying caregiving,” adds senior author Ted Kaptchuk, director of the PiPS and Associate Professor of Medicine at Harvard Medical School. “Our findings provide early evidence of the importance of interacting brain networks between patients and caregivers and acknowledge the doctor/patient relationship as a valued component of health care, alongside medications and procedures.”

Previous investigations have demonstrated that a brain region associated with pain relief (right ventrolateral prefrontal cortex, VLPFC) and a region associated with reward (rostral anterior cingulate cortex, rACC) are activated when patients experience the placebo effect, which occurs when patients show improvement from treatments that contain no active ingredients. The placebo effect accounts for significant portions of clinical outcomes in many illnesses — including pain, depression and anxiety.

Although behavioral research has suggested that physicians’ expectations influence patients’ clinical outcomes and help determine patients’ placebo responses, until now little effort has been directed to understanding the biology underlying the physician component of the clinical relationship. Jensen and her colleagues hypothesized that the same brain regions that are activated during patients’ placebo responses – the VLPFC and rACC — would similarly be activated in the brains of physicians as they treated patients. They also hypothesized that a physician’s perspective-taking skills would influence the outcomes.

To test these hypotheses, the scientists developed a unique equipment arrangement that would enable them to conduct functional magnetic resonance imaging (fMRI) of the physicians’ brains while the doctors had face-to-face  interactions with patients, including observing patients as they underwent pain treatments.

The experiment included 18 physicians (all of whom had received their medical degree within the last 10 years and represented nine separate medical specialties). Two 25-year-old females played the role of “patients” and followed a rehearsed script. The experiment called for the participating physicians to  administer pain relief with what they thought was a pain-relieving electronic device, but which was actually a non-active “sham” device.

To ensure that the physicians believed that the sham device really worked, the investigators first administered a dose of “heat pain” to the physicians’ forearms to gauge pain threshold and then “treated” them with the fake machine. During the treatments, the investigators reduced the heat stimulation, to demonstrate to the participants that the therapy worked. The physicians underwent fMRI scans while they experienced the painful heat stimulation so that investigators could see exactly which brain regions were activated during first-person perception of pain.

In the second portion of the experiment,each physician was introduced to a patient and asked to perform a standardized clinical examination, which was conducted in a typical exam room for approximately 20 minutes. (The clinical exam was performed in order to establish a realistic rapport between the physician and patient before fMRI scanning took place, and was comparable to a standard U.S. doctor’s appointment.) At this point the physician also answered a questionnaire, the Interpersonal Reactivity Index, used to measure the participant’s self-reported perspective-taking skills.

During the third step, says Jensen, the physician and patient were led into the scanner room. “The physician went inside the scanner and was equipped with a remote control that could activate the ‘analgesic device’ when prompted,” she explains. Mirrors inside the scanner enabled physicians to maintain eye contact with the patient, who was seated on a chair next to the scanner’s bed and hooked up to both the thermal pain stimulator and the pain-relieving device.

Then, in a randomized order, physicians were instructed to either treat a patient’s pain or to press a control button that provided no relief. When physicians were told not to activate pain relief, the “patient” exhibited a painful facial expression while the physicians watched. When the physicians were instructed to treat the patients’ pain, they could see that the subjects’ faces were neutral and relaxed, the result of pain relief. During these doctor-patient interactions, fMRI scans measured the doctors’ brain activations.

Following the scanning session, the physicians were removed from the scanner and told exactly how the experiment had been performed, says Jensen. “If the physician did not agree with the deceptive component of the study, they were given the opportunity to withdraw their data. No one did this.”

As predicted, the authors found that while treating patients, the physicians activated the right VLPFC region of the brain, a region previously implicated in the placebo response. Furthermore, Jensen adds, the physicians’ ability to take the patients’ viewpoints correlated to brain activations and subjective ratings; physicians who reported high perspective-taking skills were more likely to show activation in the rACC brain region, which is associated with reward.

“We already know that the physician-patient relationship provides solace and can even relieve many symptoms,” adds Kaptchuk. “Now, for the first time, we’ve shown that caring for patients encompasses a unique neurobiology in physicians. Our ultimate goal is to transform the ‘art of medicine’ into the ‘science of care,’ and this research is an important first step in this process as we continue investigations to find out how patient-clinician interactions can lead to measurable clinical outcomes in patients.”

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In addition to Jensen and Kaptchuk, study coauthors include MGH and PiPS investigators Jacqueline Raicek, Alexandra Cheetham, Rosa Spaeth, Amanda Cook, Randy L. Gollub, and Jian Kong; Predrag Petrovic of the Karolinska Institute, Stockholm, Sweden;  and Irving Kirsch of the PiPS.

This study was funded, in part, by the Swedish Society for Medical Research and the Swedish Council for Working Life and Social Research, Osher Center for Integrative Medicine (Karolinska Institute) and by NIH grants from the National Center on Complementary and Alternative Medicine (K24AT004095; P01 AT003883; R21AT004497; R01AT006364; R01AT005280), the National Institute on Drug Abuse (R03AT218317); and the National Center for Research Resources (M01-RR-01066 and UL1 RR025758-01; and P41RR14075).

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and currently ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2012, MGH moved into the number one spot on the 2012-13 U.S. News & World Report list of “America’s Best Hospitals.”

Wanted: ‘Adventurous woman’ to give birth to Neanderthal man – Harvard professor seeks mother for cloned cave baby

EEV: Update: Professor Claims his was misunderstood, and is not looking for a Neanderthal Mother:

http://www.independent.co.uk/news/science/im-no-dr-moreau-harvard-professor-says-he-is-not-looking-for-a-woman-to-give-birth-to-a-neanderthal-blaming-reports-on-a-poor-translation-8461707.html

By  Allan Hall

PUBLISHED: 10:36 EST, 20  January 2013 |  UPDATED: 12:49 EST, 20 January 2013

Back to life: This model of Neanderthal Man shows what the extinct species may have once looked like
Back to life: This model of Neanderthal Man shows what  the extinct species may have once looked like

A leading geneticist is on the hunt for an  ‘adventurous woman’ to help turn back the hands of time – and give birth to a  Neanderthal baby.

George Church, a genetics professor at Harvard Medical  School, believes he can bring back the extinct ancestor of modern man after more  than 33,000 years.

Contrary to popular belief, Neanderthals were  in fact a highly intelligent race and  Prof Church believes they could be recreated through modern medicine.

He told German magazine, Der  Spiegel: ‘I  have already managed to  attract enough DNA from fossil bones to  reconstruct the DNA of the human  species largely extinct. Now I need an  adventurous female human.

‘It depends on a lot of things, but I think  it can be done. The reason I would  consider it a  possibility is that a bunch of technologies are developing faster  than  ever before.

‘In particular, reading and writing DNA is  now about a  million times faster than seven or eight years ago.

‘Another technology that the  de-extinction  of a Neanderthal would require is human cloning.

‘We can  clone all kinds of mammals, so it’s  very likely that we could clone a  human. Why shouldn’t we be able to do so?”

Prof Church, 58, is a pioneer in synthetic  biology, which aims is to create synthetic DNA and organisms in the  laboratory.

During the 1980s, he helped initiate the  Human Genome Project that created a map of the human genome.

Cloning the caveman: Geneticist Professor George Church
Cloning the caveman: Geneticist Professor George  Church

He admits his project may have shades of  Frankenstein about it, but he believes recreating Neanderthals would benefit  mankind.

Prof Church added: ‘Neanderthals might think  differently than we do. We know that they had a larger cranial size. They could  even be more intelligent than us.

‘When the time comes to deal with an epidemic  or getting off the planet or whatever, it’s conceivable that their way of  thinking could be beneficial.

‘They could maybe even create a new  neo-Neanderthal culture and become a political force. The main goal is to  increase diversity. The one thing that is bad for society is low diversity.

‘This is true for culture or evolution, for  species and also for whole societies. If you become a monoculture, you are at  great risk of perishing.

‘Therefore the recreation of Neanderthals  would be mainly a question of societal risk avoidance.’

The geneticist also explains how the process  could theoretically be carried out.

‘The first thing you have to do is to  sequence the Neanderthal genome, and that has actually been done.

‘The next step would be to chop this genome  up into, say, 10,000 chunks and then synthesize these. Finally, you would  introduce these chunks into a human stem cell.

Big ideas: Contrary to belief, Neanderthals had a larger brain size and may have been more intelligent than humans
Big ideas: Contrary to belief, Neanderthals had a larger  brain size and may have been more intelligent than humans

‘If we do that often enough, then we would  generate a stem cell line that would get closer and closer to the corresponding  sequence of the Neanderthal.

‘We developed the semi-automated procedure  required to do that in my lab.

‘Finally, we assemble all the chunks in a  human stem cell, which would enable you to finally create a Neanderthal  clone.’

Bringing the past alive: A scene from the film Jurassic Park, which suggested dinosaurs could be recreated through DNA trapped in amber
Bringing the past alive: A scene from the film Jurassic  Park, which suggested dinosaurs could be recreated through DNA trapped in  amber

The missing puzzle in his plan is a surrogate  mother for the project, who would be a human female.

According to experts, Prof Church’s plan is  technically possible.

Many of his suggestions formed the central  plot-line of the 1993 Steven Spielberg film Jurassic Park, in which dinosaur DNA  that had been embedded in chunks of amber was extracted to recreate the monsters  that once dominated Earth.

Neanderthals are named after the site in the  Neander Valley, Germany, where archaeologists first discovered the species in  1856 – three years before Charles Darwin published his On The Origin Of  Species.

Read more: http://www.dailymail.co.uk/news/article-2265402/Wanted-Adventurous-woman-birth-Neanderthal-man–Harvard-professor-seeks-mother-cloned-cave-baby.html#ixzz2IY5dBIlh Follow us: @MailOnline on Twitter | DailyMail on Facebook

Some men voice complaints of shortened penis following prostate cancer treatment

Contact: Teresa Herbert teresa_herbert@dfci.harvard.edu 617-632-4090 Dana-Farber Cancer Institute

Perceived reduction in penis size linked to regrets of treatment choice

BOSTON – A small percentage of men in a prostate cancer study complained that their penis seemed shorter following treatment, with some saying that it interfered with intimate relationships and caused them to regret the type of treatment they chose.

Complaints were more common in men treated with radical prostatectomy (surgical removal of the prostate) or male hormone-blocking drugs combined with radiation therapy, according to the study by researchers from Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC). No men reported a perceived shortening of their penis following radiation therapy alone.

The study’s findings, which are being published in the January issue of the journal Urology, are based on surveys completed by physicians of 948 men treated for prostate cancer and who had suffered a recurrence of the disease.

Twenty-five men (2.63 percent of the group) complained of smaller penises after treatment – 3.73 percent for surgery, 2.67 percent for radiotherapy plus androgen deprivation therapy (ADT), and 0% for radiotherapy alone. Radiotherapy included both radiation administered by an external x-ray machine, and brachytherapy – the implantation of radioactive seeds directly into the prostate.

The scientific team, led by Paul Nguyen, MD, a radiation oncologist, and medical student Arti Parekh, said it is the first study to link men’s perceptions of a reduction in penis size to lowered life satisfaction, problems in emotional relationships, and misgivings about the specific form of prostate cancer treatment they chose.

Nguyen said that the potential side effect of a smaller penis is well-known among physicians and surgeons, said Nguyen, “but it’s almost never discussed with patients, so it can be very upsetting to some men when it occurs. Patients can deal with almost any side effect if they have some inkling ahead of time that they may happen.”

The report’s authors said physicians should discuss the possibility with their patients so that they can make more-informed treatment choices.

There were no direct measurements of penis size either before or after treatment, said the researchers. Nor did the patients’ physicians specifically ask about this side effect; the issue was brought up by patients in conversations with their doctors. For this and other reasons, the authors of the new study suggest that the problem is likely more common than reported in the survey.

“Prostate cancer is one of the few cancers where patients have a choice of therapies, and because of the range of possible side effects, it can be a tough choice,” said Nguyen. “This study says that when penile shortening does occur, it really does affect patients and their quality of life. It’s something we should be discussing up front so that it will help reduce treatment regrets.”

The likelihood and magnitude of penis shortening as a consequence of treatment have not been well studied, said the researchers. However, Jim Hu, MD, a surgeon at the University of California, Los Angeles Medical Center and a co-author of the study, said “Previous studies have concluded that there is shortened penis length following prostatectomy. This is most common with non-nerve sparing surgery, as this may result in fibrosis and atrophy of erectile tissue due to damage to nerve and vascular structures.” The present study did not find much difference on that score.

The study’s subjects were men enrolled in a registry called COMPARE that collects data on patients whose prostate cancer shows signs of recurring after initial treatment. Of the 948 men in the study, 22 percent were younger than 60 and the majority were in their 60s, 70s and 80s. Just over half – 54 percent – had undergone surgery to remove their cancerous prostate, while 24 percent received radiation therapy combined with hormone-blocking treatment, and 22 percent had radiation therapy alone.

In an editorial comment accompanying the report, Luc Cormier, MD, PhD, of Dijon University Hospital in France said the study “is really of interest because of the number of patients and that it included other treatment methods in addition to radical prostatectomy.”

The surveys of the men did not report on their sexual functioning.  Cormier observed that “sexual activity needs to be thoroughly measured owing to the obvious relationship with the patients’ perception of penile length.”

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Other authors are from Dana-Farber, the University of Connecticut, and the University of Texas M.D. Anderson Cancer Center.

The research was supported by an anonymous family foundation along with other foundation funding.

About Dana-Farber Cancer Institute:

Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States.  It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult care with Brigham and Women’s Hospital as Dana-Farber/Brigham and Women’s Cancer Center, and it provides pediatric care with Boston Children’s Hospital as Dana-Farber/Children’s Hospital Cancer Center.  Dana-Farber is the top-ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding.  Follow Dana-Farber on Twitter: @dana-farber or Facebook: facebook.com/danafarbercancerinstitute.

About Brigham and Women’s Hospital:

Brigham and Women’s Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 3.5 million annual patient visits, is the largest birthing center in New England and employs more than 15,000 people. The Brigham’s medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, involving nearly 1,000 physician-investigators and renowned biomedical scientists and faculty supported by $640 million in funding. BWH continually pushes the boundaries of medicine, including building on its legacy in organ transplantation by performing the first face transplants in the U.S. in 2011. BWH is also home to major landmark epidemiologic population studies, including the Nurses’ and Physicians’ Health Studies, OurGenes and the Women’s Health Initiative.  For more information and resources, please visit BWH’s online newsroom.

Preventing prostate cancer through androgen deprivation may have harmful effects

Contact: Jeremy Moore Jeremy.Moore@aacr.org 215-446-7109 American Association for Cancer Research

PHILADELPHIA — The use of androgen deprivation therapies to prevent precancerous prostate abnormalities developing into aggressive prostate cancer may have adverse effects in men with precancers with specific genetic alterations, according to data from a preclinical study recently published in Cancer Discovery, a journal of the American Association for Cancer Research.

“The growth and survival of prostate cancer cells are very dependent on signals that the cancer cells receive from a group of hormones, called androgens, which includes testosterone,” said Thomas R. Roberts, Ph.D., co-chair of the Department of Cancer Biology at the Dana-Farber Cancer Institute and professor of biological chemistry and molecular pharmacology at Harvard Medical School in Boston, Mass.

Previous findings from two major randomized, placebo-controlled prostate cancer chemoprevention trials revealed that androgen deprivation therapy reduced the overall risk for low-grade prostate cancer. However, both trials also revealed a high cumulative risk for high-grade prostate cancers that has caused concern among experts.

High-grade prostatic intraepithelial neoplasia is a prostate abnormality that is considered to be a major precursor to prostate cancer. Loss of the tumor suppressor PTEN is detected in 9 to 45 percent of clinical cases.

Using a mouse model of PTEN-driven high-grade prostatic intraepithelial neoplasia, Roberts and his colleagues investigated whether surgical or chemical androgen deprivation could prevent the cancer precursor from progressing to more aggressive disease.

“When we castrated the animals, we thought the tumors would shrink and they did initially,” Roberts said. “However, they then grew back and became invasive.”

The results of this preclinical study suggest that prophylactic reduction of the most active form of androgen, or blocking androgen receptor function, might have unintended consequences in some men.

“Stretching our data even further, these findings suggest that as men age and their testosterone levels decrease, loss of testosterone might actually encourage indolent prostate tumors to become more aggressive,” Roberts said. “This suggests that testosterone supplements might be a good thing for the prostate, even though current wisdom suggests the opposite.”

Roberts noted that these results should be interpreted with caution because the prostate glands of mice are different from their human counterparts. More data on human tumors are needed to evaluate whether the data from this mouse study are applicable to men.

###

Follow the AACR on Twitter: @aacr #aacr

Follow the AACR on Facebook: http://www.facebook.com/aacr.org

About the American Association for Cancer Research

Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 17,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the scientific partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

88th Health Research Report 21 AUG 2010 – Reconstruction

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Health Research Report

88th Issue 31 AUG 2010

Compiled By Ralph Turchiano

www.vit.bz

www.youtube.com/vhfilm 

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www.healthresearchreport.me 

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Editors Top Five:

1. Women who drink beer more likely to develop psoriasis

2. Pharmaceuticals: A market for producing ‘lemons’ and serious harm

3. B vitamins and the aging brain examined

4. THL Recommends Suspension of H1N1 Vaccinations

5. Kudzu Vine Extract May Treat Alcoholism, Cocaine Addiction

In this Issue:

1. Women who drink beer more likely to develop psoriasis

2. Amphetamine use increases risk of aortic tears in young adults, UT Southwestern researchers report

3. Pharmaceuticals: A market for producing ‘lemons’ and serious harm

4. Nearly 1 million children potentially misdiagnosed with ADHD

5. B vitamins and the aging brain examined

6. Prenatal exposure to pesticides linked to attention problems

7. Bottled tea beverages may contain fewer polyphenols than brewed tea

8. Eating berries may activate the brain’s natural housekeeper for healthy aging

9. Vitamin D found to influence over 200 genes, highlighting links to disease

10. Diabetes can cause a sugar coating that smothers body’s immune defences

11. Polyphenol antioxidants inhibit iron absorption

12. A case for exercising

13. Researchers study cinnamon extracts

14. Salmon baby food? Babies need omega-3s and a taste for fish, scientist says

15. Atrazine causes prostate inflammation in male rats and delays puberty

16. Grapefruit’s bitter taste holds a sweet promise for diabetes therapy

17. Exposure to low doses of BPA alters gene expression in the fetal mouse ovary

18. Plantain and broccoli fibers may block key stage in Crohn’s disease development

19. Vitamin D may treat and prevent allergic reaction to mold in cystic fibrosis patients

20. Black rice rivals pricey blueberries as source of healthful antioxidants

21. Supplement produces a ‘striking’ endurance boost

22. Kudzu Vine Extract May Treat Alcoholism, Cocaine Addiction

23. THL Recommends Suspension of H1N1 Vaccinations

Public release date: 16-Aug-2010

Women who drink beer more likely to develop psoriasis

Regular beer—but not light beer or other types of alcohol—appears to be associated with an increased risk of developing psoriasis, according to a report posted online today that will be published in the December print issue of Archives of Dermatology, one of the JAMA/Archives journals.

“Psoriasis is a common immune-mediated skin disease,” the authors write as background information in the article. “The association between alcohol consumption and increased risk of psoriasis onset and psoriasis worsening has long been suspected. For example, individuals with psoriasis drink more alcohol than individuals without psoriasis, and alcohol intake may exacerbate psoriasis severity.”

For other diseases, type of alcoholic beverage has been shown to influence risk—for instance, beer confers a larger risk for gout than wine or spirits. To evaluate the association between different types of alcohol and psoriasis risk, Abrar A. Qureshi, M.D., M.P.H., of Brigham and Women’s Hospital and Harvard Medical School, Boston, assessed data from 82,869 women who were age 27 to 44 years in 1991. The women, participants in the Nurses’ Health Study II, reported the amount and type of alcohol they consumed on biennial questionnaires. They also reported whether they had received a diagnosis of psoriasis.

Through 2005, 1,150 cases of psoriasis developed, 1,069 of which were used for analysis. Compared with women who did not drink alcohol, the risk of psoriasis was 72 percent greater among women who had an average of 2.3 drinks per week or more. When beverages were assessed by type, there was an association between non-light beer drinking and psoriasis, such that women who drank five or more beers per week had a risk for the condition that was 1.8 times higher. Light beer, red wine, white wine and liquor were not associated with psoriasis risk.

When only confirmed psoriasis cases—those in which women provided more details about their condition on a seven-item self-assessment—were considered, the risk for psoriasis was 2.3 times higher for women who drank five or more beers per week than women who did not drink beer.

“Non-light beer was the only alcoholic beverage that increased the risk for psoriasis, suggesting that certain non-alcoholic components of beer, which are not found in wine or liquor, may play an important role in new-onset psoriasis,” the authors write. “One of these components may be the starch source used in making beer. Beer is one of the few non-distilled alcoholic beverages that use a starch source for fermentation, which is commonly barley.” Barley and other starches contain gluten, to which some individuals with psoriasis show a sensitivity. Lower amounts of grain are used to make light beer as compared with non-light beer, potentially explaining why light beer was not associated with psoriasis risk, they note.

“Women with a high risk of psoriasis may consider avoiding higher intake of non-light beer,” the authors conclude. “We suggest conducting further investigations into the potential mechanisms of non-light beer inducing new-onset psoriasis.”

 

Public release date: 16-Aug-2010

Amphetamine use increases risk of aortic tears in young adults, UT Southwestern researchers report

DALLAS – Aug. 17, 2010 – Young adults who abuse amphetamines may be at greater risk of suffering a tear in the main artery leading from the heart, UT Southwestern Medical Center researchers have found.

In the study, published in the August issue of American Heart Journal, researchers examined medical records from nearly 31 million people between 18 and 49 years old hospitalized from 1995 to 2007 and found that amphetamine abuse was associated with a threefold increase in the odds of aortic dissection.

 

“Aortic dissection in young people is rare, but it frequently can lead to death,” said Dr. Arthur Westover, assistant professor of psychiatry at UT Southwestern and the study’s lead author. “Doctors should screen young adults with aortic dissection for amphetamine abuse in searching for a potential cause.”

Individual case reports have suggested a link between aortic dissection and amphetamine abuse, but this is believed to be the first epidemiological study of a large group of people on the issue, Dr. Westover said.

The aorta stems from the heart and is the largest artery in the body. Dissection occurs when a tear develops in the inner layer of the aorta, allowing blood to separate, or dissect. The blood can eventually cause a rupture in the aortic wall, often resulting in death.

Amphetamines are stimulants that can be used to treat medical conditions such as attention-deficit disorder. They also are abused illegally as recreational drugs or performance enhancers. Researchers note that the abuse of amphetamines – including methamphetamines, or “meth” – significantly increased among hospitalized young adults from 1995 to 2007.

Amphetamines act on the body in similar ways as cocaine, which also is associated with adverse effects on the heart. Medically, amphetamines are known to increase blood pressure, and hypertension is a known trigger of aortic dissection.

Researchers also analyzed medical data for more than 49 million people 50 years or older from the same time period.

“We found that the frequency of aortic dissection is increasing in young adults but not older adults,” Dr. Westover said. “It is not yet clear why.”

Researchers noted that in California, Hawaii, Oregon and Washington state, the percentage of aortic dissection cases linked to amphetamine abuse among young adults during the study period was three times greater than the national figure.

“This illustrates that in areas where amphetamine abuse is more common, there are greater public health consequences,” Dr. Westover said.

Dr. Westover’s research previously has linked amphetamine abuse to stroke and heart attack.

“This adds to our growing understanding of the cardiovascular risks associated with abuse of amphetamines,” said Dr. Paul Nakonezny, associate professor of clinical sciences and psychiatry at UT Southwestern and an author on the paper.

Public release date: 17-Aug-2010

Pharmaceuticals: A market for producing ‘lemons’ and serious harm

Incentives and protections for industry encourage development of many drugs with few new benefits over existing pharmaceuticals, but with risk of serious harm to users

ATLANTA — The pharmaceutical industry is a “market for lemons,” a market in which the seller knows much more than the buyer about the product and can profit from selling products less effective and less safe than consumers are led to believe, according to an analysis that will be presented at the 105th Annual Meeting of the American Sociological Association.

“Sometimes drug companies hide or downplay information about serious side effects of new drugs and overstate the drugs’ benefits,” said Donald Light, the sociologist who authored the study and who is a professor of comparative health policy at the University of Medicine and Dentistry of New Jersey. “Then, they spend two to three times more on marketing than on research to persuade doctors to prescribe these new drugs. Doctors may get misleading information and then misinform patients about the risks of a new drug. It’s really a two-tier market for lemons.”

Three reasons why the pharmaceutical market produces “lemons” are: Having companies in charge of testing new drugs, providing firewalls of legal protection behind which information about harms or effectiveness can be hidden, and the relatively low bar set for drug efficacy in order for a new drug to be approved, Light said.

According to his study, independent reviewers found that about 85 percent of new drugs offer few if any new benefits. Yet, toxic side effects or misuse of prescription drugs now make prescription drugs a significant cause of death in the United States.

 

Light’s paper, “Pharmaceuticals: A Two-Tier Market for Producing ‘Lemons’ and Serious Harm,” is an institutional analysis of the pharmaceutical industry and how it works based on a range of independent sources and studies, including the Canadian Patented Medicine Prices Review Board, the Food and Drug Administration, and Prescrire International.

The foundation for the paper is the work Light did for a forthcoming book he edited, titled The Risk of Prescription Drugs, which is scheduled for publication this fall by Columbia University Press.

In both his paper and his book, Light describes the “Risk Proliferation Syndrome” that is maximizing the number of patients exposed to new drugs that have relatively low efficacy and effectiveness but have greater risk of adverse side effects. Building on clinical trials designed to minimize evidence of harm and published literature that emphasizes a drug’s advantages, companies launch massive campaigns to sell it, when a controlled, limited launch would allow evidence to be gathered about the drug’s effects. Companies recruit leading clinicians to try using the drug for conditions other than those for which it is approved and to promote such off-label or unapproved uses. Physicians inadvertently become “double agents” — promoters of the new drug, yet trusted stewards of patients’ well-being, said Light. When patients complain of adverse reactions, studies show their doctors are likely to discount or dismiss them, according to Light.

Despite the extensive requirements for testing the efficacy and safety of each new drug, companies “swamp the regulator” with large numbers of incomplete, partial, substandard clinical trials, Light said. For example, in one study of 111 final applications for approval, 42% lacked adequately randomized trials, 40% had flawed testing of dosages, 39% lacked evidence of clinical efficacy, and 49% raised concerns about serious adverse side effects, said Light.

“Just recently, major reports have come out about biased, poor trials for Avandia and Avastin,” Light said, who noted that orphan drugs are tested even less well.

“The result is that drugs get approved without anyone being able to know how effective they really are or how much serious harm they will cause,” Light said. The companies control the making of scientific knowledge and then control which findings will go to the FDA or be published.

“A few basic changes could improve the quality of trials and evidence about the real risks and benefits of new drugs,” Light said. “We could also increase the percentage of new drugs that are really better for patients.

Public release date: 17-Aug-2010

 

Nearly 1 million children potentially misdiagnosed with ADHD

EAST LANSING, Mich. — Nearly 1 million children in the United States are potentially misdiagnosed with attention deficit hyperactivity disorder simply because they are the youngest – and most immature – in their kindergarten class, according to new research by a Michigan State University economist.

These children are significantly more likely than their older classmates to be prescribed behavior-modifying stimulants such as Ritalin, said Todd Elder, whose study will appear in a forthcoming issue of the Journal of Health Economics.

Such inappropriate treatment is particularly worrisome because of the unknown impacts of long-term stimulant use on children’s health, Elder said. It also wastes an estimated $320 million-$500 million a year on unnecessary medication – some $80 million-$90 million of it paid by Medicaid, he said.

Elder said the “smoking gun” of the study is that ADHD diagnoses depend on a child’s age relative to classmates and the teacher’s perceptions of whether the child has symptoms.

“If a child is behaving poorly, if he’s inattentive, if he can’t sit still, it may simply be because he’s 5 and the other kids are 6,” said Elder, assistant professor of economics. “There’s a big difference between a 5-year-old and a 6-year-old, and teachers and medical practitioners need to take that into account when evaluating whether children have ADHD.”

ADHD is the most commonly diagnosed behavioral disorder for kids in the United States, with at least 4.5 million diagnoses among children under age 18, according to the Centers for Disease Control and Prevention.

However, there are no neurological markers for ADHD (such as a blood test), and experts disagree on its prevalence, fueling intense public debate about whether ADHD is under-diagnosed or over-diagnosed, Elder said.

Using a sample of nearly 12,000 children, Elder examined the difference in ADHD diagnosis and medication rates between the youngest and oldest children in a grade. The data is from the Early Childhood Longitudinal Study Kindergarten Cohort, which is funded by the National Center for Education Statistics.

According to Elder’s study, the youngest kindergartners were 60 percent more likely to be diagnosed with ADHD than the oldest children in the same grade. Similarly, when that group of classmates reached the fifth and eighth grades, the youngest were more than twice as likely to be prescribed stimulants.

Overall, the study found that about 20 percent – or 900,000 – of the 4.5 million children currently identified as having ADHD likely have been misdiagnosed.

Elder used the students’ birth dates and the states’ kindergarten eligibility cutoff dates to determine the youngest and oldest students in a grade. The most popular cutoff date in the nation is Sept. 1, with 15 states mandating that children must turn 5 on or before that date to attend kindergarten.

The results – both from individual states and when compared across states – were definitive. For instance, in Michigan – where the kindergarten cutoff date is Dec. 1 – students born Dec. 1 had much higher rates of ADHD than children born Dec. 2. (The students born Dec. 1 were the youngest in their grade; the students born Dec. 2 enrolled a year later and were the oldest in their grade.)

Thus, even though the students were a single day apart in age, they were assessed differently simply because they were compared against classmates of a different age set, Elder said.

In another example, August-born kindergartners in Illinois were much more likely to be diagnosed with ADHD than Michigan kindergartners born in August of the same year as their Illinois counterparts. That’s because Illinois’ kindergarten cutoff date is Sept. 1, meaning those August-born children were the youngest in their grade, whereas the Michigan students were not.

According to the study, a diagnosis of ADHD requires evidence of multiple symptoms of inattention or hyperactivity, with these symptoms persisting for six or more months – and in at least two settings – before the age of seven. The settings include home and school.

Although teachers cannot diagnose ADHD, their opinions are instrumental in decisions to send a child to be evaluated by a mental health professional, Elder said.

“Many ADHD diagnoses may be driven by teachers’ perceptions of poor behavior among the youngest children in a kindergarten classroom,” he said. “But these ‘symptoms’ may merely reflect emotional or intellectual immaturity among the youngest students.”

The paper will be published in the Journal of Health Economics in conjunction with a related paper by researchers at North Carolina State University, Notre Dame and the University of Minnesota that arrives at similar conclusions as the result of a separate study.

Public release date: 17-Aug-2010

B vitamins and the aging brain examined

B vitamins–B-6, B-12 and folate–all nourish the brain. But much remains to be discovered about the relation between these essential nutrients and our brainpower.

U.S. Department of Agriculture (USDA) nutritionist Lindsay H. Allen has collaborated in ongoing research that has taken a closer look at the role these nutrients may play in preventing decline in brain function. The investigations, led by Mary N. Haan of the University of California-San Francisco, are part of the multiyear Sacramento (Calif.) Area Latino Study on Aging, or “SALSA.” Begun in 1996, the study attracted nearly 1,800 Hispanic seniors, ages 60 to 101, as volunteers.

According to Allen, the research is needed because many studies of B vitamins and brain function have given inconsistent or conflicting results. Allen is director of the Agricultural Research Service (ARS) Western Human Nutrition Research Center in Davis, Calif. ARS is the chief intramural scientific research agency of USDA. Scientists from the University of California-Davis (UCD) and the UCD Medical Center also are collaborating in the research.

An analysis of volunteers’ blood samples showed that lower levels of one B vitamin, folate, were associated with symptoms of dementia and poor brain function, also called “cognitive decline,” as determined by standard tests of memory and other factors. The impairments were detectable even though less than 1 percent of the volunteers were actually deficient in folate.

 

In women, but not men, low levels of folate were associated with symptoms of depression. In fact, female volunteers whose plasma folate levels were in the lowest third were more than twice as likely to have symptoms of depression as volunteers in the highest third. That finding provided new evidence of an association between lower blood folate and depression. Depression is already known to affect brain function.

In research with vitamin B-12, the SALSA team determined that a protein known as holoTC, short for holotranscobalamin, might be key to a new approach for detecting cognitive decline earlier and more accurately.

Public release date: 19-Aug-2010

Prenatal exposure to pesticides linked to attention problems

Berkeley — Children who were exposed to organophosphate pesticides while still in their mother’s womb were more likely to develop attention disorders years later, according to a new study by researchers at the University of California, Berkeley.

The new findings, to be published Aug. 19 in the journal Environmental Health Perspectives (EHP), are the first to examine the influence of prenatal organophosphate exposure on the later development of attention problems. The researchers found that prenatal levels of organophosphate metabolites were significantly linked to attention problems at age 5, with the effects apparently stronger among boys.

Earlier this year, a different study by researchers at Harvard University associated greater exposure to organophosphate pesticides in school-aged children with higher rates of attention deficit hyperactivity disorder (ADHD) symptoms.

“These studies provide a growing body of evidence that organophosphate pesticide exposure can impact human neurodevelopment, particularly among children,” said the study’s principal investigator, Brenda Eskenazi, UC Berkeley professor of epidemiology and of maternal and child health. “We were especially interested in prenatal exposure because that is the period when a baby’s nervous system is developing the most.”

The study follows more than 300 children participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal study led by Eskenazi that examines environmental exposures and reproductive health. Because the mothers and children in the study are Mexican-Americans living in an agricultural community, their exposure to pesticides is likely higher and more chronic, on average, than that of the general U.S. population.

Yet, the researchers pointed out that the pesticides they examined are widely used, and that the results from this study are a red flag that warrants precautionary measures.

“It’s known that food is a significant source of pesticide exposure among the general population,” said Eskenazi. “I would recommend thoroughly washing fruits and vegetables before eating them, especially if you’re pregnant.”

 

Organophosphate pesticides act by disrupting neurotransmitters, particularly acetylcholine, which plays an important role in sustaining attention and short-term memory.

“Given that these compounds are designed to attack the nervous system of organisms, there is reason to be cautious, especially in situations where exposure may coincide with critical periods of fetal and child development,” said study lead author Amy Marks, who was an analyst at UC Berkeley’s School of Public Health at the time of the study.

Many of these same UC Berkeley researchers are also finding that children with certain genetic traits may be at greater risk, a finding that is being published the same day in a separate EHP paper. That study found that 2-year-olds with lower levels of paraoxonase 1 (PON1), an enzyme that breaks down the toxic metabolites of organophosphate pesticides, had more neurodevelopmental delays than those with higher levels of the enzyme. The authors suggest that people with certain PON1 genotypes could be particularly vulnerable to pesticide exposure.

In the study on attention problems, researchers tested for six metabolites of organophosphate pesticides in mothers twice during pregnancy and in the children several times after birth. Together, the metabolites represent the breakdown products of about 80 percent of all the organophosphate pesticides used in the Salinas Valley.

The researchers then evaluated the children at age 3.5 and 5 years for symptoms of attention disorders and ADHD using maternal reports of child behavior, performance on standardized computer tests, and behavior ratings from examiners. They controlled for potentially confounding factors such as birthweight, lead exposure and breastfeeding.

Each tenfold increase in prenatal pesticide metabolites was linked to having five times the odds of scoring high on the computerized tests at age 5, suggesting a greater likelihood of a child having clinical ADHD. The effect appeared to be stronger for boys than for girls.

While a positive link between prenatal pesticide exposure and attention problems was seen for 3.5-year-olds, it was not statistically significant, a finding that did not surprise the researchers.

“Symptoms of attention disorders are harder to recognize in toddlers, since kids at that age are not expected to sit down for significant lengths of time,” said Marks. “Diagnoses of ADHD often occur after a child enters school.”

The UC Berkeley researchers are continuing to follow the children in the CHAMACOS study as they get older, and expect to present more results in the years to come.

The findings add to the list of chemical assaults that have been linked to ADHD in recent years. In addition to pesticides, studies have found associations with exposure to lead and to phthalates, which are commonly used in toys and plastics.

“High levels of the symptoms of ADHD by age 5 are a major contributor to learning and achievement problems in school, accidental injuries at home and in the neighborhood, and a host of problems in peer relationships and other essential competencies,” said UC Berkeley psychology professor Stephen Hinshaw, one of the country’s leading experts on ADHD, who was not part of this study. “Finding preventable risk factors is therefore a major public health concern.”

 

Public release date: 22-Aug-2010

Bottled tea beverages may contain fewer polyphenols than brewed tea

BOSTON, Aug. 22, 2010 — The first measurements of healthful antioxidant levels in commercial bottled tea beverages has concluded that health-conscious consumers may not be getting what they pay for: healthful doses of those antioxidants, or “poylphenols,” that may ward off a range of diseases.

Scientists reported here today at the 240th National Meeting of the American Chemical Society (ACS) that many of the increasingly popular beverages included in their study, beverages that account for $1 billion in annual sales in the United States alone, contain fewer polyphenols than a single cup of home-brewed green or black tea. Some contain such small amounts that consumers would have to drink 20 bottles to get the polyphenols present in one cup of tea.

“Consumers understand very well the concept of the health benefits from drinking tea or consuming other tea products,” said Shiming Li, Ph.D., who reported on the new study with Professor Chi-Tang Ho and his colleagues. “However, there is a huge gap between the perception that tea consumption is healthy and the actual amount of the healthful nutrients — polyphenols — found in bottled tea beverages. Our analysis of tea beverages found that the polyphenol content is extremely low.”

Li pointed out that in addition to the low polyphenol content, bottled commercial tea contains other substances, including large amounts of sugar and the accompanying calories that health-conscious consumers may be trying to avoid. He is an analytical and natural product chemist at WellGen, Inc., a biotechnology company in North Brunswick, N.J., that discovers and develops medical foods for patients with diseases, including a proprietary black tea product that will be marketed for its anti-inflammatory benefits, which are due in part to a high polyphenol content.

Li and colleagues measured the level of polyphenols — a group of natural antioxidants linked to anti-cancer, anti-inflammatory, and anti-diabetic properties — of six brands of tea purchased from supermarkets. Half of them contained what Li characterized as “virtually no” antioxidants. The rest had small amounts of polyphenols that Li said probably would carry little health benefit, especially when considering the high sugar intake from tea beverages.

“Someone would have to drink bottle after bottle of these teas in some cases to receive health benefits,” he said. “I was surprised at the low polyphenol content. I didn’t expect it to be at such a low level.”

The six teas Li analyzed contained 81, 43, 40, 13, 4, and 3 milligrams (mg.) of polyphenols per 16-ounce bottle. One average cup of home-brewed green or black tea, which costs only a few cents, contains 50-150 mg. of polyphenols.

After water, tea is the world’s most widely consumed beverage. Tea sales in the United States have quadrupled since 1990 and now total about $7 billion annually. The major reason: Scientific evidence that the polyphenols and other antioxidants in tea may reduce the risk of cancer, heart disease, and other afflictions.

Li said that some manufacturers do list polyphenol content on the bottle label. But the amounts may be incorrect because there are no industry or government standards or guidelines for measuring and listing the polyphenolic compounds in a given product. A regular tea bag, for example, weighs about 2.2 grams and could contain as much as 175 mg. of polyphenols, Li said. But polyphenols degrade and disappear as the tea bag is steeped in hot water. The polyphenol content also may vary as manufacturers change their processes, including the quantity and quality of tea used to prepare a batch and the tea brewing time.

“Polyphenols are bitter and astringent, but to target as many consumers as they can, manufacturers want to keep the bitterness and astringency at a minimum,” Li explained. “The simplest way is to add less tea, which makes the tea polyphenol content low but tastes smoother and sweeter.”

Li used a standard laboratory technique, termed high-performance liquid chromatography (HPLC), to make what he described as the first measurements of polyphenols in bottled tea beverages. He hopes the research will encourage similar use of HPLC by manufacturers and others to provide consumers with better nutritional information.

Public release date: 23-Aug-2010

Eating berries may activate the brain’s natural housekeeper for healthy aging

BOSTON, Aug. 23, 2010 — Scientists today reported the first evidence that eating blueberries, strawberries, and acai berries may help the aging brain stay healthy in a crucial but previously unrecognized way. Their study, presented at the 240th National Meeting of the American Chemical Society (ACS), concluded that berries, and possibly walnuts, activate the brain’s natural “housekeeper” mechanism, which cleans up and recycles toxic proteins linked to age-related memory loss and other mental decline.

Shibu Poulose, Ph.D., who presented the report, said previous research suggested that one factor involved in aging is a steady decline in the body’s ability to protect itself against inflammation and oxidative damage. This leaves people vulnerable to degenerative brain diseases, heart disease, cancer, and other age-related disorders.

“The good news is that natural compounds called polyphenolics found in fruits, vegetables and nuts have an antioxidant and anti-inflammatory effect that may protect against age-associated decline,” said Poulose, who is with the U. S. Department of Agriculture-Agricultural Research Service (USDA-ARS) Human Nutrition Research Center on Aging in Boston. Poulose did the research with James Joseph, Ph.D., who died June 1. Joseph, who headed the laboratory, pioneered research on the role of antioxidants in fruits and nuts in preventing age-related cognitive decline.

Their past studies, for instance, showed that old laboratory rats fed for two months on diets containing 2 percent high-antioxidant strawberry, blueberry, or blackberry extract showed a reversal of age-related deficits in nerve function and behavior that involves learning and remembering.

In the new research, Poulose and Joseph focused on another reason why nerve function declines with aging. It involves a reduction in the brain’s natural house-cleaning process. Cells called microglia are the housekeepers. In a process called autophagy, they remove and recycle biochemical debris that otherwise would interfere with brain function.

“But in aging, microglia fail to do their work, and debris builds up,” Poulose explained. “In addition, the microglia become over-activated and actually begin to damage healthy cells in the brain. Our research suggests that the polyphenolics in berries have a rescuing effect. They seem to restore the normal housekeeping function. These findings are the first to show these effects of berries.”

The findings emerged from research in which Joseph and Poulose have tried to detail factors involved in the aging brain’s loss of normal housekeeping activity. Using cultures of mouse brain cells, they found that extracts of berries inhibited the action of a protein that shuts down the autophagy process.

Poulose said the study provides further evidence to eat foods rich in polyphenolics. Although berries and walnuts are rich sources, many other fruits and vegetables contain these chemicals ― especially those with deep red, orange, or blue colors. Those colors come from pigments termed anthocyanins that are good antioxidants. He emphasized the importance of consuming the whole fruit, which contains the full range of hundreds of healthful chemicals. Frozen berries, which are available year round, also are excellent sources of polyphenolics, he added.

Public release date: 23-Aug-2010

Vitamin D found to influence over 200 genes, highlighting links to disease

The extent to which vitamin D deficiency may increase susceptibility to a wide range of diseases is dramatically highlighted in research published today. Scientists have mapped the points at which vitamin D interacts with our DNA – and identified over two hundred genes that it directly influences. The results are published today in the journal Genome Research.

It is estimated that one billion people worldwide do not have sufficient vitamin D. This deficiency is thought to be largely due to insufficient exposure to the sun and in some cases to poor diet. As well as being a well-known risk factor for rickets, there is a growing body of evidence that vitamin D deficiency also increases an individual’s susceptibility to autoimmune conditions such as multiple sclerosis (MS), rheumatoid arthritis and type 1 diabetes, as well as certain cancers and even dementia.

Now, in a study whose funders include the Medical Research Council (MRC), the MS Society, the Wellcome Trust and the MS Society of Canada, researchers at the University of Oxford have shown the extent to which vitamin D interacts with our DNA. They used new DNA sequencing technology to create a map of vitamin D receptor binding across the genome. The vitamin D receptor is a protein activated by vitamin D, which attaches itself to DNA and thus influences what proteins are made from our genetic code.

The researchers found 2,776 binding sites for the vitamin D receptor along the length of the genome. These were unusually concentrated near a number of genes associated with susceptibility to autoimmune conditions such as MS, Crohn’s disease, systemic lupus erythematosus (or ‘lupus’) and rheumatoid arthritis, and to cancers such as chronic lymphocytic leukaemia and colorectal cancer.

They also showed that vitamin D had a significant effect on the activity of 229 genes including IRF8, previously associated with MS, and PTPN2, associated with Crohn’s disease and type 1 diabetes.

“Our study shows quite dramatically the wide-ranging influence that vitamin D exerts over our health,” says Dr Andreas Heger from the MRC Functional Genomics Unit at Oxford, one of the lead authors of the study.

The first author of the paper, Dr Sreeram Ramagopalan from the Wellcome Trust Centre for Human Genetics, adds: “There is now evidence supporting a role for vitamin D in susceptibility to a host of diseases. Vitamin D supplements during pregnancy and the early years could have a beneficial effect on a child’s health in later life. Some countries such as France have instituted this as a routine public health measure.”

The main source of vitamin D in the body comes from exposing the skin to sunlight, although a diet of oily fish can provide some of the vitamin. Research has previously suggested that lighter skin colour and hair colour evolved in populations moving to parts of the globe with less sun to optimise production of vitamin D in the body. A lack of vitamin D can affect bone development, leading to rickets; in pregnant mothers, poor bone health can be fatal to both mother and child at birth, hence there are selective pressures in favour of people who are able to produce adequate vitamin D.

This new study supports this hypothesis, having found a significant number of vitamin D receptor binding sites in regions of the genome with genetic changes more commonly found in people of European and Asian descent. It is probable that skin lightening as we migrated out of Africa resulted from the necessity to be able to make more vitamin D and prevent rickets: vitamin D deficiency led to pelvic contraction resulting in increased risk of fatality of both mother and unborn child, effectively ending maternal lineages unable to find ways of increasing availability of the vitamin.

“Vitamin D status is potentially one of the most powerful selective pressures on the genome in relatively recent times,” says Professor George Ebers, Action Medical Research Professor of Clinical Neurology and one of the senior authors of the paper. “Our study appears to support this interpretation and it may be we have not had enough time to make all the adaptations we have needed to cope with our northern circumstances.”

 

Public release date: 23-Aug-2010

Diabetes can cause a sugar coating that smothers body’s immune defences

 

Research led by the Warwick Medical School at the University of Warwick has found that unhealthy glucose levels in patients with diabetes can cause significantly more problems for the body than just the well-known symptoms of the disease such as kidney damage and circulation problems. The raised glucose can also form what can be described as a sugar coating that can effectively smother and block the mechanisms our bodies use to detect and fight bacterial and fungal infections.

In diabetes, patients suffer a higher risk of chronic bacterial and fungal infections but until now little has been known about the mechanisms involved. Now new research led by Dr Daniel Mitchell at the University of Warwick’s Warwick Medical School has found a novel relationship between high glucose and the immune system in humans. The researchers have found that specialized receptors that recognize molecules associated with bacteria and fungi become “blind” when glucose levels rise above healthy levels. The new research may also help explain why diabetic complications can also include increased risk of viral infections such as influenza, and also inflammatory conditions such as cardiovascular disease.

The researchers looked at the similarities in chemical structure between glucose in blood and body fluids, and two other sugar called mannose and fucose. These sugars are found on the surfaces of bacteria and fungi and act as targets for receptors in our body that have evolved to detect and bind to microbial sugars to then combat the infection.

The research found that high levels of glucose outcompetes the binding of mannose and fucose to the specialized immune receptors, potentially blocking these receptors from detecting infectious bacteria and fungi. Glucose also binds in such a way that it inhibits the chemical processes that would normally then follow to combat infections. If this happens it can inhibit a range of key processes including:

•It can inhibit the function of immune system receptors called C-type lectins such as MBL (Mannose-binding lectin) which are known to bind to a sugar known as mannose that is present in the structure of infectious fungal bacterial cell walls. Unlike glucose, mannose does not exist in mammals as a free sugar in the blood.

•The loss of MBL function may also predispose the body to chronic inflammatory diseases, since MBL is involved in the processing and clearance of apoptotic cells (dying cells).

•A number of C-type lectins tat can be affected by raised glucose levels, including MBL, but also including immune cell surface receptors DC-SIGN and DC-SIGNR, are found in key parts of our circulation and vascular system such as plasma, monocytes, platelets and endothelial cells that line blood vessels. Inhibiting the function of these key molecules in those settings could contribute to diabetic cardiovascular and renal complications.

Public release date: 23-Aug-2010

Polyphenol antioxidants inhibit iron absorption

University Park, Pa. — Health benefits from polyphenol antioxidants — substances found in many fruits and vegetables — may come at a cost to some people. Penn State nutritional scientists found that eating certain polyphenols decreased the amount of iron the body absorbs, which can increase the risk of developing an iron deficiency.

“Polyphenols have been known to have many beneficial effects for human health, such as preventing or delaying certain types of cancer, enhancing bone metabolism and improving bone mineral density, and decreasing risk of heart disease,” said Okhee Han, assistant professor of nutritional sciences. “But so far, not many people have thought about whether or not polyphenols affect nutrient absorption.”

The researchers, led by Han, studied the effects of eating grape seed extract and epigallocatechin-3-gallate (EGCG) found in green tea. They used cells from the intestine — where iron absorption takes place — to assess the polyphenols’ effect and found that polyphenols bind to iron in the intestinal cells, forming a non-transportable complex. This iron-polyphenol complex cannot enter the blood stream. Instead, it is excreted in the feces when cells are sloughed off and replaced.

Iron is necessary to carry oxygen from the lungs throughout the body and for other cellular functions. People already at risk for iron deficiency increase that risk if they consume high amounts of grape seed extract or EGCG.

“Iron deficiency is the most prevalent nutrient deficiency in the world, especially in developing countries where meats are not plentiful,” said Han. “People at high risk of developing iron deficiency — such as pregnant women and young children — should be aware of what polyphenols they are consuming.”

Han and her colleagues looked at the heme form of iron found in meats, poultry, and fish. Last year, they performed similar research with non-heme iron found in plants. They published the results of their study on grape seed extract and EGCG in the Journal of Nutrition, showing that eating polyphenols decreased iron absorption.

Both grape seed extract and EGCG are sold in extract form. The results of these studies suggest that consumers should be cautious if using these products.

Ralph’s Note – Is should be recommended that they should not take Iron supplements at the same time.

Public release date: 24-Aug-2010

 

A case for exercising

There is now another good reason to exercise. Besides burning calories, exercise restores the sensitivity of neurons involved in the control of satiety (feeling full), which in turn contributes to reduced food intake and consequently weight loss. This is the conclusion of a study led by Brazilian researchers at the University of Campinas, and the findings will be published next week in the online, open access journal PLoS Biology. This disclosure may bring hope to over 40% of the population that suffers from weight problems and obesity around the world.

The increase in obesity has become one of the most important clinical-epidemiological phenomena. Factors such as changing eating habits and a sedentary lifestyle both have a role in the pathogenesis of this disease. It is postulated that excessive consumption of fat creates failures in the signal transmitted by neurons controlling satiety in a region of the brain called the hypothalamus. These failures can lead to uncontrollable food intake and, consequently, obesity.

The group led by José Barreto C. Carvalheira demonstrated that exercising obese rodents showed signals of restored satiety in hypothalamic neurons and decreased food intake. “In obese animals, exercise increased IL-6 and IL-10 protein levels in the hypothalamus, and these molecules were crucial for increasing the sensitivity of the most important hormones, insulin and leptin, which control appetite,” Carvalheira explained. Physical activity contributes to the prevention and treatment of obesity, not only by increasing energy expenditure but also by modulating the signals of satiety and reducing food intake.

Physical activity has always been considered a cornerstone in the treatment of obesity, however, only now have the effects of exercise on the control of body weight been understood. Thus, these findings, besides reinforcing the necessity for regular exercise also change the current paradigm established between physical activity and weight loss.

Ralph’s Note – So more exercise, less hunger.

 

Public release date: 24-Aug-2010

 

Researchers study cinnamon extracts

A study led by U.S. Department of Agriculture (USDA) chemist Richard Anderson suggests that a water soluble extract of cinnamon, which contains antioxidative compounds, could help reduce risk factors associated with diabetes and heart disease.

The work is part of cooperative agreements between the Beltsville Human Nutrition Research Center (BHNRC) operated by USDA’s Agricultural Research Service (ARS) at Beltsville, Md.; Integrity Nutraceuticals International of Spring Hill, Tenn., and the Joseph Fourier University in Grenoble, France. Anderson works in the Diet, Genomics and Immunology Laboratory of BHNRC. ARS is USDA’s principal intramural scientific research agency.

For the study, conducted in Ohio, coauthor Tim N. Ziegenfuss, now with the Center for Applied Health Sciences based in Fairlawn, Ohio, enrolled volunteers and collected samples.

Twenty-two obese participants with impaired blood glucose values–a condition classified as “prediabetes”–volunteered for the 12-week experimental research study. Prediabetes occurs when cells are resistant to the higher-than-normal levels of insulin produced by the pancreas (in an attempt to help remove elevated glucose levels from blood).

The volunteers were divided randomly into two groups and given either a placebo or 250 milligrams (mgs) of a dried water-soluble cinnamon extract twice daily along with their usual diets. Blood was collected after an overnight fast at the beginning of the study, after six weeks, and after 12 weeks to measure the changes in blood glucose and antioxidants.

The study demonstrated that the water-soluble cinnamon extract improved a number of antioxidant variables by as much as 13 to 23 percent, and improvement in antioxidant status was correlated with decreases in fasting glucose, according to Anderson.

Only more research will tell whether the investigational study supports the idea that people who are overweight or obese could reduce oxidative stress and blood glucose by consuming cinnamon extracts that have been proven safe and effective. In the meantime, weight loss remains the primary factor in improving these numbers, according to ARS scientists.

Public release date: 24-Aug-2010

Atrazine causes prostate inflammation in male rats and delays puberty

A new study shows that male rats prenatally exposed to low doses of atrazine, a widely used herbicide, are more likely to develop prostate inflammation and to go through puberty later than non-exposed animals. The research adds to a growing body of literature on atrazine, an herbicide predominantly used to control weeds and grasses in crops such as corn and sugar cane. Atrazine and its byproducts are known to be relatively persistent in the environment, potentially finding their way into water supplies.

The research, which is available online and will be featured on the cover of Reproductive Toxicology (Volume 30, Issue 4), found that the incidence of prostate inflammation went from 48 percent in the control group to 81 percent in the male offspring who were exposed to a mixture of atrazine and its breakdown products prenatally. The severity of the inflammation increased with the strength of the doses. Puberty was also delayed in the animals who received atrazine.

The doses of atrazine mixture given to the rats during the last five days of their pregnancy are close to the regulated levels in drinking water sources. The current maximum contamination level of atrazine allowed in drinking water is 3 parts per billion. The doses given to the animals were 0.09 (or 2.5 parts per million), 0.87, or 8.73 milligrams per kilogram body weight.

The research was led by Suzanne Fenton, Ph.D., and Jason Stanko, Ph.D., of the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. Fenton began the work as a researcher at the United States Environmental Protection Agency (EPA), but completed the research at NIEHS, working closely with NIEHS pathologists. Both NIEHS and EPA provided financial support for the study.

“We didn’t expect to see these kinds of effects at such low levels,” Fenton said. She adds that this is the second paper to show low dose effects of atrazine metabolite mixtures. Fenton was the senior author on a 2007 paper which demonstrated low doses of the atrazine mix delayed mammary development in female siblings from the same litters used in this current study.

“It was noteworthy that the prostate inflammation decreased over time, suggesting the effects may not be permanent,” said David Malarkey, D.V.M., Ph.D., an NIEHS pathologist and co-author on the paper.

Fenton points out that these findings may extend beyond atrazine alone, and may be relevant to other herbicides found in the same chlorotriazine family, including propazine and simazine. All three of the herbicides create the same set of breakdown products.

Fenton says more research is needed to understand the mechanism of action of the chlorotriazines and their metabolites on mammary and prostate tissue. “These tissues seem to be particularly sensitive to the effects of atrazine and its breakdown products,” Fenton added. “The effects may be due to the stage of fetal development at the time the animals were exposed.”

“We hope that this information will be useful to the EPA, as it completes its risk assessment of atrazine,” said Linda Birnbaum, Ph.D., director of NIEHS and the National Toxicology Program.

Fenton will be presenting her research findings in September to the EPA, as part of its reassessment of atrazine. EPA announced in 2009 that it had begun a comprehensive new evaluation of atrazine to determine its effects on humans. At the end of this process, the agency will decide whether to revise its current risk assessment of atrazine and whether new restrictions are necessary to better protect public health. For more information about the EPA risk assessment, please visit http://www.epa.gov/pesticides/reregistration/atrazine/atrazine_update.htm.

Public release date: 24-Aug-2010

Salmon baby food? Babies need omega-3s and a taste for fish, scientist says

URBANA – Has your toddler eaten fish today? A University of Illinois food science professor has two important reasons for including seafood in your young child’s diet, reasons that have motivated her work in helping to develop a tasty, nutritious salmon baby food for toddlers.

“First, babies need a lot of the omega-3 fatty acids found in fish for brain, nerve, and eye development, and when they switch from breast milk or formula to solid food, most of them don’t get nearly enough,” said Susan Brewer, also a registered dietitian.

“Second, children’s food preferences are largely developed by the time they’re five, so I urge parents to help their kids develop a taste for seafood early,” she said.

Fish that are high in omega-3 fatty acids, such as salmon, have huge health benefits and help to prevent coronary artery disease, but most adults don’t eat fish twice weekly as experts recommend. In predisposing children toward liking fish, parents are doing their kids a big favor, she said.

Brewer knows her recommendations might meet with some resistance. “When we started working on salmon baby food, I thought, Ewwwh! But the American Heart Association and the American Academy of Pediatrics is solidly behind the idea, and fish-based baby foods, common in Asian markets, have been marketed successfully in the United Kingdom and Italy.”

Brewer collaborated with former U of I professor Peter Bechtel, now of Alaska’s Agricultural Research Service, in the effort to create a viable product, using wild-caught salmon from Alaskan waters.

“When salmon swim upstream to spawn, their flesh begins to get very soft. At that point, the meat is not firm enough for fillets, but it’s perfect for baby food,” she noted.

She has experimented with both pink and red salmon, finding that red salmon survives the baby food production process better.

And, to boost nutrition, in separate experiments she has added bone meal and pureed salmon roe (eggs) to her entrees. The first ingredient (made by grinding the bones in the salmon into a powder) provides calcium in a form that is readily available for bone building in children. The second provides high-quality protein and contains significant quantities of vitamin D and omega-3 fatty acids, particularly docohexaenoic acid (DHA).

“A newborn infant’s brain is 50 percent DHA,” she noted. “However, babies and toddlers have immature livers and can’t synthesize enough DHA to ensure an adequate supply to their developing nerve tissues. If small children are going to get DHA, they must ingest it in their food.”

According to Brewer, the results of her experiments have been encouraging. “Salmon is very mild, and the toddler dinners, which are 27 percent meat or fish, don’t taste or smell fishy at all. They remind me of that salmon and cream cheese dip you have during the holidays.”

Besides, could 107 parents of preschoolers be wrong? In a recent sensory panel conducted in the scientist’s lab, parents found little difference in taste between formulations that contained roe or bone meal and those that didn’t. Eighty-one percent of the parent panelists—even those who don’t eat salmon themselves—said they would offer it to their children after taste testing the product.

“It’s not enough for mothers to know that toddlers need fish in their diets. They won’t buy a product unless it also appeals to the eye and the taste buds,” she said.

“Our goal is to deliver maximum nutrition in an entrée that’s aesthetically pleasing, and these studies show that we can do just that,” she added

 

Public release date: 25-Aug-2010

Grapefruit’s bitter taste holds a sweet promise for diabetes therapy

Naringenin, an antioxidant derived from the bitter flavor of grapefruits and other citrus fruits, may cause the liver to break down fat while increasing insulin sensitivity, a process that naturally occurs during long periods of fasting.

A team of researchers from the Hebrew University of Jerusalem and Massachusetts General Hospital (MGH) report that naringenin activates a family of small proteins, called nuclear receptors, causing the liver to break down fatty acids. In fact, the compound seems to mimic the actions of other drugs, such as the lipid-lowering Fenofibrate and the anti-diabetic Rosiglitazone, offering the advantages of both. If the results of this study extend to human patients, this dietary supplement could become a staple in the treatment of hyperlipidemia, type-2 diabetes, and perhaps metabolic syndrome. The report appears in this week issue of the online journal PLoS ONE.

“It is a fascinating find,” says Yaakov Nahmias, PhD, of the Hebrew University of Jerusalem the paper’s senior author. “We show the mechanism by which naringenin increases two important pharmaceutical targets, PPARα and PPARγ, while blocking a third, LXRα. The results are similar to those induced by long periods of fasting”.

The liver is the main organ responsible for the regulation of carbohydrate and lipid levels in the blood. Following a meal, the blood is flushed with sugars, which activate LXRα, causing the liver to create fatty acids for long-term storage. During fasting, the process is reversed; fatty acids are released by fat cells, activate PPARα in the liver, and are broken down to ketones. A similar process, involving PPARγ, increases sensitivity to insulin.

“It is a process which is similar to the Atkins diet, without many of the side effects,” says Martin L. Yarmush, MD, PhD, director of the MGH Center for Engineering in Medicine and one of the paper’s authors.

“The liver behaves as if fasting, breaking down fatty acids instead of carbohydrates.” Yarmush is the Helen Andrus Benedict Professor of Surgery and Bioengineering at Harvard Medical School.

“Dual PPARα and PPARγ agonists, like naringenin, were long sought after by the pharmaceutical industry,” says Nahmias, “but their development was plagued by safety concerns. Remarkably, naringenin is a dietary supplement with a clear safety record. Evidence suggests it might actually protect the liver from damage.”

Grapefruit’s bitter taste is caused the presence of the flavonoid naringin, which is broken down in the gut into naringenin. Earlier evidence has shown the compound has cholesterol lowering properties and may ameliorate some of the symptoms associated with diabetes. The researchers demonstrated that the compound activates PPARα and PPARγ by dramatically increasing the levels of a co-activator peptide of both, called PGC1α. At the same time, naringenin bound directly to LXRα, blocking its activation. These effects culminated with increased fatty acid oxidation and the inhibition of vLDL (‘bad cholesterol’) production.

Public release date: 25-Aug-2010

Exposure to low doses of BPA alters gene expression in the fetal mouse ovary

Significant changes in gene expression in the fetal ovary are evident in female mice whose mothers are exposed to low doses of bisphenol A

A study posted today (Wednesday, August 25) at the online site of the journal Biology of Reproduction reports that exposure of pregnant female mice to the endocrine-disrupting chemical bisphenol A may produce adverse reproductive consequences on gene expression in fetal ovaries as early as 12 hours after the mother has first been exposed to the chemical.

Bisphenol A (BPA) is a chemical used in plastics for making some baby and water bottles, linings of food and beverage cans, and other human consumer products.

The mice in this study were given BPA at doses thought to be equivalent to levels currently being experienced by humans.

The research, conducted in the laboratory of Dr. Patricia A. Hunt at Washington State University (WSU) in Pullman, showed that BPA exposure affects the earliest stages of egg production in the ovaries of the developing mouse fetuses, thus suggesting that the next generation (the grandchildren of the females given BPA) may suffer genetic defects in such biological processes as mitosis and DNA replication.

In addition, the WSU research team noted that their study “revealed a striking down-regulation of mitotic/cell cycle genes, raising the possibility that BPA exposure immediately before meiotic entry might act to shorten the reproductive lifespan of the female” by reducing the total pool of fetal oocytes.

Future studies in Dr. Hunt’s laboratory will focus on genetic changes produced over a range of BPA exposure.

Public release date: 25-Aug-2010

Plantain and broccoli fibers may block key stage in Crohn’s disease development

Translocation of Crohn’s disease Escherichia coli across M-cells: Contrasting effects of soluble plant fibers and emulsifiers

Plantain and broccoli fibres may block a key stage in the development of the inflammatory bowel disorder, Crohn’s disease, suggests preliminary research published online in Gut.

The causes of Crohn’s disease are thought to be a mix of genetic and environmental factors, one of which is very likely to be diet.

The disease is significantly less common in developing countries, where fibrous fruit and vegetables are dietary staples, and its incidence has recently risen rapidly in Japan, in tandem with the increasing adoption of a more Westernised diet.

One of the key stages in the development of Crohn’s is invasion of the cells lining the bowel (epithelial cells) by bacteria, particularly a “sticky” type of Escherichia coli, so the researchers looked at dietary agents that might influence this process.

They cultured M (microfold) cells, bowel lining cells that are the common entry point for invading bacteria that cause diarrhoea – a process known as translocation.

The researchers tested whether preparations of plant soluble fibres prepared from leeks, apples, broccoli, and plantains, and the fat emulsifiers polysorbate 60 and 80, commonly used in processed food manufacture, could alter E coli translocation across M cells.

Plantain and broccoli fibres (5 mg/ml) reduced translocation of E. coli by between 45% and 82%, while leek and apple fibres had no noticeable impact. By contrast, the emulsifier polysorbate 80 substantially increased translocation.

These results were then confirmed in tissue samples taken from patients undergoing surgery for other gut disorders.

The findings suggest that supplementing the diet with broccoli/plantain fibres might prevent relapse of Crohn’s disease, say the authors.

They go on to add that the results could have further implications for the treatment of Crohn’s disease as many enteral feeds contain emulsifiers, which may account for the variable response to this type of treatment.

Public release date: 25-Aug-2010

Vitamin D may treat and prevent allergic reaction to mold in cystic fibrosis patients

 

PITTSBURGH, Aug. 25 – Vitamin D may be an effective therapy to treat and even prevent allergy to a common mold that can cause severe complications for patients with cystic fibrosis and asthma, according to researchers from Children’s Hospital of Pittsburgh of UPMC, the University of Pittsburgh School of Medicine and Louisiana State University School of Medicine.

Results of the study, led by Jay Kolls, M.D., Ph.D., a lung disease researcher at Children’s Hospital and professor of pediatrics at the University of Pittsburgh School of Medicine, are published in the September 2010 issue of the Journal of Clinical Investigation.

Aspergillus fumigatus, is one of the most common airborne molds and while it does not cause illness in the vast majority of those who inhale it, it can cause life threatening allergic symptoms in patients with cystic fibrosis. As many as 15 percent of patients with cystic fibrosis will develop a severe allergic response, known as Allergic Bronchopulmonary Aspergillosis (ABPA). Some patients with asthma also can develop ABPA.

The research team led by Dr. Kolls studied cystic fibrosis patients from the Antonio J. and Janet Palumbo Cystic Fibrosis Center at Children’s Hospital who had A. fumigatus infections. One group had developed ABPA, while the other hadn’t. The researchers found that the ABPA patients had a heightened response by immune cells known as type 2 T helper (Th2) cells, and that a protein known as OX40L was critical to this heightened response. The heightened Th2 response correlated with lower levels of vitamin D as compared with the non-ABPA patients. Adding vitamin D to these cells in the laboratory substantially reduced the expression of OX40L and increased the expression of other proteins critical to the development of allergen tolerance.

“We found that adding vitamin D substantially reduced the production of the protein driving the allergic response and also increased production of the protein that promotes tolerance,” said Dr. Kolls, who also is professor and chair of genetics at LSU Health Sciences Center New Orleans. “Based on our results, we have strong rationale for a clinical trial of vitamin D to determine whether it can prevent or treat ABPA in patients with cystic fibrosis.”

Cystic fibrosis is an inherited chronic disease that affects the lungs and digestive system of about 30,000 children and adults in the United States (70,000 worldwide), according to the Cystic Fibrosis Foundation. A defective gene and its protein product cause the body to produce unusually thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections and obstructs the pancreas and stops natural enzymes from helping the body break down and absorb food.

“These important findings by Dr. Kolls’ team add to the growing body of evidence showing that vitamin D may play a critical role on immune responses and allergic diseases,” said Juan Celedón, M.D., Dr.P.H., chief of the Division of Pulmonary Medicine, Allergy and Immunology at Children’s Hospital.

 

Public release date: 26-Aug-2010

Black rice rivals pricey blueberries as source of healthful antioxidants

BOSTON, Aug. 26, 2010 — Health conscious consumers who hesitate at the price of fresh blueberries and blackberries, fruits renowned for high levels of healthful antioxidants, now have an economical alternative, scientists reported here today at the 240th National Meeting of the American Chemical Society (ACS). It is black rice, one variety of which got the moniker “Forbidden Rice” in ancient China because nobles commandeered every grain for themselves and forbade the common people from eating it.

“Just a spoonful of black rice bran contains more health promoting anthocyanin antioxidants than are found in a spoonful of blueberries, but with less sugar and more fiber and vitamin E antioxidants,” said Zhimin Xu, Associate Professor at the Department of Food Science at Louisiana State University Agricultural Center in Baton Rouge, La., who reported on the research. “If berries are used to boost health, why not black rice and black rice bran? Especially, black rice bran would be a unique and economical material to increase consumption of health promoting antioxidants.”

Like fruits, “black rice” is rich in anthocyanin antioxidants, substances that show promise for fighting heart disease, cancer, and other diseases. Food manufacturers could potentially use black rice bran or the bran extracts to boost the health value of breakfast cereals, beverages, cakes, cookies, and other foods, Xu and colleagues suggested.

Brown rice is the most widely produced rice variety worldwide. Rice millers remove only the outer husks, or “chaff,” from each rice grain to produce brown rice. If they process the rice further, removing the underlying nutrient rich “bran,” it becomes white rice. Xu noted that many consumers have heard that brown rice is more nutritious than white rice. The reason is that the bran of brown rice contains higher levels of gamma-tocotrienol, one of the vitamin E compounds, and gamma-oryzanol antioxidants, which are lipid-soluble antioxidants. Numerous studies showed that these antioxidants can reduce blood levels of low-density lipoprotein cholesterol (LDL) — so called “bad” cholesterol — and may help fight heart disease. Xu and colleagues analyzed samples of black rice bran from rice grown in the southern United States. In addition, the lipid soluble antioxidants they found in black rice bran possess higher level of anthocyanins antioxidants, which are water-soluble antioxidants. Thus, black rice bran may be even healthier than brown rice bran, suggested Dr. Xu.

The scientists also showed that pigments in black rice bran extracts can produce a variety of different colors, ranging from pink to black, and may provide a healthier alternative to artificial food colorants that manufacturers now add to some foods and beverages. Several studies have linked some artificial colorants to cancer, behavioral problems in children, and other health problems.

Black rice is used mainly in Asia for food decoration, noodles, sushi, and pudding. Dr. Xu said that farmers are interested in growing black rice in Louisiana and that he would like to see people in the country embrace its use.

Public release date: 26-Aug-2010

Supplement produces a ‘striking’ endurance boost

Research from the University of Exeter has revealed taking a dietary supplement to boost nitric oxide in the body can significantly boost stamina during high-intensity exercise.

The study has important implications for athletes, as results suggest that taking the supplement can allow people to exercise up to 20% longer and could produce a 1-2% improvement in race times.

This comes on the back of previous research from Exeter which showed that the high nitrate content of beetroot juice, which also boosts nitric oxide in the body, has a similar effect on performance.

However, the latest study gets the nitric oxide into the body through a different biological process – and now the researchers are hoping to find out whether combining the two methods could bring an even greater improvement in athletic performance.

Professor Andrew Jones, from the University’s School of Sport and Health Sciences, said: “The research found that when the dietary supplement was used there was a striking increase in performance by altering the use of oxygen during exercise.

“This is important for endurance athletes as we would expect the supplement to bring a 1-2% improvement in race times. While this may seem small, this is a very meaningful improvement – particularly at elite levels where small gains can be the difference between winning and losing.”

For the research, nine healthy males were put through several different physical challenges on a cycling ergometer to measure their performance under different levels of exercise intensity.

Participants were randomly assigned to take either a blackcurrant cordial placebo drink or the genuine supplement, which was Ark 1 from Arkworld International Limited – which contains the L-arginine amino acid which enhances the production of nitric oxide in the body.

The report, published on-line by the Journal of Applied Physiology, found taking the supplement:

•Improves severe-intensity exercise endurance by 20%

•Significantly reduces systolic blood pressure

•Reduces the oxygen cost of exercise

 

Public release date: 26-Aug-2010

 

Kudzu Vine Extract May Treat Alcoholism, Cocaine Addiction

Researchers at Gilead Sciences Inc. said on Sunday that an extract of the kudzu vine being developed to treat alcoholism may also help treat cocaine addiction.

The Gilead team reported in the journal Nature Medicine that tests on rats showed the drug could stop them from giving themselves cocaine.

Gilead inherited the experimental drug a year ago after it acquired CV Therapeutics Inc.  A spokesman for the company said it was working to try to bring the drug to the market.

“There is no effective treatment for cocaine addiction despite extensive knowledge of the neurobiology of drug addiction,” Lina Yao, Ivan Diamond and colleagues wrote in the journal.

Kudzu is an old remedy for alcoholism.  The vine is native to Asia and has spread across much of the U.S. Southeast after being imported to control soil erosion.

CT Therapeutics made a synthetic extract known as selective aldehyde dehydrogenase-2 inhibitor or ALDH2i.

Tests on rats showed it might be able to help stop their cocaine addiction.  The drug can also prevent relapse after rats are weaned off cocaine.

The researchers found that the drug works by raising the levels of a compound called tetrahydropapaveroline or THP.  Cocaine cravings make levels of a brain chemical known as dopamine soar and THP interferes with this.

“We propose that a safe, selective, reversible ALDH-2 inhibitor such as ALDH2i may have the potential to attenuate human cocaine addiction and prevent relapse,” the researchers wrote.

Public release date: 26-Aug-2010

 

THL Recommends Suspension of H1N1 Vaccinations

Finland’s National Institute for Health and Welfare (THL) has recommended that vaccination against the H1N1 swine flu virus with the Pandemrix vaccine be suspended. The vaccine is not to be used until it is determined if it is linked to an increase in the number of cases of narcolepsy in the country.

THL says that the recommendation is a precautionary measure. At the moment there is no swine flu epidemic in the country that would require urgent vaccination against the virus, it notes.

“Indications of a time link between vaccinations and narcolepsy cases have been seen, but an actual link has not been established. In light of international information, a connection would even seem unlikely,” Dr Hanna Nohynek, a special researcher at THL, told YLE on Tuesday.

Exceptions can be made to the THL recommendation if needed. For instance, the vaccine can be given to people travelling to any area experiencing a swine flu epidemic.

Experts to gather

If required, a final decision on a nationwide end to the swine flu vaccination programme will be made by the Ministry of Social Affairs and Health. Such a decision will be taken if the reported cases of narcolepsy are proven to have resulted from the vaccine.

The group coordinating the investigation into the cases is scheduled to meet next Tuesday to make an overall evaluation. It is comprised of experts from THL, the Ministry of Social Affairs and Health, the National Agency for Medicines, the National Supervisory Authority for Welfare and Health Valvira, and representatives of provincial authorities.

According to the THL, the increase in the number of cases of narcolepsy may have been caused by the flu virus, by the vaccine, by the interaction of an infection with the vaccine, or some other factor. It is known that infections can cause narcolepsy.

THL has been notified of 15 cases of narcolepsy, six of which are more clearly associated with the vaccination than are the remainder. Preliminary research into the connection between the vaccine and the cases is expected to take several months. Annually up to 50 cases of narcolepsy are diagnosed in adults in Finland and fewer than 10 in children.

Worldwide, at least 90 million people have received the Pandemrix vaccine in more than 20 countries. However, so far a possible link between the swine flu vaccine and narcolepsy has been reported only in Finland and Sweden.

 

 

________________________________

 

These reports are done with the appreciation of all the Doctors, Scientist, and other

Medical Researchers who sacrificed their time and effort. In order to give people the

ability to empower themselves. Without the base aspirations for fame, or fortune.

Just honorable people, doing honorable things.

Trans fats linked to increased endometriosis risk and omega-3-rich food linked to lower risk

2010 study posted for filing

Contact: Emma Ross
rosswrite@mac.com
European Society of Human Reproduction and Embryology

Women whose diets are rich in foods containing Omega-3 oils might be less likely to develop endometriosis, while those whose diets are heavily laden with trans fats might be more likely to develop the debilitating condition, new research published today (Wednesday 24 March) suggests.

The study – which is the largest to have investigated the link between diet and endometriosis risk and the first prospective study to identify a modifiable risk factor for the condition – found that while the total amount of fat in the diet did not matter, the type of fat did. Women who ate the highest amount of long-chain Omega-3 fatty acids were 22% less likely to be diagnosed with endometriosis than those who ate the least and that those who ate the most trans fats had a 48% increased risk, compared with those who ate the least.

The findings from 70,709 American nurses followed for 12 years, published online in Europe’s leading reproductive medicine journal Human Reproduction [1], not only suggest that diet may be important in the development of endometriosis, but they also provide more evidence that a low fat diet is not necessarily the healthiest and further bolster the case for eliminating trans fats from the food supply, said the study’s leader, Dr. Stacey Missmer, an assistant professor of obstetrics, gynaecology and reproductive biology at Brigham and Women’s Hospital and Harvard Medical School in Boston, Massachusetts, USA.

“Millions of women worldwide suffer from endometriosis. Many women have been searching for something they can actually do for themselves, or their daughters, to reduce the risk of developing the disease, and these findings suggest that dietary changes may be something they can do. The results need to be confirmed by further research, but this study gives us a strong indication that we’re on the right track in identifying food rich in Omega-3 oils as protective for endometriosis and trans fats as detrimental,” Dr. Missmer added.

Endometriosis occurs when pieces of the womb lining, or endometrium, is found outside the womb. This tissue behaves in the same way as it does in the womb – growing during the menstrual cycle in response to oestrogen in anticipation of an egg being fertilized and shedding as blood when there’s no pregnancy. However, when it grows outside the womb, it is trapped and cannot leave the body as menstruation. Some women experience no symptoms, but for many it is very incapacitating, causing severe pain. The tissue can also stick to other organs, sometimes leading to infertility. It afflicts about 10% of women. The cause is poorly understood and there is no cure. Symptoms are traditionally treated with pain medication, hormone drugs or surgery.

In the study, the researchers collected information from 1989 to 2001 on 70,709 women enrolled in the U.S. Nurses Health Study cohort. They used three food-frequency questionnaires spaced at four-year intervals to record the women’s usual dietary habits over the preceding year. They categorized consumption of the various types of dietary fat into five levels and related that information to later confirmed diagnoses of endometriosis. A total of 1,199 women were diagnosed with the disease by the end of the study. The results were adjusted to eliminate any influence on the findings from factors such as total calorie intake, body mass index, number of children borne and race.

Long-chain Omega-3 fatty acids are found mostly in oily fish. They have been linked to reduced heart disease risk. In the study, the highest contributor was mayonnaise and full-fat salad dressing, followed by fatty fish such as tuna, salmon and mackerel.

Trans fats are artificially produced through hydrogenation, which turns liquid vegetable oil into solid fat. Used in thousands of processed foods, from snacks to ready-meals, they have already been linked to increased heart disease risk. Some countries and municipalities have banned them. The major sources of trans fats in this study were fried restaurant foods, margarine and crackers.

“Women tend to go to the Internet in particular to look for something they can do. The majority of the dietary recommendations they find there are the ones prescribed for heart health, but until now, those had not been evaluated specifically for endometriosis,” Dr. Missmer said. “This gives them information that is more tailored and provides evidence for another disease where it is the type of fat in the diet, rather than the total amount, that is important.”

Besides confirming the finding, a next step could be to investigate whether dietary intervention that reduces trans fats and increases Omega-3 oils can alleviate symptoms in women who already have endometriosis, Dr. Missmer added.

###

The U.S. National Institutes of Health funded the study.

[1] A prospective study of dietary fat consumption and endometriosis risk. Human Reproduction journal. doi:10.1093/humrep/deq044

Batteries not required, just plug into ear cells

 

For the first time, an electrical device has been powered by the ear alone.

The team behind the technology used a natural electrochemical gradient in cells within the inner ear of a guinea pig to power a wireless transmitter for up to five hours.

The technique could one day provide an autonomous power source for brain and cochlear implants, says Tina Stankovic, an auditory neuroscientist at Harvard University Medical School in Boston, Massachusetts.

Nerve cells use the movement of positively charged sodium ions and negatively charged potassium ions across a membrane to create an electrochemical gradient that drives neural signals. Some cells in the cochlear have the same kind of gradient, which is used to convert the mechanical force of the vibrating eardrum into electrical signals that the brain can understand.

Tiny voltage

A major challenge in tapping such electrical potential is that the voltage created is tiny – a fraction of that generated by a standard AA battery.

“We have known about DC potential in the human ear for 60 years but no one has attempted to harness it,” Stankovic says.

Now, Stankovic and her colleagues have developed an electronic chip containing several tiny, low resistance electrodes that can harness a small amount of this electrical activity without damaging hearing.

The implant was inserted into a guinea pig’s inner ear and the electrodes attached to both sides of cochlear cell membranes. Attached to the chip was a low power radio transmitter.

Guinea pig

The device needed kick-starting with a short burst of radio waves, but was then able to use the electrical gradient running across the membrane to sustain the transmitter for up to five hours. Tests showed that the guinea pig’s hearing was not affected.

The device works well for short durations but long-term use of the electrodes risks damaging the sensitive tissue inside the ear. The next step will be to make the electrodes even smaller, reducing their invasiveness.

Stankovic says that this is proof of concept that biological sources of energy exist that have not yet been fully considered. “A very futuristic view is that maybe we will be able to extract energy from individual cells using similar designs,” she says.

Journal reference: Nature Biotechnology, DOI: 10.1038/nbt.2394

http://www.newscientist.com/article/dn22482-batteries-not-required-just-plug-into-ear-cells.html

 

Could we copy a specific brain or transfer our minds to another device? Research suggests this amazing idea might be feasible

Mind transfer: human brains in different materials

02 November 2012 by Randal A. Koene
Magazine issue 2888Subscribe and save
For similar stories, visit the The Big Idea , The Human Brain and Death Topic Guides

HUMAN brains and the minds that emerge from them have allowed us to create culture and civilisation. But ensuring the survival of those marvels (not to mention of our species) in the face of technological and environmental onslaughts will depend on how well those minds adapt. We have always augmented ourselves in the face of challenges, creating artefacts from clothing to cellphones to cochlear implants. As ever, human survival will depend on us being ever more adaptable.

Fortunately, we may be on the brink of fundamentally surpassing our limits: there is no reason why the complex information processing at the core of human experience should continue to be unique to one biological implementation. Moving the functions of minds from brains to other types of materials, other substrates, to become substrate-independent minds (SIMs), would be an extraordinary adaptation.

At a survival level, a SIM could be embodied in a variety of ways, and so would perhaps be better able to survive potential societal collapse. At a human level, the goal would be continued existence of personality, individual characteristics, a manner of experiencing and a personal way of processing experiences. Continuity of self could be assured, despite minds having novel embodiments.

Some years ago, I set up carboncopies.org, a nonprofit organisation. Its work is to keep the big picture of SIM and its key problems clear, with different ways of solving them – routes on a road map – discussed among researchers. It also provides funding where there is a gap.

So how might SIM be realised? For the past 100 years, neuroscientists have been learning how to identify neuroanatomy, to measure neural responses to stimuli, and what regulates the responses. Most SIM research builds on this approach. We call it “whole brain emulation”, a term I coined in 2000.

We use the word “emulation” because it indicates a precise copying of a specific brain, compared with “simulation”, by which people try to build a general model of how some piece of a brain (or a whole brain) of a human or animal could work. The Blue Brain project is an example of simulation. It is run by Henry Markram at the École Polytechnique Fédérale de Lausanne, Switzerland. There, researchers are trying to create a synthetic brain by reverse-engineering the mammalian brain down to the molecular level, drawing on statistical data from many animals.

At present, most SIM researchers aim to emulate the basic computational functions carried out by elements of the brain and then faithfully re-implement them in other substrates – at the same time also faithfully re-implementing the neural connectivity. Such a vast undertaking has to be broken down into much smaller pieces: there are many things we need to know. For example, can we get good enough resolution of neurons – individual electrically spiking neurons, morphologically detailed neurons, or the molecular processes going on in synapses – to make emulation truly feasible?

Exploring such questions is already paying off in real products, such as the cochlear implant, or the hippocampal chip pioneered by Ted Berger at the University of Southern California, Los Angeles. Berger is trying to build artificial neural cells, initially to act as an implanted prosthesis for people who have lost brain cells to diseases such as Alzheimer’s.

We are still left with a mountain to climb. Much of what we need to understand relates to neurons or pieces of a neuron. For example, the time at which each neuron generates a spike in electrical activity – called an action potential – appears to be a key currency of the brain. That timing determines whether a synapse will be modified to create a memory, when a muscle will contract (enabling movement or speech), and perception of sensory input such as sight. In other words, the timing determines all our interactions with the environment.

There are four parts to the Carboncopies road map, each representing a consensus of all those involved in whole brain emulation. The parts all work in parallel, and are all equally essential. We must test our hypotheses about what to include in the emulation and at what level of detail. We need to devise suitable hardware and software to run emulations. We need data about how the neurons and synapses interconnect – the kind of work of various ongoing “connectome” projects. And we need to record the shape of the electrical responses during activity throughout the brain so that the parameters of the emulation can be tuned correctly – we call these “reference responses”.

Hypothesis testing is being carried out by various researchers. For example, David Dalrymple is now on leave from Harvard University to work on emulating the brain of Caenorhabditis elegans, a nematode worm which has only 302 neurons. He wants to determine the function, behaviour, and biophysics of each neuron, and aims to build a complete simulation of the creature’s nervous system. This should provide valuable information about what to include in the worm emulation, and at what level of detail.

As for the hardware, the human brain uses a highly parallel network of billions of mostly inactive, low-power processors, or neurons. A good emulation will use a similar substrate, such as brain-like hardware. One example of such “neuromorphic” hardware is the neuron-like chip developed as part of the multimillion-dollar SyNAPSE project by the US Defense Advanced Research Projects Agency.

If we tried to fine-tune and correct the parameters of the billions of neurons in the human brain without a high-resolution map of the “shape” of how they fire, we would probably be computing until the end of time. Instead, we must break the problem down, which is why our map combines both brain structure and function measurements at large scale and high resolution. By the way, in this field, millimetres of tissue or anything beyond a few hundred neurons is considered large.

As for the connectome, the answer is to look at the morphology of brain cells and fibres. Electron microscopy provides the right resolution, while automated brain-sectioning and imaging helps us cope with the vast amount of data needed to map a brain.

Last year, Kevin Briggman and colleagues at the Max Planck Institute for Medical Research in Heidelberg, Germany, and Davi Bock and colleagues at Harvard Medical School, separately provided proofs of principle for whole brain emulation. They showed it was possible to reconstruct neural circuitry from a brain scan and use it to predict function. (They validated their reconstructions using earlier recordings of the scanned tissue.)

And what about those reference responses? We can get a whole-brain idea of electrical activity at a lower resolution using devices like MRI. And there are new technologies being developed, such as a “molecular ticker tape” pioneered by Konrad Kording at Northwestern University in Evanston, Illinois, and his colleagues. This should simultaneously allow us to register brain activity at a much higher resolution, and register activity from many more neurons.

So where are we now? Clearly, there is a lot to a whole brain, and we extend beyond our brains by continuously interacting with the world. But we do not need a complete understanding of all that in order to emulate a whole brain. Instead, we need to describe the behaviour of functional brain components and work out how they communicate – using today’s knowledge and technology. Quite amazingly, a programme to achieve whole brain emulation is emerging. Just follow the science.

Profile

This article is inspired by two papers by Randal A. Koene in a special issue of the International Journal of Machine Consciousness on mind uploading. Many of the projects cited were presented and discussed at the Whole Brain Circuit Reconstruction symposium, a satellite to the Annual Meeting of the Society for Neuroscience in New Orleans earlier this month, or will be in 2013 at the Global Future 2045 Congress. Koene is a former professor at Boston University and co-founder of the Neural Engineering Corporation of Massachusetts

 

http://www.newscientist.com/article/mg21628880.400-mind-transfer-human-brains-in-different-materials.html?full=true&print=true

Challenging Parkinson’s dogma: May be more to due with the Loss of GABA than Dopamine

Contact: David Cameron david_cameron@hms.harvard.edu 617-432-0441 Harvard Medical School

Scientists may have discovered why the standard treatment for Parkinson’s disease is often effective for only a limited period of time. Their research could lead to a better understanding of many brain disorders, from drug addiction to depression, that share certain signaling molecules involved in modulating brain activity.

A team led by Bernardo Sabatini, Takeda Professor of Neurobiology at Harvard Medical School, used mouse models to study dopamine neurons in the striatum, a region of the brain involved in both movement and learning. In people, these neurons release dopamine, a neurotransmitter that allows us to walk, speak and even type on a keyboard. When those cells die, as they do in Parkinson’s patients, so does the ability to easily initiate movement. Current Parkinson’s drugs are precursors of dopamine that are then converted into dopamine by cells in the brain.

The flip side of dopamine dearth is dopamine hyperactivity. Heroin, cocaine and amphetamines rev up or mimic dopamine neurons, ultimately reinforcing the learned reward of drug-taking. Other conditions such as obsessive-compulsive disorder, Tourette syndrome and even schizophrenia may also be related to the misregulation of dopamine.

In the October 11 issue of Nature, Sabatini and co-authors Nicolas Tritsch and Jun Ding reported that midbrain dopamine neurons release not only dopamine but also another neurotransmitter called GABA, which lowers neuronal activity. The previously unsuspected presence of GABA could explain why restoring only dopamine could cause initial improvements in Parkinson’s patients to eventually wane. And if GABA is made by the same cells that produce other neurotransmitters, such as depression-linked serotonin, similar single-focus treatments could be less successful for the same reason.

“If what we found in the mouse applies to the human, then dopamine’s only half the story,” said Sabatini.

The surprising GABA story began in the Sabatini lab with a series of experiments designed to see what happens when cells release dopamine. The scientists used optogenetics, a powerful technique that relies on genetic manipulation to selectively sensitize cells to light. In laboratory dishes, researchers tested brain tissue from mice engineered to show activity in dopamine neurons. Typically in such experiments, other neurotransmitters would be blocked in order to highlight dopamine, but Tritsch, a postdoctoral fellow in the Sabatini lab, decided instead to keep the cell in as natural a state as possible.

When Tritsch activated the dopamine neurons and examined their effects on striatal neurons, he naturally expected to observe the effects of dopamine release. Instead, he saw rapid inhibition of the striatal neurons, making it clear that another neurotransmitter – which turned out to be the quick-acting GABA – was at work.  This was so unusual that the team launched a series of experiments to confirm that GABA was being released directly by these dopamine neurons.

A standard way to detect GABA is to look for vesicular GABA transporter, or VGAT, a protein that packages and carries GABA into neurotransmitter vesicles. The scientists silenced the gene that makes VGAT in mice and found that the dopamine neurons released GABA even in the absence of VGAT.

The researchers then tested other transporters, zeroing in on one that ferries dopamine and a variety of other neurotransmitters. For reasons they don’t yet understand, this protein – the vesicular monoamine transporter – also shuttles GABA.

“What makes this important now is that every manipulation that has targeted dopamine by targeting the vesicular monoamine transporter has altered GABA as well. And nobody’s paid any attention to it,” said Sabatini. “Every Parkinsonian model that we have in which we’ve lost dopamine has actually lost GABA, too. So we really have to go back now and think: Which of these effects are due to loss of GABA and which are due to loss of dopamine?”

Anatol Kreitzer, an assistant investigator at the Gladstone Institute of Neurological Disease in San Francisco, who was not involved in the research, called the findings remarkable.

“It was totally unexpected,” said Kreitzer, who is also an assistant professor of physiology and neurology at the University of California, San Francisco. “At the molecular level, nobody really expected dopamine neurons to be releasing significant amounts of GABA. At the functional level, it’s surprising that this major modulator of plasticity in the brain, which is so critical for Parkinson’s, for learning and rewards, and for other psychiatric illnesses, can also release GABA. That raises a question as to what role GABA has.”

GABA can very quickly change the electrical state of cells, inhibiting their activity by making them less excitable. Sabatini wonders if the loss of GABA in dopamine neurons could explain why hyperactivity is sometimes seen after chronic loss of these neurons.

The next challenge will be to explore whether other neurons that express the vesicular monoamine transporter also release GABA in addition to neurotransmitters such as serotonin and noradrenaline.

“These findings highlight how little we actually know about the most basic features of cell identity in the brain,” said Sabatini.

Tritsch said what started out as a straightforward project to understand dopamine quickly changed direction, with lots of starts and stops on the way to some exciting new findings.

“It can be nice to come up with a hypothesis, test it, verify it, and have everything fall into place,” he said. “But biology rarely works that way.”

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This research was funded by a Nancy Lurie Marks Family Foundation postdoctoral fellowship and by grants from the National Institutes of Health (NS046579 and 4R00NS075136).

Study finds autistics better at problem-solving

2009 study posted for filing

Contact: Sylvain-Jacques Desjardins
sylvain-jacques.desjardins@umontreal.ca
514-343-7593
University of Montreal

University of Montreal and Harvard University research in Human Brain Mapping

This release is available in French.

Montreal, June 16, 2009 — Autistics are up to 40 percent faster at problem-solving than non-autistics, according to a new Université de Montréal and Harvard University study published in the journal Human Brain Mapping. As part of the investigation, participants were asked to complete patterns in the Raven’s Standard Progressive Matrices (RSPM) – test that measures hypothesis-testing, problem-solving and learning skills.

“While both groups performed RSPM test with equal accuracy, the autistic group responded more quickly and appeared to use perceptual regions of the brain to accelerate problem-solving,” says lead author Isabelle Soulières, a post-doctoral fellow at Harvard University who completed the experiment at the Université de Montréal. “Some critics agued that autistics would be unable to complete the RSPM because of its complexity, yet our study shows autistics complete it as efficiently and have a more highly developed perception than non-autistics.”

Fifteen autistics and 18 non-autistics were recruited for the study. Participants were 14 to 36 years old and matched according to their preliminary results on the Wechsler Adult Intelligence Scale. All subjects underwent magnetic resonance imaging to explore their neural activity during RSPM problem-solving. While autism is a common neurodevelopmental disability characterized by profound differences in information processing and analysis, this study showed that autistics have efficient reasoning abilities that build on their perceptual strengths.

“This study builds on our previous findings and should help educators capitalize on the intellectual abilities of autistics,” says senior researcher Laurent Mottron, the new Marcel & Rolande Gosselin Research Chair in Autism Cognitive Neuroscience of the Université de Montréal and psychiatry professor. “The limits of autistics should constantly be pushed and their educational materials should never be simplified.”

Adds Dr. Soulières: “The Raven’s Standard Progressive Matrices are among the most complex tests to provide insight on how a person understands and formulates rules, manages goal hierarchies and performs high-level abstractions. Our wager was that autistics could complete such a test and they surpassed our expectations.”

 

###

 

About the study:
The study, “Enhanced Visual Processing Contributes to Matrix Reasoning in Autism, published in the journal Human Brain Mapping, was authored by Isabelle Soulières, Gary E. Strangman, Cherif Sahyoun and Thomas A. Zeffiro of the Harvard University and Laurent Mottron, Michelle Dawson, Fabienne Samson and Elise B. Barbeau of the Université de Montréal.

Partners in research:
This study was funded by the Canadian Institutes of Health Research and Autism Speaks.

On the Web:
About the cited article: http://www3.interscience.wiley.com/cgi-bin/fulltext/122456693/HTMLSTART
About the Université de Montréal: www.umontreal.ca/english/index.htm
About the Harvard Medical School: http://hms.harvard.edu/hms/home.asp
About Isabelle Soulières: www.nmr.mgh.harvard.edu/martinos/people/showPerson.php?people_id=747
About Laurent Mottron: www.lnc-autisme.umontreal.ca

Illness, medical bills linked to nearly two-thirds of bankruptcies: 77.9 percent were insured, 2/3 Home owners, 3/5 Had College,

2009 study posted for filing

Contact: Mark Almberg
mark@pnhp.org
312-782-6006
Physicians for a National Health Program

Harvard study finds 50 percent increase from 2001

Medical problems contributed to nearly two-thirds (62.1 percent) of all bankruptcies in 2007, according to a study in the August issue of the American Journal of Medicine that will be published online Thursday. The data were collected prior to the current economic downturn and hence likely understate the current burden of financial suffering. Between 2001 and 2007, the proportion of all bankruptcies attributable to medical problems rose by 49.6 percent. The authors’ previous 2001 findings have been widely cited by policy leaders, including President Obama.

Surprisingly, most of those bankrupted by medical problems had health insurance. More than three-quarters (77.9 percent) were insured at the start of the bankrupting illness, including 60.3 percent who had private coverage. Most of the medically bankrupt were solidly middle class before financial disaster hit. Two-thirds were homeowners and three-fifths had gone to college. In many cases, high medical bills coincided with a loss of income as illness forced breadwinners to lose time from work. Often illness led to job loss, and with it the loss of health insurance.

Even apparently well-insured families often faced high out-of-pocket medical costs for co-payments, deductibles and uncovered services. Medically bankrupt families with private insurance reported medical bills that averaged $17,749 vs. $26,971 for the uninsured. High costs – averaging $22,568 – were incurred by those who initially had private coverage but lost it in the course of their illness.

Individuals with diabetes and those with neurological disorders such as multiple sclerosis had the highest costs, an average of $26,971 and $34,167 respectively. Hospital bills were the largest single expense for about half of all medically bankrupt families; prescription drugs were the largest expense for 18.6 percent.

The research, carried out jointly by researchers at Harvard Law School, Harvard Medical School and Ohio University, is the first nationwide study on medical causes of bankruptcy. The researchers surveyed a random sample of 2,314 bankruptcy filers during early 2007 and examined their bankruptcy court records. In addition, they conducted extensive telephone interviews with 1,032 of these bankruptcy filers.

Their 2001 study, which was published in 2005, surveyed debtors in only five states. In the current study, findings for those five states closely mirrored the national trends.

Subsequent to the 2001 study, Congress made it harder to file for bankruptcy, causing a sharp drop in filings. However, personal bankruptcy filings have soared as the economy has soured and are now back to the 2001 level of about 1.5 million annually.

Dr. David Himmelstein, the lead author of the study and an associate professor of medicine at Harvard, commented: “Our findings are frightening. Unless you’re Warren Buffett, your family is just one serious illness away from bankruptcy. For middle-class Americans, health insurance offers little protection. Most of us have policies with so many loopholes, co-payments and deductibles that illness can put you in the poorhouse. And even the best job-based health insurance often vanishes when prolonged illness causes job loss – precisely when families need it most. Private health insurance is a defective product, akin to an umbrella that melts in the rain.”

“For many families, bankruptcy is a deeply shameful experience,” noted Elizabeth Warren, Leo Gottlieb Professor of Law at Harvard and a study co-author. Professor Warren, a leading expert on personal bankruptcy, went on: “People arrive at the bankruptcy courts exhausted – financially, physically and emotionally. For most, bankruptcy is a last choice to deal with unmanageable circumstances.”

According to study co-author Dr. Steffie Woolhandler, an associate professor of medicine at Harvard and primary care physician in Cambridge, Mass.: “We need to rethink health reform. Covering the uninsured isn’t enough. Reform also needs to help families who already have insurance by upgrading their coverage and assuring that they never lose it. Only single-payer national health insurance can make universal, comprehensive coverage affordable by saving the hundreds of billions we now waste on insurance overhead and bureaucracy. Unfortunately, Washington politicians seem ready to cave in to insurance firms and keep them and their counterfeit coverage at the core of our system. Reforms that expand phony insurance – stripped-down plans riddled with co-payments, deductibles and exclusions – won’t stem the rising tide of medical bankruptcy.”

Dr. Deborah Thorne, associate professor of sociology at Ohio University and study co-author, stated: “American families are confronting a panoply of social forces that make it terribly difficult to maintain financial stability – job losses and wages that have not kept pace with the cost of living, exploitation from the various lending industries, and, probably most consequential and disgraceful, a health care system that is so dysfunctional that even the most mundane illness or injury can result in bankruptcy. Families who file medical bankruptcies are overwhelmingly hard-working, middle-class families who have played by the rules of our economic system, and they deserve nothing less than affordable health care.”

 

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A copy of the study is available at http://pnhp.org/new_bankruptcy_study or through the American Journal of Medicine, ajmmedia@elsevier.com , (212) 633-3944. The authors have also prepared a supplementary “Fact Sheet” and a “Q&A” on medical bankruptcy, both of which detail the study’s methods and findings. See the same link above.

“Medical bankruptcy in the United States, 2007: Results of a national study,” David U. Himmelstein, M.D; Deborah Thorne, Ph.D.; Elizabeth Warren, J.D.; Steffie Woolhandler, M.D., M.P.H. American Journal of Medicine, June 4, 2009 (online).

Physicians for a National Health Program (www.pnhp.org), a membership organization of over 16,000 physicians, supports a single-payer national health insurance program. To contact a physician-spokesperson in your area, visit www.pnhp.org/stateactions or call (312) 782-6006

Glutamine supplements show promise in treating stomach ulcers

2009 study posted for filing

Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center

Amino acid helps offset stomach damage caused by H. pylori bacteria; animal study suggests popular supplement could also reduce risk of gastric cancers

BOSTON – Nearly 20 years ago, it was discovered that bacteria known as Helicobacter pylori were responsible for stomach ulcers. Since then, antibiotics have become the primary therapy used to combat the H. pylori infection, which affects approximately six percent of the world population and is also a primary cause of stomach cancer. But today the bacteria is growing increasingly resistant to antibiotics.

Now a study led by scientists at Beth Israel Deaconess Medical Center (BIDMC) and the Massachusetts Institute of Technology demonstrates that the amino acid glutamine, found in many foods as well as in dietary supplements, may prove beneficial in offsetting gastric damage caused by H. pylori infection. Reported in the May 2009 issue of the Journal of Nutrition., the findings offer the possibility of an alternative to antibiotics for the treatment of stomach ulcers.

“Our findings suggest that extra glutamine in the diet could protect against gastric damage caused by H. pylori,” says senior author Susan Hagen, PhD, Associate Director of Research in the Department of Surgery at BIDMC and Associate Professor of Surgery at Harvard Medical School. “Gastric damage develops when the bacteria weakens the stomach’s protective mucous coating, damages cells and elicits a robust immune response that is ineffective at ridding the infection.” Eventually, she notes, years of infection result in a combination of persistent gastritis, cell damage and an environment conducive to cancer development.

Glutamine is a nonessential amino acid naturally found in certain foods, including beef, chicken, fish, eggs, dairy products and some fruits and vegetables. L-glutamine – the biologically active isomer of glutamine – is widely used as a dietary supplement by body builders to increase muscle mass.

Hagen and her coauthors had previously shown that glutamine protects against cell death from H. pylori-produced ammonia. “Our work demonstrated that the damaging effects of ammonia on gastric cells could be reversed completely by the administration of L-glutamine,” explains Hagen. “The amino acid stimulated ammonia detoxification in the stomach – as it does in the liver – so that the effective concentration of ammonia was reduced, thereby blocking cell damage.”

She and her coauthors, therefore, hypothesized that a similar mechanism might be at work in the intact stomach infected with H. pylori. To test this hypothesis, the investigators divided 105 mice into two groups, which were fed either a standardized diet (containing 1.9 percent glutamine) or the same diet with supplemental L-glutamine (containing 6.9 percent glutamine) replacing carbohydrates for five percent of the total calories. After two weeks, the mice were subdivided into two more groups, with one group receiving a sham (fake) dose and the other group receiving a real dose containing H. pylori. (This resulted in four separate mouse groups: an uninfected control group; an uninfected glutamine group; an infected control group; and an infected glutamine group.)

The mice were then followed for a 20-week period, during which time samples of blood and stomach tissue were removed. Blood was analyzed for antibodies to specific types of T-helper immune cells, which mediate the body’s response to H. pylori infection. Stomach tissues were examined for evidence of damage and cancer progression and also chemically analyzed for cytokines (inflammatory substances) which are produced by T-helper cells.

Their results showed that at six-weeks-post infection, the animals exhibited increased expression of three cytokines – interleukin 4, interleukin 10 and transforming growth factor-alpha mRNA. “These all play an important role in the stomach’s ability to protect against damaging effects resulting from other responses to H. pylori infection,” explains Hagen.

Of even greater significance, by week 20, the study results showed that, among the H. pylori-infected animals, the mice that were fed the L-glutamine diet exhibited lower levels of inflammation than did the mice that received the standard control diet.

“Because many of the stomach pathologies during H. pylori infection [including cancer progression] are linked to high levels of inflammation, this result provides us with preliminary evidence that glutamine supplementation may be an alternative therapy for reducing the severity of infection,” explains Hagen, adding that studies in human subjects will be the next step to determine the relevance of this finding in the clinical setting.

H. pylori bacteria infect more than half of the world’s population and were recently identified as a Group 1 carcinogen by the World Health Organization,” she adds. “Approximately 5.5 percent of the entire global cancer burden is attributed to H. pylori infection and, worldwide, over 900,000 new cases of gastric cancer develop each year. The possibility that an inexpensive, easy-to-use treatment could be used to modify the damaging effects of H. pylori infection warrants further study in clinical trials.”

 

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Study coauthors include MIT investigators James Fox, Nancy Taylor and Barry Rickman and BIDMC investigators Jin-Rong Zhou and George Blackburn.

This study was supported by grants from the National Institutes of Health.

BIDMC is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks in the top four in National Institutes of Health funding among independent hospitals nationwide. BIDMC is a clinical partner of the Joslin Diabetes Center and is a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit

Mother Nature, Version 2.0

Welcome to the world of synthetic biology, where micro-organisms can be programmed to invade and destroy cancer cells

By    SCOTT GOTTLIEB

It once seemed that the most profound feats stemming from DNA-based science would spring from our ability to read and detect genes, which we call the science of genomics. But the real opportunities lie in our ability to write DNA, to synthesize new gene sequences and insert them into organisms, resulting in brand-new biological functions. Printing novel DNA might open the way to achievements once only conceivable in science fiction: designer bacteria that can produce new chemicals, such as more efficient fuels, or synthetic versions of our cells that make us resistant to the effects of radiation.

The first such genome was made in 2000 in an experiment where scientists synthesized their own version of the hepatitis C virus so that they could alter it and discover a way to disable the infection. Today it is possible to read gene sequences into computers, where we can alter them and then print a modified gene into living cells. In “Regenesis,” a book exploring the science of synthetic biology, George Church and Ed Regis imagine a world where micro-organisms are capable of producing clean petroleum or detecting arsenic in drinking water, where people sport genetic modifications that render their bodies impervious to the flu, or where a synthetic organism can be programmed to invade and destroy cancer cells.

Mr. Church is currently a professor of genetics at the Harvard Medical School. He arrived there after a storied career as one of the early pioneers in the science of identifying and reading genes. With fellow scientist Walter Gilbert, he developed the first consistent process for sequencing strands of DNA and, in 1984, helped launch the historic project to map the entire human genome while he was a research scientist at the then newly formed biotech company Biogen.

 

image

Regenesis

By George Church and Ed Regis (Basic Books, 284 pages, $28)

“Regenesis” begins with a historical look at the evolution of genomics, providing a primer on the science that underlies the field. The authors then describe the ways in which different applications of synthetic biology may transform established science and effectively make obsolete current principles in medicine and manufacturing. Along the way, they offer a definitive account of the advances and business ventures that define this new science.

Mr. Church and Mr. Regis, a broadly published science writer, spend a lot of time describing the latest industrial applications of synthetic genomics. For example, researchers are using genetically altered cyanobacteria to convert sunlight and carbon dioxide into alkanes, the molecular constituents of diesel fuel. This green science isn’t yet cost effective. When the Navy recently bought 21,000 gallons of algae-derived jet fuel, it cost $424 per gallon. (Currently, the oil-derived fuel costs around $5 per gallon.) But the ability to alter organisms to increase their yield is growing at an exponential tempo. And our ability to manipulate DNA sequences on microprocessors and write the strands into living organisms is taking a similar trajectory. As the tools for doing these things become more powerful, industrial exploitation will become more widespread and effective.

Then there is the multiplex automated genetic engineering machine invented by Mr. Church and three colleagues from Harvard. This tool makes the process of synthesizing new genes much faster. One of the most promising, although controversial, applications is to re-engineer the human genome itself “for the purpose of preventing many diseases from occurring in the first place.” The tool holds great promise. Imagine if we could remove from our genomes the “host machinery” that viruses need to replicate, potentially making us immune to illnesses as ordinary as the flu.

Such developments promise a great deal, but they also make people uncomfortable and prompt calls for limits on what scientists are allowed to do. But recent history suggests that, when new scientific developments have created theoretical risks, scientists themselves have come together to set boundaries on their work until any uncertainties can be better understood and resolved. The self-imposed limits have also made sure that new science wasn’t used in dangerous or untoward ways. When there were concerns about recombinant DNA in the early days of synthetic biology, for example, researchers imposed a moratorium until the risks could be contained. When gene therapy was believed to harbor latent risks, research was largely put on hold until the risks were better understood. Sometimes, the theoretical risks have led to a principle of absolutist precaution that impedes progress. Today the Food and Drug Administration so tightly regulates gene therapy that few new ventures go forward. But, Messrs. Church and Regis argue, the practical promise of a technology will ultimately prevail. “The industrial revolution that the Luddites tried to prevent in 1811 has brought us enormous benefits,” they write.

The more elusive problem isn’t safety but security—”preventing the deliberate misuse of engineered organisms,” as the authors define the concept. DNA synthesizers are small, cheap and easy to procure. The technical means for harnessing these tools is relatively straightforward—within the grasp of scientists of modest training. The instruction sets are also easily found on the Internet. Rogue regimes and lone villains could one day exploit these scientific methods for diabolical aims. Such a security breach could play like the plot of the 1995 hit film “Twelve Monkeys,” where a wicked scientist engineers a virus that nearly drives mankind to extinction. With the advent of what the authors call “garage biology,” Messrs. Church and Regis think, such scenarios are no longer wildly implausible. “In the end, we found no magic bullets for absolutely preventing worst-case scenarios, no fail-safe fail-safes.”

Many point to the Internet as the defining technology of our age. When history is written centuries from now, it is more likely that writing DNA will be the most enduring innovation, so long as we keep it in safe hands.

Dr. Gottlieb is a physician and a resident fellow at the American Enterprise Institute

Diverse intestinal viruses may play a role in AIDS progression

Contact: Elisabeth Lyons
elyons@cell.com
617-386-2121
Cell Press

In monkeys and humans with AIDS, damage to the gastrointestinal tract is common, contributing to activation of the immune system, progressive immune deficiency, and ultimately advanced AIDS. How this gastric damage occurs has remained a mystery, but now researchers reporting in the Cell Press journal Cell provide new clues, implicating the presence of potentially pathogenic virus species other than the main virus that causes AIDS. The findings could provide an opportunity to explain and eventually intervene in the processes that lead to AIDS progression.

To investigate what causes gastrointestinal damage in monkeys and humans with AIDS, researchers used a sequencing method that allows them to obtain genetic sequences of all of the bacterial, viral, and other organisms residing in the gastrointestinal tract. Using this technique, they examined the feces of monkeys with SIV-induced AIDS, monkeys without SIV infection, and monkeys infected with SIV strains that do not cause AIDS. (SIV is the monkey counterpart to HIV.)

“We found that the gastrointestinal tract of the animals with AIDS contained a large number of previously undescribed viruses—including potential pathogens, but we did not see any obvious changes in the bacteria. This means that previously unrecognized viruses may contribute to AIDS disease progression in monkeys,” explains co-author Dr. Dan Barouch, of Harvard Medical School and the Beth Israel Deaconess Medical Center, in Boston. It’s not clear why monkeys with AIDS have more intestinal viruses, but it may be related to their compromised immune system.

The researchers also noted that some of the viruses in the feces of monkeys with AIDS were also found circulating in the animals’ blood. In addition, many were RNA viruses, meaning that their genetic material is made up of RNA rather than DNA. “This is the first time anyone has looked at both DNA- and RNA-based organisms in the fecal matter in association with AIDS. The striking finding of so many RNA viruses to go along with DNA viruses opens up the broader issue of whether we need to rethink how we study the genomes of microorganisms that may affect disease,” says senior author Dr. Herbert Virgin, of the Washington University School of Medicine, in Saint Louis.

In addition to providing new information on how AIDS advances, and therefore how to potentially intervene to slow it down, the results indicate that the viruses found in AIDS patients’ intestines could indicate how progressive their disease will be.

 

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Handley et al.: “Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome.”

Compelling evidence that brain parts evolve independently

Contact: Morwenna Grills Morwenna.Grills@manchester.ac.uk 44-161-275-2111 University of Manchester

An Evolutionary Biologist at The University of Manchester, working with scientists in the United States, has found compelling evidence that parts of the brain can evolve independently from each other. It’s hoped the findings will significantly advance our understanding of the brain.

The unique 15 year study with researchers at the University of Tennessee and Harvard Medical School also identified several genetic loci that control the size of different brain parts.

The aim of the research was to find out if different parts of the brain can respond independently of each other to evolutionary stimulus (mosaic evolution) or whether the brain responds as a whole (concerted evolution). Unlike previous studies the researchers compared the brain measurements within just one species. The findings have been published in the journal Nature Communications.

The brains of approximately 10,000 mice were analysed. Seven individual parts of each brain were measured by volume and weight. The entire genome, except the Y chromosome, was scanned for each animal and the gene set for each brain part identified.

Dr Reinmar Hager from the Faculty of Life Sciences compared variation in the size of the brain parts to variation in the genes. He found that the variation in the size of brain parts is controlled by the specific gene set for that brain part and not a shared set of genes.

He also compared the measurements for each mouse to the overall size of its brain. Surprisingly he found very little correlation between the sizes of the brain parts and the overall size of the brain.

Dr Hager says: “If all the different brain parts evolved as a whole we would expect that the same set of genes influences size in all parts. However, we found many gene variations for each different part of the brain supporting a mosaic scenario of brain evolution. We also found very little correlation between the size of the brain parts and the overall size of the brain. This again supports the mosaic evolutionary hypothesis.”

Using the data collected from the mice Dr Hager and colleagues analysed the genes that influence the size of the brain to the genes that control the size of the body. They wanted to find out how independent size regulation of the brain is to that of the body.

They found evidence that the size of the brain is governed by an independent gene set to the one that controls the size of the body. Again they found vey little correlation between variations in the size of the body and the brain.

The evidence means that overall brain size can evolve independently of body size.

Following this research more work will be carried out to identify the specific genes that underlie the size of different parts in the brain

Dr Hager says: “If we can identify the specific genes that cause variations in the size of brain parts then there will be big implications for researchers looking at neuronal disease and brain development. We hope this research will significantly advance our understanding of the brain.”

Statins increase risk of postoperative delirium in elderly patients: 28% Increase

Contact: Kristine Galka
kristine.galka@ices.on.ca
416-480-4780
Canadian Medical Association Journal

The use of statins is associated with a 28% increased risk of postoperative delirium in elderly patients, found University of Toronto professor Dr. Donald Redelmeier and colleagues in a retrospective cohort analysis involving more than 280 000 patients.

Ontario’s Institute for Clinical Evaluative Sciences (ICES) looked at elderly patients who underwent elective surgery in Ontario and who had received 2 or more prescriptions for statins in the year before surgery, including at least one prescription in the 90 days preceding surgery. Many patients took multiple medications, underwent abdominal, musculoskeletal or urogenital surgery which had a mean duration of about 115 minutes.

Delirium, in addition to causing anxiety in patients and families, contributes to longer hospital stays, a prolonged need for intensive care, and can disrupt and delay care.

They found that 1 in 14 elderly patients were taking statins before surgery and 1 in 90 experienced delirium. Longer surgeries and age over 70 years increased the risk of delirium.

“Our results suggest that this association was more than a coincidence, particularly among patients who received higher doses of statins and had longer duration noncardiac surgeries,” state Dr. Redelmeier and colleagues. “The association between statins and risk of delirium was distinct and was not observed with other lipid-lowering medications, cardiovascular medications or common drugs that reflect underlying chronic diseases but have no major effects on the cardiovascular system.”

The researchers suggest patients temporarily stop taking statins before surgery to lower their risk. If needed, restarting statins after surgery might provide their heart protecting benefits without the risk of delirium.

 

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In a related commentary, Dr. Marcantonio of Harvard Medical School says that it is premature to recommend stopping statin therapy in this patient population and that more research is needed before changing practice.

Contact for research: Kristine Galka, ICES, 416-480-4780, kristine.galka@ices.on.ca, for Dr. Donald Redelmeier

Contact for commentary: Sydney Balise, Harvard Medical School, 617-754-1409 for Dr. Marcantonio

Pacemakers Vulnerable to Hackers: Malicious hackers can kill

2008 posted for filing
Contact: Claire Bowles
claire.bowles@newscientist.com
44-207-611-1210
New Scientist

How to stop a new type of heart attack

PACEMAKERS are supposed to protect people from heart attacks. But to do that they have to provide digital as well as biological security.

Earlier this year, a team led by William Maisel at Harvard Medical School demonstrated how a commercial radio transmitter could be used to modify wireless communications from a pacemaker (New Scientist, 22 March, p 23). Doctors normally use these signals to monitor and adjust the implanted device, but a malicious hacker could reprogram the pacemaker to give its wearer damaging shocks, or run down its batteries.

Such irresponsible attacks might seem inconceivable, but Tamara Denning, a computer scientist at the University of Washington in Seattle, points out that in 2007 hackers posted flashing images to the Epilepsy Foundation’s website, apparently with the aim of triggering attacks in people with photosensitive epilepsy.

Pacemaker users could be similarly targeted, and there are a growing number of other implantable medical devices (IMDs) – such as drug pumps, neural stimulators, swallowable cameras and prosthetics – which could also be undermined by pranksters or even killers. Researchers like Denning believe it’s worth being prepared. “We wanted to draw attention not to a prevalent threat, but to a possible future one,” she says.

Securing IMDs is problematic, however, because it is difficult to distinguish between malicious and benevolent communications. Some seemingly obvious solutions are unsuitable: for example, encrypting the IMD signals would be risky because doctors might not be able to get hold of the encryption key in an emergency.

Denning and her colleagues have proposed that IMD users wear a “cloaker” device that tells the IMD to ignore any unexpected instructions. When doctors need to talk to the device, they can simply remove the cloaker.

Designing the system poses unique challenges. The cloaker itself has to be resistant to electronic attack, and the system must “fail open” rather than “fail closed”, allowing doctors access to the IMD if the cloaker breaks down or is lost. And continual communication with the cloaker will eat into the IMD’s battery life.

The researchers have built a PC-based simulation of how a cloaker might work, and suggest that it could be worn like a wristwatch.

Maisel, however, thinks the proposal is unrealistic. In an emergency, the cloaker might be hard for doctors to find – hidden in the patient’s clothing, for example. “You’re asking hundreds of thousands or millions of people to wear something every day for a theoretical risk.”

 

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IF REPORTING ON THIS STORY, PLEASE MENTION NEW SCIENTIST AS THE SOURCE AND, IF REPORTING ONLINE, PLEASE CARRY A LINK TO: http://www.newscientist.com

UK CONTACT – Claire Bowles, New Scientist Press Office, London:
Tel: +44(0)20 7611 1210 or email claire.bowles@newscientist.co.uk

US CONTACT – New Scientist Boston office:
Tel: +1 617 386 2190 or email j.heselton@elsevier.com

More pregnant women taking high blood pressure drugs, yet safety unclear

Contact: Karen Astle
karen.astle@heart.org
214-706-1392
American Heart Association

Nearly 5 percent of pregnant women are prescribed drugs to treat high blood pressure, including some drugs that aren’t considered safe for mothers or their babies, according to new research in the American Heart Association’s journal Hypertension.

Use of high blood pressure drugs during pregnancy is becoming increasingly common, said Brian T. Bateman, M.D., lead author and Assistant Professor of anesthesia at Harvard Medical School in Boston, Mass.

“While we know high blood pressure, or hypertension, occurs in about 6 percent to 8 percent of all pregnancies, we know little about how women and their doctors treat the condition,” he said.

Researchers studied a database of more than 1 million Medicaid patients, of whom 48,453 (4.4 percent) filled prescriptions for high blood pressure drugs during their pregnancies.

They found:

  • Antihypertensive drug use increased from 3.5 percent to 4.9 percent between 2000 and 2006.
  • Antihypertensive drug users were older than non-users, more likely to have diabetes or kidney disease, and more likely to be Caucasian or African-American than Hispanic or Asian.
  • Nearly 2 percent of pregnant women filled prescriptions for these drugs during the first trimester; 1.7 percent during the second trimester; and 3.2 percent during the third trimester.
  • The drugs prescribed included ACE inhibitors and angiotensin receptor blockers — both of which have been shown in studies to have harmful side effects during pregnancy.

Limited information is available about which antihypertensive drugs are safest and most effective for treating high blood pressure during pregnancy, Bateman said. In general, methyldopa and labetalol are the recommended antihypertensives for use during pregnancy. More research on which antihypertensives to prescribe during pregnancy and how to use them safely is urgently needed, he said.

“We know from reports that a number of harmful effects can occur from using ACE inhibitors or angiotensin receptor blockers, especially during the second and third trimester,” Bateman said. “These drugs can cause poor growth, kidney problems and even death of the newborn. If women are taking one of these blood pressure medications and they become pregnant or plan to do so, they and their doctors should discuss treatment choices during pregnancy.”

 

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Co-authors are Sonia Hernandez-Diaz, M.D., Dr.P.H.; Krista F. Huybrechts, M.S., Ph.D.; Kristin Palmsten, M.S.; Helen Mogun, M.S.; Jeffrey L. Ecker, M.D. and Michael A. Fischer, M.D., M.S. Author disclosures are on the manuscript.

The National Institutes of Health funded the study.

For more information, visit American Heart Association about high blood pressure and pregnancy.

For the latest heart and stroke news, follow us on twitter: @HeartNews.

For the updates and new science from the Hypertension journal, follow @HyperAHA.

Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association’s policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at www.heart.org/corporatefunding.

Harvard pediatrics professor arrested after police found ‘up to 100 DVDs and 500 images of child porn at his home’

  • Dr Richard Keller was medical director at  Phillips Academy for 19 years
  • Spent almost $3,000 on child porn over two  years
  • Some pornographic content was delivered to  his office at the boarding school
  • Faces 20 years in jail

By Rachel Quigley

PUBLISHED:15:14 EST, 13  September 2012| UPDATED:15:14 EST, 13 September 2012

Dr Richard Keller, 56, of Andover, 'knowingly received films depicting minors engaged in sexually explicit conduct'
Dr Richard Keller, 56, of Andover, ‘knowingly received films depicting minors engaged in sexually explicit conduct’

A pediatrician at Boston Children’s Hospital  was arrested today after police found almost 100 child pornography DVDs and more  than 500 similar images at his home.

Dr Richard Keller, 56, of Andover,  Massachusetts, ‘knowingly received films  depicting minors engaged in sexually explicit conduct’, according to the U.S.  attorney’s office.

Keller was the medical director at Phillips  Academy for almost 20 years before leaving in 2011.

Phillips Academy is a  highly prestigious boarding school for students in grades nine to 12 and the oldest incorporated academy in the  United States, established in 1778 by Samuel Phillips, Jr.

Andover has educated two American presidents,  George H. W. Bush and George W. Bush.

Keller is also a pediatrics instructor at  Harvard Medical School.

In a  statement released this afternoon, federal prosecutors said Keller ‘purchased  and ordered over 50 DVDs of child pornography online.

‘At this time, more than 500 photographs and  between 60 – 100 DVDs have been recovered during an ongoing search of Dr  Keller’s home today.’

The case began with an investigation of an  oversea’s movie production company that offered films featuring naked young boys  having food fights, wrestling, showering together and playing Twister.

When investigators accessed the company  website and reviewed film previews and summaries, one of the videos was  described as: ‘We bring you action-packed discs of ooey-gooey slippery goodness.  This two set disc features (name) and his buddies going commando in a very  unique way.

‘They’re sweet enough but that didn’t stop  them from breaking out sugary cupcakes and giving you a whole new perspective on  nudist food fighting.’

An investigation into the pediatric  endocrinologist’s account showed that between January 2009 and July 2011, he  ordered titles on 19 separate occasions, spending $2,695.

On five of the 19 occasions, the pornographic  material was sent to Phillips Academy’s student health center, according to the  arrest warrant.

Keller was placed on immediate leave from Boston Children's Hospital Boston pending an investigation Concerns: Keller was placed on immediate leave from  Boston Children’s Hospital Boston pending an investigation
Famous boarding school: Keller worked at prestigious Phillips Academy in Andover, Massachusetts, for almost 20 years before he left last year Famous boarding school: Keller worked at prestigious  Phillips Academy in Andover, Massachusetts, for almost 20 years before he left  last year

It also states that 60 to 100 DVDs and 500  high-gloss images were seized from his bedroom.

If Keller is convicted of all charges, he  faces up to 20 years in prison and will be placed on the sex offender’s register  for life.

Children’s Hospital spokesman Rob Graham  released this statement: ‘Providing safe  and appropriate care in a safe and protective environment is the absolute  paramount priority for Boston Children’s Hospital.

‘When the hospital learned of the allegations  against Dr Richard Keller earlier today, he was immediately put on  administrative leave pending results of the investigation by the US Attorney’s  Office. We will cooperate fully with the US Attorney’s Office and all other  involved regulatory and legal authorities.

‘No complaints or concerns have been  expressed by any patients or family members about the care Dr Keller provided  while he was at Children’s.’

Because Keller would have been in  contact  with countless minors through the nature of his work, the U.S.  Attorney’s  Office said: ‘Members of the public who  have  questions, concerns or information regarding this case should call  617-748-3274, and messages will be promptly  returned.’

Read more: http://www.dailymail.co.uk/news/article-2202887/Harvard-pediatrics-director-Richard-Keller-arrested-police-100-DVDs-500-images-child-porn-home.html#ixzz26PXoUOfU

Drug reverses mental retardation caused by genetic disorder : Rapamycin

Re-posted 2008
 
Contact: Elaine Schmidt
eschmidt@mednet.ucla.edu
310-794-2272
University of California – Los Angeles

UCLA mouse study offers hope for correcting how autism disrupts brain

UCLA researchers discovered that an FDA-approved drug reverses the brain dysfunction inflicted by a genetic disease called tuberous sclerosis complex (TSC). Because half of TSC patients also suffer from autism, the findings offer new hope for addressing learning disorders due to autism. Nature Medicine publishes the findings in its online June 22 edition.

Using a mouse model for TSC, the scientists tested rapamycin, a drug approved by the FDA to fight tissue rejection following organ transplants. Rapamycin is well-known for targeting an enzyme involved in making proteins needed for memory. The UCLA team chose it because the same enzyme is also regulated by TSC proteins.

“This is the first study to demonstrate that the drug rapamycin can repair learning deficits related to a genetic mutation that causes autism in humans. The same mutation in animals produces learning disorders, which we were able to eliminate in adult mice,” explained principal investigator Dr. Alcino Silva, professor of neurobiology and psychiatry at the David Geffen School of Medicine at UCLA. “Our work and other recent studies suggest that some forms of mental retardation can be reversed, even in the adult brain.”

“These findings challenge the theory that abnormal brain development is to blame for mental impairment in tuberous sclerosis,” added first author Dan Ehninger, postgraduate researcher in neurobiology. “Our research shows that the disease’s learning problems are caused by reversible changes in brain function — not by permanent damage to the developing brain.”

TSC is a devastating genetic disorder that disrupts how the brain works, often causing severe mental retardation. Even in mild cases, learning disabilities and short-term memory problems are common. Half of all TSC patients also suffer from autism and epilepsy. The disorder strikes one in 6,000 people, making it twice as common as Huntington’s or Lou Gehrig’s disease.

Silva and Ehninger studied mice bred with TSC and verified that the animals suffered from the same severe learning difficulties as human patients. Next, the UCLA team traced the source of the learning problems to biochemical changes sparking abnormal function of the hippocampus, a brain structure that plays a key role in memory.

“Memory is as much about discarding trivial details as it is about storing useful information,” said Silva, a member of the UCLA Department of Psychology and UCLA Brain Research Institute. “Our findings suggest that mice with the mutation cannot distinguish between important and unimportant data. We suspect that their brains are filled with meaningless noise that interferes with learning.”

“After only three days of treatment, the TSC mice learned as quickly as the healthy mice,” said Ehninger. “The rapamycin corrected the biochemistry, reversed the learning deficits and restored normal hippocampal function, allowing the mice’s brains to store memories properly.”

In January, Silva presented his study at the National Institute of Neurological Disorders and Stroke meeting, where he was approached by Dr. Petrus de Vries, who studies TSC patients and leads rapamycin clinical trials at the University of Cambridge. After discussing their respective findings, the two researchers began collaborating on a clinical trial currently taking place at Cambridge to examine whether rapamycin can restore short-term memory in TSC patients.

“The United States spends roughly $90 billion a year on remedial programs to address learning disorders,” noted Silva. “Our research offers hope to patients affected by tuberous sclerosis and to their families. The new findings suggest that rapamycin could provide therapeutic value in treating similar symptoms in people affected by the disorder.”‘

 

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The research was funded by National Institute of Neurological Disorders and Stroke, Autism Speaks and Deutsche Forschungsgemeinschaft (German Research Foundation). Silva and Ehninger’s coauthors included Yu Zhou, Carrie Shilyansky and Weidong Li of UCLA; and Sangyeul Han, Vijaya Ramesh and David Kwiatkowski of Harvard Medical School

Intestinal bacteria promote — and prevent — inflammatory bowel disease

2008 – re-post for filing

Contact: David Cameron
david_cameron@hms.harvard.edu
617-432-0441
Harvard Medical School

BOSTON, Mass. (May 28, 2008)—Scientists search for drug candidates in some very unlikely places. Not only do they churn out synthetic compounds in industrial-scale laboratories, but they also scour coral reefs and scrape tree bark in the hope of stumbling upon an unsuspecting molecule that just might turn into next year’s big block buster. But one region that scientists have not been searching is their guts. Literally.

Now, a team of researchers at Harvard Medical School, Brigham and Women’s Hospital, and the California Institute of Technology have demonstrated that a molecule produced by bacteria in the gut’s intestinal microflora can eliminate symptoms of inflammatory bowel disease (IBD), a condition that includes Crohn’s disease and ulcerative colitis, in animal models.

“Given the sheer number of bacteria in the gut, the potential for discovering new molecules that can treat a whole range of these diseases is promising,” says Dennis Kasper, co-lead author on the study, professor of medicine and microbiology and molecular genetics at Harvard Medical School, and director of the Channing Laboratory at Brigham and Women’s Hospital.

The study will appear as the cover story in the May 29 issue of Nature.

Scientists have known for many decades that the mammalian gut is an ecosystem teeming with approximately 1,000 different species of bacteria, species as distinct from the host as a single-cell amoeba in pond scum. Rather than causing disease, these bacteria are responsible for protecting against infection and aiding digestion. An increasing number of scientists also suspect that recent increases in asthma and even certain food allergies are caused by disruptions in the delicate balance of this intestinal ecosystem.

In 2005, Kasper and Sarkis Mazmanian, then a postdoc in Kasper’s lab and now an assistant professor of biology at the California Institute of Technology, discovered that a species of intestinal bacteria called Bacteroides fragilis could restore immune system balance in mice that were bred to lack intestinal bacteria. A particular product of B. fragilis, a sugar molecule called polysaccharide A (PSA), recovered the equilibrium of a certain subclass of immune system cells (called Th1 and Th2) whose levels became skewed when bacteria in the gut were absent. The researchers referred to PSA as a “symbiosis factor,” one that established a beneficial link between bacteria and mammals. This was the first study in which such a link was demonstrated.

Interestingly, when the study was completed, Kasper and Mazmanian found in these mice an abundance of immune system cells that were known to protect against colitis and Crohn’s disease. In the current report, the groups decided to expand these findings and explore potential links between PSA and inflammatory bowel disease.

When immunocompromised mice with a specific pathogen-free microbiota were given an intestinal bacterium called Helicobacter hepaticus, they soon developed “rip roaring” IBD, according to Kasper. However, when Helicobacter was combined with B. fragilis, the mice were fine. Further experiments revealed that PSA—the special sugar molecule—was the key factor in preventing IBD. In fact, when mice were given Helicobacter combined with PSA purified from B. fragilis bacteria, they showed no symptoms of IBD.

“But then the key question was, if PSA was essential for preventing these animals from coming down with either colitis or Crohn’s, how did it do it”” says Kasper. “What was the mechanism””

The answer came by studying a subset of interleukins, that is, molecules secreted by immune cells.

Previous studies had shown that two particular interleukins, called IL-17 and IL-23, promote intestinal inflammation and are present at high levels in IBD patients. Here, while the researchers found IL-17 and IL-23 in the guts of animals who had received Heliobacter alone, these interleukins were absent from animals who had also received both PSA-producing B. fragilis and purified PSA.

“We realized that something in PSA must be preventing the inflammation that causes colitis and Crohn’s, which would explain the reduction in IL-17 and IL-23,” says Kasper.

This hunch brought the researchers to consider a third interleukin, IL-10. The opposite of IL-17 and IL-23, IL-10 is anti-inflammatory and had previously been shown to protect against experimental colitis.

The researchers once again administered Helicobacter and PSA-active B. fragilis (the combination that had previously led to healthy mice), only this time they included an antibody that blocked IL-10. As a result, the mice all came down with IBD.

“This demonstrated for us the mechanism by which PSA protects against IBD,” says Kasper.

Indeed, the researchers deduced that PSA prompts immune system cells to secrete IL-10, which in turn suppresses the inflammation caused by IBD. In other words, PSA is an anti-inflammatory.

This research should encourage people (including many scientists) to consider the vast potential for beneficial contributions to human health by “good” bacteria. And what’s more, “This is the first time that a beneficial molecule produced by intestinal bacteria has been shown to work therapeutically in an animal model,” says Mazmanian.

The researchers caution that these findings do not promise any near-term treatments for IBD. “PSA might do the same thing in humans, and it might not,” says Kasper.

However, the mechanism that they’ve discovered should persuade scientists and drug manufacturers to consider new sources for expanding the drug pipeline.

“There is currently no effort to develop molecules that are naturally made by bacteria to use therapeutically,” continues Mazmanian. “This study opens up that possibility.”

 

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Full citation:
Nature, May 29, 2008, 453 (7195), 620-624
“A microbial symbiosis factor prevents intestinal inflammatory disease”
Sarkis K. Mazmanian(1), June L. Round(1) & Dennis L. Kasper(2,3)

1-Division of Biology, California Institute of Technology, Pasadena, California.
2-Channing Laboratory, Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts
3-Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts

Harvard Medical School (http://hms.harvard.edu/hms/home.asp) has more than 7,500 full-time faculty working in 11 academic departments located at the School’s Boston campus or in one of 47 hospital-based clinical departments at 18 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Cambridge Health Alliance, Children’s Hospital Boston, Dana-Farber Cancer Institute, Forsyth Institute, Harvard Pilgrim Health Care, Hebrew SeniorLife, Joslin Diabetes Center, Judge Baker Children’s Center, Immune Disease Institute, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital, and VA Boston Healthcare System.

Brigham and Women’s Hospital (http://www.brighamandwomens.org/) is a 747-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 860 physician-investigators and renowned biomedical scientists and faculty supported by more than $416 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses’ and Physicians’ Health Studies and the Women’s Health Initiative.

Researchers detail chemotherapy’s damage to the brain” Chemotherapy drugs used to treat a wide range of cancers were more toxic to healthy brain cells than the cancer cells they were intended to treat

Re-post from 2008: This is not the watered down Chemo brain article released 5 Sep 2012..4 years later

contact: Mark Michaud
mark_michaud@urmc.rochester.edu
585-273-4790
University of Rochester Medical Center

A commonly used chemotherapy drug causes healthy brain cells to die off long after treatment has ended and may be one of the underlying biological causes of the cognitive side effects – or “chemo brain” – that many cancer patients experience. That is the conclusion of a study published today in the Journal of Biology.

A team of researchers at the University of Rochester Medical Center (URMC) and Harvard Medical School have linked the widely used chemotherapy drug 5-fluorouracil (5-FU) to a progressing collapse of populations of stem cells and their progeny in the central nervous system.

“This study is the first model of a delayed degeneration syndrome that involves a global disruption of the myelin-forming cells that are essential for normal neuronal function,” said Mark Noble, Ph.D., director of the University of Rochester Stem Cell and Regenerative Medicine Institute and senior author of the study. “Because of our growing knowledge of stem cells and their biology, we can now begin to understand and define the molecular mechanisms behind the cognitive difficulties that linger and worsen in a significant number of cancer patients.”

Cancer patients have long complained of neurological side effects such as short-term memory loss and, in extreme cases, seizures, vision loss, and even dementia. Until very recently, these cognitive side effects were often dismissed as the byproduct of fatigue, depression, and anxiety related to cancer diagnosis and treatment. Now a growing body of evidence has documented the scope of these conditions, collectively referred to as chemo brain. And while it is increasingly acknowledged by the scientific community that many chemotherapy agents may have a negative impact on brain function in a subset of cancer patients, the precise mechanisms that underlie this dysfunction have not been identified.

Virtually all cancer survivors experience short-term memory loss and difficulty concentrating during and shortly after treatment. A study two years ago by researchers with the James P. Wilmot Cancer Center at the University of Rochester showed that upwards of 82% of breast cancer patients reported that they suffer from some form of cognitive impairment.

While these effects tend to wear off over time, a subset of patients, particularly those who have been administered high doses of chemotherapy, begin to experience these cognitive side effects months or longer after treatment has ceased and the drugs have long since departed their systems. For example, a recent study estimates that somewhere between 15 and 20 percent of the nation’s 2.4 million female breast cancer survivors have lingering cognitive problems years after treatment. Another study showed that 50 percent of women had not recovered their previous level of cognitive function one year after treatment.

Two years ago, Noble and his team showed that three common chemotherapy drugs used to treat a wide range of cancers were more toxic to healthy brain cells than the cancer cells they were intended to treat. While these experiments were among the first to establish a biological basis for the acute onset of chemo brain, they did not explain the lingering impact that many patients experience.

The scientists conducted a similar series of experiments in which they exposed both individual cell populations and mice to doses of 5-fluorouracil (5-FU) in amounts comparable to those used in cancer patients. 5-FU is among a class of drugs called antimetabolites that block cell division and has been used in cancer treatment for more than 40 years. The drug, which is often administered in a “cocktail” with other chemotherapy drugs, is currently used to treat breast, ovarian, stomach, colon, pancreatic and other forms of cancer.

The researchers discovered that months after exposure, specific populations of cells in the central nervous – oligodendrocytes and dividing precursor cells from which they are generated – underwent such extensive damage that, after 6 months, these cells had all but disappeared in the mice.

Oligodendrocytes play an important role in the central nervous system and are responsible for producing myelin, the fatty substance that, like insulation on electrical wires, coats nerve cells and enables signals between cells to be transmitted rapidly and efficiently. The myelin membranes are constantly being turned over, and without a healthy population of oligodendrocytes, the membranes cannot be renewed and eventually break down, resulting in a disruption of normal impulse transmission between nerve cells.

These findings parallel observations in studies of cancer survivors with cognitive difficulties. MRI scans of these patients’ brains revealed a condition similar to leukoencephalopathy. This demyelination – or the loss of white matter – can be associated with multiple neurological problems.

“It is clear that, in some patients, chemotherapy appears to trigger a degenerative condition in the central nervous system,” said Noble. “Because these treatments will clearly remain the standard of care for many years to come, it is critical that we understand their precise impact on the central nervous system, and then use this knowledge as the basis for discovering means of preventing such side effects.”

Noble points out that not all cancer patients experience these cognitive difficulties, and determining why some patients are more vulnerable may be an important step in developing new ways to prevent these side effects. Because of this study, researchers now have a model which, for the first time, allows scientists to begin to examine this condition in a systematic manner.

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Other investigators participating in the study include Ruolan Han, Ph.D., Yin M. Yang, M.D., Anne Luebke, Ph.D., Margot Mayer-Proschel, Ph.D., all with URMC, and Joerg Dietrich, M.D., Ph.D., formerly with URMC and now with Harvard Medical School. The study was funded by the National Institutes of Neurological Disorders and Stroke, the Komen Foundation for the Cure, and the Wilmot Cancer Center

Are America’s war vets ageing prematurely? Alarming study reveals how a young traumatized U.S. soldier can suffer same brain deterioration as a 70-year-old

  • Consortium in  Boston is studying PTSD in young veterans and those exposed to traumatic brain  injury
  • In veterans  no older than 30, brain imaging sometimes looks like that of a  70-year-old
  • Current  diagnosis includes self-reporting, but scientists hope to create concrete  biological factors for measuring disorder

By Beth Stebner

PUBLISHED:12:50 EST, 6  September 2012| UPDATED:15:33 EST, 6 September 2012

American soldiers who return from wars abroad  in Iraq and Afghanistan have a host of difficulties in front of them once they  hang up their weapons and put their uniforms in the storage  chest.

But for many veterans, the horrors of war are  haunting, and effects of Post-Traumatic Stress Disorder are utterly  debilitating, and may cause them to age prematurely.

Researchers are seeing alarming patterns in young veterans’ health, with many otherwise healthy young men developing early-onset diabetes, heart disease, and slow metabolism leading to obesity.

Shell shock: A U.S. Army Private takes cover during a controlled detonation to clear an area for setting up a check point Kandahar; scientists now claim that PTSD is causing vets to age more quicklyShell shock: A U.S. Army Private takes cover during a  controlled detonation to clear an area for setting up a check point Kandahar;  scientists now claim that PTSD is causing vets to age more quickly

Flashbacks: Traumatic events, combined with adrenaline, make it easy for the brain to go back to the worst moments experienced by a soldierFlashbacks: Traumatic events, combined with adrenaline,  make it easy for the brain to go back to the worst moments experienced by a  soldier

In a ground-breaking consortium led by  researchers from Boston University’s School of Medicine, Harvard Medical School  and the Veterans Affairs office in Boston’s Jamaica Plain, data shows that about  30 per cent of veterans studied demonstrate these symptoms.

Those with apparent PTSD even have signs of  loss of grey matter in the brain, which USA  Today  notes should not happen until old  age.

According to the Pentagon, the number of  soldiers with PTSD or brain injury has increased exponentially in recent years.

The government organisation says that since  2000, more than 240,000 soldiers have reported traumatic brain  injury.

Many who have returned from warfare  experience vivid flashbacks to horrific moments in combat – the sound of  gunfire, explosions, and carnage.

In the study, fronted by Draper Laboratory,  the consortium of PTSD experts will look at gene data and psychophysiology to  evaluate the disorder, as well as using MRIs to map out images of the  brain.

A sample of 2,953 American civilians and 345  military veterans was collected.

Troubling signs: Researchers in Boston have been studying more than 340 veterans to further investigate physical factors of PTSD, including heart disease and obesity Troubling signs: Researchers in Boston have been  studying more than 340 veterans to further investigate physical factors of PTSD,  including heart disease and obesity

Collaboration: Scientists and doctors are looking at the negative effects of PTSD on the brainCollaboration: Scientists and doctors are looking at the  negative effects of PTSD on the brain

In many cases, MRI images of veterans aged  20-30 showed deteriorated brain matter likened to that of a  70-year-old.

Ann Rasmusson, a psychiatrist and  neurobiologist, told USA Today that traumatic stress, when left untreated, can  cause the brain to become fixated on those moments and go back to them too  easily.

As a response to the relentless stress, the  body simply ages faster, the researchers hypothesize.

‘No  one tells you how to shut it off. I spent a lot of time dealing with my  demons.’

-Veteran Ed  Fox

Ed Fox, a 31-year-old veteran of the National  Guard, witnessed nightly attacks during his tour to Iraq in  2004-2005.

He told USA Today that he has constant  flashbacks of mortar attacks and visions of dead bodies, adding that it was  difficult to make stop. ‘No one tells you how to shut it off,’ he said.  ‘I  spent a lot of time dealing with my demons.’

Dr William Milberg, a professor of Psychiatry  at Harvard who is the co-director of the Translation Research Center for  Traumatic Brain Injury and Stress Disorders (TRACTS) study based at the VA  Boston Healthcare System, told MailOnline in an email that the brains of 150  veterans showed significant signs of stress.

He wrote: ‘The red areas are places where  there are statistically consistent correlation’s for a sample of over 150  participants in our study.  You are looking at the maps on two different  sides of the brain.

‘Another way of thinking of this is that the  figure shows that in the places that are red and yellow the higher the degree of  stress the thinner the top layer of cerebral cortex.’

The statistical map shows that key areas of  the 150 veterans’ brains were similarly effected by trauma.

Preliminary data: This is a composite of 150 veterans measuring areas of the brain effected by PTSD; in the places that are red and yellow the higher the degree of stress the thinner the top layer of cerebral cortexPreliminary data: This is a composite of 150 veterans  measuring areas of the brain effected by PTSD; in the places that are red and  yellow the higher the degree of stress the thinner the top layer of cerebral  cortex

On the rise: Traumatic brain injury, including PTSD, has risen alarmingly since 2005On the rise: Traumatic brain injury, including PTSD, has  risen alarmingly since 2005

More than eight per cent of the  population  will suffer from PTSD at some point in their lives, according to Boston  University’s School of Medicine.

In addition to military fighters, civilians  who have been exposed to traumatic events – such as car accidents – are prone to  suffer from the condition.

When left untreated, PTSD can lead to panic  attacks, depression, substance abuse, weight gain, and heart  disease.

According to Draper Laboratory, more than  half of those with the disorder are not properly diagnosed. This consortium  hopes to find concrete chemical evidence to better diagnose and treat the  disorder.

‘Although some biological characteristics  that point to a PTSD diagnosis have already been identified, more comprehensive  study is critical to examine the integrated roles of multiple potential  biological factors of the condition,’Dr Roger Pitman, the director of the PTSD  Research Laboratory at Massachusetts General Hospital and Professor of  Psychiatry at Harvard Medical School, said in a statement.

‘This will help clinicians develop  personalized treatment plans to improve outcomes, rather than relying on  one-size-fits-all approaches.

Read more: http://www.dailymail.co.uk/news/article-2199346/Alarming-study-reveals-young-US-soldier-suffer-brain-deterioration-70-year-old.html#ixzz25lYJszWo

Scientists successfully awaken sleeping stem cells: ” might be possible to turn on the eye’s own resources to regenerate damaged retinas, without the need for transplanting outside retinal tissue or stem cells,”

Contact: Patti Jacobs pjacobs12@comcast.net 617-868-0077 Schepens Eye Research Institute

New hope for regenerating the human retina damaged by disease or injury

Boston, MA—Scientists at Schepens Eye Research Institute have discovered what chemical in the eye triggers the dormant capacity of certain non-neuronal cells to transform into progenitor cells, a stem-like cell that can generate new retinal cells. The discovery, published in the March issue of Investigative Ophthalmology and Visual Science (IOVS), offers new hope to victims of diseases that harm the retina, such as macular degeneration and retinitis pigmentosa.

“This study is very significant. It means it might be possible to turn on the eye’s own resources to regenerate damaged retinas, without the need for transplanting outside retinal tissue or stem cells,” says Dr. Dong Feng Chen, associate scientist at Schepens Eye Research Institute and Harvard Medical School, and the principal investigator of the study.  “If our next steps work in animal disease models, we believe that clinical testing could happen fairly quickly.”

Scientists have long been aware of Müller cells (which exist in great abundance in the eye) and have generally assumed that they were responsible for keeping retinal tissue protected and clear of debris. In recent years, however, researchers have reported that these cells sometimes exhibit progenitor cell behavior and re-enter the cell cycle (dividing and differentiating into other type of cells).  Progenitor cells are similar to stem cells but are more mature and are more limited in the number of cells types they can become.

But until this study, scientists have not understood what triggers the transformation. In their study, Chen and her team observed that when the naturally occurring chemicals known as glutamate and aminoadipate (which is a derivative of glutamate) were injected into the eye, the Müller cells began to divide and proliferate. Not certain if these chemicals directly signaled the transformation, they tested them in the laboratory and in mice.

They added each chemical separately to cultures of pure Müller cells and injected each into the space below the retina in healthy mice. In both cases, the cells became progenitor cells and then changed into retinal cells. And with aminoadipate, the newly minted retinal cells migrated to where they might be needed in the retina and turned into desirable cell types. Specifically, they showed that by injecting the chemical below the retina, the cells give rise to new photoreceptors – the type of cells that are lost in retinitis pigmentosa or macular degeneration, as a result, leading to blindness.

The team’s next step will be to test this process in animals that have been bred to have diseases that mimic macular degeneration and retinitis pigmentosa. The goal would be to learn if damaged retinas regenerate and vision improves. The team will likely use just aminoadipate because it only binds with Müller cells without the side effects of glutamate, which can actually harm retina cells in large doses.

“We believe that a drug created from the chemical aminoadipate or a similar compound has great potential for healing damaged retinas,” says Chen.

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Other authors of the study include:

Masumi Takeda 1,2,3 Akira Takamiya 1,2,3 Jian-wei Jiao 1,2 Kin-Sang Cho 1,2 Simon G. Trevino 1 Takahiko Matsuda 4  Dong F. Chen 1,2

1 The Schepens Eye Research Institute, Boston, Massachusetts 2 Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts  3 Department of Ophthalmology, Asahikawa Medical College,  Asahikawa, Japan 4 Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts.

Schepens Eye Research Institute is an affiliate of Harvard Medical School and the largest independent eye research institute in the nation.

Repost 2008

Grapefruit compound may help combat hepatitis C infection ” may be able to block the secretion of hepatitis C virus “

Contact: Sue McGreevey smcgreevey@partners.org 617-724-2764 Massachusetts General Hospital

MGH study reveals mechanism key to maintaining chronic infection, potential therapy target

A compound that naturally occurs in grapefruit and other citrus fruits may be able to block the secretion of hepatitis C virus (HCV) from infected cells, a process required to maintain chronic infection.  A team of researchers from the Massachusetts General Hospital Center for Engineering in Medicine (MGH-CEM) report that HCV is bound to very low-density lipoprotein (vLDL, a so-called “bad” cholesterol) when it is secreted from liver cells and that the viral secretion required to pass infection to other cells may be blocked by the common flavonoid naringenin.

If the results of this study extend to human patients, a combination of naringenin and antiviral medication might allow patient to clear the virus from their livers.  The report will appear in an upcoming issue of the journal Hepatology and has been released online.

“By finding that HCV is secreted from infected cells by latching onto vLDL, we have identified a key pathway in the viral lifecycle,” says Yaakov Nahmias, PhD, of the MGH-CEM, the paper’s lead author. “These results suggest that lipid-lowering drugs, as well as supplements, such as naringenin, may be combined with traditional antiviral therapies to reduce or even eliminate HCV from infected patients”

HCV is the leading cause of chronic viral liver disease in the United States and infects about 3 percent of the world population. Current antiviral medications are effective in only half of infected patients, 70 percent of whom develop chronic infection that can lead to cirrhosis or liver cancer.  Since the virus does not integrate its genetic material into the DNA of infected cells the way HIV does, totally clearing the virus could be possible if new cells were not being infected by secreted virus.

“Identifying the route by which HCV is released from cells introduces a new therapeutic target,” says Martin Yarmush, MD, PhD, director of the MGH-CEM and the paper’s senior author. “That pathway’s dependence on cholesterol metabolism could allow us to interfere with viral  propagation to other cells and tissues, using tools already developed for atherosclerosis treatment.”  Yarmush is the Helen Andrus Benedict Professor of Surgery and Bioengineering at Harvard Medical School (HMS).

Grapefruit’s bitter taste is caused the presence of the flavonoid naringin, which is metabolized into naringenin, an antioxidant previously reported to help lower cholesterol levels. Considerable research has suggested that HCV infects liver cells by, in essence, “hitching a ride” onto the natural lipoprotein-cholesterol metabolic pathway.  Since earlier evidence has shown that naringenin can reduce secretion of vLDL from liver cells, the researchers examined whether the compound might also lower HCV secretion from infected cells. Their experiments confirmed that naringenin does reduce the secretion of HCV from infected cell lines and showed that the compound inhibits the mechanism for secreting a specific lipoprotein that binds HCV.

“This work presents the possibility that non-toxic levels of a dietary supplement, such as naringenin, could effectively block HCV secretion,” says Raymond Chung, MD, MGH director of Hepatology and one of the study authors, “This approach might eventually be used to treat patients who do not respond to or cannot take traditional interferon-based treatment or be used in combination with other agents to boost success rates.”

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Chung is an associate professor of Medicine at HMS, and Nahmias is an instructor in Surgery and Bioengineering. Additional co-authors of the Hepatology paper are Jonathan Goldwasser, Monica Casali, PhD, Daan van Poll, MD, MGH-CEM; and Takaji Wakita, MD, Tokyo Metropolitan Institute. The work was supported by grants from the National Institutes of Health and Shriners Hospitals for Children.

Massachusetts General Hospital (www.massgeneral.org), established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

Study targets key molecule to reverse kidney damage in mice

Test likely to proceed to clinical trials

BOSTON — In findings that may lead to clinical trials of a promising new drug for kidney disease, researchers at Beth Israel Deaconess Medical Center (BIDMC) and their colleagues have identified a key molecular player and shown how a targeted experimental drug can reverse kidney damage in mouse models of diabetes, high blood pressure, genetic kidney disease, and other kidney injuries.

The study builds on a discovery that, in mice, a key protein can repair and reverse renal fibrosis, the critical damage caused by different kidney diseases in humans. The new paper details 10 years of methodical follow-up experiments to understand, verify and harness the protective molecular process with a new drug that can be tested in people. The paper appears in the March 2012 issue of Nature Medicine.

“This paper reports the discovery of one of the first targeted drugs specifically developed to reverse fibrosis and regenerate the kidney,” said senior author Raghu Kalluri, MD, PhD, Chief of the Division of Matrix Biology at BIDMC and Professor of Medicine at Harvard Medical School (HMS). “We’re optimistic about the benefits, but the real proof will come from clinical testing.”

Chronic kidney disease is becoming a major public health problem, partly due to the increase in obesity, diabetes, hypertension and an aging population. It affects one out of every 10 people older than 20, and is most prevalent in those over 60. Most people with impaired kidney function are in the early stages and have no symptoms, but deteriorating kidneys significantly raise the risk of death by cardiovascular disease. Those who survive heart attacks and strokes can progress to end-stage renal disease, which requires dialysis in most cases or transplants when donor kidneys are available.

“The field is desperate for new interventions that can halt or slow the progression of renal failure,” said nephrologist Qais Al-Awqati, MB, ChB, a professor of medicine and physiology at Columbia University and immediate past editor of the journal Kidney International. Al-Awqati, who was not involved in the study, notes that kidney disease is the third leading cause of death in the U.S.

In the kidneys and other organs, fibrosis develops from normal repair mechanisms that do not stop. Scar tissue slowly builds up and replaces the working cells of the organ. In 2003, Kalluri’s lab reported that the destructive fibrosis in mice can be countered by the human protein BMP-7, originally named for its ability to spur bone growth. A manmade version of BMP-7 is approved by the U.S. Food & Drug Administration (FDA) to help repair long bones and vertebrate disks. However, the large protein needs to be injected or surgically implanted and, therefore, is not useful for long-term treatment protocols.

Kalluri and his colleagues continued their studies, seeking a smaller molecule that could be taken by mouth in a pill form in order to more specifically exert its protective effect on the kidney. Probing deeper into the biology of the kidney, they identified the protein Alk3, which is not the protein’s primary partner in bone.

Soon after the BIDMC team identified the key receptor Alk3 in the lab, they collaborated with a Canadian biotechnology company, Thrasos Therapeutics, interested in developing targeted therapies for the prevention and treatment of severe organ failure, especially kidney disease. Based on the details about the molecular interaction between the BMP protein and the ALK receptor, company scientists developed a class of small functional peptides, including THR-123, which then underwent further testing.

Researchers in the Kalluri lab used the experimental compound to document the role of the receptor in reversing the fibrosis and allowing normal tissue to regenerate in one mouse model after another. “This receptor must be present for the new molecule to function,” said Kalluri. Working through the receptor, the molecule suppressed inflammation, cell death and fibrosis formation, as well as reversing established fibrosis and allowing kidneys to regenerate functional cells, he adds.

Further experiments showed that the test drug worked even better in the mice when given in combination with ACE inhibitors, the anti-hypertensive drugs now considered a standard therapy for chronic kidney disease which work by targeting another molecular process.

“Targeting the receptor not only stops fibrosis, it removes established fibrosis, and it works in combination with an existing drug used in patients,” Kalluri notes. “The next step is to test this molecule in the clinic.”

The mice studies are “a good first step,” said Al-Awqati. “It will be interesting to pin down the role of the BMP-7 pathway in kidney fibrosis in people.”

Going forward, Kalluri’s group will continue to study these molecular players and their roles in fibrosis in other organs, including the liver, lung, intestine and heart in the hopes of expanding the experimental-drug pipeline. “If you don’t have a pipeline of experimental drugs, how will you succeed in coming up with new drugs?” he asks.

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This study was supported by several project and training grants from the National Institutes of Health, and the Else Kroner-Memorial-Stipend. Kalluri discloses that in the past he has held stock options (subsequently returned to the company unexercised) and received de minimus payments for consulting for Thrasos Therapeutics, Inc.

Study coauthors include BIDMC investigators Hikaru Sugimoto, Valerie S. LeBleu, Gangadhar Taduri, Wibke Bechtel, Hirokazu Okada, Keizo Kanasaki and Michael Zeisberg; Thrasos Therapeutic investigators Dattatreyamurty Basukonda, and Peter Keck; William Carlson Jr. of Thrasos Therapeutics and Massachusetts General Hospital; Mary Rusckowski of the University of Massachusetts Medical College; and Bjorn Tampe and Desiree Tampe of Goettingen University Medical Center, Goettingen, Germany.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is a clinical partner of the Joslin Diabetes Center and a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

New study demonstrates bone protein can reverse kidney failure

Contact: Bonnie Prescott bprescot@bidmc.harvard.edu 617-667-7306 Beth Israel Deaconess Medical Center

BOSTON – A new study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) has shown that a protein used to heal fractured bones is effective in repairing and reversing chronic renal disease, a leading cause of morbidity and mortality throughout the U.S.

These findings, which are reported in the July 2003 issue of Nature Medicine, could help lead to the development of a therapeutic alternative for the nearly 300,000 kidney disease patients who are currently undergoing dialysis.

“Dialysis is not really a treatment, it’s just a means of survival until an opportunity for a transplant opens up,” notes the study’s senior author Raghu Kalluri, Ph.D., director of the Center for Matrix Biology at BIDMC and Associate Professor of Medicine at Harvard Medical School. “This is a very tedious way of living life,” he adds, explaining that the process of mechanically filtering blood through a machine to remove waste products must be performed several times a week for a period of three to four hours per visit, posing risks of infection and other side effects. Furthermore, the procedure is extremely costly.

The kidneys function as a filtration system, keeping the body’s blood supply healthy by removing excess fluids and wastes, as well as by producing hormones.  When kidneys “fail” – as can result from complications associated with diabetes, lupus or several other diseases – harmful wastes accumulate in the bloodstream, excess fluids build up in the body, and red blood cell production is impeded. Once chronic kidney disease develops, it cannot be reversed or repaired; when the organs cease to function, patients have no alternative but to undergo dialysis while awaiting a kidney transplant.

This new study looked at the role of a molecule called bone morphogenic protein (BMP)- 7 which, in its recombinant form, has been approved by the U.S. Food and Drug Administration for the treatment of bone fractures. Earlier studies had revealed that BMP-7 is highly expressed in the kidneys of healthy individuals. “We wanted to learn if this protein was somehow offering protection against kidney injury,” explains Kalluri.

The investigators used mouse models of chronic renal injury, characterized by the presence of scar tissue known as renal fibrosis; once kidney disease was well-established in the animals, they administered human recombinant BMP-7.

“We found that in the kidneys, BMP-7 reverses a process known as epithelial-to-mesenchymal transition, which generates scar-causing cells known as fibroblasts,” says Kalluri, explaining that BMP-7 first reduces the number of the fibroblast cells, and then replaces the damaged areas of the kidney tubules with healthy epithelial cells. “In effect,” he adds, “BMP-7 is decreasing the bad cells [in this context, fibroblasts] and converting them into good cells [in this context, epithelial cells].”

Although therapies exist to slow progression of kidney disease, once it has developed it becomes intractable, eventually leaving patients no alternative but to undergo dialysis. “The possibility of creating a cost-effective drug that would actually reverse renal injury could significantly reduce the need for dialysis and significantly improve the quality of life for these patients,” says Kalluri.

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Study co-authors include BIDMC investigators Michael Zeisberg, M.D., Jun-ichi Hanai, M.D., Hikaru Sugimoto, M.D., Ph.D., Tadanori Mammoto, Ph.D., David Charytan, M.D., and Frank Strutz, M.D.

This study was funded by grants from the National Institutes of Health, Deutsche Forschungsgemeinschaft, and support from the Center for Matrix Biology, BIDMC. Ortho Biotech Products, L.P., is the exclusive licensee of BMP-7.

Beth Israel Deaconess Medical Center is a major patient care, teaching and research affiliate of Harvard Medical School, and ranks third in National Institutes of Health funding among independent hospitals nationwide. BIDMC is clinically affiliated with the Joslin Diabetes Center and is a founding member of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox

* Requested Repost

N-acetyl glucosamine and niacinamide, significantly reduced the amount and appearance of hyperpigmentation, age spots and uneven melanin distribution

Contact: Shirley Johnson shirley.johnson@mslpr.com 212-468-3292 Manning Selvage & Lee

Science finds new fix for UV-damaged skin in arthritis treatment

IMAGE:Researchers found that the topical application of a N-acetyl glucosamine (4 percent) and niacinamide (2 percent) complex produced visible improvement in pigmentation after 8 weeks. Photos were taken under polarized…

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Cincinnati, OH – For many women, accumulated sun exposure has already permanently damaged their skin cells, causing them to overproduce pigment that shows up as unsightly dark splotches and uneven skin tone over time. But new research indicates that glucosamine – a compound best known for treating arthritis – can actually help stop the formation of new age spots, and help fade existing ones.

“These findings on glucosamine may impact the way dermatologists treat UV-related skin damage in the future. Right now we have prescription and surgical options, which some people aren’t willing to try,” says Alexa Kimball, M.D., assistant professor of dermatology, Harvard Medical School and lead researcher on one of the studies testing glucosamine. “It’s exciting to see this level of research being done on topical cosmetic applications of glucosamine, and the promising results.”

IMAGE:N-acetyl glucosamine and niacinamide block melanin production by interfering in the process at two different points – reducing formation and appearance of age spots. A key enzyme in melanin biosynthesis…

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An International Consensus on Glucosamine Skin Benefits

In early 2006, a group of leading dermatologists from around the world and Procter & Gamble Beauty scientists convened in Rome to review and discuss the glucosamine data.  The panel determined that n-acetyl glucosamine, a more stable form of glucosamine, reduced the amount of melanin in skin cells, meaning there was less excess pigment in the skin to cause age spots.  Additionally, the panel concluded that a formulation of n-acetyl glucosamine and niacinamide, a vitamin B derivative, significantly reduced the amount and appearance of hyperpigmentation, age spots and uneven melanin distribution. Researchers paired n-acetyl glucosamine with niacinamide because they knew that niacinamide had similar effects on slowing down pigment production and hypothesized that the two might work better together.

The panel reviewed data from three studies involving the n-acetyl glucosamine /niacinamide formulation.  Tissue studies showed a reduction in melanin and an increase in collagen – a key structural protein in skin. Three double-blinded placebo- controlled clinical studies involving more than 200 subjects, including a study supervised by Dr. Kimball, showed improvement in hyperpigmentation and skin tone and a decrease in the size of age spots. The research is set to be presented in July at the “Academy ’06” meeting of the American Academy of Dermatology (AAD), and was first presented at the AAD annual meeting in March 2006.

IMAGE:A series of events occur within pigment cells to trigger the production of melanin.  The process can be activated by both external influences, such as UV radiation or irritants,…

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Skin Biology Gives Researchers Clues for Developing New Treatments The interest in glucosamine as a possible treatment comes in part from what scientists already know happens on a cellular level when skin is exposed to UV radiation. Chronic UV exposure can damage melanocytes, cells in the skin responsible for producing melanin, in a variety of different ways. Often, this damage can lead to a loss of cellular control, and the production of chemicals that allow the cells to keep producing more and more melanin – which eventually leads to age spots and uneven discoloration. Additionally, as skin ages, cell turnover slows down and melanin “dust” – microscopic particles of melanin – can become trapped in the upper layers of skin, resulting in a duller appearance.

Researchers are familiar with these processes and that has helped them focus on substances – such as n-acetyl glucosamine – that are known to interrupt the UV-triggered chemical signals that turn on melanin production. Skin care products that utilize signal-blocking ingredients currently exist in the marketplace, but products with n-acetyl glucosamine/niacinamide  – which block melanin at two different points in the pigment producing process – are among the newest and most studied.

“Pigmentation is an appearance issue that strikes an emotional chord for women, and even though we’re constantly telling our patients about the importance of UV-protection, once the damage is done, we need to be able to provide them with ways to help,” says Dr. Kimball.  “The level of research and validation on topical cosmetic application of glucosamine will help it stand apart from other ingredients when it comes to improving tone and treating hyperpigmentation.”

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About P&G Beauty

P&G Beauty science has more than 1,800 scientists and technical employees working at nine global technical centers with an unparalleled commitment to technology development. Company scientific efforts have resulted in over 3,500 active beauty care patents. This allows P&G to develop products uniquely suited for different types of hair and skin, and tailored to different cultures and climates. P&G scientists are constantly seeking new ways of turning inspiration into innovation.

P&G Beauty sells more than 130 different brands in over 180 countries worldwide that touch and improve lives daily.  P&G Beauty had more than $19 billion in global sales in fiscal year 2004/05, making it one of the world’s largest beauty companies.  The global leading beauty company at mass, P&G Beauty brands include: Pantene®, Head and Shoulders®, Olay®, Max Factor®, Cover Girl®, Gillette® Complete Skin Care for Men, Always®, Joy®, Hugo Boss®, Wella®, Herbal Essences®, Clairol Nice ‘n Easy® and SK-II®.  Please visit www.pg.com for the latest news and in-depth information about P&G Beauty and its brands.

Contact Info: Shirley Johnson/Erin Ortiz MS&L Public Relations 212.468.3292/3752

Reposted for Filing

Varenicline (Chantix™) Responsible for 90% of all reported suicides related to smoking- cessation drugs since 1998

Requested Repost 2Nov2011

WINSTON-SALEM, N.C. — The poor safety profile of the smoking-cessation drug varenicline (Chantix™) makes it unsuitable for first-line use, according to a study published in the Nov. 2 edition of the journal PLoS One, an online publication of the Public Library of Science.

Varenicline, which already carries a “black box warning” from the U.S. Food and Drug Administration (FDA), showed a substantially increased risk of reported depression or suicidal behavior compared to other smoking-cessation treatments, according to researchers at Wake Forest Baptist Medical Center, the Institute for Safe Medication Practices, Harvard Medical School and Johns Hopkins University School of Medicine.

The researchers found that 90 percent of all reported suicides related to smoking- cessation drugs since 1998 implicated varenicline, even though it was on the market only four years in the nearly 13-year study period. They also found that varenicline was eight times more likely to result in a reported case of suicidal behavior or depression than nicotine replacement products.

“Our study contradicts the implications of a recent review by the FDA showing no difference in psychiatric hospitalizations between varenicline and nicotine replacement patches,” said Curt D. Furberg, M.D., Ph.D., professor of Public Health Sciences at Wake Forest Baptist, co-author of the study and a nationally recognized leader in drug safety research. “The FDA hospitalization studies were flawed because they could not capture most of the serious psychiatric side effects, including suicide, depression, aggression and assaults. These can be catastrophic events but do not normally result in hospitalization.

“We found that Chantix is associated with more suicidal behavior reports than any other smoking-cessation drug on the U.S. market. The risks simply outweigh the benefits.”

In this study, the team of scientists analyzed 3,249 case reports of serious injury included in the FDA’s Adverse Event Reporting System from 1998 through September 2010 for self-injurious behavior or depression linked to varenicline, bupropion (Zyban™), an antidepressant approved for smoking cessation, and nicotine replacement products. They identified 2,925 (90 percent) cases of suicidal behavior or depression for varenicline, 229 (7 percent) for bupropion, and 95 (3 percent) cases for nicotine replacement products.

Furburg said that although a growing body of research from multiple sources establishes that varenicline substantially increases the risk of psychiatric side effects, it remains uncertain how frequently these events occur.

“While suicidal behavior or depression appear to be prominent side effects of varenicline, they are by no means the only safety issues,” said Thomas J. Moore, senior scientist at the Institute for Safe Medication Practices and lead author of the study. “Varenicline has been associated with aggression and violence in three studies and carries a warning about this behavior. Its effects on vision, cognition and motor control and other risks have led to its being banned for airline pilots, air traffic controllers, military pilots and missile crews, and restricted for truck drivers.”

Varenicline also is associated with an increase in the risk of serious cardiovascular events, as reported in the July 4, 2011, issue of the Canadian Medical Association Journalby Furberg and scientists at Wake Forest Baptist, Johns Hopkins University School of Medicine and the University of East Anglia in the United Kingdom.

“We strongly recommend that the FDA should revise the ‘black box warning’ to say what this study and the FDA’s own data show – that varenicline has higher risks for suicidal behavior and depression than other smoking-cessation treatments,” Furberg said.

“We agree with the recommendations of the U.S. Veterans Administration (VA) that varenicline should be prescribed only after failure of nicotine replacement, bupropion or a combination,” he added. “The VA also recommends a mental status examination to assess risk of suicidal or violent behavior prior to prescribing varenicline.”

Tobacco use is responsible for one in five deaths in the United States each year and adds $193 billion to health care costs. It is among the most treatment-resistant forms of drug dependency, with 36 percent of the nation’s smokers attempting to quit each year but only 3 percent succeeding for six months or more, according to the Department of Health and Human Services.

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Along with Furberg and Moore, co-authors on the study are: Joseph Glenmullen, M.D., and John T. Maltsberger, M.D., of Harvard Medical School; and Sonal Singh, M.D., Ph.D., of Johns Hopkins University School of Medicine.

Media Contacts: Marguerite Beck, marbeck@wakehealth.edu, 336-716-2415; Jessica Guenzel, jguenzel@wakehealth.edu, 336-716-3497.

Wake Forest Baptist Medical Center is a fully integrated academic medical center located in Winston-Salem, North Carolina. The institution comprises the medical education and research components of Wake Forest School of Medicine, the integrated clinical structure and consumer brand Wake Forest Baptist Health, which includes North Carolina Baptist Hospital and Brenner Children’s Hospital, the commercialization of research discoveries through the Piedmont Triad Research Park, as well a network of affiliated community-based hospitals, physician practices, outpatient services and other medical facilities.  Wake Forest School of Medicine is ranked among the nation’s best medical schools and is a leading national research center in fields such as regenerative medicine, cancer, neuroscience, aging, addiction and public health sciences. Wake Forest Baptist’s clinical programs are consistently ranked as among the best in the country by U.S. News & World Report.