US ranks near bottom among industrialized nations in efficiency of health care spending

Contact: Carla Denly cdenly@support.ucla.edu 310-825-6738 University of California – Los Angeles

UCLA, McGill study also shows women fare worse than men in most countries

A new study by researchers at the UCLA Fielding School of Public Health and McGill University in Montreal reveals that the United States health care system ranks 22nd out of 27 high-income nations when analyzed for its efficiency of turning dollars spent into extending lives.

The study, which appears online Dec. 12 in the “First Look” section of the American Journal of Public Health, illuminates stark differences in countries’ efficiency of spending on health care, and the U.S.’s inferior ranking reflects a high price paid and a low return on investment.   Continue reading “US ranks near bottom among industrialized nations in efficiency of health care spending”

Does getting rich mean giving less? Research shows the more money you have, the more tight fisted you become

  • A study from UC  Berkeley’s Dacher Keltner finds that isolation and a decrease in generosity  occur as personal wealth increases
  • Another  study tracked a Mexican village and watched giving and community activities drop  as wealth grew
  • Since 1800,  Americans have used the word ‘get’ in print progressively more than the word  ‘give’

By  Daily Mail Reporter

PUBLISHED: 13:30 EST, 4  September 2013 |  UPDATED: 16:22 EST, 4 September 2013

A recent study shows that the more wealth a  person gains, the more likely they are to become both stingier and  lonelier.

Patricia Greenfield studied a Mexican village  for forty years and watched its residents grow progressively distant from one  another as they became richer. And she says the same thing has happened to the  United States as a nation.

By surveying the contents of a million books  printed between 1800 and 2000, Greenfield found that Americans have used  progressively fewer words like ‘give’ and more like ‘get’ over the last 200  years, indicating a serious trend toward individualism she says is all because  of money.

Care to give: Studies find that getting richer often means getting stingier and lonelier because people require communities less as they become wealthier 

Care to give: Studies find that getting richer often  means getting stingier and lonelier because people require communities less as  they become wealthier

 

‘The frequency of the word “get” went up, and  the frequency of the word “give” went down,’ Greenfield told NPR.

Greenfield, a researcher with UCLA’s  department of Psychology, used Google’s  Ngram viewer to assess changes in  word use over the years.

 

‘Words that would show an individualistic  orientation became more frequent,’ Greenfield said. ‘Examples of those words  were “individual,” “self,” “unique.” Words that would represent a more communal  or more family orientation went down in frequency. Some examples of those words  are “give,” “obliged,” “belong.”’

Greenfield’s findings also use her forty years of tracking families in Chiapas, Mexico, where she  found that as villagers grew richer, tendencies toward individualism grew  stronger and community bonds became weaker.

Make more, give less: A study in 2001 found that the less money a household makes, the higher percentage of their income they contribute to charity 

Make more, give less: A study in 2001 found that the  less money a household makes, the higher percentage of their income they  contribute to charity

 

 

 

And Greenfield is not alone in her assessment  that poorer people are more communal.

‘I saw it personally — I feel it in myself,’  said UC Berkeley researcher Dacher Keltner. ‘That somehow, when I am thinking  hard about making more money and rising in wealth and enjoying materialistic  benefits, I do feel personally that I am not as responsive to the needs of  others.’

Keltner grew up poor and says he frequently  attended barbecues and other community events. As he’s become wealthier and more  independent, those backyard cook-outs have become much less frequent.

To give or receive? Greenfiled assessed a million American books and found that the use of 'give' has declined markedly since 1800 

To give or receive? Greenfiled assessed a million  American books and found that the use of ‘give’ has declined markedly since  1800

 

 

Still going: After the 1970s, the word 'get' sees a spike in use in American books, while give continues to drop 

Still going: After the 1970s, the word ‘get’ sees a  spike in use in American books, while give continues to drop

 

The professor of psychology studied money’s  effect on individualism and generosity. He found that increased wealth leads to  less generosity, charitableness, trust, and helpfulness.

‘In just about every way you can study it,’  he said. ‘Our lower-class individuals volunteer more, they give more of their  resources — they’re more generous.’

Both researchers have concluded that the poor  simply need social connections more, that they’re more reliable on the community  safety net.

‘The wife may make the clothes for the whole  family,’ Greenfield found while studying the Mexican village. ‘The husband grows  food and builds the shelter for the whole family. Therefore giving, social  obligation, belonging to a family are very important.’

America’s wealth has come at a price, said  Keltner.

‘As we rise in wealth, along with that rise  in wealth comes ideas of individuality and self-expression and autonomy and  freedom,’ he said. ‘And loneliness.’

Read more: http://www.dailymail.co.uk/news/article-2411771/Does-getting-rich-mean-giving-Research-shows-money-charitable-become.html#ixzz2dzELhAgW Follow us: @MailOnline on Twitter | DailyMail on Facebook

Health Research Report 19 AUG 2013 – Video

 

Topics:

Sugar is Toxic, Doubles the Death rates in mammals * Aug 13 Journal of Nature Communications

6 Months of Fish Oil Reverses liver disease in Children * Online Journal of Parenteral and Enteral Nutrition — The Fish Oil report took extra time primarily because of two factors 1. The Soybean oil they give children causes Intestinal failure and liver disease

2. Insurance Companies will not cover Fish Oil because it is considered to expensive and experimental

3. Plus a few other reasons to they let children suffer and die because of bureaucracy.

 

Linked the Full Study as is…Please Read

 

Contact: Amy Albin aalbin@mednet.ucla.edu 310-794-8672 University of California – Los Angeles Health Sciences

6 months of fish oil reverses liver disease in children with intestinal failure, study shows

Children who suffer from intestinal failure, most often caused by a shortened or dysfunctional bowel, are unable to consume food orally. Instead, a nutritional cocktail of sugar, protein and fat made from soybean oil is injected through a small tube in their vein.

For these children, the intravenous nutrition serves as a bridge to bowel adaptation, a process by which the intestine recovers and improves its capacity to absorb nutrition. But the soybean oil, which provides essential fatty acids and calories, has been associated with a potentially lethal complication known as intestinal failure–associated liver disease, which may require a liver and/or intestinal transplant. Such a transplant can prevent death, but the five-year post-transplant survival rate is only 50 percent.

Previous studies have shown that replacing soybean oil with fish oil in intravenous nutrition can reverse intestinal failure–associated liver disease. However, the necessary duration of fish oil treatment had not been established in medical studies.

Now, a clinical trial conducted at the Children’s Discovery and Innovation Institute at Mattel Children’s Hospital UCLA has found that, compared with soybean oil, a limited duration (24 weeks) of fish oil is safe and effective in reversing liver disease in children with intestinal failure who require intravenous nutrition. The researchers believe that fish oil may also decrease the need for liver and/or intestinal transplants — and mortality — associated with this disease.

The researchers’ study, “Six Months of Intravenous Fish Oil Reverses Pediatric Intestinal Failure Associated Liver Disease,” is published online in the Journal of Parenteral and Enteral Nutrition.

“With this particular study, we set out to determine if a finite period of six months of intravenous fish oil could safely reverse liver damage in these children, and we have had some promising results,” said lead author Dr. Kara Calkins, an assistant professor in the department of pediatrics in the division of neonatology and developmental biology at UCLA. “But because intravenous fish oil is not yet approved by the Food and Drug Administration and is much more costly than soybean oil, it is typically not covered by insurance. As a result, this oil is considered experimental and is currently available only under special protocols. If it proves safe and effective for patients, we hope it would eventually be available for wider use.”

For the study, intravenous soybean oil was replaced with intravenous fish oil in 10 patients between the ages of 2 weeks and 18 years who had advanced intestinal failure–associated liver disease and who were at high risk for death and/or transplant. The researchers compared these subjects with 20 historical controls who had received soybean oil.

Results showed that the children receiving fish oil had a much higher rate of reversal of liver disease than those who received the standard soybean oil. In fact, after 17 weeks of fish oil, nearly 80 percent of patients experienced a reversal of their liver disease, while only 5 percent of the soybean patients saw a reversal.

The next phase of research will involve following children for up to five years after they stop fish oil to determine if their liver disease returns and if transplant rates are truly decreased, the study authors said.

“We are also trying to better understand how fish oil reverses this disease by investigating changes in proteins and genes in the blood and liver,” Calkins said. “These studies will provide the scientific and medical community with a better understanding of this disease and how intravenous fish oil works.”

For Isabella Piscione, who was one of the first patients at UCLA to receive the fish oil treatment under compassionate use, her outcome with the treatment paved the way for researchers to establish the six-month protocol. Because of multiple surgeries due to an obstruction in her intestines, Isabella was left with only 10 centimeters of intestine. She depended on intravenous nutrition for survival, which unfortunately resulted in liver damage.

When Isabella started the fish oil treatment, she was just over 6 months old and was listed for a liver and bowel transplant. Within a month of starting the treatment, her condition started to improve. By six months, her liver had healed, and she no longer needed a transplant.

“We cried tears of joy each week that we saw her getting better and better,” said her father, Laureano Piscione. “She is a success story.”

###

Study co-authors from UCLA included Dr. James Dunn; Dr. Stephen Shew; Laurie Reyen, R.N.; Dr. Douglas Farmer; Dr. Sherin Devaskar; and Dr. Robert Venick.

The study was funded by a grant from a National Institutes of Health (NIH/NCRR M01-RR00865). Calkins has received funding from NIH K12HD00140 and T32G075776. Calkins and Venick have received funding from the Today’s and Tomorrow’s Children Fund.

Intravenous fish oil was purchased with funds from the UCLA Department of Pediatric Surgery, the Women’s Auxiliary Club at UCLA and Dr. James Yoo of the UCLA Department of Surgery.

 

 

For more information on Mattel Children’s Hospital UCLA, visit http://www.uclahealth.org/mattel.

 

6 Months of Fish Oil Reverses Liver Disease

Caption: Isabella was born with short bowel syndrome which meant she could not eat food normally. She was given nutrition intravenously through a food substitute called total parenteral nutrition (TPN). But then, she developed liver damage probably caused by the soybean oil in the TPN. Her condition worsened and she was listed for a liver and bowel transplant. However, the doctors at Mattel Children’s Hospital UCLA offered an experimental treatment under compassionate use that replaced the soybean oil with fish oil. After six months, her liver had healed and she no longer needed a transplant. This photo shows Isabella in October 2009 after her treatment.

Credit: The Piscione family

 

Dr. Kara Calkins, University of California — Los Angeles Health Sciences

Caption: UCLA’s Dr. Kara Calkins and colleagues found that six months of fish oil treatment can reverse liver disease in children with intestinal failure.

Credit: UCLA

6 months of fish oil reverses liver disease in children with intestinal failure, study shows

Contact: Amy Albin aalbin@mednet.ucla.edu 310-794-8672 University of California – Los Angeles Health Sciences

Children who suffer from intestinal failure, most often caused by a shortened or dysfunctional bowel, are unable to consume food orally. Instead, a nutritional cocktail of sugar, protein and fat made from soybean oil is injected through a small tube in their vein.

For these children, the intravenous nutrition serves as a bridge to bowel adaptation, a process by which the intestine recovers and improves its capacity to absorb nutrition. But the soybean oil, which provides essential fatty acids and calories, has been associated with a potentially lethal complication known as intestinal failure–associated liver disease, which may require a liver and/or intestinal transplant. Such a transplant can prevent death, but the five-year post-transplant survival rate is only 50 percent.

Previous studies have shown that replacing soybean oil with fish oil in intravenous nutrition can reverse intestinal failure–associated liver disease. However, the necessary duration of fish oil treatment had not been established in medical studies.

Now, a clinical trial conducted at the Children’s Discovery and Innovation Institute at Mattel Children’s Hospital UCLA has found that, compared with soybean oil, a limited duration (24 weeks) of fish oil is safe and effective in reversing liver disease in children with intestinal failure who require intravenous nutrition. The researchers believe that fish oil may also decrease the need for liver and/or intestinal transplants — and mortality — associated with this disease.

The researchers’ study, “Six Months of Intravenous Fish Oil Reverses Pediatric Intestinal Failure Associated Liver Disease,” is published online in the Journal of Parenteral and Enteral Nutrition.

“With this particular study, we set out to determine if a finite period of six months of intravenous fish oil could safely reverse liver damage in these children, and we have had some promising results,” said lead author Dr. Kara Calkins, an assistant professor in the department of pediatrics in the division of neonatology and developmental biology at UCLA. “But because intravenous fish oil is not yet approved by the Food and Drug Administration and is much more costly than soybean oil, it is typically not covered by insurance. As a result, this oil is considered experimental and is currently available only under special protocols. If it proves safe and effective for patients, we hope it would eventually be available for wider use.”

For the study, intravenous soybean oil was replaced with intravenous fish oil in 10 patients between the ages of 2 weeks and 18 years who had advanced intestinal failure–associated liver disease and who were at high risk for death and/or transplant. The researchers compared these subjects with 20 historical controls who had received soybean oil.

Results showed that the children receiving fish oil had a much higher rate of reversal of liver disease than those who received the standard soybean oil. In fact, after 17 weeks of fish oil, nearly 80 percent of patients experienced a reversal of their liver disease, while only 5 percent of the soybean patients saw a reversal.

The next phase of research will involve following children for up to five years after they stop fish oil to determine if their liver disease returns and if transplant rates are truly decreased, the study authors said.

“We are also trying to better understand how fish oil reverses this disease by investigating changes in proteins and genes in the blood and liver,” Calkins said. “These studies will provide the scientific and medical community with a better understanding of this disease and how intravenous fish oil works.”

For Isabella Piscione, who was one of the first patients at UCLA to receive the fish oil treatment under compassionate use, her outcome with the treatment paved the way for researchers to establish the six-month protocol. Because of multiple surgeries due to an obstruction in her intestines, Isabella was left with only 10 centimeters of intestine. She depended on intravenous nutrition for survival, which unfortunately resulted in liver damage.

When Isabella started the fish oil treatment, she was just over 6 months old and was listed for a liver and bowel transplant. Within a month of starting the treatment, her condition started to improve. By six months, her liver had healed, and she no longer needed a transplant.

“We cried tears of joy each week that we saw her getting better and better,” said her father, Laureano Piscione. “She is a success story.”

###

Study co-authors from UCLA included Dr. James Dunn; Dr. Stephen Shew; Laurie Reyen, R.N.; Dr. Douglas Farmer; Dr. Sherin Devaskar; and Dr. Robert Venick.

The study was funded by a grant from a National Institutes of Health (NIH/NCRR M01-RR00865). Calkins has received funding from NIH K12HD00140 and T32G075776. Calkins and Venick have received funding from the Today’s and Tomorrow’s Children Fund.

Intravenous fish oil was purchased with funds from the UCLA Department of Pediatric Surgery, the Women’s Auxiliary Club at UCLA and Dr. James Yoo of the UCLA Department of Surgery.

For more information on Mattel Children’s Hospital UCLA, visit http://www.uclahealth.org/mattel.

Health Research Report 156 1 JUN 2013 (Synopsis)

 

In this issue:

1.   Coffee consumption associated with reduced risk of autoimmune liver disease

2.   Ginger compounds may be effective in treating asthma symptoms

3.   The compound in the Mediterranean diet that makes cancer cells ‘mortal’

4.   Study finds vitamin C can kill drug-resistant TB

5.   Common Food Supplement Fights Degenerative Brain Disorders

6.   Calcium supplements linked to longer lifespans in women

7.   Soda and illegal drugs cause similar damage to teeth

8.   Changing gut bacteria through diet affects brain function, UCLA study shows

 ScreenHunter_42 Dec. 31 12.07

Vitamin and Herb Stores

Health Research Report

156th Issue Date 1 Jun 2013

Compiled By Ralph Turchiano

www.vit.bz

www.youtube.com/vhfilm

 www.facebook.com/engineeringevil

www.healthresearchreport.me 

 

 

Changing gut bacteria through diet affects brain function, UCLA study shows

Contact: Kim Irwin kirwin@mednet.ucla.edu 310-794-2262 University of California – Los Angeles Health Sciences

UCLA researchers now have the first evidence that bacteria ingested in food can affect brain function in humans. In an early proof-of-concept study of healthy women, they found that women who regularly consumed beneficial bacteria known as probiotics through yogurt showed altered brain function, both while in a resting state and in response to an emotion-recognition task.

The study, conducted by scientists with UCLA’s Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress and the Ahmanson–Lovelace Brain Mapping Center at UCLA, appears in the June edition of the peer-reviewed journal Gastroenterology.

The discovery that changing the bacterial environment, or microbiota, in the gut can affect the brain carries significant implications for future research that could point the way toward dietary or drug interventions to improve brain function, the researchers said.

“Many of us have a container of yogurt in our refrigerator that we may eat for enjoyment, for calcium or because we think it might help our health in other ways,” said Dr. Kirsten Tillisch, an associate professor of medicine at UCLA’s David Geffen School of Medicine and lead author of the study. “Our findings indicate that some of the contents of yogurt may actually change the way our brain responds to the environment. When we consider the implications of this work, the old sayings ‘you are what you eat’ and ‘gut feelings’ take on new meaning.”

Researchers have known that the brain sends signals to the gut, which is why stress and other emotions can contribute to gastrointestinal symptoms. This study shows what has been suspected but until now had been proved only in animal studies: that signals travel the opposite way as well.

“Time and time again, we hear from patients that they never felt depressed or anxious until they started experiencing problems with their gut,” Tillisch said. “Our study shows that the gut–brain connection is a two-way street.”

The small study involved 36 women between the ages of 18 and 55. Researchers divided the women into three groups: one group ate a specific yogurt containing a mix of several probiotics — bacteria thought to have a positive effect on the intestines — twice a day for four weeks; another group consumed a dairy product that looked and tasted like the yogurt but contained no probiotics; and a third group ate no product at all.

Functional magnetic resonance imaging (fMRI) scans conducted both before and after the four-week study period looked at the women’s brains in a state of rest and in response to an emotion-recognition task in which they viewed a series of pictures of people with angry or frightened faces and matched them to other faces showing the same emotions. This task, designed to measure the engagement of affective and cognitive brain regions in response to a visual stimulus, was chosen because previous research in animals had linked changes in gut flora to changes in affective behaviors.

The researchers found that, compared with the women who didn’t consume the probiotic yogurt, those who did showed a decrease in activity in both the insula — which processes and integrates internal body sensations, like those form the gut — and the somatosensory cortex during the emotional reactivity task.

Further, in response to the task, these women had a decrease in the engagement of a widespread network in the brain that includes emotion-, cognition- and sensory-related areas. The women in the other two groups showed a stable or increased activity in this network.

During the resting brain scan, the women consuming probiotics showed greater connectivity between a key brainstem region known as the periaqueductal grey and cognition-associated areas of the prefrontal cortex. The women who ate no product at all, on the other hand, showed greater connectivity of the periaqueductal grey to emotion- and sensation-related regions, while the group consuming the non-probiotic dairy product showed results in between.

The researchers were surprised to find that the brain effects could be seen in many areas, including those involved in sensory processing and not merely those associated with emotion, Tillisch said.

The knowledge that signals are sent from the intestine to the brain and that they can be modulated by a dietary change is likely to lead to an expansion of research aimed at finding new strategies to prevent or treat digestive, mental and neurological disorders, said Dr. Emeran Mayer, a professor of medicine, physiology and psychiatry at the David Geffen School of Medicine at UCLA and the study’s senior author.

“There are studies showing that what we eat can alter the composition and products of the gut flora — in particular, that people with high-vegetable, fiber-based diets have a different composition of their microbiota, or gut environment, than people who eat the more typical

Western diet that is high in fat and carbohydrates,” Mayer said. “Now we know that this has an effect not only on the metabolism but also affects brain function.”

The UCLA researchers are seeking to pinpoint particular chemicals produced by gut bacteria that may be triggering the signals to the brain. They also plan to study whether people with gastrointestinal symptoms such as bloating, abdominal pain and altered bowel movements have improvements in their digestive symptoms which correlate with changes in brain response.

Meanwhile, Mayer notes that other researchers are studying the potential benefits of certain probiotics in yogurts on mood symptoms such as anxiety. He said that other nutritional strategies may also be found to be beneficial.

By demonstrating the brain effects of probiotics, the study also raises the question of whether repeated courses of antibiotics can affect the brain, as some have speculated. Antibiotics are used extensively in neonatal intensive care units and in childhood respiratory tract infections, and such suppression of the normal microbiota may have longterm consequences on brain development.

Finally, as the complexity of the gut flora and its effect on the brain is better understood, researchers may find ways to manipulate the intestinal contents to treat chronic pain conditions or other brain related diseases, including, potentially, Parkinson’s disease, Alzheimer’s disease and autism.

Answers will be easier to come by in the near future as the declining cost of profiling a person’s microbiota renders such tests more routine, Mayer said.

###

 

The study was funded by Danone Research. Mayer has served on the company’s scientific advisory board. Three of the study authors (Denis Guyonnet, Sophie Legrain-Raspaud and Beatrice Trotin) are employed by Danone Research and were involved in the planning and execution of the study (providing the products) but had no role in the analysis or interpretation of the results.

UCLA’s Oppenheimer Family Center for Neurobiology of Stress is an NIH-funded multidisciplinary, translational research program partially supported by philanthropy. Its mission is to identify the role of the brain in health and medical disease.  The Center is comprised of several research programs which focus on the interactions of the brain with the digestive, cardiovascular and urological systems, chronic pain and mind brain body interactions.

For more news, visit the UCLA Newsroom and follow us on Twitter.

Research suggests popular diabetes drugs can cause abnormal pancreatic growth in humans

Contact: Enrique Rivero erivero@mednet.ucla.edu 310-794-2273 University of California – Los Angeles Health Sciences

Individuals who had taken a type of drug commonly used to treat Type 2 diabetes showed abnormalities in the pancreas, including cell proliferation, that may be associated with an increased risk of neuroendocrine tumors, according to a new study by researchers from UCLA and the University of Florida. Their findings were published online March 22 in the journal Diabetes.

The researchers, from the Larry L. Hillblom Islet Research Center at UCLA and the Diabetes Center at the University of Florida, found that cell mass was increased approximately 40 percent in the pancreases of deceased organ donors who had Type 2 diabetes and who had been treated with incretin therapy. This widely used type of treatment takes advantage of the action of a gut hormone known as glucagon-like peptide 1 (GLP-1) to lower blood sugar in the body.

Although there have been conflicting reports on the effects of the incretin class of drugs on the pancreas in animal studies, this is the first study to note such changes in the human pancreas. The research was made possible by a unique research consortium called nPOD (Network for Pancreatic Organ Donors with Diabetes), led by Dr. Mark Atkinson, a professor of pathology and pediatrics at the University of Florida. The network, which is funded by the Juvenile Diabetes Research Foundation, obtains pancreases from deceased organ donors, with permission of their next of kin, to better understand diabetes by investigating tissues of those with the disease.

“There is an increasing appreciation that animal studies do not always predict findings in humans,” said Dr. Peter Butler, director of UCLA’s Hillblom Islet Research Center and chief of the endocrinology, diabetes and hypertension unit. “The nPOD program is therefore a very precious resource.”  The researchers examined the pancreases of 20 deceased organ donors with Type 2 diabetes. Eight had been treated for at least a year with incretin therapy, while the other 12 had received therapies that didn’t include incretin-based drugs. The researchers also evaluated 14 pancreases from a control group of non-diabetic individuals of similar age.

The pancreases of the individuals who had been on incretin therapy were larger than those of patients on other types of diabetes therapies, and this larger size was associated with increased cellular proliferation. Incretin-treated individuals showed an increase in pancreas dysplasia, an abnormal form of cell proliferation that is a risk factor for pancreatic cancer, as well as an expansion of alpha cells, endocrine cells that make the hormone glucagon.

This latter finding is likely a consequence of GLP-1–based therapies’ suppression of the release of glucagon by alpha cells, since decreasing the availability or action of the hormone glucagon has been shown in a variety of prior studies to induce a proliferation of pancreatic alpha cells. This alpha-cell expansion has been associated with the development of pancreatic neuroendocrine tumors. Three of the eight incretin-treated individuals had microadenomas and one has a neuroendocrine tumor composed of alpha cells.

Of the eight donors who were on incretin therapy, seven had been taking sitagliptin, sold in pill form as Januvia and marketed by Merck, and one had been on exenatide, sold as Byetta by Bristol-Myers Squibb. These and similar drugs are currently under investigation by the U.S. Food and Drug Administration for their possible links to pancreatitis and pancreatic cancer.

“These findings lend additional weight to concerns regarding the effects of long term GLP-1–related therapy, with respect to both unintended proliferative actions on the exocrine pancreas and now also a possible increased risk of neuroendocrine tumors,” the researchers write. “In addition to the surveillance previously recommended for the potential association of GLP-1– based therapy and pancreatic cancer risk, the current data imply that surveillance for a possible increased risk of pancreatic neuroendocrine tumors is warranted.”

Such surveillance approaches might include MRI imaging of the pancreas and screening for neuroendocrine tumors, Butler said.

“The present studies are only from a small number of individuals, and while the findings do raise concerns, it will be important that other approaches are now used in a larger group of living individuals to further investigate these findings,” he said.

A recent study led by Dr. Sonal Singh of Johns Hopkins University School of Medicine and Public Health and published in JAMA Internal Medicine suggested a doubling in the risk of hospitalization for acute pancreatitis with the GLP-1–based therapies and also recommended further research.

“Since most risk factors for acute pancreatitis are also linked to an increased risk of pancreatic cancer, these findings of changes in the human pancreas are very concerning,” said Singh, an assistant professor of medicine and international health. “Now that GLP-1–based therapies have been shown to increase the risk of pancreatic inflammation and abnormal cell proliferation, further studies are needed to urgently clarify whether these linkages lead to pancreatic cancer with long-term use.”

###

Study co-authors, in addition to Butler and Atkinson, are Alexandra  E. Butler, Tatyana Gurlo and David W. Dawson, all of UCLA, and Martha Campbell-Thompson of the University of Florida.

Grants from National Institute of Diabetes and Digestive and Kidney Diseases (DK059579, DK061539 and DK077967), the Hillblom Foundation, and the Peter and Valerie Kompaniez Foundation funded this study. The Juvenile Diabetes Research Foundation funds the nPOD program.

For more news, visit the UCLA Newsroom and follow us on Twitter.

UCLA study could explain why some people get zits and others don’t

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

2 strains of acne bacteria linked to pimples, another to healthy skin

The bacteria that cause acne live on everyone’s skin, yet one in five people is lucky enough to develop only an occasional pimple over a lifetime. What’s their secret?

In a boon for teenagers everywhere, a UCLA study conducted with researchers at Washington University in St. Louis and the Los Angeles Biomedical Research Institute has discovered that acne bacteria contain “bad” strains associated with pimples and “good” strains that may protect the skin.

The findings, published in the Feb. 28 edition of the Journal of Investigative Dermatology, could lead to a myriad of new therapies to prevent and treat the disfiguring skin disorder.

“We learned that not all acne bacteria trigger pimples — one strain may help keep skin healthy,” said principal investigator Huiying Li, an assistant professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA. “We hope to apply our findings to develop new strategies that stop blemishes before they start, and enable dermatologists to customize treatment to each patient’s unique cocktail of skin bacteria.”

The scientists looked at a tiny microbe with a big name: Propionibacterium acnes, bacteria that thrive in the oily depths of our pores. When the bacteria aggravate the immune system, they cause the swollen, red bumps associated with acne.

Using over-the-counter pore-cleansing strips, LA BioMed and UCLA researchers lifted P. acnes bacteria from the noses of 49 pimply and 52 clear-skinned volunteers. After extracting the microbial DNA from the strips, Li’s laboratory tracked a genetic marker to identify the  bacterial strains in each volunteer’s pores and recorded whether the person suffered from acne.

Next, Li’s lab cultured the bacteria from the strips to isolate more than 1,000 strains. Washington University scientists sequenced the genomes of 66 of the P. acnes strains, enabling UCLA co-first author Shuta Tomida to zero in on genes unique to each strain.

“We were interested to learn that the bacterial strains looked very different when taken from diseased skin, compared to healthy skin,” said co-author Dr. Noah Craft, a dermatologist and director of the Center for Immunotherapeutics Research at LA BioMed at Harbor–UCLA Medical Center. “Two unique strains of P. acnes appeared in one out of five volunteers with acne but rarely occurred in clear-skinned people.”

The biggest discovery was still to come.

“We were extremely excited to uncover a third strain of P. acnes that’s common in healthy skin yet rarely found when acne is present,” said Li, who is also a member of UCLA’s Crump Institute for Molecular Imaging. “We suspect that this strain contains a natural defense mechanism that enables it to recognize attackers and destroy them before they infect the bacterial cell.”

Offering new hope to acne sufferers, the researchers believe that increasing the body’s friendly strain of P. acnes through the use of a simple cream or lotion may help calm spotty complexions.

“This P. acnes strain may protect the skin, much like yogurt’s live bacteria help defend the gut from harmful bugs,” Li said. “Our next step will be to investigate whether a probiotic cream can block bad bacteria from invading the skin and prevent pimples before they start.”

Additional studies will focus on exploring new drugs that kill bad strains of P. acnes while preserving the good ones; the use of viruses to kill acne-related bacteria; and a simple skin test to predict whether a person will develop aggressive acne in the future.

“Our research underscores the importance of strain-level analysis of the world of human microbes to define the role of bacteria in health and disease,” said George Weinstock, associate director of the Genome Institute and professor of genetics at Washington University in St. Louis. “This type of analysis has a much higher resolution than prior studies that relied on bacterial cultures or only made distinctions between bacterial species.”

Acne affects 80 percent of Americans at some point in their lives, yet scientists know little about what causes the disorder and have made limited progress in developing new strategies for treating it. Dermatologists’ arsenal of anti-acne tools — benzoyl peroxide, antibiotics and Accutane (isotretinoin) — hasn’t expanded in decades. Most severe cases of acne don’t respond to antibiotics, and Accutane can produce serious side effects.

###

The research was supported by a grant (UH2AR057503) from the National Institutes of Health’s Human Microbiome Project through the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Co-authors include co-first author Sorel Fitz-Gibbon, Bor-Han Chiu, Lin Nguyen, Christine Du, Dr. Minghsun Liu, David Elashoff, Dr. Jenny Kim, Anya Loncaric, Dr. Robert Modlin and Jeff F. Miller of UCLA; Erica Sodergren of Washington University; and Dr. Marie Erfe of LA BioMed.

UCLA:  Elaine Schmidt, eschmidt@mednet.ucla.edu                         310-794-2272

Washington University: Caroline Arbanas, arbanasc@wustl.edu                    314-286-0109

LA BioMed: Laura Mecoy, lmecoy@labiomed.org 310-546-5860

Newly identified natural protein blocks HIV, other deadly viruses

EEV:  25-hydroxycholesterol/Statin?

Contact: Enrique Rivero erivero@mednet.ucla.edu 310-794-2273 University of California – Los Angeles Health Sciences

A team of UCLA-led researchers has identified a protein with broad virus-fighting properties that potentially could be used as a weapon against deadly human pathogenic viruses such as HIV, Ebola, Rift Valley Fever, Nipah and others designated “priority pathogens” for national biosecurity purposes by the National Institute of Allergy and Infectious Disease.

In a study published in the January issue of the journal Immunity, the researchers describe the novel antiviral property of the protein, cholesterol-25-hydroxylase (CH25H), an enzyme that converts cholesterol to an oxysterol called 25-hydroxycholesterol (25HC), which can permeate a cell’s wall and block a virus from getting in.

Interestingly, the CH25H enzyme is activated by interferon, an essential antiviral cell-signaling protein produced in the body, said lead author Su-Yang Liu, a student in the department of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA.

“Antiviral genes have been hard to apply for therapeutic purposes because it is difficult to express genes in cells,” said Liu, who performed the study with principal investigator Genhong Cheng, a professor of microbiology, immunology and molecular genetics. “CH25H, however, produces a natural, soluble oxysterol that can be synthesized and administered.

“Also, our initial studies showing that 25HC can inhibit HIV growth in vivo should prompt further study into membrane-modifying cholesterols that inhibit viruses,” he added.

The discovery is particularly relevant to efforts to develop broad-spectrum antivirals against an increasing number of merging viral pathogens, Liu said.

Working with Jerome Zack, a professor of microbiology, immunology and molecular genetics and an associate director of the UCLA AIDS Institute, the researchers initially found that 25HC dramatically inhibited HIV in cell cultures. Next, they administered 25HC in mice  implanted with human tissues and found that it significantly reduced their HIV load within seven days. The 25HC also reversed the T-cell depletion caused by HIV.

By contrast, mice that had the CH25H gene knocked out were more susceptible to a mouse gammaherpes virus, the researchers found.

In collaboration with Dr. Benhur Lee, a professor of pathology and laboratory medicine and a member of the UCLA AIDS Institute, they discovered that 25HC inhibited HIV entry into the cell. Furthermore, in cell cultures, it was found to inhibit the growth of other deadly viruses, such as Ebola, Nipah and the Rift Valley Fever virus.

Intriguingly, CH25H expression in cells requires interferon. While interferon has been known for more than 60 years to be a critical part of the body’s natural defense mechanism against viruses, the protein itself does not have any antiviral properties. Rather, it triggers the expression of many antiviral genes. While other studies have identified some antiviral genes that are activated by interferon, this research gives the first description of an interferon-induced antiviral oxysterol through the activation of the enzyme CH25H. It provides a link to how interferon can cause inhibition of viral membrane fusion, Liu said.

He noted some weaknesses in the research. For instance, 25HC is difficult to deliver in large doses, and its antiviral effect against Ebola, Nipah and other highly pathogenic viruses have yet to be tested in vivo. Also, the researchers still need to compare 25HC’s antiviral effect against other HIV antivirals.

###

Additional study co-authors were Roghiyh Aliyari, Kelechi Chikere, Matthew D. Marsden and Olivier Pernet, of UCLA; Jennifer K. Smith, Rebecca Nusbaum and Alexander N. Frieberg, of the University of Texas–Galveston; and Guangming Li, Haitao Guo and Lishan Su, of the University of North Carolina–Chapel Hill.

The National Institutes of Health (grants R01 AI078389, AI069120, AI080432, AI095097, AI077454, AI070010 and AI028697), the Warsaw Fellowship, the UCLA Center for AIDS Research (CFAR), the UCLA AIDS Institute, the UCLA Clinical and Translational Science Institute (CTSI), and the Pacific Southwest Regional Center of Excellence (PSWRCE) for Biodefense and Emerging Infectious Diseases funded this study.

The UCLA AIDS Institute, established in 1992, is a multidisciplinary think tank drawing on the skills of top-flight researchers in the worldwide fight against HIV and AIDS, the first cases of which were reported in 1981 by UCLA physicians. Institute members include researchers in virology and immunology, genetics, cancer, neurology, ophthalmology, epidemiology, social sciences, public health, nursing and disease prevention. Their findings have led to advances in treating HIV, as well as other diseases, such as hepatitis B and C, influenza and cancer.

For more news, visit the UCLA Newsroom and follow us on Twitter.

Childhood obesity linked to more immediate health problems than previously thought

Contact: Amy Albin aalbin@mednet.ucla.edu 310-794-8672 University of California – Los Angeles Health Sciences

While a great deal of research on childhood obesity has spotlighted the long-term health problems that emerge in adulthood, a new UCLA study focuses on the condition’s immediate consequences and shows that obese youngsters are at far greater risk than had been supposed.

Compared to kids who are not overweight, obese children are at nearly twice the risk of having three or more reported medical, mental or developmental conditions, the UCLA researchers found. Overweight children had a 1.3 times higher risk.

“This study paints a comprehensive picture of childhood obesity, and we were surprised to see just how many conditions were associated with childhood obesity,” said lead author Dr. Neal Halfon, a professor of pediatrics, public health and public policy at UCLA, where he directs the Center for Healthier Children, Families and Communities. “The findings should serve as a wake-up call to physicians, parents and teachers, who should be better informed of the risk for other health conditions associated with childhood obesity so that they can target interventions that can result in better health outcomes.”

With the dramatic rise in childhood obesity over the past two decades, there has been a parallel rise in the prevalence of other childhood-onset health conditions, such as attention deficit–hyperactivity disorder, asthma and learning disabilities. But previous studies on the topic have been limited due to a narrow focus on a specific region of the county, a small sample size or a single condition.

The new UCLA research, a large population-based study of children in the United States, provides the first comprehensive national profile of associations between weight status and a broad set of associated health conditions, or co-morbidities, that kids suffer from during childhood.

Overall, the researchers found, obese children were more likely than those who were classified as not overweight to have reported poorer health; more disability; a greater  tendency toward emotional and behavioral problems; higher rates of grade repetition, missed school days and other school problems; ADHD; conduct disorder; depression; learning disabilities; developmental delays; bone, joint and muscle problems; asthma; allergies; headaches; and ear infections.

For the study, the researchers used the 2007 National Survey of Children’s Health, analyzing data on nearly 43,300 children between the ages 10 and 17. They assessed associations between weight status and 21 indicators of general health, psychosocial functioning and specific health disorders, adjusting for sociodemographic factors.

Of the children in the study, 15 percent were considered overweight (a body mass index between the 85th and 95th percentiles), and 16 percent were obese (a BMI in the 95th percentile or higher).

The study, which is currently available online, will be published in the January–February print issue of the journal Academic Pediatrics.

The UCLA researchers speculate that the ongoing shift in chronic childhood conditions is likely related to decades of underappreciated changes in the social and physical environments in which children live, learn and play. They propose that obesity-prevention efforts should target these social and environmental influences and that kids should be screened and managed for the co-morbid conditions.

The researchers add that while the strength of the current study lies in its large population base, future studies need to examine better longitudinal data to tease out causal relationships that cannot be inferred from a cross-sectional study.

“Obesity might be causing the co-morbidity, or perhaps the co-morbidity is causing obesity — or both might be caused by some other unmeasured third factor,” Halfon said. “For example, exposure to toxic stress might change the neuroregulatory processes that affect impulse control seen in ADHD, as well as leptin sensitivity, which can contribute to weight gain. An understanding of the association of obesity with other co-morbidities may provide important information about causal pathways to obesity and more effective ways to prevent it.”

###

Halfon’s co-authors on the study included Kandyce Larson and Dr. Wendy Slusser, both of UCLA.

The study was supported by funding from the Maternal and Child Health Bureau of the Health Resource Services Administration.

The authors have no financial ties to disclose.

For more information on the UCLA Center for Healthier Children, Families and Communities, please visit www.healthychild.ucla.edu.

Obesity gene, carried by more than a third of the US population, leads to brain tissue loss

2010 study posted for filing

Contact: Mark Wheeler mwheeler@mednet.ucla.edu 310-794-2265 University of California – Los Angeles

Three years ago, geneticists reported the startling discovery that nearly half of all people in the U.S. with European ancestry carry a variant of the fat mass and obesity associated (FTO) gene, which causes them to gain weight — from three to seven pounds, on average — but worse, puts them at risk for obesity.

Now, UCLA researchers have found that the same gene allele, which is also carried by roughly one-quarter of U.S. Hispanics, 15 percent of African Americans and 15 percent of Asian Americans, may have another deleterious effect.

Reporting in the early online edition of the journal Proceedings of the National Academy of Sciences, senior study author Paul Thompson, a UCLA professor of neurology; lead authors April Ho and Jason Stein, graduate students in Thompson’s lab; and colleagues found that the FTO variant is also associated with a loss of brain tissue. This puts more than a third of the U.S. population at risk for a variety of diseases, such as Alzheimer’s.

Using magnetic resonance imaging, the researchers generated three-dimensional “maps” of brain volume differences in 206 healthy elderly subjects drawn from 58 sites in the U.S. as part of the Alzheimer’s Disease Neuroimaging Initiative, a large, five-year study aimed at better understanding factors that help the brain resist disease as it ages.

They found that there was consistently less tissue in the brains of those who carry the FTO allele, compared with non-carriers. Individuals with the “bad” version of the FTO gene had an average of 8 percent less tissue in the frontal lobes, the “command center” of the brain, and 12 percent less in the occipital lobes, areas in the back of the brain responsible for vision and perception. Further, the brain differences could not be directly attributed to other obesity-related factors such as cholesterol levels, diabetes or high blood pressure.

Thompson called the findings worrying and mysterious.

“The results are curious. If you have the bad FTO gene, your weight affects your brain adversely in terms of tissue loss,” he said. “If you don’t carry FTO, higher body weight doesn’t translate into brain deficits; in fact, it has nothing to do with it. This is a very mysterious, widespread gene.”

People who carry this specific DNA sequence are heavier on average, and their waist circumference is half an inch bigger.

This is a large percentage of the population, said Thompson, who is also a member of UCLA’s Brain Research Institute and the UCLA Laboratory of Neuro Imaging.

“This is a shocking finding. Any loss of brain tissue puts you at greater risk for functional decline,” he said. “The risk gene divides the world into two camps ― those who have the FTO allele and those who don’t.”

But the news is not necessarily completely negative, Thompson said, because “carriers of the risk gene can exercise and eat healthily to resist both obesity and brain decline.”

Thompson sees both a public health message and a science message in this finding.

“Half of the world carries this dangerous gene. But a healthy lifestyle will counteract the risk of brain loss, whether you carry the gene or not. So it’s vital to boost your brain health by being physically active and eating a balanced diet,” he said.

And from a scientific standpoint, he said, “the gene discovery will help to develop and fine tune the anti-dementia drugs being developed to combat brain aging.”

###

Funding for the study came from the National Institutes of Health and from private industry. The authors report no conflict of interest.

The UCLA Department of Neurology encompasses more than a dozen research, clinical and teaching programs that cover brain mapping and neuroimaging, movement disorders, Alzheimer’s disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks first among its peers nationwide in National Institutes of Health funding.

For more news, visit the UCLA Newsroom and follow us on Twitter.

Sleeping Brain Behaves as If It’s Remembering Something

In the background is an entorhinal cortex neuron that was studied. The blue-green trace shows neocortical slow oscillation while the yellow trace shows the persistent activity of entorhinal cortical neuron, even when the inputs from neocortex were silent. (Credit: Mayank Mehta)

ScienceDaily (Oct. 7, 2012) — UCLA researchers have for the first time measured the activity of a brain region known to be involved in learning, memory and Alzheimer’s disease during sleep. They discovered that this part of the brain behaves as if it’s remembering something, even under anesthesia, a finding that counters conventional theories about memory consolidation during sleep.

The research team simultaneously measured the activity of single neurons from multiple parts of the brain involved in memory formation. The technique allowed them to determine which brain region was activating other areas of the brain and how that activation was spreading, said study senior author Mayank R. Mehta, a professor of neurophysics in UCLA’s departments of neurology, neurobiology, physics and astronomy.

In particular, Mehta and his team looked at three connected brain regions in mice — the new brain or the neocortex, the old brain or the hippocampus, and the entorhinal cortex, an intermediate brain that connects the new and the old brains. While previous studies have suggested that the dialogue between the old and the new brain during sleep was critical for memory formation, researchers had not investigated the contribution of the entorhinal cortex to this conversation, which turned out to be a game changer, Mehta said. His team found that the entorhinal cortex showed what is called persistent activity, which is thought to mediate working memory during waking life, for example when people pay close attention to remember things temporarily, such as recalling a phone number or following directions.

“The big surprise here is that this kind of persistent activity is happening during sleep, pretty much all the time.” Mehta said. “These results are entirely novel and surprising. In fact, this working memory-like persistent activity occurred in the entorhinal cortex even under anesthesia.”

The study appears Oct. 7, 2012 in the early online edition of the journal Nature Neuroscience.

The findings are important, Mehta said, because humans spend one-third of their lives sleeping and a lack of sleep results in adverse effects on health, including learning and memory problems.

It had been shown previously that the neocortex and the hippocampus “talk” to each other during sleep, and it is believed that this conversation plays a critical role in establishing memories, or memory consolidation. However, no one was able to interpret the conversation.

“When you go to sleep, you can make the room dark and quiet and although there is no sensory input, the brain is still very active,” Mehta said. “We wanted to know why this was happening and what different parts of the brain were saying to each other.”

Mehta and his team developed an extremely sensitive monitoring system that allowed them to follow the activities of neurons from each of three targeted portions of the brain simultaneously, including the activity of a single neuron. This allowed them to decipher the precise communications, even when the neurons were seemingly quiet. They then developed a sophisticated mathematical analysis to decipher the complex conversation.

During sleep, the neocortex goes into a slow wave pattern for about 90 percent of that time. During this period, its activity slowly fluctuates between active and inactive states about once every second. Mehta and his team focused on the entorhinal cortex, which has many parts.

The outer part of the entorhinal cortex mirrored the neocortical activity. However, the inner part behaved differently. When the neocortex became inactive, the neurons in the inner entorhinal cortex persisted in the active state, as if they were remembering something the neocortex had recently “said,” a phenomenon called spontaneous persistent activity. Further, they found that when the inner part of the entorhinal cortex became spontaneously persistent, it prompted the hippocampus neurons to become very active. On the other hand, when the neocortex was active, the hippocampus became quieter. This data provided a clear interpretation of the conversation.

“During sleep the three parts of the brain are talking to each other in a very complex way,” he said. “The entorhinal neurons showed persistent activity, behaving as if they were remembering something even under anesthesia when the mice could not feel or smell or hear anything. Remarkably, this persistent activity sometimes lasted for more than a minute, a huge timescale in brain activity, which generally changes on a scale of one thousandth of a second.”

The findings challenge theories of brain communication during sleep, in which the hippocampus is expected to talk to, or drive, the neocortex. Mehta’s findings instead indicate that there is a third key actor in this complex dialogue, the entorhinal cortex, and that the neocortex is driving the entorhinal cortex, which in turn behaves as if it is remembering something. That, in turn, drives the hippocampus, while other activity patterns shut it down.

“This is a whole new way of thinking about memory consolidation theory. We found there is a new player involved in this process and it’s having an enormous impact,” Mehta said. “And what that third player is doing is being driven by the neocortex, not the hippocampus. This suggests that whatever is happening during sleep is not happening the way we thought it was. There are more players involved so the dialogue is far more complex, and the direction of the communication is the opposite of what was thought.”

Mehta theorizes that this process occurs during sleep as a way to unclutter memories and delete information that was processed during the day but is irrelevant. This results in the important memories becoming more salient and readily accessible. Notably, Alzheimer’s disease starts in the entorhinal cortex and patients have impaired sleep, so Mehta’s findings may have implications in that arena.

For this study, Mehta teamed with Thomas Hahn and Sven Berberich of Heidelberg University in Germany and the Max Planck Institute for Medical Research and James McFarland of Brown University and the UCLA Department of Physics. Going forward, the team will further study this brain activity to uncover the mechanisms behind it and determine if it influences subsequent behavioral performance.

“These results provide the first direct evidence for persistent activity in medial entorhinal cortex layer neurons in vivo, and reveal its contribution to cortico-hippocampal interactions, which could be involved in working memory and learning of long behavioral sequences during behavior, and memory consolidation during sleep,” the study states.

The study was funded by the Whitehall Foundation, the National Institutes of Health, the National Science Foundation, the W. M. Keck Foundation, the German Ministry of Education and Research and the Max Planck Society.

http://www.sciencedaily.com/releases/2012/10/121007134729.htm

UCLA/Pitt scientists uncover virus with potential to stop pimples in their tracks

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

Going viral to kill zits

Watch out, acne.  Doctors soon may have a new weapon against zits:  a harmless virus living on our skin that naturally seeks out and kills the bacteria that cause pimples.

The Sept. 25 online edition of the American Society for Microbiology’s mBio publishes the findings by scientists at UCLA and the University of Pittsburgh.

“Acne affects millions of people, yet we have few treatments that are both safe and effective,” said principal investigator Dr. Robert Modlin, chief of dermatology and professor of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA.  “Harnessing a virus that naturally preys on the bacteria that causes pimples could offer a promising new tool against the physical and emotional scars of severe acne.”

The scientists looked at two little microbes that share a big name:  Propionibacterium acnes, a bacterium thriving in our pores that can trigger acne; and P. acnes phages, a family of viruses that live on human skin.  The viruses are harmless to humans, but programmed to infect and kill the aforementioned P. acnes bacteria.

When P. acnes bacteria aggravate the immune system, it causes the swollen, red bumps associated with acne.  Most effective treatments work by reducing the number of P. acnes bacteria on the skin.

“We know that sex hormones, facial oil and the immune system play a role in causing acne, however, a lot of research implicates P. acnes as an important trigger,” explained first author Laura Marinelli, a UCLA postdoctoral researcher in Modlin’s laboratory.  “Sometimes they set off an inflammatory response that contributes to the development of acne.”

Using over-the-counter pore cleansing strips from the drugstore, the researchers lifted acne bacteria and the P. acnes viruses from the noses of both pimply and clear-skinned volunteers.

When the team sequenced the bacteriophages’ genomes, they discovered that the viruses possess multiple features – such as small size, limited diversity and the broad ability to kill their hosts – that make them ideal candidates for the development of a new anti-acne therapy.

“Our findings provide valuable insights into acne and the bacterium that causes it,” observed corresponding author Graham Hatfull, Eberly Family Professor of Biotechnology, professor of biological sciences at the University of Pittsburgh and a Howard Hughes Medical Institute researcher.  “The lack of genetic diversity among the phages that attack the acne bacterium implies that viral-based strategies may help control this distressing skin disorder.”

“Phages are programmed to target and kill specific bacteria, so P. acnes phages will attack only P. acnes bacteria, but not others like E. coli,” added Marinelli.  “This trait suggests that they offer strong potential for targeted therapeutic use.”

Acne affects nearly 90 percent of Americans at some point in their lives, yet scientists know little about what causes the disorder and have made narrow progress in developing new strategies for treating it.  Dermatologists’ arsenal of anti-acne tools — benzoyl peroxide, antibiotics and Accutane – hasn’t expanded in decades.

“Antibiotics such as tetracycline are so widely used that many acne strains have developed resistance, and drugs like Accutane, while effective, can produce risky side effects, limiting their use,” explained coauthor Dr. Jenny Kim, director of the UCLA Clinic for Acne, Rosacea and Aesthetics.  “Acne can dramatically disfigure people and undermine their self-esteem, especially in teens.  We can change patients’ lives with treatment.  It’s time we identified a new way to safely treat the common disorder.”

The research team plans to isolate the active protein from the P. acnes virus and test whether it is as effective as the whole virus in killing acne bacteria. If laboratory testing proves successful, the researchers will study the compound’s safety and effectiveness in combating acne in people.

###

The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR060382, R01 AR053542 and F32AR060655) at the National Institutes of Health in Bethesda, Md.

Additional coauthors included Sorel Fitz-Gibbon, Megan Inkeles, Shawn Cokus, Matteo Pellegrini and Jeffrey F. Miller, all of UCLA; former UCLA researchers Clarmyra Hayes and Anya Loncaric, now of the California Institute of Technology and Solta Medical, respectively; and  Charles Bowman, Daniel Russell and Deborah Jacobs-Sera of the University of Pittsburgh.

The Clinic for Acne, Rosacea and Aesthetics at the UCLA Division of Dermatology at the David Geffen School of Medicine offers comprehensive care for acne and rosacea, as well as the scarring and discoloration that can result from these conditions.  The clinic’s goal is to educate the public and help patients develop habits leading to healthy skin.  Current research projects include studying the effect of Vitamin-D on immune response to acne, the effect of Omega-3 fatty acids on acne and its treatment, and the use of a mobile device application for acne management.  To schedule an appointment, call (310) 825-6911

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.”‘

 

###

 

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

UCSB scientists examine effects of manufactured nanoparticles on soybean crops: zinc oxide and cerium oxide

Contact: Gail Gallessich gail.g@ia.ucsb.edu 805-893-7220 University of California – Santa Barbara

IMAGE:These are soybean plants growing in a UCSB greenhouse.Click here for more information.

(Santa Barbara, Calif.) –– Sunscreens, lotions, and cosmetics contain tiny metal nanoparticles that wash down the drain at the end of the day, or are discharged after manufacturing. Those nanoparticles eventually end up in agricultural soil, which is a cause for concern, according to a group of environmental scientists that recently carried out the first major study of soybeans grown in soil contaminated by two manufactured nanomaterials (MNMs).

The team was led by scientists at UC Santa Barbara’s Bren School for Environmental Science & Management. The team is also affiliated with the UC Center for Environmental Implications of Nanotechnology (CEIN), a $24 million collaboration based at UCLA, with researchers from UCSB, UC Davis, UC Riverside, University of Texas at El Paso, Columbia University, and other national and international partners. The results of the study are published this week in the Proceedings of the National Academy of Sciences.

“Our society has become more environmentally aware in the last few decades, and that results in our government and scientists asking questions about the safety of new types of chemical ingredients,” said senior author Patricia Holden, a professor with the Bren School. “That’s reflected by this type of research.”

She explained that the research, which is funded by the National Science Foundation (NSF) and the U.S. Environmental Protection Agency (EPA), is helping to discover potential environmental implications of a new industry that includes nanomaterials. The ultimate goal is to help find more environmentally compatible substitutes, Holden said.

IMAGE:Pictured are Patricia Holden and John H. Priester.Click here for more information.

Soybean was chosen for the study due to its importance as a food crop –– it is the fifth largest crop in global agricultural production and second in the U.S. –– and because it is vulnerable to MNMs. The findings showed that crop yield and quality are affected by the addition of MNMs to the soil.

The scientists studied the effects of two common nanoparticles, zinc oxide and cerium oxide, on soybeans grown in soil in greenhouses. Zinc oxide is used in cosmetics, lotions, and sunscreens. Cerium oxide is used as an ingredient in catalytic converters to minimize carbon monoxide production, and in fuel to increase fuel combustion. Cerium can enter soil through the atmosphere when fuel additives are released with diesel fuel combustion.

The zinc oxide nanoparticles may dissolve, or they may remain as a particle, or re-form as a particle, as they are processed through wastewater treatment. At the final stage of wastewater treatment there is a solid material, called biosolids, which is applied to soils in many parts of the U.S. This solid material fertilizes the soil, returning nitrogen and phosphorus that are captured during wastewater treatment. This is also a point at which zinc oxide and cerium oxide can enter the soil.

The scientists noted that the EPA requires pretreatment programs to limit direct industrial metal discharge into publicly owned wastewater treatment plants. However, the research team conveyed that “MNMs –– while measurable in the wastewater treatment plant systems –– are neither monitored nor regulated, have a high affinity for activated sludge bacteria, and thus concentrate in biosolids.”

IMAGE:Pictured are soybean stem, leaves, bean pods, and roots. The roots contain nodules where bacteria accumulate and convert atmospheric nitrogen into ammonium, which fertilizes the plant.Click here for more information.

The authors pointed out that soybean crops are farmed with equipment powered by fossil fuels, and thus MNMs can also be deposited into the soil through exhaust.

The study showed that soybean plants grown in soil that contained zinc oxide bioaccumulated zinc; they absorbed it into the stems, leaves, and beans. Food quality was affected, although it may not be harmful to humans to eat the soybeans if the zinc is in the form of ions or salts, in the plants, according to Holden.

In the case of cerium oxide, the nanoparticles did not bioaccumulate, but plant growth was stunted. Changes occurred in the root nodules, where symbiotic bacteria normally accumulate and convert atmospheric nitrogen into ammonium, which fertilizes the plant. The changes in the root nodules indicate that greater use of synthetic fertilizers might be necessary with the buildup of MNMs in the soil.

Holden commented on the likelihood of high concentrations of these nanoparticles in agriculture: “There could be hotspots, places where you have accumulation, including near manufacturing sites where the materials are being made, or if there are spills. We have very limited information about the quantity or state of these synthetic nanomaterials in the environment right now. We know they’re being used in consumer goods, and we know they’re going down the drain.”

First author John H. Priester is a staff scientist in the Holden lab at UCSB. Other co-authors from UC CEIN are Yuan Ge, Randall E. Mielke, Allison M. Horst, Shelly Cole Moritz, Roger M. Nisbet, Joshua P. Schimel, Jose A. Hernandez-Viezcas, Lijuan Zhao, and Jorge L. Gardea-Torresdey. Co-authors Katherine Espinosa and Reid G. Palmer are affiliated with Iowa State University; Jeff Gelb is affiliated with Xradia Corporation; and Sharon L. Walker is with UC Riverside. NASA/JPL-Caltech, the USDA, and The University of Texas at El Paso were substantially involved in the research.

Big Tobacco knew radioactive particles in cigarettes posed cancer risk but kept quiet

Public release date: 28-Sep-2011 -Requested Repost
Contact: Kim Irwin kirwin@mednet.ucla.edu 310-206-2805 University of California – Los Angeles Health Sciences

Tobacco companies knew that cigarette smoke contained radioactive alpha particles for more than four decades and developed “deep and intimate” knowledge of these particles’ cancer-causing potential, but they deliberately kept their findings from the public, according to a new study by UCLA researchers.

The analysis of dozens of previously unexamined internal tobacco industry documents, made available in 1998 as the result of a legal settlement, reveals that the industry was aware of cigarette radioactivity some five years earlier than previously thought and that tobacco companies, concerned about the potential lung cancer risk, began in-depth investigations into the possible effects of radioactivity on smokers as early as the 1960s.

“The documents show that the industry was well aware of the presence of a radioactive substance in tobacco as early as 1959,” the authors write. “Furthermore, the industry was not only cognizant of the potential ‘cancerous growth’ in the lungs of regular smokers, but also did quantitative radiobiological calculations to estimate the long-term lung radiation absorption dose of ionizing alpha particles emitted from cigarette smoke.” The study, published online Sept. 27 in Nicotine & Tobacco Research, the peer-reviewed journal of the Society for Research on Nicotine and Tobacco, adds to a growing body of research detailing the industry’s knowledge of cigarette smoke radioactivity and its efforts to suppress that information.

“They knew that the cigarette smoke was radioactive way back then and that it could potentially result in cancer, and they deliberately kept that information under wraps,” said the study’s first author, Hrayr S. Karagueuzian, a professor of cardiology who conducts research at UCLA’s Cardiovascular Research Laboratory, part of the David Geffen School of Medicine at UCLA. “Specifically, we show here that the industry used misleading statements to obfuscate the hazard of ionizing alpha particles to the lungs of smokers and, more importantly, banned any and all publication on tobacco smoke radioactivity.”

The radioactive substance – which the UCLA study shows was first brought to the attention of the tobacco industry in 1959 – was identified in 1964 as the isotope polonium-210, which emits carcinogenic alpha radiation. Polonium-210 can be found in all commercially available domestic and foreign cigarette brands, Karagueuzian said, and is absorbed by tobacco leaves through naturally occurring radon gas in the atmosphere and through high-phosphate chemical fertilizers used by tobacco growers. The substance is eventually inhaled by smokers into the lungs.

The study outlines the industry’s growing concerns about the cancer risk posed by polonium-210 inhalation and the research that industry scientists conducted over the decades to assess the radioactive isotope’s potential effect on smokers – including one study that quantitatively measured the potential lung burden from radiation exposure in a two-pack-a-day smoker over a two-decade period.

Karagueuzian and his colleagues made independent calculations using industry and academic data and arrived at results that very closely mirrored those of that industry study, which was conducted nearly a quarter-century ago. They then compared those results to rates used by the Environmental Protection Agency to estimate lung cancer risk among individuals exposed to similar amounts of alpha particle-emitting radon gas in their homes.

“The gathered data from the documents on the relevant radiobiological parameters of the alpha particles – such as dose, distribution and retention time – permitted us to duplicate the industry’s secretly estimated radiation absorbed dose by regular smokers over a 20- or 25-year period, which equaled 40 to 50 rads,” he said. “These levels of rads, according to the EPA’s estimate of lung cancer risk in residents exposed to radon gas, equal 120 to 138 deaths per 1,000 regular smokers over a 25-year period.”

Despite the potential risk of lung cancer, tobacco companies declined to adopt a technique discovered in 1959 and then another developed in 1980 that could have helped eliminate polonium-210 from tobacco, the researchers said. The 1980 technique, known as an acid-wash, was found to be highly effective in removing the radioisotope from tobacco plants, where it forms a water-insoluble complex with the sticky, hair-like structures called trichomes that cover the leaves.

And while the industry frequently cited concerns over the cost and the possible environmental impact as rationales for not using the acid wash, UCLA researchers uncovered documents that they say indicate the real reason may have been far different.

“The industry was concerned that the acid media would ionize the nicotine, making it more difficult to be absorbed into the brains of smokers and depriving them of that instant nicotine rush that fuels their addiction,” Karagueuzian said. “The industry also were well aware that the curing of the tobacco leaves for more than a one-year period also would not eliminate the polonium-210, which has a half-life of 135 days, from the tobacco leaves because it was derived from its parent, lead-210, which has a half-life of 22 years.”

Karagueuzian said the insoluble alpha particles bind with resins in the cigarette smoke and get stuck and accumulate at the bronchial bifurcations of the lungs, forming “hot spots,” instead of dispersing throughout the lungs. In fact, previous research on lung autopsies in smokers who died of lung cancer showed that malignant growths were primarily located at the same bronchial bifurcations where these hot spots reside.

“We used to think that only the chemicals in the cigarettes were causing lung cancer,” Karagueuzian said. “But the case of the these hot spots, acknowledged by the industry and academia alike, makes a strong case for an increased probability of long-term development of malignancies caused by the alpha particles. If we’re lucky, the alpha particle-irradiated cell dies. If it doesn’t, it could mutate and become cancerous.”

Karagueuzian said the findings are very timely in light of the June 2009 passage of the Family Smoking Prevention and Tobacco Control Act, which grants the U.S. Food and Drug Administration broad authority to regulate and remove harmful substances – with the exception of nicotine – from tobacco products. The UCLA research, he said, makes a strong case that the FDA ought to consider making the removal of alpha particles from tobacco products a top priority.

“Such a move could have a considerable public health impact, due to the public’s graphic perception of radiation hazards,” he said.

To uncover the information, Karagueuzian and his team combed through the internal tobacco industry documents made available online as part of the landmark 1998 Tobacco Master Settlement Agreement. Documents from Philip Morris, R.J. Reynolds, Lorillard, Brown I Williamson, the American Tobacco Company, the Tobacco Institutes and the Council for Tobacco Research, as well as the Bliley documents, were examined, Karagueuzian said.

The team searched for key terms such as “polonium-210,” “atmospheric fallout,” “bronchial epithelium,” “hot particle” and “lung cancer,” among others.

Karagueuzian said the earliest causal link between alpha particles and cancer was made in around 1920, when alpha particle-emitting radium paint was used to paint luminescent numbers on watch dials. The painting was done by hand, and the workers commonly used their lips to produce a point on the tip of the paint brush. Many workers accumulated significant burdens of alpha particles through ingestion and absorption of radium-226 into the bones and subsequently developed jaw and mouth cancers. The practice was eventually discontinued.

Another example involves liver cancer in patients exposed to chronic low-dose internal alpha particles emitted from the poorly soluble deposits of thorium dioxide after receiving the contrast agent Thorotrast. It has been suggested that the liver cancers resulted from point mutations of the tumor suppressor gene p53 by the accumulated alpha particles present in the contrast media. The use of Thorotrast as contrast agent was stopped in the 1950s.

###

In addition to Karagueuzian, authors of the study include the late Amos Norman, professor emeritus in the departments of radiation oncology and radiological sciences at UCLA; James Sayre, of the departments of biostatistics and radiological sciences at UCLA; and Celia White, who served from 1999 to 2002 as director of content and services at the Legacy Tobacco Documents Library, which contains more than 13 million documents created by major tobacco companies related to their advertising, manufacturing, marketing, sales and scientific research activities.

The study was funded by the University of California Tobacco-Related Disease Research Program, established by the passage of California’s SB1613 in 1989 to fund a comprehensive University of California grant program to support research into the prevention, causes and treatment of tobacco-related diseases.

The authors report no conflict of interest.

Why Do Pertussis Vaccines Fail? It Suggest Corrupted Science

Original Abstract:
Why Do Pertussis Vaccines Fail?
James D. Cherry, MD, MSc
Pediatric Infectious Diseases, Mattel Children’s Hospital University of California Los Angeles, and the Department of Pediatrics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California
KEY WORDSpertussis
DTP
DTaP
adolescent- and adult-formulated tetanus and diphtheria toxoids and acellular pertussis vaccine
•Abbreviations: DTaP — pediatric diphtheria and tetanus toxoids and acellular pertussis vaccineDTP — pediatric diphtheria and tetanus toxoids and whole-cell pertussis vaccineFHA — filamentous hemagglutininFIM — fimbriaePCR — polymerase chain reactionPRN — pertactinPT — pertussis toxinWHO — World Health Organization

Possible Reasons Why DTP, DTaP, and Adolescent- and Adult-Formulated Tetanus and Diphtheria Toxoids and Acellular Pertussis Vaccines Fail

The first reason, and perhaps the most important one, is that our estimates of vaccine efficacy have been inflated because of case definition.3–11 At the time of the pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine efficacy trials in the early 1990s, it was hoped that a universal case definition could be developed so that the results of the various trials could be compared. To this end, the World Health Organization (WHO) case definition was developed.3 The primary case definition required laboratory confirmation and ≥21 days of paroxysmal cough. I was a member of the WHO committee and disagreed with the primary case definition because it was clear at that time that this definition would eliminate a substantial number of cases and therefore inflate reported efficacy values.4–11 Nevertheless, the Center for Biologics Evaluation and Research of the Food and Drug Administration accepted this definition, and package inserts of the US-licensed DTaP vaccines reflect this. For example, Infanrix (containing 25 μg pertussis toxin [PT], 25 μg filamentous hemagglutinin [FHA], and 8 μg pertactin [PRN]) and Daptacel (containing 10 μg PT, 5 μg FHA, 5 μg fimbriae [FIM]-2/3, and 3 μg

Big Tobacco knew radioactive particles in cigarettes posed cancer risk but kept quiet

Big Tobacco knew radioactive particles in cigarettes posed cancer risk but kept quiet

Tobacco companies knew that cigarette smoke contained radioactive alpha particles for more than four decades and developed “deep and intimate” knowledge of these particles’ cancer-causing potential, but they deliberately kept their findings from the public, according to a new study by UCLA researchers.

The analysis of dozens of previously unexamined internal tobacco industry documents, made available in 1998 as the result of a legal settlement, reveals that the industry was aware of cigarette radioactivity some five years earlier than previously thought and that tobacco companies, concerned about the potential lung cancer risk, began in-depth investigations into the possible effects of radioactivity on smokers as early as the 1960s.

“The documents show that the industry was well aware of the presence of a radioactive substance in tobacco as early as 1959,” the authors write. “Furthermore, the industry was not only cognizant of the potential ‘cancerous growth’ in the lungs of regular smokers, but also did quantitative radiobiological calculations to estimate the long-term lung radiation absorption dose of ionizing alpha particles emitted from cigarette smoke.” The study, published online Sept. 27 in Nicotine & Tobacco Research, the peer-reviewed journal of the Society for Research on Nicotine and Tobacco, adds to a growing body of research detailing the industry’s knowledge of cigarette smoke radioactivity and its efforts to suppress that information.

“They knew that the cigarette smoke was radioactive way back then and that it could potentially result in cancer, and they deliberately kept that information under wraps,” said the study’s first author, Hrayr S. Karagueuzian, a professor of cardiology who conducts research at UCLA’s Cardiovascular Research Laboratory, part of the David Geffen School of Medicine at UCLA. “Specifically, we show here that the industry used misleading statements to obfuscate the hazard of ionizing alpha particles to the lungs of smokers and, more importantly, banned any and all publication on tobacco smoke radioactivity.”

The radioactive substance – which the UCLA study shows was first brought to the attention of the tobacco industry in 1959 – was identified in 1964 as the isotope polonium-210, which emits carcinogenic alpha radiation. Polonium-210 can be found in all commercially available domestic and foreign cigarette brands, Karagueuzian said, and is absorbed by tobacco leaves through naturally occurring radon gas in the atmosphere and through high-phosphate chemical fertilizers used by tobacco growers. The substance is eventually inhaled by smokers into the lungs.

The study outlines the industry’s growing concerns about the cancer risk posed by polonium-210 inhalation and the research that industry scientists conducted over the decades to assess the radioactive isotope’s potential effect on smokers – including one study that quantitatively measured the potential lung burden from radiation exposure in a two-pack-a-day smoker over a two-decade period.

Karagueuzian and his colleagues made independent calculations using industry and academic data and arrived at results that very closely mirrored those of that industry study, which was conducted nearly a quarter-century ago. They then compared those results to rates used by the Environmental Protection Agency to estimate lung cancer risk among individuals exposed to similar amounts of alpha particle-emitting radon gas in their homes.

“The gathered data from the documents on the relevant radiobiological parameters of the alpha particles – such as dose, distribution and retention time – permitted us to duplicate the industry’s secretly estimated radiation absorbed dose by regular smokers over a 20- or 25-year period, which equaled 40 to 50 rads,” he said. “These levels of rads, according to the EPA’s estimate of lung cancer risk in residents exposed to radon gas, equal 120 to 138 deaths per 1,000 regular smokers over a 25-year period.”

Despite the potential risk of lung cancer, tobacco companies declined to adopt a technique discovered in 1959 and then another developed in 1980 that could have helped eliminate polonium-210 from tobacco, the researchers said. The 1980 technique, known as an acid-wash, was found to be highly effective in removing the radioisotope from tobacco plants, where it forms a water-insoluble complex with the sticky, hair-like structures called trichomes that cover the leaves.

And while the industry frequently cited concerns over the cost and the possible environmental impact as rationales for not using the acid wash, UCLA researchers uncovered documents that they say indicate the real reason may have been far different.

“The industry was concerned that the acid media would ionize the nicotine, making it more difficult to be absorbed into the brains of smokers and depriving them of that instant nicotine rush that fuels their addiction,” Karagueuzian said. “The industry also were well aware that the curing of the tobacco leaves for more than a one-year period also would not eliminate the polonium-210, which has a half-life of 135 days, from the tobacco leaves because it was derived from its parent, lead-210, which has a half-life of 22 years.”

Karagueuzian said the insoluble alpha particles bind with resins in the cigarette smoke and get stuck and accumulate at the bronchial bifurcations of the lungs, forming “hot spots,” instead of dispersing throughout the lungs. In fact, previous research on lung autopsies in smokers who died of lung cancer showed that malignant growths were primarily located at the same bronchial bifurcations where these hot spots reside.

“We used to think that only the chemicals in the cigarettes were causing lung cancer,” Karagueuzian said. “But the case of the these hot spots, acknowledged by the industry and academia alike, makes a strong case for an increased probability of long-term development of malignancies caused by the alpha particles. If we’re lucky, the alpha particle-irradiated cell dies. If it doesn’t, it could mutate and become cancerous.”

Karagueuzian said the findings are very timely in light of the June 2009 passage of the Family Smoking Prevention and Tobacco Control Act, which grants the U.S. Food and Drug Administration broad authority to regulate and remove harmful substances – with the exception of nicotine – from tobacco products. The UCLA research, he said, makes a strong case that the FDA ought to consider making the removal of alpha particles from tobacco products a top priority.

“Such a move could have a considerable public health impact, due to the public’s graphic perception of radiation hazards,” he said.

To uncover the information, Karagueuzian and his team combed through the internal tobacco industry documents made available online as part of the landmark 1998 Tobacco Master Settlement Agreement. Documents from Philip Morris, R.J. Reynolds, Lorillard, Brown I Williamson, the American Tobacco Company, the Tobacco Institutes and the Council for Tobacco Research, as well as the Bliley documents, were examined, Karagueuzian said.

The team searched for key terms such as “polonium-210,” “atmospheric fallout,” “bronchial epithelium,” “hot particle” and “lung cancer,” among others.

Karagueuzian said the earliest causal link between alpha particles and cancer was made in around 1920, when alpha particle-emitting radium paint was used to paint luminescent numbers on watch dials. The painting was done by hand, and the workers commonly used their lips to produce a point on the tip of the paint brush. Many workers accumulated significant burdens of alpha particles through ingestion and absorption of radium-226 into the bones and subsequently developed jaw and mouth cancers. The practice was eventually discontinued.

Another example involves liver cancer in patients exposed to chronic low-dose internal alpha particles emitted from the poorly soluble deposits of thorium dioxide after receiving the contrast agent Thorotrast. It has been suggested that the liver cancers resulted from point mutations of the tumor suppressor gene p53 by the accumulated alpha particles present in the contrast media. The use of Thorotrast as contrast agent was stopped in the 1950s.