Hormone disruptors rise from the dead
Broken-down pollutants reform in the dark, casting doubt on environmental risk assessments.
Hormone-disrupting chemicals may be far more prevalent in lakes and rivers than previously thought. Environmental scientists have discovered that although these compounds are often broken down by sunlight, they can regenerate at night, returning to life like zombies.
“The assumption is that if it’s gone, we don’t have to worry about it,” says environmental engineer Edward Kolodziej of the University of Nevada in Reno, joint leader of the study. “But we’re under-predicting their environmental persistence.”
“Risk assessments have been built on the basis that light exposure is enough to break down these products,” adds Laura Vandenberg, an endocrinologist at the University of Massachusetts in Amherst who was not involved in the study. “This work undermines that idea completely.”
Endocrine disruptors — pollutants that unbalance hormone systems — are known to harm fish, and there is growing evidence linking them to health problems in humans, including infertility and various cancers1. But pinpointing specific culprits from the vast array of trace chemicals in the environment has proved difficult. Indeed, concentrations of known endocrine disruptors in rivers often seem to be too low to explain harmful effects in aquatic wildlife, says Kolodziej.
He and his colleague David Cwiertny, an environmental engineer at the University of Iowa in Iowa City, decided to find out whether the breakdown products of endocrine disruptors could be boosting their environmental impact. Their team focused on trenbolone acetate, a synthetic anabolic steroid used as a growth promoter in more than 20 million cattle in the United States each year (this practice is banned in the European Union).
Cattle metabolize the steroid into compounds such as 17α-trenbolone, a potent endocrine disrupter commonly found in agricultural run-off water. In laboratory tests, just a few tens of nanograms of these compounds per litre can skew sex ratios and decrease fertility in fish2, 3. Some manufacturers have argued that these metabolites pose little risk in rivers, however, because sunlight breaks them down rapidly.
Kolodziej and his team put solutions of 17α-trenbolone and related compounds through several cycles of light and dark in the laboratory. Although concentrations fell during the simulated daytime, the scientists were surprised to see that levels rebounded during the dark periods. At neutral pH and 25 ºC, it took about five days to regenerate 60% of a sample of 17α-trenbolone from its breakdown products. Higher temperatures or slightly acidic or alkaline conditions accelerated this process.
“I’ve never seen anything like it,” says Vandenberg. Field biologists usually collect water samples during the day, she says, and nocturnal regeneration “would certainly have the potential to impact those results.” Moreover, field studies have rarely reported the pH and temperature of water samples, which could have a big effect on true concentrations of contaminants. “I don’t think that anyone had conceived it could be so important,” she says.
The team found the same regeneration process occurring in water samples taken from the Iowa River, and from a test pond seeded with manure from cattle that had been treated with trenbolone acetate. They also note that other steroids with similar chemical structures can regenerate in the same way, including dienogest, an oral contraceptive, and dienedione, an illicit anabolic steroid. The results are published in Science4.
Hiding in plain sight
Kolodziej says that the work casts considerable uncertainty over sampling results for steroid endocrine disruptors, and suggests that a survey of their breakdown compounds in the environment is now urgently needed.
It also highlights a serious drawback in relying on studies that look for single environmental contaminants, rather than a spectrum of their derivatives, he adds. Chemical studies should be complemented with bioassays that use living cells to detect endocrine disruptors, Vandenberg adds.
Last year, a bioassay of this kind found androgens in 35% of freshwater samples tested, far more than chemical assays would suggest5. “What you really want to know is if there’s anything in there that can cause biological activity,” says molecular biologist Gordon Hager, at the National Cancer Institute in Bethesda, Maryland, who developed the assay. Yet current environmental monitoring procedures still rely on checking “a list of chemicals, and they only know how to look for one thing at a time”, he says. “It’s a fool’s errand.”
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- DOI: doi:10.1038/nature.2013.13831
Some people may joke about living on caffeine, but scientists now have genetically engineered E. coli bacteria to do that — literally. Their report in the journal ACS Synthetic Biology describes bacteria being “addicted” to caffeine in a way that promises practical uses ranging from decontamination of wastewater to bioproduction of medications for asthma.
Jeffrey E. Barrick and colleagues note that caffeine and related chemical compounds have become important water pollutants due to widespread use in coffee, soda pop, tea, energy drinks, chocolate and certain medications. These include prescription drugs for asthma and other lung diseases. The scientists knew that a natural soil bacterium, Pseudomonas putida CBB5, can actually live solely on caffeine and could be used to clean up such environmental contamination. So they set out to transfer genetic gear for metabolizing, or breaking down, caffeine from P. putida into that old workhorse of biotechnology, E. coli, which is easy to handle and grow.
The study reports their success in doing so, as well as use of the E. coli for decaffeination and measuring the caffeine content of beverages. It describes development of a synthetic packet of genes for breaking down caffeine and related compounds that can be moved easily to other microbes. When engineered into certain E. coli, the result was bacteria literally addicted to caffeine. The genetic packet could have applications beyond environmental remediation, the scientists say, citing potential use as a sensor to measure caffeine levels in beverages, in recovery of nutrient-rich byproducts of coffee processing and for the cost-effective bioproduction of medicines.
The author and co-authors acknowledge financial support from the University of Texas at Austin and the University of Iowa.
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With policymakers and political leaders increasingly unable to combat global climate change, more scientists are considering the use of manual manipulation of the environment to slow warming’s damage to the planet.
But a University of Iowa law professor believes the legal ramifications of this kind of geo-engineering need to be thought through in advance and a global governance structure put in place soon to oversee these efforts.
“Geo-engineering is a global concern that will have climate and weather impacts in all countries, and it is virtually inevitable that some group of people will be harmed in the process,” says Jon Carlson, professor of law at the UI College of Law. “The international community must act now to take charge of this activity to ensure that it is studied and deployed with full attention to the rights and interests of everyone on the planet.”
Carlson is an expert in environmental law and international law who believes geo-engineering is inevitable and will likely happen sooner than later. He considers the issue in a new paper, “Reining in Phaethon’s Chariot: Principles for the Governance of Geoengineering,” published in the current issue of the journal Transnational Law and Contemporary Problems. His co-author, Adam D.K. Abelkop, is a UI law graduate now in the doctoral program at the Indiana University School of Public Health and Environmental Affairs.
Carlson says the concept of geo-engineering goes back to at least the 19th century, when scientists proposed seeding clouds to increase rainfall. Today, scientists have a long list of geo-engineering ideas that could be used to slow the impact of global warming while other methods are developed to actually mitigate the damage. Some ideas are simple and locally focused, such as planting new forests to absorb carbon dioxide, or painting roofs and paved areas white to reduce solar heat absorption.
Others are more complex and controversial—manually cooling oceans so carbon dioxide-laden water sinks to the bottom more quickly; building space-based shields and mirrors to deflect solar heat from the planet; or injecting chemicals like hydrogen sulfide or sulfur dioxide into the upper atmosphere, creating an aerosol shield that reduces the amount of solar heat reaching the earth’s surface.
But Carlson says geo-engineering comes with obvious international legal implications because no one country can implement its own geo-engineering plan without causing weather or climate changes in other countries. There’s also the law of unintended consequences, because while many geo-engineering concepts have proved hopeful in the lab, nobody knows what will happen when actually put into practice. For instance, Carlson says that while manually cooling the ocean may be seen as a generally good idea, what impact will that have on farmers in India whose crops depend on rain from heat-induced tropical monsoons?
To address these issues, Carlson urges the creation of an international governing body separate from any existing organization that approves or rejects geo-engineering plans, taking into consideration the best interests of people and countries around the world. He says any legal regimen involving geo-engineering activities should require they be publicly announced in the planning stage, and all countries are notified so they have a voice in deliberations.
As a model for his oversight body, Carlson suggests the International Monetary Fund (IMF). Like the IMF, his proposed organization would give all countries a place during discussions, but decisions would be made by a relatively small group of directors, each of which has a weighted vote that’s based on their country’s greenhouse gas production. That is, countries that produce more greenhouse gases will spend more money to combat global climate change, and so will have more votes.
Carlson’s proposed body would oversee a compensation fund to help people and countries that are harmed by other country’s approved geo-engineering activities, or by unseen effects of those activities.
In older adults, antipsychotic drugs are commonly prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications – schizophrenia and bipolar disorder. The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia, some of which carry FDA warnings on prescription information for these drugs.
In a new study – led by researchers at the University of California, San Diego School of Medicine, Stanford University and the University of Iowa, and funded by the National Institute of Mental Health – four of the antipsychotics most commonly prescribed off label for use in patients over 40 were found to lack both safety and effectiveness. The results will be published November 27 in The Journal of Clinical Psychiatry.
The study looked at four atypical antipsychotics (AAPs) – aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) – in 332 patients over the age of 40 diagnosed with psychosis associated with schizophrenia, mood disorders, PTSD, or dementia.
“Our study suggests that off-label use of these drugs in older people should be short-term, and undertaken with caution,” said Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences, and director of the Stein Institute for Research on Aging at UC San Diego.
Results of the five-year study led by Jeste, who is also current president of the American Psychiatric Association (which was not involved in this research), showed that within one year of treatment, one-third of the patients enrolled in the study developed metabolic syndrome (medical disorders that can increase the risk of cardiovascular disease or diabetes). Within two years, nearly a quarter of the patients developed serious adverse effects and just over half developed non-serious adverse effects.
Because the patients enrolled in the study were all diagnosed with conditions with psychotic symptoms that required antipsychotic drug treatment according to their treating physicians, no placebo was used in the trial. Instead, the researchers used a technique called “equipoise stratified randomization” which is a hybrid of complete randomization and a clinician’s choice method.
“Our goal was to ensure clinical relevance,” said Jeste. Patients had to agree to be randomized to 2, 3 or 4 of the study drugs, as they or their physicians were allowed to exclude one or two of the study AAPs, due to past experience or anticipated risk of the particular drug. Treating clinicians could determine the optimal dosage. “We attempted to make the study as ‘user-friendly’ as possible, to allow the drugs the best chance of success, while seeking to minimize the amount of bias,” he explained.
While the researchers’ intent was to continue the patients on the randomized medications for two years, the average length turned out to be only six months, after which the medications were halted or switched because they didn’t work and/or had side effects.
Because of a notably high incidence of serious adverse events, quetiapine had to be discontinued midway through the trial. The researchers found that there were significant differences among patients willing to be randomized to different AAPs – thus, treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with existing metabolic problems. Yet, the different AAP groups did not appreciably differ in most outcome measures.
Using a common scale called the Brief Psychiatric Rating Scale (BPRS), to measure symptoms such as delusions, hallucinations, unusual behavior, depression, and anxiety, assessments were made at 6 weeks, 12 weeks, and then every 12 weeks. Results using “blind” raters showed no significant improvement in BPRS over a six-month period.
“While there were a few significant differences among the four drugs, the overall risk-benefit ratio for the AAPs in patients over age 40 was not favorable, irrespective of diagnosis and drug,” said Jeste.
Jeste points out that clinicians, patients, and caregivers are often left with difficult and unclear choices for treatment for older persons with psychosis, such as that associated with dementia. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there are no FDA-approved alternatives to antipsychotics for this population, and the high cost of newer AAPs also makes their use problematic.
While the researchers say their findings do not suggest that these AAPs should be banned in older patients with psychiatric disorders, they do indicate that considerable caution is warranted in off-label, long-term use of the drugs in older persons.
“When these medications are used off-label, they should be given in low dosages and for short durations, and their side effects monitored closely,” said Jeste. “Clearly, there is also a critical need to develop and test new interventions that are safe and effective in older people with psychotic disorders.”
Other authors of this paper are Hua Jin, MD, Pei-an Betty Shih, PhD, Shahrokh Golshan, PhD, Sunder Mudaliar, MD, Robert Henry, MD, and Danielle K. Glorioso, MSW, from University of California, San Diego; Helena C. Kraemer, PhD, emerita professor of biostatistics in psychiatry at Stanford University, and Stephan Arndt, PhD, professor of psychiatry and biostatistics at the University of Iowa.
The study was supported in part by National Institutes of Health grants MH071536, P30 MH080002-01, 1K01DK087813-01, NCRS UL1RR031980 and by the Department of Veteran Affairs.
Most people consume far too much salt, and a University of Iowa researcher has discovered one potential reason we crave it: it might put us in a better mood.
UI psychologist Kim Johnson and colleagues found in their research that when rats are deficient in sodium chloride, common table salt, they shy away from activities they normally enjoy, like drinking a sugary substance or pressing a bar that stimulates a pleasant sensation in their brains.
“Things that normally would be pleasurable for rats didn’t elicit the same degree of relish, which leads us to believe that a salt deficit and the craving associated with it can induce one of the key symptoms associated with depression,” Johnson said.
The UI researchers can’t say it is full-blown depression because several criteria factor into such a diagnosis, but a loss of pleasure in normally pleasing activities is one of the most important features of psychological depression. And, the idea that salt is a natural mood-elevating substance could help explain why we’re so tempted to over-ingest it, even though it’s known to contribute to high blood pressure, heart disease and other health problems.
Past research has shown that the worldwide average for salt intake per individual is about 10 grams per day, which is greater than the U.S. Food and Drug Administration recommended intake by about 4 grams, and may exceed what the body actually needs by more than 8 grams.
Johnson, who holds appointments in psychology and integrative physiology in the College of Liberal Arts and Sciences and in pharmacology in the Carver College of Medicine, published a review of these findings in the July issue of the journal Physiology & Behavior with Michael J. Morris and Elisa S. Na, UI graduate students. In addition to reporting their own findings, the authors reviewed others’ research on the reasons behind salt appetite.
High levels of salt are contained in everything from pancakes to pasta these days, but once upon a time, it was hard to come by. Salt consumption and its price skyrocketed around 2000 B.C. when it was discovered as a food preservative. Roman soldiers were paid in salt; the word salary is derived from the Latin for salt. Even when mechanical refrigeration lessened the need for salt in the 19th century, consumption continued in excess because people liked the taste and it had become fairly inexpensive. Today, 77 percent of our salt intake comes from processed and restaurant foods, like frozen dinners and fast food.
Evolution might have played an important part in the human hankering for salt. Humans evolved from creatures that lived in salty ocean water. Once on land, the body continued to need sodium and chloride because minerals play key roles in allowing fluids to pass in and out of cells, and in helping nerve cells transfer information throughout the brain and body. But as man evolved in the hot climate of Africa, perspiration robbed the body of sodium. Salt was scarce because our early ancestors ate a veggie-rich diet and lived far from the ocean.
“Most of our biological systems require sodium to function properly, but as a species that didn’t have ready access to it, our kidneys evolved to become salt misers,” Johnson said.
Behavior also came to play a key role in making sure we have enough salt on board. Animals like us come equipped with a taste system designed to detect salt and a brain that remembers the location of salt sources — like salt licks in a pasture. A pleasure mechanism in the brain is activated when salt is consumed.
So the body needs salt and knows how to find it and how to conserve it. But today scientists are finding evidence that it’s an abused, addictive substance — almost like a drug.
One sign of addiction is using a substance even when it’s known to be harmful. Many people are told to reduce sodium due to health concerns, but they have trouble doing so because they like the taste and find low-sodium foods bland.
Another strong aspect of addiction is the development of intense cravings when drugs are withheld. Experiments by Johnson and colleagues indicate similar changes in brain activity whether rats are exposed to drugs or salt deficiency.
“This suggests that salt need and cravings may be linked to the same brain pathways as those related to drug addiction and abuse,” Johnson said.
STORY SOURCE: University of Iowa News Services, 300 Plaza Centre One, Suite 371, Iowa City, Iowa 52242-2500
A research team from the Peninsula Medical School, the University of Exeter, the University of Plymouth and the University of Iowa, have found evidence linking bisphenol A to diabetes and heart disease in adults
A research team from the Peninsula Medical School, the University of Exeter, the University of Plymouth and the University of Iowa, have found evidence linking Bisphenol A (BPA) to diabetes and heart disease in adults.
Their research paper is to be published in the Journal of the American Medical Association on Wednesday 17 September and it is the first time that evidence has emerged of the association between higher BPA levels and disease in adults.
BPA is a controversial chemical commonly used in food and drink containers. It has previously caused concerns over health risks to babies, as it is present in some baby’s bottles.
BPA is used in polycarbonate plastic products such as refillable drinks containers, compact disks, some plastic eating utensils and many other products in everyday use. It is one of the world’s highest production volume chemicals, with over 2.2 million tonnes (6.4 billion pounds) produced in 2003, with an annual growth in demand of between six and 10 per cent each year.
Many previous studies in laboratory animals have suggested that BPA is safe, but some laboratory studies have raised doubts. Experiments in which mice and rats were exposed to BPA have shown that higher doses of the chemical can lead to liver damage, insulin resistance, diabetes and obesity. The laboratory animal evidence is complicated and controversial. Some scientists believe that BPA can disrupt the work done by hormones, especially oestrogen, but the full biological effects of BPA in humans is far from clear.
The research team analysed information from the US government’s National Health and Nutrition Examination Survey (NHANES) 2003-2004, the only large-scale data available on BPA concentrations excreted in urine. The research team analysed the results for the 1455 adults aged between 18 and 74 years old for whom measures were available. This study group is representative of the general population of the USA.
The analysis found that the 25 per cent of the population with the highest BPA levels were more than twice as likely to have heart disease and/or diabetes, compared to the 25 per cent with the lowest BPA levels. Higher BPA levels were also associated with clinically abnormal liver enzyme concentrations.
While this study has identified a statistical association between BPA and adult diseases for the first time, much more research is needed. Future work needs to exclude the small possibility that the association is due to some other unstudied factor, or that people with these diseases somehow become more exposed to BPA. It is also unclear whether the liver enzyme changes are linked to liver damage.
Professor David Melzer, Professor of Epidemiology and Public Health at the Peninsula Medical School (Exeter, UK), who led the team commented: “Our study has revealed, for the first time, an association between raised BPA loads and two common diseases in adults. At the moment we can’t be absolutely sure that BPA is the direct cause of the extra cases of heart disease and diabetes: if it is, some cases of these serious conditions could be prevented by reducing BPA exposure. This is therefore an exciting finding, but it is also just the first step in understanding the role of BPA.”
He emphasised that this new possible link does not detract from the existing health advice to people on how to prevent heart disease and diabetes. Professor Melzer also praised the NHANES study and the US Division of Environmental Health Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, who released these data for analysis by researchers.
Tamara Galloway, Professor of eco-toxicology from the School of Biosciences, the University of Exeter, added: “Our results illustrate how important human bio-monitoring programmes such as NHANES are in providing high quality information on the extent of human exposure to common chemicals such as BPA, allowing us to explore the relationship between exposure and health outcomes more fully.”
*Requested Repost From 2007 – Info is Historical
A vaccine that has dramatically curbed pneumonia and other serious illnesses in children is also having an unfortunate effect: promoting new superbugs that cause ear infections
On Monday, doctors reported discovering the first such germ that is resistant to all drugs approved to treat childhood ear infections. Nine toddlers in Rochester, N.Y., have had the bug and researchers say it may be turning up elsewhere, too.
Wyeth anticipated this and is testing a second-generation vaccine. But it is at least two years from reaching the market, and the new strains could become a public health problem in the meantime if they spread hard-to-treat infections through day care centers and schools.
It is a strain of strep bacteria not included in the pneumococcal vaccine, Wyeth’s Prevnar, which came on the market in 2000. It is recommended for children under age 2.
Prevnar, however, is losing its punch because strains not covered by the vaccine are filling the biological niche that the vaccine strains used to occupy, and they are causing disease.
One strain in particular, called 19A, is big trouble. A new subtype of it caused ear infections in the nine Rochester children, ages 6 months to 18 months, that were resistant to all pediatric medications, said Dr. Michael Pichichero, a microbiologist at the University of Rochester Medical Center.
The children had been unsuccessfully treated with two or more antibiotics, including high-dose amoxicillin and multiple shots of another drug. Many needed surgery to place ear tubes to drain the infection, and some recovered only after treatment with a newer, powerful antibiotic whose safety in children has not been established.
–Scientists from a drug company and two labs analyzed more than 21,000 bacterial samples from around the nation and found 19A increasing. Among children 2 and under, the portion of samples that were this strain rose to 15 percent in 2005-2006, from 4 percent in the previous three years.
–A British lab tracking respiratory infections in U.S. kids found that the 19A strain accounted for 40 percent of drug-resistant cases.
–University of Iowa researchers found 19A accounted for 35 percent of penicillin-resistant infections in 2004-05, compared with less than 2 percent the year before the new vaccine came out.