Health Technology Research Synopsis
123rd Issue Date 24FEB2012
Compiled By Ralph Turchiano
Editors Top Five:
1. Common flame retardant linked to social, behavioral and learning deficits
2. Cranky today? Even mild dehydration can alter our moods
3. Stronger intestinal barrier may prevent cancer in the rest of the body, new study suggests
4. Fake drug sales are increasing on the Internet and turning up in legitimate supply chains
5. New street drug ‘bath salts’ packs double punch
In This Issue:
6. Overeating may double risk of memory loss
7. Researchers discover molecular secrets of ancient Chinese herbal remedy
8. Treating acute sinusitis with antibiotic does not appear helpful
9. Turmeric-based drug effective on Alzheimer flies
10. Mayo Clinic: Hospitalization of US underage drinkers common, costs $755 million a year
11. Study: Weight training improves Parkinson’s symptoms
12. To kill off parasites, an insect self-medicates with alcohol
13. Common flame retardant linked to social, behavioral and learning deficits
14. Hazardous medications
15. Cranky today? Even mild dehydration can alter our moods
16. Alzheimer’s drugs may have adverse side effects
17. Serotonin could play a large role in bone loss
18. Stronger intestinal barrier may prevent cancer in the rest of the body, new study suggests
19. Environmental pollutant linked with overweight
20. Fake drug sales are increasing on the Internet and turning up in legitimate supply chains
21. Eating citrus fruit may lower women’s stroke risk
22. Researchers Discover How Vitamin D Inhibits Inflammation
23. First study to show that bisphenol A exposure increases risk of future onset of heart disease
24. New street drug ‘bath salts’ packs double punch
Overeating may double risk of memory loss
NEW ORLEANS – New research suggests that consuming between 2,100 and 6,000 calories per day may double the risk of memory loss, or mild cognitive impairment (MCI), among people age 70 and older. The study was released today and will be presented at the American Academy of Neurology’s 64th Annual Meeting in New Orleans April 21 to April 28, 2012. MCI is the stage between normal memory loss that comes with aging and early Alzheimer’s disease.
“We observed a dose-response pattern which simply means; the higher the amount of calories consumed each day, the higher the risk of MCI,” said study author Yonas E. Geda, MD, MSc, with the Mayo Clinic in Scottsdale, Arizona and a member of the American Academy of Neurology.
The study involved 1,233 people between the ages of 70 and 89 and free of dementia residing in Olmsted County, Minn. Of those, 163 had MCI. Participants reported the amount of calories they ate or drank in a food questionnaire and were divided into three equal groups based on their daily caloric consumption. One-third of the participants consumed between 600 and 1,526 calories per day, one-third between 1,526 and 2,143 and one-third consumed between 2,143 and 6,000 calories per day.
The odds of having MCI more than doubled for those in the highest calorie-consuming group compared to those in the lowest calorie-consuming group. The results were the same after adjusting for history of stroke, diabetes, amount of education, and other factors that can affect risk of memory loss. There was no significant difference in risk for the middle group.
“Cutting calories and eating foods that make up a healthy diet may be a simpler way to prevent memory loss as we age,” said Geda.
Researchers discover molecular secrets of ancient Chinese herbal remedy
2,000-year-old herb regulates autoimmunity and inflammation
BOSTON, Mass. (February 12, 2012)—For roughly two thousand years, Chinese herbalists have treated Malaria using a root extract, commonly known as Chang Shan, from a type of hydrangea that grows in Tibet and Nepal. More recent studies suggest that halofuginone, a compound derived from this extract’s bioactive ingredient, could be used to treat many autoimmune disorders as well. Now, researchers from the Harvard School of Dental Medicine have discovered the molecular secrets behind this herbal extract’s power.
It turns out that halofuginone (HF) triggers a stress-response pathway that blocks the development of a harmful class of immune cells, called Th17 cells, which have been implicated in many autoimmune disorders.
“HF prevents the autoimmune response without dampening immunity altogether,” said Malcolm Whitman, a professor of developmental biology at Harvard School of Dental Medicine and senior author on the new study. “This compound could inspire novel therapeutic approaches to a variety of autoimmune disorders.”
“This study is an exciting example of how solving the molecular mechanism of traditional herbal medicine can lead both to new insights into physiological regulation and to novel approaches to the treatment of disease,” said Tracy Keller, an instructor in Whitman’s lab and the first author on the paper.
This study, which involved an interdisciplinary team of researchers at Massachusetts General Hospital and elsewhere, will be published online February 12 in Nature Chemical Biology.
Prior research had shown that HF reduced scarring in tissue, scleroderma (a tightening of the skin), multiple sclerosis, scar formation and even cancer progression. “We thought HF must work on a signaling pathway that had many downstream effects,” said Keller.
In 2009, Keller and colleagues reported that HF protects against harmful Th17 immune cells without affecting other beneficial immune cells. Recognized only since 2006, Th17 cells are “bad actors,” implicated in many autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis and psoriasis. The researchers found that minute doses of HF reduced multiple sclerosis in a mouse model. As such, it was one of a new arsenal of drugs that selectively inhibits autoimmune pathology without suppressing the immune system globally. Further analysis showed that HF was somehow turning on genes involved in a newly discovered pathway called the amino acid response pathway, or AAR.
Scientists have only recently appreciated the role of the nutrient sensing-AAR pathway in immune regulation and metabolic signaling. There is also evidence that it extends lifespan and delays age-related inflammatory diseases in animal studies on caloric restriction. A conservationist of sorts, AAR lets cells know when they need to preserve resources. For example, when a cell senses a limited supply of amino acids for building proteins, AAR will block signals that promote inflammation because inflamed tissues require lots of protein.
“Think about how during a power outage we conserve what little juice we have left on our devices, foregoing chats in favor of emergency calls,” said Whitman. “Cells use similar logic.”
For the current study, the researchers investigated how HF activates the AAR pathway, looking at the most basic process that cells use to translate a gene’s DNA code into the amino acid chain that makes up a protein.
The researchers were able to home in on a single amino acid, called proline, and discovered that HF targeted and inhibited a particular enzyme (tRNA synthetase EPRS) responsible for incorporating proline into proteins that normally contain it. When this occurred, the AAR response kicked in and produced the therapeutic effects of HF-treatment.
Providing supplemental proline reversed the effects of HF on Th17 cell differentiation, while adding back other amino acids did not, establishing the specificity of HF for proline incorporation. Added proline also reversed other therapeutic effects of HF, inhibiting its effectiveness against the malaria parasite as well as certain cellular processes linked to tissue scarring. Again, supplementation with other amino acids had no such effect. Such mounting evidence clearly demonstrated that HF acts specifically to restrict proline.
The researchers think that HF treatment mimics cellular proline deprivation, which activates the AAR response and subsequently impacts immune regulation. Researchers do not yet fully understand the role that amino acid limitation plays in disease response or why restricting proline inhibits Th17 cell production.
Nevertheless, “AAR pathway is clearly an interesting drug target, and halofuginone, in addition to its potential therapeutic uses, is a powerful tool for studying the AAR pathway,” said Whitman.
Treating acute sinusitis with antibiotic does not appear helpful
CHICAGO – Treatment with the antibiotic amoxicillin for patients with acute uncomplicated rhinosinusitis (inflammation of the nasal cavity and sinuses) did not result in a significant difference in symptoms compared to patients who received placebo, according to a study in the February 15 issue of JAMA. Antibiotics are commonly used to treat this condition even though there is limited evidence supporting their effectiveness.
Acute rhinosinusitis is a common disease associated with significant illness, lost time from work, and treatment costs. “Considering the public health threat posed by increasing antibiotic resistance, strong evidence of symptom relief is needed to justify prescribing of antibiotics for this usually self-limiting disease. Placebo-controlled clinical trials to evaluate antibiotic treatment have had conflicting results, likely due to differences in diagnostic criteria and outcome assessment,” according to background information in the article. Evidence-based guidelines for this condition recommend reserving antibiotic treatment for patients with moderately severe or severe symptoms. Antibiotics for sinusitis account for 1 in 5 antibiotic prescriptions for adults in the United States.
Jane M. Garbutt, M.B.Ch.B., and colleagues from the Washington University School of Medicine, St. Louis, conducted a study to examine the effect of amoxicillin treatment over symptomatic treatments on disease-specific quality of life in adults with clinically diagnosed acute bacterial rhinosinusitis. The trial included 166 adults (36 percent male) who were randomized to receive a 10-day course of either amoxicillin (1,500 mg/d; n = 85) or placebo (n = 81) administered in 3 doses per day. Some of the most common symptoms reported by participants at the beginning of the study included facial pain or pressure, postnasal discharge, and cough and runny nose. All patients received a 5- to 7-day supply of symptomatic treatments for pain, fever, cough, and nasal congestion to use as needed; 92 percent concurrently used 1 or more symptomatic treatments (94 percent for amoxicillin group vs. 90 percent for control group).
The primary outcome for the study was the improvement in disease-specific quality of life after 3 to 4 days of treatment as assessed with the Sinonasal Outcome Test-16 (minimally important difference of 0.5 units on a 0-3 scale). Secondary outcomes included the patient’s assessment of change in sinus symptoms and functional status, recurrence or relapse, and satisfaction with and adverse effects of treatment. The outcomes were assessed by a telephone interview at days 3, 7, 10, and 28.
The researchers found that the average change in test scores was similar in both groups at day 3 (amoxicillin group, 0.59; control group, 0.54) and at day 10 (average difference between groups, 0.01), but differed at day 7, favoring amoxicillin (average difference between groups of 0.19). “There were no statistically significant differences in reported symptom improvement at day 3 (37 percent for amoxicillin group vs. 34 percent for control group) or at day 10 (78 percent for amoxicillin group vs. 80 percent for control group). At day 7, more participants treated with amoxicillin reported symptom improvement (74 percent for amoxicillin group vs. 56 percent for control group).”
The authors found there was also no difference by study group in terms of days missed from work or inability to perform usual activities; rates of relapse and recurrence by 28 days; additional health care use; and satisfaction with treatment. No serious adverse events occurred. The study groups did not differ in reporting adverse effects from the study medication.
“There is now a considerable body of evidence from clinical trials conducted in the primary care setting that antibiotics provide little if any benefit for patients with clinically diagnosed acute rhinosinusitis. Yet, antibiotic treatment for upper respiratory tract infections is often both expected by patients and prescribed by physicians,” the researchers write. “The National Institute for Health and Clinical Excellence guidelines in the United Kingdom, and more recent guidelines in the United States, suggest watchful waiting as an alternative approach to the management of patients for whom reassessment is possible; this approach delays and may preclude antibiotic treatment while providing symptomatic treatments and an explanation of the natural history of the disease.”
Turmeric-based drug effective on Alzheimer flies
IMAGE:Above left are the survival curves for “Alzheimer flies ” treated (dashed line) and those not treated with curcumin. The flies that were administered curcumin lived longer and were more active….
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Curcumin, a substance extracted from turmeric, prolongs life and enhances activity of fruit flies with a nervous disorder similar to Alzheimers. The study conducted at Linköping University, indicates that it is the initial stages of fibril formation and fragments of the amyloid fibrils that are most toxic to neurons.
Ina Caesar, as the lead author, has published the results of the study in the prestigious journal PLoS One.
For several years curcumin has been studied as a possible drug candidate to combat Alzheimer’s disease, which is characterized by the accumulation of sticky amyloid-beta and Tau protein fibres. Linköping researchers wanted to investigate how the substance affected transgenic fruit flies (Drosophila melanogaster), which developed evident Alzheimer’s symptoms. The fruit fly is increasingly used as a model for neurodegenerative diseases.
Five groups of diseased flies with different genetic manipulations were administered curcumin. They lived up to 75 % longer and maintained their mobility longer than the sick flies that did not receive the substance.
However, the scientists saw no decrease of amyloid in the brain or eyes. Curcumin did not dissolve the amyloid plaque; on the contrary it accelerated the formation of fibres by reducing the amount of their precursor forms, known as oligomers.
–The results confirm our belief that it is the oligomers that are most harmful to the nerve cells, says Professor Per Hammarstrom, who led the study.
–We now see that small molecules in an animal model can influence the amyloid form. To our knowledge the encapsulation of oligomers is a new and exciting treatment strategy.
Several theories have been established about how oligomers can instigate the disease process. According to one hypothesis, they become trapped at synapses, inhibiting nerve impulse signals. Others claim that they cause cell death by puncturing the cell membrane.
Curcumin is extracted from the root of herbaceous plant turmeric and has been used as medicine for thousands of years. More recently, it has been tested against pain, thrombosis and cancer.
Mayo Clinic: Hospitalization of US underage drinkers common, costs $755 million a year
ROCHESTER, Minn. — Hospitalization for underage drinking is common in the United States, and it comes with a price tag — the estimated total cost for these hospitalizations is about $755 million per year, a Mayo Clinic study has found. Researchers also found geographic and demographic differences in the incidence of alcohol-related hospital admissions. The findings were published online today in the Journal of Adolescent Health.
Of the roughly 40,000 youth ages 15 to 20 hospitalized in 2008, the most recent data available, 79 percent were drunk when they arrived at the hospital, researchers say. Alcohol abuse and addiction and drinking-related emotional problems were among the diagnoses.
Among all U.S. teens, roughly 18 of every 10,000 adolescent males and 12 of every 10,000 females were hospitalized after consuming alcohol in the year studied. In all, 700,000 young people in that age group were hospitalized for various reasons, including non-alcohol-related conditions, in 2008.
“When teenagers drink, they tend to drink excessively, leading to many destructive consequences including motor vehicle accidents, injuries, homicides and suicides,” says researcher Terry Schneekloth, M.D., a Mayo Clinic addiction expert and psychiatrist.
Underage drinking is common in the United States: 36 percent of high-school students report having consumed alcohol at least once, although the prevalence of heavy drinking (more than five drinks in a row within the preceding two weeks) is lower (7 percent).
“Alcohol use necessitating acute-care hospitalization represents one of the most serious consequences of underage drinking,” Dr. Schneekloth says. “Harmful alcohol use in adolescence is a harbinger of alcohol abuse in adulthood.”
The average age of those with alcohol-related discharges was 18; 61 percent were male. Nearly a quarter of the alcohol-use disorder hospitalizations included an injury, most commonly traffic accidents, assaults and altercations.
The analysis used the most recent (2008) Nationwide Inpatient Sample data, the largest all-payer inpatient care database in the United States. It is approximately a 20 percent stratified sample of all U.S. hospitals, accounting for about 90 percent of all discharges in the United States. To calculate the incidence rate of hospitalizations, researchers took population denominator data from the U.S. Census Bureau for 2008.
For adolescent males and females, hospitalization incidence was highest in the Northeast and Midwest, lowest in the South, and intermediate in the West. On multivariable analysis, older age and male gender were associated with alcohol-use disorder hospitalizations. In general, black Americans had lower hospitalization rates than whites, and Hispanics and Asian/Pacific Islanders had the lowest rates. The rates tended to be highest for Native and other/mixed-race Americans; however, the number of hospitalizations was relatively small, making estimates imprecise. The findings may help target substance abuse prevention efforts toward geographic and demographic groups at greatest risk.
Much of the hospitalization cost ($505 million) involved treatment of injuries. A total of 107 of those hospitalized died (.27 percent): Their age was 18.6 years, and 82 percent were male. Seventy-three percent of the deaths occurred during a hospitalization for injuries.
Study: Weight training improves Parkinson’s symptoms
NEW ORLEANS – New research suggests weight training for two years significantly improves the motor symptoms of Parkinson’s disease compared to other forms of exercise such as stretching and balance exercises. The clinical trial, which compared two forms of exercise for Parkinson’s disease, was released today and will be presented at the American Academy of Neurology’s 64th Annual Meeting in New Orleans April 21 to April 28, 2012.
“While we have known that many different types of exercise can benefit Parkinson’s patients over short time periods, we did not know whether exercise improves the motor symptoms of Parkinson’s over the long term,” said study author Daniel Corcos, PhD, with the University of Illinois at Chicago.
For the study, 48 people with Parkinson’s disease were randomized to progressive resistance exercise, known as weight training, or they were assigned to the exercise known as fitness counts, which includes flexibility, balance and strengthening exercises. The groups exercised for one hour, twice a week for two years.
The severity of motor symptoms, including tremors, was measured using the Unified Parkinson’s Disease Rating Scale (UPDRS) after six, 12, 18 and 24 months of exercise. Scores were taken when the participants were not taking their medication.
While both forms of exercise reduced motor symptoms at six months of exercise, participants who did weight training saw a 7.3 point improvement in their UPRDS score after two years while the fitness counts group returned to the same scores they had at the start of the study.
“Our results suggest that long-term weight training could be considered by patients and doctors as an important component in managing Parkinson’s disease,” said Corcos.
To kill off parasites, an insect self-medicates with alcohol
Alcoholic drinks aren’t generally put into the category of health food, but in some cases they might be just the cure for nasty parasites. That’s according to a study published online on February 16 in Current Biology, a Cell Press publication, showing that fruit flies will actually seek out alcohol to kill off blood-borne parasitic wasps living within them.
The discovery offers some of the first evidence that alcohol might be used to fight infection, the researchers say.
“We found that environmental alcohol protects fruit flies from being parasitized by wasps, and that, even after being infected, fruit fly consumption of alcohol leads to death of the wasps growing within them,” said Todd Schlenke of Emory University. “Surprisingly, fly larvae actively seek out ethanol-containing food when infected, showing they use alcohol as an antiwasp medicine.”
Wasp mothers will lay their eggs in fruit fly larvae. Their young hatchlings then eat the flies from the inside out. Fortunately for flies of the species Drosophila melanogaster, they have developed a tolerance for alcohol over evolutionary time, a necessity for a life living in and feeding on rotting and fermented fruit.
“D. melanogaster has a special ability to tolerate high levels of alcohol,” Schlenke said. “It seemed possible that this ability might protect the flies from generalist parasites.” In fact, those parasites might have even helped push the flies toward an alcohol-drinking existence, he added.
Indeed, the new evidence shows that ethanol exposure discourages wasps from laying their eggs in young fruit flies. When infected flies consume ethanol, it tips the balance in favor of the flies. Those flies are more likely to live and the wasps to die, even if the flies forego launching their normal antiwasp immune response.
It is tempting to think that the findings in flies might have application to other alcohol-drinking animals, including humans, the researchers say. Until now, the notion that alcohol consumption might cure human ailments—particularly stomach infections—has been the stuff of online chat sites and not the scientific literature, they note. As a simple first test, they suggest that ethanol could be added to parasite cultures in the lab to find out what sort of effect it might have.
Either way, it turns out, the findings are yet another example of the beauty and complexity of nature. “These little fruit flies, the same that hover around the brown bananas in your fruit bowl, are making complex decisions about how much alcohol to consume based on whether or not they have internal parasites,” Schlenke said. “Who knows, maybe they can teach us something about how to fight off our own parasites.”
Common flame retardant linked to social, behavioral and learning deficits
Study highlights the interaction between epigenetics and genetics and exposure to a flame retardant in mice
Mice genetically engineered to be susceptible to autism-like behaviors that were exposed to a common flame retardant were less fertile and their offspring were smaller, less sociable and demonstrated marked deficits in learning and long-term memory when compared with the offspring of normal unexposed mice, a study by researchers at UC Davis has found. The researchers said the study is the first to link genetics and epigenetics with exposure to a flame retardant chemical.
The research was published online today in the journal Human Molecular Genetics. It will be presented during a symposium on Saturday, Feb. 18, at the annual meeting of the American Association for the Advancement of Science (AAAS) by Janine LaSalle, a professor in the Department of Medical Microbiology and Immunology in the UC Davis School of Medicine and the UC Davis Genome Center. (LaSalle will discuss her research during a news briefing with other autism researchers at 9 a.m. on Feb. 19 in Room 221 on the second Level of the Vancouver Convention Center).
“This study highlights the interaction between epigenetics and the effects of early exposure to flame retardants,” said Janine LaSalle, the study’s senior author and a researcher affiliated with the UC Davis MIND Institute. “Our experiments with wild-type and mutant mice indicate that exposure to flame retardants presents an independent risk of neurodevelopmental deficits associated with reduced sociability and learning.”
Epigenetics describes the heritable changes in gene expression caused by mechanisms other than those in the DNA sequence. One such mechanism is DNA methylation, in which genes are silenced when their activation no longer is required. DNA methylation is essential for normal development. The researchers chose a mouse that was genetically and epigenetically susceptible to social behavioral deficits in order to understand the potential effect of this environmental pollutant on genetically susceptible humans.
LaSalle and her colleagues examined the effects of the chemical BDE-47 (Tetrabromodiphenl ether), a member of the class of flame retardants called polybrominated diphenylethers, or PBDEs. PBDEs have been used in a wide range of products, including electronics, bedding, carpeting and furniture. They have been shown to persist in the environment and accumulate in living organisms, and toxicological testing has found that they may cause liver toxicity, thyroid toxicity and neurodevelopmental toxicity, according to U.S. Environmental Protection Agency. BDE-47 is the PBDE found at highest concentrations in human blood and breast milk, raising concerns about its potential neurotoxic effects during pregnancy and neonatal development.
The research was conducted in the offspring of mice genetically engineered for the autism phenotype found in Rett syndrome, a disorder that occurs primarily in females and causes regression in expressive language, motor skills and social reciprocity in late infancy. The condition affects about 1 in 10,000 children.
Autism spectrum disorders are a group of neurodevelopmental disabilities that can cause significant social, communication and behavioral deficits. The U.S. Centers for Disease Control and Prevention estimates that an average of 1 in 110 children born in the United States today will be diagnosed with an autism spectrum disorder.
Rett syndrome is causally linked to defects in the methyl-CpG-binding protein 2 gene MECP2 situated on the X chromosome. Mutations in MECP2 result in a nonfunctional MeCP2 protein, which is required for normal brain development. The researchers evaluated the effects of exposure to BDE-47 on mice genetically engineered to have mutations in MECP2 and their offspring, or pups. The genetically engineered Mecp2 mother mice, or dams, were bred with non-mutant wild-type males. The dams were monitored for 10 weeks — for four weeks prior to conception, three weeks during gestation and three weeks of lactation. They were then compared with a control group of normal, unexposed dams and pups over several generations and hundreds of mice.
The study found that that the weights of the pups of the lactating BDE-47-exposed dams were diminished when compared with the controls, as were their survival rates. To assess the effects of the flame retardant exposure on the pups and their genotypes, the researchers placed them through more than 10 cognitive, social and physical tests.
Female offspring of dams exposed with BDE-47 spent half as much time interacting with another mouse in a 10-minute sociability test compared to controls. The reduced sociability in BDE-47 exposed females corresponded to reduced DNA methylation in females regardless of genotype. In addition, genetic and environmental interaction effects in this study were specifically observed in females.
In a short-term memory test of social novelty, although all mice showed the expected preference for interacting with a novel over a familiar mouse, BDE-47-exposed mutant female mice spent about half as much time interacting with the familiar mouse than their non-mutant littermates. In a long-term memory test of swimming to reach a hidden platform in a cloudy pool, female mice who were both mutant and BDE-47 exposed did not learn to reach the platform faster after fourdays of training. These behavioral changes in social and cognitive learning specifically in the interaction group corresponded to changes in a known epigenetic regulator of DNA methylation in brain, DNA methyltransferase 3a (Dnmt3a).
LaSalle said that the study results are important because better understanding of the epigenetic pathways implicated in social behavior and cognition may lead to improved treatments for autism spectrum disorders.
“While the obvious preventative step is to limit the use and accumulation of PBDEs in our environment, this would likely be a long-term solution,” LaSalle said. “These pollutants are going to be hard to get rid of tomorrow. However, one important preventative that all women could do tomorrow is to start taking prenatal vitamins before becoming pregnant, as these may counteract the toxins in our environment through DNA methylation,” she said.
A study by researchers at UC Davis conducted in 2011 found that women who reported not taking a daily prenatal vitamin immediately before and during the first month of pregnancy were nearly twice as likely to have a child with an autism spectrum disorder as women who did take the supplements — and the associated risk rose to seven times as great when combined with a high-risk genetic make-up.
More than one in four elderly patients was given potentially hazardous medication during 2007. That is the conclusion of a study by Ute Amann and her co-authors in the current issue of the Deutsches Ärzteblatt International (Dtsch Arztebl Int 2012; 109: 69-75).
Giving certain medical drug substances to over-65-year-olds can increase the risk of undesired drug effects, and for this reason experts describe them as “potentially inappropriate medications” (PIMs).
This study used information from a large database to attempt to estimate the risk of PIM for older people according to age, sex, and drug substance. The researchers used the data of 447 592 men and 356 808 women aged 65 or over to assess how often PIMs were prescribed per patient.
Women had more PIM prescriptions than men. The potentially hazardous drugs that were most often prescribed were amitriptyline, acetyldigoxin, tetrazepam, and oxazepam. Overall, 8.8% of all patients in the database received four or more prescriptions for the same or an equivalent drug during the study period.
Cranky today? Even mild dehydration can alter our moods
Most people only think about drinking water when they are thirsty; but by then it may already be too late.
Even mild dehydration can alter a person’s mood, energy level, and ability to think clearly, according to two studies recently conducted at the University of Connecticut’s Human Performance Laboratory.
The tests showed that it didn’t matter if a person had just walked for 40 minutes on a treadmill or was sitting at rest – the adverse effects from mild dehydration were the same. Mild dehydration is defined as an approximately 1.5 percent loss in normal water volume in the body.
The test results affirm the importance of staying properly hydrated at all times and not just during exercise, extreme heat, or exertion, says Lawrence E. Armstrong, one of the studies’ lead scientists and a professor of physiology in UConn’s Department of Kinesiology in the Neag School of Education.
“Our thirst sensation doesn’t really appear until we are 1 [percent] or 2 percent dehydrated. By then dehydration is already setting in and starting to impact how our mind and body perform,” says Armstrong, an international expert on hydration who has conducted research in the field for more than 20 years. “Dehydration affects all people, and staying properly hydrated is just as important for those who work all day at a computer as it is for marathon runners, who can lose up to 8 percent of their body weight as water when they compete.”
Separate groups of young women and men were tested. Twenty-five women took part in one study. Their average age was 23. The men’s group consisted of 26 men with an average age of 20. All of the participants were healthy, active individuals, who were neither high-performance athletes nor sedentary – typically exercising for 30 to 60 minutes per day.
Each participant took part in three evaluations that were separated by 28 days. All of the participants walked on a treadmill to induce dehydration, and all of the subjects were hydrated the evening before the evaluations commenced. As part of the evaluation, the subjects were put through a battery of cognitive tests that measured vigilance, concentration, reaction time, learning, memory, and reasoning. The results were compared against a separate series of tests when the individuals were not dehydrated.
In the tests involving the young women, mild dehydration caused headaches, fatigue, and difficulty concentrating, according to one of the studies, which appears in the February issue of The Journal of Nutrition. The female subjects also perceived tasks as more difficult when slightly dehydrated, although there was no substantive reduction in their cognitive abilities.
In the tests involving the young men, mild dehydration caused some difficulty with mental tasks, particularly in the areas of vigilance and working memory, according to the results of the second UConn study. While the young men also experienced fatigue, tension, and anxiety when mildly dehydrated, adverse changes in mood and symptoms were “substantially greater in females than in males, both at rest and during exercise,” according to the study. The men’s study was published in the British Journal of Nutrition in November 2011.
“Even mild dehydration that can occur during the course of our ordinary daily activities can degrade how we are feeling – especially for women, who appear to be more susceptible to the adverse effects of low levels of dehydration than men,” says Harris Lieberman, one of the studies’ co-authors and a research psychologist with the Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine in Natick, Mass. “In both sexes these adverse mood changes may limit the motivation required to engage in even moderate aerobic exercise. Mild dehydration may also interfere with other daily activities, even when there is no physical demand component present.”
Why women and men are so adversely affected by mild dehydration is unclear, and more research is necessary. But other research has shown that neurons in the brain detect dehydration and may signal other parts of the brain regulating mood when dehydration occurs. This process could be part of an ancient warning system protecting humans from more dire consequences, and alerting them to the need for water to survive.
In order to stay properly hydrated, experts like Armstrong recommend that individuals drink eight, 8-ounce glasses of water a day, which is approximately equivalent to about 2 liters of water. People can check their hydration status by monitoring the color of their urine. Urine should be a very pale yellow in individuals who are properly hydrated. Urine that is dark yellow or tan in color indicates greater dehydration. Proper hydration is particularly important for high-risk groups, such as the elderly, people with diabetes, and children.
Alzheimer’s drugs may have adverse side effects
Drugs may act like bad electrician, messing up wiring in brain and nervous system
CHICAGO — Alzheimer’s disease drugs now being tested in clinical trials may have potentially adverse side effects, according to new Northwestern Medicine research. A study with mice suggests the drugs could act like a bad electrician, causing neurons to be miswired and interfering with their ability to send messages to the brain.
The findings, from the scientist whose original research led to the drug development, are published in the journal Molecular Neurodegeneration and will be presented Saturday, Feb. 18, at the 2012 annual meeting for the American Association for the Advancement of Science in Vancouver.
“Let’s proceed with caution,” said Robert Vassar, professor of cell and molecular biology at Northwestern University Feinberg School of Medicine. “We have to keep our eyes open for potential side effects of these drugs.” Ironically, he says, the drugs could impair memory.
The drugs are designed to inhibit BACE1, the enzyme Vassar originally discovered that promotes the development of the clumps of plaque that are a hallmark of Alzheimer’s. BACE1 acts as a molecular scissors, cutting up and releasing proteins that form the plaques. Thus, drug developers believed blocking the enzyme might slow the disease.
But in Vassar’s new study, he found BACE1 also has a critical role as the brain’s electrician. In that role, the enzyme maps out the location of axons, the wires that connect neurons to the brain and the rest of the nervous system. This mapping is called axonal guidance.
Working with mice from which BACE1 was genetically removed, Vassar discovered the animals’ olfactory system – used for the sense of smell — was incorrectly wired. The axons of the olfactory neurons were not wired properly to the olfactory bulb of the brain. The findings show the key role of BACE1 in axonal guidance.
“It’s like a badly wired house,” Vassar said. “If the electrician doesn’t get the wiring pattern correct, your lights won’t turn on and the outlets won’t work.”
The olfactory system is a good model for axonal guidance or wiring. If the axons aren’t being properly connected in the olfactory system, Vassar said, the problem likely exists elsewhere in the brain and nervous system. The hippocampus could be particularly vulnerable to BACE1 blockers, he noted, because its population of neurons is continually being reborn, which may play a role in forming new memories. The neurons need to grow new axons that in turn must connect them with new targets. Axonal guidance is a continuous need.
“It’s not all bad news,” Vassar noted. “These BACE1 blockers might be useful at a specific dose that will reduce the amyloid plaques but not high enough to interfere with the wiring. Understanding the normal function of BACE1 may help us avoid potential drug side effects.”
Serotonin could play a large role in bone loss
Bethesda, Md.—Scientists have long known that calcium leaches from the bones both during lactation and in certain types of cancer. The driver behind these phenomena is a molecule called parathyroid hormone related protein (PTHrP), which is secreted by the mammary glands. The signal that regulates the secretion of PTHrP, and where this other unknown molecule exerts its influence, has remained a mystery. Now, in a new study using cells and tissues from mice, cows, and people, a team of researchers at the University of Cincinnati have identified this mystery molecule as serotonin, a neurotransmitter most often recognized for its role in happiness and well-being. The scientists also identified the specific receptor that serotonin acts on in mammary tissue. Understanding these two findings more deeply could lead to better ways to combat bone loss, potentially by using drugs that affect serotonin signaling.
The study is entitled “Mammary Gland Serotonin Regulates Parathyroid Hormone-Related Protein and Other Bone-Related Signals” (http://bit.ly/yeB5uQ). It appears in the Articles in PresS section of the American Journal of Physiology – Endocrinology and Metabolism, published by the American Physiological Society (APS).
The researchers first examined lactating mice with a genetic mutation that prevented them from making serotonin efficiently and compared the amount of PTHrP in these animals to that in lactating normal, healthy mice. Next, they treated mouse and cow mammary cells with serotonin to see if it could induce secretion of PTHrP. They then treated human breast cancer lines with serotonin to see if the neurotransmitter could change expression of PTHrP and a gene called Runx2, which is known to be involved in metastatic breast cancer and bone loss. Finally, they examined mice genetically modified to be missing a particular type of serotonin receptor, as well as mouse mammary cells, to determine which serotonin receptor might be responsible for influencing PTHrP secretion.
The researchers found that lactating mice genetically modified to prevent them from making serotonin efficiently (tryptophan hydoxylase 1 mutation) had significantly less PTHrP in their mammary glands compared to lactating normal, healthy mice, suggesting that serotonin is pivotally important for producing PTHrP. Supporting these findings, mouse and cow mammary cells treated with serotonin increased their expression of the gene responsible for PTHrP production by 8- and 20-fold, respectively. Treating three human breast cancer cell lines with serotonin increased expression of the PTHrP gene by 20-fold, and also increased expression of Runx2 as well. Though previous studies have shown that a serotonin receptor known as 5-HT7 is important for some mammary gland functions, this current study suggests that a different receptor, known as 5-HT2, is the target responsible for stimulating PTHrP levels.
Importance of the Findings
These findings suggest that serotonin is a molecule that regulates PTHrP production, which in turn affects how calcium leaches from the bones during lactation and soft tissue cancer metastases. The authors suggest that this finding isn’t completely surprising, since many antidepressants that act on serotonin have bone loss as a side effect. Understanding the action of serotonin better could help researchers develop better ways to preserve bone, they say, potentially through the action of drugs that act on the serotonin system.
“The complexity of 5-HT (serotonin) signaling demands cautious interpretations and the testing of new hypotheses and additional model systems. With improved knowledge, serotonergic drugs may provide novel opportunities for therapeutic interventions,” the authors say.
Stronger intestinal barrier may prevent cancer in the rest of the body, new study suggests
Thomas Jefferson University researchers found that silencing hormone receptor weakens intestinal barrier, making body more susceptible to cancer
IMAGE:Scott Waldman, M.D., Ph.D., chair of the Department of Pharmacology and Experimental Therapeutics at Jefferson and director of the Gastrointestinal Cancer Program at Jefferson’s Kimmel Cancer Center, and colleagues found…
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PHILADELPHIA— A leaky gut may be the root of some cancers forming in the rest of the body, a new study published online Feb. 21 in PLoS ONE by Thomas Jefferson University researchers suggests.
It appears that the hormone receptor guanylyl cyclase C (GC-C)—a previously identified tumor suppressor that exists in the intestinal tract—plays a key role in strengthening the body’s intestinal barrier, which helps separate the gut world from the rest of the body, and possibly keeps cancer at bay. Without the receptor, that barrier weakens.
A team led by Scott Waldman, M.D., Ph.D., chair of the Department of Pharmacology and Experimental Therapeutics at Jefferson and director of the Gastrointestinal Cancer Program at Jefferson’s Kimmel Cancer Center, discovered in a pre-clinical study that silencing GC-C in mice compromised the integrity of the intestinal barrier. It allowed inflammation to occur and cancer-causing agents to seep out into the body, damaging DNA and forming cancer outside the intestine, including in the liver, lung and lymph nodes.
Conversely, stimulating GC-C in intestines in mice strengthened the intestinal barrier opposing these pathological changes.
A weakened intestinal barrier has been linked to many diseases, like inflammatory bowel disease, asthma and food allergies, but this study provides fresh evidence that GC-C plays a role in the integrity of the intestine. Strengthening it, the team says, could potentially protect people against inflammation and cancer in the rest of the body.
“If the intestinal barrier breaks down, it becomes a portal for stuff in the outside world to leak into the inside world,” said Dr. Waldman. “When these worlds collide, it can cause many diseases, like inflammation and cancer.”
The role of GC-C outside the gut has remained largely elusive. Dr. Waldman and his team have previously shown its role as a tumor suppressor and biomarker that reveals occult metastases in lymph nodes. They’ve used to it better predict cancer risk, and have even shown a possible correlation with obesity.
Reporting in the Journal of Clinical Investigation, Dr. Waldman colleagues found that silencing GC-C affected appetite in mice, disrupting satiation and inducing obesity. Conversely, mice who expressed the hormone receptor knew when to call it quits at mealtime.
However, its role in intestinal barrier integrity, inflammation, and cancer outside the intestine is new territory in the field.
A new drug containing GC-C is now on the verge of hitting the market, but its intended prescribed purpose is to treat constipation.
This study helps lays the groundwork, Dr. Waldman said, for future pre-clinical and clinical studies investigating GC-C’s abilities beyond those treatments in humans, including prevention and treatment of inflammatory bowel disease and cancer.
“We’ve shown that when you pull away GC-C in animals, you disrupt the intestinal barrier, putting them at risk for getting inflammatory bowel disease and cancer. And when you treat them with hormones that activate GC-C it helps strengthen the integrity of the intestinal barrier,” Dr. Waldman said. “Now, if you want to prevent inflammation or cancer in humans, then we need to start thinking about feeding people hormones that activate GC-C to tighten up the barrier.”
Environmental pollutant linked with overweight
Published 20.02.2012 , updated: 20.02.2012, 15:24
The levels of the environmental pollutant perfluorooctanoic acid (PFOA) that mothers had in their blood during pregnancy increased the risk of obesity in their daughters at 20 years of age. The findings come from a recent study of Danish women in which the Norwegian Institute of Public Health participated.
In recent decades, there has been a sharp increase in the number of overweight children and adults in both Norway and worldwide. It is suspected that diet and exercise alone cannot explain this large weight increase. Researchers suggest that the increasing levels of endocrine disrupters in the environment may be a possible contributing factor. Therefore, this study was established and discovered the following:
Daughters of mothers with the highest concentrations of PFOA in the blood during p
regnancy were three times as likely to be overweight at the age of about 20 years as daughters of mothers with the lowest PFOA levels.
The calculations took into account many variables, such as maternal weight and lifestyle factors.
An association was also found between PFOA exposure before birth and elevated levels of insulin and leptin, two hormones that are linked to obesity.
Levels of insulin and leptin were also elevated in the sons of mothers with high PFOA, but the relationship was weaker than for girls.
There was no increased risk of development of obesity among the sons.
What does this mean for us?
“It is still too early to say what this might mean for us. The study indicates that factors such as environmental pollutants, in addition to diet and physical activity, play a role in the obesity epidemic we see today. But this remains to be confirmed by similar studies,” says Line Småstuen Haug at the Norwegian Institute of Public Health. “In the late 1980s the levels of PFOAs and other PFCs in Norway were similar to the Danish study, which makes the findings also relevant for Norway. It is also important to note that the levels of several of these environmental pollutants in the blood of Norwegian women have decreased significantly since about 2000. However, this does not apply to all the substances and so we should try to limit our exposure to persistent pollutants to reduce the risk of adverse health effects,” says Småstuen Haug.
About the study
In 1988-1989, around 1,000 pregnant women in Aarhus, Denmark were recruited for a study where a sample of blood of women in week 30 of pregnancy was collected and frozen. In 2008-2009, the children from these pregnancies were contacted and asked to participate in a follow-up study in which, for instance, body mass index and waist circumference were recorded.
Approximately 650 of the children agreed to participate. Employees at the Norwegian Institute of Public Health analysed the levels of a variety of PFCs in the mothers’ blood.
Halldorsson TI, Rider D, Haug LS, Bech BH, Danielsen I, Becher G, Henriksen TB, Olsen SF. Prenatal Exposure two Perfluorooctanoate and Risk of Over Weight at 20 Years of Age: A prospective cohort study. Environmental Health Perspectives. DOI: dx.doi.org/10.1289/ehp.1104034
Fake drug sales are increasing on the Internet and turning up in legitimate supply chains
Major review contains wealth of international facts and figures
Criminal gangs are increasingly using the internet to market life-threatening counterfeit medicines and some have even turned up in legitimate outlets such as pharmacies, according to a review led by Dr Graham Jackson, editor of IJCP, the International Journal of Clinical Practice, and published in the March edition.
Latest estimates suggest that global sales of counterfeit medicines are worth more than $75 billion, having doubled in just five years between 2005 and 2010. Numerous studies have also reported large numbers of websites supplying prescription only drugs without a prescription and people buying internet drugs despite being aware of the dangers.
“Counterfeit medicines pose an every-increasing threat to public health, including death and inadequate healthcare as a result of self medication” says Dr Jackson. “Particularly worrying examples include counterfeit cancer and heart drugs and fake vaccines sold during the bird and swine flu scares.
“The majority of medicines people buy from unverified internet sites are counterfeit and often lack the active ingredients they claim. Others have variable concentrations of active ingredients or even contain dangerous toxins, such as arsenic, boric acid, leaded road paint, floor and shoe polish, talcum powder, chalk and brick dust and nickel.
Counterfeit medicines are a major concern to the authorities and significant European Union legislation is being developed, including stronger penalties. As outgoing European Commissioner for Enterprise and Industry Gunter Verheugen said in 2010: “Every faked drug is a potential massacre. Even when a medicine only contains an ineffective substance, this can lead to people dying because they think they are fighting their illness with a real drug.”
Facts and figures highlighted in Dr Jackson’s review include:
European Union seizures and detentions are increasing and medicines accounted for 10% of all detained materials in 2009.
There is clear evidence that counterfeit drugs are being found in legitimate supply chains. For example, the UK has had nine product recalls in the last three years after counterfeit medicines reached pharmacy and patient levels and a further five were discovered at wholesaler level.
A UK study of 96 websites selling painkillers, found that 48% sold drugs that should be only supplied on prescription and 76% of those did so without a prescription. And a US study of 159 sites offering controlled drugs found that 85% did not require a prescription.
21% of the 14,000 plus people who took part in a 14-country European study had bought prescription only medicines without a prescription. The figure was 12% in the UK.
Another study estimated that 9% of Europeans had bought online prescription only drugs, even though 69% agreed that it was a ‘bad idea’ or ‘dangerous’. Cheaper costs (46%) and convenience (30%) were the most common reasons.
The UK medical newspaper GP reported that 33% of the 423 doctors it surveyed said that they had treated, or suspect they had treated, a patient for the side-effects of substandard prescription only drugs purchased online.
A study carried out by the European Alliance for Access to Safe Medicines found that 62% of medicines ordered on the internet were substandard or counterfeit. Of these, 68% were unlicensed imitations and the rest were counterfeit branded medicines. The study also found that 90% of sites did not require a prescription for prescription only drugs.
Five ‘Tamiflu’ vaccines tested by the American Food and Drugs Administration contained no active ingredient at all and a further four contained varying levels unapproved for use in the USA.
An analysis of 2,383 seized ‘Viagra’ samples carried out by Pfizer found that only 14% were authentic.
Internet security experts estimate that 25% of all email is spam advertising counterfeit and/or unlicensed drugs.
“Counterfeiters produce medicines with no regard for the health consequences of those using them, with cancer and heart drugs being increasingly targeted, along with opportunist drugs like flu vaccines” says Dr Jackson.
“We even found reports that a 13-year-old had bought the psychostimulant drug Ritalin online, that underweight, underage patients were able to buy diet drugs and that men were able to buy impotence drugs despite clear indications that taking them could have serious health consequences.
“There have also been reports of deaths from Internet drugs and some investigators suspect that many more have been overlooked or wrongly attributed to other causes.
“It is vital that healthcare professionals play a proactive role in fighting the rise in counterfeit medicines by reporting all suspected cases to the relevant health authorities. And patients should be advised to avoid unregulated internet pharmacies and to be suspicious of sites offering prescription only medication without a prescription or at substantial discounts.”
Ralph’s Note: If 62% of Prescriptions online are counterfeits just imagine supplements.
Eating citrus fruit may lower women’s stroke risk
A compound in citrus fruits may reduce your stroke risk, according to research reported in Stroke: Journal of the American Heart Association.
This prospective study is one of the first in which researchers examine how consuming flavonoid subclasses affects the risk of stroke. Flavonoids are a class of compounds present in fruits, vegetables, dark chocolate and red wine.
“Studies have shown higher fruit, vegetable and specifically vitamin C intake is associated with reduced stroke risk,” said Aedín Cassidy, Ph.D., the study’s lead author and professor of nutrition at Norwich Medical School in the University of East Anglia in Norwich, United Kingdom. “Flavonoids are thought to provide some of that protection through several mechanisms, including improved blood vessel function and an anti-inflammatory effect.”
Cassidy and colleagues used 14-years of follow-up data from the Nurse’s Health Study, which included 69,622 women who reported their food intake, including details on fruit and vegetable consumption every four years. Researchers examined the relationship of the six main subclasses of flavonoids commonly consumed in the U.S. diet — flavanones, anthocyanins, flavan-3-ols, flavonoid polymers, flavonols and flavones — with risk of ischemic, hemorrhagic and total stroke.
As expected, the researchers didn’t find a beneficial association between total flavonoid consumption and stroke risk, as the biological activity of the sub-classes differ. However, they found that women who ate high amounts of flavanones in citrus had a 19 percent lower risk of blood clot-related (ischemic) stroke than women who consumed the least amounts.
In the study, flavanones came primarily from oranges and orange juice (82 percent) and grapefruit and grapefruit juice (14 percent). However, researchers recommended that consumers increase their citrus fruit intake, rather than juice, due to the high sugar content of commercial fruit juices.
A previous study found that citrus fruit and juice intake, but not intake of other fruits, protected against risk of ischemic stroke and intracerebral hemorrhage. Another study found no association between yellow and orange fruits and stroke risk, but did link increased consumption of white fruits like apples and pears with lower stroke risk. An additional study found that Swedish women who ate the highest levels of antioxidants – about 50 percent from fruits and vegetables – had fewer strokes than those with lower antioxidant levels.
More studies are needed to confirm the association between flavanone consumption and stroke risk, and to gain a better understanding about why the association occurs, the authors said.
Researchers Discover How Vitamin D Inhibits Inflammation
Researchers at National Jewish Health have discovered specific molecular and signaling events by which vitamin D inhibits inflammation. In their experiments, they showed that low levels of Vitamin D, comparable to levels found in millions of people, failed to inhibit the inflammatory cascade, while levels considered adequate did inhibit inflammatory signaling. They reported their results in the March 1, 2011, issue of The Journal of Immunology.
“This study goes beyond previous associations of vitamin D with various health outcomes. It outlines a clear chain of cellular events, from the binding of DNA, through a specific signaling pathway, to the reduction of proteins known to trigger inflammation,” said lead author Elena Goleva, assistant professor of pediatrics at National Jewish Health. “Patients with chronic inflammatory diseases, such as asthma, arthritis and prostate cancer, who are vitamin D deficient, may benefit from vitamin D supplementation to get their serum vitamin D levels above 30 nanograms/milliliter.”
Current national guidelines suggest that people should maintain a minimum blood serum level of 20 ng/ml, although there is much scientific debate about optimum levels. Vitamin D has long been known to contribute to bone health by promoting the absorption of calcium. In recent years, much attention has been paid to its possible immune and inflammatory benefits. Low vitamin D levels have been associated with several diseases including asthma, cancer, diabetes, and arthritis.
In the current study researchers examined the specific mechanisms by which vitamin D might act on immune and inflammatory pathways. They incubated human white blood cells with varying levels of vitamin D, then exposed them to lipopolysaccharide (LPS), a molecule associated with bacterial cell walls that is known to promote intense inflammatory responses.
Cells incubated with no vitamin D and in solution containing 15 ng/ml of vitamin D produced high levels of cytokines IL-6 and TNF-alpha, major actors in the inflammatory response. Cells incubated in 30 ng/ml vitamin D and above showed significantly reduced response to the LPS. The highest levels of inflammatory inhibition occurred at 50 ng/ml.
Through a complex series of experiments, the researchers identified a new location where the vitamin-D receptor appears to bind directly to DNA and activate a gene known as MKP-1. MKP-1 interferes with the inflammatory cascade triggered by LPS, which includes a molecule known as p38, and results in higher levels of IL-6 and TNF-alpha.
“This newly identified DNA-binding site for the vitamin-D receptor, and the specific pathways inhibited by higher levels of vitamin D provide a plausible mechanism for many of the benefits that have been associated with vitamin D,” said Dr. Goleva. ‘The fact that we showed a dose-dependent and varying response to levels commonly found in humans also adds weight to the argument for vitamin D’s role in immune and inflammatory conditions.”
First study to show that bisphenol A exposure increases risk of future onset of heart disease
Bisphenol A (BPA) is a controversial chemical widely used in the plastics industry. A new study followed people over a 10-year time period and shows that healthy people with higher urine concentrations of BPA were more likely to later develop heart disease.
The study was carried out by researchers at the Peninsula College of Medicine and Dentistry, the University of Exeter and the European Centre for the Environment and Human Health, in association with the University of Cambridge. The analysis was funded by the British Heart Foundation. The paper is published online in Circulation – a Journal of the American Heart Association.
The research team had previously identified the link between BPA and the increased risk of cardiovascular disease by using two sets of US data, which are effectively snapshots in time. The previous data showed a correlation between exposure to BPA and cardiovascular disease but it could not help researchers to predict how exposure to the chemical might affect future health.
The most recent study uses data from the European Prospective Investigation of Cancer (EPIC) in Norfolk, UK, a long term population study led by the University of Cambridge, supported by the Medical Research Council UK and Cancer Research UK. It is the first time that data has been used to establish a link between exposure to BPA and future onset of cardiovascular disease.
The study compared urine BPA measures from 758 initially healthy EPIC study respondents who later developed cardiovascular disease, and 861 respondents who remained heart disease free. The findings of the study show that those who developed heart disease tended to have higher urinary BPA concentrations at the start of the 10-year period. The extent of the effect is very difficult to estimate given that just one urine specimen from each participant was available for testing at the beginning of the 10-year follow-up.
Professor David Melzer of the Peninsula Medical School, who led the team, said: “This study strengthens the statistical link between BPA and heart disease, but we can’t be certain that BPA itself is responsible. It is now important that government agencies organise drug style safety trials of BPA in humans, as much basic information about how BPA behaves in the human body is still unknown.”
Professor Tamara Galloway of the University of Exeter, senior author on the paper, said: “If BPA itself is directly responsible for this increase in risk, the size of effect is difficult to estimate. However, it adds to the evidence that BPA may be an additional contributor to heart disease risk alongside the major risk factors, such as smoking, high blood pressure and high cholesterol levels.”
BPA is one of the world’s highest production volume chemicals. The global population is exposed to BPA primarily through packaged food and drink, but also through drinking water, dental sealants, exposure to the skin and the inhalation of household dust.
New street drug ‘bath salts’ packs double punch
Mimicking effects of 2 powerful narcotics
San Diego, Calif. – The street drug commonly referred to as “bath salts” is one of a growing list of synthetic and unevenly regulated narcotics that are found across the United States and on the Internet. New research on this potent drug paints an alarming picture, revealing that bath salts pack a powerful double punch, producing combined effects similar to both methamphetamine (METH) and cocaine.
“This combination of effects is particularly novel and unexpected,” said Louis J. De Felice of Virginia Commonwealth University’s School of Medicine in Richmond. “Methamphetamine and cocaine operate in the brain in completely opposite ways. It would be atypical that both drugs would be taken together, but that’s the effect that occurs with bath salts.”
De Felice and his colleagues will present their research at the 56th Annual Meeting of the Biophysical Society (BPS), held Feb. 25-29 in San Diego, Calif.
The team’s research reveals that bath salts contain two structurally similar chemicals that produce quite dissimilar effects on the brain’s dopamine transport system. Dopamine is a neurotransmitter that plays an important role in the brain’s pleasure and reward centers. Though bath salts’ chemicals are structurally similar, both acting as potent psycho-stimulants, they use completely opposite mechanisms in the brain.
The first component is a dopamine-releasing agent known as mephedrone (MEPH), which – like METH – causes the brain to release more dopamine. The other chemical is methylenedioxypyrovalerone (MDPV), which – like cocaine – is a dopamine reuptake inhibitor. Both compounds increase dopamine availability to receptors, and both – through different mechanisms – produce feelings of euphoria.
The surprising finding is that rather than canceling each other out, as would be anticipated, the chemicals combine to enhance the effects of the other. “The two drugs have different kinetics, so rather than cancel each other they exacerbate the effect of either drug applied alone,” said De Felice.
The researchers began this particular project as part of a larger study on how amphetamine and METH affect the human dopamine transporter molecule. They made the novel finding that both chemicals create long-lasting effects that endure 30 minutes or more after the drugs are removed. This initial research continued with cathinone (CATH), which is a naturally occurring compound found in the khat shrub (Catha edulis). The drugs found in bath salts (MEPH and MDPV) are synthetic derivatives of CATH.
“The stimulant and blocker features of these drugs have been studied previously,” said De Felice, “but the evidence for long-lasting stimulation by MEPH and inhibition by MDPV is novel. It also is in some sense unexpected that two structurally similar agents could act oppositely at the dopamine transporter.”
The researchers do not yet know why these drugs have a persistent effect. They also don’t understand the fundamental reason why two structurally similar drugs act oppositely on the dopamine transporter.
“There also are many questions on the meaning of these findings for the dozens of other illicit synthetic drugs that have found their way to the street,” concludes De Felice. “We do suspect, however, that the combination that is found in bath salts could be behind its powerful physiological and neurological effect on users.”
According to the American Association of Poison Control Centers, there were more than 6,000 calls to poison control centers pertaining to bath salts in 2011, more than ten times the number in 2010. Reported symptoms of exposure include increased blood pressure, increased heart rate, agitation, hallucinations, extreme paranoia, and delusions.
The presentation, “‘Bath Salts’: A synthetic cathinone whose two major components act similar to methamphetamine and cocaine on the human dopamine transporter,” is at 9:15 a.m. on Monday, Feb. 27, 2012, in the San Diego Convention Center, Room 24ABC. ABSTRACT: http://tinyurl.com/7qppna8
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