Health Technology Research Synopsis
132nd Issue Date 29 JUN 2012
Compiled By Ralph Turchiano
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Editors Top Five:
1. Intestinal bacteria produce neurotransmitter, could play role in inflammation
2. Controversial vaccine trial should never have been run in India, researchers say
3. Mayo Clinic: Common blood pressure drug linked to severe GI problems
4. Fungicide used on farm crops linked to insulin resistance
5. Neuroprotective dietary supplements for chronic spinal cord injury
In this issue:
1. Intestinal bacteria produce neurotransmitter, could play role in inflammation
2. Study indicates promise in Huntington’s treatment
3. Peaches, plums, nectarines give obesity, diabetes slim chance
4. Sun exposure and sun-sensitive skin type decreased risk for pancreatic cancer
5. Resveratrol may be a natural exercise performance enhancer: U of A medical research
6. Physicians are biased when evaluating medical conflict of interest policies
7. Trouble on the horizon for GM crops?
8. Apple peel compound boosts calorie burning, reduces obesity in mice
9. How active is your child really?
10. Controversial vaccine trial should never have been run in India, researchers say
11. OMEGA-3 LOWERS INFLAMMATION IN OVERWEIGHT OLDER ADULTS
12. Study links carcinogens to cancer stem cells – but spinach can help
13. Selenium controls staph on implant material
14. Study shows stagnating life expectancies in US
15. Mayo Clinic: Common blood pressure drug linked to severe GI problems
16. Pasta made from green banana flour a tasty alternative for gluten-free diets
17. Declining testosterone levels in men not part of normal aging, study finds
18. Fungicide used on farm crops linked to insulin resistance
19. Vitamin D tests are inaccurate
20. Statins appear associated with reduced risk of recurrent cardiovascular events in men, women
21. Overweight men can boost low testosterone levels by losing weight
22. Treating vitamin D deficiency may improve depression
23. Removing estrogen from drinking water
24. Prenatal exposure to common household chemical increases risk for childhood eczema, study says
25. Neuroprotective dietary supplements for chronic spinal cord injury
26. Phthalate, environmental chemical is linked to higher rates of childhood obesity
27. Moderate coffee consumption offers protection against heart failure
28. Glucose deprivation activates feedback loop that kills cancer cells, UCLA study shows
29. Diet rich in vegetables may help stave off acute pancreatitis
30. Menopausal women could ‘work out’ their hot flashes
31. Dietary fiber alters gut bacteria, supports gastrointestinal health
32. Caffeine boosts power for elderly muscles
33. Flu immunity is affected by how many viruses actually cause the infection
34. Researchers discover potential explanation for why a diet high in DHA improves memory
35. Necrosis after cortisone injections
Intestinal bacteria produce neurotransmitter, could play role in inflammation
Researchers at Baylor College of Medicine and Texas Children’s Hospital have identified commensal bacteria in the human intestine that produce a neurotransmitter that may play a role in preventing or treating inflammatory bowel diseases such as Crohn’s disease.
“We identified, to our knowledge, the first bifidobacterial strain, Bifidobacterium dentium, that is capable of secreting large amounts of gamma-aminobutyric acid (GABA). This molecule is a major inhibitory neurotransmitter in the central and enteric nervous systems,” says Karina Pokusaeva, a researcher on the study and a member of the laboratory of James Versalovic.
GABA is one of the chief inhibitory neurotransmitters in the human central nervous system. It plays a role in regulating pain and some pain relieving drugs currently on the market act by targeting GABA receptors on neural cells.
Pokusaeva and her colleagues were interested in understanding the role the human microbiome might play in pain and scanned the genomes of potentially beneficial intestinal microorganisms, identified by the Human Microbiome Project, for evidence of a gene that would allow them to create GABA.
“Lab analysis of metagenomic DNA sequencing data allowed us to demonstrate that microbial glutamate decarboxylase encoding gene is very abundant in intestinal microbiota as compared to other body sites,” says Pokusaeva. One of the most prolific producers of GABA was B. dentium, which appears to secrete the compound to help it survive the acid environment.
In addition to its pain modulating properties, GABA may also be capable of inhibiting inflammation. Recent studies have shown that immune cells called macrophages also possess GABA receptors. When these receptors were activated on the macrophages there was a decrease in the production of compounds responsible for inflammation.
“Our lab was curious to explore if GABA produced by intestinal human isolate B. dentium could have an effect on GABA receptors present in immune cells,” says Pokusaeva. Together with their collaborators Dr. Yamada and Dr. Lacorazza they found that when the cells were exposed to secretions from the bacteria, they exhibited increased expression of the GABAA receptor in the immune cells.
While the findings are preliminary, they suggest the possibility that B. dentium and the compounds it secretes could play a role in reducing inflammation associated with inflammatory bowel diseases.
The next step, says Pokusaeva is to conduct in vitro experiments to determine if the increased GABAA expression correlates with a decrease in production of cytokines associated with inflammation. GABAA receptor signaling may also contribute to pain signaling in the gut and may somehow be involved in abdominal pain disorders.
“Our preliminary findings suggest that Bifidobacterium dentium could potentially have an inhibitory role in inflammation; however more research has to be performed to further prove our hypothesis,” says Pokusaeva.
Study indicates promise in Huntington’s treatment
A new study shows that the compound Coenzyme Q10 (CoQ) reduces oxidative damage, a key finding that hints at its potential to slow the progression of Huntington disease. The discovery, which appears in the inaugural issue of the Journal of Huntington’s Disease, also points to a new biomarker that could be used to screen experimental treatments for this and other neurological disorders.
“This study supports the hypothesis that CoQ exerts antioxidant effects in patients with Huntington’s disease and therefore is a treatment that warrants further study,” says University of Rochester Medical Center neurologist Kevin M. Biglan, M.D., M.P.H., lead author of the study. “As importantly, it has provided us with a new method to evaluate the efficacy of potential new treatments.”
Huntington’s disease (HD) is a genetic, progressive neurodegenerative disorder that impacts movement, behavior, cognition, and generally results in death within 20 years of the disease’s onset. While the precise causes and mechanism of the disease are not completely understood, scientists believe that one of the important triggers of the disease is a genetic “stutter” which produces abnormal protein deposits in brain cells. It is believed that these deposits – through a chain of molecular events – inhibit the cell’s ability to meet its energy demands resulting in oxidative stress and, ultimately, cellular death.
Scientists had previously identified the correlation between a specific fragment of genetic code, called 8-hydroxy-2′-deoxyguanosine (80HdG) and the presence of oxidative stress in brain cells. 80HdG can be detected in a person’s blood, meaning that it could serve as a convenient and accessible biomarker for the disease. Researchers have also been evaluating the compound Coenzyme Q10 as a possible treatment for HD because of its ability to support the function of mitochondria – the tiny power plants the provide cells with energy – and counter oxidative stress.
The study’s authors evaluated a series of blood samples of 20 individuals with HD who had previously undergone treatment with CoQ in clinical trial titled Pre-2Care. While these studies showed that CoQ alleviated some symptoms of the disease, it was not known what impact – if any – the treatment had at the molecular level in the brain. Upon analysis, the authors found that 80HdG levels dropped by 20 percent in individuals who had been treated with CoQ.
CoQ is currently being evaluated in a Phase 3 clinical trial, which is the largest therapeutic clinical study to date for HD. The trial – called 2Care – is being run by the Huntington Study Group, an international networks or investigators.
“Identifying treatments that slow the progression or delay the onset of Huntington’s disease is a major focus of the medical community,” said Biglan. “This study demonstrates that 80HdG could be an ideal marker to identify the presence oxidative injury and whether or not treatment is having an impact.”
Peaches, plums, nectarines give obesity, diabetes slim chance
COLLEGE STATION – Peaches, plums and nectarines have bioactive compounds that can potentially fight-off obesity-related diabetes and cardiovascular disease, according to new studies by Texas AgriLife Research.
The study, which will be presented at the American Chemical Society in Philadelphia next August, showed that the compounds in stone fruits could be a weapon against “metabolic syndrome,” in which obesity and inflammation lead to serious health issues, according to Dr. Luis Cisneros-Zevallos, AgriLife Research food scientist.
“In recent years obesity has become a major concern in society due to the health problems associated to it,” said Cisneros-Zevallos, who also is an associate professor at Texas A&M University. “In the U.S., statistics show that around 30 percent of the population is overweight or obese, and these cases are increasing every year in alarming numbers.”
While he acknowledged that lifestyle, genetic predisposition and diet play a major role in one’s tendency toward obesity, “the major concern about obesity is the associated disease known as metabolic syndrome.
“Our studies have shown that stone fruits – peaches, plums and nectarines – have bioactive compounds that can potentially fight the syndrome,” Cisneros-Zevallos said. “Our work indicates that phenolic compounds present in these fruits have anti-obesity, anti-inflammatory and anti-diabetic properties in different cell lines and may also reduce the oxidation of bad cholesterol LDL which is associated to cardiovascular disease.”
What is unique to these fruits, he said, is that their mixture of the bioactive compounds work simultaneously within the different components of the disease.
“Our work shows that the four major phenolic groups – anthocyanins, clorogenic acids, quercetin derivatives and catechins – work on different cells – fat cells, macrophages and vascular endothelial cells,” he explained. “They modulate different expressions of genes and proteins depending on the type of compound.
“However, at the same time, all of them are working simultaneously in different fronts against the components of the disease, including obesity, inflammation, diabetes and cardiovascular disease,” he explained.
Cisneros-Zevallos said this is believed to be the first time that “bioactive compounds of a fruit have been shown to potentially work in different fronts against a disease.”
“Each of these stone fruits contain similar phenolic groups but in differing proportions so all of them are a good source of health promoting compounds and may complement each other,” he said, adding that his team plans to continue studying the role of each type of compound on the molecular mechanisms and confirm the work with mice studies.
Sun exposure and sun-sensitive skin type decreased risk for pancreatic cancer
LAKE TAHOE, Nev. — High levels of ultraviolet radiation at an individual’s birth location, sun-sensitive skin type and a history of skin cancer each decreased risk for pancreatic cancer, according to study results presented at the American Association for Cancer Research’s Pancreatic Cancer: Progress and Challenges conference, held here June 18-21.
Rachel Neale, Ph.D., principal investigator at Queensland Institute of Medical Research in Queensland, Australia, presented the results of a population-based, case-control study that adds to the already conflicting data about sun exposure, vitamin D gained from sun exposure and cancer risk.
“Several ecological studies, including one conducted in Australia, have suggested that people living in areas with high sun exposure have lower risk for pancreatic cancer,” Neale said. “However, some studies of circulating vitamin D indicate that people with high vitamin D are at increased risk, and one study of vitamin D intake supports this increased risk.”
The results of this study support the existing ecological data which indicate that sun exposure has a protective effect against pancreatic cancer.
Neale and colleagues recruited 714 people in Queensland, Australia, between 2007 and 2011. They were matched by age and sex to 709 control participants. All participants were interviewed about socio-demographic information and medical history. In addition, they were asked about the location of their birth, skin cancer history and skin type, defined by skin color, tanning ability and propensity to sunburn.
Using NASA’s Total Ozone Mapping Spectrometer, the researchers assigned a level of ultraviolet radiation to each birth location and then split them into thirds based on how much radiation was present.
Participants born in areas with the highest levels of ultraviolet radiation had a 24 percent lower risk for pancreatic cancer compared with those born in areas of low ultraviolet radiation.
In addition, although all skin types had some significant association with pancreatic cancer risk, those classified as having the most sun-sensitive skin had a 49 percent decreased risk for pancreatic cancer compared with those classified as having the least sun-sensitive skin. Finally, participants with a history of skin cancer or other sun-related skin lesions had a 40 percent lower risk for pancreatic cancer than those who had not reported skin lesions.
“There is increasing interest in the role of sun exposure, which has been largely attributed to the effect of vitamin D, on cancer incidence and mortality,” Neale explained. “It is important that we understand the risks and benefits of sun exposure because it has implications for public health messages about sun exposure, and possibly about policy related to vitamin D supplementation or food fortification.”
Moving forward, Neale recommended that researchers conduct large cohort studies that measure sun exposure comprehensively, and serum vitamin D.
“There are several trials of vitamin D that are either under way or planned, and pooling data from these might give some clue about vitamin D and pancreatic cancer,” Neale said.
Resveratrol may be a natural exercise performance enhancer: U of A medical research
Natural compound found in fruit, nuts and wine led to improved strength and endurance
A natural compound found in some fruits, nuts and red wine may enhance exercise training and performance, demonstrates newly published medical research from the University of Alberta.
Principal investigator Jason Dyck and his team found out in experiments that high doses of the natural compound resveratrol improved physical performance, heart function and muscle strength in lab models.
“We were excited when we saw that resveratrol showed results similar to what you would see from extensive endurance exercise training,” says Dyck, who works in the Faculty of Medicine & Dentistry as a researcher in the department of Pediatrics and the department of Pharmacology. “We immediately saw the potential for this and thought that we identified ‘improved exercise performance in a pill.’ ”
His team’s findings were published in the peer-reviewed Journal of Physiology in late May.
Dyck and his team will soon start starting testing resveratrol on diabetics with heart failure to see if the natural compound can improve heart function for this patient group. The 10-week study is expected to start within the next few months.
“I think resveratrol could help patient populations who want to exercise but are physically incapable. Resveratrol could mimic exercise for them or improve the benefits of the modest amount of exercise that they can do,” says Dyck. “It is very satisfying to progress from basic research in a lab to testing in people, in a short period of time.”
Physicians are biased when evaluating medical conflict of interest policies
Same patterns found in finance industry; Researchers suggest need for third parties in conflict of interest policy-making process
PITTSBURGH—Medical institutions have been under pressure to develop and implement policies to avoid conflicts of interest between physicians and pharmaceutical companies. In most cases, medical professionals who have a stake in the issues at hand craft the conflict of interest policies.
New research from Carnegie Mellon University’s George Loewenstein and Zachariah Sharek and the University of Pittsburgh’s Robert Schoen investigated whether medical professionals making conflict of interest policy decisions are able to separate their policy judgments from their personal, vested interests. The research, which will be published in an upcoming issue of the Journal of Law, Medicine and Ethics, shows that physicians are subject to motivated bias when it comes to assessing the policies intended to regulate their behavior. The research team also tested financial planners and found similar stronger patterns of motivated bias.
Loewenstein, the Herbert A. Simon University Professor of Psychology and Economics, noted that the genesis of the research was “when we became aware of a hospital implementing a conflict of interest policy, heard the objections that were being raised against the policy, and wondered whether they would seem as ridiculous if they were disguised as dealing with a different field.
“Generally, the medical and financial industries have made their own rules,” continued Loewenstein, an expert on bias, conflicts of interest and decision-making. “This research suggests that, while medical and financial professionals should be involved in drafting and implementing their respective conflict of interest policies, they should also bring third parties into the process.”
For the study, the researchers surveyed a mix of physicians, financial planners and a comparably educated control group who were randomly assigned to provide their reactions to a conflict of interest policy that was presented as applying either in a medical context, involving relationships between physicians and the pharmaceutical industry, or in a financial context, dealing with relationships between personal financial planners and companies that market investments. After reading the proposed policies, participants rated how reasonable they thought the policies were. Then, they were presented with objections to the policies and asked to evaluate those. Finally, in light of the objections they had seen and evaluated, they were asked whether their views on the original policy had changed.
The results revealed a strikingly consistent pattern of motivated bias for both physicians and financial planners. Physicians evaluating a conflict of interest policy in a medical context evaluated it negatively, and perceived objections to the policy as largely reasonable. However, when examining the same policies in a financial planning context, physicians were supportive of policies to limit conflict of interest. Financial planners displayed a similar pattern, reacting negatively to the policy that would affect them, but positively when examining the restrictions in a medical context. Finally, the control group with no vested interest evaluated both policies positively, and dismissed the objections as being unreasonable.
“Physicians and financial planners were supportive of a conflict of interest policy, as long as it did not apply to their own industry,” emphasized Schoen, professor of medicine at Pitt.
Sharek, a doctoral candidate in CMU’s Tepper School of Business and lead author of the study, added, “These results suggest that people with vested interests are not only biased, but that they are not aware that they are biased. Additionally, there is nothing to indicate that physicians and financial planners are unique in this regard, so we would expect that this pattern of bias would occur in other domains, such as politics, public policy, and business.”
Trouble on the horizon for GM crops?
Pests are adapting to genetically modified crops in unexpected ways, researchers have discovered – The findings underscore the importance of closely monitoring and countering pest resistance to biotech crops
|IMAGE:Caterpillars of the cotton bollworm, Helicoverpa armigera,feed on many different plants and pose a serious threat to cotton farming.|
Resistance of cotton bollworm to insect-killing cotton plants involves more diverse genetic changes than expected, an international research team reports in the journal Proceedings of the National Academy of Sciences.
To decrease sprays of broad-spectrum insecticides, which can harm animals other than the target pests, cotton and corn have been genetically engineered to produce toxins derived from the bacterium Bacillus thuringiensis, or Bt.
Bt toxins kill certain insect pests but are harmless to most other creatures including people. These environmentally friendly toxins have been used for decades in sprays by organic growers and since 1996 in engineered Bt crops by mainstream farmers.
Over time, scientists have learned, initially rare genetic mutations that confer resistance to Bt toxins are becoming more common as a growing number of pest populations adapt to Bt crops.
In the first study to compare how pests evolve resistance to Bt crops in the laboratory vs. the field, researchers discovered that while some the of the lab-selected mutations do occur in the wild populations, some mutations that differ markedly from those seen in the lab are important in the field.
Caterpillars of the cotton bollworm, Helicoverpa armigera, can munch on a wide array of plants before emerging as moths. This species is the major cotton pest in China, where the study was carried out.
|IMAGE:Bruce Tabashnik, head of the University of Arizona department of entomology, works with Chinese scientists on monitoring and countering pest resistance to genetically engineered crops, which have drastically reduced insecticide…|
Bruce Tabashnik, head of the department of entomology at the University of Arizona College of Agriculture and Life Sciences, who co-authored the study, considers the findings an early warning to farmers, regulatory agencies and the biotech industry.
“Scientists expected the insects to adapt, but we’re just finding out now how they’re becoming resistant in the field,” Tabashnik said.
To avoid surprises, researchers have exposed cotton bollworm populations to Bt toxins in controlled lab experiments and studied the genetic mechanisms by which the insects adapt.
“We try to stay ahead of the game,” he said. “We want to anticipate what genes are involved, so we can proactively develop strategies to sustain the efficacy of Bt crops and reduce reliance on insecticide sprays. The implicit assumption is what we learn from lab-selected resistance will apply in the field.”
That assumption, according to Tabashnik, had never been tested before for resistance to Bt crops.
Now for the first time, the international team gathered genetic evidence from pests in the field, enabling them to directly compare the genes involved in the resistance of wild and lab-reared populations.
They found some resistance-conferring mutations in the field were the same as in lab-reared pests, but some others were strikingly different.
“We found exactly the same mutation in the field that was detected in the lab,” Tabashnik said. “But we also found lots of other mutations, most of them in the same gene and one in a completely different gene.”
|IMAGE:This is an adult cotton bollworm moth.|
A major surprise came when the team identified two unrelated, dominant mutations in the field populations. “Dominant” means that one copy of the genetic variant is enough to confer resistance to Bt toxin. In contrast, resistance mutations characterized before from lab selection are recessive – meaning it takes two copies of the mutation, one provided by each parent, to make an insect resistant to Bt toxin.
“Dominant resistance is more difficult to manage and cannot be readily slowed with refuges, which are especially useful when resistance is recessive,” Tabashnik said.
Refuges consist of plants that do not have a Bt toxin gene and thus allow survival of insects that are susceptible to the toxin. Refuges are planted near Bt crops with the goal of producing enough susceptible insects to dilute the population of resistant insects, by making it unlikely two resistant insects will mate and produce resistant offspring.
According to Tabashnik, the refuge strategy worked brilliantly against the pink bollworm in Arizona, where this pest had plagued cotton farmers for a century, but is now scarce.
The dominant mutations discovered in China throw a wrench in the refuge strategy because resistant offspring arise from matings between susceptible and resistant insects.
He added that the study will enable regulators and growers to better manage emerging resistance to Bt crops.
“We have been speculating and using indirect methods to try and predict what would happen in the field. Only now that resistance is starting to pop up in many places is it possible to actually examine resistance in the field. I think the techniques from this study will be applied to many other situations around the world, and we’ll begin to develop a general understanding of the genetic basis of resistance in the field.”
The current study is part of a collaboration funded by the Chinese government, involving a dozen scientists at four institutions in China and the U.S. Yidong Wu at Nanjing Agricultural University designed the study and led the Chinese effort. He emphasized the importance of the ongoing collaboration for addressing resistance to Bt crops, which is a major issue in China. He also pointed out that the discovery of dominant resistance will encourage the scientific community to rethink the refuge strategy.
Tabashnik said China is the world’s top cotton producer, with about 16 billion pounds of cotton per year. India is number two, followed by the U.S., which produces about half as much cotton as China.
In 2011, farmers worldwide planted 160 million acres of Bt cotton and Bt corn. The percentage of cotton planted with Bt cotton reached 75 per cent in the U.S. in 2011, but has exceeded 90 per cent since 2004 in northern China, where most of China’s cotton is grown.
The researchers report that resistance-conferring mutations in cotton bollworm were three times more common in northern China than in areas of northwestern China where less Bt cotton has been grown.
Even in northern China, however, growers haven’t noticed the emerging resistance yet, Tabashnik said, because only about 2 percent of the cotton bollworms there are resistant.
“As a grower, if you’re killing 98 percent of pests with Bt cotton, you wouldn’t notice anything. But this study tells us there is trouble on the horizon.”
Apple peel compound boosts calorie burning, reduces obesity in mice
Ursolic acid — a waxy substance found in apple peel — increases muscle and brown fat in mice on a high-fat diet: These mice burn more calories and have reduced obesity, pre-diabetes and fatty liver disease than mice not receiving the supplement
Obesity and its associated problems such as diabetes and fatty liver disease are increasingly common global health concerns. A new study by University of Iowa researchers shows that a natural substance found in apple peel can partially protect mice from obesity and some of its harmful effects.
The findings suggest that the substance known as ursolic acid reduces obesity and its associated health problems by increasing the amount of muscle and brown fat, two tissues recognized for their calorie-burning properties.
The study, which was published June 20 in the journal PLoS ONE, was led by Christopher Adams, M.D., Ph.D., UI associate professor of internal medicine and a Faculty Scholar at the Fraternal Order of Eagles Diabetes Research Center at the UI.
“From previous work, we knew that ursolic acid increases muscle mass and strength in healthy mice, which is important because it might suggest a potential therapy for muscle wasting,” Adams says. “In this study, we tested ursolic acid in mice on a high-fat diet — a mouse model of obesity and metabolic syndrome. Once again, ursolic acid increased skeletal muscle. Interestingly, it also reduced obesity, pre-diabetes and fatty liver disease.
“Since muscle is very good at burning calories, the increased muscle in ursolic acid-treated mice may be sufficient to explain how ursolic acid reduces obesity. However, we were surprised to find that ursolic acid also increased brown fat, a fantastic calorie burner. This increase in brown fat may also help protect against obesity.”
Until quite recently, researchers believed that only infants had brown fat, which then disappeared during childhood. However, improved imaging techniques have shown that adults do retain a very small amount of the substance mostly in the neck and between the shoulder blades. Some studies have linked increased levels of brown fat with lower levels of obesity and healthier levels of blood sugar and blood lipid, leading to the suggestion that brown fat may be helpful in preventing obesity and diabetes.
The UI team, which also included Steven Kunkel, Christopher Elmore, Kale Bongers, Scott Ebert, Daniel Fox, Michael Dyle, and Steven Bullard, studied mice on a high-fat diet over a period of several weeks. Half of the animals also received ursolic acid in their high-fat food. Interestingly, mice whose diet included ursolic acid actually ate more food than mice not getting the supplement, and there was no difference in activity between the two groups. Despite this, the ursolic acid-treated mice gained less weight and their blood sugar level remained near normal. Ursolic acid-treated mice also failed to develop obesity-related fatty liver disease, a common and currently untreatable condition that affects about one in five American adults.
Further study showed that ursolic acid consumption increased skeletal muscle, increasing the animals’ strength and endurance, and also boosted the amount of brown fat. Because both muscle and brown fat burn calories, the researchers investigated energy expenditure in the mice and showed that ursolic acid-fed mice burned more calories than mice that didn’t get the supplement.
“Our study suggests that ursolic acid increases skeletal muscle and brown fat leading to increased calorie burning, which in turn protects against diet-induced obesity, pre-diabetes and fatty liver disease,” Adams says. “Brown fat is beneficial and people are trying to figure out ways to increase it. At this point, we don’t know how ursolic acid increases brown fat, or if it increases brown fat in healthy mice. And, most importantly, we don’t know if ursolic acid will benefit people. Our next step is to determine if ursolic acid can help patients.”
How active is your child really?
In work published in the open access journal PLoS ONE today, more than 500 8 to 10-year-olds wore activity monitors providing Newcastle University and University of Strathclyde researchers with a very accurate picture of how little time children spent being physically active.
They were monitored for a range of actions from moving around, climbing stairs to running, playing games and skipping.
Children spent only 4% of awake time in moderate to vigorous intensity physical activity, this is about 20 minutes per day while the recommended amount for health is 60 minutes per day.
At age 8, girls were already less active than boys – something known to occur at secondary school – but this study has shown that the difference in physical activity between boys and girls starts much earlier on.
Older fathers tended to have less active children.
Children who took part in sports clubs outside of school were significantly more active than those who did not.
Parents who restricted access to television were shown to have children who were less active.
Newcastle University’s Dr Mark Pearce led this study funded by the National Prevention Research Initiative. He said: “Given the importance of physical activity in maintaining good health, we know we need to get our kids more active. What we hadn’t known until now is how young we need to be catching them, or the reasons that lay behind their lack of activity.
“Already at the age of eight, we are seeing girls being less active than boys. This is something which we know then gets worse as they approach their teenage years.
“One of the important things is that most girls don’t see sport as cool. We need to be tackling these issues earlier by encouraging girls to exercise, by providing a wider range of opportunities than are currently on offer and by ensuring they see positive female role models, particularly in the media.”
As to why the children of older fathers were found to be less active, Dr Pearce said: “We think there may be a variety of explanations for this such as older fathers reaching more senior posts and having to work longer hours or maybe seeing themselves in a more traditional role so spend less time in active play with their children.”
Professor John Reilly from the University of Strathclyde, one of the researchers involved in this study said: “There is an urgent need for interventions, at home and at school, which will help primary school children become more physically active.”
In the Gateshead Millennium Study, 508 children wore activity monitors for at least three days and their movement was registered which meant their activity levels were objectively measured. The data were then related to an accompanying questionnaire and data collected previously in this study which has been on-going since birth.
Findings included that the average daily percentage of time spent doing moderate or vigorous physical activity was just 4.1%. Girls, on average spent 2.5% less of their day doing activity.
Controversial vaccine trial should never have been run in India, researchers say
Research published today in the Journal of the Royal Society of Medicine raises further questions about a trial of HPV vaccines in India.
The trial, which has now been halted and is the subject of an investigation by the Indian government, was examining the safety and feasibility of offering a vaccine against the virus associated with cervical cancer.
The new study by researchers at Queen Mary, University of London and the University of Edinburgh suggests that lack of data on cervical cancer in India does not support a trial of the vaccine to prevent the disease.
The trial was run by the international health charity PATH and involved more than 23,000 girls from Gujarat and Andhra Pradesh states. A committee of scientists commissioned by the Indian Government to look into the trial said that the study involved a number of serious ethical violations.
The research by Professor Allyson Pollock and colleagues examined a series of claims made by PATH about cervical cancer in India, among them that ‘in raw numbers, India has the largest burden of cancer of the cervix of any country worldwide’.
They found that cancer surveillance, registration and monitoring in India in general – and specifically in the Gujarat and Andhra Pradesh regions – was incomplete, meaning that it would be impossible to tell whether the vaccine would be successful in preventing the disease.
In addition, figures that do exist for India show that incidence rates for cervical cancer are low and fell from around 43 cases per 100,000 in 1982/83 to around 22 per 100,000 in 2004/05. Brazil and Zimbabwe are reported to have around twice the rate.
Professor Pollock explained: “This trial has clearly raised serious concerns for the people and government of India. The aim of our study was to look at whether data on cervical cancer in the country justify the introduction of HPV vaccination.
“We found that current data on cervical cancer incidence do not support PATH’s claim that India has a large burden of cervical cancer or its decision to roll out the vaccine programme.
“The lack of information is important because it means that World Health Organisation criteria for monitoring the effectiveness of the vaccine cannot be fulfilled.
“Neither the epidemiological evidence nor current cancer surveillance systems justify the general rollout ofan HPV vaccination programme in India or in the two states where PATH was conducting its research.”
Professor Pollock continued: “It’s important to compare the burden of cervical cancer in India to other major health concerns, such as primary care, malaria, maternal anaemia and malnutrition, and consider best use of financial resources.
“HPV vaccine which is among the most expensive vaccines on the market is not justified as a health care priority for India.”
OMEGA-3 LOWERS INFLAMMATION IN OVERWEIGHT OLDER ADULTS
COLUMBUS, Ohio – New research shows that omega-3 fatty acid supplements can lower inflammation in healthy, but overweight, middle-aged and older adults, suggesting that regular use of these supplements could help protect against and treat certain illnesses.
Four months of omega-3 supplementation decreased one protein in the blood that signals the presence of inflammation by an average of more than 10 percent, and led to a modest decrease in one other inflammation marker. In comparison, participants taking placebos as a group saw average increases of 36 percent and 12 percent, respectively, of those same markers.
Chronic inflammation is linked to numerous conditions, including coronary heart disease, Type 2 diabetes, arthritis and Alzheimer’s disease, as well as the frailty and functional decline that can accompany aging.
Study participants took either 2.5 grams or 1.25 grams of active omega-3 polyunsaturated fatty acids in their supplements. Polyunsaturated fatty acids are considered“good fats” that, when consumed in proper quantities, are associated with a variety of health benefits. Study participants taking a placebo consumed pills containing less than 2 teaspoons per day of a mix of oils representing a typical American’s daily dietary oil intake.
“Omega-3 fatty acids may be both protective so that inflammation doesn’t go up, as well as therapeutic by helping inflammation go down,” said Jan Kiecolt-Glaser, professor of psychiatry and psychology at Ohio State University and lead author of the study.
“This is the first study to show that omega-3 supplementation leads to changes in inflammatory markers in the blood in overweight but otherwise healthy people. In terms of regulating inflammation when people are already healthy, this is an important study, in that it suggests one way to keep them healthy.”
The study is published online and scheduled for later print publication in the journal Brain, Behavior and Immunity.
The scientists recruited 138 adults – 45 men and 93 women – who were in good health, but who were either overweight or obese and lived sedentary lives. Their average age was 51 years. Based on body mass index, a measure of weight relative to height, 91 percent of the participants were overweight and 47 percent were obese.
Inflammation tends to accompany excess body fat, so the researchers recruited participants who were most likely high in pro-inflammatory blood compounds at the beginning of the study.
“We wanted to have enough room to see a downward trend. Most other trials testing the effects of omega-3 supplements on inflammation used people who were seriously diseased or skinny and healthy,” said Kiecolt-Glaser, also an investigator in Ohio State’s Institute for Behavioral Medicine Research (IBMR). “You can see results in people with serious diseases, but there’s a lot of other noise in that system. We wanted to make sure we were studying results in people who were fairly fit but who weren’t exercising, because exercise can clearly lower inflammation.”
The researchers also excluded from participation people taking a variety of medications to control mood, cholesterol and blood pressure as well as vegetarians, patients with diabetes, smokers, those routinely taking fish oil, people who got more than two hours of vigorous exercise each week and those whose body mass index was either below 22.5 or above 40.
Participants received either a placebo or one of two different doses of omega-3 fatty acids – either 2.5 grams or 1.25 grams per day. The supplements were calibrated to contain a ratio of the two fish oil fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of seven to one. Previous research has suggested that EPA has more anti-inflammatory properties than does DHA.
After four months, participants who had taken the omega-3 supplements had significantly lower levels in their blood of two proteins that are markers of inflammation, also called pro-inflammatory cytokines. The low-dose group showed an average 10 percent decrease in the cytokine interleukin-6 (IL-6), and the high-dose group’s overall IL-6 dropped by 12 percent. In comparison, those taking a placebo saw an overall 36 percent increase in IL-6 by the end of the study.
Levels of the cytokine tumor necrosis factor-alpha (TNF-a) also dropped, but in a more modest way, by 0.2 percent and 2.3 percent in the low- and high-dose groups, respectively. The placebo group’s TNF-a increased by an average of 12 percent.
IL-6 and TNF-a are two of a family of six cytokines that, when stimulated, produce an inflammatory response to a stressor such as an injury or infection, said study co-author Ron Glaser, professor of molecular virology, immunology and medical genetics and director of the IBMR.
“You need this good inflammation for an initial response, but if it stays up, and inflammation becomes chronic, then you’ve got a problem,” Glaser said. “Our research and studies done by others have shown that these two cytokines are clearly related to overall health – and when they’re elevated in the blood, that is not good for overall health. So the more ways we can find to lower them, the better.”
Statistically, there was no significant difference in lowered inflammation between the two doses, but each dose clearly produced cytokine reductions that differed significantly from the placebo group. However, levels of omega-3 fatty acids in participants’ blood increased according to which dose they consumed, which improved their ratio of omega-6 fatty acids to omega-3 fatty acids. The current typical American diet contains between 15 and 17 times more omega-6 than omega-3, a ratio that researchers suggest should be lowered to 4-to-1, or even 2-to-1, to improve overall health.
“Scientists tend to agree that the best way to gauge a person’s omega-3 status is to see whether that ratio goes down,” Belury said. “That’s what we saw in this study, and it was achieved through supplementation. We wanted participants to maintain normal diets and simply add this modest amount of oil to their existing diet. We expected and we found that their blood plasma omega-3 fatty acids went up in a dose-responsive manner.”
The Food and Drug Administration considers daily omega-3 supplementation of up to 3 grams to be “generally regarded as safe.” The doses in this study were within those safety parameters, but the researchers did not extend their findings to make a general recommendation about omega-3 supplementation.
“Although omega-3 fatty acids cannot take the place of good health behaviors, people with established inflammatory diseases or conditions may benefit from their use,” Kiecolt-Glaser said.
The researchers also sought to determine whether omega-3 fatty acids could reduce depression symptoms, but participants had relatively few symptoms to begin with so no significant reductions were seen. Depression is also associated with chronic inflammation, but research hasn’t yet fully defined the mechanisms behind that relationship.
This work was supported in part by grants from the National Institutes of Health. OmegaBrite, a company based in Waltham, Mass., supplied the supplements as an unrestricted gift but did not participate in the study design, results or publication.
Additional co-authors, all at Ohio State, include Rebecca Andridge of the Division of Biostatistics; William Malarkey of the IBMR and the departments of Psychiatry and Internal Medicine; and Beom Seuk Hwang of the IBMR and biostatistics.
Study links carcinogens to cancer stem cells – but spinach can help
CORVALLIS, Ore. – Researchers at Oregon State University have for the first time traced the actions of a known carcinogen in cooked meat to its complex biological effects on microRNA and cancer stem cells.
The findings are part of a growing awareness of the role of epigenetics in cancer, or the ways in which gene expression and cell behavior can be changed even though DNA sequence information is unaltered.
The scientists also found that consumption of spinach can partially offset the damaging effects of the carcinogen. In tests with laboratory animals, it cut the incidence of colon tumors almost in half, from 58 percent to 32 percent.
The research at OSU’s Linus Pauling Institute was recently reported in the journal Molecular Nutrition and Food Research, in work supported by the National Institutes of Health.
“Cancer development is a complex, multi-step process, with damaged cells arising through various means,” said Mansi Parasramka, a postdoctoral scholar with LPI. “This study showed that alterations of microRNAs affect cancer stem cell markers in colon cancer formation.
“MicroRNAs are very small factors that do very big things in cells,” she said.
Traditionally, cancer was thought to be caused by changes in DNA sequence, or mutations, that allowed for uncontrolled cell growth. That’s still true. However, there’s also increasing interest in the role played by epigenetics, in which such factors as diet, environmental toxins, and lifestyle affect the expression of genes – not just in cancer, but also cardiovascular disease, diabetes, and neurological disorders.
Included in this epigenetic equation is the formation of microRNAs – once thought to be “junk DNA” – which researchers were at a loss to understand. It’s now known that they influence which areas of DNA get expressed or silenced.
There are hundreds of microRNAs, and the OSU scientists monitored 679 in their experiments. When they don’t work right, bad things can happen, including abnormal gene expression leading to cancer.
“Recent research is showing that microRNAs are one of the key epigenetic mechanisms regulating cellular functions in normal and diseased tissues,” said Rod Dashwood, the Helen P. Rumbel Professor for Cancer Prevention and director of LPI’s Cancer Chemoprotection Program.
“But unlike mutations which are permanent genetic changes in DNA,” he said, “the good news about epigenetics and microRNA alterations is that we may be able to restore normal cell function, via diet and healthy life style choices, or even drug treatments.”
Epigenetics essentially makes every person biologically unique, Dashwood said, a product of both their genetics and their environment. That includes even identical twins.
The findings of the new study should lead to advances in understanding microRNAs, their effects on cancer stem cells, and the regulatory processes disrupted in disease development, the OSU scientists said. This might lead one day to tailored or “patient specific” therapies for cancer, Dashwood said.
About the Linus Pauling Institute: The Linus Pauling Institute at OSU is a world leader in the study of micronutrients and their role in promoting optimum health or preventing and treating disease. Major areas of research include heart disease, cancer, aging and neurodegenerative disease.
Selenium controls staph on implant material
PROVIDENCE, R.I. [Brown University] — Selenium is an inexpensive element that naturally belongs in the body. It is also known to combat bacteria. Still, it had not been tried as an antibiotic coating on a medical device material. In a new study, Brown University engineers report that when they used selenium nanoparticles to coat polycarbonate, the material of catheters and endotracheal tubes, the results were significant reductions in cultured populations of Staphylococcus aureus bacteria, sometimes by as much as 90 percent.
“We want to keep the bacteria from generating a biofilm,” said Thomas Webster, professor of engineering and orthopaedics, who studies how nanotechnology can improve medical implants. He is the senior author of the paper, published online this week in the Journal of Biomedical Materials Research A.
Biofilms are notoriously tough colonies of bacteria to treat because they are often able to resist antibiotic drugs.
“The longer we can delay or inhibit completely the formation of these colonies, the more likely your immune system will clear them,” Webster said. “Putting selenium on there could buy more time to keep an endotracheal tube in a patient.”
Meanwhile, Webster said, because selenium is actually a recommended nutrient, it should be harmless in the body at the concentrations found in the coatings. Also, it is much less expensive than silver, a less biocompatible material that is the current state of the art for antibacterial medical device coatings.
Webster has been investigating selenium nanoparticles for years, mostly for their possible anticancer effects. As he began to look at their antibiotic properties, he consulted with Hasbro Children’s Hospital pediatrician Keiko Tarquinio, assistant professor of pediatrics, who has been eager to find ways to reduce biofilms on implants.
For this study, Webster and first author Qi Wang grew selenium nanoparticles of two different size ranges and then used solutions of them to coat pieces of polycarbonate using a quick, simple process. On some of the polycarbonate, they then applied and ripped off tape not only to test the durability of the coatings but also to see how a degraded concentration of selenium would perform against bacteria.
On coated polycarbonate — both the originally coated and the tape-tested pieces — Wang and Webster used electron and atomic force microscopes to measure the concentration of nanoparticles and how much surface area of selenium was exposed to interact with bacteria.
One of their findings was that after the tape test, smaller nanoparticles adhered better to the polycarbonate than larger ones.
Then they were ready for the key step: experiments that exposed cultured staph bacteria to polycarbonate pieces, some of which were left uncoated as controls. Among the coated pieces, some had the larger nanoparticles and some had the smaller ones. Some from each of those groups had been degraded by the tape, and others had not.
All four types of selenium coatings proved effective in reducing staph populations after 24, 48, and 72 hours compared to the uncoated controls. The most potent effects — reductions larger than 90 percent after 24 hours and as much as 85 percent after 72 hours — came from coatings of either particle size range that had not been degraded by the tape. Among those coatings that had been subjected to the tape test, the smaller nanoparticle coatings proved more effective.
Staph populations exposed to any of the coated polycarbonate pieces peaked at the 48-hour timeframe, perhaps because that is when the bacteria could take fullest advantage of the in vitro culture medium. But levels always fell back dramatically by 72 hours.
The next step, Webster said, is to begin testing in animals. Such in vivo experiments, he said, will test the selenium coatings in a context where the bacteria have more available food but will also face an immune system response.
The results may ultimately have commercial relevance. Former graduate students developed a business plan for the selenium nanoparticle coatings while in school and have since licensed the technology from Brown for their company, Axena Technologies.
The Hermann Foundation funded the research.
STUDY SHOWS STAGNATING LIFE EXPECTANCIES IN US
HOUSTON – (June 21, 2012) – Despite modest gains in lifespan over the past century, the United States still trails many of the world’s countries when it comes to life expectancy, and its poorest citizens live approximately five years less than more affluent persons, according to a new study from Rice University and the University Colorado at Boulder.
The study, “Stagnating Life Expectancies and Future Prospects in an Age of Uncertainty,” used time-series analysis to evaluate historical data on U.S. mortality from the Human Mortality Database. The study authors reviewed data from 1930 through 2000 to identify trends in mortality over time and forecast life expectancy to the year 2055. Their research will be published in an upcoming issue of Social Science Quarterly.
Although the researchers found that the U.S. can expect very moderate gains in coming years (less than an additional three years through 2055), the U.S. still trails its developed counterparts in life expectancy. For example, the average life expectancy in the U.S. for a person born today is is 78.49, which is significantly lower than people born in Monaco, Macau and Japan, which have the three highest life expectancies (89.68, 84.43 and 83.91 years, respectively). In addition, the most deprived U.S. citizens tend to live five years less than their more affluent countrymen, according to Justin Denney, Rice assistant professor of sociology, who was principal author for the study.
Denney said that in 1930, average life expectancy in the United States was 59.85. By 2000, it rose to 77.1 years. “But when broken down, these numbers show that those gains were mostly experienced between 1930 the 1950s and 1960s,” he said. “Since that time, gains in life expectancy have flattened out.
“During periods of expansion in length of life, a similar expansion has occurred between more and less advantaged groups – the rich get richer, the poor get poorer, inequality grows and life expectancy is dramatically impacted,” Denney said. “And despite disproportionate spending on health care, life expectancy in the U.S. continues to fall down the ladder of international rankings of length of life. It goes to show that prosperity doesn’t necessarily equal long-term health.”
Denney said many of the chronic conditions that have led to smaller gains in life expectancy are more easily treated when people are more financially stable. He said the study shows “the ugly side of inequality,” and he hopes it will draw attention to the fact that more needs to be done to address stagnating life expectancies in the U.S. and eliminate inequalities in the U.S.
“Even in uncertain times, it is important to look forward in preparing for the needs of future populations,” Denney said. “The results presented here underscore the relevance of policy and health initiatives aimed at improving the nation’s health and reveal important insight into possible limits to mortality improvement over the next five decades.”
The paper was co-authored by Robert McNown, Richard Rogers and Steven Doubilet at the University of Colorado-Boulder.
Rice University and the University of Colorado-Boulder funded this study.
Mayo Clinic: Common blood pressure drug linked to severe GI problems
Patients in clinical trial taking Olmesartan ( Benicar) had symptoms of celiac disease
ROCHESTER, Minn. — Mayo Clinic researchers have discovered an association between a commonly prescribed blood pressure drug, Olmesartan, and severe gastrointestinal issues such as nausea, vomiting, diarrhea, weight loss and electrolyte abnormalities — symptoms common among those who have celiac disease. The findings are published online today in the medical journal Mayo Clinic Proceedings.
From 2008-11, Mayo Clinic physicians treated 22 patients with symptoms similar to celiac disease, including intestinal inflammation and abnormalities. Patients came from 17 states, and some had been diagnosed with celiac disease. They had chronic diarrhea and weight loss; the median weight loss was 39 pounds, and one patient lost 125 pounds. Fourteen of the 22 were hospitalized because of the severity of their symptoms. When given a blood test, however, these patients didn’t come back with results typical of celiac disease. They also didn’t respond to treatments such as gluten-free diets.
After examining their medications, Mayo Clinic gastroenterologist Joseph Murray, M.D., pulled several of the patients off Olmesartan. Their symptoms dramatically improved. Eventually, all 22 were taken off the drug, and all showed improvement. Eighteen of the 22 patients had intestinal biopsies after stopping the medication and showed improvement.
“We thought these cases were celiac disease initially because their biopsies showed features very like celiac disease, such as inflammation,” says Dr. Murray, the lead author. “What made them different was they didn’t have the antibodies in their blood that are typical for celiac disease.”
Olmesartan — prescribed for the treatment of hypertension, or high blood pressure — works by blocking substances that tighten blood vessels, allowing blood to flow more smoothly and the heart to pump more efficiently, according to the U.S. National Library on Medicine.
“It’s really an awareness issue. We want doctors to be aware of this issue, so if they see a patient who is having this type of syndrome — they think about medications as a possible association,” Dr. Murray says. “We’ve reported an association. What needs to be known next is the science to understand why there is such an association.”
Pasta made from green banana flour a tasty alternative for gluten-free diets
New option for patients with celiac disease, study in the Journal of the Academy of Nutrition and Dietetics reports
Philadelphia, PA, June 22, 2012 – People with celiac disease struggle with limited food choices, as their condition makes them unable to tolerate gluten, found in wheat and other grains. Researchers from the University of Brazil have developed a gluten-free pasta product from green banana flour, which tasters found more acceptable than regular whole wheat pasta. The product has less fat and is cheaper to produce than standard pastas. Their research is published today in the Journal of the Academy of Nutrition and Dietetics.
“There was no significant difference between the modified pasta and standard samples in terms of appearance, aroma, flavor, and overall quality,” reports lead investigator Renata Puppin Zandonadi, PhD, Department of Nutrition, University of Brazil. “Green bananas are considered a sub-product of low commercial value with little industrial use. For banana growers and pasta product makers, there is the possibility of diversifying and expanding their market.”
Researchers compared a standard whole-wheat pasta preparation made from whole wheat flour and whole eggs with one made from green banana flour, egg whites, water, and gums. The alterations reduced the fat content and increased the protein value of the modified pasta, important because gluten removal typically reduces some proteins responsible for some sensory characteristics of pasta products. The egg whites and gum result in pasta that is less sticky than typical gluten-free pastas, and promote firmness, elasticity, moisture, and uniformity.
The modified pasta decreased fat content by over 98%. This reduction is particularly important to patients with celiac disease, because many gluten-free products compensate for the removal of gluten with high levels of lipid content.
Fifty testers who did not have celiac disease and 25 celiac disease patients compared the pastas. In both groups, the modified pasta was better accepted than the standard in aroma, flavor, texture, and overall quality, indicating that the product can possibly be commercialized to a wider market than just those with celiac disease.
The modified pasta had a high quantity of resistant starch, which may help control glycemic indexes, cholesterol, intestinal regularity, and fermentation by intestinal bacteria. “Considering that untreated celiac disease promotes cancer in intestinal cells and a highly inflammatory mucosal status, developing gluten-free products with bioactive compounds such as the ones present in green banana flour is important for celiac disease patients,” concludes Dr. Zandonadi. “Patients will benefit from ingesting a product with a better nutritional profile made from an ingredient that is produced and consumed throughout the world.”
In an accompanying podcast presentation, Raquel Braz Assunção Botelho, PhD, discusses the potential benefits of green banana flour-based pasta for people with celiac disease.
Declining testosterone levels in men not part of normal aging, study finds
A new study finds that a drop in testosterone levels over time is more likely to result from a man’s behavioral and health changes than by aging. The study results will be presented Monday at The Endocrine Society’s 94th Annual Meeting in Houston.
“Declining testosterone levels are not an inevitable part of the aging process, as many people think,” said study co-author Gary Wittert, MD, professor of medicine at the University of Adelaide in Adelaide, Australia. “Testosterone changes are largely explained by smoking behavior and changes in health status, particularly obesity and depression.”
Many older men have low levels of the sex hormone testosterone, but the cause is not known. Few population-based studies have tracked changes in testosterone levels among the same men over time, as their study did, Wittert said.
In this study, supported by the National Health and Medical Research Council of Australia, the authors analyzed testosterone measurements in more than 1,500 men who had measurements taken at two clinic visits five years apart. All blood testosterone samples underwent testing at the same time for each time point, according to Wittert.
After the researchers excluded from the analysis any men who had abnormal lab values or who were taking medications or had medical conditions known to affect hormones, they included 1,382 men in the data analysis. Men ranged in age from 35 to 80 years, with an average age of 54.
On average, testosterone levels did not decline significantly over five years; rather, they decreased less than 1 percent each year, the authors reported. However, when the investigators analyzed the data by subgroups, they found that certain factors were linked to lower testosterone levels at five years than at the beginning of the study.
“Men who had declines in testosterone were more likely to be those who became obese, had stopped smoking or were depressed at either clinic visit,” Wittert said. “While stopping smoking may be a cause of a slight decrease in testosterone, the benefit of quitting smoking is huge.”
Past research has linked depression and low testosterone. This hormone is important for many bodily functions, including maintaining a healthy body composition, fertility and sex drive. “It is critical that doctors understand that declining testosterone levels are not a natural part of aging and that they are most likely due to health-related behaviors or health status itself,” he said.
Unmarried men in the study had greater testosterone reductions than did married men. Wittert attributed this finding to past research showing that married men tend to be healthier and happier than unmarried men. “Also, regular sexual activity tends to increase testosterone,” he explained.
Fungicide used on farm crops linked to insulin resistance
A fungicide used on farm crops can induce insulin resistance, a new tissue-culture study finds, providing another piece of evidence linking environmental pollutants to diabetes. The results will be presented Saturday at The Endocrine Society’s 94th Annual Meeting in Houston.
“For the first time, we’ve ascribed a molecular mechanism by which an environmental pollutant can induce insulin resistance, lending credence to the hypothesis that some synthetic chemicals might be contributors to the diabetes epidemic,” said investigator Robert Sargis, M.D., Ph.D., instructor in the endocrinology division at the University of Chicago.
The chemical, tolylfluanid, is used on farm crops in several countries outside of the United States to prevent fungal infestation, and sometimes is used in paint on ships to prevent organisms from sticking to their hulls. Animal studies have indicated that the chemical may adversely affect the thyroid gland, as well as other organs, and that it may increase the risk of cancer in humans.
Within the last decade, research attention has increasingly focused on the link between environmental contaminants and the rising rates of obesity and diabetes throughout many parts of the world. In the United States alone, nearly 26 million adults and children have some form of diabetes, according to the American Diabetes Association. A serious disease by itself, diabetes also increases the risk of other medical complications, including heart and blood-vessel diseases.
Normally, the pancreas secretes the hormone insulin, which acts to regulate blood-sugar levels. Among diabetic patients, insulin secretion either decreases or stops altogether, or cells become resistant to the hormone’s activity. These conditions then disrupt the process that transports sugar, or glucose, from the blood to the body’s other cells, which can lead to the dangerously high blood-sugar levels associated with diabetes.
In this project, Sargis and his co-investigators used mouse fat to examine the effects of tolylfluanid on insulin resistance at the cellular level. They found that exposure to tolylfluanid induced insulin resistance in fat cells, which play a critical role in regulating the body’s blood glucose and fat levels. When exposed to tolylfluanid in culture the ability of insulin to trigger action inside the fat cell, or adipocyte, was reduced, which is an early indication of diabetes.
“The fungicide and antifouling agent tolylfluanid may pose a threat to public health through the induction of adipocytic-insulin resistance, an early step in the pathogenesis of type 2 diabetes,” Sargis said. “Based on these studies, further efforts should be undertaken to clarify human exposure to tolylfluanid and the possible metabolic consequences of that exposure.”
At the same time, tolylfluanid-exposed cells stored more fat, or lipids, in a similar action to a steroid called corticosterone. Like this steroid, tolylfluanid bound receptors in fat cells, called glucocorticoid receptors, which help regulate blood-sugar levels, as well as many other important body processes.
“For the public, this raises the specter of environmental pollutants as potential contributors to the metabolic disease epidemic,” said Sargis, adding that, “hopefully, it will put further pressure on public policy makers to reassess the contribution of environmental pollution as a contributor to human disease in order to encourage the development of strategies for reversing those effects.”
Vitamin D tests are inaccurate
MAYWOOD, Il. — Blood tests to measure vitamin D deficiency are among the most frequently ordered tests in medicine.
But a Loyola University Chicago Stritch School of Medicine study of two new vitamin D tests found the kits are inaccurate in many cases. Earle W. Holmes, PhD, presented findings at ENDO 2012, the 94th Annual Meeting and Expo in Houston.
Holmes and colleagues examined how well the two new tests, Abbott Architect and Siemans Centaur2, performed on 163 randomly selected blood samples. In 40 percent of the Abbott Architect specimens and 48 percent of the Siemans Centaur2 specimens, results were at least 25 percent too high or 25 percent too low. (The maximum recommended total allowable error is plus-or-minus 25 percent.)
“There has been an exponential increase in the number of vitamin D tests ordered for patients,” Holmes said. “But our study of two newly approved tests showed they had pretty poor performance.”
The study by Holmes and colleagues included 163 specimens — 123 from women (median age 54) and 40 from men (median age 59). Researchers used the two new test kits on the specimens, and compared results with findings from a gold standard method called LCMS, which has been shown to provide accurate vitamin D measurements. (LCMS stands for liquid chromatography/tandem mass spectrometry.)
The new tests tended to overestimate vitamin D deficiency. According to the LCMS measurements, 33 of the 163 specimens showed vitamin D deficiency. But the Abbott test showed that 45 specimens had vitamin D deficiency and the Siemens test showed that 71 subjects had vitamin D deficiency. Such inaccuracies could lead to overtreatment of vitamin D deficiency, Holmes said.
Holmes said inaccurate test results could lead to misdiagnoses of patients and confound efforts of physicians, nutritionists and researchers to identify the optimal levels of vitamin D for good health.
People get vitamin D from their diet, from exposure to the sun and from supplements. Vitamin D aids in the absorption of calcium, which is needed for strong bones. Vitamin D helps increase bone density and decrease fractures. Recent studies have found vitamin D also may decrease the risk of osteoporosis, high blood pressure, cancer, heart disease and diabetes.
Populations that may be at high risk for vitamin D deficiency include the elderly, people who are obese, babies who are exclusively breast fed and people who don’t get enough sun.
Statins appear associated with reduced risk of recurrent cardiovascular events in men, women
CHICAGO – Cholesterol-lowering statin drugs appear to be associated with reduced risk of recurrent cardiovascular events in men and women, but do not appear to be associated with reduced all-cause mortality or stroke in women, according to a report of a meta-analysis published June 25 in the Archives of Internal Medicine, a JAMA Network publication.
Statins have been used to lower cholesterol levels for the last 20 years, but most of the clinical trials on the drugs have predominantly enrolled men. There have been conflicting results on the benefits of statins for women with cardiovascular disease compared with men in secondary cardiovascular disease prevention, according to the study background.
Jose Gutierrez, M.D., M.P.H., of Columbia University Medical Center, New York, and colleagues conducted a meta-analysis of 11 clinical trials (a total of 43,191 participants) to examine whether statin therapy was more effective than placebo in preventing recurrence of cardiovascular events and all-cause mortality in men and women. Researchers also sought to determine the sex-specific effect of statins on the risk of recurrent cardiac and cerebrovascular events.
“In our results, statin therapy reduced the recurrence rate of any type of cardiovascular event, all-cause mortality, coronary death, any MI [myocardial infarction or heart attack], cardiac intervention, and any stroke type. The stratification by sex showed no statistically significant risk reduction for women taking statins compared with women taking placebo for the reduction of all-cause mortality and any type of stroke,” the authors comment.
However, the authors observe that the results of their meta-analysis “underscore” the low rate of women being enrolled in cardiovascular prevention clinical trials.
“Women represented only a fifth of the studied sample, limiting the strength of our conclusions. In our results, the benefit associated with statin administration in women did not reach statistical significance compared with placebo in at least two outcomes, all-causes mortality and any stroke type. The reason for this difference is uncertain. One possibility is that the small sample size of women limits the power of the study,” the authors note.
The authors conclude “this meta-analysis supports the use of statins in women for the secondary prevention of cardiovascular events.”
(Arch Intern Med. 2012;172:909-919. Available pre-embargo to the media at http://media.jamanetwork.com.)
Ralphs Note…Soooo there is no study showing anywhere at anytime there is any benefit for woman..(Industry sponsored and Non) for over 20 years. But they assume it works anyways, because 8,600 women must not have been enough to show how great these drugs are….Be curious to know what their idea of significant was for cardiovascular disease.
Overweight men can boost low testosterone levels by losing weight
Weight loss can reduce the prevalence of low testosterone levels in overweight, middle-aged men with prediabetes by almost 50 percent, a new study finds. Results will be presented Monday at The Endocrine Society’s 94th Annual Meeting in Houston.
“Doctors should first encourage overweight men with low testosterone levels to try to lose weight through diet and exercise before resorting to testosterone therapy to raise their hormone levels,” said study co-author Frances Hayes, MD, professor at St. Vincent’s University Hospital, Dublin.
The new study involved nearly 900 men with prediabetes (also called impaired glucose tolerance) who had participated in the Diabetes Prevention Program. That now-completed U.S. study showed that people at high risk of Type 2 diabetes could delay or avoid developing the disease through weight loss. Because overweight men are more likely to have low testosterone levels, Hayes and her colleagues studied the effect of weight loss on men’s testosterone levels.
The investigators excluded men from the study who had a known diagnosis of hypogonadism or were taking medications that could interfere with testosterone levels. Hypogonadism is a condition characterized by low testosterone levels with symptoms of male hormone deficiency. Symptoms can include reduced sex drive, poor erections, enlarged breasts and low sperm counts.
The study population had 891 middle-aged men, with an average age of 54 years. The men were randomly assigned to receive one of three treatments: 293 men to lifestyle modification, 305 to the diabetes drug metformin and 293 to inactive placebo pills. Lifestyle modifications consisted of exercising for 150 minutes a week and eating less fat and fewer calories.
The results showed that low testosterone levels are common in overweight men with prediabetes, Hayes said. At the beginning of the study, nearly one in four men had low testosterone levels, considered to be below 300 nanograms per deciliter.
With lifestyle modification, the prevalence of low testosterone levels decreased from about 20 percent to 11 percent after one year, a 46 percent decrease, the authors reported. The prevalence of low testosterone was unchanged in the metformin group (24.8 versus 23.8 percent) and the placebo group (25.6 versus 24.6 percent).
Men in the lifestyle modification group lost an average of about 17 pounds (7.8 kilograms) over the one-year study, according to the abstract. The increase in testosterone levels in that group correlated with decreasing body weight and waist size.
“Losing weight not only reduces the risk of prediabetic men progressing to diabetes but also appears to increase their body’s production of testosterone,” Hayes said.
Treating vitamin D deficiency may improve depression
Women with moderate to severe depression had substantial improvement in their symptoms of depression after they received treatment for their vitamin D deficiency, a new study finds. The case report series will be presented Saturday at The Endocrine Society’s 94th Annual Meeting in Houston.
Because the women did not change their antidepressant medications or other environmental factors that relate to depression, the authors concluded that correction of the patients’ underlying shortage of vitamin D might be responsible for the beneficial effect on depression.
“Vitamin D may have an as-yet-unproven effect on mood, and its deficiency may exacerbate depression,” said Sonal Pathak, MD, an endocrinologist at Bayhealth Medical Center in Dover, Del. “If this association is confirmed, it may improve how we treat depression.”
Pathak presented the research findings in three women, who ranged in age from 42 to 66. All had previously diagnosed major depressive disorder, also called clinical depression, and were receiving antidepressant therapy. The patients also were being treated for either Type 2 diabetes or an underactive thyroid (hypothyroidism).
Because the women had risk factors for vitamin D deficiency, such as low vitamin D intake and poor sun exposure, they each underwent a 25-hydroxyvitamin D blood test. For all three women, the test found low levels of vitamin D, ranging from 8.9 to 14.5 nanograms per milliliter (ng/mL), Pathak reported. Levels below 21 ng/mL are considered vitamin D deficiency, and normal vitamin D levels are above 30 ng/mL, according to The Endocrine Society.
Over eight to 12 weeks, oral vitamin D replacement therapy restored the women’s vitamin D status to normal. Their levels after treatment ranged from 32 to 38 ng/mL according to the study abstract.
After treatment, all three women reported significant improvement in their depression, as found using the Beck Depression Inventory. This 21-item questionnaire scores the severity of sadness and other symptoms of depression. A score of 0 to 9 indicates minimal depression; 10 to 18, mild depression; 19 to 29, moderate depression; and 30 to 63, severe depression.
One woman’s depression score improved from 32 before vitamin D therapy to 12, a change from severe to mild depression. Another woman’s score fell from 26 to 8, indicating she now had minimal symptoms of depression. The third patient’s score of 21 improved after vitamin D treatment to 16, also in the mild range.
Other studies have suggested that vitamin D has an effect on mood and depression, but there is a need for large, good-quality, randomized controlled clinical trials to prove whether there is a real causal relationship, Dr Pathak said.
“Screening at-risk depressed patients for vitamin D deficiency and treating it appropriately may be an easy and cost-effective adjunct to mainstream therapies for depression,” she said.
Removing estrogen from drinking water
Bielefeld University students participating in MIT competition
This release is available in German.
|IMAGE:Love of detail and a great deal of patience are needed to spend hours of one’s free time standing in the laboratory like Derya Kirasi, a student of Genome-Based Systems…|
A biological filter to remove estrogens from waste water and drinking water — 15 Bielefeld students submitting this project to the ‘international Genetically Engineered Machine competition’ (iGEM) at the Massachusetts Institute of Technology (MIT) in Boston, USA are setting their sights high. They are persuading internationally active companies and associations in the biotechnology and chemistry sector to contribute several ten thousands of Euros to cover the costs of entering this rapidly expanding global competition in synthetic biology. Since May, they have been spending their free time in the laboratory making new DNA building blocks, reproducing them, and producing enzymes. First results give reason for optimism.
The birth control pill is a widespread contraception method. However, large amounts of these modified estrogens leave the body again in urine. The conventional methods in sewage treatment plants are unable to treat this waste water sufficiently because the most frequently used estrogen ethinylestradiol is very difficult to break down. As a result, the hormone finds its way into rivers and lakes and also accumulates in drinking water with serious consequences for fish and other aquatic life. These range from reproductive and severe developmental disorders to the formation of female sexual characteristics in males. The long-term consequences of increasing estrogen pollution for human beings are still largely unknown. Nonetheless, declining sperm counts and thereby increasing infertility in men living in industrial nations may well relate to this hormonal pollution. In addition, testicular and prostate cancers as well as osteoporosis (a reduction in bone density) could be a consequence of overly high concentrations of estrogen in the human body.
|IMAGE:This is Bielefeld University’s 2012 iGEM team. Starting in the back row from the left: Agatha Walla, Saskia Scheibler, Moritz Müller, Kevin Jarosch, Robert Braun, Miriam Fougeras. Front row from…|
Bio filters from tree fungi
The goal of the Bielefeld iGEM team is to develop a biological filter in which certain enzymes (so-called laccases) break down the estrogen. Laccases are to be found in many organisms, and one of their properties is an ability to break down aromatic compounds – to which the estrogens belong. One source of particularly efficient laccases for this process is the turkey tail, a type of fungus that likes to grow on trees. The Bielefeld students are aiming to manufacture this enzyme economically and safely with the help of methods from synthetic biology. It should also be possible to extend the concept to other, in part poisonous and carcinogenic pollutants in drinking and waste water. The students already have one first success to announce: they have managed to isolate the genes of several laccases from various bacteria and have placed them in a standard, allowing further development. By the time of the European Jamboree in October, they want to have confirmed how the enzymes break down various substrates such as estrogens, pesticides, and pharmaceuticals and to be starting to immobilize them to filter materials.
Doing research in their own time
The Bielefeld team is composed of 15 students in the Genome-Based Systems Biology, Molecular Cell Biology, and Molecular Biotechnology degree programmes. Participating in the international competition means sacrificing many hours of their own free time, because the Bielefeld students have to carry out the research on top of their regular studies. Moritz Müller, a Master student of Molecular Biotechnology, explains why participating is nonetheless attractive: ‘Taking part in the competition gives you a chance to build up your own laboratory work while you are still studying, to pursue your own ideas, and even carry out your own project. These are the sort of challenges you will be facing in your professional career’. The students are being supported by Professor Dr. Alfred Pühler, Professor Dr. Erwin Flaschel, Dr. Jörn Kalinowski, and Dr. Christian Rückert from Bielefeld University’s CeBiTec (Center for Biotechnology).
Prenatal exposure to common household chemical increases risk for childhood eczema, study says
Phthalate commonly used in vinyl flooring is found in nearly 100 percent of mothers studied
Prenatal exposure to a ubiquitous household chemical called butylbenzyl phthalate (BBzP) can increase a child’s risk for developing eczema, according to research conducted at the Columbia Center for Children’s Environmental Health at the Mailman School of Public Health.
Widely used in vinyl flooring, artificial leather and other materials, BBzB can be slowly released into air in homes.
Details are published in the advance online edition of Environmental Health Perspectives, a journal of the National Institute of Environmental Health Sciences.
Eczema, which is characterized by dry, itchy red skin on the face, scalp, or extremities, is common in early childhood. “While hereditary factors, allergens, and exposure to tobacco smoke are known to contribute to the condition, our study is the first to show that prenatal exposure to BBzB is a risk factor,” says Allan C. Just, PhD, first author on the Mailman School study and currently a postdoctoral researcher at the Harvard School of Public Health.
The study looked at 407 nonsmoking African-American and Dominican women and their children in New York City. Exposure to BBzB was measured through a urine test during the third trimester of pregnancy. Following birth, the mothers were asked if their child had been diagnosed with eczema. The result: onset of eczema by age 2 was 52 percent more likely in children whose mothers had been exposed to higher concentrations of BBzP, compared with those whose mothers had been exposed to lower concentrations. All but one of the women in the study showed some level of exposure to the chemical.
How BBzP might induce eczema remains murky. To explore that question, the researchers looked at allergies as a possible mechanism. Children were tested for three common indoor allergens: cockroaches, dust mites, and mice, as well as for total IgE, a biomarker for an immune response to all allergens. But they found no evidence of a link between BBzP exposure and allergy.
“We know allergies are a factor with some childhood eczema, but our data suggest that is not the case when BBzP is involved,” says senior author Rachel Miller, MD, Director of the Allergy and Immunology fellowship program and Associate Professor of Medicine (in Pediatrics) and Environmental Health Sciences, NewYork-Presbyterian Hospital/Columbia University Medical Center; and a Co-Deputy Director of the Columbia Center for Children’s Environmental Health. “However, these are important findings, given that eczema is a common and uncomfortable disease of early childhood.”
The researchers also found that while African-American mothers in the study were twice as likely as their Dominican-American counterparts to report that their child had been diagnosed with eczema, both groups had a similar association between BBzP exposure and the disease.
Previous research by study co-author Robin M. Whyatt, DrPH, Professor of Clinical Environmental Health Sciences and Co-Deputy Director of the Columbia Center for Children’s Environmental Health, found that exposure to BBzP and other phthalates was shown to delay motor skill development in young children and to increase risk for behavioral problems. Phthalates are also known to disrupt the body’s endocrine system.
Neuroprotective dietary supplements for chronic spinal cord injury
Charlottesville, VA (June 26, 2012). Researchers from the Department of Neurosurgery at the David Geffen School of Medicine and the Department of Integrative Biology and Physiology at UCLA have found that a diet enriched with docosahexaenoic acid (DHA), an omega-3 fatty acid, and curcumin, a component of the Indian spice turmeric, can protect the injured spinal cord and minimize the clinical and biochemical effects of spinal cord myelopathy in rats. This finding is fleshed out in the article “Dietary therapy to promote neuroprotection in chronic spinal cord injury. Laboratory investigation,” by Langston Holly, M.D., and colleagues, published today online in the Journal of Neurosurgery: Spine. DHA reduces inflammation and provides structural material to plasma membranes. Curcumin produces strong anti-inflammatory and antioxidant effects. Both agents are safe to use and have been documented to have positive effects on the injured brain. Thus the researchers hypothesized that the combined effects of DHA and curcumin could protect the spinal cord from the cascade of cellular and related biological injuries that result from chronic cord injury.
Cervical spondylotic myelopathy is the most common disorder of the spine found in middle-aged patients. Neurological deficits associated with this disorder are related to a primary mechanical spinal injury that is followed by a secondary biological injury. Wear and tear on the spine, due to age or congenital narrowing of the spinal canal, leads to mechanical compression of the spinal cord. This cord compression in turn leads to biological cell injury or death and consequent neurological dysfunction. The primary mechanical injury can usually be corrected by surgery or other management strategies; to date, the secondary biological injury has been more difficult to treat.
The authors set out to develop a noninvasive way to promote neuroprotection from the biological injury that follows spinal cord compression in cervical spondylotic myelopathy. In the laboratory, the authors studied three groups of rats. To simulate cervical spondylotic myelopathy, the researchers placed an expandable polyvinyl alcohol sponge between two laminae of the spine in the animals. This produced delayed myelopathy. After the procedure, the first group of rats was fed a “Western diet” (a form of rat chow high in saturated fats and sugar), whereas the second group was fed a diet enriched with DHA and curcumin. A third group was given a standard rat diet and the animal’s spines were left intact.
The animals’ walking ability was examined before the procedure and repeatedly for several weeks following it. The researchers compared each group’s walking behavior before and after the procedure and noted any differences between groups. Animals fed the Western diet demonstrated significant gait dysfunction as early as three weeks postoperatively, which continued throughout the six-week test period. Animals fed a diet enriched with DHA and curcumin displayed no significant difference in walking ability compared with preoperatively and demonstrated significantly better gait function six weeks after the procedure than animals fed the Western diet. Accompanying this paper, the authors provide two videos showing differences in gait function between these two groups.
The authors also examined the effects of diet after spinal injury on the molecular level. They measured levels of 4-hydroxynonenal (4-HNE), brain-derived neurotrophic factor (BDNF), and syntaxin-3 in the region of the rat spine that was compressed as well as in a region lower in the spine—the lumbar enlargement—where nerves controlling the lower limbs are attached to the spinal cord. The lumbar enlargement was included because cord injury can extend downward from the original site. Significantly higher levels of 4-HNE, an indication of severe cellular membrane damage, were found in both spinal sites in rats fed the Western diet. There was no significant difference between the levels of 4-HNE found in rats fed a diet enriched with DHA and curcumin and control rats with intact spines. Levels of BDNF and syntaxin-3 were significantly lower in both spinal sites in rats fed the Western diet. There were no significant differences in the levels of BDNF and syntaxin-3 between rats fed the diet enriched with DHA and curcumin and control rats. BDNF is a key factor involved in neural repair and promotes the transmission of information across synapses. Syntaxin-3 plays an important role in the release of neurotransmitters into the synapses.
This study shows that diet can play an important role in the response of the rat body to spinal injury. Rats fed a diet enriched with DHA and curcumin displayed significantly better walking ability than animals fed a “Western diet” high in saturated fats and sugar. In addition, there were significant differences in the levels of 4-HNE, BDNF, and syntaxin-3 between rats fed the Western diet and rats fed the DHA and curcumin–enriched diet. On the other hand, there were no significant differences in any of the parameters examined between rats fed the enriched diet and control rats with intact spines.
On the basis of their findings, the authors conclude: “DHA and curcumin can counteract the effects of chronic spinal cord compression through several molecular mechanisms, resulting in the preservation of neurological function.”
Phthalate, environmental chemical is linked to higher rates of childhood obesity
Obese children show greater exposure than nonobese children to a phthalate, a chemical used to soften plastics in some children’s toys and many household products, according to a new study, which found that the obesity risk increases according to the level of the chemical found in the bloodstream. The study will be presented Saturday at The Endocrine Society’s 94th Annual Meeting in Houston.
The chemical, di-ethylhexyl phthalate (DEHP), is a common type of phthalate, a group of industrial chemicals that are suspected endocrine disruptors, or hormone-altering agents.
In the study, children with the highest DEHP levels had nearly five times the odds of being obese compared with children who had the lowest DEHP levels, study co-author Mi Jung Park, MD, PhD, said.
“Although this study cannot prove causality between childhood obesity and phthalate exposure, it alerts the public to recognize the possible harm and make efforts to reduce this exposure, especially in children,” said Park, a pediatric endocrinologist in Seoul, Korea, at Sanggye Paik Hospital and professor at Inje University College of Medicine.
Phthalates are found in some pacifiers, plastic food packages, medical equipment and building materials such as vinyl flooring, and even in nonplastic personal care products, including soap, shampoo and nail polish.
Prior research has shown that phthalates may change gene expression associated with fat metabolism, according to Dr. Park. Because past research suggested a link between concentrations of phthalate metabolites and increased waist size in adults, her group studied a possible connection with childhood obesity.
Dr.Park and colleagues measured serum levels of DEHP in 204 children: 105 obese and 99 healthy-weight youth ages 6 to 13 years. The researchers divided these DEHP measurements into four groups from the lowest detectable level (40.2 nanograms per milliliter, or ng/mL) to the highest (69.7 to 177.1 ng/mL).
They found that the obese children had a significantly higher average DEHP level than did the nonobese controls (107 versus 53.8 ng/mL, respectively). In particular, a high DEHP level correlated with body mass index and percentage of fat mass. This increased risk of obesity with elevation of DEHP levels was independent of factors such as physical activity and daily calorie intake, according to the authors.
“More research in people is needed to determine whether DEHP exposure contributes to childhood obesity,” Dr.Park said.
Moderate coffee consumption offers protection against heart failure
Study proposes a change to current guidelines
BOSTON – While current American Heart Association heart failure prevention guidelines warn against habitual coffee consumption, some studies propose a protective benefit, and still others find no association at all. Amidst this conflicting information, research from Beth Israel Deaconess Medical Center attempts to shift the conversation from a definitive yes or no, to a question of how much.
“Our results did show a possible benefit, but like with so many other things we consume, it really depends on how much coffee you drink,” says lead author Elizabeth Mostofsky, MPH, ScD, a post-doctoral fellow in the cardiovascular epidemiological unit at BIDMC. “And compared with no consumption, the strongest protection we observed was at about four European, or two eight-ounce American, servings of coffee per day.”
The study published June 26 online in the Journal Circulation: Heart Failure, found that these moderate coffee drinkers were at 11 percent lower risk of heart failure.
Data was analyzed from five previous studies – four conducted in Sweden, one in Finland – that examined the association between coffee consumption and heart failure. The self-reported data came from 140,220 participants and involved 6,522 heart failure events.
In a summary of the published literature, the authors found a “statistically significant J-shaped relationship” between habitual coffee consumption and heart failure, where protective benefits begin to increase with consumption maxing out at two eight-ounce American servings a day. Protection slowly decreases the more coffee is consumed until at five cups, there is no benefit and at more than five cups a day, there may be potential for harm.
It’s unclear why moderate coffee consumption provides protection from heart failure, but the researchers say part of the answer may lie in the intersection between regular coffee drinking and two of the strongest risk factors for heart failure – diabetes and elevated blood pressure.
“There is a good deal of research showing that drinking coffee lowers the risk for type 2 diabetes, says senior author Murray Mittleman, MD, DrPH, a physician in the Cardiovascular Institute at Beth Israel Deaconess Medical Center, an Associate Professor of Medicine at Harvard Medical School and director of BIDMC’s cardiovascular epidemiological research program. “It stands to reason that if you lower the risk of diabetes, you also lower the risk of heart failure.”
There may also be a blood pressure benefit. Studies have consistently shown that light coffee and caffeine consumption are known to raise blood pressure. “But at that moderate range of consumption, people tend to develop a tolerance where drinking coffee does not pose a risk and may even be protective against elevated blood pressure,” says Mittleman.
This study was not able to assess the strength of the coffee, nor did it look at caffeinated versus non-caffeinated coffee.
“There is clearly more research to be done,” says Mostofsky. “But in the short run, this data may warrant a change to the guidelines to reflect that coffee consumption, in moderation, may provide some protection from heart failure.”
Glucose deprivation activates feedback loop that kills cancer cells, UCLA study shows
Compared to normal cells, cancer cells have a prodigious appetite for glucose, the result of a shift in cell metabolism known as aerobic glycolysis or the “Warburg effect.” Researchers focusing on this effect as a possible target for cancer therapies have examined how biochemical signals present in cancer cells regulate the altered metabolic state.
Now, in a unique study, a UCLA research team led by Thomas Graeber, a professor of molecular and medical pharmacology, has investigated the reverse aspect: how the metabolism of glucose affects the biochemical signals present in cancer cells.
In research published June 26 in the journal Molecular Systems Biology, Graeber and his colleagues demonstrate that glucose starvation — that is, depriving cancer cells of glucose —activates a metabolic and signaling amplification loop that leads to cancer cell death as a result of the toxic accumulation of reactive oxygen species, the cell-damaging molecules and ions targeted by antioxidants like vitamin C.
The research, which involved UCLA scientists from the Crump Institute for Molecular Imaging, the Institute for Molecular Medicine, the California NanoSystems Institute, the Jonsson Comprehensive Cancer Center, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and the Department of Pathology and Laboratory Medicine, demonstrates the power of systems biology in uncovering relationships between metabolism and signaling at the network level.
“Most strikingly, our discovery that glucose withdrawal causes both cell death and increased tyrosine phosphorylation is intriguing because increased tyrosine kinase signaling is normally associated with cell growth,” said Nicholas A. Graham, a senior postdoctoral scholar in Graeber’s lab who helped design the project.
To explain the seemingly contradictory result that glucose deprivation reduced viability and at the same time increased signaling, the authors used an unbiased systems-biology approach that included phospho-tyrosine mass spectrometry and other biochemical profiling techniques.
Assessing the “crosstalk” between metabolism and signaling, they discovered that the glucose deprivation activates a positive feedback loop whereby the withdrawal of glucose induces increased levels of reactive oxygen species, which in turn inhibit negative regulators of tyrosine signaling. The resulting supra-physiological levels of tyrosine phosphorylation then generate additional reactive oxygen species.
“Because cancer cells live on the edge of what is metabolically feasible, this amplifying cycle of oxidative stress ultimately overwhelms and kills the cancer cell,” Graeber explained. “These findings illustrate the delicate balance that exists between metabolism and signaling in the maintenance of cancer cell homeostasis.”
In addition, the authors showed the possibility of exploiting this positive feedback loop for therapeutic intervention. Combining short-term glucose deprivation with an inhibitor of tyrosine phosphatases, they demonstrated synergistic cell death in a cancer cell line.
“Understanding the links between metabolism and signaling will empower new therapeutic approaches toward inducing this metabolic catastrophe,” Graham said. “This study provides a framework for rational design of combinatorial therapeutics targeting both metabolism and signaling in cancer.”
The findings by Graeber and his colleagues add to the emerging concept of systems integration between oncogenic signaling networks and the metabolism of malignant tumors. The work lays a foundation for future studies delineating how signaling and metabolism are linked, with the ultimate goal of refining therapeutic strategies targeting cancer metabolism.
Ralph’s Note – Sugar Feeds Cancer
Diet rich in vegetables may help stave off acute pancreatitis
Vegetables, fruit and the risk of non-gallstone-related acute pancreatitis: A population-based prospective cohort study
A diet rich in vegetables could help stave off the development of the serious condition acute pancreatitis, suggests a large study published online in the journal Gut.
Pancreatitis refers to inflammation of the pancreas – the gland behind the stomach, which, among other things, releases digestive enzymes to break down food. Occasionally these enzymes become active inside the pancreas, and start to digest the gland itself. In up to one in five of those with acute pancreatitis symptoms are severe and potentially life threatening.
Previous research suggests that excessive production of free radicals, which are by-products of cellular activity, is associated with acute pancreatitis. Furthermore, levels of antioxidant enzymes, which mop up free radicals, are increased during an attack. The authors therefore wanted to know if an imbalance in antioxidant levels, associated with dietary factors, might make the pancreas more sensitive to the effects of free radicals and so increase the risk of acute pancreatitis.
They tracked the health of a population-based sample of 80,000 adults living in central Sweden for an average of 11 years, following the completion of a comprehensive dietary questionnaire in 1997 on how often they had eaten from a range of 96 food items over the preceding year.
Average vegetable and fruit consumption was around 2.5 and just under 2 servings, respectively, every day. In general, those who ate the fewest daily servings of vegetables were men, smokers, and those who had not gone on to higher education.
A similar profile was seen for fruit consumption, although people in this group were more likely to drink alcohol and to have diabetes.
During the monitoring period, 320 people developed acute pancreatitis that was not associated with the complications of gallstones – a relatively common cause of the condition.
The amount of fruit consumed did not seem to influence the risk of developing acute pancreatitis, but this was not the case for vegetables.
After taking account of factors likely to influence the results, the analysis showed that those who ate the most vegetables – more than 4 servings a day – were 44% less likely to develop acute pancreatitis than were those who ate the least – less than 1 serving a day.
The protection afforded by a diet rich in vegetables seemed to be the strongest among those who consumed more than one drink of alcohol a day and those who were overweight (BMI of 25 or more).
The risk of developing the condition fell by 71% among drinkers and by 51% among those who were overweight, when comparing those in the highest with those in the lowest, category of vegetable consumption.
The most likely explanation for the protective effect of vegetables is the high level of antioxidants they contain, say the authors.
The reason why fruit (which also contains high levels of antioxidants) did not seem to affect the risk of acute pancreatitis may lie in its fructose content, which might counter the effects of antioxidants say the authors. Previous research has linked fructose to free radical production.
If their findings are confirmed by other research, the authors suggest that boosting dietary intake of vegetables may help to stave off the development of acute pancreatitis that is unrelated to gallstones.
Menopausal women could ‘work out’ their hot flashes
Menopausal women who exercise may experience fewer hot flashes in the 24 hours following physical activity, according to health researchers.
In general, women who are relatively inactive or are overweight or obese tend to have a risk of increased symptoms of perceived hot flashes, noted Steriani Elavsky, assistant professor of kinesiology at Penn State.
Perceived hot flashes do not always correspond to actual hot flashes. Most previous research analyzed only self-reported hot flashes. This is the first study known to the researchers to look at objective versus subjective hot flashes.
Elavsky and colleagues studied 92 menopausal women for 15 days. The women recruited for this study were different from many earlier menopause studies, said Elavsky. In the past, women in menopause studies were experiencing severe symptoms and seeking help. They were probably not representative of the general population.
“Our sample included women with mild to moderate symptoms and they were recruited for a study of physical activity, not for a study of menopause,” said Elavsky. “We recruited women residing in the community. We used recruitment sources that included a variety of outlets in the community frequented by women, like libraries, fairs, gyms, advertisements in local newspapers, etc.”
The women were 40 to 59 years old, with an average of two children and were not on hormone therapy. During analysis the researchers separated the women into normal weight and overweight/obese categories and higher fit and lower fit categories. These categories were not necessarily mutually exclusive.
The participants wore accelerometers to monitor their physical activity and also wore monitors that measured skin conductance, which varies with the moisture level of the skin. Each participant recorded the individual hot flashes she had throughout the 15-day period on a personal digital assistant.
Through these two methods of recording hot flashes, the researchers found the frequency of objective and subjective hot flashes. Objective hot flashes occurred when the monitor recorded them; subjective hot flashes occurred when the woman reported them. When an objective and a subjective hot flash were recorded within five minutes of each other, it was considered a “true positive” hot flash, the researchers report in the current issue of Menopause.
“Some physiological explanations would suggest that performing physical activity could increase hot flashes because it acutely increases body core temperature,” said Elavsky.
To the contrary, the researchers found that this premise was not true, as on average the women in the study experienced fewer hot flash symptoms after exercising. However, the women who were classified as overweight, having a lower level of fitness or were experiencing more frequent or more intense hot flashes, noticed the smallest reduction in symptoms.
It is not yet known if a woman could use diet and exercise to lose weight and become more fit and therefore experience fewer hot flashes, but it is a possibility worthy of future investigation, noted the researchers.
“For women with mild to moderate hot flashes, there is no reason to avoid physical activity for the fear of making symptoms worse,” said Elavsky. “In fact, physical activity may be helpful, and is certainly the best way to maximize health as women age. Becoming and staying active on a regular basis as part of your lifestyle is the best way to ensure healthy aging and well being, regardless of whether you experience hot flashes or not.”
Also working on this research were Joaquin U. Gonzales, assistant professor of exercise physiology, Texas Tech University; David N. Proctor and Nancy I. Williams, both professors of kinesiology and physiology, Penn State; and Victor W. Henderson, professor of health research and policy and neurology and neurological sciences, Stanford University.
Dietary fiber alters gut bacteria, supports gastrointestinal health
URBANA – A University of Illinois study shows that dietary fiber promotes a shift in the gut toward different types of beneficial bacteria. And the microbes that live in the gut, scientists now believe, can support a healthy gastrointestinal tract as well as affect our susceptibility to conditions as varied as type 2 diabetes, obesity, inflammatory bowel disease, colon cancer, and autoimmune disorders such as rheumatoid arthritis.
As these microbes ferment fiber in the intestine, short-chain fatty acids and other metabolites are produced, resulting in many health benefits for the host, said Kelly Swanson, a U of I professor of animal sciences.
“When we understand what kinds of fiber best nurture these health-promoting bacteria, we should be able to modify imbalances to support and improve gastrointestinal health,” he said.
This research suggests that fiber is good for more than laxation, which means helping food move through the intestines, he added.
“Unfortunately, people eat only about half of the 30 to 35 grams of daily fiber that is recommended. To achieve these health benefits, consumers should read nutrition labels and choose foods that have high fiber content,” said Swanson.
In the placebo-controlled, double-blind intervention study, 20 healthy men with an average fiber intake of 14 grams a day were given snack bars to supplement their diet. The control group received bars that contained no fiber; a second group ate bars that contained 21 grams of polydextrose, which is a common fiber food additive; and a third group received bars with 21 grams of soluble corn fiber.
On days 16-21, fecal samples were collected from the participants, and researchers used the microbial DNA they obtained to identify which bacteria were present. DNA was then subjected to 454 pyrosequencing, a “fingerprinting” technique that provides a snapshot of all the bacterial types present.
Both types of fiber affected the abundance of bacteria at the phyla, genus, and species level. When soluble corn fiber was consumed, Lactobacillus, often used as a probiotic for its beneficial effects on the gut, increased. Faecalibacterium populations rose in the groups consuming both types of fiber.
According to Swanson, the shifts in bacteria seen in this study—which occurred when more and differing types of fiber were consumed—were the opposite of what you would find in a person who has poor gastrointestinal health. That leads him to believe that there are new possibilities for using pre- and probiotics to promote intestinal health.
“For example, one type of bacteria that thrived as a result of the types of fiber fed in this study is inherently anti-inflammatory, and their growth could be stimulated by using prebiotics, foods that promote the bacteria’s growth, or probiotics, foods that contain the live microorganism,” he said.
Caffeine boosts power for elderly muscles
A new study to be presented at the Society for Experimental Biology meeting on 30th June has shown that caffeine boosts power in older muscles, suggesting the stimulant could aid elderly people to maintain their strength, reducing the incidence of falls and injuries.
For adults in their prime, caffeine helps muscles to produce more force. But as we age, our muscles naturally change and become weaker.
Sports scientists at Coventry University looked for the first time at whether these age-related changes in muscle would alter the effect of caffeine. They found that caffeine continued to enhance muscle performance in two different muscles from mice, although it was less effective in older muscles.
Jason Tallis, the study’s primary author, said: “Despite a reduced effect in the elderly, caffeine may still provide performance-enhancing benefits.”
For adults in their prime, caffeine helps muscles to produce more force. But as we age, our muscles naturally change and become weaker. So, sports scientists at Coventry University looked for the first time at whether these age-related changes in muscle would alter the effect of caffeine.
Caffeine’s effect was smallest for juvenile muscles, suggesting caffeine may not have an enhancing effect in developing muscles.
The decline in muscle strength that occurs as we age contributes to injuries and reduces quality of life. The process is not well understood, but it is clear that preserving muscle tone is key.
Tallis said: “With the importance of maintaining a physically active lifestyle to preserve health and functional capacity, the performance-enhancing benefit of caffeine could prove beneficial in the aging population.”
The researchers isolated muscles from mice ranging in age from juvenile to elderly, then tested their performance before and after caffeine treatment. They looked at two different skeletal muscles, which are the muscles we can control voluntarily. The first was the diaphragm, a core muscle used for respiration; the second was a leg muscle called the extensor digitorum longus (EDL), used for locomotion.
Flu immunity is affected by how many viruses actually cause the infection
New research published in the Journal of Leukocyte Biology suggests that the immune response differs depending on the amount of virus received during infection
Bethesda, MD—Not only does the type of flu virus affect a patient’s outcome, but a new research report appearing in the Journal of Leukocyte Biology suggests that the number of viruses involved in the initial infection may be important too. Scientists from Canada found that when mice were infected by relatively high concentrations of the flu virus, they not only developed immunity against the virus that infected them, but this also promoted the generation of a type of immune cell in the lungs poised to rapidly react against infections with other strains of the flu, as well. Mice that were infected with a relatively low concentration of the virus developed weaker immunity against the strain that infected them, did not build up this crucial population of immune cells in the lungs, and showed only delayed immunity toward other flu strains. This discovery could pave the way for new prophylactic strategies to fight flu infections and provides a novel basis for vaccine design.
“Hopefully, the findings of our study will help to develop better vaccine preparations that will be more effective in inducing protective cellular immunity to fight against infectious pathogens such as bacteria, viruses and fungi,” said Martin V. Richter, Ph.D., the lead researcher involved in the work from the Department of Medicine at the Université de Sherbrooke and Centre de Recherche Clinique Étienne-Le Bel in Québec, Canada.
To make this discovery, scientists infected two groups of mice with two different infectious doses of influenza A (H3N2) and analyzed several aspects of inflammation and immunity during the initial infection as well as during reinfection with a different strain of virus. The first group was infected with a low dose of the virus whereas the second group was infected with a high dose of the same virus. Mice infected with the high dose showed increased morbidity, a greater degree of lung inflammation, but also a greater recruitment of influenza-specific immune cells (CD8+ T cells) into their lungs, and a better generation of long-lived respiratory CD8+ T cells called memory CD8+ T cells. In contrast, the mice infected with the low dose of virus suffered less from primary infection but all of the immune responses were induced to lower levels. Consequently, reinfection of mice, 60 days after primary infection, revealed that mice previously infected with a higher dose showed increased protection due to greater magnitude of the memory CD8+ T cell pool present in their lungs before reinfection. This is the first demonstration that the initial infectious dose has an important impact on the generation of specific types of immune memory cells and on the degree of immune protection against reinfection.
“Recent experience with emerging and mutating strains of influenza virus highlight how very few changes in this virus could lead to a catastrophic flu crisis,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. “While considerable efforts have been invested in predicting new emerging flu strains for our yearly vaccines, it is impossible to prepare for every possible way the flu can mutate. This new research shows that it may be possible to enhance current vaccines to offer broader protection against different flu strains, known and unknown.”
Researchers discover potential explanation for why a diet high in DHA improves memory
We’ve all heard that eating fish is good for our brains and memory. But what is it about DHA, an omega-3 fatty acid found in fish, that makes our memory sharper?
Medical researchers at the University of Alberta discovered a possible explanation and just published their findings in the peer-reviewed journal Applied Physiology, Nutrition, and Metabolism.
Principal investigator Yves Sauve and his team discovered lab models fed a high-DHA diet had 30 per cent higher levels of DHA in the memory section of the brain, known as the hippocampus, when compared to animal models on a regular, healthy diet.
“We wanted to find out how fish intake improves memory,” says Sauve, a researcher in the Faculty of Medicine & Dentistry who works in the department of physiology, the department of ophthalmology and the Centre for Neuroscience.
“What we discovered is that memory cells in the hippocampus could communicate better with each other and better relay messages when DHA levels in that region of the brain were higher. This could explain why memory improves on a high-DHA diet.”
Sauve noted it is a key finding that when a diet is supplemented with DHA, that additional stores of the omega-3 fatty acid are deposited in the brain. His team confirmed this finding, a discovery other labs have noted as well.
Supplementing your diet with DHA, such as increasing fish intake or taking supplements, could prevent declining DHA levels in the brain as we age, says Sauve.
This research was funded by Alberta Innovates – Health Solutions.
Earlier this year, Sauve and other colleagues discovered DHA prevents the accumulation of a toxic molecule at the back of the eye that causes age-related vision loss. He is continuing his research in this area.
Necrosis after cortisone injections
Injections of corticoid preparations can have severe side effects. In this issue of Deutsches Ärzteblatt International, Christian Holland and coauthors contribute to physicians’ awareness of problems of this type with a report on the relevant findings of medicolegal expert committees in Germany (Dtsch Arztebl Int 2012; 109: 425-30.
One patient, for example, received multiple intramuscular injections of dexamethasone and diclofenac for the treatment of back pain. Six weeks after the last injection, 500 g of necrotic tissue had to be surgically removed from the site of the injections; a subsequent wound infection led to multiple further hospitalizations. The authors describe both aseptic and septic complications, including abscesses and purulent joint infections. When they affect the spine, such complications can cause weakness of varying degrees of severity, ranging all the way to para- or tetraplegia. Fatal sepsis can also occur.
From 2005 to 2009, the German medicolegal expert committees and arbitration panels dealt with 278 cases of complications after corticoid injections. Medical errors were found to have been committed in 40% of cases. Typical errors were faulty asepsis, treatment without indication, and injections that were too closely spaced in time or in excessive doses. Furthermore, whenever it is determined that a patient has not given legally valid informed consent for an injection, the physician is liable for any and all adverse consequences of the injection for the patient’s health. By giving physician readers the appropriate knowledge base, the article is intended to help them avoid such difficult medicolegal situations.
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