Health Technology Research Synopsis
131st Issue Date 15 JUN 2012
Compiled By Ralph Turchiano
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Please Excuse the Poor Formating. Was Copied and Pasted from my Original
Editors Top Five:
1. The real culprit behind hardened arteries? Stem cells, says landmark study
2. Ginseng fights fatigue in cancer patients, Mayo Clinic-led study
3. Fish show autism-like gene expression in water with psychoactive pharmaceuticals
4. Hidden vitamin in milk yields remarkable health benefits
5. Epileptic seizures linked to common childhood viral infection
In this issue:
1. How infectious disease may have shaped human origins
2. Acetaminophen overdoses in children can be life-threatening but are avoidable
3. Ginseng fights fatigue in cancer patients, Mayo Clinic-led study finds
4. Joslin researchers find ‘good fat’ activated by cold, not ephedrine
5. High blood caffeine levels in older adults linked to avoidance of Alzheimer’s disease
6. Milk ingredient does a waistline good
7. Team determines how estrogens to persist in dairy wastewater
8. Calorie-restricted diet keeps heart young
9. The real culprit behind hardened arteries? Stem cells, says landmark study
10. Fish show autism-like gene expression in water with psychoactive pharmaceuticals
11. 1 million billion billion billion billion billion billion: Number of undiscovered drugs
12. Some adults with sleep disturbances are actually afraid of the dark, study says
13. Have no fear: Most cases of thyroid cancer do not affect survival
14. Statins shown to cause fatigue
15. Sweet minty relief for cough
16. Breast cancer risk can be lowered by avoiding unnecessary medical imaging
17. Sick from your stomach: Bacterial changes may trigger diseases like rheumatoid arthritis
18. Western diet changes gut bacteria and triggers colitis in those at risk
19. Folic acid intake during early pregnancy associated with reduced risk of autism in offspring
20. Epileptic seizures linked to common childhood viral infection
21. Breast milk kills HIV and blocks its oral transmission in humanized mouse
22. Hidden vitamin in milk yields remarkable health benefits
23. Vitamin D with calcium shown to reduce mortality in elderly
24. BPA exposure effects may last for generations
How infectious disease may have shaped human origins
Inactivation of 2 genes may have allowed escape from bacterial pathogens, researchers say
IMAGE:Escherichia colibacteria, like these in a false-color scanning electron micrograph by Thomas Deerinck at UC San Diego’s National Center for Microscopy and Imaging Research, cause a variety of often…
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Roughly 100,000 years ago, human evolution reached a mysterious bottleneck: Our ancestors had been reduced to perhaps five to ten thousand individuals living in Africa. In time, “behaviorally modern” humans would emerge from this population, expanding dramatically in both number and range, and replacing all other co-existing evolutionary cousins, such as the Neanderthals.
The cause of the bottleneck remains unsolved, with proposed answers ranging from gene mutations to cultural developments like language to climate-altering events, among them a massive volcanic eruption.
Add another possible factor: infectious disease.
In a paper published in the June 4, 2012 online Early Edition of The Proceedings of the National Academy of Sciences, an international team of researchers, led by scientists at the University of California, San Diego School of Medicine, suggest that inactivation of two specific genes related to the immune system may have conferred selected ancestors of modern humans with improved protection from some pathogenic bacterial strains, such as Escherichia coli K1 and Group B Streptococci, the leading causes of sepsis and meningitis in human fetuses, newborns and infants.
“In a small, restricted population, a single mutation can have a big effect, a rare allele can get to high frequency,” said senior author Ajit Varki, MD, professor of medicine and cellular and molecular medicine and co-director of the Center for Academic Research and Training in Anthropogeny at UC San Diego. “We’ve found two genes that are non-functional in humans, but not in related primates, which could have been targets for bacterial pathogens particularly lethal to newborns and infants. Killing the very young can have a major impact upon reproductive fitness. Species survival can then depend upon either resisting the pathogen or on eliminating the target proteins it uses to gain the upper hand.”
In this case, Varki, who is also director of the UC San Diego Glycobiology Research and Training Center, and colleagues in the United States, Japan and Italy, propose that the latter occurred. Specifically, they point to inactivation of two sialic acid-recognized signaling receptors (siglecs) that modulate immune responses and are part of a larger family of genes believed to have been very active in human evolution.
Working with Victor Nizet, MD, professor of pediatrics and pharmacy, Varki’s group had previously shown that some pathogens can exploit siglecs to alter the host immune responses in favor of the microbe. In the latest study, the scientists found that the gene for Siglec-13 was no longer part of the modern human genome, though it remains intact and functional in chimpanzees, our closest evolutionary cousins. The other siglec gene – for Siglec-17 – was still expressed in humans, but it had been slightly tweaked to make a short, inactive protein of no use to invasive pathogens.
“Genome sequencing can provide powerful insights into how organisms evolve, including humans,” said co-author Eric D. Green, MD, PhD, director of the National Human Genome Research Institute at the National Institutes of Health.
In a novel experiment, the scientists “resurrected” these “molecular fossils” and found that the proteins were recognized by current pathogenic strains of E. coli and Group B Streptococci. “The modern bugs can still bind and could potentially have altered immune reactions,” Varki said.
Though it is impossible to discern exactly what happened during evolution, the investigators studied molecular signatures surrounding these genes to hypothesize that predecessors of modern humans grappled with a massive pathogenic menace between 100,000 and 200,000 years ago. This presumed “selective sweep” would have devastated their numbers. Only individuals with certain gene mutations survived – the tiny, emergent population of anatomically modern humans that would result in everyone alive today possessing a non-functional Siglec-17 gene and a missing Siglec-13 gene.
Varki said it’s probable that humanity’s evolutionary bottleneck was the complex result of multiple, interacting factors. “Speciation (the process of evolving new species from existing ones) is driven by many things,” he said. “We think infectious agents are one of them.”
Acetaminophen overdoses in children can be life-threatening but are avoidable
Acetaminophen, a widely available over-the-counter medication, can cause liver toxicity in children if doses are exceeded, and more public education is needed to warn of potential adverse effects, states an article published in CMAJ (Canadian Medical Association Journal).
“Acetaminophen overdose is a major cause of acute liver failure and is the most common identifiable cause of acute liver failure in children,” writes Dr. Rod Lim, Department of Pediatrics, Children’s Hospital, London Health Sciences Centre, London, Ontario, with coauthors. “Repeated supratherapeutic dosing [above the recommended dose], accidental overdose due to error and intentional ingestion can all result in acute liver failure and even death.”
The authors cite a case study of a 22-day-old baby in which the parents misunderstood the correct dose of acetaminophen and administered too much analgesic for a circumcision. After the procedure, when the doctor instructed the parents to give another dose, they discovered the error. In this case, N-acetylcysteine with dextrose was given intravenously, and the child recovered within about 24 hours after ingesting the medication.
N-acetylcysteine is the standard treatment for liver toxicity related to an overdose of acetaminophen and is usually successful if started within eight hours after ingesting the drug.
Medication errors involving children are a serious issue, and dosing is complicated by the need to dose by the child’s weight and convert this dose to a volume because many medications for children are in liquid form. A report from the US poison control centres and the American Academy of Pediatrics, which analyzed 238 instances of serious medication errors in children under age six, found that 11% of children who are given pharmaceuticals experience a medication error such as an incorrect medication, incorrect dose or method of administering. Acetaminophen overdose was the most common single agent responsible for a life-threatening event, longer-term illness or death.
A better approach is needed to prevent these avoidable, and life-threatening, errors.
“Although physicians and pharmacists should continue to educate parents and caregivers regarding the medications prescribed, one-to-one communication cannot be the sole approach to reducing errors in medication administration,” write the authors. “Error reduction on a large scale requires systems-based interventions and prevention.”
Suggestions include better labelling and dosing information, improved dosing devices — many parents use spoons, which are not standard sizes and can lead to overdoses — and placing acetaminophen behind the counter to ensure that a pharmacist can counsel parents on correct dosing.
Ginseng fights fatigue in cancer patients, Mayo Clinic-led study finds
ROCHESTER, Minn. — High doses of the herb American ginseng (Panax quinquefolius) over two months reduced cancer-related fatigue in patients more effectively than a placebo, a Mayo Clinic-led study found. Sixty percent of patients studied had breast cancer. The findings are being presented at the American Society of Clinical Oncology’s annual meeting.
Researchers studied 340 patients who had completed cancer treatment or were being treated for cancer at one of 40 community medical centers. Each day, participants received a placebo or 2,000 milligrams of ginseng administered in capsules containing pure, ground American ginseng root.
“Off-the-shelf ginseng is sometimes processed using ethanol, which can give it estrogen-like properties that may be harmful to breast cancer patients,” says researcher Debra Barton, Ph.D., of the Mayo Clinic Cancer Center.
At four weeks, the pure ginseng provided only a slight improvement in fatigue symptoms. However, at eight weeks, ginseng offered cancer patients significant improvement in general exhaustion — feelings of being “pooped,” “worn out,” “fatigued,” “sluggish,” “run-down,” or “tired” — compared to the placebo group.
“After eight weeks, we saw a 20-point improvement in fatigue in cancer patients, measured on a 100-point, standardized fatigue scale,” Dr. Barton says. The herb had no apparent side effects, she says.
Ginseng has long been used in traditional Chinese medicine as a natural energy booster. Until this study, its effects had not been tested extensively against the debilitating fatigue that occurs in up to 90 percent of cancer patients. Fatigue in cancer patients has been linked to an increase in the immune system’s inflammatory cytokines as well as poorly regulated levels of the stress-hormone cortisol. Ginseng’s active ingredients, called ginsenosides, have been shown in animal studies to reduce cytokines related to inflammation and help regulate cortisol levels.
Dr. Barton’s next study will look closely at ginseng’s effects on the specific biomarkers for fatigue. “Cancer is a prolonged chronic stress experience and the effects can last 10 years beyond diagnosis and treatment,” she says. “If we can help the body be better modulated throughout treatment with the use of ginseng, we may be able to prevent severe long-term fatigue.”
Joslin researchers find ‘good fat’ activated by cold, not ephedrine
Finding could help fight obesity epidemic
IMAGE:Aaron Cypess, M.D., Ph.D., is an Assistant Investigator in the Section on Integrative Physiology & Metabolism at Joslin Diabetes Center and an Assistant Professor of Medicine at Harvard Medical School….
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BOSTON — June 4, 2012 — Researchers at Joslin Diabetes Center have shown that while a type of “good” fat found in the body can be activated by cold temperatures, it is not able to be activated by the drug ephedrine.
The finding, published in today’s issue of PNAS USA Early Edition, may lead to drugs or other methods aimed at activating the good fat, known as brown fat. When activated, brown fat burns calories and can help in the battle against obesity.
“We propose that agents that work similarly to cold in activating brown fat specifically can provide promising approaches to fighting obesity while minimizing other side effects,” said Aaron Cypess, M.D., Ph.D., an assistant investigator and staff physician at Joslin and lead author of the paper.
“At the same time, we now know that ephedrine is not the way to do it,” he added.
Brown fat is found in humans naturally and consumes calories to generate heat. Prior studies had shown that brown fat can be activated by cold exposure in a process called non-shivering thermogenesis.
Researchers have been working for years to find ways to activate brown fat.
Ephedrine, a decongestant and bronchodilator, has been used as a weight loss drug because it increases the number of calories burned. However, there are side effects.
In this study, the Joslin team tested 10 study subjects in three ways. They were each separately given injections of ephedrine, given injections of saline as a control, and made to wear “cooling vests” that had water cooled to 57 degrees pumped into them. After each intervention, the brown fat activity was measured using PET/CT scans.
The researchers found that brown fat activity was the same following both the ephedrine and saline injections. However, after the subjects wore the cooling vests for two hours, their brown fat activity was stimulated significantly.
Both interventions — ephedrine injections and the wearing of the cooling vests — did result in the same number of calories being burned, Dr. Cypess noted.
“But we found that ephedrine was not using brown fat to do it,” he said. “This is the first time it has been found that ephedrine does not turn on brown fat.”
Both interventions had other effects on the sympathetic nervous system — which activates the fight or flight response — such as increased blood pressure, but those associated with brown fat activation were fewer, the study showed.
“Mild cold exposure stimulates (brown fat) energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways,” the paper concludes. “Agents that mimic cold activation of (brown fat) could provide a promising approach to treating obesity while minimizing systemic effects.”
As a result of the findings, drug companies may find it easier to come up with agents that stimulate brown fat to help people lose weight, Dr. Cypess said.
One method may be simply to design cooling vests that people can wear to help them lose weight. A future study will have subjects wear the vests for several weeks to see what happens, Dr. Cypess said.
“Will they get the same health benefits they would have seen with several weeks of exercise? That’s the billion dollar question.”
The findings should also be of interest to heart researchers interested in the mechanisms of activation of the sympathetic nervous system, he added.
High blood caffeine levels in older adults linked to avoidance of Alzheimer’s disease
Tampa, FL (June 4, 2012) Those cups of coffee that you drink every day to keep alert appear to have an extra perk – especially if you’re an older adult. A recent study monitoring the memory and thinking processes of people older than 65 found that all those with higher blood caffeine levels avoided the onset of Alzheimer’s disease in the two-to-four years of study follow-up. Moreover, coffee appeared to be the major or only source of caffeine for these individuals.
Researchers from the University of South Florida (www.usf.edu) and the University of Miami (www.miami.edu)say the case control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset. Their findings will appear in the online version of an article to be published June 5 in the Journal of Alzheimer’s Disease, published by IOS Press (http://health.usf.edu/nocms/publicaffairs/now/pdfs/JAD111781.pdf). The collaborative study involved 124 people, ages 65 to 88, in Tampa and Miami.
“These intriguing results suggest that older adults with mild memory impairment who drink moderate levels of coffee — about 3 cups a day — will not convert to Alzheimer’s disease — or at least will experience a substantial delay before converting to Alzheimer’s,” said study lead author Dr. Chuanhai Cao, a neuroscientist at the USF College of Pharmacy (http://health.usf.edu/nocms/pharmacy/) and the USF Health Byrd Alzheimer’s Institute (http://health.usf.edu/nocms/byrd/). “The results from this study, along with our earlier studies in Alzheimer’s mice, are very consistent in indicating that moderate daily caffeine/coffee intake throughout adulthood should appreciably protect against Alzheimer’s disease later in life.”
The study shows this protection probably occurs even in older people with early signs of the disease, called mild cognitive impairment, or MCI. Patients with MCI already experience some short-term memory loss and initial Alzheimer’s pathology in their brains. Each year, about 15 percent of MCI patients progress to full-blown Alzheimer’s disease. The researchers focused on study participants with MCI, because many were destined to develop Alzheimer’s within a few years.
Blood caffeine levels at the study’s onset were substantially lower (51 percent less) in participants diagnosed with MCI who progressed to dementia during the two-to-four year follow-up than in those whose mild cognitive impairment remained stable over the same period.
No one with MCI who later developed Alzheimer’s had initial blood caffeine levels above a critical level of 1200 ng/ml – equivalent to drinking several cups of coffee a few hours before the blood sample was drawn. In contrast, many with stable MCI had blood caffeine levels higher than this critical level.
“We found that 100 percent of the MCI patients with plasma caffeine levels above the critical level experienced no conversion to Alzheimer’s disease during the two-to-four year follow-up period,” said study co-author Dr. Gary Arendash.
The researchers believe higher blood caffeine levels indicate habitually higher caffeine intake, most probably through coffee. Caffeinated coffee appeared to be the main, if not exclusive, source of caffeine in the memory-protected MCI patients, because they had the same profile of blood immune markers as Alzheimer’s mice given caffeinated coffee. Alzheimer’s mice given caffeine alone or decaffeinated coffee had a very different immune marker profile.
Since 2006, USF’s Dr. Cao and Dr. Arendash have published several studies investigating the effects of caffeine/coffee administered to Alzheimer’s mice. Most recently, they reported that caffeine interacts with a yet unidentified component of coffee to boost blood levels of a critical growth factor that seems to fight off the Alzheimer’s disease process.
“We are not saying that moderate coffee consumption will completely protect people from Alzheimer’s disease,” Dr. Cao cautioned. “However, we firmly believe that moderate coffee consumption can appreciably reduce your risk of Alzheimer’s or delay its onset.”
Alzheimer’s pathology is a process in which plaques and tangles accumulate in the brain, killing nerve cells, destroying neural connections, and ultimately leading to progressive and irreversible memory loss. Since the neurodegenerative disease starts one or two decades before cognitive decline becomes apparent, the study authors point out, any intervention to cut the risk of Alzheimer’s should ideally begin that far in advance of symptoms.
“Moderate daily consumption of caffeinated coffee appears to be the best dietary option for long-term protection against Alzheimer’s memory loss,” Dr. Arendash said. “Coffee is inexpensive, readily available, easily gets into the brain, and has few side-effects for most of us. Moreover, our studies show that caffeine and coffee appear to directly attack the Alzheimer’s disease process.”
In addition to Alzheimer’s disease, moderate caffeine/coffee intake appears to reduce the risk of several other diseases of aging, including Parkinson’s disease, stroke, Type II diabetes, and breast cancer. However, supporting studies for these benefits have all been observational (uncontrolled), and controlled clinical trials are needed to definitively demonstrate therapeutic value.
A study tracking the health and coffee consumption of more than 400,000 older adults for 13 years, and published earlier this year in the New England Journal of Medicine, found that coffee drinkers reduced their risk of dying from heart disease, lung disease, pneumonia, stroke, diabetes, infections, and even injuries and accidents.
With new Alzheimer’s diagnostic guidelines encompassing the full continuum of the disease, approximately 10 million Americans now fall within one of three developmental stages of Alzheimer’s disease — Alzheimer’s disease brain pathology only, MCI, or diagnosed Alzheimer’s disease. That number is expected to climb even higher as the baby-boomer generation continues to enter older age, unless an effective and proven preventive measure is identified.
“If we could conduct a large cohort study to look into the mechanisms of how and why coffee and caffeine can delay or prevent Alzheimer’s disease, it might result in billions of dollars in savings each year in addition to improved quality of life,” Dr. Cao said.
Milk ingredient does a waistline good
A natural ingredient found in milk can protect against obesity even as mice continue to enjoy diets that are high in fat. The researchers who report their findings in the June Cell Metabolism, a Cell Press publication, liken this milk ingredient to a new kind of vitamin.
“This is present in what we’ve all been eating since day one,” says Johan Auwerx of École Polytechnique Fédérale de Lausanne.
The researchers identified this ingredient, known as nicotinamide riboside, as they were searching for alternative ways to boost the well-known gene SIRT1, which comes with benefits for both metabolism and longevity. One way to do that is to target SIRT1 directly, as the red wine ingredient resveratrol appears to do, at least at some doses.
Auwerx’s team suspected there might be a simpler way to go about it, by boosting levels of one of SIRT1’s molecular sidekicks, the cofactor NAD+.
This milk ingredient does just that in a rather appealing way. Not only is it a natural product, but it also gets trapped within cells, where it can do its magic.
Mice that take nicotinamide riboside in fairly high doses along with their high-fat meals burn more fat and are protected from obesity. They also become better runners thanks to muscles that have greater endurance.
The benefits they observe in mice wouldn’t be easy to get from drinking milk alone, Auwerx says. It may be more likely that the compound would serve as a new kind of metabolism-boosting supplement. Tests done in people are now needed to help sort out those details.
On the other hand, he says, this milk substance ultimately offers the same benefits attributed to resveratrol, but in a different way. It’s possible that many small effects of ingredients found in our diets could add
Team determines how estrogens to persist in dairy wastewater
IMAGE:Illinois Sustainable Technology Center senior research scientist Wei Zheng and his colleagues found that estrogenic compounds in dairy waste biodegrade very slowly in the absence of oxygen.
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CHAMPAIGN, Ill. — Wastewater from large dairy farms contains significant concentrations of estrogenic hormones that can persist for months or even years, researchers report in a new study. In the absence of oxygen, the estrogens rapidly convert from one form to another; this stalls their biodegradation and complicates efforts to detect them, the researchers found.
The study, led by scientists at the Illinois Sustainable Technology Center, is the first to document the unusual behavior of estrogens in wastewater lagoons. The study appears in the journal Environmental Science & Technology.
IMAGE:Estrogens in dairy wastewater degrade quickly when exposed to the air, but persist in wastewater, the researchers found.
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Just as new mothers undergo hormonal changes that enable them to breastfeed, lactating cows generate estrogenic hormones that are excreted in urine and feces, said ISTC senior research scientist Wei Zheng, who led the study. In large “confined animal feeding operations” (CAFOs) the hormones end up in wastewater. Farmers often store the wastewater in lagoons and may use it to fertilize crops.
Federal laws regulate the flow of nutrients such as nitrogen and phosphorous from CAFOs to prevent excess nutrients from polluting rivers, streams, lakes or groundwater. Environmental officials assume that such regulations also protect groundwater and surface waters from contamination with animal hormones and veterinary pharmaceuticals, but this has not been proven.
Hormone concentrations in livestock wastes are 100 to 1,000 times higher than those emitted from plants that treat human sewage, and large dairy farms are a primary source of estrogens in the environment, Zheng said. Recent studies have detected estrogenic hormones in soil and surrounding watersheds after dairy wastewater was sprayed on the land as fertilizer.
IMAGE:Wastewater from large dairies is a major source of estrogenic compounds in the environment.
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“These estrogens are present at levels that can affect the (reproductive functions of) aquatic animals,” Zheng said. Even low levels of estrogens can “feminize” animals that spend their lives in the water, causing male fish, for example, to have low sperm counts or to develop female characteristics (such as producing eggs), undermining their ability to reproduce.
Hormones that end up in surface or groundwater could contaminate sources of drinking water for humans, Zheng said. “The estrogens may also be taken up by plants – a potential new route into the food chain,” he said. When exposed to the air, estrogenic hormones in animal waste tend to break down into harmless byproducts. But the hormones persist in anoxic conditions.
While conducting the new study on dairy waste lagoon water in the lab, the researchers were surprised at first to see levels of three primary estrogens (17 alpha-estradiol, 17 beta-estradiol and estrone) fall and then rise again in their samples. Further analysis revealed that the estradiols were being converted to estrone, undergoing the normal first step of biodegradation. But then the process reversed itself: Estrone was reverting to the alpha- and beta-estradiols.
“We call this a reverse transformation,” Zheng said. “It inhibits further degradation. Now we have a better idea of why (the estrogens) can persist in the environment.”
The degradation rates of the three hormones in the wastewater solution were temperature-dependent, and very slow. After 52 days at 35 degrees Celsius (95 degrees Fahrenheit) – an ideal temperature for hormone degradation, Zheng said – less than 30 percent of the hormones in the solution had broken down.
The fluctuating levels of estrone and estradiols may lead to detection errors, Zheng said, giving the impression that the total estrogen load of wastewater is decreasing when it is not.
“We need to develop a strategy to prevent these hormones from building up in the environment,” he said.
up to slimmer waistlines—perhaps longer lives, too.
Calorie-restricted diet keeps heart youngArticle Body 2010
Portable heart monitors were worn by study volunteers who practiced calorie restriction and others of about the same age who ate standard diets so that scientists could measure their heart rate variability.
People who restrict their caloric intake in an effort to live longer have hearts that function more like those in people who are 20 years younger. Researchers at Washington University School of Medicine in St. Louis have found that a key measure of the heart’s ability to adapt to physical activity, stress, sleep and other factors that influence the rate at which the heart pumps blood, doesn’t decline nearly as rapidly in people who have significantly restricted their caloric intake for an average of seven years.
The study is available online in the journal Aging Cell.
“This is really striking because in studying changes in heart rate variability, we are looking at a measurement that tells us a lot about the way the autonomic nervous system affects the heart,” says Luigi Fontana, MD, PhD, the study’s senior author. “And that system is involved not only in heart function, but in digestion, breathing rate and many other involuntary actions. We would hypothesize that better heart rate variability may be a sign that all these other functions are working better, too.”
Fontana
The researchers hooked portable heart monitors to 22 practitioners of calorie restriction (CR) who ate healthy diets but consumed 30 percent fewer calories than normal. Their average age was just over 51. For comparison purposes, researchers also studied 20 other people of about the same age who ate standard Western diets. Heart rates were significantly lower in the CR group, and their heart rate variability was significantly higher.
“Higher heart rate variability means the heart can adjust to changing needs more readily,” says lead author Phyllis K. Stein, PhD. “Heart rate variability declines with age as our cardiovascular systems become less flexible, and poor heart rate variability is associated with a higher risk of cardiovascular death.”
Stein, a research associate professor of medicine in the Division of Cardiology, has measured heart rate variability in a number of different groups, from older adults to those with depression. This study was her first experience evaluating heart rate variability in the group often referred to as CRONies (Calorie Restriction with Optimal Nutrition), but members of that group have been studied extensively by Fontana, a research associate professor of medicine at Washington University and investigator at the Istituto Superiore di Sanita in Rome, Italy.
Stein
“The idea was to learn, first of all, whether humans on CR, like the calorie-restricted animals that have been studied, have a similar adaptation in heart rate variability,” Fontana says. “The answer is yes. We also looked at normal levels of heart rate variability among people at different ages, and we found that those who practice CR have hearts that look and function like they are years younger.”
Laboratory animals with a restricted calorie intake tend to live 30 percent to 40 percent longer than those that eat standard diets. Many humans who practice calorie restriction believe they also will live significantly longer, but that won’t be known for several more years. Still, Fontana says much of his research suggests calorie restriction with optimal nutrition contributes to significant changes in people that are similar to changes seen in animals.
“In many of our studies, we have found that a number of metabolic and physiologic changes that occur in calorie-restricted animals also occur in people who practice CR,” Fontana says.
And he says the finding that heart rate variability is better in people who practice CR means more than just that their cardiovascular systems are flexible. He says the better ratio suggests improved health in general.
“But we can’t be absolutely positive that the practice of CR is solely responsible for the flexibility of the cardiovascular system,” Stein says. “People who practice CR tend to be very healthy in other areas of life, too, so I’m pretty sure they don’t say to themselves, ‘Okay, I’ll restrict my calorie intake to lengthen my life, but I’m still going to smoke two packs a day.’ These people are very motivated, and they tend to engage in a large number of very healthy behaviors.”
The real culprit behind hardened arteries? Stem cells, says landmark study
IMAGE:Within the walls of blood vessels are smooth muscle cells and newly discovered vascular stem cells. The stem cells are multipotent and are not only able to differentiate into smooth…
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Berkeley — One of the top suspects behind killer vascular diseases is the victim of mistaken identity, according to researchers from the University of California, Berkeley, who used genetic tracing to help hunt down the real culprit.
The guilty party is not the smooth muscle cells within blood vessel walls, which for decades was thought to combine with cholesterol and fat that can clog arteries. Blocked vessels can eventually lead to heart attacks and strokes, which account for one in three deaths in the United States.
Instead, a previously unknown type of stem cell — a multipotent vascular stem cell — is to blame, and it should now be the focus in the search for new treatments, the scientists report in a new study appearing June 6 in the journal Nature Communications.
“For the first time, we are showing evidence that vascular diseases are actually a kind of stem cell disease,” said principal investigator Song Li, professor of bioengineering and a researcher at the Berkeley Stem Cell Center. “This work should revolutionize therapies for vascular diseases because we now know that stem cells rather than smooth muscle cells are the correct therapeutic target.”
The finding that a stem cell population contributes to artery-hardening diseases, such as atherosclerosis, provides a promising new direction for future research, the study authors said.
“This is groundbreaking and provocative work, as it challenges existing dogma,” said Dr. Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease at UC San Francisco, who provided some of the mouse vascular tissues used by the researchers. “Targeting the vascular stem cells rather than the existing smooth muscle in the vessel wall might be much more effective in treating vascular disease.”
It is generally accepted that the buildup of artery-blocking plaque stems from the body’s immune response to vessel damage caused by low-density lipoproteins, the bad cholesterol many people try to eliminate from their diets. Such damage attracts legions of white blood cells and can spur the formation of fibrous scar tissue that accumulates within the vessel, narrowing the blood flow.
The scar tissue, known as neointima, has certain characteristics of smooth muscle, the dominant type of tissue in the blood vessel wall. Because mature smooth muscle cells no longer multiply and grow, it was theorized that in the course of the inflammatory response, they revert, or de-differentiate, into an earlier state where they can proliferate and form matrices that contribute to plaque buildup.
IMAGE:Zhenyu Tang (seated at microscope) examines vascular stem cells in culture along with Aijun Wang (left) and Song Li. The UC Berkeley researchers say that newly discovered stem cells contribute…
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However, no experiments published have directly demonstrated this de-differentiation process, so Li and his research team remained skeptical. They turned to transgenic mice with a gene that caused their mature smooth muscle cells to glow green under a microscope.
In analyzing the cells from cross sections of the blood vessels, they found that more than 90 percent of the cells in the blood vessels were mature smooth muscle cells. They then isolated and cultured the cells taken from the middle layer of the mouse blood vessels.
After one month of cell expansion, the researchers saw a threefold increase in the size of the cell nucleus and the spreading area, along with an increase in stress fibers. Notably, none of the new, proliferating cells glowed green, which meant that their lineage could not be traced back to the mature smooth muscle cells originally isolated from the blood vessels.
“Not only was there a lack of green markers in the cell cultures, but we noticed that another type of cell isolated from the blood vessels exhibited progenitor traits for different types of tissue, not just smooth muscle cells,” said Zhenyu Tang, co-lead author of the study and a Ph.D. student in the UC Berkeley-UCSF Graduate Program in Bioengineering.
The other co-lead author of the study, Aijun Wang, was a post-doctoral researcher in Li’s lab.
“The different phenotypes gave us the clue that stem cells were involved,” said Wang, who is now an assistant professor and the co-director of the Surgical Bioengineering Laboratory at the UC Davis Medical Center. “We did further tests and detected proteins and transcriptional factors that are only found in stem cells. No one knew that these cells existed in the blood vessel walls because no one looked for them before.”
Further experiments determined that the newly discovered vascular stem cells were multipotent, or capable of differentiating into various specialized cell types, including smooth muscle, nerve, cartilage, bone and fat cells. This would explain why previous studies misidentified the cells involved in vessel clogs as de-differentiated smooth muscle cells after vascular injury.
“In the later stages of vascular disease, the soft vessels become hardened and more brittle,” said Li. “Previously, there was controversy about how soft tissue would become hard. The ability of stem cells to form bone or cartilage could explain this calcification of the blood vessels.”
Other tests in the study showed that the multipotent stem cells were dormant under normal physiological conditions. When the blood vessel walls were damaged, the stem cells rather than the mature smooth muscle cells became activated and started to multiply.
The researchers analyzed human carotid arteries to confirm that the same type of multipotent vascular stem cells are found in human blood vessels.
“If your target is wrong, then your treatment can’t be very effective,” said Dr. Shu Chien, director of the Institute of Engineering in Medicine at UC San Diego, and Li’s former adviser. “These new findings give us the right target and should speed up the discovery of novel treatments for vascular diseases.”
Fish show autism-like gene expression in water with psychoactive pharmaceuticals
Results may suggest environmental trigger for autism, but only in genetically predisposed individuals
Psychoactive medications in water affect the gene expression profiles of fathead minnows in a way that mimics the gene expression patterns associated with autism spectrum disorder in genetically susceptible humans, according to research published June 6 in the open access journal PLoS ONE. These results suggest a potential environmental trigger for autism spectrum disorder in this vulnerable population, the authors write.
The researchers, led by Michael A. Thomas of Idaho State University, exposed the fish to three psychoactive pharmaceuticals – fluoxetine, a selective serotonin reuptake inhibitor, or SSR1; venlafaxine, a serotonin-norepinephrine reuptake inhibitor, and carbamazepine, used to control seizures – at concentrations comparable to the highest estimated environmental levels.
They found that the only gene expression patterns affected were those associated with idiopathic autism spectrum disorders, caused by genetic susceptibility interacting with unknown environmental triggers. These results suggest that exposure to environmental psychoactive pharmaceuticals may play a role in the development of autism spectrum disorder in genetically predisposed individuals.
Lead researcher Michael A. Thomas remarks, “While others have envisioned a causal role for psychotropic drugs in idiopathic autism, we were astonished to find evidence that this might occur at very low dosages, such as those found in aquatic systems.”
1 million billion billion billion billion billion billion: Number of undiscovered drugs
A new voyage into “chemical space” – occupied not by stars and planets but substances that could become useful in everyday life – has concluded that scientists have synthesized barely one tenth of 1 percent of the potential medicines that could be made. The report, in the journal ACS Chemical Neuroscience, estimates that the actual number of these so-called “small molecules” could be 1 novemdecillion (that’s 1 with 60 zeroes), 1 million billion billion billion billion billion billion, which is more than some estimates of the number of stars in the universe.
Jean-Louis Reymond and Mahendra Awale explain that small molecules, which are able to cross cell walls and interact with biological molecules in the body, are prime targets for scientists who develop new medicines. Most existing medications are small molecules. The authors focused on the “chemical space” inhabited by all of the small molecules that could possibly exist according to the laws of physics and chemistry. Researchers have identified millions of these compounds – the ACS’ Chemical Abstracts Service database contains almost 67 million substances. Reymond and Awale estimate that the molecules synthesized and tested as potential drugs so far represent less than 0.1 percent of chemical space. To aid researchers looking for new ways to prevent and treat disease, they set out to find the best ways to search for new small molecules.
The authors discuss several ways of getting a handle on chemical space, including by the size, shape and makeup of molecules. They show how computers can help researchers efficiently narrow a search for a new drug candidate. Computer modeling of chemical interactions can help researchers find a handful of promising molecules to synthesize and test in the lab. “Small molecule drugs are essential to the success of modern medicine,” the authors note, and suggest that their methods may be particularly useful for finding new pharmaceuticals that target the central nervous system.
Some adults with sleep disturbances are actually afraid of the dark, study says
Researchers suggest some insomnia be treated differently after nearly half of a small sample of students were roused at bedtime because of a dark-related phobia
DARIEN, IL – A small study of Toronto college students is shedding light on a contributing factor of insomnia that might be hard to admit – an adult fear of the dark.
Nearly half of the students who reported having poor sleep also reported a fear of the dark. Researchers confirmed this objectively by measuring blink responses to sudden noise bursts in light and dark surroundings. Good sleepers became accustomed to the noise bursts but the poor sleepers grew more anticipatory when the lights were down.
“The poor sleepers were more easily startled in the dark compared with the good sleepers,” said Taryn Moss, the study’s lead author. “As treatment providers, we assume that poor sleepers become tense when the lights go out because they associate the bed with being unable to sleep. Now we’re wondering how many people actually have an active and untreated phobia.”
The abstract “Are people with insomnia afraid of the dark? A pilot study” from Ryerson University Sleep & Depression Lab is being presented today at SLEEP 2012, the 26th annual meeting of the Associated Professional Sleep Societies (APSS) in Boston.
Colleen Carney, PhD, the principal investigator, said insomnia treatments are highly effective but not everyone responds or completely recovers. New approaches may be warranted. For example, the most effective insomnia treatments encourage people to leave the dark bedroom and go into another, lit room; however, this would not be a way to treat a dark-related phobia.
“We may need to add treatment components for these patients and adapt existing treatment components in light of the phobia,” Carney said. “A lot more research is needed, but we believe we have stumbled across an unmet treatment need for some poor sleepers.”
Have no fear: Most cases of thyroid cancer do not affect survival
Study finds that the majority of patients with thyroid cancer, except for those in the most advanced stage, continue to have the same chance of survival as those who are disease-free
Miami Beach, Fla.—Research presented at the Society of Nuclear Medicine’s 59th Annual Meeting reveals that patients with differentiated thyroid cancer live as long as people in perfect health, unless they are in the minority and have reached the most advanced stages of disease. Survival did not vary based on age, sex, or even if patients’ cancer had reached the beginning of stage IV.
“This highlights the excellent diagnostic and therapeutic strategies available to patients with differentiated thyroid cancer,” says Alexis Vrachimis, M.D., lead investigator for the department of nuclear medicine at University Hospital Muenster, Germany. “The excellent survival rates of almost all of our patients are predominantly due to the multidisciplinary optimization of their diagnostic and therapeutic management, including advanced molecular imaging techniques, highly sensitive laboratory assays, excellent endocrine surgery, individualized high-dose radioiodine therapy and lifelong medical surveillance.”
The thyroid is an endocrine gland that produces thyroid hormones, which increase rates of cellular metabolism and protein synthesis as well as activity in the sympathetic nervous system that controls the fight-or-flight response. The U.S. National Cancer Institute estimates that 56,460 Americans will be diagnosed and 1,780 people expected to die of thyroid cancer in 2012. There are different classifications for thyroid cancer, but most cases are considered differentiated, a term given to two forms called papillary and follicular thyroid cancer. There are four stages of the disease increasing from stages I through IV. The last stage includes subtypes a, b and c, however, stage IVb is extremely rare, and as such, no patients with this subtype were included in the study.
Investigators analyzed 1,502 consecutive patients with differentiated thyroid cancer who had been treated with radioiodine therapy. Only those patients with stage IVc differentiated thyroid cancer were found to have lower chance of survival than the normal population. This evidence should allay the fears of patients diagnosed with the disease.
“With these survival rates, patients with differentiated thyroid cancer in stages I-IVa could even be considered healthy patients,” says Vrachimis.
Statins shown to cause fatigue
In a study of more than 1,000 adults, researchers at the University of California, San Diego, found that individuals taking cholesterol-lowering statin drugs are more likely than non-users to experience decreased energy, fatigue upon exertion, or both. The researchers suggest that these findings should be taken into account by doctors when weighing risk versus benefit in prescribing statins.
Statin drugs are among the best selling and most widely used prescription drugs on the market. Recently, increasing attention has focused on statins’ side effects, particularly their effect on exercise. While some patients have reported fatigue or exercise intolerance when placed on statins, randomized trials had not previously addressed occurrence of fatigue-with-exertion or impaired energy in patients on statins relative to placebo.
In the June 11 issue of Archives of Internal Medicine Beatrice Golomb, MD, PhD, associate professor of medicine at UC San Diego School of Medicine, and colleagues present randomized trial data which show that these side effects were significantly greater in persons placed on statins than those on a placebo.
More than 1,000 adults from San Diego were randomly allocated to identical capsules with placebo, or one of two statins at relatively low potencies: pravastatin (Pravachol) at 40mg, or simvastatin (Zocor) at 20mg – chosen as the most water-soluble and most fat-soluble of the statins, at doses expected to produce similar LDL (“bad cholesterol”) reduction. According to the researchers, the cholesterol reduction would be similar to that expected with atorvastatin (Lipitor) at 10mg, or rosuvastatin (Crestor) at 2.5-5mg.
Persons with heart disease and diabetes were excluded. Neither subjects nor investigators knew which agent the subject had received. Subjects rated their energy and fatigue with exertion relative to baseline, on a five-point scale, from “much worse” to “much better.”
Those placed on statins were significantly more likely than those on placebo to report worsening in energy, fatigue-with-exertion, or both. Both statins contributed to the finding, though the effect appeared to be stronger in those on simvastatin. (Simvastatin led to significantly greater cholesterol reduction.)
“Side effects of statins generally rise with increasing dose, and these doses were modest by current standards,” said Golomb. “Yet occurrence of this problem was not rare – even at these doses, and particularly in women.”
The magnitude of the effect observed can be seen in the research findings if, for example, 4 of 10 treated women on simvastatin cited worsened energy or exertional fatigue; 2 in 10 cited worsening in both, or rated either one as “much worse”; or if 1 in 10 study participants rated energy and exertional fatigue as “much worse.”
“Energy is central to quality of life. It also predicts interest in activity,” said Golomb. “Exertional fatigue not only predicts actual participation in exercise, but both lower energy and greater exertional fatigue may signal triggering of mechanisms by which statins may adversely affect cell health.”
For these reasons, the researchers state that decreases in energy, and increases in exertional fatigue on statins represent important findings which should be taken into account in risk-benefit determinations for statins. According to Golomb, this is particularly true for groups for whom evidence does not support mortality benefit on statins – such as most patients without heart disease, and women and those over 70 or 75, even if heart disease is present.
Sweet minty relief for cough
PHILADELPHIA (June 11, 2012) – Millions of Americans reach for their cough drops or syrup at the first sign of a cough. However, scientists are unsure if and how these popular remedies work. Now, new findings from the Monell Center suggest that sucrose and menthol, ingredients commonly regarded as flavorings in these preparations, each act independently to reduce coughing.
Cough is a vital protective reflex that clears the respiratory tract of threats from mechanical stimuli like food and chemical stimuli such as airborne toxins and pollutants. As such, cough is necessary to protect the lungs, keep airways clear, and preserve life.
“Individuals with a weak cough reflex are at increased risk of pneumonia and of choking. Conversely, many acute and chronic conditions involve frequent coughing, leading to 30 million health care visits annually, with billions spent on over-the-counter medications and billions more lost due to reduced productivity,” said lead author, Paul M. Wise, Ph.D., a sensory psychologist at Monell.
However, many aspects of coughing remain poorly understood, including how chemicals act to trigger and modulate cough.
In the current study, which appears in the June 2012 issue of Pulmonary Pharmacology and Therapeutics, 12 healthy young adults inhaled from a nebulizer containing capsaicin, the burning ingredient in chili peppers and a potent chemical stimulus for cough.
After each inhalation, the amount of capsaicin was doubled. This procedure continued until the subject coughed three times within 10 seconds. The capsaicin concentration that induced the three coughs was labeled as the individual’s cough threshold.
In some sessions, the subjects held either a very sweet sucrose or plain water in their mouths for three seconds, spat the liquid into a sink, and then inhaled from the nebulizer.
In other sessions, subjects inhaled three breaths of either menthol-saturated air or clean air before each capsaicin inhalation. The menthol concentration was selected to approximate the cooling intensity of a menthol cigarette.
Both sucrose and menthol increased the amount of capsaicin needed to elicit a cough relative to plain water or clean air, respectively. Sucrose increased cough threshold by about 45 percent, while menthol increased it by approximately 25 percent.
“This is the first study to empirically show that sweet taste reduces cough. This also is the first study to show that menthol alone can reduce coughing in response to a cough-eliciting agent,” said Monell sensory scientist Paul Breslin, Ph.D., an author on the study.
The findings support the hypothesis that adding menthol to cigarettes, popularly known as “menthols,” may make it easier to begin smoking by suppressing the cough reflex, thus making the first cigarettes less distressing.
“Menthol may dull the sensitivity of sensory nerves in the airways and thereby actually disable an important reflex mechanism that would otherwise protect smokers from the chemical and particulate irritants present in cigarette smoke,” said Wise.
Studies at Monell will continue to explore the chemical elicitation of cough, along with the receptors and genes involved in this system.
Breast cancer risk can be lowered by avoiding unnecessary medical imaging
UCSF analysis of IOM report on environmental causes of breast cancer suggests there is at least 1 way women can reduce risk
A report issued by the Institute of Medicine (IOM) last December reviewed all the available scientific data compiled to date about potential environmental risks of breast cancer—factors such as pesticides, beauty products, household chemicals, and the plastics used to make water bottles.
Commissioned by the breast cancer foundation Susan G. Komen for the Cure, the IOM report concluded that there was not enough data to confirm or rule out that exposure to most of these factors caused breast cancer. However, the report did identify two factors that definitely increased risk: post-menopausal hormone replacement therapy and radiation exposure from medical imaging.
Now, a special article in the journal Archives of Internal Medicine details the findings of the IOM report as they relate to medical imaging and what women can do to minimize their risk of breast cancer.
“The single thing that the IOM highlighted that a woman can do to lower her risk of breast cancer is to avoid unnecessary medical imaging,” said Rebecca Smith-Bindman, MD, a professor of radiology and biomedical imaging, epidemiology and biostatistics at UCSF, who wrote the article, and who contributed to the IOM report.
What a Woman Should Know to Ask Her Doctor
While CT scans and other forms of medical imaging have revolutionized medicine and can be life-saving, said Smith-Bindman, women need to engage their doctors in the decision-making process and insist on the necessity and safety of all radiological scans they undergo.
“They should understand the risks and benefits and ask their doctor to explain the risks and benefits,” said Smith-Bindman.
She suggested that patients ask their doctors questions like:
Is this scan absolutely necessary?
Is it necessary to do it now?
Are there other, alternative tests?
How can I be sure the test will be done in the safest way possible?
Will having the scan information change the management of my disease?
Can I wait until after seeing a specialist before getting the scan?
Sick from your stomach: Bacterial changes may trigger diseases like rheumatoid arthritis
ROCHESTER, Minn. — The billions of bugs in our guts have a newfound role: regulating the immune system and related autoimmune diseases such as rheumatoid arthritis, according to researchers at Mayo Clinic and the University of Illinois at Urbana-Champaign.
Larger-than-normal populations of specific gut bacteria may trigger the development of diseases like rheumatoid arthritis and possibly fuel disease progression in people genetically predisposed to this crippling and confounding condition, say the researchers, who are participating in the Mayo Illinois Alliance for Technology Based Healthcare.
The study is published in the April 2012 issue of PloS ONE.
“A lot of people suspected that gut flora played a role in rheumatoid arthritis, but no one had been able to prove it because they couldn’t say which came first — the bacteria or the genes,” says senior author Veena Taneja, Ph.D., a Mayo Clinic immunologist. “Using genomic sequencing technologies, we have been able to show the gut microbiome may be used as a biomarker for predisposition.”
The roughly 10 trillion cells that make up the human body have neighbors: mostly bacteria that often help, training the immune system and aiding in digestion, for example. The bacteria in the intestines, in addition to a relatively small number of other microorganisms (the gut microbiome), outnumber human cells 10-to-1.
Researchers found that hormones and changes related to aging may further modulate the gut immune system and exacerbate inflammatory conditions in genetically susceptible individuals.
Nearly 1 percent of the world’s population has rheumatoid arthritis, a disease in which the immune system attacks tissues, inflaming joints and sometimes leading to deadly complications such as heart disease. Other diseases with suspected gut bacterial ties include type I diabetes and multiple sclerosis.
Researchers with the Mayo Illinois Alliance for Technology Based Healthcare say that identifying new biomarkers in intestinal microbial populations and maintaining a balance in gut bacteria could help physicians stop rheumatoid arthritis before it starts.
“This study is an important advance in our understanding of the immune system disturbances associated with rheumatoid arthritis. While we do not yet know what the causes of this disease are, this study provides important insights into the immune system and its relationship to bacteria of the gut, and how these factors may affect people with genetic susceptibilities to disease,” says Eric Matteson, M.D., chairman of rheumatology at Mayo Clinic, who was not a study author.
Dr. Taneja and her team genetically engineered mice with the human gene HLA-DRB1*0401, a strong indicator of predisposition to rheumatoid arthritis. A set of control mice were engineered with a different variant of the DRB1 gene, known to promote resistance to rheumatoid arthritis. Researchers used these mice to compare their immune responses to different bacteria and the effect on rheumatoid arthritis.
“The gut is the largest immune organ in the body,” says co-author Bryan White, Ph.D., director of the University of Illinois’ Microbiome Program in the Division of Biomedical Sciences and a member of the Institute for Genomic Biology. “Because it’s presented with multiple insults daily through the introduction of new bacteria, food sources and foreign antigens, the gut is continually teasing out what’s good and bad.”
The gut has several ways to do this, including the mucosal barrier that prevents organisms — even commensal or “good” bacteria — from crossing the lumen of the gut into the human body. However, when commensal bacteria breach this barrier, they can trigger autoimmune responses. The body recognizes them as out of place, and in some way this triggers the body to attack itself, he says.
These mice mimic human gender trends in rheumatoid arthritis, in that females were about three times as likely to generate autoimmune responses and contract the disease. Researchers believe these “humanized” mice could shed light on why women and other demographic groups are more vulnerable to autoimmune disorders and help guide development of new future therapies.
“The next step for us is to show if bugs in the gut can be manipulated to change the course of disease,” Dr. Taneja says.
Western diet changes gut bacteria and triggers colitis in those at risk
Certain saturated fats that are common in the modern Western diet can initiate a chain of events leading to complex immune disorders such as inflammatory bowel diseases (IBD) in people with a genetic predisposition, according to a study to be published early online in the journal Nature.
The finding helps explain why once-rare immune-mediated diseases have become more common in westernized societies in the last half century. It also provides insights into why many individuals who are genetically prone to these diseases are never affected and how certain environmental factors can produce inflammation in individuals already at risk.
Researchers at the University of Chicago found that concentrated milk fats, which are abundant in processed and confectionary foods, alter the composition of bacteria in the intestines. These changes can disrupt the delicate truce between the immune system and the complex but largely beneficial mix of bacteria in the intestines. The emergence of harmful bacterial strains in this setting can unleash an unregulated tissue-damaging immune response that can be difficult to switch off.
“This is the first plausible mechanism showing step-by-step how Western-style diets contribute to the rapid and ongoing increase in the incidence of inflammatory bowel disease,” said study author Eugene B. Chang, MD, PhD, the Martin Boyer Professor of Medicine at the University of Chicago. “We know how certain genetic differences can increase the risk for these diseases, but moving from elevated risk to the development of disease seems to require a second event which may be encountered because of our changing lifestyle.”
The researchers worked with a mouse model that has many of the characteristics of human IBD. Genetically deleting a molecule, interleukin 10, which acts as a brake on the immune system’s response to intestinal bacteria, caused about 20 percent of mice to develop colitis when fed a low-fat diet or a diet high in polyunsaturated fats. But when exposed to a diet high in saturated milk fats, the rate of disease development within six months tripled, increasing to more than 60 percent. In addition, the onset, severity and extent of colitis were much greater than that observed in mice fed low-fat diets.
Why would milk fat — a powdered substance that remains when fat has been separated from butter and dehydrated — trigger inflammation when polyunsaturated fat did not? The researchers traced the answer to the gut microbiome, the complex mix of hundreds of bacterial strains that reside in the bowels.
The researchers found that an uncommon microbe called Bilophila wadsworthia was preferentially selected in the presence of milk fat. Previous studies had found high levels of B. wadsworthia in patients with appendicitis and other intestinal inflammatory disorders, including inflammatory bowel disease.
“That piqued our interest,” Chang said. “These pathobionts, which are usually non-abundant, seem to be quite prominent in these diseases.”
Indeed, while Bilophila wadsworthia levels were almost undetectable in mice on a low-fat or unsaturated-fat diet, the bacteria made up about 6 percent of all gut bacteria in mice fed a high milk-fat diet.
“Here we show how the trend in consumption of Western-type diets by many societies can potentially tip the mutualistic balance between host and microbe to a state that favors the onset of disease,” Chang said.
As its name implies, Bilophila wadsworthia has an affinity for bile, a substance produced by the liver and released into the intestines to help break down ingested fats. Milk fats are particularly difficult to digest and require the liver to secrete a form of bile that is rich in sulfur. B. wadsworthia thrives in the presence of sulfur. So when the bile created to dissolve milk fats reaches the colon, it enables wadsworthia to blossom.
“Unfortunately, these can be harmful bacteria,” Chang said. “Presented with a rich source of sulfur, they bloom, and when they do, they are capable of activating the immune system of genetically prone individuals.”
The byproducts of B. wadsworthia’s interaction with bile also can amplify the effect. They serve as “gut mucosal barrier breakers,” said Suzanne Devkota, PhD, a member of Chang’s laboratory and first author of the study. “By increasing the permeability of the bowel, they enhance immune-cell infiltration, and that can induce tissue damage.”
Much of the recent progress in understanding the biology of inflammatory bowel disease has focused on gene variants that can increase risk, beginning with the discovery in 2001 of Nod2 by researchers at the University of Chicago. But the new study puts the focus on changing environmental factors that might trigger the disease in high-risk patients.
“Right now we can’t do much about correcting genes that predispose individuals to increased risk for these diseases,” Chang said, “and while we could encourage people to change their diets, this is seldom effective and always difficult.”
“However, the balance between host and microbes can be altered back to a healthy state to prevent or treat these diseases,” he added. “In essence, the gut microbiome can be ‘re-shaped’ in sustainable and predictable ways that restore a healthy relationship between host and microbes, without significantly affecting the lifestyles of individuals who are genetically prone to these diseases. We are testing that right now.”
Folic acid intake during early pregnancy associated with reduced risk of autism in offspring
June 13, 2012
(SACRAMENTO, Calif.) —
A new study by researchers at the UC Davis MIND Institute suggests that women who consume the recommended daily dosage of folic acid, the synthetic form of folate or vitamin B-9, during the first month of pregnancy may have a reduced risk of having a child with autism.
The study furthers the researchers’ earlier investigations, which found that women who take prenatal vitamins around the time of conception have a reduced risk of having a child with autism. The current study sought to determine whether the folic acid consumed in those supplements was the source of the protective effect. The finding suggests that, in addition to women who already have conceived, those who are attempting to become pregnant should consider consuming folic acid supplements, the authors said.
Rebecca J. Schmidt
The study found that women who each day consumed the recommended amount of folic acid (600 micrograms, or .6 milligrams) during the first month of pregnancy experienced a reduced risk of having a child with autism spectrum disorder, specifically when the mother and/or her child had a specific genetic variant (MTHFR 677 C>T) associated with less efficient folate metabolism. The study will be published in the July issue of the American Journal of Clinical Nutrition.
“This research is congruent with the findings of earlier studies that suggest that improved neurodevelopmental outcomes are associated with folic acid intake in early pregnancy,” said lead study author Rebecca J. Schmidt, assistant professor of public health sciences in the UC Davis School of Medicine and a researcher with the UC Davis MIND Institute. “It further supports recommendations that women with any chance of becoming pregnant should consider consuming folic acid at levels of 600 micrograms or greater per day.” Autism is a neurodevelopmental disorder characterized by impairments in social interaction, communication deficits and repetitive behaviors and often is accompanied by intellectual disability. An estimated 1 in 88 children born today will be diagnosed with autism spectrum disorder, according to the U.S. Centers for Disease Control and Prevention.
“What’s reassuring here is knowing that, by taking specific action in terms of their intake of folic acid from food or supplements, women can reduce the risk of autism spectrum disorder in their future children,” said study senior author Irva Hertz-Picciotto, chief of the division of environmental and occupational health in the Department of Public Health Sciences and a MIND Institute researcher.
The study authors said that folic acid might offer protection against problems in embryonic brain development by facilitating DNA methylation reactions that can lead to changes in the way that the genetic code is read. An ample supply of methyl donors such as folic acid could be especially important in the period around conception, when the DNA methylation road map is set forth.
For the study, the researchers collected data from approximately 835 Northern California mothers of 2- to 5-year-old children who had autism, developmental delay or typical development and who were participants in the Childhood Autism Risk from Genetics and the Environment (CHARGE) study between 2003 and 2009.
The study found that women who each day consumed the recommended amount of folic acid (600 micrograms, or .6 milligrams) during the first month of pregnancy experienced a reduced risk of having a child with autism spectrum disorder.
Each mother’s average daily folic acid intake was assessed on the basis of the amount and the frequency of consumption of folic acid-containing dietary supplements such as prenatal vitamins and multivitamins, as well as the consumption of food supplemented with folic acid such as fortified breakfast cereals or energy bars. Information was collected for the period when the women were pregnant and for the three months before they became pregnant.
The study found that mothers of typically developing children reported greater-than-average intake of folic acid, and were more likely to meet intake recommendations during the first month of pregnancy than were mothers of children with autism spectrum disorder. Among study participants, as the amount of folic acid consumed increased, the associated risk for autism spectrum disorder decreased. Mothers of children with developmental delay tended to have lower estimated folic acid intake when compared with mothers of typically developing children during the three months before pregnancy.
The mothers of infants who were developing normally said they consumed an estimated average of 779 micrograms of folic acid daily and 69 percent of them at least met the daily guidelines. The mothers of children with autism consumed an estimated average of 655 micrograms of folic acid. Fifty-four percent of them consumed the recommended 600 micrograms or more per day.
Consuming supplemental folic acid before and during early pregnancy has been recommended for decades, after studies demonstrated its potential to prevent up to 70 percent of neural tube defects, or improper formation of the embryonic brain and spinal cord. Folic acid’s protective effect on neural tube defects also was stronger when mothers and/or children carried the MTHFR 677 C>T gene variant. Early maternal folic acid supplementation has more recently been shown to improve other social, attention and behavioral outcomes in the developing child.
Additional study authors include Daniel J. Tancredi, Sally Ozonoff, Robin Hansen, Linda Schmidt and Flora Tassone of UC Davis and Jaana Hartiala and Hooman Allayee of the University of Southern California.
The study was funded by grants from the National Institutes of Health for both the CHARGE Study and this work (1R01-ES015359, 5R01-ES015359-03S1, P01-ES11269, 2K12HD051958-06, and T32-MH073124) and by grants R-829388 and R833292 from the U.S. Environmental Protection Agency’s Science to Achieve Results (STAR) program and the UC Davis MIND Institute.
Epileptic seizures linked to common childhood viral infection
Could antiviral treatment prevent some cases of epilepsy?
SANTA BARBARA, CA (June 14, 2012) A ten-year NIH-funded study has determined that a third of infants with prolonged seizures and fever suffer from either a new or reactivated roseola virus infection. Roseola viruses are the cause of the common childhood rash, but can also cause limbic encephalitis, a condition that frequently progresses to epilepsy. Investigators discovered one of the roseola viruses, human herpesvirus-6B (HHV-6B) in the blood of 32% of 169 infants with prolonged seizures, a condition known as status epilepticus. They found HHV-7 (another roseola virus) in 7.1% of the patients, usually as a co-infection with HHV-6B.
The study strengthens the link between HHV-6B and mesial temporal lobe epilepsy. HHV-6B is the primary cause of limbic encephalitis in transplant patients and half of those cases go on to develop epilepsy within 3-5 years. Furthermore, several studies have found HHV-6B DNA at high levels in the brain tissue of patients with refractory epilepsy. “A clinical trial is urgently needed to determine if repeat seizures and some cases of temporal lobe epilepsy might be prevented using existing antiviral therapy,” said Kristin Loomis, executive director of the HHV-6 Foundation.
These viruses persist in the brain cells and can be activated during periods of immunosuppression or stress. HHV-6 and HHV-7 are spread via the saliva and nearly 100% of the population has been infected by early adulthood.
Do childhood viruses smolder and emerge later as full-blown epilepsy?
“It is possible that these patients harbor latent virus in the brain tissue that reactivates later in response to unknown triggers,” said Leon Epstein, MD, a pediatric neurologist at the Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Hospital of Chicago. Dr. Epstein is the lead author of this new study published in the journal Epilepsia.
While febrile or fever–related seizures occur in 2-5% of infants, most of whom recover with no consequences, less is known about the outcome in children who suffer from the prolonged febrile seizures associated with HHV-6 or HHV-7. These children are still being followed and investigators expect that 30-40% of them will develop epilepsy within five years.
Would some infants with prolonged seizures benefit from antiviral treatment?
Currently infants with seizures are not tested for HHV-6B or HHV-7 and treatment consists of anti-seizure drugs. However, the authors expect clinical trials to be established as soon as more evidence is gathered. Transplant patients suffering with seizures from HHV-6 reactivation are routinely treated with antivirals and antiviral treatment is now common practice for symptomatic infants infected with a closely virus: cytomegalovirus or CMV (HHV-5). Infants who contract CMV from their mothers during pregnancy or shortly following birth can develop seizures and mental retardation as well as permanent losses in both hearing and vision. Antiviral therapy reduces neurological complications and seizures in these infants. The neurologists who conducted the study remain cautious about antiviral therapy. They note that the oral antiviral drug used to treat CMV infections, valganciclovir, can cause reversible neutropenia, a form of anemia; less toxic antivirals such as CMX001 are in the pipeline.
“HHV-6B can cause a strong cytokine response, and there is emerging data that inflammatory mechanisms may be involved in developing epilepsy after an insult such as a prolonged seizure,” explained, Shlomo Shinnar, MD, PhD, of Montefiore Medical Center and Albert Einstein College of Medicine, and principal investigator of the study, “So it is possible that anti-inflammatory treatment could benefit these patients whether or not HHV-6B is the cause of the prolonged seizure. This is an area that needs further research.
HHV-6B reactivation associated with cognitive impairment
Investigators will also be studying the roseola virus subset to determine if they develop cognitive problems in the years following the seizures. “We know that children and adults with temporal lobe epilepsy have cognitive problems. It will be interesting to see whether those who started out with an HHV-6B infection have more cognitive impairment down the road,” said Shinnar.
A study by Danielle Zerr, an infectious disease specialist at Seattle Children’s Hospital and the University of Washington, suggests that Shinnar may be on the right track. She reported last year that patients who reactivate with HHV-6B during a transplant procedure are far more likely to develop cognitive dysfunction or delirium. The declines were especially significant in areas of attention, processing speed, and concentration, as well as cognitive flexibility or the ability to operate with divided attention.
Children who develop seizures in response to these common viruses may harbor genes that cause them to be susceptible. A mutation in the SCN1A gene has been linked to several epilepsy conditions. Variants of another gene, IRF5, have been associated with active HHV-6A infections in multiple sclerosis patients.
Breast milk kills HIV and blocks its oral transmission in humanized mouse
IMAGE:The humanized “BLT ” mouse is created by introducing human bone marrow, liver and thymus tissues into animals without an immune system of their own. The BLT mouse has a fully…
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CHAPEL HILL – More than 15 percent of new HIV infections occur in children. Without treatment, only 65 percent of HIV-infected children will live until their first birthday, and fewer than half will make it to the age of two. Although breastfeeding is attributed to a significant number of these infections, most breastfed infants are not infected with HIV, despite prolonged and repeated exposure.
HIV researchers have been left with a conundrum: does breast milk transmit the virus or protect against it?
New research from the University of North Carolina School of Medicine explores this paradox in a humanized mouse model, demonstrating that breast milk has a strong virus killing effect and protects against oral transmission of HIV.
“This study provides significant insight into the amazing ability of breast milk to destroy HIV and prevent its transmission,” said J. Victor Garcia, PhD, senior author on the study and professor of medicine in the UNC Center for Infectious Diseases and the UNC Center for AIDS Research. “It also provides new leads for the isolation of natural products that could be used to combat the virus.”
Garcia and colleagues pioneered the humanized “BLT” mouse model, which is created by introducing human bone marrow, liver and thymus tissues into animals without an immune system of their own. Humanized BLT mice have a fully functioning human immune system and can be infected with HIV in the same manner as humans.
In the study, the researchers first determined that the oral cavity and upper digestive tract of BLT mice have the same cells that affect oral transmission of HIV in humans and then successfully transmitted the virus to the mice through these pathways. When the mice were given virus in whole breast milk from HIV-negative women, however, the virus could not be transmitted.
“These results are highly significant because they show that breast milk can completely block oral transmission of both forms of HIV that are found in the breast milk of HIV-infected mothers: virus particles and virus-infected cells,” said Angela Wahl, PhD, a post-doctoral researcher in Garcia’s lab and lead author on the paper. “This refutes the ‘Trojan horse’ hypothesis which says that HIV in cells is more stubborn against the body’s own innate defenses than HIV in virus particles.”
Finally, the researchers studied the effectiveness of pre-exposure prophylaxis (PrEP) with antiretroviral medication for oral transmission of HIV. Garcia and his team have previously shown that PrEP is effective against intravenous, vaginal and rectal transmission of HIV in humanized BLT mice. In this study, they gave the mice antiretroviral drugs for seven days (3 days before and 4 days after exposing them to the virus) and found 100 percent protection against virus transmission.
These latest findings provide important leads to alternative treatments that could be used to prevent transmission.
“No child should ever be infected with HIV because it is breastfed. Breastfeeding provides critical nutrition and protection from other infections, especially where clean water for infant formula is scarce,” Garcia said. “Understanding how HIV is transmitted to infants and children despite the protective effects of milk will help us close this important door to the spread of AIDS.”
The study appears in the June 14, 2012 issue of the online journal PLoS Pathogens.
Hidden vitamin in milk yields remarkable health benefits
Weill Cornell researchers show tiny vitamin in milk, in high doses, makes mice leaner, faster and stronger
NEW YORK (June 14, 2012) — A novel form of vitamin B3 found in milk in small quantities produces remarkable health benefits in mice when high doses are administered, according to a new study conducted by researchers at Weill Cornell Medical College and the Polytechnic School in Lausanne, Switzerland.
The findings, recently reported in the June 2012 issue of the journal, Cell Metabolism, reveal that high doses of the vitamin precursor, nicotinamide riboside (NR) — a cousin of niacin — prevent obesity in mice that are fed a fatty diet, and also increase muscle performance, improve energy expenditure and prevent diabetes development, all without side effects.
The Swiss researchers, led by Dr. Johan Auwerx, performed the mouse experiments, while the ability to give the animals sufficient doses of NR was made possible by Weill Cornell Medical College researchers, who played key roles in uncovering the biological story of NR.
“This study is very important. It shows that in animals, the use of NR offers the health benefits of a low-calorie diet and exercise — without doing either one,” says Dr. Anthony Sauve, associate professor of Pharmacology at Weill Cornell Medical College.
Dr. Sauve is the pharmacologist and organic chemist who has invented a simple method for efficiently synthesizing NR in large scale. He was first to show that NR increases nicotinamide adenine dinucleotide (NAD) levels in mammalian cells. NAD is a central player in energy metabolism. He has pioneered research into the compound, and he is a leader in investigating how NAD can signal adaptation in cells and in physiology.
“The research also suggests that the effects of NR could be even broader,” Dr. Sauve says. “The bottom line is that NR improves the function of mitochondria, the cell’s energy factories. Mitochondrial decline is the hallmark of many diseases associated with aging, such as cancer and neurodegeneration, and NR supplementation boosts mitochondrial functioning.”
The Swiss researchers call NR a “hidden vitamin” that is believed to also be present in many other foods, although levels are low and difficult to measure. Nevertheless, the effects of NR on metabolism “are nothing short of astonishing.”
Got nicotinamide riboside?
The study depended on a series of crucial discoveries by Dr. Sauve and his laboratory colleagues.
NR, related to niacin and other common forms of vitamin B3, was first investigated more than 60 years ago by a Stanford researcher and 1959 Nobel Laureate, Arthur Kornberg. But little more was known about its effects in mammals until Dr. Sauve discovered the effect NR had in stimulating levels of NAD in mammalian cells — work he published in 2007.
NAD allows sugars, fats, and proteins to be converted into energy. Dr. Sauve’s research provided the first evidence that NR enhances NAD levels in the mitochondria in mammalian cells in culture. These findings are published in the current study. These cell-based observations were key to the demonstration that NR could stimulate tissue NAD levels in animals, and that it could stimulate NAD-dependent sirtuins, which adapt physiology to the low calorie diets that are known to extend the lifespan of many organisms.
Dr. Sauve invented a relatively simple method for efficiently synthesizing NR in large scale so that its health benefits can be studied. This methodology, which makes it possible to make NR commercially available, was patented by Cornell’s Center for Technology Enterprise and Commercialization and subsequently licensed to ChromaDex Corporation.
The development of a means to synthesize NR in adequate quantities was crucial to the current research, and the Sauve lab provided methods and NR to make the study possible. In addition, the biological observations on the effects of NR on NAD levels in cells and on mitochondria were key to the study. Finally, the Sauve laboratory has developed state of the art analytical methods to determine NAD levels in cells, tissues and organelles, and the laboratory provided several key metabolic measurements highlighted in the study.
“Our published scientific work has verified that NR is perhaps the most potent NAD enhancing agent ever identified,” he says. His laboratory is also widely recognized for developing an expertise in the measurement of NAD metabolism in cell tissues.
With this compound, the Swiss researchers found that mice on a high-fat diet supplemented with NR gained significantly less weight (60 percent) than mice fed the same diet without NR, even though the mice supplemented with NR ate the same amount of food as mice on the high fat diet not treated with NR. They had improved energy. They were in better shape than the untreated mice, with significantly better endurance and stronger muscles. Additionally, none of the treated mice developed diabetes, as seen in the untreated mice on the high fat diet. And when fed a normal diet, NR treated mice had improved sensitivity to insulin. The NR treated mice also showed lower cholesterol levels. All of these benefits came without toxicity.
While the new study demonstrates that high doses of NR can largely prevent the negative health consequences of a poor diet in mice, Dr. Sauve stresses that the effects of high doses of the vitamin in humans have not been evaluated. “It is important to keep in mind that the amount of NR in milk and other foods appears to be small. We don’t know what effects NR would have in humans at relatively high doses,” he says.
“Still, we have very encouraging evidence of benefits of NR and NAD augmentation in general from this animal study — and much more work to do,” he says.
Vitamin D with calcium shown to reduce mortality in elderly
Study shows vitamin D and calcium reduce mortality but not vitamin D alone
A study recently published in the Endocrine Society’s Journal of Clinical Endocrinology and Metabolism (JCEM) suggests that vitamin D—when taken with calcium—can reduce the rate of mortality in seniors, therefore providing a possible means of increasing life expectancy.
During the last decade, there has been increasing recognition of the potential health effects of vitamin D. It is well known that calcium with vitamin D supplements reduces the risk of fractures. The present study assessed mortality among patients randomized to either vitamin D alone or vitamin D with calcium. The findings from the study found that the reduced mortality was not due to a lower number of fractures, but represents a beneficial effect beyond the reduced fracture risk.
“This is the largest study ever performed on effects of calcium and vitamin D on mortality,” said Lars Rejnmark, PhD, of Aarhus University Hospital in Denmark and lead author of the study. “Our results showed reduced mortality in elderly patients using vitamin D supplements in combination with calcium, but these results were not found in patients on vitamin D alone.”
In this study, researchers used pooled data from eight randomized controlled trials with more than 1,000 participants each. The patient data set was comprised of nearly 90 percent women, with a median age of 70 years. During the three-year study, death was reduced by 9 percent in those treated with vitamin D with calcium.
“Some studies have suggested calcium (with or without vitamin D) supplements can have adverse effects on cardiovascular health,” said Rejnmark. “Although our study does not rule out such effects, we found that calcium with vitamin D supplementation to elderly participants is overall not harmful to survival,
BPA exposure effects may last for generations
New study shows gestational exposure to BPA leads to behavioral changes for 4 generations
Chevy Chase, MD—Exposure to low doses of Bisphenol A (BPA) during gestation had immediate and long-lasting, trans-generational effects on the brain and social behaviors in mice, according to a recent study accepted for publication in the journal Endocrinology, a publication of The Endocrine Society.
BPA is a man-made chemical present in a variety of products including food containers, receipt paper and dental sealants and is now widely detected in human urine and blood. Public health concerns have been fueled by findings that BPA exposure can influence brain development. In mice, prenatal exposure to BPA is associated with increased anxiety, aggression and cognitive impairments.
“We have demonstrated for the first time to our knowledge that BPA has trans-generational actions on social behavior and neural expression,” said Emilie Rissman, PhD, of the University of Virginia School of Medicine and lead author of the study. “Since exposure to BPA changes social interactions in mice at a dose within the reported human levels, it is possible that this compound has trans-generational actions on human behavior. If we banned BPA tomorrow, pulled all products with BPA in them, and cleaned up all landfills tomorrow it is possible, if the mice data generalize to humans, that we will still have effects of this compound for many generations.”
In this study, female mice received chow with or without BPA before mating and throughout gestation. Plasma levels of BPA in supplemented female mice were in a range similar to those measured in humans. Juveniles in the first generation exposed to BPA in utero displayed fewer social interactions as compared with control mice. The changes in genes were most dramatic in the first generation (the offspring of the mice that were exposed to BPA in utero), but some of these gene changes persisted into the fourth generation.
“BPA is a ubiquitous chemical, it is in the air, water, our food, and our bodies,” said Rissman. “It is a man-made chemical, and is not naturally occurring in any plant or animal. The fact that it can change gene expression in mice, and that these changes are heritable, is cause for us to be concerned about what this may mean for human health.”
and may have beneficial effects on general health”.
Ralph’s Note: Why is this not Banned yet?
These reports are done with the appreciation of all the Doctors, Scientist, and other
Medical Researchers who sacrificed their time and effort. In order to give people the
ability to empower themselves. Without the base aspirations for fame, or fortune. Just honorable people, doing honorable things.