CNO Report 187
Release Date 15 AUG 2014
Draft Report Compiled by
- Drinking sugar-sweetened beverages during adolescence impairs memory
- Common drugs adversely impair older adults’ physical as well as cognitive functioning
- ‘Normal’ bacteria vital for keeping intestinal lining intact
- New mums still excessively sleepy after four months: CARRS-Q study
- Pepper and halt: Spicy chemical may inhibit gut tumors
- Analysis of African plant reveals possible treatment for aging brain
- Study: Link between vitamin D and dementia risk confirmed
- Caffeine intake associated with lower incidence of tinnitus
- Pregnant women and fetuses exposed to antibacterial compounds face potential health risks
- Common household chemicals decrease reproduction in mice, Virginia Tech study finds
- Disruption of gut bacteria early in life can lead to obesity in adulthood
- Reduced testosterone tied to endocrine-disrupting chemical exposure
Drinking sugar-sweetened beverages during adolescence impairs memory
7/29/2014, Seattle, WA. Research to be presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, finds that daily consumption of beverages sweetened with high-fructose corn syrup or sucrose can impair the ability to learn and remember information, particularly when consumption occurs during adolescence. Both adult and adolescent rats were given daily access to sugar-sweetened beverages that mirror sugar concentrations found in common soft drinks. Adult rats that consumed the sugar-sweetened beverages for one month performed normally in tests of cognitive function; however, when consumption occurred during adolescence the rats were impaired in tests of learning and memory capability.
The lead author, Dr. Scott Kanoski from the University of Southern California, says, “It’s no secret that refined carbohydrates, particularly when consumed in soft drinks and other beverages, can lead to metabolic disturbances. However, our findings reveal that consuming sugar-sweetened drinks is also interfering with our brain’s ability to function normally and remember critical information about our environment, at least when consumed in excess before adulthood”. In addition to causing memory impairment, adolescent sugar-sweetened beverage consumption also produced inflammation in the hippocampus, an area of the brain that controls many learning and memory functions. “The hippocampus is such a critical brain region for memory function”, says Kanoski. “In many ways this region is a canary in the coal mine, as it is particularly sensitive to insult by various environmental factors, including eating foods that are high in saturated fat and processed sugar.”
Common drugs adversely impair older adults’ physical as well as cognitive functioning
INDIANAPOLIS — A class of medications previously linked to cognitive impairment in older adults also appears to negatively affect their physical functioning according to investigators from the Regenstrief Institute, the Indiana University Center for Aging Research, the University of East Anglia and several other United Kingdom institutions.
In a systemic review of more than a decade of studies on the effects of drugs with anticholinergic properties, they report that these drugs have a significant adverse effect on both cognitive and physical functioning, including the ability to feed and dress oneself. Anticholinergic medications affect the brain by blocking acetylcholine, a nervous system neurotransmitter. They are sold over the counter as sleep aids and bladder leakage preventives and prescribed for many diseases including hypertension and congestive heart failure.
The review found that these 46 studies, which followed 60,944 patients, showed only limited evidence of a connection between anticholinergics and delirium, a short-term decline in cognition. Additionally the review indicated that the studies did not demonstrate a strong tie between medications with anticholinergic properties and death. According to Regenstrief Institute investigator Noll Campbell, Pharm.D., senior author of the review paper, this may be because most studies were insufficient in length to reveal a significant link between the medications and death.
This is the first systematic review to assess the effects of medications with anticholinergic properties on physical function and delirium. The authors say it also provides an important update on cognitive function and mortality.
“Anticholinergics, both over-the-counter and prescription medications, impact the lives of older adults in ways doctors, patients and their families may not realize,” said Dr. Campbell, who is also a research assistant professor in the Purdue University College of Pharmacy. “I don’t see use of these medications declining. Doctors and patients are familiar with these drugs and unfortunately are far less familiar with equally effective alternatives.”
For example, Dr. Campbell advised, rather than taking sleeping pills with anticholinergic properties, one could refrain from napping, limit evening exercise and remove distractions from the bedroom. Institutions like hospitals and nursing homes could work to keep older adults awake and stimulated during the day, naturally encouraging nighttime slumber.
Dr. Campbell and colleagues from the Regenstrief Institute and the IU Center for Aging Research are working to identify diagnosis- and patient-dependent alternatives to exposure to anticholinergic medications as well as methods to inform physicians of their advisability via prompts within electronic medical record systems.
“Significant ongoing concerns remain about these medicines, and this review paper for the first time in one place has highlighted the impact on function as well as memory and death,” said Chris Fox, M.D., of the University of East Anglia, the review paper’s first author. Dr. Fox is a psychiatrist. In 2011, he and Regenstrief and IU Center for Aging Research collaborators published the results of a study of 13,000 men and women age 65 and older in which they found a link between anticholinergic medications and death.
‘Normal’ bacteria vital for keeping intestinal lining intact
August 1, 2014 — (BRONX, NY) — Scientists at Albert Einstein College of Medicine of Yeshiva University have found that bacteria that aid in digestion help keep the intestinal lining intact. The findings, reported online in the journal Immunity, could yield new therapies for inflammatory bowel disease (IBD) and a wide range of other disorders.
The research involved the intestinal microbiome, which contains some 100 trillion bacteria. The role of these microorganisms in promoting or preventing disease is a major emerging field of study. Einstein scientists found that absorption of a specific bacterial byproduct is crucial for maintaining the integrity of the intestinal epithelium—the single-cell layer responsible for keeping intestinal bacteria and their toxins inside the gut and away from the rest of the body. Breaching of the intact intestinal epithelium is associated with a number of diseases.
“Intestinal bacteria secrete a wide variety of chemicals known as metabolites,” said Sridhar Mani, M.D., co-corresponding author of the paper. “These bacteria and their metabolites were known to influence the intestinal epithelium’s integrity, but precisely how they did so wasn’t known.” Dr. Mani is professor of medicine and of genetics and the Miriam Mandel Faculty Scholar in Cancer Research at Einstein and attending physician, oncology at the Montefiore Einstein Center for Cancer Care and Montefiore Medical Center.
Dr. Mani and his colleagues suspected that bacterial metabolites exert their influence by binding to and activating a protein in the nuclei of intestinal epithelial cells called the pregnane X receptor (PXR). PXR was known to be activated by chemicals within the body (such as bile acids) as well as by drugs including steroids and antibiotics.
In a series of mouse studies, the researchers found that a metabolite called indole 3-propionic acid (IPA)—produced exclusively by so-called commensal bacteria, which aid in digestion—both strengthens the intestinal epithelium’s barrier function and prevents its inflammation by activating PXR. More specifically, PXR activation suppresses production of an inflammatory protein called tumor necrosis factor alpha (TNF-α) while increasing levels of a protein that strengthens the junctions between adjacent intestinal epithelial cells.
“By adding probiotics in the form of IPA-producing bacteria to the intestine or by administering IPA directly, we may be able to prevent or treat IBD and other inflammatory disorders that occur when the intestinal epithelium has been compromised,” said Dr. Mani. “Such a strategy could also be tried for other health problems that may occur when the intestinal epithelium breaks down, including certain forms of liver disease, diabetes, asthma, allergies, obesity and heart disease.”
Dr. Mani’s team is now developing novel probiotics aimed at restoring the intestinal epithelium’s barrier function by encouraging IPA’s interaction with PXR.
New mums still excessively sleepy after four months: CARRS-Q study
01 August 2014
New mums are being urged to be cautious about returning to work too quickly, after a QUT study found one in two were still excessively sleepy four months after giving birth.
Dr Ashleigh Filtness, from QUT’s Centre for Accident Research & Road Safety – Queensland (CARRS-Q), studied the sleep patterns and tiredness of postpartum mums and found despite new mums recording stable night sleep times at 18 weeks, they continued to report being excessively tired.
The CARRS-Q study, published in PLoS One, followed 33 healthy new mums who recorded their postpartum sleep patterns in 15 minute increments during weeks 6, 12 and 18.
“Sleep disruption strongly influences daytime function, with sleepiness recognised as a risk-factor for people performing critical and dangerous tasks,” she said.
Dr Filtness said the study had significant implications for decisions-makers about when women should return to work, with current government paid parental leave entitlements ceasing at 18 weeks.
“This brings into question whether four months parental leave is sufficient to ensure daytime sleepiness has diminished to a manageable level before returning to work,” she said.
“It is important when developing regulations for parental leave entitlements that policy makers take into account the high prevalence of excessive daytime sleepiness experienced by new mothers.
“With the birth of every baby the new mother must adjust to the demands of parenting and one aspect of that is to remain functional while experiencing potentially severe sleep disruption.
“To put this into context, the assessment tool used to determine new mums’ sleepiness is also used by GPs to determine clinically relevant levels of sleepiness.
“If any other otherwise healthy person presented to a doctor with this degree of sleepiness they would likely have been offered advice regarding implications for daytime impairment including the impact on sustaining attention and decision making.”
Dr Filtness said the study also found while new mums were still waking on average twice a night to attend to their babies at 6, 12 and 18 weeks – their total sleep time was about 7 hours and 20 minutes.
She said Australian new mothers actually slept more than the average American worker (6h 53mins).
“So while postpartum women experienced disturbed sleep, they didn’t necessarily experience total reduced sleep time,” she said.
“What we found was that inevitably, new mothers will wake in the night to attend to their infant and the number of times they wake remains consistent during the first 18 postpartum weeks.
“Sleep disruption reduced over time and it appears this was driven by a reduction in the time it took for new mums to return to sleep, suggesting improved efficiency by mothers at settling their infant or the development of the infant’s circadian rhythm.
“These findings highlight the importance of sleep quality as opposed to sleep quantity, especially during the first 12 weeks.”
“Soon-to-be mums should be aware of the importance of their own sleep and consider how they are going to preserve their own sleep during the first few months of caring for a baby,” she said.
CARRS-Q is undertaking a program to inform women who are pregnant with their first baby about the potential sleep and sleepiness experience after the baby arrives, which will also provide an opportunity to plan strategies to get through the period. To take part in the program visit, http://www.carrsq.qut.edu.au/sleepymums/index.jsp
The study titled: Longitudinal change in sleep and daytime sleepiness in postpartum women is available here.
Pepper and halt: Spicy chemical may inhibit gut tumors
Researchers at the University of California, San Diego School of Medicine report that dietary capsaicin – the active ingredient in chili peppers – produces chronic activation of a receptor on cells lining the intestines of mice, triggering a reaction that ultimately reduces the risk of colorectal tumors.
The findings are published in the August 1, 2014 issue of The Journal of Clinical Investigation.
The receptor or ion channel, called TRPV1, was originally discovered in sensory neurons, where it acts as a sentinel for heat, acidity and spicy chemicals in the environment. “These are all potentially harmful stimuli to cells,” said Eyal Raz, MD, professor of Medicine and senior author of the study. “Thus, TRPV1 was quickly described as a molecular ‘pain receptor.’ This can be considered to be its conventional function, which all takes place in the nervous system.”
But Raz and colleagues have found that TPRV1 is also expressed by epithelial cells of the intestines, where it is activated by epidermal growth factor receptor or EGFR. EGFR is an important driver of cell proliferation in the intestines, whose epithelial lining is replaced approximately every four to six days.
“A basic level of EGFR activity is required to maintain the normal cell turnover in the gut,” said Petrus de Jong, MD, first author of the study. “However, if EGFR signaling is left unrestrained, the risk of sporadic tumor development increases.”
The scientists discovered that TRPV1, once activated by the EGFR, initiates a direct negative feedback on the EGFR, dampening the latter to reduce the risk of unwanted growth and intestinal tumor development. They found that mice genetically modified to be TRPV1-deficient suffered higher-than-normal rates of intestinal tumor growths.
“These results showed us that epithelial TRPV1 normally works as a tumor suppressor in the intestines,” said de Jong. In addition, molecular studies of human colorectal cancer samples recently uncovered multiple mutations in the TRPV1 gene, though Raz noted that currently there is no direct evidence that TRPV1 deficiency is a risk factor for colorectal cancer in humans.
“A direct association between TRPV1 function and human colorectal cancer should be addressed in future clinical studies,” he said.
But if such proves to be the case, the current study suggests one potential remedy might be spicy capsaicin, which acts as an irritant in mammals, generating a burning sensation in contact with tissue. Capsaicin is already broadly used as an analgesic in topical ointments, where its properties as an irritant overwhelm nerves, rendering them unable to report pain for extended periods of time. It’s also the active ingredient in pepper spray.
The researchers fed capsaicin to mice genetically prone to developing multiple tumors in the gastrointestinal tract. The treatment resulted in a reduced tumor burden and extended the lifespans of the mice by more than 30 percent. The treatment was even more effective when combined with celecoxib, a COX-2 non-steroidal anti-inflammatory drug already approved for treating some forms of arthritis and pain.
“Our data suggest that individuals at high risk of developing recurrent intestinal tumors may benefit from chronic TRPV1 activation,” said Raz. “We have provided proof-of-principle.”
Analysis of African plant reveals possible treatment for aging brain
Salk scientists find that a plant used for centuries by healers of São Tomé e Príncipe holds lessons for modern medicine
August 01, 2014
LA JOLLA—For hundreds of years, healers in São Tomé e Príncipe—an island off the western coast of Africa—have prescribed cata-manginga leaves and bark to their patients. These pickings from the Voacanga africana tree are said to decrease inflammation and ease the symptoms of mental disorders.
Now, scientists at the Salk Institute for Biological Studies have discovered that the power of the plant isn’t just folklore: a compound isolated from Voacanga africana protects cells from altered molecular pathways linked to Alzheimer’s disease, Parkinson’s disease and the neurodegeneration that often follows a stroke.
“What this provides us with is a source of potential new drug targets,” says senior author Pamela Maher, a senior staff scientist in Salk’s Cellular Neurobiology Laboratory. The results were published this week in the Journal of Ethnopharmacology.
Antonio Currais, a research associate who works with Maher, was visiting family in his native Portugal when he crossed paths with Maria do Céu Madureira, an ethnopharmacology researcher at the University of Coimbra. For the past twenty years, Madureira has been surveying the use of herbal medicine on the island. Currais and Maher had recently developed a series of tests to screen compounds for their potential use in treating neurodegenerative disorders and Currais saw the perfect chance to put the assay to the test. He began a collaboration with Madureira’s team.
“There was already a lot of descriptive information of particular plants that have potential effects on the nervous system,” Currais says. “We took that further to quantitatively document the real neuroprotective action of the compounds in these plants.”
Currais and Maher began studying seven different extracts collected from five species of plants in São Tomé e Príncipe. Three of the five had been reported by local healers to have effects on the nervous system and two were used as controls. The Salk research team put each sample through different assays—all conducted in living human and mouse cells—designed to test their potential impact against neurodegeneration.
One assay tested the ability of the plant extracts to protect cells against oxidative stress, a byproduct of metabolism that can cause DNA damage and has been linked to age-related neurodegeneration. Another tested anti-inflammatory properties of the compounds. A third test measured whether the samples could block the build-up of beta-amyloid peptides in neurons, which has been linked to Alzheimer’s disease.
“I was surprised at how potent they were,” says Maher. “I thought maybe we’d see a little bit of activity in some of the assays and then have to separate out individual components to see a more profound effect.” But one sample in particular—Voacanga africana—performed exceptionally on all assays, even in its most dilute form.
When Currais and Maher isolated different components of the plant, they found that the anti-inflammatory and neuroprotective effects of the plant were mostly due to one molecule, called voacamine. The compound hasn’t yet been tested in animal models but its performance in the assays suggests that it may have pharmaceutical potential for treating Alzheimer’s, Parkinson’s or stroke.
“There are still a lot of potential sources of drugs in plants that are native to countries around the world and most of them haven’t been tested to any extent,” says Maher. “You can’t test everything, so the best way to approach plant research for drugs is to use the knowledge that’s been around for thousands of years to help you pick and choose what to study with modern techniques. That way you’re not just shooting in the dark.”
Maher, Currais and Madureira are planning more follow up studies on voacamaine and also hope to apply their assays to more plants of interest.
Other researchers on the study were Chandramouli Chiruta and Marie Goujon-Svrzic of the Salk Institute for Biological Studies; Gustavo Costa, Tania Santos, Maria Teresa Batista, Jorge Paiva, and Maria do Ceu Madureira of the University of Coimbra.
Both the Portuguese and American researchers worked in full partnership with local institutions, traditional healers and communities in order to respectfully conduct research in the area of indigenous knowledge, assuring the intellectual property rights and the sharing of benefits that may arise as a result of the study of these local medicinal plants.
Study: Link between vitamin D and dementia risk confirmed
MINNEAPOLIS – In the largest study of its kind, researchers suggests that in older people, not getting enough vitamin D may double the risk of developing dementia and Alzheimer’s disease. The study is published in the August 6, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology.
The study looked at blood levels of vitamin D, which includes vitamin D from food, supplements and sun exposure. Dietary vitamin D is found in fatty fish such as salmon, tuna or mackerel and milk, eggs and cheese.
“We expected to find an association between low Vitamin D levels and the risk of dementia and Alzheimer’s disease, but the results were surprising—we actually found that the association was twice as strong as we anticipated,” said study author David J. Llewellyn, PhD, of the University of Exeter Medical School in the United Kingdom.
For the study, 1,658 people over the age of 65 who were dementia-free had their vitamin D blood levels tested. After an average of six years, 171 participants developed dementia and 102 had Alzheimer’s disease.
The study found that people with low levels of vitamin D had a 53-percent increased risk of developing dementia and those who were severely deficient had a 125-percent increased risk compared to participants with normal levels of vitamin D.
People with lower levels of vitamin D were nearly 70 percent more likely to develop Alzheimer’s disease and those who had severe deficiency were over 120 percent more likely to develop the disease.
The results remained the same after researchers adjusted for other factors that could affect risk of dementia, such as education, smoking and alcohol consumption.
“Clinical trials are now needed to establish whether eating foods such as oily fish or taking vitamin D supplements can delay or even prevent the onset of Alzheimer’s disease and dementia. We need to be cautious at this early stage and our latest results do not demonstrate that low vitamin D levels cause dementia. That said, our findings are very encouraging, and even if a small number of people could benefit, this would have enormous public health implications given the devastating and costly nature of dementia,” said Llewellyn.
Caffeine intake associated with lower incidence of tinnitus
Researchers observe that women with a higher intake of caffeine had a lower incidence of unexplained ear ringing
Boston, MA – New research from Brigham and Women’s Hospital (BWH) finds that higher caffeine intake is associated with lower rates of tinnitus, often described as a ringing or buzzing sound in the ear when there is no outside source of the sounds, in younger and middle-aged women. This research is published in the August issue of the American Journal of Medicine.
In this prospective study, which followed more than 65,000 women in the Nurses’ Health Study II, researchers tracked self-reported results regarding lifestyle and medical history from these women, aged 30 to 44 years and without tinnitus in 1991. Information on self-reported tinnitus and date of onset was obtained from questionnaires returned in 2009, with cases defined as women who reported symptoms “a few days/week” or “daily.” After 18 years of follow up, researchers identified 5,289 cases of reported incident tinnitus.
“We observed a significant inverse association between caffeine intake and the incidence of tinnitus among these women,” said Gary Curhan, MD, ScD, senior author of the paper and a physician-researcher in the Channing Division of Network Medicine at BWH and Professor of Medicine at Harvard Medical School.
Specifically, researchers report that when compared with women with caffeine intake less than 150 milligrams/day (approximately one and a half 8-ounce cups of coffee), the incidence of reported tinnitus was 15 percent lower among those women who consumed 450 to 599 mg/day of caffeine. The majority of caffeine consumed among the women was from coffee and the results did not vary by age.
“The reason behind this observed association is unclear,” said Curhan. “We know that caffeine stimulates the central nervous system, and previous research has demonstrated that caffeine has a direct effect on the inner ear in both bench science and animal studies. Researchers note that further evidence is needed to make any recommendations about whether the addition of caffeine would improve tinnitus symptoms.
Pregnant women and fetuses exposed to antibacterial compounds face potential health risks
SAN FRANCISCO, Aug. 10, 2014 — As the Food and Drug Administration (FDA) mulls over whether to rein in the use of common antibacterial compounds that are causing growing concern among environmental health experts, scientists are reporting today that many pregnant women and their fetuses are being exposed to these substances. They will present their work at the 248th National Meeting & Exposition of the American Chemical Society (ACS), the world’s largest scientific society.
The meeting, which takes place here through Thursday, features nearly 12,000 presentations on a wide range of science topics.
“We looked at the exposure of pregnant women and their fetuses to triclosan and triclocarban, two of the most commonly used germ-killers in soaps and other everyday products,” says Benny Pycke, Ph.D. “We found triclosan in all of the urine samples from the pregnant women that we screened. We also detected it in about half of the umbilical cord blood samples we took, which means it transfers to fetuses. Triclocarban was also in many of the samples.”
The problem with this, explains Pycke, a research scientist at Arizona State University (ASU), is that there is a growing body of evidence showing that the compounds can lead to developmental and reproductive problems in animals and potentially in humans. Also, some research suggests that the additives could contribute to antibiotic resistance, a growing public health problem.
Although the human body is efficient at flushing out triclosan and triclocarban, a person’s exposure to them can potentially be constant.
“If you cut off the source of exposure, eventually triclosan and triclocarban would quickly be diluted out, but the truth is that we have universal use of these chemicals, and therefore also universal exposure,” says Rolf Halden, Ph.D., the lead investigator of the study at ASU.
The compounds are used in more than 2,000 everyday products marketed as antimicrobial, including toothpastes, soaps, detergents, carpets, paints, school supplies and toys, the researchers say.
Showing what effect antimicrobials have on people is a challenge. But Halden and Pycke’s colleague Laura Geer, Ph.D., of the State University of New York, found at least one interesting result. Geer says the study yielded a link between women with higher levels of another ubiquitous antimicrobial, butyl paraben, which is commonly used in cosmetics, and shorter newborn lengths. The long-term consequences of this are not clear, but Geer adds that, if this finding is confirmed in larger studies, it could mean that widespread exposure to these compounds could cause a subtle but large-scale shift in birth sizes.
State policymakers, the FDA and industry have taken notice of the mounting evidence against triclosan. Minnesota became the first state to pass a ban on the antimicrobial’s use in certain products, and it will take effect in January 2017. Some companies, such as Johnson & Johnson and Procter & Gamble, have announced that they are phasing out the compound from some products. At the federal level, the FDA and Environmental Protection Agency are reviewing the use and effects of the compounds.
Common household chemicals decrease reproduction in mice, Virginia Tech study finds
Virginia Tech researchers who were using a disinfectant when handling mice have discovered that two active ingredients in it cause declines in mouse reproduction.
Although the chemicals responsible for the declines are common in household cleaning products and disinfectants used in medical and food preparation settings, including hand sanitizers, academic scientists have never published a rigorous study, until now, on their safety or toxicity.
“It is likely that you have these chemicals in your house,” said Dr. Terry Hrubec, a research assistant professor in the Department of Biomedical Sciences and Pathobiology at the Virginia-Maryland College of Veterinary Medicine. “The answer to the question, ‘Are these chemicals harmful to humans?’ is that we simply don’t know.”
Hrubec and her research team at the veterinary college saw a decline in reproductive performance of her mice.
Stumped by her initial findings, Hrubec noticed animal care staff in her laboratory wetting their hands with a disinfectant before touching the mice.
This observation led her to a letter published in Nature by co-author Patricia Hunt, a geneticist at Washington State University, who had made the same discovery. These two independent observations were the impetus for the study.
When Hrubec tested whether the disinfectant might be causing reproductive decline, she came up with the unexpected finding.
Hrubec and Hunt are co-authors of the study, which will appear in an upcoming issue of Reproductive Toxicology, a leading journal on the effects of toxic substances on the reproductive system.
“These chemicals have been around for 50 years,” said Hrubec, who is also an associate professor of anatomy at Blacksburg, Virginia’s Edward Via College of Osteopathic Medicine. “They are generally considered safe, but no one has done rigorous scientific research to confirm this.”
The two active ingredients in the disinfectant — alkyl dimethyl benzalkonium chloride and didecyl dimethylammonium chloride — are typically listed by their abbreviations, ADBAC and DDAC, on ingredient lists.
They are a part of a larger class of chemicals called “quaternary ammonium compounds,” which are used for their antimicrobial and antistatic properties as well as their ability to lower surface tension between two liquids or a liquid and a solid.
They are found in commercial and householder cleaners, disinfectants, hand sanitizers, preservatives in makeup and other cosmetics, fabric softeners, and dryer sheets.
“We just tested the two active ingredients in the disinfectant, not the entire class of compounds,” Hrubec explained. “To be on the safe side, we need to do more research on these chemicals and find out how they could be affecting human health.”
The research team found that the female mice took longer to get pregnant and had fewer offspring when they did. Forty percent of the mothers exposed to ADBAC and DDAC died in late pregnancy or during delivery.
Graduate students Vanessa Melin and Haritha Potineni in the veterinary college’s Department of Biomedical Sciences and Pathobiology assisted with the study.
Hrubec drew comparisons between her research team’s work and similar research on bisphenol A, commonly known as BPA. In 1998, Washington State’s Hunt discovered the toxic effects of BPA, which could be found on baby bottles, medical and dental devices, and coatings on beverage cans, among other uses.
“If these chemicals are toxic to humans, they could also be contributing to the decline in human fertility seen in recent decades, as well as the increased need for assistive reproductive technologies such as in-vitro fertilization,” Hrubec said.
Quaternary ammonium compounds like the ones used for the disinfectant in Hrubec’s lab were introduced in the 1950s and 1960s. Although some toxicity testing took place during this period, it was conducted by chemical manufacturers and not published.
“These industry-sponsored studies took place before toxicity studies were standardized,” Hrubec said. “In the 1980s, toxicity researchers developed and implemented Good Laboratory Practices, or GLPs. These are guidelines and rules for conducting research so that it is reproducible and reliable. All of the research on these chemicals happened before that.”
Although these chemicals are harmful to mice, Hrubec explained that they might not be dangerous for humans.
But considering the widespread human exposure to the compounds through cleaning products and disinfectants, more research is needed to verify human implications.
Hrubec noted that an epidemiological study could determine whether people who have a high rate of exposure to the chemicals, such as healthcare workers or restaurant servers, have a harder time b ecoming pregnant.
Disruption of gut bacteria early in life can lead to obesity in adulthood
Certain microbes found in the gut may protect against obesity and diabetes. A study published by Cell Press August 14th in the journal Cell reveals that these microbes shape their hosts’ metabolism very early in life and that disrupting them with short-term exposure to antibiotics during infancy can cause metabolic changes that appear to increase the risk of obesity in adulthood. These findings in mice are helping researchers identify which gut bacteria are crucial to metabolic health. Such information could be used to help restore levels of those helpful microbes after an infant has received life-saving antibiotics, thereby promoting healthy metabolism in adulthood.
“We identified infancy as a critical window where host metabolism is especially vulnerable to microbiota disruption with antibiotics,” says senior study author Martin Blaser of the NYU Langone Medical Center. “This highlights a need for judicious use of antibiotics in clinical practice in early life.”
Microbes begin to colonize the gut at birth, and disruption of these communities with antibiotics early in life can have long-term effects on weight. Farmers have been taking advantage of this phenomenon for decades by exposing livestock to low doses of antibiotics to promote growth. Blaser and his team wanted to examine whether the exact timing and duration of early exposure to antibiotics could make a difference, as well as identify specific bacteria that may protect against the potentially harmful health effects.
To address these questions, the researchers gave long-term, low-dose penicillin treatment to two groups of mice: 4-week-old mice after weaning and mouse mothers beginning shortly before their pups’ birth. They found that earlier penicillin exposure led to more substantial obesity in adulthood and worse metabolic health, especially in males. Early exposure to antibiotics also reduced levels of several types of potentially protective bacteria and exacerbated the effects of a high-fat diet on obesity. In a separate experiment, the researchers found that only 4 weeks of antibiotic exposure beginning shortly before birth was sufficient to produce obesity, which lasted well after penicillin treatment ended.
Moreover, the researchers demonstrated that altered gut microbes rather than antibiotics per se caused these metabolic changes: “Our findings imply that restoring good bacteria could prevent the long-term metabolic effects of early antibiotic exposure,” says lead study author Laura Cox of the NYU Langone Medical Center. “We identified four candidate bacteria that may be metabolically protective, and we’re working on follow-up studies to determine if we can prevent weight gain by giving these bacteria back following antibiotic therapy.”
Reduced testosterone tied to endocrine-disrupting chemical exposure
Phthalates found in plastics could block hormone involved in sexual, cognitive function
Washington, DC—Men, women and children exposed to high levels of phthalates – endocrine-disrupting chemicals found in plastics and some personal care products – tended to have reduced levels of testosterone in their blood compared to those with lower chemical exposure, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).
Testosterone is the main sex hormone in men. It contributes to a variety of functions in both sexes, including physical growth and strength, brain function, bone density and cardiovascular health. In the last 50 years, research has identified a trend of declining testosterone in men and a rise in related health conditions, including reduced semen quality in men and genital malformations in newborn boys.
Animal and cellular studies have found that some phthalates block the effects of testosterone on the body’s organs and tissues. Researchers set out to examine whether these chemicals, which are widely used in flexible PVC plastics and personal care products, had a similar effect in humans.
“We found evidence reduced levels of circulating testosterone were associated with increased phthalate exposure in several key populations, including boys ages 6-12, and men and women ages 40-60,” said one of the study’s authors, John D. Meeker, MS, ScD, of the University of Michigan School of Public Health in Ann Arbor, MI. “This may have important public health implications, since low testosterone levels in young boys can negatively impact reproductive development, and in middle age can impair sexual function, libido, energy, cognitive function and bone health in men and women.”
The cross-sectional study examined phthalate exposure and testosterone levels in 2,208 people who participated in the U.S. National Health and Nutrition Examination Survey, 2011-2012. Researchers analyzed urine samples to measure concentrations of 13 substances left after the body metabolizes phthalates. Each participant’s testosterone level was measured using a blood sample.
Researchers found an inverse relationship between phthalate exposure and testosterone levels at various life stages. In women ages 40-60, for example, increased phthalate concentrations were associated with a 10.8 to 24 percent decline in testosterone levels. Among boys ages 6-12, increased concentrations of metabolites of a phthalate called di-(2-ethylhexyl) phthalate, or DEHP, was linked to a 24 to 34.1 percent drop in testosterone levels.
“While the study’s cross-sectional design limit the conclusions we can draw, our results support the hypothesis that environmental exposure to endocrine-disrupting chemicals such as phthalates could be contributing to the trend of declining testosterone and related disorders,” Meeker said. “With mounting evidence for adverse health effects, individuals and policymakers alike may want to take steps to limit human exposure to the degree possible.”