Health Research Report

149th Issue Date 22 FEB 2013

Compiled By Ralph Turchiano

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In this Issue:

 

1. Infant gut microbiota influenced by cesarean section and breastfeeding practices

 

2. Analysis finds vitamin D potency varies widely in dietary supplements

 

3. Yale study links common chemicals to osteoarthritis

 

4. Building healthy bones takes guts : Lactobacillus reuteri, significant increase in bone density after four weeks

 

5. Study advances LSUHSC research, shows fish oil component reduces brain damage in newborns – DHA

 

6. Omega-3 lipid emulsions markedly protect brain after stroke in mouse study

 

7. Increasing evidence links high glycemic index foods and dairy products to acne

 

8. Study: Resveratrol shows promise to protect hearing, cognition

 

9. Mushroom-supplemented soybean extract shows therapeutic promise for advanced prostate cancer

 

10. OMEGA-3s Inhibit Breast Cancer Tumour Growth, U of G Study Finds

 

11. Scientists unveil secrets of important natural antibiotic

 

 

 

 

 

Infant gut microbiota influenced by cesarean section and breastfeeding practices

Practices may affect health in later life

Method of birth (vaginal birth s. cesarean delivery) and feeding practices (breastfeeding v. formula-feeding) influence the development of gut bacteria in newborns and thus may affect lifelong health, according to a new study in CMAJ (Canadian Medical Association Journal).

Bacteria in the gut play an important role in health, helping digest food, stimulating the development of the immune system, regulating bowels and protecting against infection. Disruption of the gut microbiota has been linked to a range of diseases, such as inflammatory bowel disease, allergies, asthma, cancer and others.

“Our study addresses an important knowledge gap, since the infant gut microbiota has rarely been characterized with sequencing methods that provide sufficient coverage of the entire bacterial community,” writes Dr. Anita Kozyrskyj, University of Alberta, with coauthors. “Our findings are particularly timely given the recent affirmation of the gut microbiota as a “super organ” with diverse roles in health and disease, and the increasing concern over rising cesarean delivery and insufficient exclusive breastfeeding in Canada.”

As little is known about the development of this gut microbiota, a team of Canadian researchers sought to understand how the gut microbiome is established during early life, and what factors might disrupt this process. They looked at data on 24 healthy infants as part of the larger Canadian Healthy Infant Longitudinal Development (CHILD) study. CHILD involves more than 10 000 people, including 3 500 infants in 4 provinces (British Columbia, Alberta, Manitoba and Ontario) born after 2010 as well as their parents. The sample was representative of the Canadian newborn population, with 25% born by cesarean delivery, and 42% breastfed exclusively at 4 months of age.

New DNA sequencing technology was used by the research team to better understand the infant gut microbiome. Previous studies of this type have been conducted on laboratory cultures, although they were limited, as about 80% of intestinal microbes cannot be grown in culture. The DNA-based methods used in this study allow detection of virtually all bacteria since laboratory culture is not required.

The researchers found that infants born by cesarean delivery were lacking a specific group of bacteria found in infants delivered vaginally, even if they were breastfed. Infants strictly formula-fed, compared with babies that were exclusively or partially breastfed, also had significant differences in their gut bacteria.

“We want parents (and physicians) to realize that their decisions regarding c-section and breastfeeding can impact their infant’s gut microbiome, and this can have potentially lifelong effects on the child’s health,” says postdoctoral student and first author Meghan Azad, University of Alberta.

“The potential long-term consequences of decisions regarding mode of delivery and infant diet are not to be underestimated,” write the authors. “Infants born by cesarean delivery are at increased risk of asthma, obesity and type 1 diabetes, whereas breastfeeding is variably protective against these and other disorders.”

Beginning before birth, CHILD collects a range of information on environmental exposures such as pets, air pollution, household cleaning products, maternal and infant diet and more, and child health outcomes (including biological samples and clinical assessments). The researchers will use this information to study the development of the gut microbiome and its relationship to conditions such as wheeze and allergies in future studies.

“Children born by cesarean delivery or fed with formula may be at increased risk of a variety of conditions later in life; both processes alter the gut microbiota in healthy infants, which could be the mechanism for the increased risk,” writes Dr. Rob Knight, a Howard Hughes Medical Institute Early Career Scientist and an Associate Professor with the BioFrontiers Institute and Departments of Chemistry and Biochemistry and Computer Science, University of Colorado, Boulder, Colorado, United States, in a related commentary.

“These issues are of direct relevance to pregnant women and health practitioners and should be considered when choices such as elective cesarean delivery and other interventions are discussed,” state the commentary authors

Analysis finds vitamin D potency varies widely in dietary supplements

Kaiser Permanente analysis finds consumers may not be getting the amount of vitamin D they expect

PORTLAND, Ore., February 11, 2013 – Vitamin D supplement potency varies widely, and the amount of vitamin D in over-the counter and compounded supplements does not necessarily match the amount listed on the label, according to a research letter published in the journal JAMA Internal Medicine.

The analysis showed that the amount of vitamin D in these supplements ranged from 9 percent to 146 percent of the amount listed on the label. Not only was there variation among different brands and manufacturers, but also among different pills from the same bottle.

“We were surprised by the variation in potency among these vitamin D pills,” says Erin S. LeBlanc, M.D., MPH, lead author and investigator with the Kaiser Permanente Center for Health Research in Portland, Ore. “The biggest worry is for someone who has low levels of vitamin D in their blood. If they are consistently taking a supplement with little vitamin D in it, they could face health risks.”

According to a recent editorial in the New England Journal of Medicine, more than 100 million Americans spend a combined $28 billion on vitamins, herbs, and supplements each year. The U.S. Food and Drug Administration is considering new safety guidelines for some supplements but, for the most part, the industry remains unregulated.

Some manufacturers participate in a voluntary quality verification program operated by the U.S. Pharmacopeial Convention (USP)—an independent, nonprofit organization that sets public standards for the quality of dietary supplements. In order to receive the USP verification mark, manufacturers’ facilities undergo annual good manufacturing practice audits, and their products are tested for quality, potency, and purity. LeBlanc and her colleagues included one supplement from a USP Verified manufacturer in their sample. They found the amount of vitamin D in pills from that bottle was generally more accurate than the other bottles tested.

“The USP verification mark may give consumers some reassurance that the amount of vitamin D in those pills is close to the amount listed on the label,” said Dr. LeBlanc. “There are not many manufacturers that have the USP mark, but it may be worth the extra effort to look for it.”

The researchers tested 55 bottles of over-the-counter vitamin D from 12 different manufacturers. The over-the-counter vitamin D pills used in the analysis were purchased at five different stores in Portland, Ore. The compounded vitamin D was made by a compounding pharmacy in Portland. The analysis was conducted by an independent lab in Houston.

Yale study links common chemicals to osteoarthritis

New Haven, Conn. – A new study has linked exposure to two common perfluorinated chemicals (PFCs) with osteoarthritis. PFCs are used in more than 200 industrial processes and consumer products including certain stain- and water-resistant fabrics, grease-proof paper food containers, personal care products, and other items. Because of their persistence, PFCs have become ubiquitous contaminants of humans and wildlife. The study, published in Environmental Health Perspectives, is the first to look at the associations between perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), and osteoarthritis, in a study population representative of the United States.

“We found that PFOA and PFOS exposures are associated with higher prevalence of osteoarthritis, particularly in women, a group that is disproportionately impacted by this chronic disease,” said Sarah Uhl, who authored the study along with Yale Professor Michelle L. Bell and Tamarra James-Todd, an epidemiologist at the Harvard Medical School and Brigham and Women’s Hospital. The research was the focus of Uhl’s Master’s of Environmental Science Program at the Yale School of Forestry and Environmental Studies.

The authors analyzed data from six years of the National Health and Nutrition Examination Survey (NHANES, 2003-2008), which enabled them to account for factors such as age, income, and race/ethnicity. When the researchers looked at men and women separately, they found clear, strong associations for women, but not men. Women in the highest 25% of exposure to PFOA had about two times the odds of having osteoarthritis compared to those in the lowest 25% of exposure.

Although production and usage of PFOA and PFOS have declined due to safety concerns, human and environmental exposure to these chemicals remains widespread. Future studies are needed to establish temporality and shed light on possible biological mechanisms. Reasons for differences in these associations between men and women, if confirmed, also need further exploration. Better understanding the health effects of these chemicals and identifying any susceptible subpopulations could help to inform public health policies aimed at reducing exposures or associated health impacts.

Building healthy bones takes guts :  Lactobacillus reuteri, significant increase in bone density after four weeks

In what could be an early step toward new treatments for people with osteoporosis, scientists at Michigan State University report that a natural probiotic supplement can help male mice produce healthier bones.

Interestingly, the same can’t be said for female mice, the researchers report in the Journal of Cellular Physiology.

“We know that inflammation in the gut can cause bone loss, though it’s unclear exactly why,” said lead author Laura McCabe, a professor in MSU’s departments of Physiology and Radiology. “The neat thing we found is that a probiotic can enhance bone density.”

Probiotics are microorganisms that can help balance the immune system. For the study, the researchers fed the mice Lactobacillus reuteri, a probiotic known to reduce inflammation, a sometimes harmful effect of the body’s immune response to infection.

“Through food fermentation, we’ve been eating bacteria that we classify as probiotics for thousands of years,” said co-author Robert Britton, associate professor in the Department of Microbiology and Molecular Genetics. “There’s evidence that this bacterium as a species has co-evolved with humans. It’s indigenous to our intestinal tracts and is something that, if missing, might cause problems.”

In the study, the male mice showed a significant increase in bone density after four weeks of treatment. There was no such effect when the researchers repeated the experiment with female mice, an anomaly they’re now investigating.

By 2020, half of all Americans over 50 are expected to have low bone density or osteoporosis, according to the National Osteoporosis Foundation. About one in two women and one in four men over 50 will break a bone due to osteoporosis.

Drugs to prevent bone loss in osteoporosis patients are already in wide use, but over the long term they can disrupt the natural remodeling of bone tissue and could potentially have negative side effects that include unusual bone fractures and joint and muscle pain.

McCabe and Britton are quick to point out that this line of research is in its early stages and that results in mice don’t always translate to humans. But they’re hopeful the new study could point the way toward osteoporosis drugs that aren’t saddled with such side effects, especially for people who lose bone density from an early age because of another chronic condition.

“People tend to think of osteoporosis as just affecting postmenopausal women, but what they don’t realize is that it can occur with other conditions such as inflammatory bowel disease and Type 1 diabetes,” she said. “You don’t want to put your child on medications that reduce bone remodeling for the rest of their life, so something natural could be useful for long-term treatment of bone loss that begins at childhood.”

The research was supported by grants from the National Institutes of Health and MSU. Research assistants Regina Irwin and Laura Schaefer co-authored the paper

Study advances LSUHSC research, shows fish oil component reduces brain damage in newborns – DHA

New Orleans, LA – Research conducted by a team of scientists from Columbia University College of Physicians and Surgeons and Dr. Nicolas Bazan, Boyd Professor and Director of the Neuroscience Center of Excellence at LSU Health Sciences Center New Orleans, found the novel use of a component of fish oil reduced brain trauma in newborn mice. The study reports that neonatal brain damage decreased by about 50% when a triglyceride lipid emulsion containing docosahexaenoic acid (DHA) was injected within two hours of the onset of ischemic stroke. The paper, n-3 Fatty Acid Rich Triglyceride Emulsions are Neuroprotective after Cerebral Hypoxic-Ischemic Injury in Neonatal Mice, is published in the journal, PLOS ONE, available online at http://dx.plos.org/10.1371/journal.pone.0056233.

The study compared the effectiveness of emulsions with two omega-3 fatty acids – DHA and eicosapentaenoic acid (EPA) – as well as optimal doses and therapeutic window. The researchers found that DHA provided protection while EPA did not. The therapeutic window ranged from 90 minutes prior to several hours after with the optimal window for treatment 0 – 2 hours. There was no protective effect at hour 4.

DHA is an essential omega-3-fatty acid and is vital for proper brain function. It is also necessary for the development of the nervous system, including vision. Moreover, omega-3 fatty acids, found in cold water fatty fish, including salmon, tuna, mackerel, sardines, shellfish, and herring, are part of a healthy diet that helps lower the risk of heart disease. DHA has potent anti-inflammatory effects. Since inflammation is at the root of many chronic diseases, DHA treatment has been widely demonstrated to have beneficial effects in patients with coronary heart disease, asthma, rheumatoid arthritis, osteoporosis, sepsis, cancer, dry eye disease, and age-related macular degeneration. Its potential benefit in stroke is now being documented.

EPA is also an omega-3 fatty acid found in coldwater fish. EPA can prevent the blood from clotting easily. Often paired with DHA in fish oil supplements, these fatty acids are known to reduce pain and swelling.

Ischemic strokes, representing about 87% of strokes, result from loss of blood flow to an area of the brain due to a blockage such as a clot or atherosclerosis. The damage includes an irreversibly injured core of tissue at the site of the blockage. The area of tissue surrounding the core, called the penumbra, is also damaged but potentially salvageable. The penumbra has a limited life span and appears to undergo irreversible damage within a few hours unless blood flow is reestablished and neuroprotective therapy is administered. A cascade of chemicals floods the tissue along with restored blood flow, including damaging free radicals and pro-inflammatory enzymes which can cause further damage and cell death.

Administering clot-busting drugs (thrombolysis) is currently the only treatment for ischemic stroke. But due to a narrow therapeutic window and complexity of administration, only 3–5% of patients typically benefit from thrombolysis.

Dr. Bazan’s group at the LSU Health Sciences Center New Orleans Neuroscience Center of Excellence has increasingly shown that DHA is a potentially powerful treatment for stroke for nearly ten years. His study published in 2011 found DHA triggered production of Neuroprotectin D1 (NPD1), a naturally occurring neuroprotective molecule in the brain derived from DHA and discovered by Dr. Bazan. Not only did DHA treatment salvage stroke-damaged brain tissue that would have died, its repair mechanisms rendered some areas indistinguishable from normal tissue by 7 days.

“Stroke is a brain attack that each year kills 130,000 Americans,” notes Dr. Bazan. “Strokes can occur at any age, including in newborns, with long-term and devastating consequences. DHA is already widely consumed as a dietary supplement in the US, and from a therapeutic point of view, we can now see a light at the end of the tunnel.”

The researchers conclude that the findings suggest a need for further studies to determine if acute injection of these emulsions could be neuroprotective after stroke injury in humans. They also suggest that the emulsion rich in DHA will prove to be a novel and important therapy to treat stroke and could decrease mortality and increase long-term functional recovery after stroke in humans of different ages. The paper’s senior author is Richard Deckelbaum, MD, director of the Institute of Human Nutrition at Columbia’s College of Physicians & Surgeons.

According to the Centers for Disease Control and Prevention, 795,000 Americans have a stroke each year, and stroke causes 1 in every 18 deaths. Stroke is also a leading cause of long-term disability. Louisiana is among the states with the highest prevalence of stroke. It has been estimated that the direct and indirect costs of stroke in the United States totaled nearly $74 billion in 2010. In addition, with an estimated incidence of 1 in 2300 to 5000 births, stroke is more likely to occur in the perinatal period than at other times in childhood. Ischemic stroke in newborns is a disorder associated with significant long-term neurologic impairment. Twenty to 60% of survivors exhibit long-term detrimental neuropsychological consequences which include mental retardation, cerebral palsy, and behavioral disorders.

Omega-3 lipid emulsions markedly protect brain after stroke in mouse study

New York, NY (February 20, 2013) — Triglyceride lipid emulsions rich in an omega-3 fatty acid injected within a few hours of an ischemic stroke can decrease the amount of damaged brain tissue by 50 percent or more in mice, reports a new study by researchers at Columbia University Medical Center.

The results suggest that the emulsions may be able to reduce some of the long-term neurological and behavioral problems seen in human survivors of neonatal stroke and possibly of adult stroke, as well. The findings were published today in the journal PLoS One.

Currently, clot-busting tPA (recombinant tissue-type plasminogen activator) is the only treatment shown to improve recovery from ischemic stroke. If administered soon after stroke onset, the drug can restore blood flow to the brain but may not prevent injured, but potentially salvageable, neurons from dying.

Drugs with neuroprotective qualities that can prevent the death of brain cells damaged by stroke are needed, but even after 30 years of research and more than 1000 agents tested in animals, no neuroprotectant has been found effective in people.

Omega-3 fatty acids may have more potential as neuroprotectants because they affect multiple biochemical processes in the brain that are disturbed by stroke, said the study’s senior author, Richard Deckelbaum, MD, director of the Institute of Human Nutrition at Columbia’s College of Physicians & Surgeons. “The findings also may be applicable to other causes of ischemic brain injury in newborns and adults,” added co-investigator Vadim S. Ten, MD, PhD, an associate professor of pediatrics from the Department of Pediatrics at Columbia.

The effects of the omega-3 fatty acids include increasing the production of natural neuroprotectants in the brain, reducing inflammation and cell death, and activating genes that may protect brain cells. Omega-3 fatty acids also markedly reduce the release of harmful oxidants into the brain after stroke. “In most clinical trials in the past, the compounds tested affected only one pathway. Omega-3 fatty acids, in contrast, are very bioactive molecules that target multiple mechanisms involved in brain death after stroke,” Dr. Deckelbaum said.

The study revealed that an emulsion containing only DHA (docosahexaenoic acid), but not EPA (eicosapentaenoic acid), in a triglyceride molecule reduced the area of dead brain tissue by about 50 percent or more even when administered up to two hours after the stroke. Dr. Deckelbaum noted, “Since mice have a much faster metabolism than humans, longer windows of time for therapeutic effect after stroke are likely in humans.” Eight weeks after the stroke, much of the “saved” mouse brain tissue was still healthy, and no toxic effects were detected.

Studies are currently under way to test the emulsion in older mice and in mice with different types of stroke. The researchers are also conducting additional studies to identify more precisely how the omega-3 emulsion works and to optimize the emulsion in order to improve functional recovery after stroke.

After animal studies on dosages and timing, and if the emulsions continue to show promising results, Dr. Deckelbaum said, clinical trials could begin quickly, as such emulsions have already been shown to be safe in people. Similar emulsions are used in European ICUs for nutrition support, and in the US they have been found to be safe when tested in babies for their nutritive and anti-inflammatory effects.

Increasing evidence links high glycemic index foods and dairy products to acne

Medical nutrition therapy can play an important role, according to Journal of the Academy of Nutrition and Dietetics report

Philadelphia, PA, February 20, 2013 – A study published in the Journal of the Academy of Nutrition and Dietetics has determined that there is increasing evidence of a connection between diet and acne, particularly from high glycemic load diets and dairy products, and that medical nutrition therapy (MNT) can play an important role in acne treatment.

More than 17 million Americans suffer from acne, mostly during their adolescent and young adult years. Acne influences quality of life, including social withdrawal, anxiety, and depression, making treatment essential. Since the late 1800s, research has linked diet to this common disease, identifying chocolate, sugar, and fat as particular culprits, but beginning in the 1960s, studies disassociated diet from the development of acne.

“This change occurred largely because of the results of two important research studies that are repeatedly cited in the literature and popular culture as evidence to refute the association between diet and acne,” says Jennifer Burris, MS, RD, of the Department of Nutrition, Food Studies, and Public Health, Steinhardt School of Culture, Education, and Human Development, New York University. “More recently, dermatologists and registered dietitians have revisited the diet-acne relationship and become increasingly interested in the role of medical nutritional therapy in acne treatment.”

Burris and colleagues, William Rietkerk, Department of Dermatology, New York Medical College, and Kathleen Woolf, of New York University’s Department of Nutrition, Food Studies, and Public Health, conducted a literature review to evaluate evidence for the diet-acne connection during three distinctive time periods: early history, the rise of the diet-acne myth, and recent research.

Culling information from studies between 1960 and 2012 that investigated diet and acne, investigators compiled data for a number of study characteristics, including reference, design, participants, intervention method, primary outcome, results and conclusions, covariate considerations, and limitations.

They concluded that a high glycemic index/glycemic load diet and frequent dairy consumption are the leading factors in establishing the link between diet and acne. They also note that although research results from studies conducted over the last 10 years do not demonstrate that diet causes acne, it may influence or aggravate it.

The study team recommends that dermatologists and registered dietitians work collaboratively to design and conduct quality research. “This research is necessary to fully elucidate preliminary results, determine the proposed underlying mechanisms linking diet and acne, and develop potential dietary interventions for acne treatment,” says Burris. “The medical community should not dismiss the possibility of diet therapy as an adjunct treatment for acne. At this time, the best approach is to address each acne patient individually, carefully considering the possibility of dietary counseling.”

Study: Resveratrol shows promise to protect hearing, cognition

DETROIT – Resveratrol, a substance found in red grapes and red wine, may have the potential to protect against hearing and cognitive decline, according to a published laboratory study from Henry Ford Hospital in Detroit.

The study shows that healthy rats are less likely to suffer the long-term effects of noise-induced hearing loss when given resveratrol before being exposed to loud noise for a long period of time.

“Our latest study focuses on resveratrol and its effect on bioinflammation, the body’s response to injury and something that is believed to be the cause of many health problems including Alzheimer’s disease, cancer, aging and hearing loss,” says study lead author Michael D. Seidman, director of the Division of Otologic/Neurotologic Surgery in the Department of Otolaryngology-Head & Neck Surgery at Henry Ford Hospital.

“Resveratrol is a very powerful chemical that seems to protect against the body’s inflammatory process as it relates to aging, cognition and hearing loss.”

The study is published online this week ahead of print in the journal Otolaryngology-Head and Neck Surgery: http://oto.sagepub.com.

Hearing loss affects nearly one in five Americans. For most, hearing steadily declines with age. Noise-induced hearing loss, too, is a growing medical issue among American troops, with more than 12 percent returning home from Iraq and Afghanistan with significant hearing loss.

Noise-induced hearing loss not only impacts a person’s ability to hear, it can cause difficulties with sleep and communication, and even raises the risk for heart disease by increasing a person’s blood pressure, lipids and blood sugar.

Dr. Seidman and his colleagues have published multiple papers exploring noise-induced hearing loss, as well as the use of resveratrol, a grape constituent noted for its antioxidant and anti-inflammatory properties.

The latest study focuses the inflammatory process as it relates to aging, cognition and hearing loss.

It was designed to identify the potential protective mechanism of resveratrol following noise exposure by measuring its effect on cyclooxygenase-2 (or COX-2, key to the inflammatory process) protein expression and formation of reactive oxygen species, which plays an important role in cell signaling and homeostasis.

The study reveals that acoustic overstimulation causes a time-depended, up-regulation of COX-2 protein expression. And, resveratrol significantly reduces reactive oxygen species formation, inhibits COX-2 expression and reduces noise-induced hearing loss following noise exposure in rats.

“We’ve shown that by giving animals resveratrol, we can reduce the amount of hearing and cognitive decline,” notes Dr. Seidman.

Ultimately, these findings suggest that resveratrol may exert a protective effect from noise-induced hearing loss by the inhibition of COX-2 expression and reactive oxygen species formation, although other mechanism may also be involved.

 

Mushroom-supplemented soybean extract shows therapeutic promise for advanced prostate cancer

February 20, 2013

(SACRAMENTO, Calif.) —

A natural, nontoxic product called genistein-combined polysaccharide, or GCP, which is commercially available in health stores, could help lengthen the life expectancy of certain prostate cancer patients, UC Davis researchers have found.

Men with prostate cancer that has spread to other parts of the body, known as metastatic cancer, and who have had their testosterone lowered with drug therapy are most likely to benefit. The study, recently published in Endocrine-Related Cancer, was conducted in prostate cancer cells and in mice.

Lowering of testosterone, also known as androgen-deprivation therapy, has long been the standard of care for patients with metastatic prostate cancer, but life expectancies vary widely for those who undergo this treatment. Testosterone is an androgen, the generic term for any compound that stimulates or controls development and maintenance of male characteristics by binding to androgen receptors.

The current findings hold promise for GCP therapy as a way to extend life expectancy of patients with low response to androgen-deprivation therapy.

Paramita Ghosh, an associate professor in the UC Davis School of Medicine, led the pre-clinical study with a team that included UC Davis Comprehensive Cancer Center Director Ralph de Vere White, a UC Davis distinguished professor of urology. Ruth Vinall in the UC Davis Department of Urology and Clifford Tepper in the UC Davis Department of Biochemistry and Molecular Medicine directed the studies in mice; Ghosh’s laboratory conducted the cell studies.

The research focused on GCP, a proprietary extract cultured from soybeans and shiitake mushrooms and marketed by Amino-Up of Sapporo, Japan. Researchers found that the combination of the compounds genistein and daidzein, both present in GCP, helps block a key mechanism used by prostate cancer cells to survive in the face of testosterone deprivation.

The research team had earlier shown that when a patient’s androgen level goes down, cancerous prostate cells kick out a protein known as filamin A, which is otherwise attached to the androgen receptor in the cell’s nucleus. The androgen receptor regulates growth of prostate cancer cells. Once filamin A leaves the cancerous cell’s nucleus, that cell no longer requires androgens to survive. Thus, loss of filamin A allows these cells to survive androgen deprivation, at and the cancer essentially becomes incurable.

The paper, titled “Enhancing the effectiveness of androgen deprivation in prostate cancer by inducing Filamin A nuclear localization,” shows for the first time that GCP keeps filamin A in the nucleus. As long as this protein remains attached to the androgen receptor, the cancerous cells need androgens to survive and grow. They die off when starved of androgens, thus prolonging the effects of androgen deprivation, which ultimately prolongs the patient’s life.

The team’s hypothesis is that metastatic prostate cancer patients with the weakest response to androgen-deprivation therapy could be given GCP concurrently with androgen deprivation therapy to retain Filamin A in the nucleus, thereby allowing cancer cells to die off. 

De Vere White is now pursuing funding to begin GCP human clinical trials. Because GCP is a natural product rather than a drug, and requires fewer government approvals, it’s expected that these trials will proceed rapidly once funded.

“We should know within the first eight months or so of human clinical trials if GCP works to reduce PSA levels,” says de Vere White, referring to prostate-specific antigen levels, a tumor marker to detect cancer. “We want to see up to 75 percent of metastatic prostate cancer patients lower their PSA levels, and GCP holds promise of accomplishing this goal. If that happens, it would probably be a greater therapy than any drug today.”

The research was supported by a Biomedical Laboratory Research and Development service Merit Award (I01BX000400) from the Department of Veterans Affairs and by R01CA133209 from the National Cancer Institute.

Other authors were Benjamin A. Mooso, Sheetal Singh, Salma Siddiqui, and Maria Mudryj of the VA Northern California Health Care System; Ruth L. Vinall, Rosalinda M. Savoy, Jean P. Cheung, and Yu Wang of the UC Davis Department of Urology; Clifford G. Tepper, Anthony Martinez, and Hsing-Jien Kung of the UC Davis Department of Biochemistry and Molecular Medicine; and Roble G. Bedolla of the University of Texas Health Science Center at San Antonio.  

OMEGA-3s Inhibit Breast Cancer Tumour Growth, U of G Study Finds

 

February 21, 2013 – News Release

A lifelong diet rich in omega-3 fatty acids can inhibit growth of breast cancer tumours by 30 per cent, according to new research from the University of Guelph.

The study, published recently in the Journal of Nutritional Biochemistry, is believed to be the first to provide unequivocal evidence that omega-3s reduce cancer risk.

“It’s a significant finding,” said David Ma, a professor in Guelph’s Department of Human Health and Nutritional Sciences, and one of the study’s authors.

“We show that lifelong exposure to omega-3s has a beneficial role in disease prevention – in this case, breast cancer prevention. What’s important is that we have proven that omega-3s are the driving force and not something else.”

Breast cancer remains the most common form of cancer in women worldwide and is the second leading cause of female cancer deaths.

Advocates have long believed diet may significantly help in preventing cancer. But epidemiological and experimental studies to back up such claims have been lacking, and human studies have been inconsistent, Ma said.

“There are inherent challenges in conducting and measuring diet in such studies, and it has hindered our ability to firmly establish linkages between dietary nutrients and cancer risk,” he said.

“So we’ve used modern genetic tools to address a classic nutritional question.”

For their study, the researchers created a novel transgenic mouse that both produces omega-3 fatty acids and develops aggressive mammary tumours. The team compared those animals to mice genetically engineered only to develop the same tumours.

“This model provides a purely genetic approach to investigate the effects of lifelong omega-3s exposure on breast cancer development,” Ma said.

“To our knowledge, no such approach has been used previously to investigate the role of omega-3s and breast cancer.”

Mice producing omega-3s developed only two-thirds as many tumours – and tumours were also 30-per-cent smaller – as compared to the control mice.

“The difference can be solely attributed to the presence of omega-3s in the transgenic mice – that’s significant,” Ma said.

“The fact that a food nutrient can have a significant effect on tumour development and growth is remarkable and has considerable implications in breast cancer prevention.”

Known as an expert in how fats influence health and disease, Ma hopes the study leads to more research on using diet to reduce cancer risk and on the benefits of healthy living.

“Prevention is an area of growing importance. We are working to build a better planet, and that includes better lifestyle and diet,” he said.

“The long-term consequences of reducing disease incidence can have a tremendous effect on the health-care system.”

The study also involved lead author Mira MacLennan, a former U of G graduate student who is now studying medicine at Dalhousie University; U of G pathobiology professor Geoffrey Wood; former Guelph graduate students Shannon Clarke and Kate Perez; William Muller from McGill University; and Jing Kang from Harvard Medical School.

Funding for this research came from the Canadian Breast Cancer Research Alliance/Canadian Institutes of Health Research, the Canada Foundation for Innovation and the Ontario Research Fund.

Scientists unveil secrets of important natural antibiotic

An international team of scientists has discovered how an important natural antibiotic called dermcidin, produced by our skin when we sweat, is a highly efficient tool to fight tuberculosis germs and other dangerous bugs.

Their results could contribute to the development of new antibiotics that control multi-resistant bacteria.

Scientists have uncovered the atomic structure of the compound, enabling them to pinpoint for the first time what makes dermcidin such an efficient weapon in the battle against dangerous bugs.

Although about 1700 types of these natural antibiotics are known to exist, scientists did not until now have a detailed understanding of how they work.

The study, carried out by researchers from the University of Edinburgh and from Goettingen, Tuebingen and Strasbourg, is published in Proceedings of the National Academy of Sciences.

Sweat spreads highly efficient antibiotics on to our skin, which protect us from dangerous bugs. If our skin becomes injured by a small cut, a scratch, or the sting of a mosquito, antibiotic agents secreted in sweat glands, such as dermcidin, rapidly and efficiently kill invaders.

These natural substances, known as antimicrobial peptides (AMPs), are more effective in the long term than traditional antibiotics, because germs are not capable of quickly developing resistance against them.

The antimicrobials can attack the bugs’ Achilles’ heel – their cell wall, which cannot be modified quickly to resist attack. Because of this, AMPs have great potential to form a new generation of antibiotics.

Scientists have known for some time that dermcidin is activated in salty, slightly acidic sweat. The molecule then forms tiny channels perforating the cell membrane of bugs, which are stabilised by charged particles of zinc present in sweat. As a consequence, water and charged particles flow uncontrollably across the membrane, eventually killing the harmful microbes.

Through a combination of techniques, scientists were able to determine the atomic structure of the molecular channel. They found that it is unusually long, permeable and adaptable, and so represents a new class of membrane protein.

The team also discovered that dermcidin can adapt to extremely variable types of membrane. Scientists say this could explain why active dermcidin is such an efficient broad-spectrum antibiotic, able to fend off bacteria and fungi at the same time.

The compound is active against many well-known pathogens such as tuberculosis, Mycobacterium tuberculosis, or Staphylococcus aureus. Multi-resistant strains of Staphylococcus aureus, in particular, have become an increasing threat for hospital patients. They are insensitive towards conventional antibiotics and so are difficult to treat. Staphylococcus aureus infections can lead to life-threatening diseases such as sepsis and pneumonia. The international team of scientists hopes that their results can contribute to the development of a new class of antibiotics that is able to attack such dangerous germs.

Dr Ulrich Zachariae of the University of Edinburgh’s School of Physics, who took part in the study, said: “Antibiotics are not only available on prescription. Our own bodies produce efficient substances to fend off bacteria, fungi and viruses. Now that we know in detail how these natural antibiotics work, we can use this to help develop infection-fighting drugs that are more effective than conventional antibiotics.”

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