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211 CNO Report 23 JUL 2015

211CNO25JUL2015

clip_image002CNO Report 211

Release Date 23 JUL 2015

Draft Report Compiled by

Ralph Turchiano

http://www.clinicalnews.org

 

In This Issue:

1.      Antioxidants help treat skin-picking disorder in mice, Stanford researcher says

2.      Nutrients turn on key tumor signaling molecule, fueling resistance to cancer therapy, Ludwig Cancer Research study shows

3.      Antidepressant trials exclude most ‘real world’ patients with depression

4.      How GPR40, a known receptor for dietary fatty acids, may protect from osteoarthritis?

5.      Study finds autism, ADHD run high in children of chemically intolerant mothers

6.      Antibiotic exposure could increase the risk of juvenile arthritis

7.      PNAS: Evolution not just mutation drives development of cancer

8.      Elderberry benefits air travelers

9.      Blood vessels can actually get better with age

10.   Teeth reveal lifetime exposures to metals, toxins

11.   Soybean oil causes more obesity than coconut oil and fructose

 

Public Release: 13-Jul-2015

Antioxidants help treat skin-picking disorder in mice, Stanford researcher says

Stanford University Medical Center

 

Two antioxidant supplements are effective in treating skin-picking disorder in mice, according to a study led by a Stanford University School of Medicine researcher.

The finding suggests that people with the potentially serious disorder might benefit from this therapy.

An estimated 4 percent of the population — or about 1 in 25 — suffer from skin-picking disorder, in which repeated, compulsive picking or scratching of the skin can lead to severe disfigurement and life-threatening infection. Skin picking is also common among laboratory mice, which may develop potentially fatal ulcerative dermatitis, or skin lesions, caused by excessive grooming.

The condition is the single leading avoidable cause of death among laboratory mice, said Joseph Garner, PhD, associate professor of comparative medicine and senior author of the study, which was published online today in PLOS ONE. The lead author is Nneka George, DVM, of the University of North Carolina at Chapel Hill.

In the study, the researchers experimented with two antioxidant supplements — N-acetylcysteine and glutathione — to treat mice with skin-picking disorder. NAC is used by cells to make glutathione, which is the brain’s main, naturally occurring antioxidant. NAC has been used experimentally in people with a variety of conditions, including Parkinson’s disease, autism and cystic fibrosis, and reports of individual cases suggest it could be useful in treating skin picking.

Potentially fewer side effects from glutathione

“With NAC, almost every mouse got a little bit better,” Garner said. “But there is a huge variability is response, anywhere from a slight improvement to complete cure, which is what you see in humans.”

NAC also took a long time to show an effect: If an animal was cured, it took six to eight weeks. With glutathione, the pattern was very different. Fifty percent responded, but in these animals it was a rapid, all-or-nothing response: If they got better, they were completely cured in two to three weeks. The animals that didn’t get better were worse off to start with, the researchers found.

Garner said the results suggest that glutathione might be an even more powerful therapeutic, with potentially fewer side effects.

“What’s exciting is that we have a compound that works. It works as well as NAC. It’s clearly working differently, or at least more directly. This different response profile gives us some hope that there may be some nonresponders, or people who can’t tolerate NAC, who may be helped by glutathione,” he said.

Skin-picking disorder is a surprisingly common condition, yet many patients avoid seeking help because of the shame and embarrassment, Garner said.

“This can lead to really serious disfigurement in extreme cases,” he said. “People suffer in complete silence. They think they are the only one who has it, despite the fact that it’s very common, and it kills people.”

By the time people do seek help, about 35 percent have required some kind of antibiotic treatment, and 5 percent have required intravenous antibiotics to treat potentially life-threatening infections, he said. Some are referred for psychiatric help. Although cognitive behavioral therapy can be an effective form of treatment, there are few practitioners equipped to do this form of therapy, Garner said.

People with the condition also may be prone to compulsive hair pulling, another body-focused, repetitive-behavior disorder. A clinical trial among patients with the hair-pulling disorder, also known as trichotillomania, showed NAC to be an effective treatment in 56 percent of cases.

Study methods

In the latest study, the researchers selected 16 mice with lesions on the face, neck and limbs — signs of skin picking. Because the condition is painful and potentially fatal, the researchers treated all the mice with a thin film of topical antibiotic and steroidal ointment to relieve their discomfort. A third of the mice received a high dose of NAC in their drinking water. Another third were given drops of glutathione on the nose. (Because mice are nose breathers, they easily inhaled the compound.) A control group was given neither of the compounds.

Almost all the animals treated with NAC showed some improvement, though the improvement was slow. By the end of the study, 40 percent were fully cured. Among the animals treated with glutathione, results were more rapid: Within two to four weeks, about half were cured; the other half did not respond. There was no change among the control animals.

Garner believes that NAC works by combating oxidative stress that causes certain cells in the brain to die or become inactive.

“Our thought is maybe NAC works because in the brain it is the precursor to glutathione, and the brain has to make glutathione to protect itself against oxidative stress,” he said.

NAC, however, isn’t easily tolerated by many people, causing gastrointestinal distress, he said. Intra-nasal glutathione, on the other hand, may avoid these potential side effects by bypassing the gut and liver, delivering the compound directly to the brain. He first presented the results in April to a patient advocacy group.

“The sense of excitement from patients, advocates and researchers was palpable,” he said. “This is the first new potential drug for this disorder in years.”

Garner said his next step is to plan a clinical trial in patients to test the value of intra-nasal glutathione.

Public Release: 13-Jul-2015

Nutrients turn on key tumor signaling molecule, fueling resistance to cancer therapy, Ludwig Cancer Research study shows

Ludwig Institute for Cancer Research

 

July 13, 2015, New York — Tumors can leverage glucose and another nutrient, acetate, to resist targeted therapies directed at specific cellular molecules, according to Ludwig Cancer Research scientists studying glioblastoma, a deadly brain cancer.

The findings, published in the July 13 Proceedings of the National Academy of Sciences, demonstrate that nutrients can strongly affect the signaling molecules that drive tumors. “This study shows that metabolic and nutritional factors might be quite important in cancer development and treatment,” says Ludwig San Diego member Paul Mischel, the lead author of the study, and Professor of Pathology at the University of California, San Diego.

The study also highlights one way that tumors can evade targeted drugs such as erlotinib and gefitinib, inhibitors of a mutant form of the cellular molecule EGFR (epidermal growth factor receptor) that drives the growth of many glioblastomas and other tumor types.

Cancer researchers have known for years that tumors have unusual metabolisms – their rapid use of glucose is used as a diagnostic tool for tumors in PET scans. But only recently have scientists begun to flesh out the details of this metabolic shift. Mischel and other researchers have previously shown that this shift can occur through the activation of a central cellular signal, mTORC2 (mTOR complex 2). mTORC2 is involved in switching cancer cells to a hyperactive metabolic state, for instance prompting the increased influx of glucose and acetate into cancer cells. Glucose and acetate provide fuel and cellular building blocks to perpetuate the rapid growth of tumors.

In the new study, Mischel and his colleagues, including Ludwig postdoctoral fellow Kenta Masui, now an independent researcher in Japan, and Web Cavenee of Ludwig Cancer Research, found that glucose and acetate in turn regulate mTORC2, propelling tumor growth and fending off targeted drugs. “This is a two way street,” explains Mischel. “Signaling molecules like mTORC2 can change metabolism, and metabolites can change mTORC2.”

The findings first emerged from experiments in glioblastoma cells cultivated in a petri dish. In one experiment, the researchers treated the cells with either glucose or acetate and found that at least one of these nutrients was required in order to turn on mTORC2 in response. The researchers also tested glioblastoma cells with a mutant form of EGFR that turns on mTORC2 and propels tumor growth. In the absence of glucose and acetate, EGFR inhibitors can switch off mTORC2 signaling. But when the researchers added glucose and acetate, the drugs did not work – mTORC2 stayed on and the cells thrived. The researchers delved further, showing how acetate and glucose activate mTORC2 through a molecule formed from these metabolites, acetyl-coA, which is critical for activating a key component of mTORC2.

Together, the experiments show that glucose or acetate can activate mTORC2 through the production of acetyl-coA, enabling tumors to resist targeted therapies such as EGFR inhibitors. Activated mTORC2 in turn propels tumor growth by regulating metabolism and other cellular processes. The researchers provide evidence that a similar mechanism operates in cells taken directly from glioblastoma patients and in human glioblastoma cells implanted into mice.

The findings provide a window into the treatment of glioblastoma, which leaves most newly diagnosed patients with less than two years to live. To reduce deadly brain swelling, many glioblastoma patients require treatment with steroids, which are known to raise blood glucose levels. The new study suggests that the drugs, which may be necessary to control brain swelling, could also have the paradoxical effect of propelling tumor growth through activation of mTORC2. Findings in the study also suggest that developing drugs to effectively target mTORC2 may be one avenue to shutting down glioblastoma and possibly other types of tumors.

“We think this may be a general mechanism in cancer,” adds Mischel, who is planning to investigate the role of glucose and acetate in other types of tumors.

The researchers are also beginning to think about how to modify diet in mice to affect the production of these and other metabolites. Mischel notes that the study does not point to the value of any particular diet for counteracting cancer. “How do you turn these findings into something you do for patients? It is going to take diligent and careful work to determine how lifestyle changes, including diet, can alter tumor cell metabolism. We are actively studying this process and hope that this information can be used to develop more effective prevention and treatment strategies for cancer patients.”

From a broader perspective, Mischel is intrigued by long-standing arguments among scientists about how much of cancer can be ascribed to environment and how much is random and uncontrollable. The new study suggests that there may be more interplay between genes involved in cancer and the environment than previously thought.

Public Release: 14-Jul-2015

Antidepressant trials exclude most ‘real world’ patients with depression

Wolters Kluwer Health

 

July 14, 2015 – More than 80 percent of people with depression in the general population aren’t eligible for clinical trials of antidepressant drugs, according to a study in the Journal of Psychiatric Practice. The journal is published by Wolters Kluwer.

At least five patients would need to be screened to enroll just one patient meeting the typical inclusion and exclusion criteria for antidepressant registration trials (ARTs), suggests the new research by Drs. Sheldon Preskorn and Matthew Macaluso of University of Kansas School of Medicine-Wichita and Dr. Madhukar Trivedi of Southwestern Medical School, Dallas. The study highlights some major differences between patients with depression seen in everyday clinical practice and those enrolled in ARTs–the studies of antidepressants that lead to FDA drug approval.

Most Patients with Major Depression Aren’t Eligible for ARTs

Antidepressant registration trials use certain inclusion and exclusion criteria to create a group of patients with similar characteristics. These criteria increase the chances of detecting true drug effects, while reducing “false signals” of safety problems or side effects. For example, ARTs commonly exclude patients with other medical problems–if their illness worsened during the study, it might raise inaccurate safety concerns about the drug being studied.

To find out how these inclusion and exclusion criteria affect patient selection for ARTs, the researchers analyzed more than 4,000 patients from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Funded by the National Institute of Mental Health, STAR*D was the largest and longest study of depression treatment ever conducted. To ensure that the “real world” population of patients with depression was represented, STAR*D used minimal exclusion criteria.

The researchers found that more than 82 percent of STAR*D patients would not be eligible for enrollment in current ARTs, based on a list of “usual” inclusion and exclusion criteria. Fourteen percent would be excluded on the basis of age alone–that’s because most ARTs exclude patients older than 65. Another 15 percent would be excluded because their depression was less severe than a commonly used cutoff point.

More than 20 percent of STAR*D patients would be excluded from ARTs because of a “clinically significant or unstable general medical condition.” Twenty-one percent of women would be excluded because they were not using birth control to prevent pregnancy during the study.

Because many ARTs use stricter criteria, the true exclusion rate is probably even higher, the authors note. For example, more recent studies have used even higher severity thresholds for enrollment, which would eliminate more than 90 percent of the STAR*D population. The researchers also point out that all of the STAR*D patients had obviously agreed to participate in that research study–which is something many people with depression might be unwilling to do.

The researchers hope their work will help drug developers understand how inclusion and exclusion criteria may affect enrollment in ARTs, and help them in developing an appropriate recruitment plan and timeline. “The timelines in most drug studies are unrealistically short and their recruitment plans are often woefully inadequate, resulting in studies that take longer than expected to complete and frequent budget overruns,” Drs. Preskorn, Macaluso, and Trivdei write. Failure to consider the effort needed for ART recruitment might lead to lost revenue, delays in bringing a drug to market, or failure to develop a potentially effective medication.

The findings may also help to explain to healthcare practitioners why ARTs tend to overestimate the benefits of antidepressant treatment in “real world” patients with depression. “Obviously,” the researchers add, “the more patients who are excluded from the ARTs, the greater the chances that the results will not generalize to the routine clinical practice.”

Public Release: 15-Jul-2015

How GPR40, a known receptor for dietary fatty acids, may protect from osteoarthritis?

Society for Experimental Biology and Medicine

 

Osteoarthritis (OA) is one of the most common age-related degenerative joint concerns. Although articular cartilage degradation is its main feature, this disease induces whole-joint damage characterized by synovitis, bone remodelling and osteophyte formation. Regarding bone, Yohann Wittrant, a researcher at the Human Nutrition Unit (INRA -France), has recently reported that stimulation of the orphan receptor GPR40, a fatty acid-activated receptor, preserved bone mass. Dietary fatty acids were described to improve joint function and reduce pain in OA patients and to decrease both inflammatory markers and cartilage catabolism factors in preclinical studies.

To test the hypothesis that GPR40 may prevent or protect from OA, a whole body GPR40 deficient mouse strain was used. Primary chondrocytes, isolated from these rodents, exhibited a higher pattern of inflammatory mediators’ secretion and an enhanced cartilage catabolic activity after their stimulation. An in vivo study using a model of surgical joint destabilization, revealed that GPR40 deficiency led to an aggravated OA phenotype characterized by a higher cartilage breakdown associated with subchondral bone sclerosis and osteophyte formation. “Our results clearly demonstrate that GPR40 invalidation heightens inflammation, cartilage catabolism, and bone remodelling resulting in an aggravated OA phenotype;” stated Laurent-Emmanuel Monfoulet, researcher at the Human Nutrition Unit. These data, reported in the July 2015 issue of Experimental Biology and Medicine, demonstrates for the first time that the activation of GPR40 protects joints from OA. These findings provide new insights into the design of innovative strategies for OA management especially by nutritional approaches.

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said “This intriguing study by Monfoulet et al provides both in vitro and in vivo evidence that GPR40 deficiency results in a more severe OA phenotype. This raises the promise that GPR40 can be an important therapeutic target for OA”

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Experimental Biology and Medicine is a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences. The journal was first established in 1903. Experimental Biology and Medicine is the journal of the Society of Experimental Biology and Medicine. To learn about the benefits of society membership visit http://www.sebm.org. If you are interested in publishing in the journal please visit http://ebm.sagepub.com/

Public Release: 20-Jul-2015

Study finds autism, ADHD run high in children of chemically intolerant mothers

Mothers with chemical intolerances are 2-3 times more likely than other women to have a child with autism or ADHD, according to a new study by the University of Texas Health Science Center at San Antonio

University of Texas Health Science Center at San Antonio

 

A new study from The University of Texas Health Science Center at San Antonio found that mothers with chemical intolerances are two to three times more likely than other women to have a child with autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD).

The medical study was published in the July-August 2015 issue of the Journal of the American Board of Family Medicine.

People who are chemically intolerant often have serious reactions to common chemicals and some become too sick to carry out routine functions. Chemical intolerance affects about 10 percent to 30 percent of the U.S. population. Developmental disorders such as autism and attention-deficit disorder affect one in six children in the United States.

The study included 282 mothers of children who had ASD and 258 mothers of children diagnosed with ADHD. The control group consisted of 154 mothers whose children had no developmental disorders.

The study was based on maternal responses to the Quick Environmental Exposure and Sensitivity Inventory, or QEESI, a 50-question survey used by physicians worldwide to diagnose chemical intolerance.

“We are most concerned about how vulnerable the children with ADHD and autism were to environmental exposures,” said the primary author, Lynne P. Heilbrun, M.P.H., autism research coordinator for the Department of Family and Community Medicine at the UT Health Science Center San Antonio. “Mothers reported that their children were significantly more sensitive to everyday exposures such as engine exhaust, gasoline, smoke, fragrances and cleaners than their neurotypical peers.” The children reportedly also were more sensitive to adverse effects from infections, medications, chemicals, foods and allergens, the authors said.

The authors said chemically intolerant mothers were three times more likely to report having a child with ASD and 2.3 times more likely to have a child with ADHD. The study did not assess fathers.

Mothers in the study who had a child with ASD or ADHD reported that their children had more illnesses or symptoms associated with chemical intolerance than control mothers.

·        The children with ADHD were 1.7 times more likely than control children (ASD were 4.9 times more likely) to have had multiple infections requiring prolonged use of antibiotics.

·        Children with ADHD were twice as likely as control children (ASD were 1.6 times more likely) to have allergies.

·        Children with ADHD were twice as likely (ASD were 3.5 times more likely) to have had nausea, headaches, dizziness or trouble breathing when exposed to smoke, nail polish remover, engine exhaust, gasoline, air fresheners or cleaning agents than control children.

·        Children with ADHD were twice as likely as controls (ASD were 4.8 times more likely) to have strong food preferences or cravings for cheese, chips, bread, pasta, rice, sugar, salt and chocolate.

“The American College of Obstetrics and Gynecology issued a consensus statement in 2013 saying that there is sufficient evidence linking toxic exposures to adverse birth and developmental outcomes, calling for physicians to inform women to avoid specific environmental exposures even before conception. Studies that linked tobacco and alcohol to neurological disorders were available for decades before recommendations to avoid these became a major public health initiative. Physicians have the opportunity right now to become proactive in helping mothers protect their children from neurological disorders plaguing U.S. families,” Heilbrun said.

The authors recommend that all mothers and pregnant women adopt preventive measures to avoid potentially harmful chemicals. Preventive measures include avoiding exposure to pesticides, solvents, combustion products, and chemicals used during construction and remodeling.

The authors urged doctors to use the QEESI to assess patients for potential chemical intolerance. Senior author Claudia S. Miller, M.D., professor emeritus at the Health Science Center and a visiting senior scientist for the Harvard School of Public Health, said, “It’s important for everyone to know that doctors can use a readily available tool to identify more susceptible mothers and to suggest environmental interventions to help protect themselves and their developing children.”

Public Release: 20-Jul-2015

Antibiotic exposure could increase the risk of juvenile arthritis

 

Findings may offer another reason to judiciously prescribe antibiotics to children

Rutgers University

Taking antibiotics may increase the risk that a child will develop juvenile arthritis, according to a study from Rutgers University, University of Pennsylvania and Nemours A.I. duPont Hospital for Children published today in Pediatrics.

Researchers found that children who were prescribed antibiotics had twice the risk of developing juvenile arthritis compared to children the same age who were not prescribed antibiotics. The more courses of antibiotics prescribed, the higher the associated risk, they found. The risk was strongest within one year of receiving antibiotics.

Between 4,300 and 9,700 children under the age of 16 are diagnosed with juvenile arthritis a year, according to the latest Centers for Disease Control and Prevention statistics. Juvenile arthritis, a form of autoimmune disease, involves chronic inflammation of the joints and eyes that can lead to pain, vision loss, and disability. Genetics explains only why about one quarter of children develop arthritis, which means environmental triggers may also play an important role in the onset of disease.

Previous studies indicate that about a quarter of antibiotics prescribed to children – and half of antibiotics prescribed for acute respiratory infections – are probably unnecessary. “Our research suggests another possible reason to avoid antibiotic overuse for infections that would otherwise get better on their own,” said Daniel Horton, a postdoctoral research fellow working in the Department of Pediatrics at Rutgers Robert Wood Johnson Medical School. He is also a biomedical informatics master’s degree candidate in the Rutgers School of Health Related Professions. Formerly a graduate student at the University of Pennsylvania and a physician at Nemours A.I. duPont Hospital for Children, Horton is lead author of the study published today in Pediatrics, a peer-reviewed journal of the American Academy of Pediatrics.

Researchers began the study in 2014 because of previous studies showing that antibiotics could predispose children to develop other chronic diseases, including inflammatory bowel disease. Disruption of microbial communities in the intestines and elsewhere appears to play a role in inflammatory bowel disease and other autoimmune diseases, including rheumatoid arthritis in adults. “Antibiotics are one of the better known disruptors of human microbial communities,” Horton noted.

Using The Health Improvement Network (THIN), a database with information on over 11 million people across the United Kingdom, the researchers compared children with newly diagnosed juvenile arthritis with age- and gender-matched control subjects. THIN provides researchers with high quality data on diagnoses and prescriptions for people under general practitioners’ care, Horton said.

Of the roughly 450,000 children studied, 152 were diagnosed with juvenile arthritis. After adjusting for other autoimmune conditions and previous infection, children who received prescriptions for antibiotics had an increased risk for developing juvenile arthritis.

Researchers also found that upper respiratory tract infections treated with antibiotics were more strongly associated with juvenile arthritis than untreated upper respiratory tract infections. Additionally, they noted that antiviral and antifungal drugs were not linked to juvenile arthritis, suggesting that risk for arthritis was specific to antibacterial medicines.

“This is an extremely important clue about the etiology of this serious and potentially crippling disease. If confirmed, it also provides a means for preventing it,” said Brian Strom, chancellor of Rutgers Biomedical and Health Sciences and a senior author on the study.

Viral infections have been suggested as triggers for juvenile arthritis, but multiple studies argue against this hypothesis. What is more clear, Horton said, is that children with juvenile arthritis have a higher risk of serious infections, in part because the immune system does not protect against infections as well as it should.

“So an alternative explanation to our findings is that this abnormal immune system makes children more susceptible to serious infection even before they are diagnosed with arthritis. Under this hypothesis, antibiotics would be a marker for abnormal immunity rather than a direct cause of arthritis,” Horton added. “A majority of children get antibiotics, but only about 1 in 1,000 get arthritis. So even if antibiotics do contribute to the development of arthritis, it’s clearly not the only factor.”

Horton cautioned that additional research is warranted to confirm these findings and to understand the mechanism that might link antibiotic use and arthritis in children.

Public Release: 21-Jul-2015

PNAS: Evolution not just mutation drives development of cancer

 

Solving ‘Peto’s Paradox,’ new model shows selection pressure of healthy tissue keeps cells with cancerous mutations in check

University of Colorado Anschutz Medical Campus

A paper published today in the Proceedings of the National Academy of Sciences argues against the commonly held “accumulation of mutations” model of oncogenesis in favor of a model that depends on evolutionary pressures acting on populations of cells. Basically, the paper states that the ecosystem of a healthy tissue landscape lets healthy cells outcompete ones with cancerous mutations; it is when the tissue ecosystem changes due to aging, smoking, or other stressors, that cells with cancerous mutations can suddenly find themselves the most fit, allowing their population to expand over generations of natural selection.

This new thinking about oncogenesis has profound implications for cancer therapy and drug design.

“We’ve been trying to make drugs that target mutations in cancer cells. But if it’s the ecosystem of the body, and not only cancer-causing mutations, that allows the growth of cancer, we should also be prioritizing interventions and lifestyle choices that promote the fitness of healthy cells in order to suppress the emergence of cancer,” says James DeGregori, PhD, associate director for basic science at University of Colorado Cancer Center, and the paper’s senior author.

The proposed model helps to answer a longstanding question in cancer science known as Peto’s Paradox – if cancer is due to random activating mutation, larger animals with more cells should be at greater risk of developing the disease earlier in their lives. Why then do mammals of vastly different sizes and lifespans all seem to develop cancer mostly late in life?

“Blue whales have more than a million times more cells and live about 50 times longer than a mouse, but the whale has no more risk than a mouse of developing cancer over its lifespan,” DeGregori says.

The answer that DeGregori and CU Cancer Center colleague Andrii Rozhok, PhD propose is that in addition to activating mutation, cancer may require age-associated changes to the tissue landscape in order for evolution to favor the survival and growth of cancer cells over the competition of healthy cells.

Consider the following two evolutionary scenarios: In a grassy lawn, the health of the lawn is the best defense against dandelions; and in the time of the dinosaurs, the environment selected for giant lizards until the meteor hit at which point the new context favored the evolution of new species better adapted to the changed environment, including larger mammals.

Let’s start with the lawn: “Healthy cells are optimized for the ecosystem of the healthy body. But when the tissue ecosystem changes, such as with aging or smoking, cancer-causing mutations are often very good at exploiting the conditions of a damaged tissue landscape,” DeGregori says. In this scenario, DeGregori’s suggestion to explore the development of interventions supporting the fitness of healthy tissues is like applying fertilizer to the lawn rather than herbicide to the weeds.

DeGregori’s model is supported by studies showing that mutations that can cause cancer do not necessarily increase a cell’s fitness. “In fact, healthy cells are so optimized to the healthy tissue landscape that almost any mutation makes them less fit,” DeGregori says.

For example, some cancer cells mutate in a way that allows them to survive in the oxygen-poor tissue environments found in the center of developing tumors. But this adaptation only confers a fitness benefit in oxygen-poor tissues. In a healthy, oxygen-rich tissue, this mutation would not confer this advantage. In healthy tissue, cells with this mutation lose the evolutionary race to the healthy cells; cancer cells are outcompeted and they die, or at least their population is held in check and remains insignificantly small.

But what happens when the tissue landscape changes? This brings us to the dinosaurs. Sixty-five million years ago, a warm, wet planet favored dinosaurs, though a few early mammals scurried among them. Then the giant meteor hit (among other environmental changes happening around this time), altering the basic dynamics of the ecosystem. It was this adjustment to the ecosystem that allowed furry and feathered, warm-blooded creatures to eventually dominate the earth.

It seems as if new, successful species are produced by new, successful genetic changes. But in this example, as in cancer, individuals with these “new” genetics may already exist and it is changes to the ecosystem that allow them to flourish. Yet cancer biologists focus on how cancer risk factors like aging and smoking create new mutations, instead of focusing on how these contexts alter tissue landscapes and thus alter selection for already-existing mutations. Supporting this idea, DeGregori points out that studies modeling stem-cell pools show that selection pressure from the tissue landscape is more powerful than mutations at deciding the makeup of a population of stem cells.

“When the body changes due to aging, smoking, inherited genetic differences or other factors, it changes the tissue ecosystem, allowing a new kind of cell to replace the healthy ones,” DeGregori says.

Certainly, cancer development requires mutations and other genetic alterations. But how do these mutations cause cancer? It may not be that these mutations create accidental “super cells” that immediately run amok. Oncogenic mutations are often or always present in the body, but are kept at bay by selection pressures set against them. That is, until the tissue ecosystem and its pressures change in ways that make cells with cancerous mutations more likely to survive than healthy cells, over time allowing the population of cancer cells to overcome that of healthy cells.

We can avoid some of these tissue changes by lifestyle choices, such as by not smoking. Unfortunately, we can’t put off aging forever. But there may be features of the tissue landscape that, with new therapies and new understanding, could be reinforced in ways resist cancer better, longer.

Public Release: 21-Jul-2015

Elderberry benefits air travellers

The negative health effects of international air travel are well documented but now it seems that the common elderberry can provide some relief

Griffith University

 

The negative health effects of international air travel are well documented but now it seems that the common elderberry can provide some relief.

Associate Professor Evelin Tiralongo and Dr Shirley Wee from Griffith’s Menzies Health Institute Queensland (MHIQ) have completed a clinical trial showing that an elderberry supplement can provide some protection from cold and flu-like symptoms following long-haul flights.

Intercontinental air travel can be stressful and affect a passenger’s physical and psychological wellbeing. Whilst jet lag and fatigue remain the best known problems, holidaymakers also often experience upper respiratory symptoms.

Presenting their results at the 21st Annual International Integrative Medicine Conference in Melbourne, the research team showed how elderberry appears to reduce the duration and severity of the cold.

The randomised, double-blind placebo controlled clinical trial was conducted with 312 economy class passengers travelling from Australia to an overseas destination. Cold episodes, cold duration and symptoms were recorded in a daily diary and participants also completed surveys before, during and after travel.

“We found that most cold episodes occurred in the placebo group, but the difference between the placebo and active group was not significant. However, the placebo group had a significantly higher number of cold episode days, and the symptom score in the placebo group over these days was also significantly higher,” says Associate Professor Tiralongo.

“Complementary medicines are used by two in three Australians, thus increasing the evidence base of these medicines should be at the forefront of our efforts. It’s often forgotten that the evidence for various herbal medicines is extract specific,” says Associate Professor Tiralongo.

The trial used capsules containing 300mg of a standardised, proprietary membrane-filtered elderberry extract which has shown to be effective in working against respiratory bacteria and influenza viruses.

The Griffith study follows recent European research published in the open access journal Current Therapeutic Research which suggests that a combination of Echinacea herb and root extract supplemented with elderberry can be as effective as the conventional antiviral medicine Tamiflu for the early treatment of influenza.

Blood vessels can actually get better with age

 

Study finds that arteries adapt to oxidative stress caused by aging

University of Missouri-Columbia

Columbia, Mo. — Although the causes of many age-related diseases remain unknown, oxidative stress is thought to be the main culprit. Oxidative stress has been linked to cardiovascular and neurodegenerative diseases including diabetes, hypertension and age-related cancers. However, researchers at the University of Missouri recently found that aging actually offered significant protection against oxidative stress. These findings suggest that aging may trigger an adaptive response to counteract the effects of oxidative stress on blood vessels.

“Molecules known as reactive oxygen species, or ROS, play an important role in regulating cellular function,” said Steven Segal, a professor of medical pharmacology and physiology at the MU School of Medicine and senior author of the study. “However, the overproduction of ROS can help create a condition referred to as oxidative stress, which can alter the function of cells and interfere with their growth and reproduction.”

To understand the effects of aging on the function of blood vessels when they are exposed to oxidative stress, Segal’s team studied the inner lining, or endothelium, of small resistance arteries. Resistance arteries are important to cardiovascular function because they regulate both the amount of blood flow into tissues and systemic blood pressure.

“We studied the endothelium from resistance arteries of male mice at 4 months and 24 months of age, which correspond to humans in their early 20s and mid-60s,” Segal said. “We first studied the endothelium under resting conditions and in the absence of oxidative stress. We then simulated oxidative stress by adding hydrogen peroxide. When oxidative stress was induced for 20 minutes, the endothelial cells of the younger mice had abnormal increases in calcium when compared to the endothelial cells of the older mice. This finding is important because when calcium gets too high, cells can be severely damaged.”

When oxidative stress was extended to 60 minutes, Segal’s team found that the death of endothelial cells in the younger mice was seven times greater than those from the older mice. These findings indicated that with advancing age, the endothelium had adapted to preserve cellular integrity when confronted with oxidative stress.

“The most surprising thing we found is that the endothelium was much less perturbed by oxidative stress during advanced age when compared to younger age,” Segal said. “This finding contrasts with the generally held belief that the functional integrity of the endothelium is compromised as we age. Our study suggests that blood vessels adapt during the aging process to regulate ROS and minimize cell death when subjected to an abrupt increase in oxidative stress. This adaptation helps to ensure that the arteries of older individuals can still do their jobs.”

“Although more studies are needed to identify the mechanism by which the endothelium adapts to advanced age, our study provides evidence that the natural tendency of the body is to adapt to oxidative stress during healthy aging,” Segal said.

Public Release: 22-Jul-2015

Teeth reveal lifetime exposures to metals, toxins

The Mount Sinai Hospital / Mount Sinai School of Medicine

 

 (NEW YORK CITY – July 22, 2015) Is it possible that too much iron in infant formula may potentially increase risk for neurodegenerative diseases like Parkinson’s in adulthood — and are teeth the window into the past that can help us tell? This and related theories were described in a “Perspectives” article authored by researchers from the Icahn School of Medicine at Mount Sinai and the University of Technology Sydney and Florey Institute of Neuroscience and Mental Health in Australia, and published online recently in Nature Reviews Neurology.

“Teeth are of particular interest to us for the measurement of chemical exposure in fetal and childhood development: they provide a chronological record of exposure from their microchemical composition in relation to defined growth lines, much like the rings in a tree trunk,” said Manish Arora, BDS, MPH, PhD, Director of Exposure Biology at the Senator Frank Lautenberg Environmental Health Sciences Laboratory at Mount Sinai and Associate Professor in Preventive Medicine and Dentistry at the Icahn School of Medicine. “Our analysis of iron deposits in teeth as a method for retrospective determination of exposure is just one application: we believe teeth have the potential to help track the impact of pollution on health globally.”

Dr. Arora, along with Dominic Hare, PhD, used the dental biomarker technology to distinguish breast-fed babies from formula fed babies. Now this technology can be applied to study the link between early iron exposure and late-life brain diseases like Parkinson’s and Alzheimer’s, which are associated with the abnormal processing of iron. While not all formula fed babies will experience neurodegeneration in adulthood, the combination of increased iron intake during infancy with a predisposition to impaired metal metabolism such as the inability of brain cells to remove excessive metals may damage those cells over time.

Dr. Hare, a Chancellor’s Research Fellow in the Elemental Bio-imaging Facility at the University of Technology Sydney, says “Only now do we have the technology available to use to look back in time at someone’s diet as a child, more than 60 years after they stopped wearing diapers. State-of-the-art imaging technology is a chemical time machine that can tell us about decades-old chemical exposures that are equivalent to a drop of ink in a swimming pool.”

In the case of baby formula, the need to better understand human iron metabolism has become more urgent with the global popularity of formula and fortified cereals. Adding iron to formula has been an industry standard for decades, in part because about two billion people worldwide – mostly in developing nations – are thought to have chronic anemia and iron deficiency. Evidence, however, that children in the United States or Europe, for instance, get too little iron is insufficient, according to the authors, and the reported developmental and nutritional benefits of iron are modest. The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition have since stated that there’s no evidence that babies of normal birthweight need iron supplementation, yet in the U.S. it’s still commonplace. Dr. Hare continues: “While it might seem like drawing a long bow linking what happens in childhood to diseases we think of as associated with growing old, the increasing rates of these diseases mean we need to do everything we can to find out what might play a role in how the disease starts. Knowing this gives us something to target when designing new treatments.”

Beyond the wide-reaching hypothesis that iron supplementation may increase risk of neurodegeneration, the authors think a priority in pediatric research should be the rigorous determination of iron supplementation needs of infants according to their individual iron status. Formula manufacturers have a responsibility to replicate the chemical composition of breast milk, particularly with regard to iron content. The current ‘one size fits all’ approach to iron supplementation may be both clinically unnecessary and introduce an unacceptable risk later in life. Whether this hypothesis proves to be true or not, it calls into question decades of treatment dogma that deserves to be revisited with the most cutting-edge technology available.

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Public Release: 22-Jul-2015

Soybean oil causes more obesity than coconut oil and fructose

UC Riverside scientists found mice on high soybean oil diet showed increased levels of weight gain and diabetes compared to mice on a high fructose diet or high coconut oil diet

University of California – Riverside

 

RIVERSIDE, Calif. — A diet high in soybean oil causes more obesity and diabetes than a diet high in fructose, a sugar commonly found in soda and processed foods, according to a just published paper by scientists at the University of California, Riverside.

The scientists fed male mice a series of four diets that contained 40 percent fat, similar to what Americans currently consume. In one diet the researchers used coconut oil, which consists primarily of saturated fat. In the second diet about half of the coconut oil was replaced with soybean oil, which contains primarily polyunsaturated fats and is a main ingredient in vegetable oil. That diet corresponded with roughly the amount of soybean oil Americans currently consume.

The other two diets had added fructose, comparable to the amount consumed by many Americans. All four diets contained the same number of calories and there was no significant difference in the amount of food eaten by the mice on the diets. Thus, the researchers were able to study the effects of the different oils and fructose in the context of a constant caloric intake.

Compared to mice on the high coconut oil diet, mice on the high soybean oil diet showed increased weight gain, larger fat deposits, a fatty liver with signs of injury, diabetes and insulin resistance, all of which are part of the Metabolic Syndrome. Fructose in the diet had less severe metabolic effects than soybean oil although it did cause more negative effects in the kidney and a marked increase in prolapsed rectums, a symptom of inflammatory bowel disease (IBD), which like obesity is on the rise.

The mice on the soybean oil-enriched diet gained almost 25 percent more weight than the mice on the coconut oil diet and 9 percent more weight than those on the fructose-enriched diet. And the mice on the fructose-enriched diet gained 12 percent more weight than those on a coconut oil rich diet.

“This was a major surprise for us – that soybean oil is causing more obesity and diabetes than fructose – especially when you see headlines everyday about the potential role of sugar consumption in the current obesity epidemic,” said Poonamjot Deol, the assistant project scientist who directed the project in the lab of Frances M. Sladek, a professor of cell biology and neuroscience.

The paper, “Soybean oil is more obesogenic and diabetogenic than coconut oil and fructose in mouse: potential role for the liver,” was published July 22 in the journal PLOS ONE.

In the U.S. the consumption of soybean oil has increased greatly in the last four decades due to a number of factors, including results from studies in the 1960s that found a positive correlation between saturated fatty acids and the risk of cardiovascular disease. As a result of these studies, nutritional guidelines were created that encouraged people to reduce their intake of saturated fats, commonly found in meat and dairy products, and increase their intake of polyunsaturated fatty acids found in plant oils, such as soybean oil.

Implementation of those new guidelines, as well as an increase in the cultivation of soybeans in the United States, has led to a remarkable increase in the consumption of soybean oil, which is found in processed foods, margarines, salad dressings and snack foods. Soybean oil now accounts for 60 percent of edible oil consumed in the United States. That increase in soybean oil consumption mirrors the rise in obesity rates in the United States in recent decades.

During the same time, fructose consumption in the United States significantly increased, from about 37 grams per day in 1977 to about 49 grams per day in 2004.

The research outlined in the paper is believed to be the first side-by-side look at the impacts of saturated fat, unsaturated fat and fructose on obesity, diabetes, insulin resistance and nonalcoholic fatty liver disease, which along with heart disease and hypertension, are referred to as the Metabolic Syndrome.

The study also includes extensive analysis of changes in gene expression and metabolite levels in the livers of mice fed these diets. The most striking results were those showing that soybean oil significantly affects the expression of many genes that metabolize drugs and other foreign compounds that enter the body, suggesting that a soybean oil-enriched diet could affect one’s response to drugs and environmental toxicants, if humans show the same response as mice.

The UC Riverside researchers also did a study with corn oil, which induced more obesity than coconut oil but not quite as much as soybean oil. They are currently doing tests with lard and olive oil. They have not tested canola oil or palm oil.

The researchers cautioned that they didn’t study the impacts of the diets on cardiovascular diseases and note in the paper that the consumption of vegetable oils could be beneficial for cardiac health, even if it also induces obesity and diabetes.

They also noted that there are many different types of saturated and unsaturated fats. This is particularly true for the saturated fats in animal products that were associated with heart disease in the studies in the 1960s: they tend to have a longer chain length than the saturated fats in coconut oil.

The latest paper relates to previously released findings by scientists in Sladek’s lab and at the UC Davis West Coast Metabolomics Center, which compared regular soybean oil to a new genetically modified soybean oil.

That research, presented at a conference in March, found that the new genetically modified, high oleic soybean oil (Plenish), which has a lower amount of polyunsaturated fatty acid than traditional soybean oil, is healthier than regular soybean oil but just barely. Using mice, the researchers found that the Plenish oil also induces fatty liver although somewhat less obesity and diabetes. Importantly, it did not cause insulin resistance, a pre-diabetic condition. It should be noted that both the regular soybean oil and Plenish are from soybeans that are genetically modified to be resistant to the herbicide RoundUp.

The researchers are now finalizing a manuscript about these findings that also incorporates tests done with olive oil.

 

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