Resveratrol a Natural Compound Mitigates Effects of Methamphetamine Abuse

Nov. 19, 2013

Story Contact(s):  Jeff Sossamon, sossamonj@missouri.edu, 573-882-3346

COLUMBIA, Mo. – Studies have shown that resveratrol, a natural compound found in colored vegetables, fruits and especially grapes, may minimize the impact of Parkinson’s disease, stroke and Alzheimer’s disease in those who maintain healthy diets or who regularly take resveratrol supplements. Now, researchers at the University of Missouri have found that resveratrol may also block the effects of the highly addictive drug, methamphetamine.

Continue reading “Resveratrol a Natural Compound Mitigates Effects of Methamphetamine Abuse”

Statins block the ability of exercise to improve fitness levels

Cholesterol-Lowering Drug May Reduce Exercise Benefits for Obese Adults, MU Study Finds

May 15, 2013

Story Contact(s):

Jesslyn  Chew, ChewJ@missouri.edu, (573) 882-8353

By Kate McIntyre

COLUMBIA, Mo. – Statins, the most widely prescribed drugs worldwide, are often suggested to lower cholesterol and prevent heart disease in individuals with obesity, diabetes and metabolic syndrome, which is a combination of medical disorders including excess body fat and/or high levels of blood pressure, blood sugar and/or cholesterol. However, University of Missouri researchers found that simvastatin, a generic type of statin previously sold under the brand name “Zocor,” hindered the positive effects of exercise for obese and overweight adults.

“Fitness has proven to be the most significant predictor of longevity and health because it protects people from a variety of chronic diseases,” said John Thyfault, an associate professor of nutrition and exercise physiology at MU. “Daily physical activity is needed to maintain or improve fitness, and thus improve health outcomes. However, if patients start exercising and taking statins at the same time, it seems that statins block the ability of exercise to improve their fitness levels.”

Thyfault says many cardiologists want to prescribe statins to all patients over a certain age regardless of whether they have metabolic syndrome; the drugs also are recommended for people with Type 2 diabetes. He recommends that cardiologists more closely weigh the benefits and risks of statins given this new data about their effect on exercise training.

“Statins have only been used for about 15-20 years, so we don’t know what the long-term effects of statins will be on aerobic fitness and overall health,” Thyfault said. “If the drugs cause complications with improving or maintaining fitness, not everyone should be prescribed statins.”

Thyfault and his colleagues measured cardiorespiratory fitness in 37 previously sedentary, obese individuals ages 25-59 with low fitness levels. The participants followed the same exercise regimen on the MU campus for 12 weeks; 18 of the 37 people also took 40 mg of simvastatin daily.

Statins significantly affected participants’ exercise outcomes. Participants in the exercise-only group increased their cardiorespiratory fitness by an average of 10 percent compared to a 1.5 percent increase among participants also prescribed statins. Additionally, skeletal muscle mitochondrial content, the site where muscle cells turn oxygen into energy, decreased by 4.5 percent in the group taking statins while the exercise-only group had a 13 percent increase, a normal response following exercise training.

Thyfault suggests that future research determine whether lower doses of simvastatin or other types of statins similarly affect people’s exercise outcomes and thus their risk for diseases such as Type 2 diabetes. Starting a statin regimen after exercising and obtaining a higher fitness level may reduce the drugs’ effects on fitness, he says.

The study, “Simvastatin impairs exercise training adaptations,” was published in the Journal of the American College of Cardiology. Co-authors included first author Catherine Mikus, who is now a postdoctoral fellow at Duke University, and MU researchers Leryn Boyle, Douglas Oberlin, Scott Naples, Justin Fletcher, Harold Laughlin, Kevin Dellsperger and Paul Fadel. Funding was provided by a grant from the MU Research Board, the Veterans Affairs’ Career Development Award, an American Heart Association Midwest Affiliate Clinical Research Award and the National Institutes of Health. The Department of Nutrition and Exercise Physiology is jointly administered by the College of Agriculture, Food and Natural Resources, the College of Human Environmental Sciences and the School of Medicine. Thyfault has a joint appointment in the Department of Internal Medicine in the Division of Gastroenterology and Hepatology in the MU School of Medicine.

Bisphenol A Affects Sex-Specific Reproductive Behaviors in a Monogamous Animal Species, Says MU Researcher

Animal Findings Suggest That Gender May Also Influence Chemical Exposure Risks for Humans

Feb. 11, 2013

Story Contact(s):

Timothy Wall, walltj@missouri.edu, 573-882 3346

COLUMBIA, Mo. — Parents, teachers and psychologists know boys and girls behave differently. However, that difference isn’t taken into account by most methods used to assess the risk to children from chemical exposure, according to Cheryl Rosenfeld, associate professor of biomedical sciences in the University of Missouri’s Bond Life Sciences Center. A series of experiments by Rosenfeld studied the effects of prenatal exposure to bisphenol A (BPA) on later reproductive-associated behaviors using a socially and genetically monogamous rodent, the California mouse, which may better mirror most human societies than other rodents.

She observed harmful alterations to behaviors that affect the likelihood of successfully attracting a mate and reproducing. However, developmental exposure to BPA altered the behaviors of males differently than females. In females, BPA reduced exploratory behavior that is essential for them to forage to provide nutritional support to her offspring. In contrast, California mice males exposed to BPA demonstrated reduced territorial marking, which is essential for them to defend a home range and their mate. Rosenfeld suggests that these animal findings might provide a framework to guide human risk assessment studies in the sense that such studies may need to consider that pre- and post-natal exposure to BPA might differentially impact boys’ versus girls’ behaviors.

The American public comes into daily contact with the chemical bisphenol A (BPA) as it is present in a wide assortment of products, including some types of paper receipts, plastic containers and canned goods, including beer and soda cans. The concern of many scientists is that the chemical can mimic the effect of female hormones in the human body. Studies looking for behavioral effects of BPA in children often focus on expression of general behaviors, such as aggression, anxiety or other traits, but more refined assessments are needed for boys versus girls, according to Rosenfeld.

“We use animal models to provide informative decisions about our own health and the risks associated with BPA,” Rosenfeld said. “What we have observed in those models is that BPA affects male rodents differently than females. Risk assessment studies examining the impacts of BPA in humans could be more accurate if they took sex into account when monitoring for changes in children’s behavioral patterns.”

Rosenfeld’s most recent study observed the influence of prenatal BPA exposure on California mice, whereas earlier studies had used deer mice. The two rodent species have contrasting mating behaviors. California mice are monogamous, as opposed to the polygamous deer mice. Although BPA affected the California mice differently than the deer mice, both rodent species’ behaviors were altered in ways that would decrease their ability to successfully mate and pass on their genes to future generations. Since two species of rodents with different mating patterns were both affected, it suggests that BPA disrupts essential reproductive-associated behaviors that are species- and sex-specific.

For information on Rosenfeld’s work on deer mice see this press release: BPA-Exposed Male Deer Mice are Demasculinized and Undesirable to Females, New MU Study Finds

The study, “Effects of Developmental Bisphenol A Exposure on Reproductive-Related Behaviors in California Mice (Peromyscus californicus): A Monogamous Animal Model” was published in PLOS ONE. The study can be viewed at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0055698

Co-authors included University of Missouri researchers: Scott Williams, Eldin Jašarević, Gregory Vandas, Denise Warzak, David Geary, Mark Ellersieck and R. Michael Roberts.

Compound in grapes, red wine could be key to fighting prostate cancer

Contact: Christian Basi
BasiC@missouri.edu
573-882-4430
University of Missouri-Columbia

MU researcher finds that prostate tumor cells are more susceptible to treatment after being exposed to resveratrol, a compound found in grape skins and red wine

:Nicholl has discovered that a compound found in grape skins and red wine can make prostate tumor cells more susceptible to radiation treatment.

COLUMBIA, Mo. — Resveratrol, a compound found commonly in grape skins and red wine, has been shown to have several beneficial effects on human health, including cardiovascular health and stroke prevention. Now, a University of Missouri researcher has discovered that the compound can make prostate tumor cells more susceptible to radiation treatment, increasing the chances of a full recovery from all types of prostate cancer, including aggressive tumors.

“Other studies have noted that resveratrol made tumor cells more susceptible to chemotherapy, and we wanted to see if it had the same effect for radiation therapy,” said Michael Nicholl, an assistant professor of surgical oncology in the MU School of Medicine. “We found that when exposed to the compound, the tumor cells were more susceptible to radiation treatment, but that the effect was greater than just treating with both compounds separately.”

Cells contain very low levels of two proteins, perforin and granzyme B, which can function together to kill cells. However, both proteins need to be highly “expressed” to kill tumor cells. In his study, when Nicholl introduced resveratrol into the prostate tumor cells, the activity of the two proteins increased greatly. Following radiation treatment, Nicholl found that up to 97 percent of the tumor cells died, which is a much higher percentage than treatment with radiation alone.

“It is critical that both proteins, perforin and granzyme B, are present in order to kill the tumor cells, and we found that the resveratrol helped to increase their activity in prostate tumor cells,” Nicholl said. “Following the resveratrol-radiation treatment, we realized that we were able to kill many more tumor cells when compared with treating the tumor with radiation alone. It’s important to note that this killed all types of prostate tumor cells, including aggressive tumor cells.”

Resveratrol is present in grape skins and red wine and available over-the-counter in many health food sections at grocery stores. However, the dosage needed to have an effect on tumor cells is so great that many people would experience uncomfortable side effects.

VIDEO:University of Missouri scientists have found that resveratrol can make prostate tumor cells more susceptible to radiation treatment.

Click here for more information.

 

“We don’t need a large dose at the site of the tumor, but the body processes this compound so efficiently that a person needs to ingest a lot of resveratrol to make sure enough of it ends up at the tumor site. Because of that challenge, we have to look at different delivery methods for this compound to be effective,” Nicholl said. “It’s very attractive as a therapeutic agent since it is a natural compound and something that most of us have consumed in our lifetimes.”

Nicholl said that the next step would be to test the procedure in an animal model before any clinical trials can be initiated. Nicholl’s studies were published in the Journal of Andrology and Cancer Science. The early-stage results of this research are promising. If additional studies, including animal studies, are successful within the next few years, MU officials will request authority from the federal government to begin human drug development (this is commonly referred to as the “investigative new drug” status). After this status has been granted, researchers may conduct human clinical trials with the hope of developing new treatments for cancer.

 

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Aspirin, Tylenol May Decrease Effectiveness of Vaccines: “if you block COX-1, you might be decreasing the amount of antibodies your body is producing”

2009 study posted for filing

Contact: Kelsey Jackson JacksonKN@missouri.edu 573-882-8353 University of Missouri-Columbia

Aspirin, tylenol may decrease effectiveness of vaccines

Mizzou scientists discover aspirin and Tylenol block enzymes that could inhibit vaccines

COLUMBIA, Mo. – With flu season in full swing and the threat of H1N1 looming, demand for vaccines is at an all-time high. Although those vaccines are expected to be effective, University of Missouri researchers have found further evidence that some over-the-counter drugs, such as aspirin and Tylenol, that inhibit certain enzymes could impact the effectiveness of vaccines.

“If you’re taking aspirin regularly, which many people do for cardiovascular treatment, or acetaminophen (Tylenol) for pain and fever and get a flu shot, there is a good chance that you won’t have a good antibody response,” said Charles Brown, associate professor of veterinary pathobiology in the MU College of Veterinary Medicine. “These drugs block the enzyme COX-1, which works in tissues throughout the body. We have found that if you block COX-1, you might be decreasing the amount of antibodies your body is producing, and you need high amounts of antibodies to be protected.”

COX enzymes play important roles in the regulation of the immune system. The role of these enzymes is not yet understood completely, and medications that inhibit them may have adverse side effects. Recent research has discovered that drugs that inhibit COX enzymes, such as COX-2, have an impact on the effectiveness of vaccines. Brown’s research indicates that inhibiting COX-1, which is present in tissues throughout the body, such as the brain or kidneys, could also impact vaccines’ effectiveness.

These MU researchers also are studying the regulation of inflammation and how that leads to the development or prevention of disease. Many diseases, such as arthritis, cardiovascular disease and diabetes, are all chronic inflammatory diseases. Contrary to previous beliefs, inflammation is generally a good thing that helps protect individuals from infection. Many of the non-steroidal drugs that treat inflammatory conditions reduce antibody responses, which are necessary for treating infections.

“So far, we’ve tested this on an animal model and have found that these non-steroidal drugs do inhibit vaccines, but the next step is to test it on humans,” Brown said. “If our results show that COX-1 inhibitors affect vaccines, the takeaway might be to not take drugs, such as aspirin, Tylenol and ibuprofen, for a couple weeks before and after you get a vaccine.”

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Brown’s research, “Cycloozygenase-1 Orchestrates Germinal Center Formation and Antibody Class-Switch via Regulation of IL-17,” has been published in The Journal of Immunology.

Young adults may outgrow bipolar disorder

2009 study posted for filing
Contact: Kelsey Jackson
JacksonKN@missouri.edu
573-882-8353
University of Missouri-Columbia

MU researchers find evidence that there may be developmentally limited forms of bipolar disorder

COLUMBIA, Mo. –Bipolar disorder, or manic-depression, causes severe and unusual shifts in mood and energy, affecting a person’s ability to perform everyday tasks. With symptoms often starting in early adulthood, bipolar disorder has been thought of traditionally as a lifelong disorder. Now, University of Missouri researchers have found evidence that nearly half of those diagnosed between the ages of 18 and 25 may outgrow the disorder by the time they reach 30.

“Using two large nationally representative studies, we found that there was a strikingly high peak prevalence of bipolar disorders in emerging adulthood,” said David Cicero, doctoral student in the Department of Psychological Sciences in the College of Arts and Science and lead author of the paper. “During the third decade of life, the prevalence of the disorder appears to resolve substantially, suggesting patients become less symptomatic and may have a greater chance of recovery.”

By examining the results of two large national surveys, MU researchers found an “age gradient” in the prevalence of bipolar disorder, with part of the population appearing to outgrow the disorder. In the survey results, 5.5 to 6.2 percent of people between the ages of 18 and 24 suffer from bipolar disorder, but only about 3 percent of people older than 29 suffer from bipolar disorder.

“Young adults between the ages of 18 and 24 are going through significant life changes and social strain, which could influence both the onset and course of the disorder,” said Kenneth J. Sher, Curators’ Professor in the Department of Psychological Sciences and co-author of the study. “During this period of life, young adults are exploring new roles and relationships and begin to leave their parents’ homes for school or work. By the mid 20s, adults have begun to adjust to these changes and begin to settle down and form committed relationships.”

Researchers predict the prevalence of the disorder also could be affected by brain development, particularly the prefrontal cortex. The prefrontal cortex, the very front part of the brain, is thought to control perception, senses, personality and intelligence. In particular, it controls reactions to social situations, which can be a challenge for people with bipolar disorder.

“The maturing of the prefrontal cortex of the brain around 25 years of age could biologically explain the developmentally limited aspect of bipolar disorder,” Cicero said. “Other researchers have found a similar pattern in young adults with alcohol or substance abuse disorders.”

While some scholars suggest that the difference could be due to discounting factors such as early mortality, the sheer number of those who are recovering rules out this possibility, Sher said.

 

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The study, “Are There Developmentally Limited Forms of Bipolar Disorder?” was published in the Journal of Abnormal Psychology. It was co-authored by Cicero, Sher and Amee Epler, a doctoral student in the Department of Psychological Sciences.

Viruses Help MU Scientists Battle Pathogenic Bacteria and Improve Water Supply

 

Newly developed technique can kill antibiotic-resistant germs

Sept. 24, 2012

Story Contact(s):
Timothy Wall, walltj@missouri.edu, 573-882-3346

COLUMBIA, Mo. — Infectious bacteria received a taste of their own medicine from University of Missouri researchers who used viruses to infect and kill colonies of Pseudomonas aeruginosa, common disease-causing bacteria. The viruses, known as bacteriophages, could be used to efficiently sanitize water treatment facilities and may aid in the fight against deadly antibiotic-resistant bacteria.

“Our experiment was the first to use bacteriophages in conjunction with chlorine to destroy biofilms, which are layers of bacteria growing on a solid surface,” said Zhiqiang Hu, associate professor of civil and environmental engineering in MU’s College of Engineering. “The advantage to using viruses is that they can selectively kill harmful bacteria. Beneficial bacteria, such as those used to break down wastes in water treatment plants, are largely unaffected. Hence, viruses could be used to get rid of pathogenic bacteria in water filters that would otherwise have to be replaced. They could save taxpayers’ money by reducing the cost of cleaning water.”

Bacteria can be difficult to kill when they form a biofilm. The outer crust of bacteria in these biofilms can be killed by chlorine, but the inner bacteria are sheltered. Viruses solve this problem because they spread through an entire colony of bacteria. Hu noted that the bacteriophages are easier to create than the enzymes used to attack biofilms. The viruses also are better at targeting specific bacterial species.

Hu, along with MU’s recent graduate, Yanyan Zhang, found the greatest success in killing biofilms by using a combination of bacteriophages and chlorine. An initial treatment with viruses followed by chlorine knocked out 97 percent of biofilms within five days of exposure. When used alone, viruses removed 89 percent of biofilms, while chlorine removed only 40 percent.

“The methods we used to kill Pseudomonas aeruginosa could be used against other dangerous bacteria, even those that have developed resistance to antibiotics,” said Hu. “Our work opened the door to a new strategy for combating the dangers and costs of bacterial biofilms. The next step is to expand our experiment into a pilot study.”

The study “Combined Treatment of Pseudomonas aeruginosa Biofilms with Bacteriophages and Chlorine” has been published in the journal Biotechnology and Bioengineering.

Higher urinary levels of commonly used chemical, BPA, linked with cardiovascular disease, diabetes

2008 post for filing

Contact: David Melzer, M.B., Ph.D. david.melzer@pms.ac.uk JAMA and Archives Journals

Higher levels of urinary Bisphenol A (BPA), a chemical compound commonly used in plastic packaging for food and beverages, is associated with cardiovascular disease, type 2 diabetes and liver-enzyme abnormalities, according to a study in the September 17 issue of JAMA. This study is being released early to coincide with a Food and Drug Administration (FDA) hearing on BPA.

BPA is one of the world’s highest production–volume chemicals, with more than two million metric tons produced worldwide in 2003 and annual increase in demand of 6 percent to 10 percent annually, according to background information in the article. It is used in plastics in many consumer products. “Widespread and continuous exposure to BPA, primarily through food but also through drinking water, dental sealants, dermal exposure, and inhalation of household dusts, is evident from the presence of detectable levels of BPA in more than 90 percent of the U.S. population,” the authors write. Evidence of adverse effects in animals has created concern over low-level chronic exposures in humans, but there is little data of sufficient statistical power to detect low-dose effects. This is the first study of associations with BPA levels in a large population, and it explores “normal” levels of BPA exposure.

David Melzer, M.B., Ph.D., of Peninsula Medical School, Exeter, U.K., and colleagues examined associations between urinary BPA concentrations and the health status of adults, using data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. The survey included 1,455 adults, age 18 through 74 years, with measured urinary BPA concentrations.

The researchers found that average BPA concentrations, adjusted for age and sex, appeared higher in those who reported diagnoses of cardiovascular diseases and diabetes. A 1-Standard Deviation (SD) increase in BPA concentration was associated with a 39 percent increased odds of cardiovascular disease (angina, coronary heart disease, or heart attack combined) and diabetes.

When dividing BPA concentrations into quartiles, participants in the highest BPA concentration quartile had nearly three times the odds of cardiovascular disease compared with those in the lowest quartile. Similarly, those in the highest BPA concentration quartile had 2.4 times the odds of diabetes compared with those in the lowest quartile.

In addition, higher BPA concentrations were associated with clinically abnormal concentrations for three liver enzymes. No associations with other diagnoses were observed.

“Using data representative of the adult U.S. population, we found that higher urinary concentrations of BPA were associated with an increased prevalence of cardiovascular disease, diabetes, and liver-enzyme abnormalities. These findings add to the evidence suggesting adverse effects of low-dose BPA in animals. Independent replication and follow-up studies are needed to confirm these findings and to provide evidence on whether the associations are causal,” the authors conclude. “Given the substantial negative effects on adult health that may be associated with increased BPA concentrations and also given the potential for reducing human exposure, our findings deserve scientific follow-up.”

(JAMA. 2008;300[11]:1303-1310. Available pre-embargo to the media at www.jamamedia.org)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.


Editorial: Bisphenol A and Risk of Metabolic Disorders

In accompanying editorial, Frederick S. vom Saal, Ph.D., of the University of Missouri, Columbia, and John Peterson Myers, Ph.D., of Environmental Health Sciences, Charlottesville, Va., comment on the findings regarding BPA.

“Since worldwide BPA production has now reached approximately 7 billion pounds per year, eliminating direct exposures from its use in food and beverage containers will prove far easier than finding solutions for the massive worldwide contamination by this chemical due its to disposal in landfills and the dumping into aquatic ecosystems of myriad other products containing BPA, which Canada has already declared to be a major environmental contaminant.”

“The good news is that government action to reduce exposures may offer an effective intervention for improving health and reducing the burden of some of the most consequential human health problems. Thus, even while awaiting confirmation of the findings of Lang et al, decreasing exposure to BPA and developing alternatives to its use are the logical next steps to minimize risk to public health.”

(JAMA. 2008;300[11]:1353-1355. Available pre-embargo to the media at www.jamamedia.org)

Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.