Thursday, August 16, 2012

Risk Of Bladder Cancer Increased For Over 15 Million Americans Taking Diabetes Drugs

A popular class of diabetes drugs increases patients' risk of bladder cancer, according to a new study published online this month in the Journal of the National Cancer Institute. Researchers from the Perelman School of Medicine at the University of Pennsylvania found that patients taking thiazolidinedione (TZDs) drugs - which account for up to 20 percent of the drugs prescribed to diabetics in the United States - are two to three times more likely to develop bladder cancer than those who took a sulfonylurea drug, another common class of medications for diabetes.

The authors say the findings are especially important since diabetic patients are known to already be at a slightly increased risk of this type of cancer as compared to the generation population, in which about 30 in 100,000 people develop bladder cancer. Among diabetes patients overall, the incidence of this cancer is typically about 40 out of 100,000.

The authors of the new study analyzed 60,000 Type 2 diabetes patients from the Health Improvement Network (THIN) database in the United Kingdom. They found that patients treated with the TZD drugs pioglitazone (Actos) or rosiglitzaone (Avandia) for five or more years had a two-to-three-fold increase in risk of developing bladder cancer when compared to those who took sulfonylurea drugs. Among patients taking TZDs for that length of time, the team's analysis indicates that 170 patients per 100,000 would be expected to develop the disease. About 60 in 100,000 of those who take sulfonylurea drugs - such as glipizide (Glucotrol) - would be expected to develop bladder cancer.

"Diabetes is one the most common chronic diseases worldwide, affecting 285 million people. There are many factors clinicians must weigh in deciding which drug to use to control a patient's diabetes, and these new data provide important information to include in that decision-making process," said the study's lead author, Ronac Mamtani, MD, an instructor in the division of Hematology-Oncology in Penn's Abramson Cancer Center. "Our study shows that doctors who care for patients with diabetes should be very aware of any bladder-related symptoms patients might be having, like blood in the urine, and take steps to further evaluate those issues."

Though most patients in the United States no longer take Avandia since it was linked to severe cardiovascular problems, Actos is the ninth most commonly prescribed drug in the nation, accounting for some 15 million prescriptions each year. The drug is a common choice when Type 2 diabetes patients' illnesses can no longer be controlled with the first-line diabetes drug Metformin.

Based on previous data examining safety risks among patients taking Actos, the FDA has already warned that it may be associated with a risk of bladder cancer, and France and Germany have removed the drug from their markets. The new findings add to mounting evidence against the entire class of TZDs, as one of the first studies examining this type of risk among people taking both types of TZDs and among those taking sulfonylurea drugs.

"The risk does seem to be common among both drugs in the TZD class, and the fact that we have compared bladder cancer risk among patients taking each of those drugs provides essential information, because a safety warning on a drug is only useful to a doctor when they have knowledge of the same risks for an alternative drug," Mamtani says. "We believe our study will help doctors and their patients weigh the potential benefits and risks when selecting between different diabetes medication."
http://www.medicalnewstoday.com/releases/248984.php


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Wednesday, August 15, 2012

Butter Flavoring Ingredient in Microwave Popcorn, Thought Safe for Food Industry Workers, Is a Respiratory Hazard

ScienceDaily (Aug. 13, 2012) — The ingredient 2,3-pentanedione (PD), used to impart the flavor and aroma of butter in microwave popcorn, is a respiratory hazard that can also alter gene expression in the brain of rats. Manufacturers started using PD when another butter flavoring, diacetyl, was found to cause bronchiolitis obliterans, a life-threatening and nonreversible lung disease in workers who inhaled the substance. New research on PD with implications for "popcorn workers' lung" is published in The American Journal of Pathology and indicates that acute PD exposure has respiratory toxicity which is comparable to diacetyl in laboratory animals.
"Our study demonstrates that PD, like diacetyl, damages airway epithelium in laboratory studies. This finding is important because the damage is believed to be the underlying cause of bronchiolitis obliterans," says lead investigator Ann F. Hubbs, DVM, PhD, DACVP, Health Effects Laboratory Division of the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV. "Our study also supports established recommendations that flavorings should be substituted only when there is evidence that the substitute is less toxic than the agent it replaces."

The study included groups of rats exposed for six hours to different concentrations of PD, a comparable concentration of diacetyl, or filtered air. Since the investigators observed signs of delayed toxicity, they exposed additional rats to PD, and further microscopically examined the brains, lungs, and nasal tissues from these rats 0-2 hours, 12-14 hours, and 18-20 hours after exposure. investigators then evaluated changes in gene expression in discrete brain regions.

The investigators found respiratory epithelial injury in the upper nose, comparable to that caused by diacetyl that progressed through 12 to 14 hours post-exposure. They also found that PD exposure caused necrosis and apoptosis in the olfactory neuroepithelium and activation of caspase 3, a protein that plays a role in cell death, in axons of olfactory nerve bundles. Signs consistent with neurotoxicity included increased expression of the inflammatory mediators, interleukin-6 and nitric oxide synthase-2, as well as decreased expression of vascular endothelial growth factor A in the olfactory bulb, striatum, hippocampus, and cerebellum.

"Our study is a reminder that a chemical with a long history of being eaten without any evidence of toxicity can still be an agent with respiratory toxicity when appropriate studies are conducted," says Dr. Hubbs. "It suggests several intriguing potential mechanisms for the toxicity of inhaled volatile α-diketones, reveals mRNA changes in the brain, documents olfactory neurotoxicity, and clearly demonstrates that the remarkable airway toxicity of diacetyl is shared with its close structural relative, PD."

http://www.sciencedaily.com/releases/2012/08/120813115450.htm


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Mediterranean diet enriched with olive oil may protect bone

New study shows intake of olive oil associated with increase in bone formation markers

Chevy Chase, MD—A study to be published in the Endocrine Society's Journal of Clinical Endocrinology and Metabolism (JCEM) shows consumption of a Mediterranean diet enriched with olive oil for two years is associated with increased serum osteocalcin concentrations, suggesting a protective effect on bone.

Age-related bone mass loss and decreased bone strength affects women and men alike are an important determinant of osteoporosis and fracture risk. Studies have shown that the incidence of osteoporosis in Europe is lower in the Mediterranean basin. The traditional Mediterranean diet, rich in fruits and vegetables, with a high intake of olives and olive oil could be one of the environmental factors underlying this difference.

"The intake of olive oil has been related to the prevention of osteoporosis in experimental and in vitro models," said José Manuel Fernández-Real, MD, PhD, of Hospital Dr. Josep Trueta in Girona, Spain and lead author of the study. "This is the first randomized study which demonstrates that olive oil preserves bone, at least as inferred by circulating bone markers, in humans."

The participants in this study were 127 community-dwelling men aged 55 to 80 years randomly selected from one of the Prevencion con Dieta Mediterranea (PREDIMED) study centers who had at least two years of follow-up. The PREDIMED study is a large, parallel group, randomized, controlled trial aimed to assess the effect of the Mediterranean diet on the prevention of cardiovascular diseases.
For this study, subjects were elderly without prior cardiovascular disease but having a diagnosis of type 2 diabetes or harboring at least three cardiovascular risk factors, namely hypertension, dyslipidemia, or a family history of premature cardiovascular disease. Participants were randomly assigned to three intervention groups: Mediterranean diet with mixed nuts, Mediterranean diet with virgin olive oil, and a low-fat diet.

Biochemical measurements of osteocalcin, glucose, total cholesterol, HDL-cholesterol and triglycerides were performed at baseline and after two year follow-up on fasting blood samples. Researchers found that only consumption of the Mediterranean diet with olive oil was associated with a significant increase in the concentrations of total osteocalcin and other bone formation markers.

There were also no significant changes in serum calcium in subjects taking olive oil whereas serum calcium decreased significantly in the other two groups.

"It's important to note that circulating osteocalcin was associated with preserved insulin secretion in subjects taking olive oil," added Fernández-Real. "Osteocalcin has also been described to increase insulin secretion in experimental models."
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Other researchers who helped with the study included Mónica Bulló, José Maria Moreno-Navarrete, Wifredo Ricart, Emilio Ros, Ramon Estruch, and Jordi Salas-Salvadó of Instituto de Salud Carlos III in Madrid, Spain.
The article, "A Mediterranean Diet Enriched with Olive Oil is Associated with Higher Serum Total Osteocalcin Levels in Elderly Men at High Cardiovascular Risk," will appear in the October 2012 issue of JCEM.
Founded in 1916, The Endocrine Society is the world's oldest, largest and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 15,000 scientists, physicians, educators, nurses and students in more than 100 countries. Society members represent all basic, applied and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society and the field of endocrinology, visit our site at www.endo-society.org. Follow us on Twitter at https://twitter.com/#!/EndoMedia.

http://www.eurekalert.org/pub_releases/2012-08/tes-mde081312.php


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Wednesday, August 8, 2012

Women With Major Depression Benefit From Creatine

Women battling stubborn major depression may have a surprising new ally in their fight - the muscle-building dietary supplement creatine.

In a new proof-of-concept study, researchers from three South Korean universities and the University of Utah report that women with major depressive disorder (MDD) who augmented their daily antidepressant with 5 grams of creatine responded twice as fast and experienced remission of the illness at twice the rate of women who took the antidepressant alone. The study, published in the American Journal of Psychiatry online, means that taking creatine under a doctor's supervision could provide a relatively inexpensive way for women who haven't responded well to SSRI (selective serotonin reuptake inhibitor) antidepressants to improve their treatment outcomes.

"If we can get people to feel better more quickly, they're more likely to stay with treatment and, ultimately, have better outcomes," says Perry F. Renshaw, M.D., Ph.D., M.B.A, USTAR professor of psychiatry at the U of U medical school and senior author on the study.

If these initial study results are borne out by further, larger trials, the benefits of taking creatine could directly affect many Utahns. The depression incidence in Utah is estimated to be 25 percent higher than the rest of the nation, meaning the state has an even larger proportion of people with the disease. This also brings a huge economic cost to both the state and individuals.

According to numbers recently compiled at the U of U, the state of Utah paid an estimated $214 million in depression-related Medicaid and disability insurance in 2008. Add the costs of inpatient and outpatient treatment, medication, and lost productivity in the workplace, and the total price of depression in Utah reached $1.3 billion in 2008, according to the U estimate. With those large numbers, any treatment that improves outcomes not only could ease the life of thousands of Utah women but also would save millions of dollars.

"There has been a misunderstanding of how crippling and common this disease is in Utah," says Renshaw, who's also medical director of the Mental Illness Research, Education and Clinical Center at the Salt Lake City Veterans Affairs Health Care System. "It begs that we understand it better than we do."

Creatine is an amino acid made in the human liver, kidneys, and pancreas. It also is found in meat and fish. Inside the body it is converted into phosphocreatine and stored in muscle. During high-intensity exercise, phosphocreatine is converted into ATP, an important energy source for cells. For this reason, creatine has become a popular supplement among bodybuilders and athletes who are trying to add muscle mass or improve athletic ability.

How creatine works against depression is not precisely known, but Renshaw and his colleagues suggest that the pro-energetic effect of creatine supplementation, including the making of more phosphocreatine, may contribute to the earlier and greater response to antidepressants.

The eight-week study included 52 South Korean women, ages 19-65, with major depressive disorder. All the women took the antidepressant Lexapro (escitalopram) during the trial. Twenty-five of the women received creatine with the Lexapro and 27 were given a placebo. Neither the study participants nor the researchers knew who received creatine or placebo. Eight women in the creatine group and five in the placebo group did not finish the trial, leaving a total of 39 participants.

Participants were interviewed at the start of the trial to establish baselines for their depression, and then were checked at two, four, and eight weeks to see how they'd responded to Lexapro plus creatine or Lexapro and a placebo. The researchers used three measures to check the severity of depression, with the primary outcomes being measured by the Hamilton Depression Rating Scale (HDRS), a widely accepted test.

The group that received creatine showed significantly higher improvement rates on the HDRS at two and four weeks (32 percent and 68 percent) compared to the placebo group (3.7 percent and 29 percent). At the end of eight weeks, half of those in the creatine group showed no signs of depression compared with one-quarter in the placebo group. There were no significant adverse side effects associated with creatine.

Antidepressants typically don't start to work until four to six weeks. But research shows that the sooner an antidepressant begins to work, the better the treatment outcome, and that's why Renshaw and his colleagues are excited about the results of this first study. "Getting people to feel better faster is the Holy Grail of treating depression," he says.

Study co-author Tae-Suk Kim, M.D., Ph.D., associate professor of psychiatry at the Catholic University of Korea College of Medicine and visiting associate professor of psychiatry at the U of U, already is recommending creatine for some of his female depression patients.

In prior studies, creatine had been shown to be effective only in female rats. But that shouldn't rule out testing the supplement in men as well, according to Renshaw.

U of U researchers expect soon to begin another trial to test creatine in adolescent and college-age females who have not responded to SSRI medications. Principal investigator Douglas G. Kondo, M.D., assistant professor of psychiatry, says he is looking for 40 females between the ages of 13-21. Recruitment of participants will begin as soon as the U of U Institutional Review Board approves the study, which is expected in early July.

After the initial eight weeks of treatment, study participants will be offered a six-month extension of close supervision and monitoring by the research team and board-certified child, adolescent, and adult psychiatrist at no charge.
http://www.medicalnewstoday.com/releases/248709.php


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