SLU scientist says findings could re-frame how to fight aging
A compound which acts in the opposite way as growth hormone can reverse some of the signs of aging, a research team that includes a Saint Louis University physician has shown. The finding may be counter-intuitive to some older adults who take growth hormone, thinking it will help revitalize them.
Their research was published in the Dec. 6 online edition of the Proceedings of the National Academy of Sciences.
The findings are significant, says John E. Morley, M.D., study co-investigator and director of the divisions of geriatric medicine and endocrinology at Saint Louis University School of Medicine, because people sometimes take growth hormone, believing it will be the fountain of youth.
“Many older people have been taking growth hormone to rejuvenate themselves,” Morley said. “These results strongly suggest that growth hormone, when given to middle aged and older people, may be hazardous.”
The scientists studied the compound MZ-5-156, a “growth hormone-releasing hormone (GHRH) antagonist.” They conducted their research in the SAMP8 mouse model, a strain engineered for studies of the aging process. Overall, the researchers found that MZ-5-156 had positive effects on oxidative stress in the brain, improving cognition, telomerase activity (the actions of an enzyme which protects DNA material) and life span, while decreasing tumor activity.
MZ-5-156, like many GHRH antagonists, inhibited several human cancers, including prostate, breast, brain and lung cancers. It also had positive effects on learning, and is linked to improvements in short-term memory. The antioxidant actions led to less oxidative stress, reversing cognitive impairment in the aging mouse.
William A. Banks, M.D., lead study author and professor of internal medicine and geriatrics at the University of Washington School of Medicine in Seattle, said the results lead the team “to determine that antagonists of growth hormone-releasing hormone have beneficial effects on aging.”
The study team included as its corresponding author Andrew V. Schally, M.D., Ph.D., a professor in the department of pathology and division of hematology/oncology at the University of Miami Miller School of Medicine.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, infectious disease, liver disease, aging and brain disease and heart/lung disease.
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2010 will go down as the year the diet pill Meridia and pain pill Darvon were withdrawn from the market and the heart-attack associated diabetes drug Avandia was severely restricted.
But it was also the year the Justice Department filed the first criminal, not civil, charges against a drug company executive. Lauren Stevens, a former VP and assistant general counsel at GlaxoSmithKline, hid some 1,000 instances of GSK-paid doctors illegally promoting Wellbutrin to other doctors, say authorities.
It was also the year prominent psychiatrists Charles Nemeroff and Alan Schatzberg were accused of writing an entire book for GSK called Recognition and Treatment of Psychiatric Disorders: A Psychopharmacology Handbook for Primary Care.
Here are the drugs which make 2010’s Hall of Shame.
Yaz and Yasmin
Soon after Bayer launched the pill Yaz in 2006, billing it as going “beyond birth control,” 18-year-olds were coming down with blood clots, gall bladder disease, heart attacks and even strokes. FDA ordered Bayer to run correction ads that detail the drugs’ risks though Yaz sales are still brisk. In fact, financial analysts attribute a third quarter slump to a Yaz generic coming online, not dangerous side effects.
Lyrica, Topamax and Lamictal
In August FDA ordered a warning on the seizure drug Lamictal for aseptic meningitis (brain inflammation) but it is still the darling of military and civilian doctors for unapproved pain and migraine uses. All three drugs increase the risk of suicidal thoughts and behaviors according to their mandated labels, in addition to the memory and hair loss patients report.
Humira, Prolia and TNF Blockers
The drug industry’s highly promoted biologic drugs are made from genetically engineered hamster cells and suppress the immune system, inviting tuberculosis and several cancers. Yet Humira is advertised to healthy people for “clearer skin” and Prolia is advertised to prevent osteoporosis in healthy women.
After 397 FDA cases of possible psychosis, 227 domestic reports of suicidal behaviors and 28 actual suicides, the government banned pilots, air-traffic controllers and interstate truck and bus drivers from taking the antismoking drug Chantix in 2008. Its neuropsychiatric effects were immortalized when New Bohemians musician Carter Albrecht was shot to death in 2007 in Texas by a neighbor after acting aggressively on the Chantix.
The sleeping pill Ambien was immortalized as the drug Tiger Woods reportedly cavorted with his consorts on and former US Rep. Patrick Kennedy crashed his Ford Mustang on, while driving to Capitol Hill in the middle of the night to “vote” in 2006. Law enforcement officials say it has increased traffic accidents from people who drive and black out and don’t even recognize arresting officers.
Is it a coincidence that Tamoxifen maker AstraZeneca founded Breast Cancer Awareness Month and makes carcinogenic agrochemicals that cause breast cancer? As a breast cancer prevention drug, an American Journal of Medicine study found the average life expectancy increase from Tamoxifen was nine days. Public Citizen says for every case of breast cancer prevented on Tamoxifen there is a life-threatening case of blood clots, stroke or endometrial cancer.
Lipitor and Crestor
Why is Lipitor the best selling drug in the world? Because every adult with high LDL or fear of high LDL is on it. And also 2.8 million children, says Consumer Reports. All statins can cause muscle breakdown called rhabdomyolysis. And Crestor is so linked to the side effect, Public Citizen calls it a Do Not Use and the FDA’s David Graham named it one of the five most dangerous drugs before at a Congressional hearing.
Boniva and other bisphosphonate bone drugs are a good example of FDA approving once unapprovable drugs by transferring risk onto the public’s shoulders. The list of dangers on the label includes waiting 60 minutes before eating or drinking anything except plain water, never taking the drug with mineral water, sparkling water, coffee, tea, milk, juice or other oral medicine, including calcium, antacids, or vitamins and not lying down after you take it.
Pfizer’s hormone drug Prempro is linked to a 26 percent increase in breast cancer, 41 percent increase in strokes, 29 percent increase in heart attacks, 22 percent increase in cardiovascular disease and double the rate of blood clots. But its cognitive and cardiovascular “benefits” are being tested right now at major universities to debut an HT “Light,” hoping the public has a short memory.
Prozac, Paxil, Zoloft, SSRIs
Selective serotonin reuptake inhibitor (SSRIs) antidepressants like Prozac, Paxil, Zoloft and Lexapro probably did more to inflate drug industry profits than Viagra. But many say the drugs have also inflated police blotters. In addition to 4,200 published reports of SSRI-related violence, including the Columbine, Red Lake and NIU shootings, SSRIs can cause serotonin syndrome and gastrointestinal bleeding when taken with certain drugs. Paxil is linked to birth defects.
Effexor, Cymbalta, Pristiq, SNRIs
Selective norepinephrine reuptake inhibitors (SNRIs) are like their SSRIs chemical cousins except their norepinephrine effects can modulate pain, which has ushered in your-depression-is-really-pain, your-pain-is-really-depression and other crossover marketing. SNRI’s are also harder to quit than SSRIs. 739,000 web sites address “Effexor” and “withdrawal.”
Seroquel, Zyprexa, Geodon, atypical antipsychotics
The antipsychotic Seroquel tops 71 drugs on the FDA’s January 2010 adverse event report and is linked to unexplained troop deaths and many research scandals. But it’s the fifth biggest-selling drug in the world. Atypical antipsychotics cause weight gain and diabetes, the tardive dyskinesia they are marketed to prevent and death in the demented elderly. Yet FDA approved Zyprexa and Seroquel for children last year and the new atypical antipsychotic, Latuda this year. Maybe the FDA is bipolar.
Ritalin, Concerta, Strattera, Adderall and ADHD Drugs
ADHD drugs rob “kids of their right to be kids, their right to grow, their right to experience their full range of emotions, and their right to experience the world in its full hue of colors,” says Anatomy of an Epidemic author Robert Whitaker. But they are a gold mine for the drug industry. During an August conference call with financial analysts, Shire specialty pharmaceuticals president Mike Cola lauded the “very dynamic ADHD market,” and the “co-administration market” (in which kids don’t need one drug but several.)
Gardasil and Cervarix Vaccines
A pharma-government plot to inoculate the public with dangerous vaccines? Maybe not but why are governors like Texas’ Rick Perry mandating vaccination of girls for HPV? And why was University of Queensland lecturer Andrew Gunn silenced when he questioned the Gardasil vaccine? The HPV vaccine doesn’t work for all viral strains, requires a boo$ter and is linked to 56 US girls’ deaths as of September, according to the CDC.
Foradil Aerolizer, Serevent Diskus, Advair and Symbicort
Unlike drugs that look safe in trials and develop “safety signals” post marketing, the long-acting beta agonists (LABA), salmeterol and formoterol, found in many asthma drugs, never looked safe. Studies link them to an increase in asthma deaths, especially in African-Americans and children. They may have contributed to 5,000 deaths said Dr. David Graham at FDA hearings about the controversial asthma drugs.
Singulair and Accolate, leukotriene receptor antagonists
Leukotriene receptor antagonists also never looked safe. Original FDA reviewers said asthma control “deteriorates” on Singulair and it may not be safe in children. Last month, Fox TV reported Singulair, Merck’s top selling drug, is suspected of producing aggression, hostility, irritability, anxiety, hallucinations and night-terrors in kids, symptoms that are being diagnosed as ADHD. It is huckstered to parents by the trusted educational service Scholastic, Inc. and the American Academy of Pediatrics.
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A study was carried out to examine the extent to which quercetin and trans-resveratrol (RSV) prevented inflammation or insulin resistance in primary cultures of human adipocytes treated with tumor necrosis factor-a (TNF-a)—an inflammatory cytokine elevated in the plasma and adipose tissue of obese, diabetic individuals. Cultures of human adipocytes were pretreated with quercetin and trans-RSV followed by treatment with TNF-a. Subsequently, gene and protein markers of inflammation and insulin resistance were measured. The authors report that quercetin, and to a lesser extent trans-RSV, attenuated the TNF-a–induced expression of inflammatory genes such as interleukin (IL)-6, IL-1b, IL-8, and monocyte chemoattractant protein-1 (MCP-1) and the secretion of IL-6, IL-8, and MCP-1.
Forum members were concerned about certain aspects of the study, especially the extrapolation of in vitro results to in vivo situations. The in vitro conditions the authors describe are minimally representative of an in vivo condition. In vivo, after consumption of quercetin or resveratrol, these compounds undergo extensive metabolism, leading to glucuronidated, sulphated or methylated compounds. In a previous study, quercetin 3-glucoside was transformed to 3,4-dihydroxyphenylacetic acid, acetate and butyrate in cells from human gut; only 3′-methylquercetin has been detected in human plasma, present at a concentration of 0.1 to 0.2 µM after 3 h. The authors of the current paper are using concentrations up to 60 µM, concentrations which have not been found in vivo.
There were also concerns with the work on cell uptake of quercetin and resveratrol. Primary adipocytes were incubated with the polyphenols, but it is not clear whether or not the concentrations used were subtoxic. Our current knowledge is limited about local concentration of the molecules we are studying in subcellular compartments, their interaction with alternative targets, and eventually their transformation into products that could be more or less active on a given specific pathway. The real difficult and important issue is the identification of a reasonable convergence — if not agreement — between data originating from extremely distant approaches. In this case, the notion that metabolic diseases are related to a homeostatic imbalance in adipose tissue, linked to a different redox status, linked to activation of specific pathways, and that different redox sensitive polyphenols do have a protective effect, encompasses the evidence produced by extremely distant approaches.
From a clinical point of view, the role of phytochemicals acting as antioxidants and anti-inflammatory agents could be extremely important in inflammation-associated chronic conditions such as cardiovascular disease, diabetes, and cancer. Quercetin and resveratrol may indeed play an important role in this regard, and need to be investigated further to establish the clinical importance of natural dietary compounds in the prevention of chronic degenerative conditions.
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A compound in dairy fat could decrease the risk of developing Type 2 diabetes, according to a new study.
People who consumed the highest levels of dairy a day — one to one-and-a-half servings of whole milk, 2 percent milk, cheese or butter — had a 60 percent lower risk of developing Type 2 diabetes than people who ate the lowest amounts of dairy, researchers said.
The compound, called trans-palmitoleic acid, promotes healthy levels of blood cholesterol, normal insulin levels and increased insulin sensitivity, said study researcher Dr. Dariush Mozaffarian, assistant professor of medicine at Harvard Medical School.
“These findings do suggest that we should think of dairy as more than a carrier of calcium and vitamin D,” Mozaffarian told MyHealthNewsDaily.
The finding is based on 20 years of health data from 3,736 people who participated in the Cardiovascular Health Study, funded by the National Heart, Lung, and Blood Institute.
Although they, too, have the word “trans” in their name, trans-palmitoleic acids are not the same as the bad kinds of trans fats that can increase heart disease risk, Mozaffarian said. Trans-palmitoleic acids are found only in dairy products, whereas bad trans fats tend to come from industrially-produced partially hydrogenated vegetable oils.
The researchers said that trans-palmitoleic acids may decrease diabetes risk by mimicking the function of a related compound, called cis-palmitoleic acid, which is produced naturally in the liver.
Thousands of years ago, cis-palmitoleic acid protected the body against high levels consumption of carbohydrates and calories during a meal, which were infrequent at the time. But modern diets are loaded with carbohydrates and calories, so cis-palmitoleic acid may no longer be able to counteract the metabolic consequences of such diets, Mozaffarian said.
“Trans-palmitoleic acid may be stepping in to function in at least some of the same protective roles,” he said, though more tests need to be done to confirm this.
Previous studies have linked dairy consumption with low diabetes risk, though those studies were mostly based on low-fat dairy products. A 2006 study in the journal Diabetes Care found that eating an additional serving per day of low-fat dairy products decreased diabetes risk in women by 4 percent.
The new study will be published tomorrow (Dec. 21) in the journal Annals of Internal Medicine.
By Amanda Chan, MyHealthNewsDaily Staff Writer
posted: 20 December 2010 06:19 pm ET