“Our work could facilitate the identification of mechanisms that disrupt the function of dopaminergic, serotonergic and cholinergic neurons in diseases such as schizophrenia, Parkinson’s and depression,” wrote Dr. Louis-Eric Trudeau of the University of Montreal’s Department of Pharmacology and Dr. Salah El Mestikawy, a researcher at the Douglas Mental Health University Institute and professor at McGill’s Department of Psychiatry.

Their results show that many neurons in the brain are able to control cerebral activity by simultaneously using two chemical messengers or neurotransmitters. This mode of communication is known as “cotransmission.” According to Dr. Trudeau, “the neurons in the nervous system – both in the brain and in the peripheral nervous system – are typically classified by the main transmitter they use.” For example, dopaminergic neurons use dopamine as a transmitter to communicate important information for many different phenomena such as motivation and learning. The malfunction of these neurons is involved in serious brain diseases such as schizophrenia and Parkinson’s. “Our recent research, carried out in part with Dr. Laurent Descarries at the University of Montreal, shows that dopaminergic neurons use glutamate as a second transmitter. That means they are able to transmit two types of messages in the brain, on two time scales: a fast one for glutamate and a slower one for dopamine.”

Other research conducted by Dr. Salah El Mestikawy’s team at the Douglas Mental Health University Institute observed the same kind of bilingualism in brain neurons that use serotonin, a group of cells that communicate important information for controlling mood, aggression, impulsivity and food intake, and also those that use acetylcholine, an important messenger for motor skills and memory that is unbalanced by Parkinson’s disease, antipsychotic drugs and in drug addiction.

Joint studies carried out with their colleague Dr. Åsa Wallen-Mackenzie at Uppsala University in Sweden and published recently in the Proceedings of the National Academy of Sciences journal suggest that the secretion of glutamate by dopaminergic neurons could, for example, be involved in the behavioural effects of psychostimulants such as amphetamines and cocaine. “We know very little about the role of cotransmission in disease and the regulation of behaviour, however,” Dr. Trudeau warned. “That will have to be the subject of future studies.”

Article Source: This article is edited by winnerscience and is originally provided by University of Montreal.

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The University of Pittsburgh’s Caterina Rosano, M.D., led the research as part of the Cardiovascular Health Study, which the NHLBI began funding in 1989 to help understand risk factors for cardiovascular disease in older adults. 643 participants in Rosano’s study, 350 did not have high blood pressure, while 293 had undiagnosed hypertension or were taking medication for the condition. The study examined the role of brain, heart, and kidney function in changes in seniors’ walking speeds over 14 years. Participating seniors, with an average age of 76 at the start of the study, who had high blood pressure, saw their average walking speeds decline 0.2 miles per hour more than seniors who did not have high blood pressure. The study’s hypertension participants were split into three groups:

• Those who were undiagnosed before the study began
• Those who were diagnosed and were able to control the condition
• Those who were diagnosed and were unable to control the condition

“The findings from this study suggest an additional reason to stress prevention of high blood pressure,” said Susan B. Shurin, M.D., acting director of the National Heart, Lung, and Blood Institute (NHLBI), part of the NIH. “Even with medications to treat high blood pressure in older adults, it appears that the condition might be linked to a serious decline in average walking speed. As the mobility of seniors declines, there is an increased risk for falls.”

About one-third of adults in the United States have high blood pressure, also known as hypertension, which can lead to coronary heart disease, heart failure, stroke, and kidney failure.

The researchers measured how long it took participants to walk a 15-foot course, starting from a standing position. At the start of the study, the average walking speed was 2.2 mph. While everyone who participated in the follow-up period walked slower, speeds decreased more steeply among all hypertension groups by about 10 percent.

“An acceptable walking speed is important for seniors to maintain their independence,” Rosano explained. “For seniors, a declining walking speed can be an indicator of other health problems and can help predict who will develop dementia or disabilities.” Rosano said further study is needed to better understand the physical link between high blood pressure and the steep decline in walking speeds. Researchers thought that brain, kidney, or heart problems might account for the slowing, but magnetic resonance imaging (MRI) brain scans of study participants showed no visible problems with blood vessels in the brain, and kidney and heart function also appeared normal.

Future studies could use more advanced brain imaging equipment, which may reveal damage too small for MRI scans to detect, according to the study authors.

In addition to the NHLBI, the National Institute of Neurological Disorders and Stroke and the National Institute on Aging supported this study.

Article Source: The article is edited by Winnerscience and is provided by National Institutes of Health.

To arrange an interview with an NHLBI spokesperson, please contact the NHLBI Communications Office at (301) 496-4236 or nhlbi_news@nhlbi.nih.gov.

Resources:

• Diseases and Conditions Index: High Blood Pressure: http://www.nhlbi.nih.gov/health/dci/Diseases/Hbp/HBP_WhatIs.html
• Clinical Guidelines on Hypertension: http://www.nhlbi.nih.gov/guidelines/hypertension/
• Clinical Trial Information: NCT00005133
  http://clinicaltrials.gov/ct2/show/NCT00005133?term=NCT00005133&rank=1

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Choosing the appropriate way to present risk statistics is key to helping people make well-informed decisions. The different ways of expressing risk can prove confusing and there has been much debate about how to improve the communication of health statistics.

A new Cochrane Systematic Review (The Cochrane Library is one of the major libraries having high quality health care information, including the Cochrane Database of Systematic Reviews, from the Cochrane Collaboration. Cochrane Systematic Reviews bring together research on the effects of health care and are considered the gold standard for determining the relative effectiveness of different interventions) found that health professionals and consumers may change their perceptions when the same risks and risk reductions are presented using alternative statistical formats.

Let us suppose that, you could read that a drug cuts the risk of hip fracture over a three year period by 50%. At first sight, this would seem like an incredible breakthrough. In fact, what it might equally mean is that without taking the drug 1% of people have fractures, and with the drug only 0.5% do. Now the benefit seems to be much less. Another way of phrasing it would be that 200 people need to take the drug for three years to prevent one incidence of hip fracture. In this case, the drug could start to look a rather expensive option.

Statisticians have terms to describe each type of presentation, like

• Relative Risk Reduction (RRR): The statement of a 50% reduction is typically expressed as a RRR
• Absolute Risk Reduction (ARR): It Means that 0.5% fewer people will have broken hips are an ARR.
• Number Needed to Treat (NNT): Saying that 200 people need to be treated to prevent one occurrence is referred to as the NNT.
• Furthermore, these effects can be shown as a frequency, where the effect is expressed as 1 out of 200 people avoiding a hip fracture.

In this review, Cochrane researchers reviewed data from 35 studies assessing understanding of risk statistics by health professionals and consumers. They found that participants in the studies understood frequencies better than probabilities. Relative risk reductions, as in “the drug cuts the risk by 50%”, were less well understood. Participants perceived risk reductions to be inappropriately greater compared to the same benefits presented using absolute risk or NNT.

“People perceive risk reductions to be larger and are more persuaded to adopt a health intervention when its effect is presented in relative terms,” said Elie Akl of the Department of Medicine, University at Buffalo, USA and first author on the review. “What we don’t know yet is whether doctors or policymakers might actually make different decisions based on the way health benefits are presented.”

Although the researchers say further studies are required to explore how different risk formats affect behaviour, they believe there are strong logical arguments for not reporting relative values alone. “Relative risk statistics do not allow a fair comparison of benefits and harms in the same way as absolute values do,” said lead researcher Holger Schünemann of the Department of Clinical Epidemiology and Biostatistics at McMaster University in Ontario, Canada. “If relative risk is to be used, then the absolute change in risk should also be given, as relative risk alone is likely to misinform decisions.”

News Source:

The above news is edited by the winnerscience staff and it is originally provided by the Wiley-Blackwell.

Reference: Akl EA, Oxman AD, Herrin J, Vist GE, Terrenato I, Sperati F, Costiniuk C, Blank D, Schünemann H. Using alternative statistical formats for presenting risks and risk reductions. Cochrane Database of Systematic Reviews 2011, Issue 3. Art. No.: CD006776. DOI: 10.1002/14651858.CD006776.pub2.

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Artesunate was recommended as the preferred treatment for adults with severe malaria by the World Health Organization (WHO) in 2006, but there was insufficient evidence at the time to recommend a change from the standard treatment of quinine in children. The researchers updated the review of artesunate by adding a new large multicentre trial of African children published in the Lancet in 2010 to the existing 8 trials. The review now includes a total of 1664 adults and 5765 children, from a variety of settings across Africa and Asia. According to the results, taking artesunate reduces the risk of death by 39% in adults and 24% in children compared to quinine. In adults, deaths caused by severe malaria were reduced from 241 per 1000 with quinine to 147 with artesunate. In children, deaths were reduced from 108 per 1000 with quinine to 83 with artesunate.

“There is now enough evidence to be confident of these results in adults and children,” said Peter Olumese of the WHO’s Global Malaria Programme. “Intravenous artesunate is now being recommended as the treatment of choice for adults and children with severe malaria anywhere in the world.”

Although more children given artesunate suffered neurological problems compared to those given quinine, these were largely resolved within a month of treatment, and were outweighed by the increase in survival rates. “The balance of benefits and harms is in favour of treatment with artesunate,” said David Sinclair of the Liverpool School of Tropical Medicine in Liverpool, UK, who led the review team.

News Source:

The above news is edited by the winnerscience staff and it is originally provided by the Wiley-Blackwell.

Full citation: Sinclair D, Donegan S, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database of Systematic Reviews 2011, Issue 3. Art. No.: CD005967. DOI: 10.1002/14651858.CD005967.pub3.

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Researchers at the Archimedes Inc. in San Francisco, investigated and concluded that Tamoxifen, saves lives and reduces medical costs. This research is published in journal Cancer (The Journal Cancer is a peer-reviewed journal of the American Cancer Society) This widely referenced publication published articles related to human cancer including, but not limited to: biologic response modifiers, clinical observations, chemotherapy, clinical trials, detection, epidemiology, ethical issues, etiology, genetics and cytogenetics, imaging, immunology and immunotherapy, oncogenes, pathology and clinicopathologic correlations, prevention, psychosocial studies, radiation therapy, screening, staging, and surgical therapy. It has impact factor of 5.418).

Let us discuss how they came to this conclusion that by taking tamoxifen prevent breast cancer, can save lives and money:

Peter Alperin, MD, of Archimedes Inc. in San Francisco, and his colleagues used a mathematical model to simulate a post-menopausal population under age 55 years in a virtual clinical trial comparing tamoxifen treatment with no treatment. This was done to to investigate those women who would benefit the most from taking tamoxifen as a cancer preventive drug, The investigators modeled tamoxifen therapy based on an analysis of four randomized, placebo-controlled cancer prevention trials, and they assessed the effects that tamoxifen would have on women’s breast cancer risk for 10 years following the end of treatment. Cancer incidences and survival information were taken from the Surveillance Epidemiology and End Results cancer registry, while factors such as non-cancer disease incidences, quality of life, and costs were taken from the medical literature.

Research has shown that tamoxifen can protect against breast cancer for years after treatment ends, but identifying the group of women who can most benefit from the drug as a cancer preventive agent, without experiencing serious side effects, is a challenge. Side effects of the drug can include pulmonary embolism, endometrial cancer, deep vein thrombosis, and cataracts, as well as hot flashes and early menopause.

The researchers found that in post-menopausal women ages 55 years and younger with a 5-year risk of developing breast cancer of 1.66 percent or greater, the benefits of tamoxifen are maximized while its side effects are minimized. Dr. Alperin said “In this group of women, using tamoxifen to prevent breast cancer saves lives and has a low frequency of side effects”. He further added that it also saves medical costs. “Specifically, chemoprevention with tamoxifen prevents 29 breast cancer cases and 9 breast cancer deaths per 1,000 women treated, and it saves $47,580 per 1,000 women treated in the United States.”

Conclusion: This study proved that Tamoxifen, saves lives and reduces medical costs. These findings may help physicians and their patients as they strive to identify optimal breast cancer prevention options for individual women based on their current health and demographic profile. Similarly, investigators can use mathematical modeling and cost-effectiveness analyses, such as those described in this research, to explore different prevention strategies and evaluate their impact on health and economic outcomes.

News Source:

The above news is edited by the winnerscience staff and it is originally provided by the Wiley-Blackwell.

Journal Reference

“Cost-effectiveness of chemoprevention of breast cancer using tamoxifen in a post-menopausal U.S. population.” Joyce Noah-Vanhoucke, Linda E. Green, Tuan A. Dinh, Peter Alperin, and Robert A. Smith. CANCER; Published Online: March 14, 2011 (DOI: 10.1002/cncr.25926).

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The research is based on nearly 70,000 analyses from patients who have undergone regular monitoring of the levels of drugs in their blood. The drugs, tacrolimus and sirolimus, taken by these patients are used to suppress the immune system in association with organ transplants. Samples taken during the winter months were compared with those taken late in the summer.

The research will be published in the scientific journal Drug Metabolism & Disposition (The Journal of Digital Investigation is published by The American Society for Pharmacology and Experimental Therapeutics . It covers important research in pharmacology (Do you know what it is, if not then read our article on it) and toxicology and is a valuable resource in drug design, drug metabolism, expression of drug metabolizing enzymes, and regulation of drug metabolizing enzyme gene expression. It has impact factor of 3.743).

Research showed that the concentrations of drugs to prevent rejection following transplantation, vary throughout the year in a manner that closely reflects changes in the level of vitamin D in the body. The ability of the body to form vitamin D depends on sunlight, and the highest levels in the patients taking part in the study were reached during that part of the year when the levels of the drugs were lowest.

The connection between sunlight, vitamin D and variations in drug concentration is believed to arise from the activation by vitamin D of the detoxification system of the liver by increasing the amount of an enzyme known as CYP3A4. This enzyme, in turn, is responsible for the breakdown of tacrolimus and sirolimus.

One of the reserarchers, Jonatan Lindh said, “If the breakdown capacity increases, then higher doses of a drug are normally required in order to achieve the same effect. More research will be needed to confirm the results, but CYP3A4 is considered to be the most important enzyme in drug turnover in the body, and the results may have significance for many drugs”.

This study shows for the first time that the mechanism can play an important role in the pharmacological treatment (Do you know what it is, if not then read our article on it) of patients, and it shows for the first time that variation in exposure to sunlight may affect the sensitivity of individuals to drugs.

News Source:

The above news is edited by the winnerscience staff and it is originally provided by the Karolinska Institutet, through alphagalileo.org.

Journal reference:

• Seasonal variation in blood drug concentrations and a potential relationship to vitamin D’, Lindh JD, Andersson ML, Eliasson E, Björkhem-Bergman L., Drug Metab Dispos, online ahead of print 24 February 2011, doi:10.1124/dmd.111.038125.

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