ErinPharm Gazette May 2008
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The first decade of human stem cell research reaches the point where now skin cells have been shown to have the potential of generating pluripotent cells capable of forming any cell type. As attention toward reversing atherosclerosis continues, with a new approach using a fibrate/statin combination, there is a need to focus attention on dietary approaches, attending to stabilizing blood pressure, looking to take care of those suffering from heart failure, and resolving the issue of the rising incidence of kidney malfunction in the general population. The NIH has begun an Undiagnosed Diseases program. An exciting new discovery in reversal of Alzheimer's disease amyloid plaque has been reported. A single progenitor cell has been identified that can lead to all three cardiac cell types. Much more work needs to be done in treating those with high blood pressure to reach normal blood pressure objectives. And we must not forget our fellow human beings suffering under the burden of malaria. ErinPharm supports spreading knowledge of the Nothing But Nets web site.
A review of May 2008. A selection of topics.
This web page is one of a number of ErinPharm web pages designed by me as a synopsis of topics that interest me as well as being a quick reference page for my newsletter subscribers and myself. I have no affiliation of any kind to any pharmaceutical company or medical group. The opinions expressed are my own. I welcome communication and debate. I am an optimist. I look forward to the future with wonder.
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Keep up to date with advances in the prevention, diagnosis, and treatment of colorectal cancer.
Know about the latest treatment guidelines for addiction.
Patients should know everything there is to know about Gastro-esophageal Reflux Disease (GERD)
Advances in lung cancer therapies are moving ahead. Keep up to date.
University of Kansas research scientist, Dr. Ann Manzardo, is exploring the link between thiamine deficiency and a genetic predisposition to alcoholism.
The first comprehensive map of Genomic copy number variations has been developed. Such copy numbers influence genetic diversity and susceptibility to disease.
The American Cancer Society is your main source of information in the ongoing battle against cancer.
Are you trying to lose weight and have been misled by the multi-billion dollar industry selling pills, potions, and 'magic cures'? You are not alone. A survey backed by a commercial drug company reports that approximately 70% of American dieters have tried scientifically unproven methods to lose weight. That's an astounding number of people who have tried dietary supplements in the form of pills and powders. About half of survey respondents incorrectly think supplements are approved by the federal Food and Drug Administration, while about two-thirds believe such products must carry warning labels for side effects. All that happens is maybe temporary loss of weight and the emptying of your pocket. Resist the temptation to believe in those seductive commercials. The only way you can lose weight and keep it off is by a commitment to a change in lifestyle. I recommend lifestyle changes.
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In a fascinating article by Gina Kolata of the New York Times we learn how a neurobiologist, Dr. Kirsty Spalding, at the Karolinska Institute in Sweden, took knowledge about the atmospheric rise in an isotope of carbon, C14, due to atomic bomb testing during 1955-1963, to determine that the fat cells we all have are continually dying and being replaced at a rate of about ten percent a year. This shifts the focus of research attention to how this process is regulated and how intervention could become a method of regulating obesity.
An article by Janet Rae-Dupree can lead us to practical means of creating new synaptic connections in our brains, developing and building upon our sense of curiosity and wonder, creating entirely new brain cells that can make us inherently more creative, consciously developing new habits, learning new things, empowering the health of our brain.
It is now ten years since the report from Dr. James Thomson that human embryonic (ES) stem cells had been isolated and thus began the first decade of practical development of these cells capable of unlimited proliferative capacity with the potential to form any human cell type. His research, and the work of other research scientists in this field of endeavor, has been condemned, restricted, and subject to the tides of public opinion since then. It is the time to put such disputes and hindrances behind us. Dr. Shinya Yamanaka, at Kyoto University, has shown that skin cells can be converted back to their embryonic state. These induced pluripotent stem (iPS) cells are expected to be able to form any cell type and tissue, in medical therapy would be derived from the skin cells of the patient, and have a potential that surely must bring us all to a sense of wonder. Dr. Thomson has confirmed the work of Dr. Yamanaka in his laboratory. This is a massive breakthrough. There are still technical details to be solved and more 'tweaking' of the procedures to be done but this development is staggering in its implications. This work can now be coupled to the work of other researchers who have been using autologous cells from specific patients to produce arteries on a scaffold matrix thus providing the technology for tissue-engineered blood vessels; that these blood vessels have already been put into patients and work well gives reason to move ahead as rapidly as possible with the necessary clinical trials. These reports are concurrent with other reports that a working heart scaffold can be produced and seeded with appropriate embryonic heart cells to generate a completely functional beating heart. Is it too much to hope that all participants in the embryonic stem cell debate, both for and against, can put their dispute behind them, see the amazing wonder in the future before us, and call for a 'Manhattan' type project to accelerate progress for us all?
For those who have already been diagnosed with atherosclerosis it is extremely important that you educate yourself on a full up-to-date medical perspective on this disease. Taking control of your lifestyle, learning of your options, putting into place changes in your life that will begin a slow steady reversal of the decades long damage to your arteries can be done. You need to decide. There are multiple factors involved. It is not as simple as taking a few pills. Your active full commitment to participation in your own personal atherosclerosis reversal is essential.
WebMD supports the lifestyle nutrition changes suggested by Dr. Dean Ornish in which coronary artery disease can be reversed by adaption to a balanced plant based food intake. This vegetable, fruit, grain nutrition program can be a major part of your lifestyle changes.
It is fortunate that simple urine tests are effective in measuring the risk of progressing to chronic kidney disease and family physicians are well prepared to notice any early signs of kidney damage revealed by creatinine levels in the panel of values obtained with regular blood tests. Primary care physicians gain experience in this area when managing diabetic patients. A recent review reveals that the incidence of chronic kidney disease is rising; reaching 13.1% of the adult population by 2004. This is of course directly related to the rising incidence of obesity, hypertension, and diabetes in the population as well as the demographics of an increase in the older population. Given this incidence researchers are turning their attention to the best strategies of management of chronic kidney disease. This Medscape review of the effect of ACE inhibitors, angiotension receptor blockers, or a combination of both in modulating the renin-angiotensin system is most timely. While it is clear that much more data in 'real world' patient environments outside limited clinical studies needs to be collected, it does appear that a combination of an ACE inhibitor (angiotensin-converting enzyme inhibitor) and an ARB (angiotensin receptor blocker) is at the moment an optimal approach. This data is encouraging but note is made that even in these small clinical studies about 11.1 - 12.5% of patients discontinued combination treatment compared to 0% for monotherapy of a single agent alone.
In an interesting initiative the National Human Genome Research Institute, the NIH Office of Rare Diseases, and the NIH Clinical Center have launched an Undiagnosed Diseases Program. Any longstanding medical condition that eludes diagnosis by a referring physician can be considered undiagnosed and may be of interest to this program. Although the total number of patients referred into this program for a free evaluation and/or treatment will initially be limited it is an encouraging beginning to what could become a valuable program in the years to come.
The American College of Cardiology 57th Annual Scientific Session marked significant steps forward in reports of research exploring adjustment of the LDL/HDL/triglyceride lipid subfractions. With the success of the statins in lowering LDL-cholesterol, focus has shifted to finding methods of safely raising HDL-cholesterol. With the setback due to the adverse mortality events in the torcetrapib CETP inhibitor trials by Pfizer attention has shifted to CETP inhibitors under investigation by other companies. Safety data presented for the CETP inhibitor RO4607381 (also R1658/JTT-705) under development by Hoffmann-La-Roche and Japan Tobacco were encouraging enough for initiation of a Phase III morbidity and mortality trial for clinically stable patients with a recent acute coronary syndrome. This global study will include 15,600 patients and is expected to be completed in 2012. Another 2-year exploratory imaging study on 100 patients will investigate the effect of RO4607381 on atherosclerotic plaque while a further 1-year 500 patient study will examine blood pressure and endothelial function. (ClinicalTrials gov. identifier: NCT00400439, NCT00655473, NCT00655538 respectively).
Abbott Laboratories and Solvay SA are conducting studies with a follow-on drug to fenofibrate. Fenofibrate is a pro-drug that, after administration, is hydrolyzed to fenofibric acid. This new drug is an active drug, choline fenofibrate, ABT-335, differs in its pharmacologic profile from fenofibrate and has been studied when dosed with a statin. Combination therapy was well tolerated and had a safety profile comparable to either agent as monotherapy. If approved, ABT-335 will be marketed as TriLipix.
It is troubling that as programs to stress lipid management among physicians and the general public alike are beginning to have a real effect as seen by the ongoing decline in heart attack and stroke, a corresponding attention to management of heart failure problems among the general public has not been attended to by physicians and even in some cases by cardiologists. A new European-wide survey reveals abysmal lack of optimal use of echocardiography, ACE inhibitors, and beta-blockers for patients suffering the symptoms of heart failure. For those with peripheral vascular disease the data from Dr Christopher Kevil, of the Louisiana State University Health Sciences Center, is most intriguing. Dr Kevil and his team have found that very low levels of sodium nitrite (low microgram/Kg doses) quickly restored ischemic tissue blood flow and vascular growth with selective angiogenesis and arteriogenesis in ischemic tissues. He and his team plan clinical trials to investigate the effects of sodium nitrite dosing in patients with peripheral vascular disease. The microgram/Kg dosing is reassuring, considering the known hazards of higher doses of sodium nitrite.
Removal of amyloid plaque in Alzheimer's patients has become a possibility with the findings in a mouse model of Alzheimer's disease that up to 90% of plaque was eliminated when the mouse was engineered to block TGF-beta signaling in peripheral macrophages. Lead investigator Dr. Terrence Town, of Yale University School of Medicine, points out that it is known brain levels of TGF-beta are increased in patients with Alzheimer's disease and if these results translate to humans it may be possible to administer a TGF-beta pathway blocking drug to a patient, mobilizing peripheral macrophages to enter the brain and remove the plaque. His team is moving their research in that direction.
Hypertension (high blood pressure) is a condition often undiagnosed or ignored in and by the general population. It is a 'silent killer' since it can exist in an individual unaware of their high blood pressure for many years insidiously and incrementally damaging the blood circulation system prior to a catastrophic cardiovascular incident. The current impetus toward having households add a home blood pressure monitor to gauge the daily blood pressure status of those with hypertension could well raise the profile of the importance of regular blood pressure monitoring. ErinPharm recommends the Omron brand of blood pressure monitor as being inexpensive and easy to use. New data revealed this month confirm that hypertension control in the general population appears to be better in the United States than in Europe though diabetics are ill served by the latest US guidelines and only about half of US patients achieve a blood pressure objective. This data comes from a comprehensive multi-country survey by investigators led by Dr. Y. Richard Wang, of Temple University and University of Pennysylvania, in which a total of 21,053 patients with a primary or secondary diagnosis of hypertension in six countries were evaluated. These patients had visited 1,284 primary care physicians and 291 cardiologists. With a definition of control with a blood pressure less than 140/90 mm Hg it was found that 53% of US patients reached that objective compared to 27% to 40% of Europeans. In Canada new guidelines for hypertension management were released to the public in January 2007 and stressed the importance of recognizing "high normal" blood pressure, i.e. 130-139/85-89 mm Hg, and the warning that more than half of such individuals will develop hypertension within four years if they do not make lifestyle changes. The point is also made that of individuals who do not follow a healthy lifestyle more than 90% will develop hypertension. Since guidelines, medications, and lifestyle changes can and will bring blood pressure to a healthy level over a time period of up to six weeks there is a need to overcome this societal inertia on the part of health care professionals and the general population to not actively seek blood pressure normalization. Yes, it does take significant effort at times, needs ongoing attention, requires a personal commitment on the part of the patient BUT it will result in a healthier way of life with a much reduced risk of heart attack or stroke. The next few years will see the launch of a number of new antihypertensive drugs and combination 'polypills'. In India a 'polypill' with two antihypertensives, aspirin, and a statin is expected to gain acceptance. The years to come will see major advances in this combined approach to arterial health.
A study led by Dr. Peter Jones, of Baylor College of Medicine in Houston, has shown that a new fenofibric acid formulation with a statin has the potential of treating patients with an HDL-cholesterol level less than 40 mg/dL accompanied by a high LDL-cholesterol level (>130 mg/dL) and high triglyceride level (>150 mg/dL). This study, of more than 1,400 patients, showed that the new fenofibric acid formulation, ABT-335, with rosuvastatin, from Abbott Laboratories, increased HDL-cholesterol by 20.3%, decreased triglycerides by 47.1% and decreased LDL-cholesterol by 37.2%. Since this study was part of several randomized phase III trials, statins atorvastatin and simvastatin with ABT-335 also studied, it seems that Abbott Laboratories is close to getting FDA approval to market this combination; which will be known as TriLipix. The combination therapy was well tolerated with a safety profile consistent with ABT-335 and rosuvastatin monotherapy. This will provide a new approach for those with intractably low HDL-cholesterol levels and thus give an interim treatment over the time period between approval of the combination and the expected CETP inhibitors as yet at least several years into the future. It also provides assurance that at least this fibrate/statin combination is safe for patients with this mixed dyslipidemia. It is a significant step forward for atherosclerosis reversal.
Dr. Gordon Keller and colleagues at the McEwen Centre for Regenerative Medicine in Toronto have moved us forward in the development of cardiac tissue for transplantation into damaged heart muscle. They have identified a single cardiovascular progenitor cell type from which all three cell lineages, cardiac, endothelial, and vascular smooth muscle were derived.
A recent Medscape Medical News report brought attention to an article in the May 6, 2008, issue of Neurology in which it was pointed out that a retrospective case study of nearly 50,000 US veterans with Alzheimer's disease matched to 197,000 control patients has shown that more than 5 years of non-steroidal anti-inflammatory drug use, particularly ibuprofen, may cut the risk of Alzheimer's disease in half. This would certainly be one simple strategem for those intent on reducing the risk of developing Alzheimer's disease.
Readers of ErinPharm Gazettes are among those aware, motivated, and seeking to take advantage of knowledge generated on the expanding frontiers of medical/scientific research. It is important to recognise that while we are privileged to be part of this future coming rapidly toward us we also live on a planet where the majority of our fellow human beings suffer under a burden of disease overwhelming and horrifying. One such disease is malaria. It threatens half the world's population, will strike up to half a billion people this year, at least a million will die, most of them under age 5, the vast majority living in Africa.
YOU can make a difference. YOU can take the time to care. YOU can reach out to our distant cousins in our common human lineage. YOU can click this link and become part of.....nothingbutnets....YOU can join the fight against malaria.
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As of March 31, 2008, Abbott Laboratories has already submitted an NDA (New Drug Application) to the US FDA for TriLipix as monotherapy and in combination with a statin.