Could some of the natural chemicals found in plants be powerful enough to improve cardiovascular health? Researchers at Wake Forest University Baptist Medical Center are conducting the first-ever clinical study to evaluate the potential cardiovascular health effects of Nature's Pearl Muscadine Grape Seed Supplement.
The scientists are evaluating the influence of this supplement on blood vessel function in 50 participants who have cardiovascular disease or are at high risk for developing it. They'll also determine whether there are effects on cholesterol and other fats in the blood, blood sugar levels and vessel inflammation, which are all associated with increased risk of cardiovascular disease.
Nature's Pearl is prepared in a way that generates a high concentration of plant chemicals, including gallic acid, ellagic acid, oligomeric proanthocyanidins (OPCs) and resveratrol. These are known to be antioxidants, or nutrients that can prevent or slow the oxidative damage to the body. The role of oxidative stress in blood vessel disease has generated interest in dietary sources of antioxidants, including black and green tea, grape seeds, olive oil and cocoa.
Muscadine grapes have been shown to be more potent in antioxidants than any other variety of grapes, and laboratory studies have suggested that grape seeds have higher antioxidant capacity than grape skins. Studies in humans have shown improved antioxidant capacity when grape seed supplement is added to the diet, as well as improvements in blood vessel function. However, the studies did not specifically include muscadine grapes, which have extremely high levels of antioxidant and anti-inflammatory compounds when compared to other fruits.
"The goal of the current study is to determine if daily doses of the Nature's Pearl supplement, which is specially prepared to maximize its natural antioxidant and anti-inflammatory concentrations, will have a favorable effect on cardiovascular risk factors," said David Herrington, M.D., M.P.H., lead investigator and a professor of cardiology.
Study participants are patients at Wake Forest Baptist's Family Medicine and Internal Medicine practices and are between 18 years and 65 years old. For the first four weeks of the study, participants are randomly assigned to take either 1,300 mg. (two capsules) of the Nature's Pearl Muscadine Grape Seed Supplement (grape seeds) daily or a placebo (inactive capsule).
For the next four weeks, participants do not take capsules to allow the product to "wash out" of their systems. Then, the groups will switch so that those who took placebo originally will take the supplement for four weeks.
Ultrasound technology is used to determine blood vessel function or "reactivity." Blood flow in the brachial artery, the major vessel in the arm, is measured both before and after the arteries are constricted with a blood pressure cuff. In a healthy subject, the artery dilates after the constriction. Decreased reactivity is a sign of reduced artery function and is thought to be a precursor to atherosclerosis, the buildup of fatty deposits in the vessels that can lead to heart attack or stroke.
The test is used in the brachial arteries because the heart's arteries cannot be directly imaged with ultrasound. However, atherosclerosis is a disease that affects vessels throughout the body, and the test is considered a good indicator of overall vessel function.
The study will also measure any effects on total cholesterol, low-density lipoprotein or "bad" cholesterol, triglycerides, high-density lipoprotein or "good" cholesterol, blood sugar levels and markers for inflammation, such as C-reactive protein and interleukin-6.
Patients have been recruited and the results are expected to be analyzed in early 2008.
"Cardiovascular disease is a significant problem in this country so it is worthwhile to examine foods that may have medicinal benefits," said Herrington. "In this case, our goal is to determine whether the Nature's Pearl supplement, which looks promising because of its extremely high antioxidant and anti-inflammatory content, will positively affect artery health."
The study is sponsored by Nature's Pearl Corporation.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. The system comprises 1,154 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of "America's Best Hospitals" by U.S. News & World Report.
четверг, 29 сентября 2011 г.
понедельник, 26 сентября 2011 г.
Simplified Clinical Tool Affects Treatment Decisions For Heart Health
Millions of Americans potentially reclassified into high-risk or low-risk groups with different treatment as a result.
The widespread use of a simplified clinical tool to estimate future coronary risk could lead to the classification of millions of Americans into different risk groups than when using the original, "gold-standard" tool. Millions of patients may have been misclassified into higher-risk groups and therefore potentially over-treated, while others may have ended up in lower-risk groups and therefore potentially under-treated for heart disease. The study, led by William Gordon from Weill Cornell Medical College in the US and colleagues, is published in the Journal of General Internal Medicine, published by Springer.
American national cholesterol guidelines use the well-known Framingham model (a mathematical equation) to calculate a person's 10-year risk of heart attack and coronary death. Based on this risk, patients are categorized into different risk groups, which are used to guide treatment decisions.
Because the original Framingham model is very complex, the formula has been simplified into a point-based clinical tool to make it available without calculators or computers. However, the rapid take-up and widespread use of computers and PDAs in clinical medicine has made it possible to implement the original, mathematically complex model at the point of care. Yet, the point-based system continues to be used widely in clinical practice.
"While the point-based system is a substantial improvement over having no standardized method for predicting risk, just about any computer or PDA in use today can calculate the original Framingham model," says principal investigator Michael Steinman, MD. "This means that your doctor can calculate your risk just as easily using the complex equation, which is likely to be more accurate than the point-based system. So there's not much reason to use the point-based system anymore in most instances."
The authors looked at whether the simplified version might lead to different risk estimates and potentially different treatment recommendations as a consequence. The researchers used data for 2,543 people (representing 39 million adults) aged 20-79 years. For each individual, the authors calculated the 10-year risk of major coronary events using both the original and simplified point-based Framingham models. They looked at the differences in these risk estimates and whether these differences would place subjects into different risk categories.
Gordon and team found that the two estimates of coronary risk differed significantly. The simplified version reclassified 15 percent of adults into different risk groups, corresponding to 5.7 million people. Of those, 10 percent (3.9 million) were reclassified into higher-risk groups and 5 percent (1.8 million) into lower-risk groups. As a consequence, 25-45 percent of reclassified adults could have been treated differently i.e. either received more or less intensive therapy than would otherwise be recommended according to drug treatment guidelines.
The authors conclude: "Current guidelines should strongly consider endorsing the original model as the preferred method of risk calculation and as the sole appropriate option for computer or PDA-based risk calculators. Patients and clinicians who made treatment decisions based on the point-based system should also consider recalculating risk based on the original Framingham model and, where appropriate, adjust treatment plans accordingly."
The original Framingham model estimates risk based on the patient's age, total and HDL cholesterol, systolic blood pressure, treatment for hypertension, and smoking status. The point-based system assigns each risk factor level a number. These risk factor values are then added up into a score; the risk for that score is then determined from a table.
Sources: Springer Science+Business Media, AlphaGalileo Foundation.
The widespread use of a simplified clinical tool to estimate future coronary risk could lead to the classification of millions of Americans into different risk groups than when using the original, "gold-standard" tool. Millions of patients may have been misclassified into higher-risk groups and therefore potentially over-treated, while others may have ended up in lower-risk groups and therefore potentially under-treated for heart disease. The study, led by William Gordon from Weill Cornell Medical College in the US and colleagues, is published in the Journal of General Internal Medicine, published by Springer.
American national cholesterol guidelines use the well-known Framingham model (a mathematical equation) to calculate a person's 10-year risk of heart attack and coronary death. Based on this risk, patients are categorized into different risk groups, which are used to guide treatment decisions.
Because the original Framingham model is very complex, the formula has been simplified into a point-based clinical tool to make it available without calculators or computers. However, the rapid take-up and widespread use of computers and PDAs in clinical medicine has made it possible to implement the original, mathematically complex model at the point of care. Yet, the point-based system continues to be used widely in clinical practice.
"While the point-based system is a substantial improvement over having no standardized method for predicting risk, just about any computer or PDA in use today can calculate the original Framingham model," says principal investigator Michael Steinman, MD. "This means that your doctor can calculate your risk just as easily using the complex equation, which is likely to be more accurate than the point-based system. So there's not much reason to use the point-based system anymore in most instances."
The authors looked at whether the simplified version might lead to different risk estimates and potentially different treatment recommendations as a consequence. The researchers used data for 2,543 people (representing 39 million adults) aged 20-79 years. For each individual, the authors calculated the 10-year risk of major coronary events using both the original and simplified point-based Framingham models. They looked at the differences in these risk estimates and whether these differences would place subjects into different risk categories.
Gordon and team found that the two estimates of coronary risk differed significantly. The simplified version reclassified 15 percent of adults into different risk groups, corresponding to 5.7 million people. Of those, 10 percent (3.9 million) were reclassified into higher-risk groups and 5 percent (1.8 million) into lower-risk groups. As a consequence, 25-45 percent of reclassified adults could have been treated differently i.e. either received more or less intensive therapy than would otherwise be recommended according to drug treatment guidelines.
The authors conclude: "Current guidelines should strongly consider endorsing the original model as the preferred method of risk calculation and as the sole appropriate option for computer or PDA-based risk calculators. Patients and clinicians who made treatment decisions based on the point-based system should also consider recalculating risk based on the original Framingham model and, where appropriate, adjust treatment plans accordingly."
The original Framingham model estimates risk based on the patient's age, total and HDL cholesterol, systolic blood pressure, treatment for hypertension, and smoking status. The point-based system assigns each risk factor level a number. These risk factor values are then added up into a score; the risk for that score is then determined from a table.
Sources: Springer Science+Business Media, AlphaGalileo Foundation.
пятница, 23 сентября 2011 г.
New study provides support for Atkins type diet
Was Atkins Right? New Study Provides Support For Those Who Advocate A High Protein Diet For Weight Loss And Better Health.
Bethesda, MD - "Shape Up America," a new coalition of various health groups recently announced their collective opinion that "booming low-carb diets were unlikely to lead to long-term weight loss and may be dangerous for health." At the same time, high protein diets are attracting their share of critics, among them the American Heart Association, which has stated that the focus on animal proteins cholesterol raises harmful LDL cholesterol levels.
The scientific community knows that high protein diets induce early marked metabolic changes in human and animal models, especially when the diet contains at least 50 percent of energy as protein, but the physiological and functional consequences of a long-term high protein (HP) diet have not been fully explored. Now, a long-term study involving male rats has found that a protein intake of three times the requirements did not produce any adverse effects in key systems.
A New Study
Researchers are aware that no long-term interventional human studies on the issue exist nor are there any complete toxicological studies on high protein diet effects. This has led to a new investigation of the wide range of biochemical, anatomical and histological parameters to determine whether long-term ingestion of a high protein diet could have adverse and/or beneficial effects in an obesity prone strain of rats.
The authors of "A long-term high-protein diet markedly reduces adipose tissue without major side-effects in Wistar male rats," are Magali Lacroix, Claire Gaudichon, Celine Morens, Veronique Mathe, Daniel Tome, and Jean-Francois Huneau, all from the Physiologie de la Nutrition et du Comportement alimentaire, Institut National Agronomique Paris-Grignon, Paris; and Antoine Martin, at the Service d'Anatomie pathologique, H?pital Avicenne, Bobigny, both in France.
Their findings appear in the Articles in Press section of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. The journal is one of 14 scientific publications issued each month by the American Physiological Society (APS) (the-aps).
Methodology
This study used male Wistar rats that were administered either a no protein diet or a high protein diet for six months. Detailed body composition, biomarkers of oxidative stress [reduced and oxidized glutathione, thiobarbituric acid reactive substances, expression of glutamy-cysteine-ligase, and detoxification function (Glutathione-S-Transferase), plasma hormones (insulin, cortisol and leptine)] and liver and kidney histopathology were investigated. Calcium balance was also assessed over four months after this protocol.
Results
This study sought to estimate the consequences of a long-term intake of high levels of protein in an obesity-prone rat strain. The results showed that the long-term effect of eating protein at will led to a markedly reduced food intake and lowered white adipose tissue. At the same time, basal blood insulin, leptin and triglyceride levels, and glucose tolerance were improved. Calcium balance was not affected by a high intake of milk proteins.
Moreover, in contrast to what has generally been admitted, no adverse effects of the high protein diet were reported, particularly regarding kidney and liver health. After six months of the experiment, the body weight of rats fed the high protein diet was 18 percent lower than that of rats fed the non-protein diet.
Body composition measurements revealed remarkable differences between the two groups, especially concerning the subcutaneous fat pad.
This study also revealed that the weight reduction in rats fed the high protein diet was strongly associated with lower basal blood sugar and insulin levels, as previously described, and improved glucose tolerance. As the isocaloric exchange between high and low protein diets was performed on carbohydrate, the flattening effect of the high protein diet on insulin and glucose basal levels could be attributed to its reduced carbohydrate content. This contrasts with the results of many studies that have acknowledged the fact that high protein intakes induce an increase in glucose and insulin concentrations.
Conclusions
This unique long-term study found that in male rats, a protein intake of three times the requirements did not produce any adverse effects on the renal and hepatic functions, on oxidative stress or on the calcium balance. On the contrary, exchanging carbohydrates for proteins was beneficial regarding body composition, basal triglycerides, glucose, leptin, and insulin plasma concentrations. The results of the present study agree with the idea that long-term dietary management is of major importance to preventing obesity.
This study will not settle the long-standing debate regarding the merits of a high protein diet. However, these findings will provide support to those who advocate such a regimen for weight loss and better health.
-end-
Bethesda, MD - "Shape Up America," a new coalition of various health groups recently announced their collective opinion that "booming low-carb diets were unlikely to lead to long-term weight loss and may be dangerous for health." At the same time, high protein diets are attracting their share of critics, among them the American Heart Association, which has stated that the focus on animal proteins cholesterol raises harmful LDL cholesterol levels.
The scientific community knows that high protein diets induce early marked metabolic changes in human and animal models, especially when the diet contains at least 50 percent of energy as protein, but the physiological and functional consequences of a long-term high protein (HP) diet have not been fully explored. Now, a long-term study involving male rats has found that a protein intake of three times the requirements did not produce any adverse effects in key systems.
A New Study
Researchers are aware that no long-term interventional human studies on the issue exist nor are there any complete toxicological studies on high protein diet effects. This has led to a new investigation of the wide range of biochemical, anatomical and histological parameters to determine whether long-term ingestion of a high protein diet could have adverse and/or beneficial effects in an obesity prone strain of rats.
The authors of "A long-term high-protein diet markedly reduces adipose tissue without major side-effects in Wistar male rats," are Magali Lacroix, Claire Gaudichon, Celine Morens, Veronique Mathe, Daniel Tome, and Jean-Francois Huneau, all from the Physiologie de la Nutrition et du Comportement alimentaire, Institut National Agronomique Paris-Grignon, Paris; and Antoine Martin, at the Service d'Anatomie pathologique, H?pital Avicenne, Bobigny, both in France.
Their findings appear in the Articles in Press section of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. The journal is one of 14 scientific publications issued each month by the American Physiological Society (APS) (the-aps).
Methodology
This study used male Wistar rats that were administered either a no protein diet or a high protein diet for six months. Detailed body composition, biomarkers of oxidative stress [reduced and oxidized glutathione, thiobarbituric acid reactive substances, expression of glutamy-cysteine-ligase, and detoxification function (Glutathione-S-Transferase), plasma hormones (insulin, cortisol and leptine)] and liver and kidney histopathology were investigated. Calcium balance was also assessed over four months after this protocol.
Results
This study sought to estimate the consequences of a long-term intake of high levels of protein in an obesity-prone rat strain. The results showed that the long-term effect of eating protein at will led to a markedly reduced food intake and lowered white adipose tissue. At the same time, basal blood insulin, leptin and triglyceride levels, and glucose tolerance were improved. Calcium balance was not affected by a high intake of milk proteins.
Moreover, in contrast to what has generally been admitted, no adverse effects of the high protein diet were reported, particularly regarding kidney and liver health. After six months of the experiment, the body weight of rats fed the high protein diet was 18 percent lower than that of rats fed the non-protein diet.
Body composition measurements revealed remarkable differences between the two groups, especially concerning the subcutaneous fat pad.
This study also revealed that the weight reduction in rats fed the high protein diet was strongly associated with lower basal blood sugar and insulin levels, as previously described, and improved glucose tolerance. As the isocaloric exchange between high and low protein diets was performed on carbohydrate, the flattening effect of the high protein diet on insulin and glucose basal levels could be attributed to its reduced carbohydrate content. This contrasts with the results of many studies that have acknowledged the fact that high protein intakes induce an increase in glucose and insulin concentrations.
Conclusions
This unique long-term study found that in male rats, a protein intake of three times the requirements did not produce any adverse effects on the renal and hepatic functions, on oxidative stress or on the calcium balance. On the contrary, exchanging carbohydrates for proteins was beneficial regarding body composition, basal triglycerides, glucose, leptin, and insulin plasma concentrations. The results of the present study agree with the idea that long-term dietary management is of major importance to preventing obesity.
This study will not settle the long-standing debate regarding the merits of a high protein diet. However, these findings will provide support to those who advocate such a regimen for weight loss and better health.
-end-
вторник, 20 сентября 2011 г.
In Pediatric Genetic Neurological Disease Niemann-Pick Type C, Researchers Report Breakthrough
A paper announcing a breakthrough discovery in the fight against Niemann-Pick Type C, coauthored by Olaf Wiest and Paul Helquist of the University of Notre Dame's Department Chemistry & Biochemistry and Frederick Maxfield, Chair of Biochemistry at Cornell University Weill College of Medicine, appears in the Proceedings of the National Academy of Sciences this week. The paper shows how use of a histone deacetylase inhibitor correct the damage done by the genetic disorder and allowed once-diseased cells to function normally.
Niemann-PickType C (NPC) involves a genetic flaw that keeps cells from using lipids appropriately and leaves the lipids trapped in the cell. Brain cells are especially impacted, and destruction of brain cells typically kills victims by their teen years and there is currently no treatment available in the U.S. NPC is an inherited cholesterol metabolism disorder that strikes one in every 150,000 children. It has been referred to by the National Institutes of Health as "childhood Alzheimer's" because of similarities in the brains of NPC and Alzheimer's disease patients.
Three of the four grandchildren of former Notre Dame head football coach Ara Parseghian died of NPC, and the University has been involved in research on the disorder for years. Last year, it formally united with the Parseghian Foundation, which sponsored this work.
Last summer, Notre Dame College of Science Dean Gregory Crawford and his wife Renate bicycled 2,300 miles from Tucson to Notre Dame to raise awareness of the newly strengthened partnership with the Parseghian Foundation. Notre Dame's Center for Rare and Neglected Diseases works to develop therapies and outreach efforts for people suffering from conditions, like NPC, that have bee3n largely ignored by pharmaceutical companies.
A team of led by Wiest and Helquist at Notre Dame and Maxfield at Cornell, uncovered evidence that histone deacetylase inhibitors correct NPC's genetic flaw. Detailed images obtained at Cornell by Maxfield's group gave vivid evidence of the drug's effectiveness, showing how NPC cells became indistinguishable from normal human cells after treatment with the drug. The histine deacetylase inhibitors have a wide range of potential uses, from rare diseases, the focus at Notre Dame, to several forms of cancer, including leukemia, where they can increase the number of bone marrow cells.
Several of the compounds studied are shown to be safe in advanced clinical studies of cancer and one compound is currently approved by the FDA.
"Our biggest single emphasis the last few years has been Niemann-Pick among these rare diseases," Helquist said. "We developed several processes for the efficient preparation of these types of drugs. There's a stream of publications and also a stream of patents starting in June 2007 and continuing this year."
"If the results in human cells can be confirmed in clinical trials, the fact that the histone deacetylase inhibitors are already in advanced clinical trials or even approved drugs could greatly accelerate the development of a treatment for this devastating disease."
Niemann-PickType C (NPC) involves a genetic flaw that keeps cells from using lipids appropriately and leaves the lipids trapped in the cell. Brain cells are especially impacted, and destruction of brain cells typically kills victims by their teen years and there is currently no treatment available in the U.S. NPC is an inherited cholesterol metabolism disorder that strikes one in every 150,000 children. It has been referred to by the National Institutes of Health as "childhood Alzheimer's" because of similarities in the brains of NPC and Alzheimer's disease patients.
Three of the four grandchildren of former Notre Dame head football coach Ara Parseghian died of NPC, and the University has been involved in research on the disorder for years. Last year, it formally united with the Parseghian Foundation, which sponsored this work.
Last summer, Notre Dame College of Science Dean Gregory Crawford and his wife Renate bicycled 2,300 miles from Tucson to Notre Dame to raise awareness of the newly strengthened partnership with the Parseghian Foundation. Notre Dame's Center for Rare and Neglected Diseases works to develop therapies and outreach efforts for people suffering from conditions, like NPC, that have bee3n largely ignored by pharmaceutical companies.
A team of led by Wiest and Helquist at Notre Dame and Maxfield at Cornell, uncovered evidence that histone deacetylase inhibitors correct NPC's genetic flaw. Detailed images obtained at Cornell by Maxfield's group gave vivid evidence of the drug's effectiveness, showing how NPC cells became indistinguishable from normal human cells after treatment with the drug. The histine deacetylase inhibitors have a wide range of potential uses, from rare diseases, the focus at Notre Dame, to several forms of cancer, including leukemia, where they can increase the number of bone marrow cells.
Several of the compounds studied are shown to be safe in advanced clinical studies of cancer and one compound is currently approved by the FDA.
"Our biggest single emphasis the last few years has been Niemann-Pick among these rare diseases," Helquist said. "We developed several processes for the efficient preparation of these types of drugs. There's a stream of publications and also a stream of patents starting in June 2007 and continuing this year."
"If the results in human cells can be confirmed in clinical trials, the fact that the histone deacetylase inhibitors are already in advanced clinical trials or even approved drugs could greatly accelerate the development of a treatment for this devastating disease."
суббота, 17 сентября 2011 г.
Cholesterol and genes
Why does it seem like some people can eat all the ice cream they want without increasing their cholesterol or gaining much weight, while others with high cholesterol have to watch their diets like a hawk? Because no matter what their lifestyle, people's genes play an overriding role in their cholesterol response.
So says a new study by researchers at the Department of Energy's Lawrence Berkeley National Laboratory and the Children's Hospital Oakland Research Institute (CHORI), conducted by Paul Williams of Berkeley Lab's Life Sciences Division in collaboration with Robin Rawlings and Patricia Blanche of CHORI and Ronald M. Krauss of CHORI and Berkeley Lab's Genomics Division. They report their findings in the July 8, 2005, issue of the American Journal of Clinical Nutrition.
The investigators analyzed how "bad" cholesterol (low-density lipoprotein, or LDL, cholesterol) responded to diets that were either high or low in fat in 28 pairs of identical male twins - one twin a vigorous exerciser, the other a comparative couch potato.
"Although identical twins share exactly the same genes, we chose these twins because they had very different lifestyles," says Williams. "One member of each pair was a regular long-distance runner, someone we contacted through Runner's World magazine or at races around the country. His brother clocked 40 kilometers a week less, at least, if he exercised at all."
For six weeks the twins ate either a high-fat diet (40 percent of its calories from fat) or a low-fat diet (only 20 percent of its calories from fat); then the pairs switched diets for another six weeks. After each six-week period the twins' blood cholesterol levels were tested.
The researchers were interested in learning if blood cholesterol changes due to the different diets would be the same or different in each pair of genetically identical twins, even though their lifestyles were very different. A correlation of zero between the two would mean that their responses to the diets had no relation to each other, while a correlation of 1.0 would mean that their responses were identical.
The researchers found an astounding 0.7 correlation in responses to the change in diet, an incredibly strong similarity in the way each pair of twins responded - even though the responses themselves among different pairs of twins differed considerably.
"If one of the twins could eat a high-fat diet without increasing his bad cholesterol, then so could his brother," says Williams. "But if one of the twins' LDL cholesterol shot up when they went on the high-fat diet, his brother's did too."
The correlations showed that the twins had very similar changes in LDL cholesterol because they had the same genes. Some twins had one or more genes that made them very sensitive to the amount of fat in their diets. Other twins had genes that made them insensitive to dietary fat, no matter how much they exercised.
"Our experiment shows how important our genes are," says Williams. "Some people have to be careful about their diets, while others have much more freedom in their dietary choices."
He adds, "This type of experiment allows us to test whether genes are important without having to identify the specific genes involved." Although several specific genes have been associated with cholesterol changes in response to changes in diet, these cannot account for the large correlations seen in this study. Williams hopes his findings will inspire additional research to identify the specific genes involved.
"Concordant lipoprotein and weight responses to dietary fat change in identical twins with divergent exercise levels," by Paul T. Williams, Patricia J. Blanche, Robin Rawlings, and Ronald M. Krauss, appears in the July 8, 2005, issue of the American Journal of Clinical Nutrition. The work was supported by Dairy Management Incorporated, with additional support from the National Institutes of Health.
Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our website at
lbl.
Berkeley Lab News Release
So says a new study by researchers at the Department of Energy's Lawrence Berkeley National Laboratory and the Children's Hospital Oakland Research Institute (CHORI), conducted by Paul Williams of Berkeley Lab's Life Sciences Division in collaboration with Robin Rawlings and Patricia Blanche of CHORI and Ronald M. Krauss of CHORI and Berkeley Lab's Genomics Division. They report their findings in the July 8, 2005, issue of the American Journal of Clinical Nutrition.
The investigators analyzed how "bad" cholesterol (low-density lipoprotein, or LDL, cholesterol) responded to diets that were either high or low in fat in 28 pairs of identical male twins - one twin a vigorous exerciser, the other a comparative couch potato.
"Although identical twins share exactly the same genes, we chose these twins because they had very different lifestyles," says Williams. "One member of each pair was a regular long-distance runner, someone we contacted through Runner's World magazine or at races around the country. His brother clocked 40 kilometers a week less, at least, if he exercised at all."
For six weeks the twins ate either a high-fat diet (40 percent of its calories from fat) or a low-fat diet (only 20 percent of its calories from fat); then the pairs switched diets for another six weeks. After each six-week period the twins' blood cholesterol levels were tested.
The researchers were interested in learning if blood cholesterol changes due to the different diets would be the same or different in each pair of genetically identical twins, even though their lifestyles were very different. A correlation of zero between the two would mean that their responses to the diets had no relation to each other, while a correlation of 1.0 would mean that their responses were identical.
The researchers found an astounding 0.7 correlation in responses to the change in diet, an incredibly strong similarity in the way each pair of twins responded - even though the responses themselves among different pairs of twins differed considerably.
"If one of the twins could eat a high-fat diet without increasing his bad cholesterol, then so could his brother," says Williams. "But if one of the twins' LDL cholesterol shot up when they went on the high-fat diet, his brother's did too."
The correlations showed that the twins had very similar changes in LDL cholesterol because they had the same genes. Some twins had one or more genes that made them very sensitive to the amount of fat in their diets. Other twins had genes that made them insensitive to dietary fat, no matter how much they exercised.
"Our experiment shows how important our genes are," says Williams. "Some people have to be careful about their diets, while others have much more freedom in their dietary choices."
He adds, "This type of experiment allows us to test whether genes are important without having to identify the specific genes involved." Although several specific genes have been associated with cholesterol changes in response to changes in diet, these cannot account for the large correlations seen in this study. Williams hopes his findings will inspire additional research to identify the specific genes involved.
"Concordant lipoprotein and weight responses to dietary fat change in identical twins with divergent exercise levels," by Paul T. Williams, Patricia J. Blanche, Robin Rawlings, and Ronald M. Krauss, appears in the July 8, 2005, issue of the American Journal of Clinical Nutrition. The work was supported by Dairy Management Incorporated, with additional support from the National Institutes of Health.
Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our website at
lbl.
Berkeley Lab News Release
среда, 14 сентября 2011 г.
QuatRx Pharmaceuticals Initiates Phase I Trial For Treatment To Reduce Both LDL Cholesterol And Lipoprotein (A)
QuatRx Pharmaceuticals, a privately held biopharmaceutical company focused on research and development of therapeutic compounds for the treatment of major endocrine,
metabolic and cardiovascular diseases, today announced that it has
initiated a Phase I clinical study of QRX-431, a novel compound in
development for the treatment of elevated cholesterol levels and obesity.
In pre-clinical primate studies, QRX-431, a selective thyroid beta agonist,
lowered LDL, lipoprotein (a) and weight without significantly increasing
heart rate. High levels of low-density lipoproteins (LDL) have been shown
to be a major cause of coronary heart disease, a condition affecting more
than 13 million Americans. Elevated lipoprotein (a) [Lp(a)] has been linked
to an increased risk of stroke and coronary heart disease.
"We are extremely encouraged by the preclinical results for QRX-431. We
feel this new drug candidate offers great promise as a therapy to help the
millions of people with elevated lipid levels and obesity who may be at
risk for stroke and coronary heart disease," said Robert L. Zerbe, M.D.,
chief executive officer and president of QuatRx.
Preclinical Study Results
In preclinical primate studies, QRX-431 significantly reduced LDL
cholesterol and Lp(a). To date, there are no approved therapies for the
treatment of elevated Lp(a) levels. Study results also suggest that QRX-431
activates reverse cholesterol transport, a protective mechanism involving
transport of cholesterol from the arteries to the liver. QRX-431 may also
act to induce weight loss. QRX-431 demonstrated a weight reduction in seven
days in a primate study and did not significantly affect heart rate.
LDL Cholesterol, Cardiovascular Disease and Current Treatments
Collectively, more than 71 million Americans have some form of
cardiovascular disease, according to the American Heart Association.
Cardiovascular disease is the number one killer in the United States,
claiming more lives than cancer, chronic lower respiratory diseases,
accidents, and diabetes combined. Statins are commonly used to lower LDL
cholesterol and reduce the risk of cardiovascular disease. Though effective
for many people with high LDL cholesterol, statins have no effect on Lp(a),
can cause many side effects and many people cannot tolerate the higher
doses needed to achieve target LDL levels. Thyroid hormone has been shown
to lower LDL levels and Lp(a), but unlike QRX-431, thyroid hormone also
stimulates the thyroid alpha receptor, which produces increases in heart
rate. For this reason, thyroid hormone has not been considered a viable
therapy for lowering cholesterol or weight.
About QuatRx
QuatRx Pharmaceuticals Company is focused on discovering, licensing,
developing and commercializing compounds in the endocrine, metabolic and
cardiovascular therapeutic areas. In addition to QRX-431, QuatRx currently
has three product candidates in clinical development. QuatRx's two lead
compounds target hormone deficiencies that result from aging in women and
men. Ophena(TM) is in Phase III development initially for the treatment of
vaginal atrophy, a common problem associated with estrogen deficiency in
post- menopausal women. Fispemifene, a treatment for testosterone
deficiency, is in Phase II clinical testing. QuatRx is also developing
Asord(TM), a topical product candidate for the treatment of psoriasis,
which has completed a Phase IIb clinical trial.
QuatRx Pharmaceuticals Company
quatrx
metabolic and cardiovascular diseases, today announced that it has
initiated a Phase I clinical study of QRX-431, a novel compound in
development for the treatment of elevated cholesterol levels and obesity.
In pre-clinical primate studies, QRX-431, a selective thyroid beta agonist,
lowered LDL, lipoprotein (a) and weight without significantly increasing
heart rate. High levels of low-density lipoproteins (LDL) have been shown
to be a major cause of coronary heart disease, a condition affecting more
than 13 million Americans. Elevated lipoprotein (a) [Lp(a)] has been linked
to an increased risk of stroke and coronary heart disease.
"We are extremely encouraged by the preclinical results for QRX-431. We
feel this new drug candidate offers great promise as a therapy to help the
millions of people with elevated lipid levels and obesity who may be at
risk for stroke and coronary heart disease," said Robert L. Zerbe, M.D.,
chief executive officer and president of QuatRx.
Preclinical Study Results
In preclinical primate studies, QRX-431 significantly reduced LDL
cholesterol and Lp(a). To date, there are no approved therapies for the
treatment of elevated Lp(a) levels. Study results also suggest that QRX-431
activates reverse cholesterol transport, a protective mechanism involving
transport of cholesterol from the arteries to the liver. QRX-431 may also
act to induce weight loss. QRX-431 demonstrated a weight reduction in seven
days in a primate study and did not significantly affect heart rate.
LDL Cholesterol, Cardiovascular Disease and Current Treatments
Collectively, more than 71 million Americans have some form of
cardiovascular disease, according to the American Heart Association.
Cardiovascular disease is the number one killer in the United States,
claiming more lives than cancer, chronic lower respiratory diseases,
accidents, and diabetes combined. Statins are commonly used to lower LDL
cholesterol and reduce the risk of cardiovascular disease. Though effective
for many people with high LDL cholesterol, statins have no effect on Lp(a),
can cause many side effects and many people cannot tolerate the higher
doses needed to achieve target LDL levels. Thyroid hormone has been shown
to lower LDL levels and Lp(a), but unlike QRX-431, thyroid hormone also
stimulates the thyroid alpha receptor, which produces increases in heart
rate. For this reason, thyroid hormone has not been considered a viable
therapy for lowering cholesterol or weight.
About QuatRx
QuatRx Pharmaceuticals Company is focused on discovering, licensing,
developing and commercializing compounds in the endocrine, metabolic and
cardiovascular therapeutic areas. In addition to QRX-431, QuatRx currently
has three product candidates in clinical development. QuatRx's two lead
compounds target hormone deficiencies that result from aging in women and
men. Ophena(TM) is in Phase III development initially for the treatment of
vaginal atrophy, a common problem associated with estrogen deficiency in
post- menopausal women. Fispemifene, a treatment for testosterone
deficiency, is in Phase II clinical testing. QuatRx is also developing
Asord(TM), a topical product candidate for the treatment of psoriasis,
which has completed a Phase IIb clinical trial.
QuatRx Pharmaceuticals Company
quatrx
воскресенье, 11 сентября 2011 г.
Link Between Apolipoprotein E Genotypes With Lipid Levels And Coronary Risk
There are linear links between apolipoprotein E (apoE) genotypes with lipid levels and coronary risk, according to an analysis of previous studies published in the Journal of the American Medical Association (JAMA).
apoE, a multifunctional protein, plays a vital part in cholesterol and triglycerides metabolism, explain the writers. A number of studies have identified a link between some apoE genotypes and lipid levels and coronary risk. However, the majority of those studies were small and perhaps biased.
Anna M. Bennet, Ph.D., University of Cambridge, England, and team looked at a number of studies in order to see whether there was really a link between apoE with circulating lipid levels and coronary risk. There were 82 studies of lipid levels, involving 86,067 healthy subjects, and 121 studies of coronary outcomes - 37,850 cases and 82,727 controls - with a focus on studies with 1,000 healthy subjects or more for lipids and those with 500 or more coronary outcomes.
In the most extreme comparison, the scientists explained, individuals with the E2/E2 genotype had 31% lower average LDL-C (low-density lipoprotein cholesterol) values compared to people with the E4/E4 genotype. The authors wrote "??¦a difference comparable with that produced by 'statin' medication. The relationship of apoE genotypes with high-density lipoprotein cholesterol (HDL-C) was shallow and inverse and that with triglycerides was nonlinear and largely confined to the E2/E2 genotype, with the latter about 2 times weaker than previously reported."
The researchers added "We found that, in comparison with the commonest E3/E3 genotype, E2 carriers had a 20 percent reduced coronary risk, in contrast with previous estimates that E2 carriage is neutral for coronary risk. We noted strong evidence of selective publication in previous estimates based on smaller studies. This is a serious concern given that apoE genotypes and coronary risk had hitherto been considered among the few quantitatively secure associations in cardiovascular disease genetics."
E4 carriers have a slightly higher risk of coronary disease compared with E3/E3 individuals, the authors wrote.
JAMA. 2007;298(11):1300-1311
jama.ama-assn
apoE, a multifunctional protein, plays a vital part in cholesterol and triglycerides metabolism, explain the writers. A number of studies have identified a link between some apoE genotypes and lipid levels and coronary risk. However, the majority of those studies were small and perhaps biased.
Anna M. Bennet, Ph.D., University of Cambridge, England, and team looked at a number of studies in order to see whether there was really a link between apoE with circulating lipid levels and coronary risk. There were 82 studies of lipid levels, involving 86,067 healthy subjects, and 121 studies of coronary outcomes - 37,850 cases and 82,727 controls - with a focus on studies with 1,000 healthy subjects or more for lipids and those with 500 or more coronary outcomes.
In the most extreme comparison, the scientists explained, individuals with the E2/E2 genotype had 31% lower average LDL-C (low-density lipoprotein cholesterol) values compared to people with the E4/E4 genotype. The authors wrote "??¦a difference comparable with that produced by 'statin' medication. The relationship of apoE genotypes with high-density lipoprotein cholesterol (HDL-C) was shallow and inverse and that with triglycerides was nonlinear and largely confined to the E2/E2 genotype, with the latter about 2 times weaker than previously reported."
The researchers added "We found that, in comparison with the commonest E3/E3 genotype, E2 carriers had a 20 percent reduced coronary risk, in contrast with previous estimates that E2 carriage is neutral for coronary risk. We noted strong evidence of selective publication in previous estimates based on smaller studies. This is a serious concern given that apoE genotypes and coronary risk had hitherto been considered among the few quantitatively secure associations in cardiovascular disease genetics."
E4 carriers have a slightly higher risk of coronary disease compared with E3/E3 individuals, the authors wrote.
JAMA. 2007;298(11):1300-1311
jama.ama-assn
четверг, 8 сентября 2011 г.
Most Americans do not know that high cholesterol comes from two sources
Results from a recent nationwide survey showed that most respondents did not know that high cholesterol comes from two sources, even though the respondents reported having high cholesterol. When asked about the sources of cholesterol, more than three-quarters of respondents (77 percent) stated incorrectly that the food they eat contributes the most to high cholesterol. In fact, the cholesterol in the bloodstream is not just absorbed from the food people eat, but the majority is produced naturally in the body.
Other findings from the survey showed that 45 percent of high cholesterol patients said they were more concerned about cholesterol compared to other personal health issues and 75 percent felt that their cholesterol should be lower.
"Patients with high cholesterol should make an extra effort to be as informed about their cholesterol levels as possible. Knowing about the sources of cholesterol is a key step in this process," says David Cohen, M.D., director of hepatology, Brigham and Women's Hospital. "The fact is that both diet and heredity play a critical role in your cholesterol levels. While diet can contribute significantly to elevated cholesterol, the body's natural chemistry can often produce dangerously high levels of LDL ("bad") cholesterol based on heredity alone. When working with a physician to manage your condition, it is important for patients to understand that there are two sources of cholesterol and in many cases both need to be addressed."
The survey results also showed:
Respondents did have a general sense that the lower their cholesterol the better; with 75 percent agreeing that their cholesterol should be lower than it currently is now.
Most respondents (85 percent) said they were aware there are national guidelines for where their overall cholesterol number should be. However, only 27 percent of those people actually knew that the optimal level for LDL cholesterol is less than 100mg/dL.
"The cholesterol awareness gap that is seen in this survey can and should be remedied," says Bonna Kol, executive director of Mended Hearts, a volunteer organization affiliated with the American Heart Association that provides supportive services to heart disease patients and their families nationwide. "High cholesterol is a serious condition, but it can be treated. Following a heart healthy diet, managing weight and staying physically active are essential lifestyle components we've encouraged for years. We've also emphasized the importance of informed patients talking with their doctor to ensure cholesterol goals are met. These findings reinforce that importance. Patients should work with their doctors on developing an approach to lowering cholesterol that is best for them."
The survey was sponsored by Merck/ Schering-Plough Pharmaceuticals in conjunction with Mended Hearts. The two organizations are developing educational materials and local awareness campaigns based on the findings to educate heart patients on the importance of reaching their cholesterol treatment goals.
About Cholesterol
Cholesterol is a form of fat or "lipid" found in the blood and all cells of the body. It is critically important in helping to form cell membranes, steroid hormones and bile acids. There are two sources of cholesterol: cholesterol comes from the food you eat and is produced naturally in the body. However, over time, excess LDL (or bad) cholesterol in the blood can build up on the inner walls of the arteries that supply blood to the heart. These deposits form plaque, which can cause the arteries to narrow, making them less efficient at transporting blood. This condition, called atherosclerosis, restricts blood flow, which can result in heart attack.
About the Survey
Merck/ Schering-Plough Pharmaceuticals, in partnership with Mended Hearts, sponsored the survey, which was conducted among 1,118 patients who reported having high cholesterol and who were members in a sub-panel of the Harris Interactive Chronic Illness Panel. This survey was composed of 566 respondents currently being treated with cholesterol lowering medicines and 552 currently untreated. The Harris Interactive Chronic Illness Panel(CIP) consists of over 1 million households where members have been screened for more than 50 separate medical conditions. The panel members are recruited from among Harris Interactive's general online consumer panel. The CIP allows targeted and effective sampling on specific populations of interest. Participants receive incentives for each survey they complete. Incentives are in the form of HI Points, which are ultimately redeemable for rewards (like pens, radios, and watches) at various point levels.
About Mended Hearts
Mended Hearts, a national nonprofit organization affiliated with the American Heart Association, has been offering the gift of hope to heart disease patients, their families and caregivers for more than 50 years. Recognized for its role in facilitating a positive patient-care experience, Mended Hearts partners with 460 hospitals and rehabilitation clinics and offers services to heart patients through visiting programs, support group meetings and educational forums. Its mission is to "inspire hope in heart disease patients and their families."
About Merck/Schering-Plough Pharmaceuticals
Merck/Schering-Plough Pharmaceuticals is a joint venture between Merck & Co., Inc. and Schering-Plough Corporation formed in May 2000 to develop and market in the United States new prescription medicines in cholesterol management. The collaboration was expanded in December 2001 to include worldwide markets (excluding Japan).
About Harris Interactive®
Harris Interactive (harrisinteractive) is a worldwide market research and consulting firm best known for The Harris Poll®, and for pioneering the Internet method to conduct scientifically accurate market research. Headquartered in Rochester, New York, Harris Interactive combines proprietary methodologies and technology with expertise in predictive, custom and strategic research. The Company conducts international research from its U.S. offices and through wholly owned subsidiaries--London-based HI Europe (hieurope), Paris-based Novatris and Tokyo-based Harris Interactive Japan--as well as through the Harris Interactive Global Network of independent market- and opinion-research firms.
For more information on cholesterol and its sources, please go to 2cholesterolsources.
Media Contacts:
Tim Elsner
214-706-1406
Mended Hearts
Kristin Francini
202-352-4806
Porter Novelli
Daphne Hoytt
212-601-8162
Porter Novelli
Other findings from the survey showed that 45 percent of high cholesterol patients said they were more concerned about cholesterol compared to other personal health issues and 75 percent felt that their cholesterol should be lower.
"Patients with high cholesterol should make an extra effort to be as informed about their cholesterol levels as possible. Knowing about the sources of cholesterol is a key step in this process," says David Cohen, M.D., director of hepatology, Brigham and Women's Hospital. "The fact is that both diet and heredity play a critical role in your cholesterol levels. While diet can contribute significantly to elevated cholesterol, the body's natural chemistry can often produce dangerously high levels of LDL ("bad") cholesterol based on heredity alone. When working with a physician to manage your condition, it is important for patients to understand that there are two sources of cholesterol and in many cases both need to be addressed."
The survey results also showed:
Respondents did have a general sense that the lower their cholesterol the better; with 75 percent agreeing that their cholesterol should be lower than it currently is now.
Most respondents (85 percent) said they were aware there are national guidelines for where their overall cholesterol number should be. However, only 27 percent of those people actually knew that the optimal level for LDL cholesterol is less than 100mg/dL.
"The cholesterol awareness gap that is seen in this survey can and should be remedied," says Bonna Kol, executive director of Mended Hearts, a volunteer organization affiliated with the American Heart Association that provides supportive services to heart disease patients and their families nationwide. "High cholesterol is a serious condition, but it can be treated. Following a heart healthy diet, managing weight and staying physically active are essential lifestyle components we've encouraged for years. We've also emphasized the importance of informed patients talking with their doctor to ensure cholesterol goals are met. These findings reinforce that importance. Patients should work with their doctors on developing an approach to lowering cholesterol that is best for them."
The survey was sponsored by Merck/ Schering-Plough Pharmaceuticals in conjunction with Mended Hearts. The two organizations are developing educational materials and local awareness campaigns based on the findings to educate heart patients on the importance of reaching their cholesterol treatment goals.
About Cholesterol
Cholesterol is a form of fat or "lipid" found in the blood and all cells of the body. It is critically important in helping to form cell membranes, steroid hormones and bile acids. There are two sources of cholesterol: cholesterol comes from the food you eat and is produced naturally in the body. However, over time, excess LDL (or bad) cholesterol in the blood can build up on the inner walls of the arteries that supply blood to the heart. These deposits form plaque, which can cause the arteries to narrow, making them less efficient at transporting blood. This condition, called atherosclerosis, restricts blood flow, which can result in heart attack.
About the Survey
Merck/ Schering-Plough Pharmaceuticals, in partnership with Mended Hearts, sponsored the survey, which was conducted among 1,118 patients who reported having high cholesterol and who were members in a sub-panel of the Harris Interactive Chronic Illness Panel. This survey was composed of 566 respondents currently being treated with cholesterol lowering medicines and 552 currently untreated. The Harris Interactive Chronic Illness Panel(CIP) consists of over 1 million households where members have been screened for more than 50 separate medical conditions. The panel members are recruited from among Harris Interactive's general online consumer panel. The CIP allows targeted and effective sampling on specific populations of interest. Participants receive incentives for each survey they complete. Incentives are in the form of HI Points, which are ultimately redeemable for rewards (like pens, radios, and watches) at various point levels.
About Mended Hearts
Mended Hearts, a national nonprofit organization affiliated with the American Heart Association, has been offering the gift of hope to heart disease patients, their families and caregivers for more than 50 years. Recognized for its role in facilitating a positive patient-care experience, Mended Hearts partners with 460 hospitals and rehabilitation clinics and offers services to heart patients through visiting programs, support group meetings and educational forums. Its mission is to "inspire hope in heart disease patients and their families."
About Merck/Schering-Plough Pharmaceuticals
Merck/Schering-Plough Pharmaceuticals is a joint venture between Merck & Co., Inc. and Schering-Plough Corporation formed in May 2000 to develop and market in the United States new prescription medicines in cholesterol management. The collaboration was expanded in December 2001 to include worldwide markets (excluding Japan).
About Harris Interactive®
Harris Interactive (harrisinteractive) is a worldwide market research and consulting firm best known for The Harris Poll®, and for pioneering the Internet method to conduct scientifically accurate market research. Headquartered in Rochester, New York, Harris Interactive combines proprietary methodologies and technology with expertise in predictive, custom and strategic research. The Company conducts international research from its U.S. offices and through wholly owned subsidiaries--London-based HI Europe (hieurope), Paris-based Novatris and Tokyo-based Harris Interactive Japan--as well as through the Harris Interactive Global Network of independent market- and opinion-research firms.
For more information on cholesterol and its sources, please go to 2cholesterolsources.
Media Contacts:
Tim Elsner
214-706-1406
Mended Hearts
Kristin Francini
202-352-4806
Porter Novelli
Daphne Hoytt
212-601-8162
Porter Novelli
понедельник, 5 сентября 2011 г.
Metabolex Begins Phase 2 Trial Of MBX-8025 For Treatment Of Dyslipidemia
Metabolex, Inc., a
biotechnology company dedicated to the discovery and development of novel
therapeutics for diabetes and related metabolic disorders, announced
that it has begun a 180 patient Phase 2 trial of MBX-8025 in overweight or
obese patients with high cholesterol and triglycerides to assess the drug's
effect on dyslipidemia, insulin-resistance and obesity.
Preclinical and clinical testing of MBX-8025 indicates that the drug
has the potential to improve a number of lipid parameters that are abnormal
in different types of dyslipidemia, including high LDL (or "bad")
cholesterol, high Apo B-100 (the atherogenic lipoprotein), low HDL (or
"good") cholesterol and high triglycerides (fats). In addition, MBX-8025
has been shown to exhibit positive effects on insulin sensitization and
body weight. The randomized, double blind Phase 2 trial will assess the
potential of the drug alone and in combination with Lipitor(R)
(atorvastatin).
"Although high LDL levels are widely treated as a risk factor for heart
disease, many patients are unable to reach increasingly low LDL targets on
a statin alone. Additionally, existing drugs do a poor job of targeting the
entire range of different lipid disorders that contribute to cardiac risk.
We believe this trial will provide us crucial evidence in assessing the
ability of MBX-8025 to lower Apo B-100, LDL and triglyceride levels, as
well as raise HDL levels, improve insulin sensitivity and reduce body
weight," said David B. Karpf, M.D., the chief medical officer of Metabolex.
"In addition, we are testing the drug in conjunction with Lipitor, the
best-selling lipid-lowering drug in the world, to determine whether
combination therapy with a statin will be well tolerated and lead to even
better results."
The study will enroll 180 overweight or obese non diabetic patients and
assess two different doses of MBX-8025, given over an 8-week treatment
period, both alone and in combination with Lipitor(R). The primary endpoint
is the reduction in Apo B-100 compared with placebo. Secondary endpoints
include measurements of the effect of treatment on LDL, HDL, triglycerides
and body weight and composition. Metabolic parameters, including glucose
and insulin levels, will also be assessed.
MBX-8025 regulates fatty acid degradation, lipid storage/transport and
insulin sensitivity. Metabolex has in-licensed the patents and the
exclusive development and commercialization rights to MBX-8025 from Janssen
Pharmaceutica NV, a Johnson & Johnson company.
About Metabolex
Metabolex is a privately held biotechnology company dedicated to the
discovery and development of novel therapeutics to transform the treatment
of diabetes and related metabolic disorders. Metabolex has drawn on its
deep understanding of diabetes to create the largest database of genes
involved in diabetes and to build a rich pipeline of product candidates and
drug discovery targets. The company has three clinical-stage compounds:
MBX-102/JNJ 39659100, in Phase 2/3 testing; MBX-2044, in Phase 2a; and
MBX-8025, being studied in dyslipidemia, now in Phase 2. Ortho-McNeil, Inc.
has the exclusive right to develop and commercialize MBX-102/JNJ 39659100
and MBX-2044. For additional information about Metabolex and its
development pipeline, visit metabolex.
Metabolex, Inc.
metabolex
biotechnology company dedicated to the discovery and development of novel
therapeutics for diabetes and related metabolic disorders, announced
that it has begun a 180 patient Phase 2 trial of MBX-8025 in overweight or
obese patients with high cholesterol and triglycerides to assess the drug's
effect on dyslipidemia, insulin-resistance and obesity.
Preclinical and clinical testing of MBX-8025 indicates that the drug
has the potential to improve a number of lipid parameters that are abnormal
in different types of dyslipidemia, including high LDL (or "bad")
cholesterol, high Apo B-100 (the atherogenic lipoprotein), low HDL (or
"good") cholesterol and high triglycerides (fats). In addition, MBX-8025
has been shown to exhibit positive effects on insulin sensitization and
body weight. The randomized, double blind Phase 2 trial will assess the
potential of the drug alone and in combination with Lipitor(R)
(atorvastatin).
"Although high LDL levels are widely treated as a risk factor for heart
disease, many patients are unable to reach increasingly low LDL targets on
a statin alone. Additionally, existing drugs do a poor job of targeting the
entire range of different lipid disorders that contribute to cardiac risk.
We believe this trial will provide us crucial evidence in assessing the
ability of MBX-8025 to lower Apo B-100, LDL and triglyceride levels, as
well as raise HDL levels, improve insulin sensitivity and reduce body
weight," said David B. Karpf, M.D., the chief medical officer of Metabolex.
"In addition, we are testing the drug in conjunction with Lipitor, the
best-selling lipid-lowering drug in the world, to determine whether
combination therapy with a statin will be well tolerated and lead to even
better results."
The study will enroll 180 overweight or obese non diabetic patients and
assess two different doses of MBX-8025, given over an 8-week treatment
period, both alone and in combination with Lipitor(R). The primary endpoint
is the reduction in Apo B-100 compared with placebo. Secondary endpoints
include measurements of the effect of treatment on LDL, HDL, triglycerides
and body weight and composition. Metabolic parameters, including glucose
and insulin levels, will also be assessed.
MBX-8025 regulates fatty acid degradation, lipid storage/transport and
insulin sensitivity. Metabolex has in-licensed the patents and the
exclusive development and commercialization rights to MBX-8025 from Janssen
Pharmaceutica NV, a Johnson & Johnson company.
About Metabolex
Metabolex is a privately held biotechnology company dedicated to the
discovery and development of novel therapeutics to transform the treatment
of diabetes and related metabolic disorders. Metabolex has drawn on its
deep understanding of diabetes to create the largest database of genes
involved in diabetes and to build a rich pipeline of product candidates and
drug discovery targets. The company has three clinical-stage compounds:
MBX-102/JNJ 39659100, in Phase 2/3 testing; MBX-2044, in Phase 2a; and
MBX-8025, being studied in dyslipidemia, now in Phase 2. Ortho-McNeil, Inc.
has the exclusive right to develop and commercialize MBX-102/JNJ 39659100
and MBX-2044. For additional information about Metabolex and its
development pipeline, visit metabolex.
Metabolex, Inc.
metabolex
пятница, 2 сентября 2011 г.
Treat The Risk, Not The Cholesterol: Study Challenges Current Cholesterol Recommendations
A new study by the University of Michigan Medical School and VA Ann Arbor Health System challenges the medical thinking that the lower the cholesterol, the better.
Tailoring treatment to a patient's overall heart attack risk, by considering all their risk factors, such as age, family history, and smoking status, was more effective, and used fewer high-dose statins, than current strategies to drive down cholesterol to a certain target, according to the U-M study.
While study authors support the use of cholesterol-lowering statins, they conclude that patients and their doctors should consider all the factors that put them at risk for heart attack and strokes.
The findings will be released online Monday ahead of print in the Annals of Internal Medicine.
"We've been worrying too much about people's cholesterol level and not enough about their overall risk of heart disease," says Rodney A. Hayward, M.D., director of the Veterans Affairs Center for Health Services Research and Development and a professor of internal medicine at the University of Michigan Medical School.
The National Cholesterol Education Program recommends harmful LDL cholesterol levels should be less than 130 for most people. High risk patients should be pushed even lower -- to less than 70.
The U-M study took a different approach, called tailored treatment, which uses a person's risk factors and mathematical models to calculate the expected benefit of treatment, by considering:
???A person's risk of a heart attack or stroke without treatment;
???How much a statin decreases the risk; and
???Potential harms from the treatment
"These are the three factors that determine the net benefit of a treatment. Our fixation on just one factor, LDL cholesterol, is leading us to often treat the wrong people," Hayward says.
In the recent study, U-M physicians who worked with Yale University School of Medicine used data from statin trials that included Americans ages 30-75 with no history of heart attack.
Study authors evaluated the benefit of five years of treatment that was tailored, on coronary artery disease risk factors such as age, family history, diabetes, high blood pressure, smoking status, and recently CRP, C-reactive protein.
The tailored approach was more efficient (more benefit per person treated) and prevented substantially more heart attacks, strokes and cardiovascular deaths than the currently recommended treat-to-target approaches.
The tailored strategy treated fewer individuals with high-dose statins and saved 500,000 more quality-adjusted life years.
"The bottom line message - knowing your overall heart attack risk is more important than knowing your cholesterol level," Hayward says. "If your overall risk is elevated, you should probably be on a statin regardless of what your cholesterol is and if your risk is very high, should probably be on a high dose of statin," the U-M physician says.
"However, if your LDL cholesterol is high, but your overall cardiac risk is low, taking a statin does not make sense for you," Hayward says. "If your cholesterol is your only risk factor and you're younger, you should work on diet and exercise."
Research has increasingly emerged questioning the value of cholesterol targets and which of statins mechanisms is most important to preventing cardiac events. Cholesterol-lowering drugs work by blocking a key enzyme linked with LDL cholesterol production, but they initiate other changes in the body.
"Statins also affect inflammation on the inside of our blood vessels which is often what causes heart attacks and strokes - it's not just a matter of cholesterol alone," he says.
Additional authors: Harlan M. Krumholz, M.D., Yale University School of Medicine, and Donna M. Zulman, M.D., Justin W. Timbie, Ph.D., and Sandeep Vijan, M.D, all of the VA Center for Health Services Research and Development, VA Ann Arbor Health Care System.
Funding: VA Health Services Research and Development Service's Quality Enhancement Research Initiative and the Measurement Core of the Michigan Diabetes Research & Training Center of the National Institutes of Health.
Source
University of Michigan Health System
Tailoring treatment to a patient's overall heart attack risk, by considering all their risk factors, such as age, family history, and smoking status, was more effective, and used fewer high-dose statins, than current strategies to drive down cholesterol to a certain target, according to the U-M study.
While study authors support the use of cholesterol-lowering statins, they conclude that patients and their doctors should consider all the factors that put them at risk for heart attack and strokes.
The findings will be released online Monday ahead of print in the Annals of Internal Medicine.
"We've been worrying too much about people's cholesterol level and not enough about their overall risk of heart disease," says Rodney A. Hayward, M.D., director of the Veterans Affairs Center for Health Services Research and Development and a professor of internal medicine at the University of Michigan Medical School.
The National Cholesterol Education Program recommends harmful LDL cholesterol levels should be less than 130 for most people. High risk patients should be pushed even lower -- to less than 70.
The U-M study took a different approach, called tailored treatment, which uses a person's risk factors and mathematical models to calculate the expected benefit of treatment, by considering:
???A person's risk of a heart attack or stroke without treatment;
???How much a statin decreases the risk; and
???Potential harms from the treatment
"These are the three factors that determine the net benefit of a treatment. Our fixation on just one factor, LDL cholesterol, is leading us to often treat the wrong people," Hayward says.
In the recent study, U-M physicians who worked with Yale University School of Medicine used data from statin trials that included Americans ages 30-75 with no history of heart attack.
Study authors evaluated the benefit of five years of treatment that was tailored, on coronary artery disease risk factors such as age, family history, diabetes, high blood pressure, smoking status, and recently CRP, C-reactive protein.
The tailored approach was more efficient (more benefit per person treated) and prevented substantially more heart attacks, strokes and cardiovascular deaths than the currently recommended treat-to-target approaches.
The tailored strategy treated fewer individuals with high-dose statins and saved 500,000 more quality-adjusted life years.
"The bottom line message - knowing your overall heart attack risk is more important than knowing your cholesterol level," Hayward says. "If your overall risk is elevated, you should probably be on a statin regardless of what your cholesterol is and if your risk is very high, should probably be on a high dose of statin," the U-M physician says.
"However, if your LDL cholesterol is high, but your overall cardiac risk is low, taking a statin does not make sense for you," Hayward says. "If your cholesterol is your only risk factor and you're younger, you should work on diet and exercise."
Research has increasingly emerged questioning the value of cholesterol targets and which of statins mechanisms is most important to preventing cardiac events. Cholesterol-lowering drugs work by blocking a key enzyme linked with LDL cholesterol production, but they initiate other changes in the body.
"Statins also affect inflammation on the inside of our blood vessels which is often what causes heart attacks and strokes - it's not just a matter of cholesterol alone," he says.
Additional authors: Harlan M. Krumholz, M.D., Yale University School of Medicine, and Donna M. Zulman, M.D., Justin W. Timbie, Ph.D., and Sandeep Vijan, M.D, all of the VA Center for Health Services Research and Development, VA Ann Arbor Health Care System.
Funding: VA Health Services Research and Development Service's Quality Enhancement Research Initiative and the Measurement Core of the Michigan Diabetes Research & Training Center of the National Institutes of Health.
Source
University of Michigan Health System
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