A new technique using the pubic bone as a source of bone for grafting may avoid the complications of harvesting bone from the iliac crest, or "hip bone," according to a report in the November/December issue of The Journal of Craniofacial Surgery.
With further study, the pubic bone could become the new standard for harvesting bone grafts for certain types of reconstructive surgery, write Dr. John W. Polley and colleagues of Rush University Medical Center, Chicago.
Dr. Polley and colleagues developed their approach to harvesting pubic bone in a series of cadaver dissections. They found that the pubic bone, found at the front of the pelvis, could be easily reached through a small incision about 1 inch. Just as importantly, minimal dissection of the soft tissue was necessary to expose the pubic bone and collect the cancellous bone (sponge-like interior bone) needed for grafting.
The researchers report on their initial experience with the pubic bone graft technique in a 10-year-old boy who needed follow-up surgery for a cleft palate defect. The procedure to collect the bone needed for grafting was quick and simple. The day after surgery the patient had little or no pain in the pubic area, which healed without problems.
The iliac crest is the standard site for harvesting bone grafts for reconstructive surgery in the face and jaws, as well as other areas. However, several types of complications can occur after the iliac crest donor procedure, including nerve injuries, pain problems, and scarring.
The pubic bone graft technique is a promising approach to avoiding these problems, Dr. Polley and colleagues point out. Because it requires a small incision with minimal dissection, the pubic bone technique is less traumatic than harvesting bone from the iliac crest site. Since there are no nerves supplying sensation to the skin in the area of the incision, the risk of nerve injury is reduced. Even scarring is less of a concern, because the incision is made in an area normally covered by hair.
"The pubic bone graft compares favorably with more traditional techniques of cancellous bone harvesting," Dr. Polley and colleagues conclude. The procedure appears safe and reliable, allowing faster collection of bone grafts and fewer complications than with the iliac crest technique. With further experience and follow-up, the researchers believe the pubic bone graft could become the new standard for patients undergoing cleft palate reconstruction.
About The Journal of Craniofacial Surgery
The Journal of Craniofacial Surgery serves as a forum of communication for all those involved in craniofacial and maxillofacial surgery. Coverage ranges from practical aspects of craniofacial surgery to the basic science that underlies surgical practice. Founded and edited by Mutaz B. Habal, MD, of Tampa, FL, the Journal is affiliated with major specialty societies worldwide, including the American Association of Pediatric Plastic Surgeons, the American Academy of Pediatrics Section of Pediatric Plastic Surgery, the American Society of Craniofacial Surgeons, the European Society of Craniofacial Surgery, the International Society of Craniofacial Surgery, the Japanese Society of Craniofacial Surgery, the Korean Society of Craniofacial Surgery, the Argentine Society of Plastic Surgery Section of Pediatric Plastic Surgery, the American Society of Maxillofacial Surgeons, the World Craniofacial Foundation, and the Brazilian Society of Craniomaxillofacial Surgery. Visit the journal website at jcraniofacialsurgery.
About Lippincott Williams & Wilkins
Lippincott Williams & Wilkins (LWW) is a leading international publisher for physicians, nurses, specialized clinicians, and students. Nearly 275 periodicals and 1,500 books in more than 100 disciplines are published under the LWW brand, as well as content-based sites and online corporate and customer services. LWW is part of Wolters Kluwer Health, a leading provider of information for professionals and students in medicine, nursing, allied health, pharmacy, and the pharmaceutical industry. Wolters Kluwer Health is a division of Wolters Kluwer, a leading multinational publisher and information services company with annual sales of ?‚¬3.4 billion (2005) and approximately 18,400 employees worldwide.
Lippincott Williams & Wilkins
530 Walnut St.
Philadelphia, PA 19106
United States
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понедельник, 16 мая 2011 г.
Tibetan Plant Worm Can Regulate Cholesterol Metabolism, NOEVIR Confirms
Tokyo (JCN) - NOEVIR announced on August 18 that it has identified a unique property of cordyceps sinensis saccardo, a plant worm native to Tibet.
In its recent experiments using rats and human white adipocytes, the company confirmed that extracts of the plant worm can promote the production of adiponectin, a kind of protein that helps promote fat-burning activities and inhibit the development of lifestyle-related diseases.
Consequently, NOEVIR has concluded that the extracts have potential to prevent and improve lifestyle-related diseases. The company plans to apply these findings to the development of dietary supplement products.
Details of the research is to be presented at the 22th Annual Meeting of the Medical and Pharmaceutical Society for WAKAN-YAKU to be held in Tokyo on August 20 and 21.
View NOEVIR company profile here
Copyright © 2005 JCN. All rights reserved. A division of Japan Corporate News Network KK.
japancorp
In its recent experiments using rats and human white adipocytes, the company confirmed that extracts of the plant worm can promote the production of adiponectin, a kind of protein that helps promote fat-burning activities and inhibit the development of lifestyle-related diseases.
Consequently, NOEVIR has concluded that the extracts have potential to prevent and improve lifestyle-related diseases. The company plans to apply these findings to the development of dietary supplement products.
Details of the research is to be presented at the 22th Annual Meeting of the Medical and Pharmaceutical Society for WAKAN-YAKU to be held in Tokyo on August 20 and 21.
View NOEVIR company profile here
Copyright © 2005 JCN. All rights reserved. A division of Japan Corporate News Network KK.
japancorp
Children May Have Cholesterol Problems, Too
High cholesterol levels
are not just found in adults. Children may have high cholesterol, too, even
without being overweight. Over years, cholesterol overload has similar
hazards as in adults -- clogged arteries and injury to the heart.
The Children's Hospital of Philadelphia recommends that children,
starting at age two years, should have a complete cholesterol profile
checked after an overnight fasting if they have a family history of high
cholesterol or of early heart disease, in line with similar recommendations
from the American Academy of Pediatrics and the American Heart Association.
Those who do not have a family history but have other risk factors for
early heart disease, such as being overweight, high blood pressure,
diabetes, smoking, poor diet, and sedentary lifestyle should also be
screened.
"Although the most common reasons for high cholesterol are poor diet,
being overweight, and not getting enough exercise, some apparently healthy
children inherit high cholesterol levels from their parents," said Julie
Brothers, M.D., medical director of the Lipid Heart Clinic at The
Children's Hospital of Philadelphia. "Overall, we've noticed an increase in
children's cholesterol levels the past several years and this is a
disturbing trend."
Children with a family history of high cholesterol or early heart
disease, even if they have normal weight, should be routinely screened, as
they may have a genetic predisposition for excess cholesterol levels --
familial hypercholesterolemia (FH). These children have high levels of
low-density lipoprotein (LDL), also called "bad cholesterol," beginning at
birth, which can lead to early thickening of the artery walls, premature
cardiovascular disease and an increased risk of early heart attack.
Familial hypercholesterolemia is underestimated in the community and in
pediatric primary care practices. Children with FH have no symptoms or
signs of their condition and often do not fit the profile of someone who is
at risk; they usually have a normal weight and a healthy lifestyle and
diet. However, in addition to a family history of high cholesterol, they
usually have a family history of early heart disease. Children with a
parent, grandparent, sibling, aunt, or uncle with high cholesterol or who
has suffered a cardiac event before the age of 55 should be routinely
monitored.
Children who are overweight or obese should also have their cholesterol
levels routinely screened by pediatric healthcare professionals, as this
also places them at increased risk of developing early heart disease.
It is important to differentiate between obese children with high
cholesterol and those with FH, which is not traditionally associated with
obesity; however, with the obesity epidemic, many children with FH now also
are overweight or obese.
"Cholesterol levels in children who are obese usually respond well to
diet and lifestyle modifications, whereas children with FH often need
medications in addition to diet and exercise," added Dr. Brothers.
Modifications to diet and increased physical activity are the
first-line treatments for children identified with raised cholesterol
levels. Another option is putting a child on statin therapy, which is a
lifetime commitment.
The Lipid Heart Clinic at The Children's Hospital of Philadelphia
evaluates and treats children and adolescents who have high levels of
lipids (fats) in their blood. Elevated lipids put young people at risk for
heart disease later in life.
The Children's Hospital of Philadelphia was founded in 1855 as the
nation's first pediatric hospital. Through its long-standing commitment to
providing exceptional patient care, training new generations of pediatric
healthcare professionals and pioneering major research initiatives,
Children's Hospital has fostered many discoveries that have benefited
children worldwide. Its pediatric research program is among the largest in
the country, ranking third in National Institutes of Health funding. In
addition, its unique family-centered care and public service programs have
brought the 430-bed hospital recognition as a leading advocate for children
and adolescents. For more information, visit chop.
The Children's Hospital of Philadelphia
chop
are not just found in adults. Children may have high cholesterol, too, even
without being overweight. Over years, cholesterol overload has similar
hazards as in adults -- clogged arteries and injury to the heart.
The Children's Hospital of Philadelphia recommends that children,
starting at age two years, should have a complete cholesterol profile
checked after an overnight fasting if they have a family history of high
cholesterol or of early heart disease, in line with similar recommendations
from the American Academy of Pediatrics and the American Heart Association.
Those who do not have a family history but have other risk factors for
early heart disease, such as being overweight, high blood pressure,
diabetes, smoking, poor diet, and sedentary lifestyle should also be
screened.
"Although the most common reasons for high cholesterol are poor diet,
being overweight, and not getting enough exercise, some apparently healthy
children inherit high cholesterol levels from their parents," said Julie
Brothers, M.D., medical director of the Lipid Heart Clinic at The
Children's Hospital of Philadelphia. "Overall, we've noticed an increase in
children's cholesterol levels the past several years and this is a
disturbing trend."
Children with a family history of high cholesterol or early heart
disease, even if they have normal weight, should be routinely screened, as
they may have a genetic predisposition for excess cholesterol levels --
familial hypercholesterolemia (FH). These children have high levels of
low-density lipoprotein (LDL), also called "bad cholesterol," beginning at
birth, which can lead to early thickening of the artery walls, premature
cardiovascular disease and an increased risk of early heart attack.
Familial hypercholesterolemia is underestimated in the community and in
pediatric primary care practices. Children with FH have no symptoms or
signs of their condition and often do not fit the profile of someone who is
at risk; they usually have a normal weight and a healthy lifestyle and
diet. However, in addition to a family history of high cholesterol, they
usually have a family history of early heart disease. Children with a
parent, grandparent, sibling, aunt, or uncle with high cholesterol or who
has suffered a cardiac event before the age of 55 should be routinely
monitored.
Children who are overweight or obese should also have their cholesterol
levels routinely screened by pediatric healthcare professionals, as this
also places them at increased risk of developing early heart disease.
It is important to differentiate between obese children with high
cholesterol and those with FH, which is not traditionally associated with
obesity; however, with the obesity epidemic, many children with FH now also
are overweight or obese.
"Cholesterol levels in children who are obese usually respond well to
diet and lifestyle modifications, whereas children with FH often need
medications in addition to diet and exercise," added Dr. Brothers.
Modifications to diet and increased physical activity are the
first-line treatments for children identified with raised cholesterol
levels. Another option is putting a child on statin therapy, which is a
lifetime commitment.
The Lipid Heart Clinic at The Children's Hospital of Philadelphia
evaluates and treats children and adolescents who have high levels of
lipids (fats) in their blood. Elevated lipids put young people at risk for
heart disease later in life.
The Children's Hospital of Philadelphia was founded in 1855 as the
nation's first pediatric hospital. Through its long-standing commitment to
providing exceptional patient care, training new generations of pediatric
healthcare professionals and pioneering major research initiatives,
Children's Hospital has fostered many discoveries that have benefited
children worldwide. Its pediatric research program is among the largest in
the country, ranking third in National Institutes of Health funding. In
addition, its unique family-centered care and public service programs have
brought the 430-bed hospital recognition as a leading advocate for children
and adolescents. For more information, visit chop.
The Children's Hospital of Philadelphia
chop
New mechanism for controlling cholesterol and lipid metabolism discovered
A team of investigators from the Uppsala Branch of the Ludwig Institute for Cancer Research (LICR) and Harvard Medical
School has uncovered novel targets for the development of drugs that would potentially complement, or replace, statins in
treating heart disease.
Statins are commonly taken drugs that reduce the levels of low density lipoprotein (LDL) and have been shown to reduce risks
associated with heart disease, the number one killer in the Western world. However, statins are not suitable for all
patients, and reduce cardiovascular events by only 20%- 40%. Additionally, some genetic causes of high cholesterol cannot be
treated with statins.
According to LICR's Dr. Johan Ericsson, the senior author of the study published today in Cell Metabolism, the team found
that a protein called Fbw7 degrades the SREBP proteins that drive lipid and cholesterol production. "We found that inhibiting
Fbw7 resulted in increased SREBP levels and an enhanced uptake of LDL, so a drug that blocks the interaction between Fbw7 and
SREBP proteins would probably enhance the removal of harmful LDL-cholesterol from the circulation. We can only speculate at
this stage, but a two-pronged attack on LDL removal, combining a statin with a treatment that prevents Fbw7/SREBP interaction
would likely be of more benefit to some patients than statins alone."
Dr. Ericsson said that the team also found that the Fbw7/SREBP interaction may also be connected to diabetes, as insulin
signaling inhibited Fbw7's ability to affect SREBP levels and thus increased lipid and cholesterol synthesis. Finally, the
Fbw7/SREBP interaction also provides a theoretical link between lipid synthesis and the aberrant growth of cancer cells. The
loss of Fbw7, which is inactivated in some breast, endometrial, ovarian and colon cancers, has been shown to make cells
multiply faster and synthesize more lipids; factors that are critical for tumor growth. Aspects of both links are under
investigation.
Contact: Sarah L. White, Ph.D.
swhitelicr
1-917-974-7952
Ludwig Institute for Cancer Research
School has uncovered novel targets for the development of drugs that would potentially complement, or replace, statins in
treating heart disease.
Statins are commonly taken drugs that reduce the levels of low density lipoprotein (LDL) and have been shown to reduce risks
associated with heart disease, the number one killer in the Western world. However, statins are not suitable for all
patients, and reduce cardiovascular events by only 20%- 40%. Additionally, some genetic causes of high cholesterol cannot be
treated with statins.
According to LICR's Dr. Johan Ericsson, the senior author of the study published today in Cell Metabolism, the team found
that a protein called Fbw7 degrades the SREBP proteins that drive lipid and cholesterol production. "We found that inhibiting
Fbw7 resulted in increased SREBP levels and an enhanced uptake of LDL, so a drug that blocks the interaction between Fbw7 and
SREBP proteins would probably enhance the removal of harmful LDL-cholesterol from the circulation. We can only speculate at
this stage, but a two-pronged attack on LDL removal, combining a statin with a treatment that prevents Fbw7/SREBP interaction
would likely be of more benefit to some patients than statins alone."
Dr. Ericsson said that the team also found that the Fbw7/SREBP interaction may also be connected to diabetes, as insulin
signaling inhibited Fbw7's ability to affect SREBP levels and thus increased lipid and cholesterol synthesis. Finally, the
Fbw7/SREBP interaction also provides a theoretical link between lipid synthesis and the aberrant growth of cancer cells. The
loss of Fbw7, which is inactivated in some breast, endometrial, ovarian and colon cancers, has been shown to make cells
multiply faster and synthesize more lipids; factors that are critical for tumor growth. Aspects of both links are under
investigation.
Contact: Sarah L. White, Ph.D.
swhitelicr
1-917-974-7952
Ludwig Institute for Cancer Research
Obesity As Protection Against Metabolic Syndrome, Not Its Cause
The collection of symptoms that is the metabolic syndrome - insulin resistance, high cholesterol, fatty liver, and a greater risk for diabetes, heart disease, and stroke - are all related to obesity, but, according to a review in the March 9th issue of the Cell Press publication Trends in Endocrinology and Metabolism, not in the way you probably think they are.
In fact, says Roger Unger of the University of Texas Southwestern at Dallas, obesity is the body's way of storing lipids where they belong, in fat tissue, in an effort to protect our other organs from lipids' toxic effects. It's when the surplus of calories coming in gets to be too much for our fat tissue to handle that those lipids wind up in other places they shouldn't be, and the cascade of symptoms known as metabolic syndrome sets in.
It comes down to simple facts that all of us know on some level or another: Americans since the 1950s eat too much high-calorie food loaded with carbs and fat (what Unger calls "potent adipogenic nutrient mixtures") and, thanks to modern technology, we move far too little. Until that changes, Unger doesn't see any end to the growing epidemic of metabolic syndrome. Still, our metabolisms aren't broken; the pathways that squirrel fat away as an energy source for use in lean times are just completely overwhelmed. "We are pushing our homeostatic capability to the maximum," says Unger, who coined the term "lipotoxicity" in 1994. "Overnutrition used to be rare - reserved for those in the castle. Today, it's just the opposite. Bad calories are so cheap that anyone can afford to get overweight."
Unger cites plenty of evidence in support of a protective role for obesity. Genetic manipulations in mice that increase or decrease fat formation have provided evidence that adipogenesis, meaning the generation of fat cells, delays other metabolic consequences of overeating. The reverse is also true, he writes. Obesity-resistant mice have in some cases been found to develop severe diabetes upon eating too much, as a result of lipid accumulation in tissues other than fat.
There is some disagreement in the field about whether insulin resistance is a primary cause of metabolic syndrome or just one of its features, Unger notes. But on this, too, he has a clear view. Insulin resistance is not the cause of metabolic syndrome, he says, it is a "passive byproduct" of fat deposition in the liver and muscle once storage in fat cells begins to fail.
It also makes sense in Unger's estimation that cells that have already taken on too much fat would begin to exclude glucose, causing its levels in blood and urine to rise. Once in cells, glucose becomes a substrate for the production of more fat. "The body is doing what we should have done - keep excess calories out - and it may be protective," Unger says.
At the center of the transition from protective obesity to metabolic syndrome is resistance to the fat hormone leptin, well known for its appetite-suppressing effects, Unger says. The hormone is also responsible for partitioning fat in the body. The rise of leptin as fat stores grow is therefore an adaptive response, but that can only go so far before resistance sets in.
Based on the genes they carry, some people will be better able to sustain lipid storage in fat and can get away with being overweight, even obese, without the other symptoms. Eventually, though, the need to cut calories is something all of us will face.
"Once you reach a certain age, almost everybody is leptin resistant," he says. "Nature stops protecting you once you pass the reproductive years," requiring all of us to watch our diets and do exercise.
Unger's perspective comes from the research he does at UT Southwestern's Touchstone Center for Diabetes Research and a thorough understanding of the scientific literature, but it also stems from his own memories in childhood when one only saw fat ladies at the circus. "That's how unusual it was," he says. "The younger you are, the more skewed your perception is of an epidemic that surrounds you."
Unger concludes his review article this way: "Based on evidence reviewed here, it seems that prevalent forms of metabolic syndrome and T2DM [type 2 diabetes mellitus] result from unremitting caloric surplus complicated by failure of adipocytes to maintain protection against lipotoxicity. If one imagines the USA population to be unwitting volunteers in the largest (300 million subjects) and longest (50 years) clinical research project in history, the specific aim of which was to determine if the deleterious effects of sustained caloric surplus in rodents also can occur in humans, the outcome of the project becomes clear - after 50 years of exposure to an inexpensive calorie-dense diet high in fat and carbohydrates, 200 million subjects are overweight and >50 million have metabolic syndrome. The failure of healthcare providers and pharmaceutical industries to contain the pandemic suggests that elimination of 'bargain basement' calories will be required to 'price obesity out of the market.' Unfortunately, this would have profound socioeconomic implications: How do we tax excessive calories while at the same time guaranteeing sufficient access to high-quality foods for the underprivileged?"
Scherer et al.: "Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity."
In fact, says Roger Unger of the University of Texas Southwestern at Dallas, obesity is the body's way of storing lipids where they belong, in fat tissue, in an effort to protect our other organs from lipids' toxic effects. It's when the surplus of calories coming in gets to be too much for our fat tissue to handle that those lipids wind up in other places they shouldn't be, and the cascade of symptoms known as metabolic syndrome sets in.
It comes down to simple facts that all of us know on some level or another: Americans since the 1950s eat too much high-calorie food loaded with carbs and fat (what Unger calls "potent adipogenic nutrient mixtures") and, thanks to modern technology, we move far too little. Until that changes, Unger doesn't see any end to the growing epidemic of metabolic syndrome. Still, our metabolisms aren't broken; the pathways that squirrel fat away as an energy source for use in lean times are just completely overwhelmed. "We are pushing our homeostatic capability to the maximum," says Unger, who coined the term "lipotoxicity" in 1994. "Overnutrition used to be rare - reserved for those in the castle. Today, it's just the opposite. Bad calories are so cheap that anyone can afford to get overweight."
Unger cites plenty of evidence in support of a protective role for obesity. Genetic manipulations in mice that increase or decrease fat formation have provided evidence that adipogenesis, meaning the generation of fat cells, delays other metabolic consequences of overeating. The reverse is also true, he writes. Obesity-resistant mice have in some cases been found to develop severe diabetes upon eating too much, as a result of lipid accumulation in tissues other than fat.
There is some disagreement in the field about whether insulin resistance is a primary cause of metabolic syndrome or just one of its features, Unger notes. But on this, too, he has a clear view. Insulin resistance is not the cause of metabolic syndrome, he says, it is a "passive byproduct" of fat deposition in the liver and muscle once storage in fat cells begins to fail.
It also makes sense in Unger's estimation that cells that have already taken on too much fat would begin to exclude glucose, causing its levels in blood and urine to rise. Once in cells, glucose becomes a substrate for the production of more fat. "The body is doing what we should have done - keep excess calories out - and it may be protective," Unger says.
At the center of the transition from protective obesity to metabolic syndrome is resistance to the fat hormone leptin, well known for its appetite-suppressing effects, Unger says. The hormone is also responsible for partitioning fat in the body. The rise of leptin as fat stores grow is therefore an adaptive response, but that can only go so far before resistance sets in.
Based on the genes they carry, some people will be better able to sustain lipid storage in fat and can get away with being overweight, even obese, without the other symptoms. Eventually, though, the need to cut calories is something all of us will face.
"Once you reach a certain age, almost everybody is leptin resistant," he says. "Nature stops protecting you once you pass the reproductive years," requiring all of us to watch our diets and do exercise.
Unger's perspective comes from the research he does at UT Southwestern's Touchstone Center for Diabetes Research and a thorough understanding of the scientific literature, but it also stems from his own memories in childhood when one only saw fat ladies at the circus. "That's how unusual it was," he says. "The younger you are, the more skewed your perception is of an epidemic that surrounds you."
Unger concludes his review article this way: "Based on evidence reviewed here, it seems that prevalent forms of metabolic syndrome and T2DM [type 2 diabetes mellitus] result from unremitting caloric surplus complicated by failure of adipocytes to maintain protection against lipotoxicity. If one imagines the USA population to be unwitting volunteers in the largest (300 million subjects) and longest (50 years) clinical research project in history, the specific aim of which was to determine if the deleterious effects of sustained caloric surplus in rodents also can occur in humans, the outcome of the project becomes clear - after 50 years of exposure to an inexpensive calorie-dense diet high in fat and carbohydrates, 200 million subjects are overweight and >50 million have metabolic syndrome. The failure of healthcare providers and pharmaceutical industries to contain the pandemic suggests that elimination of 'bargain basement' calories will be required to 'price obesity out of the market.' Unfortunately, this would have profound socioeconomic implications: How do we tax excessive calories while at the same time guaranteeing sufficient access to high-quality foods for the underprivileged?"
Scherer et al.: "Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity."
Chronic Care Model Associated With Improved Diabetes Care
Incorporating elements of the Chronic Care Model (CCM) in small independent primary care practices can be done with ease and is associated with better intermediate outcomes of diabetes care. This study of 90 clinicians and 886 patients found that clinician-reported use of CCM elements was significantly associated with lower glycosylated hemoglobin levels (the standard measure of the degree of control of diabetes) and ratios of cholesterol to high-density lipoprotein cholesterol. Specifically, for every unit increase in clinician-reported CCM use (e.g., from "rarely" to "occasionally"), there was an associated 0.30% reduction in glycosylated hemoglobin values and a 0.17 reduction in the lipid ratio.
Use of Chronic Care Model Elements Is Associated with Higher-Quality Care for Diabetes
By Paul A. Nutting, M.D., M.S.P.H., et al
Annals of Family Medicine tip sheet
Annals of Family Medicine is a peer-reviewed, indexed research journal that provides a cross-disciplinary forum for new, evidence-based information affecting the primary care disciplines. Annals of Family Medicine is sponsored by six family medical organizations, including the American Academy of Family Physicians, the American Board of Family Medicine, the Society of Teachers of Family Medicine, the Association of Departments of Family Medicine, the Association of Family Medicine Residency Directors and the North American Primary Care Research Group. Annals of Family Medicine is published six times each year and contains original research from the clinical, biomedical, social and health services areas, as well as contributions on methodology and theory, selected reviews, essays and editorials. Complete editorial content and interactive discussion groups for each published article can be accessed free of charge on the journal's Web site, annfammed/.
Contact: Kristin Robinson
American Academy of Family Physicians
Use of Chronic Care Model Elements Is Associated with Higher-Quality Care for Diabetes
By Paul A. Nutting, M.D., M.S.P.H., et al
Annals of Family Medicine tip sheet
Annals of Family Medicine is a peer-reviewed, indexed research journal that provides a cross-disciplinary forum for new, evidence-based information affecting the primary care disciplines. Annals of Family Medicine is sponsored by six family medical organizations, including the American Academy of Family Physicians, the American Board of Family Medicine, the Society of Teachers of Family Medicine, the Association of Departments of Family Medicine, the Association of Family Medicine Residency Directors and the North American Primary Care Research Group. Annals of Family Medicine is published six times each year and contains original research from the clinical, biomedical, social and health services areas, as well as contributions on methodology and theory, selected reviews, essays and editorials. Complete editorial content and interactive discussion groups for each published article can be accessed free of charge on the journal's Web site, annfammed/.
Contact: Kristin Robinson
American Academy of Family Physicians
Merck, Schering-Plough Offer Explanation For Delay In Release Of Vytorin Study Results
Merck and Schering-Plough recently offered a detailed explanation of their decision to delay the release of the results of a study of the cholesterol medication Vytorin, the Wall Street Journal reports. The study, called Enhance, ended in April 2006, but the companies did not release the results until Jan. 14 (Winslow/Wilde Mathews, Wall Street Journal, 1/26).
The study found that Vytorin is no more effective than a medication available in generic form in the prevention of accumulation of plaque on artery walls. For the study, 720 participants took either Vytorin -- a combination of Zetia, which blocks absorption of cholesterol in the intestines, and Zocor, a statin available in generic form -- or Zocor alone. The two-year study found that participants who took Vytorin experienced a 58% decrease in their LDL cholesterol levels, compared with 41% for those who took Zocor. However, the study found no statistically significant difference in the accumulation of plaque on artery walls among participants who took Vytorin and those who took Zocor (Kaiser Daily Health Policy Report, 1/17).
The companies attributed the delay in the release of the results to efforts to ensure accuracy of imaging data collected during the study. The companies in late 2005 raised concerns about the quality of the imaging data. In subsequent months, the companies established a plan to reanalyze the images that included the establishment of two panels of outside experts to discuss the issue. In January 2007, one expert said the concerns about the quality of the imaging data were similar to those in other studies, but the companies decided to continue with the plan. The companies also said that the results of the study were "blinded" throughout the process and that they remained unaware of whether the results were positive or negative until Dec. 31, 2007.
According to the Journal, "Critics said that, despite the recounting, they didn't fully understand why the companies spent so long working on the data," and the "affair shows the problems that can arise when corporate sponsors, rather than independent academic investigators, control how a study is run" (Wall Street Journal, 1/26).
The study found that Vytorin is no more effective than a medication available in generic form in the prevention of accumulation of plaque on artery walls. For the study, 720 participants took either Vytorin -- a combination of Zetia, which blocks absorption of cholesterol in the intestines, and Zocor, a statin available in generic form -- or Zocor alone. The two-year study found that participants who took Vytorin experienced a 58% decrease in their LDL cholesterol levels, compared with 41% for those who took Zocor. However, the study found no statistically significant difference in the accumulation of plaque on artery walls among participants who took Vytorin and those who took Zocor (Kaiser Daily Health Policy Report, 1/17).
The companies attributed the delay in the release of the results to efforts to ensure accuracy of imaging data collected during the study. The companies in late 2005 raised concerns about the quality of the imaging data. In subsequent months, the companies established a plan to reanalyze the images that included the establishment of two panels of outside experts to discuss the issue. In January 2007, one expert said the concerns about the quality of the imaging data were similar to those in other studies, but the companies decided to continue with the plan. The companies also said that the results of the study were "blinded" throughout the process and that they remained unaware of whether the results were positive or negative until Dec. 31, 2007.
According to the Journal, "Critics said that, despite the recounting, they didn't fully understand why the companies spent so long working on the data," and the "affair shows the problems that can arise when corporate sponsors, rather than independent academic investigators, control how a study is run" (Wall Street Journal, 1/26).
Additional Developments
Summaries of several developments related to the results of the Vytorin study appear below.
FDA recommendations: FDA on Friday said that patients should not end treatment with Vytorin immediately based on the results of the study, CQ HealthBeat reports. According to FDA officials, the study does not indicate that Vytorin is ineffective. They added that patients who take Vytorin should discuss whether they should switch medication with their physicians. FDA officials also said that the agency will review the results of the study, with results expected in six months (Lubbes, CQ HealthBeat, 1/25).
New York investigation: The office of New York Attorney General Andrew Cuomo (D) on Saturday announced that he has sent subpoenas to Merck and Schering-Plough as part of an investigation into the delay in the release of the results of the study, the Journal reports. The investigation seeks to determine whether the company "deliberately concealed" results of the study. Both companies said that they have received the subpoenas and will cooperate with the investigation (Rubenstein, Wall Street Journal, 1/28).
Lawsuits: Merck and Schering-Plough face at least 10 federal lawsuits over allegations that the companies "reaped billions of dollars in profits" through their delay in the release of the results of the study, the Philadelphia Inquirer reports. The lawsuits -- filed in California, Colorado, New Jersey, New York and Ohio -- allege that the delay prompted patients to purchase Vytorin, rather than a lower-cost, generic version. Skip Irvine, a spokesperson for the companies, said that they plan to fight the lawsuits (Stark, Philadelphia Inquirer, 1/26).
Patient response: Many patients who are "dismayed by recently released research" on Vytorin "have been asking their doctors what to do," the Arkansas Democrat-Gazette reports. According to the Democrat-Gazette, many physicians are "keeping their patients on Vytorin, while others have made changes." The American College of Cardiology has recommended that physicians not make "major clinical decisions" based on the results of the study, and the American Heart Association has recommended that patients consult with their physician before they end treatment with Vytorin (Tubbs, Arkansas Democrat-Gazette, 1/28).
Opinion Piece
"The idea that cholesterol plays a key role in heart disease is so tightly woven into modern medical thinking that it is no longer considered open to question," but based on the results of the Vytorin study, scientists should "question the role of LDL cholesterol in heart disease," Gary Taubes -- author of "Good Calories, Bad Calories: Challenging the Conventional Wisdom on Diet, Weight Control and Disease" -- writes in a New York Times opinion piece.
Taubes writes, "If the evidence continues to challenge the role of cholesterol, then rethink it, without preconceptions, and consider what these other pathways in cardiovascular disease are implying about cause and prevention." He concludes, "A different hypothesis may turn out to fit the facts better and one day help prevent considerably more deaths" (Taubes, New York Times, 1/27).
Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
View drug information on Zocor.
Statin Drugs And Risk Of Advanced Prostate Cancer
UroToday- Statins are commonly prescribed agents to lower cholesterol and the associated risks of vascular events. Statins are also known to have proapoptotic and antimetastatic effects in cancer. In fact, some studies inversely associate statin use with breast and colorectal cancers, but others to include epidemiologic ones have not supported this observation. Dr. Platz and colleagues evaluated over 30,000 men in a longitudinal health study with regard to statin use and risk of prostate cancer (CaP) and reported their findings in the December 20, 2006 issue of the Journal of the National Cancer Institute.
Study participants were enrolled in the Health Professionals Follow-up Study, an ongoing prospective cohort study of diet and other risk factors for heart disease, cancer and other conditions. It began in 1986 and questionnaires were completed biennially with an overall questionnaire response rate of 94%. Data regarding statin use began in 1990 and was thus the time of initiating study analysis. Medical records were obtained for men diagnosed with CaP. Stage T1a disease was excluded and participants were categorized as organ confined or advanced; regionally invasive, metastatic or fatal. Disease was also categorized as lower grade or higher grade. While 91% of all cholesterol drugs taken were statins, data on brand, type or dose was not acquired.
Between 1990 and 1994, 4.4% and 9.3%, respectively, of the men in the study reported using statins. This increased to 24% by the year 2000. Current use of statins was not associated with either total CaP or organ-confined disease after age adjustment or multivariable adjustment. Compared with nonuse of statins, current use was inversely associated with risk of advanced disease after adjusting for age and other CaP risk factors. The age-standardized incidence rate of advanced CaP for current statin users and nonusers was 38 and 89 per 100,000 person-years, respectively. This inverse association was even stronger for risk of metastatic and fatal CaP. Current use of statins was not associated with risk of either higher grade disease or lower grade disease. However, among ever-users of statins for 5 or more years, the relative risk of higher grade disease was lower than the relative risk of lower grade disease.
This epidemiologic study reports that men who currently used statin drugs had half the risk of advanced CaP and less than half the risk of metastatic or fatal CaP compared to men who did not currently use statins. The authors state that despite their data, it is premature to advocate the use of statins for chemoprevention of advanced CaP.
Elizabeth A. Platz, Michael F. Leitzmann, Kala Visvanathan, Eric B. Rimm, Meir J. Stampfer, Walter C. Willett, and Edward Giovannucci
J Natl Cancer Inst 2006;98:1819-25
Reviewed by UroToday Contributing Editor Christopher P. Evans, MD
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to:
urotoday
Copyright © 2006 - UroToday
Study participants were enrolled in the Health Professionals Follow-up Study, an ongoing prospective cohort study of diet and other risk factors for heart disease, cancer and other conditions. It began in 1986 and questionnaires were completed biennially with an overall questionnaire response rate of 94%. Data regarding statin use began in 1990 and was thus the time of initiating study analysis. Medical records were obtained for men diagnosed with CaP. Stage T1a disease was excluded and participants were categorized as organ confined or advanced; regionally invasive, metastatic or fatal. Disease was also categorized as lower grade or higher grade. While 91% of all cholesterol drugs taken were statins, data on brand, type or dose was not acquired.
Between 1990 and 1994, 4.4% and 9.3%, respectively, of the men in the study reported using statins. This increased to 24% by the year 2000. Current use of statins was not associated with either total CaP or organ-confined disease after age adjustment or multivariable adjustment. Compared with nonuse of statins, current use was inversely associated with risk of advanced disease after adjusting for age and other CaP risk factors. The age-standardized incidence rate of advanced CaP for current statin users and nonusers was 38 and 89 per 100,000 person-years, respectively. This inverse association was even stronger for risk of metastatic and fatal CaP. Current use of statins was not associated with risk of either higher grade disease or lower grade disease. However, among ever-users of statins for 5 or more years, the relative risk of higher grade disease was lower than the relative risk of lower grade disease.
This epidemiologic study reports that men who currently used statin drugs had half the risk of advanced CaP and less than half the risk of metastatic or fatal CaP compared to men who did not currently use statins. The authors state that despite their data, it is premature to advocate the use of statins for chemoprevention of advanced CaP.
Elizabeth A. Platz, Michael F. Leitzmann, Kala Visvanathan, Eric B. Rimm, Meir J. Stampfer, Walter C. Willett, and Edward Giovannucci
J Natl Cancer Inst 2006;98:1819-25
Reviewed by UroToday Contributing Editor Christopher P. Evans, MD
UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.
To access the latest urology news releases from UroToday, go to:
urotoday
Copyright © 2006 - UroToday
How Diet, Drugs Affect Cholesterol Varies From Person To Person
Why is it that a particular diet or drug will lower one person??™s cholesterol levels and not another??™s? A new report by Harvard Medical School explains why one size doesn??™t fit all when it comes to lowering cholesterol and provides the lowdown on a variety of treatment options.
What to Do About High Cholesterol explains that genetic and physiological differences from person to person lead to wide variation in how people??™s cholesterol levels respond to cholesterol rich foods, as well as to heart-healthy diets. Because there isn??™t a single recommendation for diet or cholesterol intake, people often have to try several different approaches until they find one that works for them.
The report, prepared with medical editor Mason Freeman, M.D., Associate Professor of Medicine at Harvard Medical School and Director of the Lipid Clinic at Massachusetts General Hospital, outlines an individualized approach to cholesterol reduction. It describes what dietary changes to make, how to get started on an exercise program, and when to talk with your doctor about medications. Although statins are probably the best-known treatment for cholesterol, they aren??™t for everyone. The report also details the other medication options available, including fibric acid derivatives, niacin, bile acid binders, and natural substances such as plant sterols that can help lower cholesterol.
Harvard Health Publications
Harvard Medical School 10 Shattuck St., Ste. 612
Cambridge, MA 02115
United States
health.harvard
What to Do About High Cholesterol explains that genetic and physiological differences from person to person lead to wide variation in how people??™s cholesterol levels respond to cholesterol rich foods, as well as to heart-healthy diets. Because there isn??™t a single recommendation for diet or cholesterol intake, people often have to try several different approaches until they find one that works for them.
The report, prepared with medical editor Mason Freeman, M.D., Associate Professor of Medicine at Harvard Medical School and Director of the Lipid Clinic at Massachusetts General Hospital, outlines an individualized approach to cholesterol reduction. It describes what dietary changes to make, how to get started on an exercise program, and when to talk with your doctor about medications. Although statins are probably the best-known treatment for cholesterol, they aren??™t for everyone. The report also details the other medication options available, including fibric acid derivatives, niacin, bile acid binders, and natural substances such as plant sterols that can help lower cholesterol.
Harvard Health Publications
Harvard Medical School 10 Shattuck St., Ste. 612
Cambridge, MA 02115
United States
health.harvard
Power-Packed Soy Breakfast Cereal Developed By U Of I Researcher
Breakfast of champions? That would be a soy protein-packed, low-fat, high-fiber cereal that meets the requirements for three different FDA health claims and leaves you feeling full so you won't be tempted to eat again until lunch.
University of Illinois scientist Soo-Yeun Lee has cooked up a "recipe" for just such a cereal, one that's passed the taste test of her sensory panel.
"There are lots of good reasons to eat soy--and even more reasons to consume soy protein at breakfast," said Soo-Yeun Lee, a U of I assistant professor of food science and human nutrition.
"Research shows that soy decreases the risk of breast and prostate cancers and lowers cholesterol and triglycerides. Diets high in soy protein are also effective in combating obesity. Soy protein is very high-quality protein, and high-protein meals eaten early in the day stick with you so you eat less," she said.
Even though it's important that people consume protein in the morning, the scientist said most breakfast foods - cereals, muffins, waffles - are high in carbohydrates.
So why don't more breakfast foods contain soy?
"If we incorporate too much soy in a product to increase its protein content, off-flavors and off-textures can develop, which may result in less consumer acceptance of the product," the researcher said.
Lee has accomplished a lot then in getting 10 grams of protein (6.5 grams of it soy protein) and 5 grams of fiber into one serving of a cereal that people find appealing. In doing so, she also met the requirements for the FDA's soy, high protein, and fiber health claims.
Other products have used soy as a fortifying ingredient rather than a major base ingredient, she said.
How does she know her soy-based cereals appeal to consumers? The researcher asked 120 people to take part in a sensory panel to evaluate her four formulations - both unflavored and cinnamon-flavored cereals served with and without skim milk. A second consumer evaluation pitted Lee's cereals against five cereals that are already commercially available and marketed for their healthful properties.
"We know we need to do some tweaking but, even at this stage, one of our formulations did better than a product that's already on store shelves. We're still experimenting with different flavors and sweeteners, but I'm confident that soy-based, high-protein cereals can not only optimize nutrition, they can also taste good," she said.
Lee said that her formulations were taste-tested as stand-alone cereals but could also be used as supplements to boost the protein and fiber content of other cereals.
"Because most Americans eat cereal for breakfast, we thought it made sense to boost the protein content of the food they're used to eating," said Lee.
Besides, a breakfast food that is high in soy protein has advantages over other protein sources (think bacon and eggs) that are high in fat and cholesterol, she said.
Lee collaborated on the project with her husband, U of I food processing engineer Youngsoo Lee, and graduate student Katherine Yeu, who has worked in Kellogg's sensory testing department and has now taken a position at Kerry Ingredients. Yeu's graduate work was supported by a Becker Fellowship, given to students who want to work in product development and food engineering.
The study was published in a recent issue of the Journal of Food Science.
University of Illinois scientist Soo-Yeun Lee has cooked up a "recipe" for just such a cereal, one that's passed the taste test of her sensory panel.
"There are lots of good reasons to eat soy--and even more reasons to consume soy protein at breakfast," said Soo-Yeun Lee, a U of I assistant professor of food science and human nutrition.
"Research shows that soy decreases the risk of breast and prostate cancers and lowers cholesterol and triglycerides. Diets high in soy protein are also effective in combating obesity. Soy protein is very high-quality protein, and high-protein meals eaten early in the day stick with you so you eat less," she said.
Even though it's important that people consume protein in the morning, the scientist said most breakfast foods - cereals, muffins, waffles - are high in carbohydrates.
So why don't more breakfast foods contain soy?
"If we incorporate too much soy in a product to increase its protein content, off-flavors and off-textures can develop, which may result in less consumer acceptance of the product," the researcher said.
Lee has accomplished a lot then in getting 10 grams of protein (6.5 grams of it soy protein) and 5 grams of fiber into one serving of a cereal that people find appealing. In doing so, she also met the requirements for the FDA's soy, high protein, and fiber health claims.
Other products have used soy as a fortifying ingredient rather than a major base ingredient, she said.
How does she know her soy-based cereals appeal to consumers? The researcher asked 120 people to take part in a sensory panel to evaluate her four formulations - both unflavored and cinnamon-flavored cereals served with and without skim milk. A second consumer evaluation pitted Lee's cereals against five cereals that are already commercially available and marketed for their healthful properties.
"We know we need to do some tweaking but, even at this stage, one of our formulations did better than a product that's already on store shelves. We're still experimenting with different flavors and sweeteners, but I'm confident that soy-based, high-protein cereals can not only optimize nutrition, they can also taste good," she said.
Lee said that her formulations were taste-tested as stand-alone cereals but could also be used as supplements to boost the protein and fiber content of other cereals.
"Because most Americans eat cereal for breakfast, we thought it made sense to boost the protein content of the food they're used to eating," said Lee.
Besides, a breakfast food that is high in soy protein has advantages over other protein sources (think bacon and eggs) that are high in fat and cholesterol, she said.
Lee collaborated on the project with her husband, U of I food processing engineer Youngsoo Lee, and graduate student Katherine Yeu, who has worked in Kellogg's sensory testing department and has now taken a position at Kerry Ingredients. Yeu's graduate work was supported by a Becker Fellowship, given to students who want to work in product development and food engineering.
The study was published in a recent issue of the Journal of Food Science.
The Metabolic Signaling Pathway Responsible For Dyslipidemia Identified By Researchers
Researchers from Boston University School of Medicine (BUSM), including Yu Li, PhD, and other colleagues, have demonstrated that a nutrient sensing pathway is involved in the disruption of cellular lipid homeostasis in obese and insulin resistant mice fed a diet high in fat and sucrose. This nutrient sensing pathway, which is described in the current on-line issue of Cell Metabolism, may also have implications for the health benefits of polyphenols containing foods against fatty liver, hyperlipidemia, and atherosclerosis associated with obesity and type 2 diabetes.
Although it is well known that elevated serum cholesterol and triglyceride levels and fatty liver are caused by increased hepatic lipid synthesis and/or decreased lipid clearance in patients with obesity and diabetes, the underlying mechanistic pathways of these changes remains unknown.
The master regulators of lipid metabolism that were studied are called AMPK and SREBP. The researchers used a molecular biology approach, cell culture system and animal models to indicate that dysregulation of AMPK, an energy sensor, and SREBP, a protein that is important regulator for lipid biosynthesis, are affected in obesity. Mice fed a diet with high fat and high sucrose became obese and had insulin resistance and elevated circulating levels of cholesterol and triglyceride which led to accelerated atherosclerosis. In contrast, dietary supplementation with S17834, a polyphenol, significantly improved the metabolic disorder, lipid levels and atherosclerosis.
"Our findings suggest that AMPK suppression and SREBP activation are a root cause of fatty liver and hyperlipidemia in type 2 diabetes and its associated vascular complications such as atherosclerosis," said senior author Mengwei Zang, MD, PhD, an assistant professor of medicine at BUSM.
According to the researchers the potential health benefits of polyphenols have been gaining increasing interest. "In our studies, AMPK is potently and persistently activated by polyphenols including the natural compound resveratrol, which is present in red wine, grapes and green tea, as well as the synthetic polyphenol S17834, which is a drug candidate provided by Servier Pharmaceutical Company," explained Zang. "AMPK directly suppresses SREBP via its phosphorylation, inhibiting the activity of its target lipogenic enzymes in the liver, and accounting for the protective effects of the polyphenols on fatty liver, blood lipids and diabetic atherosclerosis," she added.
The researchers believe these findings may lead to the development of new drugs that could stop or slow diabetes progression or improve current treatments.
Although it is well known that elevated serum cholesterol and triglyceride levels and fatty liver are caused by increased hepatic lipid synthesis and/or decreased lipid clearance in patients with obesity and diabetes, the underlying mechanistic pathways of these changes remains unknown.
The master regulators of lipid metabolism that were studied are called AMPK and SREBP. The researchers used a molecular biology approach, cell culture system and animal models to indicate that dysregulation of AMPK, an energy sensor, and SREBP, a protein that is important regulator for lipid biosynthesis, are affected in obesity. Mice fed a diet with high fat and high sucrose became obese and had insulin resistance and elevated circulating levels of cholesterol and triglyceride which led to accelerated atherosclerosis. In contrast, dietary supplementation with S17834, a polyphenol, significantly improved the metabolic disorder, lipid levels and atherosclerosis.
"Our findings suggest that AMPK suppression and SREBP activation are a root cause of fatty liver and hyperlipidemia in type 2 diabetes and its associated vascular complications such as atherosclerosis," said senior author Mengwei Zang, MD, PhD, an assistant professor of medicine at BUSM.
According to the researchers the potential health benefits of polyphenols have been gaining increasing interest. "In our studies, AMPK is potently and persistently activated by polyphenols including the natural compound resveratrol, which is present in red wine, grapes and green tea, as well as the synthetic polyphenol S17834, which is a drug candidate provided by Servier Pharmaceutical Company," explained Zang. "AMPK directly suppresses SREBP via its phosphorylation, inhibiting the activity of its target lipogenic enzymes in the liver, and accounting for the protective effects of the polyphenols on fatty liver, blood lipids and diabetic atherosclerosis," she added.
The researchers believe these findings may lead to the development of new drugs that could stop or slow diabetes progression or improve current treatments.
The Immune System's Role In Bone Loss Uncovered By UCLA Scientists
Got high cholesterol? You might want to consider a bone density test.
A new UCLA study sheds light on the link between high cholesterol and osteoporosis and identifies a new way that the body's immune cells play a role in bone loss.
Published Aug. 20 in the journal Clinical Immunology, the research could lead to new immune-based approaches for treating osteoporosis. Affecting 10 million Americans, the disease causes fragile bones and increases the risk of fractures, resulting in lost independence and mobility.
Scientists have long recognized the relationship between high cholesterol and osteoporosis, but pinpointing the exact mechanism connecting the two has proved elusive.
"We've known that osteoporosis patients have higher cholesterol levels, more severe clogging of the heart arteries and increased risk of stroke. We also knew that drugs that lower cholesterol reduce bone fractures, too," explained Rita Effros, professor of pathology at the David Geffen School of Medicine at UCLA. "What we didn't understand was why."
Effros suspected a clue to the mystery involved oxidation -- cell and tissue damage resulting from exposure of the fatty acids in cholesterol to molecules known as free radicals.
In the study, UCLA researchers focused on low-density lipoprotein (LDL), the so-called "bad" cholesterol. They examined how high levels of oxidized LDL affect bone and whether a type of immune cell called a T cell plays a role in the process.
Using blood samples from healthy human volunteers, the team isolated the participants' T cells and cultured them in a dish.
Half of the T cells were combined with normal LDL - the rest was combined with oxidized LDL. The scientists stimulated half of the T cells to mimic an immune response and left the other half alone.
"Lo and behold, both the resting and the activated T cells started churning out a chemical that stimulates cells whose sole purpose is to destroy bone," said Effros. Called RANKL, the chemical is involved in immune response and bone physiology.
To investigate further how the immune system participates in bone loss, the scientists repeated the experiment in a mouse model.
Half the animals were fed a high-fat diet starting at one month of age, while the control group ate a normal diet. At 11 months, the mice on the high-fat diet showed elevated cholesterol and thinner bones.
When Effros and her colleagues tested the T cells of the mice on the high-fat diet, they discovered that the cells acted differently than those of the mice on the normal diet.
The T cells switched on the gene that produces RANKL. The chemical also appeared in the animals' bloodstream, suggesting that the cellular activity contributed to their bone loss.
"It's normal for our T cells to produce small amounts of RANKL during an immune response," explained Effros. "But when RANKL is manufactured for long periods or at the wrong time, it results in excessive bone damage."
"That's exactly what happened to the mice on the high-fat diet," she said. "The animals' high cholesterol increased their levels of oxidized LDL, which told the T cells to keep generating RANKL. This discovery revealed to us how the immune system might play an entirely new role in bone loss."
The next step will be exploring methods to control T cell response to oxidized LDL in an effort to develop immune-based approaches to prevent or slow bone loss, Effros says.
The study was funded by the National Institute on Aging, the National Institute of Allergy and Infectious Diseases and the National Heart, Lung and Blood Institute.
Effros' coauthors were Lucia Graham, Farhad Parhami, Yin Tintut, Christina Kitchen and Linda Demer, all of UCLA.
A new UCLA study sheds light on the link between high cholesterol and osteoporosis and identifies a new way that the body's immune cells play a role in bone loss.
Published Aug. 20 in the journal Clinical Immunology, the research could lead to new immune-based approaches for treating osteoporosis. Affecting 10 million Americans, the disease causes fragile bones and increases the risk of fractures, resulting in lost independence and mobility.
Scientists have long recognized the relationship between high cholesterol and osteoporosis, but pinpointing the exact mechanism connecting the two has proved elusive.
"We've known that osteoporosis patients have higher cholesterol levels, more severe clogging of the heart arteries and increased risk of stroke. We also knew that drugs that lower cholesterol reduce bone fractures, too," explained Rita Effros, professor of pathology at the David Geffen School of Medicine at UCLA. "What we didn't understand was why."
Effros suspected a clue to the mystery involved oxidation -- cell and tissue damage resulting from exposure of the fatty acids in cholesterol to molecules known as free radicals.
In the study, UCLA researchers focused on low-density lipoprotein (LDL), the so-called "bad" cholesterol. They examined how high levels of oxidized LDL affect bone and whether a type of immune cell called a T cell plays a role in the process.
Using blood samples from healthy human volunteers, the team isolated the participants' T cells and cultured them in a dish.
Half of the T cells were combined with normal LDL - the rest was combined with oxidized LDL. The scientists stimulated half of the T cells to mimic an immune response and left the other half alone.
"Lo and behold, both the resting and the activated T cells started churning out a chemical that stimulates cells whose sole purpose is to destroy bone," said Effros. Called RANKL, the chemical is involved in immune response and bone physiology.
To investigate further how the immune system participates in bone loss, the scientists repeated the experiment in a mouse model.
Half the animals were fed a high-fat diet starting at one month of age, while the control group ate a normal diet. At 11 months, the mice on the high-fat diet showed elevated cholesterol and thinner bones.
When Effros and her colleagues tested the T cells of the mice on the high-fat diet, they discovered that the cells acted differently than those of the mice on the normal diet.
The T cells switched on the gene that produces RANKL. The chemical also appeared in the animals' bloodstream, suggesting that the cellular activity contributed to their bone loss.
"It's normal for our T cells to produce small amounts of RANKL during an immune response," explained Effros. "But when RANKL is manufactured for long periods or at the wrong time, it results in excessive bone damage."
"That's exactly what happened to the mice on the high-fat diet," she said. "The animals' high cholesterol increased their levels of oxidized LDL, which told the T cells to keep generating RANKL. This discovery revealed to us how the immune system might play an entirely new role in bone loss."
The next step will be exploring methods to control T cell response to oxidized LDL in an effort to develop immune-based approaches to prevent or slow bone loss, Effros says.
The study was funded by the National Institute on Aging, the National Institute of Allergy and Infectious Diseases and the National Heart, Lung and Blood Institute.
Effros' coauthors were Lucia Graham, Farhad Parhami, Yin Tintut, Christina Kitchen and Linda Demer, all of UCLA.
End To Fat-Free Diets A Possibility
A new study in mice raises a tantalizing possibility - that humans may one day be able to eat any kind of fat they want without raising their risk of heart disease.
"We deleted an enzyme in mice and they could eat any type of fat and not get heart disease," said Lawrence Rudel, Ph.D., a professor of comparative medicine. "If you're a mouse, it's great. Of course, we don't know yet if it will be the same in humans."
Rudel's findings are reported online by Arteriosclerosis, Thrombosis and Vascular Biology and will appear in a future print issue.
The study involved deleting a gene in the mice that causes production of ACAT2, an enzyme that alters the molecular structure of cholesterol so that it can be transported to the body's cells.
"Regardless of the type of fatty acid in the diet, even trans fat, no atherosclerosis occurs if the ACAT2 enzyme isn't present," said Rudel. "Our research in animals tells us that ACAT2 is a potential treatment target to protect people against heart disease."
Groups of female mice with and without the ACAT2 gene were fed six different diets enriched with one of these types of fat: fish oil, flax seed oil, polyunsaturated fat from vegetable oil, saturated fat, trans-monounsaturated fat and cis-monounsaturated fat, such as in olive oil.
Fish oil, flax seed oil and polyunsaturated fats are considered "healthy" fats. Saturated fat - found in meats, milk and cheeses, coconut oil, palm oil and palm kernel oil - is considered a main cause of high cholesterol.
There are two types of monounsaturated fatty acids, "cis" and "trans," which are named according to their shapes. Trans-fatty acids are formed when vegetable oil is treated to make it less likely to go rancid and are found in many fried foods, baked goods and potato chips. Cis monounsaturated fat is naturally occurring and is particularly high in canola and olive oil. Recently, the U.S. Food and Drug Administration has required that levels of trans-fats be listed on food labels.
After 20 weeks on the diets, the mice that had the active ACAT2 enzyme and were fed saturated fat and both types of monounsaturated fat had higher levels of cholesterol and more atherosclerosis than the mice that were fed polyunsaturated fats. All of the mice without the ACAT2 enzyme were protected against atherosclerosis, which is the buildup of fatty deposits in the blood vessels that can lead to heart attacks and strokes.
"Regardless of the diet fed, the mice without ACAT2 were protected from atherosclerosis," said Rudel.
Eliminating ACAT2 did not interfere with the normal processing of cholesterol. ACAT2 is one of three enzymes that can change cholesterol into a form that can be more easily carried in blood. Studies in both mice and monkeys show that when cholesterol is altered by ACAT2, it is more likely to build up in blood vessel walls and cause atherosclerosis.
Rudel hopes to get funding to repeat the study in monkeys.
"If it works in monkeys, it would be proof of concept that it could work in humans," he said.
He also hopes the research will lead to a drug that can inhibit the enzyme's actions in humans. Currently, there is a compound that can block ACAT2, but it must be injected so isn't quite as practical as a drug. He is collaborating with a pharmaceutical company that is working to find a compound that could be taken orally.
Scientists already know that humans produce ACAT2 in the liver and that women have lower levels than men. Research has shown that estrogen can lower ACAT2 production, which may partly explain why women are less likely than men to get heart disease during their estrogen-producing years.
"All of these findings tell us that a potential treatment for protecting against heart disease is a compound that decreases ACAT2 activity," said Rudel.
The research was funded by a grant from the National Heart Lung and Blood Institute. Co-researchers were Thomas Bell, Ph.D., who worked on the the project for his doctoral degree, Kathryn Kelley, B.S., Martha Wilson, Ph.D., and Janet Sawyer, M.S., all with Wake Forest.
Contact: Shannon Koontz
About Wake Forest University Baptist Medical Center: Wake Forest Baptist 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 1,282 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.
Contact: Karen Richardson
Wake Forest University Baptist Medical Center
"We deleted an enzyme in mice and they could eat any type of fat and not get heart disease," said Lawrence Rudel, Ph.D., a professor of comparative medicine. "If you're a mouse, it's great. Of course, we don't know yet if it will be the same in humans."
Rudel's findings are reported online by Arteriosclerosis, Thrombosis and Vascular Biology and will appear in a future print issue.
The study involved deleting a gene in the mice that causes production of ACAT2, an enzyme that alters the molecular structure of cholesterol so that it can be transported to the body's cells.
"Regardless of the type of fatty acid in the diet, even trans fat, no atherosclerosis occurs if the ACAT2 enzyme isn't present," said Rudel. "Our research in animals tells us that ACAT2 is a potential treatment target to protect people against heart disease."
Groups of female mice with and without the ACAT2 gene were fed six different diets enriched with one of these types of fat: fish oil, flax seed oil, polyunsaturated fat from vegetable oil, saturated fat, trans-monounsaturated fat and cis-monounsaturated fat, such as in olive oil.
Fish oil, flax seed oil and polyunsaturated fats are considered "healthy" fats. Saturated fat - found in meats, milk and cheeses, coconut oil, palm oil and palm kernel oil - is considered a main cause of high cholesterol.
There are two types of monounsaturated fatty acids, "cis" and "trans," which are named according to their shapes. Trans-fatty acids are formed when vegetable oil is treated to make it less likely to go rancid and are found in many fried foods, baked goods and potato chips. Cis monounsaturated fat is naturally occurring and is particularly high in canola and olive oil. Recently, the U.S. Food and Drug Administration has required that levels of trans-fats be listed on food labels.
After 20 weeks on the diets, the mice that had the active ACAT2 enzyme and were fed saturated fat and both types of monounsaturated fat had higher levels of cholesterol and more atherosclerosis than the mice that were fed polyunsaturated fats. All of the mice without the ACAT2 enzyme were protected against atherosclerosis, which is the buildup of fatty deposits in the blood vessels that can lead to heart attacks and strokes.
"Regardless of the diet fed, the mice without ACAT2 were protected from atherosclerosis," said Rudel.
Eliminating ACAT2 did not interfere with the normal processing of cholesterol. ACAT2 is one of three enzymes that can change cholesterol into a form that can be more easily carried in blood. Studies in both mice and monkeys show that when cholesterol is altered by ACAT2, it is more likely to build up in blood vessel walls and cause atherosclerosis.
Rudel hopes to get funding to repeat the study in monkeys.
"If it works in monkeys, it would be proof of concept that it could work in humans," he said.
He also hopes the research will lead to a drug that can inhibit the enzyme's actions in humans. Currently, there is a compound that can block ACAT2, but it must be injected so isn't quite as practical as a drug. He is collaborating with a pharmaceutical company that is working to find a compound that could be taken orally.
Scientists already know that humans produce ACAT2 in the liver and that women have lower levels than men. Research has shown that estrogen can lower ACAT2 production, which may partly explain why women are less likely than men to get heart disease during their estrogen-producing years.
"All of these findings tell us that a potential treatment for protecting against heart disease is a compound that decreases ACAT2 activity," said Rudel.
The research was funded by a grant from the National Heart Lung and Blood Institute. Co-researchers were Thomas Bell, Ph.D., who worked on the the project for his doctoral degree, Kathryn Kelley, B.S., Martha Wilson, Ph.D., and Janet Sawyer, M.S., all with Wake Forest.
Contact: Shannon Koontz
About Wake Forest University Baptist Medical Center: Wake Forest Baptist 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 1,282 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.
Contact: Karen Richardson
Wake Forest University Baptist Medical Center
FDA Advisory Panel Recommends Against Approval Of Merck's NDA For Non Prescription MEVACOR® (lovastatin) 20 Mg
Merck & Co., Inc. announced that the U.S. Food and Drug Administration's (FDA) joint panel of the Nonprescription Drugs Advisory Committee (NDAC) and the Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) voted against recommending approval at this time of the over-the-counter (OTC) use of MEVACOR® (lovastatin) 20 mg to help lower LDL cholesterol which may prevent a first heart attack.
"We are disappointed in today's outcome. We felt we presented a compelling case to the committee that non-prescription MEVACOR 20 mg would be a valuable option for motivated consumers who know they have moderately elevated cholesterol and certain risk factors, and are already talking with their healthcare provider," said Edwin L. Hemwall, PhD, vice president, Global OTC Regulatory and Scientific Affairs.
The FDA is not bound by the committee's recommendation, but takes its advice into consideration. The anticipated action date by the FDA is Jan. 26, 2008.
About Prescription MEVACOR
MEVACOR is a prescription medicine that is approved in the U.S. for the treatment of elevated cholesterol levels that lifestyle changes alone cannot control and to reduce the risk of a first heart attack, unstable angina and coronary revascularization procedures in healthy men and women with average or moderately elevated cholesterol levels.
Important Safety Information
According to the prescribing information, MEVACOR should not be used by anyone allergic to any of its components, people with liver disease, or by women who are pregnant, breast-feeding, or likely to become pregnant. It is recommended that liver function tests be performed in all patients prior to daily use of MEVACOR 40 mg or more.
Muscle pain or weakness in patients taking prescription MEVACOR should be reported to a doctor because these could be signs of a serious side effect. Patients should tell their doctors about other medications they are taking in order to avoid possible drug interactions.
The most common adverse events reported with MEVACOR 20 mg taken once daily were diarrhea, flatulence, headache and myalgia.
Further information about MEVACOR is available on merck.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit merck.
Merck forward-looking statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.
MEVACOR® (lovastatin) is a registered trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA
View drug information on Mevacor.
"We are disappointed in today's outcome. We felt we presented a compelling case to the committee that non-prescription MEVACOR 20 mg would be a valuable option for motivated consumers who know they have moderately elevated cholesterol and certain risk factors, and are already talking with their healthcare provider," said Edwin L. Hemwall, PhD, vice president, Global OTC Regulatory and Scientific Affairs.
The FDA is not bound by the committee's recommendation, but takes its advice into consideration. The anticipated action date by the FDA is Jan. 26, 2008.
About Prescription MEVACOR
MEVACOR is a prescription medicine that is approved in the U.S. for the treatment of elevated cholesterol levels that lifestyle changes alone cannot control and to reduce the risk of a first heart attack, unstable angina and coronary revascularization procedures in healthy men and women with average or moderately elevated cholesterol levels.
Important Safety Information
According to the prescribing information, MEVACOR should not be used by anyone allergic to any of its components, people with liver disease, or by women who are pregnant, breast-feeding, or likely to become pregnant. It is recommended that liver function tests be performed in all patients prior to daily use of MEVACOR 40 mg or more.
Muscle pain or weakness in patients taking prescription MEVACOR should be reported to a doctor because these could be signs of a serious side effect. Patients should tell their doctors about other medications they are taking in order to avoid possible drug interactions.
The most common adverse events reported with MEVACOR 20 mg taken once daily were diarrhea, flatulence, headache and myalgia.
Further information about MEVACOR is available on merck.
About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit merck.
Merck forward-looking statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.
Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.
MEVACOR® (lovastatin) is a registered trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA
View drug information on Mevacor.
For Children With Neurofibromatosis Type 1, Statin Does Not Improve Cognitive Function
For children with neurofibromatosis type 1 (NF1), a genetic disorder
that often leads to learning disability, cognitive function is not
improved by the statin simvastatin, according to an article released on
July 15 in JAMA.
NF1 is characterized by the development of tumors in Schwann cells in
the nervous system. It is genetically transmitted with an autosomal
dominant pattern, which means that it is not linked to sex chromosome,
but only one parent needs to contribute the variant gene for a child to
develop the disorder.
These tumors can be harmless but can also compress nerve cells thus
causing damage. Clinically, the disease symptoms include skin
disorders, problems with small and large movement skills, and cognitive
disabilities. Some examples of this cognitive disability include loss
of visual-spatial skills, nonverbal long-term memory and attention
span.
Statins are a class of drugs presently used in adults to lower
cholesterol. Previously, some studies in mice have indicated that
therapy with statins could improve some cognitive deficits. To
investigate the potential effects of a specific statin, simvastatin, on
the cognitive function of children with neurofibromatosis type 1,
Lianne C. Krab, M.Sc., of Erasmus MC University Medical Center, Sophia
Children's Hospital, Rotterdam, The Netherlands, and colleagues
performed a randomized trial. A total 62 children received simvastatin
or a placebo treatment once daily for 12 weeks.
After the period of treatment, several cognitive tests were performed
to address nonverbal long-term memory, attention, and performance on
the prism adaptation task, which measures the adaptation of hand
movements in response to distortion of a prism glass. No advantage was
shown for the test group over the placebo in this respect. Secondary
outcomes were evaluated as well, including object assembly scores,
which showed some improvement in the test population. Other measures,
such as attention fluctuation and motor-visual integration showed no
improvement.
The authors conclude that simvastatin has no effect on the improvement
of cognitive problems developed in victims of neurofibromatosis type 1.
"The negative outcome of this trial suggests that simvastatin should
not
be prescribed to ameliorate the cognitive deficits associated with NF1.
Further studies to evaluate a longer treatment period and whether the
object assembly finding is spurious may be warranted," they conclude.
Effect of Simvastatin on Cognitive Functioning in Children
With Neurofibromatosis Type 1: A Randomized Controlled Trial
Lianne C. Krab; Arja de Goede-Bolder; Femke K. Aarsen; Saskia M. F.
Pluijm; Marlies J. Bouman; Jos N. van der Geest; Maarten Lequin;
Coriene E. Catsman; Willem Frans M. Arts; Steven A. Kushner; Alcino J.
Silva; Chris I. de Zeeuw; Henri?«tte A. Moll; Ype Elgersma
JAMA. 2008;300(3):287-294.
Click Here For Journal
Written by Anna Sophia McKenney
that often leads to learning disability, cognitive function is not
improved by the statin simvastatin, according to an article released on
July 15 in JAMA.
NF1 is characterized by the development of tumors in Schwann cells in
the nervous system. It is genetically transmitted with an autosomal
dominant pattern, which means that it is not linked to sex chromosome,
but only one parent needs to contribute the variant gene for a child to
develop the disorder.
These tumors can be harmless but can also compress nerve cells thus
causing damage. Clinically, the disease symptoms include skin
disorders, problems with small and large movement skills, and cognitive
disabilities. Some examples of this cognitive disability include loss
of visual-spatial skills, nonverbal long-term memory and attention
span.
Statins are a class of drugs presently used in adults to lower
cholesterol. Previously, some studies in mice have indicated that
therapy with statins could improve some cognitive deficits. To
investigate the potential effects of a specific statin, simvastatin, on
the cognitive function of children with neurofibromatosis type 1,
Lianne C. Krab, M.Sc., of Erasmus MC University Medical Center, Sophia
Children's Hospital, Rotterdam, The Netherlands, and colleagues
performed a randomized trial. A total 62 children received simvastatin
or a placebo treatment once daily for 12 weeks.
After the period of treatment, several cognitive tests were performed
to address nonverbal long-term memory, attention, and performance on
the prism adaptation task, which measures the adaptation of hand
movements in response to distortion of a prism glass. No advantage was
shown for the test group over the placebo in this respect. Secondary
outcomes were evaluated as well, including object assembly scores,
which showed some improvement in the test population. Other measures,
such as attention fluctuation and motor-visual integration showed no
improvement.
The authors conclude that simvastatin has no effect on the improvement
of cognitive problems developed in victims of neurofibromatosis type 1.
"The negative outcome of this trial suggests that simvastatin should
not
be prescribed to ameliorate the cognitive deficits associated with NF1.
Further studies to evaluate a longer treatment period and whether the
object assembly finding is spurious may be warranted," they conclude.
Effect of Simvastatin on Cognitive Functioning in Children
With Neurofibromatosis Type 1: A Randomized Controlled Trial
Lianne C. Krab; Arja de Goede-Bolder; Femke K. Aarsen; Saskia M. F.
Pluijm; Marlies J. Bouman; Jos N. van der Geest; Maarten Lequin;
Coriene E. Catsman; Willem Frans M. Arts; Steven A. Kushner; Alcino J.
Silva; Chris I. de Zeeuw; Henri?«tte A. Moll; Ype Elgersma
JAMA. 2008;300(3):287-294.
Click Here For Journal
Written by Anna Sophia McKenney
Lots Of Coffee Not Linked To Heart Risks, New Study
According to a new study on more than 120,000 people over a period of twenty years, there is no link between heavy coffee drinking and a raised risk of coronary heart disease. Heavy coffee drinking means you consume six or more cups per day. The study found that the heart risks for heavy coffee drinkers is no different from those who only have one cup or less per month.
The researchers said this study does not apply to the unfiltered 'expresso' type coffee.
The researchers pointed out that there may be some groups of people who are still susceptible to heart risk from drinking too much coffee. Some people carry a gene that makes it more difficult for the body to metabolise caffeine.
You can read about this study in the journal Circulation.
Health experts warned that there are things you can add to your cup of coffee which may alter your chances of developing certain diseases. If you drink eight cups a day, all of them super-sweet with four spoons of sugar each, you will probably put on a load of weight and over the long-term have a raised risk of developing diabetes type 2, as well as some other diseases.
The scientists in this study had to factor out many things which are associated with heavy coffee drinking. A much higher percentage of heavy coffee drinkers are smokers and/or drinkers of alcohol. A smaller percentage of heavy coffee drinkers do regular exercise, when compared to non-heavy coffee drinkers.
The study also found that women who regularly drink decaffeinated coffee have the same heart risk as those who don't.
Coffee drinkers, regardless of whether they consume caffeinated or decaf, have similar levels of good and bad cholesterol.
Pregnant women should limit their caffeine intake. The developing baby is sensitive to it.
The study included 44,005 men and 84,488 women. None of them had a history of cardiovascular disease or cancer at the start of the study.
The men were monitored from 1986. The women were first monitored in 1980. Both men and women were assessed every two to four years, until 2000.
The coffee drinkers were broken down into the following categories:
-- Less than 1 cup per month
-- 1 cup per month to 4 cups per week
-- 5-7 cups per week
-- 2-3 cups per day
-- 4-5 cups per day
-- 6 or more cups per day
The researchers concluded that risk of Coronary Heart Disease was the same for all groups.
They also found that people with diabetes 2 who drank coffee regularly had the same coronary heart disease risk as people with diabetes 2 who did not drink coffee regularly.
The authors of this study were:
Esther Lopez-Garcia DrPH, Rob M. van Dam PhD, Walter C. Willett MD, DrPH, Eric B. Rimm ScD, JoAnn E. Manson MD, DrPH, Meir J. Stampfer MD, DrPH, Kathryn M. Rexrode MD, MPH, and Frank B. Hu MD, PhD*
The study was carried out at:
- The Departments of Nutrition and Epidemiology, Harvard School of Public Health
- The Channing Laboratory and Division of Preventive Medicine, Harvard Medical School, Boston, Mass.
The researchers said this study does not apply to the unfiltered 'expresso' type coffee.
The researchers pointed out that there may be some groups of people who are still susceptible to heart risk from drinking too much coffee. Some people carry a gene that makes it more difficult for the body to metabolise caffeine.
You can read about this study in the journal Circulation.
Health experts warned that there are things you can add to your cup of coffee which may alter your chances of developing certain diseases. If you drink eight cups a day, all of them super-sweet with four spoons of sugar each, you will probably put on a load of weight and over the long-term have a raised risk of developing diabetes type 2, as well as some other diseases.
The scientists in this study had to factor out many things which are associated with heavy coffee drinking. A much higher percentage of heavy coffee drinkers are smokers and/or drinkers of alcohol. A smaller percentage of heavy coffee drinkers do regular exercise, when compared to non-heavy coffee drinkers.
The study also found that women who regularly drink decaffeinated coffee have the same heart risk as those who don't.
Coffee drinkers, regardless of whether they consume caffeinated or decaf, have similar levels of good and bad cholesterol.
Pregnant women should limit their caffeine intake. The developing baby is sensitive to it.
The study included 44,005 men and 84,488 women. None of them had a history of cardiovascular disease or cancer at the start of the study.
The men were monitored from 1986. The women were first monitored in 1980. Both men and women were assessed every two to four years, until 2000.
The coffee drinkers were broken down into the following categories:
-- Less than 1 cup per month
-- 1 cup per month to 4 cups per week
-- 5-7 cups per week
-- 2-3 cups per day
-- 4-5 cups per day
-- 6 or more cups per day
The researchers concluded that risk of Coronary Heart Disease was the same for all groups.
They also found that people with diabetes 2 who drank coffee regularly had the same coronary heart disease risk as people with diabetes 2 who did not drink coffee regularly.
The authors of this study were:
Esther Lopez-Garcia DrPH, Rob M. van Dam PhD, Walter C. Willett MD, DrPH, Eric B. Rimm ScD, JoAnn E. Manson MD, DrPH, Meir J. Stampfer MD, DrPH, Kathryn M. Rexrode MD, MPH, and Frank B. Hu MD, PhD*
The study was carried out at:
- The Departments of Nutrition and Epidemiology, Harvard School of Public Health
- The Channing Laboratory and Division of Preventive Medicine, Harvard Medical School, Boston, Mass.
Bayer HealthCare Announces First Fully-automated High Sensitivity And High Precision Troponin Assays
Leverkusen, Germany - Bayer HealthCare, Diagnostics Division, a member of the Bayer Group (NYSE: BAY), announced today that they have received FDA clearance on two new troponin-I assays (TnI-UltraTM). The TnI-Ultra assays are the first fully-automated troponin assays meeting the European Society of Cardiology/American College of Cardiology recommendation of a < 10% level of imprecision at the 99th percentile of a healthy population. Meeting the ESC/ACC criteria is a key attribute in the definition of a high sensitivity troponin test. The TnI-Ultra assay has been cleared on Bayer's ADVIA IMS® 800i and ADVIA Centaur®Immunoassay System. These assays aid physicians in the diagnosis of myocardial infarction (MI) and the assessment of risk in patients with acute coronary syndrome.
The ADVIA IMS and the ADVIA Centaur Immunoassay TnI-Ultra assays have the same 99 percentile value and show the equivalent precision at this very low level. This strong concordance between assays allows for equivalent results in core and satellite laboratory situations. The high degree of precision seen with the TnI-Ultra assays is expected to show an increased level of accuracy, contributing to improved patient care in those suspected of MI.
Bayer has a strong heritage of TnI "firsts" as they were also the first to receive FDA clearance of their cTnI assay in the risk stratification of patients with non-ST segment elevation acute coronary syndromes.
"The addition of TnI-Ultra to the cardiovascular menu meets customers' needs for a troponin assay that meets ESC/ACC guidelines and strengthens Bayer's already impressive portfolio - which includes CK-MB, myoglobin, homocysteine, and BNP - allowing for workstation consolidation and rapid turnaround of results on highly productive Immunoassay systems," said Tom Warekois, Senior Vice President of Global Strategic Marketing for Bayer HealthCare's Diagnostics Division.
Prevalence of Heart Attacks
Heart attacks are a serious, sudden heart condition usually characterized by varying degrees of chest pain or discomfort, weakness, sweating, nausea, vomiting, and arrhythmias, sometimes causing loss of consciousness1. Heart attack occurrences are on the rise and have become a growing concern worldwide1. According to the American Heart Association, an estimated 700,000 Americans will have a new heart attack and an estimated 500,000 will have a recurrent attack annually. It is estimated that an additional 175,000 silent first heart attacks occur each year1.
About Bayer HealthCare AG
Bayer HealthCare AG, a subsidiary of Bayer AG, is one of the world's leading, innovative companies in the health care and medical products industry. In 2004, the Bayer HealthCare subgroup generated sales amounting to some 8.5 billion Euro.
The company combines the global activities of the divisions Animal Health, Consumer Care, Diabetes Care, Diagnostics and Pharmaceuticals. Since January 1, 2006 the new Pharmaceutical Division consists of the former Biological Products and Pharmaceutical Division and now comprises three business units: Hematology/Cardiology; Oncology and Primary Care.
Bayer HealthCare employed 35,300 people worldwide in 2004.
Bayer HealthCare's aim is to discover and manufacture innovative products that will improve human and animal health worldwide. The products enhance well-being and quality of life by diagnosing, preventing and treating disease.
We are only one click away - our press service online:
viva.vita.bayerhealthcare
Forward-Looking Statements
This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our public reports filed with the Frankfurt Stock Exchange and with the U.S. Securities and Exchange Commission (including our Form 20-F).The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
1 - American Heart Association. Heart Disease and Stroke Statistics - 2006 Update. Dallas, Tex.: American Heart Association; 2004.
The ADVIA IMS and the ADVIA Centaur Immunoassay TnI-Ultra assays have the same 99 percentile value and show the equivalent precision at this very low level. This strong concordance between assays allows for equivalent results in core and satellite laboratory situations. The high degree of precision seen with the TnI-Ultra assays is expected to show an increased level of accuracy, contributing to improved patient care in those suspected of MI.
Bayer has a strong heritage of TnI "firsts" as they were also the first to receive FDA clearance of their cTnI assay in the risk stratification of patients with non-ST segment elevation acute coronary syndromes.
"The addition of TnI-Ultra to the cardiovascular menu meets customers' needs for a troponin assay that meets ESC/ACC guidelines and strengthens Bayer's already impressive portfolio - which includes CK-MB, myoglobin, homocysteine, and BNP - allowing for workstation consolidation and rapid turnaround of results on highly productive Immunoassay systems," said Tom Warekois, Senior Vice President of Global Strategic Marketing for Bayer HealthCare's Diagnostics Division.
Prevalence of Heart Attacks
Heart attacks are a serious, sudden heart condition usually characterized by varying degrees of chest pain or discomfort, weakness, sweating, nausea, vomiting, and arrhythmias, sometimes causing loss of consciousness1. Heart attack occurrences are on the rise and have become a growing concern worldwide1. According to the American Heart Association, an estimated 700,000 Americans will have a new heart attack and an estimated 500,000 will have a recurrent attack annually. It is estimated that an additional 175,000 silent first heart attacks occur each year1.
About Bayer HealthCare AG
Bayer HealthCare AG, a subsidiary of Bayer AG, is one of the world's leading, innovative companies in the health care and medical products industry. In 2004, the Bayer HealthCare subgroup generated sales amounting to some 8.5 billion Euro.
The company combines the global activities of the divisions Animal Health, Consumer Care, Diabetes Care, Diagnostics and Pharmaceuticals. Since January 1, 2006 the new Pharmaceutical Division consists of the former Biological Products and Pharmaceutical Division and now comprises three business units: Hematology/Cardiology; Oncology and Primary Care.
Bayer HealthCare employed 35,300 people worldwide in 2004.
Bayer HealthCare's aim is to discover and manufacture innovative products that will improve human and animal health worldwide. The products enhance well-being and quality of life by diagnosing, preventing and treating disease.
We are only one click away - our press service online:
viva.vita.bayerhealthcare
Forward-Looking Statements
This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in our public reports filed with the Frankfurt Stock Exchange and with the U.S. Securities and Exchange Commission (including our Form 20-F).The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
1 - American Heart Association. Heart Disease and Stroke Statistics - 2006 Update. Dallas, Tex.: American Heart Association; 2004.
Health Canada Is advising Canadians about a possible association between Crestor(reg) and rhabdomyolysis
OTTAWA -Health Canada is advising Canadians about a possible association between the cholesterol lowering drug Crestor(reg), and a serious condition called rhabdomyolysis.
Rhabdomyolysis is a condition that results in muscle breakdown and the release of muscle cell contents into the bloodstream. Symptoms of rhabdomyolysis include muscle pain, weakness, tenderness, fever, dark urine, nausea, and vomiting. In severe cases, rhabdomyolysis can result in kidney failure and can be life-threatening.
Rhabdomyolysis has also been reported with other cholesterol lowering drugs in the "statin" family. "Statins" are a specific type of cholesterol lowering medication. Between February 2003 and June 2004 there have been eight cases of rhabdomyolysis reported in Canadian patients taking Crestor(reg).
In five of those cases the patients were taking the maximum recommended dose (40 mg) of the drug, in two cases the patients were taking the lowest recommended starting dosage (10 mg) and in the remaining case, the dosage was not stated. All of the Canadian reported cases were associated with predisposing risk factors, and no deaths have been reported.
There are certain factors that might cause an individual to have a greater risk of developing muscle related problems, including rhabdomyolysis, if they are taking a statin.
These factors include: kidney problems, an underactive thyroid gland, alcohol abuse, a past history of significant muscle pain or significant muscle weakness while on statin therapy, a personal or family history of inherited muscle problems, and Japanese or Chinese ethnicity.
The risk is also increased for patients who may be taking other medications which might interact with statins. Health Canada recommends that all patients taking Crestor(reg) consult with their doctors to determine if any of these factors apply to them.
Because the risk of rhabdomyolysis is increased at higher doses, Health Canada recommends that all patients taking Crestor(reg), or any cholesterol lowering drug, should be on the lowest dose that will meet their treatment goal.
All patients taking Crestor(reg), or any cholesterol lowering drug, are advised to report any unexplained muscle pain, muscle weakness or cramps, or any brown or discoloured urine, to their physician immediately.
This advisory is in addition to a letter issued by the manufacturers of Crestor(reg), following consultation with Health Canada, to health care professionals reminding them of the above mentioned safety concerns.
If you have questions regarding your current prescription, please contact your physician or pharmacist. Any suspected adve
rse drug reactions in patients receiving Crestor(reg) can be reported to:
Canadian Adverse Drug Reaction Monitoring Program (CADRMP)
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0701C
OTTAWA, Ontario, K1A 0K9
Tel: (613) 957-0337 or Fax: (613) 957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Tel: 866 234-2345
Fax: 866 678-6789
hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/adr_guideline_e.html
The Adverse Reaction Reporting Form and the Adverse Reaction Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.
hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/adverse_e.html
hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/adr_guideline_e.html
Media Inquiries:
Jirina Vlk
Health Canada
(613) 957-2988
Public Inquiries:
(613) 957-2991
hc-sc.gc.ca/english/protection/warnings/2004/2004_34.htm
Rhabdomyolysis is a condition that results in muscle breakdown and the release of muscle cell contents into the bloodstream. Symptoms of rhabdomyolysis include muscle pain, weakness, tenderness, fever, dark urine, nausea, and vomiting. In severe cases, rhabdomyolysis can result in kidney failure and can be life-threatening.
Rhabdomyolysis has also been reported with other cholesterol lowering drugs in the "statin" family. "Statins" are a specific type of cholesterol lowering medication. Between February 2003 and June 2004 there have been eight cases of rhabdomyolysis reported in Canadian patients taking Crestor(reg).
In five of those cases the patients were taking the maximum recommended dose (40 mg) of the drug, in two cases the patients were taking the lowest recommended starting dosage (10 mg) and in the remaining case, the dosage was not stated. All of the Canadian reported cases were associated with predisposing risk factors, and no deaths have been reported.
There are certain factors that might cause an individual to have a greater risk of developing muscle related problems, including rhabdomyolysis, if they are taking a statin.
These factors include: kidney problems, an underactive thyroid gland, alcohol abuse, a past history of significant muscle pain or significant muscle weakness while on statin therapy, a personal or family history of inherited muscle problems, and Japanese or Chinese ethnicity.
The risk is also increased for patients who may be taking other medications which might interact with statins. Health Canada recommends that all patients taking Crestor(reg) consult with their doctors to determine if any of these factors apply to them.
Because the risk of rhabdomyolysis is increased at higher doses, Health Canada recommends that all patients taking Crestor(reg), or any cholesterol lowering drug, should be on the lowest dose that will meet their treatment goal.
All patients taking Crestor(reg), or any cholesterol lowering drug, are advised to report any unexplained muscle pain, muscle weakness or cramps, or any brown or discoloured urine, to their physician immediately.
This advisory is in addition to a letter issued by the manufacturers of Crestor(reg), following consultation with Health Canada, to health care professionals reminding them of the above mentioned safety concerns.
If you have questions regarding your current prescription, please contact your physician or pharmacist. Any suspected adve
rse drug reactions in patients receiving Crestor(reg) can be reported to:
Canadian Adverse Drug Reaction Monitoring Program (CADRMP)
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0701C
OTTAWA, Ontario, K1A 0K9
Tel: (613) 957-0337 or Fax: (613) 957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Tel: 866 234-2345
Fax: 866 678-6789
hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/adr_guideline_e.html
The Adverse Reaction Reporting Form and the Adverse Reaction Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.
hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/adverse_e.html
hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/adr_guideline_e.html
Media Inquiries:
Jirina Vlk
Health Canada
(613) 957-2988
Public Inquiries:
(613) 957-2991
hc-sc.gc.ca/english/protection/warnings/2004/2004_34.htm
Low Carb And Mediterranean May Be Effective Alternatives To Low Fat Diets, Study
A new large scale 2 year study by an international team of scientists concluded that Mediterranean and low carbohydrate diets may be just as
safe and effective as standard medically prescribed low fat diets for losing weight and if continued beyond the weight loss target, may confer long
term health benefits. A particularly noteworthy feature of the study is the high proportion of participants who stuck to the diets for the whole 2 years:
85 per cent.
The study was led by researchers from Ben-Gurion University of the Negev (BGU) in Israel and is published in the 17th July issue of the New
England Journal of Medicine, NEJM. Other members of the study team came from Nuclear Research Center in Dimona, Israel, Harvard
University, Boston, US, The University of Leipzig, Germany and the University of Western Ontario, Canada.
The authors wrote that one of the main difficulties of assessing the safety and effectiveness of weight loss diets is that trials usually have a high drop
out rate and don't last long enough.
For this 2 year trial, they intensively monitored 322 moderately obese adults of mean age 52 years, and mean BMI (body mass index) of 31 that had been
randomly assigned to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie. 86
per cent of the participants were men.
The trial was conducted at the Nuclear Research Center in Israel and "involved unparalleled and significant cooperation between staff, participants
and their spouses", said the authors in a press statement.
The workplace cafeterias underwent a sort of "health revolution" to provide the right foods for each of the three diets and to integrate easily with
clinical requirements. For example, dishes were clearly labelled using different colours for each diet, and participants and their spouses had
nutritional counselling and education on how to stick to the diets not only at work but also at home.
The participants also filled in electronic questionnaires developed specifically for the study.
The results showed that:
95.4 per cent of the participants stuck to their diets for at least 1 year and 84.6 per cent for the whole 2 years.
The group on the Mediterranean diet consumed the most dietary fiber and had the highest ratio of monounsaturated to saturated fat
intake.
The low carbohydrate group ate the least carbohydrates and the most fat, protein and cholesterol and had the highest proportion of members with
ketones in their urine.
The average weight loss was: 2.9 kg (6.4 lbs) in the low fat diet group; 4.4 kg (9.7 lbs) in the Mediterranean diet group; and 4.7 kg (10.4 lbs) in the
low carbohydrate group.
The average weight loss was greater among the 272 participants who kept to the diets for the whole 2 years: 3.3 kg (7.3 lbs) in the low fat, 4.6 kg
(10.1 lbs) in the Mediterranean, and 5.5 kg (12.1 lbs) in the low carbohydrate groups.
The relative reduction in total cholesterol to high-density lipoprotein cholesterol (the so called "good" cholesterol) ratio was 20 per cent in the low carbohydrate group and 12 per cent in the low fat group.
Among the 36 participants with diabetes, more favourable levels in fasting plasma glucose and insulin were reached by those on the
Mediterranean diet than those on the low fat diet.
Liver function and inflammatory biomarkers improved in all three diets.
The authors concluded that:
"Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might
inform individualized tailoring of dietary interventions."
Lead author Dr Iris Shai, a researcher at the S. Daniel Abraham International Center for Health and Nutrition in the Department of Epidemiology at
BGU, said that the weight loss achieved by all the diets were "comparable to results from physician-prescribed weight loss medications".
Shai said that "clearly, there is not one diet that is ideal for everyone".
"We believe that this study will open clinical medicine to considering low-carb and Mediterranean diets as safe effective alternatives for patients,
based on personal preference and the medical goals set for such intervention."
"Furthermore, the improvement in levels of some biomarkers continued until the 24-month point, although maximum weight loss was achieved by 6
months. This suggests that healthy diet has beneficial effects beyond weight loss," she added.
The authors acknowledged that one limitation of the study was the low percentage of women (14 per cent).
"Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet."
Shai, Iris, Schwarzfuchs, Dan, Henkin, Yaakov, Shahar, Danit R., Witkow, Shula, Greenberg, Ilana, Golan, Rachel, Fraser, Drora, Bolotin, Arkady,
Vardi, Hilel, Tangi-Rozental, Osnat, Zuk-Ramot, Rachel, Sarusi, Benjamin, Brickner, Dov, Schwartz, Ziva, Sheiner, Einat, Marko, Rachel, Katorza,
Esther, Thiery, Joachim, Fiedler, Georg Martin, Bluher, Matthias, Stumvoll, Michael, Stampfer, Meir J., the Dietary Intervention Randomized Controlled
Trial (DIRECT) Group.
N Engl J Med Volume 359, Number 3, pages 229-241, July 17, 2008.
Click here for article.
Sources: Journal abstract, American Associates, Ben-Gurion University of the Negev press statement.
,
safe and effective as standard medically prescribed low fat diets for losing weight and if continued beyond the weight loss target, may confer long
term health benefits. A particularly noteworthy feature of the study is the high proportion of participants who stuck to the diets for the whole 2 years:
85 per cent.
The study was led by researchers from Ben-Gurion University of the Negev (BGU) in Israel and is published in the 17th July issue of the New
England Journal of Medicine, NEJM. Other members of the study team came from Nuclear Research Center in Dimona, Israel, Harvard
University, Boston, US, The University of Leipzig, Germany and the University of Western Ontario, Canada.
The authors wrote that one of the main difficulties of assessing the safety and effectiveness of weight loss diets is that trials usually have a high drop
out rate and don't last long enough.
For this 2 year trial, they intensively monitored 322 moderately obese adults of mean age 52 years, and mean BMI (body mass index) of 31 that had been
randomly assigned to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie. 86
per cent of the participants were men.
The trial was conducted at the Nuclear Research Center in Israel and "involved unparalleled and significant cooperation between staff, participants
and their spouses", said the authors in a press statement.
The workplace cafeterias underwent a sort of "health revolution" to provide the right foods for each of the three diets and to integrate easily with
clinical requirements. For example, dishes were clearly labelled using different colours for each diet, and participants and their spouses had
nutritional counselling and education on how to stick to the diets not only at work but also at home.
The participants also filled in electronic questionnaires developed specifically for the study.
The results showed that:
95.4 per cent of the participants stuck to their diets for at least 1 year and 84.6 per cent for the whole 2 years.
The group on the Mediterranean diet consumed the most dietary fiber and had the highest ratio of monounsaturated to saturated fat
intake.
The low carbohydrate group ate the least carbohydrates and the most fat, protein and cholesterol and had the highest proportion of members with
ketones in their urine.
The average weight loss was: 2.9 kg (6.4 lbs) in the low fat diet group; 4.4 kg (9.7 lbs) in the Mediterranean diet group; and 4.7 kg (10.4 lbs) in the
low carbohydrate group.
The average weight loss was greater among the 272 participants who kept to the diets for the whole 2 years: 3.3 kg (7.3 lbs) in the low fat, 4.6 kg
(10.1 lbs) in the Mediterranean, and 5.5 kg (12.1 lbs) in the low carbohydrate groups.
The relative reduction in total cholesterol to high-density lipoprotein cholesterol (the so called "good" cholesterol) ratio was 20 per cent in the low carbohydrate group and 12 per cent in the low fat group.
Among the 36 participants with diabetes, more favourable levels in fasting plasma glucose and insulin were reached by those on the
Mediterranean diet than those on the low fat diet.
Liver function and inflammatory biomarkers improved in all three diets.
The authors concluded that:
"Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might
inform individualized tailoring of dietary interventions."
Lead author Dr Iris Shai, a researcher at the S. Daniel Abraham International Center for Health and Nutrition in the Department of Epidemiology at
BGU, said that the weight loss achieved by all the diets were "comparable to results from physician-prescribed weight loss medications".
Shai said that "clearly, there is not one diet that is ideal for everyone".
"We believe that this study will open clinical medicine to considering low-carb and Mediterranean diets as safe effective alternatives for patients,
based on personal preference and the medical goals set for such intervention."
"Furthermore, the improvement in levels of some biomarkers continued until the 24-month point, although maximum weight loss was achieved by 6
months. This suggests that healthy diet has beneficial effects beyond weight loss," she added.
The authors acknowledged that one limitation of the study was the low percentage of women (14 per cent).
"Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet."
Shai, Iris, Schwarzfuchs, Dan, Henkin, Yaakov, Shahar, Danit R., Witkow, Shula, Greenberg, Ilana, Golan, Rachel, Fraser, Drora, Bolotin, Arkady,
Vardi, Hilel, Tangi-Rozental, Osnat, Zuk-Ramot, Rachel, Sarusi, Benjamin, Brickner, Dov, Schwartz, Ziva, Sheiner, Einat, Marko, Rachel, Katorza,
Esther, Thiery, Joachim, Fiedler, Georg Martin, Bluher, Matthias, Stumvoll, Michael, Stampfer, Meir J., the Dietary Intervention Randomized Controlled
Trial (DIRECT) Group.
N Engl J Med Volume 359, Number 3, pages 229-241, July 17, 2008.
Click here for article.
Sources: Journal abstract, American Associates, Ben-Gurion University of the Negev press statement.
,
News From The Journal Of Lipid Research
Articles to be published in the November 2007 issue of the Journal of Lipid Research (Vol. 48, No. 11):
Preventing Alzheimer's disease early on
Dayan B. Goodenowe and colleagues have shown that people with Alzheimer's disease and related conditions exhibit decreased blood levels of an important brain chemical called ethanolamine plasmalogen, even at the very early stages of the disease. The scientists have also found that this decrease is more pronounced when the symptoms are more severe.
Alzheimer's disease and related conditions, grouped under the name dementia of the Alzheimer's type (DAT), mostly affect elderly people. These conditions are not easily diagnosed because they can arise from many different causes, some of which that are not well known. Although the relationship between blood levels of ethanolamine plasmalogens and the severity of DAT is not completely understood, the new discovery may improve the diagnosis of DAT and help patients make decisions about how to cope with the disease.
The scientists suggest that the observed decrease of ethanolamine plasmalogens may result in decreased release and subsequent decreased activity of acetylcholine, a critical brain chemical involved in memory formation and whose activity is known to be reduced in DAT patients. So correcting the ethanolamine plasmalogen deficit in DAT may slow or correct the acetylcholine deficit in DAT patients.
The researchers conclude that clinical trials involving restoration of ethanolamine plasmalogens should be undertaken to determine its efficacy in the treatment and/or prevention of DAT.
Article: "Peripheral Ehanolamine Plasmalogen Deficiency: A Logical Causative Factor in Alzheimer's Disease and Dementia," by Dayan B. Goodenowe, Lisa L. Cook, Jun Liu, Yingshen Lu, Dushmanthi A. Jayasinghe, Pearson W.K. Ahiahonu, Doug Heath, Yasuyo Yamazaki, John Flax, Kevin F. Krenitsky, D. L. Sparks, Alan Lerner, Robert P. Friedland, Takashi Kudo, Kouzin Kamino, Takashi Morihara, Masatoshi Takeda, and Paul L. Wood
Improving the assessment of coronary heart disease risk in Chinese
Scientists report that the concentration of a compound called apolipoprotein B in the blood is better at predicting whether Chinese have coronary heart disease -- in which fatty deposits clog arteries that supply blood and oxygen to the heart -- than other substances such as blood cholesterol levels. This finding could help improve the diagnostic and treatment of coronary heart disease in Chinese and maybe in other populations as well.
To diagnose the early stages of coronary heart disease, physicians usually measure levels of substances present in the blood, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and apolipoprotein B, which act as "markers" of the disease. But these markers are not very accurate and whether some of them are better at predicting the onset of the disease is not clear yet.
Kuo-Liong Chien, Yuan-Teh Lee and colleagues compared the levels of the markers in over 3,500 participants who did not have the disease at the time of recruitment but some of whom (122 individuals) developed the disease 13 years later. The scientists then compared which of the three substances would have best predicted the onset of the disease and found that the risk of developing coronary heart disease was more than three times as high in participants with the highest values of both apolipoprotein B and the ratio of the total cholesterol over HDL-C than patients who did not have the disease.
The scientists conclude that apolipoprotein B is more strongly associated than LDL-C with the risk of developing coronary heart disease. They add that non-HDL cholesterol is an important predictive factor for CHD among Chinese, more so than LDL cholesterol and that the ratio of total cholesterol over HDL cholesterol can strongly predict coronary heart disease.
Based on these results, the researchers recommend that apolipoprotein B should be included in the comprehensive evaluation of risk for this disease in Asian populations.
Article: "Apoliporotein B and non-high-density lipoprotein cholesterol and risk of coronary heart disease in Chinese," by Kuo-Liong Chien, Hsiu-Ching Hsu, Ta-Chen Su, Ming-Fong Chen, Yuan-Teh Lee, and Frank B. Hu
Slowing down the development of heart disease
Scientists have shown that a protein called transthyretin (TTR) that is present in the blood may accelerate the development of atherosclerosis -- a potentially fatal heart disease in which the arteries are progressively narrowed and hardened over time, reducing blood flow to the heart.
TTR has been shown to cleave a blood compound called apolipoprotein A-I (ApoA-I), which can produce structures called fibrils that are shaped like strands and accumulate in blood vessels. These fibrils have been observed in people with a mutation of the gene that makes ApoA-I, but whether cleavage by TTR promotes the formation of such fibrils has not been assessed yet.
Monica Mendes Sousa and colleagues determined that when ApoA-I is cleaved by TTR, it tends to form fibrils faster than the uncleaved ApoA-I. This discovery may provide new ways to treat people with atherosclerosis by stopping TTR from cleaving ApoA-I and slowing down the formation of fibrils in blood vessels
Article: "ApoA-I cleaved by transthyretin has reduced ability to promote cholesterol efflux and increased amyloidogenicity," by Marcia Almeida Liz, Claudio M. Gomes, Maria Joao Saraiva, and Monica Mendes Sousa
Potential health benefits of fish oil in baby formula
Scientists report that adding long-chain polyunsaturated fatty acids -- typically found in fish oil -- to baby formula may help infants better regulate their blood sugar and make more proteins in their muscle cells. These results may help make better decisions when dealing with pre-term birth, low-birth weight, and feeding of infants in intensive care.
Although infant formula is now considered nutritionally acceptable for infants under the age of one year, its composition is not a perfect match with breast milk, so the nutritional content of infant formula is regularly refined. Recent improvements include the addition of long-chain n-3 fatty acids, which can improve brain and visual development.
To better understand the role of these n-3 fatty acids in the early development of babies, M. Carole Thivierge and colleagues investigated how these fatty acids affect protein metabolism in neonatal pigs. The scientists weaned 28 piglets at two days of age and raised them for a month on either a control formula that didn't contain the fatty acid or a "test" formula that contained 3.5 percent of the fatty acid from fish oil.
The researchers noticed that in the piglets that were fed the control formula, fewer proteins were produced in their body over time and, at the same time, their insulin became less effective at lowering blood sugar levels. But piglets that drunk the test formula showed increased protein production and their insulin was as effective at using the proteins in the test formula for their growth as when they were born.
The scientists also noticed that most of the long-chain n-3 fatty acids were absorbed by muscle cell membranes and replaced another type of fatty acid known to promote inflammation. The long-chain n-3 fatty acids were also added to fats called triglycerides, but they did not replace at a similar extent the pro-inflammatory fatty acids there.
These results show that the long-chain n-3 fatty acids are preferably taken up by cell membranes and favor cellular activities that make new proteins which otherwise quickly decline after birth. This preferential incorporation of long-chain n-3 fatty acids in membranes and their impact on cellular activities could help understand better the role of these fatty acids in the development and future health of piglets -- and presumably infants too.
The scientists conclude that elevated amounts of long-chain n-3 fatty acids in muscle membranes have beneficial effects on the early development of piglets and may help babies in regulating muscle growth that affect early development and future metabolic health.
Article: "Long-chain n-3 fatty acids enhance neonatal insulin-regulated protein metabolism in neonate piglets by differentially altering muscle lipid composition," by Karen Bergeron, Pierre Julien, Teresa A. Davis, Alexandre Myre, and M. Carole Thivierge
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at asbmb/.
Preventing Alzheimer's disease early on
Dayan B. Goodenowe and colleagues have shown that people with Alzheimer's disease and related conditions exhibit decreased blood levels of an important brain chemical called ethanolamine plasmalogen, even at the very early stages of the disease. The scientists have also found that this decrease is more pronounced when the symptoms are more severe.
Alzheimer's disease and related conditions, grouped under the name dementia of the Alzheimer's type (DAT), mostly affect elderly people. These conditions are not easily diagnosed because they can arise from many different causes, some of which that are not well known. Although the relationship between blood levels of ethanolamine plasmalogens and the severity of DAT is not completely understood, the new discovery may improve the diagnosis of DAT and help patients make decisions about how to cope with the disease.
The scientists suggest that the observed decrease of ethanolamine plasmalogens may result in decreased release and subsequent decreased activity of acetylcholine, a critical brain chemical involved in memory formation and whose activity is known to be reduced in DAT patients. So correcting the ethanolamine plasmalogen deficit in DAT may slow or correct the acetylcholine deficit in DAT patients.
The researchers conclude that clinical trials involving restoration of ethanolamine plasmalogens should be undertaken to determine its efficacy in the treatment and/or prevention of DAT.
Article: "Peripheral Ehanolamine Plasmalogen Deficiency: A Logical Causative Factor in Alzheimer's Disease and Dementia," by Dayan B. Goodenowe, Lisa L. Cook, Jun Liu, Yingshen Lu, Dushmanthi A. Jayasinghe, Pearson W.K. Ahiahonu, Doug Heath, Yasuyo Yamazaki, John Flax, Kevin F. Krenitsky, D. L. Sparks, Alan Lerner, Robert P. Friedland, Takashi Kudo, Kouzin Kamino, Takashi Morihara, Masatoshi Takeda, and Paul L. Wood
Improving the assessment of coronary heart disease risk in Chinese
Scientists report that the concentration of a compound called apolipoprotein B in the blood is better at predicting whether Chinese have coronary heart disease -- in which fatty deposits clog arteries that supply blood and oxygen to the heart -- than other substances such as blood cholesterol levels. This finding could help improve the diagnostic and treatment of coronary heart disease in Chinese and maybe in other populations as well.
To diagnose the early stages of coronary heart disease, physicians usually measure levels of substances present in the blood, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and apolipoprotein B, which act as "markers" of the disease. But these markers are not very accurate and whether some of them are better at predicting the onset of the disease is not clear yet.
Kuo-Liong Chien, Yuan-Teh Lee and colleagues compared the levels of the markers in over 3,500 participants who did not have the disease at the time of recruitment but some of whom (122 individuals) developed the disease 13 years later. The scientists then compared which of the three substances would have best predicted the onset of the disease and found that the risk of developing coronary heart disease was more than three times as high in participants with the highest values of both apolipoprotein B and the ratio of the total cholesterol over HDL-C than patients who did not have the disease.
The scientists conclude that apolipoprotein B is more strongly associated than LDL-C with the risk of developing coronary heart disease. They add that non-HDL cholesterol is an important predictive factor for CHD among Chinese, more so than LDL cholesterol and that the ratio of total cholesterol over HDL cholesterol can strongly predict coronary heart disease.
Based on these results, the researchers recommend that apolipoprotein B should be included in the comprehensive evaluation of risk for this disease in Asian populations.
Article: "Apoliporotein B and non-high-density lipoprotein cholesterol and risk of coronary heart disease in Chinese," by Kuo-Liong Chien, Hsiu-Ching Hsu, Ta-Chen Su, Ming-Fong Chen, Yuan-Teh Lee, and Frank B. Hu
Slowing down the development of heart disease
Scientists have shown that a protein called transthyretin (TTR) that is present in the blood may accelerate the development of atherosclerosis -- a potentially fatal heart disease in which the arteries are progressively narrowed and hardened over time, reducing blood flow to the heart.
TTR has been shown to cleave a blood compound called apolipoprotein A-I (ApoA-I), which can produce structures called fibrils that are shaped like strands and accumulate in blood vessels. These fibrils have been observed in people with a mutation of the gene that makes ApoA-I, but whether cleavage by TTR promotes the formation of such fibrils has not been assessed yet.
Monica Mendes Sousa and colleagues determined that when ApoA-I is cleaved by TTR, it tends to form fibrils faster than the uncleaved ApoA-I. This discovery may provide new ways to treat people with atherosclerosis by stopping TTR from cleaving ApoA-I and slowing down the formation of fibrils in blood vessels
Article: "ApoA-I cleaved by transthyretin has reduced ability to promote cholesterol efflux and increased amyloidogenicity," by Marcia Almeida Liz, Claudio M. Gomes, Maria Joao Saraiva, and Monica Mendes Sousa
Potential health benefits of fish oil in baby formula
Scientists report that adding long-chain polyunsaturated fatty acids -- typically found in fish oil -- to baby formula may help infants better regulate their blood sugar and make more proteins in their muscle cells. These results may help make better decisions when dealing with pre-term birth, low-birth weight, and feeding of infants in intensive care.
Although infant formula is now considered nutritionally acceptable for infants under the age of one year, its composition is not a perfect match with breast milk, so the nutritional content of infant formula is regularly refined. Recent improvements include the addition of long-chain n-3 fatty acids, which can improve brain and visual development.
To better understand the role of these n-3 fatty acids in the early development of babies, M. Carole Thivierge and colleagues investigated how these fatty acids affect protein metabolism in neonatal pigs. The scientists weaned 28 piglets at two days of age and raised them for a month on either a control formula that didn't contain the fatty acid or a "test" formula that contained 3.5 percent of the fatty acid from fish oil.
The researchers noticed that in the piglets that were fed the control formula, fewer proteins were produced in their body over time and, at the same time, their insulin became less effective at lowering blood sugar levels. But piglets that drunk the test formula showed increased protein production and their insulin was as effective at using the proteins in the test formula for their growth as when they were born.
The scientists also noticed that most of the long-chain n-3 fatty acids were absorbed by muscle cell membranes and replaced another type of fatty acid known to promote inflammation. The long-chain n-3 fatty acids were also added to fats called triglycerides, but they did not replace at a similar extent the pro-inflammatory fatty acids there.
These results show that the long-chain n-3 fatty acids are preferably taken up by cell membranes and favor cellular activities that make new proteins which otherwise quickly decline after birth. This preferential incorporation of long-chain n-3 fatty acids in membranes and their impact on cellular activities could help understand better the role of these fatty acids in the development and future health of piglets -- and presumably infants too.
The scientists conclude that elevated amounts of long-chain n-3 fatty acids in muscle membranes have beneficial effects on the early development of piglets and may help babies in regulating muscle growth that affect early development and future metabolic health.
Article: "Long-chain n-3 fatty acids enhance neonatal insulin-regulated protein metabolism in neonate piglets by differentially altering muscle lipid composition," by Karen Bergeron, Pierre Julien, Teresa A. Davis, Alexandre Myre, and M. Carole Thivierge
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
For more information about ASBMB, see the Society's Web site at asbmb/.
Incyte's Selective Oral Inhibitor Of 11beta-HSD1 Demonstrates Improvements In Insulin Sensitivity And Lowers Cholesterol Levels In Type 2 Diabetics
Incyte Corporation (Nasdaq:INCY) announced clinical results presented today at the American Diabetes Association 68th Scientific Sessions of its Phase IIa trial of INCB13739, an orally bioavailable inhibitor of the 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme. These results showed that 28 days of treatment with INCB13739 significantly improved hepatic insulin sensitivity and decreased plasma LDL- and total-cholesterol levels in patients with type 2 diabetes. Results from this double-blind, placebo-controlled trial in 31 subjects diagnosed with type 2 diabetes were presented during an oral session entitled, "New and Novel Treatments for Diabetic Complications" by Meredith Hawkins, M.D., Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine and Principal Investigator for the trial.
"These findings indicate that inhibition of 11beta-HSD1 can improve insulin sensitivity and plasma cholesterol levels in patients with type 2 diabetes. The insulin sensitivity data obtained after INCB13739 therapy in this trial are comparable to those obtained following pioglitazone treatment for a similar duration. The results from this trial suggest that INCB13739 has the potential to produce clinically meaningful benefit on macrovascular risk in patients with type 2 diabetes mellitus," stated Dr. Hawkins.
Summary of Results
Stepped pancreatic clamp studies were designed to optimally study hepatic and peripheral insulin sensitivity using two distinct levels of insulin. In this trial, INCB13739 treatment resulted in:
- a placebo-adjusted mean 0.614 mg/kg/min decrease in glucose production (P = 0.018), indicating markedly enhanced hepatic insulin sensitivity
- a mean 0.752 mg/kg/min trend toward increased insulin-stimulated glucose uptake (P = 0.177), an indicator of peripheral insulin sensitivity
Fasting blood tests were used to assess the secondary endpoints of the study, plasma glucose concentrations and lipid profiles. INCB13739 treatment resulted in:
- a trend toward reduced fasting plasma glucose (-19.5 mg/dL), with the treatment effect being of greater magnitude in patients with higher (>160 mg/dL) baseline hyperglycemia (-45.0 mg/dL, P = 0.075)
- a significant decrease in plasma total cholesterol (-26.9 mg/dL, P = 0.007) and LDL-cholesterol (-22.3 mg/dL, P = 0.001).
Summary of Safety Results
INCB13739 was safe and very well tolerated over the course of the trial with no serious adverse events noted. The most frequent adverse events occurring in more than one subject were headache, nausea, hyporeflexia, diarrhea and upper respiratory tract infection, all mild to moderate in intensity. Headache, nausea and hyporeflexia were also reported by subjects randomized to the placebo arm. No other adverse trends in vital signs, ECGs, or laboratory parameters were observed. As expected, fasted morning plasma ACTH levels increased after INCB13739 treatment relative to baseline (+9.5 pg/mL), likely reflecting compensatory pharmacology to maintain plasma cortisol levels. In line with this finding and consistent with Phase I data presented from an earlier trial, morning plasma cortisol levels were unchanged after INCB13739 therapy.
About the Trial
This was a 28-day Phase IIa clinical trial in type 2 diabetic patients who were either treatment-na??ve or had been withdrawn from other anti-hyperglycemic medication for 14 days. Subjects receiving thiazolidinediones (TZDs), exenatide, or insulin in the three-months prior to screening were excluded. Subjects received either 100 mg INCB13739 BID or placebo. In addition to evaluating the safety and tolerability of INCB13739, several key efficacy measures were assessed including:
- insulin sensitivity as determined by a stepped hyperinsulinemic, euglycemic, pancreatic clamp
- fasting blood glucose
- fasting plasma lipid profiles
Current Status of INCB13739
INCB13739 is currently being evaluated in a randomized, double-blind, placebo-controlled, dose-ranging Phase IIb clinical trial in patients with type 2 diabetes. This is a multi-national trial designed to evaluate the safety and efficacy of multiple once-daily dose regimens of INCB13739 when added to failing metformin monotherapy. The primary endpoint of the trial is the change from baseline to week 12 in hemoglobin A1c, a recognized surrogate endpoint for integrated glycemic control over a 2-3 month period.
About INCB13739
INCB13739 is a potent, selective, non-steroidal small molecule inhibitor of 11beta-HSD1 with 1.1 nM potency in cellular assays. The compound is > 1000-fold selective over 11beta-HSD2, glucocorticoid receptor, and mineralocorticoid receptor and exhibits good oral pharmacokinetics with an estimated half-life of 11 hours.
Data from prior clinical trials indicates that the dose level of INCB13739 selected for this study achieves complete inhibition of adipose tissue and liver 11beta-HSD1 activity throughout the dosing interval.
About 11beta-HSD1
11beta-HSD1 is an enzyme that converts inactive cortisone into the potent biologically active hormone cortisol. This conversion occurs within cells of key metabolic tissues including liver, adipose, muscle and pancreas. Importantly, preclinical studies have shown that the enzyme does not significantly affect neuroendocrine control of glucocorticoid biosynthesis in the adrenal gland, but rather provides a mechanism to specifically increase local glucocorticoid exposure within cells in a tissue-specific manner. Unlike the hormone insulin, which is produced by beta-cells in the pancreas and maintains normal blood glucose levels, cortisol elevates blood glucose levels by driving glucose production in the liver, and inhibiting the uptake and disposal of glucose in muscle and adipose. Thus, cortisol acts as an antagonist of insulin action, and 11beta-HSD1 mediated production of cortisol has been hypothesized to contribute to human insulin resistance, type 2 diabetes, and the often-associated cardiovascular comorbidities.
Current treatments for type 2 diabetes typically address individual components of the disease, and few therapies target the multiple risk factors that lead to the elevated cardiovascular risk associated with this condition. By selectively inhibiting 11beta-HSD1 and reducing the level of cortisol in key metabolic tissues, INCB13739 has the potential to simultaneously target multiple cardiovascular risk factors in patients with type 2 diabetes.
About Type 2 Diabetes
According to the Centers for Disease Control and Prevention (CDC), nearly 21 million Americans have diabetes. The majority of these patients have type 2 diabetes. The CDC also reports that 41 million people are estimated to have pre-diabetes, a pre-disposing condition that occurs before the onset of type 2 diabetes.
About Incyte
Incyte Corporation is a Wilmington, Delaware-based drug discovery and development company focused on developing proprietary small molecule drugs to treat serious unmet medical needs. Incyte's pipeline includes multiple compounds in Phase I and Phase II development for oncology, inflammation and diabetes. For additional information on Incyte, visit the Company's web site at incyte.
Forward Looking Statements
Except for the historical information contained herein, the matters set forth in this press release, including statements with respect to the potential for INCB13739 to produce clinically meaningful benefit on macrovascular risk in patients with type 2 diabetes mellitus and to simultaneously target multiple cardiovascular risk factors in patients with type 2 diabetes, are all forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially, including the high degree of risk associated with drug development and clinical trials, the uncertainty of the FDA approval process, results of further research and development, the impact of competition and of technological advances and the ability of Incyte to compete against parties with greater financial or other resources, Incyte's ability to enroll a sufficient number of patients for its clinical trials, and other risks detailed from time to time in Incyte's filings with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended March 31, 2008. Incyte disclaims any intent or obligation to update these forward-looking statements.
incyte
"These findings indicate that inhibition of 11beta-HSD1 can improve insulin sensitivity and plasma cholesterol levels in patients with type 2 diabetes. The insulin sensitivity data obtained after INCB13739 therapy in this trial are comparable to those obtained following pioglitazone treatment for a similar duration. The results from this trial suggest that INCB13739 has the potential to produce clinically meaningful benefit on macrovascular risk in patients with type 2 diabetes mellitus," stated Dr. Hawkins.
Summary of Results
Stepped pancreatic clamp studies were designed to optimally study hepatic and peripheral insulin sensitivity using two distinct levels of insulin. In this trial, INCB13739 treatment resulted in:
- a placebo-adjusted mean 0.614 mg/kg/min decrease in glucose production (P = 0.018), indicating markedly enhanced hepatic insulin sensitivity
- a mean 0.752 mg/kg/min trend toward increased insulin-stimulated glucose uptake (P = 0.177), an indicator of peripheral insulin sensitivity
Fasting blood tests were used to assess the secondary endpoints of the study, plasma glucose concentrations and lipid profiles. INCB13739 treatment resulted in:
- a trend toward reduced fasting plasma glucose (-19.5 mg/dL), with the treatment effect being of greater magnitude in patients with higher (>160 mg/dL) baseline hyperglycemia (-45.0 mg/dL, P = 0.075)
- a significant decrease in plasma total cholesterol (-26.9 mg/dL, P = 0.007) and LDL-cholesterol (-22.3 mg/dL, P = 0.001).
Summary of Safety Results
INCB13739 was safe and very well tolerated over the course of the trial with no serious adverse events noted. The most frequent adverse events occurring in more than one subject were headache, nausea, hyporeflexia, diarrhea and upper respiratory tract infection, all mild to moderate in intensity. Headache, nausea and hyporeflexia were also reported by subjects randomized to the placebo arm. No other adverse trends in vital signs, ECGs, or laboratory parameters were observed. As expected, fasted morning plasma ACTH levels increased after INCB13739 treatment relative to baseline (+9.5 pg/mL), likely reflecting compensatory pharmacology to maintain plasma cortisol levels. In line with this finding and consistent with Phase I data presented from an earlier trial, morning plasma cortisol levels were unchanged after INCB13739 therapy.
About the Trial
This was a 28-day Phase IIa clinical trial in type 2 diabetic patients who were either treatment-na??ve or had been withdrawn from other anti-hyperglycemic medication for 14 days. Subjects receiving thiazolidinediones (TZDs), exenatide, or insulin in the three-months prior to screening were excluded. Subjects received either 100 mg INCB13739 BID or placebo. In addition to evaluating the safety and tolerability of INCB13739, several key efficacy measures were assessed including:
- insulin sensitivity as determined by a stepped hyperinsulinemic, euglycemic, pancreatic clamp
- fasting blood glucose
- fasting plasma lipid profiles
Current Status of INCB13739
INCB13739 is currently being evaluated in a randomized, double-blind, placebo-controlled, dose-ranging Phase IIb clinical trial in patients with type 2 diabetes. This is a multi-national trial designed to evaluate the safety and efficacy of multiple once-daily dose regimens of INCB13739 when added to failing metformin monotherapy. The primary endpoint of the trial is the change from baseline to week 12 in hemoglobin A1c, a recognized surrogate endpoint for integrated glycemic control over a 2-3 month period.
About INCB13739
INCB13739 is a potent, selective, non-steroidal small molecule inhibitor of 11beta-HSD1 with 1.1 nM potency in cellular assays. The compound is > 1000-fold selective over 11beta-HSD2, glucocorticoid receptor, and mineralocorticoid receptor and exhibits good oral pharmacokinetics with an estimated half-life of 11 hours.
Data from prior clinical trials indicates that the dose level of INCB13739 selected for this study achieves complete inhibition of adipose tissue and liver 11beta-HSD1 activity throughout the dosing interval.
About 11beta-HSD1
11beta-HSD1 is an enzyme that converts inactive cortisone into the potent biologically active hormone cortisol. This conversion occurs within cells of key metabolic tissues including liver, adipose, muscle and pancreas. Importantly, preclinical studies have shown that the enzyme does not significantly affect neuroendocrine control of glucocorticoid biosynthesis in the adrenal gland, but rather provides a mechanism to specifically increase local glucocorticoid exposure within cells in a tissue-specific manner. Unlike the hormone insulin, which is produced by beta-cells in the pancreas and maintains normal blood glucose levels, cortisol elevates blood glucose levels by driving glucose production in the liver, and inhibiting the uptake and disposal of glucose in muscle and adipose. Thus, cortisol acts as an antagonist of insulin action, and 11beta-HSD1 mediated production of cortisol has been hypothesized to contribute to human insulin resistance, type 2 diabetes, and the often-associated cardiovascular comorbidities.
Current treatments for type 2 diabetes typically address individual components of the disease, and few therapies target the multiple risk factors that lead to the elevated cardiovascular risk associated with this condition. By selectively inhibiting 11beta-HSD1 and reducing the level of cortisol in key metabolic tissues, INCB13739 has the potential to simultaneously target multiple cardiovascular risk factors in patients with type 2 diabetes.
About Type 2 Diabetes
According to the Centers for Disease Control and Prevention (CDC), nearly 21 million Americans have diabetes. The majority of these patients have type 2 diabetes. The CDC also reports that 41 million people are estimated to have pre-diabetes, a pre-disposing condition that occurs before the onset of type 2 diabetes.
About Incyte
Incyte Corporation is a Wilmington, Delaware-based drug discovery and development company focused on developing proprietary small molecule drugs to treat serious unmet medical needs. Incyte's pipeline includes multiple compounds in Phase I and Phase II development for oncology, inflammation and diabetes. For additional information on Incyte, visit the Company's web site at incyte.
Forward Looking Statements
Except for the historical information contained herein, the matters set forth in this press release, including statements with respect to the potential for INCB13739 to produce clinically meaningful benefit on macrovascular risk in patients with type 2 diabetes mellitus and to simultaneously target multiple cardiovascular risk factors in patients with type 2 diabetes, are all forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially, including the high degree of risk associated with drug development and clinical trials, the uncertainty of the FDA approval process, results of further research and development, the impact of competition and of technological advances and the ability of Incyte to compete against parties with greater financial or other resources, Incyte's ability to enroll a sufficient number of patients for its clinical trials, and other risks detailed from time to time in Incyte's filings with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended March 31, 2008. Incyte disclaims any intent or obligation to update these forward-looking statements.
incyte
Cholesterol, Blood Pressure Control May Reverse Atherosclerosis In Adults With Diabetes
Aggressively lowering cholesterol and blood pressure levels below current targets in adults with type 2 diabetes may help to prevent - and possibly reverse - hardening of the arteries, according to new research supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. Hardening of the arteries, also known as atherosclerosis, is the number one cause of heart disease and can lead to heart attack, stroke, and death.
The three-year study of 499 participants is the first to compare two treatment targets for LDL ("bad") cholesterol and systolic blood pressure levels, key risk factors for heart disease, in people with diabetes. Results are published in the April 9 issue of the Journal of the American Medical Association.
"This study provides good news for adults with type 2 diabetes," said Elizabeth G. Nabel, M.D., NHLBI director. "These patients are two to four times more likely than people without diabetes to die from heart disease. For the first time, we have evidence that aggressively lowering LDL cholesterol and blood pressure can actually reverse damage to the arteries in middle-aged adults with diabetes."
In the Stop Atherosclerosis in Native Diabetics Study (SANDS), approximately one-half of the participants (247) were asked to lower to standard levels their LDL cholesterol (to 100 milligrams per deciliter) and blood pressure (systolic blood pressure of 130 mmHg or lower), while the other half (252) aimed for more aggressive lowering of LDL cholesterol to 70 mg/dL or lower and of systolic blood pressure to 115 mmHg or lower. All participants were American Indians 40 years or older (average age of 56) who had diabetes, high blood cholesterol, and high blood pressure but no history of heart attack or other evidence of heart disease. The study was conducted at four clinical centers in southwestern Oklahoma; Phoenix, Ariz.; northeastern Arizona; and South Dakota. All participants continued to receive their medical care, including diabetes management, dietary and exercise counseling, and smoking cessation, from their health care providers with the Indian Health Service. Like the NIH, the Indian Health Service is part of the U.S. Department of Health and Human Services.
"American Indians have a high rate of diabetes and cardiovascular disease related to diabetes, but there are few clinical trials that address these issues in this population," said Barbara V. Howard, Ph.D., of MedStar Research Institute in Hyattsville, Md., lead author of the paper. "These study results provide needed evidence to help develop community-based programs to treat and prevent the epidemic of cardiovascular disease among American Indians. At the same time, we are increasing our understanding of the effects of intensively lowering cholesterol and blood pressure in adults with type 2 diabetes, which might also apply to other populations."
During the three-year study, participants were examined by study clinicians one month after enrollment, then every three months, to assess their blood cholesterol and blood pressure levels and general well being. Food and Drug Administration-approved blood pressure and cholesterol medications were added and adjusted as needed to help participants achieve their treatment goals. The same medications were available to participants in the standard and the aggressive treatment groups. Participants were also encouraged to follow lifestyle approaches to help meet their blood pressure and cholesterol treatment targets, such as following a heart-healthy eating plan, being physically active, maintaining a healthy weight, and not smoking.
To assess the impact of the treatments on the participants' cardiovascular health, researchers used ultrasound to measure the thickness of the carotid (neck) artery -- an indication of hardening of the arteries, a leading effect of high blood pressure and cholesterol and an early sign of cardiovascular disease. In addition, ultrasound was also used to measure the size and function of the left ventricle, the heart's main pumping chamber. Enlarged hearts are known to be predictors of increased risk of heart attack and stroke. These measurements were taken at enrollment, at 18 months, and at 36 months, when the study ended.
On average, participants in both groups reached and maintained their target goals for blood cholesterol and blood pressure levels. The numbers of heart attacks and other cardiovascular events were similar between the two groups and lower than expected.
In addition, carotid artery thickness measurements of participants in the aggressive treatment group were significantly lower than those in the standard treatment group. Researchers report that, compared to baseline, carotid artery thickness increased slightly in the standard group and regressed in the aggressive treatment group, indicating a partial reversal of atherosclerosis. Furthermore, although heart size decreased from baseline in both groups, the beneficial change was significantly greater among participants in the aggressive treatment group.
"Many patients with diabetes do not reach their blood pressure and cholesterol goal levels and thus remain at high risk for heart attacks and stroke," noted Howard. "In our study, participants successfully managed their blood cholesterol and blood pressure to reach their goal levels. Our message to doctors, nurses, and patients is that you can reach your goal levels, and we should work together to help you do that."
As with any therapy, the benefits and risks must be considered for each patient. In SANDS, participants in the aggressive treatment group on average needed more medications and higher doses than the standard treatment group, and they were slightly more likely to have side effects from blood pressure-lowering medications than those in the standard group. Such adverse effects generally resolved, however, after the medication was changed or the dose reduced. There were no differences in side effects related to cholesterol-lowering drugs between the standard and the aggressive treatment groups.
"These encouraging findings from SANDS suggest that more aggressive blood pressure and cholesterol targets than those currently recommended in patients with diabetes may reduce their future cardiovascular risk," said Jerome L. Fleg, M.D., NHLBI project officer of the study and a coauthor of the paper. "Longer term followup of this population as well as additional studies in other populations are needed to confirm the benefit and cost-effectiveness of these lower targets."
Medications used in this study were donated by First Horizon Pharmacy, Merck and Co., and Pfizer, Inc.
An estimated 21 million Americans have diabetes and 284,000 die from it each year. Sixty-five percent of the deaths are related to cardiovascular causes.
Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at nhlbi.nih.
The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih.
Resources:
* Your Guide to Living Well With Heart Disease, nhlbi.nih/health/public/heart/other/your_guide/living_well.htm
* Atherosclerosis, nhlbi.nih/health/dci/Diseases/Atherosclerosis/Atherosclerosis_WhatIs.html
* National Diabetes Information Clearinghouse, diabetes.niddk.nih/
* National Diabetes Education Program ndep.nih/
The three-year study of 499 participants is the first to compare two treatment targets for LDL ("bad") cholesterol and systolic blood pressure levels, key risk factors for heart disease, in people with diabetes. Results are published in the April 9 issue of the Journal of the American Medical Association.
"This study provides good news for adults with type 2 diabetes," said Elizabeth G. Nabel, M.D., NHLBI director. "These patients are two to four times more likely than people without diabetes to die from heart disease. For the first time, we have evidence that aggressively lowering LDL cholesterol and blood pressure can actually reverse damage to the arteries in middle-aged adults with diabetes."
In the Stop Atherosclerosis in Native Diabetics Study (SANDS), approximately one-half of the participants (247) were asked to lower to standard levels their LDL cholesterol (to 100 milligrams per deciliter) and blood pressure (systolic blood pressure of 130 mmHg or lower), while the other half (252) aimed for more aggressive lowering of LDL cholesterol to 70 mg/dL or lower and of systolic blood pressure to 115 mmHg or lower. All participants were American Indians 40 years or older (average age of 56) who had diabetes, high blood cholesterol, and high blood pressure but no history of heart attack or other evidence of heart disease. The study was conducted at four clinical centers in southwestern Oklahoma; Phoenix, Ariz.; northeastern Arizona; and South Dakota. All participants continued to receive their medical care, including diabetes management, dietary and exercise counseling, and smoking cessation, from their health care providers with the Indian Health Service. Like the NIH, the Indian Health Service is part of the U.S. Department of Health and Human Services.
"American Indians have a high rate of diabetes and cardiovascular disease related to diabetes, but there are few clinical trials that address these issues in this population," said Barbara V. Howard, Ph.D., of MedStar Research Institute in Hyattsville, Md., lead author of the paper. "These study results provide needed evidence to help develop community-based programs to treat and prevent the epidemic of cardiovascular disease among American Indians. At the same time, we are increasing our understanding of the effects of intensively lowering cholesterol and blood pressure in adults with type 2 diabetes, which might also apply to other populations."
During the three-year study, participants were examined by study clinicians one month after enrollment, then every three months, to assess their blood cholesterol and blood pressure levels and general well being. Food and Drug Administration-approved blood pressure and cholesterol medications were added and adjusted as needed to help participants achieve their treatment goals. The same medications were available to participants in the standard and the aggressive treatment groups. Participants were also encouraged to follow lifestyle approaches to help meet their blood pressure and cholesterol treatment targets, such as following a heart-healthy eating plan, being physically active, maintaining a healthy weight, and not smoking.
To assess the impact of the treatments on the participants' cardiovascular health, researchers used ultrasound to measure the thickness of the carotid (neck) artery -- an indication of hardening of the arteries, a leading effect of high blood pressure and cholesterol and an early sign of cardiovascular disease. In addition, ultrasound was also used to measure the size and function of the left ventricle, the heart's main pumping chamber. Enlarged hearts are known to be predictors of increased risk of heart attack and stroke. These measurements were taken at enrollment, at 18 months, and at 36 months, when the study ended.
On average, participants in both groups reached and maintained their target goals for blood cholesterol and blood pressure levels. The numbers of heart attacks and other cardiovascular events were similar between the two groups and lower than expected.
In addition, carotid artery thickness measurements of participants in the aggressive treatment group were significantly lower than those in the standard treatment group. Researchers report that, compared to baseline, carotid artery thickness increased slightly in the standard group and regressed in the aggressive treatment group, indicating a partial reversal of atherosclerosis. Furthermore, although heart size decreased from baseline in both groups, the beneficial change was significantly greater among participants in the aggressive treatment group.
"Many patients with diabetes do not reach their blood pressure and cholesterol goal levels and thus remain at high risk for heart attacks and stroke," noted Howard. "In our study, participants successfully managed their blood cholesterol and blood pressure to reach their goal levels. Our message to doctors, nurses, and patients is that you can reach your goal levels, and we should work together to help you do that."
As with any therapy, the benefits and risks must be considered for each patient. In SANDS, participants in the aggressive treatment group on average needed more medications and higher doses than the standard treatment group, and they were slightly more likely to have side effects from blood pressure-lowering medications than those in the standard group. Such adverse effects generally resolved, however, after the medication was changed or the dose reduced. There were no differences in side effects related to cholesterol-lowering drugs between the standard and the aggressive treatment groups.
"These encouraging findings from SANDS suggest that more aggressive blood pressure and cholesterol targets than those currently recommended in patients with diabetes may reduce their future cardiovascular risk," said Jerome L. Fleg, M.D., NHLBI project officer of the study and a coauthor of the paper. "Longer term followup of this population as well as additional studies in other populations are needed to confirm the benefit and cost-effectiveness of these lower targets."
Medications used in this study were donated by First Horizon Pharmacy, Merck and Co., and Pfizer, Inc.
An estimated 21 million Americans have diabetes and 284,000 die from it each year. Sixty-five percent of the deaths are related to cardiovascular causes.
Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI press releases and other materials are available online at nhlbi.nih.
The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih.
Resources:
* Your Guide to Living Well With Heart Disease, nhlbi.nih/health/public/heart/other/your_guide/living_well.htm
* Atherosclerosis, nhlbi.nih/health/dci/Diseases/Atherosclerosis/Atherosclerosis_WhatIs.html
* National Diabetes Information Clearinghouse, diabetes.niddk.nih/
* National Diabetes Education Program ndep.nih/
The Metabolic Benefits Of Birch Bark Ingredient
An ingredient found in abundance in birch bark appears to have an array of metabolic benefits, according to new studies in animals that are reported in the January issue of Cell Metabolism, a Cell Press publication. In mice, the compound known as betulin lowered cholesterol, helped prevent diet-induced obesity, and improved insulin sensitivity. Betulin-treated mice were also more resistant to developing atherosclerotic plaques in their arteries.
Betulin works by targeting so-called sterol regulatory element-binding proteins (SREBPs), transcription factors that are known to be important for activating the expression of genes involved in the biosynthesis of cholesterol, fatty acids, and triglycerides.
"Our study shows that the SREBP pathway is a good target for several metabolic diseases," said Bao-Liang Song of the Shanghai Institutes for Biological Sciences. "We also identify a leading compound."
In the new study, Song and his colleagues went in search of a compound that might act directly on SREBP. That chemical screen turned up betulin as a top contender. They then confirmed in cells that betulin lowered the activity of genes that are normally switched "on" by SREBP. It also lowered lipid levels within cells.
Song's team then treated mice on a high-fat, Western diet with betulin, the cholesterol-lowering statin known as lovastatin, or a placebo (saline) for 6 weeks. Compared to placebo, both drugs led the mice to gain less weight on the high-fat diet, though by different means. Betulin caused the animals to burn more calories while lovastatin appeared to reduce the amount of lipid taken up from the diet.
Further investigations showed that betulin also lowered lipid levels in blood, liver, and fat tissue. Betulin also made the animals more sensitive to insulin. Mice with a mutation that makes them prone to develop atherosclerosis showed fewer plaques when treated with either lovastatin or betulin.
"Betulin has several major metabolic effects," Song said.
The researchers say that their findings suggest that betulin may have similar or even better effects than lovastatin, a member of the most widely prescribed drug class for treating high cholesterol. For instance, in their studies betulin decreased lipids in liver and fat to a greater extent than lovastatin did. Betulin also improved insulin resistance through its effects on fatty acid and triglyceride synthesis.
Song notes that betulin is a readily available compound and is already in use as a precursor in the manufacture of other drugs.
Although betulin appears to have very low toxicity, he says future studies will need to further investigate the safety of betulin and its metabolic effects. Researchers will also explore the possibility that a derivative of betulin might have even greater potency. "That may be the path forward to move this clinically," Song said.
Betulin works by targeting so-called sterol regulatory element-binding proteins (SREBPs), transcription factors that are known to be important for activating the expression of genes involved in the biosynthesis of cholesterol, fatty acids, and triglycerides.
"Our study shows that the SREBP pathway is a good target for several metabolic diseases," said Bao-Liang Song of the Shanghai Institutes for Biological Sciences. "We also identify a leading compound."
In the new study, Song and his colleagues went in search of a compound that might act directly on SREBP. That chemical screen turned up betulin as a top contender. They then confirmed in cells that betulin lowered the activity of genes that are normally switched "on" by SREBP. It also lowered lipid levels within cells.
Song's team then treated mice on a high-fat, Western diet with betulin, the cholesterol-lowering statin known as lovastatin, or a placebo (saline) for 6 weeks. Compared to placebo, both drugs led the mice to gain less weight on the high-fat diet, though by different means. Betulin caused the animals to burn more calories while lovastatin appeared to reduce the amount of lipid taken up from the diet.
Further investigations showed that betulin also lowered lipid levels in blood, liver, and fat tissue. Betulin also made the animals more sensitive to insulin. Mice with a mutation that makes them prone to develop atherosclerosis showed fewer plaques when treated with either lovastatin or betulin.
"Betulin has several major metabolic effects," Song said.
The researchers say that their findings suggest that betulin may have similar or even better effects than lovastatin, a member of the most widely prescribed drug class for treating high cholesterol. For instance, in their studies betulin decreased lipids in liver and fat to a greater extent than lovastatin did. Betulin also improved insulin resistance through its effects on fatty acid and triglyceride synthesis.
Song notes that betulin is a readily available compound and is already in use as a precursor in the manufacture of other drugs.
Although betulin appears to have very low toxicity, he says future studies will need to further investigate the safety of betulin and its metabolic effects. Researchers will also explore the possibility that a derivative of betulin might have even greater potency. "That may be the path forward to move this clinically," Song said.
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