The human body is home to a diverse range of microorganisms, estimated to outnumber human cells in a healthy adult by ten fold. The importance of characterizing human microbiota for understanding health and disease is highlighted by the recent launch of the Human Microbiome Project by the National Institutes of Health. This report, published online in Genome Research, describes the investigation of healthy human skin for microbiota diversity and establishes the basis for determining a core microbiome.
The Human Microbiome Project aims to characterize the microbial communities of several regions of the body, including skin, where determining the core microbiome is essential to understanding and developing new treatments for skin conditions and diseases such as acne and atopic dermatitis (eczema).
In this study, researchers led by Dr. Julie Segre of the National Human Genome Research Institute have generated a diversity profile of human skin microbiota by sequencing 16S rRNA, a component of the prokaryotic ribosome, isolated from a specific region of skin. "We focused this study on the inner elbow to inform future clinical studies of the extremely common inflammatory skin disorder atopic dermatitis, which affects this area of the skin and is associated with Staphylococcus infections," explains Segre.
The researchers find that in the healthy subjects tested, Proteobacteria (predominantly Pseudomonas and Janthinobacterium) constituted the majority of inner elbow microbiota. Furthermore, this survey indicated that a common core skin microbiome exists between these individuals. Segre adds that this finding is critical for studying disease. "Our long-term goal is to clarify the microbial contribution to a myriad of skin disorders both with known and suspected bacterial infections." Segre's group also found that the microbiota of mouse skin is comparable to that of the human inner elbow, suggesting a potential model for human skin disorders related to microbiota.
Segre explains that this work has established a foundation for answering questions about microbiota and skin disease, with the potential for novel drugs and treatments. "It's not surprising that microbes play a vital role in human health and disease," says Segre. "Unfortunately the public is conditioned to view microbes antagonistically, when in fact they may hold the key to a whole new array of therapeutic options."
Scientists from the National Human Genome Research Institute (Bethesda, MD) and the National Cancer Institute (Bethesda, MD) contributed to this study.
This work was supported by the National Institute of General Medical Sciences, the National Human Genome Research Institute, and the National Cancer Institute.
Monday, 26 May 2008
Anti-HIV Drugs Reduce The Cause Of Some Forms Of Vision Loss
A potential new therapeutic use for anti-HIV drugs known as protease inhibitors has been suggested by a team of researchers from Harvard Medical School, Boston, and Inserm U848, France, as a result of their work in a mouse model of retinal detachment.
An important cause of vision loss in many diseases of the eye is the death (by a process known as apoptosis) of nerve cells in the eye (known as photoreceptors) after retinal detachment. In the study, administration of HIV protease inhibitors by mouth markedly decreased photoreceptor apoptosis in the mouse model of retinal detachment.
Mechanistic analysis in mouse retinal cell cultures and in mice expressing decreased amounts of specific proteins established that the HIV protease inhibitors disrupted two molecular pathways that cause apoptotic cell death, both of which affect the cell compartments known as mitochondria.
As the same apoptotic cell death--inducing pathways were shown to be activated in human retinas after retinal detachment, the authors suggest that although the HIV protease inhibitors cannot reattach the retina, they might be of clinical benefit through their ability to prevent the photoreceptor apoptosis that has a central role in vision loss after retinal detachment.
An important cause of vision loss in many diseases of the eye is the death (by a process known as apoptosis) of nerve cells in the eye (known as photoreceptors) after retinal detachment. In the study, administration of HIV protease inhibitors by mouth markedly decreased photoreceptor apoptosis in the mouse model of retinal detachment.
Mechanistic analysis in mouse retinal cell cultures and in mice expressing decreased amounts of specific proteins established that the HIV protease inhibitors disrupted two molecular pathways that cause apoptotic cell death, both of which affect the cell compartments known as mitochondria.
As the same apoptotic cell death--inducing pathways were shown to be activated in human retinas after retinal detachment, the authors suggest that although the HIV protease inhibitors cannot reattach the retina, they might be of clinical benefit through their ability to prevent the photoreceptor apoptosis that has a central role in vision loss after retinal detachment.
Anti-rejection Drug May Increase Risk Of Diabetes After Kidney Transplant
For patients undergoing kidney transplantation, treatment with the anti-rejection drug sirolimus may lead to an increased risk of diabetes, reports a new study.
"We demonstrated a robust association between sirolimus and diabetes after transplantation in a large group of kidney transplant recipients in the United States," comments Dr. John S. Gill of University of British Columbia, Vancouver. "The risk of diabetes was independent of other factors that are known to increase the risk of diabetes."
The researchers analyzed US Renal Data System data on approximately 20,000 Medicare beneficiaries undergoing kidney transplantation between 1995 and 2003. None of the patients had diabetes before their kidney transplant. Treatment with sirolimus was analyzed as a possible contributor to the risk of diabetes developing after transplantation, along with other known and potential risk factors.
"Sirolimus is a newer type of anti-rejection drug that has not been associated with diabetes in transplant recipients," Dr. Gill explains. "However, a number of animal studies and small clinical studies have suggested that sirolimus may increase the risk of diabetes."
The results suggested a higher rate of post-transplant diabetes among patients treated with sirolimus, compared to other anti-rejection drugs. Depending on which additional drugs they received, diabetes risk was 36 to 66 percent higher for patients receiving sirolimus.
Separate analysis of patients who stayed on the same anti-rejection drugs throughout the first year after transplantation showed similar results. The increase in risk was unrelated to any of the other drugs used in combination with sirolimus, or to other risk factors such as age, race/ethnicity, or obesity.
Diabetes is a serious and increasingly common complication occurring after kidney transplantation. "Patients who develop diabetes after transplantation have roughly the same risk of transplant failure as patients who develop acute transplant rejection," says Dr. Gill. Several factors are known to increase the risk of post-transplant diabetes, including some other anti-rejection drugs. The new report is the first large clinical study to suggest that sirolimus may be a risk factor as well.
"Further studies should be done to further clarify the risk of diabetes in sirolimus-treated patients," Dr. Gill adds. He also notes some important limitations of the study, including the fact that it was based on a review of previous data and limited to Medicare patients.
"We demonstrated a robust association between sirolimus and diabetes after transplantation in a large group of kidney transplant recipients in the United States," comments Dr. John S. Gill of University of British Columbia, Vancouver. "The risk of diabetes was independent of other factors that are known to increase the risk of diabetes."
The researchers analyzed US Renal Data System data on approximately 20,000 Medicare beneficiaries undergoing kidney transplantation between 1995 and 2003. None of the patients had diabetes before their kidney transplant. Treatment with sirolimus was analyzed as a possible contributor to the risk of diabetes developing after transplantation, along with other known and potential risk factors.
"Sirolimus is a newer type of anti-rejection drug that has not been associated with diabetes in transplant recipients," Dr. Gill explains. "However, a number of animal studies and small clinical studies have suggested that sirolimus may increase the risk of diabetes."
The results suggested a higher rate of post-transplant diabetes among patients treated with sirolimus, compared to other anti-rejection drugs. Depending on which additional drugs they received, diabetes risk was 36 to 66 percent higher for patients receiving sirolimus.
Separate analysis of patients who stayed on the same anti-rejection drugs throughout the first year after transplantation showed similar results. The increase in risk was unrelated to any of the other drugs used in combination with sirolimus, or to other risk factors such as age, race/ethnicity, or obesity.
Diabetes is a serious and increasingly common complication occurring after kidney transplantation. "Patients who develop diabetes after transplantation have roughly the same risk of transplant failure as patients who develop acute transplant rejection," says Dr. Gill. Several factors are known to increase the risk of post-transplant diabetes, including some other anti-rejection drugs. The new report is the first large clinical study to suggest that sirolimus may be a risk factor as well.
"Further studies should be done to further clarify the risk of diabetes in sirolimus-treated patients," Dr. Gill adds. He also notes some important limitations of the study, including the fact that it was based on a review of previous data and limited to Medicare patients.
Scientists Image A Single HIV Particle Being Born
A mapmaker and a mathematician may seem like an unlikely duo, but together they worked out a way to measure longitude -- and kept millions of sailors from getting lost at sea. Now, another unlikely duo, a virologist and a biophysicist at Rockefeller University, is making history of their own. By using a specialized microscope that only illuminates the cell's surface, they have become the first to see, in real time and in plain view, hundreds of thousands of molecules coming together in a living cell to form a single particle of the virus that has, in less than 25 years, claimed more than 25 million lives: HIV.
This work, published in the May 25 advanced online issue of Nature, may not only prove useful in developing treatments for the millions around the globe still living with the lethal virus but the technique created to image its assembly may also change the way scientists think about and approach their own research.
"The use of this technique is almost unlimited," says Nolwenn Jouvenet, a postdoc who spearheaded this project under the direction of HIV expert Paul Bieniasz and cellular biophysicist Sandy Simon, who has been developing the imaging technique since 1992. "Now that we can actually see a virus being born, it gives us the opportunity to answer previously unanswered questions, not only in virology but in biology in general."
Unlike a classical microscope, which shines light through a whole cell, the technique called total internal reflection microscopy only illuminates the cell's surface where HIV assembles. "The result is that you can see, in exquisite detail, only events at the cell surface. You never even illuminate anything inside of the cell so you can focus on what you are interested in seeing the moment it is happening," says Simon, professor and head of the Laboratory of Cellular Biophysics.
When a beam of light passes through a piece of glass to a cell's surface, the energy from the light propagates upward, illuminating the entire cell. But when that beam is brought to a steeper angle, the light's energy reflects off the cell's surface, illuminating only the events going on at its most outer membrane. By zeroing in at the cell's surface, the team became the first to document the time it takes for each HIV particle, or virion, to assemble: five to six minutes. "At first, we had no idea whether it would take milliseconds or hours," says Jouvenet. "We just didn't know."
"This is the first time anyone has seen a virus particle being born," says Bieniasz, who is an associate professor and head of the Laboratory of Retrovirology at Rockefeller and a scientist at the Aaron Diamond AIDS Research Center. "Not just HIV," he clarifies, "any virus."
To prove that what they were watching was virus particles assembling at the surface (rather than an already assembled virion coming into their field of view from inside the cell), the group tagged a major viral protein, called the Gag protein, with molecules that fluoresce, but whose color would change as they packed closer together. Although many different components gather to form a single virion, the Gag protein is the only one necessary for assembly. It attaches to the inner face of the cell's outer membrane and when enough Gag molecules flood an area, they coalesce in a way that spontaneously forms a sphere.
Simon, Bieniasz and Jouvenet found that the Gag molecules are recruited from the inside of the cell and travel to the cell's surface. When enough Gag molecules get close and start bumping into each other, the cell's outer membrane starts to bulge outward into a budding virion and then pinches off to form an individual, infectious particle. At this point, the researchers showed that the virion is a lone entity, no longer exchanging resources with the cell. By using tricks from optics and physiology, they were able to watch the steps of viral assembly, budding, and even scission off the cell surface. With such a view they can start to describe the entire lifeline in the birth of the virus.
"I think that you can begin to understand events on a different level if you actually watch them happen instead of inferring that they might occur using other techniques," says Bieniasz. "This technique and this collaboration made that possible."
This research was supported in part by the National Institutes of Health, the National Science Foundation and amFAR, the Foundation for AIDS Research.
This work, published in the May 25 advanced online issue of Nature, may not only prove useful in developing treatments for the millions around the globe still living with the lethal virus but the technique created to image its assembly may also change the way scientists think about and approach their own research.
"The use of this technique is almost unlimited," says Nolwenn Jouvenet, a postdoc who spearheaded this project under the direction of HIV expert Paul Bieniasz and cellular biophysicist Sandy Simon, who has been developing the imaging technique since 1992. "Now that we can actually see a virus being born, it gives us the opportunity to answer previously unanswered questions, not only in virology but in biology in general."
Unlike a classical microscope, which shines light through a whole cell, the technique called total internal reflection microscopy only illuminates the cell's surface where HIV assembles. "The result is that you can see, in exquisite detail, only events at the cell surface. You never even illuminate anything inside of the cell so you can focus on what you are interested in seeing the moment it is happening," says Simon, professor and head of the Laboratory of Cellular Biophysics.
When a beam of light passes through a piece of glass to a cell's surface, the energy from the light propagates upward, illuminating the entire cell. But when that beam is brought to a steeper angle, the light's energy reflects off the cell's surface, illuminating only the events going on at its most outer membrane. By zeroing in at the cell's surface, the team became the first to document the time it takes for each HIV particle, or virion, to assemble: five to six minutes. "At first, we had no idea whether it would take milliseconds or hours," says Jouvenet. "We just didn't know."
"This is the first time anyone has seen a virus particle being born," says Bieniasz, who is an associate professor and head of the Laboratory of Retrovirology at Rockefeller and a scientist at the Aaron Diamond AIDS Research Center. "Not just HIV," he clarifies, "any virus."
To prove that what they were watching was virus particles assembling at the surface (rather than an already assembled virion coming into their field of view from inside the cell), the group tagged a major viral protein, called the Gag protein, with molecules that fluoresce, but whose color would change as they packed closer together. Although many different components gather to form a single virion, the Gag protein is the only one necessary for assembly. It attaches to the inner face of the cell's outer membrane and when enough Gag molecules flood an area, they coalesce in a way that spontaneously forms a sphere.
Simon, Bieniasz and Jouvenet found that the Gag molecules are recruited from the inside of the cell and travel to the cell's surface. When enough Gag molecules get close and start bumping into each other, the cell's outer membrane starts to bulge outward into a budding virion and then pinches off to form an individual, infectious particle. At this point, the researchers showed that the virion is a lone entity, no longer exchanging resources with the cell. By using tricks from optics and physiology, they were able to watch the steps of viral assembly, budding, and even scission off the cell surface. With such a view they can start to describe the entire lifeline in the birth of the virus.
"I think that you can begin to understand events on a different level if you actually watch them happen instead of inferring that they might occur using other techniques," says Bieniasz. "This technique and this collaboration made that possible."
This research was supported in part by the National Institutes of Health, the National Science Foundation and amFAR, the Foundation for AIDS Research.
Thursday, 22 May 2008
More Patients With Drug-coated Cardiac Stents Survive, Avoid Costly Follow-up Procedures
The more than ten million Americans who've received drug-eluting stents to open their blocked coronary arteries have a bright future, according to new research from the University of Pennsylvania School of Medicine. Patients with drug-coated stents are less apt to die, have heart attacks or require extra stents or bypass surgery in the two years following placement of the stent, compared to those who receive bare metal stents, according to University of Pennsylvania School of Medicine research that will be published in the May 27 issue of the Journal of the American College of Cardiology.
The findings, among the first large follow-up studies to show a clear, lifesaving benefit of drug-eluting stents compared to bare metal stents, will be published in the May 27 issue of the Journal of the American College of Cardiology. Patients with the drug-coated stents -- designed not only to open blocked coronary arteries but also to chemically inhibit future blockage -- were less apt to die, have heart attacks or require extra stents or bypass surgery in the two years following placement of the stent.
"This might be a hidden nugget of goodness that could not be detected in clinical trials," says Peter W. Groeneveld, MD, MS, assistant professor in Penn's Division of General Internal Medicine. "There is a distinct possibility that drug-eluting stents not only reduce the need for future cardiac procedures, but also save lives."
Groeneveld and his colleagues studied Medicare data to identify about 72,000 patients who received drug-eluting stents during a nine-month period in 2003, the first year the devices were approved for use in the United States. Overall, the findings showed a clear survival benefit compared to a control group of patients who got bare metal stents -- at 90 days, 1 year and 2 years, patients with drug-coated stents were less likely to die.
In a separate study which will be published in the June issue of the American Heart Journal, Groeneveld also found that drug-eluting stents also offer cost savings during the first year after placement. Although the initial cost of the device -- averaging $16,000 -- outpaces that of a bare metal stent, which costs about $14,000, the Penn researchers found that among patients with the drug-coated stents, 12 percent of those studied needed additional stents placed in the first year, compared to 15 percent of patients who received bare-metal stents.
Few patients in either arm required bypass surgery in the first year following stent placement, but those who received bare-metal stents were twice as likely to need the procedure, leading to an additional cost savings of $714 per patient treated with drug-coated stents. Overall, researchers found that patients with drug-eluting stents each saved an average of $1,350 worth of follow-up care during the year, which projects a total savings of approximately $100 million dollars among the 72,000 drug-eluting stent patients studied.
The researchers note that future studies should focus on how drug therapies including clopidogrel and cholesterol-reducing statin drugs may play a role in outcomes and costs for both types of stent patients. Since recent evidence shows that clopidogrel therapy -- aimed at reducing the risk of blood clots following stent placement -- is an essential step for reducing "late" drug-eluting stent complications or failure, Groeneveld theorizes that clinical outcomes for drug-eluting stent patients might be boosted even further when patients follow an appropriate long-term drug regimen.
This work was supported by an unrestricted grant from the Institute for Health Technology Studies (InHealth), a 501(c)3 foundation based in Washington, DC.
Adapted from materials provided by University of Pennsylvania School of Medicine, via EurekAlert!, a service of AAAS.
The findings, among the first large follow-up studies to show a clear, lifesaving benefit of drug-eluting stents compared to bare metal stents, will be published in the May 27 issue of the Journal of the American College of Cardiology. Patients with the drug-coated stents -- designed not only to open blocked coronary arteries but also to chemically inhibit future blockage -- were less apt to die, have heart attacks or require extra stents or bypass surgery in the two years following placement of the stent.
"This might be a hidden nugget of goodness that could not be detected in clinical trials," says Peter W. Groeneveld, MD, MS, assistant professor in Penn's Division of General Internal Medicine. "There is a distinct possibility that drug-eluting stents not only reduce the need for future cardiac procedures, but also save lives."
Groeneveld and his colleagues studied Medicare data to identify about 72,000 patients who received drug-eluting stents during a nine-month period in 2003, the first year the devices were approved for use in the United States. Overall, the findings showed a clear survival benefit compared to a control group of patients who got bare metal stents -- at 90 days, 1 year and 2 years, patients with drug-coated stents were less likely to die.
In a separate study which will be published in the June issue of the American Heart Journal, Groeneveld also found that drug-eluting stents also offer cost savings during the first year after placement. Although the initial cost of the device -- averaging $16,000 -- outpaces that of a bare metal stent, which costs about $14,000, the Penn researchers found that among patients with the drug-coated stents, 12 percent of those studied needed additional stents placed in the first year, compared to 15 percent of patients who received bare-metal stents.
Few patients in either arm required bypass surgery in the first year following stent placement, but those who received bare-metal stents were twice as likely to need the procedure, leading to an additional cost savings of $714 per patient treated with drug-coated stents. Overall, researchers found that patients with drug-eluting stents each saved an average of $1,350 worth of follow-up care during the year, which projects a total savings of approximately $100 million dollars among the 72,000 drug-eluting stent patients studied.
The researchers note that future studies should focus on how drug therapies including clopidogrel and cholesterol-reducing statin drugs may play a role in outcomes and costs for both types of stent patients. Since recent evidence shows that clopidogrel therapy -- aimed at reducing the risk of blood clots following stent placement -- is an essential step for reducing "late" drug-eluting stent complications or failure, Groeneveld theorizes that clinical outcomes for drug-eluting stent patients might be boosted even further when patients follow an appropriate long-term drug regimen.
This work was supported by an unrestricted grant from the Institute for Health Technology Studies (InHealth), a 501(c)3 foundation based in Washington, DC.
Adapted from materials provided by University of Pennsylvania School of Medicine, via EurekAlert!, a service of AAAS.
Study Links Gene To Success Of A Treatment For High Blood Pressure
Someday, people taking medications for high blood pressure may undergo genetic screening tests that help identify which drug therapies are best for them. University of Washington researchers and colleagues found that people with hypertension who have a particular genetic variant were twice as likely to avoid heart attacks and strokes if they took a diuretic medication.
The study will be published in the April 3 edition of the Journal of the American Medical Association. About 50 million Americans have high blood pressure; about 25 million take medication for it.
"If these findings are confirmed in other studies, screening for the adducin variant could identify hypertensive patients especially likely to benefit from low-dose diuretic therapy," says Dr. Bruce M. Psaty, a professor of medicine, epidemiology and health services and co-director of the UW's Cardiovascular Health Research Unit.
The test for the adducin variant is now a research tool, and Psaty says it’s not appropriate for clinical testing. Additional studies need to define the risks and benefits of genetic testing.
Psaty and co-authors studied the alpha-adducin (pronounced A-dew-sin) gene in a case-control study conducted at Group Health Cooperative, a large health maintenance organization based in Seattle. Adducin is a protein linked to the inner surface of cell membranes, and one adducin genetic variant (Gly460Trp) is known to increase sodium retention by the kidney. High-salt diets, as well as sodium retention, are one cause of high blood pressure. (Table salt is sodium chloride.)
Diuretics are currently recommended as first-line drug therapy for hypertension by the U.S. Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Diuretics lower blood pressure by making the kidney excrete sodium. The idea for the study arose from the observation that diuretics and the adducin variant have opposing effects on sodium handling by the kidney.
The investigators studied 323 hypertensive patients who suffered a first non-fatal heart attack or stroke between 1995 and 1998. The control group included 715 hypertensive patients matched to the cases by age and sex. All participants were taking medications for their high blood pressure.
About one-third of the people in this study had the adducin variant. Diuretics were compared with other drug therapies. The effect of diuretic therapy on the risk of heart attack or stroke depended on the adducin gene variant. Among hypertensive patients who had the normal (wild type) adducin gene, diuretics did not differ from other antihypertensive medications. Among patients with the adducin gene variant, diuretic therapy was associated with a 50 percent lower risk of heart attack or stroke than other blood pressure medications.
"The finding of an adducin-diuretic interaction is a potentially important application of recent work on the human genome, but it needs to be confirmed in other studies," Psaty said.
The interaction persisted when the investigators adjusted for many known risk factors. It was similar in subgroups, and it was specific to diuretics. "Most importantly," Psaty says, "low-dose diuretics prevent complications such as heart attack and stroke." While they may be particularly effective in patients with the adducin variant, large long-term clinical trials have consistently shown that low-dose diuretics are safe and effective for the treatment of high blood pressure in all people. They are also inexpensive.
"If you are taking medicines for high blood pressure, and if you are not on a low-dose diuretic," Psaty adds, "it is reasonable to ask your physician, 'Why not?'"
Psaty's co-investigators are Drs. Nicholas L. Smith, Rozenn N. Lemaitre, Susan R. Heckbert, Alexander Reiner, David Siscovick, Joshua Bis, Thomas Lumley and W.T. Longstreth, Jr, all from the University of Washington; and Hans L. Vos and Frits R. Rosendaal, from the Leiden University Medical Center, the Netherlands. This work represents part of a long-standing collaboration between the UW and the Leiden group. Psaty and Heckbert are also affiliate investigators at Group Health’s Center for Health Studies.
This study was funded by grants from the National Heart, Lung and Blood Institute and the American Heart Association.
Adapted from materials provided by University Of Washington.
The study will be published in the April 3 edition of the Journal of the American Medical Association. About 50 million Americans have high blood pressure; about 25 million take medication for it.
"If these findings are confirmed in other studies, screening for the adducin variant could identify hypertensive patients especially likely to benefit from low-dose diuretic therapy," says Dr. Bruce M. Psaty, a professor of medicine, epidemiology and health services and co-director of the UW's Cardiovascular Health Research Unit.
The test for the adducin variant is now a research tool, and Psaty says it’s not appropriate for clinical testing. Additional studies need to define the risks and benefits of genetic testing.
Psaty and co-authors studied the alpha-adducin (pronounced A-dew-sin) gene in a case-control study conducted at Group Health Cooperative, a large health maintenance organization based in Seattle. Adducin is a protein linked to the inner surface of cell membranes, and one adducin genetic variant (Gly460Trp) is known to increase sodium retention by the kidney. High-salt diets, as well as sodium retention, are one cause of high blood pressure. (Table salt is sodium chloride.)
Diuretics are currently recommended as first-line drug therapy for hypertension by the U.S. Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Diuretics lower blood pressure by making the kidney excrete sodium. The idea for the study arose from the observation that diuretics and the adducin variant have opposing effects on sodium handling by the kidney.
The investigators studied 323 hypertensive patients who suffered a first non-fatal heart attack or stroke between 1995 and 1998. The control group included 715 hypertensive patients matched to the cases by age and sex. All participants were taking medications for their high blood pressure.
About one-third of the people in this study had the adducin variant. Diuretics were compared with other drug therapies. The effect of diuretic therapy on the risk of heart attack or stroke depended on the adducin gene variant. Among hypertensive patients who had the normal (wild type) adducin gene, diuretics did not differ from other antihypertensive medications. Among patients with the adducin gene variant, diuretic therapy was associated with a 50 percent lower risk of heart attack or stroke than other blood pressure medications.
"The finding of an adducin-diuretic interaction is a potentially important application of recent work on the human genome, but it needs to be confirmed in other studies," Psaty said.
The interaction persisted when the investigators adjusted for many known risk factors. It was similar in subgroups, and it was specific to diuretics. "Most importantly," Psaty says, "low-dose diuretics prevent complications such as heart attack and stroke." While they may be particularly effective in patients with the adducin variant, large long-term clinical trials have consistently shown that low-dose diuretics are safe and effective for the treatment of high blood pressure in all people. They are also inexpensive.
"If you are taking medicines for high blood pressure, and if you are not on a low-dose diuretic," Psaty adds, "it is reasonable to ask your physician, 'Why not?'"
Psaty's co-investigators are Drs. Nicholas L. Smith, Rozenn N. Lemaitre, Susan R. Heckbert, Alexander Reiner, David Siscovick, Joshua Bis, Thomas Lumley and W.T. Longstreth, Jr, all from the University of Washington; and Hans L. Vos and Frits R. Rosendaal, from the Leiden University Medical Center, the Netherlands. This work represents part of a long-standing collaboration between the UW and the Leiden group. Psaty and Heckbert are also affiliate investigators at Group Health’s Center for Health Studies.
This study was funded by grants from the National Heart, Lung and Blood Institute and the American Heart Association.
Adapted from materials provided by University Of Washington.
Hypertension Treatment With Diuretics Recommended In New Guide
A study based at The University of Texas Health Science Center at Houston provides added justification that a thiazide-type diuretic is the best first-choice drug for hypertensive patients.
According to the American Heart Association, about one in three U.S. adults has high blood pressure. Uncontrolled high blood pressure can lead to stroke, heart attack, heart failure or kidney failure. A joint national committee (JNC) on the prevention, detection and evaluation of high blood pressure meets on a regular basis to summarize suggested guidelines for doctors on treating hypertension based on medical research.
The findings of the JNC are based on information stemming from a landmark investigation at the UT School of Public Health, which in 2002 established that diuretics were "as good or better" than three other classes of medications for high blood pressure. The original investigation was called ALLHAT - Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
"We found that further analyses of the original ALLHAT trial and information from more recent studies confirmed the original findings that diuretics are the preferred choice for antihypertensive therapy, alone or in combination with other drugs," said Barry Davis, M.D., Ph.D., professor of biostatistics and the director of the Coordinating Center for Clinical Trials at the UT School of Public Health.
"Five years after the ALLHAT results were published, the JNC recommendation still holds," added Davis, who co-authored the study with Jeffrey A. Cutler, M.D., MPH, a consultant to the National Heart, Lung and Blood Institute (NHLBI).
The most recent committee highlighted ALLHAT's findings in the revision of its guidelines, meaning the information will now be used for practical treatments. The committee states that when compared to calcium channel blockers, ACE inhibitors and alpha blockers, thiazide-type diuretics are better first-line drug treatments for hypertensive patients. The diuretics excelled in controlling blood pressure, preventing cardiovascular events, are well tolerated by patients and are relatively inexpensive.
Original ALLHAT findings appear in two articles in a 2002 issue of The Journal of the American Medical Association (JAMA). The project consisted of two clinical trials: one compared a diuretic with newer and more expensive antihypertensive drugs to start blood pressure-lowering treatment to ascertain which was best at preventing cardiovascular outcomes; the other compared a statin drug to usual care in lowering cholesterol levels to determine if treatment would lower the occurrence of deaths over the study period. The articles and details of the study and its findings can be found on the study's web site, http://www.allhat.org.
According to the American Heart Association, about one in three U.S. adults has high blood pressure. Uncontrolled high blood pressure can lead to stroke, heart attack, heart failure or kidney failure. A joint national committee (JNC) on the prevention, detection and evaluation of high blood pressure meets on a regular basis to summarize suggested guidelines for doctors on treating hypertension based on medical research.
The findings of the JNC are based on information stemming from a landmark investigation at the UT School of Public Health, which in 2002 established that diuretics were "as good or better" than three other classes of medications for high blood pressure. The original investigation was called ALLHAT - Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
"We found that further analyses of the original ALLHAT trial and information from more recent studies confirmed the original findings that diuretics are the preferred choice for antihypertensive therapy, alone or in combination with other drugs," said Barry Davis, M.D., Ph.D., professor of biostatistics and the director of the Coordinating Center for Clinical Trials at the UT School of Public Health.
"Five years after the ALLHAT results were published, the JNC recommendation still holds," added Davis, who co-authored the study with Jeffrey A. Cutler, M.D., MPH, a consultant to the National Heart, Lung and Blood Institute (NHLBI).
The most recent committee highlighted ALLHAT's findings in the revision of its guidelines, meaning the information will now be used for practical treatments. The committee states that when compared to calcium channel blockers, ACE inhibitors and alpha blockers, thiazide-type diuretics are better first-line drug treatments for hypertensive patients. The diuretics excelled in controlling blood pressure, preventing cardiovascular events, are well tolerated by patients and are relatively inexpensive.
Original ALLHAT findings appear in two articles in a 2002 issue of The Journal of the American Medical Association (JAMA). The project consisted of two clinical trials: one compared a diuretic with newer and more expensive antihypertensive drugs to start blood pressure-lowering treatment to ascertain which was best at preventing cardiovascular outcomes; the other compared a statin drug to usual care in lowering cholesterol levels to determine if treatment would lower the occurrence of deaths over the study period. The articles and details of the study and its findings can be found on the study's web site, http://www.allhat.org.
Common Foodborne Pathogen In Poultry Finds Resistance To Antibiotic Used By Humans
Recent studies have shown a connection between people who became infected with Campylobacter jejuni, a pathogen found in poultry, and their contact with certain chicken products that contained the pathogen. It also turned out that the Campylobacter jejuni from those products was becoming resistant to ciprofloxacin, a synthetic antibiotic used by humans to fight bacterial infections.
The prevalence of Campylobacter – which is a major cause of foodborne illness – is common on raw poultry. Of these bacteria only Campylobacter jejuni is predominantly pathogenic to humans. The U.S. Department of Agriculture recommends thorough cooking of poultry as a safeguard against pathogenic contamination.
The situation prompted Food Safety Consortium scientists at the University of Arkansas System Division of Agriculture to examine raw chicken carcasses purchased in two Fayetteville, Ark., grocery stores each week for nearly a year.
After examining the 392 chicken carcasses, they found that 85 percent of the chickens purchased from one store had countable levels of Campylobacter (including its non-pathogenic species), with 27 percent of it resistant to ciprofloxacin. At the other store, 46 percent of the carcasses had detectable Campylobacter and 6 percent of that was resistant to ciprofloxacin.
Ramakrishna Nannapaneni, who conducted the research while at Arkansas as a food science post-doctoral associate, said that ciprofloxacin has never been used in animals. However, it is closely related to two other antibiotics, enrofloxacin and sarafloxacin, which were previously approved for usage in poultry between 1995 and 2000 before they were banned on Sept. 12, 2005.
“When Campylobacter became resistant to enrofloxacin or sarafloxacin, it also showed cross-resistance to other fluoroquinolones (a group of antibiotics), such as in human medicine against ciprofloxacin,” said Nannapaneni, now an assistant professor of food science at Mississippi State University.
The results showed a variance in the levels of Campylobacter between the two stores and also the levels of resistance to ciprofloxacin, with one store having markedly lower numbers in each category. Nannapaneni said the difference could be because of variations in packing and storage conditions at the two stores or differences in management of the poultry before harvesting.
“There is a clear need for monitoring the persistence and quantitative reduction of the total antibiotic-resistant Campylobacter loads in the food chain, particularly on raw animal food products, in efforts to control human campylobacteriosis,” Nannapaneni said.
Adapted from materials provided by University of Arkansas, Food Safety Consortium, via Newswise.
The prevalence of Campylobacter – which is a major cause of foodborne illness – is common on raw poultry. Of these bacteria only Campylobacter jejuni is predominantly pathogenic to humans. The U.S. Department of Agriculture recommends thorough cooking of poultry as a safeguard against pathogenic contamination.
The situation prompted Food Safety Consortium scientists at the University of Arkansas System Division of Agriculture to examine raw chicken carcasses purchased in two Fayetteville, Ark., grocery stores each week for nearly a year.
After examining the 392 chicken carcasses, they found that 85 percent of the chickens purchased from one store had countable levels of Campylobacter (including its non-pathogenic species), with 27 percent of it resistant to ciprofloxacin. At the other store, 46 percent of the carcasses had detectable Campylobacter and 6 percent of that was resistant to ciprofloxacin.
Ramakrishna Nannapaneni, who conducted the research while at Arkansas as a food science post-doctoral associate, said that ciprofloxacin has never been used in animals. However, it is closely related to two other antibiotics, enrofloxacin and sarafloxacin, which were previously approved for usage in poultry between 1995 and 2000 before they were banned on Sept. 12, 2005.
“When Campylobacter became resistant to enrofloxacin or sarafloxacin, it also showed cross-resistance to other fluoroquinolones (a group of antibiotics), such as in human medicine against ciprofloxacin,” said Nannapaneni, now an assistant professor of food science at Mississippi State University.
The results showed a variance in the levels of Campylobacter between the two stores and also the levels of resistance to ciprofloxacin, with one store having markedly lower numbers in each category. Nannapaneni said the difference could be because of variations in packing and storage conditions at the two stores or differences in management of the poultry before harvesting.
“There is a clear need for monitoring the persistence and quantitative reduction of the total antibiotic-resistant Campylobacter loads in the food chain, particularly on raw animal food products, in efforts to control human campylobacteriosis,” Nannapaneni said.
Adapted from materials provided by University of Arkansas, Food Safety Consortium, via Newswise.
Exhibiting A Pepper For Every Pot
Peppers don't have to be just green and bell shaped and relegated to the supermarket shelf or home garden plot. This genus of plants has the genetic potential to provide a wide array of possibilities for the kitchen and the ornamental garden and sometimes both at once.
Research on peppers from the Agricultural Research Service (ARS) is being featured from June to November in an exhibit called “A Pepper for Every Pot” at the U.S. Botanic Gardens in Washington, D.C. This exhibit explores the diversity of peppers, including recently introduced varieties, and celebrates peppers’ beauty, flavors and nutritional benefits.
Among new pepper varieties that ARS has already developed are Tangerine Dream and Black Pearl. Tangerine Dream is a sweet, edible ornamental pepper that produces small orange banana-shaped fruit on a prostrate plant. Black Pearl, an All America Selections award winner, offers gardeners a new dark choice: black leaves and shiny black fruit that ripen to bright scarlet. Both varieties are commercially available.
The pretty Black Pearl pepper can also serve as a hot pepper for the kitchen, making it a dual purpose pepper for today's smaller urban gardens.
The pod-type pepper genus—Capsicum—is native to the Western hemisphere and figured strongly in the Aztec, Mayan and Incan cultures, second only in importance to maize. Today, peppers are just as likely to show off in flower gardens as in vegetable gardens. Ornamental peppers have become a profitable crop for commercial growers and retailers. The ornamental plant market is worth nearly $5 billion in the United States each year and specialty peppers could capture a larger portion of those dollars.
ARS plant geneticists John Stommel and Robert Griesbach were drawn to the idea of developing new colorful ornamentals for the garden and the kitchen because considerable diversity exists in the Capsicum genus for fruit and leaf shape, size and color as well as plant habit.
Stommel is with the Genetic Improvement of Fruits and Vegetables Laboratory and Griesbach is with the Floral and Nursery Plants Research Unit, both part of the ARS Henry A. Wallace Beltsville Agricultural Research Center in Beltsville, MD.
ARS is the U.S. Department of Agriculture's chief scientific research agency.
Research on peppers from the Agricultural Research Service (ARS) is being featured from June to November in an exhibit called “A Pepper for Every Pot” at the U.S. Botanic Gardens in Washington, D.C. This exhibit explores the diversity of peppers, including recently introduced varieties, and celebrates peppers’ beauty, flavors and nutritional benefits.
Among new pepper varieties that ARS has already developed are Tangerine Dream and Black Pearl. Tangerine Dream is a sweet, edible ornamental pepper that produces small orange banana-shaped fruit on a prostrate plant. Black Pearl, an All America Selections award winner, offers gardeners a new dark choice: black leaves and shiny black fruit that ripen to bright scarlet. Both varieties are commercially available.
The pretty Black Pearl pepper can also serve as a hot pepper for the kitchen, making it a dual purpose pepper for today's smaller urban gardens.
The pod-type pepper genus—Capsicum—is native to the Western hemisphere and figured strongly in the Aztec, Mayan and Incan cultures, second only in importance to maize. Today, peppers are just as likely to show off in flower gardens as in vegetable gardens. Ornamental peppers have become a profitable crop for commercial growers and retailers. The ornamental plant market is worth nearly $5 billion in the United States each year and specialty peppers could capture a larger portion of those dollars.
ARS plant geneticists John Stommel and Robert Griesbach were drawn to the idea of developing new colorful ornamentals for the garden and the kitchen because considerable diversity exists in the Capsicum genus for fruit and leaf shape, size and color as well as plant habit.
Stommel is with the Genetic Improvement of Fruits and Vegetables Laboratory and Griesbach is with the Floral and Nursery Plants Research Unit, both part of the ARS Henry A. Wallace Beltsville Agricultural Research Center in Beltsville, MD.
ARS is the U.S. Department of Agriculture's chief scientific research agency.
Plant Flavonoid In Celery And Green Peppers Found To Reduce Inflammatory Response In The Brain
Researchers at the University of Illinois report that a plant compound found in abundance in celery and green peppers can disrupt a key component of the inflammatory response in the brain. The findings have implications for research on aging and diseases such as Alzheimer's and multiple sclerosis.
Inflammation can be a blessing or a blight. It is a critical part of the body's immune response that in normal circumstances reduces injury and promotes healing. When it goes awry, however, the inflammatory response can lead to serious physical and mental problems.
Inflammation plays a key role in many neurodegenerative diseases and also is implicated in the cognitive and behavioral impairments seen in aging.
The new study looked at luteolin (LOO-tee-OH-lin), a plant flavonoid known to impede the inflammatory response in several types of cells outside the central nervous system. The purpose of the study was to determine if luteolin could also reduce inflammation the brain, said animal sciences professor and principal investigator Rodney Johnson.
"One of the questions we were interested in is whether something like luteolin, or other bioactive food components, can be used to mitigate age-associated inflammation and therefore improve cognitive function and avoid some of the cognitive deficits that occur in aging," Johnson said.
The researchers first studied the effect of luteolin on microglia. These brain cells are a key component of the immune defense. When infection occurs anywhere in the body, microglia respond by producing inflammatory cytokines, chemical messengers that act in the brain to orchestrate a whole-body response that helps fight the invading microorganism.
This response is associated with many of the most obvious symptoms of illness: sleepiness, loss of appetite, fever and lethargy, and sometimes a temporary diminishment of learning and memory. Neuroinflammation can also lead some neurons to self-destruct, with potentially disastrous consequences if it goes too far.
Graduate research assistant Saebyeol Jang studied the inflammatory response in microglial cells. She spurred inflammation by exposing the cells to lipopolysaccharide (LPS), a component of the cell wall of many common bacteria.
Those cells that were also exposed to luteolin showed a significantly diminished inflammatory response. Jang showed that luteolin was shutting down production of a key cytokine in the inflammatory pathway, interleukin-6 (IL-6). The effects of luteolin exposure were dramatic, resulting in as much as a 90 percent drop in IL-6 production in the LPS-treated cells.
"This was just about as potent an inhibition as anything we had seen previously," Johnson said.
But how was luteolin inhibiting production of IL-6?
Jang began by looking at a class of proteins involved in intracellular signaling, called transcription factors, which bind to specific "promoter" regions on DNA and increase their transcription into RNA and translation into proteins.
Using electromobility shift assays, which measure the binding of transcription factors to DNA promoters, Jang eventually determined that luteolin inhibited IL-6 production by preventing activator protein-1 (AP-1) from binding the IL-6 promoter.
AP-1 is in turn activated by JNK, an upstream protein kinase. Jang found that luteolin inhibited JNK phosphorylation in microglial cell culture. The failure of the JNK to activate the AP-1 transcription factor prevented it from binding to the promoter region on the IL-6 gene and transcription came to a halt.
To see if luteolin might have a similar effect in vivo, the researchers gave mice luteolin-laced drinking water for 21 days before injecting the mice with LPS.
Those mice that were fed luteolin had significantly lower levels of IL-6 in their blood plasma four hours after injection with the LPS. Luteolin also decreased LPS-induced transcription of IL-6 in the hippocampus, a brain region that is critical to spatial learning and memory.
The findings indicate a possible role for luteolin or other bioactive compounds in treating neuroinflammation, Johnson said.
"It might be possible to use flavonoids to inhibit JNK and mitigate inflammatory reactions in the brain," he said. "Inflammatory cytokines such as interleukin-6 are very well known to inhibit certain types of learning and memory that are under the control of the hippocampus, and the hippocampus is also very vulnerable to the insults of aging," he said. "If you had the potential to decrease the production of inflammatory cytokines in the brain you could potentially limit the cognitive deficits that result."
The study appeared recently in Proceedings of the National Academy of Sciences.
Inflammation can be a blessing or a blight. It is a critical part of the body's immune response that in normal circumstances reduces injury and promotes healing. When it goes awry, however, the inflammatory response can lead to serious physical and mental problems.
Inflammation plays a key role in many neurodegenerative diseases and also is implicated in the cognitive and behavioral impairments seen in aging.
The new study looked at luteolin (LOO-tee-OH-lin), a plant flavonoid known to impede the inflammatory response in several types of cells outside the central nervous system. The purpose of the study was to determine if luteolin could also reduce inflammation the brain, said animal sciences professor and principal investigator Rodney Johnson.
"One of the questions we were interested in is whether something like luteolin, or other bioactive food components, can be used to mitigate age-associated inflammation and therefore improve cognitive function and avoid some of the cognitive deficits that occur in aging," Johnson said.
The researchers first studied the effect of luteolin on microglia. These brain cells are a key component of the immune defense. When infection occurs anywhere in the body, microglia respond by producing inflammatory cytokines, chemical messengers that act in the brain to orchestrate a whole-body response that helps fight the invading microorganism.
This response is associated with many of the most obvious symptoms of illness: sleepiness, loss of appetite, fever and lethargy, and sometimes a temporary diminishment of learning and memory. Neuroinflammation can also lead some neurons to self-destruct, with potentially disastrous consequences if it goes too far.
Graduate research assistant Saebyeol Jang studied the inflammatory response in microglial cells. She spurred inflammation by exposing the cells to lipopolysaccharide (LPS), a component of the cell wall of many common bacteria.
Those cells that were also exposed to luteolin showed a significantly diminished inflammatory response. Jang showed that luteolin was shutting down production of a key cytokine in the inflammatory pathway, interleukin-6 (IL-6). The effects of luteolin exposure were dramatic, resulting in as much as a 90 percent drop in IL-6 production in the LPS-treated cells.
"This was just about as potent an inhibition as anything we had seen previously," Johnson said.
But how was luteolin inhibiting production of IL-6?
Jang began by looking at a class of proteins involved in intracellular signaling, called transcription factors, which bind to specific "promoter" regions on DNA and increase their transcription into RNA and translation into proteins.
Using electromobility shift assays, which measure the binding of transcription factors to DNA promoters, Jang eventually determined that luteolin inhibited IL-6 production by preventing activator protein-1 (AP-1) from binding the IL-6 promoter.
AP-1 is in turn activated by JNK, an upstream protein kinase. Jang found that luteolin inhibited JNK phosphorylation in microglial cell culture. The failure of the JNK to activate the AP-1 transcription factor prevented it from binding to the promoter region on the IL-6 gene and transcription came to a halt.
To see if luteolin might have a similar effect in vivo, the researchers gave mice luteolin-laced drinking water for 21 days before injecting the mice with LPS.
Those mice that were fed luteolin had significantly lower levels of IL-6 in their blood plasma four hours after injection with the LPS. Luteolin also decreased LPS-induced transcription of IL-6 in the hippocampus, a brain region that is critical to spatial learning and memory.
The findings indicate a possible role for luteolin or other bioactive compounds in treating neuroinflammation, Johnson said.
"It might be possible to use flavonoids to inhibit JNK and mitigate inflammatory reactions in the brain," he said. "Inflammatory cytokines such as interleukin-6 are very well known to inhibit certain types of learning and memory that are under the control of the hippocampus, and the hippocampus is also very vulnerable to the insults of aging," he said. "If you had the potential to decrease the production of inflammatory cytokines in the brain you could potentially limit the cognitive deficits that result."
The study appeared recently in Proceedings of the National Academy of Sciences.
Physicists Demonstrate Precise Manipulation Of DNA-Drug Interactions
Being able to target the genetic code to develop an effective treatment of a disease is the ultimate goal for many scientists. Focusing on how the DNA interacts with a potential drug is an important element of DNA therapy research. Mark Williams, Ph.D., Associate Professor of Physics at Northeastern University’s College of Arts and Sciences, and his research team have developed a method using optical tweezers to better understand how those interactions occur.
This research, performed primarily by graduate student Thaya Paramanathan, published in a recent edition of the Journal of the American Chemical Society (vol. 130, p. 3752), has the potential to uncover crucial information about how to target DNA in order to develop therapies for chronic diseases such as cancer and AIDS.
DNA, the structure that holds the human genetic code, is composed of nucleic acid bases pairing up and bonding together to form a double helix. Intercalators are molecules that bind between DNA base pairs and have been found to inhibit cell replication, a highly desired quality for potential drug targets. Novel “threading” intercalators have recently been developed to optimize DNA binding. Due to the strength of these bonds and the slow rate of binding, however, it is hard to study the interactions of these intercalators using normal methods, resulting in a limited availability of data and research options.
To address these issues, Mark Williams and his team stretched single DNA molecules using optical tweezers to better control the interactions between the DNA and the potential drug target molecules.
“By studying this threading mechanism on a single DNA molecule, we were able to directly measure the physical characteristics of the interactions between the DNA and potential DNA binding drugs,” said Williams.
The optical tweezers grab the ends of the DNA strand and stretch it out, allowing for the DNA strands to separate more quickly. When the DNA bases separate, the drug molecule, which is dumbbell-shaped and binds with the DNA in the center of the dumb-bell, slides in between the base pairs. When the bond re-forms between the base pairs, the potential drug molecule remains stuck between the DNA strands that form the double helix, and therefore it has formed a very strong bond.
The observations lead to the understanding of how and under what circumstances these bonds occur, which can help in the development of drug therapies that would inhibit or prevent mutated cells from replicating.
“The ability to precisely quantify and characterize the physical mechanism of this threading intercalation should help to fine-tune the desired DNA binding properties,” added Williams.
This research, performed primarily by graduate student Thaya Paramanathan, published in a recent edition of the Journal of the American Chemical Society (vol. 130, p. 3752), has the potential to uncover crucial information about how to target DNA in order to develop therapies for chronic diseases such as cancer and AIDS.
DNA, the structure that holds the human genetic code, is composed of nucleic acid bases pairing up and bonding together to form a double helix. Intercalators are molecules that bind between DNA base pairs and have been found to inhibit cell replication, a highly desired quality for potential drug targets. Novel “threading” intercalators have recently been developed to optimize DNA binding. Due to the strength of these bonds and the slow rate of binding, however, it is hard to study the interactions of these intercalators using normal methods, resulting in a limited availability of data and research options.
To address these issues, Mark Williams and his team stretched single DNA molecules using optical tweezers to better control the interactions between the DNA and the potential drug target molecules.
“By studying this threading mechanism on a single DNA molecule, we were able to directly measure the physical characteristics of the interactions between the DNA and potential DNA binding drugs,” said Williams.
The optical tweezers grab the ends of the DNA strand and stretch it out, allowing for the DNA strands to separate more quickly. When the DNA bases separate, the drug molecule, which is dumbbell-shaped and binds with the DNA in the center of the dumb-bell, slides in between the base pairs. When the bond re-forms between the base pairs, the potential drug molecule remains stuck between the DNA strands that form the double helix, and therefore it has formed a very strong bond.
The observations lead to the understanding of how and under what circumstances these bonds occur, which can help in the development of drug therapies that would inhibit or prevent mutated cells from replicating.
“The ability to precisely quantify and characterize the physical mechanism of this threading intercalation should help to fine-tune the desired DNA binding properties,” added Williams.
Tuesday, 20 May 2008
Low Cholesterol Leads To Lower PSA, Lower Prostate Cancer Risk, Study Suggests
Managing your cholesterol may also help you manage your prostate- specific antigen (PSA) level. Data presented at the 103rd Annual Scientific Meeting of the American Urological Association explored the relationship between low-density lipoprotein (LDL) cholesterol and PSA prior to beginning statin therapy
Data collected from a study of 1,214 men prescribed cholesterol-lowering drugs (statins) between 1990 and 2006 at the Durham Veteran Affairs Medical Center in North Carolina shows that PSA levels were reduced after starting statin medications and that this decline was proportional to the decline in LDL cholesterol.
In 2007, a retrospective study showed that men taking statins to lower their cholesterol also experienced a proportional decline in their PSA levels. This new study confirms that evidence and highlights the fact that cholesterol may play a role in prostate cancer development and progression.
Data was collected from men who were free of prostate cancer, had not undergone prostate surgery or taken medicine to alter androgen levels, and whose PSA was between 0.1 and 10.0 ng/ml. The outcome of this study, if confirmed by additional research, could provide further evidence for the role cholesterol plays in prostate biology.
The results of this study indicate that cholesterol and PSA are valuable indicators of overall health for men and should continue to be monitored together. It remains to be seen whether or not lowering your PSA through statin medications could potentially mask the presence of prostate disease.
--------------------------------------------------------------------------------
Journal reference:
Hamilton RJ, Platz EA, Goldberg KC, Freedland SJ: The association between cholesterol and PSA. J Urol, suppl., 2008; 179: 721, abstract 2094. [link]
Adapted from materials provided by American Urological Association.
Data collected from a study of 1,214 men prescribed cholesterol-lowering drugs (statins) between 1990 and 2006 at the Durham Veteran Affairs Medical Center in North Carolina shows that PSA levels were reduced after starting statin medications and that this decline was proportional to the decline in LDL cholesterol.
In 2007, a retrospective study showed that men taking statins to lower their cholesterol also experienced a proportional decline in their PSA levels. This new study confirms that evidence and highlights the fact that cholesterol may play a role in prostate cancer development and progression.
Data was collected from men who were free of prostate cancer, had not undergone prostate surgery or taken medicine to alter androgen levels, and whose PSA was between 0.1 and 10.0 ng/ml. The outcome of this study, if confirmed by additional research, could provide further evidence for the role cholesterol plays in prostate biology.
The results of this study indicate that cholesterol and PSA are valuable indicators of overall health for men and should continue to be monitored together. It remains to be seen whether or not lowering your PSA through statin medications could potentially mask the presence of prostate disease.
--------------------------------------------------------------------------------
Journal reference:
Hamilton RJ, Platz EA, Goldberg KC, Freedland SJ: The association between cholesterol and PSA. J Urol, suppl., 2008; 179: 721, abstract 2094. [link]
Adapted from materials provided by American Urological Association.
Hypertension Treatment With Diuretics Recommended In New Guide
A study based at The University of Texas Health Science Center at Houston provides added justification that a thiazide-type diuretic is the best first-choice drug for hypertensive patients.
According to the American Heart Association, about one in three U.S. adults has high blood pressure. Uncontrolled high blood pressure can lead to stroke, heart attack, heart failure or kidney failure. A joint national committee (JNC) on the prevention, detection and evaluation of high blood pressure meets on a regular basis to summarize suggested guidelines for doctors on treating hypertension based on medical research.
The findings of the JNC are based on information stemming from a landmark investigation at the UT School of Public Health, which in 2002 established that diuretics were "as good or better" than three other classes of medications for high blood pressure. The original investigation was called ALLHAT - Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
"We found that further analyses of the original ALLHAT trial and information from more recent studies confirmed the original findings that diuretics are the preferred choice for antihypertensive therapy, alone or in combination with other drugs," said Barry Davis, M.D., Ph.D., professor of biostatistics and the director of the Coordinating Center for Clinical Trials at the UT School of Public Health.
"Five years after the ALLHAT results were published, the JNC recommendation still holds," added Davis, who co-authored the study with Jeffrey A. Cutler, M.D., MPH, a consultant to the National Heart, Lung and Blood Institute (NHLBI).
The most recent committee highlighted ALLHAT's findings in the revision of its guidelines, meaning the information will now be used for practical treatments. The committee states that when compared to calcium channel blockers, ACE inhibitors and alpha blockers, thiazide-type diuretics are better first-line drug treatments for hypertensive patients. The diuretics excelled in controlling blood pressure, preventing cardiovascular events, are well tolerated by patients and are relatively inexpensive.
Original ALLHAT findings appear in two articles in a 2002 issue of The Journal of the American Medical Association (JAMA). The project consisted of two clinical trials: one compared a diuretic with newer and more expensive antihypertensive drugs to start blood pressure-lowering treatment to ascertain which was best at preventing cardiovascular outcomes; the other compared a statin drug to usual care in lowering cholesterol levels to determine if treatment would lower the occurrence of deaths over the study period. The articles and details of the study and its findings can be found on the study's web site, http://www.allhat.org.
--------------------------------------------------------------------------------
Journal reference:
Thiazide-type diuretics and beta-adrenergic blockers as first-line drug treatments for hypertension. American Heart Association's Circulation. Volume 117, Issue 20
Adapted from materials provided by University of Texas Health Science Center at Houston.
According to the American Heart Association, about one in three U.S. adults has high blood pressure. Uncontrolled high blood pressure can lead to stroke, heart attack, heart failure or kidney failure. A joint national committee (JNC) on the prevention, detection and evaluation of high blood pressure meets on a regular basis to summarize suggested guidelines for doctors on treating hypertension based on medical research.
The findings of the JNC are based on information stemming from a landmark investigation at the UT School of Public Health, which in 2002 established that diuretics were "as good or better" than three other classes of medications for high blood pressure. The original investigation was called ALLHAT - Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
"We found that further analyses of the original ALLHAT trial and information from more recent studies confirmed the original findings that diuretics are the preferred choice for antihypertensive therapy, alone or in combination with other drugs," said Barry Davis, M.D., Ph.D., professor of biostatistics and the director of the Coordinating Center for Clinical Trials at the UT School of Public Health.
"Five years after the ALLHAT results were published, the JNC recommendation still holds," added Davis, who co-authored the study with Jeffrey A. Cutler, M.D., MPH, a consultant to the National Heart, Lung and Blood Institute (NHLBI).
The most recent committee highlighted ALLHAT's findings in the revision of its guidelines, meaning the information will now be used for practical treatments. The committee states that when compared to calcium channel blockers, ACE inhibitors and alpha blockers, thiazide-type diuretics are better first-line drug treatments for hypertensive patients. The diuretics excelled in controlling blood pressure, preventing cardiovascular events, are well tolerated by patients and are relatively inexpensive.
Original ALLHAT findings appear in two articles in a 2002 issue of The Journal of the American Medical Association (JAMA). The project consisted of two clinical trials: one compared a diuretic with newer and more expensive antihypertensive drugs to start blood pressure-lowering treatment to ascertain which was best at preventing cardiovascular outcomes; the other compared a statin drug to usual care in lowering cholesterol levels to determine if treatment would lower the occurrence of deaths over the study period. The articles and details of the study and its findings can be found on the study's web site, http://www.allhat.org.
--------------------------------------------------------------------------------
Journal reference:
Thiazide-type diuretics and beta-adrenergic blockers as first-line drug treatments for hypertension. American Heart Association's Circulation. Volume 117, Issue 20
Adapted from materials provided by University of Texas Health Science Center at Houston.
Erectile Dysfunction May Signal A Broken Heart
Erectile dysfunction is always a matter of the heart, but new research shows that more than romance is at stake. Two new studies of men with type 2 diabetes found that erectile dysfunction (ED) was a powerful early warning sign for serious heart disease, including heart attack and death.
One of the studies also showed that cholesterol-lowering medications could cut the risk of heart problems by about one-third--and suggested that Viagra and other compounds in the same drug family might offer similar protection.
The research, which was published in the May 27, 2008, issue of the Journal of the American College of Cardiology (JACC), underscores the importance of encouraging men to report ED to their physicians, and of focusing treatment not only on overcoming sexual dysfunction but also on improving overall cardiovascular health.
"The development of erectile dysfunction should alert both patients and healthcare providers to the future risk of coronary heart disease," said Peter Chun-Yip Tong, Ph.D., an associate professor in the Department of Medicine & Therapeutics at The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong. "Other risk factors such as poor blood glucose control, high blood pressure, high cholesterol levels, smoking and obesity should be reviewed and addressed aggressively."
Diabetes, erectile dysfunction and heart disease share an ominous link: damage to the blood vessels by high blood sugar levels. The same process that hinders the extra blood flow needed to maintain an erection can have even more serious consequences in the heart. "The first event is probably endothelial dysfunction--when the smoothness and reactivity of the blood vessel are damaged," said Dr. Tong. "This process encourages local inflammation on the inner surface of the blood vessels and the deposition of cholesterol, resulting in formation of clots and atherosclerosis. Therefore, there is a high risk of blockage of blood vessels in the heart, which can lead to a heart attack."
Men typically show signs of ED more than three years before the onset of symptoms of coronary heart disease. In one study of diabetic men, symptoms of ED always preceded coronary symptoms.
In the Hong Kong-based study, Dr. Tong and his colleagues set out to determine whether ED could be used as an early warning sign of poor cardiovascular health. Researchers recruited 2,306 men with type 2 diabetes, performing a thorough medical evaluation of diabetic control and complications, including damage to the kidneys, eyes and cardiovascular system. At the beginning of the study, just over one-quarter of the study participants had ED. None of the participants had any signs or history of heart disease, vascular disease or stroke.
The researchers followed-up the patients for an average of four years. During that time, 123 men either suffered a heart attack, died from heart disease, developed chest pain caused by clogged arteries, or needed bypass surgery or a catheter procedure to restore blood flow to the heart. Men who had ED at the beginning of the study were far more likely to develop one of these signs of coronary heart disease--or a "CHD event"--than were men who initially did not have ED. Statistical analysis showed that out of every 1,000 diabetic men with ED, 19.7 could be expected to experience a CHD event each year, as compared to only 9.5 of 1,000 diabetic men without ED.
The research team then performed an analysis that included many different characteristics that, like erectile dysfunction, were associated with the development of CHD, including age, high blood pressure, the need for cholesterol- or blood-pressure-lowering medications, the duration of diabetes, and damage to the kidneys or the eyes as a result of diabetes. Even when these characteristics were taken into account, ED was found to be an independent early warning sign of coronary heart disease. In fact, ED signaled a 58 percent increase in the risk of CHD. Only spillage of large amounts of protein in the urine--a sign of extensive kidney damage--was a stronger warning sign, doubling the risk of heart disease.
The second study, conducted by researchers from four medical centers in Italy, focused on 291 men who not only had type 2 diabetes but also silent CHD discovered by stress testing and confirmed by x-ray angiography. Of these, 118 had ED at the beginning of the study. Lead investigator Carmine Gazzaruso, M.D., Ph.D., and his colleagues followed-up patients for an average of nearly four years, documenting major adverse cardiac events (MACE), which they defined as not only CHD events but also stroke, mini-stroke (transient ischemic attacks) and arterial disease in the legs. They found that patients who had ED at the beginning of the study were twice as likely to suffer a major adverse cardiac event when compared to those without ED.
The study also showed that among patients who were taking cholesterol-lowering statins, the risk of MACE was reduced by one third (hazard ratio, 0.66, p = 0.036). Viagra and other medications in a family known as 5-phosphodiesterase (5PDE) inhibitors also appeared to reduce the MACE risk (hazard ratio, 0.68); however this finding was just beyond the cusp of being statically significant (p = 0.056).
"These are important studies," said Robert A. Kloner, M.D., Ph.D., F.A.C.C., a professor of medicine at the Keck School of Medicine at the University of Southern California, and director of research for the Heart Institute at Good Samaritan Hospital in Los Angeles. "While we have known that ED shares many common risk factors with CHD, such as hypertension, smoking, dyslipidemia and diabetes, what is new here is that ED remained a significant risk factor for developing heart disease after controlling for other cardiovascular risk factors.
"Men should know that ED is a true harbinger of atherosclerotic coronary heart disease," he said.
Dr. Kloner, who wrote an editorial about the new studies in the same issue of JACC, also noted that not only have statins been shown to reduce the risk of cardiovascular illness in diabetic patients, controlling blood pressure and other risk factors is also critical.
"In diabetic patients, it is important to not only control the blood sugar level, but also to keep blood pressure below 130/80 mmHg and reduce 'bad' (low-density-lipoprotein, or LDL) cholesterol to less than 100 mg/dL. If a patient smokes, a smoking cessation program is crucial," Dr. Kloner said.
Dr. Tong said that he and his colleagues are continuing to analyze a database of nearly 10,000 patients with diabetes in an attempt to answer several remaining questions about the link between ED, diabetes and heart disease. For example, will improvements in the control of blood sugar and other cardiovascular risk factors reduce the likelihood of developing erectile dysfunction or suffering a heart attack or other serious heart disease" Are patients who have ED in addition to diabetes-related eye problems and kidney problems at higher risk for death or cardiovascular disease" And if so, how great is the increased risk"
"All of these questions are relevant to those who suffer from diabetes," Dr. Tong said. "The information we find will help patients to focus on improving their own health."
--------------------------------------------------------------------------------
Adapted from materials provided by American College of Cardiology.
One of the studies also showed that cholesterol-lowering medications could cut the risk of heart problems by about one-third--and suggested that Viagra and other compounds in the same drug family might offer similar protection.
The research, which was published in the May 27, 2008, issue of the Journal of the American College of Cardiology (JACC), underscores the importance of encouraging men to report ED to their physicians, and of focusing treatment not only on overcoming sexual dysfunction but also on improving overall cardiovascular health.
"The development of erectile dysfunction should alert both patients and healthcare providers to the future risk of coronary heart disease," said Peter Chun-Yip Tong, Ph.D., an associate professor in the Department of Medicine & Therapeutics at The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong. "Other risk factors such as poor blood glucose control, high blood pressure, high cholesterol levels, smoking and obesity should be reviewed and addressed aggressively."
Diabetes, erectile dysfunction and heart disease share an ominous link: damage to the blood vessels by high blood sugar levels. The same process that hinders the extra blood flow needed to maintain an erection can have even more serious consequences in the heart. "The first event is probably endothelial dysfunction--when the smoothness and reactivity of the blood vessel are damaged," said Dr. Tong. "This process encourages local inflammation on the inner surface of the blood vessels and the deposition of cholesterol, resulting in formation of clots and atherosclerosis. Therefore, there is a high risk of blockage of blood vessels in the heart, which can lead to a heart attack."
Men typically show signs of ED more than three years before the onset of symptoms of coronary heart disease. In one study of diabetic men, symptoms of ED always preceded coronary symptoms.
In the Hong Kong-based study, Dr. Tong and his colleagues set out to determine whether ED could be used as an early warning sign of poor cardiovascular health. Researchers recruited 2,306 men with type 2 diabetes, performing a thorough medical evaluation of diabetic control and complications, including damage to the kidneys, eyes and cardiovascular system. At the beginning of the study, just over one-quarter of the study participants had ED. None of the participants had any signs or history of heart disease, vascular disease or stroke.
The researchers followed-up the patients for an average of four years. During that time, 123 men either suffered a heart attack, died from heart disease, developed chest pain caused by clogged arteries, or needed bypass surgery or a catheter procedure to restore blood flow to the heart. Men who had ED at the beginning of the study were far more likely to develop one of these signs of coronary heart disease--or a "CHD event"--than were men who initially did not have ED. Statistical analysis showed that out of every 1,000 diabetic men with ED, 19.7 could be expected to experience a CHD event each year, as compared to only 9.5 of 1,000 diabetic men without ED.
The research team then performed an analysis that included many different characteristics that, like erectile dysfunction, were associated with the development of CHD, including age, high blood pressure, the need for cholesterol- or blood-pressure-lowering medications, the duration of diabetes, and damage to the kidneys or the eyes as a result of diabetes. Even when these characteristics were taken into account, ED was found to be an independent early warning sign of coronary heart disease. In fact, ED signaled a 58 percent increase in the risk of CHD. Only spillage of large amounts of protein in the urine--a sign of extensive kidney damage--was a stronger warning sign, doubling the risk of heart disease.
The second study, conducted by researchers from four medical centers in Italy, focused on 291 men who not only had type 2 diabetes but also silent CHD discovered by stress testing and confirmed by x-ray angiography. Of these, 118 had ED at the beginning of the study. Lead investigator Carmine Gazzaruso, M.D., Ph.D., and his colleagues followed-up patients for an average of nearly four years, documenting major adverse cardiac events (MACE), which they defined as not only CHD events but also stroke, mini-stroke (transient ischemic attacks) and arterial disease in the legs. They found that patients who had ED at the beginning of the study were twice as likely to suffer a major adverse cardiac event when compared to those without ED.
The study also showed that among patients who were taking cholesterol-lowering statins, the risk of MACE was reduced by one third (hazard ratio, 0.66, p = 0.036). Viagra and other medications in a family known as 5-phosphodiesterase (5PDE) inhibitors also appeared to reduce the MACE risk (hazard ratio, 0.68); however this finding was just beyond the cusp of being statically significant (p = 0.056).
"These are important studies," said Robert A. Kloner, M.D., Ph.D., F.A.C.C., a professor of medicine at the Keck School of Medicine at the University of Southern California, and director of research for the Heart Institute at Good Samaritan Hospital in Los Angeles. "While we have known that ED shares many common risk factors with CHD, such as hypertension, smoking, dyslipidemia and diabetes, what is new here is that ED remained a significant risk factor for developing heart disease after controlling for other cardiovascular risk factors.
"Men should know that ED is a true harbinger of atherosclerotic coronary heart disease," he said.
Dr. Kloner, who wrote an editorial about the new studies in the same issue of JACC, also noted that not only have statins been shown to reduce the risk of cardiovascular illness in diabetic patients, controlling blood pressure and other risk factors is also critical.
"In diabetic patients, it is important to not only control the blood sugar level, but also to keep blood pressure below 130/80 mmHg and reduce 'bad' (low-density-lipoprotein, or LDL) cholesterol to less than 100 mg/dL. If a patient smokes, a smoking cessation program is crucial," Dr. Kloner said.
Dr. Tong said that he and his colleagues are continuing to analyze a database of nearly 10,000 patients with diabetes in an attempt to answer several remaining questions about the link between ED, diabetes and heart disease. For example, will improvements in the control of blood sugar and other cardiovascular risk factors reduce the likelihood of developing erectile dysfunction or suffering a heart attack or other serious heart disease" Are patients who have ED in addition to diabetes-related eye problems and kidney problems at higher risk for death or cardiovascular disease" And if so, how great is the increased risk"
"All of these questions are relevant to those who suffer from diabetes," Dr. Tong said. "The information we find will help patients to focus on improving their own health."
--------------------------------------------------------------------------------
Adapted from materials provided by American College of Cardiology.
How Small Molecule Can Take Apart Alzheimer's Disease Protein Fibers
Researchers from the University of Pennsylvania School of Medicine have shown, in unprecedented detail, how a small molecule is able to selectively take apart abnormally folded protein fibers connected to Alzheimer's disease and prion diseases. The findings appear online in the Proceedings of the National Academy of Sciences. Finding a way to dismantle misfolded proteins has implications for new treatments for a host of neurodegenerative diseases.
Abnormal accumulation of amyloid fibers and other misfolded forms in the brain cause neurodegenerative diseases. Similarly, build-up of abnormally folded prion proteins between neurons causes the human version of mad cow disease, Creutzfeldt-Jakob disease.
"Surprisingly, a small molecule called DAPH selectively targets the areas that hold fibers together, and converts fibers to a form that is unable to grow. Normally fibers grow from their ends, but the drug stops this activity," says senior author James Shorter, PhD, Assistant Professor of Biochemistry and Biophysics. "Our data suggest that it is possible to generate effective small molecules that can attack amyloid fibers, which are associated with so many devastating diseases."
The researchers are now working on how DAPH acts as a wedge to stop the fibers from growing. "Presumably DAPH fits very neatly into the crevices between fiber subunits," explains Shorter. "When we grow yeast cells with the prion in the presence of DAPH, they begin to lose the prion. We also saw this in the test tube using pure fibers. The small molecule directly remodels fiber architecture. We've really been able to get at the mechanism by which DAPH, or any small molecule, works for the first time." DAPH was originally found in a screen of small molecules that reduce amyloid-beta toxicity in the lab of co-author Vernon Ingram, Shorter's collaborator at the Massachusetts Institute of Technology (MIT).
In a test tube, if a small amount of amyloid or prion fiber is added to the normal form of the protein, it converts it to the fiber form. But when DPAH is added to the mix, the yeast prion protein does not aggregate into fibers. "It's essentially stopping fiber formation in its tracks," says Huan Wang, first author and research specialist in Shorter's lab. "We were surprised to see two very different proteins, amyloid-beta and Sup35, sensitive to this same small molecule."
The next step is to identify more potent DAPH variants with greater selectivity for deleterious amyloids. Since some amyloids may turn out to be beneficial -- for example, one form may be involved in long-term memory formation -- it will be necessary to find a drug that does not hit all amyloids indiscriminately. "We'd need one that hits only problem amyloids, and DAPH gives us a hint that such selectivity is possible" says Shorter.
This work was initiated in Susan Lindquist's lab at MIT and completed at Penn. The study was funded by the National Institute of General Medical Sciences, the Alzheimer's Association, the Kurt and Johanna Immerwahr Fund for Alzheimer Research, a DuPont-MIT alliance, the American Heart Association, and pilot grants from the University of Pennsylvania Alzheimer's Disease Core Center and Institute on Aging.
.
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Adapted from materials provided by University of Pennsylvania School of Medicine.
Abnormal accumulation of amyloid fibers and other misfolded forms in the brain cause neurodegenerative diseases. Similarly, build-up of abnormally folded prion proteins between neurons causes the human version of mad cow disease, Creutzfeldt-Jakob disease.
"Surprisingly, a small molecule called DAPH selectively targets the areas that hold fibers together, and converts fibers to a form that is unable to grow. Normally fibers grow from their ends, but the drug stops this activity," says senior author James Shorter, PhD, Assistant Professor of Biochemistry and Biophysics. "Our data suggest that it is possible to generate effective small molecules that can attack amyloid fibers, which are associated with so many devastating diseases."
The researchers are now working on how DAPH acts as a wedge to stop the fibers from growing. "Presumably DAPH fits very neatly into the crevices between fiber subunits," explains Shorter. "When we grow yeast cells with the prion in the presence of DAPH, they begin to lose the prion. We also saw this in the test tube using pure fibers. The small molecule directly remodels fiber architecture. We've really been able to get at the mechanism by which DAPH, or any small molecule, works for the first time." DAPH was originally found in a screen of small molecules that reduce amyloid-beta toxicity in the lab of co-author Vernon Ingram, Shorter's collaborator at the Massachusetts Institute of Technology (MIT).
In a test tube, if a small amount of amyloid or prion fiber is added to the normal form of the protein, it converts it to the fiber form. But when DPAH is added to the mix, the yeast prion protein does not aggregate into fibers. "It's essentially stopping fiber formation in its tracks," says Huan Wang, first author and research specialist in Shorter's lab. "We were surprised to see two very different proteins, amyloid-beta and Sup35, sensitive to this same small molecule."
The next step is to identify more potent DAPH variants with greater selectivity for deleterious amyloids. Since some amyloids may turn out to be beneficial -- for example, one form may be involved in long-term memory formation -- it will be necessary to find a drug that does not hit all amyloids indiscriminately. "We'd need one that hits only problem amyloids, and DAPH gives us a hint that such selectivity is possible" says Shorter.
This work was initiated in Susan Lindquist's lab at MIT and completed at Penn. The study was funded by the National Institute of General Medical Sciences, the Alzheimer's Association, the Kurt and Johanna Immerwahr Fund for Alzheimer Research, a DuPont-MIT alliance, the American Heart Association, and pilot grants from the University of Pennsylvania Alzheimer's Disease Core Center and Institute on Aging.
.
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Adapted from materials provided by University of Pennsylvania School of Medicine.
Cancer Drug May Help Patients With Heart-lung Disease
A drug developed to fight cancer is showing early promise as a treatment for pulmonary hypertension, researchers from the University of Chicago Medical Center report May 19 at the American Thoracic Society International Conference in Toronto, Canada.
In the first human trial of sorafenib (Nexavar®) as a treatment for pulmonary hypertension, eight out of the first nine patients increased their ability to exercise. Six out of nine had significant improvements in right ventricular ejection fraction, the ability of the heart to pump blood to the lungs. Four had a significant decrease in pulmonary artery pressures.
"This is not a disease where we are used to seeing people who have been stable on the strongest medications we have suddenly get better," said study author Mardi Gomberg-Maitland, MD, MSc, assistant professor of medicine at the University of Chicago. "We have drugs that may slow progression of the disease but nothing that can stop or reverse the process."
"To see these improvements in such a short time," she said, "is quite promising. Although evaluation of this drug is at a very early stage, and this study focused on safety and tolerability, we are genuinely excited about the results."
Pulmonary hypertension and cancer share certain features. Both diseases involve abnormal cellular growth. In pulmonary hypertension, these abnormal cells line the blood vessels leading from the heart to the lungs. These abnormal cells release signals that stimulate the growth of small new blood vessels. This enables the renegade cells to grow even faster, which thickens the vessel walls and reduces blood flow.
As the arteries close off, pressures within them build up. This requires the heart to pump harder to force blood through the narrowed tubes to the lungs. Eventually the heart can no longer keep up and damage to the overworked muscle begins to accumulate. Sorafenib appears to interfere with that harmful process.
The drug was originally evaluated at the University of Chicago as a treatment for kidney cancer. Gomberg-Maitland -- who is married to a member of the sorafenib-cancer team -- recognized with her husband that its effects also might slow the growth and thickening of the pulmonary artery walls. In an important preclinical trial, she and colleagues demonstrated that sorafenib was effective in reducing pulmonary hypertension in a rat model. With these encouraging results, they organized this trial.
The trial enrolled patients with pulmonary hypertension who had stable disease. Patients in the study continued to take their standard medications, primarily prostacyclin, in combination with sildenafil. They also took sorafenib for 16 weeks, but at doses lower than those given to cancer patients.
"All patients had some improvement," Gomberg-Maitland said. "Some had dramatic improvement."
Most patients in the trial increased their exercise capacity, as measured by time on a treadmill or a six-minute walk test. They had an eight-percent improvement, on average, in right ventricular ejection fraction, as measured by three-dimensional echocardiography. Four patients had significant improvements in the ability of the heart to pump blood to the lungs, as measured by cardiac catheterization.
For Martha Wheeler, 50, of Indianapolis, Indiana, the change in her lifestyle meant more than the study's quantifiable endpoints. Diagnosed 13 years ago, she hadn't been able to play with her granddaughter, ride a bicycle or walk for more than a minute or two. Now she can do all three, including walk three-quarters of a mile. "I can do more than that," she said, "if I push myself."
"Best of all," she added, "I feel like walking. When I get home from work, I want to go out for a good walk. I am thoroughly amazed by it," she said. " I'm going to buy a bike. All that from two little round pills a day."
The side effects of the drug have been relatively mild. The most common adverse effects in cancer patients were rashes, tenderness and itching on the hands and feet and some mild diarrhea and fatigue.
For patients with pulmonary hypertension, diarrhea and hair loss were often the biggest concerns. Patients taking prostacyclins often have facial rashes and flushing but the sorafenib appears to have reduced this effect. Several patients did have their doses reduced because of the skin reaction or hair loss without any detectable loss of benefit.
Wheeler had some hair thinning, "and that bothered me," she said. "But my husband just repeats: 'Grow hair, or breathe? Grow hair, or breathe?' That puts it back in perspective." She has had no other complications and her persistent rash from the prostacylin went away after two weeks on sorafenib.
Although the trial was designed to last only 16 weeks, all of the patients enrolled continue to take the drug. Some have been on it for more than one year.
"This was my first time in a study," said Wheeler. "Here's what it meant to me. I love to sing songs with my granddaughter, but I used to stop after one verse. Yesterday we sang six songs, long songs, with many verses."
Because of the drug's apparent potential and limited side effects, a multi-center, phase-2, placebo-controlled, cross-over study is being organized. It will likely enroll patients with stable disease on pre-existing prostacyclin-based therapy.
"This is an important first step in defining the potential of this new therapy," said pulmonary hypertension specialist Stephen Archer, MD, section chief of cardiology at the University of Chicago Medical Center.
The Doris Duke Foundation, the Section of Cardiology and the Department of Medicine at the University of Chicago Medical Center funded this research.
--------------------------------------------------------------------------------
Adapted from materials provided by University of Chicago Medical Center, via EurekAlert!, a service of AAAS.
In the first human trial of sorafenib (Nexavar®) as a treatment for pulmonary hypertension, eight out of the first nine patients increased their ability to exercise. Six out of nine had significant improvements in right ventricular ejection fraction, the ability of the heart to pump blood to the lungs. Four had a significant decrease in pulmonary artery pressures.
"This is not a disease where we are used to seeing people who have been stable on the strongest medications we have suddenly get better," said study author Mardi Gomberg-Maitland, MD, MSc, assistant professor of medicine at the University of Chicago. "We have drugs that may slow progression of the disease but nothing that can stop or reverse the process."
"To see these improvements in such a short time," she said, "is quite promising. Although evaluation of this drug is at a very early stage, and this study focused on safety and tolerability, we are genuinely excited about the results."
Pulmonary hypertension and cancer share certain features. Both diseases involve abnormal cellular growth. In pulmonary hypertension, these abnormal cells line the blood vessels leading from the heart to the lungs. These abnormal cells release signals that stimulate the growth of small new blood vessels. This enables the renegade cells to grow even faster, which thickens the vessel walls and reduces blood flow.
As the arteries close off, pressures within them build up. This requires the heart to pump harder to force blood through the narrowed tubes to the lungs. Eventually the heart can no longer keep up and damage to the overworked muscle begins to accumulate. Sorafenib appears to interfere with that harmful process.
The drug was originally evaluated at the University of Chicago as a treatment for kidney cancer. Gomberg-Maitland -- who is married to a member of the sorafenib-cancer team -- recognized with her husband that its effects also might slow the growth and thickening of the pulmonary artery walls. In an important preclinical trial, she and colleagues demonstrated that sorafenib was effective in reducing pulmonary hypertension in a rat model. With these encouraging results, they organized this trial.
The trial enrolled patients with pulmonary hypertension who had stable disease. Patients in the study continued to take their standard medications, primarily prostacyclin, in combination with sildenafil. They also took sorafenib for 16 weeks, but at doses lower than those given to cancer patients.
"All patients had some improvement," Gomberg-Maitland said. "Some had dramatic improvement."
Most patients in the trial increased their exercise capacity, as measured by time on a treadmill or a six-minute walk test. They had an eight-percent improvement, on average, in right ventricular ejection fraction, as measured by three-dimensional echocardiography. Four patients had significant improvements in the ability of the heart to pump blood to the lungs, as measured by cardiac catheterization.
For Martha Wheeler, 50, of Indianapolis, Indiana, the change in her lifestyle meant more than the study's quantifiable endpoints. Diagnosed 13 years ago, she hadn't been able to play with her granddaughter, ride a bicycle or walk for more than a minute or two. Now she can do all three, including walk three-quarters of a mile. "I can do more than that," she said, "if I push myself."
"Best of all," she added, "I feel like walking. When I get home from work, I want to go out for a good walk. I am thoroughly amazed by it," she said. " I'm going to buy a bike. All that from two little round pills a day."
The side effects of the drug have been relatively mild. The most common adverse effects in cancer patients were rashes, tenderness and itching on the hands and feet and some mild diarrhea and fatigue.
For patients with pulmonary hypertension, diarrhea and hair loss were often the biggest concerns. Patients taking prostacyclins often have facial rashes and flushing but the sorafenib appears to have reduced this effect. Several patients did have their doses reduced because of the skin reaction or hair loss without any detectable loss of benefit.
Wheeler had some hair thinning, "and that bothered me," she said. "But my husband just repeats: 'Grow hair, or breathe? Grow hair, or breathe?' That puts it back in perspective." She has had no other complications and her persistent rash from the prostacylin went away after two weeks on sorafenib.
Although the trial was designed to last only 16 weeks, all of the patients enrolled continue to take the drug. Some have been on it for more than one year.
"This was my first time in a study," said Wheeler. "Here's what it meant to me. I love to sing songs with my granddaughter, but I used to stop after one verse. Yesterday we sang six songs, long songs, with many verses."
Because of the drug's apparent potential and limited side effects, a multi-center, phase-2, placebo-controlled, cross-over study is being organized. It will likely enroll patients with stable disease on pre-existing prostacyclin-based therapy.
"This is an important first step in defining the potential of this new therapy," said pulmonary hypertension specialist Stephen Archer, MD, section chief of cardiology at the University of Chicago Medical Center.
The Doris Duke Foundation, the Section of Cardiology and the Department of Medicine at the University of Chicago Medical Center funded this research.
--------------------------------------------------------------------------------
Adapted from materials provided by University of Chicago Medical Center, via EurekAlert!, a service of AAAS.
Compound Has Potential For New Class Of AIDS Drugs
Researchers have developed what they believe is the first new mechanism in nearly 20 years for inhibiting a common target used to treat all HIV patients, which could eventually lead to a new class of AIDS drugs.
Researchers at the University of Michigan used computer models to develop the inhibiting compound, and then confirmed in the lab that the compound does indeed inhibit HIV protease, which is an established target for AIDS treatment. The protease is necessary to replicate the virus, says Heather Carlson, U-M professor of medicinal chemistry and principal investigator of the study.
Carlson stresses this is a preliminary step, but still significant.
"It's very easy to make an inhibitor, (but) it's very hard to make a drug," said Carlson, who also has an appointment in chemistry. "This compound is too weak to work in the human body. The key is to find more compounds that will work by the same mechanism."
What's so exciting is how differently that mechanism works from the current drugs used to keep the HIV from maturing and replicating, she says. Current drugs called protease inhibitors work by debilitating the HIV-1 protease. This does the same, but in a different way, Carlson says.
A protease is an enzyme that clips apart proteins, and in the case of HIV drugs, when the HIV-1 protease is inhibited it cannot process the proteins required to assemble an active virus. In existing treatments, a larger molecule binds to the center of the protease, freezing it closed.
The new mechanism targets a different area of the HIV-1 protease, called the flap recognition pocket, and actually holds the protease open. Scientists knew the flaps opened and closed, but didn't know how to target that as a mechanism, Carlson says.
Carlson's group discovered that this flap, when held open by a very small molecule—half the size of the ones used in current drug treatments—also inhibits the protease.
In addition to a new class of drugs, the compound is key because smaller molecules have better drug-like properties and are absorbed much more easily.
"This new class of smaller molecules could have better drug properties (and) could get around current side effects," Carlson said. "HIV dosing regimes are really difficult. You have to take medicine several times in the day. Maybe you wouldn't have to do that with these smaller molecules because they would be absorbed differently."
Kelly Damm, a former student and now at Johnson & Johnson, initially had the idea to target the flaps in this new way, Carlson says.
"In a way, this works like a door jam. If you looked only at the door when it's shut, you'd not know you could put a jam in it," she said. "We saw a spot where we could block the closing event, but because everyone else was working with the closed form, they couldn't see it."
--------------------------------------------------------------------------------
Journal reference:
Kelly L. Damm, Peter M. U. Ung, Jerome J. Quintero, Jason E. Gestwicki, Heather A. Carlson. A poke in the eye: Inhibiting HIV-1 protease through its flap-recognition pocket. Biopolymers. Volume 89, Issue 8 , Pages 643 - doi: 652.10.1002/bip.20993 [link]
Adapted from materials provided by University of Michigan
Researchers at the University of Michigan used computer models to develop the inhibiting compound, and then confirmed in the lab that the compound does indeed inhibit HIV protease, which is an established target for AIDS treatment. The protease is necessary to replicate the virus, says Heather Carlson, U-M professor of medicinal chemistry and principal investigator of the study.
Carlson stresses this is a preliminary step, but still significant.
"It's very easy to make an inhibitor, (but) it's very hard to make a drug," said Carlson, who also has an appointment in chemistry. "This compound is too weak to work in the human body. The key is to find more compounds that will work by the same mechanism."
What's so exciting is how differently that mechanism works from the current drugs used to keep the HIV from maturing and replicating, she says. Current drugs called protease inhibitors work by debilitating the HIV-1 protease. This does the same, but in a different way, Carlson says.
A protease is an enzyme that clips apart proteins, and in the case of HIV drugs, when the HIV-1 protease is inhibited it cannot process the proteins required to assemble an active virus. In existing treatments, a larger molecule binds to the center of the protease, freezing it closed.
The new mechanism targets a different area of the HIV-1 protease, called the flap recognition pocket, and actually holds the protease open. Scientists knew the flaps opened and closed, but didn't know how to target that as a mechanism, Carlson says.
Carlson's group discovered that this flap, when held open by a very small molecule—half the size of the ones used in current drug treatments—also inhibits the protease.
In addition to a new class of drugs, the compound is key because smaller molecules have better drug-like properties and are absorbed much more easily.
"This new class of smaller molecules could have better drug properties (and) could get around current side effects," Carlson said. "HIV dosing regimes are really difficult. You have to take medicine several times in the day. Maybe you wouldn't have to do that with these smaller molecules because they would be absorbed differently."
Kelly Damm, a former student and now at Johnson & Johnson, initially had the idea to target the flaps in this new way, Carlson says.
"In a way, this works like a door jam. If you looked only at the door when it's shut, you'd not know you could put a jam in it," she said. "We saw a spot where we could block the closing event, but because everyone else was working with the closed form, they couldn't see it."
--------------------------------------------------------------------------------
Journal reference:
Kelly L. Damm, Peter M. U. Ung, Jerome J. Quintero, Jason E. Gestwicki, Heather A. Carlson. A poke in the eye: Inhibiting HIV-1 protease through its flap-recognition pocket. Biopolymers. Volume 89, Issue 8 , Pages 643 - doi: 652.10.1002/bip.20993 [link]
Adapted from materials provided by University of Michigan
Cure For The Common Cold? Smallpox Drug May Also Target Some Upper-Respiratory Infections
Scientists at Saint Louis University have made two key discoveries that could lead to the first-ever human testing of a drug to target the adenovirus, which causes a number of severe upper-respiratory infections and is one of many viruses that causes the common cold.
There are currently no drugs approved specifically to treat adenovirus infections in large part because there has been no animal model in which to test drug candidates, a key prerequisite before testing in humans.
SLU researchers and their collaborators, however, have made two breakthrough findings: an animal model suitable for adenovirus testing -- in this case using Syrian hamsters -- and a drug that successfully attacks the adenovirus in those animals. The drug, hexadecyloxypropyl-cidofovir or CMX001, is currently under development by Chimerix, Inc. as a biodefense agent to meet the threat of smallpox or monkeypox viruses and as an antiviral agent in transplant patients.
The SLU research is published the week of May 19 in an early online edition of the Proceedings of the National Academy of Sciences.
"This is exciting news and a major step forward in finding a drug to treat adenovirus infections in humans," said William Wold, Ph.D., professor and chair of the department of molecular microbiology and immunology at the Saint Louis University School of Medicine and the study's lead author.
One of the key obstacles to finding an animal model for adenovirus testing involves the fact that the virus is generally species-specific; meaning the human version of the virus doesn't replicate well in animals commonly used in laboratory research.
The SLU researchers, however, found that the adenovirus replicates in Syrian hamsters (also called golden hamsters) with suppressed immune systems in much the same manner as it replicates in humans whose immune systems are weakened -- making Syrian hamsters ideal for animal model testing.
"We are pleased to see that CMX001, a drug candidate showing broad antiviral activity that is being developed under a federal grant for smallpox, also has potential benefit against adenovirus," said George R. Painter, Ph.D., president and CEO of Chimerix.
Said Samuel Stanley Jr., director of the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (MRCE): "It is exciting to see work funded by the National Institute of Allergy and Infectious Diseases' MRCE program lead to potential new therapies for this important virus."
There are 52 known serotypes, or strains, of adenovirus in humans. They generally cause acute upper respiratory infections including colds, tonsillitis and ear infections, but they can also cause conjunctivitis, gastroenteritis and bladder infections.
Most people are able to recover from an adenovirus infection, but in some young children and people with weakened immune systems, adenovirus infections can turn virulent and even deadly. Adenovirus can also cause disease and even death in organ transplant recipients. Severe adenovirus outbreaks have occurred among groups of military recruits likely due to crowded living conditions.
CMX001 is an oral pro-drug, or derivative, of cidofovir, a drug developed by Gilead Sciences, Inc. to treat a type of retinitis in AIDS patients. Chimerix licensed from Gilead the rights to develop CMX001.
Cidofovir has long been a possible candidate to treat a number of virus infections, including the herpes virus, poxvirus and adenovirus infections in humans. The drug, however, is quite toxic to the liver and kidneys and is not available in oral form, which limits widespread use.
Using the new animal model, the SLU researchers found that CMX001 provided protection from the adenovirus when it was administered prophylactically (before infection with the virus) or therapeutically (after infection). The scientists found that the drug worked by greatly reducing the ability of the virus to replicate in key organs, mostly notably the liver.
The SLU team also found that CMX001 was much less toxic and far more powerful than cidofovir. In addition, scientists discovered, two weeks after infection with the virus CMX001 had reduced the viral load in the liver and blood to undetectable levels.
In addition to Wold and Painter, others who participated in the research include Karoly Toth, D.V.M., Jacqueline F. Spencer, John E. Sagartz, D.V.M., Ph.D., and R. Mark Buller, Ph.D., all of the Saint Louis University School of Medicine.
There are currently no drugs approved specifically to treat adenovirus infections in large part because there has been no animal model in which to test drug candidates, a key prerequisite before testing in humans.
SLU researchers and their collaborators, however, have made two breakthrough findings: an animal model suitable for adenovirus testing -- in this case using Syrian hamsters -- and a drug that successfully attacks the adenovirus in those animals. The drug, hexadecyloxypropyl-cidofovir or CMX001, is currently under development by Chimerix, Inc. as a biodefense agent to meet the threat of smallpox or monkeypox viruses and as an antiviral agent in transplant patients.
The SLU research is published the week of May 19 in an early online edition of the Proceedings of the National Academy of Sciences.
"This is exciting news and a major step forward in finding a drug to treat adenovirus infections in humans," said William Wold, Ph.D., professor and chair of the department of molecular microbiology and immunology at the Saint Louis University School of Medicine and the study's lead author.
One of the key obstacles to finding an animal model for adenovirus testing involves the fact that the virus is generally species-specific; meaning the human version of the virus doesn't replicate well in animals commonly used in laboratory research.
The SLU researchers, however, found that the adenovirus replicates in Syrian hamsters (also called golden hamsters) with suppressed immune systems in much the same manner as it replicates in humans whose immune systems are weakened -- making Syrian hamsters ideal for animal model testing.
"We are pleased to see that CMX001, a drug candidate showing broad antiviral activity that is being developed under a federal grant for smallpox, also has potential benefit against adenovirus," said George R. Painter, Ph.D., president and CEO of Chimerix.
Said Samuel Stanley Jr., director of the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (MRCE): "It is exciting to see work funded by the National Institute of Allergy and Infectious Diseases' MRCE program lead to potential new therapies for this important virus."
There are 52 known serotypes, or strains, of adenovirus in humans. They generally cause acute upper respiratory infections including colds, tonsillitis and ear infections, but they can also cause conjunctivitis, gastroenteritis and bladder infections.
Most people are able to recover from an adenovirus infection, but in some young children and people with weakened immune systems, adenovirus infections can turn virulent and even deadly. Adenovirus can also cause disease and even death in organ transplant recipients. Severe adenovirus outbreaks have occurred among groups of military recruits likely due to crowded living conditions.
CMX001 is an oral pro-drug, or derivative, of cidofovir, a drug developed by Gilead Sciences, Inc. to treat a type of retinitis in AIDS patients. Chimerix licensed from Gilead the rights to develop CMX001.
Cidofovir has long been a possible candidate to treat a number of virus infections, including the herpes virus, poxvirus and adenovirus infections in humans. The drug, however, is quite toxic to the liver and kidneys and is not available in oral form, which limits widespread use.
Using the new animal model, the SLU researchers found that CMX001 provided protection from the adenovirus when it was administered prophylactically (before infection with the virus) or therapeutically (after infection). The scientists found that the drug worked by greatly reducing the ability of the virus to replicate in key organs, mostly notably the liver.
The SLU team also found that CMX001 was much less toxic and far more powerful than cidofovir. In addition, scientists discovered, two weeks after infection with the virus CMX001 had reduced the viral load in the liver and blood to undetectable levels.
In addition to Wold and Painter, others who participated in the research include Karoly Toth, D.V.M., Jacqueline F. Spencer, John E. Sagartz, D.V.M., Ph.D., and R. Mark Buller, Ph.D., all of the Saint Louis University School of Medicine.
Immunosuppressive Drugs Are A Double-edged Sword To Type 1 Diabetics
Type 1 diabetes is caused when immune cells attack and destroy the insulin producing beta-cells of the pancreas.
Although insulin injections have changed the life of type I diabetics, they neither cure the disease nor prevent its severe complications. It was hoped that islet transplantation would provide a cure, however, transplant success is short-lived and accompanied by significant side effects.
New data from Yuval Dor and colleagues at the Hebrew University-Hadassah Medical School, Jerusalem, have indicated that the immunosuppressive drugs used to prevent rejection of islet transplants suppress beta-cell regeneration in diabetic mice.
As mentioned by the authors and discussed in the accompanying commentary by Klaus Kaestner from the University of Pennsylvania, Philadelphia, this raises the possibility that if immunosuppressive drugs that do not inhibit beta-cell regeneration can be identified successful regenerative islet transplantation might become a reality.
Article: Recovery from diabetes in mice by beta-cell regeneration
Although insulin injections have changed the life of type I diabetics, they neither cure the disease nor prevent its severe complications. It was hoped that islet transplantation would provide a cure, however, transplant success is short-lived and accompanied by significant side effects.
New data from Yuval Dor and colleagues at the Hebrew University-Hadassah Medical School, Jerusalem, have indicated that the immunosuppressive drugs used to prevent rejection of islet transplants suppress beta-cell regeneration in diabetic mice.
As mentioned by the authors and discussed in the accompanying commentary by Klaus Kaestner from the University of Pennsylvania, Philadelphia, this raises the possibility that if immunosuppressive drugs that do not inhibit beta-cell regeneration can be identified successful regenerative islet transplantation might become a reality.
Article: Recovery from diabetes in mice by beta-cell regeneration
Doctors Combine Cell Biology, Endocrinology to Eliminate Insulin Implants
Some diabetes patients who cannot live without insulin injections now have a new option: a transplant of islet cells, which produce insulin in the body. Drawing upon advances in cell biology and endocrinology, surgeons go through a 14-hour process to isolate and purify the islet cells from a donated pancreas. While there's no guarantee the success will last, it may prevent some life-threatening situations.
CHARLOTTE, N.C.--Diabetic patients who couldn't live without insulin injections are now enjoying insulin independence thanks to a new type of transplant.
Annie Anderson has a refreshing outlook on life, but that wasn't the case a few months ago. Anderson, an islet cell transplant patient says, "Totally unaware of where I was ... didn't know what had happened ... very confused -- I couldn't speak. My mind was working, but I couldn't get words out." Anderson is describing the scene that unfolded when her diabetes caused her to slip into unconsciousness. Episodes like that are no longer a threat for her. Becasue her type 1 diabetes was corrected through an experimental cell transplant.
Dr. Paul Gores, director of pancreas and islet transplantation at Carolinas Medical Center in Charlotte, N.C., says, "An islet cell transplant is a means of reversing diabetes in a patient who has lost their beta cells, which are the important cells within the little clusters of cells we call islets, which reside inside the pancreas, which produce insulin."
Transplant surgeons go through a painstaking 14-hour process to isolate and purify the islet cells from a donated pancreas. Those cells will produce insulin. Patients who go through the procedure must take immune-suppressing drugs for life with no guarantee the success will last. Dr. Gores says, "Of course, we don't know that at six, seven, eight, nine years maybe the insulin production they have right now might just totally go away and they might get totally back to square one."
For Anderson, there is no question the transplant was the right choice. She says, "It's totally changed my life, and I am so fortunate and grateful."
The longest study shows about 80 percent of patients still produce some insulin five years after their islet cell transplant, but not enough to continue to go without insulin injections. Only about 2 percent of type 1 diabetics are considered candidates for islet cell transplantation at this point, but doctors hope that number will increase.
CHARLOTTE, N.C.--Diabetic patients who couldn't live without insulin injections are now enjoying insulin independence thanks to a new type of transplant.
Annie Anderson has a refreshing outlook on life, but that wasn't the case a few months ago. Anderson, an islet cell transplant patient says, "Totally unaware of where I was ... didn't know what had happened ... very confused -- I couldn't speak. My mind was working, but I couldn't get words out." Anderson is describing the scene that unfolded when her diabetes caused her to slip into unconsciousness. Episodes like that are no longer a threat for her. Becasue her type 1 diabetes was corrected through an experimental cell transplant.
Dr. Paul Gores, director of pancreas and islet transplantation at Carolinas Medical Center in Charlotte, N.C., says, "An islet cell transplant is a means of reversing diabetes in a patient who has lost their beta cells, which are the important cells within the little clusters of cells we call islets, which reside inside the pancreas, which produce insulin."
Transplant surgeons go through a painstaking 14-hour process to isolate and purify the islet cells from a donated pancreas. Those cells will produce insulin. Patients who go through the procedure must take immune-suppressing drugs for life with no guarantee the success will last. Dr. Gores says, "Of course, we don't know that at six, seven, eight, nine years maybe the insulin production they have right now might just totally go away and they might get totally back to square one."
For Anderson, there is no question the transplant was the right choice. She says, "It's totally changed my life, and I am so fortunate and grateful."
The longest study shows about 80 percent of patients still produce some insulin five years after their islet cell transplant, but not enough to continue to go without insulin injections. Only about 2 percent of type 1 diabetics are considered candidates for islet cell transplantation at this point, but doctors hope that number will increase.
Embryonic Pathway Delivers Stem Cell Traits
Studies of how cancer cells spread have led to a surprising discovery about the creation of cells with adult stem cell characteristics, offering potentially major implications for regenerative medicine and for cancer treatment.
Some cancer cells acquire the ability to migrate through the body by re-activating biological programs that have lain dormant since the embryo stage, as the lab of Whitehead Member Robert Weinberg has helped to demonstrate in recent years. Now scientists in the Weinberg lab have shown that both normal and cancer cells that are induced to follow one of these pathways may gain properties of adult stem cells, including the ability to self-renew.
In a paper published online by Cell on May 15, former postdoctoral researcher Sendurai Mani and his colleagues demonstrated in mice and in human cells that cells that have undergone an "epithelial-to-mesenchymal" (EMT) transition acquire several important characteristics of stem cells. Conversely, the researchers also showed that naturally existing normal stem cells as well as tumor-seeding cancer stem cells show characteristics of the post-EMT cells, including the acquisition of mesenchymal cell traits, which are usually associated with connective tissue cells.
Epithelial cells, which make up most of the human body, bind together in sheet-like structures. In embryonic development, the EMT process breaks up cell-cell adhesion in the epithelial layer, and converts epithelial cells into more loosely associated mesenchymal cells. In the context of cancer development, some cancer cells within a primary cancer may undergo an EMT, migrate through the body to their end destination, and there resume their epithelial form through a reverse process (the mesenchymal-to-epithelial transition).
Mani and his colleagues have identified FOXC2, one of the key genes involved in invasion and metastasis. In addition, FOXC2 appears to program the metastatic ability of some breast cancers.
Mani knew that during embryonic development, FOXC2 expression is restricted to mesoderm and mesoderm-derived cells when they are in an undifferentiated state, and its expression disappears once these cells differentiate. Similarly, his experiments showed that epithelial cells that undergo EMT express FOXC2, but that expression is lost when they revert back to an epithelial state.
In collaboration with Andrea Richardson and Jeffery Kutok, pathologists at Boston's Brigham and Women's Hospital, Mani went on to study FOXC2 expression in normal human breast tissue. It turned out that such cells were located precisely where researchers expect to find mammary epithelial stem cells.
As he pondered these findings and the earlier results about FOXC2's role in metastasis, Mani wondered: Just what were these cells generated by EMT that expressed FOXC2?
Were they simply fibroblasts, the most common cells in normal connective tissue? Or were they actually stem cells?
"I asked Mai-Jing Liao, another postdoc in the Weinberg lab, to check whether the cells generated by EMT would have any stem cell properties," recalls Mani, now an assistant professor in the department of molecular pathology at the University of Texas's M. D. Anderson Cancer Center in Houston. "He said, 'You must be out of your mind, but it won't take more than half an hour to check.'"
Much to Liao's surprise, when he examined cells that had undergo an EMT, his tests did highlight surface proteins that are key markers for stem cells.
The researchers found that the cells that underwent the EMT process were mesenchymal-like in appearance and demonstrated stem-cell surface markers. The cells also displayed an increased ability to grow in suspension, forming structures called mammospheres--another trait of mammary stem cells. Some cells in the resulting mammospheres showed, in turn, stem cell markers, indicating they could differentiate into two kinds of mammary cells. And cells in the mammospheres retained their stem cell properties even after the EMT induction process was stopped.
Furthermore, when the Weinberg lab scientists isolated stem-cell-like cells from cultured human mammary epithelial cells or from mouse breast tissue, their properties were very similar to the EMT-induced cells. Working with Kornelia Polyak of Dana-Farber Cancer Institute and Harvard Medical School, Mani found that this was also true with normal and tumor cells obtained from human patients.
"This for us is a very exciting discovery, not only because of its unexpectedness but because it offers a route by which one could in principle generate unlimited numbers of stem cells committed to create a specific cell type," says Weinberg, who is also a professor of biology at Massachusetts Institute of Technology. "One could imagine, for example, that if one takes skin cells and induces them to undergo an EMT, they could become skin stem cells."
Importantly, the researchers also demonstrated that inducing the EMT process can produce cells with many characteristics of cancer stem cells. (Beginning in 2003, scientists in various labs have identified these self-renewing, tumor-seeding cells in a number of solid tumors.)
This finding could help to answer a key question about metastasis: When tumor cells spread into different sites, how do they multiply enough to form a dangerous new tumor?
"If you take a population of human cancer cells that normally form a tumor very inefficiently and induce an EMT, their tumor-initiating abilities increase by about a hundred-fold, so that it takes about 10,000 cells rather than a million cells to form a tumor," says Wenjun Guo, co-lead author on the paper and postdoctoral researcher in the Weinberg lab. "This suggests cancer stem cells are using pre-existing normal stem cell machinery to propagate their own self-renewal and therefore their tumor-initiating ability."
Mani is continuing his research on the EMT/cancer stem cell connection and its role in cancer metastasis at the M. D. Anderson Cancer Center. Researchers in the Weinberg lab will investigate the EMT process with other cell lines. They also will attempt to give final proof in mice that the process creates completely defined stem cells, by taking cells from mouse mammary fat pads, inducing an EMT for some of the cells, returning the resulting cells to the fat pad, and seeing if they can regenerate the mammary gland.
This research was supported by the Breast Cancer Research Foundation, the MIT Ludwig Center for Molecular Oncology and the National Cancer Institute. Mani was supported by a Department of Defense postdoctoral fellowship.
--------------------------------------------------------------------------------
Journal reference:
Sendurai A. Mani, Wenjun Guo, Mai-Jing Liao, Elinor Ng Eaton, Ayyakkannu Ayyanan, Alicia Zhou, Mary Brooks, Ferenc Reinhard, Cheng Cheng Zhang, Michail Shipitsin, Lauren L. Campbell, Kornelia Polyak, Cathrin Brisken, Jing Yang , Robert A. Weinberg. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, online publication May 15, Print Edition, Volume 133 (4).
Adapted from materials provided by Whitehead Institute for Biomedical Research.
Some cancer cells acquire the ability to migrate through the body by re-activating biological programs that have lain dormant since the embryo stage, as the lab of Whitehead Member Robert Weinberg has helped to demonstrate in recent years. Now scientists in the Weinberg lab have shown that both normal and cancer cells that are induced to follow one of these pathways may gain properties of adult stem cells, including the ability to self-renew.
In a paper published online by Cell on May 15, former postdoctoral researcher Sendurai Mani and his colleagues demonstrated in mice and in human cells that cells that have undergone an "epithelial-to-mesenchymal" (EMT) transition acquire several important characteristics of stem cells. Conversely, the researchers also showed that naturally existing normal stem cells as well as tumor-seeding cancer stem cells show characteristics of the post-EMT cells, including the acquisition of mesenchymal cell traits, which are usually associated with connective tissue cells.
Epithelial cells, which make up most of the human body, bind together in sheet-like structures. In embryonic development, the EMT process breaks up cell-cell adhesion in the epithelial layer, and converts epithelial cells into more loosely associated mesenchymal cells. In the context of cancer development, some cancer cells within a primary cancer may undergo an EMT, migrate through the body to their end destination, and there resume their epithelial form through a reverse process (the mesenchymal-to-epithelial transition).
Mani and his colleagues have identified FOXC2, one of the key genes involved in invasion and metastasis. In addition, FOXC2 appears to program the metastatic ability of some breast cancers.
Mani knew that during embryonic development, FOXC2 expression is restricted to mesoderm and mesoderm-derived cells when they are in an undifferentiated state, and its expression disappears once these cells differentiate. Similarly, his experiments showed that epithelial cells that undergo EMT express FOXC2, but that expression is lost when they revert back to an epithelial state.
In collaboration with Andrea Richardson and Jeffery Kutok, pathologists at Boston's Brigham and Women's Hospital, Mani went on to study FOXC2 expression in normal human breast tissue. It turned out that such cells were located precisely where researchers expect to find mammary epithelial stem cells.
As he pondered these findings and the earlier results about FOXC2's role in metastasis, Mani wondered: Just what were these cells generated by EMT that expressed FOXC2?
Were they simply fibroblasts, the most common cells in normal connective tissue? Or were they actually stem cells?
"I asked Mai-Jing Liao, another postdoc in the Weinberg lab, to check whether the cells generated by EMT would have any stem cell properties," recalls Mani, now an assistant professor in the department of molecular pathology at the University of Texas's M. D. Anderson Cancer Center in Houston. "He said, 'You must be out of your mind, but it won't take more than half an hour to check.'"
Much to Liao's surprise, when he examined cells that had undergo an EMT, his tests did highlight surface proteins that are key markers for stem cells.
The researchers found that the cells that underwent the EMT process were mesenchymal-like in appearance and demonstrated stem-cell surface markers. The cells also displayed an increased ability to grow in suspension, forming structures called mammospheres--another trait of mammary stem cells. Some cells in the resulting mammospheres showed, in turn, stem cell markers, indicating they could differentiate into two kinds of mammary cells. And cells in the mammospheres retained their stem cell properties even after the EMT induction process was stopped.
Furthermore, when the Weinberg lab scientists isolated stem-cell-like cells from cultured human mammary epithelial cells or from mouse breast tissue, their properties were very similar to the EMT-induced cells. Working with Kornelia Polyak of Dana-Farber Cancer Institute and Harvard Medical School, Mani found that this was also true with normal and tumor cells obtained from human patients.
"This for us is a very exciting discovery, not only because of its unexpectedness but because it offers a route by which one could in principle generate unlimited numbers of stem cells committed to create a specific cell type," says Weinberg, who is also a professor of biology at Massachusetts Institute of Technology. "One could imagine, for example, that if one takes skin cells and induces them to undergo an EMT, they could become skin stem cells."
Importantly, the researchers also demonstrated that inducing the EMT process can produce cells with many characteristics of cancer stem cells. (Beginning in 2003, scientists in various labs have identified these self-renewing, tumor-seeding cells in a number of solid tumors.)
This finding could help to answer a key question about metastasis: When tumor cells spread into different sites, how do they multiply enough to form a dangerous new tumor?
"If you take a population of human cancer cells that normally form a tumor very inefficiently and induce an EMT, their tumor-initiating abilities increase by about a hundred-fold, so that it takes about 10,000 cells rather than a million cells to form a tumor," says Wenjun Guo, co-lead author on the paper and postdoctoral researcher in the Weinberg lab. "This suggests cancer stem cells are using pre-existing normal stem cell machinery to propagate their own self-renewal and therefore their tumor-initiating ability."
Mani is continuing his research on the EMT/cancer stem cell connection and its role in cancer metastasis at the M. D. Anderson Cancer Center. Researchers in the Weinberg lab will investigate the EMT process with other cell lines. They also will attempt to give final proof in mice that the process creates completely defined stem cells, by taking cells from mouse mammary fat pads, inducing an EMT for some of the cells, returning the resulting cells to the fat pad, and seeing if they can regenerate the mammary gland.
This research was supported by the Breast Cancer Research Foundation, the MIT Ludwig Center for Molecular Oncology and the National Cancer Institute. Mani was supported by a Department of Defense postdoctoral fellowship.
--------------------------------------------------------------------------------
Journal reference:
Sendurai A. Mani, Wenjun Guo, Mai-Jing Liao, Elinor Ng Eaton, Ayyakkannu Ayyanan, Alicia Zhou, Mary Brooks, Ferenc Reinhard, Cheng Cheng Zhang, Michail Shipitsin, Lauren L. Campbell, Kornelia Polyak, Cathrin Brisken, Jing Yang , Robert A. Weinberg. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, online publication May 15, Print Edition, Volume 133 (4).
Adapted from materials provided by Whitehead Institute for Biomedical Research.
Wednesday, 14 May 2008
The role of melanin as protector against free radicals in skin and its role as free radical indicator in hair
Throughout the body, melanin is a homogenous biological polymer containing a population of intrinsic, semiquinone-like radicals. Additional extrinsic free radicals are reversibly photo-generated by UV and visible light. Melanin photochemistry, particularly the formation and decay of extrinsic radicals, has been the subject of numerous electron spin resonance (ESR) spectroscopy studies. Several melanin monomers exist, and the predominant monomer in a melanin polymer depends on its location within an organism. In skin and hair, melanin differs in content of eumelanin or pheomelanin.
Its bioradical character and its susceptibility to UV irradiation makes melanin an excellent indicator for UV-related processes in both skin and hair.
The existence of melanin in skin is strongly correlated with the prevention against free radicals/ROS generated by UV radiation. Especially in the skin melanin (mainly eumelanin) ensures the only natural UV protection by eliminating the generated free radicals/ROS. Melanin in hair can be used as a free radical detector for evaluating the efficacy of hair care products.
The aim of this study was to investigate the suitability of melanin as protector of skin against UV generated free radicals and as free radical indicator in hair.
Keywords: Skin; Hair; Melanin; UV irradiation; Free radical; ESR spectroscopy
Author: Thomas Herrlinga, , , Katinka Jungb and Jürgen Fuchsc
Its bioradical character and its susceptibility to UV irradiation makes melanin an excellent indicator for UV-related processes in both skin and hair.
The existence of melanin in skin is strongly correlated with the prevention against free radicals/ROS generated by UV radiation. Especially in the skin melanin (mainly eumelanin) ensures the only natural UV protection by eliminating the generated free radicals/ROS. Melanin in hair can be used as a free radical detector for evaluating the efficacy of hair care products.
The aim of this study was to investigate the suitability of melanin as protector of skin against UV generated free radicals and as free radical indicator in hair.
Keywords: Skin; Hair; Melanin; UV irradiation; Free radical; ESR spectroscopy
Author: Thomas Herrlinga, , , Katinka Jungb and Jürgen Fuchsc
INGREDIENTS OF SKIN WHITENING
Kojic dipalmitate is derived from Japanese mushrooms. Kojic dipalmitate inhibits the production of Melanine by deactivating the enzyme Tyrosinase (which stimulates Melanine formation). Kojic dipalmitate also possesses both antibacterial and antifungal activities.
Glycyrrhiza Glabra Extract Licorice has an anti-inflammatory and lightening activity similar to cortisone. This enhances the active ingredient, Kojic Dipalmitate.
Imperata Cylindrica Extract -used for it’s analgesic and anti-inflammatory effect. It is also a whitening agent which works together with the Kojic Dipalmitate.
Butyrospermum Parkii (Shea Butter) This precious vegetable oil, commonly referred to as Shea Butter, comes from the Shea Tree. Comprised of saturated and unsaturated fatty acids, as well as Vitamin E and Carotene, this oil acts as a soothing moisturizer and emollient for the skin. It possesses protective properties against environmental influences, including UV rays and sun allergies. Rosa gallica Rosa gallica is an old fashioned, sweetly fragrant rose whose precious, rich oil is used to soften, balance, and restore the skin.
Arctostaphylos uva-ursi L. Sprengel. Bearberry-leaf extract possesses marked antioxidant activity.
Mitracarpus Scaber Extract Mitracarpus scaber extract is a botanically derived lightening agent from the leaves of this tropical plant. It prevents the actions of tyrosinase which causes melanin formation. The active ingredient found in Mitracarpus scaber extract is harounoside, which is effective in skin lightening.
Carthamis Tinctorius Oil. A highly moisturizing oil with an exceptionally high amount of Oleic acids. Deeply soothing and one of the first choices for skin care blends or recipes requiring moisturizing benefits.
Prunus Amygdalus Dulcis oil. Sweet almond oil is obtained from the dried kernels of the almond tree. It is an excellent emollient, softening and soothing to the skin. It also helps to balance the loss and absorption of moisture, resulting in moisturised skin.
Daucus Carota Sativa (carrot) root extract Carrot root extract. Can help protect the skin from free-radical damage and promotes production of new cells. Excellent for dry and mature skins.
Aloe Barbadensis The latin name for the Aloe plant. It rehydrates and softens the skin and helps soothe irritated or sensitive areas. It is considered one of nature's most effective remedies for sunburn and skin irritations, and a superb hydrator for dry skin.
Glyceryl Stearate A monoester of glycerin and stearic acid. An emollient and emulsifier.
Ceteareth 20 - Used in oil-in-water emulsions. Provides exceptionally stable emulsions when used in combination with another emulsifier such as glyceryl stearate Ceteareth-10 Is an non-ionic surfactants compond, fequently used as emulsifiers in cosmetics
Cetearyl Alcohol A mixture of fatty alcohols derived from coconut oil consisting predominantly of cetyl and stearyl alcohols. Used as emollients, thickeners and emulsion stabilizers.
Cetyl Palmitate Emollient.
Caprilic / Capric Triglyceride Various vegetable oils, dairy fats, plants and sweat are the sources of this ingredient with good emollient properties.
Glycerin A humectant that absorbs moisture from the air to keep hair and skin moist. It is also used as an emollient (skin smoothener and softener), lubricant (skin lubricator that helps prevents moisture loss), emulsifier (thickener) and diluting agent in cosmetics.
Butylene Glycol Solvents used to dilute. An organic humectant (promotes the retention of moisture in the skin) similar to propylene glycol.
PEG-8. Polymeric forms of ethylene oxide that is used to produce a wide range of cosmetic materials.
Carbomer White powder that reacts with fatty particles forming thick and stable emulsions. It is mostly used as thickener and as gelling agent, like a wax.
Dimethicone An organic silicone, used as a skin protectant and moisturizer. Well tolerated by even the most sensitive skins, dimethicone has a filming action on the skin surface which helps slow down moisture loss and further helps smooth fine, dry lines.
Isopropyl Palmitate An ester of palmitic acid from coconut oil used to impart silkiness to the skin and hair. A synthetic moisturizer.
Octocrylene is an organic compound used as an ingredient in sunscreens and cosmetics. The extended conjugation of the acrylate portion of the molecule absorbs ultraviolet light, protecting skin from the harmful effects of exposure to sunlight. The ethylhexanol portion is a fatty alcohol, adding emollient and oil-like (water resistant) properties.
Tocopheryl Acetate Vitamin E acetate is a powerful antioxidant, possessesing the ability to increase the moisturisation of the skin's horny layer and thereby improve surface relief. D-Alpha-tocopheryl acetate is used in topical skin care products. It appears that it can diffuse into skin cells where it is converted to d-alpha-tocopherol. D-alpha-tocopherol may protect skin against ultraviolet damage and is also a skin moisturizer.
Ascorbyl Palmitate Salt of ascorbic acid used as a preservative and antioxidant in cosmetic creams (see also ascorbic acid).
Linoleic acid. Unsaturated fatty acid used as an emollient and thickening agent in cosmetics. There is some research showing it to be effective in cell regulation and skin-barrier repair, as well as an antioxidant and an anti-inflammatory.
strong>Panthenol, Participates in the release of energy from carbohydrates, fats & protein, aids in the utilization of vitamins; improves the body's resistance to stress; helps in cell building & the development of the central nervous system. On the skin it acts as a penetrating moisturizer. Plumps and moisturizes hair shaft to make it appear thicker, reduces split ends, smoothes skin and strengthens nails.
Cetyl Alcohol Derived from coconut oil or produced synthetically, no longer derived from cetaceans (whales), this wax-like substance helps emulsify oils into a water base and can also be used as an emollient.
Acrylates/C 10-30 Alkyl Acrylate Crosspolymer This thickener is specially designed for thickening surfactant systems It delivers excellent thickening efficiency and suspending capability, long viscous flow and sparkling clarity in gel systems.
TEA: (Triethanolamine) Produced by ammonolysis of ethylene oxide. An alkanomine used as part of an emulsion system in conjunction with organic acids like stearic acid. Neutralizes carbomer solutions to form gels. Neutralizes stearic acid to form anionic emulsions and acts as an alkalizing agent to control pH.
DMDM Hydantoin Preservative, antimicrobial to fight bacteria. Iodopropynyl butylcarbamate- is mainly used as a cosmetic preservative. Arachis Hypogaea Oil Also known as peanut oil, this can be used in sunscreen and after sun preparations. It can have emollient and anti-inflammatory properties for skin. Isopropyl myristate. Used in cosmetics as a thickening agent and emollient.
Tocopherol (Vitamin E) Accumulates in the epidermis and forms a barrier against moisture evaporation from the skin. An anti-oxidant, Vitamin E helps prevent free radical damage in the skin tissues. Major anti-oxidant nutrient; retards cellular aging due to oxidation; aids in bringing nourishment to cells; strengthens the capillary walls prevents the red blood cells from destructive poisons. Aids against dry skin. Used as an antioxidant in cosmetics.
Methylparaben preservative used to ensure shelf life, hygienic stability of all cosmetic creams; non-irritating, non-sensitizing and non-toxic. It is effective against a wide range of bacteria and fungi.
Disodium EDTA Disodium EDTA is a chelating agent and a viscosity adjuster. The function of a chelating compound is to prevent ingredients from binding to any trace elements that may be present, resulting in a more stable product. EDTA stands for ethylene diamine tetra acetic acid.
Ethylparaben Anti-microbial substance used as preservative in cosmetic products.
Propylparaben Common cosmetic preservative that is anti-fungal and anti-microbial. It is less water-soluble than methylparaben.
Hexyl cinnamal, is a common additive in perfume and cosmetic industry as aroma substance.
Limonene Chemical used as a fragrance additive.
Linalool A natural fragrance chemical that is found in several fragrant oils such as lavender oil, bergamot oil and coriander oil. Used for its do-odorising properties and as an additive.
Geraniol A naturally occurring fragrant compound found in many essential oils, including geranium oil, that can be prepared synthetically.
The time it takes to clear pigmentation varies from one person to another. Whilst some can see a difference in 6-8 weeks, it can take upto 6 months, depending on skin type, age, extent and spread of pigmentation. Lightenex will need to be used as an ongoing treatment to prevent further pigmentation.
Glycyrrhiza Glabra Extract Licorice has an anti-inflammatory and lightening activity similar to cortisone. This enhances the active ingredient, Kojic Dipalmitate.
Imperata Cylindrica Extract -used for it’s analgesic and anti-inflammatory effect. It is also a whitening agent which works together with the Kojic Dipalmitate.
Butyrospermum Parkii (Shea Butter) This precious vegetable oil, commonly referred to as Shea Butter, comes from the Shea Tree. Comprised of saturated and unsaturated fatty acids, as well as Vitamin E and Carotene, this oil acts as a soothing moisturizer and emollient for the skin. It possesses protective properties against environmental influences, including UV rays and sun allergies. Rosa gallica Rosa gallica is an old fashioned, sweetly fragrant rose whose precious, rich oil is used to soften, balance, and restore the skin.
Arctostaphylos uva-ursi L. Sprengel. Bearberry-leaf extract possesses marked antioxidant activity.
Mitracarpus Scaber Extract Mitracarpus scaber extract is a botanically derived lightening agent from the leaves of this tropical plant. It prevents the actions of tyrosinase which causes melanin formation. The active ingredient found in Mitracarpus scaber extract is harounoside, which is effective in skin lightening.
Carthamis Tinctorius Oil. A highly moisturizing oil with an exceptionally high amount of Oleic acids. Deeply soothing and one of the first choices for skin care blends or recipes requiring moisturizing benefits.
Prunus Amygdalus Dulcis oil. Sweet almond oil is obtained from the dried kernels of the almond tree. It is an excellent emollient, softening and soothing to the skin. It also helps to balance the loss and absorption of moisture, resulting in moisturised skin.
Daucus Carota Sativa (carrot) root extract Carrot root extract. Can help protect the skin from free-radical damage and promotes production of new cells. Excellent for dry and mature skins.
Aloe Barbadensis The latin name for the Aloe plant. It rehydrates and softens the skin and helps soothe irritated or sensitive areas. It is considered one of nature's most effective remedies for sunburn and skin irritations, and a superb hydrator for dry skin.
Glyceryl Stearate A monoester of glycerin and stearic acid. An emollient and emulsifier.
Ceteareth 20 - Used in oil-in-water emulsions. Provides exceptionally stable emulsions when used in combination with another emulsifier such as glyceryl stearate Ceteareth-10 Is an non-ionic surfactants compond, fequently used as emulsifiers in cosmetics
Cetearyl Alcohol A mixture of fatty alcohols derived from coconut oil consisting predominantly of cetyl and stearyl alcohols. Used as emollients, thickeners and emulsion stabilizers.
Cetyl Palmitate Emollient.
Caprilic / Capric Triglyceride Various vegetable oils, dairy fats, plants and sweat are the sources of this ingredient with good emollient properties.
Glycerin A humectant that absorbs moisture from the air to keep hair and skin moist. It is also used as an emollient (skin smoothener and softener), lubricant (skin lubricator that helps prevents moisture loss), emulsifier (thickener) and diluting agent in cosmetics.
Butylene Glycol Solvents used to dilute. An organic humectant (promotes the retention of moisture in the skin) similar to propylene glycol.
PEG-8. Polymeric forms of ethylene oxide that is used to produce a wide range of cosmetic materials.
Carbomer White powder that reacts with fatty particles forming thick and stable emulsions. It is mostly used as thickener and as gelling agent, like a wax.
Dimethicone An organic silicone, used as a skin protectant and moisturizer. Well tolerated by even the most sensitive skins, dimethicone has a filming action on the skin surface which helps slow down moisture loss and further helps smooth fine, dry lines.
Isopropyl Palmitate An ester of palmitic acid from coconut oil used to impart silkiness to the skin and hair. A synthetic moisturizer.
Octocrylene is an organic compound used as an ingredient in sunscreens and cosmetics. The extended conjugation of the acrylate portion of the molecule absorbs ultraviolet light, protecting skin from the harmful effects of exposure to sunlight. The ethylhexanol portion is a fatty alcohol, adding emollient and oil-like (water resistant) properties.
Tocopheryl Acetate Vitamin E acetate is a powerful antioxidant, possessesing the ability to increase the moisturisation of the skin's horny layer and thereby improve surface relief. D-Alpha-tocopheryl acetate is used in topical skin care products. It appears that it can diffuse into skin cells where it is converted to d-alpha-tocopherol. D-alpha-tocopherol may protect skin against ultraviolet damage and is also a skin moisturizer.
Ascorbyl Palmitate Salt of ascorbic acid used as a preservative and antioxidant in cosmetic creams (see also ascorbic acid).
Linoleic acid. Unsaturated fatty acid used as an emollient and thickening agent in cosmetics. There is some research showing it to be effective in cell regulation and skin-barrier repair, as well as an antioxidant and an anti-inflammatory.
strong>Panthenol, Participates in the release of energy from carbohydrates, fats & protein, aids in the utilization of vitamins; improves the body's resistance to stress; helps in cell building & the development of the central nervous system. On the skin it acts as a penetrating moisturizer. Plumps and moisturizes hair shaft to make it appear thicker, reduces split ends, smoothes skin and strengthens nails.
Cetyl Alcohol Derived from coconut oil or produced synthetically, no longer derived from cetaceans (whales), this wax-like substance helps emulsify oils into a water base and can also be used as an emollient.
Acrylates/C 10-30 Alkyl Acrylate Crosspolymer This thickener is specially designed for thickening surfactant systems It delivers excellent thickening efficiency and suspending capability, long viscous flow and sparkling clarity in gel systems.
TEA: (Triethanolamine) Produced by ammonolysis of ethylene oxide. An alkanomine used as part of an emulsion system in conjunction with organic acids like stearic acid. Neutralizes carbomer solutions to form gels. Neutralizes stearic acid to form anionic emulsions and acts as an alkalizing agent to control pH.
DMDM Hydantoin Preservative, antimicrobial to fight bacteria. Iodopropynyl butylcarbamate- is mainly used as a cosmetic preservative. Arachis Hypogaea Oil Also known as peanut oil, this can be used in sunscreen and after sun preparations. It can have emollient and anti-inflammatory properties for skin. Isopropyl myristate. Used in cosmetics as a thickening agent and emollient.
Tocopherol (Vitamin E) Accumulates in the epidermis and forms a barrier against moisture evaporation from the skin. An anti-oxidant, Vitamin E helps prevent free radical damage in the skin tissues. Major anti-oxidant nutrient; retards cellular aging due to oxidation; aids in bringing nourishment to cells; strengthens the capillary walls prevents the red blood cells from destructive poisons. Aids against dry skin. Used as an antioxidant in cosmetics.
Methylparaben preservative used to ensure shelf life, hygienic stability of all cosmetic creams; non-irritating, non-sensitizing and non-toxic. It is effective against a wide range of bacteria and fungi.
Disodium EDTA Disodium EDTA is a chelating agent and a viscosity adjuster. The function of a chelating compound is to prevent ingredients from binding to any trace elements that may be present, resulting in a more stable product. EDTA stands for ethylene diamine tetra acetic acid.
Ethylparaben Anti-microbial substance used as preservative in cosmetic products.
Propylparaben Common cosmetic preservative that is anti-fungal and anti-microbial. It is less water-soluble than methylparaben.
Hexyl cinnamal, is a common additive in perfume and cosmetic industry as aroma substance.
Limonene Chemical used as a fragrance additive.
Linalool A natural fragrance chemical that is found in several fragrant oils such as lavender oil, bergamot oil and coriander oil. Used for its do-odorising properties and as an additive.
Geraniol A naturally occurring fragrant compound found in many essential oils, including geranium oil, that can be prepared synthetically.
The time it takes to clear pigmentation varies from one person to another. Whilst some can see a difference in 6-8 weeks, it can take upto 6 months, depending on skin type, age, extent and spread of pigmentation. Lightenex will need to be used as an ongoing treatment to prevent further pigmentation.
Thursday, 8 May 2008
Natural Secretion Marks Difference Between Mole And Melanoma
One might call it a tale of two melanocytes. Given the same genetic mutation, why does one melanocyte shut down growth and become a relatively benign mole, while another rages out of control and develops into deadly melanoma?
In trying to tease out the answer to this simple question, Howard Hughes Medical Institute (HHMI) researchers have uncovered a protein that stops the growth of melanoma, a cancer that develops from pigment-producing cells in the skin called melanocytes. HHMI investigator Michael Green and colleagues at the University of Massachusetts Medical School reported their identification of the genetic underpinnings of a new way to thwart one of the deadliest forms of cancer in the February 8, 2008, issue of the journal Cell.
Green and his colleagues began by designing experiments that would help them determine what separates melanomas from ordinary moles at the genetic level. Moles, also known as nevi, and melanoma often result from the same genetic mutation, and the biological pathway that differentiates the two had been a mystery. The new study uncovers a relatively unknown protein that regulates the melanocyte's "decision" to ward off cancer by either entering a programmed hibernation or committing suicide.
According to the American Cancer Society, 60,000 people in the United States developed melanoma in 2007, and more than 8,000 died of the disease. Melanoma is caused by the uncontrolled proliferation of melanocytes, whose pigment, melanin, protects the skin against the sun's ultraviolet rays. Nevi, which are benign, are also caused by abnormal growth and differentiation of melanocytes.
While nevi are, by definition, non-cancerous, more than half the time the same mutation is at fault in melanoma and nevi: a single amino acid change in a protein called BRAF. BRAF is part of a signaling system that is important for cell growth and proliferation. The BRAF mutation found in nevi and melanoma increases the activity of the BRAF protein, prompting cells to multiply abnormally. In some melanocytes with this mutation, the proliferation cannot be stopped, and cancer develops.
But sometimes when the mutated BRAF gene is expressed in melanocytes, those cells go into a state of permanent hibernation via a process known as senescence. These cells form nevi, not melanoma. This, according to Green, indicates that the genetic checks and balances within those cells are working correctly. "The cell has sensed this oncogenic influence--activated BRAF--and that induces an anti-cancer mechanism to throw the cell into this frozen state," he said. Green added that sometimes cells simply commit suicide instead of senescing.
Cancer results when something blocks this failsafe mechanism, said Green. "While this phenomenon was known, the components and the pathways involved were not," he said.
Green, his postdoctoral fellow Narendra Wajapeyee, and their colleagues did a genome-wide search for the proteins involved. They used engineered retroviruses to insert short bits of RNA to selectively turn off individual genes in a series of melanocytes. Some of the cells progressed to cancer, while others did not. After testing thousands of genes, they found 17 that were required for activated BRAF to induce either senescence or suicide. Together, Green said, the proteins made by these genes make up the body's melanoma defense pathway.
Green's group found that three of those proteins are required for both the senescence and programmed cell death pathways. The identity of one of those proteins, insulin-like growth factor binding protein 7 (IGFBP7), surprised the researchers. Not much was known about IGFBP7, except that it was secreted, said Green. A secreted protein does not stay inside the cell that produces it, but instead is released from the cell and moves through the blood to other cells. Green said that a secreted protein's role in the pathway caught them off guard, because "we would have thought this process would be purely intracellular."
Green and his colleagues focused their attention on IGFBP7 because its presence suggested something intriguing: If one otherwise healthy melanocyte begins expressing BRAF, the IGFBP7 it produces can enter cells around it, prompting lots of melanocytes to "switch off," rather than risking a tumor.
In the experiments reported in Cell, the researchers exposed human melanoma cells in culture to recombinant IGFBP7. The protein had the same genetic code as the human version, but was produced using genetically modified insect cells. The melanoma cells that were treated with IGFBP7 committed suicide-- just as though their anti-cancer mechanism was working correctly.
The researchers also injected the protein into the bloodstream of mice on to which human melanoma tumors had been grafted. IGFBP7 entered the tumor cells and stopped their growth in the mice. "Melanoma cells [caused by BRAF mutations] shut off expression of this key regulator," said Green. "Because of that, the cells escape from senescence and form a tumor."
According to Green, the research also answers another controversy in the field: Are nevi dead-ends or are they precursors to melanoma" "If you go in and see a dermatologist, if they see a mole, they will generally... cut it off," he said. "They don't want to take the chance that it could be a precursor."
However, Green thinks his results point in the other direction. Because IGFBP7 is a secreted protein, even if one activated BRAF-containing -- but otherwise healthy -- cell in the nevi stopped producing IGFBP7 and threatened to form a tumor, the IGFBP7 being secreted from the cells around it would kill it. "It's an extremely powerful anti-cancer mechanism," said Green.
The team's findings are important not only from a research standpoint, but also for future clinical treatments, Green noted. Melanoma can be surgically removed if caught early, but in advanced cases there is really no treatment for it. Green said IGFBP7's ability to target melanoma tumors throughout the body may make it a powerful tool for cancer therapy. "We're really very excited about the prospects of trying to advance this as a melanoma treatment," he said.
If this natural anti-cancer agent, called IGFBP7, can be produced and delivered to tumors, it might serve as a targeted chemotherapy for metastatic melanoma, a condition which is "basically untreatable" today, said Green. It might also be used to treat other cancers with mutations in the oncogene known as BRAF.
Adapted from materials provided by Howard Hughes Medical Institute.
In trying to tease out the answer to this simple question, Howard Hughes Medical Institute (HHMI) researchers have uncovered a protein that stops the growth of melanoma, a cancer that develops from pigment-producing cells in the skin called melanocytes. HHMI investigator Michael Green and colleagues at the University of Massachusetts Medical School reported their identification of the genetic underpinnings of a new way to thwart one of the deadliest forms of cancer in the February 8, 2008, issue of the journal Cell.
Green and his colleagues began by designing experiments that would help them determine what separates melanomas from ordinary moles at the genetic level. Moles, also known as nevi, and melanoma often result from the same genetic mutation, and the biological pathway that differentiates the two had been a mystery. The new study uncovers a relatively unknown protein that regulates the melanocyte's "decision" to ward off cancer by either entering a programmed hibernation or committing suicide.
According to the American Cancer Society, 60,000 people in the United States developed melanoma in 2007, and more than 8,000 died of the disease. Melanoma is caused by the uncontrolled proliferation of melanocytes, whose pigment, melanin, protects the skin against the sun's ultraviolet rays. Nevi, which are benign, are also caused by abnormal growth and differentiation of melanocytes.
While nevi are, by definition, non-cancerous, more than half the time the same mutation is at fault in melanoma and nevi: a single amino acid change in a protein called BRAF. BRAF is part of a signaling system that is important for cell growth and proliferation. The BRAF mutation found in nevi and melanoma increases the activity of the BRAF protein, prompting cells to multiply abnormally. In some melanocytes with this mutation, the proliferation cannot be stopped, and cancer develops.
But sometimes when the mutated BRAF gene is expressed in melanocytes, those cells go into a state of permanent hibernation via a process known as senescence. These cells form nevi, not melanoma. This, according to Green, indicates that the genetic checks and balances within those cells are working correctly. "The cell has sensed this oncogenic influence--activated BRAF--and that induces an anti-cancer mechanism to throw the cell into this frozen state," he said. Green added that sometimes cells simply commit suicide instead of senescing.
Cancer results when something blocks this failsafe mechanism, said Green. "While this phenomenon was known, the components and the pathways involved were not," he said.
Green, his postdoctoral fellow Narendra Wajapeyee, and their colleagues did a genome-wide search for the proteins involved. They used engineered retroviruses to insert short bits of RNA to selectively turn off individual genes in a series of melanocytes. Some of the cells progressed to cancer, while others did not. After testing thousands of genes, they found 17 that were required for activated BRAF to induce either senescence or suicide. Together, Green said, the proteins made by these genes make up the body's melanoma defense pathway.
Green's group found that three of those proteins are required for both the senescence and programmed cell death pathways. The identity of one of those proteins, insulin-like growth factor binding protein 7 (IGFBP7), surprised the researchers. Not much was known about IGFBP7, except that it was secreted, said Green. A secreted protein does not stay inside the cell that produces it, but instead is released from the cell and moves through the blood to other cells. Green said that a secreted protein's role in the pathway caught them off guard, because "we would have thought this process would be purely intracellular."
Green and his colleagues focused their attention on IGFBP7 because its presence suggested something intriguing: If one otherwise healthy melanocyte begins expressing BRAF, the IGFBP7 it produces can enter cells around it, prompting lots of melanocytes to "switch off," rather than risking a tumor.
In the experiments reported in Cell, the researchers exposed human melanoma cells in culture to recombinant IGFBP7. The protein had the same genetic code as the human version, but was produced using genetically modified insect cells. The melanoma cells that were treated with IGFBP7 committed suicide-- just as though their anti-cancer mechanism was working correctly.
The researchers also injected the protein into the bloodstream of mice on to which human melanoma tumors had been grafted. IGFBP7 entered the tumor cells and stopped their growth in the mice. "Melanoma cells [caused by BRAF mutations] shut off expression of this key regulator," said Green. "Because of that, the cells escape from senescence and form a tumor."
According to Green, the research also answers another controversy in the field: Are nevi dead-ends or are they precursors to melanoma" "If you go in and see a dermatologist, if they see a mole, they will generally... cut it off," he said. "They don't want to take the chance that it could be a precursor."
However, Green thinks his results point in the other direction. Because IGFBP7 is a secreted protein, even if one activated BRAF-containing -- but otherwise healthy -- cell in the nevi stopped producing IGFBP7 and threatened to form a tumor, the IGFBP7 being secreted from the cells around it would kill it. "It's an extremely powerful anti-cancer mechanism," said Green.
The team's findings are important not only from a research standpoint, but also for future clinical treatments, Green noted. Melanoma can be surgically removed if caught early, but in advanced cases there is really no treatment for it. Green said IGFBP7's ability to target melanoma tumors throughout the body may make it a powerful tool for cancer therapy. "We're really very excited about the prospects of trying to advance this as a melanoma treatment," he said.
If this natural anti-cancer agent, called IGFBP7, can be produced and delivered to tumors, it might serve as a targeted chemotherapy for metastatic melanoma, a condition which is "basically untreatable" today, said Green. It might also be used to treat other cancers with mutations in the oncogene known as BRAF.
Adapted from materials provided by Howard Hughes Medical Institute.
Beauty-sleeping Night Cream
It is natural that we need sleep every day and we feel absolutely really refreshed and full of energy, ready to start the day in the morning. During sleeping, brain cells re-centers, re-vitalizes, re-balances, re-generates, rejuvenates and recuperates the body and mind for a new day. The body, including the skin, has the time to repair and fix problems that were experienced during the day.
After using a day cream daytime, a more nurturing cream needs to be used at night to work in synergy with the day cream. Some younger people are of the opinion that only more mature people need to use a night cream. However, sleeping at night provides the best environment, to repair skin damage, regenerate itself and fight aging. The body skin would be getting to the “mature” category faster if losing the sight of your skin, struggling the attack from the time and environment.
Beauty-sleeping Night Cream is uniquely formulated to stimulate collagen synthesis while you sleep. It delivers heavy vitamin c & e and comprehensive nutrients to exfoliate, renew, moisturize and replenish your skin overnight. You can feel your fresh and bright look and much more benefit in the morning. A healthier and youthful appearance can be seen in a short period of use. AuRas Beauty-sleeping Night Cream applies its power to further help retard the aging process.
*
reduce the fines and wrinkles;
*
recover skin elasticity;
*
soften and sooth skin texture;
*
enrich skin hydration and moisture
After using a day cream daytime, a more nurturing cream needs to be used at night to work in synergy with the day cream. Some younger people are of the opinion that only more mature people need to use a night cream. However, sleeping at night provides the best environment, to repair skin damage, regenerate itself and fight aging. The body skin would be getting to the “mature” category faster if losing the sight of your skin, struggling the attack from the time and environment.
Beauty-sleeping Night Cream is uniquely formulated to stimulate collagen synthesis while you sleep. It delivers heavy vitamin c & e and comprehensive nutrients to exfoliate, renew, moisturize and replenish your skin overnight. You can feel your fresh and bright look and much more benefit in the morning. A healthier and youthful appearance can be seen in a short period of use. AuRas Beauty-sleeping Night Cream applies its power to further help retard the aging process.
*
reduce the fines and wrinkles;
*
recover skin elasticity;
*
soften and sooth skin texture;
*
enrich skin hydration and moisture
Super Skin-lightening Gel
Skin whitening products have become increasingly popular in the past few years. The main purpose for skin whitening products is to lighten the skin as well as even to skin tone or to treat pigmentation disorders such as freckles, pregnancy marks and age spots. Skin color is a function of the size, number and the distribution of melanin cells, which of darkly pigmented skin have thicker, longer and branched dendrites. The racial difference in human color may primarily be due to difference in the tyrosinase activity in the melanin cells. The more active, the tyrosinase is; the darker, the melanin cells are.
Melanin is the pigment in your skin, responsible for splotchy or uneven tanning. The increased dark yellow, light brown, yellowish brown pigmentation or age spots may be brought on or increased by over exposure to the sun or other forms of ultraviolet light, bad health, problems with the liver functions, or other causes, both known and unknown. These spots are often first noticed on the arms and hands after 55 years old. They also appear, occasionally, on the chest, back, and less frequently on the legs and torso. Melanin is harmless and painless but may affect the cosmetic appearance. The melanin can and should be prevented by diligent skin care and careful, protected exposure to the sun.
AuRas Super Skin-lightening gel is dramatically effective as skin whitener for any skin type. Not only because it contains very affective whitening ingredients and active ingredients for nourishment, but also because the excellent formulation produces a cooperating efficacy, that accelerate and help in increasing the skin whitening and nourishment for natural health and beauty. The Kojic acid is known to inhibit tyrosinase successfully in the reduction of age spots and pigmentation on face and body, as typically caused by sun damage. Vitamin C has a wide variety of role in human health and skin beauty for collagen production, inhibition of melanin production as well. Vitamin E is weaker than vitamin C as antioxidant, but vitamin C can regenerate vitamin E and enable vitamin E to provide sustained antioxidant protection in the skin elastin fibers.
Beside, AuRas Super Skin-lightening gel uses the α-glycolic acid (AHA) and aloe Vera gel. The AHA cosmetics are believed to help remove undesirable signs of skin aging, such as discoloration, roughness and wrinkling, revealing a fresher-looking layer of skin. Known as chemical exfoliation, the procedure is controlled to prevent deep skin burns from the highly acidic solutions. Exfoliation stimulates the skin and healthy cells are regenerated. Both AHA and Aloe Vera are excellent moisturizer. The aloe Vera is popularly as rich nutrients with multi-vitamins and minerals to soothe, heal, moisturize and generate skin.
Beside, AuRas Super Skin-lightening gel uses the α-glycolic acid (AHA) and aloe Vera gel. The AHA cosmetics are believed to help remove undesirable signs of skin aging, such as discoloration, roughness and wrinkling, revealing a fresher-looking layer of skin. Known as chemical exfoliation, the procedure is controlled to prevent deep skin burns from the highly acidic solutions. Exfoliation stimulates the skin and healthy cells are regenerated. Both AHA and Aloe Vera are excellent moisturizer. The aloe Vera is popularly as rich nutrients with multi-vitamins and minerals to soothe, heal, moisturize and generate skin.
Melanin is the pigment in your skin, responsible for splotchy or uneven tanning. The increased dark yellow, light brown, yellowish brown pigmentation or age spots may be brought on or increased by over exposure to the sun or other forms of ultraviolet light, bad health, problems with the liver functions, or other causes, both known and unknown. These spots are often first noticed on the arms and hands after 55 years old. They also appear, occasionally, on the chest, back, and less frequently on the legs and torso. Melanin is harmless and painless but may affect the cosmetic appearance. The melanin can and should be prevented by diligent skin care and careful, protected exposure to the sun.
AuRas Super Skin-lightening gel is dramatically effective as skin whitener for any skin type. Not only because it contains very affective whitening ingredients and active ingredients for nourishment, but also because the excellent formulation produces a cooperating efficacy, that accelerate and help in increasing the skin whitening and nourishment for natural health and beauty. The Kojic acid is known to inhibit tyrosinase successfully in the reduction of age spots and pigmentation on face and body, as typically caused by sun damage. Vitamin C has a wide variety of role in human health and skin beauty for collagen production, inhibition of melanin production as well. Vitamin E is weaker than vitamin C as antioxidant, but vitamin C can regenerate vitamin E and enable vitamin E to provide sustained antioxidant protection in the skin elastin fibers.
Beside, AuRas Super Skin-lightening gel uses the α-glycolic acid (AHA) and aloe Vera gel. The AHA cosmetics are believed to help remove undesirable signs of skin aging, such as discoloration, roughness and wrinkling, revealing a fresher-looking layer of skin. Known as chemical exfoliation, the procedure is controlled to prevent deep skin burns from the highly acidic solutions. Exfoliation stimulates the skin and healthy cells are regenerated. Both AHA and Aloe Vera are excellent moisturizer. The aloe Vera is popularly as rich nutrients with multi-vitamins and minerals to soothe, heal, moisturize and generate skin.
Beside, AuRas Super Skin-lightening gel uses the α-glycolic acid (AHA) and aloe Vera gel. The AHA cosmetics are believed to help remove undesirable signs of skin aging, such as discoloration, roughness and wrinkling, revealing a fresher-looking layer of skin. Known as chemical exfoliation, the procedure is controlled to prevent deep skin burns from the highly acidic solutions. Exfoliation stimulates the skin and healthy cells are regenerated. Both AHA and Aloe Vera are excellent moisturizer. The aloe Vera is popularly as rich nutrients with multi-vitamins and minerals to soothe, heal, moisturize and generate skin.
Superbug Genome Sequenced: Steno Has Remarkable Capacity For Drug Resistance
The genome of a newly-emerging superbug, commonly known as Steno, has just been sequenced. The results reveal an organism with a remarkable capacity for drug resistance. The research was carried out by scientists at the Wellcome Trust Sanger Institute near Cambridge and the University of Bristol.
Understanding the genome of this bacterium will help researchers discover how to deal with this particularly resistant organism. The paper will be published in Genome Biology.
Dr Matthew Avison from the University of Bristol, and senior author on the paper said: "This is the latest in an ever-increasing list of antibiotic-resistant hospital superbugs. The degree of resistance it shows is very worrying. Strains are now emerging that are resistant to all available antibiotics, and no new drugs capable of combating these 'pan-resistant' strains are currently in development."
Pan-resistant Steno infections are at least as hard to treat as MRSA and C.diff infections. But although it is common in the environment, Steno infections are rarer than MRSA and C.diff infections and are exclusively hospital-acquired.
Steno flourishes in moist environments, such as around taps and shower heads, and can be transferred to patients. It is distinct in the way it causes infection and can only get into the body via devices such as catheters or ventilation tubes that are left in place for long periods of time. Long-dwelling catheters are used most often for seriously ill patients and some undergoing chemotherapy.
Steno can stick to the catheter and grow into a 'biofilm'. When the catheter is next flushed, the Steno biofilm can enter the patient's bloodstream. If their immune system is impaired (which is often the case in the seriously ill and those undergoing chemotherapy) the organism can multiply and cause septicaemia. The gravity of this situation has been underlined by the new research, since these patients will be treated with antibiotics against which Steno is largely resistant.
There are approximately 1,000 reports of Stenotrophomonas maltophilia (Steno) blood poisoning in the UK each year, with a mortality rate of about 30%. The organism is also found in the lungs of many adults with cystic fibrosis, and causes ventilator-associated pneumonias, particularly in elderly intensive-care patients.
The key questions that need to be addressed are: How does Steno stick to surfaces like catheters and ventilator tubes" How does it form biofilms and so survive attempts to decontaminate and clean" Why is it resistant to antibiotics"
Dr Lisa Crossman from the Sanger Institute and first author on the paper explained how the research might address these questions: "The genome sequence should help us to combat these properties. For example, if we know which proteins cause it to stick to surfaces, we could try to develop biochemical compounds that interfere with this interaction. If we understand its antibiotic resistance mechanisms, we might be able to design inhibitors that block them."
While Steno infections are still relatively uncommon, they are on the increase. Furthermore, there are two other organisms that cause similar types of infections, but are more common.
Dr Avison added: "Genome sequences for these two also exist, and so now we can look at what they all have in common genetically that might explain why they are so resistant to antibioitics."
Adapted from materials provided by University of Bristol.
Understanding the genome of this bacterium will help researchers discover how to deal with this particularly resistant organism. The paper will be published in Genome Biology.
Dr Matthew Avison from the University of Bristol, and senior author on the paper said: "This is the latest in an ever-increasing list of antibiotic-resistant hospital superbugs. The degree of resistance it shows is very worrying. Strains are now emerging that are resistant to all available antibiotics, and no new drugs capable of combating these 'pan-resistant' strains are currently in development."
Pan-resistant Steno infections are at least as hard to treat as MRSA and C.diff infections. But although it is common in the environment, Steno infections are rarer than MRSA and C.diff infections and are exclusively hospital-acquired.
Steno flourishes in moist environments, such as around taps and shower heads, and can be transferred to patients. It is distinct in the way it causes infection and can only get into the body via devices such as catheters or ventilation tubes that are left in place for long periods of time. Long-dwelling catheters are used most often for seriously ill patients and some undergoing chemotherapy.
Steno can stick to the catheter and grow into a 'biofilm'. When the catheter is next flushed, the Steno biofilm can enter the patient's bloodstream. If their immune system is impaired (which is often the case in the seriously ill and those undergoing chemotherapy) the organism can multiply and cause septicaemia. The gravity of this situation has been underlined by the new research, since these patients will be treated with antibiotics against which Steno is largely resistant.
There are approximately 1,000 reports of Stenotrophomonas maltophilia (Steno) blood poisoning in the UK each year, with a mortality rate of about 30%. The organism is also found in the lungs of many adults with cystic fibrosis, and causes ventilator-associated pneumonias, particularly in elderly intensive-care patients.
The key questions that need to be addressed are: How does Steno stick to surfaces like catheters and ventilator tubes" How does it form biofilms and so survive attempts to decontaminate and clean" Why is it resistant to antibiotics"
Dr Lisa Crossman from the Sanger Institute and first author on the paper explained how the research might address these questions: "The genome sequence should help us to combat these properties. For example, if we know which proteins cause it to stick to surfaces, we could try to develop biochemical compounds that interfere with this interaction. If we understand its antibiotic resistance mechanisms, we might be able to design inhibitors that block them."
While Steno infections are still relatively uncommon, they are on the increase. Furthermore, there are two other organisms that cause similar types of infections, but are more common.
Dr Avison added: "Genome sequences for these two also exist, and so now we can look at what they all have in common genetically that might explain why they are so resistant to antibioitics."
Adapted from materials provided by University of Bristol.
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