Even when our eyes are closed, the visual centers in our brain are humming with activity. Weizmann Institute scientists and others have shown in the last few years that the magnitude of sense-related activity in a brain that's disengaged from seeing, touching, etc., is quite similar to that of one exposed to a stimulus. New research at the Institute has now revealed details of that activity, explaining why, even though our sense centers are working, we don't experience sights or sounds when there's nothing coming in through our sensory organs.
The previous studies of Prof. Rafael Malach and research student Yuval Nir of the Neurobiology Department used functional magnetic resonance imaging (fMRI) to measure brain activity in active and resting states. But fMRI is an indirect measurement of brain activity; it can't catch the nuances of the pulses of electricity that characterize neuron activity.
Together with Prof. Itzhak Fried of the University of California at Los Angeles and a team at the EEG unit of the Tel Aviv Sourasky Medical Center, the researchers found a unique source of direct measurement of electrical activity in the brain: data collected from epilepsy patients who underwent extensive testing, including measurement of neuronal pulses in various parts of their brain, in the course of diagnosis and treatment.
An analysis of this data showed conclusively that electrical activity does, indeed, take place even in the absence of stimuli. But the nature of the electrical activity differs if a person is experiencing a sensory event or undergoing its absence. In results that appeared recently in Nature Neuroscience, the scientists showed that during rest, brain activity consists of extremely slow fluctuations, as opposed to the short, quick bursts that typify a response associated with a sensory percept. This difference appears to be the reason we don't experience hallucinations or hear voices that aren't there during rest. The resting oscillations appear to be strongest when we sense nothing at all - during dream-free sleep.
The slow fluctuation pattern can be compared to a computer screen-saver. Though its function is still unclear, the researchers have a number of hypotheses. One possibility is that neurons, like certain philosophers, must 'think' in order to be. Survival, therefore, is dependant on a constant state of activity. Another suggestion is that the minimal level of activity enables a quick start when a stimulus eventually presents itself, something like a getaway car with the engine running. Nir: 'In the old approach, the senses are 'turned on' by the switch of an outside stimulus. This is giving way to a new paradigm in which the brain is constantly active, and stimuli change and shape that activity.'
Malach: 'The use of clinical data enabled us to solve a riddle of basic science in a way that would have been impossible with conventional methods. These findings could, in the future, become the basis of advanced diagnostic techniques.' Such techniques might not necessarily require the cooperation of the patient, allowing them to be used, for instance on people in a coma or on young children.
Prof. Rafael Malach's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; Ms. Vera Benedek, Israel; Benjamin and Seema Pulier Charitable Foundation, Inc.; and Ms. Mary Helen Rowen, New York, NY. Prof. Malach is the incumbent of the Barbara and Morris Levinson Professorial Chair in Brain Research.
For the scientific paper, please see: nature/neuro/journal/v11/n9/full/nn.2177.html
The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
Source: Yivsam Azgad
Weizmann Institute of Science
среда, 29 июня 2011 г.
воскресенье, 26 июня 2011 г.
Some Degenerative Diseases Prove Similar At The Molecular Level
Alzheimer's disease, Parkinson's disease, type 2 diabetes, the human version of mad cow disease (Creutzfeldt-Jakob disease), and other degenerative diseases are more closely related at the molecular level than many scientists realized, an international team of researchers, including an ESRF researcher, report in the journal Nature.
The brains of patients with these diseases contain harmful rope-like structures known as amyloid fibrils, which are protein molecules linked by water-tight "molecular zippers".
"We have shown that the fibrils have a common atomic-level structure," said David Eisenberg, a UCLA-DOE professor of chemistry and biology and a member of the research team. "All of these diseases are similar at the molecular level; all of them have a dry steric zipper. With each disease, a different protein transforms into amyloid fibrils, but the proteins are very similar at the atomic level."
The UCLA team, together with scientists from the University of Copenhagen and the ESRF, carried out part of their research at the microfocus beamline at the ESRF, where they used a very small beam of X-rays to study micro-crystals. "It has been a great international collaboration," Eisenberg said.
The research, while still preliminary, could help scientists develop tools for diagnosing these diseases, and potentially for treating them through "structure-based drug design," said Eisenberg.
The researchers report 11 new three-dimensional structures of fibril forming segments, including those for both of the main proteins that form amyloid fibrils in Alzheimer's disease.
"It has been a joy to see so many new structures," said Michael Sawaya, member of the team. "We see many similarities, but some details are different. As we study more structures, we expect to determine the common features among them".
"It is clear from the positions of the atoms where the zipper is," Sawaya added. "Like pieces in a jigsaw puzzle, they have to fit together just right. We are finding out how they fit together. We don't yet know all the ways of forming the zippers; we are working to fill in the missing pieces and are hopeful of doing so."
The research shows that very short segments of proteins are involved in forming amyloid fibrils; Eisenberg and his colleagues know some of the segments. Knowing the segments makes it easier to design tests to detect whether a new drug is effective, Eisenberg noted. Several of the disease-related proteins contain more than one amyloid fibril-forming segment.
If the molecular zipper is universal in amyloid fibrils, as Eisenberg believes, is it possible to pry open the zipper or prevent its formation? The team can now produce fibrils and has developed a test to determine whether the fibrils break up, using a wide variety of chemical compounds. This strategy could be potentially used to break up the fibrils.
A mystery on which the new Nature paper sheds light is what causes different strains of prions (infectious proteins) in which the protein sequence is identical. Scientists present a strong hypothesis that the origin of prion strains is encoded in the packing of the molecules in the fibrils.
In an earlier Nature paper (9 June 2005), Eisenberg and his colleagues presented the three-dimensional structure of an amyloid-like protein from yeast that revealed the surprising molecular zipper."In 2005, we were like prospectors who found flakes of gold in a stream," Eisenberg said. "Now we see the real nuggets. In this paper, we present atomic-level structures for crystals related to fibrils from proteins associated with numerous human diseases."
European Synchrotron Radiation Facility (ESRF)
esrf.fr
The brains of patients with these diseases contain harmful rope-like structures known as amyloid fibrils, which are protein molecules linked by water-tight "molecular zippers".
"We have shown that the fibrils have a common atomic-level structure," said David Eisenberg, a UCLA-DOE professor of chemistry and biology and a member of the research team. "All of these diseases are similar at the molecular level; all of them have a dry steric zipper. With each disease, a different protein transforms into amyloid fibrils, but the proteins are very similar at the atomic level."
The UCLA team, together with scientists from the University of Copenhagen and the ESRF, carried out part of their research at the microfocus beamline at the ESRF, where they used a very small beam of X-rays to study micro-crystals. "It has been a great international collaboration," Eisenberg said.
The research, while still preliminary, could help scientists develop tools for diagnosing these diseases, and potentially for treating them through "structure-based drug design," said Eisenberg.
The researchers report 11 new three-dimensional structures of fibril forming segments, including those for both of the main proteins that form amyloid fibrils in Alzheimer's disease.
"It has been a joy to see so many new structures," said Michael Sawaya, member of the team. "We see many similarities, but some details are different. As we study more structures, we expect to determine the common features among them".
"It is clear from the positions of the atoms where the zipper is," Sawaya added. "Like pieces in a jigsaw puzzle, they have to fit together just right. We are finding out how they fit together. We don't yet know all the ways of forming the zippers; we are working to fill in the missing pieces and are hopeful of doing so."
The research shows that very short segments of proteins are involved in forming amyloid fibrils; Eisenberg and his colleagues know some of the segments. Knowing the segments makes it easier to design tests to detect whether a new drug is effective, Eisenberg noted. Several of the disease-related proteins contain more than one amyloid fibril-forming segment.
If the molecular zipper is universal in amyloid fibrils, as Eisenberg believes, is it possible to pry open the zipper or prevent its formation? The team can now produce fibrils and has developed a test to determine whether the fibrils break up, using a wide variety of chemical compounds. This strategy could be potentially used to break up the fibrils.
A mystery on which the new Nature paper sheds light is what causes different strains of prions (infectious proteins) in which the protein sequence is identical. Scientists present a strong hypothesis that the origin of prion strains is encoded in the packing of the molecules in the fibrils.
In an earlier Nature paper (9 June 2005), Eisenberg and his colleagues presented the three-dimensional structure of an amyloid-like protein from yeast that revealed the surprising molecular zipper."In 2005, we were like prospectors who found flakes of gold in a stream," Eisenberg said. "Now we see the real nuggets. In this paper, we present atomic-level structures for crystals related to fibrils from proteins associated with numerous human diseases."
European Synchrotron Radiation Facility (ESRF)
esrf.fr
четверг, 23 июня 2011 г.
Metagene 'Portraits' Used By UC San Diego Researchers To Reveal Distinct Stages Of Kidney Formation
In the art world, the most successful portraits are often those that reveal the true essence of the subject - a subject that on canvas, at least, will never age. In the science world, researchers are relying on portraits of gene expression patterns - but, in this case, the images are helping to reveal how various tissues form.
Now, a multi-disciplinary team at UC San Diego has used novel computational methods to gain insight into kidney formation. By performing time-series analyses of global gene expression, and clustering these genes into larger groups known as metagene portraits and also calculating entropy values, the researchers have identified distinct stages of organ formation.
The research, published in the December 9 edition of Science Signaling, is also significant in that it suggests additional genes that had not been previously implicated in orchestration of kidney development.
"The approach may also be helpful for understanding tissue regeneration and pathological states," said Sanjay K. Nigam, Professor of UC San Diego's Department of Pediatrics, Department of Medicine (Nephrology-Hypertension) and the Department of Cellular and Molecular Medicine. "Analysis of the metagene portraits suggested points of stability and transition which are not as evident using conventional methods."
Additional research members in the study include Igor F. Tsigelny, a project scientist with UC San Diego's Department of Chemistry and Biochemistry and the San Diego Supercomputer Center at UC San Diego; and Valentina L. Kouznetsova; Derina E. Sweeney; Wei Wu; and Kevin T. Bush; all with UC San Diego's School of Medicine.
In efforts to provide a more comprehensive view of organogenesis, the researchers compared and analyzed visual representations of gene expression patterns during kidney development. Approximately 30,000 genes were organized into 650 groups called metagenes, or gene clusters known as self-organizing maps (SOMs).
Essentially acting as unsupervised learning neural networks, SOMs cluster genes with similar temporal expression profiles into metagene portraits. In this case, the SOMs were collected using microarray gene expression data and a high-dimensional data analysis program called Gene Expression Dynamics Inspector, or GEDI. UC San Diego scientists then performed a detailed time-series analysis of the kidney SOMs reflecting various stages of organogenesis. That was followed by entropy calculations for each SOM to measure the differences in states during the various stages, before correlating these results with morphometric parameters and specific gene networks.
Taken together, analysis of the metagene portraits suggested that kidney formation could be divided into as many as eight distinct stages.
"Although there is morphological support for the notion of stages, the beginning and end points of those stages can be difficult to define because many basic morphogenetic processes occur simultaneously," said Tsigelny. "Our research suggests that with the metagene analysis and entropy calculations, global gene expression can be used to more clearly define these stages and allow us to have a fuller understanding about how organs form."
Research for this UC San Diego study was supported by grants from the National Institutes of Health. For the full research article in Science Signaling, please see: stke.sciencemag/cgi/content/full/1/49/ra16
Source: Jan Zverina
University of California - San Diego
Now, a multi-disciplinary team at UC San Diego has used novel computational methods to gain insight into kidney formation. By performing time-series analyses of global gene expression, and clustering these genes into larger groups known as metagene portraits and also calculating entropy values, the researchers have identified distinct stages of organ formation.
The research, published in the December 9 edition of Science Signaling, is also significant in that it suggests additional genes that had not been previously implicated in orchestration of kidney development.
"The approach may also be helpful for understanding tissue regeneration and pathological states," said Sanjay K. Nigam, Professor of UC San Diego's Department of Pediatrics, Department of Medicine (Nephrology-Hypertension) and the Department of Cellular and Molecular Medicine. "Analysis of the metagene portraits suggested points of stability and transition which are not as evident using conventional methods."
Additional research members in the study include Igor F. Tsigelny, a project scientist with UC San Diego's Department of Chemistry and Biochemistry and the San Diego Supercomputer Center at UC San Diego; and Valentina L. Kouznetsova; Derina E. Sweeney; Wei Wu; and Kevin T. Bush; all with UC San Diego's School of Medicine.
In efforts to provide a more comprehensive view of organogenesis, the researchers compared and analyzed visual representations of gene expression patterns during kidney development. Approximately 30,000 genes were organized into 650 groups called metagenes, or gene clusters known as self-organizing maps (SOMs).
Essentially acting as unsupervised learning neural networks, SOMs cluster genes with similar temporal expression profiles into metagene portraits. In this case, the SOMs were collected using microarray gene expression data and a high-dimensional data analysis program called Gene Expression Dynamics Inspector, or GEDI. UC San Diego scientists then performed a detailed time-series analysis of the kidney SOMs reflecting various stages of organogenesis. That was followed by entropy calculations for each SOM to measure the differences in states during the various stages, before correlating these results with morphometric parameters and specific gene networks.
Taken together, analysis of the metagene portraits suggested that kidney formation could be divided into as many as eight distinct stages.
"Although there is morphological support for the notion of stages, the beginning and end points of those stages can be difficult to define because many basic morphogenetic processes occur simultaneously," said Tsigelny. "Our research suggests that with the metagene analysis and entropy calculations, global gene expression can be used to more clearly define these stages and allow us to have a fuller understanding about how organs form."
Research for this UC San Diego study was supported by grants from the National Institutes of Health. For the full research article in Science Signaling, please see: stke.sciencemag/cgi/content/full/1/49/ra16
Source: Jan Zverina
University of California - San Diego
понедельник, 20 июня 2011 г.
Muscle Cells Point The Finger At Each Other
A new study reveals that muscle cells fuse together during development by poking "fingers" into each other to help break down the membranes separating them. The study appears online in the Journal of Cell Biology.
During muscle development, individual muscle cells fuse together to form long myotubes containing multiple cell nuclei. In the fruit fly Drosophila melanogaster, fusion occurs between two different types of muscle cell: founder cells and fusion-competent myoblasts. Using electron microscopy to analyze developing fly embryos, Elizabeth Chen and colleagues from the Johns Hopkins University School of Medicine in Baltimore, MD, discovered that fusion-competent myoblasts send multiple "finger-like" protrusions into neighboring founder cells. These fingers contained large amounts of the cytoskeletal protein actin, and their formation required several proteins that stimulate the assembly of actin molecules into long filaments.
The actin-rich fingers helped form a small pore connecting the founder cell and fusion-competent myoblast, which gradually expands to fuse the two cell types together. The researchers think that the fingers assist pore formation by pushing the two cell membranes extremely close to each other.
The structure and behavior of these myoblast fingers are very similar to other types of actin-rich protrusions called invadosomes that researchers have previously identified in cancer cells and other cell types in culture. But this is the first example of this type of structure in a developing tissue. The researchers now want to investigate how these invasive myoblast fingers are formed and controlled.
Source:
Sati Motieram
Rockefeller University Press
During muscle development, individual muscle cells fuse together to form long myotubes containing multiple cell nuclei. In the fruit fly Drosophila melanogaster, fusion occurs between two different types of muscle cell: founder cells and fusion-competent myoblasts. Using electron microscopy to analyze developing fly embryos, Elizabeth Chen and colleagues from the Johns Hopkins University School of Medicine in Baltimore, MD, discovered that fusion-competent myoblasts send multiple "finger-like" protrusions into neighboring founder cells. These fingers contained large amounts of the cytoskeletal protein actin, and their formation required several proteins that stimulate the assembly of actin molecules into long filaments.
The actin-rich fingers helped form a small pore connecting the founder cell and fusion-competent myoblast, which gradually expands to fuse the two cell types together. The researchers think that the fingers assist pore formation by pushing the two cell membranes extremely close to each other.
The structure and behavior of these myoblast fingers are very similar to other types of actin-rich protrusions called invadosomes that researchers have previously identified in cancer cells and other cell types in culture. But this is the first example of this type of structure in a developing tissue. The researchers now want to investigate how these invasive myoblast fingers are formed and controlled.
Source:
Sati Motieram
Rockefeller University Press
пятница, 17 июня 2011 г.
Potential Risks To Native Species And Human Health From The Wildlife Trade
Wildlife imports into the United States are fragmented and insufficiently coordinated, failing to accurately list more than four in five species entering the country.
So reports a team of scientists from the Wildlife Trust, Brown University, Pacific Lutheran University, the Centers for Disease Control and Prevention, and the Global Invasive Species Programme.
A paper on their findings is published in this week's issue of the journal Science.
The poorly regulated U.S. wildlife trade can lead to devastating effects on ecosystems, native species, food supply chains and human health.
"As our world, in many senses, grows smaller and smaller with the ease of international travel, the network of connections has increased, facilitating the spread of diseases," said Rita Teutonico, senior advisor for integrative activities in the National Science Foundation's (NSF) Directorate for Social, Behavioral & Economic Sciences (SBE).
SBE co-funded this research through the agency's Human and Social Dynamics (HSD) priority area. HSD was supported by all NSF Directorates, and by NSF's Office of International Science and Engineering and Office of Polar Programs.
"These scientists report a pattern of trade in wildlife that includes a very large number of animals, coupled with a poor understanding of what species are traded," said James Collins, NSF Assistant Director for Biological Sciences. "The findings highlight the need for further research because of the unknown effects these animals and their pathogens can have on native organisms."
A global trade in wildlife generates hundreds of billions of dollars each year. The researchers report that during a six-year period from 2000 through 2006, the U.S. imported more than 1.5 billion live animals.
"That's more than 200 million animals a year--unexpectedly high," said scientist Peter Daszak, president of the Wildlife Trust, who co-led the research.
The animals collected were from wild populations in more than 190 countries around the world, and were intended for commercial sale in the U.S.--primarily in the pet trade.
"This incredible number of imports is equivalent to every single person in the U.S. owning at least five pets," said biologist Katherine Smith of Brown University, co-leader of the study.
More than 86 percent of shipments contained animals that were not classified to the level of species, making it impossible to assess the full diversity of animals imported, or calculate the risk of non-native species introductions or disease transmission.
"Shipments are coming in labeled 'live vertebrate' or 'fish,'" said Daszak. "If we don't know what animals are in there, how do we know which are going to become invasive species or carry diseases that could affect livestock, wildlife--or ourselves?"
The wildlife trade has previously led to disease introductions such as the 2003 monkeypox outbreak following the import of infected African rodents for the pet trade.
"The threat to public health is real, as the majority of emerging diseases come from wildlife," said Smith. "Most of these imported animals originate in Southeast Asia--a hotspot for emerging diseases."
The research team calls for direct measures to decrease the risk of such "pathogen pollution" and proposes guidelines to protect human, animal, and ecosystem health.
Recommendations:
Stricter record keeping should be required to inform risk analysis on animal imports.
Third-party surveillance and testing should be established for both known and unknown pathogens at the exportation points in foreign countries.
Greater public education is needed to educate individuals, importers, veterinarians and pet industry advocates about the dangers of diseases that emerge from wildlife and that can make their way to domesticated animals and humans.
"We need to look at all the factors that impact ecosystems--the whole picture," said Daszak. "The global wildlife trade is promoting a process that will impact our health and the health of the planet."
Source:
Cheryl Dybas
National Science Foundation
So reports a team of scientists from the Wildlife Trust, Brown University, Pacific Lutheran University, the Centers for Disease Control and Prevention, and the Global Invasive Species Programme.
A paper on their findings is published in this week's issue of the journal Science.
The poorly regulated U.S. wildlife trade can lead to devastating effects on ecosystems, native species, food supply chains and human health.
"As our world, in many senses, grows smaller and smaller with the ease of international travel, the network of connections has increased, facilitating the spread of diseases," said Rita Teutonico, senior advisor for integrative activities in the National Science Foundation's (NSF) Directorate for Social, Behavioral & Economic Sciences (SBE).
SBE co-funded this research through the agency's Human and Social Dynamics (HSD) priority area. HSD was supported by all NSF Directorates, and by NSF's Office of International Science and Engineering and Office of Polar Programs.
"These scientists report a pattern of trade in wildlife that includes a very large number of animals, coupled with a poor understanding of what species are traded," said James Collins, NSF Assistant Director for Biological Sciences. "The findings highlight the need for further research because of the unknown effects these animals and their pathogens can have on native organisms."
A global trade in wildlife generates hundreds of billions of dollars each year. The researchers report that during a six-year period from 2000 through 2006, the U.S. imported more than 1.5 billion live animals.
"That's more than 200 million animals a year--unexpectedly high," said scientist Peter Daszak, president of the Wildlife Trust, who co-led the research.
The animals collected were from wild populations in more than 190 countries around the world, and were intended for commercial sale in the U.S.--primarily in the pet trade.
"This incredible number of imports is equivalent to every single person in the U.S. owning at least five pets," said biologist Katherine Smith of Brown University, co-leader of the study.
More than 86 percent of shipments contained animals that were not classified to the level of species, making it impossible to assess the full diversity of animals imported, or calculate the risk of non-native species introductions or disease transmission.
"Shipments are coming in labeled 'live vertebrate' or 'fish,'" said Daszak. "If we don't know what animals are in there, how do we know which are going to become invasive species or carry diseases that could affect livestock, wildlife--or ourselves?"
The wildlife trade has previously led to disease introductions such as the 2003 monkeypox outbreak following the import of infected African rodents for the pet trade.
"The threat to public health is real, as the majority of emerging diseases come from wildlife," said Smith. "Most of these imported animals originate in Southeast Asia--a hotspot for emerging diseases."
The research team calls for direct measures to decrease the risk of such "pathogen pollution" and proposes guidelines to protect human, animal, and ecosystem health.
Recommendations:
Stricter record keeping should be required to inform risk analysis on animal imports.
Third-party surveillance and testing should be established for both known and unknown pathogens at the exportation points in foreign countries.
Greater public education is needed to educate individuals, importers, veterinarians and pet industry advocates about the dangers of diseases that emerge from wildlife and that can make their way to domesticated animals and humans.
"We need to look at all the factors that impact ecosystems--the whole picture," said Daszak. "The global wildlife trade is promoting a process that will impact our health and the health of the planet."
Source:
Cheryl Dybas
National Science Foundation
вторник, 14 июня 2011 г.
In Alzheimer's Models Growth Factor Protects Key Brain Cells
Memory loss, cognitive impairment, brain cell degeneration and cell death were prevented or reversed in several animal models after treatment with a naturally occurring protein called brain-derived neurotrophic factor (BDNF). The study by a University of California, San Diego-led team - published in the February 8, 2009 issue of Nature Medicine - shows that BDNF treatment can potentially provide long-lasting protection by slowing, or even stopping the progression of Alzheimer's disease in animal models.
"The effects of BDNF were potent," said Mark Tuszynski, MD, PhD, professor of neurosciences at the UC San Diego School of Medicine and neurologist at the Veterans Affairs San Diego Health System. "When we administered BDNF to memory circuits in the brain, we directly stimulated their activity and prevented cell death from the underlying disease."
BDNF is normally produced throughout life in the entorhinal cortex, a portion of the brain that supports memory. Its production decreases in the presence of Alzheimer's disease. For these experiments, the researchers injected the BDNF gene or protein in a series of cell culture and animal models, including transgenic mouse models of Alzheimer's disease; aged rats; rats with induced damage to the entorhinal cortex; aged rhesus monkeys, and monkeys with entorhinal cortex damage.
In each case, when compared with control groups not treated with BDNF, the treated animals demonstrated significant improvement in the performance of a variety of learning and memory tests. Notably, the brains of the treated animals also exhibited restored BDNF gene expression, enhanced cell size, improved cell signaling, and activation of function in neurons that would otherwise have degenerated, compared to untreated animals. These benefits extended to the degenerating hippocampus where short-term memory is processed, one of the first regions of the brain to suffer damage in Alzheimer's disease.
The demonstration of the effectiveness and safety of BDNF administration in animals provides "a rationale for exploring clinical translation" to humans, the team concludes, suggesting that the protective and restorative effects of BDNF on damaged neurons and neuronal signaling may offer a new approach to treating Alzheimer's disease.
This work builds on previous studies by Tuszynski and others, demonstrating the therapeutic affects of nerve growth factor (NGF) administered to patients with Alzheimer's disease. In 2001, Tuszynski and his team at UC San Diego Medical Center performed the first surgical implants of NGF genes into the brains of Alzheimer's patients, with follow-up results showing these patients experienced a possible slowing in cognitive decline and increased metabolic function in the brain. The NGF studies continue today, with Phase 2, multi-center studies currently underway.
"NGF therapy aims to stimulate the function of specific cholinergic neurons, which are like the air traffic controllers of the brain, helping to direct the activities of cells in broad regions of the brain," Tuszynski explained. However, he added that the benefits of NGF therapy, if validated in ongoing trials, will not be curative. Eventually, the effect of the NGF "boost" will be countered by the widespread death of neurons in the cerebral cortex as a result of advancing Alzheimer's disease.
"In contrast, BDNF acts directly on dying cells in specific memory circuits of the brain," Tuszynski said. "In this series of studies, we have shown that BDNF targets the cortical cells themselves, preventing their death, stimulating their function, and improving learning and memory. Thus, BDNF treatment can potentially provide long-lasting protection by slowing, or even stopping disease progression in the cortical regions that receive treatment."
The protective and restorative effects of BDNF occurred independently of the build-up of amyloid, a protein that accumulates in the brain to form plaques in Alzheimer's disease. Many current experimental treatments for Alzheimer's disease target amyloid production, so the potential role of BDNF as an alternative protective intervention is of great potential interest, said Tuszynski. Because BDNF targets a different set of disease mechanisms than amyloid modulation, there is also potential to combine BDNF and amyloid-based treatments, theoretically providing a two-pronged attack on the disease.
The study was supported by the National Institutes of Health, the California Regional Primate Research Center, the Veterans Administration, the Alzheimer's Association, the State of California, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Shiley Family Foundation. Tuszynski is scientific founder of Trophin Therapeutics, a company that may potentially benefit from the research results.
Study co-authors are Alan H. Nagahura, David A. Merrill, Shingo Tsukada, Brock E. Schroeder, Gideon M. Shaked, Ling Want, Armin Blesch, James M. Conner, Edward Rockenstein, Edward H. Koo, and Eliezer Masliah of the UC San Diego Department of Neurosciences, and Andrea A. Chiba of the UC San Diego Departments of Neurosciences and Cognitive Science. Giovanni Coppola and Daniel Geschwind of the Program in Neurogenetics, Department of Neurology at UCLA, and Albert Kim and Moses V. Chao, Skirball Institute of Biomolecular Medicine at New York University School of Medicine.
Source: Debra Kain
University of California - San Diego
"The effects of BDNF were potent," said Mark Tuszynski, MD, PhD, professor of neurosciences at the UC San Diego School of Medicine and neurologist at the Veterans Affairs San Diego Health System. "When we administered BDNF to memory circuits in the brain, we directly stimulated their activity and prevented cell death from the underlying disease."
BDNF is normally produced throughout life in the entorhinal cortex, a portion of the brain that supports memory. Its production decreases in the presence of Alzheimer's disease. For these experiments, the researchers injected the BDNF gene or protein in a series of cell culture and animal models, including transgenic mouse models of Alzheimer's disease; aged rats; rats with induced damage to the entorhinal cortex; aged rhesus monkeys, and monkeys with entorhinal cortex damage.
In each case, when compared with control groups not treated with BDNF, the treated animals demonstrated significant improvement in the performance of a variety of learning and memory tests. Notably, the brains of the treated animals also exhibited restored BDNF gene expression, enhanced cell size, improved cell signaling, and activation of function in neurons that would otherwise have degenerated, compared to untreated animals. These benefits extended to the degenerating hippocampus where short-term memory is processed, one of the first regions of the brain to suffer damage in Alzheimer's disease.
The demonstration of the effectiveness and safety of BDNF administration in animals provides "a rationale for exploring clinical translation" to humans, the team concludes, suggesting that the protective and restorative effects of BDNF on damaged neurons and neuronal signaling may offer a new approach to treating Alzheimer's disease.
This work builds on previous studies by Tuszynski and others, demonstrating the therapeutic affects of nerve growth factor (NGF) administered to patients with Alzheimer's disease. In 2001, Tuszynski and his team at UC San Diego Medical Center performed the first surgical implants of NGF genes into the brains of Alzheimer's patients, with follow-up results showing these patients experienced a possible slowing in cognitive decline and increased metabolic function in the brain. The NGF studies continue today, with Phase 2, multi-center studies currently underway.
"NGF therapy aims to stimulate the function of specific cholinergic neurons, which are like the air traffic controllers of the brain, helping to direct the activities of cells in broad regions of the brain," Tuszynski explained. However, he added that the benefits of NGF therapy, if validated in ongoing trials, will not be curative. Eventually, the effect of the NGF "boost" will be countered by the widespread death of neurons in the cerebral cortex as a result of advancing Alzheimer's disease.
"In contrast, BDNF acts directly on dying cells in specific memory circuits of the brain," Tuszynski said. "In this series of studies, we have shown that BDNF targets the cortical cells themselves, preventing their death, stimulating their function, and improving learning and memory. Thus, BDNF treatment can potentially provide long-lasting protection by slowing, or even stopping disease progression in the cortical regions that receive treatment."
The protective and restorative effects of BDNF occurred independently of the build-up of amyloid, a protein that accumulates in the brain to form plaques in Alzheimer's disease. Many current experimental treatments for Alzheimer's disease target amyloid production, so the potential role of BDNF as an alternative protective intervention is of great potential interest, said Tuszynski. Because BDNF targets a different set of disease mechanisms than amyloid modulation, there is also potential to combine BDNF and amyloid-based treatments, theoretically providing a two-pronged attack on the disease.
The study was supported by the National Institutes of Health, the California Regional Primate Research Center, the Veterans Administration, the Alzheimer's Association, the State of California, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Shiley Family Foundation. Tuszynski is scientific founder of Trophin Therapeutics, a company that may potentially benefit from the research results.
Study co-authors are Alan H. Nagahura, David A. Merrill, Shingo Tsukada, Brock E. Schroeder, Gideon M. Shaked, Ling Want, Armin Blesch, James M. Conner, Edward Rockenstein, Edward H. Koo, and Eliezer Masliah of the UC San Diego Department of Neurosciences, and Andrea A. Chiba of the UC San Diego Departments of Neurosciences and Cognitive Science. Giovanni Coppola and Daniel Geschwind of the Program in Neurogenetics, Department of Neurology at UCLA, and Albert Kim and Moses V. Chao, Skirball Institute of Biomolecular Medicine at New York University School of Medicine.
Source: Debra Kain
University of California - San Diego
суббота, 11 июня 2011 г.
How Viruses Collectively Decide The Fate Of A Bacterial Cell
A new study suggests that bacteria-infecting viruses -called phages - can make collective decisions about whether to kill host cells immediately after infection or enter a latent state to remain within the host cell.
The research, published in the September 15 issue of the Biophysical Journal, shows that when multiple viruses infect a cell, this increases the number of viral genomes and therefore the overall level of viral gene expression. Changes in viral gene expression can have a dramatic nonlinear effect on gene networks that control whether viruses burst out of the host cell or enter a latent state.
"What has confounded the virology community for quite some time is the observation that the cell fate of a bacteria infected by a single virus can be dramatically different than that infected by two viruses," said Joshua Weitz, an assistant professor in the School of Biology at the Georgia Institute of Technology. "Our study suggests that viruses can collectively decide whether or not to kill a host, and that individual viruses 'talk' to each other as a result of interactions between viral genomes and viral proteins they direct the infected host to produce."
To study viral infections, Weitz teamed with postdoctoral fellow Yuriy Mileyko, graduate student Richard Joh and Eberhard Voit, who is a professor in the Wallace H. Coulter Department of Biomedical Engineering, the David D. Flanagan Chair Georgia Research Alliance Eminent Scholar in Biological Systems and director of the new Integrative BioSystems Institute at Georgia Tech.
Nearly all previous theoretical studies have claimed that switching between "lysis" and "latency" pathways depends on some change in environmental conditions or random chance. However, this new study suggests that the response to co-infection can be an evolvable feature of viral life history.
For this study, the researchers analyzed the decision circuit that determines whether a virus initially chooses the pathway that kills the host cell - called the lytic pathway - or the pathway where it remains dormant inside the host cell - called the lysogenic pathway.
When the lytic pathway is selected, the virus utilizes bacterial resources to replicate and then destroys the host cell, releasing new viruses that can infect other cells. In contrast, in the lysogenic pathway, the viral genome inserts itself into the bacterial genome and replicates along with it, while repressing viral genes that lead to lysis. The virus remains dormant until host conditions change, which can result in a switch to the lytic pathway.
The decision of the genetic circuit that controls whether a virus initially chooses lysis or lysogeny is not random. Instead, cell fate is controlled by the number of infecting viruses in a coordinated fashion, according to the new study, which was funded by the Defense Advanced Research Projects Agency, the National Science Foundation and the Burroughs Wellcome Fund.
"In the case of perhaps the most extensively studied bacteriophage, lambda phage, experimental evidence indicates that a single infecting phage leads to host cell death and viral release, whereas if two or more phages infect a host the outcome is typically latency," explained Weitz, who is a core member of the new Integrative BioSystems Institute at Georgia Tech. "We wanted to know why two viruses would behave differently than a single virus, given that the infecting viruses possess the same genetic decision circuit."
To find out, the researchers modeled the complex gene regulatory dynamics of the lysis-lysogeny switch for lambda phage. They tracked the dynamics of three key genes - cro, cI and cII - and their protein production. The decision circuit involved both negative and positive feedback loops, which responded differently to changes in the total number of viral genomes inside a cell. The positive feedback loop was linked to the lysogenic pathway and the negative feedback loop was linked to the lytic pathway.
With a single virus, cro dominated and the lytic pathway prevailed. If the number of co-infecting viruses exceeded a certain threshold, the positive feedback loop associated with cI dominated, turning the switch to the lysogenic pathway. The differences in bacterial cell fate were stark and hinged upon whether or not one or two viruses were inside a given cell.
The researchers found that the cII gene acted as the gate for the system. Increasing the number of viruses drove the dynamic level of cII proteins past a critical point facilitating production of cI proteins leading to the lysogenic pathway.
"The decision circuit is a race between two pathways and in the case of a single virus, the outcome is biased toward lysis," explained Weitz. "In our model, when multiple viruses infect a given cell, the overall production of regulatory proteins increases. This transient increase is reinforced by a positive feedback loop in the latency pathway, permitting even higher production of lysogenic proteins, and ultimately the latent outcome."
The central idea in the model proposed by Weitz and collaborators is that increases in the overall amount of viral proteins produced from multiple viral genomes can have a dramatic effect on the nonlinear gene networks that control cell fate.
"Many questions still remain, including to what extent subsequent viruses can change the outcome of previously infected, but not yet committed, viruses, and to what extent microenvironments inside the host impact cell fate," added Weitz. "Nonetheless, this study proposes a mechanistic explanation to a long-standing paradox by showing that when multiple viruses infect a host cell, those viruses can make a collective decision rather than behaving as they would individually."
Source: Abby Vogel
Georgia Institute of Technology Research News
The research, published in the September 15 issue of the Biophysical Journal, shows that when multiple viruses infect a cell, this increases the number of viral genomes and therefore the overall level of viral gene expression. Changes in viral gene expression can have a dramatic nonlinear effect on gene networks that control whether viruses burst out of the host cell or enter a latent state.
"What has confounded the virology community for quite some time is the observation that the cell fate of a bacteria infected by a single virus can be dramatically different than that infected by two viruses," said Joshua Weitz, an assistant professor in the School of Biology at the Georgia Institute of Technology. "Our study suggests that viruses can collectively decide whether or not to kill a host, and that individual viruses 'talk' to each other as a result of interactions between viral genomes and viral proteins they direct the infected host to produce."
To study viral infections, Weitz teamed with postdoctoral fellow Yuriy Mileyko, graduate student Richard Joh and Eberhard Voit, who is a professor in the Wallace H. Coulter Department of Biomedical Engineering, the David D. Flanagan Chair Georgia Research Alliance Eminent Scholar in Biological Systems and director of the new Integrative BioSystems Institute at Georgia Tech.
Nearly all previous theoretical studies have claimed that switching between "lysis" and "latency" pathways depends on some change in environmental conditions or random chance. However, this new study suggests that the response to co-infection can be an evolvable feature of viral life history.
For this study, the researchers analyzed the decision circuit that determines whether a virus initially chooses the pathway that kills the host cell - called the lytic pathway - or the pathway where it remains dormant inside the host cell - called the lysogenic pathway.
When the lytic pathway is selected, the virus utilizes bacterial resources to replicate and then destroys the host cell, releasing new viruses that can infect other cells. In contrast, in the lysogenic pathway, the viral genome inserts itself into the bacterial genome and replicates along with it, while repressing viral genes that lead to lysis. The virus remains dormant until host conditions change, which can result in a switch to the lytic pathway.
The decision of the genetic circuit that controls whether a virus initially chooses lysis or lysogeny is not random. Instead, cell fate is controlled by the number of infecting viruses in a coordinated fashion, according to the new study, which was funded by the Defense Advanced Research Projects Agency, the National Science Foundation and the Burroughs Wellcome Fund.
"In the case of perhaps the most extensively studied bacteriophage, lambda phage, experimental evidence indicates that a single infecting phage leads to host cell death and viral release, whereas if two or more phages infect a host the outcome is typically latency," explained Weitz, who is a core member of the new Integrative BioSystems Institute at Georgia Tech. "We wanted to know why two viruses would behave differently than a single virus, given that the infecting viruses possess the same genetic decision circuit."
To find out, the researchers modeled the complex gene regulatory dynamics of the lysis-lysogeny switch for lambda phage. They tracked the dynamics of three key genes - cro, cI and cII - and their protein production. The decision circuit involved both negative and positive feedback loops, which responded differently to changes in the total number of viral genomes inside a cell. The positive feedback loop was linked to the lysogenic pathway and the negative feedback loop was linked to the lytic pathway.
With a single virus, cro dominated and the lytic pathway prevailed. If the number of co-infecting viruses exceeded a certain threshold, the positive feedback loop associated with cI dominated, turning the switch to the lysogenic pathway. The differences in bacterial cell fate were stark and hinged upon whether or not one or two viruses were inside a given cell.
The researchers found that the cII gene acted as the gate for the system. Increasing the number of viruses drove the dynamic level of cII proteins past a critical point facilitating production of cI proteins leading to the lysogenic pathway.
"The decision circuit is a race between two pathways and in the case of a single virus, the outcome is biased toward lysis," explained Weitz. "In our model, when multiple viruses infect a given cell, the overall production of regulatory proteins increases. This transient increase is reinforced by a positive feedback loop in the latency pathway, permitting even higher production of lysogenic proteins, and ultimately the latent outcome."
The central idea in the model proposed by Weitz and collaborators is that increases in the overall amount of viral proteins produced from multiple viral genomes can have a dramatic effect on the nonlinear gene networks that control cell fate.
"Many questions still remain, including to what extent subsequent viruses can change the outcome of previously infected, but not yet committed, viruses, and to what extent microenvironments inside the host impact cell fate," added Weitz. "Nonetheless, this study proposes a mechanistic explanation to a long-standing paradox by showing that when multiple viruses infect a host cell, those viruses can make a collective decision rather than behaving as they would individually."
Source: Abby Vogel
Georgia Institute of Technology Research News
среда, 8 июня 2011 г.
New NIST Mini-Sensor May Have Biomedical And Security Applications
A tiny sensor that can detect magnetic field changes as small as 70 femtoteslas-equivalent to the brain waves of a person daydreaming-has been demonstrated at the National Institute of Standards and Technology (NIST). The sensor could be battery-operated and could reduce the costs of non-invasive biomagnetic measurements such as fetal heart monitoring. The device also may have applications such as homeland security screening for explosives.
Described in the November issue of Nature Photonics,* the prototype device is almost 1000 times more sensitive than NIST's original chip-scale magnetometer demonstrated in 2004 and is based on a different operating principle. Its performance puts it within reach of matching the current gold standard for magnetic sensors, so-called superconducting quantum interference devices or SQUIDs. These devices can sense changes in the 3- to 40-femtotesla range but must be cooled to very low (cryogenic) temperatures, making them much larger, power hungry, and more expensive.
The NIST prototype consists of a single low-power (milliwatt) infrared laser and a rice-grain-sized container with dimensions of 3 by 2 by 1 millimeters. The container holds about 100 billion rubidium atoms in gas form. As the laser beam passes through the atomic vapor, scientists measure the transmitted optical power while varying the strength of a magnetic field applied perpendicular to the beam. The amount of laser light absorbed by the atoms varies predictably with the magnetic field, providing a reference scale for measuring the field. The stronger the magnetic field, the more light is absorbed.
"The small size and high performance of this sensor will open doors to applications that we could previously only dream about," project leader John Kitching says.
The new NIST mini-sensor could reduce the equipment size and costs associated with some non-invasive biomedical tests. (The body's electrical signals that make the heart contract or brain cells fire also simultaneously generate a magnetic field.) The NIST group and collaborators have used a modified version of the original sensor to detect magnetic signals from a mouse heart.** The new sensor is already powerful enough for fetal heart monitoring; with further work, the sensitivity can likely be improved to a level in the 10 femtotesla range, sufficient for additional applications such as measuring brain activity, the designers say. A femtotesla is one quadrillionth (or a millionth of a billionth) of a tesla, the unit that defines the strength of a magnetic field. For comparison, the Earth's magnetic field is measured in microteslas, and a magnetic resonance imaging (MRI) system operates at several teslas.
To make a complete portable magnetometer, the laser and vapor cell would need to be packaged with miniature optics and a light detector. The vapor cell can be fabricated and assembled on semiconductor wafers using existing techniques for making microelectronics and microelectromechanical systems (MEMS). This design, adapted from a previously developed NIST chip-scale atomic clock, offers the potential for low-cost mass production.
As described in the new paper, NIST scientists demonstrated that the prototype mini-sensor produces a strong signal that changes rapidly with the strength of a magnetic field from the outside world. The device exhibits a consistent minimum level of electromagnetic static, or "white noise," which indicates a stable limit on its overall sensitivity. The authors also estimated that a well-designed compact magnetometer with present sensitivity could operate continuously for weeks on a single AA battery. Magnetometers need to be designed with applications in mind; smaller vapor cells require less power but are also less sensitive. Thus, an application for which low power is critical would benefit from a very small magnetometer, whereas a larger magnetometer would be more suitable for a different application requiring high sensitivity. The NIST work evaluates the tradeoffs between size, power and performance in a quantifiable way.
"This result suggests that millimeter-scale, low-power, inexpensive, femtotesla magnetometers are feasible ... Such an instrument would greatly expand the range of applications in which atomic magnetometers could be used," the paper states.
The NIST device could be used in a heart monitoring technique known as magnetocardiography (MCG), which is sensitive enough to measure fields of few picoteslas emitted by the fetal heart from small currents in heart muscle cells, providing complementary and perhaps better information than an electrocardiogram. With further improvements, the NIST sensor also might be used in magnetoencephalography (MEG), which measures the magnetic fields produced by electrical activity in the brain, helping to pinpoint tumors or determine function of various parts of the brain. The existing mini-sensor likely will be able to detect some brain activity, such as the signals from alpha waves, which are about 1 picotesla in magnitude at a distance of 1 centimeter from the skull surface, but not the fainter signals from the full range of brain function. (Signals of magnitude 1 picotesla are identifiable with a magnetometer sensitivity of 70 femtotesla per root Hertz.) MCG and MEG offer the advantage of not requiring contrast agents or injected tracers as do other medical procedures such as MRI or positron emission tomography (PET).
Potential NIST collaborators are interested in making a portable MEG helmet that could be worn by epileptics to record brain activity before and during seizures. The devices would be much smaller and lighter than the SQUID helmets currently used for such studies. Kitching said the NIST sensor also may have applications in MRI or in airport screening for explosives based on detection of nuclear quadrupole resonance in nitrogen compounds.
As a non-regulatory agency of the Commerce Department, NIST promotes U.S. innovation and industrial competitiveness by advancing measurement science, standards and technology in ways that enhance economic security and improve our quality of life.
* Vishal Shah, Svenja Knappe, Peter D.D. Schwindt, and John Kitching. Femtotesla Atomic Magnetometry with a Microfabricated Vapor Cell. Nature Photonics. 1 November 2007.
** Brad Lindseth, Peter Schwindt, John Kitching, David Fischer, Vladimir Shusterman. 2007. Non-contact Measurement of Cardiac Electromagnetic Field in Mice Using an Ultra-small Atomic Magnetometer. Feasibility Study. Presented at Computers in Cardiology, Durham, NC, Sept 30-Oct. 3, 2007.
Background: How the NIST Mini-Sensor Works
The NIST compact magnetometer is based on the so-called SERF (spin-exchange relaxation free) principle, which was used by a group at Princeton University in 2003 to enhance the sensitivity of larger, tabletop-sized magnetometers to outperform SQUIDs. The NIST group developed novel approaches and technologies to adapt the SERF concept for tiny and practical devices.
At zero magnetic field, the atoms' electron "spins" (which can be roughly visualized as tiny magnetic arrows pointing through the electrons) all point in the same direction as the laser beam, and the atoms absorb virtually no light. As the magnetic field is increased, the electrons jump to higher-energy levels and their spins go out of sync, causing the atoms to absorb some of the light.
Ordinarily, the atoms would collide randomly and the electron spins would change direction in between collisions, degrading the sensor signal. The SERF approach maintains consistent spins for a relatively long time (10 milliseconds) by combining a low magnetic field with high temperatures of 150 degrees C (302 degrees F). The spins have little time to adjust in between the collisions. Like cars on a highway, the atoms behave more consistently when conditions are crowded.
Source: Laura Ost
National Institute of Standards and Technology (NIST)
Described in the November issue of Nature Photonics,* the prototype device is almost 1000 times more sensitive than NIST's original chip-scale magnetometer demonstrated in 2004 and is based on a different operating principle. Its performance puts it within reach of matching the current gold standard for magnetic sensors, so-called superconducting quantum interference devices or SQUIDs. These devices can sense changes in the 3- to 40-femtotesla range but must be cooled to very low (cryogenic) temperatures, making them much larger, power hungry, and more expensive.
The NIST prototype consists of a single low-power (milliwatt) infrared laser and a rice-grain-sized container with dimensions of 3 by 2 by 1 millimeters. The container holds about 100 billion rubidium atoms in gas form. As the laser beam passes through the atomic vapor, scientists measure the transmitted optical power while varying the strength of a magnetic field applied perpendicular to the beam. The amount of laser light absorbed by the atoms varies predictably with the magnetic field, providing a reference scale for measuring the field. The stronger the magnetic field, the more light is absorbed.
"The small size and high performance of this sensor will open doors to applications that we could previously only dream about," project leader John Kitching says.
The new NIST mini-sensor could reduce the equipment size and costs associated with some non-invasive biomedical tests. (The body's electrical signals that make the heart contract or brain cells fire also simultaneously generate a magnetic field.) The NIST group and collaborators have used a modified version of the original sensor to detect magnetic signals from a mouse heart.** The new sensor is already powerful enough for fetal heart monitoring; with further work, the sensitivity can likely be improved to a level in the 10 femtotesla range, sufficient for additional applications such as measuring brain activity, the designers say. A femtotesla is one quadrillionth (or a millionth of a billionth) of a tesla, the unit that defines the strength of a magnetic field. For comparison, the Earth's magnetic field is measured in microteslas, and a magnetic resonance imaging (MRI) system operates at several teslas.
To make a complete portable magnetometer, the laser and vapor cell would need to be packaged with miniature optics and a light detector. The vapor cell can be fabricated and assembled on semiconductor wafers using existing techniques for making microelectronics and microelectromechanical systems (MEMS). This design, adapted from a previously developed NIST chip-scale atomic clock, offers the potential for low-cost mass production.
As described in the new paper, NIST scientists demonstrated that the prototype mini-sensor produces a strong signal that changes rapidly with the strength of a magnetic field from the outside world. The device exhibits a consistent minimum level of electromagnetic static, or "white noise," which indicates a stable limit on its overall sensitivity. The authors also estimated that a well-designed compact magnetometer with present sensitivity could operate continuously for weeks on a single AA battery. Magnetometers need to be designed with applications in mind; smaller vapor cells require less power but are also less sensitive. Thus, an application for which low power is critical would benefit from a very small magnetometer, whereas a larger magnetometer would be more suitable for a different application requiring high sensitivity. The NIST work evaluates the tradeoffs between size, power and performance in a quantifiable way.
"This result suggests that millimeter-scale, low-power, inexpensive, femtotesla magnetometers are feasible ... Such an instrument would greatly expand the range of applications in which atomic magnetometers could be used," the paper states.
The NIST device could be used in a heart monitoring technique known as magnetocardiography (MCG), which is sensitive enough to measure fields of few picoteslas emitted by the fetal heart from small currents in heart muscle cells, providing complementary and perhaps better information than an electrocardiogram. With further improvements, the NIST sensor also might be used in magnetoencephalography (MEG), which measures the magnetic fields produced by electrical activity in the brain, helping to pinpoint tumors or determine function of various parts of the brain. The existing mini-sensor likely will be able to detect some brain activity, such as the signals from alpha waves, which are about 1 picotesla in magnitude at a distance of 1 centimeter from the skull surface, but not the fainter signals from the full range of brain function. (Signals of magnitude 1 picotesla are identifiable with a magnetometer sensitivity of 70 femtotesla per root Hertz.) MCG and MEG offer the advantage of not requiring contrast agents or injected tracers as do other medical procedures such as MRI or positron emission tomography (PET).
Potential NIST collaborators are interested in making a portable MEG helmet that could be worn by epileptics to record brain activity before and during seizures. The devices would be much smaller and lighter than the SQUID helmets currently used for such studies. Kitching said the NIST sensor also may have applications in MRI or in airport screening for explosives based on detection of nuclear quadrupole resonance in nitrogen compounds.
As a non-regulatory agency of the Commerce Department, NIST promotes U.S. innovation and industrial competitiveness by advancing measurement science, standards and technology in ways that enhance economic security and improve our quality of life.
* Vishal Shah, Svenja Knappe, Peter D.D. Schwindt, and John Kitching. Femtotesla Atomic Magnetometry with a Microfabricated Vapor Cell. Nature Photonics. 1 November 2007.
** Brad Lindseth, Peter Schwindt, John Kitching, David Fischer, Vladimir Shusterman. 2007. Non-contact Measurement of Cardiac Electromagnetic Field in Mice Using an Ultra-small Atomic Magnetometer. Feasibility Study. Presented at Computers in Cardiology, Durham, NC, Sept 30-Oct. 3, 2007.
Background: How the NIST Mini-Sensor Works
The NIST compact magnetometer is based on the so-called SERF (spin-exchange relaxation free) principle, which was used by a group at Princeton University in 2003 to enhance the sensitivity of larger, tabletop-sized magnetometers to outperform SQUIDs. The NIST group developed novel approaches and technologies to adapt the SERF concept for tiny and practical devices.
At zero magnetic field, the atoms' electron "spins" (which can be roughly visualized as tiny magnetic arrows pointing through the electrons) all point in the same direction as the laser beam, and the atoms absorb virtually no light. As the magnetic field is increased, the electrons jump to higher-energy levels and their spins go out of sync, causing the atoms to absorb some of the light.
Ordinarily, the atoms would collide randomly and the electron spins would change direction in between collisions, degrading the sensor signal. The SERF approach maintains consistent spins for a relatively long time (10 milliseconds) by combining a low magnetic field with high temperatures of 150 degrees C (302 degrees F). The spins have little time to adjust in between the collisions. Like cars on a highway, the atoms behave more consistently when conditions are crowded.
Source: Laura Ost
National Institute of Standards and Technology (NIST)
воскресенье, 5 июня 2011 г.
Loss And Regain Of Consciousness During General Anesthesia Regulated By Two Different Neural Pathways
University of Pennsylvania School of Medicine researchers have answered long-running questions about the way that anesthetics act on the body, by showing that the cellular pathway for emerging from anesthesia is different from the one that drugs take to put patients to sleep during operations. The findings will be published in Proceedings of the National Academy of Sciences.
The research focuses on orexins, the small, specialized fraction of the brain's 100 billion neurons that play a key role in regulating the body's wakeful state. Studying mice whose orexin systems had been genetically destroyed - a state similar to humans suffering from narcolepsy, a neurological condition that causes unusual daytime sleepiness - Max B. Kelz, MD, PhD, an assistant professor in Penn's Department of Anesthesiology and Critical Care and the Mahoney Institute of Neurological Sciences, found that these mice took much longer to emerge from general anesthesia than those with normal orexin signaling systems. However, the mice with faulty orexin systems did not appear to fall asleep faster during anesthesia, which suggests that different processes are at play when transitioning to and from the anesthetized stated.
"The modern expectation is that anesthesiologists can simply flip a consciousness switch as easily as we might turn the room lights on or off," says lead author Max B. Kelz, MD, PhD, an assistant professor in Penn's Department of Anesthesiology and Critical Care and the Mahoney Institute of Neurological Sciences. "However, what patients do not realize is that despite 160 years of widespread clinical use, the mechanisms through which the state of anesthesia arises and dissipates remain unknown."
Kelz became interested in these questions after treating a narcoleptic patient who took more than six hours to regain consciousness after anesthesia, compared to the typical six minutes or so. By probing what's different about the narcoleptic brain, the Penn study has established for the first time that the process of entry into and exit from the anesthetized state are not mirror images of one another.
Kelz and his colleagues, including Sigrid Veasey, MD, associate professor in the Department of Medicine's Sleep Medicine division, hope that further research on the brain's neural signaling systems will lead to novel ways to administer anesthesia and "jump start" a speedy, safe return to consciousness - particularly among patients who struggle to wake up or in patient groups that may be more prone to anesthesia side effects such as the elderly and patients with neurodegenerative disorders. The findings might also be used to create designer anesthetic agents that "hijack" the body's natural sleep cycles to mimic a state closer to natural sleep than a chemically-induced coma, Kelz says.
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals - its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center - a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
Source: Holly Auer
University of Pennsylvania School of Medicine
The research focuses on orexins, the small, specialized fraction of the brain's 100 billion neurons that play a key role in regulating the body's wakeful state. Studying mice whose orexin systems had been genetically destroyed - a state similar to humans suffering from narcolepsy, a neurological condition that causes unusual daytime sleepiness - Max B. Kelz, MD, PhD, an assistant professor in Penn's Department of Anesthesiology and Critical Care and the Mahoney Institute of Neurological Sciences, found that these mice took much longer to emerge from general anesthesia than those with normal orexin signaling systems. However, the mice with faulty orexin systems did not appear to fall asleep faster during anesthesia, which suggests that different processes are at play when transitioning to and from the anesthetized stated.
"The modern expectation is that anesthesiologists can simply flip a consciousness switch as easily as we might turn the room lights on or off," says lead author Max B. Kelz, MD, PhD, an assistant professor in Penn's Department of Anesthesiology and Critical Care and the Mahoney Institute of Neurological Sciences. "However, what patients do not realize is that despite 160 years of widespread clinical use, the mechanisms through which the state of anesthesia arises and dissipates remain unknown."
Kelz became interested in these questions after treating a narcoleptic patient who took more than six hours to regain consciousness after anesthesia, compared to the typical six minutes or so. By probing what's different about the narcoleptic brain, the Penn study has established for the first time that the process of entry into and exit from the anesthetized state are not mirror images of one another.
Kelz and his colleagues, including Sigrid Veasey, MD, associate professor in the Department of Medicine's Sleep Medicine division, hope that further research on the brain's neural signaling systems will lead to novel ways to administer anesthesia and "jump start" a speedy, safe return to consciousness - particularly among patients who struggle to wake up or in patient groups that may be more prone to anesthesia side effects such as the elderly and patients with neurodegenerative disorders. The findings might also be used to create designer anesthetic agents that "hijack" the body's natural sleep cycles to mimic a state closer to natural sleep than a chemically-induced coma, Kelz says.
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals - its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center - a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
Source: Holly Auer
University of Pennsylvania School of Medicine
пятница, 3 июня 2011 г.
NOVA To Air Two-hour Documentary On Pioneering African American Chemist
The remarkable life story of pioneering African American chemist Percy Julian is the subject of a two-hour PBS/NOVA documentary to air Feb. 6 during Black History Month. The grandson of Alabama slaves, Julian won world-wide fame for his accomplishments in organic chemistry, especially in the synthesis of medicinal drugs.
Entitled "Forgotten Genius," the film, in the words of Jim Shoffner, Ph.D., a former member of the Board of Directors of the American Chemical Society, honors a man who "was an inspirational and motivational figure for many young men and women. Although this was especially true for students and researchers of color, it was more generally true for all, no matter what their race, ethnicity or gender."
Percy Lavon Julian was born in Montgomery, Ala., on April 11, 1899, the son of a railway clerk. Julian's schooling was spotty in the segregated South of the early 20th century. Even so, he was accepted at DePauw University in Greencastle, Ind., where he excelled, graduating in 1920 as class valedictorian.
Julian chose chemistry as a career, but he was discouraged from seeking admission to graduate school because of racial prejudice. Instead, he took the advice of an advisor and accepted a position as an instructor of chemistry at Fisk University in Nashville, Tenn. After two years at Fisk, Julian won an Austin Fellowship to Harvard where he received his M.A. in 1923.
In 1929 Julian won a Rockefeller Foundation grant, which he used to earn his doctorate in natural products chemistry at the University of Vienna in 1931. Julian returned to DePauw University in 1933 as a research fellow. It was at DePauw in 1935 that Julian completed research on the synthesis of physostigmine, a drug used in the treatment of glaucoma. This work established Julian as world-renowned chemist, but he was denied a faculty position at DePauw.
DePauw's decision forced Julian out of the university and into the corporate world. He accepted a position with the Glidden Company in Chicago as director of research for the Soya Product Division. Over the next 18 years the results of Julian's research led to numerous patents and successful products for Glidden, among them a fire-retardant foam used widely in World War II to extinguish gasoline fires. His biomedical research paved the way for the production of large quantities of inexpensive synthetic progesterone from soybeans. He also developed a synthetic version of cortisone, used to relieve the pain of rheumatoid arthritis. Natural cortisone was extremely expensive but Julian's discovery of a soy-based substitute helped millions of arthritis sufferers find relief at a reasonable price.
In 1953, he established Julian Laboratories which he sold eight years later for $2 million. In 1973, he was elected to the National Academy of Sciences. Julian died on April 19, 1975. (For more on Percy Julian's life, please visit the National Historic Chemical Web site at chemistry/landmarks/julian.html.)
"Forgotten Genius" had financial support from the Alfred P. Sloan Foundation, the National Endowment for the Humanities, and the National Science Foundation as well as seed money from the American Chemical Society. Anne O'Brien, Ph.D., a current member of the ACS Board of Directors, says "the chance to honor this American chemist, to offer Dr. Julian as a role model??¦. and to have that message reach an audience as large as NOVA's, was an opportunity not to be missed."
The American Chemical Society -- the world's largest scientific society -- is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
Contact: Judah Ginsberg
American Chemical Society
Entitled "Forgotten Genius," the film, in the words of Jim Shoffner, Ph.D., a former member of the Board of Directors of the American Chemical Society, honors a man who "was an inspirational and motivational figure for many young men and women. Although this was especially true for students and researchers of color, it was more generally true for all, no matter what their race, ethnicity or gender."
Percy Lavon Julian was born in Montgomery, Ala., on April 11, 1899, the son of a railway clerk. Julian's schooling was spotty in the segregated South of the early 20th century. Even so, he was accepted at DePauw University in Greencastle, Ind., where he excelled, graduating in 1920 as class valedictorian.
Julian chose chemistry as a career, but he was discouraged from seeking admission to graduate school because of racial prejudice. Instead, he took the advice of an advisor and accepted a position as an instructor of chemistry at Fisk University in Nashville, Tenn. After two years at Fisk, Julian won an Austin Fellowship to Harvard where he received his M.A. in 1923.
In 1929 Julian won a Rockefeller Foundation grant, which he used to earn his doctorate in natural products chemistry at the University of Vienna in 1931. Julian returned to DePauw University in 1933 as a research fellow. It was at DePauw in 1935 that Julian completed research on the synthesis of physostigmine, a drug used in the treatment of glaucoma. This work established Julian as world-renowned chemist, but he was denied a faculty position at DePauw.
DePauw's decision forced Julian out of the university and into the corporate world. He accepted a position with the Glidden Company in Chicago as director of research for the Soya Product Division. Over the next 18 years the results of Julian's research led to numerous patents and successful products for Glidden, among them a fire-retardant foam used widely in World War II to extinguish gasoline fires. His biomedical research paved the way for the production of large quantities of inexpensive synthetic progesterone from soybeans. He also developed a synthetic version of cortisone, used to relieve the pain of rheumatoid arthritis. Natural cortisone was extremely expensive but Julian's discovery of a soy-based substitute helped millions of arthritis sufferers find relief at a reasonable price.
In 1953, he established Julian Laboratories which he sold eight years later for $2 million. In 1973, he was elected to the National Academy of Sciences. Julian died on April 19, 1975. (For more on Percy Julian's life, please visit the National Historic Chemical Web site at chemistry/landmarks/julian.html.)
"Forgotten Genius" had financial support from the Alfred P. Sloan Foundation, the National Endowment for the Humanities, and the National Science Foundation as well as seed money from the American Chemical Society. Anne O'Brien, Ph.D., a current member of the ACS Board of Directors, says "the chance to honor this American chemist, to offer Dr. Julian as a role model??¦. and to have that message reach an audience as large as NOVA's, was an opportunity not to be missed."
The American Chemical Society -- the world's largest scientific society -- is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
Contact: Judah Ginsberg
American Chemical Society
Costs Related To Arthritis, Similar Conditions Increased To $128B In 2003, CDC Says
The cost of arthritis and related conditions in the U.S. increased to $128 billion in 2003, the most recent year for which data were available, and the amount will continue to increase as the population becomes older and heavier, CDC said on Thursday, the AP/Long Island Newsday reports. According to CDC, the $128 billion in costs included $80.8 billion in direct costs, such as medical expenses, and $47 billion in indirect costs, such as lost wages. The $128 billion in costs represented a 48% increase from $86.2 billion in 1997, in large part because federal surveys identified nine million more cases of arthritis and related conditions, CDC said. CDC estimated that 46.1 million residents received treatment for arthritis and related conditions in 2003 and that 29.5 million of them lost wages. CDC said eight million additional residents likely will develop arthritis and related conditions from 2005 through 2015 and recommended broader use of self-management programs, which teach patients to manage their pain and continue to work with the condition, to help reduce costs (Yee, AP/Long Island Newsday, 1/12).
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
Proteolix, Inc. Drug Candidate, PR-957, Prevents Disease Progression In Rheumatoid Arthritis Models By Selective Inhibition Of The Immunoproteasome
Proteolix, Inc. announced that in an article published in Nature Medicine, Proteolix's selective immunoproteasome inhibitor PR-957 was shown to block disease progression in mouse models of rheumatoid arthritis in a dose-dependent manner and to completely eliminate visible signs of disease at the highest dose. The anti-inflammatory effect induced by PR-957 was rapid and long-lasting, lowering expression of multiple inflammatory mediators, including TNF-a and IL-6. Disease regression was evident 24 hours after dosing and a complete amelioration of disease was achieved with a single dose. When compared to anti-TNF-a therapy (etanercept), PR-957 mediated a more rapid resolution of clinical symptoms, including joint inflammation, and was more effective than etanercept in a model of aggressive arthritis.
These data were published in the June 14, 2009 online edition of Nature Medicine and will be published in the upcoming July 2009 print edition in an article titled: A Selective Inhibitor of the Immunoproteasome Subunit LMP7 Blocks Cytokine Production and Attenuates Progression of Experimental Arthritis. The authors of the article included members of the laboratory of Dr. Marcus Groettrup at the University of Constance (Konstanz, Germany) and researchers, led by Dr. Christopher Kirk, at Proteolix, Inc. (South San Francisco, CA), where the drug candidate was discovered and developed.
PR-957 is the first highly selective, small molecule inhibitor of the immunoproteasome. The proteasome is an intracellular complex present in most cells that mediates the degradation of intracellular proteins, including key components of pathways that contribute to cancer cell growth and immune signaling. It is a proven and validated target for therapeutic intervention in oncology, but the side effect profiles of existing inhibitors have restricted the potential of this target for therapeutic intervention in autoimmune diseases. However, a specific form of the proteasome, known as the immunoproteasome, is found in many cells of the immune system. PR-957 selectively targets a subunit of the immunoproteasome, known as LMP7. Inhibition of this subunit results in a decrease of the immune cell signaling cascade and a halt of the production of cytokines associated with autoimmune inflammation, without affecting proteasome function in non-immune cells. As a consequence, PR-957 induces an anti-inflammatory response at doses less than one tenth the Maximum Tolerated Dose (MTD). In contrast, nonselective inhibitors, such as bortezomib and carfilzomib, induce anti-inflammatory responses only at or near their MTD. These findings also underline the key role played by the immunoproteasome in development of the inflammatory process.
"Targeting protein degradation pathways via the proteasome represents a completely novel approach to regulating the immune response. Using a specially designed proprietary assay, our team of researchers was able to discover and optimize a small molecule capable of demonstrating exquisite selectivity for the LMP7 immunoproteasome subunit," said Susan Molineaux, Ph.D., Chief Scientific Officer at Proteolix. "This selective inhibition of the immunoproteasome results in an increased therapeutic margin compared to that achieved with non-selective proteasome inhibitors, and can have dramatic impact on the inflammatory response without risking broad suppression of immune system function."
Proteolix plans to file an Investigational New Drug Application for PR-957 in mid-2010.
"The research published today in Nature Medicine provides a strong rationale for clinical development of PR-957 in rheumatoid arthritis and other inflammatory and autoimmune diseases," said John A. Scarlett, M.D., President and Chief Executive Officer of Proteolix. "Proteolix has now discovered and developed carfilzomib, a proteasome inhibitor in late Phase 2 clinical trials for the treatment of multiple myeloma, PR-047 as an oral proteasome inhibitor also targeted in oncology, and now PR-957 as a strong drug candidate for the treatment of autoimmune disorders. This demonstrates the Company's unique discovery and development capabilities, as well as its leadership in the field of proteasome inhibition."
About Proteolix
Founded in December 2003, Proteolix, Inc. is a privately-held biotechnology company, headquartered in South San Francisco, dedicated to discovering, developing and commercializing novel therapeutics that target protein degradation pathways for cancer and autoimmune diseases. Proteolix's lead product, carfilzomib, is the first in a new class of selective, irreversible proteasome inhibitors. Proteolix is also developing a pipeline of novel proteasome inhibitors, including a selective, oral proteasome inhibitor and a selective immunoproteasome inhibitor.
Source: Proteolix, Inc
These data were published in the June 14, 2009 online edition of Nature Medicine and will be published in the upcoming July 2009 print edition in an article titled: A Selective Inhibitor of the Immunoproteasome Subunit LMP7 Blocks Cytokine Production and Attenuates Progression of Experimental Arthritis. The authors of the article included members of the laboratory of Dr. Marcus Groettrup at the University of Constance (Konstanz, Germany) and researchers, led by Dr. Christopher Kirk, at Proteolix, Inc. (South San Francisco, CA), where the drug candidate was discovered and developed.
PR-957 is the first highly selective, small molecule inhibitor of the immunoproteasome. The proteasome is an intracellular complex present in most cells that mediates the degradation of intracellular proteins, including key components of pathways that contribute to cancer cell growth and immune signaling. It is a proven and validated target for therapeutic intervention in oncology, but the side effect profiles of existing inhibitors have restricted the potential of this target for therapeutic intervention in autoimmune diseases. However, a specific form of the proteasome, known as the immunoproteasome, is found in many cells of the immune system. PR-957 selectively targets a subunit of the immunoproteasome, known as LMP7. Inhibition of this subunit results in a decrease of the immune cell signaling cascade and a halt of the production of cytokines associated with autoimmune inflammation, without affecting proteasome function in non-immune cells. As a consequence, PR-957 induces an anti-inflammatory response at doses less than one tenth the Maximum Tolerated Dose (MTD). In contrast, nonselective inhibitors, such as bortezomib and carfilzomib, induce anti-inflammatory responses only at or near their MTD. These findings also underline the key role played by the immunoproteasome in development of the inflammatory process.
"Targeting protein degradation pathways via the proteasome represents a completely novel approach to regulating the immune response. Using a specially designed proprietary assay, our team of researchers was able to discover and optimize a small molecule capable of demonstrating exquisite selectivity for the LMP7 immunoproteasome subunit," said Susan Molineaux, Ph.D., Chief Scientific Officer at Proteolix. "This selective inhibition of the immunoproteasome results in an increased therapeutic margin compared to that achieved with non-selective proteasome inhibitors, and can have dramatic impact on the inflammatory response without risking broad suppression of immune system function."
Proteolix plans to file an Investigational New Drug Application for PR-957 in mid-2010.
"The research published today in Nature Medicine provides a strong rationale for clinical development of PR-957 in rheumatoid arthritis and other inflammatory and autoimmune diseases," said John A. Scarlett, M.D., President and Chief Executive Officer of Proteolix. "Proteolix has now discovered and developed carfilzomib, a proteasome inhibitor in late Phase 2 clinical trials for the treatment of multiple myeloma, PR-047 as an oral proteasome inhibitor also targeted in oncology, and now PR-957 as a strong drug candidate for the treatment of autoimmune disorders. This demonstrates the Company's unique discovery and development capabilities, as well as its leadership in the field of proteasome inhibition."
About Proteolix
Founded in December 2003, Proteolix, Inc. is a privately-held biotechnology company, headquartered in South San Francisco, dedicated to discovering, developing and commercializing novel therapeutics that target protein degradation pathways for cancer and autoimmune diseases. Proteolix's lead product, carfilzomib, is the first in a new class of selective, irreversible proteasome inhibitors. Proteolix is also developing a pipeline of novel proteasome inhibitors, including a selective, oral proteasome inhibitor and a selective immunoproteasome inhibitor.
Source: Proteolix, Inc
Statins Not Routinely Indicated For Children And Adolescents With Lupus
While statins are known to help prevent the progression of atherosclerosis, research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta indicates they should not be routinely prescribed in children and adolescents with lupus despite their increased risk of premature atherosclerosis.
Lupus, or SLE, is a chronic inflammatory disease that can affect the skin, joints, kidneys, lungs, nervous system, and other organs of the body. Usually, patients have skin rashes and arthritis, as well as fatigue and fever. It is often more severe when it begins in childhood. Lupus has been identified as a strong independent risk factor for heart attack and stroke, and children with lupus are at a particularly high risk because of their lifelong exposure to the disease. Atherosclerosis a buildup of fatty deposits in the artery walls which normally leads to heart attack and strokes in older adults, starts at an at an unusually early age and progresses more quickly in people with lupus.
Statins have been shown to reduce cardiovascular complications and death among the general adult population, but they have not been studied in the prevention of atherosclerosis among young people with lupus. In the largest trial of its kind and the first major trial completed by the Childhood Arthritis and Rheumatology Research Alliance (called CARRA) researchers recently completed a study looking at whether the use of statins would be helpful enough in the prevention of atherosclerosis in children and adolescents with lupus to make it worthwhile for them to start taking at such a young age.
With funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, researchers followed 221 participants (ages 10 to 21) with lupus who were recruited through 21 CARRA sites. The participants were randomly placed into two groups: one received atorvastatin (Lipitor®) and one received placebo for 36 months. Participants also received hydroxychloroquine, aspirin, a daily multi-vitamin, as well as recommendations for a low cholesterol diet and cardiovascular risk factor counseling. All participants continued routine care for lupus as prescribed by their local pediatric rheumatologist.
The researchers used a very accurate ultrasound technique that can detect even tiny differences in the thickening of the arterial wall of the carotid arteries, which has been shown to predict future heart attacks and strokes.
They also studied blood lipid levels, blood markers of inflammation, lupus disease activity and damage as well as each participant's quality of life.
The study showed no clinically important differences in measurements of the carotid artery thickening for those participants taking atorvastatin. However, the study did show that participants on atorvastatin showed improvements in levels of inflammation and lipids in the blood (e.g., lower levels of high-sensitivity C-reactive protein, total cholesterol, and low-density lipoprotein [a combination of protein and fat]). There were no differences in overall lupus disease activity.
"This study shows that while statins decrease CRP and lipid levels in young people with SLE as they do in other populations, statins do not have enough of a positive effect to routinely prescribe them for children with lupus," says Laura E. Schanberg, MD; principal investigator and professor of pediatrics at Duke University Medical Center. "There are risks with all medications, and this data doesn't convince us that the risks are worth it for all children with lupus."
One thing the study did convince researchers of is the safety of statins in people with lupus. In this study, atorvastatin was shown to be safe and well-tolerated among participants with no increase in the number of serious side effects in the atorvastatin group compared to the placebo group. "This shows that statins are safe for most people with lupus," explains Christy Sandborg, MD; co-principal investigator and professor at Stanford University.
This is the first trial studying the use of statins in children with lupus and the longest trial of statins among children, but there is still more work to be done. In particular, there are likely subsets of young people with lupus who will benefit from early statin therapy, and the researchers believe this deserves future investigation. "We think the take home message for pediatric rheumatologists is that they shouldn't plan on routinely prescribing statins to their patients just yet," agree Drs. Sandborg and Schanberg.
Editor's Notes: Laura E. Schanberg, MD will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 3:00 PM on Wednesday, November 10 in the Thomas J. Murphy Ballroom. Dr. Schanberg and Dr. Sandborg will be available for media questions and briefing at 8:30 AM on Tuesday, November 9 in the on-site press conference room, B 212.
Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care.
Presentation Number: L10
Does Atorvastatin Reduce Carotid Atherosclerosis in Pediatric SLE? Results from the Atherosclerosis Prevention in Pediatric Lupus Trial: The Largest Multicenter, Randomized, Double-Blind, Placebo-Controlled Study in Pediatric SLE.
Laura E Schanberg, MD (Department of Pediatrics, Duke University Medical Center, Durham, NC)
Christy I Sandborg, MD 2Pediatric Rheumatology PTD, Stanford Medical Center, Stanford, CA)
Huiman X Barnhart (Duke University Medical Center)
Stacy P. Ardoin (Childhood Arthritis and Rheumatology Research Alliance)
Eric Yow (University Medical Center)
Greg W Evans (Wake Forest University)
Kelly L Mieszkalski (Duke University Medical Center)
Norm T Ilowite (Childhood Arthritis and Rheumatology Research Alliance)
Anne Eberhard (Childhood Arthritis and Rheumatology Research Alliance)
Lisa F Imundo (Childhood Arthritis and Rheumatology Research Alliance)
Yukiko Kimura (Childhood Arthritis and Rheumatology Research Alliance)
Emily von Scheven (Childhood Arthritis and Rheumatology Research Alliance)
Earl Silverman (Childhood Arthritis and Rheumatology Research Alliance)
Suzanne L Bowyer (Childhood Arthritis and Rheumatology Research Alliance)
Lynn Punaro(Childhood Arthritis and Rheumatology Research Alliance)
Nora G Singer (Childhood Arthritis and Rheumatology Research Alliance)
David D Sherry (Childhood Arthritis and Rheumatology Research Alliance)
Deborah McCurdy (Childhood Arthritis and Rheumatology Research Alliance)
Marisa Klein-Gitelman (Childhood Arthritis and Rheumatology Research Alliance)
Carol Wallace (Childhood Arthritis and Rheumatology Research Alliance)
Richard Silver (Childhood Arthritis and Rheumatology Research Alliance)
Linda Wagner-Weiner (Childhood Arthritis and Rheumatology Research Alliance)
Gloria C Higgins (Childhood Arthritis and Rheumatology Research Alliance)
Hermine I Brunner (Childhood Arthritis and Rheumatology Research Alliance)
Lawrence Jung (Childhood Arthritis and Rheumatology Research Alliance)
Jennifer B Soep (Childhood Arthritis and Rheumatology Research Alliance)
Ann M Reed (Childhood Arthritis and Rheumatology Research Alliance)
Purpose: Systemic lupus erythematosus (SLE) is an independent risk factor for premature myocardial infarction and stroke. Given their lifelong exposure to increased atherogenic potential, children and adolescents with SLE are at particularly high risk for developing premature atherosclerosis. Statins reduce cardiovascular morbidity and mortality in the general adult population but statin efficacy in preventing atherosclerosis progression in SLE is not known. The Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial was designed to assess the efficacy and safety of statins in preventing progression of carotid intima medial thickening (CIMT).
Methods: 221 children and adolescents (10-21 yrs) with SLE from 21 Childhood Arthritis and Rheumatology Research Alliance (CARRA) sites were randomized to receive atorvastatin or placebo in addition to hydroxychloroquine and standard care for 36 months. The primary endpoint was progression of mean-mean common CIMT measured by ultrasound. The study was powered to detect a 0.0045 mm/yr difference in CIMT progression between the treatment groups. Secondary endpoints included progression of mean maximal CIMT, other segment or wall specific CIMT endpoints, SLE disease activity and damage outcome measures and health-related quality of life (HR-QOL).
Results: There was no statistically significant difference in the progression of mean-mean common CIMT between the treatment groups (0.0010 mm/yr [placebo] vs. 0.0024 mm/yr [atorvastatin], p = 0.24). Although not reaching statistical significance, the progression of mean maximal CIMT was slower in the atorvastatin group than the placebo group (0.0037 mm/yr vs. 0.0064 mm/yr, p = 0.08). In models adjusting for baseline covariates imbalanced in the two groups or known to impact CIMT, the adjusted difference in mean-mean common CIMT progression rate remained non-significant while the adjusted difference in mean maximal CIMT progression was 0.0042 mm/yr (p = 0.006). The atorvastatin group achieved lower levels of high sensitivity c-reactive protein (p = 0.04), total cholesterol (p =
Lupus, or SLE, is a chronic inflammatory disease that can affect the skin, joints, kidneys, lungs, nervous system, and other organs of the body. Usually, patients have skin rashes and arthritis, as well as fatigue and fever. It is often more severe when it begins in childhood. Lupus has been identified as a strong independent risk factor for heart attack and stroke, and children with lupus are at a particularly high risk because of their lifelong exposure to the disease. Atherosclerosis a buildup of fatty deposits in the artery walls which normally leads to heart attack and strokes in older adults, starts at an at an unusually early age and progresses more quickly in people with lupus.
Statins have been shown to reduce cardiovascular complications and death among the general adult population, but they have not been studied in the prevention of atherosclerosis among young people with lupus. In the largest trial of its kind and the first major trial completed by the Childhood Arthritis and Rheumatology Research Alliance (called CARRA) researchers recently completed a study looking at whether the use of statins would be helpful enough in the prevention of atherosclerosis in children and adolescents with lupus to make it worthwhile for them to start taking at such a young age.
With funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health, researchers followed 221 participants (ages 10 to 21) with lupus who were recruited through 21 CARRA sites. The participants were randomly placed into two groups: one received atorvastatin (Lipitor®) and one received placebo for 36 months. Participants also received hydroxychloroquine, aspirin, a daily multi-vitamin, as well as recommendations for a low cholesterol diet and cardiovascular risk factor counseling. All participants continued routine care for lupus as prescribed by their local pediatric rheumatologist.
The researchers used a very accurate ultrasound technique that can detect even tiny differences in the thickening of the arterial wall of the carotid arteries, which has been shown to predict future heart attacks and strokes.
They also studied blood lipid levels, blood markers of inflammation, lupus disease activity and damage as well as each participant's quality of life.
The study showed no clinically important differences in measurements of the carotid artery thickening for those participants taking atorvastatin. However, the study did show that participants on atorvastatin showed improvements in levels of inflammation and lipids in the blood (e.g., lower levels of high-sensitivity C-reactive protein, total cholesterol, and low-density lipoprotein [a combination of protein and fat]). There were no differences in overall lupus disease activity.
"This study shows that while statins decrease CRP and lipid levels in young people with SLE as they do in other populations, statins do not have enough of a positive effect to routinely prescribe them for children with lupus," says Laura E. Schanberg, MD; principal investigator and professor of pediatrics at Duke University Medical Center. "There are risks with all medications, and this data doesn't convince us that the risks are worth it for all children with lupus."
One thing the study did convince researchers of is the safety of statins in people with lupus. In this study, atorvastatin was shown to be safe and well-tolerated among participants with no increase in the number of serious side effects in the atorvastatin group compared to the placebo group. "This shows that statins are safe for most people with lupus," explains Christy Sandborg, MD; co-principal investigator and professor at Stanford University.
This is the first trial studying the use of statins in children with lupus and the longest trial of statins among children, but there is still more work to be done. In particular, there are likely subsets of young people with lupus who will benefit from early statin therapy, and the researchers believe this deserves future investigation. "We think the take home message for pediatric rheumatologists is that they shouldn't plan on routinely prescribing statins to their patients just yet," agree Drs. Sandborg and Schanberg.
Editor's Notes: Laura E. Schanberg, MD will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 3:00 PM on Wednesday, November 10 in the Thomas J. Murphy Ballroom. Dr. Schanberg and Dr. Sandborg will be available for media questions and briefing at 8:30 AM on Tuesday, November 9 in the on-site press conference room, B 212.
Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care.
Presentation Number: L10
Does Atorvastatin Reduce Carotid Atherosclerosis in Pediatric SLE? Results from the Atherosclerosis Prevention in Pediatric Lupus Trial: The Largest Multicenter, Randomized, Double-Blind, Placebo-Controlled Study in Pediatric SLE.
Laura E Schanberg, MD (Department of Pediatrics, Duke University Medical Center, Durham, NC)
Christy I Sandborg, MD 2Pediatric Rheumatology PTD, Stanford Medical Center, Stanford, CA)
Huiman X Barnhart (Duke University Medical Center)
Stacy P. Ardoin (Childhood Arthritis and Rheumatology Research Alliance)
Eric Yow (University Medical Center)
Greg W Evans (Wake Forest University)
Kelly L Mieszkalski (Duke University Medical Center)
Norm T Ilowite (Childhood Arthritis and Rheumatology Research Alliance)
Anne Eberhard (Childhood Arthritis and Rheumatology Research Alliance)
Lisa F Imundo (Childhood Arthritis and Rheumatology Research Alliance)
Yukiko Kimura (Childhood Arthritis and Rheumatology Research Alliance)
Emily von Scheven (Childhood Arthritis and Rheumatology Research Alliance)
Earl Silverman (Childhood Arthritis and Rheumatology Research Alliance)
Suzanne L Bowyer (Childhood Arthritis and Rheumatology Research Alliance)
Lynn Punaro(Childhood Arthritis and Rheumatology Research Alliance)
Nora G Singer (Childhood Arthritis and Rheumatology Research Alliance)
David D Sherry (Childhood Arthritis and Rheumatology Research Alliance)
Deborah McCurdy (Childhood Arthritis and Rheumatology Research Alliance)
Marisa Klein-Gitelman (Childhood Arthritis and Rheumatology Research Alliance)
Carol Wallace (Childhood Arthritis and Rheumatology Research Alliance)
Richard Silver (Childhood Arthritis and Rheumatology Research Alliance)
Linda Wagner-Weiner (Childhood Arthritis and Rheumatology Research Alliance)
Gloria C Higgins (Childhood Arthritis and Rheumatology Research Alliance)
Hermine I Brunner (Childhood Arthritis and Rheumatology Research Alliance)
Lawrence Jung (Childhood Arthritis and Rheumatology Research Alliance)
Jennifer B Soep (Childhood Arthritis and Rheumatology Research Alliance)
Ann M Reed (Childhood Arthritis and Rheumatology Research Alliance)
Purpose: Systemic lupus erythematosus (SLE) is an independent risk factor for premature myocardial infarction and stroke. Given their lifelong exposure to increased atherogenic potential, children and adolescents with SLE are at particularly high risk for developing premature atherosclerosis. Statins reduce cardiovascular morbidity and mortality in the general adult population but statin efficacy in preventing atherosclerosis progression in SLE is not known. The Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial was designed to assess the efficacy and safety of statins in preventing progression of carotid intima medial thickening (CIMT).
Methods: 221 children and adolescents (10-21 yrs) with SLE from 21 Childhood Arthritis and Rheumatology Research Alliance (CARRA) sites were randomized to receive atorvastatin or placebo in addition to hydroxychloroquine and standard care for 36 months. The primary endpoint was progression of mean-mean common CIMT measured by ultrasound. The study was powered to detect a 0.0045 mm/yr difference in CIMT progression between the treatment groups. Secondary endpoints included progression of mean maximal CIMT, other segment or wall specific CIMT endpoints, SLE disease activity and damage outcome measures and health-related quality of life (HR-QOL).
Results: There was no statistically significant difference in the progression of mean-mean common CIMT between the treatment groups (0.0010 mm/yr [placebo] vs. 0.0024 mm/yr [atorvastatin], p = 0.24). Although not reaching statistical significance, the progression of mean maximal CIMT was slower in the atorvastatin group than the placebo group (0.0037 mm/yr vs. 0.0064 mm/yr, p = 0.08). In models adjusting for baseline covariates imbalanced in the two groups or known to impact CIMT, the adjusted difference in mean-mean common CIMT progression rate remained non-significant while the adjusted difference in mean maximal CIMT progression was 0.0042 mm/yr (p = 0.006). The atorvastatin group achieved lower levels of high sensitivity c-reactive protein (p = 0.04), total cholesterol (p =
Psoriasis Linked To Seven New Genetic Variations
Seven new sites of common DNA variation have been discovered that
increase the risk of psoriasis. Some of these variations, in one area
of the genome, link psoriasis and psoriatic arthritis to other
autoimmune disorders. This work was published on April 4, 2008 in the
open-access journal PLoS Genetics.
Psoriasis is an autoimmune disease characterized by a mistaken immune
attack to the skin. It is identified by red, scaly patches on the skin
that are itchy, painful, or both. It affects an estimated 7 million
Americans. Additionally, 10-30% of patients with psoriasis develop
psoriatic arthritis, a painful and debilitating arthritic condition
additionally characterized by pitting or complete loss of fingernails.
There are many factors that may come into play in this condition, which
make it difficult to study. This is true concerning its genetics as
well. "Common diseases like psoriasis are incredibly complex at the
genetic
level," says lead investigator Anne Bowcock, Ph.D.. "Our research shows
that
small but common DNA differences are important in the development of
psoriasis. Although each variation makes only a small
contribution to the disease, patients usually have a number of
different genetic variations that increases their risk of psoriasis and
psoriatic arthritis."
The study, performed at the Washington University School of Medicine in
St. Louis, was a comprehensive examination of the genetic basis of
psoriasis. The researchers directed their attentions to points of
common variation in the genome, known as single nucleotide
polymorphisms (SNPs.) A large portion of the 3 billion nucleotides that
make up the genome are identical from one person to the next, but some
10 million SNPs make someone unique. Of these, certain SNPs can
influence disease and health in a person.
In a whole genome association study, the investigators scanned over
300,000 SNPs in the genomes of 223 psoriasis patients. This included 91
with psoriatic arthritis. The DNA of these patients was compared to
that of 519 healthy patients in a control group, seeking specific
differences between the groups. Then, a second study was performed with
577 psoriasis patients, 576 with psoriatic arthritis, and over 1,200
healthy controls.
The team discovered seven new variations that were linked to psoriasis.
Additionally, the DNA variations that were located on chromosome 4 were
strongly linked to psoriatic arthritis. These variations were also
associated with type 1 diabetes, rheumatoid arthritis, Graves' disease
(the result of an overproductive thyroid gland), and celiac disease (an
inability to digest gluten).
These variations point scientists in the direction of different
biological pathways that could underlie psoriasis on a basic level.
This could eventually lead to new targeted drugs and treatments that
attack specific pathways, according to Bowcock. She is now conducting a
larger, genome-wide association study of psoriasis patients, and she
expects to find additional genetic variations that are associated with
the disease.
About PLoS Genetics
PLoS Genetics (plosgenetics)
reflects the full breadth and interdisciplinary nature of genetics and
genomics research by publishing outstanding original contributions in
all areas of biology. All works published in PLoS Genetics
are
open access. Everything is immediately and freely available online
throughout the world subject only to the condition that the original
authorship and source are properly attributed. Copyright is retained by
the authors. The Public Library of Science uses the Creative Commons
Attribution License.
About the Public Library of Science
The
Public Library of Science (PLoS) is a non-profit organization of
scientists and physicians committed to making the world's scientific
and medical literature a freely available public resource. For more
information, visit plos.
A Genome-Wide Association Study of Psoriasis and Psoriatic
Arthritis Identifies New Disease Loci.
Liu Y, Helms C, Liao W, Zaba LC, Duan S, et al.
PLoS Genet 4(3): e1000041.
doi:10.1371/journal.pgen.1000041
Click
Here For Full Length Article
Written by Anna Sophia McKenney
increase the risk of psoriasis. Some of these variations, in one area
of the genome, link psoriasis and psoriatic arthritis to other
autoimmune disorders. This work was published on April 4, 2008 in the
open-access journal PLoS Genetics.
Psoriasis is an autoimmune disease characterized by a mistaken immune
attack to the skin. It is identified by red, scaly patches on the skin
that are itchy, painful, or both. It affects an estimated 7 million
Americans. Additionally, 10-30% of patients with psoriasis develop
psoriatic arthritis, a painful and debilitating arthritic condition
additionally characterized by pitting or complete loss of fingernails.
There are many factors that may come into play in this condition, which
make it difficult to study. This is true concerning its genetics as
well. "Common diseases like psoriasis are incredibly complex at the
genetic
level," says lead investigator Anne Bowcock, Ph.D.. "Our research shows
that
small but common DNA differences are important in the development of
psoriasis. Although each variation makes only a small
contribution to the disease, patients usually have a number of
different genetic variations that increases their risk of psoriasis and
psoriatic arthritis."
The study, performed at the Washington University School of Medicine in
St. Louis, was a comprehensive examination of the genetic basis of
psoriasis. The researchers directed their attentions to points of
common variation in the genome, known as single nucleotide
polymorphisms (SNPs.) A large portion of the 3 billion nucleotides that
make up the genome are identical from one person to the next, but some
10 million SNPs make someone unique. Of these, certain SNPs can
influence disease and health in a person.
In a whole genome association study, the investigators scanned over
300,000 SNPs in the genomes of 223 psoriasis patients. This included 91
with psoriatic arthritis. The DNA of these patients was compared to
that of 519 healthy patients in a control group, seeking specific
differences between the groups. Then, a second study was performed with
577 psoriasis patients, 576 with psoriatic arthritis, and over 1,200
healthy controls.
The team discovered seven new variations that were linked to psoriasis.
Additionally, the DNA variations that were located on chromosome 4 were
strongly linked to psoriatic arthritis. These variations were also
associated with type 1 diabetes, rheumatoid arthritis, Graves' disease
(the result of an overproductive thyroid gland), and celiac disease (an
inability to digest gluten).
These variations point scientists in the direction of different
biological pathways that could underlie psoriasis on a basic level.
This could eventually lead to new targeted drugs and treatments that
attack specific pathways, according to Bowcock. She is now conducting a
larger, genome-wide association study of psoriasis patients, and she
expects to find additional genetic variations that are associated with
the disease.
About PLoS Genetics
PLoS Genetics (plosgenetics)
reflects the full breadth and interdisciplinary nature of genetics and
genomics research by publishing outstanding original contributions in
all areas of biology. All works published in PLoS Genetics
are
open access. Everything is immediately and freely available online
throughout the world subject only to the condition that the original
authorship and source are properly attributed. Copyright is retained by
the authors. The Public Library of Science uses the Creative Commons
Attribution License.
About the Public Library of Science
The
Public Library of Science (PLoS) is a non-profit organization of
scientists and physicians committed to making the world's scientific
and medical literature a freely available public resource. For more
information, visit plos.
A Genome-Wide Association Study of Psoriasis and Psoriatic
Arthritis Identifies New Disease Loci.
Liu Y, Helms C, Liao W, Zaba LC, Duan S, et al.
PLoS Genet 4(3): e1000041.
doi:10.1371/journal.pgen.1000041
Click
Here For Full Length Article
Written by Anna Sophia McKenney
Axis-Shield And Bio-Rad Announce Launch Of New Anti-CCP Test For Bio-Rad's BioPlex 2200 System
Bio-Rad Laboratories, Inc. (NYSE: BIO) and (NYSE: BIO.B), a multinational manufacturer and distributor of life science research and clinical diagnostics products, and Axis-Shield plc (LSE: ASD) (OSE: ASD), an international in-vitro diagnostics (IVD) company, announced the launch of Bio-Rad's BioPlex® 2200 Anti-CCP test for the early detection of rheumatoid arthritis. The assay, which will run on Bio-Rad's BioPlex® 2200 system, measures anti-CCP (anti-cyclic citrullinated peptide antibodies), a novel marker that has been shown to have superior specificity in the diagnosis of rheumatoid arthritis. The BioPlex 2200 Anti-CCP kit is based on Axis-Shield's proprietary anti-CCP technology. The assay is available for sale in certain countries outside the U.S.
"The anti-CCP testing market is one of the fastest growing markets in autoimmune diagnostics," said John Goetz, Bio-Rad Vice President and Group Manager of Clinical Diagnostics. "The addition of this assay will add significantly to our growing menu of autoimmune tests on the BioPlex 2200 system."
"We are very pleased that Bio-Rad has reached this important commercial milestone in our agreement and believe that availability on the BioPlex system will help expand the market for this important early marker for this debilitating condition," said Ian Gilham, Axis-Shield CEO. "The measurement of these antibodies has recently been cited as a key parameter in the definitive diagnosis of rheumatoid arthritis by the influential American College of Rheumatology."
The BioPlex 2200 system is a fully automated, random-access multiplex testing platform with an assay menu targeting autoimmune diagnostics and infectious diseases. In the U.S., the BioPlex 2200 Anti-CCP kit is pending clearance by the FDA.
Source
Bio-Rad
Axis-Shield
"The anti-CCP testing market is one of the fastest growing markets in autoimmune diagnostics," said John Goetz, Bio-Rad Vice President and Group Manager of Clinical Diagnostics. "The addition of this assay will add significantly to our growing menu of autoimmune tests on the BioPlex 2200 system."
"We are very pleased that Bio-Rad has reached this important commercial milestone in our agreement and believe that availability on the BioPlex system will help expand the market for this important early marker for this debilitating condition," said Ian Gilham, Axis-Shield CEO. "The measurement of these antibodies has recently been cited as a key parameter in the definitive diagnosis of rheumatoid arthritis by the influential American College of Rheumatology."
The BioPlex 2200 system is a fully automated, random-access multiplex testing platform with an assay menu targeting autoimmune diagnostics and infectious diseases. In the U.S., the BioPlex 2200 Anti-CCP kit is pending clearance by the FDA.
Source
Bio-Rad
Axis-Shield
Lupus Drug Benlysta Gets Thumbs Up From FDA Advisory Panel
An FDA Arthritis Advisory Committee voted 13 to 2 in favor of approving Benlysta (belimumab), a lupus medication. The FDA (Food and Drug Administration) Advisory Committee consists of 15 outside experts, their recommendations are not binding, however, the FDA nearly always goes along with what they recommend. Benlysta was developed by GSK (GlaxoSmithkline) and Human Genome Sciences.
A Human Genome Sciences communiqu?© states that the Committee has recommended the approval of Benlysta for:
"..autoantibody-positive patients with active systemic lupus erythematosus (SLE)."
If the FDA eventually goes ahead with Benlysta's approval for patients with Systemic Lupus Erythematosus, which is now much more likely, it will be the first new treatment for the condition in over half a century. The Committee also voted that according to reviewed data, the drug appears to be safe and effective. GSK says the FDA should make a decision before the end of this year.
As lupus patients tend to have a wide range of differing symptoms, organizing large-scale clinical trials has been a challenge - this is probably the main reason pharmaceutical companies have found it hard to develop new medications. Although there have been several attempts, apart from this one, all the others have failed.
According to comments today in the financial press, such as The Wall Street Journal, Benlysta sales could top the $5 billion mark by 2020. There are rumors that GSK may now be eyeing Human Genome Sciences Inc. for a takeover.
Lupus is an autoimmune disease - the individual's immune system is overactive and attacks healthy, normal tissue as if it were a foreign pathogen (organism that harms). This results in inflammation (swelling), damage to skin, joints, heart, lungs and kidneys. Experts have identified several types of lupus. The most common is SLE (systemic lupus arythematosus); other types include neonatal, drug induced, and discoid lupus.
About 1.5 million Americans are affected by lupus annually.
Benlysta has been found to help lupus patients with joint pain and severe arthritis-like swelling, skin rash, and kidney inflammation. Benlysta is a fully human monoclonal antibody, it identifies and inhibits (blocks) the activity of B-Lymphocyte stimulator (BLyS), a protein that helps antibody-producing beta cells mature.
The Advisory Committee said that if approved, the labeling should explain that the medication has not been tested on patients with certain problems, such as severe kidney disease.
Human Genome Sciences (HGS) wrote:
"HGS and GSK are developing belimumab under a definitive co-development and co-commercialization agreement entered into in 2006. Under the agreement, HGS has responsibility for conducting the belimumab Phase 3 trials, with assistance from GSK. The companies will share equally in Phase 3/4 development costs, sales and marketing expenses, and profits of any product commercialized under the current agreement."
Although the medication was only moderately more effective than a placebo in easing lupus symptoms, those on Benlysta were on lower steroid doses. Corticosteroids significantly increase the risk of infection.
Source: GSK, FDA, Human Genome Sciences
Written by
A Human Genome Sciences communiqu?© states that the Committee has recommended the approval of Benlysta for:
"..autoantibody-positive patients with active systemic lupus erythematosus (SLE)."
If the FDA eventually goes ahead with Benlysta's approval for patients with Systemic Lupus Erythematosus, which is now much more likely, it will be the first new treatment for the condition in over half a century. The Committee also voted that according to reviewed data, the drug appears to be safe and effective. GSK says the FDA should make a decision before the end of this year.
As lupus patients tend to have a wide range of differing symptoms, organizing large-scale clinical trials has been a challenge - this is probably the main reason pharmaceutical companies have found it hard to develop new medications. Although there have been several attempts, apart from this one, all the others have failed.
According to comments today in the financial press, such as The Wall Street Journal, Benlysta sales could top the $5 billion mark by 2020. There are rumors that GSK may now be eyeing Human Genome Sciences Inc. for a takeover.
Lupus is an autoimmune disease - the individual's immune system is overactive and attacks healthy, normal tissue as if it were a foreign pathogen (organism that harms). This results in inflammation (swelling), damage to skin, joints, heart, lungs and kidneys. Experts have identified several types of lupus. The most common is SLE (systemic lupus arythematosus); other types include neonatal, drug induced, and discoid lupus.
About 1.5 million Americans are affected by lupus annually.
Benlysta has been found to help lupus patients with joint pain and severe arthritis-like swelling, skin rash, and kidney inflammation. Benlysta is a fully human monoclonal antibody, it identifies and inhibits (blocks) the activity of B-Lymphocyte stimulator (BLyS), a protein that helps antibody-producing beta cells mature.
The Advisory Committee said that if approved, the labeling should explain that the medication has not been tested on patients with certain problems, such as severe kidney disease.
Human Genome Sciences (HGS) wrote:
"HGS and GSK are developing belimumab under a definitive co-development and co-commercialization agreement entered into in 2006. Under the agreement, HGS has responsibility for conducting the belimumab Phase 3 trials, with assistance from GSK. The companies will share equally in Phase 3/4 development costs, sales and marketing expenses, and profits of any product commercialized under the current agreement."
Although the medication was only moderately more effective than a placebo in easing lupus symptoms, those on Benlysta were on lower steroid doses. Corticosteroids significantly increase the risk of infection.
Source: GSK, FDA, Human Genome Sciences
Written by
Shedding Light On Aromatase Inhibitor Joint Pain Syndrome
Breast cancer patients are more likely to have joint pain from taking aromatase inhibitors (AIs) if they have advanced stage cancer, according to a study presented at the American College of Rheumatology's annual meeting, held Nov. 7-11, in Atlanta. The study is one of the first to identify factors that increase the likelihood that a patient will suffer joint pain from AI therapy.
AIs, the standard adjuvant therapy for post-menopausal breast cancer, can cause joint pain in patients, mostly in the hands and wrists. This pain can sometimes be debilitating. "Patients complain bitterly about this pain that they can get in their hands after starting these medications," said Lisa Mandl, M.D., an assistant attending rheumatologist at Hospital for Special Surgery in New York, who was involved with the study. "It is so bad that sometimes patients stop taking AIs, even though we know the drugs are literally life-saving - they decrease the risk of dying from breast cancer." Studies have shown that up to 15% of patients on AIs discontinue their therapy due to pain.
Because few clinical trials have characterized this syndrome, investigators at Hospital for Special Surgery launched a prospective study to shed some light on the condition. "Nobody has really properly described this syndrome or tried to figure out what might predict you getting it," said Dr. Mandl. "What is the pain? Is it joint arthritis? Is it tendonitis? Is it inflammation of the muscle? We wanted to describe it better than it has been described in the literature to date."
The investigators enrolled 35 post-menopausal women with hormone-sensitive, non-metastatic breast cancer who didn't have rheumatic disease. Subjects were evaluated at baseline, at three months, and at six months after starting aromatase inhibitor therapy. They underwent physical exams and filled out questionnaires about quality of life, health status and pain. Patients also underwent magnetic resonance imaging (MRI) scans at baseline, at the point they complained of any pain, and at six months.
"We were trying to detect inflammation and the anatomic location of their symptoms. Was the pain caused by inflammation in the joints or around the tendon, for example?" Dr. Mandl said.
The study classified women who reported new or worsening musculoskeletal symptoms as symptomatic. Of the 35 women enrolled, 19 (54%) were symptomatic and of these 2 (5.7%) discontinued AI therapy. The mean time to onset of symptoms was six weeks, range two to 18, and 58 percent of symptomatic subjects had pain in their hands. Roughly 11 percent had tenderness of tendons in their hand and 14 percent had generalized wrist stiffness.
The investigators found that MRIs were not always abnormal in symptomatic patients, although in some individual patients who experienced pain, doctors could detect abnormalities on their MRIs. There was no evidence of inflammatory arthritis on MRI, but some of the women who complained of pain had tenosynovitis, inflammation of the fluid-filled sheath that surrounds a tendon in the hand.
The investigators did not find any correlation between depression and pain. Other researchers have hypothesized that the syndrome might be caused by an autoimmune condition, but this study showed no association between autoimmune markers in the blood and pain. "I think it's interesting that we didn't find any autoimmune disease predisposition. We thought we might," Dr. Mandl said.
Only one factor predicted whether women had pain - having later stage cancer. "If you have stage II or stage III cancer, you are more likely to have this pain than if you have stage I cancer," Dr. Mandl said. She pointed out that women who had cancer that had metastasized to the bone were excluded from the study, so metastases were not the root of the problem.
"Before this study, we knew some women got this pain. Now we know that it is more likely in patients with later stage cancer and at least some of these women have tenosynovitis but not all," Dr. Mandl said. "We were not able to identify any other predisposing factors."
The lead investigator of the study was Ora Singer, M.D., who was at HSS during the study but is now a rheumatologist at the Medical College of Georgia Hospitals and Clinics. Other investigators involved with the study are Alana Levine, M.D., Tessa Cigler, M.D., Anne Moore, M.D., and Huong Do.
Source:
Phyllis Fisher
Hospital for Special Surgery
AIs, the standard adjuvant therapy for post-menopausal breast cancer, can cause joint pain in patients, mostly in the hands and wrists. This pain can sometimes be debilitating. "Patients complain bitterly about this pain that they can get in their hands after starting these medications," said Lisa Mandl, M.D., an assistant attending rheumatologist at Hospital for Special Surgery in New York, who was involved with the study. "It is so bad that sometimes patients stop taking AIs, even though we know the drugs are literally life-saving - they decrease the risk of dying from breast cancer." Studies have shown that up to 15% of patients on AIs discontinue their therapy due to pain.
Because few clinical trials have characterized this syndrome, investigators at Hospital for Special Surgery launched a prospective study to shed some light on the condition. "Nobody has really properly described this syndrome or tried to figure out what might predict you getting it," said Dr. Mandl. "What is the pain? Is it joint arthritis? Is it tendonitis? Is it inflammation of the muscle? We wanted to describe it better than it has been described in the literature to date."
The investigators enrolled 35 post-menopausal women with hormone-sensitive, non-metastatic breast cancer who didn't have rheumatic disease. Subjects were evaluated at baseline, at three months, and at six months after starting aromatase inhibitor therapy. They underwent physical exams and filled out questionnaires about quality of life, health status and pain. Patients also underwent magnetic resonance imaging (MRI) scans at baseline, at the point they complained of any pain, and at six months.
"We were trying to detect inflammation and the anatomic location of their symptoms. Was the pain caused by inflammation in the joints or around the tendon, for example?" Dr. Mandl said.
The study classified women who reported new or worsening musculoskeletal symptoms as symptomatic. Of the 35 women enrolled, 19 (54%) were symptomatic and of these 2 (5.7%) discontinued AI therapy. The mean time to onset of symptoms was six weeks, range two to 18, and 58 percent of symptomatic subjects had pain in their hands. Roughly 11 percent had tenderness of tendons in their hand and 14 percent had generalized wrist stiffness.
The investigators found that MRIs were not always abnormal in symptomatic patients, although in some individual patients who experienced pain, doctors could detect abnormalities on their MRIs. There was no evidence of inflammatory arthritis on MRI, but some of the women who complained of pain had tenosynovitis, inflammation of the fluid-filled sheath that surrounds a tendon in the hand.
The investigators did not find any correlation between depression and pain. Other researchers have hypothesized that the syndrome might be caused by an autoimmune condition, but this study showed no association between autoimmune markers in the blood and pain. "I think it's interesting that we didn't find any autoimmune disease predisposition. We thought we might," Dr. Mandl said.
Only one factor predicted whether women had pain - having later stage cancer. "If you have stage II or stage III cancer, you are more likely to have this pain than if you have stage I cancer," Dr. Mandl said. She pointed out that women who had cancer that had metastasized to the bone were excluded from the study, so metastases were not the root of the problem.
"Before this study, we knew some women got this pain. Now we know that it is more likely in patients with later stage cancer and at least some of these women have tenosynovitis but not all," Dr. Mandl said. "We were not able to identify any other predisposing factors."
The lead investigator of the study was Ora Singer, M.D., who was at HSS during the study but is now a rheumatologist at the Medical College of Georgia Hospitals and Clinics. Other investigators involved with the study are Alana Levine, M.D., Tessa Cigler, M.D., Anne Moore, M.D., and Huong Do.
Source:
Phyllis Fisher
Hospital for Special Surgery
Virtually The Same Percentage Of Surveyed Rheumatologists Selected Enbrel And Humira As The Most Efficacious Agent For The Treatment Of RA
Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that virtually the same percentage of surveyed rheumatologists selected Amgen/Pfizer/Takeda's Enbrel (43 percent) and Abbott/Eisai's Humira (42 percent) as the most efficacious agent for the treatment of rheumatoid arthritis. The shrinking gap in the percentage of surveyed rheumatologists who favor Enbrel over Humira in terms of efficacy suggests that Humira is threatening Enbrel's sales-leading position in rheumatoid arthritis. Nevertheless, physicians continue to regard Enbrel as the agent with the best overall clinical profile, owing to the strength of its perceived safety and tolerability advantages over Humira.
The findings from Decision Resources' analysis of the rheumatoid arthritis drug market also reveal that a slightly higher percentage of surveyed managed care organizations' (MCOs) pharmacy directors selected Humira (50 percent) over Enbrel (40 percent) as the most efficacious rheumatoid arthritis agent. In contrast, no surveyed pharmacy directors selected rituximab (Biogen Idec/Roche/Chugai/Zenyaku Kogyo's Rituxan, Roche's MabThera) or tocilizumab (Roche/Chugai's Actemra/RoActemra) as the most efficacious agent for the indication. The prescription of both agents is restricted primarily to patients who are refractory to treatment with tumor necrosis factor-alpha (TNF-alpha) inhibitors.
"Rheumatologists' perceptions of tocilizumab's efficacy are likely influenced by the drug's infrequent use, given its recent launch in 2010 and less-favorable tier positioning, as well as payer-imposed cost-control measures," said Decision Resources Analyst Irene Koulinska, M.D. "Although tocilizumab has demonstrated efficacy in clinical trails comparable to that of the TNF-alpha inhibitors, less familiarity with the agent is the likely driver behind the low number of surveyed rheumatologists who selected it as having the best efficacy or best overall clinical profile among currently available therapies."
The findings also reveal that, based on clinical data and the opinions of interviewed thought leaders, Enbrel is the current gold-standard therapy for the treatment of rheumatoid arthritis, due to its strongest clinical profile among key marketed agents for the indication. However, owing to its competitive advantages in safety and tolerability, Bristol-Myers Squibb's subcutaneous formulation of Orencia will displace Enbrel and will earn Decision Resources' proprietary clinical gold-standard status for rheumatoid arthritis in 2014, following its expected launch for the indication later this year.
Over the next decade, the rheumatoid arthritis drug market will experience modest annual growth as sales will increase from $8.8 billion in 2009 to $12 billion in 2019 in the United States, France, Germany, Italy, Spain, United Kingdom and Japan. In 2009, sales of the TNF-alpha inhibitors accounted for 75 percent of major-market sales as they continue to dominate as first-line biological agents but as the number of effective alternative biologics and novel oral immunomodulators increases, the market share of TNF-alpha inhibitors will fall by 2019. The interleukin-6 inhibitor Actemra/RoActemra, the most recent novel entrant to the rheumatoid arthritis market, is forecast to emerge as the preferred biologic for TNF-alpha-refractory patients and will earn blockbuster sales of $1.5 billion in 2019.
Source:
Decision Resources, Inc.
View drug information on Enbrel; Humira; Orencia.
The findings from Decision Resources' analysis of the rheumatoid arthritis drug market also reveal that a slightly higher percentage of surveyed managed care organizations' (MCOs) pharmacy directors selected Humira (50 percent) over Enbrel (40 percent) as the most efficacious rheumatoid arthritis agent. In contrast, no surveyed pharmacy directors selected rituximab (Biogen Idec/Roche/Chugai/Zenyaku Kogyo's Rituxan, Roche's MabThera) or tocilizumab (Roche/Chugai's Actemra/RoActemra) as the most efficacious agent for the indication. The prescription of both agents is restricted primarily to patients who are refractory to treatment with tumor necrosis factor-alpha (TNF-alpha) inhibitors.
"Rheumatologists' perceptions of tocilizumab's efficacy are likely influenced by the drug's infrequent use, given its recent launch in 2010 and less-favorable tier positioning, as well as payer-imposed cost-control measures," said Decision Resources Analyst Irene Koulinska, M.D. "Although tocilizumab has demonstrated efficacy in clinical trails comparable to that of the TNF-alpha inhibitors, less familiarity with the agent is the likely driver behind the low number of surveyed rheumatologists who selected it as having the best efficacy or best overall clinical profile among currently available therapies."
The findings also reveal that, based on clinical data and the opinions of interviewed thought leaders, Enbrel is the current gold-standard therapy for the treatment of rheumatoid arthritis, due to its strongest clinical profile among key marketed agents for the indication. However, owing to its competitive advantages in safety and tolerability, Bristol-Myers Squibb's subcutaneous formulation of Orencia will displace Enbrel and will earn Decision Resources' proprietary clinical gold-standard status for rheumatoid arthritis in 2014, following its expected launch for the indication later this year.
Over the next decade, the rheumatoid arthritis drug market will experience modest annual growth as sales will increase from $8.8 billion in 2009 to $12 billion in 2019 in the United States, France, Germany, Italy, Spain, United Kingdom and Japan. In 2009, sales of the TNF-alpha inhibitors accounted for 75 percent of major-market sales as they continue to dominate as first-line biological agents but as the number of effective alternative biologics and novel oral immunomodulators increases, the market share of TNF-alpha inhibitors will fall by 2019. The interleukin-6 inhibitor Actemra/RoActemra, the most recent novel entrant to the rheumatoid arthritis market, is forecast to emerge as the preferred biologic for TNF-alpha-refractory patients and will earn blockbuster sales of $1.5 billion in 2019.
Source:
Decision Resources, Inc.
View drug information on Enbrel; Humira; Orencia.
President Bush's Supplements Don't Help Treat Mild Arthritic Pain In The Knee
Many people, including President George Bush, take glucosamine and chondroitin for mild arthritic pain in the knee, in the belief they will help. According to recent tests carried out at 16 medical centers, they are no better than a placebo.
However, the researchers did say that if you combine them, glucosamine and chondroitin, then you may experience some relief from moderate-to-severe pain in the knee.
So, it seems that moderate-to-severe pain is helped by combining the two supplements. But not mild pain, either alone or in combination.
You can read about this study in the New England Journal of Medicine. The study was led by Daniel Clegg, Utah University School of Medicine.
Clegg added that the supplements, regardless whether taken on their own, or combined, are not likely to prevent the pain from developing in the first place.
Arthritis is a huge business in the USA. It is estimated that one third of American adults experience arthritis. The annual health bill for arthritis (in the USA) is more than $80 billion dollars. Supplements represent about $700 million dollars a year (less than 1% of total expenditure).
This is not the first test on supplements for arthritis pain. Previous ones have indicated that supplements do offer some benefit for the patient.
The study was funded by the National Institutes of Health.
Written by:
However, the researchers did say that if you combine them, glucosamine and chondroitin, then you may experience some relief from moderate-to-severe pain in the knee.
So, it seems that moderate-to-severe pain is helped by combining the two supplements. But not mild pain, either alone or in combination.
You can read about this study in the New England Journal of Medicine. The study was led by Daniel Clegg, Utah University School of Medicine.
Clegg added that the supplements, regardless whether taken on their own, or combined, are not likely to prevent the pain from developing in the first place.
Arthritis is a huge business in the USA. It is estimated that one third of American adults experience arthritis. The annual health bill for arthritis (in the USA) is more than $80 billion dollars. Supplements represent about $700 million dollars a year (less than 1% of total expenditure).
This is not the first test on supplements for arthritis pain. Previous ones have indicated that supplements do offer some benefit for the patient.
The study was funded by the National Institutes of Health.
Written by:
Orthopedic Research Society Honor BIDMC Scientist
Christopher Evans, PhD, director of the Center for Advanced Orthopaedic Studies at Beth Israel Deaconess Medical Center (BIDMC) and Maurice Edmond Mueller Professor of Orthopaedic Surgery at Harvard Medical School, were presented with the 2010 Arthur Steindler Award at this week's annual meeting of the Orthopaedic Research Society in New Orleans.
The prestigious award is made biannually to recognize senior scientists, clinicians and educators who have made significant contributions to the understanding of the musculoskeletal system and musculoskeletal diseases and injuries. Evans is a molecular biologist and leader in the development of gene therapies for the treatment of arthritis and other conditions affecting the skeletal system.
"Arthritis is our nation's most common cause of disability," notes Mark Gebhardt, MD, Chief of the Department of Orthopaedic Surgery at BIDMC. "Nearly 50 million Americans are dealing with some form of this extremely painful condition, and that number will only grow larger as our population ages. The innovative research being conducted by Chris Evans holds great promise as a new treatment option for managing this widespread disease."
Evans was the principal investigator on the world's first clinical trial of gene therapy for arthritis, and last year published the first clinical evidence demonstrating a clinical response to gene therapy in rheumatoid arthritis. He is in the process of developing a further clinical study in the gene therapy of osteoarthritis and has advanced pre-clinical research programs in bone healing and the repair of damage to cartilage.
The author of more than 300 papers, Evans received his doctorate from Swansea University, Wales, UK, which recently bestowed him with an honorary fellowship. Evans is also the recipient of the Marshall R. Urist Award (for excellence in tissue regeneration) from the Orthopaedic Research Society and is an elected fellow of the Hastings Center, a leading bioethics research institute. Last year, Evans' laboratory received a National Institutes of Health Challenge Grant of more than $980,000 to develop innovative ways to heal broken bones.
Source:
Bonnie Prescott
Beth Israel Deaconess Medical Center
The prestigious award is made biannually to recognize senior scientists, clinicians and educators who have made significant contributions to the understanding of the musculoskeletal system and musculoskeletal diseases and injuries. Evans is a molecular biologist and leader in the development of gene therapies for the treatment of arthritis and other conditions affecting the skeletal system.
"Arthritis is our nation's most common cause of disability," notes Mark Gebhardt, MD, Chief of the Department of Orthopaedic Surgery at BIDMC. "Nearly 50 million Americans are dealing with some form of this extremely painful condition, and that number will only grow larger as our population ages. The innovative research being conducted by Chris Evans holds great promise as a new treatment option for managing this widespread disease."
Evans was the principal investigator on the world's first clinical trial of gene therapy for arthritis, and last year published the first clinical evidence demonstrating a clinical response to gene therapy in rheumatoid arthritis. He is in the process of developing a further clinical study in the gene therapy of osteoarthritis and has advanced pre-clinical research programs in bone healing and the repair of damage to cartilage.
The author of more than 300 papers, Evans received his doctorate from Swansea University, Wales, UK, which recently bestowed him with an honorary fellowship. Evans is also the recipient of the Marshall R. Urist Award (for excellence in tissue regeneration) from the Orthopaedic Research Society and is an elected fellow of the Hastings Center, a leading bioethics research institute. Last year, Evans' laboratory received a National Institutes of Health Challenge Grant of more than $980,000 to develop innovative ways to heal broken bones.
Source:
Bonnie Prescott
Beth Israel Deaconess Medical Center
Researchers Identify Genes Associated With Increased Gout Risk
A team of researchers from the United States and the Netherlands has identified mutations in three genes that are associated with high levels of uric acid in the blood, which is a risk factor for gout. The team developed a genetic risk score composed of the number of uric acid-increasing mutations that each person carries (0 to 6), which was associated with up to a 40-fold increased risk for developing gout when comparing persons at lowest and highest risk. The findings are published in the October 4 issue of The Lancet.
More than 3 million adults in the United States have gout. Gout is a painful inflammation of the joints, which can occur with a build-up of uric acid in the blood (hyperuricaemia). Besides a genetic disposition, obesity, a diet high in meat and cheese, as well as alcohol consumption and certain medications can increase the risk for developing the disease.
The researchers conducted genome-wide association studies of more than 20,000 people enrolled in three large population-based studies investigating cardiovascular disease risk factors: the Framingham Heart Study based at Boston University Medical Center; the Rotterdam Study based at Erasmus Medical Centre in Rotterdam, the Netherlands; and the Atherosclerosis Risk in Communities (ARIC) study based at Johns Hopkins University. Of more than 500,000 genetic variations that were evaluated, the analysis identified two genes, ABCG2 and SLC17A3, as novel risk genes for gout and confirmed the association of a third gene, SLC2A9.
"This research gives us a better understanding of the underlying causes of gout, which could lead to better prevention and treatment. Our evidence supports that a common pathway, the handling of uric acid by the kidney, is important in uric acid build-up and therefore for the development of gout," said study author, Anna K?¶ttgen, MD, MPH, an assistant scientist in the Johns Hopkins Bloomberg School of Public Health's Department of Epidemiology.
"Genetic risk scores like the one we developed for gout can help alert people at a very early age, well before uric acid levels rise, that they are susceptible to gout. The new insights are promising for drug development," said Josef Coresh, MD, PhD, MHS, professor in the Bloomberg School's departments of Epidemiology and Biostatistics. "An important unanswered question is whether we can use genetic risk information to motivate people to change their behavior. For gout, we know that moderate changes in diet and alcohol consumption can lower uric acid levels. In the future, we will need to test if identification of high-risk individuals can lead to behavior change."
Johns Hopkins Bloomberg School of Public Health
615 N Wolfe St., W1600
Baltimore, MD 21205
United States
jhsph
More than 3 million adults in the United States have gout. Gout is a painful inflammation of the joints, which can occur with a build-up of uric acid in the blood (hyperuricaemia). Besides a genetic disposition, obesity, a diet high in meat and cheese, as well as alcohol consumption and certain medications can increase the risk for developing the disease.
The researchers conducted genome-wide association studies of more than 20,000 people enrolled in three large population-based studies investigating cardiovascular disease risk factors: the Framingham Heart Study based at Boston University Medical Center; the Rotterdam Study based at Erasmus Medical Centre in Rotterdam, the Netherlands; and the Atherosclerosis Risk in Communities (ARIC) study based at Johns Hopkins University. Of more than 500,000 genetic variations that were evaluated, the analysis identified two genes, ABCG2 and SLC17A3, as novel risk genes for gout and confirmed the association of a third gene, SLC2A9.
"This research gives us a better understanding of the underlying causes of gout, which could lead to better prevention and treatment. Our evidence supports that a common pathway, the handling of uric acid by the kidney, is important in uric acid build-up and therefore for the development of gout," said study author, Anna K?¶ttgen, MD, MPH, an assistant scientist in the Johns Hopkins Bloomberg School of Public Health's Department of Epidemiology.
"Genetic risk scores like the one we developed for gout can help alert people at a very early age, well before uric acid levels rise, that they are susceptible to gout. The new insights are promising for drug development," said Josef Coresh, MD, PhD, MHS, professor in the Bloomberg School's departments of Epidemiology and Biostatistics. "An important unanswered question is whether we can use genetic risk information to motivate people to change their behavior. For gout, we know that moderate changes in diet and alcohol consumption can lower uric acid levels. In the future, we will need to test if identification of high-risk individuals can lead to behavior change."
Johns Hopkins Bloomberg School of Public Health
615 N Wolfe St., W1600
Baltimore, MD 21205
United States
jhsph
Risk Of Developing Several Arthritic Conditions Decreased By Alcohol Consumption
Alcohol consumption is associated with a significantly reduced risk of developing several arthritic conditions including Rheumatoid Arthritis (RA), Osteoarthritis (OA), reactive arthritis, psoriatic arthritis and spondylarthropathy, according to results of a new study presented at EULAR 2010, the Annual Congress of the European League Against Rheumatism in Rome, Italy. Regardless of the type of arthritis, all patients reported drinking less alcohol than controls, leading to questions around the inflammatory pathways behind the effects seen.
In this Dutch study, alcohol consumption was associated with a significantly lower risk of developing RA (Odds Ratio (OR) 0.27 (0.22-0.34), Osteoarthritis (OR 0.31, (0.16-0.62), spondylarthropathy (OR 0.34, 0.17-0.67), psoriatic arthritis (OR 0.38, 0.23-0.62), and reactive arthritis (OR 0.27, 0.14-0.52). A particularly protective effect was shown in the RA population with the presence of Anti-Citrullinated Protein Antibodies (ACPA, potentially important surrogate markers for diagnosis and prognosis in RA), (OR 0.59, 0.30-0.99).
Interestingly, researchers also found that the degree of systemic inflammation in patients was shown to increase as the amount of alcohol consumed decreased (p=0.001) and that there was no dose response relationship (low 0.12 (0.08-0.18), moderate 0.46 (0.36-0.59), high 0.17 (0.12-0.25)) between the amount of alcohol consumed and the risk of arthritis development. Researchers hypothesise that there could be two explanations for this inflammatory effect; either that patients with more severe disease activity consume less alcohol due to associated changes in their lifestyle, or that the presence of alcohol in the system could protect against the development of systemic inflammation.
"We know from previous research that alcohol consumption may confer a protective effect against developing RA, our data have shown that this effect may apply to other arthritic conditions too," said Dr Annekoos Leonoor Huidekoper, Leiden University Medical Centre, Netherlands and lead author of the study. "What intrigues us now is that the findings related to systemic inflammation, further research into the inflammatory pathways involved is needed to determine the exact nature of the association."
Patients with arthritic conditions (n=997; RA n=651, reactive arthritis, spondylaropathy or psoriatic arthritis n=273, osteoarthritis n=73) were enrolled from the Leiden Early Arthritis Cohort and healthy controls (n=6,874) recruited from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study. Alcohol consumption was recorded at baseline (units per week), and the effect of alcohol consumption on risk of disease development was analysed by univariate and multivariate logistic regression (statistical tests that predict the probability of an event occurring). Odds ratios and confidence intervals (95%) were adjusted for age, sex, Body Mass Index (BMI) and smoking.
Professor Paul Emery, President of EULAR and arc Professor of Rheumatology, Leeds Institute of Molecular Medicine, University of Leeds, UK said: "These are very interesting findings but we should assert the need for caution in the interpretation of these data. Alcohol should be consumed in moderation, with consideration for local public health recommendations. A number of social and medical problems are associated with increased consumption of alcohol; therefore any positive implications of its use must be understood within the wider health context."
Abstract Number: AB0179
Source: European League Against Rheumatism
In this Dutch study, alcohol consumption was associated with a significantly lower risk of developing RA (Odds Ratio (OR) 0.27 (0.22-0.34), Osteoarthritis (OR 0.31, (0.16-0.62), spondylarthropathy (OR 0.34, 0.17-0.67), psoriatic arthritis (OR 0.38, 0.23-0.62), and reactive arthritis (OR 0.27, 0.14-0.52). A particularly protective effect was shown in the RA population with the presence of Anti-Citrullinated Protein Antibodies (ACPA, potentially important surrogate markers for diagnosis and prognosis in RA), (OR 0.59, 0.30-0.99).
Interestingly, researchers also found that the degree of systemic inflammation in patients was shown to increase as the amount of alcohol consumed decreased (p=0.001) and that there was no dose response relationship (low 0.12 (0.08-0.18), moderate 0.46 (0.36-0.59), high 0.17 (0.12-0.25)) between the amount of alcohol consumed and the risk of arthritis development. Researchers hypothesise that there could be two explanations for this inflammatory effect; either that patients with more severe disease activity consume less alcohol due to associated changes in their lifestyle, or that the presence of alcohol in the system could protect against the development of systemic inflammation.
"We know from previous research that alcohol consumption may confer a protective effect against developing RA, our data have shown that this effect may apply to other arthritic conditions too," said Dr Annekoos Leonoor Huidekoper, Leiden University Medical Centre, Netherlands and lead author of the study. "What intrigues us now is that the findings related to systemic inflammation, further research into the inflammatory pathways involved is needed to determine the exact nature of the association."
Patients with arthritic conditions (n=997; RA n=651, reactive arthritis, spondylaropathy or psoriatic arthritis n=273, osteoarthritis n=73) were enrolled from the Leiden Early Arthritis Cohort and healthy controls (n=6,874) recruited from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study. Alcohol consumption was recorded at baseline (units per week), and the effect of alcohol consumption on risk of disease development was analysed by univariate and multivariate logistic regression (statistical tests that predict the probability of an event occurring). Odds ratios and confidence intervals (95%) were adjusted for age, sex, Body Mass Index (BMI) and smoking.
Professor Paul Emery, President of EULAR and arc Professor of Rheumatology, Leeds Institute of Molecular Medicine, University of Leeds, UK said: "These are very interesting findings but we should assert the need for caution in the interpretation of these data. Alcohol should be consumed in moderation, with consideration for local public health recommendations. A number of social and medical problems are associated with increased consumption of alcohol; therefore any positive implications of its use must be understood within the wider health context."
Abstract Number: AB0179
Source: European League Against Rheumatism
Living Well With Osteoarthritis - Tips on Activity Participation
When you have arthritis - and nearly 70 million Americans do have some arthritis-related condition - daily life can be filled with many challenges, both physical and mental. Ordinary activities you once took for granted, from driving to climbing stairs to doing laundry, can be difficult and painful when you have arthritis. You may feel stressed, depressed, tired and angry at your pain and loss of independence.
But you don't have to let the stiffness, pain, swelling and fatigue associated with arthritis keep you from doing what you need and love to do. You can take control of your arthritis and achieve good living simply by modifying the ways in which you participate in your favorite activities. Taking the proper precautions can allow you to continue to do many of your favorite things, even with arthritis.
Gardening
Don't sit on the ground when you pull weeds or plant bulbs. Sit on a low step-stool or a turned-over metal basin instead. Make sure the seat is low enough that you can bend over easily to do your gardening.
Use a wheeled cart or basket to carry bulbs and gardening tools around your yard. You can push the cart with your feet if you find it difficult to stoop down to move it, or tie a rope or old bathrobe belt to the basket and pull it around the yard.
If you like flower gardening but can't sit on the ground or stoop to low flower beds, try planting flowers in window-box containers or clay pots that sit on tables outside your house. Consider building a greenhouse with raised shelves and tables to hold pots of flowers and plants.
Buy gardening tools with adaptive handles that are easy to grasp, or build up handles yourself by wrapping them with electrical tape, bubble wrap or foam padding.
Traveling
During a flight, try exercising in your seat. Roll your shoulders in a circle, and flex your ankles, hands and fingers. Whenever possible, walk up and down the aisle or to the restroom.
When traveling, use a small, compartmented pill container to organize your daily medications. Keep the container in your purse, carry-on bag or suit pocket where you won't lose it and can access it easily during your trip.
If you are traveling to a different time zone, particularly overseas, keep a log of when you need to take your medications. Take an extra watch with you that is set to your home time, so that you can take your pills at the appropriate time. If the watch has an alarm, set it for dosage times.
If you are taking a long car trip, plan periodic stops at rest areas. Get out of the car, stretch and have a snack. Schedule these stops and figure them into the total travel time.
Don't wait until the last minute to pack for a trip. Plan out beforehand what you will need. Take clothing items that can be mixed and matched to cut down on the amount you pack in your suitcase. A suitcase with fewer items is easier to carry, and clothing stays fresher.
Activities With Families
If you have arthritis and need to help your children dress in the morning, sit on a chair and have the child stand in front of you. This puts you both at the same height and makes dressing easier.
Pack children's lunches the evening before, or pack several days' worth at once. Store these meals in paper sacks in the refrigerator if the items are perishable. Advance preparation cuts down on morning rush.
Create an assembly line in the kitchen for food preparation and clean-up. When washing dishes, one person can wash, one can rinse, one can dry and stack, and one can put away dishes.
If you are spending a long evening with family or friends at a restaurant, sitting for a long period of time may make your joints stiff. Between courses, get up and walk to the restroom or to the bar area. This tip also may keep you from nibbling too much from the contents of the bread basket.
Your joints may become stiff during a long movie. Get to the theater early, so you can choose an aisle seat or a handicapped-accessible seat that allows you to stretch your legs periodically.
A level, well-mowed back yard can be a great place for light exercise. Try kicking a ball back and forth with the children in your family, or toss a rubber ball to your dog and let him fetch it and bring it back to you. Croquet might be another entertaining exercise. Build up the croquet mallet handles with padding to make them easier to grip.
Hiking can be an enjoyable and leisurely form of exercise. Investigate any hiking trails before you embark on your hike. Avoid trails with any uneven or slippery footing or steep inclines or any trails that require you to climb using your hands. Pick an easy, beginner's trail that is well-marked. Hike with friends - never alone - and bring a cellular phone and identification card with you.
While you're watching TV, get off the couch and walk around about once every 30 minutes - perhaps in between your favorite shows or during commercial breaks - to keep joints from stiffening. Don't just walk to the refrigerator and back.
If you find it difficult to handle playing cards or game pieces, play games with your friends or family in a team format. Divide into twos and let your partner handle cards, dice, play money or game pieces while you help with strategy.
How to Fight Fatigue
Stick to the time you've allotted for work. At times, you may have to stay longer to get your job done. But if a task can wait until the next day, leave it until then.
You'll get more done in the long run if you don't wear yourself out.
Don't rush. You'll be more efficient working at a comfortable pace than at a hectic one that invites mistakes and accidents. Schedule time for the unexpected.
Discuss with your supervisor the possibility of adjusting your work schedule. You may be able to come to work later and leave later, allowing you extra time in the morning to take a warm bath or to stretch.
Talk to your fellow workers about swapping duties when possible and approved by your supervisor. When you're having a flare, it may be too difficult for you to do certain tasks, and you may be able to trade for less strenuous duties.
Cooking
Buy meat already cut into chunks or have your butcher cut it for you.
If you need to fill a large pot with water, don't fill it in the sink. Using both hands, place the pot on the stove. Then, fill a glass, small pitcher, watering can or kettle and pour water into the pot until you have the amount needed.
When washing dishes, using a mitt made of sponge material may be more comfortable than trying to hold a sponge or scouring pad. These mitts are available at hardware stores, in the automotive accessories departments.
Use tongs instead of a fork to turn food, such as chicken breasts, during cooking or grilling.
Griddles with low sides may be easier to use than skillets for cooking chicken breasts, chops or fried eggs. The low sides make it easier to turn food with a spatula, or to slide it off the griddle and onto a platter.
Buy cheese already grated or shredded. These cheeses come in resealable plastic bags, and will save your hands from strenuous grating. If you have a hard time resealing these bags, close them with bag clips.
Try opening jars with a rubber jar opener. Or, try placing it in a shallow drawer. Close the drawer enough to squeeze the jar between drawer and countertop, then use both hands to twist the lid open. Use this method for bottles as well.
Many kitchen appliances and cooking utensils come with easy-to-grip handles. Be a proactive consumer - look for these items at your local cookware store, or ask the manager if the store can order these items for you. There also are a number of catalog and Web site companies that sell easy-to-use cooking items.
Use pre-chopped, bagged vegetables and salad mixes to save energy when preparing meals. Bags of frozen mixed vegetables can be defrosted and used in casseroles, stir-fries, salads and omelets. Bags of frozen vegetables can double as a handy ice pack for stiff, painful joints.
Use kitchen scissors to cut open slices of individually wrapped cheese, then pull off the plastic wrap. Large-grip scissors also can be used to cut off pats of stick butter or margarine, and chop the tops off celery stalks.
Don't transfer a cooked dish from the pot to a serving dish. Put the pot on a heatproof trivet right on the dinner table, or put servings on the plates in the kitchen and then serve them to your guests.
Use a large plastic pitcher or a bowl with a spout at one end for mixing cake batters. This method makes it easier to pour batter into the pan. Hold the pitcher or bowl with both hands when you pour.
Treatment Plan and New Developments
For some people who suffer from pain associated with arthritis, their symptoms can be managed with exercise, heat/cold therapy, joint protection, assistive devices, weight control, or in some severe cases, surgery. For others, medications are needed to help manage the symptoms associated with arthritis.
COX-2 inhibitors
COX-2 inhibitors are the newest members of the NSAID class of medications. Available by prescription only, they became widely used in recent years to reduce joint pain and swelling. COX-2 inhibitors work by selectively blocking, or inhibiting, one of the two enzymes associated with inflammation. Some experts have hypothesized that this selective inhibition may be the reason for the negative cardiovascular effects currently associated with COX-2 inhibitors.
Non-selective NSAIDs
Non-selective NSAIDs were developed earlier than COX-2 inhibitors and have been widely used to relieve arthritis pain and inflammation for many years. Unlike COX-2 inhibitors, non-selective NSAIDs inhibit both major enzymes involved in the inflammatory process, COX-1 and COX-2. The non-selective NSAID category includes a number of different medications that are available in both prescription and over-the-counter (OTC) products.
However, recent controversy about the safety of pain medications for arthritis has left patients and health care professionals alike uncertain about which medications are safe to use. In fact, a recent survey by the Boston-based Rippe Lifestyle Institute indicated that many people with arthritis are suffering unnecessarily because they have stopped or reduced their use of pain relievers due to confusion about which drugs are considered safe.
To clarify the confusion around recent news about arthritis medications, here are some facts:
On April 7, 2005, the FDA announced the following:
• Bextra, a COX-2 inhibitor manufactured by Pfizer, was being voluntarily withdrawn from the market.
• All prescription NSAIDs must revise their labeling to include a "black box" warning that highlights the potential increased risk for cardiovascular (CV) events as well as the potentially life threatening gastrointestinal (GI) bleeding associated with these drugs. Celebrex, the only COX-2 inhibitor remaining on the US market, was included in this directive.
• All OTC NSAIDs (except aspirin) will be required to revise their labeling to include more specific information about the potential for GI and CV side effects, a stronger reminder to follow label instructions, as well as a warning about potential skin reactions.
To further evaluate the potential for increased CV risk, the FDA also announced that all NSAIDs must conduct and submit to the Agency a comprehensive review and analysis of pertinent safety data from clinical trials.
The FDA emphasized that when label directions are followed, OTC pain relievers such as Aleve (naproxen sodium) provide a safe and effective way to treat mild to moderate pain of minor arthritis. If patients have questions, they should consult their health care professional about which treatment option is most appropriate.
More Information
By taking precautions such as these, you may find that you will not have to abandon those things you love to do. For more information about osteoarthritis, and living with it, visit the ALEVE website at aleve. ALEVE is an over-the-counter (OTC) pain reliever that provides relief for a variety of pain conditions, including minor pains associated with arthritis.
The above Tips on Activity Participation was excerpted from The Arthritis Foundation's Tips for Good Living with Arthritis, copyright ©2001, Arthritis Foundation. Want more? Get your own copy of Tips for Good Living with Arthritis by calling (800) 283-7800.
arthritis
But you don't have to let the stiffness, pain, swelling and fatigue associated with arthritis keep you from doing what you need and love to do. You can take control of your arthritis and achieve good living simply by modifying the ways in which you participate in your favorite activities. Taking the proper precautions can allow you to continue to do many of your favorite things, even with arthritis.
Gardening
Don't sit on the ground when you pull weeds or plant bulbs. Sit on a low step-stool or a turned-over metal basin instead. Make sure the seat is low enough that you can bend over easily to do your gardening.
Use a wheeled cart or basket to carry bulbs and gardening tools around your yard. You can push the cart with your feet if you find it difficult to stoop down to move it, or tie a rope or old bathrobe belt to the basket and pull it around the yard.
If you like flower gardening but can't sit on the ground or stoop to low flower beds, try planting flowers in window-box containers or clay pots that sit on tables outside your house. Consider building a greenhouse with raised shelves and tables to hold pots of flowers and plants.
Buy gardening tools with adaptive handles that are easy to grasp, or build up handles yourself by wrapping them with electrical tape, bubble wrap or foam padding.
Traveling
During a flight, try exercising in your seat. Roll your shoulders in a circle, and flex your ankles, hands and fingers. Whenever possible, walk up and down the aisle or to the restroom.
When traveling, use a small, compartmented pill container to organize your daily medications. Keep the container in your purse, carry-on bag or suit pocket where you won't lose it and can access it easily during your trip.
If you are traveling to a different time zone, particularly overseas, keep a log of when you need to take your medications. Take an extra watch with you that is set to your home time, so that you can take your pills at the appropriate time. If the watch has an alarm, set it for dosage times.
If you are taking a long car trip, plan periodic stops at rest areas. Get out of the car, stretch and have a snack. Schedule these stops and figure them into the total travel time.
Don't wait until the last minute to pack for a trip. Plan out beforehand what you will need. Take clothing items that can be mixed and matched to cut down on the amount you pack in your suitcase. A suitcase with fewer items is easier to carry, and clothing stays fresher.
Activities With Families
If you have arthritis and need to help your children dress in the morning, sit on a chair and have the child stand in front of you. This puts you both at the same height and makes dressing easier.
Pack children's lunches the evening before, or pack several days' worth at once. Store these meals in paper sacks in the refrigerator if the items are perishable. Advance preparation cuts down on morning rush.
Create an assembly line in the kitchen for food preparation and clean-up. When washing dishes, one person can wash, one can rinse, one can dry and stack, and one can put away dishes.
If you are spending a long evening with family or friends at a restaurant, sitting for a long period of time may make your joints stiff. Between courses, get up and walk to the restroom or to the bar area. This tip also may keep you from nibbling too much from the contents of the bread basket.
Your joints may become stiff during a long movie. Get to the theater early, so you can choose an aisle seat or a handicapped-accessible seat that allows you to stretch your legs periodically.
A level, well-mowed back yard can be a great place for light exercise. Try kicking a ball back and forth with the children in your family, or toss a rubber ball to your dog and let him fetch it and bring it back to you. Croquet might be another entertaining exercise. Build up the croquet mallet handles with padding to make them easier to grip.
Hiking can be an enjoyable and leisurely form of exercise. Investigate any hiking trails before you embark on your hike. Avoid trails with any uneven or slippery footing or steep inclines or any trails that require you to climb using your hands. Pick an easy, beginner's trail that is well-marked. Hike with friends - never alone - and bring a cellular phone and identification card with you.
While you're watching TV, get off the couch and walk around about once every 30 minutes - perhaps in between your favorite shows or during commercial breaks - to keep joints from stiffening. Don't just walk to the refrigerator and back.
If you find it difficult to handle playing cards or game pieces, play games with your friends or family in a team format. Divide into twos and let your partner handle cards, dice, play money or game pieces while you help with strategy.
How to Fight Fatigue
Stick to the time you've allotted for work. At times, you may have to stay longer to get your job done. But if a task can wait until the next day, leave it until then.
You'll get more done in the long run if you don't wear yourself out.
Don't rush. You'll be more efficient working at a comfortable pace than at a hectic one that invites mistakes and accidents. Schedule time for the unexpected.
Discuss with your supervisor the possibility of adjusting your work schedule. You may be able to come to work later and leave later, allowing you extra time in the morning to take a warm bath or to stretch.
Talk to your fellow workers about swapping duties when possible and approved by your supervisor. When you're having a flare, it may be too difficult for you to do certain tasks, and you may be able to trade for less strenuous duties.
Cooking
Buy meat already cut into chunks or have your butcher cut it for you.
If you need to fill a large pot with water, don't fill it in the sink. Using both hands, place the pot on the stove. Then, fill a glass, small pitcher, watering can or kettle and pour water into the pot until you have the amount needed.
When washing dishes, using a mitt made of sponge material may be more comfortable than trying to hold a sponge or scouring pad. These mitts are available at hardware stores, in the automotive accessories departments.
Use tongs instead of a fork to turn food, such as chicken breasts, during cooking or grilling.
Griddles with low sides may be easier to use than skillets for cooking chicken breasts, chops or fried eggs. The low sides make it easier to turn food with a spatula, or to slide it off the griddle and onto a platter.
Buy cheese already grated or shredded. These cheeses come in resealable plastic bags, and will save your hands from strenuous grating. If you have a hard time resealing these bags, close them with bag clips.
Try opening jars with a rubber jar opener. Or, try placing it in a shallow drawer. Close the drawer enough to squeeze the jar between drawer and countertop, then use both hands to twist the lid open. Use this method for bottles as well.
Many kitchen appliances and cooking utensils come with easy-to-grip handles. Be a proactive consumer - look for these items at your local cookware store, or ask the manager if the store can order these items for you. There also are a number of catalog and Web site companies that sell easy-to-use cooking items.
Use pre-chopped, bagged vegetables and salad mixes to save energy when preparing meals. Bags of frozen mixed vegetables can be defrosted and used in casseroles, stir-fries, salads and omelets. Bags of frozen vegetables can double as a handy ice pack for stiff, painful joints.
Use kitchen scissors to cut open slices of individually wrapped cheese, then pull off the plastic wrap. Large-grip scissors also can be used to cut off pats of stick butter or margarine, and chop the tops off celery stalks.
Don't transfer a cooked dish from the pot to a serving dish. Put the pot on a heatproof trivet right on the dinner table, or put servings on the plates in the kitchen and then serve them to your guests.
Use a large plastic pitcher or a bowl with a spout at one end for mixing cake batters. This method makes it easier to pour batter into the pan. Hold the pitcher or bowl with both hands when you pour.
Treatment Plan and New Developments
For some people who suffer from pain associated with arthritis, their symptoms can be managed with exercise, heat/cold therapy, joint protection, assistive devices, weight control, or in some severe cases, surgery. For others, medications are needed to help manage the symptoms associated with arthritis.
COX-2 inhibitors
COX-2 inhibitors are the newest members of the NSAID class of medications. Available by prescription only, they became widely used in recent years to reduce joint pain and swelling. COX-2 inhibitors work by selectively blocking, or inhibiting, one of the two enzymes associated with inflammation. Some experts have hypothesized that this selective inhibition may be the reason for the negative cardiovascular effects currently associated with COX-2 inhibitors.
Non-selective NSAIDs
Non-selective NSAIDs were developed earlier than COX-2 inhibitors and have been widely used to relieve arthritis pain and inflammation for many years. Unlike COX-2 inhibitors, non-selective NSAIDs inhibit both major enzymes involved in the inflammatory process, COX-1 and COX-2. The non-selective NSAID category includes a number of different medications that are available in both prescription and over-the-counter (OTC) products.
However, recent controversy about the safety of pain medications for arthritis has left patients and health care professionals alike uncertain about which medications are safe to use. In fact, a recent survey by the Boston-based Rippe Lifestyle Institute indicated that many people with arthritis are suffering unnecessarily because they have stopped or reduced their use of pain relievers due to confusion about which drugs are considered safe.
To clarify the confusion around recent news about arthritis medications, here are some facts:
On April 7, 2005, the FDA announced the following:
• Bextra, a COX-2 inhibitor manufactured by Pfizer, was being voluntarily withdrawn from the market.
• All prescription NSAIDs must revise their labeling to include a "black box" warning that highlights the potential increased risk for cardiovascular (CV) events as well as the potentially life threatening gastrointestinal (GI) bleeding associated with these drugs. Celebrex, the only COX-2 inhibitor remaining on the US market, was included in this directive.
• All OTC NSAIDs (except aspirin) will be required to revise their labeling to include more specific information about the potential for GI and CV side effects, a stronger reminder to follow label instructions, as well as a warning about potential skin reactions.
To further evaluate the potential for increased CV risk, the FDA also announced that all NSAIDs must conduct and submit to the Agency a comprehensive review and analysis of pertinent safety data from clinical trials.
The FDA emphasized that when label directions are followed, OTC pain relievers such as Aleve (naproxen sodium) provide a safe and effective way to treat mild to moderate pain of minor arthritis. If patients have questions, they should consult their health care professional about which treatment option is most appropriate.
More Information
By taking precautions such as these, you may find that you will not have to abandon those things you love to do. For more information about osteoarthritis, and living with it, visit the ALEVE website at aleve. ALEVE is an over-the-counter (OTC) pain reliever that provides relief for a variety of pain conditions, including minor pains associated with arthritis.
The above Tips on Activity Participation was excerpted from The Arthritis Foundation's Tips for Good Living with Arthritis, copyright ©2001, Arthritis Foundation. Want more? Get your own copy of Tips for Good Living with Arthritis by calling (800) 283-7800.
arthritis
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