High doses of some traditional non-steroidal anti-inflammatory drugs (NSAIDS) are associated with similar cardiovascular risks as the new generation of anti-inflammatory drugs known as COX 2 inhibitors (like Vioxx ®), finds a study in this week's BMJ.
Researchers from the UK and Italy performed a combined analysis (known as a "meta-analysis") of all the available randomised trials that compared a COX 2 inhibitor with placebo, or a COX 2 inhibitor with a traditional NSAID, and had recorded serious cardiovascular events. By including data from 138 trials among 140,000 patients, this meta-analysis provides a much more reliable estimate of the cardiovascular risks of these drugs, since individual trials were too small to study this question.
The study showed, as expected, that, COX 2 inhibitors were associated with an increased risk of vascular events, mainly heart attack. Unfortunately, there were insufficient data to reliably assess whether these risks were dose dependent, or whether the risks might differ among aspirin and non-aspirin users.
But the study also showed that high doses of two of the NSAIDs studied, diclofenac and ibuprofen, were associated with a similar increase in the risk of vascular events to COX 2 inhibitors, although the risks of high doses of another NSAID, naproxen, were smaller.
However, the average increased risk of vascular events was modest among the people studied in the trials: For every 1,000 people taking an NSAID or COX 2 inhibitor, around three extra people per year would have a vascular event, most likely a heart attack.
The authors conclude that very large randomised trials are needed to identify which anti-inflammatory drug regimens minimise serious cardiovascular and gastrointestinal problems.
An accompanying editorial discusses other options for treating chronic pain and suggests that doctors work with their patients to choose the best solutions for them.
Do cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials; BMJ Volume 332, pp 1302-5
Emma Dickinson
edickinsonbmj
BMJ-British Medical Journal
bmj
View drug information on Vioxx.
воскресенье, 11 сентября 2011 г.
четверг, 8 сентября 2011 г.
Othopaedists Say Biomarker Could Make Diagnosing Knee Injury Easier, Less Costly
A recently discovered biomarker could help doctors diagnose a common type of knee injury, according to a new study.
A team of researchers led by Gaetano Scuderi, MD, clinical assistant professor of orthopaedic surgery at Stanford University School of Medicine and an orthopaedic surgeon at Stanford Hospital & Clinics, has confirmed that a particular protein complex appears in patients with painful meniscal tears. The finding, to be published Feb. 16 in /i>The Journal of Bone and Joint Surgery, could be used to prevent needless surgery and to save billions of dollars in medical-imaging costs.
The menisci are two crescent-shaped pieces of cartilage in each knee joint. Contact sports, such as football, as well as sports that involve lot of pivoting, such as basketball and tennis, increase the risk of the cartilage tearing. It is also prone to tear as a result of natural degeneration, meaning older people are at increased risk. Meniscal tears are painful and usually accompanied by swelling and stiffness. Sometimes the knee joint feels as though it is locked in place.
Patients are generally advised to elevate and apply ice to the knee, as well as to take a break from physical activity that could aggravate the injury. These measures might not be enough, however, so patients can undergo a minimally invasive procedure, arthroscopic surgery, to trim away or repair the meniscus.
But identifying whether a patient's knee pain stems from a meniscal tear, as opposed to joint arthritis or another type of leg injury, is difficult. For example, in an older patient, magnetic-resonance imaging might reveal an abnormal-looking meniscus that doctors mistake as evidence of a painful tear, even though it is just due to natural degeneration from lots of wear over the years. For such a patient, who is perhaps really suffering from joint arthritis, meniscal surgery would offer no relief.
Knee pain also can stem from other parts of the body. For example, a young athlete who complains of symptoms similar to those of a torn meniscus may undergo a costly MRI that reveals no cartilage abnormalities. In reality, an injured hip ligament could be causing the knee to hurt. "It's like someone with heart disease feeling pain in his left shoulder," Scuderi said.
In the study, Scuderi and his co-authors found that the biomarker appeared in the knee fluid of 30 patients who had suffered a painful meniscal tear. It was not present in the knees of 10 asymptomatic patients. The biomarker, a fibronectin-aggrecan complex, holds out the promise of allowing orthopaedists to quickly and accurately diagnose whether the source of a patient's discomfort is a meniscal tear, as opposed to another type of injury or abnormality, simply by taking a sample of knee fluid. It could thus obviate the need for expensive medical scans and help to prevent surgery that does not address the true cause of a patient's pain.
"The challenge is not identifying molecular markers of cartilage degeneration, dozens of which are now known," said co-author Raymond Golish, MD, PhD, who recently completed a fellowship in spine surgery at Stanford. "The difficulty is in finding markers that correlate with painful injuries, as opposed to age-related degeneration that is painless. This study is a big step in that direction."
Scuderi and his colleagues undertook the prospective study to validate their findings from an earlier study in which they first noted the presence of the protein complex in patients with torn menisci and knee pain. (Those results were published in the July 2010 issue of Clinical Biochemistry.)
The researchers are now running experiments to confirm that the biomarker does not show up in other types of knee injuries, such as ACL tears unaccompanied by meniscal tears. They also are studying whether the protein complex, which is implicated in knee inflammation, could serve as a therapeutic target. "We could envision several things, such as blocking the fibronectin and aggrecan protein fragments from coming together to form a complex, or interfering with the activation of white blood cells at the site," Scuderi said.
Notes:
The research was supported by Cytonics Inc., a Florida-based company founded by Scuderi in 2006 to pursue possible clinical applications of the fibronectin-aggrecan complex. Researchers from the Jupiter Medical Center, the New York University Hospital for Joint Diseases, the University of Pittsburgh and Cytonics Inc. were also co-authors of the study. Stanford's Department of Orthopaedic Surgery also supported this work.
Source:
John Sanford
Stanford University Medical Center
A team of researchers led by Gaetano Scuderi, MD, clinical assistant professor of orthopaedic surgery at Stanford University School of Medicine and an orthopaedic surgeon at Stanford Hospital & Clinics, has confirmed that a particular protein complex appears in patients with painful meniscal tears. The finding, to be published Feb. 16 in /i>The Journal of Bone and Joint Surgery, could be used to prevent needless surgery and to save billions of dollars in medical-imaging costs.
The menisci are two crescent-shaped pieces of cartilage in each knee joint. Contact sports, such as football, as well as sports that involve lot of pivoting, such as basketball and tennis, increase the risk of the cartilage tearing. It is also prone to tear as a result of natural degeneration, meaning older people are at increased risk. Meniscal tears are painful and usually accompanied by swelling and stiffness. Sometimes the knee joint feels as though it is locked in place.
Patients are generally advised to elevate and apply ice to the knee, as well as to take a break from physical activity that could aggravate the injury. These measures might not be enough, however, so patients can undergo a minimally invasive procedure, arthroscopic surgery, to trim away or repair the meniscus.
But identifying whether a patient's knee pain stems from a meniscal tear, as opposed to joint arthritis or another type of leg injury, is difficult. For example, in an older patient, magnetic-resonance imaging might reveal an abnormal-looking meniscus that doctors mistake as evidence of a painful tear, even though it is just due to natural degeneration from lots of wear over the years. For such a patient, who is perhaps really suffering from joint arthritis, meniscal surgery would offer no relief.
Knee pain also can stem from other parts of the body. For example, a young athlete who complains of symptoms similar to those of a torn meniscus may undergo a costly MRI that reveals no cartilage abnormalities. In reality, an injured hip ligament could be causing the knee to hurt. "It's like someone with heart disease feeling pain in his left shoulder," Scuderi said.
In the study, Scuderi and his co-authors found that the biomarker appeared in the knee fluid of 30 patients who had suffered a painful meniscal tear. It was not present in the knees of 10 asymptomatic patients. The biomarker, a fibronectin-aggrecan complex, holds out the promise of allowing orthopaedists to quickly and accurately diagnose whether the source of a patient's discomfort is a meniscal tear, as opposed to another type of injury or abnormality, simply by taking a sample of knee fluid. It could thus obviate the need for expensive medical scans and help to prevent surgery that does not address the true cause of a patient's pain.
"The challenge is not identifying molecular markers of cartilage degeneration, dozens of which are now known," said co-author Raymond Golish, MD, PhD, who recently completed a fellowship in spine surgery at Stanford. "The difficulty is in finding markers that correlate with painful injuries, as opposed to age-related degeneration that is painless. This study is a big step in that direction."
Scuderi and his colleagues undertook the prospective study to validate their findings from an earlier study in which they first noted the presence of the protein complex in patients with torn menisci and knee pain. (Those results were published in the July 2010 issue of Clinical Biochemistry.)
The researchers are now running experiments to confirm that the biomarker does not show up in other types of knee injuries, such as ACL tears unaccompanied by meniscal tears. They also are studying whether the protein complex, which is implicated in knee inflammation, could serve as a therapeutic target. "We could envision several things, such as blocking the fibronectin and aggrecan protein fragments from coming together to form a complex, or interfering with the activation of white blood cells at the site," Scuderi said.
Notes:
The research was supported by Cytonics Inc., a Florida-based company founded by Scuderi in 2006 to pursue possible clinical applications of the fibronectin-aggrecan complex. Researchers from the Jupiter Medical Center, the New York University Hospital for Joint Diseases, the University of Pittsburgh and Cytonics Inc. were also co-authors of the study. Stanford's Department of Orthopaedic Surgery also supported this work.
Source:
John Sanford
Stanford University Medical Center
понедельник, 5 сентября 2011 г.
Psoriasis: Effects Don't Always Stop With The Skin
Psoriasis, a chronic disease that causes red, raised patches of skin, is increasingly seen as a systemic disease with links to arthritis and cardiovascular disease. The December issue of Mayo Clinic Women's HealthSource provides an overview of this sometimes embarrassing condition, what's known about it and how it's treated. Highlights of the overview include:
-- Symptoms: Patches of thick, red skin covered with silvery, flaky scales commonly appear on the elbows and knees, but can appear anywhere on the body. They result from skin cells on overdrive, reproducing much faster than normal. Doctors aren't sure why this overproduction occurs, although genetic and environmental factors likely play roles. Psoriasis symptoms come and go and flare in response to triggers that can include infections, some medications, alcohol, smoking, stress, sunburn, skin irritation or injury.
-- A systemic illness: Doctors are finding that psoriasis is more than a skin disorder. About one in four people with psoriasis develop a form of arthritis called psoriatic arthritis that can cause pain, stiffness and swelling in the joints. Studies have shown that people with psoriasis face a higher risk of heart attack, stroke and other cardiovascular problems. The underlying link may be chronic inflammation, which plays a role in psoriasis and heart disease.
-- Treatment: While psoriasis can't be cured, a variety of topical and systemic treatment options can help control the condition. For mild-to-moderate psoriasis, topical treatments often are effective. Options include corticosteroids or retinoids to reduce inflammation; vitamin D analogs to slow skin growth; and tar, to reduce scaling, itching and inflammation. Calcineurin inhibitors (tacrolimus and pimecrolimus) can help reduce inflammation and skin cell buildup.
In addition, ultraviolet light slows the rapid growth of skin cells. Ultraviolet light therapy may be used alone or in combination with other treatments. Several systemic medications are used for severe forms of psoriasis, though these options pose the risk of serious side effects.
-- Self-help measures: Home-care measures can help prevent or manage symptoms. A daily bath removes scales and calms inflamed skin. Adding bath oil, colloidal oatmeal, Epsom salts or Dead Sea salts can offer additional relief. After bathing, applying a thick moisturizing cream or ointment, such as petroleum jelly, can be helpful. During cold, dry weather, it's beneficial to apply moisturizer several times a day. Short sessions in sunlight three or more times a week can improve psoriasis, as can avoiding known triggers.
Source: Mayo Clinic
-- Symptoms: Patches of thick, red skin covered with silvery, flaky scales commonly appear on the elbows and knees, but can appear anywhere on the body. They result from skin cells on overdrive, reproducing much faster than normal. Doctors aren't sure why this overproduction occurs, although genetic and environmental factors likely play roles. Psoriasis symptoms come and go and flare in response to triggers that can include infections, some medications, alcohol, smoking, stress, sunburn, skin irritation or injury.
-- A systemic illness: Doctors are finding that psoriasis is more than a skin disorder. About one in four people with psoriasis develop a form of arthritis called psoriatic arthritis that can cause pain, stiffness and swelling in the joints. Studies have shown that people with psoriasis face a higher risk of heart attack, stroke and other cardiovascular problems. The underlying link may be chronic inflammation, which plays a role in psoriasis and heart disease.
-- Treatment: While psoriasis can't be cured, a variety of topical and systemic treatment options can help control the condition. For mild-to-moderate psoriasis, topical treatments often are effective. Options include corticosteroids or retinoids to reduce inflammation; vitamin D analogs to slow skin growth; and tar, to reduce scaling, itching and inflammation. Calcineurin inhibitors (tacrolimus and pimecrolimus) can help reduce inflammation and skin cell buildup.
In addition, ultraviolet light slows the rapid growth of skin cells. Ultraviolet light therapy may be used alone or in combination with other treatments. Several systemic medications are used for severe forms of psoriasis, though these options pose the risk of serious side effects.
-- Self-help measures: Home-care measures can help prevent or manage symptoms. A daily bath removes scales and calms inflamed skin. Adding bath oil, colloidal oatmeal, Epsom salts or Dead Sea salts can offer additional relief. After bathing, applying a thick moisturizing cream or ointment, such as petroleum jelly, can be helpful. During cold, dry weather, it's beneficial to apply moisturizer several times a day. Short sessions in sunlight three or more times a week can improve psoriasis, as can avoiding known triggers.
Source: Mayo Clinic
пятница, 2 сентября 2011 г.
The impact of genetic variations on the treatment of early rheumatoid arthritis
Characterized by inflammation in the connective tissues of the joints, rheumatoid arthritis (RA) can be a painful, crippling autoimmune disease. Traditionally, patients have been treated with disease-modifying antirheumatic drugs, or DMARDs, such as methotrexate (MTX). Several new therapies, however, focus on blocking tumor necrosis factor, or TNF, one of the body's chemical messengers with a role in regulating the inflammation. Although MTX and TNF blockers work well in the treatment of RA, they vary widely with regard to effectiveness and side effects, and there are currently no markers to predict response to particular drugs.
In a recent study, published in the September 2004 issue of Arthritis & Rheumatism, researchers set out to examine whether specific genetic variations could predict the response to treatment of early RA. Led by S. Louis Bridges, Jr., M.D., Ph.D. of the University of Alabama at Birmingham and Lindsey A. Criswell, M.D., M.P.H. of the University of California, San Francisco, the group analyzed genetic and clinical data on 457 patients in the early stages of RA who participated in a clinical trial comparing weekly methotrexate, 10 milligrams twice weekly of the anti-TNF drug etanercept, and 25 milligrams of etanercept twice weekly (the currently approved dose for RA). The results of this clinical trial have been previously published (Bathon et al. New Engl J Med 343:1586-1593, 2000).
Researchers examined patients for a particular genetic marker in the HLA region associated with susceptibility to RA (the so-called shared epitope), as well as genetic variants in the TNF gene region. Results of genetic testing were then correlated with treatment responses. Among patients treated with standard-dose etanercept, those with two copies of the shared epitope were four times more likely to achieve 50 percent improvement in disease activity (according to the criteria of the American College of Rheumatology) at 12 months than were patients with one copy or no copies of the shared epitope. Furthermore, patients with particular HLA genes in addition to particular genetic variations in the TNF gene region were found to have better responses to treatment, regardless of which drug was used.
"Results of the current study suggest that, at least for RA patients with early active disease, genetic variations in the HLA and TNF gene regions are associated with response to treatment," Dr. Criswell concludes. "Additional work is required to confirm these results," Dr. Bridges adds, acknowledging the complexity of genetic involvement in RA, "as well as to extend these observations to patients of other ethnicities, and more precisely define the individual genes and haplotypes responsible for these associations."
Article: "The Influence of Genetic Variation in the HLA-DRB1 and LTA-TNF Regions on the Response to Treatment of Early Rheumatoid Arthritis With Methotrexate or Etanercept," Lindsey A. Criswell, Raymond F. Lum, Kevin N. Turner, Blanche Woehl, Yuanqing Zhu, Jinyi Wang, Hemant K. Tiwari, Jeffrey C. Edberg, Robert P. Kimberly, Larry W. Moreland, Michael F. Seldin, and S. Louis Bridges, Jr., Arthritis & Rheumatism, September 2004, 50:9; pp. 2750-2756.
Contact: Amy Molnar
amolnarwiley
201-748-8844
John Wiley & Sons, Inc.
In a recent study, published in the September 2004 issue of Arthritis & Rheumatism, researchers set out to examine whether specific genetic variations could predict the response to treatment of early RA. Led by S. Louis Bridges, Jr., M.D., Ph.D. of the University of Alabama at Birmingham and Lindsey A. Criswell, M.D., M.P.H. of the University of California, San Francisco, the group analyzed genetic and clinical data on 457 patients in the early stages of RA who participated in a clinical trial comparing weekly methotrexate, 10 milligrams twice weekly of the anti-TNF drug etanercept, and 25 milligrams of etanercept twice weekly (the currently approved dose for RA). The results of this clinical trial have been previously published (Bathon et al. New Engl J Med 343:1586-1593, 2000).
Researchers examined patients for a particular genetic marker in the HLA region associated with susceptibility to RA (the so-called shared epitope), as well as genetic variants in the TNF gene region. Results of genetic testing were then correlated with treatment responses. Among patients treated with standard-dose etanercept, those with two copies of the shared epitope were four times more likely to achieve 50 percent improvement in disease activity (according to the criteria of the American College of Rheumatology) at 12 months than were patients with one copy or no copies of the shared epitope. Furthermore, patients with particular HLA genes in addition to particular genetic variations in the TNF gene region were found to have better responses to treatment, regardless of which drug was used.
"Results of the current study suggest that, at least for RA patients with early active disease, genetic variations in the HLA and TNF gene regions are associated with response to treatment," Dr. Criswell concludes. "Additional work is required to confirm these results," Dr. Bridges adds, acknowledging the complexity of genetic involvement in RA, "as well as to extend these observations to patients of other ethnicities, and more precisely define the individual genes and haplotypes responsible for these associations."
Article: "The Influence of Genetic Variation in the HLA-DRB1 and LTA-TNF Regions on the Response to Treatment of Early Rheumatoid Arthritis With Methotrexate or Etanercept," Lindsey A. Criswell, Raymond F. Lum, Kevin N. Turner, Blanche Woehl, Yuanqing Zhu, Jinyi Wang, Hemant K. Tiwari, Jeffrey C. Edberg, Robert P. Kimberly, Larry W. Moreland, Michael F. Seldin, and S. Louis Bridges, Jr., Arthritis & Rheumatism, September 2004, 50:9; pp. 2750-2756.
Contact: Amy Molnar
amolnarwiley
201-748-8844
John Wiley & Sons, Inc.
вторник, 30 августа 2011 г.
Human Articular Cartilage Repaired With Amniotic Membrane
"The objective was to evaluate the utility of cryo-preserved human amniotic membrane (HAM) as a support for repairing human articular cartilage injuries, which have a very limited capacity for self-healing", Francisco J. Blanco, lead author of the study and a researcher at the Institute of Biomedical Research of La Coruna (INIBIC), tells SINC.
The results, which have been published in the journal Cell and Tissue Banking, show that cryo-preserved HAM is useful as a scaffold for growing human chondrocytes in cell therapy and for repairing human cartilage injuries. "It provides a more regular surface and fills in the cavities and fissures", explains Blanco.
The authors cultivated the chondrocytes (cells that form part of the cartilaginous tissue), isolated from human articular cartilage, on the amniotic membrane over a period of three and four weeks. The amniotic membranes were used to develop 44 repair models of arthritic human articular cartilage in vitro, which was assessed between four and 16 weeks later.
The HAM also bonds well with the native cartilage. "In some models, we could not differentiate between where the native tissue stopped and the neo-synthesised tissue began", says the expert. This tissue had a fibrous appearance and high cellular density (cellularity), which in some cases was greater than that of the actual native cartilage.
The use of differentiated chondrocytes is a useful therapeutic option for repairing articular cartilage injuries. However, there are limitations to implanting these cells, since many patients will be ruled out due to their lack of healthy chondrocytes, and this technique also causes additional damage to the joint.
"Transplanting chondrocytes cultivated on different natural or synthetic 'scaffolds' is used today in cell tissue engineering. The HAM has sparked great interest over recent years, above all in the field of regenerative medicine", concludes Blanco.
Clinical solutions to osteoarthritis
Osteoarthritis (OA) is a major articular pathology that is characterised by alteration of the cartilage and the bone that supports it, the subchondral bone. As the current pharmacological and surgical treatments have only palliative effects, cell therapy is a new clinical approach for repairing damaged or destroyed tissues.
HAM has many clinical advantages as a support - it is an anti-microbial, anti-angiogenic, anti-tumour tissue, which reduces inflammation and pain and improves scarring. In addition, the amnios of the HAM has no immune response, meaning there are no risks associated with transplanting it, and it contains many of the components of natural cartilage.
References: Silvia D?az-Prado; M?? Esther Rendal-V??zquez; Emma Mui?±os-L??pez; Tamara Hermida-G??mez; Margarita Rodr?guez-Cabarcos; Isaac Fuentes-Boquete; Francisco J. de Toro; Francisco J. Blanco. "Potential use of the human amniotic membrane as a scaffold in human articular cartilage repair". Cell Tissue Bank (2010) 11:183-195 DOI 10.1007/s10561-009-9144-1.
Source:
SINC
FECYT - Spanish Foundation for Science and Technology
The results, which have been published in the journal Cell and Tissue Banking, show that cryo-preserved HAM is useful as a scaffold for growing human chondrocytes in cell therapy and for repairing human cartilage injuries. "It provides a more regular surface and fills in the cavities and fissures", explains Blanco.
The authors cultivated the chondrocytes (cells that form part of the cartilaginous tissue), isolated from human articular cartilage, on the amniotic membrane over a period of three and four weeks. The amniotic membranes were used to develop 44 repair models of arthritic human articular cartilage in vitro, which was assessed between four and 16 weeks later.
The HAM also bonds well with the native cartilage. "In some models, we could not differentiate between where the native tissue stopped and the neo-synthesised tissue began", says the expert. This tissue had a fibrous appearance and high cellular density (cellularity), which in some cases was greater than that of the actual native cartilage.
The use of differentiated chondrocytes is a useful therapeutic option for repairing articular cartilage injuries. However, there are limitations to implanting these cells, since many patients will be ruled out due to their lack of healthy chondrocytes, and this technique also causes additional damage to the joint.
"Transplanting chondrocytes cultivated on different natural or synthetic 'scaffolds' is used today in cell tissue engineering. The HAM has sparked great interest over recent years, above all in the field of regenerative medicine", concludes Blanco.
Clinical solutions to osteoarthritis
Osteoarthritis (OA) is a major articular pathology that is characterised by alteration of the cartilage and the bone that supports it, the subchondral bone. As the current pharmacological and surgical treatments have only palliative effects, cell therapy is a new clinical approach for repairing damaged or destroyed tissues.
HAM has many clinical advantages as a support - it is an anti-microbial, anti-angiogenic, anti-tumour tissue, which reduces inflammation and pain and improves scarring. In addition, the amnios of the HAM has no immune response, meaning there are no risks associated with transplanting it, and it contains many of the components of natural cartilage.
References: Silvia D?az-Prado; M?? Esther Rendal-V??zquez; Emma Mui?±os-L??pez; Tamara Hermida-G??mez; Margarita Rodr?guez-Cabarcos; Isaac Fuentes-Boquete; Francisco J. de Toro; Francisco J. Blanco. "Potential use of the human amniotic membrane as a scaffold in human articular cartilage repair". Cell Tissue Bank (2010) 11:183-195 DOI 10.1007/s10561-009-9144-1.
Source:
SINC
FECYT - Spanish Foundation for Science and Technology
суббота, 27 августа 2011 г.
Renowned Bone Health Experts To Lead Interactive Sessions At The World Congress On Osteoporosis 2010
The International Osteoporosis Foundation (IOF) and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) will hold a joint global congress, IOF WCO- ECCEO10, in Florence, Italy from May 5-8, 2010.
Complete programme information, online registration and abstract submission will be available on iofwco-ecceo10 .
IOF WCO-ECCEO10 will be an excellent forum for interaction and the exchange of ideas among researchers and clinicians as well as specialists from allied health fields. It will offer an overview of the most recent developments and cutting-edge research in the pathophysiology, diagnosis, prevention and treatment of osteoporosis and osteoarthritis, as well as policy related issues such as health economics.
Offering a broad global perspective, the scientific programme will provide a mix of stimulating plenary lectures on 'hot' topics in the field and more clinically-oriented meet-the-expert sessions led by world experts. There will also be poster presentations, late breaking news, satellite symposia, and a large exhibition area.
Meet-the-expert sessions to be led by world experts:
Each day specialists will lead exchanges on 20 key topics. Small groups, on a first come first served basis, will be encouraged to not only ask questions but to also provide feedback about their own experiences. The following topics and speakers are scheduled:
Assessing bone strength beyond DXA, C. Gl??er (Germany)
Optimal dose of vitamin D, B. Dawson-Hughes (USA)
Muscle and bone interaction, D. Felsenberg (Germany)
Practical approach of glucocorticoid-treated patients, J. Adachi (Canada)
Health economics and treatment selection, J-Y. Reginster (Belgium)
BMU balance: effects of anti-osteoporotic agents, Jpston (UK)
Premenopausal osteoporosis, E. Siris (USA)
Bone mass/structure measurements during growth, R. Rizzoli (Switzerland)
Bone disease in primary hyperparathyroidism, J.P. Bilezikian (USA)
Bisphosphonates in chronic renal failure, S. Papapoulos (NL)
Pharmaco-genomics, M.L. Brandi (Italy)
Vertebro/kyphoplasty, S. Boonen (Belgium)
Issues in designing and conducting clinical trials, S. Cummings (USA)
Osteoporosis in men, E. Seeman (Australia)
Post-fracture management, K. Akesson (Sweden)
Fracture healing: can we influence it?, J. Goldhahn (Switzerland)
Genetics and osteoporosis: how to assess it?, S. Ferrari (Switzerland)
Side effects of anti fracture drugs, S. Adami (Italy)
Developmental origins of osteoporotic fracture, C. Cooper (UK)
Gait and falls, T. Masud (UK)
Don't miss the premiere global skeletal health meeting of 2010 - reserve May 5-8, 2010 on your calendar.
Notes:
Abstract submission deadline: February 4, 2010.
ABOUT IOF
The International Osteoporosis Foundation (IOF) is a nongovernmental umbrella organization dedicated to the worldwide fight against osteoporosis, the disease known as "the silent epidemic". IOF's members - committees of scientific researchers, patient, medical and research societies and industry representatives from around the world - share a common vision of a world without osteoporotic fractures. Launched in 1998 with the merger of the European Foundation for Osteoporosis (EFFO, founded in 1987) and the International Federation of Societies on Skeletal Diseases, IOF now represents 191 societies in 91 locations.
ABOUT ESCEO
The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) is a non-profit organization, dedicated to a close interaction between clinical scientists dealing with rheumatic disorders, pharmaceutical industry developing new compounds in this field, regulators responsible for the registration of such drugs and health policy makers, to integrate the management of osteoporosis and osteoarthritis within the comprehensive perspective of health resources utilization. The objective of ESCEO is to provide practitioners with the latest clinical and economic information, allowing them to organize their daily practice, in an evidence-based medicine perspective, with a cost-conscious perception.
Source:
L. Misteli
International Osteoporosis Foundation
Complete programme information, online registration and abstract submission will be available on iofwco-ecceo10 .
IOF WCO-ECCEO10 will be an excellent forum for interaction and the exchange of ideas among researchers and clinicians as well as specialists from allied health fields. It will offer an overview of the most recent developments and cutting-edge research in the pathophysiology, diagnosis, prevention and treatment of osteoporosis and osteoarthritis, as well as policy related issues such as health economics.
Offering a broad global perspective, the scientific programme will provide a mix of stimulating plenary lectures on 'hot' topics in the field and more clinically-oriented meet-the-expert sessions led by world experts. There will also be poster presentations, late breaking news, satellite symposia, and a large exhibition area.
Meet-the-expert sessions to be led by world experts:
Each day specialists will lead exchanges on 20 key topics. Small groups, on a first come first served basis, will be encouraged to not only ask questions but to also provide feedback about their own experiences. The following topics and speakers are scheduled:
Assessing bone strength beyond DXA, C. Gl??er (Germany)
Optimal dose of vitamin D, B. Dawson-Hughes (USA)
Muscle and bone interaction, D. Felsenberg (Germany)
Practical approach of glucocorticoid-treated patients, J. Adachi (Canada)
Health economics and treatment selection, J-Y. Reginster (Belgium)
BMU balance: effects of anti-osteoporotic agents, Jpston (UK)
Premenopausal osteoporosis, E. Siris (USA)
Bone mass/structure measurements during growth, R. Rizzoli (Switzerland)
Bone disease in primary hyperparathyroidism, J.P. Bilezikian (USA)
Bisphosphonates in chronic renal failure, S. Papapoulos (NL)
Pharmaco-genomics, M.L. Brandi (Italy)
Vertebro/kyphoplasty, S. Boonen (Belgium)
Issues in designing and conducting clinical trials, S. Cummings (USA)
Osteoporosis in men, E. Seeman (Australia)
Post-fracture management, K. Akesson (Sweden)
Fracture healing: can we influence it?, J. Goldhahn (Switzerland)
Genetics and osteoporosis: how to assess it?, S. Ferrari (Switzerland)
Side effects of anti fracture drugs, S. Adami (Italy)
Developmental origins of osteoporotic fracture, C. Cooper (UK)
Gait and falls, T. Masud (UK)
Don't miss the premiere global skeletal health meeting of 2010 - reserve May 5-8, 2010 on your calendar.
Notes:
Abstract submission deadline: February 4, 2010.
ABOUT IOF
The International Osteoporosis Foundation (IOF) is a nongovernmental umbrella organization dedicated to the worldwide fight against osteoporosis, the disease known as "the silent epidemic". IOF's members - committees of scientific researchers, patient, medical and research societies and industry representatives from around the world - share a common vision of a world without osteoporotic fractures. Launched in 1998 with the merger of the European Foundation for Osteoporosis (EFFO, founded in 1987) and the International Federation of Societies on Skeletal Diseases, IOF now represents 191 societies in 91 locations.
ABOUT ESCEO
The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) is a non-profit organization, dedicated to a close interaction between clinical scientists dealing with rheumatic disorders, pharmaceutical industry developing new compounds in this field, regulators responsible for the registration of such drugs and health policy makers, to integrate the management of osteoporosis and osteoarthritis within the comprehensive perspective of health resources utilization. The objective of ESCEO is to provide practitioners with the latest clinical and economic information, allowing them to organize their daily practice, in an evidence-based medicine perspective, with a cost-conscious perception.
Source:
L. Misteli
International Osteoporosis Foundation
среда, 24 августа 2011 г.
New Way To Block Destructive Rush Of Immune Cells
Researchers have found a way to selectively block the ability of white blood cells to "crawl" toward the sites of injury and infection when such mobility drives disease, according to a study published in The Journal of Experimental Medicine. The results suggest a new treatment approach for autoimmune diseases like rheumatoid arthritis, lupus and multiple sclerosis, and for conditions made worse by misplaced inflammation, like atherosclerosis, stroke and transplant rejection, researchers said.
Where a single-celled amoeba moves to find food, human cells migrate as part of complex bodily functions like immunity. Disease-fighting cells for instance move toward bacteria and cells infected with viruses, which they target for destruction. Unfortunately, the same cells can mistakenly attack the body's own cells or drive inflammation too far, worsening the problem they rushed in to solve.
A team of researchers at the University of Rochester Medical Center has been studying proteins called integrins that enable T cells, a major subset of immune cells, to migrate. The integrin-related mechanisms described for the first time in the current paper suggest a way to shut down only those T cells currently in the act of disease-related migration, while leaving in place reserves needed in the likely event that another infection occurs during treatment. Making the mechanistic discoveries possible was a successful effort by the team to capture on video the first detailed images of fast-migrating T cells and the behavior of key proteins related to migration, which had been tagged with fluorescence. Twelve videos of T cells, and their key migration proteins, in action are part of the publication and are available online.
"There are many cases where it would be incredibly useful to precisely block integrin activation, and thus T cell migration," said Minsoo Kim, Ph.D., assistant professor of Microbiology and Immunology within the David H. Smith Center for Vaccine Biology and Immunology at the Medical Center, and lead author of the article. "Good examples include when our immune system attacks our own cells, or rejects a lifesaving transplant or clogs our blood vessels by mistake. The problem is that past, system-wide attempts that block all integrin activation, like the multiple sclerosis drug Tysabri, shut down not only unwanted inflammation in one locale, but also vital immune defenses elsewhere, leaving patients vulnerable to infection."
The Great Migration
Two mechanisms make cell migration, or programmed directional movement, possible. The first, called chemotaxis, tells the cell which direction to move in. Cell surface proteins sense and follow chemicals and molecules they are attracted to toward wherever those attractants are most concentrated. T cells, named after the thymus (T) where they mature, move toward the byproducts of bacteria and viruses.
The second migratory mechanism is propulsion. In between infections and injuries, inactive T cells ride along with the bloodstream. T cells "realize" when they pass by part of a blood vessel wall close to the site of an injury or infection. Integrins on their surfaces unfold and grab onto key proteins on the surface of blood vessel wall cells (e.g. ICAM), resisting the surrounding blood flow. The T cells then pass through the vessel wall, and once outside the bloodstream, crawl along the tissue scaffolding toward the site of injury.
In a T cell at rest, integrins are distributed evenly over the entire surface of the T cell. When the cell gets ready to move, however, activated integrins cluster on the leading edge of the cell in the direction the cell wants to move in. They bind to their counterpart adhesion proteins like ICAM on the surface that the T cell is moving across. The T cell then contracts using its cell skeleton to pull itself over the leading edge integrins. Finally, the integrins on the trailing edge of the cell let go. Without precise changes that enable the front end to gain traction, and the tail to let go, the cell cannot migrate.
Kim's team found that a subset of integrins, including lymphocyte function???"associated antigen-1 (LFA-1), control whether or not the tail end of the T cell can "let go" (de- adhesion). Data revealed for the first time that a protein called non-muscle myosin heavy chain-IIA (MyH9) is recruited to LFA-1 at the trailing end of migrating T lymphocytes. Experiments that interfered with the association between MyH9 and the LFA-1 integrin were found to prevent the trailing edge of the crawling T cell from letting go, dramatically reducing the ability of T cells to move. Myosins are motor proteins that expend energy to enable cell skeletons to contract. That contraction creates force that is used in many cases to move muscle fibers, but in the case of MyH9, to rip the trailing end of a migrating T cell foot away from the surface it is migrating across by breaking integrin-ICAM bonds. The results provide the first evidentiary support of the longstanding theory that cell skeleton contractile force is used to drive T cell migration, with MyH9 as the mechanical link. Captured images show fluorescently tagged actin (which partners with LFA-1 to grip the surface) gathering at the front end of the cell, and fluorescently tagged MyH9 gathering at the tail end in cycles, each time the cell takes a "step."
The study was a joint effort by the Department of Surgery at Rhode Island Hospital, Brown Medical School, the Department of Physics at Brown University, the CBR Institute for Biomedical Research at Harvard Medical School and the departments of Chemical Engineering, Biomedical Engineering and Department of Microbiology and Immunology at the University of Rochester. The project was supported by the American Heart Association, the Rhode Island Foundation, the National Institutes of Health, the National Science Foundation and the Brown University Seed Grant.
In the next phase, the team will seek to develop better-targeted, anti-integrin therapies, with MyH9 among the rational targets for new classes of drugs. Toward that end, experiments currently underway are designed to determine which molecules regulate MyH9 activity during T cell migration.
"Initial clinical studies on T cell migration focused on overall blocking of migration, but general inhibition is a blunt tool," said Tim Mosmann, Ph.D., director of the David H. Smith Center for Vaccine Biology and Immunology. "As studies such as Dr. Kim's help us to understand the process more precisely, we should be able to design much more precise methods to block migration in the selected circumstances that cause problems, without crippling the essential immune responses to infections."
Source: Greg Williams
University of Rochester Medical Center
View drug information on Tysabri.
Where a single-celled amoeba moves to find food, human cells migrate as part of complex bodily functions like immunity. Disease-fighting cells for instance move toward bacteria and cells infected with viruses, which they target for destruction. Unfortunately, the same cells can mistakenly attack the body's own cells or drive inflammation too far, worsening the problem they rushed in to solve.
A team of researchers at the University of Rochester Medical Center has been studying proteins called integrins that enable T cells, a major subset of immune cells, to migrate. The integrin-related mechanisms described for the first time in the current paper suggest a way to shut down only those T cells currently in the act of disease-related migration, while leaving in place reserves needed in the likely event that another infection occurs during treatment. Making the mechanistic discoveries possible was a successful effort by the team to capture on video the first detailed images of fast-migrating T cells and the behavior of key proteins related to migration, which had been tagged with fluorescence. Twelve videos of T cells, and their key migration proteins, in action are part of the publication and are available online.
"There are many cases where it would be incredibly useful to precisely block integrin activation, and thus T cell migration," said Minsoo Kim, Ph.D., assistant professor of Microbiology and Immunology within the David H. Smith Center for Vaccine Biology and Immunology at the Medical Center, and lead author of the article. "Good examples include when our immune system attacks our own cells, or rejects a lifesaving transplant or clogs our blood vessels by mistake. The problem is that past, system-wide attempts that block all integrin activation, like the multiple sclerosis drug Tysabri, shut down not only unwanted inflammation in one locale, but also vital immune defenses elsewhere, leaving patients vulnerable to infection."
The Great Migration
Two mechanisms make cell migration, or programmed directional movement, possible. The first, called chemotaxis, tells the cell which direction to move in. Cell surface proteins sense and follow chemicals and molecules they are attracted to toward wherever those attractants are most concentrated. T cells, named after the thymus (T) where they mature, move toward the byproducts of bacteria and viruses.
The second migratory mechanism is propulsion. In between infections and injuries, inactive T cells ride along with the bloodstream. T cells "realize" when they pass by part of a blood vessel wall close to the site of an injury or infection. Integrins on their surfaces unfold and grab onto key proteins on the surface of blood vessel wall cells (e.g. ICAM), resisting the surrounding blood flow. The T cells then pass through the vessel wall, and once outside the bloodstream, crawl along the tissue scaffolding toward the site of injury.
In a T cell at rest, integrins are distributed evenly over the entire surface of the T cell. When the cell gets ready to move, however, activated integrins cluster on the leading edge of the cell in the direction the cell wants to move in. They bind to their counterpart adhesion proteins like ICAM on the surface that the T cell is moving across. The T cell then contracts using its cell skeleton to pull itself over the leading edge integrins. Finally, the integrins on the trailing edge of the cell let go. Without precise changes that enable the front end to gain traction, and the tail to let go, the cell cannot migrate.
Kim's team found that a subset of integrins, including lymphocyte function???"associated antigen-1 (LFA-1), control whether or not the tail end of the T cell can "let go" (de- adhesion). Data revealed for the first time that a protein called non-muscle myosin heavy chain-IIA (MyH9) is recruited to LFA-1 at the trailing end of migrating T lymphocytes. Experiments that interfered with the association between MyH9 and the LFA-1 integrin were found to prevent the trailing edge of the crawling T cell from letting go, dramatically reducing the ability of T cells to move. Myosins are motor proteins that expend energy to enable cell skeletons to contract. That contraction creates force that is used in many cases to move muscle fibers, but in the case of MyH9, to rip the trailing end of a migrating T cell foot away from the surface it is migrating across by breaking integrin-ICAM bonds. The results provide the first evidentiary support of the longstanding theory that cell skeleton contractile force is used to drive T cell migration, with MyH9 as the mechanical link. Captured images show fluorescently tagged actin (which partners with LFA-1 to grip the surface) gathering at the front end of the cell, and fluorescently tagged MyH9 gathering at the tail end in cycles, each time the cell takes a "step."
The study was a joint effort by the Department of Surgery at Rhode Island Hospital, Brown Medical School, the Department of Physics at Brown University, the CBR Institute for Biomedical Research at Harvard Medical School and the departments of Chemical Engineering, Biomedical Engineering and Department of Microbiology and Immunology at the University of Rochester. The project was supported by the American Heart Association, the Rhode Island Foundation, the National Institutes of Health, the National Science Foundation and the Brown University Seed Grant.
In the next phase, the team will seek to develop better-targeted, anti-integrin therapies, with MyH9 among the rational targets for new classes of drugs. Toward that end, experiments currently underway are designed to determine which molecules regulate MyH9 activity during T cell migration.
"Initial clinical studies on T cell migration focused on overall blocking of migration, but general inhibition is a blunt tool," said Tim Mosmann, Ph.D., director of the David H. Smith Center for Vaccine Biology and Immunology. "As studies such as Dr. Kim's help us to understand the process more precisely, we should be able to design much more precise methods to block migration in the selected circumstances that cause problems, without crippling the essential immune responses to infections."
Source: Greg Williams
University of Rochester Medical Center
View drug information on Tysabri.
Подписаться на:
Сообщения (Atom)