1,721,081 research outputs found
Statins and bone morphogenetic proteins: new pathways in bone formation
No full textIntroduction:
Osteoporosis is a major public health problem leading to morbidity and mortality in many individuals. Treatment for
osteoporosis has generally relied on mechanisms that decrease osteoclastic bone resorption. This review outlines new evidence that the cholesterol synthetic pathway may be important in bone metabolism and that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins may increase bone formation. Results:
An experimental observation reported that statins increase bone
formation in rodents and that statins have an important role for the cholesterol synthetic pathway in bone formation. This may be via potent bone-forming growth factors, the bone morphogenetic proteins (BMPs). Subsequent epidemiological studies (including a meta-analysis of 8 studies) have suggested that statin use may be associated with increased bone mineral density (BMD) and decreased fracture risk in humans. However, more recently published studies have challenged the effect on fracture risk. Conclusion:
The effect of statins on bone mineral density and fracture risk in retrospective studies suggests an exciting new direction for research in bone formation that may lead to advances in the therapy of osteoporosis
Immunological therapies for rheumatoid arthritis
No full textRheumatoid arthritis (RA) is a chronic inflammatory arthritis of the synovial joints that causes loss of function and a shortened life expectancy. In the last 10 years there have been major advances in the treatment of RA, including more aggressive use of disease-modifying anti-rheumatic drugs and the development of immune therapies targeted to molecules and cells important in the immunopathogenesis of RA. Molecular messengers that travel between cells (cytokines) have been found to be of major importance. Blocking the cytokine tumour necrosis factor (TNF-) produces significant improvement in RA, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. The use of cytokine blockers has shown the extent to which immune and inflammatory pathways are shared in a number of inflammatory diseases. There has also been an important proof of principle that blocking single cytokines can produce profound effects in inflammatory diseases
Hughes syndrome (the antiphospholipid syndrome): 25 years old
No full textThe antiphospholipid (Hughes) syndrome (APS) is a unique thrombotic disorder, causing both arterial and venous thrombosis, linked to the presence of antibodies directed against phospholipid–protein complexes. The first papers describing the syndrome were published in 1983 and, over the next two years, a series of publications described in detail the various clinical manifestations of the syndrome. Laboratory standardisation workshops were also set up and, in 1984, the first “world” symposium on APS was held. The international APS conferences have continued to grow in numbers and in stature. The APS has already had an impact in obstetrics, in medicine, in psychiatry, and in surgery. The approximate figure of 1 in 5 is a useful guide—1 in 5 of all young strokes, 1 in 5 recurrent miscarriages, 1 in 5 DVTs. More precise data will become available in the worlds of epilepsy, migraine, Alzheimer’s, and MS. The advent of newer “biologic” immunosuppressives such as rituximab may offer help in selected cases. Intravenous immunoglobulin has proved successful, especially in the emergency setting
The role of interleukin-6 in rheumatoid arthritis-associated osteoporosis
No full textIntroduction: Osteoporosis is highly prevalent in patients with rheumatoid arthritis (RA) and is a frequent cause of fractures, disability, reduced quality of life and increased use of healthcare resources. Discussion: Factors associated with the development of osteoporosis and fractures in patients with RA include disease activity, inflammation, gender, age, low body mass and glucocorticoid exposure. Several processes contribute towards the pathology of RA-associated osteoporosis, and increased osteoclast activation and subsequent bone resorption mediated by pro-inflammatory cytokines are thought to play major roles. Given the key effects of interleukin-6 (IL-6) in both RA and osteoporosis, and its ability to modulate other inflammatory mediators, IL-6 may be an important factor specifically associated with osteoporosis in patients with RA. Conclusion: The development of agents that modulate the actions of IL-6 and those of other pro-inflammatory mediators of bone loss may provide alternative osteoporosis management strategies for patients with RA than existing general osteoporosis therapies. <br/
Melioidosis in systemic lupus erythematosus: the importance of early diagnosis and treatment in patients from endemic areas
No full textSerious infection is a common problem in immunosuppressed patients with systemic lupus erythematosus (SLE). Melioidosis is caused by the Gram-negative bacterium Burkholderia pseudomallei and may present as an acute fulminant pneumonia or septicaemia that is often fatal. The organism is endemic in much of South-east Asia but is being increasingly reported from other parts of the world, including India, Northern Australia and North and South America. In addition to occurring in people who come into contact with contaminated soil or water in endemic areas, the infection is more common in immunosuppressed patients and must be recognised early and treated with appropriate antibiotics. Importantly, it can activate many years after the initial exposure, causing diagnostic confusion. We present the cases of three patients with SLE who were admitted with fever and in whom Burkholderia pseudomallei was isolated from blood cultures. Following treatment with intravenous ceftazidime all patients made a good recovery. These cases demonstrate the importance of considering this infectious organism in patients from endemic areas with unexplained fever. They also illustrate how successful outcomes can be achieved in a frequently fatal disease if an early diagnosis is made and appropriate antibiotics are started promptly.<br/
Early environmental factors and rheumatoid arthritis
No full textThe precise cause of autoimmune diseases such as rheumatoid arthritis (RA) remains uncertain. In recent years there has been extensive investment in pursuing genes important in RA. However, estimates suggest that the risk of developing RA is at most 50% determined by genes. There has been limited success defining the environmental factors important in developing RA. We hypothesize that this lack of success may be due to a concentration on the time around disease onset. There is evidence of production of the autoantibodies rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP) and increased levels of C-reactive protein (CRP) years before RA becomes clinically apparent. In addition, early life events including intrauterine growth retardation (IUGR) may have long lasting effects on immune function. We review the evidence that the early environment through effects on growth and infectious exposure may influence the likelihood of developing autoimmune diseases such as R
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