ISSN:1040-8711    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

This has been an unusual year for the accumulation of evidence regarding the clinical effects of inhibition of cyclooxygenase (COX)-1 and COX-2. This article reviews the available data regarding the clinical effects of the new COX-2-specific inhibitors, and speculates about the importance of the data as they relate to the treatment of patients with chronic pain and/or inflammation.

ISSN:1040-8711    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The year 2000 marks the fiftieth anniversary of the awarding of the Nobel Prize for Medicine to Hench, Kendall, and Reichstein for their discovery of glucocorticoid treatment of rheumatic diseases. The efficacy and toxicity of glucocorticoids has remained a matter of contention ever since, with debate continuing over their place in the therapeutic armamentarium of rheumatologists. Few if any rheumatologists would not prescribe glucocorticoids, however, and review of new data on their use, efficacy, and toxicity remains topical. Perceived advances in the ability to manage osteoporosis arising from glucocorticoid use has allowed focus to shift onto other toxicities, including vascular disease, but important advances in our understanding of the mechanism of action of glucocorticoids are still lacking.

ISSN:1040-8711    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1040-8711    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

T cells have been directly associated with rheumatoid arthritis (RA) because they represent the largest cell population infiltrating the synovium. Their direct contribution to disease and joint destruction has been more difficult to demonstrate. Locally, they interact with other blood-derived and resident cells. Some T cells may contribute to disease through the secretion of cytokines. Indeed, interleukin-17, a T-cell-specific cytokine, is produced by RA synovium and acts as a bone and cartilage destructive factor. In addition, it increases the production of proinflammatory cytokines by monocytes and further enhances their effects on matrix destruction. Once considered bystanders in RA, T cells can now be classified as aggressors through their direct and indirect contribution to destruction. In particular, a subset of Th1 T cells can aggravate the proinflammatory and destructive pattern associated with monocyte activation. Manipulation of this subset may control the destructive pattern. Such a result can be achieved when a switch can be induced from a destructive pattern to a protective one leading to repair.

ISSN:1040-8711    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The evaluation of molecular pathways has revealed various novel insights into rheumatoid arthritis pathophysiology during the past year. In addition, there is an increasing tendency toward analysis not merely of a single mechanism but rather of data addressing a substantial part of the cascade of events leading to cellular activation. Because synovial fibroblasts are key cells involved in joint destruction, this review outlines the events that trigger or inhibit the crucial pathways leading to their aggressive behavior. Major topics include cellular and humoral interactions (frequently modulated by cytokines), intracellular signaling and upregulation of gene transcription, and the deleterious effects on articular homeostasis.

ISSN:1040-8711    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Patients with rheumatoid arthritis are at risk for the development of a generalized form of bone loss affecting the axial and appendicular skeleton. In addition, juxtaarticular osteopenia and focal erosion of marginal and subchondral bone are commonly seen. The pathogenesis of focal bone erosions is an area of active investigation. Studies of tissue sections from sites of bone erosion in rheumatoid arthritis and in animal models of inflammatory arthritis have identified multinucleated cells with the phenotype of osteoclasts in bone resorption lacunae in these sites, suggesting that osteoclasts mediate a component of this pathologic bone loss. Numerous soluble and cell-membrane factors produced by rheumatoid synovial tissues are likely to play a role in the initiation and progression of bone erosions. In addition, recent studies suggest a role for T lymphocytes and their products in osteoclast-mediated bone loss. This paper reviews the cellular mechanisms and factors implicated in bone erosions in rheumatoid arthritis, and discusses the possible therapeutic strategies suggested by these findings.

ISSN:1040-8711    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Substantial progress can be noted in the efforts to demonstrate the usefulness of tissue-related markers of disease in rheumatoid arthritis and other joint diseases. The most informative studies use longitudinal analyses of well-characterized patient groups. Emphasis should be on searching for markers which can be of prognostic significance. New markers need to be assessed in relation to existing ones, such as C-polysaccharide reacting protein and erythrocyte sedimentation rate, which, although not specific, are hard to beat as measures of inflammation. A newly identified matrix component, cartilage intermediate layer protein, has features which make it attractive as a potential cartilage specific marker. Many markers may not in the end prove clinically useful. They will, however, give important insight into pathogenic processes, and may help in evaluating new therapy. Finally, markers originally identified in humans have now proven their value in experimental arthritis.

ISSN:1040-8711    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

In the last few years, several novel strategies have been proposed for the treatment of rheumatoid arthritis (RA). Among them, gene therapy is considered a promising concept bearing the potential of highly specific targeting of relevant pathomechanisms. Early studies using gene transfer focused mainly on studying disease mechanisms, whereas recent research has put potential clinical applications to the forefront of attention. This has provided new answers to the question of how to deliver genes into the rheumatoid synovium as well as which pathways to target. Thus, significant progress has been made in the continued development of viral systems, including retro-and adenoviruses, as well as in the exploration of novel tools such as herpes virus-based systems or liposomes in combination with viral fusion proteins. When potential targets for gene transfer in RA are considered, two strategies have emerged: the first focuses on the delivery of secreted proteins, mainly cytokines and cytokine receptors, to inhibit inflammation in arthritic joints. Based on our growing knowledge about the pathogenesis of RA, however, there has also been substantial progress in exploring approaches that aim at interfering specifically with signaling pathways involved in the activation and apoptosis of synovial cells. The data from recent studies indicate the ability to selectively target specific disease processes by the differential expression of therapeutic genes in varying cell types and at different stages of disease, thus demonstrating the potential of gene transfer as an arthritis therapy.

ISSN:1040-8711    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1040-8711    

出版商:OVID    

年代:2000

数据来源: OVID