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  • 1
    ISSN: 1420-908X
    Keywords: Arthritis model ; Cytokines ; IL-6 ; Immunosuppression ; Cyclosporin A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the T-cell-directed immunosuppressant cyclosporin A (CsA) on the developmnnt of antigen-induced arthritis (AIA) in rats as well as on cytokine levels in synovial fluid and serum were determined. The treatment with CsA effectively inhibited the chronic phase of arthritis as demonstrated by decreased joint swelling and reduced histological arthritic score. In animals with AIA the level of IL-6 in the synovial fluid and serum is increased, showing good correlation with the severity of the disease. The CsA treatment reduced IL-6 levels to normal. IL-1, IL-2 and TNF-α do not seem to be directly involved in the pathogenic mechanisms of chronic arthritis.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 32 (1991), S. 103-105 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1420-908X
    Keywords: Antigen-induced arthritis ; Leflunomide ; Inflammation ; Tissue destruction ; Autoantibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the new immunomodulating isoxazol derivative leflunomide, in comparison with cyclosporin A, on established antigen-induced arthritis in rats as well as serum antibody levels were determined. When treatment with leflunomide, at concentrations from 2.5 to 10 mg/kg/d, was started on day 3 of arthritis, the acute and chronic phases of arthritis were effectively inhibited. This was demonstrated by decreased joint swelling and reduced histopathological arthritis score at the end of experiment (day 26). Furthermore, the treatment resulted in a significantly reduced level of serum antibodies to the matrix components collagen type I, type II and proteoglycans. Neither leflunomide nor cyclosporin A, at doses of 1 mg/kg/d, had an effect on the severity of arthritis and antibody levels. However, when both drugs were used together, at these non-effective doses, the histopathological score of chronic arthritis was significantly reduced. The results of our experiments demonstrate that leflunomide has a strong suppressive effect on both acute and chronic phases of antigen-induced arthritis and formation of autoantibodies in rats. Furthermore, orally administered doses of leflunomide were as effective as doses of cyclosporin A given intraperitoneally. The combination of sub-effective doses of leflunomide and cyclosporin A resulted in significant inhibition of chronic arthritis.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1420-908X
    Keywords: Key words: Antigen-induced arthritis - Clodronate - Inflammation - Joint destruction - Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Objective: To investigate the effects of clodronate on clinical disease activity, inflammatory alterations and cartilage destruction, periarticular and axial bone volume and bone turnover in chronic antigen-induced arthritis (AIA; day 28).¶Methods: Rats with AIA were treated with clodronate (5 mg/kg/day continuously; 20 mg/kg/day intermittently or high-dose with 300 mg/kg 3 hours after arthritis induction +20 mg/kg/day continuously, respectively). Joint pathology was examined by histology. Bone volume and cellular turnover parameters of the right tibia head and the third lumbar vertebra were evaluated by histomorphometry. The findings were compared with those of healthy controls, sham-treated AIA and AIA treated continuously with 250 μg/kg of dexamethasone.¶Results: All three therapy regimens with clodronate resulted in a significant reduction of joint swelling, histopathological inflammatory changes and cartilage destruction in comparison with sham-treated AIA. The antiinflammatory effect of high-dose clodronate was comparable with dexamethasone. The intermittent administration of 20 mg/kg/day of clodronate completely prevented periarticular bone loss by reduction of bone resorption without affecting bone formation at the periarticular and axial bone. Both continuous treatment with 5 mg/kg/day of clodronate and high-dose clodronate therapy partially prevented periarticular bone loss and reduced parameters of bone formation at the axial bone to values below those of healthy controls.¶Conclusion: High-dose clodronate therapy exerts an excellent preventive effect on clinical disease activity and on joint destruction in AIA. However, continuous treatment with high doses of clodronate may result in a low turnover state of bone remodelling.¶
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 2 prothoracotropical factors (activation factor I and II) have been obtained by gel filtration techniques from brains and corpora cardiaca of the cockroachPeriplaneta americana. In contrast to activation factor II, activation factor I caused significant influence of RNA synthesis. The RNA pattern of prothoracic glands stimulated by activation factor I as demonstrated by polyacrylamide gel electrophoresis consists of different kinds of RNA. Short time incubation revealed effects on sRNA synthesis, while long time incubation demonstrated predominantly increase of ribosomal RNA synthesis. Measurements of the membrane potential of the prothoracic gland cells of the wax mothGalleria mellonella indicated an increase by activation factor II; activation factor I was without any visible effect. Our results demonstrate for the first time that the two activation factors induce different effects at cellular level.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 35 (1992), S. 96-103 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-term treatment with the immunomodulator diacetyl-splenopentin reduces the severity of chronic joint inflammation and cartilage destruction in rabbits with antigen-induced arthritis. The level of specific antibodies as well as specific and non-specific cell-mediated immune reactivities including the proliferative response of spleen lymphocytes to cartilage proteoglycans in treated animals are lower than in untreated arthritic rabbits. Moreover, suppressor cell activity, which normally decreases during the early phase of inflammation, is enhanced and hyperreactive helper cell potential is reduced. These findings suggest that treatment with diacetyl-splenopentin normalizes the immune regulation, which is disturbed in the early phase of inflammation. This might result in a depression of the hyperreactive immune system including the autoimmunity developed against cartilage. Lowered immune reactivity in the joint in turn reduces the severity of chronic joint inflammation.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-term treatment with natural and synthetic thymic and splenic peptides as well as cyclosporin A inhibited the development of antigen-induced arthritis in rats. This was demonstrated by decreased joint swelling and reduced degree of macroscopically and histologically evaluated severity of synovitis. The drug treatment also decreased serum levels of antibodies against the specific antigen methylated bovine serum albumin (mBSA) and against cartilage proteoglycans and collagens type I and II. The conclusion from these studies is that the treatment with immunomodulatory thymic and splenic peptides and with the T-cell-directed immunosuppressive drug cyclosporin A inhibits the specific immune response against mBSA and/or the development of autoimmunity against cartilage constituents. The decreased immune reactivity in the joint may reduces the severity of chronic joint inflammation.
    Type of Medium: Electronic Resource
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