Animal experiments have shown that weekly intraarticular injections of various antiphlogistic/antirheumatic drugs into the knee joint induce progressive degenerative alterations in joint cartilage. The observed degenerations and destructions are most similar to the pathophysiology of osteoarthrosis in humans. By X-ray and macroscopic techniques the degenerative processes can be studied qualitatively and quantitatively. A decrease of joint space is a sensitive and early indicator of osteoarthrosis and showed that 10 weeks after intraarticular application of Ibuprofen, Phenylbutazone, Oxyphenbutazone, Flufenamic acid, Niflumic acid, Na-salicylate, Clofezone, Bumadizone and Dexamethasone the degenerative alterations in the injected knee joints were more severe than by applications of Chloroquine,D-penicillamine, Salicylamide and Indometacin. The degenerative effect on articular cartilage by the investigated drugs can be explained by their inhibitory potency on anabolic metabolism of connective tissue. The results of our animal experiments lead to the conclusion, that antiinflammatory drugs may also in man induce or accelerate degenerative joint diseases especially after long term treatment with high doses of these drugs.

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[Autoradiography studies of the effect of oxaceprol on the metabolism of joint cartilage in vitro and in vivo].

Using the radiolabelled precursors (3H-Glucosamine, 3H-proline) and a new procedure of quantitative microautoradiography we investigated the influence of N-acetyl-L-hydroxyproline (Oxaceprol) on anabolic processes in joint cartilage tissue of hens. After in vitro incubation, Oxaceprol stimulated the uptake of 3H-glucosamine and 3H-proline in chondrocytes and enhanced the incorporation of 3H-proline into the macromolecular structures of the cartilage matrix. Also, after in vivo intra-articular injection of Oxaceprol into the knee joints we could demonstrate a significant increase of intracellular glucosamine uptake. Because in our micro-autoradiographic detection method low molecular substances are excluded, the higher rate of precursor incorporation into cells and matrix can be interpreted as a stimulation of proteoglycan and collagen synthesis.

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[Orienting animal experiment studies on the effect of fenbufen on healthy and arthrosis-induced articular cartilage tissue in vivo].

Over a period of 3 months weekly intraarticular injections of fenbufen into the knee joint of hens did not induce any significant degenerative alterations of the articular cartilage. Experimental osteoarthrosis biochemically induced by iodoacetate in the knee joint of our laboratory animals was not enhanced by weekly intraarticular applications of fenbufen or its metabolite biphenyl-acetic acid. Joint space measurements as well as other radiological and macroscopical examinations of the knee joints confirmed that fenbufen and biphenyl-acetic acid had no negative influence on articular cartilage. In this respect these antiphlogistic agents differ from many other antiinflammatory drugs and may be particularly useful in the treatment of inflammatory phases of osteoarthrosis.

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PubMedDate not supplied

[Experimental gonarthrosis in rats and its therapy with glycosaminoglycan polysulfate (GAGPS)].

In good correlation to earlier results in hens we found that after intraarticular injections of iodo-acetate into the knee joint of rats, degenerative alterations of the articular cartilage and subchondral bone tissue develop within 2-4 months. The radiological, histological and macroscopical appearance of these degenerative processes in rats is quite similar to those in human osteoarthrosis (OA). Drug treatment of these rats with twice weekly subcutaneous doses of 1.0 mg, 2.0 mg or 5.0 mg glycosaminoglycan polysulphate = GAGPS (Arteparon) per kg body weight caused a pronounced and in many cases highly significant reduction of the intensity of experimental osteoarthrosis within the first 9 weeks. Due to the very severe acceleration of OA (induced by the high dose of 1.0 mg iodo-acetate) GAGPS could not influence the further progression of cartilage degeneration and destruction during the period of 12-15 weeks. The present results on rats confirm our preceding studies with biochemically induced OA in hens and demonstrate the identical reactions of both animal species to induction and therapy of degenerative joint disease.

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[Pharmacologic evaluation of the feasibility of cartilage therapy in degenerative joint diseases (arthroses)].

Due to their pharmacological properties most antiphlogistic/antirheumatic drugs are successfully used for treatment of inflammatory rheumatic diseases, but they are not able to counteract cartilage degeneration in osteoarthrosis. For specific therapy of osteoarthrosis only those drugs are suitable, which are able to inhibit enzymatic breakdown of articular cartilage, stimulate anabolic processes in cartilage, and to enhance the supply of nutritional and energy substrates for the cartilage cells. In this respect drugs such as Arteparon, Rumalon, Dona 200-S, Glyvenol or Pentosan polysulfate are of interest. A great number of pharmacological experiments have shown, that certain chondroprotective agents exert pronounced anti-degenerative effects, which can be quantitatively demonstrated in laboratory animals within 3 to 4 months by macroscopical, radiological and histological methods. Additional biochemical and in-vitro studies have elucidated some interesting chondro-protective, chondro-stimulatory or chondro-nutritive properties of certain drugs. In agreement with our experimental results clinical experiences have proved the efficacy of chondro-protective agents. Due to the bradytrophia of human articular cartilage a chondro-protective therapy may be only effective in long-term applications, resulting in a significant reduction of the intensity and progression of the degenerative joint destruction.

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[Chondroprotective and antiarthrotic properties of glycosaminoglycan polysulfate (GAGPS) in gonarthrosis in animal experiments].

In the pharmacotherapy of degenerative joint disease certain chondroprotective drugs are in use. Due to their biochemical properties and mode of action these agents have the power to reduce or stop the catabolic breakdown of articular cartilage in osteoarthrosis. Because of the bradytrophy of human articular cartilage, clinical trials involving such drugs require very lengthy periods of investigations (5-10 years). By the use of a biochemically induced animal model of osteoarthrosis we studied the chondroprotective properties and anti-arthritic potency of glycosaminoglycanpolysulfate (GAGPS; Arteparon) in-vivo. Under reproducible experimental conditions and using quantitative analytical methods (joint space measurements, radiological and macroscopic evaluations) we were able to demonstrate that intraarticular or intramuscular applications of GAGPS can significantly reduce the intensity and progression of joint degeneration. The therapeutic effect of GAGPS was dose-dependent, and noticeable not only in the early stages of experimental osteoarthrosis but also when therapy was begun only in the more advanced phases of joint degeneration. The degenerative effect of locally applied phenylbutazone was counteracted by GAGPS, confirming the chondroprotective potency of this compound. The interesting biochemical and pharmacological properties of GAGPS support and explain the anti-arthritic effects demonstrated in our in-vivo animal model of osteoarthrosis. The pronounced inhibition of cartilage-degrading enzymes by GAGPS and the stimulatory effect of this drug on hyaluronate synthesis may be regarded as important and clinically relevant properties.

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PubMedDate not supplied

[Experimental confirmation of the antiarthritic activity of glycosaminoglycan polysulfate].

By the use of a biochemically induced animal model of osteoarthrosis we studied the chondroprotective properties and antiarthrotic potency of glycosaminoglycan-polysulfate (GAGPS: Arteparon) in-vivo. Under reproducible experimental conditions and using quantitative analytical methods (joint space measurements, radiological and macroscopic evaluations) we were able to demonstrate that intraarticular or intramuscular applications of GAGPS can significantly reduce the intensity and progression of joint degeneration. The therapeutic effect of GAGPS was dose-dependent, and noticeable not only in the early stages of experimental osteoarthrosis but also when therapy was begun in the more advanced phases of joint degeneration. The degenerative effect of locally applied phenylbutazone was counteracted by GAGPS, confirming the chondroprotective potency of this compound. The interesting biochemical and pharmacological properties of GAGPS support and explain the antiarthrotic effects demonstrated in our in-vivo animal model of osteoarthrosis. The pronounced inhibition of cartilage-degrading enzymes by GAGPS and the stimulatory effect of this drug on hyaluronate synthesis may be regarded as important and clinically relevant properties.

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PubMedDate not supplied

[Ultrastructural studies of the protective effect of GAG peptide complex-containing cartilage substance in experimentally damaged chicken cartilage].

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