Pharmacologic studies on the antidegenerative effect of ademetionine in experimental arthritis in animals

A standardized pharmacological model of biochemically induced osteoarthritis in the knee joint of laboratory animals was used for the study of a possible antidegenerative effect of ademetionine (S-adenosyl-methionine, active substance of Gumbaral) in-vivo. Four days after the initial induction of osteoarthritis by 2 intraarticular injections of 0.6 mg sodium iodoacetate into the left knee joint of adult hens, the therapy started with once-weekly intraarticular doses of 0.5 mg, 1.0 mg and 2.0 mg ademetionine over a period of 14 weeks. Quantitative monitoring of the intensity and progression of osteoarthritis was performed every 2 weeks by joint space measurements, topographic-radiological evaluations, and by a macroscopic post-mortem assessment of the joint cartilage and bone. These objective analytical parameters clearly demonstrated that weekly intraarticular doses of 1.0 mg ademetionine significantly reduced the intensity of degenerative processes compared to the placebo (saline) treated joints. The antidegenerative effect of doses of 0.5 mg or 2.0 mg ademetionine were less pronounced and of no statistical significance. Our findings indicate an interesting therapeutic potency of ademetionine in experimental osteoarthritis and confirm the positive clinical observations as well as in-vitro results with this new drug by other researchers.     

Influence of some natural and semisynthetic agents on elastase and cathepsin G from polymorphonuclear granulocytes.

The in vitro effect of eglin C, glycosaminoglycan-peptide complex "DAK 16", glycosaminoglycan polysulfate and sodium pentosan polysulfate on the PMN-enzymes elastase and cathepsin G was investigated. The activity of elastase and cathepsin G was measured with the highly specific chromogenic substrates methoxysuccinyl-l-ala-l-ala-l-pro-l-val-p-nitroaniline and succinyl-l-ala-l-ala-l-pro-l-phenyl-alanin-p-nitroaniline. Eglin C and DAK 16 displayed a pronounced inhibition of PMN-elastase and PMN-cathepsin G. Surprisingly a higher amount of product in the elastase containing assays were found in the presence of glycosaminoglycan polysulfate and sodium pentosan polysulfate. The higher cleavage of the elastase substrate is related back to an electrostatic interaction of the polysulfates with this substrate. Both polysulfates strongly inhibited cathepsin G. The qualitatively and quantitatively different behavior of the drugs on elastase and cathepsin G are discussed with regard to their in vivo contribution to the therapy of chronic inflammatory joint diseases.     

Human recombinant interleukin-1 alpha and beta and articular tissue integrity. An in vivo study on hens and rats.

Human recombinant interleukin-1 alpha or beta was injected intraarticularly several times into the knee joints of rats and hens at different dosages (50-2000 ng) and intervals. No loss of cartilage detectable by width of the radiological joint space and no degenerative changes of subchondral bone could be observed during 16 weeks using X-ray analysis. The macroscopical examination of articular cartilage of hens after this period and of rats after one year showed no morphological cartilage damages. These data suggest that human recombinant Il-1 alpha and beta alone may not be sufficient to induce a progressing osteoarthritic process in these animals.     

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.