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[Significance of coagulation disorders and inflammatory immune reaction in an infectious model of rheumatoid arthritis. I. Systemic, shock-like coagulopathy and fibrin incorporation as indicators of rheumatoid manifestations in the erysipelas model].

A combined study employing plethysmographical, scintillation counting and coagulation methods indicates that a coagulation crisis in combination with fibrin overproduction may be an indicator of a beginning arthritis of rheumatoid character. Rats which received a single subcutaneous infection with erysipelas bacteria exhibit a shock resembling crisis two days post inoculation as substantiated by the consumption of coagulation factors II, V, VIII, XII and decrease of platelets. This consumption of coagulation factors is characterized by a rapid compensatory increase of platelets, antihaemophilic factor VIII and fibrin, 5 times more in the pig and 3 1/2 times more in the rat than in control animals. In adult rats the overproduction of fibrin is combined with an intense concealed consumption of fibrin in all organs of manifestation. Only in young rats an absolute consumption of fibrin is observed. The incorporation of fibrin into connective tissue is accompanied by fibrin consumption as demonstrated by immunofluorescence, by oedema of the paw, and by mesenchymal proliferation as substantiated by scintillation counting of incorporated 35SO4 and 3H-Proline, as markers for the beginning synthesis of ground substances and collagen. This model supports the importance of an initial vascular phase for the subsequent phase of manifestation in chronic rheumatoid diseases. It is discussed whether the organ specific permeability of the affected organs (joints, heart, arteries and eyes) may be a localizing factor of organ manifestation, parallel to the hormonal mesenchymal reaction.

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[The significance of coagulation disorders and the inflammatory reaction in an infectious model of rheumatoid arthritis. II. Inhibition trials with antirheumatic drugs in the inflammatory reaction phase of erysipelas polyarthritis in rats].

The arthritic activity in the initial phase and during manifestation of experimental erysipelas in rats, an animal model for human rheumatoid arthritis, was studied by plethysmometrical methods. The development of body weight and specific pathologic alterations peculiar to the model such as keratitis, thrombosis of the aorta and gangrene of the tip of the tail served as additional parameters. In the volumetric analysis it could be shown that the first arthritic swelling on both hind legs develops symmetrically up to day 6 post infection in rats with about 200 g of body weight-and in contrast-on the 2nd p.i. in younger animals with about 120 g. The first maximal paw volume was measured on day 9 p. i., the greatest decrease in body weight-a reduction of 25%-on day 10 p. i. In addition the reaction of the animal model following the application of steroid and non-steroid symptomatically as well as cytostatically acting antirheumatic drugs was tested. Daily treatment with acetylsalicylic acid, indomethacine or hydrocortisone provoked more or less significant inhibition of arthritic swelling in the paw. Only at the onset of arthritis acetylsalicylic acid was more effective than the other antiphlogistic drugs. No measurable increase of paw volume during cyclophosphamide treatment could be evaluated. None of the antirheumatics used had a positive effect on body weight developement. In hydrocortisone and also in cyclophosphamide treated rats a greater decrease was obtained than in the infected controls. No thrombosis developed after cytostasis with cyclophosphamide. The advantages of this systemic connective tissue disease with regard to its comparability with human rheumatoid arthritis and due to the course of its arthritic manifestation are discussed, together with the disadvantages specific to the model and the experimental conditions.

Animals↗