Biomedical subjects
Publications and source records attributed to K Trnavský.
This review paper presents some basic information of a "rediscovered" nonsteroidal anti-inflammatory drug Nimesulid which is one of the first selective inhibitors of cyclooxygenase-2, has a history of good clinical results, and is relatively well tolerated with patients. Nimesulid enhances possible ways of analgesia treatment of rheumatic diseases.
The authors of this article discuss the pharmacotherapy of pain control in patients with rheumatic diseases, and they describe the relevant groups of drugs available, including their adverse events. They focus on non-steroidal antirheumatic drugs, selectice cyclooxygenase-2 inhibitors (coxibs) in particular. They summarise the experience with use of coxibs so far, and also report on drugs soon to be marketed in our country.
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BACKGROUND: In the treatment of rheumatoid arthritis an irreplaceable position is held by so-called disease modifying drugs. Recently among the latter cyclosporin A was included. The objective of the present study was to assess its therapeutic effect in patients with rheumatoid arthritis refractory to treatment. METHODS AND RESULTS: To a group of 20 patients with the refractory form of rheumatoid arthritis cyclosporin A (Consupren-Galena) was administered for 6 months in a mean daily dose of 3.5 mg. Clinical and laboratory examinations were made after one-month intervals. Cyclosporin administration influenced the clinical indicators of disease activity but did not lead to changes of red cell sedimentation values or the titre of the latex fixation test. Three patients did not complete the study because of serious undesirable effects. CONCLUSIONS: The results of the investigation indicate the clinical effectiveness of cyclosporin in patients with rheumatoid arthritis who do not react to other forms of disease modifying drugs. It is not clear whether cyclosporin affects the progression of rheumatoid tissue changes or whether is its effect is close to symptomatic treatment.
Bovine intervertebral disc- and articular cartilage extracts contain a metalloproteinase system capable of degrading type XI collagen. The collagen-degrading activity is rather low in unmodified extracts but increases considerably on metalloproteinase activation. The similarity between intervertebral disc and articular cartilage in their patterns of (casein-degrading) metalloproteinases and type XI and type II collagen degradation is believed to suggest a similarity in the events underlying the degradative disorders of articular cartilage and intervertebral disc.
The author gives an account of the incidence of extraarticular organ manifestations of rheumatoid arthritis. These manifestations cause deterioration of the prognosis of the disease and are evidence of the systemic character of rheumatoid arthritis, which cannot be conceived as an articular disease.
The effect of glycosaminoglycan-peptide complex (GPC) (Rumalon, made by Robapharm, Switzerland) on cells of the inflammatory periarticular infiltrate and on the articular chondrocytes was studied in experimentally induced papain arthropathy by means of image cytometry and biochemistry. The GPC therapy exhibited some antiinflammatory effect as documented by the reduction of DNA proliferative activity in the inflammatory infiltrate and lowered the activity of hydrolytic enzymes and enzyme inhibitors detected in chondrocytes.
The author presents an overview of the state of pharmacotherapy of rheumatoid arthritis in 1992. In the area of non-steroidal antirheumatic drugs attention is drawn to some problems associated with their undesirable action on the digestive tract and articular cartilage. The problem of interindividual reactivity to this group of drugs has not been resolved so far. The mechanism of their action, in particular analgetic action, is also still open. It was found that they can exert not only a central but also a peripheral action. Drugs modifying the disease have been extended by sulphasalazine, methotrexate and cyclosporin. Interest in combined treatment with these drugs is increasing as well as attitudes to the strategy of their application. The corticoid group has been extended by the preparation deflazacort which does not have a catabolic effect on osseous tissue. In the posology of corticoids pulsed treatment is gaining support.
A method for the purification of serine proteinases from the bovine intervertebral disc using affinity chromatography on basic pancreatic trypsin inhibitor (BPTI) immobilized to the hydroxyalkyl methacrylate copolymer Separon HEMA 1000 E is reported. Its advantage is the possibility of obtaining serine proteinases without an artificial alteration in relative molecular mass.
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The effects of several antirheumatic drugs on the activity of degradative enzymes in normal and pathologic knee joint cartilage and on the proliferative activity of synovial tissue cells were studied. Inflammatory arthropathy was induced in rabbits by intraarticular papain administration. Elevated contents of proteoglycanase and collagenase, together with an increase in serine and cysteine proteinase inhibitors, were found in animals with papain-induced arthropathy. Inflammation also accelerated the rate of proliferation of cells present in the synovial tissue. In the treated animals, the reduction in enzyme activity, decrease in inhibitor content and decreased DNA proliferation rate were registered to a different degree. The suppression of protein synthesis by nonsteroidal antiinflammatory drugs may explain our findings. The best therapeutic results were achieved with glycosaminoglycan polysulphate (Arteparon).
Using the Western blot method, the authors analyzed 85 sera obtained from patients with rheumatic diseases, focused on the presence of antihistones and antiactin autoantibodies. The authors detected a 32% incidence of the two investigated autoantibody specificities. In a group of 42 patients with systemic lupus erythematosus in 22 sera (52%) positive antihistone antibodies were present, whereby autoantibodies anti-H1 and anti-H2B were most frequent. In 15 sera in this group of patients (36%) antiactin autoantibodies were present.
Detection of proteoglycans in biological fluids is a perspective method for the evaluation of the degree of catabolic processes in articular cartilage. The demand of accuracy and specificity of detection of substructures of the degradation products of the cartilaginous matrix, with the perspective of routine large scale examinations, restricts available possible methods practically only to the use of immunochemical methods. In the present investigation in the inhibitory ELISA test polyclonal antibodies with a double specificity in relation to basic structures of the cartilage--proteoglycans--were used. The highest concentrations of degradation products of proteoglycans in punctates of synovial fluid were found in diseases where the clinical picture is dominated by repeated attacks of the joints with longer remission periods, and where the attack is stimulated, usually by stimuli of an intermittent systemic or exogenous character (gout, reactive arthritis incl. Reiter's syndrome, Lyme disease).
Using the Western blot method, the authors analyzed 85 sera obtained from patients with rheumatic diseases, focused on the presence of antihistones and antiactin autoantibodies. The authors detected a 32% incidence of the two investigated autoantibody specificities. In a group of 42 patients with systemic lupus erythematosus in 22 sera (52%) positive antihistone antibodies were present, whereby autoantibodies anti-H1 and anti-H2B were most frequent. In 15 sera in this group of patients (36%) antiactin autoantibodies were present.
The authors describe a case of primary Sjögren's syndrome, which was complicated with severe autoimmune agranulocytosis quite sensitive to immunosuppressive therapy. Agranulocytosis is a very rare complication of this autoimmune rheumatic disease as opposed to leucopenia. A remarkable feature of the presented case is the fact that correct diagnosis of primary Sjögren's syndrome has not been settled for almost 25 years. The disease has manifested only in the form of arthropathy imitating rheumatoid arthritis.
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