[Molecular biology studies of synovial fluid cells of patients with chronic polyarthritis after intra-articular prednisolone medication].
In the course of molecular biological research on patients with classical rheumatoid arthritis (according to ARA criteria), an investigation was carried out on the influence of different doses of prednisolone on semiconservative DNA synthesis, the sedimentation of nucleoids before and after gamma-irradiation and protein synthesis in synovial fluid cells. A significant dose-dependent suppression of semiconservative DNA synthesis was demonstrated with 5, 10 and 25 mg prednisolone. Granulocytes and cell detritus were removed by Ficoll urografin separation. In the presence of high saline concentrations and non ionic detergents nucleoids were extracted from synovial cells. These contained, besides nuclear proteins, almost the complete nuclear RNA and DNA in a superhelical structure. After ultracentrifugation, the nucleoid sedimentation profiles were determined by saccharose gradients. The individual sedimentation profiles were determined and statistically evaluated before and after irradiation causing strand breaks by Co60 at a dose of 1 Gy. No difference in nucleoid sedimentation was seen at a dosage of 5 mg of prednisolone, but after administration of 10, 25 and 40 mg a decrease in sedimentation velocity was observed and this effect might be explained by the DNA destabilizing effect of a steroid receptor complex followed by DNA strand breaks which had migrated into the nucleus. In vitro, no significant inhibition of supercoiled DNA repair was found after gamma-irradiation when prednisolone was administered. This is an argument against a damaging influence of prednisolone on the DNA repair of the genetic material of synovial fluid cells, which are predominantly lymphocytes. For the investigation of protein synthesis, 3H-labelled L-aminoacids were incorporated into the cells, and the activity measured after repeated washings. Following the administration of the lower prednisolone doses (5 and 10 mg) the incorporation of 3H-labelled L-aminoacids increases, whereas a significant inhibition of protein synthesis is found with doses of 25 mg or more. The possible clinical relevance of this phenomenon is discussed.
D000596:Amino Acids / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis*; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D004261:DNA Replication; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007270:Injections, Intra-Articular; D009698:Nucleoproteins / Q000378:metabolism; D011239:Prednisolone / Q000008:administration & dosage* / Q000494:pharmacology; D014176:Protein Biosynthesis; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000596:Amino Acids; D009698:Nucleoproteins; D004247:DNA; D011239:Prednisolone
Molekularbiologische Untersuchungen an Zellen der Synovialflüssigkeit von Patienten mit chronischer Polyarthritis nach intraartikulärer Prednisolonmedikation.