An altered heparan sulfate structure in the articular cartilage protects against osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a progressive degenerative disease of the articular cartilage caused by an unbalanced activity of proteases, cytokines and other secreted proteins. Since heparan sulfate (HS) determines the activity of many extracellular factors, we investigated its role in OA progression. METHODS: To analyze the role of the HS level, OA was induced by anterior cruciate ligament transection (ACLT) in transgenic mice carrying a loss-of-function allele of Ext1 in clones of chondrocytes (Col2-rtTA-Cre;Ext1e2fl/e2fl). To study the impact of the HS sulfation pattern, OA was surgically induced in mice with a heterozygous (Ndst1+/-) or chondrocyte-specific (Col2-Cre;Ndst1fl/fl) loss-of-function allele of the sulfotransferase Ndst1. OA progression was evaluated using the OARSI scoring system. To investigate expression and activity of cartilage degrading proteases, femoral head explants of Ndst1+/- mutants were analyzed by qRT-PCR, Western Blot and gelatin zymography. RESULTS: All investigated mouse strains showed reduced OA scores (Col2-rtTA-Cre;Ext1e2fl/e2fl: 0.83; 95% HDI 0.72-0.96; Ndst1+/-: 0.83, 95% HDI 0.74-0.9; Col2-Cre;Ndst1fl/fl: 0.87, 95% HDI 0.76-1). Using cartilage explant cultures of Ndst1 animals, we detected higher amounts of aggrecan degradation products in wildtype samples (NITEGE 4.24-fold, 95% HDI 1.05-18.55; VDIPEN 1.54-fold, 95% HDI 1.54-2.34). Accordingly, gelatin zymography revealed lower Mmp2 activity in mutant samples upon RA-treatment (0.77-fold, 95% HDI: 0.60-0.96). As expression of major proteases and their inhibitors was not altered, HS seems to regulate cartilage degeneration by affecting protease activity. CONCLUSION: A decreased HS content or a reduced sulfation level protect against OA progression by regulating protease activity rather than expression.

[Clinical late results after long-term treatment of acute femoro-iliacal thrombophlebitis]. / Klinische Spätergebnisse nach Langzeitbehandlung von akuten femoro-iliakalen Phlebothrombosen.

The development of subfacial chronic insufficiency of veins (SCIV) was investigated after medicamentous treatment of acute femoroilliacal phlebothrombosises. Streptokinase (streptase) or heparin were used as medicaments. A control group of patients was treated without medicaments for the purpose of comparison. With the exception of the patients of the control group, all others were treated with oral anticoagulants for 6-7 months. Simultaneously, part of those patients treated with heparin were given a benzopyron preparation (venolat). After 1, 2, and 5 years a check-up was made for evaluating the stage of SCIV development. The best clinical late results could be found in patients of the streptokinase group. The effect of the combined administration of dicumarol and benzupyronan was markedly better than the sole anticoagulant treatment. SCIV developed most rapidly in patients of the control group. However, a check-up made 5 years after the beginning of therapy could not reveal the development of ulcers cruris in any patient.

Soluble fibrin-monomer complexes in normal pregnancy.

The protamine sulphate test of Lipinski and Worovski was used by the authors investigate the amount of soluble fibrin-monomer complexes (SFMC) in women with normal pregnancy. Those complexes were found to increase considerably during the second and even more the third trimester of pregnancy. The high level of SFMC in plasma, probably, reflected increased activity of blood coagulability toward the end of normal pregnancy.