Chondrocyte apoptosis following intraarticular fracture in humans.

OBJECTIVE: The primary objective of the present study was to establish the degree to which chondrocyte apoptosis occurs in vivo following intraarticular fractures in humans. DESIGN: Fracture cartilage specimens were obtained from patients undergoing surgical intervention for fractures of the articular surface of the proximal tibia. Normal proximal tibia cartilage specimens served as controls. Apoptotic chondrocytes were identified and quantified using TUNEL analysis. RESULTS: The percentage of TUNEL positive chondrocytes in the fractured articular cartilage specimens (mean 18.5%, range 1-44%) was found to be an order of magnitude higher than the percentage observed in control specimens (mean 1.9%, range 0-4%). CONCLUSIONS: The percentage of TUNEL positive chondrocytes following intraarticular fracture is much higher than that reported for chronic degenerative conditions such as osteoarthritis and rheumatoid arthritis. These data provide strong evidence that chondrocyte apoptosis is a consequence of intraarticular fracture and suggest that chondrocyte apoptosis may play a particularly significant role in the subsequent development of post-traumatic arthritis.

The in vitro inhibitory effect of tannin derivatives on 3-hydroxy-3-methylglutaryl-coenzyme a reductase on vero cells.

Coronary heart disease is still the major cause of death in industrialized countries. Multiple primary or secondary interventional trials to lower serum cholesterol in humans have resulted in significant reduction of coronary events and death, one of the major reasons attributed to developing a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor such as pravastatin. Developing new inhibitors of cholesterol synthesis is still common in the pharmaceutical industry. Tannin comprises a large group of natural polyphenolic compounds possessing antioxidant effects. The methods for analysis of specific inhibitors of mevalonate biosynthesis have already been well established by using Vero cells, a cell line obtained from kidneys of African green monkeys. Tannin derivatives isolated from different traditional Chinese herbs were dissolved in DMSO and incubated with Vero cells with or without the addition of 1 mmol/l mevalonate or 5 mmol/l sodium acetate for 24 h in order to observe cell growth. Pravastatin, a specific HMG-CoA reductase inhibitor, was used as positive control which could inhibit Vero cells growth effectively and cell growth inhibition was reversible after adding 1 mmol/l mevalonate. More than 50 tannin derivatives were used for the study, but only two compounds - proanthrocyanidin A-2 (belonging to the flavan-3-ol group) and 1,2,3,6-tetra-O-galloyl-beta-D-glucose (belonging to the gallotannin group) - showed significant growth inhibition of Vero cells. This study showed that some isolated tannin derivatives from traditional herbs were effective HMG-CoA reductase inhibitors which might be developed into new hypocholesterolemic agents.