The role of TGF-ß1 in osteoarthritis of the temporomandibular joint in two genetic mouse models.

OBJECTIVE: The objective of this study is to elucidate osteoarthritis (OA) progression in the temporomandibular joint (TMJ) in two genetic mouse models by assessing the expression of an identified inflammatory marker associated with OA, viz., Tgf-ß1. This study provides mechanistic insight into disease progression based on the temporal expression of Tgf-ß1 in the TMJ. DESIGN: The two models included the heterozygous chondrodysplasia mutation (cho/+), a Coll11a1 mutation, and the autosomal semidominant disproportionate micromelia mutation (Dmm/+), a Col2a1 mutation. To determine OA status histologically, TMJs from each mutant were fixed, sectioned and stained with Safranin O to identify proteoglycans in condylar cartilage and counterstained with Fast Green. The extent of staining and onset of OA-like changes were quantified using the Modified Mankin scoring system. Using immunofluorescence, selected tissue sections of each genotype were stained for the presence of Tgf-ß1, HtrA1, and p-Smad2. RESULTS: The results revealed Mankin scores of the condylar cartilage of both mutants that are consistent with established histopathological changes of OA. Immunofluorescence indicated increased expression of all three molecular markers and their co-localization within condylar chondrocytes of both mutants. CONCLUSIONS: Elevated Tgf-ß1 expression in mutant condylar cartilage supports the hypothesis that this inflammatory mediator is mechanistically involved in the pathogenesis of TMJ OA. Compared to basal expression in control TMJs, the positive co-localized staining for Tgf-ß1, HtrA1, and p-Smad2 in both mutants demonstrates involvement of these molecules in the degradative pathway of OA. Tgf-ß1 therefore is a potential target for further study for the diagnosis and treatment of TMJ OA.

Reduction in infarct size, arrhythmias and chest pain by early intravenous beta blockade in suspected acute myocardial infarction.

Four hundred seventy-seven patients suspected of having had acute myocardial infarction within less than 12 hours were randomized to receive i.v. atenolol followed by oral treatment for 10 days or to a control group. In patients with ECG changes indicative of infarction at entry, i.v. atenolol significantly reduced enzyme release by one-third and enhanced R-wave preservation. In patients without such ECG changes, treatment significantly prevented the development of infarction in a proportion of patients. There was also a significant reduction in R-on-T ectopics, repetitive ventricular arrhythmias and supraventricular arrhythmias. Treated patients had significantly greater pain relief and required fewer opiate analgesics. Significantly fewer atenolol-treated patients died by 10 days (the treatment period), had nonfatal cardiac arrests, developed heart failure, or suffered reinfarction.

Serum high density lipoprotein cholesterol determination: a simple modification.

A simple modification to the method of Burnstein et al. (Burnstein, M., Scholnick, H.R. and Morfin, R. (1970) J. Lip. Res. 11, 583) [1] for the measurement of serum high-density lipoprotein (HDL) cholesterol concentrations is reported. The modification obviates the need for a refrigerated centrifuge and makes the method suitable for routine use in almost any laboratory. Good correlation was obtained for values in 80 healthy adults using the method as originally described by Burnstein et al. [1] and then with the modification. The presented method was linear and precise and the study showed that it was not necessary to fast before giving a blood sample for the assay. It was found that HDL cholesterols were higher in women than in men, but did not change significantly with age in either group.

Transport of axonal enzymes in surviving segments of frog sciatic nerve.

Redistribution of axonal enzymes as a function of time in vitro was studied in an unbranched segment of frog sciatic nerve. Cholinesterase activity moved peripherally at a rate of 99 mm/day and centrally at 19 mm/day. One-quarter of the total nerve content of the enzyme was estimated to be in motion, one-eighth in each direction. Mitochondrial enzymes (hexokinase and glutamic dehydrogenase) moved peripherally at 20-31 mm/day, centrally at 11-20 mm/day. Only 10% of the total content of these mitochondrial enzymes was in motion. No movement of choline acetylase or 6-phosphogluconic dehydrogenase activity was seen even after 4 days in vitro. However, in a 12 day in vivo experiment choline acetylase moved toward the periphery at a rate of 0.34 mm/day. After a day or so in vitro the distal accumulations of cholinesterase and glutamic dehydrogenase decreased, with a concomitant and quantitatively equivalent increase in enzyme activities at the proximal end of the nerve. It is postulated that during incubation a mechanism for reversing the direction of flow develops in the peripheral stump of the nerve. Vinblastine inhibited central and peripheral flow of both cholinesterase and glutamic dehydrogenase. Movement of cholinesterase was not affected by ouabain, thalidomide, or phenobarbital, nor by K(+) excess (110 mM) or absence.