Mechanisms of connective tissue damage by crystals containing calcium

From available clinical, radiographic, and synovial fluid findings, coupled with in vivo radiolabelled crystal turnover data and in vitro experimental data, a hypothesis has been formulated relative to the pathogenesis of BCP crystal deposition diseases (Fig. 2). Synovial lining cells phagocytose BCP crystals and particulate collagens in the joint fluid. During and/or after internalization these cells are stimulated in a variety of ways: 1) protease synthesis and secretion is relentlessly stimulated, which may damage joint tissues producing clinically evident loss of collagenous tissues including cartilage, bone, and tendon, and which may release additional amounts of crystals and particulate collagens into the synovial fluid, completing a vicious cycle; 2) PGE2 production is greatly augmented; 3) DNA synthesis is stimulated as a result of increased inositol phospholipid turnover and intracellular crystal dissolution. The increased number of synovial cells also augments the total local generation of proteases and prostenoids. Mechanical factors such as trauma or joint overuse also contribute to the pathogenesis of joint destruction as discussed in the article on the clinical aspects of BCP crystal deposition.     

Development of cardiac sympathetic and adrenal-medullary responses in borderline hypertensive rats

Borderline hypertensive (BHR) rats are the first generation offspring of a cross of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats. In adulthood, BHRs have systolic blood pressures in the 140-160 mm Hg range. If subjected to chronic stress paradigms, however, BHRs develop sustained and permanent elevations in systolic blood pressure (180-200 mm Hg). In the present study, we examined the functional development of cardiac and adrenal medullary responses to reflex activation of the sympathetic nervous system in preweanling BHR and WKY rats. Pups of the two groups were injected with insulin or saline at 4, 8, 12, or 16 days of age and sacrificed 3 h later. Insulin produces an acute lowering of blood glucose which is attended by a centrally mediated increase in sympathetic activity. The induction of ornithine decarboxylase (ODC) activity in heart and the depletion of epinephrine from the adrenal medulla were biochemical indicators of functional sympathetic neurotransmission. WKY and BHR pups had similar levels of cardiac ODC activity under basal conditions and following administration of insulin. In contrast, BHRs had higher amounts of adrenal norepinephrine and epinephrine from 4 to 16 days of age and greater depletion of adrenal epinephrine following insulin administration at 8, 12 and 16 days of age. These findings indicate that BHRs have a greater capacity for catecholamine biosynthesis, storage and release in the adrenal medulla during the preweanling period compared to age-matched normotensive WKY controls. This alteration in the adrenal medulla during the preweanling period may contribute to the susceptibility of adult BHR rats to stress-induced hypertension.