Evidence that peroxynitrite affects human osteoblast proliferation and differentiation.

Peroxynitrite (PN), a nitric oxide (NO*)-derived anion, has been associated with NO* damage in various cell types. We examined the effects of adding PN to cultured human osteoblast-like (hOB) cells obtained after hip arthroplasty. Exposure to PN (0.1-0.4 mM) decreased both hOB proliferation and differentiation, measured by [3H]thymidine uptake and alkaline phosphatase production, respectively. Incubation with 3-morpholinosydnonimine (SIN-1; 0.25-1 mM), an NO* and O2- donor that leads to PN release, also reduced both hOB proliferation and differentiation. Coincubation with both superoxide dismutase (SOD; 100 U/ml) and catalase (CAT; 50 U/ml), rendering SIN-1 a pure NO* donor, reversed its effects on hOB proliferation and differentiation. However, SIN-1-induced NO* production, measured by nitrite release to the hOB medium, was not altered by cotreatment with SOD and CAT. Expression of nitrotyrosine by hOB, a marker of PN action, was significantly increased after SIN-1 addition, as compared with untreated cells, as revealed by Western blot analysis. Interleukin-1alpha (IL-1alpha) and interferon gamma (IFN-gamma) but not tumor necrosis factor alpha (TNF-alpha) also significantly increased nitrotyrosine expression in these cells. These data show that PN is at least partially responsible for osteoblast derangement by NO* and that cytokines released during inflammatory arthropathies can induce PN production in hOB cells.     

Percutaneous selective thermorhizotomy in the treatment of "essential" trigeminal neuralgia. The importance of lesion selectivity

Results following percutaneous thermorhizotomy for trigeminal neuralgia are described in 111 patients. Recurrences and side effects are more frequent whenever selectivity of the surgical lesion has been imperfect (exceeding the original pain area and causing marked hypoesthesia), and less frequent in the cases with strictly selective lesion.     

The effect of protein restriction on the severity and recovery from ischemic renal failure

The effects of chronic dietary protein restriction on ischemic renal failure were evaluated in rats subjected to 90 min of bilateral renal clamping. The rats were kept on either 20% casein (regular) diet or casein-free (protein-free) diet 10 days before and 21 days after renal injury. Rats on regular protein diet showed higher levels of BUN and serum creatinine and had a lower inulin clearance (microliter/min/100 g BW) than animals on protein-free diet (289 +/- 34 vs 582 +/- 103, p less than 0.05) 2 days after ischemia. However, the inulin clearance measured 21 days following ischemia was significantly higher in rats on regular diet (1468 +/- 181) than those maintained on protein-free diet after ischemia (560 +/- 167). When unilateral 90 min ischemia was performed in rats on regular diet, the postischemic kidneys showed an incomplete recovery of the inulin clearance (226 +/- 35) compared to the contralateral kidney (900 +/- 116), 21 days after ischemia; whereas in rats on a protein-free diet the inulin clearance averaged 106 +/- 17 in the postischemic kidney and 345 +/- 41 in the right kidney. When left renal ischemia and contralateral nephrectomy were performed, the inulin clearance was 1149 +/- 74 in rats on regular diet and 534 +/- 60 in rats on protein-free diet, 21 days following renal insult. These results suggest that protein restriction can play a protective role against renal ischemia in an initial phase, but it limits the late recovery from ischemia. The presence of a normal contralateral kidney inhibits the functional recovery of the postischemic kidney and a contralateral nephrectomy produces a compensatory functional hypertrophy of the postischemic kidney, even in rats on a protein-free diet.     

Effects of retinol on proliferation, cell adherence and extracellular matrix synthesis in a liver myofibroblast or lipocyte cell line (GRX).

We have studied the effect of retinol on an established murine cell line (GRX), representative of liver connective tissue cells. This cell line has myofibroblast characteristics; under retinol treatment it is induced into the lipocyte (Ito-cell) phenotype. Retinol decreased the proliferation rate in the entire cell population. It increased cell adherence to the substrate, which was correlated with the increased secretion of fibronectin. Collagen secretion was specifically decreased, whilst the total protein secretion remained stable. Heparan sulphate was decreased in the pericellular compartment, but other glycosaminoglycans were not affected by retinol treatment. Modulations of pericellular components induced by retinol may alter the relations among liver mesenchymal cells, and may be related to vitamin-A-induced modifications of the homoeostasis of hepatic connective tissue and hepatic fibrosis.