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.     

Effect of ritanserin, specific 5HT-2 antagonist, on PRL secretion in normal subjects and in different hyperprolactinaemic conditions

The availability of a new specific anti 5HT-2 compound, ritanserin (RTS), led us to further investigate the role of serotonin in controlling PRL secretion. The drug was administered to normoprolactinaemic subjects and to patients with differing hyperprolactinaemic conditions. While RTS failed to modify PRL levels in normoprolactinaemic subjects and in patients with PRL-secreting pituitary adenomas, a marked decrease in the hormone was obtained in patients with functional and puerperal hyperprolactinaemia. The lack of effect of RTS in PRL-secreting pituitary adenomas suggests that the reported suppression of PRL by other antiserotoninergic drugs, such as metergoline, is probably due to their concomitant dopaminergic activity.     

Evidence that tolerance to cultured thyroid allografts is an active immunological process. Protection of third-party grafts bearing new antigens when associated with tolerogenic antigens.

We studied the tolerance phenomenon that develops in long-term recipients of cultured thyroid allografts. Allogeneic mouse thyroids were cultured under hyperbaric oxygen or acidic conditions and then transplanted beneath the kidney capsule of C57BL/6 recipients. Donors differed from the recipients in minor antigens alone, major histocompatibility complex antigens alone, or both. At 35-77 weeks after the first cultured graft, recipients received two more cultured grafts under the capsule of the opposite kidney and were immunized with donor spleen cells (SC). At 5 weeks after the second transplantation, we observed that whereas second grafts carrying new antigens alone were rejected, second grafts carrying new antigens in association with antigens in the first graft were significantly protected. In another set of experiments, normal mice became tolerant to cultured allografts after 2 weeks in parabiosis with tolerant individuals. Tolerant mice showed reduced specific in vivo and in vitro cytotoxic T lymphocyte responses. However, the frequency of CTL precursors of tolerant mice was the same as in normal mice. The reduced in vitro CTL responses were restored to normal levels by the addition of a lymphokine rich medium. Also, we observed that the injection of specifically activated immune SC caused the rejection of cultured allografts in normal but not in tolerant recipients. We conclude that the tolerance that develops in recipients of cultured allografts is an active immunological process that affects the activation and effector function of CTL.     

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.