We have recently shown that serotonin (5-HT) stimulates cortisol secretion from human adrenocortical tissue in vitro through activation of 5-HT4 receptors. The aim of the present study was to investigate the effect of the 5-HT4 agonist racemic zacopride on aldosterone secretion from the human adrenal gland in vivo and in vitro. In vivo studies were conducted on 28 healthy volunteers pretreated with dexamethasone. The subjects received a single oral dose of placebo, 10 micrograms zacopride, or 400 micrograms zacopride. Plasma aldosterone levels increased significantly within 90 min after the administration of 400 micrograms zacopride, remained elevated for 60 min, and gradually returned to the baseline within 180 min. In contrast, the administration of 10 micrograms zacopride or placebo did not modify the aldosterone concentration. No significant changes were observed in renin, ACTH, or cortisol levels. In vitro studies were conducted on perifused human adrenocortical slices. Administration of 20-min pulses of zacopride (from 10(-11) - 10(-6) mol/L) induced a dose-dependent increase in aldosterone secretion. The minimal effective dose was 10(-10) mol/L, and half-maximal stimulation was obtained with a dose of 7 x 10(-8) mol/L. Zacopride was 100 times more potent in stimulating aldosterone than cortisol release. Taken together, the present data suggest that 5-HT-evoked aldosterone secretion involves the activation of 5-HT4 receptors.

A patient with refractory human immunodeficiency virus (HIV)-related immune thrombocytopenic purpura (ITP) was treated with 3G8 (anti-CD16) monoclonal antibody on days 1, 3, and 8 (25, 25, and 50 mg were administered intravenously, respectively). Side effects were those expected after the administration of a xenogenic protein, but a severe bone pain occurred from the second injection. At the time of the initiation of the treatment the platelet count was 20,000/mm3 and the absolute CD4 number was 100/mm3. We obtained a long-term correction of thrombocytopenia and, to a lesser extent, there was a stabilization of CD4 lymphocytes for 18 months. We observed a significant stimulation of natural killer (NK) function and an elevation in the serum level of tumor necrosis factor alpha, interferon gamma, and granulocyte- macrophage colony-stimulating factor. This suggests that in HIV-related ITP the removal of platelets is mediated by low-affinity Fc gamma receptors (CD16). The stimulation of NK function and elevation in CD4+ lymphocytes may be related to the production of cytokines by activated human NK cells through the interaction of their CD16-bearing receptor with the 3G8 monoclonal antibody. This observation warrants confirmation and further clinical trials.

Ninety-eight patients with locally advanced breast cancer (Stage IIIA-IIIB) were entered into a pilot study combining intensive induction (neoadjuvant) chemotherapy (VTMFAP) with or without hormonochemotherapy, external and interstitial radiotherapy, and consolidation chemotherapy with or without hormonochemotherapy. Tumor regression over 50% was observed in 91% patients after chemotherapy, and complete clinical remission occurred in 100% patients after irradiation. The rate of local relapse is 13%. The 3-year disease-free survival is 62% and 3-year global survival is 77%. Initial chemotherapeutic tumor regression greater than 75% is the main predictive factor for disease-free survival.

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