Antidepressant-like effects of trazodone on a behavioral screen are mediated by trazodone, not the metabolite m-chlorophenylpiperazine

Trazodone is an atypical antidepressant drug (i.e. blocks neither monoamine uptake nor monoamine oxidase) which tests as an antidepressant drug on the differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement by increasing the reinforcement rate and decreasing the response rate. m-Chlorophenylpiperazine (m-CPP) is a 5-HT1B and 5-HT1C agonist, weak 5-HT2 antagonist, and trazodone metabolite. It has been suggested that formation of m-CPP is responsible for the antidepressant action of trazodone. Administration of m-CPP (1-10 mg/kg i.p.) 60, 30 or 10 min before the behavioral session did not mimic the reinforcement rate-increasing effects of trazodone (10-20 mg/kg i.p.) on rats performing under the DRL 72-s schedule of water reinforcement. Pretreatment with proadifen (50 mg/kg i.p.), an inhibitor of trazodone metabolism, caused a greater than 30-fold leftward shift in the dose-response curve for both the reinforcement rate and the response rate. These results suggest that the parent compound and not the trazodone metabolite m-CPP, mediates the antidepressant-like effects of trazodone on DRL 72-s behavior.     

Effects of acute thioridazine, metoclopramide and SCH 23390 on the basal activity of A9 and A10 dopamine cells

Extracellular single-unit recording techniques were employed to examine the effects of various dopamine (DA) antagonists on the basal activity of spontaneously active DA cells. Metoclopramide and thioridazine were both effective in reversing apomorphine-induced suppression of A9 and A10 DA cells. SCH 23390 produced only a partial reversal of this suppression. When the antagonists were given without any pretreatment, thioridazine preferentially increased the firing rate of A10 DA cells, and was relatively ineffective in altering A9 activity. Metoclopramide, on the other hand, increased the activity of most A9 DA cells, but was less effective in doing so with A10 cells. SCH 23390 did not significantly affect the basal activity of either cell subpopulation. These data support the hypothesis that the so-called 'atypical' antipsychotic drugs act preferentially on the A10 DA system. Taken together with previous results, they also suggest that the acute effects of DA antagonists on DA cell subpopulations coincide with their chronic effects.     

吻合腓肠浅动脉的游离小腿后侧皮瓣修复手掌软组织及神经缺损

目的 探讨修复手掌软组织及神经同时缺损的新方法。方法 利用吻合腓肠浅动脉的游离小腿后侧皮瓣修复手掌软组织及神经缺损6例。结果 临床应用6例，全部成活，术后10～13个月随访，皮瓣外形近似正常手掌，两点辨别觉为5mm，感觉为S4；患指感觉恢复为S3两例，S4四例。结论 利用吻合腓肠浅动脉皮瓣修复手掌软组织及神经缺损是理想的方法。     

Differential distribution of a carbohydrate epitope (Y) on human salivary gland cell membranes.

Monoclonal antibody 303 (mAb 303) reacts with the high molecular weight agglutinin present in human saliva. Its reactivity is periodate sensitive, and it has been shown to recognize the Y epitope. Immunogold labeling of thin sections of human parotid and submandibular glands with mAb 303 showed reactivity in secretory granules of serous acinar, intercalated and striated duct cells (Takano et al., 1988). We now report that the apical and basolateral membranes of salivary acinar and duct cells are labeled by mAb 303, but not myoepithelial cells, endothelial cells and other mesenchymal cells. Gold particles were confined to acinar and duct cell membranes even when myoepithelial cells were directly adjacent, suggesting that the epitope resides on a membrane glycoprotein and that the label does not represent secreted agglutinin bound to the cell surface. Although myoepithelial cells are thought to differentiate from epithelial stem cells, the present results indicate that substantial compositional differences exist between the membranes of myoepithelial cells and other salivary parenchymal cells. Earlier studies also showed that mAb 303 labels normal pancreatic acinar cells and certain salivary (pleomorphic adenoma) and mammary (lactating adenoma) tumors (Bogert et al., 1988). This antibody thus may be a useful reagent for characterizing the origin of exocrine gland-derived cell cultures and neoplastic cells. Further, localization studies may provide insight into the role of the Lewis blood group-related epitope in secretory cells.     

Endothelin receptor expression in human decidua

The endothelins are signalling peptides that act via two receptors, ET(A) and ET(B). In the human endometrium, endothelin receptors have been demonstrated in glands and stroma and have been shown to vary during the course of the menstrual cycle. The present study was undertaken to determine whether or not expression of endothelin receptors changes during pregnancy or after administration of exogenous progestagens. The expression of the receptors was correlated with the appearance of basement membrane components during decidualization of the endometrial stroma. Decidual specimens (n = 15) were obtained during the first trimester of pregnancy and 10 at term. Sixteen pairs of endometrial biopsies were obtained from women with menorrhagia before and after exposure to exogenous progestagens. A total of 15 hysterectomy specimens were used as controls for the expression of stromal basement membrane proteins in the absence of decidualization. Autoradiography was carried out with selective ligands for ET(A) ([125I]-PD 151242) and ET(B) ([125I]-BQ3020). The distribution of ligand binding was then compared with the distribution of laminin alpha2 light chain and collagen IV. ET(A), ET(B), laminin alpha2 light chain, and collagen IV were expressed in stromal decidual cells in the first trimester of pregnancy. ET(B) was also found on endometrial glandular epithelium. Quantitative macro-autoradiography and multiple regression analysis demonstrated a highly significant positive correlation (P < 0.001) between expression of ET(B) and laminin alpha2 light chain. In the third trimester qualitative examination suggested a reduction of ET(A) in the stroma. Progestagen-induced decidua exhibited a similar pattern to that found in first trimester decidua. This study has demonstrated up-regulation of ET(B) during the progesterone- dependent process of decidualization and suggests a paracrine or autocrine role for endothelins in the decidua.      

Permanent impairment of embryo development by hydrosalpinges

Recent reports suggest a deleterious effect of hydrosalpinges on pregnancy outcome for in-vitro fertilization (IVF) and improvement following surgical treatment. We compared the effect of hydrosalpinx on pregnancy outcome in 286 patients having 348 IVF cycles and followed the development of untransferred embryos for 7 days to determine if hydrosalpinges affect oocyte quality or embryo development. The delivery rate per retrieval was significantly lower for patients with hydrosalpinx, but was restored by surgical treatment to that of patients without hydrosalpinx. However, the implantation rate per embryo transferred and normal blastulation of untransferred embryos, which were significantly decreased in patients with hydrosalpinx, and growth arrest and degeneration of untransferred embryos, which were significantly increased compared to patients without hydrosalpinx, were not restored by surgical treatment of hydrosalpinges. We conclude that surgical treatment of hydrosalpinges decreases early pregnancy loss and improves pregnancy outcome, possibly by diminishing reversible deleterious effects exerted on the endometrium. As we have seen in our laboratory, hydrosalpinges may have a permanent negative influence on ovarian function, follicular development and oocyte quality since implantation of transferred embryos and normal blastulation of untransferred embryos remain low, and in-vitro growth arrest and degeneration remain high despite surgical treatment of hydrosalpinges.