Expression of the calmodulin-dependent protein phosphatase, calcineurin, in rat brain: developmental patterns and the role of nigrostriatal innervation.

The distribution of neurons expressing the calmodulin-dependent protein phosphatase, calcineurin (CN) was characterized in developing and adult rat brain using a combination of immunocytochemical, immunoblot and in situ hybridization approaches. Immunoblot analysis revealed a strong increase postnatally in CN protein expression. Four differently-charged isoforms of CN were observed in adult brain with apparent regional differences in isoform expression. Immunocytochemistry showed highest levels of CN in hippocampus, striatum, substantia nigra, amygdala and septal nuclei with immunoreactivity first appearing in striatum and septal nuclei, followed by hippocampus, neocortex and limbic structures. In situ hybridization demonstrated that mRNA for the catalytic subunit of CN was seen as early as postnatal day (PND) 1 in striatum, cortex and hippocampus. Since immunoreactivity was not detectable until day 4, this suggests that mRNA expression may precede that of protein by several days in these regions. Lesioning of developing and adult nigrostriatal dopamine neurons either with 6-hydroxydopamine or by surgical hemitransection had little effect on expression of CN, suggesting that CN expression is not influenced transsynaptically by dopamine. Collectively, these findings demonstrate that CN protein and mRNA expression are subject to regional and temporal control during brain development suggesting that specific synaptic connections may influence CN gene expression. However, in striatum, dopaminergic innervation does not appear to affect CN levels.     

Time-dependent alterations in the deformability of human neutrophils in response to chemotactic activation

Transit times of individual human neutrophils through single capillary- sized pores were measured to determine the time-dependent changes in the mechanical behavior of the cells during activation by the chemotactic agent formyl-methionyl-leucyl-phenylalanine (FMLP) and in response to cytochalasin B (CTB) and colchicine. FMLP elicited a two- phase response consisting of a rapid increase in cell stiffness, which peaked between 2 and 3 minutes, followed by a partial recovery of deformability to a level significantly above that of control after 5 minutes. The mechanical changes closely followed changes in F-actin content, although the peak in cell stiffness appeared to lag the F- actin response. Treatment with 3 mumols/L CTB produced a transient decrease in cell rigidity followed by a return to control level in 10 minutes, whereas treatment with 30 mumols/L CTB resulted in a sustained decrease in cell transit times to a level 60% of control. Addition of 3 mumols/L CTB to cells prestimulated with FMLP produced a rapid (1 to 2 minutes) cessation of changes in cellular deformability produced by the FMLP. Colchicine treatment did not decrease cell rigidity, but produced a delayed increase in F-actin content accompanied by increased stiffness of the cells. These results implicate actin as the major determinant of the mechanical behavior of the neutrophil, as measured by whole cell deformability tests. The significant changes in cell deformability that occur in response to fractional changes in F-actin content suggest that changes in the structure of the actin network occur during these processes.     

The influence of the clinical course and diagnosis on the length of surgical stays]

The length of stay (LOS) is one of the major determinants of rising costs in surgical patient care. We studied the timing of the diagnostic procedures performed in 323 surgical patients admitted to 8 surgical departments of a large hospital. Of these: 50 underwent gastrectomy, 28 colectomy, 90 biliary tract (BT) operation, 94 appendectomy and 61 saphenectomy. The average total and preoperative LOS were respectively 27 and 11 days in the gastrectomy group, 26 and 10 in the colectomy group, 10 and 4 in the appendectomy group, 20 and 11 in the BT group, 12 and 6 in the saphenectomy group. The LOS was not affected by the presence of a benign or malignant lesion in gastrectomy and colectomy. In the appendectomy and BT groups, patients admitted from the emergency room had a significantly lower total LOS when compared to elective admissions (8 vs 12 and 9 vs 21 days respectively, p < 0.01). The multiple regression model showed that global and preoperative LOS were influenced by the number of instrumental exams (contrastographic, endoscopic, echographic).     

Beneficial effects of intranasal applications of capsaicin in patients with vasomotor rhinitis

Summary Capsaicin, a nonenamide derived from Capsicum plants, has proven useful in patients with vasomotor rhinitis. In the present study, we studied the effects of 15 µg capsaicin suspended in 100 µl solution in patients with known vasomotor rhinitis. Drug was given 3 times/ day for 3 days to each patient by means of a spray delivered to the nasal mucosa. Acute effects induced by the drug included painful sensation and secretion of nasal fluid but were no longer observed at the last capsaicin application. Patients recorded their symptoms over a 1-month period. The mean symptom score involving nasal obstruction and nasal secretion was markedly reduced by capsaicin treatment. We advance the hypothesis that the beneficial effect of drug treatment may be due to its specific action on the peripheral endings of primary sensory neurons leading to their functional blockade. Further randomized, double-blind, placebo-controlled trial is now needed.     

浙贝母化学成分的研究——Ⅲ.浙贝酮的分离和鉴定

A new C-nor D-homo steroidal alkaloid named zhebeinone was iso-lated from the bulbs of Fritillaria thunbergii Miq..Its structure was determined by spe-tral analyses and chenmical conversion as 5α, 14α-cevanine-3β, 20β-dihydroxy-6-one or C-27 epimer of periminine.     

Inhibition of proliferation of human leukaemic cell populations by deferoxamine

Deferoxamine is a hydroxylamine which binds ferric ions to form a highly stable complex. Since iron is thought to be required at a critical stage for cell proliferation, we investigated the effect of deferoxamine on the proliferative activity of human leukaemic cell populations in vitro by means of 3 permanent cell lines, HL60, U937 and 8402. We found deferoxamine to be a potent inhibitor of DNA synthesis and proliferation of leukaemic cells, acting by accumulating treated cells at the early S phase of the cell cycle. Suppression of leukaemic proliferation was obtained at deferoxamine concentrations in the range usually achieved in the treatment of patients for iron overload. Deferoxamine might therefore warrant further investigation as a potentially useful agent for leukaemia chemotherapy.