A loudspeaker-driven system for rapid and multiple solution exchanges in patch-clamp experiments

A new and inexpensive system allowing rapid and synchronized changes of solutions around a membrane patch or a cell under voltage-clamp conditions is described. Four plastic capillary tubings (OD 640 m; ID 430 m) were glued together horizontally and attached to a coil of a commercially available loudspeaker. Servo-control of the position of the coil allowed the mouth of any of the capillaries to be positioned near the pipette tip within 6 ms. A high flow speed of the test solution was crucial to achieve rapid solution exchange. At a flow speed of 5 cm/s, complete exchange of the external environment of a frog ventricular cell was achieved within 20–30 ms. The time course of solution change was found to be 3–5 times faster at the tip of an open patch pipette. To preserve the physical integrity of the cell, the cell was usually perfused by a control capillary at a slow velocity (0.2 –0.4 cm/s) and test solutions flowing out of adjacent capillaries at high velocity (4–5 cm/s) were applied to the cell only for short periods. Determination of the three-dimensional contamination profile around the mouth of the control capillary allowed the optimal conditions for the use of the system to be established and possible sources of contamination to be avoided between adjacent capillaries with unmatched flow speeds. Successive and multiple changes in external solutions could be easily synchronized with voltage-clamp depolarizations to examine the time course of the effect of drugs on voltage-operated ion channels. An example of this application is given with rapid applications of the dihydropyridine agonist (-)BayK 8644 to the L-type Ca²⁺ channel current in frog ventricular myocytes.     

Serotonergic and noradrenergic function in depression: clinical correlates

The present study was conducted in order to investigate the relationships between central noradrenergic (NA) and serotonergic (5-HT) function and clinical characteristics of a major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We measured growth hormone response (ΔGH) to clonidine (CLO) (an α2 NA agonist), as an index of central NA function, and prolactin response (APRL) to d-fenfluramine (d-FEN) (a specific 5-HT releaser/uptake inhibitor), as an index of central 5-HT function, in 53 medication-free depressed inpatients. On the basis of their CLO and d-FEN test responses, patients were classified into 4 groups. Group 1 (blunted ΔPRL(d-FEN) alone [11 %]) was characterized by a recent violent suicide attempt, a high degree of medical damage, and mild anxiety. Group 2 (blunted ΔGH(CLO) alone [32%]) was characterized by an absence of a history of suicide attempt and by severe anxiety. Group 3 (combination of blunted ΔGH(CLO) and APRL(d-FEN) [18%]) was characterized by a history of suicide attempts, total duration of the illness of over W years, age over 40 years, and more than 3 previous hospitalizations. Group 4 (no abnormality [39%]) had no specific clinical profile. These results suggest that, in depression, specific psychopathological features may be linked to 5-HT and/or NA dysfunction. However, our results also suggest that NA and/or 5-HT dysfunction are less likely to be the primary cause of mood disorders but are more indicative of failure of compensatory mechanisms involved in affective homeostatic processes.     

氟西汀市场透析

目的:了解氟西汀的市场现状及发展趋势。方法:对氟西汀国内、外生产和销售情况进行分析。结果与结论:氟西汀市场潜力巨大,我国制药企业应密切关注市场变化,以求进一步发展。     

奥美拉唑肠溶片生物利用度测定

目的　考察奥美拉唑肠溶片人体相对生物利用度及生物等效性。方法　 10名健康男性志愿者 ,采用交叉给药方案 ,分别单剂量po 2 0mg国产奥美拉唑肠溶片和进口奥美拉唑胶囊 ,用高效液相色谱紫外检测法测定血浆中奥美拉唑浓度 ,进行人体相对生物利用度和生物等效性评价。结果　单次po 2 0mg国产奥美拉唑肠溶片和进口奥美拉唑胶囊后 ,达峰时间tmax分别为 3 0 1± 0 5 2h和 2 6 2± 0 76h ;峰值血药浓度Cmax分别为 5 4 3 5± 2 14 9ng·ml-1和 5 2 0 9± 16 7 8ng·ml-1;药时曲线下面积AUC0→∞ 分别为 10 2 3 0± 5 4 2 5h·ng·ml-1和 10 71 2± 5 73 8h·ng·ml-1。结论　国产奥美拉唑肠溶片的相对生物利用度为96 4 0 % ,主要参数的双单侧t检验 ,结果显示两种制剂为生物等效制剂。     

紫外分光光度法测定吉非罗齐含量

目的建立用紫外分光光度法到定吉非罗齐的含量；方法以乙醇为溶剂，采用分光光度法，在276nm到定吉非罗齐含量；结果 吉非罗齐在0—219．2μg／m1范围内，其吸收度呈良好的线性，R＝0．9999，平均回收率100．1％，RSD为0．36％。结论 本法简便快速，结果与药典法基本一致。     

钴辐照对板蓝根抗内毒素作用的影响

目的：研究Co辐射灭菌法对板蓝根抗内毒素作用的影响。方法：本文用3个剂量的Co射线辐照板蓝根药材，并用鲎试剂法与家兔法测定辐照前后板蓝根内毒素作用的变化，结果表明Co辐照对板蓝根抗内毒素作用的影响与辐照剂量有关，10Kgy及以下剂量的辐照不会造成明显影响.     

青霉素过滤工艺改进

目的：为了进一步解决青霉素生产过过程中的过滤问题和进一步扩大产量，克服原设备的缺陷。方法：我们采用了目前国内制药企业广泛使用的鼓式过滤机过滤技术及利用热交换器进行热量交换以达到生产工艺的要求同时改进相应工艺。结果：达到降低生产成本、扩大生产产量、加快生产速度，提高生产产率的结果。结论：通过实际生产证明完全符合实际生产的需要。本文就目前青霉素过滤过程中的几个关键环节作简要讨论。     

HPLC法测定苦参素注射液中氧化苦参碱的含量

目的：建立HPLC法测定苦参素注射液中氧化苦参碱的含量。方法：采用C8柱为固定相；乙腈：1％H3PO4(9：220)为流动相；检测波长220nm；柱温为室温。结果：线性范围0．0162～0.1293mg／ml。R=0．9990。此方法分离效果好，操作简便，快捷，重现性好，可作为质控方法。     

Analysis of the p21 gene in gliomas

The p21 gene encodes a cyclin dependent kinase inhibitor protein (p21) which has a tumor suppressive activity in a variety of tumor cell lines. Since, the p21 gene is up-regulated by the p53 tumor suppressor gene, which is frequently mutated in gliomas, acting therefore in the same control pathway, it constitutes a good candidate gene to be also inactivated in these tumors. To test this hypothesis, DNAs from 81 gliomas (48 glioblastomas, 11 anaplastic astrocytomas, 10 low-grade astrocytomas, 12 oligodendrogliomas and mixed gliomas), were investigated for mutations in the p21 coding sequence by denaturant gradient gel electrophoresis followed by sequencing. All these tumors have been previously screened for p53 mutations. Three different DNA variants were identified on codon 31 (17 cases), 27 (1 case) and 117 (1 case) and shown to be also present in matching constitutional DNA, suggesting they were polymorphisms. None of the tumors demonstrated a somatic mutation. No significant correlation between the presence of a p21 variant and the p53 mutation tumor status was observed. In conclusion, mutation in the p21 gene unlikely contributes to the development of gliomas.