Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants

This study demonstrated that distinct patterns of active behaviors are produced by antidepressants that selectively inhibit norepinephrine (NE) or serotonin (5-HT) uptake in the rat forced swimming test (FST). A behavior sampling technique was developed to score the active behaviors swimming, climbing and diving, as well as immobility. The rat's behavior was recorded at the end of each 5-s period during the test session. The sampling technique was both reliable, as demonstrated by test-retest reliability and inter-rater reliability, and valid, as shown by comparison to the timing of behavior durations. Five different antidepressant drugs which block monoamine uptake and two 5-HT_1A receptor agonists were shown to decrease immobility in the FST; however, they produced distinct patterns of active behaviors. The selective NE uptake inhibitors desipramine and maprotiline selectively increased climbing, whereas the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline and paroxetine selectively increased swimming. The 5-HT_1A receptor agonists 8-OH-DPAT and gepirone also selectively increased swimming. These results show that:1) SSRIs are not false negatives in the FST; 2) at least two behaviorally distinct processes occur in the FST; and 3) enhancement of NE neurotransmission may mediate climbing in the FST, whereas enhancement of 5-HT neurotransmission may mediate swimming.     

精氨酸加压素（AVP）的衍生物AVP4—8不能作用于AVPV1a受体而诱发电流反应

在微量注射大量肝脏ｍＲＮＡ之后，通过电压箝方法进行功能鉴定，两栖类卵母细胞成功地表达了ＡＶＰＶ１ａ受体。但在灌流ＡＶ４－８溶液时，却不能诱导卵母细胞产生内向振荡电流反应。提示ＡＶＰ４－８不能通过ＡＶＰＶ１ａ受体而介导生理学效应。     

Serotonin 5- HT (2C) receptor knockout mice: autoradiographic analysis of multiple serotonin receptors.

Quantitative receptor autoradiography was used to study possible alterations of the densities of multiple serotonin (5-HT) receptor subtypes and of serotonin transporter in the brain of 5-HT(2C) receptor knockout mice. The radioligands employed were [(3)H]citalopram, [(3)H]WAY100,635, [(3)H]8-OH-DPAT, [(3)H]GR125743, [(3)H]sumatriptan, [(3)H]MDL100,907, [(125)I](+/-)DOI, [(3)H]mesulergine, [(3)H]5-HT, [(3)H]GR113808, and [(3)H]5-CT. As expected, radioligands that label 5-HT(2C) receptors showed a complete absence of labeling in mutant mice choroid plexus and significantly reduced densities in other brain regions expressing 5-HT(2C) receptors. With the rest of the radioligands, no significant alterations in the densities of labeled sites were found in any brain region. In situ hybridization showed no changes in 5-HT(2A) receptor and serotonin transporter mRNA levels, whereas 5-HT(2C) receptor mRNA levels were reduced in certain brain regions. The present results indicate that the mouse serotonergic system does not exhibit compensatory up- or down-regulation of the majority of its components (serotonin transporter and most 5-HT receptor subtypes) in response to the absence of 5-HT(2C) receptors.     

X-刀立体定向放射治疗颅内肿瘤的近期疗效分析

目的:分析立体定向X-刀放射治疗颅内肿瘤后的近期疗效,并进行阶段性工作总结。材料和方法:53例不同类型脑瘤患者,以CT、MR、DSA图像资料作为定位依据,用德国Brain LAB治疗计划系统设计三维优化方案,西门子MD-2型直线加速器旋转照射。结果:53例患者经X-刀治疗后,近期均取得了满意效果,诸如以卡氏评分法评价,临床症状有所改善;以CT增强扫描复查观察,肿瘤大小趋于缩小或消失。结论:立体定向放射治疗后的追踪观察表明,只要严格掌握适应症,精确定位,精确计划,精心治疗,X-刀是一种安全、有效、无痛苦的治疗脑肿瘤的方法。它可起到改善临床症状,提高患者生活质量,延长生存期限的作用。     

3,5-diBr-PADAP直接光度法测定血清锌

目的　建立一种不去除血清蛋白、简便灵敏的直接光度法测定血清锌。方法　以新的有机试剂2 -(3 ,5 二溴 -2 -吡啶偶氮 ) -5 -二乙氨基酚 (3 ,5 diBr -PADAP)为显色剂 ,在有表面活性剂存在的Tris-HC1介质中 ,手工分析法和自动分析法测定血清锌。结果　该法线性范围 0～ 80 μmol/L ,手工分析法和自动分析法平均回收率为 99 9%和 10 0 2 % ,批内变异系数 (CV)和批间变异系数分别为 0 0 18、 0 0 17和 0 0 2 8、0 0 2 6,与原子吸收分光光度法比较具有良好的相关性 ,线性回归方程和相关系数分别为Y =1 0 0 4X -0 12 6,r=0 9912和Y =1 0 0 6X -0 195 ,r =0 0 992 8。 89例健康人血清锌含量分别为 8 96～ 2 2 5 2 μmol/L和 8 63～2 2 43 μmol/L (x± 2s)。结论　用 3 ,5 diBr-PADAP直接光度法测定血清锌方法简便、灵敏可靠 ,适合临床应用。     

Natural killer cell activity and CSF monoamine metabolites in suicide attempters

The aim of this study was to investigate markers of serotonin and immune function in suicidal patients. Cytotoxic activity of natural killer cells (NK) and CD16 lymphocytes were studied in 28 suicide attempters and 26 healthy controls, and related in patients to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Patients with CSF 5-HIAA below the median had significantly lower NK cell activity than other patients. CD16 cell frequency was significantly lower in patients than in controls, and patients also tended to have lower NK cell cytotoxicity than healthy controls. There were no statistically significant correlations between 4-hydroxy-3methoxyphenyl glycol (HMPG), homovanillic acid (HVA), CSF cortisol and NK cell activity. The results support the hypothesis of compromised immune function in suicidal patients with evidence of disordered serotonin function.     

口服Sumatriptan治疗偏头痛的临床评价

本文报告口服Sumatriptan 100mg对偏头痛急性发作119例次的治疗结果。治疗后4h内显效91例次(76.5％),好转16例次(13.4％),无效12例次(10.1％),总有效率为89.9％。对偏头痛伴随症状恶心、呕吐和畏光、畏声的缓解率分别为94.2％、96％和94.3％。     

Sensitive Detection of p53 Gene Mutations in Esophageal Endoscopic Biopsy Specimens by Cell Sorting Combined with Polymerase Chain Reaction Single-strand Conformation Polymorphism Analysis

For the rapid and sensitive detection of p53 gene mutations in esophageal endoscopic biopsy specimens, we combined cell sorting with the polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) analysis. Mutations in exons 5–8 of the p53 gene were investigated by FCR-SSCF analysis using 10³ sorted nuclei obtained from each endoscopic biopsy specimen of 16 patients with esophageal cancer. DNAs extracted from their respective surgical specimens were investigated by a conventional method of PCR-SSCP analysis. Mutations in the biopsy specimens were detected in 6 of the 12 aneuploid tumors but in none of the 4 diploid tumors. After tumor cell enrichment by cell sorting, one mutation in exon 8 became apparent, which could not be detected from the surgical specimen by a conventional method of PCR-SSCP analysis. This method should improve the sensitivity of detecting p53 gene mutations, and provides additional information concerning the DNA ploidy pattern in the tumors.     

Initial evaluation of123|-5-|-R91150, a selective 5-HT2A ligand for single-photon emission tomography, in healthy human subjects

The mapping of 5-HT₂ receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (¹²³I-5-I-R91150 or¹²³I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT_2A receptors. This study reports on preliminary¹²³I-5-I-R91150 SPET, wholebody and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SEM-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT_2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100–120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT_2A receptors in (cerebral cortex>striatum>cerebellum). These findings suggest that¹²³I-5-I-R91150 may be used for the imaging of 5-HT_2A receptors in the living human brain with SPET.     

An experimental model for canine visceral leishmaniasis

Seven mixed-breed dogs were challenged with either promastigotes or amastigotes of Leishmania donovani infantum strains recently isolated from naturally infected dogs. Different routes and numbers of parasites were utilized and each dog was monitored for at least 1 year post-infection. Anti-parasite specific antibody levels were measured by enzyme-linked immunosorbence, immunofluorescence, crossed-immune electrophoresis and Western blotting on crude antigen. Western blotting on two pure parasite proteins, dp72 and gp70-2, was also done. Mitogenic and antigen-specific stimulation of peripheral blood lymphocytes was monitored; and the haematological, clinical and parasitological parameters measured. Dogs challenged with amastigotes exhibited a more pronounced humoral response to leishmanial antigens. Only in one case was strong antigen-specific proliferation detected. Clinical signs of disease, including hypergammaglobulinaemia, enlarged lymph nodes and the presence of parasites, were also more apparent in the dogs challenged with amastigotes. None of the seven dogs died. Serum antibodies to leishmanial antigens were apparent between 1.5 to 3 months following challenge and correlated with the appearance of enlarged lymph nodes, hypergammaglobulinaemia and the presence of parasites in tissue biopsies. Serum antibodies remained chronically high in these dogs throughout the period of the study. Only one dog (1/3) challenged intravenously with promastigotes and the dog challenged intradermally with amastigotes produced transient antibody responses to leishmanial antigen.