Effect produced by acute and chronic administration of the selective 5-HT3 receptor antagonist BRL 46470 on the number of spontaneously active midbrain dopamine cells in the rat

This study examined the effect of acute and chronic administration of the selective 5-HT₃ receptor antagonist BRL 46470A, an analog of granisetron, on the number of spontaneously active dopamine (DA) cells in the substantia nigra pars compacta (A9 or SNC) and the ventral tegmental area (A10 or VTA) in the rat. In the A10 area, the acute administration of BRL 46470A decreased the number of spontaneously active DA cells at a dose of 0.1 mg/kg (0.28 μmol/kg) ip, yet increased the number of spontaneously active DA cells at a dose of 0.3 mg/kg (0.84 μmol/kg). The chronic administration (21 days) of BRL 46470A appeared to produce a multiphasic dose-response curve. Thus, the chronic treatment with BRL 46470A increased the number of spontaneously active A10 DA cells at 0.03 (0.084 μmol) and 0.3 mg/kg, but decreased the number of spontaneously active A10 DA cells at a dose of 0.1 mg/kg. In contrast, BRL 46470A did not decrease the number of spontaneously active A9 DA cells after either acute or chronic administration (0.01-0.3 mg/kg). However, BRL 46470A did increase the number of spontaneously active A9 DA cells at acute and chronic doses similar to those that were effective in A10. The iv administration of (+)-apomorphine (APO) not only failed to reverse the decrease produced by chronic administration of BRL 46470A at 0.1 mg/kg, but further decreased the number of spontaneously active A10 DA cells. Similar to the results obtained with granisetron, the pretreatment of naive rats with either 0.01 or 0.1 mg/kg iv of BRL 46470A significantly potentiated (2-fold) the suppressant action of APO on the basal firing rate of A10, but not A9 DA cells. Overall, our results indicate that similar to granisetron, chronic BRL 46470A at 0.1 mg/kg selectively decreases the number of spontaneously active A10 DA cells, via a mechanism not related to depolarization inactivation. Presently, it is not clear what factors may contribute to the multiphasic dose-response curve of BRL 46470A. © 1994 Wiley-Liss, Inc.     

Disposition of Tablet and Capsule Formulations of Digoxin in the Elderly

Study Objective . To compare digoxin tablets and liquid-filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state. Design . A randomized, crossover trial, each period lasting 3 weeks, with no washout period. Setting . A university hospital. Patients . Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease. Interventions . The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites. Measurements and Main Results . No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p=0.05). One subject had a 4-fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability. Conclusions . Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products.     

THE INCREASE OF FEMORAL ARTERIAL FLOW BY STIMULATING THE DORSAL AND VENTRAL MEDULLA IN CATS

1. In chloralose-urethane anaesthetized cats, the dorsal cardiovascular reactive area (DCRA) in the parvocellular reticular nucleus dorsomedial to the facial nucleus, and the ventral cardiovascular reactive area (VCRA) ventromedial to the facial nucleus, were stimulated by microinjections of sodium glutamate (100–200 nmol) or electric current. 2. Stimulation of DCRA, with a long latency of 15–20 s, elicited a marked increase of blood flow in the contralateral femoral artery with little change to moderate increase in systemic arterial blood pressure (ABP). In the relatively dorsal portion of DCRA, however, a smaller increase of blood flow in the ipsilateral femoral artery was elicited. 3. On the other hand, stimulation of VCRA with a short latency (3–5 s) evoked an increase of blood flow in both femoral arteries which was more prominent on the contralateral side. The responses were accompanied with decreases in the blood flow of other vascular beds with only a slight increase or minimal change in ABP. 4. The data suggest that DCRA and VCRA are both viscerotopically organized to alter the resistance of individual vascular beds for redistribution of blood flow.     

Induction of DNA synthesis by sodium phenobarbital, uracil, and sodium saccharin in urinary bladder of the F344 rat

DNA synthesis in urothelial cells was determined 2, 4, 6, 10, and 16 weeks following dietary administration of promoters of bladder tumors to weanling male F344 rats. The experimental groups were fed AIN-76A diet or this diet containing 0.15% sodium phenobarbital, 3% uracil, 5% sodium saccharin, 2% sodium bicarbonate, or a combination of 5% sodium saccharin and 2% sodium bicarbonate. Two other groups were given Wayne rodent chow alone or in combination with 5% sodium saccharin. A group of rats given a drinking water containing 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine served as a positive control. With the exception of phenobarbital which increased the labeling index but did not induce hyperplasia, all other compounds increased the labeling index and induced hyperplasia. The combination of sodium saccharin and sodium bicarbonate was more effective than either compound alone in increasing the labeling index. Sodium saccharin was equally active when incorporated in either the AIN diet or the Wayne rodent chow. The present results suggest that a fundamental mechanism of bladder tumor promotion may be due to an increased DNA synthesis which leads to an increased turnover rate of urothelial cells rather than hyperplasia. However, since sodium saccharin is a promoter when incorporated into the Wayne diet but not into the AIN diet, the ability to stimulate DNA synthesis may be an important but insufficient condition for promotion by saccharin.     

Carotid-cavernous sinus fistula associated with a primitive trigeminal artery

Carotid-cavernous sinus fistulas are not rare, but they have never been reported in association with persistent primitive trigeminal artery. We recently encountered such a case. The Jaeger-Hamby procedure was employed, with mandatory occlusion of the primitive trigeminal artery.     

不同术后镇痛模式对红细胞免疫功能的影响

目的探讨不同术后镇痛模式对红细胞免疫功能的影响。方法50例妇科手术患者,按术后不同镇痛模式分为硬膜外自控镇痛(PCEA)组和静脉自控镇痛(PCIA)组。并分别于术前、术后1、3、7 d采静脉血样检测红细胞C3b受体花环率(RCR)、红细胞免疫复合物花环率(RICR)、红细胞免疫粘附促进因子(RFER)和红细胞免疫粘附抑制因子(RFIR)。结果与术前比,PCEA组术后1 d RCR、RFER显著上升(P<0.05),RFIR显著下降(P<0.05),术后3 d RCR、RFER仍显著上升(P<0.05),而RICR显著下降(P<0.05);PCIA组术后1 d RCR、RFER显著下降(P<0.05),RFIR、RICR显著上升(P<0.05);PCIA组术后1、3 d RCR、RFER比PCEA组显著降低(P<0.05),而RICR显著上升(P<0.05);两组各参数在术后7 d基本恢复至术前水平。结论PCEA对红细胞免疫功能的稳定和恢复作用明显强于PCIA。     

不典型脑转移瘤CT和MR的诊断分析

目的：提高CT与MR对不典型脑转移瘤的诊断准确性。方法：回顾性分析58例经临床手术证实的有完整资料的不典型脑转移瘤的CT和MR表现。结果：病变大部分位于幕上，有钙化者较多，约2／3有强化和水肿，且多发。部分有出血和囊变。结论：不典型脑转移瘤的CT和MR表现多种多样，多发者相对容易诊断，单发者诊断不易。颅外肿瘤的检查有助于鉴别诊断。肺部的影像学检查是必不可少的。     

有效控制与控制不佳的MRI阴性的GTCS病人发作间期SPECT对照研究

目的:利用单光子发射计算机断层摄影(SPECT)半定量分析有效控制与控制不良的MRI阴性的全面性强直阵挛发作癫(GTCS)病人的局部脑血流差异,探讨脑血流灌注与其预后的关系.材料和方法:对29例有效控制的和12例控制不佳的MRI阴性的GTCS病人进行发作间期99mTc-ECD-SPECT脑血灌流显像,10例年龄匹配的健康人作对照,用感兴趣区(ROI)的不对称指数(%AI)进行半定量分析.将SPECT分析结果与病人的临床表现与EEG相比较.结果:①控制不佳组与有效控制组在丘脑和基底节区的%AI存在显著性差异(P<0.05);②控制不佳组SPECT脑显像的异常率(83.3%,10/12)明显高于有效控制组的异常率(17.2%,5/29),两组具有显著性差异(P<0.01);而两组病人的EEG异常率分别为58.3%、44.8%(7/12、13/29),无显著性差异(P>0.05).结论:控制不佳的MRI阴性的GTCS病人往往存在发作间期的低血流灌注脑区,提示癫的难治性;而控制良好的病人多无明显异常发现,可能预后较好.     

影响脐血IgE值因素的研究

目的　本研究对影响脐血IgE值的可疑因素进行分析 ,探讨影响儿童食物过敏的可疑因素。方法　选取孕期妇女 10 5名及其所生婴儿 ,采用标准问卷调查获取资料 ,对影响脐血IgE的因素进行分析。 结果　母亲的过敏性疾病史、父亲过敏性疾病史中的皮炎表现型、孕期妇女过敏性疾病发作史、有过敏史妇女孕后期摄入过量的牛奶和鸡蛋均与脐血IgE值的上升有关 ,且上述 5个因素对脐血IgE水平的影响依次降低。 结论　母亲的过敏性疾病史和父亲过敏性疾病史中的皮炎表现型是导致新生儿脐血IgE值升高的主要危险因素 ;同时 ,妊娠期加强对有过敏史妇女的保护 ,防止过敏性疾病的复发 ,在孕后期控制有过敏史妇女牛奶、鸡蛋等大分子食物致敏原的摄入 ,有助于降低脐血IgE值。