环丙沙星、氧氟沙星及左氧氟沙星对大鼠致病作用的研究

目的观察氧氟沙星(OFLX)和左氧氟沙星(LVLX)对大鼠中枢神经的毒性与环丙沙星(CPLX)毒性的差异,及抗痫药物对环丙沙星引发的癫痫的阻断作用.方法 Wistar大鼠,随机分为3组,以用药前皮层脑电图(ECOG)其脑电图功率谱作为自身对照.颈静脉注射药物100mg/kg,记录给药后10、20、30、60、120min时的ECOG和脑电图,及大鼠的行为变化,并在癫痫发作后静脉注射抗痫药物,阻断癫痫发作.结果 CPLX组大鼠中7只ECOG出现棘波和慢棘波,其中5只大鼠ECOG出现频发棘波,频发棘波能被地西泮迅速阻断.用药后10min脑电功率谱δ波功率和总功率较用药前明显降低(P＜0.05),之后又逐渐升高.用药后θ、α、β波功率逐渐升高,120min时明显高于给药前(P＜0.05);OFLX、LVLX组大鼠ECOG均无异常改变,脑电功率谱δ、θ、α、β波功率及总功率与用药前比较均无显著性差异(P＜0.05).但LVLX组的ECOG,脑电功率谱δ、θ、α、β波功率及总功率均较OFLX组变化小.结论 CPLX对大鼠有明显的致痫作用,OFLX和LVLX无致痫作用,且LVLX组大鼠ECOG、脑电功率谱变化最小.地西泮对CPLX引发的大鼠癫痫有阻断作用.     

环丙沙星、氧氟沙星及左氧氟沙星对大鼠致痫作用的研究

目的　观察氧氟沙星 (OFL X)和左氧氟沙星 (L VL X)对大鼠中枢神经的毒性与环丙沙星 (CPL X)毒性的差异 ,及抗痫药物对环丙沙星引发的癫痫的阻断作用。方法　 Wistar大鼠 ,随机分为 3组 ,以用药前皮层脑电图 (ECOG)其脑电图功率谱作为自身对照。颈静脉注射药物 10 0 mg/kg,记录给药后 10、2 0、30、6 0、12 0 min时的 ECOG和脑电图 ,及大鼠的行为变化 ,并在癫痫发作后静脉注射抗痫药物 ,阻断癫痫发作。结果　CPL X组大鼠中 7只 ECOG出现棘波和慢棘波 ,其中 5只大鼠 ECOG出现频发棘波 ,频发棘波能被地西泮迅速阻断。用药后 10 min脑电功率谱 δ波功率和总功率较用药前明显降低 (P<0 .0 5 ) ,之后又逐渐升高。用药后θ、α、β波功率逐渐升高 ,12 0 min时明显高于给药前 (P<0 .0 5 ) ;OFL X、L VL X组大鼠 ECOG均无异常改变 ,脑电功率谱δ、θ、α、β波功率及总功率与用药前比较均无显著性差异 (P<0 .0 5 )。但 L VL X组的 ECOG,脑电功率谱δ、θ、α、β波功率及总功率均较 OFL X组变化小。结论　 CPL X对大鼠有明显的致痫作用 ,OFL X和 L VL X无致痫作用 ,且 L VL X组大鼠 ECOG、脑电功率谱变化最小。地西泮对 CPL X引发的大鼠癫痫有阻断作用。     

诺氟沙星的致痫作用及对大鼠脑电功率谱,频率分配的影响

诺氟沙星１５０和３００μｇ／ｋｇｉｃｖ后，大鼠脑电图均出现痫样放电。放电幅度及频率逐渐增高、波形多变，并伴有肢体抽搐等行为学改变，１５０μｇ／ｋｇ组脑电总功率增高，δ、δ／θ、δ／（θ＋α＋β）下降，频谱右移，提示脑抑制过程降低而功能状态升高。３００μｇ／ｋｇ组总功率增高，而频率分配指标中除β＿２短暂增高外均无明显变化。     

大剂量免疫球蛋白抑制马桑内酯诱发的大脑神经元痫样放电

目的：研究大剂量免疫球蛋白的抗癫痫作用。方法：本实验采用大脑皮层应用化学致痫剂马桑内酯致痫大鼠，预先静脉注射大剂量免疫球蛋白致痫动物皮层脑电图痫样波频率，振幅，发生的潜伏期和皮层诱发电位振幅的影响。结果：大剂量免疫球蛋白可抑制部分致痫大鼠皮层诱发电位的振幅，脑电图痫样波的频率和振幅，使诱发痫样波发生的潜伏期延长。腹腔注射儿茶酚胺能神经元化学切割剂6－羟多巴可部分抑制免疫球蛋白的效应。结论：免疫球蛋白的上述作用可能与抑制去甲肾上腺有神经递质释放有关。     

加锡果宁抑制荷包牡丹碱在大鼠海马脑片CAl区诱发的痫样放电

在大鼠离体海马脑片标本表面灌流荷包牡丹碱(10μmol·L~(-1)),单脉冲电刺激Schaffer侧支,激活CAl区锥体细胞,给出痫样放电,作者在这种痫样放电模型上研究了加锡果宁对该痫样放电的影响,结果表明,微量推注不同浓度的加锡果宁到脑片CAl区表面,对荷包牡丹碱诱发的CAl区锥体细胞痫样放电呈剂量依赖性抑制,提示加锡果宁可对抗荷包牡丹碱的致痫作用,并讨论了可能机理。     

不同剂量肝素经肺给药的血药浓度变化

目的：探讨不同剂量肝素经肺给药后血药浓度变化。方法：实验猪和慢性支气管炎（慢支）急性发作患者给予不同剂量肝素钠注射液,经气管切开和经纤支镜,定时检测给药后血药浓度。结果：实验猪经气管内注入１～８ｍｇ／ｋｇ肝素,血中可检出低浓度肝素１４ｄ,剂量与浓度无平行关系。慢支患者经纤支镜注入１００～２００ｍｇ肝素,血中可测出低浓度肝素１４ｄ,剂量与逍度也无平行关系。结论：肝素可经人肺及猪肺人血,不同剂量肝素（猪１～８ｍｇ／ｋｇ,人２～４ｍｇ／ｋｇ）经肺给药后血中可检出低浓度肝素１４ｄ,药物剂量与血药浓度无平行关系。     

诺氟沙星侧脑室点燃大鼠癫痫及脑超微结构变化

目的：观察诺氟沙星对ＥＥＧ的影响和对脑组织超微结构的毒性作用，方法：大鼠右侧脑室注射诺氟沙星１５０和３００μｇ．ｋｇ＾－１，于皮层感觉运动区记录ＥＥＧ并观察脑组织超微结构的变化。结果：大鼠ＥＥＧ均出现痫样放电，两组大鼠右侧和左侧棘波发生时间为１６８±１２９，５１±３５ｓ和２７６±１３８，１１８±６５ｓ，以注射侧较早发生，波形多变，幅度和频率逐步增大，并伴肢体抽搐的行为改变，电镜下３００μｇ．ｋｇ＾     

大剂量免疫球蛋白抑制马桑内酯诱发的大脑神经元痫样放电

目的:研究大剂量免疫球蛋白的抗癫痫作用。方法:本实验采用大脑皮层应用化学致痫剂马桑内酯致痫大鼠,预先静脉注射大剂量免疫球蛋白观察对致痫动物皮层脑电图痫样波频率、振辐、发生的潜伏期和皮层诱发电位振幅的影响。结果:大剂量免疫球蛋白可抑制部分致痫大鼠皮层诱发电位的振幅、脑电图痫样波的频率和振幅,使诱发痫样波发生的潜伏期延长。腹腔注射儿茶酚胺能神经元化学切割剂6-羟多巴可部分抑制免疫球蛋白的效应。结论:免疫球蛋白的上述作用可能与抑制去甲肾上腺素能神经递质释放有关     

小鼠口服免疫人乳头状瘤病毒样颗粒可诱生病毒中和抗体

本文评估了口眼免疫人乳头状瘤病毒（ＨＰＶ）样颗粒（ＶＩＰ）预防ＨＰＶ病的可行性。ＨＰＶ－１１Ｌｌ／ｌ－２ＶＬＰ得自重组杆状病毒ＡｃｌｌＬ１．１和Ａ。１１Ｌ２共感染的昆虫细胞培养物，经管饲法给小鼠口腔接种。ＶＬＰ剂量分别为１００、５０和１０μｇ，每个剂量组５只雌性Ｂａｌｂ／ｃ／小鼠（８～１０周龄）。初免后的１４和４１天加强免疫，对照组不接种。初免后每间隔两周采集血清。用ＶＬＰＥＬＩＳＡ法检测口服免疫的小鼠血清，表明有特异性ＩｇＧ应答。免后８周，中高剂量组的ＶＬＰ特异性抗体滴度＞４０９６；１０μｇ组…     

定痫丸对青霉素致痫大鼠脑组织环核苷酸(cAMP、cGMP)影响

目的观察探讨定痫丸治疗癫痫的作用及作用机制。方法各组大鼠按不同剂量灌胃给药7 d后,采用腹腔注射青霉素制备癫痫急性模型,青霉素注射剂量为600万U.kg-1,分别测定各组大鼠脑组织中环核苷酸(cAMP、cGMP)的含量,并进行各组大鼠脑电波观察。结果定痫丸能明显减轻青霉素的致痫作用,减少模型大鼠癫痫发作的频率,显著升高模型大鼠脑组织中SOD活性、降低MDA含量,显著升高脑组织中cAMP含量、降低cGMP含量。结论定痫丸抗癫痫作用机制与其抑制自由基引起的脂质过氧化反应、增加自由基的清除,调节脑内cAMP、cGMP含量变化有关。     

诺氟沙星在清醍大鼠的神经毒性和毒代动力学(英文)

AIM:To study the neurotoxicity and toxicokinetics of norfloxacin (NFLX) in freely moving rats. METHODS: Rats were assigned randomly to four treatment groups that received a single iv dose of 50, 100, 200 mg/kg of NFLX and 0.9% saline, respectively. Electroencephalogram (EEG) was continuously recorded with a computerized system in freely moving rats. Venous blood samples were collected for determination of the NFLX concentration by microbioassay method with Escherichia coli 441102 as the test strain. Toxicokinetic parameters were determined from serum concentration-time data with the 3p97 program. RESULTS: (1) The epileptiform discharges appeared in all NFLX groups with different latent periods, accompanied with limb twitching and clonictonic seizures. The relative total power of the EEG increased. (2) Drug serum concentration-time curves of different doses conformed to a two-compartmental model. The values of clearance, volume of distribution, and terminal half-life were dose-independent, while maximum serum concentrations(Cmax) and the areas under the concentration-time curve (AUC0→∞) of NFLX increased with dosage. (3) The relative total powers of EEG were lished a suitable approach to quantitatively determine central nervous system (CNS) stimulant effect of NFLX. There is a significant correlation between AUC0→∞ and the changes of relative total power, which may serve as the index for judgement and prediction of the CNS toxic effect induced by NFLX.     

Neonatal lead exposure in the rat: Decreased learning as a function of age and blood lead concentrations

Suckling rats were treated with lead both through the milk of lead-treated dams and direct injection ip. Lead was administered daily to three age groups: group 1 from Days 1–10; group 2 from Days 11–20; group 3 from Days 1–20; and learning was measured by use of the T-maze in all groups at 8–10 wk of age. Organ weights, body weights, and blood lead concentrations were determined in suckling, weanling, and 10-wk-old rats. Learning ability was decreased in 8- to 10-week-old male and female rats which had been nursed 20 days by dams treated with 17.5 or 25 mg Pb/kg daily after parturition. Administration of lead to the dam 1–10 days similarly decreased learning, but administration 11–20 days did not. None of the doses used produced overt signs of lead toxicity, altered growth rate, or altered organ-to-body-weight ratios in either the pups or the dams. Blood lead concentrations were increased in the pup at 11 days but not at 21 days or 10 wk (45.8 ± 2.0; 20.4 ± 2.0, and 23.4 ± 2.4 μg/100 ml, respectively; mean ± SE). These results show that the brain of the 1- to 10-day-old suckling rat pup is particularly sensitive to lead exposure with residual effects produced on learning present in the 8- to 10-wk-old adult after blood lead concentrations have returned to control values.     

氨氯地平与硝苯地平治疗老年单纯性收缩期高血压病的比较

目的：比较氨氯地平与硝苯地平治疗老年单纯性收缩期高血压病的疗效及安全性。方法：氨氯地平组３４例（男性２０例,女性１４例,年龄６８．８ａ±ｓ１．２ａ）用氨氯地平５～１０ｍｇ,ｐｏ,ｑｄ×８ｗｋ;硝苯地平组３４例（男性１８例,女性１６例,年龄６７．８ａ±１．３ａ）用硝苯地平１０～２０ｍｇ,ｐｏ,ｔｉｄ×８ｗｋ。结果：氨氯地平降压总有效率９４％,硝苯地平９１％,２组疗效差别无显著意义（Ｐ＞０．０５）,不良反应发生率氨氯地平组１２％,硝苯地平组２４％,差别有非常显著意义（Ｐ＜０．０１）。结论：氨氯地平治疗老年收缩期高血压病疗效好,在安全性方面优于硝苯地平。     

氟桂利嗪抗癫痫及逆转难治性癫痫病人多药耐受基因的表达

目的 :了解氟桂利嗪对多药耐受基因 1(MDR 1)表达阴性或阳性癫痫病人的抗癫痫作用及其逆转MDR 1表达的可能性。方法 :54例病人随机分成 2组。实验组用免疫组化法测定P糖蛋白(P gp) ,加用氟桂利嗪 5～ 10mg ,po ,qn ,2wk随访 1次 ,6～ 8wk后评价临床疗效 ,发作减少 50 %者为有效。用药前P gp阳性有效者同时复查P gp。对照组加用安慰剂同步观察。结果 :P gp阳性组的2 2例病人中有效 14例 ,阴性组 12例中有效 2例 ,对照组有效 4例。P gp阳性有效的 11例完成了P gp复查 ,其中 10例病人的P gp表达下降 50 %以上。氟桂利嗪的不良反应发生率为 2 3 %。结论 :氟桂利嗪辅助治疗有效 ,其抗癫痫机制可能与逆转P gp表达有关。     

4—16周龄高血压大鼠脑与脊髓苯环利定受体的变化(英文)

目的:研究高血压大鼠(SHR)脑和胸髓中苯环利定受体密度变化与高血压发生的关系.方法:4,8,12,16周大鼠中枢中[~3H]Phe标记的苯环利定受体密度用放射自显影法检测.结果:高血压稳定期(12,16周),SHR海马和胸髓背角中苯环利定受体明显少于非高血压大鼠(WKY);而血压升高前,4周的SHR则相反;8周血压开始上升时,SHR海马苯环利定受体增加,而在背角无差别.结论:苯环利定受体可能参与了SHR的发病过程.     

维吾尔族癫痫患儿奥卡西平活性代谢产物血药浓度监测分析

目的:探讨维吾尔族癫痫患儿奥卡西平(OXC)活性代谢产物10-羟基卡马西平(MHD)血药浓度与年龄、性别及给药剂量的相关性。方法:建立高效液相色谱法(HPLC)测定79例维吾尔族癫痫患儿MHD的稳态血药浓度,记录患儿年龄、性别及给药剂量等详细信息,利用SPSS 17.0软件进行数据分析。结果:服用8~46 mg·kg^-1·d^-1的奥卡西平后,不同年龄组患儿MHD的稳态血药浓度随着年龄的增加有所升高,但是差异没有统计学意义(P>0.05);相同条件下,不同性别组患儿MHD的稳态血药浓度差异没有统计学意义(P>0.05)。结论:在每千克体质量给药剂量无差异的情况下,维吾尔族癫痫患儿MHD的血药浓度虽随年龄增加而升高,但差异无统计学意义,且与性别无相关性。因此选用奥卡西平治疗癫痫时应定期监测MHD血药浓度并及时调整剂量,为维吾尔族癫痫患儿制订个体化给药方案提供基础,以避免不良反应的发生。     

Carcinogenicity study of sodium hypochlorite in F344 rats

The carcinogenic potential of sodium hypochlorite was examined in F344 rats. Groups of 50 males or 50 females were given sodium hypochlorite in their drinking-water, at concentrations of 0.1 and 0.05% for males and 0.2 and 0.1% for females, for 104 wk. Similar numbers of male and female rats received distilled water without supplement throughout the experiment. All surviving rats were killed at wk 112 (after 8 wk on untreated tap-water). Rats of both sexes given the chemical showed a reduction in body-weight gain, but haematological and biochemical examination of the blood showed no changes due to treatment, and no significant lesions attributable to the treatment were detected in any tissue in the histopathological investigation. Although a variety of tumours developed in all groups, no dose-related change in either the incidence or latent period of tumours was observed for any organ or tissue in either sex. Under the experimental conditions described, therefore, sodium hypochlorite was not carcinogenic in F344 rats.     

Evaluation of inflammatory kinin-forming components in experimental epilepsy in rats

The study was conducted to evaluate the total and active brain tissue kallikrein levels as well as plasma kininogen concentrations in the experimental models of epilepsy induced by maximal electroshock (MES), submaximal electroshock (SMES) and pentylenetetrazole (PTZ) in adult Sprague-Dawley rats. There was significant increase in the total brain tissue kallikrein (P < 0.001) and active tissue kallikrein (P < 0.05) after MES, SMES and PTZ induced epilepsy. Also, the total plasma kininogen levels fell significantly (P < 0.05) after production of MES, SMES and PTZ epilepsy. These results may suggest that these changes may indicate the formation of proinflammatory mediator, kinins, in the brain and peripheral circulation in experimental epilepsy.     

国产与进口洛伐他汀治疗高脂血症的比较

目的 :比较国产与进口洛伐他汀治疗高脂血症的疗效。方法 :2 0 6例原发性高脂血症病人分为国产组 113例 (男性 68例 ,女性 45例 ,年龄 5 6a±s10a) ,给国产洛伐他汀 2 0mg ,po ,qd× 8wk ;进口组 93例 (男性 5 8例 ,女性 35例 ,年龄 5 7a±10a) ,给进口洛伐他汀 2 0mg ,po ,qd× 8wk。结果 :国产与进口洛伐他汀治疗前后所降低总胆固醇(TC)、三酰甘油 (TG)和低密度脂蛋白胆固醇 (LDL_Ch)差异均有显著意义 (P <0 .0 5 ) ,但 2组间比较差异无显著意义 (P >0 .0 5 )。结论 :国产与进口洛伐他汀有相似的调节血脂效果 ,两者使用均较安全