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.     

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。     

左氧氟沙星致老年人不良反应25例分析

盐酸左氧氟沙星(levofloxacin,LOFLX)是新一代光学活性氟喹诺酮类抗菌药物,具有抗菌谱广,抗菌作用强的特点,适用于治疗包括厌氧菌在内的革兰阳性菌及革兰阴性菌引起的感染。其抗菌活性是氧氟沙星的2倍,耐药性低,安全性好。与其他喹诺酮类药物相比,其毒性小,不良反应常见为消化道反应,如厌食、恶心、便秘、腹泻,其发生率较低,一般耐受良好。此外有中枢兴奋,如失眠,头晕等。近年来,有文献报道左氧氟沙星出现不良反应,尤其对老年患者不良反应更为突出。本文对25例左氧氟沙星致老年人不良反应(ADR)进行分析探讨。1方法通过网络及手工检索,收…     

静脉滴注左氧氟沙星致精神异常1例

左氧氟沙星为氟喹诺酮类抗菌药,具有抗菌谱广、抗菌作用强的特点,对大多数革兰阴性菌和阳性菌以及军团菌、支原体、衣原体也有良好的抗菌作用,且用药前不需要做皮试,故广泛应用于临床。现就用药中出现1例精神异常,报道如下。     

25例左氧氟沙星致肝损害患者的相关因素分析

目的：分析左氧氟沙星致肝损害的特点,为临床安全用药提供参考。方法：利用《中国知网》、《万方医学网》和Pubmed数据库,检索左氧氟沙星致肝损害病例报告文献,分析左氧氟沙星致肝损害的特点。结果：收集左氧氟沙星致肝损害患者病例25例报告,其特点是男性患者和60岁以上的老年患者占比较高,其大多数为肝细胞型肝损害（17例）,潜伏期变异性较大,致病机制以过敏反应为主,联合使用肝毒性药物以及患有自身病毒性肝病、肾功能不全、心脏病、糖尿病等可能是危险因素,其中5例患者死亡。结论：左氧氟沙星的肝损害应引起临床医务人员的高度重视。     

乳酸左氧氟沙星致过敏性休克1例

乳酸左氧氟沙星属氟喹诺酮类抗菌药物。其抗菌谱广,抗菌作用强,对肺炎链球菌等具有良好的抗菌作用。乳酸左氧氟沙星的不良反应发生率较低．主要包括胃肠道症状、神经系统症状、皮肤症状等。本文报告了1例应用乳酸左氧氟沙星后致过敏性休克的病例。     

左氧氟沙星可致精神障碍

左氧氟沙星属于第三代喹诺酮类广谱抗菌药,是治疗感染性疾病的重要药物。2005年北京市5500余例由抗生素引起的不良反应中,喹诺酮类药物占38.1%。左氧氟沙星虽为喹诺酮类抗菌药中较为安全的品种,但近几年来,随着在临床上的广泛应用,有关其不良反应的报道也日趋增多。     

环丙沙星致肝损害32例文献分析

目的探讨环丙沙星致肝损害的规律与特点,为临床医生合理用药提供参考。方法检索国内外有关医药数据库,下载病例报告原文进行统计与分析。结果环丙沙星致肝损害病例报告32例,其中男性22例,40岁以上的中老年人23例。肝损害的主要临床表现为黄疸、恶心、腹痛、转氨酶升高,以肝细胞型为主,胆汁淤积型次之,混合型少见。中老年、男性、药物过敏史、原患肝病、合并肝毒性药物、再次用药、剂量过大、疗程过长等属高危人群和危险因素。经停药、采取相应治疗措施,大部分可恢复正常,但也可进展为慢性化、肝衰竭,严重者死亡。已有至少3例死亡报告。结论环丙沙星的肝损害严重不良反应应引起临床医务人员的高度重视。     

对喹诺酮类药物致癫痫能力进行早期评价的一种新方法

由于脑脊液为喹诺酮类药物的生物相部位，通过测定实验动物最大癫痫发作时脑脊液中喹酮类药物的浓度，可以评价该药物的致癫痫危险性，而且是早期提供致癫痫危险性信息的唯一途径。将该方法与传统的γ－氨基丁酸结合实验相结合，用于喹诺酮类药和开发早期预测药物的致癫痫危险性，确定药物化学结构与惊厥活性间的相互关系。     

环丙沙星注射液致精神异常1例

<正>1病例介绍患者,男,63岁,曾因反复胸闷、心悸、气促2月余诊断为心律失常(阵发性心房纤颤)住院1周,出院后3d突感胸痛、胸闷、出冷汗、烦燥不安来院就诊。检查:心电图及心肌酶检查(拟诊:冠心病,     

磁共振波谱分析及皮层脑电图在难治性癫痫手术中的定位意义

目的 探讨磁共振波谱分析结合皮层脑电图在手术治疗难治性癫痫定位癫痫灶的意义.方法 对16例难治性癫痫患者,根据其临床发作类型、体征、磁共振波谱分析、皮层脑电图定位癫痫灶,同时对癫痫灶进行手术干预.结果 随诊6个月～5年.根据1996年Engel疗效分级标准评测:Ⅰ级为10例、Ⅱ级为2例、Ⅲ级为3例、Ⅳ级为1例.Ⅰ级、Ⅱ级12例为临床治愈,Ⅲ级3例为好转,治愈率为75％,治愈好转率为93.8％.结论 磁共振波谱分析可在癫痫外科术前评估中发挥重要作用,结合皮层脑电图可提高致痫灶定位的准确率,提高手术的效果.     

神经肽Y对海人酸致痫大鼠中GABAB受体的影响

目的 探讨重组腺相关病毒载体神经肽Y(rAAV2/1-NPY-EGF-P)干预前后海人酸致痫大鼠海马中GABABR表达的变化.方法 将36只雄性Wistar大鼠随机分为三组:KA组(海人酸致痫大鼠组)、NPY组(神经肽Y干预组)及NS组(对照组).KA组大鼠海马CA3区注射海人酸,完成慢性模型,造模成功后不注射病毒;NPY组大鼠海马CA3区注射海人酸,完成慢性模型,造模成功后向脑室注射10μL滴度为5×10u vg/mL的神经肽Y进行基因转染;NS组海马CA3区注射等量的0.9％NaCl.三组大鼠各12只,在基因转染后2周、4周分别取6只观察其发作行为学变化,并采用RT-PCR检测GABABR的表达,以GAPDH为标准参照基因,以之定量分析基因表达的RQ值(相对定量值).结果 通过RT-PCR发现,KA组、NPY组及NS组、海马组织均有GABABR表达.KA组GABABR的基因表达较NS组呈下降趋势(P＜0.05),NPY组GABABR的基因表达呈上升趋势,差异有统计学意义(P＜0.05).结论 KA组中GABABR的表达明显下降,NPY组中GABABR的表达呈上升趋势.说明GABABR基因表达的降低可能是导致癫痫发生、发展的重要因素.NPY可能通过改变抑制性神经递质的GAB-ABR的表达来达到调控癫痫发作的目的.     

Penetration of ciprofloxacin, norfloxacin and ofloxacin into the aqueous humour of patients by different topical application modes

Objectives: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humour. Methods: Two hundred and twenty-four patients undergoing cataract extraction received 0.3% ciprofloxacin, norfloxacin or ofloxacin eye drops by two different administration modes with different frequencies and intervals of application. At the beginning of cataract extraction (0.5–3 h after the last drop), 50–100 μl aqueous fluid was aspirated from the anterior chamber and immediately stored at −80 °C. Antibiotic concentrations were measured using high-performance liquid chromatography. Results: Generally, topical ofloxacin and ciprofloxacin yielded aqueous humour levels higher than topical norfloxacin. The highest concentrations of all tested fluoroquinolones were measured after using an application mode, in which one drop was given every 15 min between 0600 hours and 0800 hours, prior to operation. When applied by this mode, ciprofloxacin achieved a mean aqueous level of 0.380 (±0.328) μg · ml⁻¹ (range 0.033–1.388 μg · ml⁻¹), norfloxacin 0.182 (0.118) μg · ml⁻¹ (range 0.038–0.480 μg · ml⁻¹) and ofloxacin 0.564 (0.372) μg · ml⁻¹ (range 0.064–1.455 μg · ml⁻¹). These mean concentrations were above the minimum inhibitory concentration (MIC₉₀), concentrations required for inhibition of 90% of pathogen strains in vitro of gram-negative bacteria, such as Proteus mirabilis and Escherichia coli. Therapeutic values above the MIC₉₀ of Staphylococcus epidermidis, the pathogen causing eye infections most frequently, were reached by 67.5% of patients after ofloxacin and by 41% after ciprofloxacin, but never after norfloxacin treatment. Conclusion: Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humour concentration. This fluoroquinolone may be an useful ophthalmic agent for topical antibacterial management, but it does not seem to be prophylactically effective against Streptococcus pneumoniae or Pseudomonas aeruginosa. Received: 22 April 1997 / Accepted: 8 June 1997     

环丙沙星致痫大鼠脑脊液氨基酸含量的变化

目的观察环丙沙星(CPLX)致痫大鼠脑脊液(CSF)中兴奋性氨基酸[天冬氨酸(Asp)、谷氨酸(Glu)]和抑制性氨基酸[7-氨基丁酸(GABA)、甘氨酸(Gly)]含量的变化,探讨CPLX致痫的发生机制.方法给雄性大鼠静脉注射CPLX 100mg/kg,于用药前,在小脑延髓池抽取CSF作为对照,用药后癞痫发作40min时抽取CSF作为试验样本.CSF中氨基酸的含量用高效液相色谱法测定.结果癫痫发作后40min时,CSF中7-氨基酸(GABA)含量为(1.72士0.94μ)mol/L,明显高于用药前的(0.31士0.23)μmol/L(P＜0.01),而天冬氨酸(Asp)、谷氨酸(Glu)、甘氨酸(Gly)的含量分别为(9.64士2.62)μmol/L、(9.54士8.58)μmol/L、(18.96±2.84)μmol/L,均明显低于用药前的(14.57±5.85)μmol/L、(16.19士7.56)μmol/L、(27.66士8.01)μmol/L(P＜0.05～0.01).结论静注CPLX引起大鼠癫痫发作是由于CPLX明显影响了中枢神经系统内兴奋性氨基酸和抑制性氨基酸的代谢平衡,氨基酸含量的变化并可通过CSF中的氨基酸含量反映出来.     

Behaviour-related effects of nicotine on slow EEG waves in basal nucleus-lesioned rats

The basal magnocellular nucleus is assumed to play a crucial role in cholinergic activation of the cortical EEG. The aim of this study was to establish whether intraperitoneally applied nicotine may counteract the power asymmetry of the slow waves in the cortical EEG of both hemispheres after an unilateral lesion in the basal nucleus. In 17 rats the basal nucleus (substantia innominata/ventral pallidum) was unilaterally lesioned by ibotenic acid. The lesion produced unilateral power increases of all frequencies up to 20 Hz in the frontal EEG that increased with higher arousal level. Additionally, synchronized spike and wave discharges appeared in the frontal EEG. The results indicate that the basal nucleus suppresses especially the delta EEG waves in the frontal motor cortex during motor active behaviour. Nicotine (0.1 and 1 mg/kg) partially counteracts the power asymmetry of frontal slow waves (2–6 Hz) only during exploratory sniffing but not during grooming and waking immobility. Physostigmine (1 mg/kg) was also effective during exploratory sniffing. The results may indicate a role of nicotinic mechanisms in the information input component of exploratory behaviour.     

The bactericidal activity of levofloxacin against ampicillin-resistant and ampicillin-susceptible Haemophilus influenzae in comparison with ofloxacin, ciprofloxacin and sparfloxacin

The bactericidal activity of levofloxacin against four Haemophilus influenzae clinical isolates (two ampicillin-resistant and two susceptible) was compared with that of ofloxacin, ciprofloxacin and sparfloxacin at concentrations simulating the peak serum concentrations obtained with the recommended oral doses. Bactericidal activity was assessed using time-kill curves and minimum kill-time values. Both concentrations of levofloxacin rapidly killed all the study strains, with mean kill times of 4 h and no viable bacteria remaining after 18-h exposure. The bactericidal activities of levofloxacin, ofloxacin and sparfloxacin were similar. The minimum kill-times for both concentrations of ciprofloxacin were 28-35% longer than those of levofloxacin. These results support the use of levofloxacin for H. influenzae infections, including ampicillin-resistant strains.     

Oral toxicity of pefloxacin, norfloxacin, ofloxacin and ciprofloxacin: comparison of biomechanical and histopathological effects on Achilles tendon in rats

Four fluoroquinolones (pefloxacin, norfloxacin, ofloxacin and ciprofloxacin) were compared according to their biomechanical and histopathological effects on rat Achilles tendon. Wistar rats were divided into one untreated control and four treatment groups in parallel. Pefloxacin mesylate dihydrate (40 mg/kg), norfloxacin (40 mg/kg), ofloxacin (20 mg/kg) and ciprofloxacin (50 mg/kg) were administered by gavage twice daily for three consecutive weeks. 6 weeks after treatment, the test animals were euthanised and Achilles tendon specimens were collected. A computer monitored tensile testing machine was utilised for biomechanical testing. The mean elastic modulus of the control group was significantly higher than that of the norfloxacin and pefloxacin groups (p<0.05 and p<0.01, respectively). The mean yield force (YF) of the control group was significantly higher than those of ciprofloxacin, norfloxacin and pefloxacin groups (p<0.001, p<0.05 and p<0.01, respectively). The mean ultimate tensile force (UTF) of the control group was significantly higher than of the ciprofloxacin, norfloxacin, and pefloxacin groups (p<0.001, p<0.05 and p<0.01, respectively). Hyaline degeneration and fibre disarrangement were observed in the tendons of the ciprofloxacin, pefloxacin, and ofloxacin treated-groups, whereas myxomatous degeneration was observed only in the ciprofloxacin and pefloxacin groups. In conclusion, these findings in our rat model reveal significant deterioration of biomechanical parameters following fluoroquinolone exposure, and indicate significantly higher biomechanical toxicity for ciprofloxacin and pefloxacin.     

茶多酚对大鼠肠缺血再灌注肠损伤的保护作用

目的:研究茶多酚(TP)对大鼠肠缺血再灌注(I/R)所致肠损伤的保护作用及其可能的作用机制,为其临床新用途提供实验依据。方法:大鼠随机分为肠I/R损伤对照组、假手术组及TP给药组(100,50,25和12.5 mg.kg-1),通过夹闭肠系膜上动脉1 h、再灌注2 h,建立肠I/R损伤模型。于缺血前20 m in舌下静脉注射药物,假手术组仅分离、不夹闭肠系膜上动脉。再灌2 h后,各组取血及中段小肠组织,测定血清及小肠组织中超氧化物歧化酶(SOD)、丙二醛(MDA)和一氧化氮(NO)含量,光镜下观察小肠组织形态学改变。结果:与假手术组相比,肠I/R损伤对照组血清及小肠组织中的SOD活力降低,MDA和NO含量升高,镜检发现小肠有明显组织形态学损伤。与肠I/R损伤对照组相比,TP组呈剂量依赖性增强SOD活力,减少MDA及NO含量,减轻小肠组织形态学损伤。结论:TP对肠I/R所致肠急性损伤有显著的及剂量依赖性的保护作用,可能与其自由基清除作用有关。