盐酸米托蒽醌氯化钠注射液急性毒性研究

盐酸米托蒽醌氯化钠注射液小鼠静脉给药的LD_(50)无法实测出来,最大耐受量为12.5mg/ kg,盐酸米托蒽醌氯化钠注射液小鼠的腹腔给药的最大耐受量为12.5mg/kg。据文献记载,米托蒽醌小鼠静脉给药LD_(50)为13.92mg/kg,小鼠静脉给药LD_(10)为10.43mg/kg;大鼠静脉给药的LD_(50)为7.17mg/kg,大鼠静脉给药LD_(10)为4.86mg/kg;说明盐酸米托蒽醌氯化钠注射液的急性毒性不大于米托蒽醌的毒性,是较为安全的制剂。     

溴莫普林与甲氧苄啶体内抗菌作用比较

试验用昆明种小鼠腹腔感染致死量的临床分离菌株,再给予溴莫普林(BDP)与甲氧苄啶(TMP)口服及皮下给药,分别求其ED50。试验结果表明口服BDP及TMP对感染金葡菌95191的ED50分别为31．6与62．0mg/kg,皮下注射分别为9．4与17．3mg/kg;对感染大肠杆菌小鼠BDP与'MP的ED50口服分别为25．2与63．0mg/kg,与下注射为16．0与59．1mg/kg;对感染嗜血流感杆菌9501的ED50,口服分别为9．2与83．0mg/kg;皮下注射则分别为7．5与28．4mg/kg;对感染肺炎链球菌9511的口服ED50分别为50．4与101．1mg/kg。结果表明BDP口服体内抗菌作用比TMP强,对嗜血流感杆菌要强9倍,对其它细菌要强2倍左右(p值均小于0．05～0．01)。BDP皮下给药的抗菌作用要强于口服。     

国产环丙沙星的急性和亚急性毒性

环丙沙星(Ciprofloxacin)是第三代吡酮酸类抗菌药物,具有抗菌谱广,抗菌活性强的特点。急性毒性:小鼠和大鼠口服LD_(50)大于5000mg/kg。小鼠静注和肌注给药的LD_(50)分别为223.88 mg/kg和大于1000mg/kg。亚急性毒性:Wistar大鼠,随机分成4组;环丙沙星3个剂量组(100、250和500mg/kg/天)和溶剂对照组,每组20只,雌雄各半,每天口服一次,共给药2月结果表明环丙沙星各组的给药初期摄水量均高于对照组,雄鼠250和500mg/kg组体重增长     

国产诺氟沙星注射液的体内抗菌作用及毒性研究

国产诺氟沙星注射液对大肠杆菌、克氏肺炎杆菌及绿脓杆菌感染小鼠,一次肌注的ED_(50)值分别为1.08、3.10用6.42mg/kg,而对照的诺氟沙星口服片剂二次口服的ED_(50)分别为6.26、15.33及12.45mg/kg,显示诺氟沙星注射给药较片剂口服疗效更好。该注射液静注和肌注对小鼠的LD_(50)分别为87.88及562.65mg/kg,静注或静脉滴注未见血管及组织损伤,但肌注时局部刺激性较大。     

感昌康毒理学与药效学的开发研究

感冒康是仿制日本80年代上市的MP系列混合抗感冒药。报告其毒理药理试验结果。一、毒理学:小鼠口服的LD_(50)为825mg/kg,腹腔注射的LD_(50)为361mg/kg,大鼠口服的LD_(50)在3500mg/kg以上。大鼠连续给药三周,家犬连续给药一月,对象、肝     

DHAQ的急性毒性及对小鼠移植性肿瘤的实验治疗

本文就国产DHAQ对小鼠和兔的急性毒性和小鼠移植性肿瘤的实验治疗进行了研究并与同类药阿霉素作了比较。结果测得小鼠一次静脉及腹腔注射本品观察21天的LD_(50)分别为6.58及6.48mg/kg与同期所测阿霉素的LD_(50)值相近而略低,二药在剂量范围为5—25mg/kg时引起动物死亡的最早日期为给药后3天,直到21天仍有个别动物陆续死亡,显示毒性的延     

青萬素衍生物预防血吸虫病的初步实验研究

对一硝基苯甲酰还原青蒿素(代号79019)为上海医工院合成的又一种青蒿素衍生物。一、急性毒性试验:79019对小鼠口服与肌肉注射的急性LD(50)分别为:1307.12mg/kg(95％可信限为1159.9-1446.3mg/kg);177.5mg/kg(158.5-192.6mg/kg);     

氟啶酸的毒性研究

氟啶酸(Fudinic Acid)为一合成广谱抗菌药,对革兰氏阳性细菌和革兰氏阴性细菌均有较强的抗菌作用,我们对氟啶酸进行的急性毒性和亚急性毒性研究如下: 急性毒性:氟啶酸对小鼠和大鼠口服急性毒性很低,LD_(50)在5000mg/kg以上;小鼠静脉LD(50)雄性为370mg/kg,雌性为350mg/kg,小鼠皮下LD(50)雄性为1220mg/kg,     

安定联合赖氨匹林直肠给药用于小儿高热惊厥急救临床观察

目的 观察安定联合赖氨匹林溶液直肠给药治疗小儿高热惊厥的疗效.方法 将40例高热惊厥患儿随机分为对照组19例和治疗组21例.治疗组直肠注入赖氨匹林和安定混合液(赖氨匹林20mg/kg,安定0.05mg/kg),对照组给予赖氨匹林注射剂(20mg/kg)稀释后肌肉注射,安定注射液(剂量:0.5mg/kg,最大剂量不超过20mg)肌肉注射.比较两组在用药后5min、15min的止惊效果和30min、60min内的退热效果.结果 治疗组的止惊效果和退热效果明显高于对照组(P＜0.01),差异有统计学意义.结论 安定联合赖氨匹林直肠给药用于治疗小儿高热惊厥,是静脉或口服给药困难时重要的替代途径,能有效保证高热惊厥的及时抢救.     

牛磺酸锌对血管性痴呆小鼠学习和记忆能力的影响

目的:研究牛磺酸锌(taurine-zinc,TZC)对血管性痴呆(vascular dementia,VD)小鼠学习和记忆能力的影响及其相关机制。方法:将小鼠随机分为模型组、假手术组及TZC 50 mg/kg组、100 mg/kg和200 mg/kg给药组。给药组每天按10 m L/kg灌胃,假手术组和模型组给予等体积蒸馏水,灌胃14 d后,利用双侧颈总动脉阻断合并尾静脉放血法制备小鼠VD模型。ELISA检测脑组织中肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)的水平;分光光度计法检测脑组织诱导型一氧化氮合酶(i NOS)活性和一氧化氮(NO)含量的变化;利用跳台和水迷宫实验观察小鼠的学习和记忆能力。结果:TZC 50 mg/kg、100 mg/kg和200 mg/kg组小鼠脑组织中TNF-α、IL-1β、i NOS和NO水平均降低。在水迷宫实验中,与模型组相比,TZC 100 mg/kg和200 mg/kg组的潜伏期缩短,TZC 50mg/kg、100 mg/kg和200 mg/kg组的错误次数减少;在跳台实验中,TZC 50 mg/kg、100 mg/kg和200 mg/kg组较模型组潜伏期延长,错误次数减少(P0.05)。结论:TZC对VD小鼠的学习和记忆能力有改善作用,其机制可能与降低脑组织TNF-α、IL-1β、i NOS和NO水平有关。     

Comparative efficacy of ampicillin, chloramphenicol, cefotaxime, ceftriaxone and pefloxacin in experimental Salmonella typhimurium infection

The efficacies of various antibiotics were compared in Salmonella typhimurium infection in mice. Treatment began 24 h after challenge. Antibiotics were given subcutaneously every 12 or 24 h in the following daily doses: 200 mg/kg for ampicillin, 100 mg/kg for chloramphenicol, cefotaxime and ceftriaxone, 50 mg/kg for pefloxacin. The number of bacteria in the spleens was determined after 3 and 7 days of treatment. In animals treated with ceftriaxone or pefloxacin the mean number of bacteria per spleen was from one to two log10 lower than in animals treated with other antibiotics. Similar results were obtained in genetically susceptible or resistant mice. The MIC being similar for cefotaxime, ceftriaxone and pefloxacin, the better in vivo activity of the two latter drugs appears to be related to their pharmacokinetic properties.     

Enhanced Toxicity for Mice of Combinations of Antibiotics with Escherichia coli Cells or Salmonella typhosa Endotoxin

Enhanced lethality for BALB/c mice has been observed after the administration of Salmonella typhosa endotoxin with either actinomycin D, cycloheximide, or nogalamycin. The dose of actinomycin D required to kill half of the mice (LD₅₀) was 0.8 mg/kg in normal animals, 0.35 mg/kg in mice administered 0.08 mg of endotoxin per kg, and 0.28 mg/kg in mice administered 0.2 mg of endotoxin per kg. The LD₅₀ of endotoxin in normal mice was 12 mg/kg and in mice given 0.4 mg of actinomycin D per kg was 0.067 mg/kg. The LD₅₀ of actinomycin D in mice administered 1.8 × 10⁸ live Escherichia coli cells per kg or 1.8 × 10⁹ heat-killed E. coli cells per kg was reduced to 0.4 mg/kg. The LD₅₀ of cycloheximide was 181 mg/kg in normal animals and 28 mg/kg in mice administered 4 mg of endotoxin per kg. The LD₅₀ of endotoxin in mice given 120 mg of cycloheximide per kg was 0.02 mg/kg. Enhanced lethality due to various combinations of cycloheximide and endotoxin was abolished by pretreatment of mice with endotoxin. The LD₅₀ of nogalamycin was 21 mg/kg in normal mice and 13 mg/kg in mice receiving 1 mg of endotoxin per kg.     

BDNF在Parkinson病小鼠的表达及丙戊酸盐对其影响的研究

为观察Parkinson病(PD)小鼠脑源性神经营养因子(BDNF)含量的变化及丙戊酸盐(valproate,VPA)对BDNF表达的影响,探讨VPA对PD病神经元的保护作用,本研究采用C57BL/6小鼠1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methy1-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)法建立PD模型。小鼠随机分为4组:盐水对照组(NS+NS)、模型组(NS+MPTP)、模型给药组(VPA+MPTP)和单独给药组(VPA+NS)。MPTP造模方法为每日颈部皮下注射MPTP(20 mg/kg),连续8 d。VPA在MPTP造模前1 d开始给药(400 mg/kg,i.p.),共14 d。单独给药组给予VPA,同时用等量的生理盐水代替MPTP。盐水对照组仅给予等量的生理盐水。采用原位分子杂交方法观察BDNF的表达,并对检测部位恒定视野内BDNF的阳性细胞进行灰度扫描和统计学分析。结果显示:与盐水对照组相比,模型组、模型给药组和单独给药组小鼠纹状体、海马、皮质内BDNF的表达均增强。该结果提示,PD小鼠神经元内BDNF增多,可能有利于受损神经元的修复;丙戊酸盐可能通过促进BDNF的表达而保护神经元。     

Modification of Immune Response by Cinnarizine

Effects of cinnarizine on immune response in mice were investigated. Mice were orally administered with cinnarizine and were immunized with sheep red blood cells (SRBC) intravenously. Numbers of plaque forming cells (PFC) to SRBC in spleen of these mice were assayed and delayed-type hypersensitivity (DTH) response to SRBC was measured. 1) PFC response in immunization with 5 × 10⁶ cells/mouse of SRBC was enhanced by administration of 25 mg/kg of cinnarizine, while the response in immunization with 5 × 10⁸ cells/mouse was suppressed by 25 to 200 mg/kg of cinnarizine. 2) From study on timing of administration, suppression of PFC response by 6.25 to 200 mg/kg of cinnarizine was observed at 24 hr. after the immunization. 3) 12.5 to 200 mg/kg of cinnarizine suppressed polyclonal B cell activation induced by lipopolysaccharide (LPS). 4) Colchicine induced suppressor T cell inactivation was prevented by administration of 50 mg/kg of cinnarizine and it was suggested that cinnarizine may induce suppressor T cells from the study of adoptive cell transfer system. 5) 50 mg/kg of cinnarizine showed the suppression of DTH response in expression phase, but not in induction phase. It was concluded that immune responses in mice were modified by cinnarizine.     

Modification of Immune Response by Cinnarizine

Abstract

Effects of cinnarizine on immune response in mice were investigated. Mice were orally administered with cinnarizine and were immunized with sheep red blood cells (SRBC) intravenously. Numbers of plaque forming cells (PFC) to SRBC in spleen of these mice were assayed and delayed-type hypersensitivity (DTH) response to SRBC was measured. 1) PFC response in immunization with 5 × 10⁶ cells/mouse of SRBC was enhanced by administration of 25 mg/kg of cinnarizine, while the response in immunization with 5 × 10⁸ cells/mouse was suppressed by 25 to 200 mg/kg of cinnarizine. 2) From study on timing of administration, suppression of PFC response by 6.25 to 200 mg/kg of cinnarizine was observed at 24 hr. after the immunization. 3) 12.5 to 200 mg/kg of cinnarizine suppressed polyclonal B cell activation induced by lipopolysaccharide (LPS). 4) Colchicine induced suppressor T cell inactivation was prevented by administration of 50 mg/kg of cinnarizine and it was suggested that cinnarizine may induce suppressor T cells from the study of adoptive cell transfer system. 5) 50 mg/kg of cinnarizine showed the suppression of DTH response in expression phase, but not in induction phase. It was concluded that immune responses in mice were modified by cinnarizine.     

Neuromodulatory role of serotonin in the anticonvulsant activity of 2-phenylbenzoate of 3-diethylamino-1-propanol.HCl (JAW-669)

The role of serotonin in the mediation of the anticonvulsant activity of JAW-669 was investigated against maximal electric shock (MES)-induced seizures in mice. A dose-dependent protection against seizures was provided by JAW-669 (4, 6 and 8 mg/kg, IP) and the calculated ED50 value was 6.01 mg/kg, IP. Pretreatment of mice with 5-hydroxytryptophan (50 mg/kg, IP) 2 hr before the administration of JAW-669 (6.01 mg/kg, IP) was found to cause a 40% increase in the ability of JAW-669 to provide protection against MES-induced seizures. Similar pretreatment with tryptophan (100 mg/kg, IP, 1 hr) caused a 30% decrease in the anticonvulsant activity of JAW-669. Prior administration of p-chlorophenylalanine (300 mg/kg, IP, 48 hr) and methysergide (10 mg/kg, IP; 0.5 hr) before administration of JAW-699 caused a 66% and 74% decrease, respectively, in the ability of JAW-669 to provide protection against MES-induced seizures. These results suggest a facilitatory role of serotonin in the anticonvulsant activity of JAW-669.     

Neuroprotection by caffeine: time course and role of its metabolites in the MPTP model of Parkinson's disease

Epidemiological studies have raised the possibility of caffeine serving as a neuroprotective agent in Parkinson's disease (PD). This possibility has gained support from findings that dopaminergic neuron toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or other neurotoxins is attenuated by co-administration of caffeine in mice. Here we examined the time window of caffeine's neuroprotection as well as the effects of caffeine's metabolites (theophylline and paraxanthine) in the MPTP mouse model of PD. In the first experiment, caffeine pre-treatment (30 mg/kg ip) significantly attenuated MPTP-induced striatal dopamine depletion when it was given 10 min, 30 min, 1 h, or 2 h but not 6 h before MPTP (40 mg/kg ip) treatment. Meanwhile, caffeine post-treatment also significantly attenuated striatal dopamine loss when it was given 10 min, 30 min, 1 h or 2 h but not 4 h, 8 h or 24 h after MPTP injection. In the second experiment, both theophylline (10 or 20 mg/kg) and paraxanthine (10 or 30 mg/kg) administration (10 min before MPTP) significantly attenuated MPTP-induced dopamine depletion in mice, as did caffeine (10 mg/kg) treatment. Thus the metabolites of caffeine also provide neuroprotective effects in this mouse model of PD. The data suggest that if caffeine protects against putative toxin-induced dopaminergic neuron injury in humans, then precise temporal pairing between caffeine and toxin exposures may not be critical because the duration of neuroprotection by caffeine may be extended by protective effects of its major metabolites.     

Assessment of the effects of ISIS 2302, an anti-sense inhibitor of human ICAM-1, on cellular and humoral immunity in mice

ISIS 2302 is a phosphorothioate oligonucleotide designed to inhibit human ICAM-1 and is intended for treatment of inflammatory diseases. Molecules of this class are known to elicit pro-inflammatory effects, and immunotoxicity studies were performed in mice to elucidate the nature of effects of ISIS 2302 on mammalian immune function. ISIS 2302 (1, 5, 20, or 50 mg/kg/dose) was administered intravenously every other day for 27 days. The pro-inflammatory properties of the drug were observed at doses > or = 20 mg/kg. A dose-dependent increase in spleen weight was associated with increased absolute splenocyte and B-lymphocyte counts after the 50 mg/kg/dose regimen. The mitogenic response of B-lymphocytes to bacterial lipopolysaccharide was increased after the 20 and 50 mg/kg/doses but antibody-forming cell activities remained unchanged. Total serum IgG concentration was decreased after the 20 and 50 mg/kg/dose regimens but IgM titers were unchanged. Increases in IL-6, IL-12, and MCP-1 as well as NK cell activity were observed after administration of 20 and 50 mg/kg/dose. Cytotoxic T-lymphocyte activity was decreased by the 50 mg/kg/dose regimen. Other changes in immune function were not observed in ISIS 2302-dosed mice. ISIS 3082, a murine active ICAM-1 inhibitor, was used to demonstrate the anti-inflammatory activity of ICAM-1 inhibition in the 2,4-dinitrofluorobenzene-induced contact sensitization model. Intravenous administration of 1 mg/kg of ISIS 3082 every other day for 27 days was unequivocally anti-inflammatory in the contact sensitization test. The results of these experiments support the conclusion that the prophlogistic effects of ISIS 2302 in mice are observed only at suprapharmacologic doses.     

尼古丁对Parkinson小鼠黑质多巴胺能神经元及小胶质细胞的影响

为探讨尼古丁对多巴胺能神经元的保护作用,本研究采用尼古丁(0.25mg/kg)预处理C57BL/6J小鼠,再给予1-甲基-2-乙基-1,2,3,6-四氢吡啶(MPTP;20mg/kg)诱导Parkinson病(PD)小鼠模型。通过行为学检测和中脑黑质致密部(SNc)的酪氨酸羟化酶(TH)以及OX-42的免疫组织化学染色,观察了尼古丁对PD小鼠的行为以及黑质多巴胺能神经元和小胶质细胞的影响。结果显示:经尼古丁预处理可以明显减轻PD小鼠的行为障碍,增加TH免疫阳性的多巴胺能神经元的数量,并且可以抑制SNc内小胶质细胞的增生。本研究结果提示,尼古丁可保护多巴胺能神经元,而抑制小胶质细胞的增生可能是其作用机制。     

Eradication of convalescent-phaseSalmonella carriage in children with two oral doses of pefloxacin

Fifteen children (age range 1.5 months to 7.2 years), who were excluded from schools or nurseries due to asymptomatic convalescent-phase non-typhoidalSalmonella carriage, received two oral doses of pefloxacin (12 mg/kg on days 1 and 4) and were examined on days 10, 30, 45 and 60. Definitive eradication was observed in 13 patients, all of whom had initial lowSalmonella counts in stools and were culture-negative by day 10. In the two patients who failed to respond, the same treatment was effective when repeated 4 and 6 months later respectively. No side-effects were observed. In six other children, considered as controls, eradication by day 10 was observed in only one case after administration of amoxicillin for eight days. Two oral doses of pefloxacin could be a useful and safe means for eleminatingSalmonella carriage in young children.