国产甲磺酸培氟沙星体内抗菌活性试验

口服和静脉给予国产甲磺酸培氟沙星对大肠杆菌-12、克氏肺炎杆菌-64和绿脓杆菌-14感染小鼠均有保护作用,其中口服给药的PD_(50)分别为1.08,5.87和8.10mg/kg;静脉给药的PD_(50)分别为0.54,3.10和7.02mg/kg。     

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     

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。     

萘普酮的解热,镇痛及抗炎作用

1、萘普酮,阿斯匹林及消炎痛对小鼠经醋酸诱导的血管通透性亢进的抑制作用,其ED_(50)分别为9.38mg/kg,26.25mg/kg及0.829mg/kg。 2、对致霉菌素,角叉菜胶及急性佐剂诱导的炎肿的抑制作用:25mg/kg的萘普酮的抗炎效力优于75mg/kg的阿斯匹林P<0.05。(大鼠)     

新合成抗菌剂—IMB-86001的毒理学研究

IBM-86001系新的喹诺酮类广谱抗菌剂。初步毒理学研究表明:本品急性毒性较低。小鼠口服LD_(50)为4571mg/kg,静注LD_(50)为     

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。     

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,     

国产甲磺酸培氟沙星体内抗菌活性试验

甲磺酸培氟沙星为新的氟喹诺酮类药。该药在体内对大肠杆菌、克氏肺炎杆菌和绿脓杆菌引起的小鼠全身性感染无论口服和静脉注射均有显著的保护作用,其疗效(ED_(50))与诺氟沙星相当或更好,明显地优于庆大霉素。甲磺酸培氟沙星静脉给药的体内抗菌活性比口服给药更好。     

三氯异氰酸,二氯异氰尿酸钠的毒性作用研究

1、本实验做了DccNa和TCCA对小鼠、大鼠、幼鱼、兔等动物的急性毒性实验。DccNa和TCCA一次口服给药对小鼠、大鼠、兔等动物的影响较小。小鼠口服的LD_(50)为1309mg/kg,属于基本无毒物。DccNa500mg/kg一次给药对兔的呼吸、血压、心率无明显的影响。故该产品对高等动物是比较安完的用于饮水和餐具的消毒,对人体是不会出现     

载羟基喜树碱聚乳酸-羟基乙酸微球的制备及相关性能研究

目的制备一种载羟基喜树碱的聚乳酸-羟基乙酸(PLGA)缓释微球,并考察其相关性能。方法采用乳化-溶剂挥发法制备羟基喜树碱PLGA微球,用扫描电子显微镜观察载药微球表面形态,测定平均粒径及跨距,高效液相色谱检测包封率、载药率及体外释放情况,改良寇氏法计算小鼠半数致死量。结果制备的载药PLGA微球呈圆球形,表面光滑,无粘连,平均粒径30.8μm,跨距0.9,包封率为85.5%、载药率4.28%,在体外28 d累积释放药物81.4%。羟基喜树碱小鼠静脉注射的半数致死量为18.4 mg/kg,肌内注射半数致死量为71.3 mg/kg,而羟基喜树碱PLGA微球肌内注射的半数致死量为138.5 mg/kg。结论乳化-溶剂挥发法制备的羟基喜树碱PLGA微球粒径适宜,包封率、载药率高,缓释效果好,毒性低,具有潜在的临床应用价值。     

Immunoregulatory effect of antibody on delayed-type hypersensitivity in mice

We analyzed the conditions for in vivo toleration of delayed-type hypersensitivity (DTH). The intravenous injection of a high dose of keyhole-limpet hemocyanin (KLH) into BALB/c mice did not induce DTH in vivo, but the serum titers of the anti-KLH antibody were significantly elevated. This lack of DTH response was antigen-specific, and the intravenous injection of the antigen induced effector-phase suppressor T cells. The findings suggested that the lack of a DTH response brought about by the intravenous injection of a high dose of antigen was not immunological tolerance. Treatment with a high dose (250 mg/kg) of cyclophosphamide - but not a low dose (50 mg/kg) - enhanced the DTH, but suppressed antibody production. These results indicate that humoral immune response participate in the regulation of DTH. In addition, the transfer of serum or immunoglobulin from mice that were injected intravenously with a high dose of the antigen suppressed the DTH. We concluded that the antibodies regulate DTH in the antigen-specific manner.     

Curative activity of spiramycin adipate by parenteral route in experimental septicemia in mice. Comparison with orally administered basic spiramycin

Experimental septicemia was induced in mice by intraperitoneal injection of 10 to 100 lethal doses of Staphylococcus aureus and Streptococcus pneumoniae. Animals were treated by a mixture of adipic acid and spiramycin (subcutaneous route) or by spiramycin base (oral route), 1 and 6 hours after infection. To determine the effective dose 50% that achieves survival of half the mice after 7 days, each drug was used in 6 dosages (mg/kg) and each dosage was given to 12 mice. In 21 independent experiments, ED50S of spiramycin adipate by the subcutaneous route were found to be 5 to 50 times lower than those of spiramycin base per os. These results are consistent with the high serum peak concentrations of spiramycin adipate observed following subcutaneous administration.     

Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice

Mesoporous hollow silica nanoparticles (MHSNs) are emerging as one of the new and promising nanomaterials for biomedical applications, but the biocompatibility of MHSNs in vivo has received little attention. In the present study, the systematic single and repeated dose toxicity, biodistribution and clearance of MHSNs in vivo were demonstrated after intravenous injection in mice. For single dose toxicity, lethal dose 50 (LD(50)) of 110?nm MHSNs was higher than 1000?mg/kg. Further repeated dose toxicity studies indicated no death was observed when mice were exposed to MHSNs at 20, 40 and 80?mg/kg by continuous intravenous administration for 14 days. These results suggest low toxicity of MHSNs when intravenous injection at single dose or repeated administrations. ICP-OES and TEM results show that the MHSNs mainly accumulate in mononuclear phagocytic cells in liver and spleen. In addition, these particles could be excreted from the body and the entire clearance time of the particles should be over 4 weeks. These findings would be useful for future development of nanotechnology-based drug delivery system and other biomedical applications.     

Effect of a novel interleukin-5 receptor antagonist, YM-90709, on antigen-induced eosinophil infiltration into the airway of BDF1 mice

A newly synthesized compound, YM-90709, 2,3-dimethoxy-6,6-dimethyl-5,6-dihydrobenzo[7,8]indolizino[2,3-b]quinoxaline, was previously reported to specifically inhibit the binding of interleukin-5 (IL-5) to its receptor (R) on human eosinophils. In this study, the intravenous injection of YM-90709 inhibited antigen-induced infiltration of eosinophils into the bronchoalveolar lavage fluid (BALF) of BDF1 mice, with an ED(50) value of 0.050mg/kg. Anti-murine IL-5 monoclonal antibody (mAb) also inhibited the infiltration of eosinophils with an ED(50) value of 0.035mg/kg. These results indicate that YM-90709, which is a novel IL-5R antagonist, inhibits antigen-induced eosinophil recruitment into the airway, the same as anti-IL-5 mAb does.     

Inhibition by prostaglandin E1 of gastric secretion in the dog

1. The effect of prostaglandin E(1) (PGE(1)) on gastric secretion was studied in dogs equipped with gastric fundic pouches, either innervated (Pavlov) or denervated (Heidenhain).2. PGE(1) inhibited gastric secretion (volume, acid concentration, acid output, pepsin output) when given either by constant intravenous infusion or by single intravenous injection. The degree of inhibition was dose dependent.3. The antisecretory effect of PGE(1) was demonstrated against gastric stimulants which operate through different mechanisms. Thus, PGE(1) counteracted the secretogogue effect of:(a) histamine dihydrochloride; the ED(50) was 0.5-1.0 mug/kg. min for a submaximal dose, and 1.0-1.5 mug/kg. min for a maximal dose;(b) pentagastrin; the ED(50) was around 0.25 mug/kg. min;(c) food; the ED(50) was 0.5 to 0.75 mug/kg. min;(d) 2-deoxyglucose; the ED(50) was less than 0.1 mug/kg. min.4. Although in some experiments, nausea and vomiting were observed during administration of PGE(1), the antisecretory property of the substance is not related to a vomiting reflex, since(a) an antiemetic, such as atropine, prevented vomiting without interfering with the effect of PGE(1), and(b) profuse vomiting elicited by apomorphine did not reduce gastric secretion stimulated by either histamine or pentagastrin.5. The mechanism by which PGE(1) inhibits gastric secretion is unknown. Studies by others have shown that the compound reduces gastric mucosal blood flow, inhibits acid formation from gastric mucosa when applied in vitro and may change the rate of formation of gastric cyclic AMP. It is likely that PGE(1) interferes with biochemical processes, within parietal and chief cells, which lead to elaboration of gastric juice.6. Unlike most gastric inhibitors, PGE(1) appears to act as a protective shield against most, if not all, gastric stimulants. Since prostaglandins of the E series are naturally occurring substances and are normally present in the stomach, they may play a role in the regulation of gastric secretion.     

Mouse strain differences in apomorphine-induced behavior: an empirical and methodological study

The behavioral response to 0.5-32.0 mg/kg apomorphine was evaluated in BALB/cJ, CBA/J, and C57BL/6J mice. Dose-response curves for each component of the drug-induced behavioral repertoire were derived, and ED50 (the dose at which 50% of the subjects meet or exceed a given rating) and slope were calculated for each. This method of analysis allows for a more quantitative estimate of drug sensitivity. Although some strain differences were observed in the qualitative characteristics of the response, differences in actual drug sensitivity (ED50s) were significant only at the higher ratings.     

褪黑素对胃肠运动的影响

目的: 研究不同浓度褪黑素(melatonin)对小鼠胃肠运动的影响。方法: 雄性C57BL小鼠腹腔内注射1 mg/kg、5 mg/kg、50 mg/kg和75 mg/kg浓度的褪黑素,分别在15 min和45 min后,检测结肠排出玻璃珠的变化;同时,在注射褪黑素75 mg/kg前腹腔内注射褪黑素拮抗剂luzindole(5 mg/kg),研究其对褪黑素作用的影响。另外,通过全胃肠道运输实验(伊文斯蓝排出实验)检测腹腔内注射不同浓度褪黑素(1 mg/kg、5 mg/kg、25 mg/kg和75 mg/kg)时胃肠运动的变化。结果: 腹腔内注射褪黑素后15 min,在低剂量组(1 mg/kg)结肠排出玻璃珠的时间缩短,与对照组比较差异显著(P<0.01);在高剂量组(75 mg/kg)结肠排出玻璃珠的时间明显延长(P<0.01),该抑制作用可被褪黑素拮抗剂luzindole有效拮抗(P<0.01)。腹腔内注射褪黑素后45 min,在5 mg/kg剂量时,结肠排出玻璃珠的时间明显缩短(P<0.01);而在1 mg/kg和50 mg/kg时,与对照组比较并无显著差异;在高剂量组(75 mg/kg)结果同上,即结肠排出玻璃珠的时间延长(P<0.05)。在胃肠道运输实验中,腹腔内注射褪黑素1 mg/kg和5 mg/kg后,运输时间缩短,排出伊文斯蓝粪粒所需时间减少,与对照组比较差异显著(均P<0.01);大剂量褪黑素(75 mg/kg)也明显延长胃肠道运输时间(P<0.01)。结论: 低剂量褪黑素促进胃肠运动,高剂量褪黑素降低胃肠运动,后者作用可被褪黑素受体拮抗剂luzindole阻断。     

Benzo(a)pyrene inhibits ovulation in C57BL/6N mice

Successful female reproductive function requires follicle growth, ovulation, and formation of the corpus luteum. Treatment of C57BL/6N mice with a single intraperitoneal injection of benzo(a)pyrene in doses ranging from 1 to 500 mg/kg produced a dose- and time-dependent decrease in the number of corpora lutea. This effect on the number of corpora lutea is most pronounced at 1 week after treatment, with a threshold of about 1 mg/kg, and an ED50 of 1.6 mg/kg. By 2 weeks after treatment partial recovery of follicle growth and ovulation occurred, as indicated by an increase in the ED50 to 20 mg/kg. Complete recovery of normal corpora lutea number occurs in mice treated with less than 100 mg/kg by 3 weeks after treatment, with little change in the ED50 noted between 3 and 4 weeks post-treatment, 78 mg/kg at both times. Mice treated with 100 or 500 mg/kg did not recover normal corpora lutea number over the course of this experiment. These data indicate that acute exposure to benzo(a)pyrene, and perhaps other polycyclic aromatic hydrocarbons, may have a transient adverse effect on follicle growth, ovulation, or formation of corpora lutea. A consequence of this effect, transient infertility, has been observed previously when exploring the effect of polycyclic aromatic hydrocarbons on murine reproduction.     

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.