美金胺重复用药对新生大鼠的毒性反应

目的N-甲基-D-天冬氨酸受体离子通道拮抗剂美金胺对缺氧缺血具有明显的脑保护效果,观察重复应用大剂量美金胺对SD新生大鼠可能造成的不良影响。方法实验于2003-10/2004-03在新华医院中心实验室进行。选用7日龄SD新生大鼠80只,随机分为美金胺54,35,23m g/(kg·d)组及对照组4组,每组20只。连续14d分别经腹腔注射美金胺54,35,23mg/(kg·d)或注射用水(10μL/g)。14d后每组取13只大鼠给予断头处死,余7只大鼠停药恢复1周后断头处死,分别观察大鼠用药后的毒性反应及体质量增长情况。结果78只大鼠进入结果分析。①各剂量美金胺组动物在用药后均有不同程度的不良反应,主要发生在用药后第1～5天,但均能在用药后三四个小时内恢复正常。②美金胺54,35,23m g/(kg·d)组分别在用药后第6,5,4天出现耐受。其中美金胺54m g/(kg·d)组2只大鼠分别在连续用药第10天和第12天死亡,其他动物均存活。③各剂量组动物在用药后均有不同程度的体质量增长减缓,连续用药14d后美金胺54,35,23mg/(kg·d)组大鼠体质量明显低于对照组[(29.26±3.61),(30.46±4.10),(30.57±2.82),(37.72±3.04)g,P<0.01]。④停药7d后,美金胺35,23mg/(kg·d)组大鼠体质量与对照组比较差异已不明显,但美金胺54mg/(kg·d)组大鼠体质量仍显著低于对照组[(56.52±10.68),(74.05±5.13)g,P<0.01]。结论①不同剂量的美金胺连续应用14d,可能会对大鼠的生长有抑制作用,但停药后可获代偿性恢复。②新生大鼠对美金胺有较好的耐受性。     

84消毒液重复染毒对大鼠毒性试验研究

摘要 目的 研究SD大鼠反复暴露于84消毒液对多种器官的伤害情况。方法 SD大鼠30只,雌雄各半,在密闭空间内分别按100 mL/m2喷洒含0(对照组)、400、10 000 mg/L 次氯酸钠的84消毒液,大鼠暴露2次/d,每次1 h,持续28 d,腹主动脉穿刺收集血样,用于血液学和血液生化指标检测,于第29天,所有大鼠麻醉后实施安乐死,采集肝、肾、心、脾、肺、气管、眼球和皮肤等重要脏器进行进一步检查。结果 高剂量组大鼠重复染毒28 d后,气管、肺、肝、肾、血液系统出现病变,眼和呼吸道出现急性刺激症状,血细胞增多和凝血功能障碍,气管、肺、肝和肾发生病理学改变。低剂量组和对照组无异常改变。结论 长期大剂量接触84消毒液可能对动物机体健康造成不良影响,在使用中应加强个人防护。     

不同剂量美金胺对HIBD新生大鼠的脑保护作用及机制分析

目的 探讨不同剂量美金胺对缺氧缺血性脑损伤(HIBD)新生大鼠的脑保护作用及机制。方法 144只新生大鼠随机分为六组,假手术组大鼠仅将颈部皮肤切开,分离右侧颈总动脉,不进行结扎及缺氧处理。其余五组建立缺氧缺血性脑损伤新生大鼠模型。药物组四组分别腹腔注射不同剂量美金胺(13 mg/kg、26 mg/kg、39 mg/kg、52 mg/kg),模型对照组分别腹腔注射等量生理盐水。分析六组新生大鼠皮质、纹状体、海马及丘脑的脑损伤评分;六组新生大鼠皮质、海马区(海马CA1、海马CA3及齿状回)、纹状体及皮质下蛋白的TUNEL阳性细胞计数;六组新生大鼠皮质、海马区(海马CA1、海马CA3及齿状回)、纹状体及皮质下蛋白的Caspase-3阳性细胞计数;比较六组新生大鼠的神经功能及六组新生大鼠的缺氧缺血处理后的12 h、48 h、72 h的胶质细胞源性营养因子(GDNF)蛋白表达水平。结果 假手术组大鼠不同脑区域损伤评分、TUNEL及Caspase-3阳性细胞计数相比,差异均无统计学意义(P> 0. 05);在其余五组新生大鼠中,皮质、纹状体、海马及丘脑区域脑损伤评分比较差异均有统计学意义(P <0. 05),模型对照组、药物1组、药物2组、药物3组及药物4组的TUNEL阳性细胞计数均明显高于假手术组,表明造模成功。在海马CA1、皮质下蛋白中的的TUNEL阳性细胞计数差异有统计学意义,在海马CA3、齿状回及皮质下蛋白中的Caspase-3阳性细胞计数差异有统计学意义(P <0. 05),以上比较顺序均为模型对照组>药物1组>药物2组>药物3组>药物4组;六组新生大鼠的神经功能比较差异有统计学意义(P <0. 05),术后12 h、48 h、72 h时,六组新生大鼠的GDNF蛋白表达水平具有统计学意义,神经功能及GDNF蛋白表达水平顺序均为模型对照组<药物1组<药物2组<药物3组<药物4组<假手术组,以上各项指标中除药物3组与药物4组间比较差异无统计学意义(P> 0. 05)外,其余组间比较差异均有统计学意义(P <0. 05)。结论 随着美金胺剂量的增加,其对HIBD新生大鼠的脑保护作用逐渐增加,最佳剂量为39 mg/kg,可能美金胺可提高HIBD大鼠的GDNF蛋白表达水平有关。     

新生大鼠反复惊厥对海马区肾上腺皮质激素受体表达的影响

目的 研究新生期大鼠反复惊厥对海马区肾上腺皮质激素受体MR和GR表达的影响,以及对成年期大鼠记忆功能的影响,探讨发育期脑损伤和脑内相关受体之间的相互关系.方法 生后7 d的SD大鼠随机分成两组,每组40只,惊厥组每日吸入三氟乙醚诱导惊厥发作1次,每次持续30 min,连续6 d;于反复惊厥后1、3、7、30、60 d处死大鼠取脑,分别采用免疫组织化学方法观察大鼠海马肾上腺皮质激素受体MR和GR表达的变化.最后一组大鼠处死前于第61～65天行Morris水迷宫实验,检测大鼠的学习记忆功能.对照组同样操作但不吸入三氟乙醚.结果 61～64 d,两组大鼠寻找平台时间均逐渐缩短,惊厥组大鼠在第64天的平均寻找平台时间[(82 424.3±35 622.0)ms]与对照组[(40 712.4±29 467.6)ms]比较明显延长(P=0.001).在第65天,惊厥组大鼠120 s内穿越原平台位置次数[(1.2±0.9)次]较对照组[(3.1±1.3)次]明显减少(P<0.001).免疫组化结果显示新生大鼠反复惊厥后的1、3、7、30、60 d海马CA1～4区GR、MR的表达较埘照组明显降低(P<0.05).结论 海马区GR及MR随脑发育成熟表达不断增高,呈现一定规律及分布特点,参与了脑发育过程.新生大鼠反复惊厥造成海马GR、MR表达的持续异常,参与发育期脑损伤.     

几种常见抗肿瘤药物的毒性反应及护理对策

肿瘤是严重威胁人类健康的常见病、多发病之一，化学治疗在肿瘤治疗中占有重要地位。抗肿瘤药因缺乏选择性，对人体正常组织细胞毒性作用是经常的，有时甚至是严重的。因此应当引起高度重视，特别是临床护理工作者，必须熟知药物的毒性，不断积累化疗护理工作经验，制定护理计划，严密观察化疗后病人的反应，同时采取减少毒性反应的措施。尽可能的降低病人的不适及痛苦反应。     

大剂量阿糖胞苷的中枢神经毒性反应

大剂量阿糖胞苷(HD-Ara-C)已应用于急淋、急非淋白血病、非何杰金淋巴瘤和慢性急变,但临床上可出现中枢神经系统毒性反应,其中以小脑者最为常见。现介绍其发生机理和防治方法。阿糖胞苷(Ara-C)是一种抗嘧啶剂,属于细胞周期特异性药物,能抑制DNA多聚酶和DNA的合成,使S期细胞死亡,并使其它细胞含成停滞在Gl-S期边缘。Ara-C注入体内后很快脱氨基成为Ars-u(uracil arabinosidc脲嘧啶阿拉伯糖苷),后者被各组织吸收,代谢成不同的复合物,成为细胞内核苷酸、草酸苷酸、双核苷酸和三核苷酸,嵌合到DNA中,在细胞内主要转化为它的活性形式一Ara-CTP(cytorabine Triphosphate三磷酸盐阿糖     

力平脂致肌肉毒性反应1例报告

1 病例资料患者，女。69岁。于2006年4月在健康体检时，化验检测甘油三酯明显增高（测定值：4．1mmol/l，正常值：0．57～1．70mmol／1）诊断：高甘油三脂血症。门诊服用力平脂0．2，每晚1次，9天后突然出现双下肢肌肉疼痛、酸软无力、跛行等症状前来就诊。既往无高血压史、高血脂史。查体：面容呈痛苦状，表情肌松弛。咽部无异常。双肺呼吸音清。心率86次／min，律齐，心界无扩大，各瓣膜听诊区未闻及杂音。腹软，肝脾肋下未触及。四肢无畸形，肌力减弱，双下肢无力。行走呈踱行，腱反射减弱。脑膜刺激征阴性。     

激活素对新生大鼠缺氧缺血性脑损伤后神经元的保护

目的：观察外源性激活素对新生大鼠缺氧缺血性脑损伤后神经元的保护作用，为进一步探讨缺氧缺血性脑病的有效防治措施提供实验依据。方法：实验于2004-07／2005-07在山东大学医学院完成。将60只新生7d龄Wistar大鼠随机分为6组，每组10只。即：正常对照组、缺氧缺血性脑损伤模型组、假手术组及高剂量激活素治疗组、中剂量激活素治疗组、低剂量激活素治疗组。缺氧缺血后，治疗组即刻腹腔注射激活素1mL（浓度依次为0．025，0．005，0．001mg／L），其他各组均腹腔注射等量生理盐水。各组于缺氧缺血结束后不同时间点（0，2，6，24，48h，每个时间点2只大鼠）采集标本，观察激活素对缺氧缺血性脑损伤模型鼠的脑组织病理学变化及脑组织超微结构变化的影响；应用流式细胞仪做细胞凋亡分析，观察激活素对缺氧缺血性脑损伤后脑细胞凋亡的影响。结果：60只大鼠均进入结果分析。①造模后各时间点，缺氧缺血性脑损伤模型组和治疗组幼鼠的脑组织肉眼可见有不同程度的瘀血。其中，缺氧缺血性脑损伤模型组最明显且逐渐加重；各治疗组脑组织瘀血情况弱于缺氧缺血性脑损伤模型组，且于造模6h后的各时间点逐渐好转。②光镜及电镜下，治疗组脑组织细胞结构较缺氧缺血性脑损伤模型组均有不同程度的修复。③各组幼鼠脑组织细胞凋亡：假手术组[（0．76&;#177;0．09）％]明显低于缺氧缺血性脑损伤模型组[（7．46&;#177;0．12）％]及高、中、低剂量激活素治疗组[（5．91&;#177;0．15）％，（3．47&;#177;0．08）％，（5．23&;#177;0．17）％]（P〈0．01）；缺氧缺血性脑损伤模型组明显高于各治疗组（P〈0．05）；中剂量激活素治疗组明显低于高、低剂量激活素治疗组（P〈0．05）；后两组组间差异无显著性（P〉0．05）。结论：外源性激活素对新生大鼠缺氧缺血性脑损伤后的神经元具有保护作用，可明显减轻缺氧缺血性脑损伤后的神经元损伤和细胞凋亡。     

针刺治疗对紫杉醇所致的神经毒性反应的控制作用

目的探讨应用针刺治疗紫杉醇化疗所引起的神经毒性反应的疗效.方法选择2002-01/2003-10在解放军第四军医大学西京医院肿瘤中心和解放军西安451医院住院和门诊的恶性肿瘤患者共36例.其中乳腺癌9例,肺癌13例,食管癌8例,睾丸瘤1例,卵巢癌5例.取双侧足三里、三阴交、阳陵泉、合谷、曲池.采用28-30号2寸不锈钢针,1次/d,疗程7～15 d.神经毒性反应有周围神经病变、便秘及肌肉疼痛.按WHO推荐的抗癌药物不良事件分5级（0级为无,Ⅰ级为轻度,Ⅱ级为中度,Ⅲ级为重度,Ⅳ级为极重）.结果治疗5～15 d后,抗癌药物的不良事件均有不同程度的改善,Ⅰ、Ⅱ级不良事件患者症状均消失,Ⅲ、Ⅳ级不良事件患者只有4例患者恢复到Ⅰ级,其余患者症状均消失.治愈率为89%,有效率为100%.结论针刺疗法在抑制癌性疼痛方面疗效肯定,且具有见效快特点.提示针刺疗法可有效控制紫杉醇所引起的神经毒性反应.     

Serum magnesium concentrations after repetitive magnesium cathartic administration

Severe hypermagnesemia has been reported by several authors after multiple doses of magnesium-containing cathartic are administered during management of a toxic ingestion. To evaluate the frequency and magnitude of serum magnesium elevations after the use of repetitive magnesium catharsis, we prospectively evaluated 102 patients who received multiple doses of magnesium citrate as a part of treatment of an overdose. Commonly ingested substances for which repetitive cathartic was administered were tricyclic antidepressants in 47%, aspirin in 17%, and phenytoin in 10%. For each case, serial electrolytes, blood urea nitrogen, creatinine, calcium and magnesium were obtained. Mean initial serum magnesium concentration was 1.8 +/- .03 mEq/L. After a mean 960 mL of magnesium citrate (9.22 g magnesium), final mean serum magnesium concentration was 2.5 +/- .05 mEq/L. Forty-seven patients (47%) developed an elevated (greater than 2.4 mEq/L) serum magnesium concentration, with 12 greater than 3.0 mEq/L. No correlation was found between total quantity of magnesium citrate administered and the increment in serum magnesium concentration. Our data indicate that serum magnesium concentrations consistently rise after repetitive magnesium citrate use. However, the magnitude of this rise appears modest. The elevation in serum magnesium concentration does not correlate with the quantity of magnesium administered. We conclude that with close monitoring, repetitive magnesium citrate can be administered without inducing severe hypermagnesemia (serum magnesium concentration greater than 5.0 mEq/L).     

Cardiovascular collapse after amiodarone administration in neonatal supraventicular tachycardia.

Amiodarone is recommended by the International Liaison Committee on Resuscitation and has been adapted by the Resuscitation Council (UK) and the Advanced Life Support Group for use in paediatric advanced life support and advanced paediatric life support for the treatment of refractory supraventricular tachycardia. The International Liaison Committee on Resuscitation has stated that resuscitation guidelines should be evidence based. We present a case report of a cardiovascularly stable infant with supraventricular tachycardia who had a variety of arrthymias requiring cardiopulmonary resucitation for a prolonged period of time after loading with intravenous amiodarone. We believe that this report, together with other evidence, may suggest caution with the use of amiodarone.     

Rare systemic dermatologic reaction after pneumococcal vaccine administration

This case report describes a rare dermatologic reaction in a patient after administration of pneumococcal vaccine. A 65-year-old man developed an extensive dermatitis with pruritus, urticaria, and petechiae 1 week after receiving an intramuscular injection o the vaccine. The reaction resolved with application of topical steroids and oral diphenhydramine hydrochloride. This case report and others in the literature suggest the importance of recognizing the possibility of cutaneous adverse reactions with vaccines, such as the pneumococcal vaccine, which in general have a good safety profile.     

Airway epithelial CFTR mRNA expression in cystic fibrosis patients after repetitive administration of a recombinant adenovirus

We sought to evaluate the ability of an E1(-), E3(-) adenovirus (Ad) vector (Ad(GV)CFTR.10) to transfer the normal human cystic fibrosis transmembrane conductance regulator (CFTR) cDNA to the airway epithelium of individuals with cystic fibrosis (CF). We administered Ad(GV)CFTR.10 at doses of 3 x 10(6) to 2 x 10(9) plaque-forming units over 9 months by endobronchial spray to 7 pairs of individuals with CF. Each 3-month cycle, we measured vector-derived versus endogenous CFTR mRNA in airway epithelial cells prior to therapy, as well as 3 and 30 days after therapy. The data demonstrate that (a) this strategy appears to be safe; (b) after the first administration, vector-derived CFTR cDNA expression in the CF airway epithelium is dose-dependent, with greater than 5% endogenous CFTR mRNA levels at the higher vector doses; (c) expression is transient, lasting less than 30 days; (d) expression can be achieved with a second administration, but only at intermediate doses, and no expression is observed with the third administration; and (e) the progressive lack of expression with repetitive administration does not closely correlate with induction of systemic anti-Ad neutralizing antibodies. The major advantage of an Ad vector is that it can deliver sufficient levels of CFTR cDNA to the airway epithelium so that CFTR expression protects the lungs from the respiratory manifestations of CF. However, this impressive level of expression is linked to the challenging fact that expression is limited in time. Although this can be initially overcome by repetitive administration, unknown mechanisms eventually limit this strategy, and further repetitive administration does not lead to repetitive expression.     

Toxicological evaluation of azumolene after repeated intraperitoneal administration in rats

We investigated the toxicity of azumolene (Az), a more water‐soluble compound than dantrolene, after 14 days of intraperitoneal (i.p.) administration in rats at doses of 1, 2.5 or 10 mg/kg/day. No animals died or presented signs of toxicity. No significant differences in water and food consumption or weight gain were noted among the groups. Blood analysis revealed no significant alteration by Az treatment in the number of blood cells. However, Az treatment induced a perivascular inflammatory reaction in the liver and non‐diffuse necrosis of skeletal muscle, both of which occurred only at the highest dose of Az and were completely reversed 14 days after cessation of treatment. Congestion and inflammation in the kidneys were only partially reversed. Caffeine‐induced contracture of skeletal muscle was not altered during 7 days of i.p. injection of Az (2.5 mg/kg/day). In conclusion, Az is a safe compound for long‐term administration, but does cause a mild, reversible reaction in skeletal muscle and kidney.