膨化人参对大鼠急性毒性及小鼠耐缺氧能力的实验观察

目的：观察膨化人参对大鼠的急性毒性及小鼠的耐缺氧能力,探讨其耐缺氧机制。方法将18只SD雄性大鼠随机均分为对照组、观察组,禁食16 h后,观察组在1 d内分3次给予膨化人参悬浊液灌胃,对照组给予等量蒸馏水灌胃,观察两组7 d内毒性反应。将32只昆明小鼠随机分为膨化人参小、中、大剂量组和对照组各8只,分别用膨化人参悬浊液0．375、0．750、1．500 g/kg和等容量蒸馏水灌胃,连续灌胃3周后,观察各组耐缺氧时间、总耗氧量;小鼠心脏采血后行血红细胞数测定。结果膨化人参的半数致死量未测得,其最大耐受量为18 g/kg 。两组大鼠的毛发、呼吸、进食、二便、口鼻分泌物、精神状态及体质量均未见明显异常（ P均＞0．05）。与对照组比较,膨化人参大剂量组耐缺氧时间延长、总耗氧量提高、血红细胞数量增加（P均＜0．05）。结论膨化人参的毒性极低,其能提高小鼠的耐缺氧能力,其机制可能与红细胞数量增加有关。     

槲寄生、钩藤、杜仲降压作用及急性毒性的实验研究

目的研究槲寄生、钩藤、杜仲的水提液及其混合液的降血压作用及急性毒性反应.方法用肾动脉结扎法制备高血压大鼠模型,灌胃给予中药水提液,考察降血压作用.用小鼠灌胃考察急性毒性.结果槲寄生杜仲混合水提液、钩藤杜仲混合水提液、槲寄生钩藤杜仲混合水提液均能降低高血压大鼠的血压,槲寄生杜仲混合水提液和槲寄生钩藤杜仲混合水提液的效果更为明显,能将大鼠血压降到正常水平,并维持稳定.结论槲寄生、钩藤、杜仲三味中药不同配伍有较好的降压作用,且三种混合水提液对小鼠按照最大耐受量灌胃,未见急性毒性反应.     

壳聚糖止血敷料止血装置在经桡动脉冠状动脉介入治疗术后的临床应用

目的 对比分析一种新型壳聚糖止血敷料止血装置在经桡动脉冠状动脉介入治疗（PCI）术后的临床应用.方法 选取2011年2月～2012年6月我院心内科因胸痛原因住院的患者包括急性冠脉综合征（不稳定性心绞痛、非ST段抬高心肌梗死、急性心肌梗死）、稳定心绞痛的患者3165例.其中冠脉造影1959例（其中经排除标准及经股动脉途径而不计入250例）,经桡动脉行介入治疗1206例（其中经排除标准及经股动脉途径和反关脉而不计入135例）,共计2780例入选.将入选病例随机分为2组,普通桡动脉止血板组1390例和壳聚糖止血敷料止血装置组1390例.观察术后即刻及出院时桡动脉主、次终点事件.主要终点包括：出血、血肿、假性动脉瘤、前臂疼痛或不适、桡动脉内膜损伤、桡动脉闭塞、桡动脉内膜直径等.次要终点包括压迫时间、压迫止血效果、患者依从性和满意度.结果 壳聚糖止血敷料止血装置组总血管并发症明显低于普通桡动脉止血板组（P＜0.01）,所需压迫时间明显缩短（P＜0.01）,治疗满意度明显较高（P＜0.01）.结论 壳聚糖止血敷料止血装置能够减少血管总并发症,减少压迫时间,提高患者术后满意度,对桡动脉内膜有一定保护作用.     

壳聚糖蜂胶胶囊的毒理学研究

目的对壳聚糖蜂胶胶囊的安全性进行毒理学研究。方法依据《保健食品检验与评价技术规范》(2003版)进行壳聚糖蜂胶胶囊的急性毒性试验和遗传毒性试验。结果急性毒性试验中,壳聚糖蜂胶胶囊LD50>21599mg/kg,根据急性毒性分级,属无毒级。Ames试验中,壳聚糖蜂胶胶囊对鼠伤寒沙门氏菌四株试验菌株,在加与不加S-9时,均未呈现遗传毒性。剂量为313mg/(kg·bw)、1250mg/(kg·bw)、5000mg/(kg·bw)时,壳聚糖蜂胶胶囊对小鼠骨髓嗜多染红细胞微核以及小鼠精子畸形均未产生影响。结论壳聚糖蜂胶胶囊急性毒性分级属无毒级,无遗传毒性。     

壳聚糖治疗大鼠非酒精性脂肪性肝病的初步实验研究

目的探索不同剂量壳聚糖治疗非酒精性脂肪性肝病的效果。方法60只大鼠随机分为空白对照组（10只）、脂肪肝模型组（20只）和3个不同剂量壳聚糖治疗组（各10只）。脂肪肝模型组和治疗组先用高脂饲料（含88％普通饲料＋10％猪油＋2％胆固醇）喂养12周。壳聚糖治疗组在13～20周每日经灌胃给予相对分子质量为127100壳聚糖溶液1次。三组的剂量分别为每公斤体质量0．094g、0．188g和0．375g。20周时处死动物,分别取肝组织切片观察脂肪变、炎症和纤维化情况,血清行生化指标检测。结果模型组动物均形成F4级脂肪变、G1～G2炎症和S1～S2纤维化。模型组动物ALT、AST、ALP、TC和LDL均较空白对照组显著升高。TG增高和HDL降低差异无统计学意义。与模型组相比,壳聚糖治疗各组大鼠肝脂肪变和炎症差异无统计学意义;但治疗组肝纤维化有明显好转。大剂量壳聚糖治疗组中60％大鼠肝纤维化减轻到S0期,无S2期。壳聚糖治疗组的生化指标也有一定程度的好转,但未恢复到空白对照组水平。结论大剂量壳聚糖（每日0．375g／kg）对改善大鼠肝组织的脂肪肝和纤维化有明显效果,对生化指标改善也有一定效果。     

壳聚糖对胃溃疡愈合质量影响的实验研究

背景：消化性溃疡是临床常见病且易复发，溃疡愈合质量与其复发有密切关系。目的：研究壳聚糖对大鼠胃溃疡愈合质量的影响及其可能机制。方法：大鼠随机分为空白对照组、两组药物对照组（硫糖铝和雷尼替丁）和三组实验组（壳聚糖、壳聚糖＋硫糖铝或雷尼替丁）。给药14天后测量溃疡面积并行HE染色、AB—PAS、第Ⅷ因子和SP法免疫组化染色，测定一系列溃疡愈合质量指标以及表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）和诱生型一氧化氮合酶（iNOS）的表达。结果：实验组溃疡面积较空白对照组和药物对照组显著缩小（P〈0．01）；再生黏膜厚度较空白对照组增加，囊状扩张腺体数量减少，腺体层数增加，PAS阳性面积增加，肉芽组织中新生微血管数量增多（P〈0．01）。壳聚糖＋硫糖铝或壳聚糖＋雷尼替丁组的囊状扩张腺体数量显著小于雷尼替丁组（P〈0．05），腺体层数显著大于三者单用（P〈0．05），PAS阳性面积和新生微血管数量显著大于雷尼替丁组（P〈0．05）。各实验组EGF和bFGF的表达均显著高于空白对照组和雷尼替丁组（P〈0．05），但iNOS在各组间的表达无显著差异。结论：壳聚糖可提高大鼠胃溃疡愈合质量。其机制可能与增强EGF、bFGF的表达和促进肉芽组织中微血管增生有关。壳聚糖与硫糖铝和雷尼替丁对提高溃疡愈合质量具有协同作用。     

广西苦丁茶老叶水提取物的急性毒性作用研究

目的 探讨广西苦丁茶老叶水提取物对小鼠的急性毒性作用.方法 以苦丁茶老叶水提取物溶液的最大浓度和最大给药体积给予小鼠灌胃,1次/d,连续7 d,观察和记录小鼠的毒副反应情况.结果 试验期间小鼠活动状况与饮食情况均正常,未出现死亡和其它不良反应,解剖和尸检见内脏器官无异常.计算小鼠对苦丁茶的最大耐受剂量为87.2 g/kg,相当于成人日用量的耐受量174.4倍.结论 广西苦丁茶老叶水提取物的毒性较低.     

黄果茄植物提取物对鱼类和大鼠急性毒性试验的观察

为掌握和了解黄果茄植物提取物对鱼类和大鼠的急性毒性 ,本研究进行了常规的鱼类急性毒性试验和大鼠急性经口毒性试验。结果表明 ,黄果茄植物提取物对鱼类稀有鱼句鲫的急性毒性试验 ,在 0 .2 70 mg/ L浓度中 ,2 4h稀有鱼句鲫死亡率为 0 % ;在 17.2 8mg/ L中 ,2 4h稀有鱼句鲫死亡率为 10 0 % ;SX对稀有鱼句鲫 2 4h L C5 0 为 2 .0 2 mg/ L ,95 %的可信限为 1.33～ 3.0 6 mg/ L。对大鼠急性经口毒性的绝对致死剂量为 2 15 0 mg/ kg· bw,L D5 0 为 794mg/ kg· bw,95 %可信限为 5 84～10 80 mg/ kg· bw,属低毒类。     

越婢加术汤的急性毒性实验

目的 通过对小鼠灌胃给药后出现的快速而剧烈的中毒反应的观察,考察越婢加术汤的临床安全性.方法 应用可供灌胃最大浓度、最大容积越婢加术汤一次性灌胃给药,连续观察并记录给药后7d内小鼠的中毒症状和死亡数,按生药量计算小鼠的最大给药量.结果 给药后7d内小鼠生存良好,活动和饮食情况均无变化,未有死亡情况,解剖尸检无肉眼可观察到的内脏异常变化.结论 经试验测得越婢加术汤最大给药量是640 g/kg,相当于临床成人一日剂量的600倍.越婢加术汤安全性好,毒性低.     

通城虎镇痛抗炎作用及急性毒性的实验研究

目的 研究通城虎的镇痛抗炎作用并进行它的急性毒性试验.方法 采用醋酸致扭体反应、热板法测定痛阈,观察通城虎的镇痛作用;抗炎实验采用二甲苯致鼠耳肿胀法、角叉菜胶致大鼠足趾肿胀法和腹腔毛细血管通透性法;采用Bliss法测定了其半数致死量(LD50).结果 通城虎能减少醋酸所致小鼠扭体次数,明显提高小鼠的痛阈;抑制二甲苯所致小鼠耳廓肿胀、角叉菜胶引起的大鼠足趾肿胀和醋酸所致小鼠腹腔毛细血管通透性增加;其LD50为100.1 g/kg,LD50的95%可信限为87.2 ～115.1 g/kg.结论 通城虎对实验动物模型具有显著的镇痛抗炎作用,使用时一定要注意其不良反应.     

The effects of esmolol on the hemodynamics of acute theophylline toxicity

The effects of esmolol, a beta 1-selective adrenergic receptor antagonist with a short duration of action, were studied in a canine model of the hemodynamics of theophylline toxicity. Animals were anesthetized, then given 50 mg/kg aminophylline IV over 20 minutes followed by a continuous infusion of 1.75 mg/kg/hr. Hemodynamic parameters, including heart rate, cardiac output, systemic blood pressure, pulmonary arterial pressure, and pulmonary artery wedge pressure, were measured every 30 minutes along with plasma catecholamines and theophylline levels. Marked tachycardia was seen in the intoxicated state, with heart rate rising from a baseline of 128.0 +/- 8.3 beats per minute (BPM) to 179.0 +/- 7.4 BPM (P = .012). This was associated with increases in catecholamines (baseline norepinephrine .04 +/- .04 ng/mL plasma rose to .42 +/- .21 ng/mL plasma after intoxication, P = .048). The average serum theophylline level during the experiment was 44.0 +/- 1.1 micrograms/mL serum. Esmolol then was given by IV infusion in these animals in doses of 25, 50, and 100 micrograms/kg/min. It returned the heart rate to the preintoxication baseline in a dose-related manner. Esmolol did not decrease cardiac output or lower blood pressure.     

Efficacy and toxicity of gemtuzumab ozogamicin in patients with acute myeloid leukemia

Gemtuzumab ozogamicin (GO) is a recently developed antibody-targeted chemotherapeutic agent and has been expected to be less toxic than conventional chemotherapy. We retrospectively evaluated the use of GO in 38 patients. Patients with acute myeloid leukemia (AML) at diagnosis and relapsed AML were treated with 6 and 9 mg/m(2) GO. Efficacy and toxicity of GO were analyzed, as well as several prognostic factors. A complete response (CR) was observed in 12 of 38 patients, including five patients with CR plus incomplete regeneration of platelets. In one patient a partial remission was observed. Twenty-five patients showed no change or progressive disease. The overall response (OR) in patients with AML at diagnosis was 47%, with the best response in patients with primary AML (OR 60%, compared with 21% OR in non-primary AML, P = 0.045). The OR in patients with relapsed AML was 22%. Median white blood cell (WBC) before treatment, CD33 expression on leukemic blasts, and kinetics of response were analyzed as prognostic factors. Median WBC was significantly lower in patients who responded to GO, compared with non-responders (2.1 x 10(9)/L vs. 6.8 x 10(9)/L, P = 0.036). CD33 expression and kinetics of response was not correlated to clinical outcome. Median days to reach 500 x 10(6)/L neutrophils and 100 x 10(9)/L platelets were 36 and 39 d, respectively. Infections and bleedings occurred in 45% and 12%, respectively. This report shows that GO has potent clinical activity and that the OR rate was by far the best in untreated primary AML patients.     

黄果茄植物提取物的灭螺效果及对鱼类和大鼠急性毒性试验研究

目的 掌握和了解黄果茄植物提取物（SX）对钉螺的杀灭效果和对鱼类以及大鼠的急性毒性作用。方法 进行了常规的灭螺试验和鱼类急性毒性试验以及大鼠急性经口毒性试验。结果 SX浓度为4．32mg/L时浸泡湖北钉螺,24h死亡率为96．7％,48h死亡率达100％;SX对鱼类稀有Ju鲫的急性毒性试验,在0．27mg/L浓度中,24h的死亡率为0,在17＝28mg/L浓度中,24h死亡率为100％;SX对稀有Ju鲫的LC50为2．02mg/L,95%的可信限为1．33－3．06mg/L。对大鼠急性经口毒性的绝对致死剂量为2150mg/kg体重,LD50为794mg/kg体重,95％可信限为584－1080mg/kg体重。结论 SX具有较好的灭螺效果,但对鱼类稀有Ju鲫有中等毒性作用,对大鼠的作用属低毒类。     

Gene polymorphisms in folate metabolizing enzymes in adult acute lymphoblastic leukemia: effects on methotrexate-related toxicity and survival

Background

The antifolate agent methotrexate is an important component of maintenance therapy in acute lymphoblastic leukemia, although methotrexate-related toxicity is often a reason for interruption of chemotherapy. Prediction of toxicity is difficult because of inter-individual variability susceptibility to antileukemic agents. Methotrexate interferes with folate metabolism leading to depletion of reduced folates.

Design and Methods

The aim of this study was to investigate the influence of polymorphisms for folate metabolizing enzymes with respect to toxicity and survival in adult patients with acute lymphoblastic leukemia treated with methotrexate maintenance therapy. To this purpose, we evaluated possible associations between genotype and hematologic and non-hematologic toxicity and effects on survival at 2 years of follow-up in patients with acute lymphoblastic leukemia.

Results

Polymorphisms in the genes encoding for methylenetetrahydrofolate reductase (MTHFR 677C>T) and in dihydrofolate reductase (DHFR 19 bp deletion) significantly increased the risk of hepatotoxicity in single (odds ratio 5.23, 95% confidence interval 1.13–21.95 and odds ratio 4.57, 95% confidence interval 1.01–20.77, respectively) and in combined analysis (odds ratio 6.82, 95% confidence interval 1.38–33.59). MTHFR 677C>T also increased the risk of leukopenia and gastrointestinal toxicity, whilst thymidylate synthase 28 bp repeat polymorphism increased the risk of anemia (odds ratio 8.48, 95% confidence interval 2.00–36.09). Finally, patients with MTHFR 677TT had a decreased overall survival rate (hazard ratio 2.37, 95% confidence interval 1.46–8.45).

Conclusions

Genotyping of folate polymorphisms might be useful in adult acute lymphoblastic leukemia to optimize methotrexate therapy, reducing the associated toxicity with possible effects on survival.     

Cytidine deaminase genotype and toxicity of cytosine arabinoside therapy in children with acute myeloid leukemia

Cytosine arabinoside (ara-C) is irreversibly deaminated to a non-toxic metabolite by cytidine deaminase (CDA). A common polymorphism, A79C, in the gene encoding cytidine deaminase ( CDA ) changes a lysine residue to glutamine resulting in decreased enzyme activity. CDA A79C genotypes were determined in 457 children with acute myeloid leukaemia (AML) treated on the Children's Cancer Group (CCG) 2941 and 2961 protocols and analyzed the impact of CDA genotype on therapy outcomes. Postinduction treatment-related mortality (TRM) was significantly elevated in children with the CC genotype (5-year TRM 17 ± 13% CC vs. 7 ± 4% AA, 5 ± 4% AC, P  = 0·05). This was more notable in children who received idarubicin, fludarabine, ara-C, and granulocyte colony-stimulating factor (IDA-FLAG; ara-C = 7590 mg/m²) (5-year TRM 24 ± 21% CC vs. 6 ± 6% AA, 6 ± 7% AC, P  = 0·07) as consolidation therapy compared to idarubicin, dexamethasone, cytarabine, thioguanine, etoposide and daunomycin (IDA-DCTER; ara-C = 800 mg/m²) (5-year TRM 15 ± 20% CC vs. 8 ± 6% AA, 4 ± 6% AC; P  = 0·29). Relapse-free survival was non-significantly increased in children with the CC genotype treated with IDA-FLAG (76 ± 20% CC vs. 59 ± 12% AA and 55 ± 14% AC; P  = 0·40). These data indicate that children with a low activity CDA genotype are at increased risk of TRM with ara-C based therapy for AML.     

Antihypertensive medication and the risk of acute pancreatitis: The European case-control study on drug-induced acute pancreatitis (EDIP)

Objective. Angiotensin-converting enzyme (ACE) inhibitors and diuretics have been associated with acute pancreatitis. We quantified the risk of acute pancreatitis associated with the use of antihypertensive medication in the European study on drug-induced acute pancreatitis (EDIP). Material and methods. The EDIP study is a multicenter population-based European case-control investigation of the association between drug use and acute pancreatitis. Patients between 40 and 85 years of age hospitalized for acute pancreatitis were included in the study between 1 October 1994 and 31 December 1998. For each case, age- and gender-matched community controls were recruited. Detailed information on drug use and potential confounders (e.g. comorbidity, alcohol use) was obtained through a structured interview. Results. In all, 724 patients with acute pancreatitis and 1791 community controls were identified and interviewed. Use of ACE inhibitors in the week prior to the index date was associated with an increased risk of acute pancreatitis (adjusted odds ratio 1.5; 95% CI: 1.1–2.2). The risk of acute pancreatitis associated with ACE inhibitors increased with higher daily doses and was highest in the first 6 months of therapy. Calcium channel blockers increased the risk of acute pancreatitis (adjusted odds ratio 1.5; 95% CI: 1.1–2.1) without an apparent dose- or response relationship. Loop and thiazide diuretic use was not associated with an increased risk of acute pancreatitis. Potassium-sparing diuretics elevated the risk of acute pancreatitis, albeit non-significantly. Conclusion. Use of ACE inhibitors is associated with a modest increase in the risk of acute pancreatitis during the first months of treatment.     

血清前白蛋白与急性冠脉综合征患者相关性的研究

【】目的 探讨急性冠脉综合征(ACS)患者血清前白蛋白(PA)水平变化的临床意义。方法 选择ACS患者110例,正常对照组96例,检测血清前白蛋白(PA)的水平,同时记录ACS组患者住院期间主要不良心脏事件(MACE)的发生情况,包括：恶性心律失常、心源性死亡、新发心力衰竭、再发心肌梗死。再根据PA中位数将ACS组分为高PA组、低PA组,比较两组间住院期间MACE的发生率。结果 ACS组的血清PA水平较正常对照组低(P<0.05),低PA组患者住院期间MACE的总发生率较高A组明显增加(P<0.05)。结论 ACS患者的血清PA水平明显降低,低PA值提示ACS患者短期预后不良。     

洋葱提取物的急性毒性及对大鼠血压的影响

目的 :探讨洋葱提取物 （Extraction of Onion,ETO）对小鼠的急性毒性和大鼠血压、心电图、心率和呼吸的影响。方法 :对正常大鼠用去甲肾上腺素药物诱导和单侧颈总动脉阻塞造成高血压动物模型 ,按 4 5 .2 4 g· kg- 1· d- 1ETO （0 .5 8g· ml- 1 × 3次 ）给小鼠灌胃 （ig） ;6 0 .32 g· kg- 1 · d- 1 ETO给小鼠腹腔注射 （ip） ;观测 ETO的小鼠急性毒性。以 2 .32 g· kg- 1 ETO给大鼠颈外静脉注射 （iv） ,用八道生理记录仪分别测量不同时间的血压、心电图、心率等指标。结果 :1ETO ig小鼠的最大耐受量 （MTD）大于 4 5 .2 4 g· kg- 1 ;ip小鼠的 MTD大于 6 0 .32 g· kg- 1 。2ETO2 .32 g· kg- 1对正常大鼠血压具有瞬间明显降血压作用 （P<0 .0 5 ） ;3ETO2 .32 g· kg- 1对药物诱导和阻塞性高血压大鼠的血压具有显著降压作用 ,给 ETO后 2 0 s时平均降低幅度分别为 3.4 8k Pa和 7.5 3k Pa（P<0 .0 1） ,且降血压的特点明显不同。前者仅表现为瞬间降压 ;而后者则为瞬间血压降低幅度大 ,之后回升至接近正常水平并维持 12 0 s。 4去甲肾上腺素药物诱导和单侧颈总动脉阻塞 ,除显著加快心率和呼吸频率外 ,对大鼠心电图无明显影响 ;ETO2 .32 g· kg- 1 iv后除有显著降血压作用外 ,未发现心电图、心率和呼吸的明显变化?