Evaluation of hepatoprotective effect of Zhi-Zi-Da-Huang decoction and its two fractions against acute alcohol-induced liver injury in rats

Aim of the study

To investigate the hepatoprotective effect of Zhi-Zi-Da-Huang decoction (ZZDHD) and its two fractions (one is extracted with diethyl ether as a solvent from the water extract and is called ZD-DE for short, the other is the remained aqueous fraction after extracted with diethyl ether and is abbreviated as ZD-AQ) against acute alcohol-induced liver injury in rats.

Materials and methods

Animals were administered orally with alcohol 6 g/kg at 2 h after the doses of ZZDHD and two fractions everyday for eight consecutive days except rats in normal group. The protective effect was evaluated by biochemical parameters including aspartate transaminase (AST), alanine transferase (ALT), reduced glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD). The biochemical observations were supplemented by histopathological examination. HPLC-UV was used for phytochemical analysis of the ZZDHD and its two fractions.

Results

The high dose of ZZDHD exhibited a significant protective effect by reversing the biochemical parameters and histopathological changes. ZD-DE and ZD-AQ demonstrated different protective action in biochemical examination. Partly assayed indexes were ameliorated after administrated the media dose of ZZDHD. HPLC analysis indicated that ZZDHD contained flavonoids, anthraquinones and iridoids, which might be the active chemicals.

Conclusions

This study demonstrated the hepatoprotective activity of ZZDHD thus scientifically supported the usage of this formula.     

高温复合脂多糖应激大鼠血清天门冬酸氨基转移酶的变化

目的:探讨高温与脂多糖(LPS)复合应激大鼠血清天门冬酸氨基转移酶(AST)含量的变化特点.方法:雄性SPF级Wistar大鼠64只随机均匀分为常温 生理盐水组(C组),高温 生理盐水组(H组),常温 LPS组(L组),高温 LPS组(HL组).置动物于模拟气候舱,HL和H组暴露环境干球温度(Tdb)为(35.0±0.5)℃,L和C组Tdb为(26±0.5)℃;HL和L组动物经尾静脉注射LPS 10 mg/kg,H和C组动物经尾静脉注射9 g/L NaCl 10 mL/kg.持续监测动物平均动脉压(MAP)的动态变化,检测动物应激0,40,80,120 min时血清AST等物质含量的变化.结果:AST在不同温度、时间、药物水平间存在统计学差异(P＜0.01);时间与温度、时间与药物、温度与药物交互作用有统计学意义(P＜0.05),120 min时相点HL组动物血清AST含量高于其余3组,差异有统计学意义(P＜0.01);AST水平与MAP存在负相关关系(r=-0.818,P=0.029).结论:高温与LPS复合应激可促发、扩大全身炎症反应综合征.     

Characterization of an Inducible Alcoholic Liver Fibrosis Model for Hepatocellular Carcinoma Investigation in a Transgenic Porcine Tumorigenic Platform

Purpose

This study used the Oncopig Cancer Model (OCM) to develop alcohol-induced fibrosis in a porcine model capable of developing hepatocellular carcinoma.

三种不同材料烤瓷冠对龈沟液内天冬氨酸转氨酶和碱性磷酸酶水平的影响

目的:通过对不同材料的烤瓷冠修复后龈沟液(gingivalcrevicularfluid,GCF)内天冬氨酸转氨酶(aspartatetransaminase,AST)和碱性磷酸酶(alkalinephosphatase,ALP)总量的测定,来探讨内冠材料对牙周的影响。方法:选择临床病例26例,采用镍铬合金烤瓷冠、钛合金烤瓷冠和金铂合金烤瓷冠修复,分别在修复前、修复后1个月和3个月进行临床检查和取GCF,进行GCF量和AST、ALP总量的测定,从而进行分析。结果:1个月时,3组之间并未见指标差异;3个月时镍铬合金组和钛合金组之间未见指标差异,此时镍铬合金组和钛合金组分别与金铂合金组在指标上均有明显差异。结论:非贵金属对牙周组织有不利影响,同时通过测定GCF中AST和ALP的总量,可以方便的动态观察烤瓷冠对牙周的影响。     

Protection of rats against 3-butene-1,2-diol-induced hepatotoxicity and hypoglycemia by N-acetyl-l-cysteine

3-Butene-1,2-diol (BDD), an allylic alcohol and major metabolite of 1,3-butadiene, has previously been shown to cause hepatotoxicity and hypoglycemia in male Sprague-Dawley rats, but the mechanisms of toxicity were unclear. In this study, rats were administered BDD (250 mg/kg) or saline, ip, and serum insulin levels, hepatic lactate levels, and hepatic cellular and mitochondrial GSH, GSSG, ATP, and ADP levels were measured 1 or 4 h after treatment. The results show that serum insulin levels were not causing the hypoglycemia and that the hypoglycemia was not caused by an enhancement of the metabolism of pyruvate to lactate because hepatic lactate levels were either similar (1 h) or lower (4 h) than controls. However, both hepatic cellular and mitochondrial GSH and GSSG levels were severely depleted 1 and 4 h after treatment and the mitochondrial ATP/ADP ratio was also lowered 4 h after treatment relative to controls. Because these results suggested a role for hepatic cellular and mitochondrial GSH in BDD toxicity, additional rats were administered N-acetyl-l-cysteine (NAC; 200 mg/kg) 15 min after BDD administration. NAC treatment partially prevented depletion of hepatic cellular and mitochondrial GSH and preserved the mitochondrial ATP/ADP ratio. NAC also prevented the severe depletion of serum glucose concentration and the elevation of serum alanine aminotransferase activity after BDD treatment without affecting the plasma concentration of BDD. Thus, depletion of hepatic cellular and mitochondrial GSH followed by the decrease in the mitochondrial ATP/ADP ratio was likely contributing to the mechanisms of hepatotoxicity and hypoglycemia in the rat.     

含不同药物排龈线引起牙龈炎症的比较研究

目的通过评价3种常用排龈药物引起牙龈炎症程度的大小,为临床选择最佳的排龈药物提供参考。方法将40颗上颌第一前磨牙按随机区组设计分为4组：硫酸铁组、氯化铝组、肾上腺素组、生理盐水组（对照组）,每组10颗牙齿,分别采用体积分数为25%氯化铝、15.5%硫酸铁、0.1%盐酸肾上腺素、生理盐水作为排龈药物,于排龈前及排龈后1、3、5、7、9 d测定龈沟液中龈沟液（GCF）量和天冬氨酸转氨酶（AST）活性的水平,计算排龈前后GCF变化量。结果排龈后,GCF变化量从小到大依次为生理盐水组、肾上腺素组、氯化铝组、硫酸铁组。肾上腺素组在排龈后第1、3天龈沟液中AST水平与排龈前基值具有统计学差异（P<0.05）,硫酸铁组及氯化铝组在排龈后第1、3、5天龈沟液中AST水平与排龈前基值具有统计学差异（P<0.05）;与生理盐水组相比,只有硫酸铁组排龈后第1、3天龈沟液中AST水平具有统计学差异（P<0.05）。结论对健康成人的口腔固定修复患者,推荐使用体积分数为0.1%肾上腺素作为排龈药物;对伴有心血管系统疾病的口腔固定修复患者,体积分数为25%氯化铝可作为0.1%肾上腺素的替代排龈药物;硫酸铁需降低体积分数才能临床应用。     

美金刚在阿尔茨海默病患者中的疗效与耐受性多中心研究

目的 评价美金刚对阿尔茨海默病（Alzheimer disease，AD）患者的疗效与安全性。方法多中心、随机、双盲、安慰剂对照研究。共纳入AD患者258例（MMSE检查5～18分），随机分入安慰剂组（PBO，n=130）或美金刚组（MEM，n=128），分别仅给予安慰剂或安慰剂及美金刚（10～20mg／d）治疗，共16周。主要疗效评估以坚持服用研究药物并在第16周接受严重障碍量表（SIB）评估的患者（完成16周研究集，CS16集）为对象，以SIB评分相对于基线的变化为指标；次要疗效评估分别以CS16集和全分析集（FAS）为对象，以MMSE、神经精神科问卷（NPI）和AD合作研究-日常生活能力量表（ADCS-ADL19）为指标。安全性评估包括体格检查、实验室检查、心电图和不良事件。结果 共236例患者（MEM 117例；PBO 119例）进入疗效分析，尽管两组的SIB评分均较基线时有所提高，两组的主要和次要疗效分析差异均无统计学意义（均P〉0．05）。Post—hoc数据评估发现有两个因素造成疗效分析结果的偏倚，舍弃受这些因素影响的患者数据后再次进行分析：美金刚组（n=94）的16周末SIB（MEM：PBO=2．2：0．3，P=0．04）、MMSE（MEM：PBO=1．0：0．1，P=0．03）和ADL评分变化（MEM：PBO=0．1：-1．6，P=0．02）与安慰剂组（n=95）差异均有统计学意义，提示美金刚的疗效优于安慰剂，显著改善AD患者的认知功能，并使日常生活能力维持稳定。美金刚的耐受性良好，其不良事件特征与安慰剂相似。结论 本研究为已有资料提供了更多支持，表明美金刚对中重度AD患者有效、安全且耐受性良好。     

Dose-escalation study of rivaroxaban (BAY 59-7939)--an oral, direct Factor Xa inhibitor--for the prevention of venous thromboembolism in patients undergoing total hip replacement

INTRODUCTION: Rivaroxaban (BAY 59-7939) is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention of thromboembolic disorders. The aim of this study was to demonstrate proof-of-principle for rivaroxaban. MATERIALS AND METHODS: This was an open-label, dose-escalation study to assess the efficacy and safety of rivaroxaban, relative to enoxaparin, for the prevention of venous thromboembolism (VTE) after total hip replacement surgery. Patients were randomized in a 3:1 ratio to rivaroxaban (2.5, 5, 10, 20 and 30 mg twice daily [bid] or 30 mg once daily [od] starting 6-8 h after surgery) or enoxaparin (40 mg od starting the evening before surgery). Therapy continued until mandatory bilateral venography was performed 5-9 days after surgery. RESULTS: A total of 625 patients received therapy, of whom 466 patients were eligible for the per-protocol efficacy analysis. The primary efficacy endpoint - deep vein thrombosis (DVT), pulmonary embolism (PE) or all-cause mortality - occurred in 22.2%, 23.8%, 20.0%, 10.2%, 17.4%, 15.1% and 16.8% of patients receiving rivaroxaban 2.5, 5, 10, 20, 30 mg bid, 30 mg od and enoxaparin, respectively. The dose-response relationship with rivaroxaban for the primary efficacy endpoint was not statistically significant (p=0.0504), although major VTE (proximal DVT, PE and VTE-related death) decreased dose dependently with rivaroxaban (p=0.0108). Major, post-operative bleeding increased dose dependently with rivaroxaban (p=0.0008), occurring in 0-10.8% of patients, compared with 0% in patients receiving enoxaparin. CONCLUSIONS: This study demonstrated proof-of-principle for rivaroxaban for the prevention of VTE after total hip replacement surgery.