缬沙坦氨氯地平片(Ⅰ)致胆红素升高1例

患者,男,61岁. 患高血压2年余,先后服用复方利血平氨苯蝶啶片、坎地沙坦西酯片. 2011年11月17日因舒张压控制不佳就医. 血压123/100 mmHg(1 mmHg＝0.133 kPa);血生化：总胆红素(T-BiL)25.8 μmol.L^-1,直接胆红素(D-BiL)7.1 μmol.L^-1,间接胆红素(I-BiL)18.7 μmol.L^-1,丙氨酸氨基转移酶(ALT) 16 U.L^-1;血管B超：右颈总动脉钙化斑形成;空腹血糖：8.4 mmol.L^-1. 医生改用缬沙坦氨氯地平片(Ⅰ) 80 mg/5 mg,qd,po,阿司匹林肠溶片0.1 g,qd,po治疗. 2011年11月23日,因“血糖升高11年,控制欠佳2个月”住院治疗. 入院体检：体温36.3 ℃,血压122/80 mmHg,呼吸率18 次.min^-1,脉搏84 次.min^-1,体质量指数(BMI)23.9 kg.(m²)^-1. 既往无药物致变态反应史,无肝炎、结核病史,2个月前发现有前列腺增生,服用爱普列特片和坦洛新缓释片治疗. 入院后予重组甘精胰岛素注射液6 U,qn,ih;阿卡波糖片50 mg,tid,po,降血糖,缬沙坦氨氯地平片(Ⅰ)80 mg/5 mg,qd,po,降压,阿司匹林肠溶片0.1 g,qd,po,抗血小板聚集等对症支持治疗,予以灯盏细辛针30 mL静脉滴注,qd,活血通络. 2011年11月30日血生化：T-BiL 33.5 μmol.L^-1,D-BiL 11.8 μmol.L^-1,I-BiL 21.7 μmol.L^-1,ALT 14 U.L^-1;患者T-BiL、D-BiL和I-BiL比入院前有所升高,但ALT正常. 排查患者所用药物,患者应用缬沙坦氨氯地平片(Ⅰ)可导致黄疸与转氨酶明显增高,临床药师建议医生停用缬沙坦氨氯地平片(Ⅰ),改为坎地沙坦西酯片治疗,医生采纳建议,其余治疗未变. 2011年12月5日复查血生化：T-BiL 21.3 μmol.L^-1,D-BiL 7.6 μmol.L^-1,I-BiL 13.7 μmol.L^-1,ALT 14 U.L^-1. 生化检测示胆红素恢复正常.     

奥曲肽治疗糖尿病并发肝纤维化上消化道出血致血糖下调1例

患者,男,80岁. 因上腹部不适、皮肤黄染6个月余,于2011年9月27日入院. 既往有糖尿病史10余年,口服格列齐特缓释片30 mg,qd,二甲双胍肠溶片0.25 g,tid,血糖仍在6.5～15.0 mmol.L^-1. 既往有血吸虫病史20余年,10年前曾因胆囊结石行胆囊切除术. 2年前曾出现上消化道出血在外院治疗(胃镜有食道胃底静脉曲张报告),2011年7月再次出现上消化道出血,给予醋酸奥曲肽注射液0.2 mg 皮下注射治疗,未出现低血糖情况. 患者于2011年11月9日傍晚出现呕吐咖啡色样胃内容物2次,量中等,隐血试验(＋). 血常规：白细胞(WBC )12.04×109.L^-1,中性粒细胞(N)：0.937,血红蛋白(HGB)：132 g.L^-1,血小板(PLT)70×10⁹.L^-1,生化：总胆红素142 μmol.L^-1,直接胆红素81.5 μmol.L^-1,丙氨酸氨基转移酶(ALT)：63 U.L^-1,天冬氨酸氨基转移酶(AST)：151 U.L^-1,糖化血红蛋白2.4 mmol.L^-1,C反应蛋白(CRP)40.9 mg.L^-1;凝血功能：凝血因子Ⅰ时间 16.4 s,活化部分凝血活酶时间(APTT)26.8 s,凝血酶时间 12.8 s,凝血酶原时间(INR)1.38,纤维蛋白原(FIB)2.3 g.L^-1,D2聚体190.0 ng.mL^-1,肝炎系列(-),大便隐血(＋＋). B超提示：血吸虫性肝硬化,门静脉直径12 mm,总胆管结石伴扩张,胆总管13～19 mm,下段见约17 mm增强光团伴声影,脾肿大,脾厚51 mm,上下径185 mm,胰未见异常. 诊断为：① 血吸虫性肝纤维化失代偿期,食管 胃底静脉曲张破裂出血;②胆总管结石;③2型糖尿病. 处理：禁食并停口服药,给予醋酸奥曲肽针0.2 mg,q8h静脉推注维持,泮托拉唑针40 mg静脉滴注,氨甲环酸针100 mL静脉滴注等治疗,同时考虑能量补充给予5%葡萄糖注射液500 mL加胰岛素6 U静脉滴注. 1 h后患者出现心慌、乏力,测血糖2.7 mmol.L^-1,给予50%葡萄糖注射液40 mL静脉推注后症状缓解,30 min后复测血糖11.3 mmol.L^-1. 4 h后继续监测血糖为3.2 mmol.L^-1,继续给予高糖治疗. 第2天奥曲肽针持续静脉维持下给予10%葡萄糖注射液500 mL静脉滴注,血糖在3.1 mmol.L^-1,继续补充葡萄糖治疗. 第3天出现类似情况,并给予相应处理. 第4天停用奥曲肽,给予米汤肠内营养支持,未加用降糖药,监测血糖空腹4.0 mmol.L^-1,餐后6.1 mmol.L^-1. 5 d后改为半流质,每餐进食米粥约75 g,仍未予降糖药,餐前、餐后血糖均在正常范围. 迄今3个月饮食正常情况下无血糖异常情况.     

何首乌致药物性肝炎1例

患者,男,36岁. 主因乏力、尿黄10 d入院,患者自述于2010年11月初因慢性肾小球肾炎自行服用中药“首乌延寿片”(主要成分为制何首乌干浸膏,含量：每片0.17 g),每次5片,tid,制首乌粉15 g.^-1治疗1个月. 10 d前逐渐出现乏力、尿黄,色呈浓茶色. 并逐渐出现皮肤瘙痒,解陶土样便3次,量正常. 遂到附近医院检测肝功能：丙氨酸氨基转移酶ALT)2 194 U.L^-1、天冬氨酸氨基转移酶(AST) 1 006 U.L^-1、总胆红素(T-BiL)30.30 μmol.L^-1、碱性磷酸酶(ALP) 241 U.L^-1、γ-谷氨酰胺转移酶(γ-GT)199 U.L^-1. 肾功能正常. 为进一步诊治故来我院. 体检：生命体征平稳. 皮肤、巩膜重度黄染,无肝掌及蜘蛛痣. 心、肺一般检查未见异常. 腹平软,无压痛及反跳痛,未触及包块,肝脾肋下未触及,未触及胆囊,Murhy征阴性,肝上界位于右锁骨中线第5肋间,下界位于右季肋缘,肝区无叩痛. 入院辅助检查：ALT 1 371 U.L^-1、AST 539 U.L^-1、T-BiL 189.10 μmol.L^-1、D-BiL 104.60 μmol.L^-1、ALP 137 U.L^-1、γ-GT 193 U.L^-1,尿酸(UA)447 μmol.L^-1. 电解质、甲胎蛋白(AFP)、凝血因子Ⅱ时间(PT)、免疫球蛋白正常. HBV-M：HBsAg(-)、HBsAb(＋)、HBeAg(-)、HBeAb(-)、HBcAb(-),抗-HAV、抗-HCV、抗-HEV、抗-EBV、抗-CMV、抗-HIV、抗梅毒螺旋体、自身抗体均阴性. 腹部B超示：肝弥漫性损害. 既往无肝病史. 根据其有服首乌中药史、临床表现及辅助检查,诊断为药物性肝炎,嘱其停服首乌制剂. 卧床休息,给予保肝、降酶、退黄对症治疗,并给予泼尼松 40 mg,po,早晨顿服,逐渐减量,治疗37 d后复查肝功能正常后出院.     

GC测定健儿清解液中6个挥发性成分的含量

目的 测定不同厂家生产的健儿清解液中挥发油成分糠醛、樟脑、苯甲醛、4-萜品醇、α-松油醇和龙脑的含量。方法 采用HP-INNOWAX毛细管柱为分离柱,以环己酮为内标,程序升温,进样口温度200 ℃,检测器：FID,温度220 ℃。结果 糠醛、樟脑、苯甲醛、4-萜品醇、α-松油醇和龙脑的线性范围分别为5.139～128.467 μg?ml_^-1(r=0.99990),1.900～47.500 μg?ml_^-1(r=0.99937),6.537～163.436 μg?ml_^-1(r=0.99996),1.057～26.423 μg?ml_^-1(r=0.99938),2.398～59.958 μg?ml_^-1(r=0.99923),1.014～25.346 μg?ml_^-1(r=0.99936);该方法的回收率分别为97.0%,99.3%,98.6%,94.6%,93.5%,101.2%。不同厂家生产的健儿清解液中上述成分含量存在较大差别。结论 该方法可为健儿清解液质量标准的提高提供科学数据。     

丁二磺酸腺苷蛋氨酸致过敏性荨麻疹1例

患者, 女, 36岁. 因反复乏力、纳差2 a余, 巩膜及皮肤黄染3 d, 于2008年入住我院感染科治疗. 否认既往药物变态反应史. 实验室检查肝功能：丙氨酸氨基转移酶(ALT)537 U•L^-1, 天冬氨酸氨基转移酶(AST) 436 U•L^-1, 碱性磷酸酶(ALP) 107 U•L^-1, r-谷氡酰转肽酶(r-GT) 113 U•L^-1, 总胆汁酸(TBA) 79.4 μmol•L^-1, 总胆红素(T-BiL) 134.8 μmol•L-1, 直接胆红素(D-BiL) 80 μmol•L^-1, TP 67g•L^-1, A/G 36/31 g•L^-1. 乙肝全套定性：HBsAg(+), HBsAb(+), HBeAg(+), HBeAb(-), HBcAb(+). 腹部B超显示胆囊壁增厚、胆汁淤积, 脾稍大. 诊断：慢性乙型肝炎急性发作期. 入院后首先单用5%葡萄糖注射液250 mL+注射用丁二磺酸腺苷蛋氨酸1 000 mg, 静脉滴注. 当丁二磺酸腺苷蛋氨酸输入后约10 min, 患者从脸部开始出现红色斑块, 逐渐扩散至颈部, 上胸部, 腹部两侧及大腿上部, 红色斑块密集, 感觉不适, 但无瘙痒, 拟诊为过敏性荨麻疹. 生命体征平稳, 体检：体温 37.0 ℃, 呼吸率 20次•min^-1, 心率 80次•min^-1, 血压126/80 mmHg(1 mmHg＝0.133 kPa). 立即停药, 换用输液器, 静脉注射10 mg地塞米松, 10%葡萄糖酸钙注射液10 mL, 约30 min后皮疹部分消退, 直至完全消退. 以后未再使用该药, 其他治疗继续, 也未再发生类似反应.     

利奈唑胺葡萄糖注射液致白细胞增多1例

1例3岁男性患儿因重症肺炎接受静脉滴注利奈唑胺治疗,用药前白细胞计数(WBC)10.51×10⁹.L^-1,C反应蛋白(CRP)409mg.L^-1,降钙素原(PCT)25.95ng.ml^-1。用药第5天患儿临床症状明显好转,WBC51.35×10⁹.L^-1,CRP51.9mg.L^-1,PCT0.42ng.ml^-1,考虑白细胞增多为利奈唑胺所致,停用利奈唑胺更改为万古霉素,10d后患儿白细胞计数降至9.99×10⁹.L^-1。     

甲巯咪唑致粒细胞减少和肝损害及皮疹1例

患者,女,30岁.因心悸,怕热多汗,消瘦2个月,于2010年9月3日来我院就诊.入院体检：体温37.2 ℃,心率93次•min^-1,呼吸20次•min^-1,血压110/70 mmHg(1 mmHg=0.133 kPa),实验室检查血白细胞 5.9×109•L^-1,中性粒细胞计数3.4×109•L^-1;血生化丙氨酸氨基转移酶(alanine aminotransferase,ALT)22 U•L^-1、天冬氨酸氨基转移酶(aspartate aminotransferase,AST) 28 U•L^-1等均正常;尿常规正常.甲状腺功能检测：总三碘甲状腺原氨酸3.19 nmol•L^-1,甲状腺素总量16.81 nmol•L^-1,促甲状腺激素0.01 U•L^-1,游离三碘甲状腺原氨酸11.24 pmol•L^-1,游离甲状腺素2.49 pmol•L^-1.甲状腺超声显示：甲状腺回声不均并血流丰富改变.诊断：甲状腺机能亢进(甲亢).给予甲巯咪唑片10 mg,bid,普萘洛尔片10 mg,tid,po.用药15 d后患者躯干、四肢及面部出现红色皮疹,高出皮面,伴有刺痒,以双髋部及膝盖等处为著,并有食欲下降、恶心等症状.体检：体温37.1 ℃,心率95次•min^-1.复查血常规及生化：白细胞3.2×109•L^-1,中性粒细胞1.8×109•L^-1,ALT 175 U•L^-1,AST 67 U•L^-1.考虑为甲巯咪唑引起的白细胞减少、肝功能异常及皮疹,遂停用甲巯咪唑,其他治疗不变,并给予还原型谷胱甘肽1.2 g + 0.9%氯化钠注射液250 mL,qd,静脉滴注;氯雷他定10 mg,qd,po;利可君40 mg,tid,po,盐酸小檗胺4片,tid,po.6 d后复查血白细胞 4.37×109•L^-1,中性粒细胞3.0×109•L^-1,皮疹逐渐消失.继续给予保肝治疗,1周后复查肝功能：ALT 24 U•L^-1,AST 18 U•L^-1.逐步恢复至正常值     

银杏内酯B对血小板活化因子刺激的大鼠中性粒细胞功能的影响银杏内酯B对血小板活化因子刺激的大鼠中性粒细胞功能的影响

目的 研究银杏内酯B对血小板活化因子(PAF)刺激的大鼠中性粒细胞粘附、趋化及脱颗粒功能的影响。方法 从大鼠外周血分离中性粒细胞,用MTT比色法、Boyden小室法及β-葡萄糖苷酸酶释放法分别检测PAF诱导的粒细胞粘附、趋化及脱颗粒反应。结果10 μmol·L^-1 银杏内酯B可显著抑制中性粒细胞的粘附反应;1～1 000 nmol·L^-1 可剂量依赖性抑制10 nmol·L^-1 PAF诱发的粒细胞趋化反应,其IC₅₀为4.84 nmol·L^-1; 0.01～10 μmol·L^-1可抑制1 μmol·L^-1 PAF诱发的粒细胞释放β-葡糖苷酸酶,其IC₅₀为3.56 μmol·L^-1。结论银杏内酯B能够抑制PAF刺激的大鼠中性粒细胞粘附、趋化及脱颗粒反应。     

甲巯咪唑致粒细胞缺乏死亡1例

患者,女, 51岁. 既往无肝炎、血液病病史, 无食物、药物变态反应史. 此次患者因消瘦乏力4 a, 加重伴高热、双下肢水肿4月, 于2007年12月14日17：00入院. 患者4 a前因无明显诱因出现乏力、进行性消瘦, 诊断为甲状腺功能亢进症(甲亢), 坚持服用2 a甲巯咪唑20 mg, tid, 甲状腺片120 mg, qd, 后觉症状好转, 自行停药. 4个月前无明显诱因再次感乏力, 消瘦明显, 同时有视物模糊, 颈部明显增粗, 自行服用甲巯咪唑10 mg, tid, 甲状腺片120 mg, qd, 症状无明显缓解. 半个月前, 患者有咽痛、腹泻、咳嗽, 自诉咳粉红色泡沫痰, 活动后气喘明显. 入院后急查血常规：WBC 0.97×109&#8226;L^-1, N 0.186, Hb 93 g&#8226;L^-1 , PLT 50×109&#8226;L^-1. 体检：体温40.2 ℃, 脉搏84次&#8226;min^-1, 呼吸率22次&#8226;min^-1, 血压114/67 mmHg(1 mmHg＝0.133 kPa), 神清, 精神萎, 面色潮红, 平卧位, 查体合作, 指颤明显, 皮肤巩膜轻微黄染, 无出血. 扁桃体Ⅱ度肿大, 颈软, 气管居中, 双侧甲状腺Ⅱ度肿大, 质中, 甲状腺区未闻及血管杂音, 未扪及震颤. 呼吸稍促, 双肺呼吸音粗, 未闻及干湿音, 心脏向两侧扩大, 心率84次&#8226;min^-1, 律不齐, 心尖区可闻及Ⅲ级收缩期杂音. 腹软, 无压痛、反跳痛, 肝、脾未触及. 双下肢轻度凹陷性水肿, 足背动脉搏动有力, 四肢肌力正常, 生理反射存在, 病理征未引出. 实验室检查：天冬氨酸氨基转移酶(AST) 81 U&#8226;L^-1,丙氨酸氨基转移酶(ALT)80 U&#8226;L^-1, γ-谷氨酰转移酶(γ-GT) 379 U&#8226;L^-1,清蛋白32.6 g&#8226;L^-1. 尿素氮(BUN)2.8 mmol&#8226;L^-1, 血肌酐(SCr) 35.5 μmol&#8226;L^-1. 血钾离子(K+)3.0 mmol&#8226;L-1,钠离子(Na+)133 mmol&#8226;L^-1,钙离子(Ca²⁺)1.48 mmol&#8226;L^-1,磷离子(P3+)0.72 mmol&#8226;L^-1, 余正常. 尿蛋白(+ +)、隐血(+ + + +). 甲状腺功能检查：游离三碘甲腺原氨酸 (FT3)38.66 pmol&#8226;L^-1, 游离甲状腺素(FT4)95.42 pmol&#8226;L^-1, 促甲状腺素(TSH) <0.005 μU&#8226;mL^-1. 心电图：窦性心律, 频发室性期前收缩、部分二联律、室性心动过速、T波高尖、QT间期延长. 诊断：甲状腺功能亢进,粒细胞缺乏症,肺部感染, 甲亢性心脏病,药物性肝损伤.     

干扰素致剥脱性皮炎1例

患者,男,17岁. 因发现HBsAg（+）5 d入院. 体检时发现乙肝病原学和肝功能异常. HBV M：HBsAg（+）,HBeAg（+）,HBcAb（+）,HBV-DNA：3.65×107拷贝&#8226;mL-1,肝功能：丙氨酸氨基转移酶（ALT）138 U&#8226;L^-1,天冬氨酸氨基转移酶（AST）47 U&#8226;L^-1,总胆红素（T-BiL）：34.5 μmol&#8226;L^-1. 无乏力、纳差、恶心、呕吐、腹痛、腹泻等不适,门诊以病毒性乙型肝炎收住我科. 体检：体温37 ℃,脉搏80次&#8226;min^-1,呼吸20次&#8226;min^-1,血压104/54 mmHg（1 mmHg＝0.133 kPa）. 皮肤巩膜轻度黄染,全身皮肤无皮疹及出血点,心、肺及腹部检查未见异常. 诊断：慢性病毒性乙型肝炎,轻度,给予重组人干扰素α-2b注射液500 万U ,im,qd. 注射12 d后患者感发冷,发热,体温呈稽留热型伴头痛,全身关节疼痛,无明显咳嗽、咯痰、胸闷、胸痛和气短等症状. 体检：颜面、颈部及躯干部潮红并可见淡红色皮疹,皮疹为麻疹样压之退色,有叶片状脱屑,反复发作,伴有明显瘙痒. 颈部淋巴结肿大. 眼结合膜充血;口腔红肿、咽充血,咽部可见白色荚膜及溃疡、疼痛,吞咽时症状加重,扁桃体Ⅱ度肿大, 右肺下野可闻及细湿音,胸部X线片示：右下肺炎. 给予静脉滴注头孢唑林,左氧氟沙星抗感染;口服泼尼松等药治疗. 第2天始,体温渐下降,上述症状减轻,治疗14 d体温正常,皮疹逐渐消退,复查胸部X线片肺部正常出院.     

Co-occurrence of the Cyanotoxins BMAA,DABA and Anatoxin-a in Nebraska Reservoirs,Fish, and Aquatic Plants

Several groups of microorganisms are capable of producing toxins in aquatic environments. Cyanobacteria are prevalent blue green algae in freshwater systems, and many species produce cyanotoxins which include a variety of chemical irritants, hepatotoxins and neurotoxins. Production and occurrence of potent neurotoxic cyanotoxins β-N-methylamino-l-alanine (BMAA), 2,4-diaminobutyric acid dihydrochloride (DABA), and anatoxin-a are especially critical with environmental implications to public and animal health. Biomagnification, though not well understood in aquatic systems, is potentially relevant to both human and animal health effects. Because little is known regarding their presence in fresh water, we investigated the occurrence and potential for bioaccumulation of cyanotoxins in several Nebraska reservoirs. Collection and analysis of 387 environmental and biological samples (water, fish, and aquatic plant) provided a snapshot of their occurrence. A sensitive detection method was developed using solid phase extraction (SPE) in combination with high pressure liquid chromatography-fluorescence detection (HPLC/FD) with confirmation by liquid chromatography-tandem mass spectrometry (LC/MS/MS). HPLC/FD detection limits ranged from 5 to 7 µg/L and LC/MS/MS detection limits were <0.5 µg/L, while detection limits for biological samples were in the range of 0.8–3.2 ng/g depending on the matrix. Based on these methods, measurable levels of these neurotoxic compounds were detected in approximately 25% of the samples, with detections of BMAA in about 18.1%, DABA in 17.1%, and anatoxin-a in 11.9%.     

Preparation,characterization and evaluation of multi-component-loaded liposomes containing Tat-TOS,phospholipase D inhibitor and doxorubicin

In the present study, we aimed to co-load the α-TOS conjugate Tat-TOS with the phospholipase D inhibitor FIPI and the antitumor drug doxorubicin (DOX) in a liposome delivery system for antitumor metastasis. Firstly, Tat-TOS was synthesized by solid-phase synthesis, and its structure was confirmed. The ability of free and liposomal Tat-TOS to induce apoptosis in vitro was evaluated by flow cytometry. Biodistribution of Tat-TOS-loaded liposomes was investigated by a molecular imaging system. Multi-component-loaded liposomes modified with Tat-TOS containing FIPI and DOX was prepared by thin film dispersion method in combination with pH gradient method and post-insertion method. Physicochemical properties were determined, and the in vitro uptake ability of the formulations was evaluated. The results showed that the prepared liposomes were characterized by a uniform particle size distribution and small particle size. The encapsulation efficiency of FIPI and DOX exceeded 85%. Both free and liposomal Tat-TOS significantly improved the activity of inducing apoptosis of tumor cells. The liposomes modified with Tat-TOS were apparently accumulated in normal lung tissue and tumor metastasized lung. Multi-component-loaded liposomes exhibited the strongest cell uptake capacity, suggesting a stronger anti-metastatic effect and anti-tumor activity in vivo.     

Epidemiology, toxicokinetics, and health effects of methyltert-butyl ether (MTBE)

This paper reviews the published information assessing the kinetics and potential for adverse health effects related to exposure to the fuel oxygenate, methyltert-butyl ether (MTBE). Data were obtained from previously published reports, using human data where possible. If human data were not available, animal studies were cited. The kinetic profile of MTBE in humans is similar for ingestion and inhalation. The concentrations of MTBE to which the general public is expected to be exposed are orders of magnitude below concentrations that have caused adverse health effects in animals. Controlled human studies have not replicated early epidemiology studies that suggested, but did not confirm, a possible association between MTBE exposure and nonspecific health complaints.     

Role of Nitric Oxide in Neurodegeneration: Function,Regulation, and Inhibition

Reactive nitrogen species (RNS) and reactive oxygen species (ROS), collectively known as reactive oxygen and nitrogen species (RONS), are the products of normal cellular metabolism and interact with several vital biomolecules including nucleic acid, proteins, and membrane lipids and alter their function in an irreversible manner which can lead to cell death. There is an imperative role for oxidative stress in the pathogenesis of cognitive impairments and the development and progression of neural injury. Elevated production of higher amounts of nitric oxide (NO) takes place in numerous pathological conditions, such as neurodegenerative diseases, inflammation, and ischemia, which occur concurrently with elevated nitrosative/oxidative stress. The enzyme nitric oxide synthase (NOS) is responsible for the generation of NO in different cells by conversion of L-arginine (Arg) to L-citrulline. Therefore, the NO signaling pathway represents a viable therapeutic target. Naturally occurring polyphenols targeting the NO signaling pathway can be of major importance in the field of neurodegeneration and related complications. Here, we comprehensively review the importance of NO and its production in the human body and afterwards highlight the importance of various natural products along with their mechanisms against various neurodegenerative diseases involving their effect on NO production.     

Accumulation of elements (S,As, Br,Sr, Cd,Hg, Pb) in two populations of Cancer pagurus: Ecological implications to human consumption

The brown crab Cancer pagurus is highly appreciated in Southern European countries and edible tissues are consumed separately or as mixtures. This species is mostly harvested along the Scottish Coast and English Channel and has different market prices depending on the catching area and sex. The aim of this study was to quantify and characterize the contents of S, As, Br, Sr, Cd, Hg and Pb in muscle, hepatopancreas, gonads and gills of female and male crabs from both catching areas. Additionally, the accumulation patterns were evaluated according to hazards for human consumption and from an ecological point of view. Crabs caught off the Scottish Coast had more S and As (gonads), while specimens from the English Channel showed more Cd (gonads) and Br (gonads, muscle). The elemental bioavailability and physiological needs likely explain these differences. Independently of catching area and sex, brown crabs’ muscle and gonads are safe food items as far as contaminants are concerned. Yet, Cd in hepatopancreas was always above the level set by international regulating organizations. Consequently, future risk assessment studies should evaluate Cd concentration in all edible tissues of crustaceans prior to the extensive use of processed tissues in food products.     

1-甲基-1,2,3,4-四氢异喹啉的简易合成

目的制备1-甲基-1,2,3,4-四氢异喹啉。方法以苯乙胺为原料,经酰化反应得乙酰苯乙胺,在多聚磷酸的作用下环合得1-甲基-3,4-二氢异喹啉,经硼氢化钠还原得1-甲基-1,2,3,4-四氢异喹啉。结果反应总收率80%,比文献收率提高了10%,产物结构由1H-NMR光谱确证。结论经酰化、环合、还原三步反应制备1-甲基-1,2,3,4-四氢异喹啉的方法简单,原料便宜,处理容易,副产物较少。     

Effects of bradykinin on signal transduction,cell proliferation,and cytokine,prostaglandin E2 and collagenase-1 release from human corneal epithelial cells

1. We recently demonstrated the presence of phospholipase C-coupled bradykinin (BK) B₂-receptors in human primary and SV40 virus-immortalized corneal epithelial (CEPI) cells.
2. The aims of the present studies were to demonstrate the specific binding of [³H]-BK to CEPI cell membranes and to study its pharmacological characteristics. In addition, we wished to study the functional coupling of the BK receptors to various physiological and pathological mechanisms in the CEPI cells, including phosphoinositide (PI) turnover, intracellular Ca²⁺-mobilization ([Ca²⁺]_i), cell proliferation (via [³H]-thymidine incorporation), and the release of various cytokines, collagenase-1 (matrix metalloproteinase-1) and prostaglandin E₂ (PGE₂).
3. Specific [³H]-BK binding comprised 83±2% of the total binding, and was of high affinity (K_d=1.66±0.52 nM, n=5), saturable (B_max=640±154 fmol g⁻¹ wet weight) and reversible. Competition studies yielded the following affinity values for BK and a number of BK-related peptides: Hoe-140 (D-Arg-[Hyp³,Thi⁵,D-Tic⁷,Oic⁸]BK; icatibant): K_i=0.17±0.07 nM; BK: K_i=1.0±0.11 nM; [Tyr⁸]-BK: K_i=12.9±2.3 nM; [des-Arg⁹]-BK: K_i>9,200 nM (all n=3–5)).
4. BK potently stimulated PI turnover (EC₅₀=2.3±0.3 nM; n=7) and [Ca²⁺]_i mobilization (EC₅₀=8–20 nM) in CEPI cells and both responses were inhibited in a concentration-dependent manner by 100 nM–10 μM Hoe-140, a selective B₂-receptor antagonist, and also inhibited by the selective phospholipase C (PLC) inhibitor, {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122 (1-(6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) (IC₅₀=3.0±1.6 μM). BK-induced [Ca²⁺]_i mobilization was reduced by about 30% in the presence of 4 mM EGTA, but was not significantly affected by 100 nM nifedipine.
5. BK (0.1 nM–10 μM) significantly (P<0.05–0.001) stimulated [³H]-thymidine incorporation into CEPI cellular DNA. However, while interleukin-1α (IL-1α; 10 ng ml⁻¹) potently stimulated the release of IL-6, IL-8 and granulocyte macrophage colony-stimulating factor from CEPI cells, BK (0.1 nM–10 μM) was without effect.
6. Whilst phorbol-12-myristate-13-acetate (PMA; 3 μg ml⁻¹) and 10% foetal bovine serum (positive control agents) significantly stimulated the release of both MMP-1 and PGE₂ from CEPI cells, BK (0.1 nM–10 μM) was without any significant effect under these conditions.
7. In conclusion, these data indicate that the CEPI cells express high-affinity [³H]-BK binding sites representing B₂-subtype BK receptors coupled to PI turnover and [Ca²⁺]_i mobilization which appear to stimulate [³H]-thymidine incorporation into cellular DNA. In contrast, BK failed to elicit the release of PGE₂, various cytokines and MMP-1 from CEPI cells. These results suggest that BK may have a potential role in corneal epithelium wound healing by stimulating cell proliferation.

     

EFFECTS OF HALOTHANE, KETAMINE, PROPOFOL AND ALFENTANIL ANAESTHESIA ON CIRCULATORY CONTROL IN RABBITS

1. We have made a within-rabbit comparison of the effects of four general anaesthetic regimens on the haemodynamic response to acute reduction in central blood volume and on baroreflex control of heart rate. 2. Acute haemorrhage was simulated by gradually inflating a cuff on the inferior vena cava in order to cause cardiac output to fall at a constant rate of 8.5%/min while the responses of systemic vascular resistance, arterial pressure and heart rate were measured. The full range of the baroreceptor-heart rate reflex was elicited by inflating aortic and vena caval cuffs. These indices of circulatory control were repeatedly measured within five protocols, to which each rabbit was exposed in randomized order. 3. In each protocol the rabbit was first studied unanaesthetized. Then a small dose of thiopentone sodium was given (16 mg/kg). In the four main protocols the rabbit was then intubated and ventilated, first with 100% oxygen and then with 50% nitrous oxide, during administration of one of four anaesthetic agents. These were halothane (2.0 and 2.5%), ketamine (2.5 mg/kg per min), propofol (0.83 and 1.25 mg/kg per min) and alfentanil (2.5 and 3.33 micrograms/kg per min). In a sham protocol the effects of 100% oxygen, then those of 50 and 75% nitrous oxide, were studied while the rabbit remained conscious. 4. In unanaesthetized rabbits, in the presence or absence of nitrous oxide, the normal biphasic haemodynamic response to simulated haemorrhage occurred. The first, vasoconstrictor, phase was attenuated by halothane, ketamine and propofol, so that arterial pressure fell more steeply than normal. Not only was the vasoconstrictor phase unaffected by alfentanil but it was extended, so that arterial pressure remained at a normal level even when cardiac output had fallen by 59%. This effect of alfentanil appeared to be mediated centrally, since it could be reproduced by injecting small doses (1.5-7.5 micrograms) into the fourth ventricle. All four anaesthetic agents and nitrous oxide attenuated the baroreceptor control of heart rate. The effect was least with nitrous oxide and alfentanil, greatest with halothane.