Delayed Enhancement of Acetaminophen Hepatotoxicity by General Anesthesia Using Diethyl Ether or Halothane

Delayed Enhancement of Acetaminophen Hepatotoxicity by GeneralAnesthesia Using Diethyl Ether or Halothane. WELLS, P. G., RAMJI,P., AND KU, M. S. W. (1986). Fundam. App. Toxicol 6, 299–306.Acetaminophen (Tylenol) is a widely used analgesic/antipyreticdrug which is enzymatically bioactivated, or toxified, by thecytochromes P-450 to a hepatotoxic reactive intermediary metabolite.Brief general anesthesia with diethyl ether has been shown toinhibit both the toxifying cytochromes P-450 and enzymatic glucuronidation,the latter constituting up to 60% of acetaminophen eliminationvia a nontoxifying pathway. Thus ether potentially could producea temporally differentiated inhibition of bioactivating and"detoxifying" pathways, resulting in an enhancement of acetaminophenhepatotoxicity if the balance favored bioactivation. To evaluatethis possibility, separate groups of male NIH strain mice weretreated with acetaminophen at different times after 5 min ofanesthesia with ether. Ether produced a 40-fold enhancementin acetaminophen hepatotoxicity as determined by plasma glutamic-pyruvictransaminase (GPT) concentrations. This toxicologic enhancementwas observed only if acetaminophen administration was delayed,with a maximal enhancement when acetaminophen was given 6 hrafter ether, and no effect with a delay of 16 hr. Similar studiesin male CD-1 mice were carried out using halothane (Fluothane)as the general anesthetic given either over 5 min or over 1hr. While halothane given over 5 min had no effect, a 1 hr anestheticduration produced a 10-fold increase in acetaminophen hepatotoxicityas determined by peak GPT concentration, with no observed hepatotoxicityin the halothane controls. Toxicologic enhancement occurredonly with delayed administration of acetaminophen; however,the maximal enhancement observed with a 6-hr delay was stillevident with a 12-hr delay. Conversely, inhibition of acetaminophenhepatotoxicity was observed if acetaminophen was given either2 hr or 18 hr after halothane. These observations may have clinicalrelevance, and they indicate potential complications in theinterpretation of results obtained from animals subjected togeneral anesthesia.     

Expert systems in the health administration curriculum

With the growing use of computers and on-line hospital information systems, a need exists for health care managers trained in computing and computer applications. This article reviews the advances in health care computing and reports on the design and implementation of a new course in a specific computer application, known as expert systems, in a health administration curriculum. The specific course framework is described and several student projects are presented and discussed.     

反相高效液相色谱法测定甘露药浴颗粒中盐酸麻黄碱的含量

目的以反相高效液相色谱法(RP-HPLC)测定甘露药浴颗粒(外用)中盐酸麻黄碱的含量。方法色谱柱:WatersC18(150mm×4.6mm);流动相:水-乙烷-十二烷基硫酸钠-磷酸(650∶350∶5∶1);流速:1.0mL/min;柱温:26℃;检测波长:210nm。结果该方法的线性范围为0.127～0.130μg/μL(r=0.9996,n=5),平均回收率为99.72%,RSD=1.12%。结论本法简便、准确、重现性好,可用于该制剂的质量控制。     

Genotoxicity of the pyrrolizidine alkaloid jacobine in rats

Jacobine (JAC) is a pyrolizidine alkaloid (PA) exhibiting adverse hepatic effects similar to those induced by another PA, monocrotaline (MCT). The in vitro reaction kinetics of JAC, however, have been reported to differ quantitively from those of MCT. We report results of experiments to detect and characterize hepatic DNA damage resulting from in vivo administration of JAC (5-60 mg/kg i.p.) to male Sprague-Dawley rats. Hepatic nuclei were isolated and served as the source of DNA in these experiments. Alkaline elution was employed to characterize the type(s) of DNA damage induced. At 4 h post administration, JAC induced significant dose-dependent DNA-DNA interstrand cross-linking over the entire range of doses. Significant DNA-protein cross-linking was also induced by doses of 15-60 mg/kg. No DNA single-strand breaks were detected. Previous studies in this laboratory have shown MCT to induce these same types of lesions. Results from these experiments demonstrate that despite a reported difference in vitro reaction kinetics, these compounds induce a similar spectrum of DNA damage in the target organ of a susceptible species, where the adverse effects induced are also similar. such similarities are consistent with the involvement of DNA damage in the adverse hepatic effects of PAs.     

解郁丸抗抑郁作用机制的初步研究

目的 :初步探讨解郁丸抗抑郁作用机制。 方法 :采用高剂量阿朴吗啡导致体温下降试验,5-羟色胺酸(5-HTP)诱导甩头行为试验以及高效液相色谱-电化学检测法测定小鼠下丘脑、皮层、海马等脑内单胺类递质及其代谢产物含量。 结果 :解郁丸能显著拮抗高剂量阿朴吗啡所致小鼠体温下降;增加5-HTP诱导甩头行为。解郁丸单次和连续14 d给药,可提高下丘脑中去甲肾上腺素(NE)、多巴胺(DA)与DA的代谢产物3,4-二羟基苯乙二醇(DOPAC)的比值;也可使皮层中5-HT,NE,5-HT的代谢产物5-羟吲哚乙酸(5-HIAA),DOPAC含量升高,降低5-HT与5-HIAA及DA与DOPAC的比值;并可提高海马中5-HT与5-HIAA及DA与DOPAC的比值。解郁丸可使利血平化小鼠下丘脑中NE,5-HIAA,海马中5-HT,5-HIAA,DA与DOPAC的比值明显升高。 结论 :解郁丸抗抑郁作用机制可能与调节不同脑区的5-HT,NE等神经递质有关。单次和连续14 d给药可增加不同脑区5-HT,NE,DA的含量,连续14 d给药对利血平化所致不同脑区单胺类递质含量下降也有不同程度的翻转效应。     

京都酚的致惊作用

京都酚为-中枢神经系统活性二肽,icv可使小鼠出现惊厥。右旋京都酚致惊活性明显强于左旋体。利血平化动物明显增强京都酚的致惊作用,对于京都酚在利血平化小鼠所引起的惊厥,L-Dopa可使之减弱。5-HTP及纳洛酮可使之增强;抗癫痫药中硝基安定、苯妥英钠和丙戊酸钠可明显延长发作潜伏期,缩短持续时间和减少发作率。     

绝经后骨质疏松症与牙周病的关系

绝经后妇女体内雌激素水平降低,从而易患骨质疏松症。绝经后骨质疏松症的形成机制,已为广大学者所证实,但它是否是牙周炎的易感因素,是否会促进牙周炎的发展,目前尚无定论。本文就绝经后骨质疏松症与牙周炎之间的关系做一简要综述。     

洛铂联合5-氟尿嘧啶与亚叶酸钙治疗晚期食管癌的Ⅱ期临床研究

目的：评价洛铂联合5-FU与亚叶酸钙治疗晚期食管癌患者的疗效及安全性。方法：对40例未经化疗的晚期食管癌患者。给予以下方案化疗;洛铂50mg,静脉滴注,2h;亚叶酸钙200mg／m^2,静脉滴注,2h,d1～d3;5-FU400mg／m^2,静脉推注,d1～d3;5-FU600mg／m^2,持续静脉滴注,22h,d1～d3。每21d重复。完成2个周期后行疗效评价。结果：可评价疗效病例37例,其中CR1例,PR16例,SD15例,PD5例,总有效率为45．9％（17／37）（95％CI为30％～63％）,其中初治患者的总体疗效为68．2％（15／22）,复治患者中总体疗效为13．3％（2／15）;中住疾病进展时间为6个月。主要不良反应为骨髓抑制,其中白细胞下降Ⅲ,Ⅳ度为21.1％,血红蛋白下降Ⅲ,Ⅳ度为10．0％,血小板下降Ⅲ度为3．3％,未发现Ⅳ度反应。结论：该联合方案显示明显的抗肿瘤作用,与其他含铂方案相比,洛铂不良反应相对较轻,耐受性好。     

Mustard operation in the 1st month of life

Since April 1976, nine infants less than 1 month of age underwent a Mustard intraatrial baffle procedure. All had transposition of the great arteries and were persistently symptomatic or hypoxic after the Rashkind balloon atrioseptostomy. Two had an associated large ventricular septal defect patched at the time of physiologic correction. The average age of the infants was 11.6 days (range 36 hours to 28 days). Weight averaged 3.4 kg (range 2.5 to 4.2). In all the Mustard procedure was performed using deep hypothermie circulatory arrest, averaging 71 minutes (range 48 to 88) at a mean core temperature of 13 °C. An average of 2.8 days of postoperative ventilatory assistance was required. One death occurred in a 28 day old male infant with an associated ventricular septal defect who, the morning after operation, had a sudden unresponsive cardiac standstill. The postoperative hospitalization period averaged 15 days (range 10 to 23). Follow-up evaluation has extended from 4 to 63 months (average 31). Six patients were restudied 2 to 21 months postoperatively. One had obstruction of the superior limb of the baffle, which had separated from the right atrial wall permitting a modest right to left shunt. She has had uneventful repair employing a unique modification of Senning's operation. Another child has asymptomatic partial obstruction of the superior limb of the baffle demonstrated angiographically. None has pulmonary venous obstruction and all have prevailing normal sinus rhythm. Significant right ventricular dysfunction has been demonstrated in one. Early correction in these persistently symptomatic or hypoxic neonates with transposition of the great arteries with or without a ventricular septal defect has obviated the need for palliative operations and produced gratifying early and late results.