Hydrolysis kinetics of propylene glycol monomethyl ether acetate in rats in vivo and in rat and human tissues in vitro.

The kinetic equivalency of propylene glycol monomethyl ether (PGME), derived from propylene glycol monomethyl ether acetate (PGMEA), as well as the parent compound (PGME) following intravenous administration to Fischer 344 rats was evaluated. In addition, in vitro hydrolysis rates of PGMEA in blood and liver tissue from rats and humans were determined. The blood kinetics were determined following iv administration to rats of PGME and PGMEA of low [10 and 14.7 mg/kg body weight (bw)] or high (100 and 147 mg/kg) equimolar dosages of PGME and PGMEA, respectively. The blood time courses of PGME elimination for both dosages of both compounds were identical. Half-lives of PGMEA elimination following iv administration of 14.7 or 147 mg PGMEA/kg bw were calculated to be 1.6 and 2.3 min, respectively. Rat and human in vitro hydrolysis rates of PGMEA were determined by incubation of 5 or 50 microg PGMEA/ml in whole blood or liver homogenate. The rate of loss of PGMEA was more rapid in rat blood than in human blood, with hydrolysis half-lives of 36 and 34 min in human blood and 16 and 15 min in rat blood for the 5 and 50 microg/ml concentrations of PGMEA, respectively. In contrast the rate of loss of PGMEA in human and rat liver homogenate incubations was similar, 27-30 min and 34 min, respectively. These data demonstrate the rapid hydrolysis of PGMEA in vivo to its parent glycol ether, PGME and that, once hydrolyzed, the kinetics for PGME derived from PGMEA are identical to that for PGME. This study supports the use of the toxicological database on PGME as a surrogate for PGMEA.     

罗红霉素在犬体内的代谢转化罗红霉素在犬体内的代谢转化

目的考察罗红霉素在犬体内的代谢转化及po和iv给药途径对药物代谢的影响。方法采用液相色谱-质谱(LC-MSⁿ)联用技术,检测在iv或po给予单剂量罗红霉素后犬胆汁中的罗红霉素及其代谢物。代谢物经LC/MSⁿ方法分离和分析,并通过与对照品比较质谱和色谱行为确定其结构。结果共检测到13种罗红霉素代谢物,包括N-去甲基和N, N-双去甲基衍生物、肟醚侧链O-去烷醚基衍生物、脱红霉糖衍生物、罗红霉素及其代谢物的Z式几何异构体衍生物。结论罗红霉素在犬体内主要经历4种代谢途径;罗红霉素及其代谢物的几何异构与脱红霉糖代谢在口服和注射两种给药途径间存在显著的差异。     

甲状腺功能对磺胺嘧啶在大鼠体内药动学的影响

目的: 测定不同甲状腺功能状态时大鼠血液中磺胺嘧啶钠(SD)的浓度,研究甲状腺功能状态对其药代动力学的影响.方法: 采用分光光度计比色法测定技术.结果: 甲亢组大鼠磺胺嘧啶在体内消除加速,峰浓度下降,AUC减少,消除t1/2缩短.甲减组大鼠则消除减慢,峰浓度增高,AUC增大,消除t1/2延长.结论: 甲状腺功能提高时,大鼠对磺胺嘧啶的代谢能力明显增加,消除加速;而甲状腺功能降低则相反.     

家兔急性缺氧后左心室舒张功能和心肌细胞内钙转运及能量代谢的研究

为探讨急性缺氧对家兔左心室舒张功能、心肌细胞内钙转运和能量代谢的影响。将２３只家兔分为对照组（６只）、吸入５％低氧混合气的缺氧１组（Ｈ１）（１２只）、吸入１０％低氧混合气的缺氧２组（Ｈ２）（５只），用心导管法测定左心室压力下降最大速率（ＬＶｄｐ／ｄｔｍａｘ）和压力下降时间常数（Ｔ值）；测定心肌肌浆网（ＳＲ）钙ＡＴＰ酶活性、心肌ＳＲ摄钙量、心肌组织ＡＴＰ和磷酸肌酸（ＣｒＰ）。结果，缺氧后ＬＶｄｐ／ｄｔｍａｘ下降，Ｔ值延长；缺氧组心肌ＳＲ钙ＡＴＰ酶活性及摄钙量下降；心肌线粒体钙含量升高；心肌组织ＡＴＰ和ＣｒＰ下降，心肌组织ＡＴＰ与线粒体钙含量呈负相关。提示，急性缺氧可引起左心室舒张功能障碍并影响心肌ＳＲ钙转运和心肌能量代谢。     

PATHOLOGY OF LONG-CHAIN 3-HYDROXYACYL-COA DEHYDROGENASE DEFICIENCY CAUSED BY THE G1528C MUTATION

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is a recently discovered disorder affecting the mitochondrial-oxidation of fatty acids. There have been few reports of the pathologic findings in-oxidation defects. We examined pathologic specimens from 16 patients with this disorder (11 patients were homozygous for the common mutation G1528C, 5 patients were siblings with a similar clinical presentation). Autopsies were performed on all 15 patients who died, and liver biopsy specimens were available from 8 patients. Hepatomegaly and steatosis of the liver, found in every patient, were often combined with fibrosis or cirrhosis. Cardiomegaly and accumulation of fat in the myocardium, renal tubules, and skeletal muscle were found in many patients. A detailed neuropathologic examination was performed on six patients, and brain specimens obtained at autopsy were examined in four others. In general, neuropathologic findings were mild and unspecific, but vacuolization was detected in the deep gray matter and in the cerebellum and brain stem nuclei of five patients. In one patient the vacuolization was prominent; in the other four it was milder and more focal. The vacuoles seemed to be either in the neuropil or associated with swollen hydropic cells. The uniform pattern of histopathologic changes facilitates the diagnostics in this severe disorder, allowing opportunities for therapy and prenatal diagnosis.     

A new case of malonyl coenzyme A decarboxylase deficiency presenting with cardiomyopathy

A new case of mitochondrial malonyl coenzyme A decarboxylase deficiency is described. The patient presented with an initial episode of metabolic acidosis, seizures, hypoglycemia, and cardiac failure at 2 months of age which slowly resolved. Subsequent evaluations at 4 years of age for developmental delay revealed a prominent elevation of malonic acid in urine. Malonyl carnitine was also elevated. The activity of malonyl CoA decarboxylase in cultured fibroblasts was 7% of normal. Conclusion Malonyl CoA decarboxylase deficiency may result in inhibition of fatty acid oxidation, which may account for the cardiomyopathy. Received: 12 April 1996 / Accepted: 24 September 1996     

突发性聋与铁代谢障碍疾病关系的临床调查

对１９７９年７月至１９９６年６月的突发性聋发病情况进行前瞻性研究与回顾性分析，探讨突聋与铁代谢障碍疾病的关系，前瞻性研究的对象分为铁代谢障碍疾病组２１８例，血液病组２１５例和正常对照组４８５０例；回顾性分析为１７年间资料完整的４２９例突聋患者史的代谢障碍疾病及其他血液病的发病情况。结果表明，铁代谢障碍疾病组的突聋调整年发病率显著高于血液病组以及正常对照组，４２９例突聋患者的无贫血缺铁，缺铁性人同血     

三七皂甙对脑组织血液供应和能量代谢的影响

目的研究三七皂甙（ＰＮＳ）对脑组织血液供应和能量代谢的影响。方法采用激光多普勒流量仪动态监测软脑膜微循环的变化以及反相高效液相法测定脑组织中高能磷酸化合物的含量。结果ＰＮＳ２５、５０ｍｇｋｇ－１ｉｖ明显扩张麻醉小鼠软脑膜微血管，增加局部血流量，加快血流速度；但对结扎双侧颈总动脉引起的脑血流量的减少没有作用。ＰＮＳ（５０、１００ｍｇｋｇ－１ｉｐ，×３ｄ）明显延缓缺血组织ＡＴＰ的分解，改善能量负荷。结论ＰＮＳ可通过增加组织血液供应改善能量代谢，从而保护脑组织。     

绞股蓝总甙复合国产1号避孕片对健康妇女脂类代谢及血压的影响

本研究将180名已婚、一孩、年龄33±5岁,需要使用避孕措施的健康妇女随机分成6组,即IUD组、绞股蓝总甙加IUD组、1号OC片组、40mg、60mg、80mg绞股蓝总甙分别与1号OC片复合的3个试验组.用双盲法给药,连续服用6个月观察脂类代谢和血压的变化.结果显示:以IUD组和1号OC片组的数据为参比值.服用不同剂量绞股蓝总甙复合口服避孕药后无升高TG和TC的趋势,有显著升高HDL-C作用和使APOA_1水平上升的趋势;亦存在降低收缩压的趋势,对舒张压无明显影响,但在服药后3个月时HDL-C水平曾发生暂时性下降.     

艾灸涌泉穴对老年大鼠自由基代谢影响的研究

目的:探讨艾灸延缓衰老的作用机理。方法:建立自然衰老大鼠模型,分为老年时照组、维生素 E 组及艾灸组,观察大鼠血清和脑组织超氧化物歧化酶(SOD)活性、过氧化脂质(LPO)含量。结果:老年大鼠组血清和脑组织 SOD 活性明显低于青年大鼠组,LPO 含量明显高于青年大鼠组。艾灸组灸涌泉穴后,与老年对照组比较,其血清和脑组织 SOD 活性明显升高(45.30±6.17、35.03±3.67u/ml,P<0.01;2399±316、2005±206u/g 脑组织湿重,P<0.01); LPO 含量明显降低(3.30±0.55、4.40±0.51μmol/L,P<0.01;341±69、446±44nmol/g 脑组织湿重,P<0.01)。维生素 E 组大鼠与老年对照组大鼠比较,其血清和脑组织 SOD 活性差异无显著性。结论:艾灸涌泉穴能增强 SOD 活性,提高老年大鼠清除自由基的能力,改善老年大鼠自由基代谢失调的状况,从而阻止自由基损害机体,保护脑功能,延缓脑衰老,推迟衰老进程。