Induction of rat hepatic UDP-glucuronosyltransferases by dietary ethoxyquin

Summary Dietary administration of 0.5% ethoxyquin markedly enhanced rat hepatic UDP-glucuronosyltransferase activities. Both 3-methylcholanthrene- and phenobarbital-inducible glucuronidation reactions were stimulated by the antioxidant. In contrast, phenobarbital-inducible bilirubin glucuronidation was not affected by ethoxyquin.     

Inhibition of some rat hepatic microsomal enzymes by ethoxyquin

Administration of single intragastric doses of ethoxyquin (500 mg/kg) to rats dramatically increased the hexobarbitone sleeping time. Conversely, dietary administration of ethoxyquin (0.5% w/w) for 14 days led to a 50 per cent decrease in the hexobarbitone sleeping time. Single doses of ethoxyquin had little effect on hepatic mixed function oxidase activity. Ethoxyquin was shown to be a potent competitive inhibitor of rat hepatic microsomal biphenyl 4-hydroxylase and ethylmorphine N-demethylase in vitro (K_i = 4.3 × 10^?6 M and 6.0 × 10^?6 M respectively) and displayed a type 1 binding spectrum with cytochrome P-450 with a very high affinity (K_s = 1.06 × 10^?5 M). Ethoxyquin had no inhibitory effect on the activity of glucose-6-phosphatase in vitro.     

不同酒类致酒精性肝损伤的病理学比较

目的 观察不同酒类对肝脏细胞的损伤作用.方法 将Waister大鼠100只随机分为3组:对照组20只,用等体积的等渗氯化钠溶液代替酒精灌胃;红酒组与白酒组各40只,分别给大鼠灌入大剂量的红葡萄酒、烈性白酒,3个月后处死动物,摘取肝脏,制备成病理切片,在光镜和电镜下观察肝脏的形态学变化.结果 烈性白酒可严重损伤肝细胞,导致酒精性肝炎与脂肪肝,与对照组及同时段红酒组比较,差异均有统计学意义(P＜0.05或0.01),红葡萄酒对肝脏损伤轻微,为可逆性病变.结论 长期或大量饮用烈性白酒可造成不可逆的肝脏损伤,导致酒精性肝炎与严重的脂肪肝.大量红葡萄酒的这种损伤作用则比较轻微.     

西酞普兰引起肝功能异常

1例70岁男性患者因咳嗽、咯痰加重,伴发热、气促,给予头孢哌酮钠-舒巴坦钠、万古霉素、奥美拉唑、泼尼松、谷胱甘肽治疗。治疗第8天,因抑郁症给予西酞普兰10mg,1次/d。第9天丙氨酸转氨酶(ALT)及天冬氨酸转氨酶(AST)分别从47U/L、52U/L升至139U/L、145U/L。第10天因抑郁症状未控制,西酞普兰加量至20mg,1次/d。之后肝酶明显增高,第19天实验室检查示ALT529U/L,AST 256U/L。考虑为西酞普兰引起的肝功能异常,遂停用该药,其他合并用药继续应用。随后肝功能水平逐渐下降。     

阿奇霉素致肝损害1例

患者,男,17岁,持续性发热5天入院,最高体温39．8℃,伴咳嗽、咳痰,痰为白色粘痰,既往体健,否认“肝炎、结核、伤寒、疟疾”等传染病史,无重大外伤、手术及输血史。发病后,曾自服中草药（具体不详）,头孢匹胺及消炎痛栓治疗1天,体温有所下降．对。青霉素”过敏。体检可见患者,神志清,精神可,     

别嘌醇致药源性肝病1例

别嘌醇(allopurinol)是通过抑制次黄嘌呤氧化酶,使尿酸合成减少,从而降低血中尿酸浓度,减少尿酸盐在骨、关节及肾脏的沉着.临床上常作口服,用于治疗慢性痛风.常见的不良反应有服药后可出现皮疹、瘙痒等皮肤反应,偶有低热和出现暂时性转氨酶增高等.多是短暂性的,停药后很快消失,但如再次用药,上述症状会复发.曾有报道[1]因服用别嘌醇引起剥脱性皮炎,伴肝、肾功能异常,最终肾功能衰竭致死.但致全身性和中毒性反应不常见.现将因服用别嘌醇致严重的药源性肝病1例报道如下.     

由微生态平衡的变化引起的有机体的熵变

本文从熵的角度说明生命过程进而解释有机体的状态变化的物理本质。生命体的各个系统在正常状态和疾病状态时,都对应着一定的熵值。当有机体内微生态平衡发生变化时,机体将产生相应的反应,出现某些疾病现象,这时相应的熵值也就发生改变。而物与细菌或病毒作用时,熵又可反映出其敏感性程度。     

DNA damage induced by ethoxyquin in human peripheral lymphocytes

Ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline, EQ) is widely used in various food products and in animal feeds because of its powerful antioxidant activity. This compound was recently found to cause not only many unfavourable side-effects in animals fed with feeds containing it, but also adverse effects in people exposed to it at work. In the present study, DNA damage induced by EQ in human lymphocytes has been assessed. The alkaline single cell gel electrophoresis assay (comet assay) was used to measure DNA damage. The cells were treated for 1 h with EQ doses ranging from 1 to 250 microM in the absence or in the presence of an exogenous metabolic activation system (S9mix). The obtained results showed that EQ-induced DNA damage in human lymphocytes in a dose-dependent manner; the observed DNA fragmentation induced by EQ in the presence of metabolic activation system was always significantly lower, as compared to cells treated with the same doses of EQ alone.     

精神药物对346例患者心电图的影响

对346例住院患者在用精神药物治疗中ECG变化作动态观察。发现ECG异常率65.0％,20a以下及60a以上年龄组ECG异常率高于其他年龄组,氯氮平及三环类药物对ECG影响明显,单用药ECG异常率显著低于合并用药。药物所致ECG改变以ST-T变化居首位。指出合理用药及定期随访的重要性。     

Accumulation of ethoxyquin in the tissue

Ethoxyquin (EQ) residue levels in the mouse tissue were determined by the HPLC-fluorometric detection method. Mice were given powdered feed containing 0, 0.125, and 0.5% EQ HCl and the EQ residue levels in liver, kidney, lung, and brain tissues were determined after 2, 4, 6, 10, and 14 wk (4 mice/group). The tissue samples were homogenized in 10 volumes (w/v) of acetonitrile-water (7:3, v/v), centrifuged, and the supernatants were stored in a freezer for 2-3 h or until the two layers separated; then the clear upper layers were analyzed. The mean EQ residue levels in the tissue ranged 0.84-4.58 micrograms EQ/g liver and 0.11-0.92 micrograms EQ/g brain. The relative weight of the liver (5.21-7.07% body weight) and the hepatic glutathione level (5.99-7.83 microM GSH/g tissue) of mice that received EQ were significantly higher than those of the controls (4.67-5.05% body weight and 4.30-5.78 microM GSH/g tissue, respectively). The mean hepatic mitochondrial glutathione level of the higher EQ feeding group, following dietary administration of EQ for 14 wk, was approximately twofold (1.68 nM GSH/mg protein) of both the control and the lower EQ feeding groups (0.83 and 0.74 nM GSH/mg protein, respectively).     

Pentopril-cimetidine interaction caused by a reduction in hepatic blood flow

The interactive effects of the coadministration of steady-state cimetidine and single-dose pentopril, an angiotensin converting enzyme inhibitor, on the pharmacokinetic disposition of each other were studied in humans. Cimetidine reduced the clearance of pentopril by 11 to 14%. This reduction in clearance was shown to be caused by a reduction in liver blood flow probably mediated through H2 receptor blockade. Meanwhile pentopril induced the oral clearance of cimetidine by 21%, presumably by a reduction in the bioavailable fraction of cimetidine. The mechanism of this interaction is unknown.     

Ovine urinary metabolites of ethoxyquin.

Metabolites of ethoxyquin (EQ, 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) in the urine of sheep and rats were separated and identified by gas chromatography-mass spectrometry (GC-MS). Sheep were given diets containing EQ or EQ.HCl (0.5% of total diet) and urine samples were collected for the first 24 h and for another 24-h period after 12 d of feeding. Rats were given EQ/corn oil (0.08 g EQ/d/rat) orally for 7 d and urine samples were collected at ambient temperature for a 24-h period following 6 d of dosing. The urine samples were extracted with ethyl acetate at pH 5, and the concentrated extracts were analyzed by GC-MS. Ethoxyquin was identified in all sheep urine samples collected during the first 24 h of feeding, and EQ and hydroxylated EQ were identified in all urine samples collected after 12 d of feeding. In contrast, EQ, hydroxylated EQ, and dihydroxylated EQ were identified in urine collected from rats fed EQ for 7 d.     

肝硬化上消化道出血病因分析

目的：探讨肝硬化上消化道出血的病因。方法：对108例肝硬化上消化道出血患者经纠正低血容量等治疗，待血压平稳后在入院48h内行急诊胃镜检查，判断出血原因。结果：食管、胃底静脉曲张破裂出血60例(55．6％)，门静脉高压性胃病(protal hypertensive gastropaty,HPG)并出血26例(24．1％)；肝源性溃疡(bepatogenic ulcer,HU)出血24例(22.2％)。结论：肝硬化上消化道出血并非都是食管、胃底静脉曲张破裂所致，PHG及HU亦是肝硬化上消化道出血的重要病因，应引以重视。     

Infection by Plasmodium changes shape and stiffness of hepatic cells

Infection of liver cells by Plasmodium, the malaria parasite, is a clinically silent, obligatory step of the parasite's life cycle. The authors studied the progression of Plasmodium infection in hepatic cells by atomic force microscopy, measuring both topographical and nanomechanical changes upon infection. In recent years, several studies have suggested that cellular nanomechanical properties can be correlated with disease progression. The authors' results show that infected cells exhibit considerable topographical changes, which can be correlated with the presence of the parasite, leading to a significant roughening of the cell membrane. The nanomechanical measurements showed that infected cells were significantly stiffer than noninfected cells. Furthermore, the stiffening of the cells appeared to be a cellular reaction to the Plasmodium infection, rather than a result of the stiffness of the invading parasites themselves. This article provides the first evidence of mechanical changes occurring in hepatic cells in response to Plasmodium infection. FROM THE CLINICAL EDITOR: The authors have studied the progression of Plasmodium infection in hepatic cells by atomic force microscopy, measuring topographical and nanomechanical changes upon infection. The nanomechanical measurements demonstrated that infected cells were significantly stiffer than noninfected cells.     

苦参素葡萄糖注射液预防化疗性肝损的临床观察

目的 评价苦参素葡萄糖(保肝中药)注射液对肿瘤化疗药物所致肝损害的预防作用.方法 采用自身对照的方法,83例肿瘤患者每例用同一化疗方案连续进行2个周期化疗.第1周期仅单用化疗,第2周期在化疗同时加用苦参素葡萄糖注射液保肝,观察化疗后肝功能变化.结果 保肝组肝功能损害的发生率(10.84%)明显低于单纯化疗组(25.30%),且其肝损害程度明显轻于化疗组(P<0.01).结论 化疗同时加用苦参素葡萄糖注射液保肝治疗可预防化疗药物对肝脏的损害.     

Purine agonists prevent trophic changes caused by sympathetic denervation

Surgical denervation of the lateral saphenous vein of the dog causes marked extraneuronal changes, both of a morphological and functional type. In an attempt to investigate the factor(s) responsible for the trophic effects exerted by the sympathetic innervation on the dog saphenous vein we studied the effects of noradrenaline, adenosine, inosine and N-ethylcarboxamidoadenosine (NECA) on vascular tissue after sympathetic denervation. The saphenous vein was denervated using either surgical or chemical (6-hydroxydopamine, 6-OHDA) methods. Noradrenaline (0.1 microgram/kg per h), adenosine (10 micrograms/kg per h), inosine (10 micrograms/kg per h) or NECA (0.1 microgram/kg per h) were delivered continuously for 5 days through Alzet minipumps connected to the vein. 6-OHDA-induced denervation resulted in morphological changes similar to those described for surgical denervation. Smooth muscle cells and fibroblasts showed ultrastructural signs of increased synthetic activity and their size was significantly increased. In confirmation of earlier studies, constant i.v. infusions of noradrenaline did not prevent the morphological changes induced by denervation. Adenosine prevented the morphological changes induced by chemical or surgical denervation. Similarly to adenosine, infused NECA prevented the structural consequences of denervation. In contrast, inosine did not prevent the changes caused by surgical denervation. The results are compatible with an involvement of purines in the trophic effects of sympathetic innervation. Moreover, the effects of adenosine do not appear to be mediated by inosine.