Variant angina induced by biliary colic

A 65 year old woman with gall stones presented with crushing chest pain after an attack of biliary colic. The electrocardiogram showed ST segment elevation in leads I, aVL, and V1-V3 while leads II, III, and aVF showed ST segment depression. Cardiac enzyme activity remained within the normal range. During the next three weeks attacks of epigastric and right hypochondrial pain preceded by crushing chest pain with identical electrocardiogram changes occurred with decreasing frequency. Coronary arteriography showed 60% obstruction of the left anterior descending coronary artery and good left ventricular function. During the next three years the patient complained both of mild abdominal pain, probably biliary colic, and mild effort related angina pectoris without a relation between the two symptoms. It is suggested that the attack of variant angina was triggered by biliary colic through sympathoadrenal discharge causing vasospasm.     

Variant angina induced by biliary colic.

A 65 year old woman with gall stones presented with crushing chest pain after an attack of biliary colic. The electrocardiogram showed ST segment elevation in leads I, aVL, and V1-V3 while leads II, III, and aVF showed ST segment depression. Cardiac enzyme activity remained within the normal range. During the next three weeks attacks of epigastric and right hypochondrial pain preceded by crushing chest pain with identical electrocardiogram changes occurred with decreasing frequency. Coronary arteriography showed 60% obstruction of the left anterior descending coronary artery and good left ventricular function. During the next three years the patient complained both of mild abdominal pain, probably biliary colic, and mild effort related angina pectoris without a relation between the two symptoms. It is suggested that the attack of variant angina was triggered by biliary colic through sympathoadrenal discharge causing vasospasm.     

Submassive hepatic necrosis induced by dichloropropanol

ABSTRACT— A hitherto undescribed industrial liver injury of fulminant form induced by dichloropropanol is reported. Two middle-aged men developed severe hepatic injury just after cleaning a dichloropropanol tank at a plant producing dichloropropanol. They died from hepatic failure 4 and 11 days respectively, after carrying out the work. Liver specimens taken at autopsy from one of the cases showed submassive hepatic necrosis. This accident prompted us to undertake an experimental study in rats of intraperitoneal one-shot injection of two isomeric substances of dichloropropanol, that is, 2,3-dichloro-l-propanol (DCIP) and 1,3-dichloro-2-propanol (DC2P). Saline was injected into the control rats. One, two, four, six, 24, 48, 72 h, and 1 week after the injection, rats in each group were sacrificed. Neither control nor DC IP-injected rats showed significant biochemical or histopathological abnormalities. DC2P-injected rats revealed elevations of transaminase from 6 h after the injections, and submassive necrosis of the liver was observed in many rats. It was concluded that the severe liver injuries in both the human cases and rats in our study were caused by DC2P.     

Cimetidine suppresses chemically induced experimental hepatic porphyria

The ability of cimetidine to reduce the activity of hepatic aminolevulinic acid synthase (ALA-S) was examined in allylisopropyl acetamide (AIA) treated porphyric adult rats. A dose of 20 mg cimetidine/100 gm body weight resulted in a 50% decrease in the AIA-induced hepatic ALA-S activity compared to rats treated with AIA alone. Heme oxygenase activity was decreased 25% compared to rats treated with AIA alone. The effects of AIA and cimetidine on cytochrome P-450 were not additive, suggesting competition for a common site of interaction. The results suggest that cimetidine may prove to be useful in treating porphyria in humans.     

肝星状细胞诱导卵圆细胞向成熟肝细胞分化的体外研究

目的 研究肝星状细胞(HSC)在体外培养的卵圆细胞向成熟肝细胞分化过程中所起的作用.方法 (1)将卵圆细胞分别与原代培养的HSC混合共培养(混合共培养组),采用Millicell小室不接触共培养(不接触共培养组),卵圆细胞单独培养作为对照组.在共培养后第7、14、21天观测,采用Western blot和荧光定量PCR检测肝细胞核因子4 α(HNF-4 α)、白蛋白和甲胎蛋白(AFP)、细胞角蛋白19(CK-19)的表达量;(2)电子透射显微镜观察卵圆细胞超微结构的变化;(3)过碘酸希夫染色检测各时间点卵圆细胞内糖原颗粒的含量;(4)酶联免疫吸附法检测各时间点卵圆细胞分泌白蛋白的含量.统计学处理采用重复测量资料的多因素方差分析和LSD-t检验.结果 (1)卵圆细胞第7、14、21天表达HNF-4 α和白蛋白的mRNA的量(相对与共培养之前的表达量的倍数):混合共培养组HNF-4 α分别为(1.9±0.2)倍、(10.7±1.2)倍、(12.0±1.3)倍;白蛋白mRNA的量分别为(5.7±1.6)倍、(110.7±13.7)倍、(173.6±22.3)倍;不接触共培养组HNF-4 α分别为(1.4±0.1)倍、(3.2±0.6)倍、(8.9±1.4)倍;白蛋白mRNA的量分别为(2.9±1.4)倍、(22.3±8.5)倍、(96.3±16.3)倍.共培养组(混合共培养与不接触共培养组)的表达量均高于对照组,LSD-t值分别为32.98,10.08;13.38,7.96; P值均<0.01,差异有统计学意义.第7、14、21天AFP、CK-19的表达量:混合共培养组AFP分别为(1.1±0.2)倍、(0.2±0.0)倍、(0.0±0.0)倍;CK-19分别为(0.2±0.1)倍、(0.0±0.0)倍、(0.0±0.0)倍;不接触共培养组AFP分别为(1.0±0.2)倍、(0.2±0.1)倍、(0.1±0.0)倍;CK-19分别为(0.6±0.1)倍、(0.1±0.0)倍,(0.0±0.0)倍.共培养组(混合共培养与不接触共培养组)的表达量均低于对照组.LSD-t值分别为37.99,34.50;13.59,22.46;P值均<0.01,差异有统计学意义.(2)卵圆细胞共培养后白蛋白分泌量明显增加:混合共培养组:14 d为(15.30±0.09)ng/ml、21 d(20.98±0.12)ng/ml,不接触共培养组14 d为(11.41±0.13)ng/ml,21 d为(15.12±0.17)ng/ml,混合共培养组高于不接触共培养组,LSD-t=251.94,P<0.01,差异有统计学意义.(3)随着共培养时间的延长,卵圆细胞内质网、线粒体和高尔基体等细胞器逐渐丰富,且细胞间形成毛细胆管结构.(4)过碘酸希夫染色显示共培养后卵圆细胞内出现大量红色糖原颗粒.结论 HSC可以诱导卵圆细胞向成熟肝细胞分化,HSC除了通过细胞因子等可溶性因子途径发挥作用外,与卵圆细胞的直接接触也有着重要作用.     

Studies on severe hepatic damage induced by galactosamine

Severe hepatic damage with submassive necrosis induced in rats by an intraperitoneal injection of a single dose of galactosamine hydrochloride was studied. In the severely damaged liver, the remarkable decreases of glycogen and UDPG in the damaged liver were seen. This means extreme decrease in the reserve power of glycolysis. Moreover, the activities of glucose-6-phosphatase and fructose-1,6-diphosphatase decreased. Therefore, the glucose release from liver into the blood stream decreases and the inhibition of gluconeogenesis occurs. In the damaged liver, the decrease of UTP which is essential for the synthesis of sugar moiety of polysaccharide, was seen. Further, the activities of L-glutamine: D-fructose-6-phosphate amidotransferase and UDP N-acetylglucosamine 2'-epimerase which are two key enzymes of polysaccharide synthesizing enzyme were seen to decrease remarkably. In the damaged liver, the glycoprotein fraction decreased more strikingly than the acid mucopolysaccharide fraction. Moreover, the decrease of fructose-1,6-diphosphatase activity seems also to effect on the inhibition of polysaccharide synthesis. In these respects, in the severe hepatic damage, the synthesis of glycoprotein which is essential for liver cell seems to be inhibited.     

Hepatic immune tolerance induced by hepatic stellate cells

The liver, which is a metabolic organ, plays a pivotal role in tolerance induction. Hepatic stellate cells(Hp SCs), which are unique non-parenchymal cells, exert potent immunoregulatory activity during cotransplantation with allogeneic islets effectively protecting the islet allografts from rejection. Multiple mechanisms participate in the immune tolerance induced by Hp SCs, including the marked expansion of myeloid-derived suppressor cells(MDSCs), attenuation of effector T cell functions and augmentation of regulatory T cells. Hp SC conditioned MDSC-based immunotherapy has been conducted in mice with autoimmune disease and the results show that this technique may be promising. This article demonstrates how Hp SCs orchestrate both innate immunity and adaptive immunity to build a negative network that leads to immune tolerance.     

肝窦内皮细胞损伤在大鼠肝纤维化形成中的作用

目的 研究肝窦内皮细胞损伤在二甲基亚硝胺大鼠肝纤维化形成中的作用。方法 采用二甲基亚硝胺(dimethylnitrosamine,DMN)4周12次腹腔注射制备大鼠肝纤维化模型,应用电镜技术、免疫组织化学及图像分析方法结合血清生化测定,24周动态观察肝纤维化形成过程中肝窦内皮细胞损伤及其表型的改变。结果 造模2d后肝结构未见明显改变,肝窦内皮细胞(sinusoidal endothelial cell,SEC)远侧胞浆窗孔数减少、造模1周SEC失窗孔更明显,肝组织内未见明显变性坏死及纤维间隔形成,造模4周时见肝组织内大片出血坏死,有大量假小叶形成,内皮下出现SEC窗孔减少。SEC失窗孔早于肝细胞发生较为严重的坏死、肝纤维化的形成以及肝窦内皮下基底膜的形成。造模4周HA(ng/ml)和肝羟脯氨酸(ug/g)平均含量分别为231.30±143.80和223.04±37.09,对照组分别为56.50±18.10和61.55±20.85,t值在3.14～8.28,P<0.05。结论 DMN引起大鼠肝窦内皮细胞损伤及其表型改变可能是其诱导肝纤维化重要的始动机制之一。     

Leukotriene inhibitors modulate hepatic injury induced by lipopolysaccharide-activated macrophages

In an attempt to elucidate the effect of lipoxygenase inhibitors on hepatic injury, we investigated D-galactosamine (GalN)-treated C57BL/6 mice receiving an intravenous (i.v.) injection of lipopolysaccharide (LPS)-activated autologous spleen cells. As compared with control spleen cells, the number of monocytes in the spleen cells isolated from LPS-treated mice and their oxidative free radical production increased markedly. Oxygen radical production by the dish-adherent cells (macrophage-rich population) was enhanced a further 4-fold. Although hepatotoxicity was not demonstrated in mice treated with 20 mg GalN alone, marked hepatic injury was found in the GalN-treated mice with a supplementation of LPS-activated spleen cells. The dish-adherent cells aggravated this hepatic injury, in contrast to minor hepatotoxicity by the nonadherent cells. Oxygen radical production by LPS-activated spleen cells was markedly reduced by the lipoxygenase inhibitors (azelastine, ketotifen and AA861). Hepatotoxicity was scarcely detected in the GalN-treated mice with a supplementation of the LPS-activated spleen cells which had been previously treated with lipoxygenase inhibitors. From these results, LPS-activated spleen macrophages contributed to hepatic injury induced by GalN, and lipoxygenase inhibitors which reduced oxygen radical production by the activated cells, protected against macrophage-induced hepatic injury in mice.     

Dress syndrome and fulminant hepatic failure induced by lamotrigine

Lamotrigine is a non-aromatic antiepileptic drug. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe idiosyncratic reaction to drugs, especially anti-epileptic drugs. Associated clinical features include cutaneous eruption, fever, multiple peripheral lymphadenopathies, and potentially life-threatening damage of one or more organs. We report a case of DRESS syndrome induced by lamotrigine presenting with a hypersensitivity syndrome and fulminant hepatic failure requiring liver transplant. A 21-year old female patient presented an episode of seizure with loss of conscience. CT and EEG studies performed were normal. Treatment with lamotrigine was prescribed. In the course of 30 days, the patient developed skin lesions, pruritus, cholestatic hepatitis, and systemic symptoms-fever, lymphadenopathies, extensive exfoliative erythematous maculopapular rash, and jaundice. Serologic and laboratory tests showed no other causes responsible for the clinical spectrum. Hematologic tests revealed peripheral eosinophilia. Fulminant hepatic failure was diagnosed and an orthotopic liver transplant was performed. Histologic sections of the ex-planted liver demonstrated submassive hepatic necrosis, with the remnant portal spaces and lobules showing a mixed inflammatory infiltrate with lymphocytes and eosinophils. Lamotrigine treatment has been associated with multiorgan failure, DRESS syndrome, acute hepatic failure, and disseminated intravascular coagulation. In conclusion, we suggest that these potentially fatal side effects should be considered in any patient with clinical deterioration following administration of this drug.     

ConA诱导肝细胞损伤机理及CsA对其损伤的影响

目的　探讨NO、脂质过氧化反应及蛋白巯基状态改变在ConA诱导肝组织细胞损伤过程中的作用以及CsA对其损伤的影响。方法 :尾静脉注射ConA( 2 0mg·kg-1)于雄性BALB/c小鼠作为试验组 ;提前半小时予以CsA( 2 5mg·kg-1)后再按试验组处理作为CsA组。观察血清中ALT、AST、NO-2 及肝组织MDA、TSH、PSH含量在 3h、6h、9h和 12h的动态变化。结果　试验组血清中ALT、AST进行性升高 ,在 12h时与对照组、CsA组比较均P <0 .0 1。试验组动物体内有大量的NO合成 ,血清中NO-2 随时间呈明显上升趋势 ,在 12h时与对照组、CsA组比较均P <0 .0 1。试验组动物肝组织MDA含量逐步升高 ,在 12h与对照组、CsA组比较P <0 .0 1。试验组动物肝组织TSH含量不断下降在 12h与对照组、CsA组比较P <0 .0 5 ;PSH含量亦不断下降在 12h与对照组、CsA组比较P <0 .0 1。对照组和CsA组血清中ALT、AST及NO-2 前后变化不大 ,肝组织MDA、TSH、PSH含量变化亦不明显。结论　在ConA所致肝损伤中 ,动物体内NO生物合成机制被激活 ,是肝细胞损伤的重要介质之一。同时脂质过氧化的发生以及蛋白巯基持续消耗致肝组织细胞的抗氧化能力和解毒能力下降也均是ConA性肝损伤机制之一。免疫抑制剂CsA预处理能阻断ConA性肝损伤的发生 ,免疫介导机制亦可能是其损伤     

Azathioprine induced hepatic veno-occlusive disease in rheumatoid arthritis.

A patient with rheumatoid arthritis developed hepatic veno-occlusive disease following the use of azathioprine. Although azathioprine induced veno-occlusive disease is suspected to occur more frequently in patients with autoimmune dysfunction, it has not previously been reported as a complication of treatment in rheumatoid arthritis. The mechanism responsible for this condition remains unknown.