Aminotransferases During Treatment Predict Long-Term Survival in Patients With Autoimmune Hepatitis Type 1: A Landmark Analysis

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Curcumin ameliorates hepatic chronic inflammation induced by bile duct obstruction in mice through the activation of heme oxygenase-1

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Lower level of serum potassium and higher level of C-reactive protein as an independent risk factor for giant aneurysms in Kawasaki disease

Giant aneurysms are the most serious issue of patients with Kawasaki disease (KD). To clarify risk factors for these giant aneurysms, we conducted a matched case-control study. Among the patients reported in nationwide surveys, 117 patients with giant aneurysms had an unequivocal new diagnosis and presented at the treatment center within 9 d of illness. We obtained clinical information on admission of about 69 patients (case) from the treatment centers. One control was selected for each case, an age- and sex-matched patient without coronary involvement, reported from the same treatment center at about the same time as the case, and we obtained the same clinical information about controls. Fourteen variables were analysed with a conditional logistic regression model: body temperature, hematocrit, hemoglobin, numbers of leukocyte and platelets, concentrations of serum albumin, globulin, total cholesterol, sodium, potassium and chloride, erythrocyte sedimentation rate, C-reactive protein and alanine aminotransferase activity. After adjustment for age, duration of illness before admission and use of intravenous gamma globulin therapy, C-reactive protein [odds ratio (OR) = 1.142, 95% confidence interval (CI) 1.054-1.237], alanine aminotransferase activity (OR = 1.008, 95% CI 1.002-1.014), serum sodium concentration (OR = 0.877, 95% CI 0.770-0.999) and serum potassium concentration (OR = 0.319, 95% CI 0.124-0.822) were significantly related to the risk for giant aneurysms. Further analyses with these four explanatory variables revealed that C-reactive protein (OR = 1.159, 95% CI 1.022-1.315) and serum potassium concentration (OR = 0.222, 95% CI 0.052-0.948) met the significant level. Thus, the values for serum C-reactive protein and potassium are independent risk factors for the development of the giant aneurysms of Kawasaki disease.     

Cyclosporine therapy affects aminotransferase activity but not hepatitis C virus RNA levels in chronic hepatitis C

Interferon (IFN) therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and is often limited by side effects. Cyclosporine A (CsA) is a potent immunosuppressant widely used in organ transplantation. We conducted a pilot study to determine whether CsA therapy could affect aminotransferase activity and hepatitis C virus RNA levels in patients with chronic hepatitis C. Cyclosporine A was administered to 10 patients (mean age of 59 years; male: female = 9:1) who did not respond to IFN therapy previously and who had elevated serum alanine aminotransferase (ALT) values for at least 6 months. All patients were positive for HCV-RNA by RT-PCR with genotype 1b. Their mean duration of hepatitis was 15 years. Oral CsA was given for 3 months in a dose that was increased at 1 month intervals from 1.5–2.0 to 2.0–3.0 and 3.0–4.0 mg/kg per day. All patients completed the treatment schedule, although two patients developed mild non-symptomatic hypertension. Serum ALT levels gradually decreased in all but one patient. The mean percentage decrease was 59.5% at the end of therapy (from 153 ± 82 to 62 ± 48 IU/L; P < 0.02). The ALT levels fell to the normal range in five patients, although once therapy was discontinued the enzyme levels tended to return to pretreatment levels. Serum aspartate aminotransferase and g-glutamyl transpeptidase levels similarly decreased. The serum HCV-RNA titre, determined by competitive RT-PCR, did not change in any patient throughout the study period. There were no appreciable alterations in other laboratory tests, such as serum creatinine levels and lymphocyte subsets, except for an increase in serum alkaline phosphatase levels. These findings suggest that CsA, even in a relatively low dose, reduces serum aminotransferase levels without serious side effects in patients with chronic-hepatitis C, although an antiviral effect was not noted.     

Role of the ventromedial nucleus of the thalamus in motor behaviour—I. Effects of focal injections of drugs

An assortment of drugs was injected into one or both ventromedial nuclei of the thalamus, to see how these influenced stereotypy, locomotion and posture in spontaneously behaving and actively rotating rats. Unilateral intrathalamic muscimol promoted weak ipsiversive circling, while bilateral treatment gave catalepsy. Similar injections of 4-amino-hex-5-enoic acid, which inhibits γ-aminobutyrate metabolism, raised γ-aminobutyrate levels in the ventromedial nuclei more than three-fold yet had none of these behavioural effects. The indirectly acting γ-aminobutyrate agonists flurazepam and cis-1,3-aminocyclohexane car☐ylic acid had little effect on posture and locomotion and, like muscimol and 4-amino-hex-5-enoic acid, elicited only very weak stereotypies. Procaine behaved like the γ-aminobutyrate antagonist bicuculline, provoking vigorous locomotor hyperactivity and teeth chattering if given uni- or bilaterally. Pretreatment of one ventromedial nucleus with muscimol or 4-amino-hex-5-enoic acid, and to a lesser extent flurazepam or cis-1,3-aminocyclohexane car☐ylic acid, gave rise to pronounced ipsilateral asymmetries when combined with a large systemic dose of apomorphine. Contraversive rotations were initiated by unilateral stereotaxic injection of muscimol into the substantia nigra pars reticulata, or with apomorphine from the supersensitive striatum in unilaterally 6-hydroxydopamine lesioned rats. Drug treatments in the ipsilateral ventromedial nucleus showed a similar rank order of potency at inhibiting these circling behaviours, seemingly by reducing apomorphine-induced posture and muscimol-induced hypermotility. The suppression of circling by muscimol in these tests was highlighted by introducing the compound into the ventromedial nucleus at the height of circling activity. Both types of circling stimulus lost the capacity to increase locomotion, but still caused head turning and stereotypy in rats made cataleptic with bilateral ventromedial muscimol. Treating one ventromedial thalamus with muscimol greatly intensified any pre-existing posture directed towards that side, and vice versa.

These data suggest that the ventromedial nucleus is not involved with the expression of stereotyped behaviours, but can profoundly influence posture and locomotion, especially in the presence of some other motor stimulus. The recovery of circus movements in rats with impaired ventromedial nucleus function implies this nucleus is not essential for the execution of circling in these models.     

Changes in glutamate-related enzyme activities in the striatum of the rat following lesion of corticostriatal fibres

Summary The behaviour of enzymes putatively involved in glutamate/aspartate transmitter metabolism (glutamate dehydrogenase, aspartate aminotransferase, alanine aminotransferase,-glutamyltranspeptidase) was studied in the striatum 3, 7, 14 days and 7 weeks after mechanical destruction of corticostriatal fibres. For a period of up to seven days after unilateral lesion, enzyme activities were significantly diminished (by up to 13% based on protein) in the ipsilateral striatum as compared to the striatum of the intact side. Later, the enzyme activities in the ipsilateral striatum recovered. After seven weeks, an increase was observed for glutamate dehydrogenase activity, whereas the activity of alanine aminotransferase showed a transient rise at the end of the second week. The decrease in enzyme levels is interpreted as being attributable to the destruction of nerve endings which are considered to be glutamatergic, interfering with various compensating processes (e.g. glial cell proliferation) which occur with advancing times after lesion.     

应用酶联—紫外连续监测法进行丙氨酸转氨酶活力测定

血清丙氨酸转氨酶(aLanine aminotrarshrase)的活力测定．对于肝脏病诊断及病情观察均有一定意义。我们自1992年应用酶促反应动力学的有关理论,以酶联—紫外连续监测法（即速率法)测定丙氨酸转酶得到了满意的效果。该法具有快速、结果准确、重复性好等优点。是目前较理想的测定方法。现介绍如下。     

Serum alanine aminotransferase activity in obese children

To confirm the significance of the serum alanine aminotransferase (ALT) test for the diagnosis of fatty liver and to clarify the relationship between serum ALT activity and the duration of obesity, we analysed 310 obese young schoolchildren (195M, 115F), who were classified into three duration groups (1–3 y, 4–6 y, 7+ y), three age groups (6–7 y, 8–9 y, 10–11 y), and four obesity groups (weight excess; mild, 20–29%: moderate, 30–39%; severe. 40–49%; very severe. 50%). Seventy-seven patients with abnormal ALT test, >30 IU/1, and 27 patients with normal ALT test were examined by ultrasound study to identify the fatty-fibrotic pattern of the liver. Abnormal results of the serum ALT test were found in 24% of all patients. The fatty-fibrotic pattern was identified in 64/77 (83%) patients with abnormal ALT test and in 5/27 (18%) patients with normal ALT test. The serum ALT test has a sensitivity of 0.92 for detecting the fatty-fibrotic pattern proven by ultrasound study Frequencies of cases with abnormal serum ALT levels increased with the duration of obesity. In the shortest duration group, however, the frequencies of abnormal results in serum ALT test did not increase with advanced ages or the grades of obesity. In conclusion, the present study confirmed the usefulness of the serum ALT test for screening fatty liver, and showed that a longer duration of obesity is generally associated with the occurrence of fatty liver in a paediatric obese population. In young patients with mild obesity or a short duration of obesity, however, fatty liver or fatty fibrosis may develop. Early intervention should be made in the case of obese children.     

病毒性脑膜脑炎262例血清线粒体天冬氨酸转氨酶同工酶变化的临床意义

目的　探讨病毒性脑膜脑炎 (病脑 )患儿血清线粒体天冬氨酸转氨酶同工酶 (m AST)变化及其临床意义。方法　应用全自动生化分析仪测定 2 62例病脑患儿和 12 1例健康儿童静脉血清中m AST、天冬氨酸转氨酶总活性 (t AST)活性 ,并计算m AST/t AST。结果　轻度病脑组血清m AST活性 15.50± 3 .91U/L ,中度组3 4 .79± 7.2 5U/L ,重度组 55.76± 11.3 3U/L ,正常对照组 7.93± 2 .80U/L ,各组间比较差异有显著性 (P均 <0 .0 5) ;m AST/t AST值 ,轻度患儿组 (3 6.76± 8.51) % ,中度患儿组 (47.63± 11.53 ) % ,重度患儿组 (61.81±7.3 3 ) % ,正常对照组 (2 5.2 6± 9.2 1) % ,各组间比较差异亦有显著性 (P均 <0 .0 5)。结论　测定血清m AST活性及m AST/t AST可作为判断小儿病脑病情及预后的指标之一     

大剂量何首乌醇提物致大鼠多脏器损伤研究

目的观察大剂量何首乌对大鼠主要脏器的损伤作用,暴露其可能的毒性作用。方法采用亚急性毒性试验,初步比较生何首乌和制何首乌不同提取物（20g生药／b）灌胃28天的毒性,观察肝脏病变频数;进一步对毒性较大的生何首乌和制何首乌醇提物进行研究,以40g生药／kg连续灌胃28天,观察大鼠体重增长情况、脏器指数变化、肝肾功能生化指标、组织病变结果。结果初步发现生何首乌和制何首乌醇提物毒性均大于各自的水提物和药材全粉,肉眼观察发现服药大鼠主要脏器中,肝脏发生显著病变的频数最高。何首乌醇提物毒性结果发现,与未给药动物比较,生何首乌组和制何首乌组大鼠体重增长显著受抑,生首乌组主要脏器指数显著升高;组织病理检查显示生何首乌组和制何首乌组肝、肾和肺脏均发生显著损伤;肝功能生化指标动态监测显示：生何首乌组谷丙转氨酶和谷草转氨酶仅在给药第3天时出现一过性显著升高,在此后第7、14、21和28天均无显著改变,而CCl。阳性对照组在实验第1周ATJT和AST即出现显著升高。结论初步实验提示何首乌的肝毒性物质可能集中在醇提物,其毒性器官主要集中在肝脏。进一步实验提示生何首乌毒性大于制何首乌,何首乌对肝、肾和肺均有损伤,其中对肺脏的损伤作用是首次报道;肝功能生化指标谷丙转氨酶和谷草转氨酶对何首乌肝损伤不敏感,提示何首乌肝损伤的机制可能与CCl。主要基于细胞膜脂质过氧化的肝损伤机制不同。