CSH guidelines for the diagnosis and treatment of drug-induced liver injury.

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.

[Correlation between level of metallic elements in urine and childhood acute leukemia].

OBJECTIVE: To explore the relation between the level of metallic elements in urine and childhood acute leukemia. METHODS: A total of 71 patients under 15 years old who were newly diagnosed with acute leukemia between September 2007 and August 2008 without Downs' syndrome or other tumors, and 113 gender- and age-matched controls without tumors or congenital diseases were enrolled for the case-control study. The general data and potential risk factors were obtained by questionnaires. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the metal concentrations in urine, which was collected randomly before chemotherapy. Logistic regression model was performed for univariate and multivariate analysis. RESULTS: The questionnaire showed that there was significant difference in the proportion of children whose mothers had taken iron supplements during or 3 months before pregnancy between case group and control group, which was 28.2% (20/71) and 14.2% (16/113) respectively (Wald χ(2) = 5.438, P = 0.02). Univariate logistic regression analysis showed that levels of vanadium, manganese, iron, cobalt, copper, arsenic, and barium in urine from case group were all higher than those of control group with significant difference. The median values for vanadium in urine from case and control groups were 5.39 and 3.04 ng/mg creatinine (Wald χ(2) = 9.03, P < 0.05); the median values for manganese were respectively 4.46 and 2.44 ng/mg creatinine (Wald χ(2) = 10.57, P < 0.05); the median values for iron were separately 58.69 and 14.09 ng/mg creatinine (Wald χ(2) = 13.41, P < 0.05); the median values for cobalt were respectively 0.98 and 0.77 ng/mg creatinine (Wald χ(2) = 4.46, P < 0.05); the median values for copper were 61.17 and 10.90 ng/mg creatinine (Wald χ(2) = 8.15, P < 0.05); the median values for arsenic were respectively 55.93 and 36.11 ng/mg creatinine (Wald χ(2) = 4.57, P < 0.05); and the median values for barium were 8.55 and 2.87 ng/mg creatinine (Wald χ(2) = 4.82, P < 0.05). Multivariate logistic regression analysis showed that the level of iron in urine had a significantly positive relation with the incidence of childhood acute leukemia (OR = 1.009, 95%CI = 1.002 - 1.016). CONCLUSION: The level of iron in urine might be related to the occurrence of childhood acute leukemia, but its specific role needs further investigation.

Herb-drug interactions: in vivo and in vitro effect of Shenmai injection, a herbal preparation, on the metabolic activities of hepatic cytochrome P450 3A1/2, 2C6, 1A2, and 2E1 in rats.

Shenmai injection (SMI), a mixture of Radix Ginseng and Radix Ophiopogonis, is one of the most popular herbal medicinal products and is widely used for the treatment of coronary atherosclerotic cardiopathy and viral myocarditis. The purpose of this study was to investigate the effect of SMI, in vivo and in vitro, on the metabolic activities of hepatic cytochrome CYP450 3A1/2, 2C6, 2E1, and 1A2 in rats. After a single or multiple pretreatment with SMI, the rats were administrated intravenously a cocktail containing midazolam (1 mg/kg), diclofenac (0.5 mg/kg), theophylline (1 mg/kg), and chlorzoxazone (0.5 mg/kg) as probe substrates of rat CYP450 3A1/2, 2C6, 1A2, and 2E1, respectively. Single and multiple SMI pretreatment to rats resulted in a rise of 33.8 % (p < 0.01) and 25.6 % (p < 0.01) in AUC for midazolam, and an increase in AUC for diclofenac by 14.7 % (p < 0.05) and 31.2 % (p < 0.01), respectively. However, the pharmacokinetics of chlorzoxazone and theophylline in rats was not altered markedly. In rat liver microsomes, linear mixed-type inhibition of SMI against the enzyme activities of CYP3A1/2, CYP2C6, and CYP1A2 was shown with IC(50) values of 3.3 %, 2.0 %, and 3.1 % and K(i) values of 3.8 %, 1.5 %. and 1.9 %, respectively. These in vivo and in vitro results demonstrated that SMI had the potential to inhibit the activities of hepatic CYP3A1/2 and CYP2C6, but might not significantly affect CYP1A2 and CYP2E1-mediated metabolism in rats.