Pathogenic molecular mechanisms in an animal model of fulminant hepatic failure: rabbit hemorrhagic viral disease

In this study we sought to determine whether molecular mechanisms involved in the pathogenesis of fulminant hepatic failure are present in rabbits experimentally infected with rabbit hemorrhagic disease virus (RHDV). The activities of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, as well as bilirubin concentration, were found to be significantly increased 36 hours after infection. Infected animals also demonstrated significant decreases in factor VII activity, in the Fischer index, and in the deterioration of prothrombin time. The concentration of reduced glutathione was significantly decreased 36 hours after infection, and we noted a marked increase in the ratio of oxidized to reduced glutathione. Infected animals showed progressive decreases in liver activity of the antioxidant enzyme superoxide dismutase. Expression of hepatocyte growth factor and c-met was found to be progressively reduced from 24 hours after infection, during which time we detected no modification in messenger RNA (mRNA) levels of transforming growth factor (TGF)-alpha. TFG-beta 1 was overexpressed 24 and 36 hours after infection, and 36 hours after infection we detected a significant increase in TNF-alpha mRNA levels. Experimental RHDV infection also induced marked activation of nuclear factor-kappaB and a significant increase in inducible nitric oxide synthase mRNA levels from 24 hours after infection. Data obtained from this animal model support its usefulness in the investigation of potential novel therapeutical modalities aimed at neutralizing reactive oxygen species and hepatocyte growth inhibitors or enhancing hepatocyte responsiveness to mitogens.     

血清学指标在肝硬化合并原发性肝癌诊断中的价值

目的探讨肝硬化患者血清学指标在肝硬化并发原发性肝癌诊断中的价值。方法收集2012年1月-2013年12月入住我院消化内科的肝硬化患者89例,其中肝硬化并发原发性肝癌(PHCC)23例,单纯性肝硬化(HC)66例。根据纳入与排除标准,最终选择55例患者作为研究对象(PHCC组14例,HC组41例)。所有患者均行血常规、肝功能、电解质、凝血指标、甲胎蛋白及肝炎标志物检查。结果 2组患者流行病学资料未见明显差异,PHCC组患者血清AFP水平显著地高于HC组患者(737.89±197.21 vs 54.29±10.08,P=0.003),与HC组患者相比,PHCC组患者AST/ALT比值(1.76±1.05 vs 1.25±0.49,P=0.018)和GGT/ALT比值(6.70±10.92 vs 2.84±3.29,P=0.047)均显著增高。在肝硬化并发原发性肝癌的诊断中,AST/ALT的敏感性为64.3%,特异性73.2%(cutoff值1.43);GGT/ALT敏感性为42.9%,特异性为85.4%(cutoff值3.72)。结论肝硬化并发原发性肝癌患者血清AFP水平显著升高,联合AST/ALT比值、GGT/ALT比值检测能够提高肝硬化患者并发原发性肝癌的检出率。     

常规试剂中加入磷酸吡哆醛(PPA)测定天门冬氨酸氨基转移酶(AST)催化活性浓度的可行性研究

目的探讨在常规试剂中加入PfIA测定AST催化活性浓度的可行性。方法用加与不加PPA两种常规方法分别比较肝脏病人、心脏病人、透析病人及其表观健康人群血清AST活性。同时对两种常规方法在参考范围、线性范围、干扰物、精密度、试剂稳定性方面进行了比较。结果无论加与不加PPA，健康男性组和女性组相比较均有显著差别。加入PPA使健康人AST升高4．0％，与不加PPA相比没有显著差别。加入PPA，急性肝炎、慢性肝炎、肝硬化和肝癌病人的AST分别升高18．1％、23．2％、18．2％和28．3％，与不加PPA有显著差别。加入PPA，透析后病人AST升高27．6％，与不加PPA相比无显著差异。加入PfIA，心绞痛病人AST升高5．6％，与不加PPA相比没有显著差异；加入PPA，AMI病人AST升高37．2％，与不加PPA相比有显著差异。AST加与不加PPA的常规方法在参考范围、线性范围、干扰物、精密度、试剂稳定性方面无显著差异。结论无论男性还是女性，加入PPA其AST参考范围仍然在40U／L以内，与目前常规方法的参考范围无差别。因此，我们认为可以推广加PPA的常规方法。     

Evaluation of safety and tolerance of microencapsulated Lactobacillus reuteri NCIMB 30242 in a yogurt formulation: A randomized,placebo-controlled,double-blind study

Probiotic organisms have shown promise in treating diseases. Previously, we have reported on the efficacy of microencapsulated Lactobacillus reuteri NCIMB 30242 in a yogurt formulation at lowering serum cholesterol levels in otherwise healthy hypercholesterolemic adults. This study investigates the safety and toxicology of oral ingestion of microencapsulated L. reuteri NCIMB 30242 in a yogurt formulation. A randomized group of 120 subjects received a dose of 5 × 10¹⁰ CFU microencapsulated L. reuteri NCIMB 30242 in yogurt (n = 59) or placebo yogurt (n = 61) twice/day for 6 weeks. Clinical chemistry and hematological parameters of safety were analyzed. Fecal samples were collected at these time points for the analysis of deconjugated bile acids. The frequency, duration and intensity of adverse events (AEs) and clinical significance of safety parameters were recorded for both groups. No clinically significant differences between the probiotic yogurt and placebo yogurt treated groups were detected in either the blood clinical chemistry or hematology results and there was no significant increase in fecal deconjugated bile acids (P > 0.05) between treated and control groups. The frequency and intensity of AEs was similar in the two groups. These results demonstrate the safe use of this formulation in food.     

A Ca2+ chelator ameliorates chromium (VI)-induced hepatocyte L-02 injury via down-regulation of voltage-Dependent anion channel 1 (VDAC1) expression

Hexavalent chromium could result in cell malfunctions. Intracellular Ca²⁺ ([Ca²⁺]_i) content and VDAC1 expression are both important features related to cell survial. This study aimed to explore the mechanism of cell injury induced by Cr(VI) and tentatively offer clues to repairing this cell damage using [Ca²⁺]_i and VDAC1. L-02 hepatocytes were treated with Cr(VI)/BAPTA, and the levels of [Ca²⁺]_i and cell injury associated with Cr(VI) were determined in addition to the effect of BAPTA. The expression of VDAC1 in Cr(VI)-induced cells was evaluated. The results showed a dose-dependent elevation of the level of VDAC1 and the mRNA level of the VDAC1 biogenesis-related gene Sam50. BAPTA could ameliorate less severe damage induced by 4 μM Cr(VI) via reducing VDAC1 and Sam50. Additionally, cell injury caused by less than 4 μM Cr(VI) could be ameliorated by VDAC1 knockdown. Taken together, the findings of this study suggest that inhibition of intracellular Ca^2± overload could protect cells from damage and that VDAC1 plays a considerable role in Cr(VI)-induced liver injury.