我院2012年冠心病患者血清胆红素检测结果分析

目的：探讨冠心病患者血清胆红素水平变化在临床诊断中的意义及应用价值。方法检测50例急性心肌梗死（AMI）组、50例不稳定型心绞痛（UAP）组、50例稳定型心绞痛（SAP）组以及50例健康对照组总胆红素（TBIL）、直接胆红素（DBIL）和间接胆红素（IBIL）含量，同时分析它们间的关系。结果冠心病各组的TBIL、DBIL和IBIL与对照组比较均显著降低，差异有统计学意义（P〈0.05）；其中AMI组的TBIL与UAP组、SAP组比较，有所升高，差异有统计学意义（P〈0.01），冠心病各组之间的DBIL、IBIL检测结果相互比较差异无统计学意义（P〉0.05）。结论检测冠心病患者血清胆红素水平对预测评估冠心病有一定临床价值。     

Acute toxicity and sub-chronic toxicity of steroidal saponins from Dioscorea zingiberensis C.H.Wright in rodents

Ethnopharmacological relevance

Steroidal saponins from Dioscorea zingiberensis are widely used in China for curing cardiovascular diseases. However, there was little toxicological information available on them.

Aim of the study

The study evaluated potential toxicity of the steroidal saponins and analyzed the metabolites in rats.

Materials and methods

For the acute study, the steroidal saponins were administered to kunming mice in single doses of 112.5–9000 mg/kg given by gavage. General behavior adverse effects, mortality and liver histopathological changes were examined. For the sub-chronic toxicity study, Sprague–Dawley rats were gavaged at doses of 127.5, 255 and 510 mg/kg/day for 30 days, then examined the biochemical and hematological parameters. Metabolites in serum were analyzed by HPLC–MS.

Results

The steroidal saponins caused dose-dependent general behavior adverse effects, mortality and liver histopathological changes in the acute toxicity study. In the sub-chronic toxicity study, 510 mg/kg/day of steroidal saponins increased total bilirubin (TBIL) in serum and decreased protein content in liver significantly. The metabolic process of TBIL in liver includes TBIL intaking, conjugated bilirubin forming, conjugated bilirubin excreting to biliary passage. Treatment with high dose of the steroidal saponins in vivo may lead to vacuolization of the cytoplasm of hepatocytes and canalicular cholestasis. In all doses used in the experiment, the steroidal saponins decreased aspartate aminotransferase (GOT), alanine aminotransferase (ALT) and alkaline phosphatase (AKP) in serum and increased reduced glutathione hormone (GSH), glutathione reductase (GR) and glutathione S-transferases (GST) in liver. Diosgenin was the main metabolite in serum.

Conclusions

The steroidal saponins did not show any sign of toxicity up to oral dose of 562.5 mg/kg in mice. No significant changes of biochemical and hematological parameters in rats (except at 510 mg/kg/day), it was concluded that the steroidal saponins did not appear to have significant toxicity in their traditional uses.     

Background incidence of liver chemistry abnormalities in pediatric clinical trials for conditions with and without underlying liver disease

Background

The FDA provides guidance regarding pre-marketing liver chemistry subject stopping criteria. This study was undertaken to determine the background rates of liver chemistry abnormalities in pediatric clinical trials for conditions with and without underlying liver disease (LD).

Methods

The study included 5410 subjects aged 0–18 years in 24 trials for conditions without LD. 3756 pediatric subjects in 14 trials for conditions with LD (malaria, HIV, HBV) were also analyzed. Prevalence and incidence of abnormal liver chemistries were calculated.

Results

In conditions without LD, the overall incidence were 0.54 (95%CI 0.20–1.17) per 1000 person–months for ALT ? 3xULN, 0.36 (95%CI 0.10–0.92) for ALT ? 5xULN, and 0.27 (95%CI 0.06–0.78) for ALT ? 8xULN, 1.03 (95%CI 0.50–1.90) for ALP ? 2xULN, and 0.22 (95%CI 0.03–0.78) for combined ALT ? 3xULN and TBIL ? 2xULN. Incidence of ALT ? 3xULN (8.17 95%CI 6.42–10.24) were much higher in trials of conditions with LD. However, combined elevations of ALT ? 3xULN and TBIL ? 2xULN were only marginally higher 0.37 (95%CI 0.10–1.08).

Conclusion

Elevations of ALT (3xULN) and TBIL (2xULN) are rare in pediatric trial populations for conditions without underlying liver disease and can be considered a safety signal. For trials in conditions with liver disease, the potential for drug-induced liver injury must be distinguished from underlying disease progression.     

Silk-elastinlike protein polymers for matrix-mediated cancer gene therapy

Silk-elastinlike protein polymers (SELPs) are recombinant polymers designed from silk fibroin and mammalian elastin amino acid repeats. These are versatile materials that have been examined as controlled release systems for intratumoral gene delivery. SELP hydrogels comprise monodisperse and tunable polymers that have the capability to control and localize the release and expression of plasmid DNA and viruses. This article reviews recent developments in the synthesis and characterization of SELP hydrogels and their use for matrix-mediated gene delivery.     

Rheum australe D. Don: a review of its botany, ethnobotany, phytochemistry and pharmacology

Ethnopharmacological relevance

Rheum australe D. Don (Polygonaceae) has been commonly used in traditional medicine for a wide range of ailments related to the circulatory, digestive, endocrine, respiratory and skeletal systems as well as to infectious diseases.

Aim of the review

To provide the up-to-date information that is available on the botany, traditional uses, phytochemistry, pharmacology and toxicology of Rheum australe. Additionally, to highlight the possible uses of this species to treat different diseases and to provide a basis for future research.

Materials and methods

The present review covers the literature available from 1980 to 2011. The information was collected from scientific journals, books, theses and reports via a library and electronic search (Google Scholar, Web of Science and ScienceDirect).

Results

Ethnomedical uses of Rheum australe have been recorded from China, India, Nepal and Pakistan for 57 different types of ailments. The phytochemical studies have shown the presence of many secondary metabolites belonging to anthraquinones, stilbenes, anthrones, oxantrone ethers and esters, chromones, flavonoids, carbohydrate, lignans, phenols and sterols. Crude extracts and isolated compounds from Rheum australe show a wide spectrum of pharmacological activities, such as antidiabetic, anti-inflammatory, antifungal, antimicrobial, antioxidant, anticancer, hepatoprotective and immune-enhancing activities, as well as a usefulness for improving renal function.

Conclusion

Rheum australe has been widely used source of medicine for years without any adverse effects. Many studies have provided evidence for various traditional uses. However, there is a need for additional studies of the isolated compounds to validate the traditional uses in human models. The present review on the botany, traditional uses, phytochemistry and toxicity has provided preliminary information for further studies and commercial exploitations of the plant.     

VPS33B mutation with ichthyosis, cholestasis, and renal dysfunction but without arthrogryposis: incomplete ARC syndrome phenotype

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare multisystem disorder first described in 1979 and recently ascribed to mutation in VPS33B, whose product acts in intracellular trafficking. Arthrogryposis, spillage of various substances in the urine, and conjugated hyperbilirubinemia define an ARC core phenotype, in some patients associated with ichthyosis, central nervous system malformation, deafness, and platelet abnormalities. We describe a patient with cholestasis, aminoaciduria, ichthyosis, partial callosal agenesis, and sensorineural deafness who, although homozygous for the novel VPS33B mutation 971delA/K324fs, predicted to abolish VPS33B function, did not exhibit arthrogryposis. The phenotypes associated with VPS33B mutation may include incomplete ARC.     

大黄酚对慢性乙型病毒性肝炎大鼠肝功能损伤及肝脏纤维化作用及机制研究

目的 探讨大黄酚对慢性乙型病毒性肝炎（CHB）大鼠肝功能损伤及肝脏纤维化的影响，并分析相关作用机制。方法 60只雄性SD大鼠随机分为对照组、模型组及大黄酚低、高剂量（7.5、30 mg/kg）组和拉米夫定（10 mg/kg）组，每组12只。除对照组外，其余各组均尾iv乙型肝炎病毒（HBV）抗原构建CHB模型，造模成功后个给药组ip相应药物。采用全自动生化分析仪检测大鼠血清中天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、总胆红素（TBIL）水平；酶联免疫吸附（ELISA）法检测大鼠血清中透明质酸（HA）、层黏连蛋白（LN）、羟脯氨酸（HYP）水平；苏木精–伊红（HE）染色及Masson染色观察大鼠肝脏组织病理形态学及纤维化；Western blotting法检测大鼠肝脏组织中相关蛋白表达。结果 与模型组比较，大黄酚7.5、30 mg/kg组和拉米夫定组大鼠血清中ALT、AST、TBIL、HA、LN、HYP水平均降低（P＜0.05），大鼠肝组织病理性损伤和胶原纤维沉积显著改善，肝组织中α-平滑肌肌动蛋白（α-SMA）、I型胶原α1基因（COL1A1）、葡萄糖调节蛋白（GRP）78、GRP94及磷酸化真核生物翻译起始因子2α（p-eIF2α）/eIF2α、磷酸化蛋白激酶R样内质网激酶（p-PERK）/PERK均显著降低（P＜0.05）；且大黄酚30 mg/kg组、拉米夫定组大鼠血清和肝组织中上述指标均显著优于大黄酚7.5 mg/kg组（P＜0.05）。结论 大黄酚可能通过调控内质网应激减轻CHB大鼠肝功能损伤，改善大鼠肝纤维化。     

Topical treatment with Tong-Luo-San-Jie gel alleviates bone cancer pain in rats

Ethnopharmacological relevance

The herbal analgesic gel Tong-Luo-San-Jie (TLSJ) and its modifications are used in traditional Chinese medicine to manage cancer pain. However, its mechanisms are still unknown.

Aim of the study

To investigate the effects and mechanisms of TLSJ gel on bone cancer pain in a rat model.

Materials and methods

A bone cancer pain rat model was established by inoculating Walker 256 rat carcinoma cells directly into the right tibial medullary cavity of Sprague–Dawley rats (150–170 g); Phosphate buffered saline (PBS) tibial inoculation was used as control. Cancer-bearing rats were treated twice a day with external TLSJ gel (0.5 g/cm²/day) or inert gel control for 21 day (n=10/group). Behavioral tests such as mechanical threshold and paw withdrawal latency (PWL) were carried out. Osteoclastic activities were determined and carboxyterminal pyridinoline cross-linked type I collagen telopeptides (ICTP) and bone-specific alkaline phosphatase (BAP) concentrations were detected with ELISA after treatment. Adverse effects were monitored, and biochemical and histological tests were performed in naïve rats treated with local TLSJ gel for six weeks.

Results

TLSJ treatment significantly restored bone cancer-induced decrease of PWL and mechanical threshold compared to inert gel. It also decreased the level of blood serum ICTP and BAP and inhibited osteoclast activities. No adverse effects or abnormal biochemical and histological changes were detected after TLSJ treatment.

Conclusion

The present study shows that TLSJ significantly inhibits bone cancer-induced thermal and mechanical sensitization. It suggests that the gel may be useful in managing cancer pain and that it may act by inhibiting osteoclastic activity.     

妊娠期肝内胆汁淤积症的临床分型与围产儿预后的关系

目的　探讨妊娠期肝内胆汁淤积症 (ICP)的临床分型及与围产儿预后的关系。方法　将 112例确诊为ICP患者 ,按其血清甘胆酸 (CG)和总胆红素 (TBIL)值的高低 ,分为轻型组和重型组 ,比较分析两组围产儿预后。结果　重型组ICP患者的围产儿羊水污染率、早产率、胎儿宫内窘迫率及剖宫产率显著高于轻型组 (P <0 .0 1或P <0 .0 5 )。结论　血清CG及TBIL值能更准确衡量病情轻重和预测围产儿预后 ;对重症ICP患者及时行剖宫产术 ,可大大降低围产儿的发病率及病死率。