Copper ions stimulate the proliferation of hepatic stellate cells via oxygen stress in vitro

This study examined the effect of copper ions on the proliferation of hepatic stellate cells (HSCs) and the role of oxidative stress in this process in order to gain insight into the mechanism of hepatic fibrosis in Wilson’s disease. LX-2 cells, a cell line of human HSCs, were cultured in vitro and treated with different agents including copper sulfate, N-acetyl cysteine (NAC) and buthionine sulfoximine (BSO) for different time. The proliferation of LX-2 cells was measured by non-radioactive cell proliferation assay. Real-time PCR and Western blotting were used to detect the mRNA and protein expression of platelet-derived growth factor receptor β subunit (PDGFβR), ELISA to determine the level of glutathione (GSH) and oxidized glutathione (GSSG), dichlorofluorescein assay to measure the level of reactive oxygen species (ROS), and lipid hydroperoxide assay to quantify the level of lipid peroxide (LPO). The results showed that copper sulfate over a certain concentration range could promote the pro- liferation of LX-2 cells in a time- and dose-dependent manner. The effect was most manifest when LX-2 cells were treated with copper sulfate at a concentration of 100 μmol/L for 24h. Additionally, copper sulfate could dose-dependently increase the levels of ROS and LPO, and decrease the ratio of GSH/GSSG in LX-2 cells. The copper-induced increase in mRNA and protein expression of PDGFβR was significantly inhibited in LX-2 cells pre-treated with NAC, a precursor of GSH, and this phenome- non could be reversed by the intervention of BSO, an inhibitor of NAC. It was concluded that copper ions may directly stimulate the proliferation of HSCs via oxidative stress. Anti-oxidative stress therapies may help suppress the copper-induced activation and proliferation of HSCs.     

遗传代谢病筛查在婴儿肝炎综合征病因诊断中的意义

目的:对临床诊断为婴儿肝炎综合征的患儿进行遗传代谢病的筛查,从而探讨遗传代谢病筛查在婴儿肝炎综合征病因诊断中的意义.方法:对2003-10/2010-03在华中科技大学同济医学院附属同济医院儿科临床诊断为婴儿肝炎综合征的患儿中筛查出的遗传代谢肝病进行回顾性分析.结果:在儿科病房住院的802例婴儿肝炎综合征中筛查出遗传代谢肝病35例,主要为酪氨酸血症9例、瓜氨酸血症4例、新生儿肝内胆汁淤积症(neonatal intrahepatic cholestasis caused by citrin deficiency,NICCD)4例、高乳酸血症3例、尼曼-匹克5例、糖原累积病2例、二羧酸尿症2例、Alagille综合征3例、进行性家族性肝内胆汁淤积(progressive familial intrahepaticcholestasis,PFIC)3例.结论:婴儿肝炎综合征病因复杂,在查找病因时应常规进行遗传代谢病筛查,有利于早期诊断及正确治疗.     

Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson’s disease

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine （PCA） in cross combination with sodium 2, 3-dimercapto-l-propane sulfonate （DMPS） repeatedly in patients with Wilson＇s disease （WD）. Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocy- topenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Im- proved or recovered liver fimction in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up pe- riod of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maitain lifelong therapy.     

急性散发性脑炎患儿脑脊液免疫球蛋白G指数及相关指标变化

目的探讨散发性脑炎患者脑脊液(CSF)IgG、IgA、IgM、IgG指数和血脑脊液屏障(BBB)变化及临床特征、MRI异常与IgG指数的关系及其病因。方法选择确诊急性散发性脑炎患者37例,急性期取脑脊液,采用速率散射比浊法测脑脊液(CSF)IgG、IgA、IgM和Alb,同时测血清中的相同指标,根据公式计算脑脊液IgG指数。28例行头颅MRI检测。取10例非脑炎的神经疾病患儿作为对照。结果散发性脑炎患儿CSF中IgG指数显著高于对照组(P=0.017);但CSFIgG、Igh、IgM和清蛋白比值相比无显著差异(P>0.05);散发性脑炎中高IgG组MRI脱髓鞘变6例(33.3%),低IgG组MRI脱髓鞘变1例(5.6%),两者较有显著差异(P=0.003),但高、低IgG指数组临床特征相比无显著差异(昏迷除外)。结论多数散发性脑炎患儿的BBB无明显破坏,而鞘内免疫反应比较明确,IgG合成增加,提示某些散发性脑炎不是病毒直接感染.而是一种免疫学反应性脱髓鞘脑病,MRI提示有白质脱髓鞘者当更明确。     

黄疸与遗传代谢病

遗传代谢病可通过影响胆红素代谢而引起高未结合胆红素血症或高结合胆红素血症,并出现黄疸;其中引起高未结合胆红素血症的病因主要包括尿苷二磷酸-葡萄糖醛酸转移酶活性部分或完全缺乏和红细胞代谢缺陷等;高结合胆红素血症的病因主要包括胆汁酸及糖、氨基酸、脂类、金属等物质代谢异常。不同类型黄疸的发病机制和预后各不相同,早期诊断和积极治疗有助于改善预后。现介绍儿童主要的遗传代谢性高胆红素血症及其诊断、治疗。     

奥卡西平单药和添加治疗儿童癫痫的疗效与安全性

目的 观察奥卡西平治疗儿童部分性发作（PS）和全面性强直-阵挛发作（ GTCS）癫痫患者的疗效、耐受性和副作用. 方法 73例癫痫患儿, 其中56例新诊断者进入单治组, 17例应用过其他抗癫痫药物治疗者进入加治组. 奥卡西平起始剂量5～10 mg•kg^-1•d^-1, 最大剂量30～40 mg•kg^-1•d^-1, 维持剂量中位值20 mg•kg^-1•d^-1, bid. 加治组其他抗癫痫药物的使用不变. 通过自身对比开放性观察, 分析单治组与加治组52周的疗效、不良反应、耐受性和安全性. 结果 全部患者总有效率84.9%、控制率54.8%、累积退出率11.0%, 其中3例（4.1%）失访, 不良反应或其他原因退出者5例（6.8%）, 其中因皮疹退出2例（2.7% ）. 常见不良反应：乏力8例、烦躁7例, 困倦和皮疹各2例. 单治组临床控制率（62.5%）显著高于加治组（29.4%）. 结论 奥卡西平是治疗儿童部分性发作和全面性强直-阵挛发作癫痫相对理想的药物选择.     

经皮黄疸仪对新生儿高胆红素血症的筛查作用

本文对５３例新生儿进行经皮黄疸指数和血清胆红素浓度的同期测定。结果发现：１．光疗和非光疗情况经皮黄疸指数和血清胆红素浓度相关良好，且光疗时前额ＴｃＢ变化与ＴＢ变化亦呈良好正相关；２．选择ＴｃＢ界值１６，筛查高胆红素血症的敏感性和阴性预测值均达１００％，准确性７４％。表明经皮黄疸仪是高胆红素血症的有效筛查工具，前额眉间眼罩内皮肤是光疗时ＴｃＢ监测的有效部位。     

小肠镜和组织活检对儿童慢性腹泻病的诊断价值

目的 评价小肠镜和活体组织病理、超微病理检查对儿童慢性腹泻病的诊断价值.方法 华中科技大学同济医学院附属同济医院儿科病房2005年2月至11月应用小肠镜和活体组织病理、超微病理检查明确诊断的3例慢性腹泻病患儿,对其临床表现、辅助检查、治疗方案及预后进行回顾性分析和总结.结果 3例患儿均表现为长期反复腹泻.其中1例IgA水平异常增高、1例明显低蛋白血症.患儿均予小肠镜检,诊断分别为免疫增生性小肠病、原发性小肠淋巴管扩张症和异位内分泌性腹泻,2例病理、超微病理检查结果具有特异性.3例患儿均予营养支持治疗,1例四环素疗效明显,1例奥曲肽治疗有效,l例补液治疗即好转.结论 小肠性慢性腹泻病诊治困难,小肠镜和活体组织病理、超微病理检查有助于提高儿童慢性腹泻病的诊治水平和深化对小肠疾病发病机制的认识.     

儿童动脉缺血性卒中的起病方式、梗死部位与病因诊断舷

目的 探讨儿童动脉缺血性卒中(AIS)的起病方式、梗死部位与卒中病因的关系.方法 回顾性分析1997年1月-2007年10月在武汉市儿章医院及华中科技大学同济医学院附属同济医院儿科住院、经头颅影像学证实并诊断为AIS的病例97例.年龄6个月～18岁.按病因分为炎性反应性动脉病组(32例)与非炎性反应性动脉病组(65例)(脑血管畸形、心源性栓塞、血液系统疾病及代谢疾病).记录二组患儿年龄、起病方式及梗死部位,并将起病方式分为急性与非急性,梗死部位分为基底核区与大脑中动脉主干供血区.采用t检验比较二组AIS患儿平均年龄差异,X2检验比较二组患儿起病方式与梗死部位差异.结果炎性反应性动脉病组与非炎性反应性动脉病组平均年龄比较差异无统计学意义(t=1.573 P＞0.05).炎性反应性动脉病组中急性起病者10例(31.2%),非炎性反应性动脉病组中急性起病者38例(58.5%),二组比较差异有统计学意义(X2=6.352 P＜O.05).炎性反应性动脉病组梗死灶位于基底核区21例(65.6%),非炎性反应性动脉病组梗死灶位于基底核区28例(43.1%),二组比较差异有统计学意义(X2=4.361 P＜0.05).结论起病方式与梗死部位可以提示儿童AIS的病因诊断.非急性起病、梗死灶位于基底核区的AIS,其病因多为炎性反应性动脉病.