AIM: To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus (HCV) liver transplant (LT) recipients.
Methylene blue (MB), a tricyclic phenothiazine drug, has been reported to enhance mitochondrial functions including mitochondrial respiration. By comparison, stress associated with abrupt ethanol withdrawal (EW) imped...Methylene blue (MB), a tricyclic phenothiazine drug, has been reported to enhance mitochondrial functions including mitochondrial respiration. By comparison, stress associated with abrupt ethanol withdrawal (EW) impedes mitochondrial functions. We investigated whether MB protects mitochondrial respiration and cell survival from EW stress through a key mitochondrial enzyme, cytochrome c oxidase (COX). We also investigated whether the MB’s protection involves the inhibition of an excitatory neurotransmitter, glutamate. Male rats were exposed to and withdrawn from ethanol-diet (7.5%, 5 weeks). MB (0.5 mg/kg, intraperitoneal) was injected for the last 5 days of ethanol-diet and on the first day of EW. Cerebellum was then harvested to measure mitochondrial respiration and COX expression using real-time XF respirometer and immunohistochemistry, respectively. Separately, HT22 cells (a murine hippocampal cell line) were exposed to and abruptly withdrawn for 4 hours from chronic ethanol (100 mM, 3 days). MB was administered during EW with or without a COX inhibitor (NaN3) or glutamate. Mitochondrial respiration, COX content, and cell viability were then assessed using real-time XF respirometer, an immunoblot method, and Calcein assay, respectively. MB attenuated the suppressing effects of EW on mitochondrial respiration, COX content, and cell survival. This protection was reduced after NaN3 or glutamate cotreatment. These results suggest that MB treatment help maintain mitochondrial respiratory and cellular integrity through COX-upregulation and glutamateinhibition upon EW stress. MB treatment may help identify mitochondrial mechanisms underlying hyperexcitatory CNS disorders.展开更多
目的采用Meta分析评价拉米夫定治疗B/C基因型乙肝病毒的疗效及其相关性。方法检索CNKI(1966~2013);Medline(1966~2013)、Pubmed(1966~2013)、Web of Science(1966~2013)中的RCT论文,按照方案设计的标准对文献进行筛选。最终所得文献使用...目的采用Meta分析评价拉米夫定治疗B/C基因型乙肝病毒的疗效及其相关性。方法检索CNKI(1966~2013);Medline(1966~2013)、Pubmed(1966~2013)、Web of Science(1966~2013)中的RCT论文,按照方案设计的标准对文献进行筛选。最终所得文献使用Revman 5.0等软件进行Meta分析。结果得19篇RCT研究文献,共涉及被试者3148人。其中,10篇文献(n=1860)为HBV DNA转阴研究;9篇文献(n=1288)为HBe Ag清除研究。应用拉米夫定后,HBV DNA转阴研究的总体RR为1.07(95%CI:0.98~1.17);HBe Ag清除可见于B基因型组,总体RR为1.27(95%CI:0.94~1.71)结论拉米夫定治疗HBV的疗效与HBV属于B或C基因型无关。需要通过进一步研究证明其中的作用机制。有必要进行大规模、多中心试验研究,评估不同基因型HBV对病程和抗病毒治疗疗效的影响。展开更多
Thirty-six randomized controlled trials and two metaanalyses were reviewed. With respect to adult patients undergoing first orthotopic liver transplantation(OLT), steroid replacement resulted in fewer cases of overall...Thirty-six randomized controlled trials and two metaanalyses were reviewed. With respect to adult patients undergoing first orthotopic liver transplantation(OLT), steroid replacement resulted in fewer cases of overall acute rejection in the corticosteroid free-immunosuppression arm. Initial steroid administration for two weeks and early tacrolimus monotherapy is a feasible immunosuppression regimen without steroid replacement, although further investigations are needed in view of chronic rejections. No significant differences were noted between the treatment groups in terms of patient and graft survival independently of steroid replacement. Renal insufficiency, de novo hypertension, neurological disorders and infectious complications did not differ significantly among steroid and steroidfree groups. Diabetes mellitus, cholesterol levels and cytomegalovirus infection are more frequent in patients within the steroid group. With respect to diabetes mellitus and hypercholesterolemia, the difference was independent of steroid replacement. In relation to transplanted hepatitis C virus patients, mycophenolate mofetil does not appear to have a significant antiviral effect despite early reports. Male gender of donors and recipients, living donors, cold ischemia times, acute rejection, and early histological recurrence were related to the development of advanced hepatitis. There is sufficient scientific clinical evidence advocating avoidance of the ab initio use of steroids in OLT.展开更多
AIM:To estimate the amount of apoptosis among healthy HBsAg carriers,patients with chronic HBV infection treated wibh lamivudine and patients with chronic HCV infection treated with interferon alpha and ribavirin.Acti...AIM:To estimate the amount of apoptosis among healthy HBsAg carriers,patients with chronic HBV infection treated wibh lamivudine and patients with chronic HCV infection treated with interferon alpha and ribavirin.Activity of apoptosis was evaluated by serum sFas/sFasL concentration measurement. Moreover dependence between apoptosis and HBV-DNA or HCV-RNA levels was studied. METHODS:Eighty-six persons were included into study:34 healthy HBsAg carders,33 patients with chronic HBV infecl^on and 19 patients with chronic HCV infection.Serum levels of sFas/sFasL were measured by ELISA assay.HBV-DNA and HCV-RNA were measured by RT-PCR assay.Levels of sFas/sFasL were determined before and 2 and 12 wk after therapy in patients with chronic hepatitis B and C infection. HBV-DNA or HCV-RNA was detected before treatment and 6 mo after treatment. RESULTS:Twenty-four (71%) healthy HBsAg carders showed HBV-DNA over 10~5/mL,which was comparable to the patients with chronic hepatitis B.independently from HBV-DNA levels, the concentration of sFas among healthy HBsAg carders was comparable to healthy persons.Among patients with chronic hepatitis B and C,the concentration of sFas was significantly higher in comparison to healthy HBsAg carriers and healthy persons.In chronic hepatitis B patients the concentration of sFas was decreased during lamivudine treatment.Among chronic hepatitis C patients the concentration of sFas was increased during IFN alpha and ribavirin treatment,sFasL was not detected in control group.Furbhermore sFasL occurred more frequently in chronic hepatitis C patients in comparison to chronic hepatitis B patients. CONCLUSION:There are no correlations between apoptosis and HBV-DNA levels.However ther is an association between apoptosis and activity of inflammation in patients with chronic HBV infection.Apoptosis can be increased in patients with chronic hepatitis C by effective treatment which may be a result of apoptosis stimulation by IFN-α.展开更多
文摘AIM: To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus (HCV) liver transplant (LT) recipients.
文摘Methylene blue (MB), a tricyclic phenothiazine drug, has been reported to enhance mitochondrial functions including mitochondrial respiration. By comparison, stress associated with abrupt ethanol withdrawal (EW) impedes mitochondrial functions. We investigated whether MB protects mitochondrial respiration and cell survival from EW stress through a key mitochondrial enzyme, cytochrome c oxidase (COX). We also investigated whether the MB’s protection involves the inhibition of an excitatory neurotransmitter, glutamate. Male rats were exposed to and withdrawn from ethanol-diet (7.5%, 5 weeks). MB (0.5 mg/kg, intraperitoneal) was injected for the last 5 days of ethanol-diet and on the first day of EW. Cerebellum was then harvested to measure mitochondrial respiration and COX expression using real-time XF respirometer and immunohistochemistry, respectively. Separately, HT22 cells (a murine hippocampal cell line) were exposed to and abruptly withdrawn for 4 hours from chronic ethanol (100 mM, 3 days). MB was administered during EW with or without a COX inhibitor (NaN3) or glutamate. Mitochondrial respiration, COX content, and cell viability were then assessed using real-time XF respirometer, an immunoblot method, and Calcein assay, respectively. MB attenuated the suppressing effects of EW on mitochondrial respiration, COX content, and cell survival. This protection was reduced after NaN3 or glutamate cotreatment. These results suggest that MB treatment help maintain mitochondrial respiratory and cellular integrity through COX-upregulation and glutamateinhibition upon EW stress. MB treatment may help identify mitochondrial mechanisms underlying hyperexcitatory CNS disorders.
基金This work was supported by the National Natural Science Foundation of China (No.30200267) the Natural Science Foundation of Educational Committee of Jiangsu Province (No. 01KJD320036).
文摘Thirty-six randomized controlled trials and two metaanalyses were reviewed. With respect to adult patients undergoing first orthotopic liver transplantation(OLT), steroid replacement resulted in fewer cases of overall acute rejection in the corticosteroid free-immunosuppression arm. Initial steroid administration for two weeks and early tacrolimus monotherapy is a feasible immunosuppression regimen without steroid replacement, although further investigations are needed in view of chronic rejections. No significant differences were noted between the treatment groups in terms of patient and graft survival independently of steroid replacement. Renal insufficiency, de novo hypertension, neurological disorders and infectious complications did not differ significantly among steroid and steroidfree groups. Diabetes mellitus, cholesterol levels and cytomegalovirus infection are more frequent in patients within the steroid group. With respect to diabetes mellitus and hypercholesterolemia, the difference was independent of steroid replacement. In relation to transplanted hepatitis C virus patients, mycophenolate mofetil does not appear to have a significant antiviral effect despite early reports. Male gender of donors and recipients, living donors, cold ischemia times, acute rejection, and early histological recurrence were related to the development of advanced hepatitis. There is sufficient scientific clinical evidence advocating avoidance of the ab initio use of steroids in OLT.
文摘AIM:To estimate the amount of apoptosis among healthy HBsAg carriers,patients with chronic HBV infection treated wibh lamivudine and patients with chronic HCV infection treated with interferon alpha and ribavirin.Activity of apoptosis was evaluated by serum sFas/sFasL concentration measurement. Moreover dependence between apoptosis and HBV-DNA or HCV-RNA levels was studied. METHODS:Eighty-six persons were included into study:34 healthy HBsAg carders,33 patients with chronic HBV infecl^on and 19 patients with chronic HCV infection.Serum levels of sFas/sFasL were measured by ELISA assay.HBV-DNA and HCV-RNA were measured by RT-PCR assay.Levels of sFas/sFasL were determined before and 2 and 12 wk after therapy in patients with chronic hepatitis B and C infection. HBV-DNA or HCV-RNA was detected before treatment and 6 mo after treatment. RESULTS:Twenty-four (71%) healthy HBsAg carders showed HBV-DNA over 10~5/mL,which was comparable to the patients with chronic hepatitis B.independently from HBV-DNA levels, the concentration of sFas among healthy HBsAg carders was comparable to healthy persons.Among patients with chronic hepatitis B and C,the concentration of sFas was significantly higher in comparison to healthy HBsAg carriers and healthy persons.In chronic hepatitis B patients the concentration of sFas was decreased during lamivudine treatment.Among chronic hepatitis C patients the concentration of sFas was increased during IFN alpha and ribavirin treatment,sFasL was not detected in control group.Furbhermore sFasL occurred more frequently in chronic hepatitis C patients in comparison to chronic hepatitis B patients. CONCLUSION:There are no correlations between apoptosis and HBV-DNA levels.However ther is an association between apoptosis and activity of inflammation in patients with chronic HBV infection.Apoptosis can be increased in patients with chronic hepatitis C by effective treatment which may be a result of apoptosis stimulation by IFN-α.
