AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS...AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS After staphylococcal enterotoxin B(SEB ) mixed with D--galactosamine (D-GaiN )were injected intraperitoneally into Balb/c miceand those previously treated with cyclosporin A,blood samples were collected and livers wereisolated at 2, 6, 12 and 24 h. Patterns othepatocellular death were studiedmorphologically and biochemically, circulatingcytokines (TNF-a, IFN--y ) and mice mortalitywithin 24h was assessed.RESU’LTS The SEB could induce the typicalapoptotic changes of hepatocytes, the D-GaiNcould induce hepatocytes apoptosis anddegeneration at the same time, and the micehaving received the SEB + D-GaiN injectionsdeveloped apoptosis at 2 and 6 h, but after 12 hhepatocytes were characterized by severein jury, whereas all the examinations in thecyclosporin A treated mice were normal.CONCLUSION Hepatic cell apoptosis might berelated to necrosis, and massive hepatocyteapoptosis is likely the initiating step of acutehepatic necrosis in mice. The effects induced bySEB and D--GaiN on hepatocytes might bemediated by T cells, and could be prevented bycyclosporin A.展开更多
Summary： The effects of cyclosporine A （CsA） on Angiontensin Ⅱ （Ang Ⅱ ）-induced protein contents, c los protein levels and cytosolic Ca^2＋ level （[Ca^2＋]i） in cultured eardiomyocytes of neonatal rats were o...Summary： The effects of cyclosporine A （CsA） on Angiontensin Ⅱ （Ang Ⅱ ）-induced protein contents, c los protein levels and cytosolic Ca^2＋ level （[Ca^2＋]i） in cultured eardiomyocytes of neonatal rats were observed. Total protein contents were determined by Bradford method. The expression of c-fos protein was detected by Western blot. （[Ca^2＋]i） labeled with fluorescent probe Fluo-3/AM was measured under a laser scanning confoeal microscope. The results revealed that as compared with control, the total protein contents were increased in cardiomyocytes treated with Ang Ⅱ （10-1 mol/ L）, which could be inhibited by CsA in a dose-dependent manner. It was found that Ang Ⅱ could increase the c-los protein expression, which could be inhibited by CsA in a dose-dependent manner. Ang Ⅱ induced the [Ca^2＋]i elevation in cardiomyocytes. CsA did not influence the resting intracellular Ca^2＋ , but inhibited significantly the Ang Ⅱ-induced [Ca^2＋]i elevation. It was concluded that CsA can suppress the Ang Ⅱ-induced c-fos protein expression and [Ca^2＋]i elevation in single cardiomyocyte, which might play a role in the prevention of Ang Ⅱ-induced cardiomyocyte hypertrophy by CsA.展开更多
Up to date,in literature,it is still debated the role of anti-tumor necrosis factors(TNF)-α treatments in hepatitis C virus(HCV) patients.TNF-α performs a lot of functions,it is an important pro-inflammatory cytokin...Up to date,in literature,it is still debated the role of anti-tumor necrosis factors(TNF)-α treatments in hepatitis C virus(HCV) patients.TNF-α performs a lot of functions,it is an important pro-inflammatory cytokine and it is involved in the host's immunity.Since TNF-α is implicated in the apoptotic signaling pathway of hepatocytes infected by HCV,anti TNF-α therapy may increase the risk of viral replication or their reactivation.However the treatment of anti TNF-α could have a healthful role because TNF-α appears to be engaged in the pathogenesis of liver fibrosis,inducing apoptotic pathways.We describe the case of a patient with plaquetype psoriasis and concomitant chronic HCV,who was treated successfully with anti-TNF agents simultaneously to cyclosporine without sign of reactivation of HCV and increase of liver enzymes.Our personal experience shows that anti-TNF-α agents are not only effective but also safe.Furthermore the combination therapy of cyclosporine and anti-TNF-α appears to be well-tolerated and able to reduce the amount of liver enzymes as well as HCV-viral-load.However systematic,large-scale studies with long follow-ups will be needed to confirm our results,in association with close liver function monitoring.展开更多
Aim. To study the effect of kanglemycin C (KC) on production and gene transcription of lymphokins. Methods.Cell proliferation and lymphokin activities were quantified with MTT colorimetry and ELISA, and gene transcrip...Aim. To study the effect of kanglemycin C (KC) on production and gene transcription of lymphokins. Methods.Cell proliferation and lymphokin activities were quantified with MTT colorimetry and ELISA, and gene transcriptions of lymphokins semi quantified with RT PCR. Results.Suppression of KC on proliferation of enriched T and B cell respectively mediated by Con A and LPS was declined by addition of exogenous IL 1, IL 2, and IL 6. KC 80 nmol/L markedly inhibited IL 2 and IL 6 production and mRNA transcription of incubated mouse splenocytes induced by Con A. Additionally, KC had some suppression on IL 1β and IL 6 productions of peritoneal macrophage stimulated by LPS (5μg/mL), whereas cyclosporine (CS) had not. [WT5”BX]Conclusion. [WT5”BZ]Immunosuppression of KC came true partially through the decrease of IL 1β, 2 and 6 productions, especially of IL 2. However, CS′s immunosuppression was mainly through the decrease of IL 2 procduction.展开更多
目的探讨环孢素A(cyclosporine A,CsA)对全基因组丙型肝炎病毒JFH-1(hepatitis C virus,HCVJFH-1)在肝细胞中复制的影响。方法以体外转录的HCVJFH-1RNA转染Huh7细胞,制备含HCV病毒颗粒的感染上清,建立全基因组HCVJFH-1感染Huh7细胞模型...目的探讨环孢素A(cyclosporine A,CsA)对全基因组丙型肝炎病毒JFH-1(hepatitis C virus,HCVJFH-1)在肝细胞中复制的影响。方法以体外转录的HCVJFH-1RNA转染Huh7细胞,制备含HCV病毒颗粒的感染上清,建立全基因组HCVJFH-1感染Huh7细胞模型,分为对照组、CsA处理组,分别予以不同浓度、不同时间、不同时机和方法的CsA处理。通过实时荧光定量聚合酶链反应(real ti me polymerase chain reaction,RT-PCR)检测CsA对HCVJFH-1在Huh7细胞中复制的影响。结果与对照组比较,CsA(0.15、0.3、0.6、1.2μg/ml)处理组Huh7细胞中HCVJFH-1RNA相对表达量分别下降为(45.7±6.5)%、(18.9±2.1)%、(4.6±0.7)%、(2.1±0.2)%,上清中HCV拷贝数(×107/ml)较对照组(29.70±0.15)下降为(0.80±0.19)、(0.44±0.07)、(0.29±0.07)、(0.17±0.06)。CsA处理组HCV蛋白合成、上清中病毒颗粒的含量及Huh7细胞裂解液和上清感染力明显下降。同时CsA预处理较感染同时及感染后处理可更显著抑制HCVJFH-1在Huh7细胞中的复制,而撤药则导致其复制的反弹。以上差异均有统计学意义。结论 CsA可有效抑制全基因组HCVJFH-1在Huh7细胞中的复制及合成,并减少有感染力的HCV病毒颗粒产生。展开更多
文摘AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS After staphylococcal enterotoxin B(SEB ) mixed with D--galactosamine (D-GaiN )were injected intraperitoneally into Balb/c miceand those previously treated with cyclosporin A,blood samples were collected and livers wereisolated at 2, 6, 12 and 24 h. Patterns othepatocellular death were studiedmorphologically and biochemically, circulatingcytokines (TNF-a, IFN--y ) and mice mortalitywithin 24h was assessed.RESU’LTS The SEB could induce the typicalapoptotic changes of hepatocytes, the D-GaiNcould induce hepatocytes apoptosis anddegeneration at the same time, and the micehaving received the SEB + D-GaiN injectionsdeveloped apoptosis at 2 and 6 h, but after 12 hhepatocytes were characterized by severein jury, whereas all the examinations in thecyclosporin A treated mice were normal.CONCLUSION Hepatic cell apoptosis might berelated to necrosis, and massive hepatocyteapoptosis is likely the initiating step of acutehepatic necrosis in mice. The effects induced bySEB and D--GaiN on hepatocytes might bemediated by T cells, and could be prevented bycyclosporin A.
文摘Summary： The effects of cyclosporine A （CsA） on Angiontensin Ⅱ （Ang Ⅱ ）-induced protein contents, c los protein levels and cytosolic Ca^2＋ level （[Ca^2＋]i） in cultured eardiomyocytes of neonatal rats were observed. Total protein contents were determined by Bradford method. The expression of c-fos protein was detected by Western blot. （[Ca^2＋]i） labeled with fluorescent probe Fluo-3/AM was measured under a laser scanning confoeal microscope. The results revealed that as compared with control, the total protein contents were increased in cardiomyocytes treated with Ang Ⅱ （10-1 mol/ L）, which could be inhibited by CsA in a dose-dependent manner. It was found that Ang Ⅱ could increase the c-los protein expression, which could be inhibited by CsA in a dose-dependent manner. Ang Ⅱ induced the [Ca^2＋]i elevation in cardiomyocytes. CsA did not influence the resting intracellular Ca^2＋ , but inhibited significantly the Ang Ⅱ-induced [Ca^2＋]i elevation. It was concluded that CsA can suppress the Ang Ⅱ-induced c-fos protein expression and [Ca^2＋]i elevation in single cardiomyocyte, which might play a role in the prevention of Ang Ⅱ-induced cardiomyocyte hypertrophy by CsA.
文摘Up to date,in literature,it is still debated the role of anti-tumor necrosis factors(TNF)-α treatments in hepatitis C virus(HCV) patients.TNF-α performs a lot of functions,it is an important pro-inflammatory cytokine and it is involved in the host's immunity.Since TNF-α is implicated in the apoptotic signaling pathway of hepatocytes infected by HCV,anti TNF-α therapy may increase the risk of viral replication or their reactivation.However the treatment of anti TNF-α could have a healthful role because TNF-α appears to be engaged in the pathogenesis of liver fibrosis,inducing apoptotic pathways.We describe the case of a patient with plaquetype psoriasis and concomitant chronic HCV,who was treated successfully with anti-TNF agents simultaneously to cyclosporine without sign of reactivation of HCV and increase of liver enzymes.Our personal experience shows that anti-TNF-α agents are not only effective but also safe.Furthermore the combination therapy of cyclosporine and anti-TNF-α appears to be well-tolerated and able to reduce the amount of liver enzymes as well as HCV-viral-load.However systematic,large-scale studies with long follow-ups will be needed to confirm our results,in association with close liver function monitoring.
文摘Aim. To study the effect of kanglemycin C (KC) on production and gene transcription of lymphokins. Methods.Cell proliferation and lymphokin activities were quantified with MTT colorimetry and ELISA, and gene transcriptions of lymphokins semi quantified with RT PCR. Results.Suppression of KC on proliferation of enriched T and B cell respectively mediated by Con A and LPS was declined by addition of exogenous IL 1, IL 2, and IL 6. KC 80 nmol/L markedly inhibited IL 2 and IL 6 production and mRNA transcription of incubated mouse splenocytes induced by Con A. Additionally, KC had some suppression on IL 1β and IL 6 productions of peritoneal macrophage stimulated by LPS (5μg/mL), whereas cyclosporine (CS) had not. [WT5”BX]Conclusion. [WT5”BZ]Immunosuppression of KC came true partially through the decrease of IL 1β, 2 and 6 productions, especially of IL 2. However, CS′s immunosuppression was mainly through the decrease of IL 2 procduction.
文摘目的探讨环孢素A(cyclosporine A,CsA)对全基因组丙型肝炎病毒JFH-1(hepatitis C virus,HCVJFH-1)在肝细胞中复制的影响。方法以体外转录的HCVJFH-1RNA转染Huh7细胞,制备含HCV病毒颗粒的感染上清,建立全基因组HCVJFH-1感染Huh7细胞模型,分为对照组、CsA处理组,分别予以不同浓度、不同时间、不同时机和方法的CsA处理。通过实时荧光定量聚合酶链反应(real ti me polymerase chain reaction,RT-PCR)检测CsA对HCVJFH-1在Huh7细胞中复制的影响。结果与对照组比较,CsA(0.15、0.3、0.6、1.2μg/ml)处理组Huh7细胞中HCVJFH-1RNA相对表达量分别下降为(45.7±6.5)%、(18.9±2.1)%、(4.6±0.7)%、(2.1±0.2)%,上清中HCV拷贝数(×107/ml)较对照组(29.70±0.15)下降为(0.80±0.19)、(0.44±0.07)、(0.29±0.07)、(0.17±0.06)。CsA处理组HCV蛋白合成、上清中病毒颗粒的含量及Huh7细胞裂解液和上清感染力明显下降。同时CsA预处理较感染同时及感染后处理可更显著抑制HCVJFH-1在Huh7细胞中的复制,而撤药则导致其复制的反弹。以上差异均有统计学意义。结论 CsA可有效抑制全基因组HCVJFH-1在Huh7细胞中的复制及合成,并减少有感染力的HCV病毒颗粒产生。
