In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose.Indeed,pharmacogenetics may exert its action on immunosuppressant drugs at three...In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose.Indeed,pharmacogenetics may exert its action on immunosuppressant drugs at three levels.Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation.Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants.Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways.Of course,not all genes have been discovered and studied,but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined.Other genes on the basis of relevant studies have been proposed as good candidates for future studies.Unfortunately,to date,clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney,heart and lung transplantation is recommended.The conclusions of the studies on the recommended candidate genes,together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.展开更多
AIM:To assess the effectiveness of immunosuppressants in the prophylaxis of corneal allograft rejection after high-risk keratoplasty and normal-risk keratoplasty.METHODS:We searched the Cochrane Central Register of Co...AIM:To assess the effectiveness of immunosuppressants in the prophylaxis of corneal allograft rejection after high-risk keratoplasty and normal-risk keratoplasty.METHODS:We searched the Cochrane Central Register of Controlled Trials(CENTRAL),MEDLINE,EMBASE,CNKI,VIP and reference lists of articles.Date of most recent search:18 June,2011.All randomised controlled trials(RCTs) assessing the use of immunosupressants in the prevention of graft rejection,irrespective of publication language.Two authors assessed trial quality and extracted data independently.Only dichotomous outcomes(clear graft survival,ratio of immune reactions and side effects) were available and were expressed as relative risk(RR) and 95% confidence intervals(CI).RESULTS:Seven studies were included in this review.In the comparing of mycophenolate mofetil(MMF) with placebo,the results showed MMF could significantly reduce immune reactions compared with placebo(RR 1.08 95% Cl 0.95 to 1.21),but no effect on clear graft survival(RR 1.11 95% Cl 0.90 to 1.35).In clear graft survival and immune reactions,MMF and cyclosporine A(CsA) showed similar effect(RR 1.11 95% Cl 0.90 to 1.35,and RR 1.48,95% Cl 0.56 to 3.93,respectively).Tacrolimus(FK506) and steroid showed similar effects on clear graft survival and immune reactions(RR 0.32,95% CI 0.02 to 6.21,and RR 1.00,95%CI 0.88 to 1.14,respectively).No drug relative side effect has been found.CONCLUSION:MMF may reduce immune reactions in both normal-risk and high-risk rejection of penetrating keratoplasty.CsA and FK506 showed similar effects as MMF.However,due to the lack of large clinical trials,the evidence remain weak,the quality of evidences were rated as very low to moderate.Large,properly randomised,placebo-controlled,double masked trials are needed to evaluate the effect of immunosuppressants.展开更多
BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multi-system fibroinflammatory disorder that can involve any organ,including the salivary glands,pancreas,and biliary tree.Treatment of immunoglobulin G4-relat...BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multi-system fibroinflammatory disorder that can involve any organ,including the salivary glands,pancreas,and biliary tree.Treatment of immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)is similar to that for IgG4-RD,but progression is irreversible in some cases.We present a case of IgG4-SC in which an immuno-suppressant induced marked clinical and radiologic improvement.CASE SUMMARY A 63-year-old male presented with a prominent itching sensation and wholebody jaundice.He showed obstructive-pattern jaundice,an elevated IgG4 level,and infiltration of a large number of IgG4-positive cells in the ampulla of Vater.The imaging findings of intrahepatic duct(IHD)and common bile duct dilation,an elevated serum IgG4 level,and characteristic histological findings led to diagnosis of IgG4-SC that compatible with the 2019 ACR/EULAR classification criteria.We planned to treat the patient with high-dose glucocorticoid(GC),followed by cyclophosphamide pulse therapy.After treatment with high-dose GC and an immunosuppressant,imaging studies showed that IHD dilatation had completely resolved.CONCLUSION Prompt diagnosis and appropriate treatment of IgG4-SC are important.Because there is a risk of relapse of IgG4-SC,the GC dose should be gradually reduced,and a maintenance immunosuppressant should be given.展开更多
AIM To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir.METHODS The antiviral activity of daclatasvir(DCV) and asunaprevir(ASV) combined with immunosuppress...AIM To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir.METHODS The antiviral activity of daclatasvir(DCV) and asunaprevir(ASV) combined with immunosuppressants was tested using two in vitro models for hepatitis C virus(HCV) infection.RESULTS Tacrolimus, rapamycin and cyclosporine did not negatively affect the antiviral action of DCV or ASV. Mycophenolic acid(MPA) showed additive antiviral effects combined with these direct acting antivirals(DAAs). MPA induces interferon-stimulated genes(ISGs) and is a potent GTP synthesis inhibitor. DCV or ASV did not induce ISGs expression nor affected ISG induction by MPA. Rather, the combined antiviral effect of MPA with DCV and ASV was partly mediated via inhibition of GTP synthesis.CONCLUSION Immunosuppressants do not negatively affect the antiviral activity of DAAs. MPA has additive effect on the antiviral action of DCV and ASV. This combined benefit needs to be confirmed in prospective clinical trials.展开更多
Immunosuppression in organ transplantation was revolutionary for its time,but technological and population changes cast new light on its use.First,metabolic syndrome(MS) is increasing as a public health issue,concomit...Immunosuppression in organ transplantation was revolutionary for its time,but technological and population changes cast new light on its use.First,metabolic syndrome(MS) is increasing as a public health issue,concomitantly increasing as an issue for post-orthotopic liver transplantation patients;yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism.Current mainstay immunosuppression involves the use of calcineurin inhibitors;these are potent,but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver.Second,the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications.Finally,immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment,which undercut what used to be inevitable viral recurrence.Overall,while traditional immunosuppressive agents remain the most used,the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient.展开更多
Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotra ns plantation from pigs to nonhuman primates.Moreover,to the best of our knowledge,no reports exist...Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotra ns plantation from pigs to nonhuman primates.Moreover,to the best of our knowledge,no reports exist on the use of fetal pigs as kidney donors.This study aimed to compare the degree of transplant rejection between neonatal and fetal kidneys,with genetically unmodified pigs as donors and cynomolgus monkeys as recipients.The left kidneys of the recipient monkeys were removed,followed by transplantation of neonatal as well as fetal pig kidneys,which had undergone vascular anastomosis at the same site,into the retroperitoneum.Immunosuppression was performed with only US Food and Drug Administration-approved drugs.The fetal kidneys were transplanted into the omentum and paraaortic regions of cynomolgus monkeys.Consequently,the engraftment and development of the transplanted tissues were pathologically examined by sampling over time(twice in each experiment).An acute rejection was observed after a few weeks in neonatal renal grafts with vascular anastomosis.However,fetal pig kidneys were spared from rejection despite the administration of the same immunosuppressive protocol to the monkeys and the recipient blood vessels flowing into the fetal kidneys.The immunogenicity of fetal kidneys in pig-monkey renal heterotransplantation was lower than that of neonatal kidneys.展开更多
Hepatitis B viral(HBV)reactivation in the immunosuppressed is a significant problem even in patients who have achieved serological clearance due to the persistence of HBV as cccDNA.HBV reactivation will continue to po...Hepatitis B viral(HBV)reactivation in the immunosuppressed is a significant problem even in patients who have achieved serological clearance due to the persistence of HBV as cccDNA.HBV reactivation will continue to pose a significant healthcare burden given the high prevalence of HBV and increasing use of immunosuppressants.Screening of hepatitis B surface antigen,antibody to Hepatitis B core antigen antibody and HBV DNA levels should be done routinely in all patients planned for significant immunosuppressant use.We aimed to examine the factors affecting reactivation risk.This depended on HBV disease status,the underlying disease requiring immunosuppression,and the specific immunosuppressive regime.While antiviral prophylaxis can prevent reactivation,it increases cost and still has risk of delayed reactivation after stopping antivirals and close follow-up and on-demand treatment is a good alternative for patients at risk of reactivation.展开更多
Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an ag...Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an aggressive course.There is increasing evidence that in the non-transplant setting,induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis,and that HCV proteins directly promote apoptosis.Recent studies have shown that post-liver transplant,there is a link between high levels of HCV replication,enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver fibrosis.Although the responsible mechanisms remain unclear,it is likely that immunosuppressive drugs play an important role.It is well known that immunosuppressants impair immune control of HCV,thereby allowing increased viral replication.However there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV replication.Thus HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid fibrosis.These findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease.展开更多
Objective: To evaluate the efficacy and safety of the immunosuppressant treatment among 10 post-renal transplantation recipients with malignant tumors. Methods: Conversion to sirolimus (SRL) treatment was performed fo...Objective: To evaluate the efficacy and safety of the immunosuppressant treatment among 10 post-renal transplantation recipients with malignant tumors. Methods: Conversion to sirolimus (SRL) treatment was performed for 10 cases which had found malignant tumors after kidney transplantation. During the follow-up period, the recurrence and diffusion of the tumor, the renal function and rejection were monitored. Results: All these cases despite the death had been followed up for at least 1 year. 9 cases had no recurrence and diffusion. 1 case died due to the tumor diffusion 7 months after the drug conversion. 1 case suffered once acute rejection 2 months after the drug conversion. This acute rejection had been inhibited by flushing dose MP. Conclusion: As a new immunosuppressant, SRL not only can prevent the generation of AR, but inhibit proliferation and development of malignant tumors in kidney transplantation recipients as well.展开更多
Liquid chromatography tandem mass spectrometry(LC-MS/MS) plays an important role in clinical diagnostics. Although LC-MS/MS is superior in terms of accurately quantifying molecules in complex matrices,instrument footp...Liquid chromatography tandem mass spectrometry(LC-MS/MS) plays an important role in clinical diagnostics. Although LC-MS/MS is superior in terms of accurately quantifying molecules in complex matrices,instrument footprint, operation and maintenance complexity also hinder its expansion as the analytical technique of choice. In this study, a compact LC-MS instrument was developed, in which an assembled liquid chromatograph was coupled with a miniature ion trap mass spectrometer. The overall instrument has a footprint of 69 cm × 31 cm × 31 cm, and it requires no gas supply as well as minimum maintenance. Furthermore, the use of LC-MS is in accord with conventional clinical diagnostic protocols, and the choice of ion trap offers tandem MS performance. The results showed that the use of LC could improve both mixture analysis capability and detection sensitivity of the miniature mass spectrometer. After optimization, feasibility of this instrument in clinical practice was demonstrated by the quantitation of four widely used immunosuppressants in blood samples. Relatively good linearities were obtained, which spanned the reference ranges of effective therapeutic concentrations of each immunosuppressant. Intraday and inter-day accuracy and precision of analytical method were also assessed. This work showed that a compact LC-MS instrument could be used in clinical diagnosis, either to replace conventional lab-scale instruments or to be used in POCT applications.展开更多
Background and amis:In our study,it was aimed to investigate the adherence of liver transplant recipients to immunosuppressant therapy,their self-control,and their self-management in the post-transplantation period.Me...Background and amis:In our study,it was aimed to investigate the adherence of liver transplant recipients to immunosuppressant therapy,their self-control,and their self-management in the post-transplantation period.Methods:The sample of this descriptive and cross-sectional study was composed of liver transplant recipients.The personal information form,Immunosuppressant Therapy Adherence Scale,and the Liver Self-Control and SelfManagement Scale were used to collect data,and descriptive statistical methods,independent samples t-test and one-way analysis of variance analysis was used to analyze the collected data.Results:In light of the data collected in this study,it was identified that,of all recipients,73.6%were 45–64 years old,72.5%were male,25.2%were workers,and 44.6%had equivalent income and expenses.It was observed that the recipients did not fully adhere to the immunosuppressant therapy regimen,and their self-control and selfmanagement levels were below the medium level.Conclusion:The social support system of liver transplant recipients is very important.Recipients with a good social support system can receive caregiver support from their relatives,thereby supporting their self-control and selfmanagement.Both liver transplant patients and the people providing care to them should be simultaneously provided with training programs and given information,and both groups should be supported in treatment and care processes.展开更多
Background and Aims:All-oral interlferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients.The aim of the study was to assess immunosuppression ...Background and Aims:All-oral interlferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients.The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR).Methods:We compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with alloral direct acting agents.Results:We identified 52 liver LT treated recipients who achieved a SVR.The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75,65).Most recipients received tacrolimus (TAC) for their immunosuppressant regimen.After achieving SVR,there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05).However,there was a statistically significant decrease in daily dose of TAC adjusted per weight,serum levels of TAC,and the product of glomerular filtration rate and TAC.No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted.Conclusions:Immunosuppression needs were increased for those patients treated with TAC but not cyclosporine.LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection.展开更多
With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune func...With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.展开更多
文摘In recent years,pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose.Indeed,pharmacogenetics may exert its action on immunosuppressant drugs at three levels.Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation.Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants.Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways.Of course,not all genes have been discovered and studied,but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined.Other genes on the basis of relevant studies have been proposed as good candidates for future studies.Unfortunately,to date,clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney,heart and lung transplantation is recommended.The conclusions of the studies on the recommended candidate genes,together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.
文摘AIM:To assess the effectiveness of immunosuppressants in the prophylaxis of corneal allograft rejection after high-risk keratoplasty and normal-risk keratoplasty.METHODS:We searched the Cochrane Central Register of Controlled Trials(CENTRAL),MEDLINE,EMBASE,CNKI,VIP and reference lists of articles.Date of most recent search:18 June,2011.All randomised controlled trials(RCTs) assessing the use of immunosupressants in the prevention of graft rejection,irrespective of publication language.Two authors assessed trial quality and extracted data independently.Only dichotomous outcomes(clear graft survival,ratio of immune reactions and side effects) were available and were expressed as relative risk(RR) and 95% confidence intervals(CI).RESULTS:Seven studies were included in this review.In the comparing of mycophenolate mofetil(MMF) with placebo,the results showed MMF could significantly reduce immune reactions compared with placebo(RR 1.08 95% Cl 0.95 to 1.21),but no effect on clear graft survival(RR 1.11 95% Cl 0.90 to 1.35).In clear graft survival and immune reactions,MMF and cyclosporine A(CsA) showed similar effect(RR 1.11 95% Cl 0.90 to 1.35,and RR 1.48,95% Cl 0.56 to 3.93,respectively).Tacrolimus(FK506) and steroid showed similar effects on clear graft survival and immune reactions(RR 0.32,95% CI 0.02 to 6.21,and RR 1.00,95%CI 0.88 to 1.14,respectively).No drug relative side effect has been found.CONCLUSION:MMF may reduce immune reactions in both normal-risk and high-risk rejection of penetrating keratoplasty.CsA and FK506 showed similar effects as MMF.However,due to the lack of large clinical trials,the evidence remain weak,the quality of evidences were rated as very low to moderate.Large,properly randomised,placebo-controlled,double masked trials are needed to evaluate the effect of immunosuppressants.
文摘BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multi-system fibroinflammatory disorder that can involve any organ,including the salivary glands,pancreas,and biliary tree.Treatment of immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)is similar to that for IgG4-RD,but progression is irreversible in some cases.We present a case of IgG4-SC in which an immuno-suppressant induced marked clinical and radiologic improvement.CASE SUMMARY A 63-year-old male presented with a prominent itching sensation and wholebody jaundice.He showed obstructive-pattern jaundice,an elevated IgG4 level,and infiltration of a large number of IgG4-positive cells in the ampulla of Vater.The imaging findings of intrahepatic duct(IHD)and common bile duct dilation,an elevated serum IgG4 level,and characteristic histological findings led to diagnosis of IgG4-SC that compatible with the 2019 ACR/EULAR classification criteria.We planned to treat the patient with high-dose glucocorticoid(GC),followed by cyclophosphamide pulse therapy.After treatment with high-dose GC and an immunosuppressant,imaging studies showed that IHD dilatation had completely resolved.CONCLUSION Prompt diagnosis and appropriate treatment of IgG4-SC are important.Because there is a risk of relapse of IgG4-SC,the GC dose should be gradually reduced,and a maintenance immunosuppressant should be given.
文摘AIM To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir.METHODS The antiviral activity of daclatasvir(DCV) and asunaprevir(ASV) combined with immunosuppressants was tested using two in vitro models for hepatitis C virus(HCV) infection.RESULTS Tacrolimus, rapamycin and cyclosporine did not negatively affect the antiviral action of DCV or ASV. Mycophenolic acid(MPA) showed additive antiviral effects combined with these direct acting antivirals(DAAs). MPA induces interferon-stimulated genes(ISGs) and is a potent GTP synthesis inhibitor. DCV or ASV did not induce ISGs expression nor affected ISG induction by MPA. Rather, the combined antiviral effect of MPA with DCV and ASV was partly mediated via inhibition of GTP synthesis.CONCLUSION Immunosuppressants do not negatively affect the antiviral activity of DAAs. MPA has additive effect on the antiviral action of DCV and ASV. This combined benefit needs to be confirmed in prospective clinical trials.
文摘Immunosuppression in organ transplantation was revolutionary for its time,but technological and population changes cast new light on its use.First,metabolic syndrome(MS) is increasing as a public health issue,concomitantly increasing as an issue for post-orthotopic liver transplantation patients;yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism.Current mainstay immunosuppression involves the use of calcineurin inhibitors;these are potent,but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver.Second,the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications.Finally,immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment,which undercut what used to be inevitable viral recurrence.Overall,while traditional immunosuppressive agents remain the most used,the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient.
基金supported by the Japan Agency for Medical Research and Development(AMED21bk0104094h0003)a grant from Sumitomo Dainippon Pharma Co.,Ltd。
文摘Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotra ns plantation from pigs to nonhuman primates.Moreover,to the best of our knowledge,no reports exist on the use of fetal pigs as kidney donors.This study aimed to compare the degree of transplant rejection between neonatal and fetal kidneys,with genetically unmodified pigs as donors and cynomolgus monkeys as recipients.The left kidneys of the recipient monkeys were removed,followed by transplantation of neonatal as well as fetal pig kidneys,which had undergone vascular anastomosis at the same site,into the retroperitoneum.Immunosuppression was performed with only US Food and Drug Administration-approved drugs.The fetal kidneys were transplanted into the omentum and paraaortic regions of cynomolgus monkeys.Consequently,the engraftment and development of the transplanted tissues were pathologically examined by sampling over time(twice in each experiment).An acute rejection was observed after a few weeks in neonatal renal grafts with vascular anastomosis.However,fetal pig kidneys were spared from rejection despite the administration of the same immunosuppressive protocol to the monkeys and the recipient blood vessels flowing into the fetal kidneys.The immunogenicity of fetal kidneys in pig-monkey renal heterotransplantation was lower than that of neonatal kidneys.
文摘Hepatitis B viral(HBV)reactivation in the immunosuppressed is a significant problem even in patients who have achieved serological clearance due to the persistence of HBV as cccDNA.HBV reactivation will continue to pose a significant healthcare burden given the high prevalence of HBV and increasing use of immunosuppressants.Screening of hepatitis B surface antigen,antibody to Hepatitis B core antigen antibody and HBV DNA levels should be done routinely in all patients planned for significant immunosuppressant use.We aimed to examine the factors affecting reactivation risk.This depended on HBV disease status,the underlying disease requiring immunosuppression,and the specific immunosuppressive regime.While antiviral prophylaxis can prevent reactivation,it increases cost and still has risk of delayed reactivation after stopping antivirals and close follow-up and on-demand treatment is a good alternative for patients at risk of reactivation.
文摘Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an aggressive course.There is increasing evidence that in the non-transplant setting,induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis,and that HCV proteins directly promote apoptosis.Recent studies have shown that post-liver transplant,there is a link between high levels of HCV replication,enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver fibrosis.Although the responsible mechanisms remain unclear,it is likely that immunosuppressive drugs play an important role.It is well known that immunosuppressants impair immune control of HCV,thereby allowing increased viral replication.However there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV replication.Thus HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid fibrosis.These findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease.
文摘Objective: To evaluate the efficacy and safety of the immunosuppressant treatment among 10 post-renal transplantation recipients with malignant tumors. Methods: Conversion to sirolimus (SRL) treatment was performed for 10 cases which had found malignant tumors after kidney transplantation. During the follow-up period, the recurrence and diffusion of the tumor, the renal function and rejection were monitored. Results: All these cases despite the death had been followed up for at least 1 year. 9 cases had no recurrence and diffusion. 1 case died due to the tumor diffusion 7 months after the drug conversion. 1 case suffered once acute rejection 2 months after the drug conversion. This acute rejection had been inhibited by flushing dose MP. Conclusion: As a new immunosuppressant, SRL not only can prevent the generation of AR, but inhibit proliferation and development of malignant tumors in kidney transplantation recipients as well.
基金supported by the National Key Research and Development Program of China (No. 2020YFF01014502)the National Natural Science of Foundation of China (Nos. 21922401,201827810)。
文摘Liquid chromatography tandem mass spectrometry(LC-MS/MS) plays an important role in clinical diagnostics. Although LC-MS/MS is superior in terms of accurately quantifying molecules in complex matrices,instrument footprint, operation and maintenance complexity also hinder its expansion as the analytical technique of choice. In this study, a compact LC-MS instrument was developed, in which an assembled liquid chromatograph was coupled with a miniature ion trap mass spectrometer. The overall instrument has a footprint of 69 cm × 31 cm × 31 cm, and it requires no gas supply as well as minimum maintenance. Furthermore, the use of LC-MS is in accord with conventional clinical diagnostic protocols, and the choice of ion trap offers tandem MS performance. The results showed that the use of LC could improve both mixture analysis capability and detection sensitivity of the miniature mass spectrometer. After optimization, feasibility of this instrument in clinical practice was demonstrated by the quantitation of four widely used immunosuppressants in blood samples. Relatively good linearities were obtained, which spanned the reference ranges of effective therapeutic concentrations of each immunosuppressant. Intraday and inter-day accuracy and precision of analytical method were also assessed. This work showed that a compact LC-MS instrument could be used in clinical diagnosis, either to replace conventional lab-scale instruments or to be used in POCT applications.
文摘Background and amis:In our study,it was aimed to investigate the adherence of liver transplant recipients to immunosuppressant therapy,their self-control,and their self-management in the post-transplantation period.Methods:The sample of this descriptive and cross-sectional study was composed of liver transplant recipients.The personal information form,Immunosuppressant Therapy Adherence Scale,and the Liver Self-Control and SelfManagement Scale were used to collect data,and descriptive statistical methods,independent samples t-test and one-way analysis of variance analysis was used to analyze the collected data.Results:In light of the data collected in this study,it was identified that,of all recipients,73.6%were 45–64 years old,72.5%were male,25.2%were workers,and 44.6%had equivalent income and expenses.It was observed that the recipients did not fully adhere to the immunosuppressant therapy regimen,and their self-control and selfmanagement levels were below the medium level.Conclusion:The social support system of liver transplant recipients is very important.Recipients with a good social support system can receive caregiver support from their relatives,thereby supporting their self-control and selfmanagement.Both liver transplant patients and the people providing care to them should be simultaneously provided with training programs and given information,and both groups should be supported in treatment and care processes.
文摘Background and Aims:All-oral interlferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients.The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR).Methods:We compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with alloral direct acting agents.Results:We identified 52 liver LT treated recipients who achieved a SVR.The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75,65).Most recipients received tacrolimus (TAC) for their immunosuppressant regimen.After achieving SVR,there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05).However,there was a statistically significant decrease in daily dose of TAC adjusted per weight,serum levels of TAC,and the product of glomerular filtration rate and TAC.No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted.Conclusions:Immunosuppression needs were increased for those patients treated with TAC but not cyclosporine.LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection.
基金The financial supports from the Key Program of the National Natural Science Foundation of China(32130082)Jiangxi High Level Talent Cultivation Project(20204BCJ24006)+1 种基金Project of State Key Laboratory of Food Science and Technology(SKLF-ZZA-201911)Central Government Guide Local Special Fund Project for Scientific and Technological Development of Jiangxi Province(20212ZDD02008)。
文摘With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.
