BACKGROUND： Tacrolimus （FK506） protects peripheral nerves located in damaged regions by inhibiting T lymphocyte proliferation and activation. OBJECTIVE： To evaluate the effect of FK506 on promoting regeneration of...BACKGROUND： Tacrolimus （FK506） protects peripheral nerves located in damaged regions by inhibiting T lymphocyte proliferation and activation. OBJECTIVE： To evaluate the effect of FK506 on promoting regeneration of rat sciatic nerve. DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Laboratory of the Department of Orthopedic Surgery, Dalian Medical University, China, from September 2007 to September 2008. MATERIALS： A total of 60 adult, male, Sprague-Dawley rats were equally and randomly divided into model, local administration and systemic administration groups. All rats received a neurotomy of bilateral sciatic nerves to establish models of nerve regeneration chambers. The powder and injection of FK506 were supplied by Fujisawa Pharmaceutical, Japan. METHODS： The regeneration chambers of the model group were infused with 0.2 mL saline. The systemic group were injected with 0.2 mL saline, followed by daily subcutaneous injections of FK506 （1 mg/kg）, for 14 days. The local administration group was infused with 0.2 mL FK506 （1 μg/mL）. MAIN OUTCOME MEASURES： Local immune response was observed using hematoxylin-eosin staining. Myelinated nerve fiber number, myelin sheath and nerve fiber thickness were observed using toluidine blue staining. Wet weight of gastrocnemius was evaluated. Compound muscle action potential amplitude, latency, and conduction time were recorded, and motor nerve conduction velocity was calculated using electrophysiology. RESULTS： The total number of myelinated nerve fibers in the local and systemic administration groups was significantly higher than in the model group. The density of myelinated nerve fibers, myelin sheath thickness and mean axon diameter were significantly increased in the systemic administration group compared with the model group （P 〈 0.05）. Lymphocyte infiltration was decreased in the local and systemic administration groups compared with the model group. The wet weight of rat gastrocnemius in the local and systemic administration groups were significantly greater compared with the model group （P 〈 0.05）. Motor nerve conduction velocity was the fastest in the systemic administration group, and the slowest in the model group. Compound muscle action potential amplitude was larger in the systemic administration group compared with the local administration and model groups （P 〈 0.05）. CONCLUSION： Systemic administration of FK506 can promote regeneration of rat sciatic nerve and recovery of neural function. Systemic administration produced better regeneration and recovery of function than local administration of FK506.展开更多
BACKGROUND Once daily tacrolimus regimen was found to exhibits similar bioavailability,safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients.AIM To compare the efficacy a...BACKGROUND Once daily tacrolimus regimen was found to exhibits similar bioavailability,safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients.AIM To compare the efficacy and safety of once-daily prolonged release tacrolimus compared to twice-daily tacrolimus in liver transplantation patients.METHODS MEDLINE,EMBASE,CENTRAL databases were searched for clinical trials until December 2020.Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection,Serum creatinine,graft loss,or death.Two reviewers independently selected studies,collected data and assessed risk of bias.The results are reported as risk ratio with 95%confidence interval(CI)for dichotomous data.RESULTS Seven studies included with 965 patients.All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool.Biopsy-proven acute rejection was reported in four studies,and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups(risk ratio:1.06,95%CI:0.84-1.34,n=758,I2=0%)and also we found no significant difference between both groups for renal outcome(serum creatinine;mean difference,0.001 mg/dL,95%CI:-0.042 to 0.043,n=846,I2=18.6%).Similarly,there was similar number of adverse events such as hypertension,headache,back pain,blood related disorders,infections and nausea observed in both groups.CONCLUSION The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.展开更多
Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplante...Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance, bone marrow mesenchymal stem cells were intramuscularly （gluteus maximus） injected with FK506 （tacrolimus） daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 ＋ bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 ＋ bone marrow mesenchymal stem cells group. The FK506 ＋ bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant.展开更多
基金the Scientific Research Foundation of Education Department of Liaoning Province in China, No.9707221070
文摘BACKGROUND： Tacrolimus （FK506） protects peripheral nerves located in damaged regions by inhibiting T lymphocyte proliferation and activation. OBJECTIVE： To evaluate the effect of FK506 on promoting regeneration of rat sciatic nerve. DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Laboratory of the Department of Orthopedic Surgery, Dalian Medical University, China, from September 2007 to September 2008. MATERIALS： A total of 60 adult, male, Sprague-Dawley rats were equally and randomly divided into model, local administration and systemic administration groups. All rats received a neurotomy of bilateral sciatic nerves to establish models of nerve regeneration chambers. The powder and injection of FK506 were supplied by Fujisawa Pharmaceutical, Japan. METHODS： The regeneration chambers of the model group were infused with 0.2 mL saline. The systemic group were injected with 0.2 mL saline, followed by daily subcutaneous injections of FK506 （1 mg/kg）, for 14 days. The local administration group was infused with 0.2 mL FK506 （1 μg/mL）. MAIN OUTCOME MEASURES： Local immune response was observed using hematoxylin-eosin staining. Myelinated nerve fiber number, myelin sheath and nerve fiber thickness were observed using toluidine blue staining. Wet weight of gastrocnemius was evaluated. Compound muscle action potential amplitude, latency, and conduction time were recorded, and motor nerve conduction velocity was calculated using electrophysiology. RESULTS： The total number of myelinated nerve fibers in the local and systemic administration groups was significantly higher than in the model group. The density of myelinated nerve fibers, myelin sheath thickness and mean axon diameter were significantly increased in the systemic administration group compared with the model group （P 〈 0.05）. Lymphocyte infiltration was decreased in the local and systemic administration groups compared with the model group. The wet weight of rat gastrocnemius in the local and systemic administration groups were significantly greater compared with the model group （P 〈 0.05）. Motor nerve conduction velocity was the fastest in the systemic administration group, and the slowest in the model group. Compound muscle action potential amplitude was larger in the systemic administration group compared with the local administration and model groups （P 〈 0.05）. CONCLUSION： Systemic administration of FK506 can promote regeneration of rat sciatic nerve and recovery of neural function. Systemic administration produced better regeneration and recovery of function than local administration of FK506.
文摘BACKGROUND Once daily tacrolimus regimen was found to exhibits similar bioavailability,safety and efficacy properties compared to twice-daily tacrolimus in kidney transplantation patients.AIM To compare the efficacy and safety of once-daily prolonged release tacrolimus compared to twice-daily tacrolimus in liver transplantation patients.METHODS MEDLINE,EMBASE,CENTRAL databases were searched for clinical trials until December 2020.Efficacy outcome measured as the rate of treatment failure indicated by biopsy-proven acute rejection,Serum creatinine,graft loss,or death.Two reviewers independently selected studies,collected data and assessed risk of bias.The results are reported as risk ratio with 95%confidence interval(CI)for dichotomous data.RESULTS Seven studies included with 965 patients.All the included studies were of moderate quality according to the risk of bias assessment using Cochrane Risk of Bias tool.Biopsy-proven acute rejection was reported in four studies,and pooled analysis of those studies indicated similar rejections in both twice daily and once daily tacrolimus groups(risk ratio:1.06,95%CI:0.84-1.34,n=758,I2=0%)and also we found no significant difference between both groups for renal outcome(serum creatinine;mean difference,0.001 mg/dL,95%CI:-0.042 to 0.043,n=846,I2=18.6%).Similarly,there was similar number of adverse events such as hypertension,headache,back pain,blood related disorders,infections and nausea observed in both groups.CONCLUSION The analysis findings confirm that both once daily and twice daily tacrolimus formulations are comparable in terms of efficacy and safety outcomes.
基金the National Natural Science Foundation of China,No.30801171，the Natural Science Foundation of Hebei Province,No.C2009001013 and No.H2012406015
文摘Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance, bone marrow mesenchymal stem cells were intramuscularly （gluteus maximus） injected with FK506 （tacrolimus） daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 ＋ bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 ＋ bone marrow mesenchymal stem cells group. The FK506 ＋ bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant.
