ABSTRACT
Highly active antiretroviral therapy (HAART) can effectively suppress thehuman immunodeficiency virus (HIV) replication andsignificantly reduce morbidity and mortality of HIV-infectedpatients,which howevercan't completely remove the virus,and eventually progressinto chronic viral-infection disease.Chronic HIVinfection destroys host immune system,leading to intestinal barrier damage,intestinal mucosal dysfunction,microbial translocation,and further accelerates the disease progress.The reconstruction of intestinalmicroflora balance and improvement of intestinal mucosa function areessential to reestablish the host immune system.This paper will review the current research advanceson intestinal barrier damage of HIV infection and gut-target therapy of AIDS.The aim is to provide valid evidences for further research targeting improvement of treatment strategiesandreduction of morbidity and mortality in HIV infection.
ABSTRACT
Objective By means of animal study,investigated the gut barrier function in severe acute pancreatitis ( SAP),and role of inflammatory factors releasing,gut mucosa oxidative stress,cell apoptosis in it.Methods The animal experiment was done in the animal center of first people' s hospital,shanghai jiaotong university.Twenty four BALB/c mice were randomized ( random number) divided into two groups with twelve mice each group.The SAP group,mice received six intraperitoneal injections of cerulein at 1-hour intervals, the dose was 50μg/kg, then given one intraperitoneal injection of 10 mg/kg lipopolysaccharide ( LPS from E.Coli) for the induction of severe acute pancreatitis.The control ( sham operation) group,the mice received intraperitoneal injection of 2 ml normal saline for six times at 1-hour intervals.All the animals of each group were averaged to two batches,4 h and 8h after being operated respectively,to be anesthetized and adopted blood and tissue specimen.Then we observed the pathological change of pancreas and gut,scored it.We measured the blood value of diamine oxidase ( DAO),amylase and tumor necrosis factor-α (TNF-α).We detected content of malondialdehyde (MDA),superoxide dismutase (SOD),glutathione (GSH) and activity of xanthine oxidase (XO) in gut mucosa.We detected the casepase-3 activity and cell apopotosis by means of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in gut mucosa,and conculated the apopotosis index (AI).Then using the PASW 18.0 software,we analyzed the data by anova and t-test,to make sure if the values were statistically different between the two groups and the mechanism of gut barrier dysfunction in panreatitis.Results At 4 h and 8 h after operation,the SAP-group-mice had significantly higher pancreas pathological score (P ＜0.01 ),blood amylase value ( P ＜ 0.05 ),gut pathological score and blood DAO and TNF-α value ( P ＜0.01 ),compared with the contral-group-mice.The gut mucosa MDA content and XO activity of mice in SAP group were significantly higher than which in control group ( P ＜ 0.01 ). The SAP-group-mice had significantly lower gut mucosa SOD content ( P ＜ 0.01 ) and GSH content ( P ＜ 0.05 ),compared with the contral-group-mice.The gut mucosa cells of mice in SAP group had significantly higher caspase-3 activity and apoptosis index than which in control group ( P ＜ 0.01 ).Conclusions In severe acute pancreatitis,inflammatory factors such as TNF-αwere waterfall-style released,induced gut mucosa suffer from ischemia-reperfusion injury,then serious oxidative stress developed in mucosa and activated caspase-3 pathway,inducing gut mucosa cells apoptose seriously,which was an important mechanism of gut barrier dysfunction.
ABSTRACT
Objective:To investigate gut barrier dysfunction and bacterial translocation (BT) in patients who underwent digestive tract reconstruction and to study the relationship between BT and acute systemic inflammatory state (SIRS). Method： Sixty patients who underwent selective digestive tract reconstruction were observed. Blood were collected before surgery and 1, 3, 5 days after surgery to detect plasma diamine oxidase(DAO) and bacterial DNA. PCR analysis was performed with β-Galactosidase gene of Eschenchia coli and 16SrRNA gene as target gene. The SIRS of all the patients were observed for 10 days. Result：All the PCR results before operation were negative, while there was positive in 14 patients after digestive tract reconstruction. There were 23 patients with SIRS after surgery, and 12 patients PCR result were positive among 23 patients with SIRS. 85.7% of the patients(12/14) with positive PCR result had SIRS, while 23.9% patients (11/46) with negative PCR result had SIRS (P<0.01).The positive PCR rate in SIRS was 52.2% (12/23), which was remarkably higher than that without SIRS(5.4%, 2/37, P<0.01).The levels of plasma DAO in patients with positive PCR result was significantly higher than those of the patients with negative PCR result (P<0.01). The levels of plasma DAO in patients with SIRS was significantly higher than those of patients without SIRS (P<0.01). Conclusion:The gut barrier dysfunction was closely related to BT, and BT was closely related to postoperative SIRS. PCR analysis can be used in early diagnosis of BT, the positive PCR result might be a useful early warning sign of postoperative SIRS.
ABSTRACT
In recent years,some investigations show that gut barrier dysfunction induced by severe acute pancreatitis was an important factor to determine the prognosis. Consequently, pathogenesis, monitoring standard was and treament of pancreatitis associated gut barrier dysfunction are becoming hot spots.