Mitochondrial uncoupler BAM15 inhibits artery constriction and potently activates AMPK in vascular smooth muscle cells

Our previous studies found that mitochondrial uncouplers CCCP and niclosamide inhibited artery constriction and the mechanism involved AMPK activation in vascular smooth muscle cells. BAM15 is a novel type of mitochondrial uncoupler. The aim of the present study is to identify the vasoactivity of BAM15 and characterize the BAM15-induced AMPK activation in vascular smooth muscle cells (A10 cells). BAM15 relaxed phenylephrine (PE)-induced constricted rat mesenteric arteries with intact and denuded endothelium. Pretreatment with BAM15 inhibited PE-induced constriction of rat mesenteric arteries with intact and denuded endothelium. BAM15, CCCP, and niclosamide had the comparable IC value of vasorelaxation in PE-induced constriction of rat mesenteric arteries. BAM15 was less cytotoxic in A10 cells compared with CCCP and niclosamide. BAM15 depolarized mitochondrial membrane potential, induced mitochondrial fission, increased mitochondrial ROS production, and increased mitochondrial oxygen consumption rate in A10 cells. BAM15 potently activated AMPK in A10 cells and the efficacy of BAM15 was stronger than that of CCCP, niclosamide, and AMPK positive activators metformin and AICAR. In conclusion, BAM15 activates AMPK in vascular smooth muscle cells with higher potency than that of CCCP, niclosamide and the known AMPK activators metformin and AICAR. The present work indicates that BAM15 is a potent AMPK activator.

Roles of aquaporin 4 in intracerebral hemorrhage / 国际脑血管病杂志

Aquaporin 4 (AQP4) is the most abundant aquaporin type in the brain.It is mainly expressed in the perivascular end feet of astrocytes.A large number of studies have shown that AQP4 is involved in the formation and elimination of brain edema in intracerebral hemorrhage,and plays important roles in the maintenance of the integrity of blood-brain barrier,secondary neuroinflammation,and apoptosis after intracerebral hemorrhage.More and more studies focus on the roles and mechanisms of AQP4 in intracerebral hemorrhage,however,the results are not completely consistent.This article reviews the roles and mechanisms of AQP4 in intracerebral hemorrhage

Causes analysis of 652 hospital stays in patients with autosomal dominant polycystic kidney disease / 中华肾脏病杂志

Objective To analyze the causes of 652 hospitalizations in the patients with autosomal dominant polycystic kidney disease (ADPKD).Methods The medical records of all ADPKD inpatients in our hospital from January 1,1990 to December 31,2010 were collected.The differences of hospitalization causes in different age,gender and period were analyzed.Results (1)In 652 hospitalizations,the most common cause was lumbar pain (15.2％),followed by cystic bleeding (14.6％),aggravating renal failure (10.1％),dialysis-related problems (9.4％),renal transplant related issues (8.3％),renal replacement therapy for ESRD (8.0％),urinary tract infection (6.4％),end stage renal failure (5.8％),hypertension (4.1％),renal cyst volume enlargement (3.7％),finding polycystic kidney disease (2.1％),urinary lithiasis (1.8％) and others (10.4％).(2)Younger patients were admitted into hospital because of polycystic kidney bleeding and finding PKD.With the increase of patients age,hospitalization due to dialysis-related problems increased,while many middle-aged patients were hospitalized because of back pain.(3)Male patients were admitted into hospital for aggravating renal failure,ESRD,kidney transplantation-related problems and urinary lithiasis,while female patients mainly for lumbar pain,dialysis-related problems and urinary tract infection.(4)The proportion was significantly reduced with time of finding PKD,renal failure and polycystic kidney bleeding,the proportion of renal cysts increasing and aggravating renal failure increased,there was a significant increase in the proportion of patients with hypertension,while a significant decrease in the proportion of patients with uncontrolled hypertension,and the average SBP was also significantly reduced.Conclusions The highest rate of hospitalization of ADPKD patients is in 40 to 60 age group.Cause of admission varies with age and gender,and changes with the change of time.Over the past decade,the proportion of hospitalization due to renal cysts enlargement and renal failure aggravation increased significantly.The incidence of hypertension is higher than that in the first 10 years,but hypertension control rate increases compared with the previous.Prevention should focus on finding the suppression measures of renal cysts enlargement.

Clinical analysis of 43 episodes of cyst infection in autosomal dominant polycystic kidney disease / 中华肾脏病杂志

Objective To summarize the clinical characteristics and outcome of renal cyst infection in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods Clinical data of 40 ADPKD patients with 43 episodes of renal cyst infection admitted in Shanghai Changzheng Hospital from 1st January 1991 to 31st December 2010 were retrospectively analyzed.Differences of microbiological data and treatments between 1st January 1991 to 31st December 2000 and 1st January 2001 to 31st December 2010 were compared. Results Among 473 identified patients with ADPKD and 662 episodes of hospitalization,40 patients had 43 episodes of renal cyst infection,including 8 definite and 35 likely cases.Microbiological documentation was available for 34 episodes (79.0％),Escherichia coli accounting for 82.4％ of all retrieved bacterial strains.Resistant Escherichia coli to quinolone and certain β-lactamine increased in recent decade.Clinical efficacy of initial antibiotic treatment was noted in 69.8％ of episodes. Antibiotic treatment modification was more frequently required for patients receiving initial monotherapy compared with those receiving combination therapy.In the first ten-year group,initial combination therapy and clinical efficacy were noted in 30.0％ and 60.0％ of episodes respectively,and hospital stay was (20.2±6.7) d.In the second ten-year group,initial combination therapy and clinical efficacy were noted in 61.9％ and 78.2％ of episodes respectively,and hospital stay was (16.3±3.2) d.Large infected cysts (diameter ＞5 cm) frequently required drainage. Conclusions In renal cyst infection,the source of the organisms is often a gram negative enteric organism.Empiric therapy is often initiated with two antibiotics.The drainage of large infected cysts remains the main treatment for cyst infection.