Using cholecystokinin to facilitate endoscopic clearance of large common bile duct stones

AIM:To evaluate the effect of cholecystokinin(CCK)during extracorporeal shockwave lithotripsy(ESWL)in the clearance of common bile duct(CBD)stones in endoscopic retrograde cholangiopancreatography(ERCP).METHODS:Between January 2007 and September2012,patients with large CBD stones who were treated with ESWL and ERCP were identified retrospectively.Patients were randomized in equal numbers to cholecystokinin(CCK)and no CCK groups.For each CCK case,a dose(3 ng/kg per min for 10 min)of sulfated octapeptide of CCK-8 was administered intravenously near the beginning of ESWL.ERCP was performed 4 h after a session of ESWL.The clearance rate of the CBD was assessed between the two groups.RESULTS:A total of 148 consecutive cases(CCK group:74,no CCK group:74)were tallied.Overall there were 234 ESWLs and 228 ERCPs in the 148 cases.The use of CCK showed a significantly higher rate of successful stone removal in the first ESWL/ERCP procedure(71.6%vs 55.4%,P=0.035),but resulted in similar outcomes in the second(42.8%vs 39.4%)and third(41.7%vs 40.0%)sessions,as well as total stone clearance(90.5%vs 83.8%).The use of mechanical lithotripsy was reduced in the CCK group(6.8%vs17.6%,P=0.023),and extremely large stone(≥30mm)removal was higher in the CCK group(72.7%vs41.7%,P=0.038).CONCLUSION:CCK during ESWL can aid with the clearance of CBD stones in the first ESWL/ERCP session.Mechanical lithotripsy usage was reduced and the extremely large stone(≥30 mm)clearance rate can be raised.

Outcome of a session of extracorporeal shock wave lithotripsy before endoscopic retrograde cholangiopancreatography for problematic and large common bile duct stones

AIM To compare the efficacy of a session of extracorporeal shock wave lithotripsy(ESWL) before endoscopic retrograde cholangiopancreatography(ERCP) vs ERCP only for problematic and large common bile duct(CBD) stones.METHODS Adult patients with CBD stones for whom initial ERCP was unsuccessful because of the large size of CBD stones were identified. The patients were randomized into two groups,an "ESWL + ERCP group" and an "ERCP-only" group. For ESWL + ERCP cases,ESWL was performed prior to ERCP. Clearance of the CBD,complications related to the ESWL/ERCP procedure,frequency of mechanical lithotripsy use and duration of the ERCP procedure were evaluated in both groups.RESULTS There was no significant difference in baseline characteristics between the two groups. A session of ESWL before ERCP compared with ERCP only resulted in similar outcomes in terms of successful stone removal within the first treatment session(74.2% vs 71.0%,P = 0.135),but a higher clearance rate within the second treatment session(84.4% vs 51.6%,P = 0.018) and total stone clearance(96.0% vs 86.0%,P = 0.029). Moreover,ESWL prior to ERCP not only reduced ERCP procedure time(43 ± 21 min vs 59 ± 28 min,P = 0.034) and the rate of mechanical lithotripsy use(20% vs 30%,P = 0.025),but also raised the clearance rate of extremely large stones(80.0% vs 40.0%,P = 0.016). Post-ERCP complications were similar for the two groups.CONCLUSION Based on the higher rate of successful stone removal and minimal complications,ESWL prior to ERCP appears to be a safe and effective treatment for the endoscopic removal of problematic and large CBD stones.

Losartan improves erectile function through suppression of corporal apoptosis and oxidative stress in rats with cavernous nerve injury

This study aimed to investigate the functional and morphological changes in the corpus cavernosum after cavernous nerve(CN)injury or neurectomy and then reveal whether treatment with the angiotensin II Type 1 receptor antagonist losartan would improve erectile function as well as its potential mechanisms.A total of 48 10-week-old Sprague-Dawley male rats,weighing 300-350 g,were randomly divided into the following four groups(n=12 per group):sham operation(Sham)group,bilateral cavernous nerve injury(BOND group,losartaretreated BCNI(BCNI+Losartan)group,and bilateral cavernous neurectomy(Neurectomy)group.Losartan was administered once daily by oral gavage at a dose of 30 mg kg^-1 day^-1 for 4 weeks starting on the day of surgery.The BCNI and the Neurectomy groups exhibited decreases in erectile response and increases in apoptosis and oxidative stress,compared with the Sham group.Treatment with losartan could have a modest effect on erectile function and significantly prevent corporal apoptosis and oxidative stress?The phospho-B-cell lymphoma 2(Bcl-2)-associated death promoter(p-Bad)/Bad and phospho-the protein kinase B(p-AKT)/AKT ratios were substantially lower,while the Bcl-2-associated X protein(Bax)/Bcl-2 ratio,nuclear factor erythroid 2-related factor 2(Nrf2)/Kelch-like ECH-associated protein 1(Keap-1),transforming growth factor-p 1(TGF-pi)and heme oxygenase-1(HO-1)levels,and caspase-3 activity were higher in the BCNI and Neurectomy groups than in the Sham group.After 4 weeks of daily administration with losartan,these expression levels were remarkably attenuated compared with the BCNI group.Taken together,our results suggested that early administration of losartan after CN injury could slightly improve erectile function and significantly reduce corporal apoptosis and oxidative stress by inhibiting the Akt/Bad/Bax/caspase-3 and Nrf2/Keap-1 pathways.

Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson＇s Disease in Han Chinese

Background： Mitochondrial dysflmction is linked to the pathogenesis of Parkinson＇s disease （PD）. However, the precise role of mitochondrial DNA （mtDNA） variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among differeni population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population. Methods： Nine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups （A, B, C, D, F, G）, were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Hart population. Results： Overall, the distribution ofmtDNA haplogroups did not show any significant differences between patients and controls. However, alter stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD （EOPD） compared to the controls （odds ratio [OR] =0.225, 95% confidence interval [CI]： 0.082-0.619, P 0.004）, while other haplogroups did not show significant differences. Alter stratification by age at examination, among subjects younger than 50 years of age： Haplogroup B also showed a lower frequency in PD cases （OR = 0. 146, 95% CI： 0.030-0.715~ P = 0.018） while haplogroup D presented a higher risk of PD （OR - 3.579, 95% CI： 1. 112-11.523, P = 0.033）, other haplogroups also did not show significant differences in the group. Conclusions： Our study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese, while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age. In brief particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Hart Chinese.

Prostate-derived IL-1βupregulates expression of NMDA receptor in the paraventricular nucleus and shortens ejaculation latency in rats with experimental autoimmune prostatitis

Experimental autoimmune prostatitis(EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid(NMDA)receptors in the paraventricular nucleus(PVN).However,the mechanism has not yet been elucidated.Herein,we screened out the target prostate-derived inflammation cytokines(PDICs)by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid(CSF)between EAP rats and their controls.After identifying the target PDIC,qualified males in initial copulatory behavior testing(CBT)were subjected to implanting tubes onto bilateral PVN.Next,they were randomly divided into four subgroups(EAP-1,EAP-2,Control-1,and Control-2).After 1-week recovery,EAP-1 rats were microinjected with the target PDIC inhibitor,Control-1 rats were microinjected with the target PDIC,while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF(aCSF).Results showed that only interleukin-1β(IL-1β)had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls(P<0.001)and significantly higher protein concentrations in both the serum(P=0.001)and CSF(P<0.001)of the EAP groups compared to the Control groups.Therefore,IL-1βwas identified as the target PDIC which crosses the blood-brain barrier,thereby influencing the central nervous system.Moreover,the EAP-1 subgroup displayed a gradually prolonged ejaculation latency(EL)in the last three CBTs(all P<0.01)and a significantly lower expression of NMDA NR1 subunit in the PVN(P=0.043)compared to the respective control groups after a 10-day central administration of IL-1βinhibitors.However,the Control-1 subgroup showed a gradually shortened EL(P<0.01)and a significantly higher NR1 expression(P=0.004)after homochronous IL-1βadministration.Therefore,we identified IL-1βas the primary PDIC which shortens EL in EAP rats.However,further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1βupregulates NMDA expression.