Success rate and cannulation time between precut sphincterotomy and double-guidewire technique in truly difficult biliary cannulation

Background and Aim: Precut sphincterotomy (PS) is usually indicated in failed standard biliary cannulation (BC). PS requires experienced endoscopists, and contains significant risk. Double‐guidewire (DG) cannulation seems to be easier, and might be useful after failed standard BC. We aimed to compare cannulation time, success rate, and complication rates between the two techniques. Methods: Patients who failed standard BC within 10 min by the expert were defined as truly difficult BC and randomized into both groups. In the DG group, the first guidewire was left in the pancreatic duct, and then a catheter, pre‐inserted with another guidewire, was used for the BC. In the PS group, a fistulotomy technique was used. Results: From June 2008 to October 2009, 534 patients underwent endoscopic retrograde cholangiopancreatography. Forty‐four patients (8.2%) who failed standard BC were randomized into the DG group (n = 23) and the PS group (n = 21). Median cannulation times and success rates in the DG and PS groups were 172 versus 394 s (P < 0.001), and 73.9% versus 80.9% (P = 0.724), respectively. The pancreatitis rate and serum amylase at 24 h in the DG and PS groups were 21.7% versus 14.3% (P = 0.701) and 937 versus 195 mg/dL (P = 0.020), respectively. Two from each group developed mild bleeding. No perforation occurred. Conclusion: In truly difficult BC, the DG technique requires a significant shorter duration for BC, with a comparable success rate to the PS technique. The post‐procedure serum amylase level in the DG group was significantly higher, and there was a trend of more pancreatitis.     

Outcome of second interventions for occluded metallic stents in patients with malignant biliary obstruction

Background  

Although self-expandable metallic stent (SEMS) has a longer patency than plastic stent (PS) for malignant biliary obstruction, stent occlusion can occur and drainage has to be reestablished in a patient with expected long survival. However, the choices are still controversial among restenting with SEMS, PS, and percutaneous transhepatic biliary drainage (PTBD). This study was designed to determine the efficacy and outcome of PS, SEMS, and PTBD for patients with occluded SEMS.     

Management of an occluded biliary metallic stent

In patients with a malignant biliary obstruction who require biliary drainage,a self-expandable metallic stent(SEMS) provides longer patency duration than a plastic stent(PS).Nevertheless,a stent occlusion by tumor ingrowth,tumor overgrowth and biliary sludge may develop.There are several methods to manage occluded SEMS.Endoscopic management is the preferred treatment,whereas percutaneous intervention is an alternative approach.Endoscopic treatment involves mechanical cleaning with a balloon and a second stent insertion as stent-in-stent with either PS or SEMS.Technical feasibility,patient survival and cost-effectiveness are important factors that determine the method of re-drainage and stent selection.     

Permeability of plumbagin across human intestinal cell in vitro

Plumbagin is the active compound isolated from plants used in traditional medicine for treatment of various diseases such as activities malaria, leishmaniasis, viral infections and cancers. The aim of the study was to investigate the permeability of plumbagin across Caco-2 (human epithelial colorectal adenocarcinoma) cell monolayer and its effects on the expression and function of P-glycoprotein. The integrity of Caco-2 cell monolayer was evaluated by measuring trans-epithelial electrical resistance and permeation (P_app) of Lucifer yellow across the cell monolayer. The effect of plumbagin on P-glycoprotein was detected by measuring its interference with the transport of the P-glycoprotein substrate (R123) and the effect on MDR-1 mRNA expression was detected by RT-PCR. The P_app of plumbagin (2–8 µM) for the apical to basolateral and basolateral to apical directions were 10.29–15.96 × 10^?6 and 7.40–9.02 × 10^?6 cm/s, respectively, with the efflux ratios of 0.57–0.73. Plumbagin is not either a substrate or inhibitor of P-glycoprotein. It did not interfere with the P-glycoprotein-mediated R123 transport across Caco-2 cell monolayer, as well as the function of P-glycoprotein and the expression of MDR-1 mRNA. Results suggest moderate permeability of plumbagin across the Caco-2 cell monolayer in both directions. The transport mechanism is likely to be a passive transport.     

Antinociceptive activity of the methanolic extract of Kaempferia galanga Linn. in experimental animals

Kaempferia galanga Linn. (Zingiberaceae) presents many chemical constituents of the volatile oil extracted from the rhizome. The rhizome of Kaempferia galanga is used by people in many regions for relieving toothache, abdominal pain, muscular swelling and rheumatism. In this study we investigated the antinociceptive activity in mice and rats using acetic acid-induced writhing, formalin, hot plate and tail-flick tests. The extract at test doses of 50, 100 and 200 mg/kg, p.o. clearly demonstrated antinociceptive activity in all tests. This activity was dose- and time-dependent. The extract administered at 200 mg/kg, p.o. had a stronger antinociceptive effect than aspirin (100 mg/kg, p.o.) but less than morphine (5 mg/kg, s.c.). Naloxone (2 mg/kg, i.p.) abolished the antinociceptive action of both morphine (5 mg/kg, s.c.) and the extract (200 mg/kg, p.o.) in a similar manner. In conclusion, the methanol extract of Kaempferia galanga markedly demonstrated the antinociceptive action in experimental animals. The antinociceptive mechanisms appear to be both peripherally and centrally mediated actions and the opioid receptors are probably involved. Therefore, our studies support the use in traditional medicine of Kaempferia galanga against pain caused by various disorders.     

Ketoconazole increases plasma concentrations of antimalarial mefloquine in healthy human volunteers

BACKGROUND: Antimalarial mefloquine has a structure related to quinine. The major metabolite of quinine is 3-hydroxyquinine formed by cytochrome P450 3A4 (CYP3A4). Ketoconazole, a potent inhibitor of CYP3A4, is known to markedly increase plasma concentrations of various co-administered drugs including quinine. OBJECTIVE: To assess the effect of ketoconazole on plasma concentrations of mefloquine in healthy Thai male volunteers. METHODS: In an open, randomized two-phase crossover study separated by a 1-month period, eight healthy Thai male volunteers received a single oral dose of 500 mg mefloquine alone or co-administration with 400 mg/day ketoconazole orally for 10 days. Serial blood samples were collected at specific time points for a 56-day period. Plasma mefloquine and mefloquine carboxylic metabolite concentrations during 56 days were measured by a modified and validated high-performance liquid chromatographic method with UV detection. RESULTS: Co-administration with ketoconazole markedly increased the mean values of mefloquine AUC0-t, t(1/2), and Cmax when compared with mefloquine alone by 79% (P < 0.001), 39% (P < 0.05) and 64% (P < 0.001) respectively. The AUC0-t , and Cmax of mefloquine carboxylic acid metabolite were decreased by 28% (P < 0.05) and 31% (P < 0.05), respectively when compared with mefloquine alone. CONCLUSIONS: Co-administration with ketoconazole increased plasma mefloquine concentrations in healthy human volunteers. One of possible mechanisms of the increase in plasma mefloquine concentrations may be the result of the inhibition of CYP3A4 by ketoconazole. In case of mefloquine is co-administered with ketoconazole, drug-drug interactions should be recognized and the dose of mefloquine should be adjusted to maximize the therapeutic efficacy and to reduce the cost of therapy.