Influence of octapeptide of cholecystokinin, vasoactive intestinal peptide and substance P on dynamics of biliary system and cardiovascular system.
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OBJECTIVE: To examine the effects of cholecystokinin octapeptide (CCK-OP), vasoactive intestinal peptide (VIP) and substance P (SP) on the dynamics of the biliary system and cardiovascular system, and the relationship between the dynamics of the biliary system and cardiodynamics. METHODS: In 91 anesthetized guinea pigs, a triple-lumen, side-hole perfusion catheter (1.0 mmOD) was inserted through the duodenal papilla into the common bile duct (CBD) and the sphincter of Oddi (OS). An end-hole PE-50 catheter was inserted into the left ventricle of heart through the left jugular artery. The left ventricle of heart motility, OS motility and CBD pressure were recorded during the intravenous administration of CCK-OP, VIP, SP and the combination of CCK-OP and VIP. RESULTS: Intravenous CCK-OP increased the fasted OS motility index (MI), decreased the basal pressure in OS, increased CBD pressure, and inhibited the motility of the left ventricle of heart. VIP alone showed no significant effect on the biliary system and cardiovascular system, but when infused together with CCK-OP, it inhibited the effects of CCK-OP on both systems. Exogenous SP acted like CCK-OP on both biliary system and cardiovascular system, but less potently. CONCLUSIONS: The gastrointestinal peptides have important effects on both biliary system and cardiovascular system. There is an important negative correlation between CBD pressure and the motility of the left ventricle of the heart during the infusion of peptides. (+info)
Non-invasive management of Ascaris lumbricoides biliary tact migration: a prospective study in 69 patients from Ecuador.
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Ascariasis is one of the most common helminthic diseases. Its most feared complication is migration into the biliary tree. Some authors recommend immediate duodenoscopy in all cases of biliary migration, with sphincterotomy for the extraction of the parasites, and surgical extraction in case of intrahepatic ascariasis. We followed prospectively 69 patients with ultrasonographical evidence of migration. Initial treatment consisted of intravenous analgesics and antispasmodics, and albendazole 800 mg by mouth. Only patients with persisting symptoms or with high amylasaemia underwent duodenoscopy, with extraction in case of a visible worm. Surgery was limited to cases with persistent or progressive complications. In 97% of our cases the worms disappeared with noninvasive therapy alone. A duodenoscopy was done in 30 (42%) cases; in 10 (14%) a worm was found in the ampulla of Vater and extracted without sphincterotomy. In none of the 6 cases with A. lumbricoides in the intrahepatic biliary tree did the parasite persist. Only one patient required surgical intervention. Treatment of A. lumbricoides migration to the biliary tract should be principally medical. Duodenoscopy with extraction of a visible worm should be limited to cases with persisting pain and/or hyperamylasaemia. Invasive methods like sphincterotomy and surgery should be restricted to patients who do not respond to conservative treatment. (+info)
Multidrug resistance p-glycoprotein 2 is essential for the biliary excretion of indocyanine green.
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Multidrug resistance P-glycoprotein 2 (Mdr2) is a phospholipid translocator in the canalicular membrane that is essential for the formation of biliary phospholipid vesicles and mixed lipid/bile salt micelles. Incorporation into biliary vesicles and micelles is thought to contribute to the hepatobiliary excretion of certain hydrophobic organic anions, such as indocyanine green (ICG). The present studies characterized the biliary excretion of two hydrophobic organic anions, ICG and estradiol-17beta(beta-D-glucuronide) (E(2)17G), in the single-pass isolated perfused liver and the biliary excretion of glutathione (GSH) in vivo in wild-type and Mdr2-/- female mice. The biliary excretion of ICG (0.4 micromol) was reduced by 90%, while the biliary excretion of total GSH was decreased by 65% in Mdr2-/- mice relative to wild-type mice. In contrast, the biliary excretion of E(2)17G (0.1 micromol) was increased by 30% in Mdr2-/- mice. These data indicate that the absence of Mdr2 differentially influences the biliary excretion of these organic anions and suggest that phospholipid vesicles and mixed micelles in bile are essential for the biliary excretion of ICG. (+info)
Hepatic portoenterostomy: an assessment of its value in the treatment of biliary atresia.
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A series of 12 infants undergoing hepatic portoenterostomy for incorrectable-type biliary atresia is reviewed. There has been no evidence of a sustained postoperative increase in bile excretion or improvement in biliary cirrhosis in any patient. Survival statistics for the group as a whole are poor with a mean postop survival time of 11 months and a mean total survival time of 15.3 months. These survival times are worse than that previously reported for infants with untreated biliary atresia. Our disappointing results with hepatic portoenterostomy raise doubts concerning its value in the treatment of biliary atresia. (+info)
Mrp2-deficiency in the rat impairs biliary and intestinal excretion and influences metabolism and disposition of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo.
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While metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant food-derived heterocyclic amine and carcinogen, has been studied extensively in several species, transport of this compound and its metabolites has not been defined yet. Therefore we studied metabolism and disposition of PhIP in Wistar and Mrp2-deficient TR(-) rats to determine the role of Mrp2 in the defence against this compound. In the first 2 h after intravenous dosing, total excretion of PhIP and its metabolites in bile was > 4-fold reduced in TR(-) rats compared with Wistar rats, while excretion in the urine of the TR(-) rat was 1.8-fold higher. This difference was the result of an almost complete absence of secretion of glucuronidated metabolites but also a reduced level of secretion of unchanged PhIP into bile of the TR(-) rat. Direct intestinal excretion of unmetabolized PhIP was 3-fold higher in Wistar versus TR(-) rats. As a consequence, PhIP tissue levels in the liver were 1.7-fold higher in TR(-) rats, and tissue binding of PhIP, determined after ethanol extraction, was elevated by a similar magnitude. Mrp2-mediated transport of the parent compound PhIP is glutathione (GSH)-dependent, because GSH depletion by L-buthionine-[S,R]-sulfoximine (BSO) treatment in Wistar rats reduced intestinal secretion to the same level as that in TR(-) rats. TR(-) rats produced less glucuronides and 4'-OH-PhIP in the 2 h following PhIP administration. We conclude that Mrp2 protects against the carcinogen PhIP by biliary excretion of the parent compound and all major phase-II metabolites, but, more importantly, also by direct extrusion of the parent compound from the gut mucosa. (+info)
Is preventive resection of the extrahepatic bile duct necessary in cases of pancreaticobiliary maljunction without dilatation of the bile duct?
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BACKGROUND: No consensus has been reached on whether preventive resection of the extrahepatic bile duct is necessary in cases of pancreaticobiliary maljunction (PBM) without dilatation of the extrahepatic bile duct (undilated type). METHODS: Sixty-eight patients with PBM underwent corrective surgery and several clinical characteristics and pathological findings including K-ras point mutation were evaluated. RESULTS: Unlike dilated bile duct, none of the patients with undilated type duct had clinical symptoms in early childhood. In patients with either cystic or spindle type duct, amylase levels in the bile duct were >10(4) U/l, whereas those in patients with undilated type duct were <10(4) U/l. Postoperative scintigraphy of the biliary system of undilated type revealed no evidence of cholestasis. After surgery, eight patients with undilated type duct, in whom the bile duct had been preserved, had no further clinical symptoms and no evidence of malignancy. Bile duct tissue specimens revealed no hyperplasia, dysplasia or cancerous lesions and they had no K-ras mutation in undilated type. CONCLUSION: The results showed that there was little bile stasis, injury to the mucosa was mild and less genetic changes could be seen in patients with undilated type duct. Therefore, in patients without dilatation of bile duct and advanced cancer, cholecystectomy alone is sufficient. (+info)
Glucose reabsorption from bile. Evidence for a biliohepatic circulation.
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Glucose is absent from human bile and present in low concentrations in bile from the rat. To study the mechanisms of this blood-bile glucose concentration difference, infusions of glucose were administered i.v. to 300-400 g male Sprague-Dawley rats with ligated renal pedicles and to two postcholecystectomy patients with indwelling t-tubes. Glucose was assayed in plasma, bile, and rat liver by a hexokinase method specific for D-glucose. In man, glucose was detected in bile when plasma glucose increased above 350 mg/100 ml. In animals studies, low concentrations of bile glucose were observed at plasma levels between 100 and 300 mg/100 ml. However, when plasma concentrations increased between 400 and 900 mg/100 ml, glucose appeared more rapidly in bile, defining by extrapolation an apparent plasma glucose threshold of 280 mg/100 ml. Intraportal phlorizin, a competitive inhibitor of glucose transport, significantly increased bile glucose concentrations. Plasma-bile concentration differences were also observed in rats after i.v. [3-14C]O-methyl glucose (3-O-MG) but not after [3H]mannitol. Hepatic glucose levels were never lower than plasma levels and liver-plasma 3-O-MG ratios were 0.92 +/- 0.22 indicating that entry of glucose and 3-O-MG into hepatocyte water was not limiting. Furthermore, when sodium dehydrocholate augmented canalicular secretion, biliary glucose excretion increased proportionally suggesting that glucose entry into bile was not impeded. When estimates of hepatic glucose secretion were compared with biliary glucose excretion, the latter increased progressively when estimated secretion rates exceeded 50 micrograms/min or when phlorizin was given. Finally, during bile stop-flow experiments, [3-14C]O-MG and [14C]glucose were selectively removed from bile compared with [3H]mannitol. The findings suggest that glucose and 3-O-MG are reabsorbed from bile after entry at the hepatocyte, accounting for their low bile-plasma ratio. The biliary glucose transport process may be described by Michaelis-Menten kinetics and is analogous to recently defined kinetics for renal tubular reabsorption of glucose. These studies provide evidence that certain products of bile secretion may undergo a "biliohepatic" circulation. (+info)
Inhibition of biliary excretion of methotrexate by probenecid in rats: quantitative prediction of interaction from in vitro data.
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This study was designed to establish a strategy to predict drug interactions involving biliary excretion. The interaction between methotrexate and probenecid was examined as an interaction model since this interaction has already been clinically reported. Coadministration of probenecid reduced the biliary clearance of methotrexate in a dose-dependent manner in rats. This inhibition by probenecid was confirmed in vivo both in the uptake and excretion processes of methotrexate across sinusoidal and canalicular membranes, respectively. That is, both hepatic uptake clearance, assessed in integration plot analysis, and steady-state biliary clearance defined with respect to hepatic unbound methotrexate, were reduced in the presence of probenecid. Probenecid inhibited the active transport of methotrexate both in isolated hepatocytes and canalicular membrane vesicles, confirming the interaction at those two membranes. The degree of inhibition of the uptake and excretion processes found in vivo was comparable with the predicted values using the inhibition constant assessed in isolated hepatocytes and canalicular membranes, respectively. This suggests that the interaction at each membrane transport process can be quantitatively estimated from in vitro data. We have also proposed the method to predict the degree of inhibition of the net excretion from circulating plasma into the bile, the predicted values being also comparable with the inhibition actually found in vivo. The present analysis demonstrates a strategic rationale for predicting drug interactions involving biliary excretion using in vitro systems to avoid any false negative predictions. (+info)