Influence of dehydrocholate and taurocholate on bromsulphthalein uptake, storage, and excretion in the dog.
(1/23)
The influence of dehydrocholate on bromsulphtalein relative-storage capacity, bilary transport maximum (Tm), and fractional transfer rates between plasma, liver and bile have been studied in unanaesthetized dogs. In six dogs, storage capacity, Tm, and fractional transfer rates from plasma to liver, liver to bile, and liver to plasma were measured during 0-15 M NaCL infusion and the measurements were repeated under a dehydrocholate infusion of 95 mumol. min-1, ie, an infusion rate approaching the known biliary Tm of bile salts. It was found that: (a) storage capacity and fractional transfer rates from plasma to liver significantly lower during dehydrocholate infusions (respectively 18-0 plus or minus SD 9-0 mg-mg-1. 100 ml-1 and 0-120 plus or minus SD 0-035 min-1) than during NaCL infusions (respectively 47-0 plus or minus 21-0 mg. mg-1. 100 ml-1 and 0-280 plus or minus SD 0-055 min-1; P smaller than 0-001); (b) Tm and fractional transfer rates from liver to bile were also significantly lower during dehydrocholate infusion (respectively 3-2 plus or minus SD 1-1 mg. min-1 and 0-013 plus or minus SD 0-004 min-1) than during NaCl infusion (4-8 plus or minus SD 1-1 mg. min-1 and 0-033 plus or minus SD 0-017 min-1; P smaller than 0-02); (c) in three additional experiments, taurocholate had similar effects on storage capacity and Tm. These findings suggest that competition occurred between bile salts and bromsulphthalein for hepaticuptake and storage. They support the hypothesis that the decreased disappearance rate and relative storage capacity of bromsulphtalein observed during biliary obstruction may be due to competition between bile salts and bromsulphthalein for hepatic uptake and storage. (+info)
Glucose reabsorption from bile. Evidence for a biliohepatic circulation.
(2/23)
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)
Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex.
(3/23)
Perturbations in the integrity of the blood-brain barrier have been reported in both humans and animals under numerous pathological conditions. Although the blood-brain barrier prevents the penetration of many blood constituents into the brain extracellular space, the effect of such perturbations on the brain function and their roles in the pathogenesis of cortical diseases are unknown. In this study we established a model for focal disruption of the blood-brain barrier in the rat cortex by direct application of bile salts. Exposure of the cerebral cortex in vivo to bile salts resulted in long-lasting extravasation of serum albumin to the brain extracellular space and was associated with a prominent activation of astrocytes with no inflammatory response or marked cell loss. Using electrophysiological recordings in brain slices we found that a focus of epileptiform discharges developed within 4-7 d after treatment and could be recorded up to 49 d postoperatively in >60% of slices from treated animals but only rarely (10%) in sham-operated controls. Epileptiform activity involved both glutamatergic and GABAergic neurotransmission. Epileptiform activity was also induced by direct cortical application of native serum, denatured serum, or albumin-containing solution. In contrast, perfusion with serum-adapted electrolyte solution did not induce abnormal activity, thereby suggesting that the exposure of the serum-devoid brain environment to serum proteins underlies epileptogenesis in the blood-brain barrier-disrupted cortex. Although many neuropathologies entail a compromised blood-brain barrier, this is the first direct evidence that it may have a role in the pathogenesis of focal cortical epilepsy, a common neurological disease. (+info)
Roles of the outer membrane protein AsmA of Salmonella enterica in the control of marRAB expression and invasion of epithelial cells.
(4/23)
Surgical outcome in relation to duct size at the porta hepatis and the use of cholagogues in patients with biliary atresia.
(5/23)
BACKGROUND: Small ductules communicating with the bile ducts have been described at the porta hepatis in extrahepatic biliary atresia (EHBA) and these form the basis for hepatic portoenterostomy. The use of cholagogues like dehydrocholic acid (DHC) and ursodeoxycholic acid (UDCA) to enhance bile flow postoperatively has been reported. AIMS: This communication describes our experience with the use of cholagogues following surgery in EHBA and attempts to correlate the outcomes with the diameter of the ductules. MATERIAL AND METHODS: Fifty five EHBA patients treated by the Kasai procedure form the basis of this study; 35 patients treated during 1979-1986 and administered DHC (3-5 mg/kg) postoperatively and 20 patients treated during 1999-2002 and administered UDCA (15 mg/kg) postoperatively. The diameter of ductules was measured using an optical micrometer on 5 microm serial sections; the ducts were classified as type I (no demonstrable ducts, n = 14), type II (< 50 microm, n=22) and type III (> 50 microm, n = 19). The clinical outcome was categorized as 1 (jaundice free survival at 5 years follow-up, n = 7), 2 (initial good response but deteriorated after one year, n = 27) and 3 (expired within one year following surgery, n = 21). The response to surgery was monitored using biochemical liver function tests (LFT), hepatobiliary scintigraphy (HIDA scan) and occurrence of cholangitis. RESULTS: Age did not affect the size of ducts in both DHC and UDCA groups but patients in the DHC group were older than those treated with UDCA (mean age DHC: 105.22 +/- 33.53 days, UDCA: 74.68 +/- 23.73 days; p = 0.009). There was no statistically significant difference between duct size and postoperative LFT in both groups (DHC p = 0.1, UDCA p = 0.5). Bile excretion on HIDA scan was significantly better with larger ducts (DHC p = 0.003, UDCA p = 0.025); overall UDCA showed significantly better bile excretion (p = 0.003) but this was not reflected in the surgical outcome. There was no significant difference in the surgical outcome of those treated with DHC or UDCA but a significantly higher incidence of cholangitis was seen with smaller ducts in the UDCA group (p = 0.02). CONCLUSIONS: There was no correlation between duct diameter and postoperative LFT but type III ducts were associated with better bile flow on HIDA scan. Cholangitis was seen more often with type I and II ducts in both DHC and UDCA groups. UDCA administration seemed to be beneficial in patients with type III ducts in increasing bile flow and reducing cholangitis. (+info)
Ursodeoxycholic acid is conjugated with taurine to promote secretin-stimulated biliary hydrocholeresis in the normal rat.
(6/23)
Studies on the origin of biliary phospholipid. Effect of dehydrocholic acid and cholic acid infusions on hepatic and biliary phospholipids.
(7/23)
The correlation between the secretion of biliary phospholipid (PL) and bile acid suggests a regulatory effect of bile acid on PL secretion. Bile acids may influence PL synthesis and/or the mobilization of a preformed PL pool. The objective of this study was to determine the contribution of these two sources to biliary PL, by using an experimental protocol in which dehydrocholic acid (DHCA) and cholic acid (CA) were infused to manipulate biliary PL secretion. In control rats, there was a steady state in bile flow. PL secretion and the biliary secretion of newly synthesized phosphatidylcholine (PC). The specific radioactivity of PC in bile was significantly higher than in plasma, microsomes and canalicular membranes. DHCA infusion decreased biliary PC secretion rate by 80%, and secretion returned to normal values at the transport maximum of CA. The specific radioactivity of biliary PC was decreased by 30% by DHCA infusion and reached normal values during CA infusion. There were no significant changes in the specific radioactivity of PC in plasma or cellular organelles during infusion of bile acids. These data indicate that: (1) newly synthesized PC contributes a small percentage to biliary PC; thus a preformed pool (microsomal and extrahepatic) is a major source of biliary PL; (2) the contribution of the extrahepatic pool to the biliary PL may be more important than the microsomal pool. (+info)
Further studies on the inhibition of pepsin by bile salts.
(8/23)
A higher incidence of peptic ulceration has been reported in patients recovering from operations that divert bile from the duodenum. Previous studies have shown that hydroxylated bile salts inhibit the proteolytic activity of pepsin, an integral agent in the production of peptic ulcer. In this study, the pepsin inhibitory activity of 16 bile salts (6 unconjugated, 5 glycoconjugated, and 5 tauroconjugated bile salts), including bile salts with no hydroxyl groups, was tested in vitro. All bile salts inhibited pepsin proteolytic activity and the degree of pepsin inhibition increased in proportion to their concentrations. The range of maximal inhibition was 90-73% for unconjugated bile salts; 74-35% for glycoconjugated bile salts; and 71-46% for tauroconjugated bile salts. These findings support the need for clinical studies to evaluate administration of bile acids to bile-diverted patients. (+info)