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B Combes

Publications and source records attributed to B Combes.

At least 37 records · Page 2Linked to original sources

Biliary excretion of infused conjugated sulfobromophthalein in sheep heterozygote for the transport defect present in mutant Corriedale sheep.

Biliary excretion of dye was measured in 2 clinically normal and 2 heterozygote Corriedale sheep (the mutant Corriedale is characterized by depressed biliary transport of conjugated sulfobromophthalein (SBP) compounds) during infusion of the preformed glutathione conjugate of SBP. Maximal rates of excretion of conjugated SBP compounds in bile were comparable in heterozygote Corriedale and clinically normal sheep. These 2 heterozygote sheep do not express the biliary transport defect observed in mutant Corriedale sheep during SBP-glutathione infusion.

Animals↗

Effect of diethyl maleate on the biliary excretion rate of infused sulfobromophthalein-glutathione.

Diethyl maleate (DEM) was given intraperitoneally to rats in a dose (4.3 mmoles/kg) known to markedly decrease glutathione levels in liver. DEM induced a choleresis previously shown to be due to the osmotic activity of DEM conjugates (DEM-glutathione and subsequent metabolic products) excreted into bile. Coincident with the choleresis, the biliary excretory Tm for the infused glutathione conjugate of sulfobromophthalein (BSP-GSH) was depressed significantly. The data are interpreted as indicating that DEM-GSH conjugates compete with BSP-GSH conjugates for a canalicular carrier mechanism.

Animals↗

A prospective trial of steroid therapy in severe viral hepatitis. The prognostic significance of bridging necrosis.

A prospective, double-blinded, randomized trial of corticosteroid therapy in patients with severe acute viral hepatitis has been conducted. At the same time, we have examined the prognostic significance of the presence of bridging necrosis in liver biopsies obtained from such patients as well as the predictive value of certain serologic markers. Forty-two of the 77 patients admitted to the trial were shown to have bridging necrosis on their initial biopsies. Two patients progressed to death with massive hepatic necrosis, while 5 patients developed chronic liver disease. A complicated course could not be predicted by the initial biopsy findings nor by any of the serologic markers assessed. We could not identify any clinical or epidemiologic features with prognostic impact. No advantage was demonstrated to be associated with the use of corticosteroids early in the course of severe viral hepatitis.

Adolescent↗

Beneficial effect of cholestyramine in sclerosing cholangitis.

Cholestyramine exerted a beneficial effect on the course of a patient with sclerosing cholangitis associated with ulcerative proctitis. Over a 6.5-yr period, discontinuation of cholestyramine resulted in episodes of RUQ pain and/or appearance of abnormalities in liver tests. Readministration of the resin was followed by disappearance of symptoms and normalization of test resuls. The mechanism of the beneficial effect of cholestyramine was not elucidated.

Adolescent↗

Apparent volume of the biliary tree in the dog.

The apparent volume of the biliary tree (ABV) in the dog was determined by measuring the mean biliary transit time of injected [14C]taurocholate ([14C]TC). After bolus injection of [14C]TC, entry of bile salt into the lumen of the biliary tree is signaled by an increase in bile flow. The volume of bile collected at the common duct from onset of choleresis until maximal concentration of 14C radioactivity is reached in bile minus the calculated quantity of bile that contains radioactivity and the cannula volume yields a value for the volume of the biliary tree present just prior to injection of [14C]TC. The mean value for ABV in 19 dogs was 2.49 +/- 0.65 microL/g liver (mean +/- SD).

Animals↗

Etiology of liver disease in renal-transplant patients.

The etiology of 72 episodes of liver disease that developed in 62 of 162 renal-transplant recipients was evaluated. Infection with hepatitis B virus was a minor problem, and none of our patients had evidence of infection with hepatitis A. Cytomegalovirus infection was ubiquitous in the population and probably accounted for many episodes of acute liver disease. This agent's role in causing chronic hepatitis is less secure. Infections with other viruses including Epstein-Barr virus, adenovirus, and the herpes viruses were only rarely associated with hepatic disease. Azathioprine was responsible for some episodes of acute cholestasis but could not be incriminated as a direct cause of chronic disease. A cause could be identified for the majority of episodes of acute hepatic dysfunction, but the cause of most of the chronic hepatitis remains undetermined. It is likely that infection with non-A, non-B hepatitis virus accounts for much of this serious, often fatal, complication of renal transplantation.

Antibodies, Viral↗

Urinary excretion of dye in dogs infused with BSP or its glutathione conjugate.

Renal clearance of BSP compounds was investigated in dogs during infusion of sulfobromophthalein (BSP) or its glutathione conjugate (BSP-GSH). Conjugated BSP compounds are more readily excreted into urine than unconjugated BSP. Dye clearance into urine was much less than simultaneously measured inulin clearance. This suggests that protein binding of BSP compounds significantly retards the glomerular filtration of the dye. BSP was found to bind more avidly to albumin than BSP-GSH. The ratio of dye clearance to inulin clearance remained relatively constant over a broad range of plasma concentrations of dye. The data support but do not prove glomerular filtration of non-protein-bound dye as the major mechanism accounting of urinary elimination of BSP compounds in the dog.

Animals↗

Erythritol and mannitol clearances with taurocholate and secretin-induced cholereses.

The biliary clearances of [14C]erythritol (Cery) and [3H]mannitol (Cmann) were measured simultaneously in dogs during cholereses induced by sodium taurocholate and by secretin. Cery increased equally with the increase in bile flow induced by taurocholate, whereas mannitol entry into bile was partially restricted; deltaCery/deltabile flow averaged 0.96; deltaCmann/deltaCery averaged 0.81. Values for erythritol clearance exceeded bile flow by a constant volume over a wide range of bile flows, a result that suggests distal reabsorption of a fixed amount of fluid, independent of canalicular bile production. During secretin-induced choleresis both Cery and Cmann accompanied 30-40% of the increase in bile flow, and the ratio of Cmann/Cery was 1.02. Thus the secretin-responsive region is permeable to both erythritol and mannitol. This affects the extent to which measured erythritol clearance accurately reflects canalicular bile formation; Cery may underestimate or overestimate canalicular bile flow. The electrolyte composition of bile remained relatively constant over a broad range of bile flows although the characteristics of taurocholate- and secretin-induced biles differed from each other. Taurocholate-stimulated bile was virtually isotonic. Secretin-induced bile had a high total concentration of electrolyte (mean concentration 367 meq/liter) rich in chloride and bicarbonate and was hypertonic.

Animals↗

Characterization of SC2644-induced choleresis in the dog. Evidence for canalicular bicarbonate secretion.

The biliary clearances of [14C]erythritol (Cery) and [3H]mannitol (Cmann) were measured simultaneously in dogs, first during choleresis induced by varying doses of sodium taurocholate and then by SC2644. Cery increased equally with the increases in bile flow induced by both compounds. Mannitol entry into bile, however, was partially restricted; deltaCmann/deltabile flow averaged 0.66 and 0.68 for taurocholate- and SC2644-induced flows, respectively. These findings suggest a common canalicular site of origin of the increased bile flow. Electrolyte composition was quite different in the increments, however. The bicarbonate concentration in the SC2644-induced increment of bile (65.8 microEq/ml) was three times higher than that associated with bile stimulated by taurocholate. SC2644- and taurocholate-induced biles were virtually isosmotic. These results in concert with other observations suggest a canalicular mechanism for bicarbonate entry into the biliary tree. Stimulation by SC2644 of ductal chloride bicarbonate exchange cannot be excluded, however.

Animals↗

Choleresis associated with metabolism and biliary excretion of diethyl maleate in the rat and dog.

Diethyl maleate (DEM) induces a choleresis in the rat and dog that appears to be canalicular in origin (bile flow and erythritol clearance increase equally) and occurs in the absence of an increase in bile salt excretion. Increased bile flow is probably accounted for by the osmotic activity of DEM compounds excreted into bile. These compounds represent the glutathione conjugate of DEM (DEM-GSH) and its subsequent metabolic products. Conjugation of DEM largely accounts for the depletion of hepatic GSH.

Animals↗

Hepatitis and pregnancy.

The maternal and fetal outcomes of 50 pregnancies complicated by acute viral hepatitis were examined. Twenty (40%) cases were due to type B hepatitis virus. The clinical course of the maternal hepatitis was unaffected by the pregnant state. Maternal hepatitis (type B or nontype B) had no effect on the incidence of congenital malformations, stillbirths, abortions, or intrauterine malnutrition; it did increase the incidence of prematurity (type B 31.6%; nontype B 25%; overall 27.6%) over that seen in the general delivery population (10 to 11%). Eight mothers acquired acute type B hepatitis during the third trimester; two of their infants (25%) were found to be chronic asymptomatic carriers of hepatitis B surface antigen and to have mild, persistent elevations of SGOT for up to 45 months.

Carrier State↗

Serum gamma-glutamyl transpeptidase activity in viral hepatitis: suppression in pregnancy and by birth control pills.

gamma-Glutamyl transpeptidase (GGT) activity in serum was increased in the majority of women with viral hepatitis occurring in the first half of pregnancy. By contrast, GGT activity was abnormal less frequently and the mean value was relatively depressed, even though hepatitis was as severe, in the second half of gestation. Mean GGT activity was also lower, and abnormal values were less frequent, in nonpregnant women with viral hepatitis who were taking birth control pills (BCP). Depressed GGT is not attributable to an inhibitor in serum in women in late pregnancy or taking BCP. The data suggest that estrogen and/or progestational compounds affect liver such that less GGT is released into blood with acute hepatocellular injury. In addition, hyperbilirubinemia was found to be associated with depressed serum GGT activity, and bilirubin added to serum in vitro interfered with measured activity of the enzyme.

Bilirubin↗

Biliary excretion of dye in dogs infused with BSP or its glutathione conjugate.

A comparison of the maximal rates of biliary excretion (Tm), of dye in dogs infused with either BSP or its glutathione conjugate (BSP-GSH) was carried out. Tm was much higher when BSP-GSH rather than BSP was infused. This was accounted for by a significantly higher concentration of dye in bile of dogs receiving BSP-GSH. Evidence is presented that BSP and its conjugated metabolites compete for a common transport carrier and that BSP disproportionately depresses the biliary excretion of conjugated dye compounds. This latter observation accounts for the depressed dye Tm found during infusion of BSP. Choleresis invariably accompanied dye excretion. When BSP-GSH was infused, enhanced bile flow could be accounted for by the predicted osmotic activity of dye transported into bile. By contrast, the choleresis measured during infusion of BSP was significantly greater than that predicted. An additional mechanism for choleresis is operative, therefore, when unconjugated BSP is infused. Administration of taurocholate enhanced dye Tm when BSP-GSH was infused. Since increments of canalicular bile flow induced by theophylline and glucagon did not enhance dye excretion into bile, this effect by taurocholate appears to be related to taurocholate excretion per se rather than to the enhanced canalicular bile flow which accompanies its excretion.

Animals↗

Solution properties of sulfobromophthalein sodium (BSP) compounds alone and in association with sodium taurocholate (TC).

A series of in vitro studies have been performed utilizing the techniques of ultracentrifugation, freezing point depression, vapor pressure osmometry, and spectrophotometry, to study the colloid-chemical characteristics of various sulfobromophthalein sodium (BSP) compounds in aqueous solution and to evaluate the possibility of a direct physicochemical interaction between BSP and taurocholate (TC). The results of these studies indicate that: (1) BSP compounds self-associate in aqueous solution to form polymolecular aggregates. These aggregates are larger with conjugated BSP, where the aggregation number appears to increase with the concentration of BSP, compared with the more polar glutathione conjugate of BSP; (2) There is a marked physicochemical interaction between unconjugated BSP and TC and a much smaller effect between the bile salt and conjugated BSP. This interaction was minor between BSP and glycodeoxycholate or taurodehydrocholate but was reproduced fully by glycocholate. Such an interaction between BSP and TC may have physiologic importance and may help to explain the previously noted facilitated excretion of BSP observed after infusion of TC in experimental animals.

Journal Article↗