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Biomedical subjects

C E Cornelius

Publications and source records attributed to C E Cornelius.

14 recordsLinked to original sources
PubMed1992

Bilirubin production and conjugation from newly formed heme in isolated rat hepatocytes.

1. Heme synthesis from delta-aminolevulinic acid (delta-ALA) in freshly isolated rat hepatocytes was maximal at 100 microM with a rate of approx. 7 nmol being synthesized per g wet weight cells. 2. Approximately 8% of synthesized heme was converted to bilirubin and 50% of the newly synthesized bilirubin was conjugated. 3. The ratio of di to monoconjugate was approx. 2.5. Incorporation of delta-ALA into bilirubin was increased by additional delta-ALA, heme and was also doubled in cells isolated from animals treated with CoCl2. 4. Bilirubin formation was inhibited approx. 90% by in vitro treatment with heme oxygenase inhibitors zinc and tin protoporphyrin.

Aminolevulinic Acid↗
PubMed1992

Bile pigments in gallbladder and freshly-secreted hepatic duct bile from fed and fasted rainbow trout, Oncorhynchus mykiss.

1. Chromatographic analyses of bile pigments in rainbow trout reveal the presence of primarily unconjugated biliverdin (BV) and bilirubin (BR) glycosyl conjugates. Only trace amounts of unconjugated BR are present in hepatic duct (HD) bile: no beta-glucuronidase activity is detectable. 2. The per cent of BV and BR in HD and gallbladder biles is similar in fasted trout; however, the per cent of BV is significantly increased in HD bile from fed fish. 3. Fasting decreases the rate of choleresis but does not alter the excretory rate of endogenous BV or BR. 4. Erythrocyte life span is estimated to be approximately 500 days.

Animals↗
PubMed1992

Fasting hyperbilirubinemia in normal squirrel monkeys.

The plasma of Bolivian squirrel monkeys, unlike that of Brazilian squirrel monkeys, is markedly yellow due to unconjugated hyperbilirubinemia after an overnight fast. The fasting hyperbilirubinemia in Bolivian squirrel monkeys is likely due to two mechanisms. First, a twofold increase in the bilirubin turnover/production rate occurs during a 24-hour fast. A second mechanism is the decreased hepatic conjugation potential for bilirubin due to the presence of a higher bilirubin UDP-glucuronosyltransferase UDPGAKm and a lower Vm; this results in higher steady-state plasma and hepatic bilirubin levels during a fast when hepatic UDP-glucuronic acid levels are low. The Bolivian squirrel monkey provides an excellent animal model for human Gilbert's syndrome type I in which to study rate-limiting mechanisms in the movement of bilirubin from plasma to bile.

Animals↗
PubMed1991

Kinetic properties of bilirubin UDP-glucuronyltransferase in squirrel monkeys exhibiting fasting hyperbilirubinemia.

1. Bolivian squirrel monkeys (BoSM), unlike Brazilian squirrel monkeys (BrSM), exhibit a marked fasting hyperbilirubinemia (FH) and serve as animal models for Gilbert's syndrome type I. 2. Compared to BrSM, BoSM possess a higher apparent UDPGAKm (0.51 vs 0.29 mM) and lower Vm (0.36 vs 0.48 nmol BR conjugated/min per mg microsomal protein) for hepatic bilirubin (BR) UDP-glucuronyl-transferase (BR UDPG-T). 3. Lineweaver-Burk plots are linear and obey Michaelis-Menten kinetics when UDP-acetylglucosamine is used as activator and UDPGA substrate concentrations are within the physiologic range present in the liver during the fed and fasted state (0.10-0.71 mM); above these concentrations, there is a discontinuity of kinetic plots as noted in other species. 4. There is no effect of fasting on the Km of BR conjugation (i.e. sum of mono- and diglucuronides) in either monkey; however, fasting is associated with lower Vm values (15-20%) in each subspecies. 5. By calculating the potential BR flux (nmol BR conjugated/min per kg) using known hepatic UDPGA concentrations, liver weights and in vitro Km and Vm, a markedly lower BR flux is observed in BoSM (58.4 nmol/min per kg) than in BrSM (91.6 nmol/min per kg). 6. Significantly higher apparent UDPGAKm and lower Vm of BR UDPG-T for conjugation of BR to BR monoglucuronide appears responsible in part for the four- to five-fold elevations in unconjugated BR in the liver and plasma in the fasted BoSM.

Animals↗
PubMed1991

Endogenous bilirubin excretion in Bolivian squirrel monkeys with a Gilbert's-like syndrome.

Fasted Bolivian squirrel monkeys (BoSM) exhibit a marked hyperbilirubinemia when compared to fed BoSM. This fasting hyperbilirubinemia (FH) is similar to that in human patients with Gilbert's syndrome. Endogenous bilirubin (BR) excretion (production) into bile was elevated two-fold in BoSM upon fasting. The fraction of injected dose of 3 H-amino-levulinic acid (ALA) incorporated into biliary BR in fasted monkeys was of less magnitude than in fed monkeys and was associated with lower specific activities of 3 H-BR. Both the lower incorporation of ALA and lower specific activities of 3H-BR in fasted BoSM suggest that increased BR excreted may have arisen from pre-existing non-labeled pools of either heme or BR.

Aminolevulinic Acid↗
PubMed1990

Hepatic bilirubin and UDP-glucuronate levels in Bolivian squirrel monkeys exhibiting fasting hyperbilirubinemia.

1. Bolivian squirrel monkeys (BoSMs), which are animal models for Gilbert's syndrome, have 40% less hepatic bilirubin UDP-glucuronyltransferase (BR-UPPG-T) activity than Brazilian squirrel monkeys (BrSMs). 2. Although fasting results in similar decreases in hepatic UDP-glucose and UDP-glucuronate levels in both simian subspecies, increased activities (55%) of BR-UDPG-T are induced only in the fasted control BrSMs, which do not exhibit the marked fasting hyperbilirubinemia (FH). 3. Total hepatic bilirubin (BR) concentrations were 50% greater in both fed and fasted BoSMs when compared to BrSMs. 4. Hepatic unconjugated BR levels increase upon fasting only in Gilbert-like BoSMs, reaching concentrations twice that observed in BrSMs. 5. Elevated hepatic BR levels in fasted BoSMs may reflect BR overproduction or inadequate glucuronidation. 6. The increased BR-UDPG-T activity induced in BrSMs during fasting could compensate in-part for the UDPGA depletion and prevent the marked FH as observed in BoSMs.

Animals↗
PubMed1990

Increased carbon monoxide excretion in Bolivian squirrel monkeys with fasting hyperbilirubinemia.

Pulmonary carbon monoxide (CO) excretion rates (VeCO) were 50% greater, on average, in Bolivian squirrel monkeys (BoSMs) which exhibit a unique fasting hyperbilirubinemia (FH), than in fasted control Brazilian squirrel monkeys (BrSMs). Since the catabolism of heme produces equimolar amounts of CO and bilirubin, the increased VeCOs are consistent with concurrent increases in endogenous bilirubin production rates. Tin-protoporphyrin, a competitive inhibitor of heme oxygenase, significantly decreased both the VeCO and serum bilirubin level in fasted BoSMs. Overproduction of bilirubin may be responsible in part for the marked FH in BoSMs.

Animals↗
PubMed1979

A new animal model with hyperbilirubinemia: the indigo snake.

An unconjugated hyperbilirubinemia has been observed in all species of normal indigo snakes. The plasma clearance of large organic anions such as sulfobromophthalein and unconjugated bilirubin was markedly delayed when compared to other snake species. Endogenous bile flow and biliverdin and bilirubin excretory rates and the excretion of bile pigments after a bilirubin load were measured in various snakes. The indigo snake represents a new animal model in which to study mechanisms important to hepatic anion uptake and biliary transport.

Animals↗
PubMed1976

Hypercholeresis in turkeys following the ingestion of Crotalaria spectabilis seeds.

Young female turkeys received diets containing Crotalaria spectabilis seeds for 18 weeks. Mean values for total bile flow, biliary bile acid excretion, bile acid-dependent flow and bile acid-independent flow were significantly higher in crotalaria-fed turkeys than in controls. The hypercholeresis observed in crotalaria-fed birds involved both bile acid-dependent and bile acid-independent components of bile. Crotalaria-fed turkeys developed biliary hyperplasia. Liver weights were similar in the two groups. Since increases in 14C-erythritol clearances paralleled increases in total bile flow in crotalaria-fed turkeys (14C-erythritol bile to plasma ratios were similar in both groups), it was evident that the hypercholeresis in crotalaria-fed turkeys did not involve the ductal/ductular component of bile. Little or no ductal/ductular bile flow occurred in either group since total bile flow was equal to erythritol clearance and extrapolation to zero erythritol clearance yielded zero bile flow rates in both groups. Crotalaria-fed turkeys exhibited significantly higher biliary concentrations of chlorides (associated with lower sodium , potassium and bicarbonate concentrations) than did control birds. Validation of the use of 14C-erythritol clearance for the estimation of canalicular bile flow in turkeys was provided both by substantial decreases in bile to plasma 14C-erythritol concentration ratios following the injection of avian vaso-active intestinal peptide and the failure to demonstrate chromatographically the presence of radioactive metabolites of 14C-erythritol in plasma.

Animals↗
PubMed1975

Experimental liver diseases.

The use of animal models in the experimental production of liver diseases similar to those of man is still in its infancy. There is a need to discover new models more closely related to counterpart syndromes in man in the fields of hepatorenal syndrome, neonatal jaundice, Wilson's disease, cholelithiasis, viral hepatitis, biliary atresia, and cirrhosis, to mention only a few. With the continued indiscriminate inbreeding of companion animals as well as the planned inbreeding of laboratory animals, there is little doubt that many more will soon be available. The current availability of mutant rats and sheep with bilirubin transport defects has allowed for a better understanding of how organic anions are transported by the liver. Many other currently available experimental animal models herein briefly reviewed have been only superficially studied. It is the intent of this chapter to provide for post-doctoral students an appreciation for the many animal model systems available for experimental hepatic research.

Alkaloids↗
PubMed1975

Biliverdin and bilirubin excretion in the turkey.

Mean endogenous bile flow in 11 turkeys was 0.81 plus or minus 0.52 mul/g of the liver per minute (10.4 plus or minus 5.3 mul/Kg of body weight per minute). Endogenous biliverdin and bilirubin excretory rates were 0.59 plus or minus 0.31 and 0.058 plus or minus 0.018 mug/g of liver per minute (7.6 plus or minus 3.6 and 0.76 plus or minus 0.23 mug/Kg of body weight per minute), respectively. Mean concentrations of biliverdin and bilirubin in endogenous bile were 92 plus or minus 55 and 8.9 plus or minus 5.2 mg/100 ml, respectively. Livers constituted 1.36 plus or minus 0.22 percent of the body weight. Thin layer chromatographic studies revealed a heterogeneity of bilirubin conjugates in bile.

Animals↗
PubMed1975

Heterogeneity of bilirubin conjugates in several animal species.

Bile was collected from various domestic and wild species (alligators, armadilirubin diazotized and subjected to thin-layer chromatography fro the separation of conjugates (as azo-dipyrroles). Diazotized canine conjugated bilirubin had Rf values in agreement with those previously reported by other; bilirubin conjugates were related to their known glycosidic composition. Variations were observed in the relative amounts of the various mono- and diconjugates among animals within species. However, it was apparent that characteristic patterns of bilirubin conjugation occur in certain animal species. Intravenous infusion of between 0.03 and 0.61 mg of bilirubin/Kg into cats resulted in little or no change in the relative percentages of the various conjugates of bilirubin to glucuronic acid in the cat continues to be the major excretory pathway under conditions of bilirubin load.

Animals↗