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Biomedical subjects

H E Rugstad

Publications and source records attributed to H E Rugstad.

At least 127 records · Page 7Linked to original sources
PubMed1970

Transfer of bilirubin uridine diphosphate-glucuronyltransferase to enzyme-deficient rats.

Cells from a clonal strain (MH(1)C(1)) of rat hepatoma were transplanted subcutaneously into two homozygous Gunn rats, which are jaundiced because the enzyme bilirubin uridine diphosphate-glucuronyltransferase is absent from the liver. Because of the enzyme activity present in the transplanted cells, the recipient rats developed the capacity to conjugate bilirubin and reverted in large part to a normal pattern of bilirubin excretion.

Animals↗
PubMed1970

Metabolism of bilirubin by a clonal strain of rat hepatoma cells.

These studies demonstrate that the MH(1)C(1) strain of rat hepatoma cells has the ability to take up and conjugate bilirubin and then excrete the conjugated pigment into the culture medium. On incubation with unconjugated bilirubin, the average rate of appearance of conjugated bilirubin in the medium was 4.4 +/- 0.20 microg per mg of cell protein per hour (mean +/- SE). The products formed from bilirubin by MH(1)C(1) cells were chromatographically identical to those found in normal rat bile. Assay of bilirubin UDP glucuronyl transferase activity in homogenates of MH(1)C(1) cells gave a value of 3.3 +/- 0.50 microg of conjugated pigment formed per mg protein per hour, only moderately less than the enzyme activity of liver from normal rats. Rat fibroblasts in culture did not conjugate bilirubin, nor did they contain bilirubin UDP-glucuronyl transferase activity. As in living animals, flavaspidic acid inhibited bilirubin metabolism by MH(1)C(1) cells, suggesting that the mechanism for bilirubin uptake is similar to that of normal liver. In contrast to the findings in animals, however, preincubation of MH(1)C(1) cells with phenobarbital led to only minimal enhancement of pigment conjugation. MH(1)C(1) cells represent the first example of a clonal strain of cells in culture in which many of the pathways of hepatic bilirubin metabolism remain intact. They should, therefore, serve as a useful model for studies of bile pigment metabolism which are not easily performed in the living animal.

Bilirubin↗
PubMedDate not supplied

Clinical pharmacokinetics of methyldopa.

Absorption of methyldopa from the gastrointestinal tract is incomplete and variable; bioavailability after oral administration is about 25% (range 8 to 62%). The average time to reach maximum plasma concentration (tmax) [chemically determined] is 2 hours, when the maximum plasma concentration of active drug accounts for 50% of the radioactivity, the remainder representing various metabolites. Physicochemical determination of methyldopa shows that bi-phasic elimination occurs after both intravenous and oral administration, the half-life of the alpha-phase being 0.21 hours (range 0.16 to 0.26 hours) and of the beta-phase 1.28 hours (range 1.02 to 1.69 hours) in normal subjects. Methyldopa is less than 15% protein bound, whereas the primary metabolite, which most probably is the O-sulphate, is about 50% protein bound. The apparent volume of distribution in the central compartment is about 0.23L/kg (range 0.19 to 0.32L/kg), and the total volume of distribution (calculated as Vdarea) is about 0.60L/kg (range 0.41 to 0.72L/kg) in healthy volunteers. Acid-labile conjugates are formed after oral administration. These acid-labile conjugates, in particular the O-sulphate, are probably formed in the intestinal cells, since they are detected in very small amounts after intravenous administration. Additionally, there is a rapid formation of partly unidentified metabolites after both intravenous and oral administration. After intravenous administration the quantitatively most prominent metabolites are methyldopamine and the glucuronide of dihydroxyphenylacetone, but traces of 5 or 6 other metabolites have also been found and identified. These metabolites are probably formed in the liver, but the complete metabolic pattern is still unknown. The renal clearance of methyldopa (95 ml/min/m2) is more than 50% higher than the endogenous creatinine clearance. Renal excretion of some metabolites is slower. Extrarenal elimination accounts for about 50% of the total body clearance of the drug. Renal excretion is very low in patients with renal failure, resulting in accumulation of both active drug and, in particular, its metabolites. There is a marked accumulation of unidentified metabolites in renal failure patients, which possibly explains the strong and prolonged hypotensive action of methyldopa in these patients.

Acute Kidney Injury↗