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Biomedical subjects

A Rane

Publications and source records attributed to A Rane.

287 records · Page 16Linked to original sources
PubMedDate not supplied

Uridine 5'-diphosphoglucuronic acid (UDPGLcUA) in the human fetal liver, kidney and placenta.

The endogenous concentration of uridine 5'-diphosphoglucoronic acid (UDPGLcUA), the endogenus substrate of UDP-glucuronosyltransferase, was measured in the human fetal and adult liver and kidney and in the placenta. The concentrations (mumol/Kg wet weight) of UDPGLcUA were 59.4 +/- 11.3 (fetal liver), 301 +/- 119 (adult liver), 11.9 +/- 3.2 (fetal kidney), 17.4 +/- 3.0 (adult kidney), 17.8 +/- 1.8 (mid-term placenta) and 17.0 +/- 1.7 (term placenta). UDPGLcUA is present in the human fetal liver at a concentration 5-fold lower than in the adult liver indicating a potential limiting factor for glucuronidation ind the human fetus.

Adult↗
PubMedDate not supplied

Valproate in the treatment of absence epilepsy in children: a study of dose-response relationships.

Seven children with absence epilepsy were treated with valproate (VPA). All but one child became free of absence seizures during VPA monotherapy. EEG was recorded for 24 h before start of VPA treatment and repeatedly during treatment. Correlation between plasma VPA concentration and reduction of the number of epileptic discharges was significant. Plasma concentration of 440-660 microM VPA was needed to achieve at least 50% reduction of seizure activity.

Adolescent↗
PubMedDate not supplied

Disposition of carbamazepine and its 10,11-epoxide metabolite in the isolated perfused rat liver.

The disposition of carbamazepine and its metabolite, the 10,11-epoxide, was investigated in isolated perfused livers from control and phenobarbital-pretreated rats. The mean hepatic clearance of carbamazepine was 0.28 ml per min per g of liver corresponding to a mean extraction ratio of 0.16 and a mean intrinsic clearance of 0.33 ml per min g of liver. In phenobarbital-pretreated rats, there was an approximately 40% increase in the hepatic clearance due to a concomitant increase in the mean extraction ratio from 0.16 to 0.26. The carbamazepine-10,11-epoxide generated in the liver approached and attained its peak concentration more rapidly in pretreated than in control rat livers. In the latter group there was virtually no disappearance of the epoxide from the perfusate, whereas in the pretreated rat livers the perfusate concentrations declined after 90 min. The extremely low clearance of the epoxide generated by metabolism in control rat liver was confirmed by administration of the epoxide per se to the perfusion system. The mean extraction ratio of the epoxide in this situation was only 0.016 and it was unaffected by prior treatment of the rats with phenobarbital. However, the epoxids exhibited dose-dependent kinetics with a 3-fold increase in the extraction ratio when the administered dose was reduced from 500 to 166 microng. The observed induction of the hepatic clearance of carbamazepine is supportive of the involvement of this mechanism in the interaction of this drug with various other anticonvulsants in both children and adults.

Animals↗
PubMedDate not supplied

Metabolic interaction between morphine and naloxone in human liver. A common pathway of glucuronidation?

Metabolic interaction between naloxone and morphine has been studied in vitro in human liver microsomes. Morphine and naloxone are metabolized by an UDP-glucuronyl transferase to their 3-glucuronides. There is a very good correlation between the rates of formation of morphine-3-glucuronide and of naloxone-3-glucuronide. Naloxone seems to have a 10-fold higher affinity for the enzyme binding site than does morphine. Morphine and naloxone show bisubstrate kinetic patterns which appear very similar.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Glutathione S-epoxidetransferase in the human placenta at different stages of pregnancy.

Glutathione S-transferase activity with styrene 7,8-oxide as substrate was studied in the soluble fraction of human placentas. Measurable enzyme activities were noted in all placental specimens studied. The mean activity was 5.61 +/- 0.59 (SE) nmol of conjugate formed per min per mg of microsomal protein in midgestational placentas obtained between the 8th and 25th weeks of gestation. The corresponding activity was only 2.07 +/- 0.34 (SE) in four term placental specimens. In this material no relation between the enzyme activities and the smoking habits of the women was observed. Linear kinetics of the enzyme were observed both with respect to styrene 7,8-oxide and glutathione as substrates. Our results show that placental tissue catalyzes not only the formation of previously demonstrated reactive metabolites but also the further metabolism of such metabolites via conjugation with glutathione. The clinical significance of our findings is unclear, but one may speculate that the balance between the placental formation of toxic metabolites and their further degradation is important in regulation of the quantities of such metabolites that reach the fetal compartment.

Cytosol↗
PubMedDate not supplied

Inhibition of morphine glucuronidation by oxazepam in human fetal liver microsomes.

Uridine diphosphoglucuronyltransferase activity toward morphine was measured in vitro in preparations of human fetal liver microsomes. The inhibition of the glucuronidation of morphine was studied at concentrations of morphine and uridine diphosphoglucuronic acid of 3 and 15 mM, respectively. Oxazepam inhibited the reaction by about 50% at concentration of 0.3 mM. The inhibition was almost complete when the concentration was 3 mM, i.e., the same as for morphine. Salicylamide was considerably less potent as an inhibitor of morphine glucuronidation with an almost 100-fold difference in potency as compared to oxazepam. Lineweaver-Burk plots of the inhibition data revealed that oxazepam exerts a competitive type of inhibition with an apparent Ki value of 0.2 mM.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

Metabolism of styrene oxide in different human fetal tissues.

Epoxide hydrolase and glutathionetransferase activities toward [7-3H]styrene 7,8-oxide were measured in the microsomal and cytosolic fractions, respectively, of human fetal liver, lungs, kidneys, adrenal glands, gut, and placenta. Both activities were present at significant rates in all the tissue specimens studied. Epoxide hydrolase activities in the liver (5.98 +/- 0.62 nmol/min/mg) and the adrenal glands (3.57 +/- 0.46 nmol/min/mg) were considerably higher than the corresponding activities in the lungs, kidneys, gut, and placenta, in which organs the mean values ranged from 0.27 to 0.55 nmol/min/mg. The glutathionetransferase activity was more uniformly distributed among the various tissues. It ranged between 5.56 +/- 0.46 and 4.21 +/- 0.39 nmol/min/mg in the liver, the adrenals, the kidneys, the lungs and the placenta. The gut had, however, significantly lower activity than the other tissues (2.56 +/- 0.24 nmol/min/mg). Our data demonstrate differences in the ontogenic development of the styrene oxide metabolism between man and animals and thus, they point out the lack of relevance of fetal animal studies for prediction of human fetal metabolism. The hepatic and extra-hepatic capacity of the human fetus to detoxify epoxides may be biologically important in view of the fact that xenobiotics traversing the placenta to a great extent reach the fetal organs directly (through the venous duct) without preceding passage through the liver.

Epoxide Hydrolases↗