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V Sinha

Publications and source records attributed to V Sinha.

7 recordsLinked to original sources

A simplified isolated perfused rat liver apparatus: characterization and measurement of extraction ratios of selected compounds.

A simplified isolated perfused rat liver (IPRL) preparation has been developed and evaluated. The liver is briefly perfused in situ prior to being placed into a 37 degrees C oven and suspended from a stand. This set-up takes about 5 min. A non-recirculatory or one-pass perfusion approach has been used. The performance of the apparatus was evaluated with use of three model compounds: antipyrine, lidocaine and ethanol. In addition, oxygen extraction was determined. The steady-state extraction ratio (ER) was determined for each compound (and oxygen) as a function of perfusate flow rate (15-35 ml/min) during sequential 45 min perfusion periods. Perfusion experiments lasted for up to 3 hr. The ERs (at 15 ml/min) of ethanol (0.65 +/- 0.15), lidocaine (0.91 +/- 0.01) and oxygen (0.65 +/- 0.10) were dependent upon perfusate flow; whereas, antipyrine ER (0.07 +/- 0.01) was independent of flow. The corresponding values for unbound intrinsic clearances (CLu,int) for antipyrine, ethanol, lidocaine and oxygen were: 1.6, 31.0, 158.0 and 27.5 ml/min, respectively. These findings are consistent with the known hepatic ER values for those compounds reported in the literature.

Animals↗

A population approach to enzyme characterization and identification: application to phenacetin O-deethylation.

PURPOSE: To determine the enzyme kinetics (EK) and identify the human cytochrome(s) P450 (CYP) involved in the deethylation of phenacetin to acetaminophen using a population-based method. METHODS: A sparse data set was generated from incubations containing human liver microsomes (n = 19) with phenacetin. Estimates of the EK parameters were obtained by fitting the concentration-velocity data to Michaelis-Menten models by using nonlinear mixed effects modeling. Relationships between the EK parameters and the CYP activities determined for these liver microsomes were examined. RESULTS: A two-enzyme kinetic model with a saturated, low KM enzyme and an unsaturated, high KM enzyme capable of forming acetaminophen best fit the data. The population estimates of the EK parameters were Vmax1, 911 pmol/min/mg protein; KM1, 11.3 microM; and Cl(int2), 0.4 microl/min/mg. The coefficients of variation for interliver variability in Vmax1 and residual error of the model were 39% and 15%, respectively. When the selective catalytic activities were examined as potential covariates, 7-ethoxyresorufin O-deethylation (CYP1A2) activity was found to be associated with the low KM enzyme, however, the high KM enzyme(s) could not be identified. CONCLUSIONS: The population approach characterized the EK parameters and identified the low KM enzyme responsible for phenacetin O-deethylation as CYP1A2. Population modeling of EK provides valuable information on inter- and intraliver variability in CYP dependent activities.

Algorithms↗

Scale for Assessment of Thought, Language and Communication in psychotic in-patients.

The reliability and usefulness of the Scale for Assessment of Thought, Language and Communication was evaluated in a group of psychotic in-patients. A very high interrater reliability (0.75-1.0) and an optimum rate-rerate reliability (0.50-1.0) were found on the individual items of the scale as well as the global rating. Since the scale has a good scope in different clinical and research settings, it was necessary to evaluate its reliability at a place other than where it originated. This study confirms its usefulness in the field of both clinical practice and research.

Adolescent↗