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Biomedical subjects

A H Neims

Publications and source records attributed to A H Neims.

At least 55 records · Page 3Linked to original sources
PubMed1976

Developmental aspects of glutathione S-transferase B (ligandin) in rat liver.

The postnatal development in male Sprague-Dawley rats of hepatic glutathione S-transferase B (ligandin) in relation to the other glutathione S-transferases is described. The concentration of glutathione S-transferase B in 1-day-old male rats is about one-fifth of that in adult animals. The enzyme reaches adult concentrations 4-5 weeks later. When assessed by substrate specificity or immunologically, the proportion of transferase B relative to the other glutathione S-transferases is high during the first week after birth. At this age, 67.5% of the transferase activity towards 1-chloro-2,4-dinitrobenzene is immunoprecipitable by anti-(transferase B), compared with about 50% in adults and older pups. Between the second and the fifth postnatal week, the fraction of transferase B increases in parallel fashion with the other transferases in hepatic cytosol. Neither L-thyroxine nor cortisol induce a precocious increase in glutathione S-transferase activity. Phenobarbital did induce transferase activity towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene in both pups and adults. The extent of induction by phenobarbital was a function of basal activity during development such that the percentage stimulation remained constant from 5 days postnatally to adulthood.

Animals↗
PubMed1976

Pharmacokinetic aspects of theophylline in premature newborns.

To characterize further the pharmacokinetics of theophylline in premature infants, its concentraion in blood was measured by high-pressure liquid chromatography after intravenous infusion given to six apneic premature newborns three to 15 days of age. Theophylline's apparent volume of distribution was 0.690 +/- 0.095 liters per kilogram (mean +/- S.E.), a value similar to that of children, but the half-life (30.2 +/- 6.5 hours) was nine times longer. Blood clearance rate (17.6 +/- 2.3 ml per kilogram per hour) was lower than plasma clearance rate (100 ml per kilogram per hour) of young children. At a total plasma concentration of 17 mg per liter, 56.4 +/- 3.8 and 36.4 +/- 3.8 per cent of the theophylline was bound to adult or full-term cord plasma proteins, respectively. Bilirubin and theophylline did not compete for plasma protein. Calculations suggest that a loading doses of 5.5 mg per kilogram and a maintenance dose rate of 1.1 mg per kilogram per eight hours would achieve and maintain a mean blood concentration of 8 mg per liter (about 10 mg per liter in plasma).

Adult↗
PubMed1976

Pharmacokinetic analysis of the disposition of intravenous theophylline in young children.

The disposition of a single intravenous dose of theophylline, 3.2 mg/kg, was studied using a high-pressure liquid chromatographic assay in ten asthmatic children one to four years of age. The man plasma theophylline clearance was 0.100 +/- 0.036 l/kg/hr, kel 0.49 +/- 0.30 hr-1, betat1/2 3.38 +/- 1.11 hr, alphat1/2 0.13 +/- 0.09 hr, and V1 0.25 +/- 0.13 1/kg. Plasma theophylline clearance was approximately 40% greater in these children than that reported in adults, mainly due to an increased rate of drug elimination. Large interindividual differences were observed. Analysis of data using either a two- or one-compartment model yielded almost identical dosage regimens designed to rapidly achieve and maintain a chosen plasma theophylline concentration. Calculations based upon mean values of pharmacokinetic constants predict that a maintenance dose rate for aminophylline of 30 mg/kg/day, after a loading dose of 5.6 mg/kg, would rapidly achieve and maintain a mean steady-state plasma concentration of theophylline of 10 mg/1. Potential toxicity of such a regimen has not been excluded, since therapeutic trials (with achievement of steady state) have not yet been conducted.

Child, Preschool↗
PubMed1975

Studies on Z-Fraction. I. Isolation and partial characterization of low molecular weight ligand-binding protein from rat hepatic cytosol.

The Z-fraction has been defined operationally as a ligand-binding (bilirubin sulfobromophthalein) portion of rat hepatic cytosol that elutes in the molecular weight region of 10(4) daltons after gel filtration. Polyacrylamide gel electrophoreses under different conditions, as well as binding stoichiometry, confirm the anticipated heterogeneity of the Z-fraction. Three factors have contributed to the subsequent resolution of the Z-fraction and partial characterization of that protein within the fraction with ligand-binding properties (Z-protein): (1) the use of hexachlorophene as ligand; (2) the inclusion of glycerol, 20%, during isolation to prevent aggregation and loss of binding-activity; and (3) the development of a charcoal binding assay. Upon ion exchange chromatography, the Z-fraction resolves into a group of distinct protein components and an unidentified material with a high 260/280 nm absorbancy ratio. The one protein component with binding capacity exhibits homogeneity on polyacrylamide gel electrophoresis (11% gel, Ann. N.Y. Acad. Sci. 121, 404-427, 1964; and 15% gel with SDS). With use of the charcoal method, apparent dissociation constants for the interaction between Z-protein and hexachlorophene, bilirubin and L-thyroxine, were found to be 20, 50, and 350 muM, respectively. The Scatchard plot generated upon extrapolation an n value of 1.0 with assumption of a molecular weight for Z-protein of 10(4) daltons.

Animals↗