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Biomedical subjects

A McGann

Publications and source records attributed to A McGann.

6 recordsLinked to original sources
PubMed1995

Comparison of drug binding interactions on human, rat and rabbit serum albumin using high-performance displacement chromatography.

The binding of warfarin, a series of non-steroidal anti-inflammatory drugs and a series of benzodiazepines to rat serum albumin (RatSA) and rabbit serum albumin (RabSA) was compared with their binding to human serum albumin (HSA) using high-performance liquid chromatography on stationary phases based on immobilized albumins. The effect of the addition to the mobile phase of compounds known to bind to HSA at site I (phenylbutazone) or at site II (R- and S-ibuprofen) or at both sites (2,3,5-triiodobenzoic acid) was investigated on all three proteins. The results indicated that for the chiral compounds studied, the stereoselectivity of drug binding was much lower on RatSA than on HSA. On RatSA and RabSA, the benzodiazepine site was not a major binding site for R- and S-ibuprofen. The results indicated the existence of two binding sites for R and S warfarin on RatSA and probably on RabSA. On RatSA, one site is the major stereoselective site and is the major binding site of phenylbutazone and piroxicam. The other one is a major binding site for R- and S-ibuprofen and R- and S-ketoprofen.

Animals↗
PubMed1993

Determination of the magnitude and enantioselectivity of ligand binding to rat and rabbit serum albumins using immobilized-protein high performance liquid chromatography stationary phases.

Rat, rabbit and human serum albumins were immobilized on an HPLC stationary phase, and the resulting phases were tested for their abilities to determine the extent and enantioselectivity of ligand binding to the respective albumins. A series of achiral and chiral compounds were chromatographed on the phases including benzodiazepinones, non-steroidal anti-inflammatory drugs, amino acids, warfarin and leucovorin. The chromatographic retentions of the benzodiazepinones and one series of nonsteroidal anti-inflammatory agents were compared with protein binding data from ultrafiltration studies. The observed correlation factors (r) were consistently 0.999, indicating that the albumin phases can be used to determine the magnitude of binding to the respective proteins. The enantioselectivity was also investigated, and the results indicate that the stationary phases can be used to determine relative enantioselectivities and intraspecies differences in this stereoselectivity. For example, when R- and S-warfarin were studied, R-warfarin was retained to a greater extent than S-warfarin by the rabbit serum albumin-stationary phase, whereas the opposite enantioselectivity was found for the rat and human albumins. Binding interaction studies were also conducted on the rabbit and rat albumin stationary phases by sequentially adding increasing concentrations of octanoic acid to the chromatographic mobile phase. The octanoic acid reduced the retention of a series of non-steroidal anti-inflammatory agents, and the results of the experiments suggest that the interaction takes place at two or more sites on the albumin molecule and by anti-cooperative allosteric interactions and competitive displacement. The results of this study demonstrate that the immobilized serum albumin columns can be used to quantitate and probe ligand binding interactions.

Animals↗
PubMed1991

A practical method of serial bedside measurement of cerebral blood flow and metabolism during neurointensive care.

Acute encephalopathy is a major cause of death and neurological handicap in children. The principle aims of treatment are to provide adequate cerebral blood flow for the brain's metabolic needs and to prevent intracranial pressure rising above the level at which brain herniation occurs. Rational management requires an understanding of the pathophysiological changes in cerebral blood flow and metabolism which occur. The paucity of data on this subject reflects the perceived difficulty of measuring cerebral blood flow and cerebral metabolism in children. A modification of the Kety Schmidt technique of measuring cerebral blood flow and cerebral metabolism is described. This modification makes it possible to perform serial bedside measurements in children receiving intensive care. This method was used to perform 348 measurements in 58 children. The method was reproducible and no significant complications were encountered. The results indicated that appreciable changes in cerebral blood flow and metabolism could occur in individual patients over time, emphasising the importance of serial measurements. This technique may provide a practical means of monitoring cerebral blood flow and metabolism in very sick children receiving neurointensive care and evaluating the efficacy of treatment.

Acute Disease↗
PubMed1990

Abnormalities of carbohydrate metabolism and of OCT gene function in the Rett syndrome.

The pathogenetic basis of the Rett syndrome (RS) is unknown: an X-linked dominant, male-lethal gene defect is thought likely. We present a girl with RS who has defects both of the urea cycle and of carbohydrate metabolism resulting in fasting hypoglycaemia, post-prandial hyperlactataemia and excess urinary orotic acid excretion after alanine load. Her sister has a similar clinical picture, but less marked metabolic anomalies. The mother of these sisters has abnormal urinary orotic acid excretion; she transmitted opposite ornithine carbomoyltransferase (OCT) alleles to the two girls. Another girl with RS has similar metabolic responses to fasting and to carbohydrate load. We conclude that RS may be an aetiologically homogeneous condition, but that it includes a variable pattern of metabolic anomalies, and that the gene defect is distinct from the OCT locus.

Adolescent↗