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Biomedical subjects

A H Short

Publications and source records attributed to A H Short.

At least 19 recordsLinked to original sources

Characterisation of the in vivo behaviour of a controlled-release formulation of levodopa (Sinemet CR).

The gastrointestinal transit and systemic absorption of Sinemet CR (50-200) controlled-release tablets and standard Sinemet (25-100) immediate-release (IR) tablets have been studied in fasted and fed healthy human subjects. Both formulations were labelled with a gamma-emitting radionuclide and their gastric emptying, colon arrival and in vivo disintegration profiles monitored using gamma scintigraphy. The IR dosage forms were found to disperse soon after administration and to empty rapidly from both fasted and fed stomachs. Erosion of the CR system was independent of food or stomach pH. The CR tablet was observed to disintegrate fully in the gastrointestinal (GI) tract, resulting in complete release of levodopa over a 3-4 h time period. Considerable intersubject variation was found to exist for levodopa absorption. Absorption was more protracted with Sinemet CR than with standard Sinemet, due to the controlled release characteristics of the tablet matrix. There was no rapid initial absorption phase and instead, a gradual build-up in the absorption profile occurred.

Adult

Glucose carriers at maternal and fetal sides of the trophoblast in guinea pig placenta.

Trophoblast uptake and unidirectional influx of 3H-labeled hexoses were measured relative to L-[14C]glucose (extracellular marker) using a single-circulation, paired-tracer dilution technique. Successive runs were performed in the fetal and maternal circulations of isolated dually perfused guinea pig placentas, obtained from anesthetized dams and perfused for 60--140 min. The leakiness, estimated from the percentage of the L-glucose dose that crossed the trophoblast, varied (25 +/- 3% (SE), n = 28). On the injection side the maximal sugar uptake (Umax) was measured from early venous concentration ratios, since rapid tracer backflux occurred: Umax = (1 -- 3H/14C) x 100. Umax was independent of the leakiness. In all 14 placentas studied, stereospecific saturable transport of D-glucose was demonstrated at fetal (Umax = 56 +/- 4% (SE), n = 14) and maternal (62 +/- 1% (SE), n = 14) surfaces. The mean unidirectional influxes were 3.3 and 3.5 mumol.min-1.g-1, respectively. Uptakes were inhibited by phloretin and less effectively by phlorizin. D-glucose, 3-O-methylglucose, D-mannose and D-galactose had similar Umax values, about four times that of D-fructose. Tracer backflux and transplacental flux were also equal from both sides. It is concluded that similar hexose carriers, which resemble the human erythrocyte carrier, exist at the membrane on both sides of the trophoblast. The nondestructive technique employed characterizes carriers and receptors at the blood side of cells and could be applied to the placenta or other organs in the intact animal.

Animals

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Education, Medical, Undergraduate

The hepatocellular uptake of glucose, galactose and fructose in conscious sheep.

1. Surgical techniques for chronic catheterization of hepatic and portal veins in the sheep are described. These catheters remained usable for 2-6 months and did not alter hepatic morphology. 2. Hepatocellular uptake of monosaccharides was estimated from their ability to pass the boundaries of the sucrose space in a double indicator dilution procedure in conscious fed sheep. 3. A large proportion (81%) of D-glucose carried in the portal blood was found to enter an hepatic cellular compartment. 4. The radioactive label of D-glucose infused in the portal vein remained associated with D-glucose in hepatic venous blood samples during the experimental period. 5. A large proportion (74%) of an infused trace of D-galactose, a smaller proportion (33%) of D-fructose, and negligible amounts of L-glucose were taken up in a single passage through the liver. 6. Raised blood concentrations of sucrose or of methyl-alpha-D-glucoside (Me-alpha-DG) significantly diminished the proportional uptake of D-glucose. Raised blood concentrations of glucose, galactose or Me-alpha-DG diminished the proportional uptake of D-galactose. Raised blood concentrations of fructose diminished the proportional uptake of fructose. 7. Neither total hepatic blood flow changes nor competitive effects within the cell could account for these findings. 8. It is concluded that these monosaccharides enter the liver cell by facilitated diffusion, and share at least some of the membrane elements that mediate this process. It seems likely that only a proportion of the glucose-transporting apparatus is accessible to galactose.

Animals