Biomedical subjects

A H Short

Publications and source records attributed to A H Short.

At least 19 recordsLinked to original sources

PubMed1991

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↗

PubMed1990

A new method for measuring power output in a single leg extension: feasibility, reliability and validity.

A method is described for measuring the explosive power of the leg in extension which has been found safe and acceptable for all age groups and levels of physical capability. The extension movement takes 0.25-0.40 s in a push through 0.165 m against a flat pedal. At the end of the push the leg is fully extended. The movement is made seated so that the forces are contained between the buttocks and the foot. The seat position is adjusted for leg length and the push is transmitted by a lever and chain to spin a flywheel. The gearing is such that resistance to the movement remains velocity of the flywheel is measured by an optoswitch and used to calculated the average leg extensor power (LEP) in the push. The reliability of the power measurement was evaluated in 46 subjects ranging in age from 20 to 86 years; they included medical students and geriatric day patients. They were tested on two occasions separated by a week. The maximal values on the first occasion (best of at least five trials) ranged from 30 to 300 W (mean +/- 1 SD = 154 +/- 88 W). There was no significant difference on re-test and the coefficient of variation was 9.4%. In a subgroup of 9 non-naive subjects who were measured by an experienced observer it was 6.3%. As expected, power was lower in women than in men and declined sharply with age. The sex difference was less when the values were expressed as power per body mass; a sharp age-related decline remained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Gastrointestinal transit of Sinemet CR in healthy volunteers.

The gastrointestinal transit and systemic absorption of Sinemet CR (50/200) and standard Sinemet (25/100) have been studied in fasting and "fed" healthy human subjects. Both formulations were labeled with a gamma-emitting radionuclide, and their gastric emptying, colon arrival, and in vivo dissolution profiles were monitored using gamma scintigraphy. The standard dosage forms were found to disperse soon after administration and to empty rapidly from both the fasting and the "fed" stomach. The erosion of the controlled-release (CR) system was independent of food. Dosing after a light breakfast altered the gastric emptying profile of the CR formulation and led to significant differences in the plasma levels of levodopa.

Antiparkinson Agents↗

PubMed1988

Relationship between the rate of appearance of oxprenolol in the systemic circulation and the location of an oxprenolol Oros 16/260 drug delivery system within the gastrointestinal tract as determined by scintigraphy.

1. The position in the gastrointestinal tract of an orally administered oxprenolol Oros drug delivery system labelled with technetium-99m DTPA was followed by gamma scintigraphy, and the corresponding plasma drug concentration-time profiles after oral and i.v. administration were used to relate pharmacokinetic and transit data. 2. Gastric emptying time (0.8 +/- 0.4 h, mean +/- s.d.), and the time to arrival in the colon (3.8 +/- 0.7 h) were reasonably consistent after administration of the Oros system to fasted subjects, as were the calculated small intestine transit times (3.0 +/- 0.7 h). As expected there were wide individual variations in colonic transit, so that recorded values for total transit ranged from 6 to 32 h (median, 24.7 h). 3. Absorption of oxprenolol occurred throughout the GI tract including the colon. Plasma drug concentration-time profiles and input functions (calculated by deconvolution) could be related to transit behaviour and in vitro release. Inflexions in the calculated rate of drug input when the Oros system was located in the colon corresponded with periods of stagnation at the hepatic and splenic flexures in two subjects and the ileocaecal junction in two others. The mechanism of these changes is unclear.

Adolescent↗

PubMed1986

Interactions between monosaccharides and disaccharides during uptake by the perfused liver of rat.

The extractions of D-glucose, L-glucose, D-fructose and D-galactose by the isolated liver of rat perfused at constant flow were estimated by paired tracer dilution. The effects on these of 25 mM concentrations of these monosaccharides, of alpha-methyl-glucoside and of the disaccharides sucrose, maltose, and lactose were measured. Inferences were drawn from these data about the transport of monosaccharides at the sinusoidal surface of the liver cells. The hepatic clearances of the isomeric monosaccharides consistently ranked D-glucose (at 5.5 X 10(-3) M) greater than D-galactose (2.5 X 10(-5) M) greater than D-fructose (3.2 X 10(-7) M) much greater than L-glucose (2 X 10(-6) M). This implies at least that there are membrane transport mechanisms with distinctly lower affinity for the other sugars than for D-glucose. Glucose entry was stereoselective, and interactions amongst some of the sugars were demonstrated. A reproducible pattern of differential inhibition of D-glucose entry by the competing sugars at 25 mM was found. The consistent lack of effect of sucrose excluded a mere osmotic effect. The pattern of inhibition of D-fructose entry by the same sugars was qualitatively similar to that of D-glucose, whereas that of D-galactose was distinctive. The disaccharide competitors, lacking cell entry, can exert their effects only at the external surface. These markedly discriminate between D-glucose and D-galactose. The penetrating sugars, however, show mutual competition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

The inhibitory effect of phlorhizin and phloretin on hexose transport in the liver.

The inhibitory effect of phlorhzin on renal tubular glucose absorption has been known for a long time now. But its aglycone, phloretin is almost completely devoid of such an action in the kidney although it is more active than phlorhzin on sugar transport mechanism in human erythrocytes. The present investigation was designed to find out the effects of these two chemically related substances on hexose transport in the liver. The effect of 1mM phlorhzin or ImM phloretin on the transport of D-stereoisomers of glucose, galactose and fructose using the first pass extraction technique. It was found that phloretin was a better inhibitor of hexose transport in the liver. The difference between the effect of phlorhizin, and the phloretin was highly significant. The inhibitory pattern of the two chemical substances on the three hexoses indicate a discrimination between galactose transport and glucose or fructose transport in the liver.

Animals↗

PubMed1985

In-vitro enhancement of cholesterol dissolution by commonly used drugs.

A rotating disc apparatus was used to study the dissolution of cholesterol in sodium cholate solutions and ox bile. Drugs with structures that render them capable of lowering interfacial resistance were tested and shown to increase cholesterol dissolution rates in both systems. In sodium cholate solutions, loperamide (3 X 10(-4)M) increased the rate of dissolution by over six times, and a similar effect was observed with amitriptyline (3 X 10(-3)M), diphenhydramine (3 X 10(-3)M), dicyclomine (3 X 10(-3)M) and propantheline (3 X 10(-3)M). These drugs are as effective as benzalkonium chloride at these concentrations. Amitriptyline, propantheline, dicyclomine and diphenhydramine also increased cholesterol dissolution rates into ox bile. If these drugs are excreted into human bile in sufficient quantities and in an active form they may be able to enhance the speed of cholesterol gallstone dissolution therapy.

Animals↗

PubMed1979

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↗

PubMed1979