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Biomedical subjects

R F Moulds

Publications and source records attributed to R F Moulds.

At least 73 records · Page 4Linked to original sources
PubMed1982

Intra-dose variation in plasma protein binding of sodium valproate in epileptic patients.

1 The fluctuations in protein binding of sodium valproate during one dosing interval were studied in five patients stabilized on valproate and taking concurrent anticonvulsant therapy. 2 The patients took their usual morning dose of valproate (400-800 mg) and serial blood samples were collected by venepuncture at 0, 1, 2, 3, 4, and 6 h post-dose. 3 Free valproate was separated from protein bound drug by plasma ultrafiltration and the ultrafiltrate and total plasma valproate concentrations were measured by a gas chromatographic method. 4 The maximum and minimum concentrations in the ultrafiltrates occurred at the same times as in the plasma. However, the percentage fluctuation was always greater in the ultrafiltrates (range 192-412%) compared with the plasma (range 153-374%) due to the concentration-dependent nature of valproate protein binding. 5 If free valproate levels are to be monitored, knowledge of sampling time and dosage history is important for interpretation of the results.

Adolescent↗
PubMed1982

Immune complexes and vasoactivity generated from platelets in pre-eclampsia.

In vivo platelet activation by circulating immune complexes has been suggested as one of the underlying mechanisms in preeclampsia. Using a modification of the polyethylene glycol protein-A immune complex assay, immune complexes were found in excess of the equivalent of 20 micrograms/ml heat aggregated IgG in fourteen out of twenty patients diagnosed as having pre-eclampsia. Only six out of nineteen normal controls were found to have similar levels of immune complexes. Furthermore, using a small volume bio-assay method, concentrations of heat aggregated IgG in excess of 20 micrograms/ml were found to activate platelets to release sufficient concentrations of vasoactive agents to constrict a human blood vessel in vitro. These results support the hypothesis that in vivo platelet activation by immune complexes can release sufficient concentrations of vasoactive agents to contribute to the hypertension characteristic of pre-eclampsia.

Adolescent↗
PubMed1981

A comparison of the effects of hydrallazine, diazoxide, sodium nitrite and sodium nitroprusside on human isolated arteries and veins.

1 Human common palmar digital arteries and dorsal metacarpal veins have been studied in vitro to investigate the responses of arterial and venous muscle to hydrallazine, diazoxide, nitroprusside and sodium nitrite. 2 Tissues were removed at autopsy, cut into helical strips and suspended in organ baths under identical conditions. The contractile response to noradrenaline was tested in the presence of the same concentrations of the vasodilator drugs in arteries and veins. 3 Hydrallazine antagonised contraction of arteries, but not veins to noradrenaline. Diazoxide, nitroprusside or sodium nitrite antagonised responses in both arteries and veins. Diazoxide and nitrite were more effective on arteries and nitroprusside was more effective on veins. 4 These results are in accord with clinical observations and confirm that there are differences in the susceptibility of human arterial and venous smooth muscle to vasorelaxant drugs.

Arteries↗
PubMed1981

Reactivity of isolated digital arteries in hypertension.

To see whether the increased peripheral vascular resistance seen in human hypertension is due to an altered reactivity of vascular smooth muscle, strips of digital arteries obtained post mortem from 13 hypertensive have been compared with those from 13 normotensives. The strips from the hypertensives were significantly thicker than those from the normotensives, as were those from male patients compared to females. This was reflected in a significantly greater response of the strips from the hypertensives and males to 80 mM KCl. The maximum responses to noradrenaline and 5-hydroxytryptamine, but not the concentrations required to produce 50% of the maximum responses, were significantly smaller in the strips from hypertensives than in those from normotensives. There were no significant differences between the strips from hypertensives and normotensives in either the maximum responses to angiotensin or barium chloride, or the concentration of those agonists required to produce 50% of the maximum response. It is concluded that the decreased reactivity to noradrenaline of the hypertensive vessels may be a sequel of either the increased pressure itself or increased exposure in vivo of the blood vessels from hypertensives to noradrenaline.

Angiotensin II↗
PubMed1981

In vitro differences between human arteries and veins in their responses to hydralazine.

The inhibitory action of hydralazine on the contractility of human blood vessels has been examined by using in vitro human digital artery and metacarpal vein preparations obtained postmortem. Cumulative contractile concentration-effect curves were performed to norepinephrine, 5-hydroxytryptamine, histamine, angiotensin, KCl and barium chloride (in both arteries and veins. With the exception of barium chloride, hydralazine shifted the concentration-effect curves to the right and reduced the maximum responses to these agonists. This effect was markedly greater in arteries than in veins in which hydralazine had no effect. The maximum responses to the agonists norepinephrine, 5-hydroxytryptamine and KCl were markedly reduced when the normal bathing solution was replaced by a calcium-free solution, and for each agonist this effect was much greater in veins than arteries. The responses to barium chloride, however, were not significantly altered by the calcium-free bathing solution. It is concluded that human arteries are much more sensitive to the effects of hydralazine than are human veins and that the mechanism of action of hydralazine is probably due to inhibition of the release of tightly bound calcium ions.

Arteries↗
PubMed1980

Prejunctional receptors in human digital arteries.

A human digital artery preparation obtained postmortem has been used to study factors influencing 3H-norepinephrine release evoked by periarterial nerve stimulation. Tetrodotoxin nearly abolished the stimulation-induced tritium outflow and the associated vasoconstrictor response. Increasing the frequency of stimulation from 1 to 6 Hz (constant number of 480 pulses) markedly enhanced the stimulation-induced tritium outflow per pulse. Cocaine only modestly increased the outflow. Phentolamine considerably increased, and clonidine significantly decreased, the stimulation-induced tritium outflow, thus indicating the presence of presynaptic alpha-adrenoceptors. Angiotensin also considerably enhanced the stimulation-induced tritium outflow. The results suggest that both frequency of stimulation and presynaptic receptors are of major importance in determining neurotransmitter release in the peripheral vasculature in man.

Angiotensin II↗
PubMed1978

Effects of the beta-receptor antagonists propranolol, oxprenolol and labetalol on human vascular smooth-muscle contraction.

1. Spiral strips of human digital arteries have been studied in vitro to investigate whether DL-propranolol, D-propranolol, oxprenolol and labetalol have peripheral vascular effects in man. 2. Labetalol was a potent inhibitor of contractile responses to noradrenaline, but had less effect on responses to 5-hydroxytryptamine and barium chloride. 3. DL-and D-propranolol were equally effective inhibitors of responses to barium chloride. They were only weak antagonists of noradrenaline responses, but stronger, non-competitive antagonists of 5-hydroxytryptamine responses. 4. Oxprenolol was only a weak inhibitor of the responses to both noradrenaline and 5-hydroxytryptamine and had little effect on responses to barium chloride. 5. It is concluded that labetalol has specific alpha-adrenoreceptor-blocking properties, which are probably relevant to its therapeutic action in man. Propranolol has non-specific inhibitory effect on vascular smooth muscle, which might contribute to its hypotensive activity at high concentrations, but oxprenolol has only slight peripheral effects that are probably therapeutically insignificant.

Adrenergic beta-Antagonists↗
PubMed1978

The action of prazosin in human vascular preparations.

To identify the mode of action of prazosin, its effects on isolated human vascular preparations were studied. Isometric tension was recorded from spiral strips of dorsal metacarpal veins, common palmar digital arteries and uterine, splenic and ileocolic arteries. Prazosin was a potent antagonist of noradrenaline, but not 5-hydroxytryptamine or barium chloride in the metacarpal veins. Higher concentrations of prazosin were necessary to antagonize noradrenaline in the visceral arteries. The digital arteries were resistant to its sympatholytic effect. It is concluded that prazosin acts as an alpha-adrenoceptor antagonist of different potency in various vascular beds. It is postulated that the initial cardiovascular side effects of prazosin are due to venous pooling and that the long term antihypertensive effect is the result of reduced peripheral resistance because of interference with arterial sympathetic tone.

Barium↗
PubMed1977

A study of the contractility, biochemistry and morphology of an isolated preparation of human skeletal muscle.

1. A new method of studying isolated human skeletal muscle has been evaluated. This involves the incubation and electrical stimulation of strips of muscle, obtained at surgical biopsy, that are tied at the cut ends of the fibre bundles. 2. Morphological examination showed that the fibres were sealed off at the cut ends. Damage appeared to be restricted to the areas immediately adjacent to the ties. 3. Contractile properties were well maintained for several hours and measurements of tissue metabolites showed that muscle contents of the high-energy phosphate compounds were well preserved. 4. The isolated preparations were found to have the same contractile properties as human quadriceps femoris studied in vivo by the methods described in the preceeding paper. 5. Correlation was found between the relaxation speed of the isolated preparations and their fibre-type composition histochemically determined. 6. It is concluded that this technique is a valid addition to the present methods of studying the physiology and pharmacology of human skeletal muscle.

Adenosine Triphosphate↗