Search PubMed⌕ Search

Biomedical subjects

R F Moulds

Publications and source records attributed to R F Moulds.

At least 91 records · Page 5Linked to original sources
PubMed1977

A comparison of the effects of sodium thiocyanate and dantrolene sodium on a mammalian isolated skeletal muscle.

1 A combination of electrical and pharmacological stimulation has been used to compare the effects of sodium thiocyanate and dantrolene sodium on the excitation-contraction coupling (ECC) mechanism of the mouse soleus muscle. 2 Thiocyanate prolonged the 'active state' after electrical stimulation and increased the response to 8 mM caffeine and 80 mM KCl. Dantrolene had an opposite effect to thiocyanate on all the indices studied. 3 It is concluded that the mechanism of action of dantrolene is by inhibition of the release of the calcium ions involved in the ECC mechanism, probably at the level of the transverse tubules.

Animals↗
PubMed1977

Is malignant hyperpyrexia muscle denervated?

To test the hypothesis that human muscular dystrophies may be secondary to denervation, the responses in vitro of muscle in human malignant hyperpyrexia to electrical and pharmacological stimuli have been compared with those of the denervated mouse soleus muscle. The results suggest that the muscle abnormality in malignant hyperpyrexia is different from that produced by denervation. This must cast doubt on the concept that other human muscular dystrophies are secondary to denervation.

Animals↗
PubMed1974

Insulin secretion in malignant hyperpyrexia.

An increased glucose-induced insulin response has been observed in patients susceptible to malignant hyperpyrexia. This raises the possibility that the membrane abnormality present in the calcium-storing membranes in the muscle cell in malignant hyperpyrexia may be present also in the beta cell of the pancreas.

Adult↗
PubMed1974

Biochemical basis of malignant hyperpyrexia.

Pharmacologically-induced muscle contracture in vitro has been used as a model to study the biochemical basis of malignant hyperpyrexia. In 15 susceptible subjects halothane, succinylcholine, and potassium chloride all produced an abnormal muscle contracture, and the caffeine-induced contracture was greater than normal. The contractures were reproducible only in the presence of extracellular calcium ions. The fact that such dissimilar pharmacological stimuli all induced contracture in the affected muscle suggests that the essential abnormality in the muscle cell in malignant hyperpyrexia is an impaired binding of calcium ions to the membranes of the sarcoplasmic reticulum and the sarcolemma. Exposure of these membranes to halothane, succinylcholine, and other anaesthetic agents then leads to a rapid and abnormally large release of calcium into the myoplasm, which in turn gives rise to all the clinical features of the syndrome.

Biopsy↗
PubMed1974

Identification of susceptibility to malignant hyperpyrexia.

While the serum level of creatine phosphokinase is useful as a screening test for malignant hyperpyrexia it does not provide certain identification of susceptible individuals. A much more accurate prediction may be made by pharmacological testing in vitro of muscle biopsy specimens. Individuals susceptible to malignant hyperpyrexia have muscle with heightened sensitivity to halothane, caffeine, succinylcholine, potassium chloride, and temperature change. Use of this test allows separation of susceptible individuals from those not at risk in families of patients who have experienced malignant hyperpyrexia.

Adolescent↗
PubMed1972

Procaine in malignant hyperpyrexia.

The caffeine contracture of normal human muscle, which has been used as a model for malignant hyperpyrexia, is greatly potentiated by halothane. Prior administration of procaine markedly reduces the halothane-potentiated caffeine contracture, and procaine given at the height of the contracture induces relaxation. Lignocaine, on the other hand, produces a variable response and sometimes increases the contracture.The muscle from a patient with an inherited susceptibility to malignant hyperpyrexia contracted spontaneously with halothane alone, and this contracture was reversed by procaine.These experiments support the therapeutic use of procaine in malignant hyperpyrexia.

Aged↗
PubMedDate not supplied

The effect of prazosin of pre- and post-synaptic alpha-receptors in the pithed rat.

1. Prazosin had a marked inhibitory effect on post-synaptic alpha-receptors in the pithed rat, as measured by the blood pressure response to the cumulative administration of clonidine. 2. Prazosin had no inhibitory effect, however, on the pre-synaptic alpha-receptor, as measured by the clonidine-induced reduction in the tachycardia produced by stimulation of the cardiac nerves. 3. These results suggest that prazosin has a selective antagonistic affinity for post-synaptic alpha-receptors.

Animals↗
PubMedDate not supplied

Are neuronal uptake mechanisms responsible for the difference in sensitivity to noradrenaline between human arteries and veins?

1. The sensitivity of human metacarpal veins and digital arteries obtained post-mortem to noradrenaline and phenylephrine has been tested. 2. pED50 values for noradrenaline were significantly higher in the veins (6.99, s.e.m. = 0.08) than in the arteries (6.56, s.e.m. = 0.09), whereas pED50 values for phenylephrine in the two tissues were not significantly different (arteries: 6.24, s.e.m. = 0.09; veins: 6.26, s.e.m. = 0.05). 3. The addition of propranolol (4 x 10(-6) mol/l) alone, or in combination with hydrocortisone (4 x 10(-5) mol/l), did not affect the responses to either noradrenaline or phenylephrine. The further addition of cocaine (3 x 10(-5) mol/l) slightly shifted the noradrenaline and phenylephrine concentration-effect curves to the left in both arteries and veins, but veins were still found to be more sensitive than arteries to noradrenaline whilst there was still no difference in the sensitivity of veins and arteries to phenylephrine. 4. Cocaine also slightly potentiated responses to barium chloride, potassium chloride and serotonin. 5. It is concluded that the difference in sensitivity to noradrenaline between arteries and veins cannot be explained by differences in neuronal uptake and it is possible that there may be differences in the properties of the postsynaptic alpha-adrenoreceptors of the two tissues. It is also concluded that the potentiation of the contractile effect of noradrenaline produced by cocaine is not solely due to inhibition of neuronal uptake of amines.

Arteries↗
PubMedDate not supplied

Reduced responses to noradrenaline of isolated digital arteries from hypertensives.

1. Strips of digital arteries obtained post-mortem from thirteen hypertensives have been compared with those from thirteen normotensives. 2. The strips from hypertensives and from males had a significantly greater response to 80 mmol/l KCl, but this was due to the increased cross-sectional areas of the strips from hypertensives and from males. 3. The maximum responses to noradrenaline and serotonin, but not the pED50 values, were significantly smaller in the strips from the hypertensives than in those from the normotensives, but there were no differences between the strips from hypertensives and normotensives in either the maximum response or pED50 values to angiotensin or barium chloride. 4. it is concluded that these results suggest a decreased number of alpha-receptors are present in human hypertensive vascular smooth muscle and this is a sequel either of the increased pressure itself, or of increased exposure in vivo of the blood vessels from hypertensives to noradrenaline.

Arteries↗
PubMedDate not supplied

Comparison of the effects of endrallazine, hydrallazine and verapamil on human isolated arteries and veins.

1. The antagonist effects of endrallazine (BQ 22-708), hydrallazine and verapamil have been studied on the contractile responses produced by various agonists on human digital arteries and metacarpal veins obtained post mortem. 2. Endrallazine and hydrallazine antagonized the contractile responses to noradrenaline and serotonin in arteries by shifting the concentration-effect curves to the right and by reducing the maximum responses to both agonists. Neither drug had any effect on responses to BaCl2 in either tissue. 3. The same concentrations of endrallazine and hydrallazine which antagonized responses to noradrenaline and serotonin in arteries, had no effect on concentration-effect curves to those agonists in veins. 4. Hydrallazine was significantly more potent than endrallazine in reducing the maximum response to noradrenaline in arteries, and was less potent than endrallazine in reducing the maximum response to serotonin. 5. Verapamil antagonized the vasoconstrictor effect of all agonists tested in both arteries and veins. 6. It is concluded that in a similar manner to hydrallazine, endrallazine has a direct effect on human vascular smooth muscle at concentrations which are probably similar to those occurring in vivo. Both hydrallazine and endrallazine may produce selective arterio-dilatation by preventing the release of bound calcium from intracellular storage sites, an effect which is different to that of verapamil.

Arteries↗
PubMedDate not supplied

Vasoactivity generated from platelets by immune complexes in pre-eclampsia.

Circulating immune complexes in excess of the equivalent of 20 micrograms/ml heat-aggregated IgG were found in fourteen out of twenty patients diagnosed as having preeclampsia. Only six of the nineteen controls tested had similar levels of immune complexes. Recent studies have established that concentrations of heat aggregated IgG in excess of 20 micrograms/ml activate human platelets to release sufficient concentrations of vasoactive agents to constrict a human blood vessel in vitro. It is therefore suggested that in vivo platelet activation by circulating immune complexes may release sufficient concentrations of vasoactive agents to contribute to the hypertension in pre-eclampsia.

Antigen-Antibody Complex↗
PubMedDate not supplied

Responses of human arterial muscle to stable vasoactive substances released from human platelets by collagen and heat aggregated IgG.

The supernatant solutions obtained after aggregation or sonication of washed human platelets were superfused over preparations of human isolated digital arteries using a small volume bioassay method. The agents released from the platelets caused strong contractions of the artery strips. Platelet aggregation induced by 10 micrograms/ml collagen or by 100 micrograms/ml heat aggregated IgG, released 31.5% and 38.5% respectively, of the contractile activity produced by sonication of the platelets. The quantitative contractile effect of supernatants from platelets aggregated by 50 micrograms/ml IgG was significantly less than that for 100 micrograms/ml HA IgG. Similarly, the maximum contractile effect of supernatants from platelets aggregated by 300 ng/ml collagen was significantly less than that for 1 microgram/ml collagen. This suggests that the concentration of contractile agents released from platelets depends on the concentration of aggregating stimulus. Comparison with concentration-effect curves for exogenous serotonin suggests that if the contractility of the platelet supernatant occurring after sonication of platelets is solely due to serotonin, then it is present in a concentration of approximately 3.3 X 10(-6) mol/l (6.6 nmol per 10(9) platelets). It is suggested from this study that in certain clinical situations characterized by hypertension, and in which circulating immune complexes have been found, in vivo platelet activation by immune complexes may be releasing sufficient concentrations of serotonin to constrict peripheral blood vessels and contribute to the hypertension.

Antigen-Antibody Complex↗
PubMedDate not supplied

In vitro calcium dependence of arterial smooth muscle in human hypertension.

Digital arteries, removed at autopsy from 12 hypertensives and 11 normotensives, have been compared in vitro for the calcium dependence of contractures produced by potassium chloride and noradrenaline, and the potency of verapamil to antagonize contractures to noradrenaline. No significant differences were found between the vessels from the hypertensives and normotensives for the pD2 values or the maximum response to either potassium chloride or noradrenaline in bathing solutions containing 2.5, 1.0, 0.5 or 0 mmol/l calcium chloride. There were also no significant differences between the vessels, from the hypertensive or normotensives, in the pD2 values for the addition of calcium chloride to arteries exposed to potassium chloride or noradrenaline in a calcium free bathing medium, in the ability of verapamil to shift the pD2 values for noradrenaline, nor in the ability of verapamil to reduce the maximum responses to noradrenaline (except at the two highest concentrations of verapamil tested). It is concluded that it is unlikely to be a primary abnormality of the mechanisms regulating calcium ion entry and release in vascular smooth muscle in human hypertension.

Aged↗