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Biomedical subjects

D J Boullin

Publications and source records attributed to D J Boullin.

At least 19 recordsLinked to original sources
PubMed1979

Responses of human and baboon arteries to prostaglandin endoperoxides and biologically generated and synthetic prostacyclin: their relevance to cerebral arterial spasm in man.

1 Isolated strips of human or baboon basilar, middle cerebral, vertebral or common carotid arteries were set up in an isolated organ bath or in a superfusion cascade system. 2 These arteries relaxed to prostacyclin but contracted to prostaglandin endoperoxide (PGH2). 3 Human and baboon isolated arteries also generated prostacyclin from exogenous endoperoxide (PGH2). 4 Human arteries generated prostacyclin 36 h post-mortem but not 40 h post-mortem. The biologically generated prostacyclin relaxed the basilar artery and overcame the contractile effects of PGH2. 5 Thromboxane A2-like activity generated during human platelet aggregation by arachidonic acid caused contractions of the human basilar artery. 6 Prostacyclin reversed contractions of human basilar arteries caused by an unidentified vasoconstrictor factor in cerebrospinal fluid obtained from patients with cerebral arterial vasospasm after subarachnoid haemorrhage following rupture of cerebral arterial aneurysms. 7. The above vasospasm may be due at least in part to disordered physiological control of the calibre of cerebral arteries caused by diminished synthesis of prostacyclin.

Animals↗
PubMed1979

Relationship between presence of vasoconstrictor activity in cerebrospinal fluid and time after subarachnoid haemorrhage from rupture of cerebral arterial aneurysms.

The relationship between clinical condition and vasoconstrictor factors in cerebrospinal fluid was studied in 19 patients for up to six weeks after subarachnoid haemorrhage. Vasoconstrictor activity was assayed biologically. Sixteen of 19 patients improved as vasoconstrictor activity declined; this pattern was not significantly influenced by surgery. Serial angiography was performed on three patients and a qualitative relationship was shown between arterial dilatation, clinical improvement, and reduced pharmacological activity.

Adult↗
PubMed1979

Responses of baboon cerebral and extracerebral arteries to prostacyclin and prostaglandin endoperoxide in vitro and in vivo.

The responses of baboon cerebral and extracerebral arteries to prostaglandin endoperoxide (PGH2) and prostacyclin (PGI2) were investigated on isolated arteries and in vivo by serial angiography. Both PGH2 and PGI2 could produce dose-dependent contraction or relaxation of isolated arteries. PGH2 induced relaxation was indicative of prostacyclin synthetase activity, the enzyme which converts PGH2 to PGI2. In isolated arteries tested one to four hours post mortem only the vertebral artery showed prostacyclin synthetase activity. Thus PGH2 induced contraction of cerebral arteries may be indicative of a physiological function. Vasomotor tone may in part be the result of a balance between PGH2 constriction and PGI2 dilatation. In vivo PGI2 infusion caused pronounced and prolonged dilatation of cerebral arteries, which lasted longer than the cardiovascular changes. As PGI2 is the most potent cerebral vasodilator drug tested, it may be of clinical use in the treatment of cerebral vasospasm.

Animals↗
PubMed1979

[Biochemical methodology for studying affective disorders].

Defects in brain neurotransmitter function are believed to be involved in the aetiology of mood disorders, and model systems are based on this concept. Abnormalities in synthesis, storage, release, reuptake or catabolism of monamines, GABA, glycine, taurine, peptides and purines may occur. There may also be an endogenous psychotogen--an aberrant metabolite of a transmitter. Models are divided into two groups. 1. Human. Brain, CSF, blood cells (platelets, erythrocytes), plasma and urine have been analysed for neurotransmitters or metabolites. Particular emphasis has been given to serotonin (5-HT) and the catecholamines, dopamine and noradrenaline. 2. Animal. Human mood disorders may be stimulated by drug-induced behavioural changes in animals (hyperactivity, stereotyped behaviour sedation). The above biochemical parameters relating to neuronal function can then be assessed. Brain neuronal pathways can be stimulated in animals with monoamine precursors and MAO inhibitor drugs. This drug-induced hyperactivity can be used to "evaluate" therapeutic techniques such as electroconvulsive therapy (ECT). Model analogues of mood disorder have limited use until human disease aetiology is known, currently the best use of models may be for demonstration and evaluation of particular similarities between human mood disorders and drug-induced alterations of animal behavioural patterns.

Animals↗
PubMed1978

Characterization of receptors mediating 5-hydroxytryptamine- and catecholamine-induced platelet aggregation, assessed by the actions of alpha- and beta-blockers, butyrophenones, 5-HT antagonists and chlorpromazine.

1 Blood platelets from normal human volunteers were isolated and aggregated in vitro with 5-hydroxytryptamine (5-HT), noradrenaline (NA), dopamine and N-dimethyldopamine (DMDA). 2 The effects of 5-HT antagonists, alpha- and beta-adrenoceptor blocking agents, butyrophenones and chlorpromazine upon aggregation induced by the four amines were investigated. 3 Only the the 5-HT antagonists, chlorpromazine and spiroperidol were potent inhibitors of 5-HT-induced aggregation, and only phentolamine was a potent inhibitor of the catecholamine-induced aggregation. 4 Evidence was obtained for two populations of receptors, one for 5-HT and one for the three catecholamines.

Adrenergic alpha-Antagonists↗
PubMed1978

The binding of haloperidol to human blood platelets and interactions with 5-hydroxytryptamine and dopamine.

1 The binding of [3H]-5-hydroxytryptamine ([3H]-5-HT), [3H]-haloperidol and [3H]-dopamine to human blood platelets was investigated and the effects of unlabelled haloperidol on [3H]-5-HT binding and (+)- and (-)-butaclamol on [3H]-haloperidol were studied. 2 Scatchard analysis did not show any specific binding of [3H]-haloperidol or [3H]-dopamine to platelets, but two binding sites were identified for binding of [3H]-5-HT. 3 Unlabelled haloperidol reduced the binding of 5-HT in concentrations comparable to those inhibigint 5-HT-induced platelet aggregation; (+)- and (-)-butaclamol did not affect the binding of [3H]-haloperidol. 4 It is concluded that haloperidol binding represents saturation of the platelet membrane, and that the platelet is not a suitable model for investigation of dopamine-drug interactions.

Adult↗
PubMed1978

Models for investigating the aetiology of cerebral arterial spasm: comparative responses of the human basilar artery with rat colon, anococcygeus, stomach fundus, and aorta and guinea-pig ileum and colon.

1 The pharmacological similarity between human basilar artery and a number of isolated tissues (rat colon, anococcygeus, stomach fundus and aorta and guinea-pig ileum and colon) has been assessed during investigations of the aetiology of cerebral arterial spasm. 2 The responses of each of the six tissues to human normal and abnormal cerebrospinal fluid (CSF) and to human serum were compared with those of the human isolated basilar artery. 3 These studies revealed the presence of a vasodilator factor in CSF from subarachnoid haemorrhage patients and several tissues may be of use for further work in identifying the vasoactive substances in CSF. 4 No tissue displayed exactly the same spectrum of biological reactivity as the human basilar artery. The rat stomach fundus showed the closest similarity and was further studied for similarities in drug-induced responses. 5 The rat stomach fundus, like the human basilar artery, was contracted by 5-hydroxytryptamine, prostaglandin F2alpha and histamine and relaxed by dopamine. However, noradrenaline relaxed the fundus but contracted the basilar artery.

Animals↗
PubMed1977

Effects of (+) and (-)-propranolol on the responses of the human isolated basilar artery to cerebrospinal fluid obtained from patients with subarachnoid haemorrhage and cerebral arterial spasm.

1. The human isolated basilar artery has been used as a model to investigate the aetiology of cerebral arterial spasm associated with rupture of intracranial aneurysms. 2. The isolated artery is contracted by 5-hydroxytryptamine, noradrenaline, six prostaglandins and cerebrospinal fluid from patients with ruptured aneurysms and cerebral arterial spasm. 3. These contractions are reversed by (+/-)--, (+)-- and (--)-propranolol in concentrations known to produce local anaesthetic effects on isolated frog sciatic nerve; the (+) isomer was 2.5 to 10 times more potent (-)-propranolol in antagonising all contractions. 4. As the two isomers are known to have similar local anaesthetic potency but (-)-propranolol has greater beta-adrenoreceptor blocking effects we conclude that the antagonistic effects described do not involve beta-adrenoreceptor blockade. 5. The data indicate that propranolol may be of clinical use in reversing cerebral arterial spasm.

Basilar Artery↗
PubMed1976

Single and repeated administration of neuroleptic drugs to rats: effects on striatal dopamine-sensitive adenylate cyclase and locomotor activity produced by tranylcypromine and L-tryptophan or L-Dopa.

Injection of tranylcypromine and L-tryptophan results in rats displaying behavioural changes including hyperactivity, probably due to stimulation of post-synaptic 5-hydroxytryptamine (5-HT) receptors. Increased locomotor activity of a different type is elicited by injection of tranylcypromine and L-dopa, a procedure which increased dopaminergic function in the brain. It has now been demonstrated that the neuroleptic drugs, chlorpromazine, alpha-flupenthixol, haloperidol and spiroperidol block both syndromes. The inhibition produced by these drugs on 5-HT-induced hyperactivity is probably because a dopaminergic system is involved in the behavioural expression of the 5-HT induced hyperactivity. The structurally related drugs with no neuroleptic activity (ethopropazine, promethazine and beta-flupenthixol)are without effect on thses hyperactivity syndromes. Also ineffective were the neuroleptics pimozide and clozapine. Striatal dopamine sensitive adenylate cyclase activity in vitro was inhibited by the administration of chlorpromazine (100 mg/kg) in vivo. Rats treated for 4 or more days with chlorpromazine, alpha-flupenthixol, spiroperidol and haloperidol subsequently showed enhanced locomotor activity in response to tranylcypromine and L-Dopa. Administration of those drugs which did not block hyperactivity acutely did not result in enhancement. Only chlorpromazine, when given for 4 days, enhanced the hyperactivity response following tranylcypromine and L-tryptophan, probably because the drug also blocks 5-HT receptors. In rats displaying enhanced behavioural responses no evidence was found for enhanced sensitivity of striatal adenylate cyclase to dopamine.

Adenylyl Cyclase Inhibitors↗