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Biomedical subjects

C J Fowler

Publications and source records attributed to C J Fowler.

At least 235 records · Page 13Linked to original sources
PubMed1986

Stimulation by noradrenaline of inositol phospholipid breakdown in the rat hippocampus: effect of the ambient potassium concentration.

The stimulation by noradrenaline (NA) of inositol phospholipid (PI) breakdown has been studied using rat hippocampal miniprisms. Pretreatment with the monoamine oxidase inhibitor, pargyline, potentiated the stimulation produced by NA. On the other hand, pargyline pretreatment did not affect the stimulation of PI breakdown by the alpha 1-adrenoceptor agonist phenylephrine. NA- and phenylephrine-stimulated PI breakdown were enhanced by increasing the ambient potassium concentration in the assay from 5.88 to 18.2 mM. This enhancement did not, in the case of NA, change either the EC50 value for this agonist (2-3 microM) or the pA2 value for the competitive antagonism of the stimulation by the alpha 1-antagonist prazosin (pA2 value 9.2). Time-courses of the NA-stimulated PI turnover in different brain regions indicated that the rate of stimulation was in the order frontal cortex greater than hypothalamus greater than or equal to hippocampus much greater than cerebellum.

Animals↗
PubMed1986

Alpha 1-adrenoceptor function in the rat hippocampus as assessed by noradrenaline-stimulated inositol phospholipid breakdown after destruction of noradrenergic neurons by neonatal 6-hydroxydopamine treatment.

Neonatal 6-hydroxydopamine treatment of male Sprague-Dawley rats resulted in a large depletion of noradrenaline 84-87 days later, as demonstrated by an 82% reduction in the intra-synaptosomal deamination of [14C]noradrenaline within noradrenergic synaptosomes with only marginal effects upon the extrasynaptosomal deamination. The hippocampal stimulation of inositol phospholipid breakdown by noradrenaline was, however, unaffected by the neonatal 6-hydroxydopamine treatment.

Animals↗
PubMed1986

A study of pain threshold in diabetics with neuropathic foot lesions.

Pain thresholds to a pinch stimulus were measured at eight sites on the dorsum of both feet from 17 diabetic patients. Sixteen feet had neuropathic ulcers and seven had Charcot arthropathy. Vibration perception thresholds, radial nerve action potentials, muscle action potentials of flexor digitorum brevis, autonomic cardiovascular reflexes and reflex sweat output were also measured. Pinch pain threshold was abnormal in 15 diabetic feet, 11 having one or more insensitive sites. There was a greater variability in threshold between sites tested in diabetic than control subjects.

Adult↗
PubMed1986

Bladder muscle biopsy and urethral sphincter EMG in patients with bladder dysfunction after pelvic surgery.

Eleven patients who suffered persistent bladder dysfunction after pelvic surgery have been investigated by needle urethral sphincter electromyography (EMG) and bladder muscle biopsy, and the results compared with those obtained in a series of controls. Individual motor units recorded from the urethral sphincter in patients who had undergone pelvic surgery were strikingly abnormal, suggesting the presence of reinnervation, and the density of detrusor innervation was significantly reduced. However, since reduction in the density of detrusor innervation may occur in circumstances other than peripheral nerve injury, we conclude that urethral sphincter EMG provides the most effective means of assessing damage to vesico-urethral innervation as a result of previous pelvic surgery.

Aged↗
PubMed1985

Is inhibition of striatal synaptosomal tyrosine hydroxylation by dopamine agonists a measure of dopamine autoreceptor function?

Rat striatal synaptosomal tyrosine hydroxylation was inhibited dose- and pH dependently by a number of dopamine agonists. The catecholic agonists apomorphine and (-)N-n-propylnorapomorphine inhibited synaptosomal tyrosine hydroxylase completely, with IC50 values of around 0.3 mumol/l at pH 6.6. The noncatechol agonists pergolide and bromocriptine and the putative dopamine autoreceptor agonists 3-PPP(-), 3-PPP(+), HW-165 and B-HT 920 produced only partial inhibition of synaptosomal tyrosine hydroxylation at high concentrations. Comparison of the inhibition of synaptosomal and soluble tyrosine hydroxylase indicated that the inhibition produced by apomorphine could be ascribed to a direct effect on the enzyme, whereas this was not the case for the noncatechol agonists. The inhibition produced by pergolide and 3-PPP(-) was not antagonised by either dopamine receptor or alpha-adrenoceptor antagonists. The present results have been compared with results reported in the literature for inhibition of synaptosomal tyrosine hydroxylation and for two other tests of dopamine autoreceptor agonist activity (inhibition of dopamine release from striatal slices in vitro, and inhibition of the gamma-butyrolactone induced increase in dopamine synthesis in vivo). It is concluded that inhibition of striatal synaptosomal tyrosine hydroxylation by dopamine agonists does not fulfil the criteria required for it to be considered as a useful measure of dopamine autoreceptor function.

Adrenergic alpha-Agonists↗
PubMed1985

Micturition disturbance in Parkinson's disease.

Ten men with longstanding idiopathic Parkinson's disease (IPD) were investigated by urodynamic and electromyographic methods. The urodynamic studies were repeated after stopping anti-Parkinsonian medication for several hours. All patients showed a difference between the two studies, but the changes were unpredictable. Three patients who had high residual urine volumes in both studies were thought to have prostatic obstruction. EMG analysis showed no evidence of a lower motor neurone lesion affecting the striated urethral sphincter. It was concluded that micturition difficulty in the patient with IPD is due to detrusor hyperreflexia, influenced by the basal ganglia, which is not associated with impaired striated urethral sphincter activity.

Adult↗
PubMed1985

Abnormal electromyographic activity (decelerating burst and complex repetitive discharges) in the striated muscle of the urethral sphincter in 5 women with persisting urinary retention.

In five women with urinary retention, recordings from the striated muscle of the urethral sphincter revealed highly abnormal electromyographic (EMG) activity. Using a concentric needle electrode, recordings revealed very striking bursts of activity, referred to here as decelerating burst (DB) and complex repetitive discharges (CRD). Such EMG activity is exceedingly unusual in skeletal striated muscle and resembles most closely the rarely encountered condition of "pseudomyotonia". We suggest that this abnormal activity is associated with a failure of relaxation of the striated muscle of the urethral sphincter, which results in chronic retention.

Adult↗
PubMed1985

"Specific" binding of [3H]imipramine to protease-sensitive and protease-resistant sites.

A number of 5-hydroxytryptamine (5-HT) uptake inhibitors have been shown to displace the binding of [3H]imipramine to rat cortical membranes in a complex manner with Hill slopes less than unity. Norzimeldine displaced the binding of [3H]imipramine in a biphasic manner with IC50 values for the two components of about 30 nM and 30 microM. This latter site alone was found in tissues that had been treated with a protease. Binding to both of these sites was displaced by 10 microM desipramine. The protease-sensitive [3H]imipramine binding sites were found to be saturable, high-affinity binding sites with a KD of 8 nM. The number of these sites varied between brain regions and was positively correlated with the regional distribution of [14C]5-HT but not [3H]noradrenaline uptake. This was not the case however for the protease-resistant but desipramine-displaceable binding sites. Since most previous [3H]imipramine binding studies have been performed with high concentrations of desipramine (10 microM) to define "specific binding," these data would suggest that either protease-sensitivity or displacability by 1 microM norzimeldine would give more reliable estimates of the specific binding.

Animals↗
PubMed1985

Increased total activity in the rat after L-tryptophan plus the monoamine oxidase-A inhibitor amiflamine but not after L-tryptophan plus clorgyline.

The effect of pretreatment with either saline or the monoamine oxidase-A inhibitors clorgyline and amiflamine upon the total activity, locomotion and rearing behaviour of the rat induced by various doses of the monoamine precursor L-tryptophan was studied by use of automated activity boxes. Amiflamine (2.5 and 5.0 mg kg-1, i.p.) increased in a dose-dependent manner total activity and to a lesser extent, locomotion when given 60 min before L-tryptophan (100 mg kg-1, i.p.). The increased activity was seen after amiflamine plus either 25 or 75 mg kg-1 L-tryptophan. Rearing behaviour was not affected. Analysis of 5-hydroxytryptamine (5-HT) and its deaminated metabolite 5-hydroxyindoleacetic acid (5-HIAA) by high performance liquid chromatography with electrochemical detection indicated that in both frontal cortex and hypothalamus, amiflamine (at both doses) increased 5-HT and reduced 5-HIAA concentrations. Combination of amiflamine with L-tryptophan (100 mg kg-1, i.p.) resulted in a higher 5-HT concentration being found than after amiflamine alone. L-Tryptophan treatment alone did not change 5-HT concentrations but increased 5-HIAA concentrations. Clorgyline, at a dose of either 1 or 5 mg kg-1 i.p. plus L-tryptophan (25 or 100 mg kg-1, i.p.) did not increase total activity, locomotion or behaviour. A number of possible explanations for the differences in the behavioural effects of clorgyline and amiflamine when given with L-tryptophan are discussed. It is concluded that in addition to monoamine oxidase-A inhibition, other pharmacological effects of the drugs, such as 5-HT release (amiflamine) and inhibition of tryptophan hydroxylation (clorgyline) may be of importance in determining the magnitude of the increase in activity when the compounds are given together with L-tryptophan.

Animals↗
PubMed1985

Monoamine oxidase-A selective inhibition in human hypothalamus and liver in-vitro by amiflamine and its metabolites.

Amiflamine (FLA 336(+] and its two metabolites, FLA 788(+) and FLA 668(+) were found to be competitive inhibitors of the activity of monoamine oxidase-A in homogenates of human hypothalamus and liver obtained at autopsy. Ki values, determined at pH 7.2, were 1.3, 0.3 and 22 microM (liver) and 0.8, 0.2 and 14 microM (hypothalamus) for amiflamine, FLA 788(+) and FLA 668(+), respectively. Monoamine oxidase-B activity was only weakly inhibited by the compounds.

Animals↗
PubMed1985

Decelerating burst and complex repetitive discharges in the striated muscle of the urethral sphincter, associated with urinary retention in women.

A type of electromyographic activity, formerly referred to as "pseudomyotonia", can be recorded from the striated muscle of the urethral sphincter using a concentric needle electrode. There are two components to this activity, complex repetitive discharges and decelerating bursts. The latter usually dominate recordings and sound very like myotonic discharges. Analysis of these discharges indicates that they are a form of "bizarre repetitive discharge", and as such, result from ephaptic spread of excitation between muscle fibres rather than from excitation arising in the terminal branches of the motor axon. Profuse activity of this type has been found in 15 women with symptoms of urethral dysfunction, including 11 with urinary retention. It is suggested that this activity is associated with a failure of urethral sphincter relaxation.

Adult↗
PubMed1985

Bladder dysfunction in distal autonomic neuropathy of acute onset.

A patient with cholinergic dysautonomia and a patient with pandysautonomia have each been investigated for disturbances of bladder and urethral function. Both patients suffered from an inability to develop or sustain a detrusor contraction, while retaining normal bladder sensation. Biopsy specimens of bladder muscle stained for acetylcholinesterase revealed a significant reduction in cholinergic nerves compared with controls; however, the prominent cholinergic subepithelial plexus was strikingly preserved. These findings lend support to the view that acetylcholinesterase-containing nerves in the bladder muscle are motor fibres responsible for detrusor contraction, while those located in the subepithelium are sensory in function. Urethral sphincter electromyography revealed no abnormality of individual motor units, confirming that motor unit integrity in this muscle is dependent upon somatic rather than autonomic innervation. In the patient with pandysautonomia the proximal urethra was incompetent, while in the patient with cholinergic dysautonomia the bladder neck remained closed, as in controls. This suggests that sympathetic rather than parasympathetic efferent activity is necessary for the maintenance of proximal urethral competence.

Acetylcholinesterase↗
PubMed1985

A study of the effects of isaxonine on vincristine-induced peripheral neuropathy in man and regeneration following peripheral nerve crush in the rat.

Administration of isaxonine (6 mg/kg powdered diet) had no effect on regeneration following sciatic nerve crush in the rat. In 10 patients undergoing treatment with vincristine (1.4 mg/m2 twice monthly) development of peripheral neuropathy was quantitated by neurological symptoms, signs and electrophysiological tests. Five also received isaxonine (1.5 g daily). All patients developed evidence of neuropathy, but in none was it severe. The three lowest disability scores were obtained in isaxonine treated patients, but the highest score was also in an isaxonine treated patient. The equivocal findings in this small study could not be amplified because the drug was withdrawn from clinical use on account of its hepatotoxicity.

Animals↗
PubMed1984

Inhibition of monoamine oxidase and semicarbazide-sensitive amine oxidase by mexiletine and related compounds.

The in vitro inhibition by mexiletine and related compounds of the activity of rat brain, heart and lung monoamine oxidase-A (MAO-A), rat brain MAO-B, human platelet-poor plasma benzylamine oxidase and a clorgyline-resistant, semicarbazide-sensitive amine oxidase (SSAO) distinct from both MAO and benzylamine oxidase has been studied. The compounds were most active towards MAO-A and SSAO. IC50 values for mexiletine towards rat heart MAO-A and SSAO were 10 mumol/l and 320 mumol/l, respectively. Replacement of the para-hydrogen atom in the mexiletine aromatic ring by bromine increased potency towards both MAO-A and SSAO. Replacement of the ortho-methyl group in the mexiletine aromatic ring by hydrogen increased the potency towards SSAO alone. FLA 1042, with both these substitutions, was found to be a reversible mixed-type inhibitor of both MAO-A (Kislopei 1.4 mumol/l, Kiinti 24 mumol/l) and of SSAO (Kislopei 12 mumol/l, Kiinti 6 mumol/l).

Amine Oxidase (Copper-Containing)↗