Search PubMed⌕ Search

Biomedical subjects

B J Jones

Publications and source records attributed to B J Jones.

At least 55 records · Page 3Linked to original sources
PubMed1990

Sites of action of ondansetron to inhibit withdrawal from drugs of abuse.

The cerebral site of action of the selective 5-HT3 receptor antagonist ondansetron to influence the behavioural consequences of withdrawal from subchronic treatment with diazepam, ethanol, nicotine or cocaine was studied in the light/dark exploration test in the mouse. The aversive response to the light compartment of the test box was reduced during a subchronic treatment with peripherally administered diazepam, ethanol, nicotine and cocaine, but was exacerbated following withdrawal from the 4 treatments. The behavioural consequences of withdrawal from diazepam (10 mg/kg IP b.i.d. 14 days), ethanol (8%/w/v drinking water for 14 days), nicotine (0.1 mg/kg IP b.i.d. 14 days) or cocaine (1.0 mg/kg IP b.i.d. 14 days) were antagonised by ondansetron injected into the amygdala and dorsal raphe nucleus (1-10 ng); injections of ondansetron (10 ng) into the median raphe nucleus, the nucleus accumbens and striatum were ineffective. It is concluded that the amygdala and dorsal raphe nucleus may be sites of action for ondansetron to antagonise the aversive behaviour caused by withdrawal from 4 common drugs of abuse in a mouse model, and that 5-HT projections from the dorsal raphe nucleus may be involved in aversive behaviour.

Amygdala↗
PubMed1990

Ondansetron inhibits a behavioural consequence of withdrawing from drugs of abuse.

The ability of the selective 5-HT3 receptor antagonist ondansetron to influence the behavioural consequences of withdrawal from chronic treatment with ethanol, nicotine or cocaine was investigated in the light/dark exploration test in the mouse and social interaction test in the rat. In both tests acute and chronic (7 days) treatments with ondansetron (0.01-1.0 microgram.kg-1 IP) disinhibited suppressed behaviour; withdrawal from chronic treatment (0.1 mg/kg IP b.i.d.) did not exacerbate the behavioural suppression. Chronic treatment for 14 days with ethanol (8% w/v in the drinking water), nicotine (0.1 mg/kg b.i.d.) or cocaine (1.0 mg/kg b.i.d.) released suppressed behaviour in the mouse and rat tests. Behavioural suppression was increased following withdrawal from ethanol, nicotine and cocaine. The administration of ondansetron (0.01 mg/kg IP b.i.d.) during the period of ethanol, nicotine and cocaine withdrawal prevented the exacerbation in suppressed behaviour. It is concluded that ondansetron potently reduces behavioural suppression during acute and chronic treatments in the rodent models, does not cause a rebound exacerbation of behavioural suppression following withdrawal, and is a highly effective inhibitor of the increased behavioural suppression following withdrawal from the drugs of abuse: ethanol, nicotine and cocaine.

Animals↗
PubMed1990

Use of the double pigtail stent in stone retrieval following unsuccessful ureteroscopy.

Insertion of a double pigtail stent is known to cause ureteric dilatation. We analysed the effect of an indwelling double pigtail stent on the success rate of calculus extraction by second ureteroscopy when the initial ureteroscopy fails. Over a 12-month period, a first ureteroscopy failed in 42 patients; 30 were then treated by ureteroscopy combined with a ureteric stent and 12 were treated without a ureteric stent. The group with an indwelling stent had a successful second ureteroscopy or spontaneously passed the calculus in 24 cases (84%) compared with 5 unstented cases (45%). Ureterolithotomy was necessary in 2 patients with a stent and 3 with no stent. It was concluded that following failed ureteroscopic manipulation of calculi, insertion of a double pigtail stent was associated with a higher subsequent success rate for removal of stone by ureteroscopy and a consequent lower rate of ureterolithotomy.

Adult↗
PubMed1990

Effect of 5-HT3 receptor antagonists on responses to selective activation of mesolimbic dopaminergic pathways in the rat.

1. The effects of 5-hydroxytryptamine3 (5-HT3) receptor antagonists on the behavioural hyperactivity response which results from injection of the neurokinin receptor agonist [pGlu5, MePhe8, Sar9]-substance P (5-11) (DiMe-C7) into the ventral tegmental area (VTA) of the rat midbrain have been determined. 2. Subcutaneous administration of ondansetron (GR38032) (0.001-0.3 mg kg-1), GR65630 (0.01 mg kg-1), ICS 205-930 (0.1 mg kg-1) and MDL 72222 (0.1 mg kg-1), inhibited the DiMe-C7-induced hyperactivity response. 3. The effects of ondansetron on DiMe-C7-induced changes in dopamine and 5-HT metabolism in discrete areas of rat forebrain were studied in order to investigate further the possible mechanism of action of 5-HT3 antagonists in modifying mesolimbic dopaminergic systems. 4. Intra-VTA administration of DiMe-C7 increased levels of dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens, olfactory tubercules and right amygdala, indicating increased mesolimbic dopamine metabolism. DOPAC levels were not significantly increased in the frontal cortex, left amygdala or striatum. Dopamine levels were not altered in any of these brain areas. DiMe-C7 also increased 5-hydroxyindoleacetic acid (5-HIAA) levels in the amygdala but this was only statistically significant in the right amygdala. 5-HT levels were not changed significantly by DiMe-C7 treatment. 5. In control rats, pretreatment with ondansetron (0.1 mg kg-1) had no effect on the levels of dopamine, 5-HT or their metabolites, but in rats given DiMe-C7, ondansetron significantly inhibited the increase in DOPAC levels in the nucleus accumbens. 6. These results are in agreement with the proposed facilitatory role of 5-HT3 receptor activation on mesolimbic dopaminergic transmission, and suggest that 5-HT3 antagonists may have important therapeutic indications for the treatment of CNS disorders in which mesolimbic dopamine systems are perturbed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Binding of the 5-HT3 ligand, [3H]GR65630, to rat area postrema, vagus nerve and the brains of several species.

The radiolabelled derivative of the potent and selective 5-HT3 receptor antagonist, GR65630, has been shown to label 5-HT3 receptors in homogenates of rat entorhinal cortex. We now report on the specific binding of this radioligand in homogenates of 16 discrete brain areas from several species and nine areas of human brain. We have further characterised specific binding to homogenates of rat area postrema and vagus nerve. In all species examined (rat, mouse, rabbit and ferret) the highest level of specific [3H]GR65630 (0.2 nM) binding was found in homogenates of the area postrema (26-83 fmol/mg protein). Binding in forebrain areas varied with species, Rat and mouse brain had relatively high levels of binding in cortical areas. The ferret and rat had relatively high levels in forebrain dopamine-containing areas. Of the areas of human brain examined the amygdala showed the highest level of specific [3H]GR65630 (0.2 nM) binding (3.0 fmol/mg protein). Specific [3H]GR65630 (0.05-2 nM) binding to homogenates of rat vagus nerve and area postrema was saturable (Bmax: vagus nerve 89.1 fmol/mg protein, area postrema 44.4 fmol/mg protein) and of high affinity (Kd: vagus nerve 0.50 nM, area postrema 0.24 nM). Selective 5-HT3 receptor agonists and antagonists potently inhibited [3H]GR65630 (0.2 nM) binding to homogenates of rat area postrema and vagus nerve. There was a close correlation between drug affinities in each area.

Animals↗
PubMed1989

Exploration of mice in a black and white test box: validation as a model of anxiety.

The validity of a black and white test box to measure changes in mouse exploratory behaviour relevant to assessment of anxiety was investigated by variation of the illumination within the test box, the use of different strains of mice, holding conditions and drug treatments. The suppression of exploratory activity in the white section caused by bright illumination was antagonised by anxiolytic agents from the benzodiazepine series, buspirone, 5-HT3 receptor antagonists, alcohol, nicotine, morphine and SCH23390. The anxiogenic agent FG7142 exacerbated the behavioural suppression. Black C57/BL/6, brown DBA2 and albino BKW mice were sensitive to the effects of drug treatments, whereas albino Tuck mice were less responsive. It is concluded that the characteristic change in mouse exploratory behaviour caused by anxiolytic agents is to preferentially increase exploratory behaviour in the white aversive section of the black and white test box. It is most consistently shown by (a) an increased time spent in the white section with proportional increases in (b) rearings and (c) ambulation and (d) a delay in the initial transition from the white to the black section.

Animals↗
PubMed1989

The effects of ondansetron (GR38032F) in rats and mice treated subchronically with diazepam.

Using rat and mouse models of aversive behaviour, we have further investigated the properties of the 5-HT3 receptor antagonist ondansetron (GR38032F) that are relevant to its proposed use as an anxiolytic agent. Tolerance to the disinhibitory properties of diazepam was readily demonstrated in the social interaction test in the rat, but did not occur after subchronic treatment with ondansetron. In both the light/dark exploration test in mice and the social interaction test in rats, withdrawal from subchronic treatment with diazepam increased behavioural suppression, whereas this was not observed with ondansetron. The behavioural suppression and weight loss induced by either the withdrawal of diazepam or the administration of the benzodiazepine receptor antagonist, flumazenil, in animals treated subchronically with diazepam, was prevented or antagonised by diazepam or ondansetron. Buspirone was ineffective. It is concluded that, in rats and mice, tolerance to the disinhibitory effects of ondansetron does not occur, that withdrawal from subchronic treatment with ondansetron is not associated with any behavioural disturbances and that ondansetron is highly effective in preventing the behavioural suppression and weight loss following withdrawal from subchronic diazepam treatment. These data suggest that ondansetron may have major therapeutic advantages over currently available anxiolytic agents, particularly in patients who have previously received prolonged benzodiazepine therapy.

Animals↗
PubMed1989

5-HT3 receptor antagonists injected into the area postrema inhibit cisplatin-induced emesis in the ferret.

1. The purpose of the present study was to identify and investigate the role of 5-hydroxytryptamine3 (5-HT3) receptors in the area postrema in the control of cisplatin-induced emesis in the ferret. 2. Homogenate binding and autoradiography experiments using the high affinity 5-HT3 receptor ligand, [3H]-GR65630, identified the presence of a high concentration of 5-HT3 receptors in the area postrema of the ferret. 3. Intraperitoneal injection of the 5-HT3 receptor antagonists, GR38032F, GR65630A and MDL72222, at doses of 1, 0.1 and 1 mg kg-1 respectively, inhibited emesis induced by cisplatin, 9 mg kg-1 i.p. 4. Discrete injection of low doses of the 5-HT3 receptor antagonists directly into the area postrema region also inhibited cisplatin-induced (9 mg kg-1 i.p.) emesis. The dose ranges used were: GR38032F, 0.01-1 microgram; GR65630A, 0.001-0.1 microgram; MDL72222, 0.1-10 micrograms. 5. Cisplatin-induced emesis was not inhibited by discrete injection of ketanserin (30 micrograms) or methiothepin (30 micrograms) into the area postrema. Injection of the 5-HT3 receptor agonist, 2-methyl-5-HT, directly into the area postrema produced an incomplete emetic response. 6. These results confirm a role of 5-HT, and in particular 5-HT3 receptors, in the control of cisplatin-induced emesis, and show that at least one functional site for these receptors in modulating the emetic response is the area postrema, the locus of the chemoreceptor trigger zone.

Animals↗
PubMed1988

The distribution of specific binding of the 5-HT3 receptor ligand [3H]GR65630 in rat brain using quantitative autoradiography.

We have examined the distribution of specific binding of the 5-HT3 receptor ligand [3H]GR65630 to rat brain using quantitative autoradiography. Brain tissue was frozen and thin sections (20 microns) cut. Slide-mounted tissue sections were incubated with [3H]GR65630 (0.2 nM) in the presence or absence of metoclopramide (30 microM, to define non-specific binding). After drying, sections were apposed to photographic film for 3 months. Films were quantified for radioactivity using image analysis. The highest level of specific binding was found in the area postrema (34.0 fmol/mg tissue). Specific binding was high in intermediate layers of the cortex, particularly the entorhinal, temporal and pyriform cortex (5.2-7.0 fmol/mg tissue). Amongst sub-cortical areas, binding was evident in the olfactory lobes, olfactory tubercle, hippocampus and basolateral amygdala (1.3-3.3 fmol/mg tissue). Specific binding was below measurable levels in other sub-cortical areas.

Animals↗
PubMed1988

Open access fibresigmoidoscopy: a comparative audit of efficacy.

A total of 541 open access referrals for fibresigmoidoscopy over five years were compared with 495 hospital initiated procedures during the same period. The number of open access fibresigmoidoscopies doubled during the five years but diagnostic yield remained unchanged at about 40% and was similar to that of the hospital initiated procedures. Colorectal carcinoma was seen in 64 open access patients compared with 47 hospital referred patients, the proportion of Dukes's type A lesions being similar (34%) in both groups. Polyps, colitis, and diverticular disease were equally common in open access and hospital referred patients. Fibresigmoidoscopy failed to detect disease in only 12 patients (1.2%) and the procedure was unsatisfactory in only 54. Referral was considered justified in 475 (88%) open access patients, and only 54 (17%) patients with normal appearances at endoscopy required further investigations. Diagnostic yields were low (19%; 30/156 cases) in open access patients under 40 and in patients with abdominal pain, constipation, or abdominal pain with constipation (0-17%). Most of these young patients presumably suffer from the irritable bowel syndrome and do not justify fibresigmoidoscopy. In contrast, there was a high diagnostic yield (90-100%) in patients of all ages referred for diarrhoea and rectal bleeding, altered blood from the rectum, and rectal bleeding associated with abdominal pain. Open access fibresigmoidoscopy is an effective service that should be freely available to general practitioners.

Ambulatory Care↗
PubMed1988

Behavioural and biochemical consequences following activation of 5HT1-like and GABA receptors in the dorsal raphé nucleus of the rat.

The behavioural and biochemical response to the 5-HT1-like receptor compounds, 5-carboxamidotryptamine (5-CT), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), buspirone and ipsapirone and the GABA agonist, muscimol, injected into the dorsal raphé nucleus (DRN) are reported. All compounds increased social interaction under high light, unfamiliar conditions and increased punished responding in a Vogel conflict test. At doses ranging from 5-25 times greater than those which were effective in these anxiety models, muscimol, 5-CT and 8-OH-DPAT induced a marked hypothermia and a flattening of body posture. Buspirone, on the other hand, failed to induce a significant reduction in core temperature or produce a marked flattening of posture in all animals, even at doses 100 times those effective in anxiety models. Following injection of muscimol, 5-CT, 8-OH-DPAT and buspirone into the dorsal raphé nucleus, all tended to reduce the 5-HIAA:5-HT ratios in the frontal cortex, hippocampus and hypothalamus. These findings, together with available electrophysiological data suggest that these behavioural responses are a consequence of a depression of the firing of cells in the dorsal raphé nucleus, with a corresponding decrease in functional activity of 5-HT in the forebrain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

The potential anxiolytic activity of GR38032F, a 5-HT3-receptor antagonist.

1. The highly selective 5-HT3-receptor antagonist, GR38032F, has been tested in five animal models predictive for anxiolytic activity. 2. In the social interaction test in the rat and in a light/dark exploration test in the mouse, GR38032F dose-dependently released suppressed behaviour without modifying locomotor activity. 3. In the cynomolgus monkey and the marmoset, GR38032F reduced anxiety-related symptoms without causing sedation. In the marmoset, the effects were clearly dose-related. 4. GR38032F did not have any detectable activity in the water-lick conflict test in the rat. 5. We conclude that GR38032F is potentially a very potent anxiolytic agent without sedative, anticonvulsant or hypnotic activity.

Animals↗
PubMed1987

The attitudes of psychiatrists toward etiological theories of schizophrenia: 1975-1985.

This study is an analysis of psychiatrists' (N = 339) attitudes with regard to the etiology of schizophrenia. A random sample of members of the American Psychiatric Association reveals a strong endorsement of a combined biogenic/environmental perspective. Attitudes are analyzed further with regard to variation by school of thought, years in practice, and treatment setting. Findings are compared with an earlier study to plot shifts in opinions among psychiatrists over time.

Attitude of Health Personnel↗
PubMed1987

Glucose absorption from maltotriose and glucose oligomers in the human jejunum.

The jejunal absorption of glucose from (1-4)-linked glucose oligomers including maltotriose has been compared with that from free glucose and sucrose in normal subjects. A steady-state perfusion technique in vivo was used to study proximal jejunal assimilation of isotonic sugar-saline solutions isocaloric with 140 mmol/l glucose. Endogenous alpha-amylase was excluded from the test segment by proximal balloon occlusion. The glucose oligomer mixture consisted mainly of maltotriose, maltotetraose, maltopentaose and maltoheptaose. Glucose absorption was significantly faster from maltotriose alone and from the glucose oligomer mixture than from 140 mmol/l glucose controls, whereas glucose absorption from 70 mmol/l sucrose was similar to that from 70 mmol/l glucose plus 70 mmol/l fructose. Hydrolysis in vivo of maltotriose, the oligomer mixture and sucrose were similar, indicating that capture of glucose released by brush border sucrose hydrolysis was less efficient than that associated with (1-4)-linked oligomer hydrolysis. This suggests that the stoichiometric relationship of the active hydrolysis sites for sucrose to the glucose transport system is less advantageous than that of active sites for maltose hydrolysis. Hydrolysis of oligomers larger than maltohexaose may be rate limiting for glucose absorption in the absence of luminal amylase activity.

Chromatography, Gel↗
PubMed1987

The relationship of sanguinaria extract concentration and zinc ion to plaque and gingivitis.

The effects of sanguinaria extract and zinc chloride on plaque growth and gingivitis inhibition were assessed on subjects with initially plaque-free tooth surfaces using a series of oral rinses in a single-blind, crossover, no-oral-hygiene study lasting 2 weeks. A placebo oral rinse containing no sanguinaria or zinc chloride (A), and test rinses containing 150 micrograms/ml sanguinaria and 0.2% zinc chloride (B), 300 micrograms/ml sanguinaria and no zinc chloride (C), and 300 micrograms/ml sanguinaria and 0.2% zinc chloride (D) were evaluated. Subjects using the higher concentration rinses C and D had significantly lower plaque scores than rinse A at 7 and 14 days (p less than 0.05 for C, p less than 0.01 for D). However, groups C and D were not significantly different from each other. Group D had significantly lower plaque (p less than 0.05) and gingivitis (p less than 0.01) scores than group B. Subjects who used rinse B and placebo rinse A had the highest plaque and gingivitis scores and comparison of these two groups revealed no significant difference. At the end of 14 days, the % distribution of 0 plaque and gingivitis scores was greatest among subjects using rinses C and D. Subjects in these 2 groups also had the lowest incidence of plaque and gingivitis scores of 2+. It is concluded that the effects of sanguinaria rinses on developing plaque and gingivitis are influenced more by sanguinaria concentrations than the presence or absence of zinc ion, but that zinc ion may provide a mild enhancement of sanguinaria effectiveness against gingivitis.

Adult↗