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T Sharp

Publications and source records attributed to T Sharp.

At least 91 records · Page 5Linked to original sources
PubMed1995

Electroconvulsive shock increases dopamine D1 and D2 receptor mRNA in the nucleus accumbens of the rat.

The present study examined the effects of acute and repeated administration of electroconvulsive shock (ECS) on levels of D1 and D2 receptor mRNAs in the nucleus accumbens and striatum (caudate-putamen) of the rat. Quantitative in situ hybridisation with 35S-labelled oligonucleotide probes specific for D1 and D2 receptor mRNAs was utilised. Compared to controls, rats receiving a single ECS showed higher levels of both D1 and D2 receptor mRNAs in the nucleus accumbens 4 h, but not 24 h, after treatment. Similarly, rats receiving ECS repeatedly (five ECS in 10 days) also exhibited higher levels of D1 and D2 receptor mRNAs in the nucleus accumbens 4 h, but not 24 h, after the last treatment. The effects of single and repeated ECS treatment on dopamine receptor mRNA levels were localised to the caudal region of the nucleus accumbens. No statistically significant changes in mRNA levels were detected in the striatum of rats treated with either acute or repeated ECS. We discuss the possibility that increased expression of D1 and D2 receptors in the nucleus accumbens may be involved in the dopamine-enhancing properties of ECS detected in behavioural studies.

Animals↗
PubMed1995

Studies on the role of 5-HT1A autoreceptors and alpha 1-adrenoceptors in the inhibition of 5-HT release--I. BMY7378 and prazosin.

UNLABELLED: The present study utilized in vivo microdialysis to investigate the importance of 5-HT1A autoreceptors and alpha 1-adrenoceptors in the decreased 5-HT release obtained following administration of the mixed 5-HT1A autoreceptor partial agonist/alpha 1-adrenoceptor antagonist BMY7378, the selective 5-HT1A receptor agonist 8-OH-DPAT and the alpha 1-adrenoceptor antagonist prazosin. BMY7378 (0.25 mg/kg, s.c.), 8-OH-DPAT (0.025 mg/kg, s.c.) and prazosin (0.1-1.0 mg/kg, s.c.) all suppressed ventral hippocampal 5-HT efflux. The BMY7378- and 8-OH-DPAT-induced inhibition of 5-HT release were reversed by a 40 min pre-treatment with either (+/-)pindolol (8 mg/kg, s.c.) or WAY-100635 (0.3 mg/kg, s.c.), to block 5-HT1A autoreceptors. Neitehr of these antagonists altered the prazosin-induced (0.3 mg/kg, s.c.) 5-HT disease. THE RESULTS: (i) confirm that both an alpha 1-adrenoceptor antagonist (prazosin) and 5-HT1A autoreceptor stimulants (BMY7378 and 8-OH-DPAT) may reduce cerebral 5-HT release; (ii) support that the BMY7378-induced decrease in 5-HT release results from 5-HT1A autoreceptor agonism, rather than alpha 1-adrenoceptor blockade; and (iii) argue against "physiological" antagonism (i.e. via blockade of beta-adrenoceptors, 5-HT1B receptors or some other mechanism) as an explanation for the reversal by pindolol of 5-HT1A autoreceptor agonist-induced suppression of 5-HT release. These data support the usefulness of pindolol, as well as the more specific compound WAY-100635, to block 5-HT1A autoreceptors.

Animals↗
PubMed1995

Release of cerebral 5-hydroxytryptamine evoked by electrical stimulation of the dorsal and median raphe nuclei: effect of a neurotoxic amphetamine.

Recent neuroanatomical data suggest that the axons and terminals of serotonergic neurons of the dorsal and median raphe nuclei are morphologically and pharmacologically distinct. Here we attempted to establish a functional in vivo model of serotonergic terminals derived from these nuclei, and then carry out a preliminary comparison of their physiological and pharmacological properties. Brain microdialysis was used to monitor extracellular 5-hydroxytryptamine in the hippocampus (dorsal and median raphe innervation) and frontal cortex (preferential dorsal raphe innervation) of the anaesthetized rat. To distinguish 5-hydroxytryptamine released by terminals of dorsal raphe neurons from that released by median raphe neurons, one or other of these nuclei was stimulated electrically. Electrical stimulation of either the dorsal or median raphe nucleus evoked a release of 5-hydroxytryptamine in the hippocampus. Whereas stimulation of the dorsal raphe nucleus also released 5-hydroxytryptamine in the frontal cortex, stimulation of the median raphe nucleus did not. No release of 5-hydroxytryptamine was evoked when electrodes were located in regions bordering the dorsal raphe nucleus and the median raphe nucleus. The amounts of hippocampal 5-HT released by stimulation of the dorsal or median raphe nucleus were found to be similarly altered by a 5-hydroxytryptamine uptake inhibitor (citalopram) and calcium-free perfusion medium, and also by increasing stimulation frequency (2-10 Hz). Furthermore, the amount of 5-hydroxytryptamine released by electrical stimulation of either the dorsal raphe nucleus or median raphe nucleus was markedly reduced in rats pretreated with p-chloroamphetamine. In summary, our data show that electrical stimulation of the dorsal or median raphe nucleus releases 5-hydroxytryptamine in a regionally specific manner (hippocampus versus frontal cortex), suggesting that serotonergic nerve terminals of the dorsal and median raphe pathways were being activated selectively. Using this model, we found no differences in the responsiveness of dorsal and median raphe pathways to a specific set of physiological and pharmacological manipulations. In particular, our data suggest that the neurotoxic action of p-chloroamphetamine may not be targeted solely on serotonergic axons and terminals of the dorsal raphe nucleus but includes those of the median raphe nucleus.

Animals↗
PubMed1995

Evidence for a repetitive (burst) firing pattern in a sub-population of 5-hydroxytryptamine neurons in the dorsal and median raphe nuclei of the rat.

Previous electrophysiological studies have shown that spontaneously active mesencephalic 5-hydroxytryptaminergic neurons of anaesthetized or freely moving animals fire solitary spikes in a slow, regular pattern. In the present study, using extracellular single unit recordings from dorsal and median raphe neurons of the anaesthetized rat, an additional electrophysiological property of a sub-population of presumed 5-hydroxytryptaminergic neurons was observed. These neurons, during their otherwise regular firing pattern, repeatedly fired two (or occasionally three or even four) spikes where only one was expected. Spikes in this burst-like repetitive firing mode (spikes in doublets or triplets) occurred in a short time interval (range: 2.4-11.5 ms), and with a diminishing spike amplitude. Cross-correlation analysis of spikes in doublets revealed a very high interdependency between them. The proportion of spikes in doublets to solitary spikes showed great variation between different neurons, ranging from 5 to 95% of the total spikes displayed. However, for each neuron the proportion of spikes in doublets to solitary spikes, and the time interval between the spikes in doublets, remained constant during control recordings. All these features are characteristic of single neurons firing in a repetitive firing pattern rather than simultaneous recordings of two separate 5-hydroxytryptaminergic neurons. Repetitive firing neurons were recorded with a similar frequency in both chloral hydrate and Saffan anaesthetized rats, and were detected using both glass and metal electrodes. Furthermore, neurons with a repetitive firing pattern were inhibited by intravenous administration of a selective 5-hydroxytryptamine1A receptor agonist and a 5-hydroxytryptamine reuptake inhibitor, thus displaying responses typical of 5-hydroxytryptaminergic neurons. Repetitive firing neurons occurred in both the dorsal and median raphe nuclei, although they were much more frequent in the dorsal raphe nucleus (91 of 332 neurons). The occurrence of repetitive firing neurons in the midbrain raphe nuclei is a newly described phenomenon which may indicate unique properties of a sub-population of 5-hydroxytryptaminergic neurons. In functional terms, it could modify both axonal and dendritic 5-hydroxytryptamine release, and provide an additional option for neuronal information signalling.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Measurement of the proportion of free to total prostate-specific antigen improves diagnostic performance of prostate-specific antigen in the diagnostic gray zone of total prostate-specific antigen.

OBJECTIVES: This study examined the clinical significance of non-complexed (free) prostate-specific antigen (PSA) in the differential diagnosis of prostate cancer with an emphasis on patients with total PSA values between 4.0 and 10.0 ng/mL (the diagnostic gray zone). METHODS: Serum samples were obtained from three specimen banks. Patient samples consisted of 55 untreated histologically confirmed primary cancer, 62 men with untreated benign prostatic disease histologically confirmed by 6 negative sextant biopsies, and 64 asymptomatic healthy male controls with normal digital rectal examinations and PSA values less than 4.0 ng/mL. All patients were between the ages of 50 and 75 years. Total PSA levels were determined using the PA immunoassay performed on the TOSOH AIA-1200 automated immunoassay instrument. Free PSA levels were determined using a monoclonal-polyclonal antibody sandwich radioimmunoassay. The proportion of free to total PSA was calculated by dividing the patient's free PSA value by the total PSA value. RESULTS: When all subjects were included, both total PSA and the proportion of free to total PSA significantly differentiated between patients with prostate cancer and patients with benign histologic conditions (P < 0.0001). However, in men with total PSA values between 4.0 and 10.0 ng/mL, the proportion of free to total PSA significantly differentiated between patients with benign and malignant histologic conditions (P = 0.0004), whereas the total PSA did not (P = 0.13). Among this subgroup of patients, the analysis of sensitivity and specificity showed that the proportion of free to total PSA had a clearly higher specificity compared with that of the total PSA at the same level of sensitivity. CONCLUSIONS: Measurement of the free PSA level in a patient's serum and calculation of the proportion of free to total PSA enhances the ability to distinguish benign histologic conditions from cancer while retaining high sensitivity for detecting cancer in men who present with total PSA levels between 4.0 and 10.0 ng/mL. A large-scale population-based study is currently in progress to confirm this preliminary finding.

Aged↗
PubMed1995

Interaction between a selective 5-HT1A receptor antagonist and an SSRI in vivo: effects on 5-HT cell firing and extracellular 5-HT.

1. The acute inhibitory effect of selective 5-hydroxytryptamine (serotonin) reuptake inhibitors (SSRIs) on 5-HT neuronal activity may offset their ability to increase synaptic 5-HT in the forebrain. 2. Here, we determined the effects of the SSRI, paroxetine, and a novel selective 5-HT1A receptor antagonist, WAY 100635, on 5-HT cell firing in the dorsal raphé nucleus (DRN), and on extracellular 5-HT in both the DRN and the frontal cortex (FCx). Extracellular electrophysiological recording and brain microdialysis were used in parallel experiments, in anaesthetized rats. 3. Paroxetine dose-dependently inhibited the firing of 5-HT neurones in the DRN, with a maximally effective dose of approximately 0.8 mg kg-1, i.v. WAY 100635 (0.1 mg kg-1, i.v.) both reversed the inhibitory effect of paroxetine and, when used as a pretreatment, caused a pronounced shift to the right of the paroxetine dose-response curve. 4. Paroxetine (0.8 mg kg-1, i.v.), doubled extracellular 5-HT in the DRN, but did not alter extracellular 5-HT in the FCx. A higher dose of paroxetine (2.4 mg kg-1, i.v.) did increase extracellular 5-HT in the FCx, but to a lesser extent than in the DRN. Whereas 0.8 mg kg-1, i.v. paroxetine alone had no effect on extracellular 5-HT in the FCx, in rats pretreated with WAY 100635 (0.1 mg kg-1), paroxetine (0.8 mg kg-1, i.v.) markedly increased extracellular 5-HT in the FCx. 5. In conclusion, pretreatment with the selective 5-HT1A receptor antagonist, WAY 100635, blocked the inhibitory effect of paroxetine on 5-HT neuronal activity in the DRN and, at the same time, markedly enhanced the effect of paroxetine on extracellular 5-HT in the FCx. These results may be relevant to recent clinical observations that 5-HT1A receptor antagonists in combination with SSRIs have a rapid onset of antidepressant effect.

Animals↗
PubMed1994

The effect of kainic acid on the release of GABA in rat neostriatum and substantia nigra.

In order to test the hypotheses that stimulation of non-N-methyl-D-aspartate (NMDA) receptors in the neostriatum causes the release of gamma-aminobutyric acid (GABA) from nigrostriatal neurones, dual microdialysis was carried out in the neostriatum and substantia nigra of freely moving rats. Application of kainic acid to the neostriatum caused a dose-dependent release of GABA both locally and, at the same time, from the ipsilateral substantia nigra. These effects were blocked by the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). Direct application of kainic acid to the substantia nigra caused a DNQX-sensitive local release of GABA. It is concluded that excitatory amino acid receptor stimulation of the neostriatum releases GABA from striatonigral neurones and that stimulation of the substantia nigra causes the release from striatonigral terminals and/or the collaterals of nigrofugal neurones.

Animals↗
PubMed1994

Measurement of GABA in rat brain microdialysates using o-phthaldialdehyde-sulphite derivatization and high-performance liquid chromatography with electrochemical detection.

A number of recent studies have detected gamma-aminobutyric acid (GABA) in brain microdialysates by measuring an electroactive o-phthaldialdehyde (OPA)-alkylthiol derivative using HPLC with electrochemical detection. A particular problem of this approach is the stench of the thiol reagents involved, and the poor stability of the electroactive GABA derivative. Here we report that these practical disadvantages can be overcome by substitution of the OPA-alkylthiol reaction with an OPA-sulphite reaction. This provides a simple, sensitive and reliable means for determination of GABA in microdialysates of rat brain.

Animals↗
PubMed1994

An investigation of the origin of extracellular GABA in rat nucleus accumbens measured in vivo by microdialysis.

GABA transmission in the nucleus accumbens is believed to play a central role in motivational processes and the expression of psychostimulant drug action. Here we report measurements of extracellular GABA in nucleus accumbens of the rat and investigate its origin. Extracellular GABA was detected using microdialysis in combination with a novel HPLC-based assay. In the awake rat, GABA in the microdialysates (1) increased 10-fold following perfusion with 0.5 mM nipecotic acid, a GABA releasing agent and uptake blocker, (2) increased 7-fold following local perfusion with 50 mM KCl, (3) decreased 50% following perfusion with tetrodotoxin, (4) decreased 50% following perfusion with a Ca(2+(-free medium and (5) decreased 40% following perfusion with high (12.5 mM) MgCl. Finally, in the anaesthetized rat, GABA in the microdialysates decreased 50% following i.p. injection of 100 mg/kg 3-mercaptoproprionic acid, a GABA synthesis inhibitor. We conclude that GABA in microdialysates from nucleus accumbens of the rat (awake) responds appropriately to selected pharmacological agents and derives at least in part (50%) from neurones.

3-Mercaptopropionic Acid↗
PubMed1994

p-Chloroamphetamine (PCA), 3,4-methylenedioxy-methamphetamine (MDMA) and d-fenfluramine pretreatment attenuates d-fenfluramine-evoked release of 5-HT in vivo.

Previous work has suggested that repeated treatment with substituted amphetamines including PCA, MDMA and d-fenfluramine produces a persistent neurodegeneration which is relatively selective for the fine serotoninergic terminals arising from the dorsal raphe nucleus. The aim of the present study was to investigate whether the acute releasing effect of d-fenfluramine might also be sensitive to lesions produced by PCA, MDMA and d-fenfluramine itself. Basal and 5-HT release evoked by d-fenfluramine or 100 mM KCl was measured by microdialysis in frontal or parietal cortex of rats 2 weeks after they had been treated with a neurodegenerative regime of PCA, MDMA, d-fenfluramine, or vehicle. In frontal cortex of vehicle controls, d-fenfluramine (10 mg/kg IP) and KCl (100 mM via microdialysis probe) evoked an increase in 5-HT of 1740% and 779% of basal, respectively. PCA pretreatment reduced d-fenfluramine-evoked 5-HT release by 90.9% while potassium-evoked release was reduced by only 66.8%. Similar results were obtained in parietal cortex. MDMA (20 mg/kg x 8) and d-fenfluramine (1.25 mg/kg x 8) pretreatment reduced d-fenfluramine-evoked release of 5-HT in frontal cortex by 45.2% and 72.0%, respectively. Overall, the present data are consistent with the hypothesis that the acute release of 5-HT evoked by d-fenfluramine occurs via those terminals destroyed by pretreatment with PCA, MDMA and d-fenfluramine, while KCl evokes release from both PCA-sensitive and PCA-insensitive terminals. The significance of these results for the interpretation of neuroendocrine data from d-fenfluramine challenge tests is discussed.

Amphetamines↗
PubMed1994

Threat of hepatitis E virus infection in Somalia during Operation Restore Hope.

In support of Operation Restore Hope, the United States military established a diagnostic laboratory for infectious diseases, the Joint Forward Laboratory, in Mogadishu, Somalia. Because sporadic hepatitis due to unknown causes was a frequent problem, staff members of the Joint Forward Laboratory evaluated 31 Somalis, five displaced Ethiopians, and three Western relief workers who had acute clinical hepatitis. Patients lived in multiple locations in Somalia--Mogadishu, Baidoa, and Merca--and became ill between December 1992 and February 1993. IgM antibody to hepatitis A virus was found in one English relief worker, and IgM antibody to hepatitis E virus was found in 20 (65%) of 31 Somalis, two (40%) of five Ethiopians, and two (67%) of three Western relief workers. No patient had evidence of acute hepatitis B, malaria, yellow fever, or other arbovirus infections. These data indicate that hepatitis E virus--the major cause of enterically transmitted non-A, non-B hepatitis--was a common cause of acute sporadic hepatitis in Somalia during the initial stages of Operation Restore Hope.

Disease Outbreaks↗
PubMed1994

Highly resistant bacterial osteomyelitis in Somalia.

Chronic osteomyelitis is a major health problem in the aftermath of the conflict in Somalia. We studied the microbiology of chronic osteomyelitis among 30 patients in a large hospital in Mogadishu. Gram-negative bacteria were isolated from 77% of patients; most of these isolates were highly resistant to standard antibiotic agents but all were sensitive to ciprofloxacin, an oral fluoroquinolone antibiotic. Ciprofloxacin may prove useful in the management of chronic osteomyelitis due to highly resistant gram-negative bacteria.

Chronic Disease↗
PubMed1993

Comparison of the effect of buspirone and 1-(2-pyrimidinyl)-piperazine on cerebral glucose utilization in the rat.

The novel anxiolytic and antidepressant, buspirone, and its main metabolite 1-(2-pyrimidinyl)-piperazine (1-PP), which is pharmacologically active, were examined for their effect on regional cerebral glucose utilization in awake rats using quantitative 2-deoxyglucose autoradiography. At a dose of 1 mg/kg, buspirone reduced glucose utilization in the hippocampus by approximately 15%, whilst 1-PP at the same dose had no effect. In comparison, at a higher dose, 10 mg/kg of both buspirone and 1-PP decreased glucose utilization in the hippocampus by 20% and 27%, respectively. In addition, widespread reductions in local cerebral glucose utilization were noted with this higher dose of 1-PP; such generalized effects are compatible with those reported for alpha 2 adrenoceptor antagonists. Buspirone at 1 and 10 mg/kg increased glucose utilization by 40% and 65%, respectively, in the lateral habenular nucleus, whilst 1-PP at 1 and 10 mg/kg had no effect. The findings suggest that buspirone's effects on glucose utilization cannot be attributed to 1-PP, unless high doses of buspirone are administered.

Animals↗
PubMed1993

Effect of acute and repeated administration of 5-HT1A receptor agonists on 5-HT release in rat brain in vivo.

1. Electrophysiological measurements of 5-HT neuronal activity report that repeated administration of 5-HT1A receptor agonists leads to desensitization of the 5-HT1A autoreceptor but this has not yet been detected in measurements of brain 5-HT synthesis or metabolism. Here we have determined the effect of repeated administration of 5-HT1A receptor agonists on brain 5-HT release using microdialysis. 2. Acute administration of the 5-HT1A receptor agonists buspirone (0.1-5 mg/kg s.c.) and ipsapirone (0.03-3 mg/kg s.c.) caused a dose-dependent decrease in 5-HT output in ventral hippocampus of the chloral hydrate anaesthetized rat. 3. The 5-HT response to buspirone (0.1 and 0.5 mg/kg s.c.) and ipsapirone (0.3 mg/kg s.c.) was significantly inhibited by pre-treatment with the 5-HT1/beta-adrenoceptor antagonist pindolol (8-16 mg/kg s.c.). The 5-HT response to buspirone (0.1 mg/kg s.c.) and ipsapirone (0.3 mg/kg s.c.) was not blocked by pretreatment with a combination of the beta 1 and beta 2-adrenoceptor antagonists metoprolol and ICI 118,551 (4 mg/kg s.c.). 4. The effect of an acute challenge of buspirone (0.5 mg/kg s.c.) on 5-HT output in ventral hippocampus was not attenuated in rats treated twice daily for 14 days with 0.5 or 5 mg/kg s.c. buspirone compared to saline-injected controls. Similarly, the decrease in 5-HT induced by an acute challenge of ipsapirone (0.5 mg/kg s.c.) was not attenuated in rats treated twice daily for 14 days with 5 mg/kg s.c. ipsapirone.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Muscle hypertrophy with large-scale weight loss and resistance training.

The combined effects of exercise and energy restriction on changes in body fat and fat-free mass (FFM) are controversial. This study was conducted to determine whether muscle hypertrophy is possible during weight loss. Fourteen obese females received a 3360-kJ/d liquid diet for 90 d. Seven subjects received a weight training (WT) regimen and seven subjects remained sedentary (C). Biopsy samples were obtained from the vastus lateralis muscle at baseline and after 90 d of treatment. The average weight loss over the 90-d period was 16 kg with approximately 24% of the weight loss from FFM and 76% from fat. The amount and composition of the weight loss did not differ between WT and C groups. The cross-sectional area of slow twitch and fast twitch fibers was unchanged by treatment in C subjects but significantly increased in WT subjects. It appears that weight training can produce hypertrophy in skeletal muscle during severe energy restriction and large-scale weight loss.

Adult↗
PubMed1993

In vivo monoamine release during naloxone-precipitated morphine withdrawal.

There is much evidence from animal work suggesting that the release of noradrenaline (NA) in the brain increases during naloxone-precipitated morphine withdrawal, but the evidence in favour of changes in release of 5-hydroxytryptamine (5-HT) and dopamine (DA) is contradictory. Here we demonstrate, using in vivo microdialysis, that whilst there is a considerable increase (300%) in release of NA in hippocampus precipitated by naloxone in morphine-dependent rats, there is no change in the release of either 5-HT (in hippocampus) or DA (in nucleus accumbens). These results are consistent with suggestions that the symptoms of morphine withdrawal in rats are due primarily to an increase in central NA release.

Animals↗
PubMed1993

Towards integrative audit: a partnership for quality.

Outlines the gradual process which led to the development of the Sunderland Integrative Audit System. Centred around the Patient's Charter rights and standards, the various modules used together form a patient-centred, multidisciplinary approach to audit that can be used to monitor a contract, clinical directorate or specialty. Founded on the principle that health care is a complex, interactive process, the system seeks to establish the extent to which the patient experiences an "integrated" service by examining the interfaces between departments, professionals and services. Extensive piloting in diverse fields has found the system capable of being used in a variety of hospital and community settings.

England↗