Biomedical subjects

T Sharp

Publications and source records attributed to T Sharp.

72 records · Page 4Linked to original sources

PubMed1986

An in vivo study of dopamine release and metabolism in rat brain regions using intracerebral dialysis.

Intracerebral dialysis was used with a specifically designed HPLC with electrochemical detection assay to monitor extracellular levels of endogenous 3,4-dihydroxyphenylethylamine (dopamine, DA) and its major metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in brain regions of the halothane-anesthetized rat. Significant amounts of DA, DOPAC, and HVA were detected in control perfusates collected from striatum and n. accumbens whereas the medial prefrontal cortex showed lower monoamine levels. The ratio of DA in perfusate to DA in whole tissue suggests that in f. cortex, compared to n. accumbens and striatum, there is a greater amount of DA in the extracellular space relative to the intraneuronal DA content. The DOPAC/HVA ratio in control perfusates varied between regions in accordance with whole tissue measurements. This ratio was highest in n. accumbens and lowest in f. cortex. The monoamine oxidase inhibitor pargyline (100 mg/kg i.p.) caused an exponential decline in DOPAC, but not of HVA, in regional perfusates, an effect that was associated with an increase in DA. The data indicated a higher turnover of extracellular DOPAC in n. accumbens than in striatum and the lowest DOPAC turnover in f. cortex. The rate of decline in extracellular DA metabolite levels was slow compared to whole tissue measurements. In the perfusates there was no statistical correlation between basal amounts of DA in the perfusates and DOPAC and HVA levels or DOPAC turnover for any of the areas, indicating that measurement of DA metabolism in the brain under basal conditions does not provide a good index of DA release. In summary, this study shows clear regional differences in basal DA release and metabolite levels, metabolite patterns, and DOPAC turnover rates in rat brain in vivo.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1985

Endoscopic evaluation of slow-release potassium chloride preparations.

In a double-blind, randomized, placebo-controlled clinical trial, 30 healthy subjects took one of two potassium chloride preparations or placebo three times a day for 1 week with concomitant oral glycopyrrolate dosing. The upper digestive tract was endoscopically examined immediately before and after the treatment period. One subject in both of the KCl treatment groups and six subjects in the placebo group developed submucosal lesions. All lesions were minor and of limited clinical significance. There may be reason to believe that glycopyrrolate plays a role in the production of such lesions. If so, the concomitant use of glycopyrrolate in clinical trials of KCl preparations may cloud the results of such studies.

Adult↗

PubMed1985

Virus-like filamentous intranuclear inclusions in a giant-cell tumor, not associated with Paget's disease of bone. A case report.

Explore the source record for details and available documents.

Adult↗

PubMed1984

Differential pulse voltammetry: simultaneous in vivo measurement of ascorbic acid, catechols and 5-hydroxyindoles in the rat striatum.

This paper describes carbon fibre electrodes that can simultaneously monitor changes in ascorbic acid, dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in vivo in the rat striatum using differential pulse voltammetry. The separation between DOPAC and 5HIAA oxidation is improved and the size of the 5HIAA peak decreased by the removal of uric acid using the enzyme uricase indicating that uric acid oxidation may contribute to the oxidation peak at + 300 mV. Haloperidol (0.5 mg/kg) decreased ascorbic acid and 5HIAA but increased DOPAC and HVA while D-amphetamine (3 mg/kg) increased ascorbic acid, decreased DOPAC and HVA but had no effect on 5HIAA. These electrodes should be a useful means of investigating interactions between dopamine and serotoninergic systems in vivo.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1984

Effect of neuroleptic drugs on striatal dopamine release and metabolism in the awake rat studied by intracerebral dialysis.

This study investigated the effect of three neuroleptic drugs, (+/-)-sulpiride, haloperidol and cis-flupenthixol, on dopamine release and metabolism in the striatum of the awake rat. Endogenous extracellular dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as the 5-hydroxytryptamine (5HT) metabolite 5-hydroxyindoleacetic acid (5HIAA), were determined in striatal perfusates in awake rats by using intracerebral dialysis together with high performance liquid chromatography with electrochemical detection. Sulpiride (10, 50 and 250 mg/kg), cis-flupenthixol (0.5 and 2 mg/kg) and haloperidol (2 mg/kg) all increased the levels of dopamine in striatal perfusates. However, the time course and magnitude of these effects differed markedly depending upon the neuroleptic used. Sulpiride (10, 50 and 250 mg/kg), cis-flupenthixol (0.05, 0.5 and 2 mg/kg) and haloperidol (0.05, 0.5 and 2 mg/kg) increased extracellular levels of DOPAC and HVA while having little effect on 5HIAA. In contrast to the effect on dopamine levels the changes in DOPAC and HVA followed similar time courses and were of similar magnitude independent of the neuroleptic used. The response of the dopamine metabolites seemed to occur at lower doses of the neuroleptics than the response of dopamine release itself. Furthermore, there was no close relationship between changes in dopamine as compared to changes in DOPAC and HVA. Finally, there was no correlation between any of the neurochemical changes measured and the occurrence of catalepsy. These data suggest that neuroleptic drugs have two separate actions on the dopamine neuron in vivo, one causing an increase in dopamine release and another producing an increase in dopamine metabolism, which is probably a consequence of increased dopamine synthesis. Furthermore neither of these effects are related to catalepsy.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1984

Analeptic effects of centrally injected TRH and analogues of TRH in the pentobarbitone-anaesthetized rat.

The effect of intracerebral injection of TRH and several biologically stable TRH analogues in the pentobarbitone anaesthetized rat was examined. Bilateral injection of TRH (5.0 micrograms total dose) and the analogues RX 77368 (0.01-1.0 microgram), CG 3509 (0.1-1.0 microgram), DN-1417 (1.0 microgram) and MK-771 (1.0 microgram) into the nucleus accumbens reduced the pentobarbitone-induced sleeping time. The TRH metabolite DKP (5 micrograms) had no effect on the sleeping time following intra-accumbens injection. Intra-septal injection of TRH (1.0-5.0 micrograms), RX 77368 (0.1-1.0 microgram) and CG 3509 (0.1-1.0 microgram) also reversed the pentobarbitone-induced sleeping time. In contrast, TRH (5 micrograms) injected into the striatum had no effect on the pentobarbitone-induced sleeping time, and CG 3509 (0.1 microgram) and RX 77368 (0.1 microgram) had weaker effects following intrastriatal injection compared to injection of these analogues into the nucleus accumbens and septum. Measurements of core temperature and respiration rate in rats following intra-accumbens or septal injection of TRH, CG 3509 and RX 77368 showed these peptides to reverse pentobarbitone-induced hypothermia and stimulate respiration rate. However, while intrastriatal injections of CG 3509 and RX 77368 caused an increase in respiration rate they had no effect on core temperature. These results suggest a close association between peptide-induced respiratory stimulation and reversal of pentobarbitone-induced anaesthesia. Since intra-accumbens and septal injection of dopamine (20-100 micrograms) failed to reverse anaesthesia, it is unlikely that the peptide-induced responses are mediated via dopamine release.

Anesthesia↗

PubMed1983

A manually-operated brain tissue slicer suitable for neurotransmitter release studies.

A simple, inexpensive device has been designed to prepare slices or prisms of brain tumor for metabolic and release experiments by means of a hand-operated method. It is particularly suitable for very rapid slicing of small, irregular pieces of brain tissue dissected from animals or specimens available at biopsy. This simple apparatus was produced as an alternative to the more widely used motor-driven tissue choppers. A comparison of the morphological and metabolic integrity of tissue produced by the new slicer and a conventional tissue chopper is presented. The hand tissue slicer has been used to measure the release of monoamine neurotransmitters and specific neuropeptides in vitro.

Animals↗

PubMed1980

Infusional 5-fluorouracil and X-ray therapy for non-resectable esophageal cancer.

Six patients with unresectable carcinoma of the esophagus received a combined course of external radiation therapy (1000 rads in four fractions in four days commencing on day 2) combined with constant infusional 5-fluorouracil (20 mg/kg every 24 hours for five days beginning on day 1). This program was repeated every other week to give a total x-ray dose of 6000 rads. This regimen has been well-tolerated by the majority of the patients and resulted in a complete response rate within the x-ray treatment field of 83% (5/6). All patients who showed a demonstrable systemic response to 5-fluorouracil reached complete response. The median survival has not yet been reached at six months with post-treatment survivors alive and without disease (four patients) at one, six, nine, and 22 months. Our previous median survival by x-ray therapy alone was 4 1/2 months. Toxicity consists primarily of hematologic suppression at a subclinical level. Although the length of therapy is substantial (11 weeks), the program appears tolerable and is capable of inducing long-term remissions. The program is currently being studied for dose escalation because neither local nor systemic side effects of a dose-limiting nature have been observed at 20 mg/kg 5-FU.

Bone Marrow↗

PubMed1977