PubMed Health⌕ Search

Biomedical subjects

G W Bennett

Publications and source records attributed to G W Bennett.

At least 91 records · Page 5Linked to original sources
PubMed1984

Decrease in levels of thyrotrophin-releasing hormone (TRH) in the n. accumbens and lumbar spinal cord following repeated electroconvulsive shock.

The study investigated the effects of single and repeated electroconvulsive shock on levels and release of TRH in specific brain regions and thoracic and lumbar spinal cord. Whilst single electroconvulsive shock had no effect on TRH in any of the regions of the brain and spinal cord studied, repeated electroshock (5 shocks over 10 days and the rats killed 24 hr after the last shock) caused a significant decrease (-42 and -40% respectively) in levels of TRH in the nucleus accumbens and lumbar spinal cord. In the thoracic cord the level of TRH was also decreased after repeated electroshock but this did not reach significance. In contrast repeated electroshock had no significant effect on the content of TRH of the septal nuclei, hypothalamus, suprachiasmatic nucleus, or dorsal and medial raphe nuclei. Release of TRH was measured from slices prepared from nucleus accumbens and septal nuclei after repeated electroshock. A decrease in release was observed in nucleus accumbens with no effect in the septal nuclei. the results are discussed in relation to the possible interaction between dopaminergic and serotoninergic neurones and TRH in the antidepressant effects of electroconvulsive therapy.

Animals↗
PubMed1984

The TRH analogue CG3509 increases in vivo catechol/ascorbate oxidation in the N. accumbens but not in the striatum of the rat.

The effects of injection of the thyrotrophin-releasing hormone (TRH) analogue, orotyl-histidyl-proline amide (CG3509) into the accumbens and striatum, was studied on dopamine metabolism by means of in vivo voltammetry. Forty minutes after infusion of CG3509 (1-5 micrograms) into the n. accumbens there was a significant dose-related increase in the oxidation peak, corresponding to the oxidation of the dopamine metabolite, dihydroxyphenylacetic acid (DOPAC) and ascorbic acid. The size of this peak returned to normal by 80 min after the infusion. There was no change in the indole oxidation peak. Infusion of CG3509 (5 micrograms) had no effect on the size of either the catechol or the indole oxidation peaks recorded in the striatum. Intraventricular injection of CG3509 (10 micrograms) also increased DOPAC/ascorbic acid oxidation peak recorded in the n. accumbens, without altering the indole peak. While the voltammetric technique used in the present experiments is not able fully to separate ascorbic acid and DOPAC in vivo, the results support the view that TRH and its analogues selectively increase dopaminergic activity in the mesolimbic region.

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↗
PubMed1984

The effects of 5,7-dihydroxytryptamine and p-chlorophenylalanine on thyrotrophin-releasing hormone in regions of the brain and spinal cord of the rat.

The distribution of thyrotrophin-releasing hormone (TRH) and 5-hydroxytryptamine (5-HT) were compared in ten regions of the rat brain and in lumbar spinal cord. After dissection, using a cutting box and tissue punches, TRH was measured by radioimmunoassay and 5-HT by HPLC with electrochemical detection. Within the brain the highest levels of TRH were found in the median eminence and the remaining hypothalamus. There were also relatively high levels in the suprachiasmatic nucleus, septal nuclei and nucleus accumbens. Highest levels of 5-HT were found in the raphe nuclei, hypothalamic nuclei, nucleus accumbens, stria terminalis, septal nuclei and hippocampus. 5,7-Dihydroxytryptamine (5,7-DHT; 200 micrograms, i.c.v.) markedly reduced levels of 5-HT in brain and spinal cord. In the ventral lumbar cord there was a comparable decrease of TRH and 5-HT (-80%) and a smaller but significant decrease in the nucleus accumbens (-55%) and septal nuclei (-38%). p-Chlorophenylalanine (PCPA; 250 mg/kg X 2) reduced levels of 5-HT (-80%), without significantly altering those of noradrenaline. p-Chlorophenylalanine also significantly reduced levels of TRH in the nucleus accumbens (-72%) but not in the other regions of brain or spinal cord taken. The results are discussed in relation to the previously described co-existence of TRH and 5-HT in the spinal cord and the possible alternative forms of interactions between amine and peptide in the nucleus accumbens.

5,7-Dihydroxytryptamine↗
PubMed1984

A comparison of the locomotor effects induced by centrally injected TRH and TRH analogues.

Thyrotrophin-releasing hormone (TRH) and its stable analogues CG3509 and RX77368 were injected directly into the nucleus accumbens, septum and striatum of the rat and locomotor activity was recorded. TRH (5-20 micrograms) caused a dose-dependent increase in locomotor activity when injected into the nucleus accumbens. TRH (20 micrograms) also increased locomotor activity after administration into the septum but not when put into the striatum. Both the TRH analogues (0.1 and 1.0 microgram) produced closely related increases in activity when injected into either the nucleus accumbens or septum but CG3509 was more potent with a longer lasting effect. Also, in contrast with TRH (20 micrograms), both TRH analogues stimulated locomotor activity when injected into the striatum at a dose of 1 microgram but the effect was less marked and delayed in onset compared to the nucleus accumbens and septum response. Dopamine (100 micrograms) injected into the accumbens or septum also produced significant increases in locomotor activity. The locomotor effects of the peptides are discussed in relation to a possible dopamine-mediated mechanism which contrasts with the actions of TRH and the analogues on barbiturate anaesthesia.

Animals↗
PubMed1984

Changes in monoamine metabolites measured by simultaneous in vivo differential pulse voltammetry and intracerebral dialysis.

A direct comparison has been made of the drug-induced changes in extracellular levels of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid measured using intracerebral dialysis and differential pulse voltammetry with carbon fibre electrodes. The comparison was carried out in chloral hydrate anaesthetized rats with a pretreated carbon fibre electrode implanted in one striatum and an intracerebral dialysis loop in the contralateral striatum. 3,4-Dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid in the dialysis perfusates were assayed by high pressure liquid chromatography with electrochemical detection. d-Amphetamine (2 mg/kg) decreased extracellular 3,4-dihydroxyphenylacetic acid and the height of the 3,4-dihydroxyphenylacetic acid oxidation peak, while haloperidol (0.5 mg/kg) increased 3,4-dihydroxyphenylacetic acid levels measured in the perfusates and the height of the 3,4-dihydroxyphenylacetic acid oxidation peak. In these experiments there were parallel changes in 3,4-dihydroxyphenylacetic acid levels and peak height and a close correlation between these changes. Tranylcypromine (10 mg/kg) produced an almost parallel decrease in extracellular 5-hydroxyindoleacetic acid (dialysis) and the height of the 5-hydroxyindoleacetic acid oxidation peak, with similar percentage changes and good correlation values being obtained. However, while 5-hydroxy-L-tryptophan (25 mg/kg) increased both the 5-hydroxyindoleacetic acid levels and the height of the 5-hydroxyindoleacetic acid oxidation peak, 5-hydroxyindoleacetic acid in the dialysis perfusates showed a greater increase than the oxidation peak. The results show a close correlation between changes in extracellular 3,4-dihydroxyphenylacetic acid and its respective voltammetric peak and strongly support the use of in vivo differential pulse voltammetry for monitoring dopamine metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Quantification of morphologic, cytologic, and kinetic parameters of unirradiated swine skin: a histologic model.

The gross changes of erythema and desquamation produced by irradiation indicate population and functional variations occurring in the epidermis, microvasculature, and dermis. However, the parameters do not distinguish the individual population kinetics. This study determines multiple histologic and cell kinetic parameters of unirradiated swine skin. The prickle cell layer exists as a shell three to six cells thick. The proliferative basal layer exists as a confluent monolayer with 2031 +/- 48 cells/cm; it has a growth fraction of 1, an average cell generation time of 12.3 +/- 2.4 days, a TS of 9.4 +/- 2.9 hr, and a TS + T1/2M of 17 to 19 hr. The labeling index is 3.9 +/- 0.1% with a diurnal variation having a 5% peak at 1800 hr and a 2.5% nadir at 0900-1100 hr. The mitotic index varies from 1.7 to 3.2% and has no clear-cut diurnal variation. These values are similar to those available for man. These data and those published previously are utilized to define a histologic model of the irradiated epidermal cell renewal system. These measured values are compared with those derived from analysis of available time-dose isoeffect data using a single-hit multitarget and a linear-quadratic model. The derived dose-survival curve is steeper with a D0 between 97 and 255 rad compared to the measured value of 337 rad.

Animals↗
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↗
PubMed1983

The ramp injection of radiotracers for blood flow measurement by emission tomography.

A prototype instrument based on the coincidence detection of annihilation radiation was built to control the arterial concentration of a radionuclide as a uniformly increasing ramp function over a preset injection interval (ranging from 1.6 min to 13.6 h). The device was designed to accommodate radionuclides of different physical and biological half-life, and the physiological characteristics of the system being studied. A kinetic model based on the Kety-Schmidt integral was developed to permit the determination of cerebral blood flow (CBF). Both the kinetic model and the ramp injector were tested in cats studied with the PETT III positron emission tomograph and 4-(18F)-fluoroantipyrine as the CBF tracer. The ratio lambda/f of the brain-to-blood partition coefficient (lambda) and blood flow (f) were determined simultaneously by serial measurements with positron emission tomography.

Animals↗
PubMed1983

Quantitative autoradiography with radiopharmaceuticals, Part 1: Digital film-analysis system by videodensitometry: concise communication.

A simple low-cost digital film-analysis system using videodensitometry was developed to quantitate autoradiograms. It is based on a TV-film analysis system coupled to a minicomputer. Digital sampling of transmitted light intensities through the autoradiogram is performed with 8-bit gray levels according to the selected array size (128 X 128 to 1024 X 1024). The performance characteristics of the system provide sufficient stability, uniformity, linearity, and intensity response for use in quantitative analysis. Digital images of the autoradiograms are converted to radioactivity content, pixel by pixel, using step-wedge standards. This type of low-cost system can be installed on conventional mini-computers commonly used in modern nuclear medical facilities. Quantitative digital autoradiography can play an important role, with applications stretching from dosimetry calculations of radiopharmaceuticals to metabolic studies in conjunction with positron-emission tomography.

Animals↗
PubMed1982

Co-existence of thyrotrophin releasing hormone and 5-hydroxytryptamine in the skin of Xenopus laevis.

1. The location, release and re-synthesis of thyrotrophin releasing hormone (TRH) and 5-hydroxytryptamine (5-HT) in the skin of Xenopus laevis (the South African clawed toad) have been determined using both morphological and analytical procedures. 2. High levels of TRH and 5-HT are located specifically within the dermal granular glands of X. laevis and discharged from these glands following alpha-adrenergic stimulation. 4. The common occurrence and separate production of high levels of TRH and 5-HT in amphibian skin may provide a model for studying the mechanisms of biosynthesis, interaction and release of these substances in mammalian tissues such as ventral spinal cord, where TRH and 5-HT are found in the same neurones.

Animals↗
PubMed1982

Localization and release of 5-hydroxytryptamine thyrotrophin releasing hormone and substance P in rat ventral spinal cord.

1. The highest spinal cord levels of 5-hydroxytryptamine (5-HT) and thyrotrophin releasing hormone (TRH) were found in the ventral lumbar cord, in contrast to substance P which was found predominantly in the dorsal cord. 2. 5,6- and 5,7-dihydroxytryptamine, administered into the lateral ventricles reduced 5-HT in the dorsal and ventral spinal cord by up to 90%. 3. There was a parallel reduction in substance P and TRH in ventral spinal cord while methionine-enkephalin and somatostatin in ventral and dorsal cord increased. 4. Reserpine and tetrabenazine depleted 5-HT and partially depleted substance P and TRH in the ventral cord, but had no effect on either methionine-enkephalin or somatostatin. 5. The rates of loss and recovery, after reserpine and tetrabenazine, of 5-HT were different from those of the two peptides. 6. Endogenous 5-HT and TRH release from slices of lumbar cord was enhanced by high potassium. 7. p-Chloroamphetamine and fenfluramine increased 5-HT release but reduced or had no effect on TRH release. The effect of p-chloroamphetamine on TRH release was not dependent on either the presence of 5-HT or 5-HT receptor activity. 8. The results are discussed in terms of the possible co-existence, co-storage and release of 5-HT, substance P and TRH in descending bulbospinal neurones.

Animals↗
PubMed1982

The effects of monoamine neurotoxins on peptides in the rat spinal cord.

The coexistence of two neuronally-localised peptides, substance P and thyrotropin-releasing hormone (TRH), in descending serotoninergic nerve fibres to the spinal cord was investigated using immunocytochemical and biochemical methods. Substance P-like material in the spinal cord was shown to be identical to the undecapeptide substance P by the criteria of gel filtration, high performance liquid chromatography and behaviour in substance P specific radioimmunoassays. Immunocytochemical staining for 5-hydroxytryptamine, substance P, and TRH showed that all three substances had a similar distribution in nerve fibres and terminals in the ventral and lateral grey matter of the spinal cord. After treatment with the serotonin neurotoxin 5,7-dihydroxytryptamine, neuronal elements containing 5-hydroxytryptamine, substance P and TRH degenerated and disappeared from these parts of the spinal cord in parallel with one another. Biochemical measurements of 5-hydroxytryptamine, substance P and TRH in the spinal cord after treatment with 5,7-dihydroxytryptamine confirmed that these three substances were all depleted from the ventral horn and, in addition, showed that there was a small depletion of substance P from the dorsal horn. Two other neuropeptides, somatostatin and methionine-enkephalin were not depleted from the spinal cord by treatment with 5,7-dihydroxytryptamine nor was substance P in other parts of the brain. Substance P in the spinal cord was unaffected by 6-hydroxydopamine, a drug known to destroy catecholamine-containing neurones. These results are consistent with coexistence of substance P and TRH together with 5-hydroxytryptamine in the descending axons and terminals of bulbospinal neurones.

5,6-Dihydroxytryptamine↗
PubMed1982

Thyrotrophin-releasing hormone analogues increase dopamine release from slices of rat brain.

Rat brain slices were incubated with a high concentration of K+, thyrotrophin-releasing hormone (TRH), or one of two biologically stable TRH analogues (CG 3509 or RX 77368). Basal release of endogenous dopamine, measured by electrochemical detection, was increased by K+ (30 mM) from slices of hypothalamus, septum, nucleus accumbens, and striatum. CG 3509 (10-(5) -10-(3) M) increased the release of dopamine from slices of nucleus accumbens, septum, and hypothalamus in a dose-dependent fashion, whereas RX 77368 (10-(4) M) increased the release of dopamine from the septum only. Neither analogue increased the release of striatal dopamine. The results provide further evidence for specific regional interactions between TRH and dopamine in rat brain.

Animals↗
PubMed1982

A computer linear regression model to determine ventilatory anaerobic threshold.

The anaerobic threshold has generally been determined by simple visual inspection of ventilation or other gas-exchange data obtained during incremental exercise. To establish objective criteria for the determination of anaerobic threshold, a computer algorithm has been developed that models the ventilatory response to exercise using multisegment linear regression. The best-fit regression model is chosen by minimizing the pooled residual sum of squares . The anaerobic threshold is reported as the first break point in that model. The computer-determined anaerobic threshold values for 37 subjects were compared with subjectively determined values as chosen by four independent observers. The observers' estimates, when pooled to yield a single a single value for each subject, gave a mean value for the gas-exchange anaerobic threshold of 2.26 +/- 0.69 l/min. The estimates by the computer method averaged 2.21 +/- 0.65 l/min. The correlation coefficient for these two methods was 0.94.

Adult↗
PubMed1981

The effects of 5-hydroxytryptamine-depleting drugs on peptides in the ventral spinal cord.

The ventral spinal cord content of several neuronally localised peptides was measured after treatment with a number of drugs which deplete spinal cord monoamines. Reserpine and tetrabenazine, but not p-chlorophenylalanine caused a partial depletion of ventral spinal cord substance P (SP) and thyrotropin-releasing hormone (TRH). Two other peptides, methionine-enkephalin and somatostatin were not depleted by any of the drugs. The rates of loss and recovery of SP and TRH after reserpine and tetrabenazine were different from that of 5-hydroxytryptamine (5-HT), though in the ventral spinal cord these two peptides probably coexist with 5-HT in the terminals of bulbospinal neurones. The results are discussed in relation to the possible costorage of SP and TRH with 5-HT in the same vesicles in nerve terminals in the ventral spinal cord.

Animals↗