PubMed Health⌕ Search

Biomedical subjects

D Slater

Publications and source records attributed to D Slater.

At least 19 recordsLinked to original sources
PubMed1992

Thermogenic actions of tryptophan in the rat are mediated independently of 5-HT.

Serotonin (5-HT) has been implicated in the central control of energy balance, via inhibition of food intake and stimulation of thermogenesis. Its rate of synthesis in brain is dependent on the availability of its precursor amino acid, tryptophan. The objective of the present study was therefore to investigate the thermogenic actions of tryptophan and to determine whether these actions are mediated by 5-HT. Central or peripheral injections of 5-HT (i.c.v.; 0.5-40 micrograms), 5-hydroxytryptophan (5-HTP) (i.c.v.; 20 micrograms) or tryptophan (i.p.; 20 mg/kg, i.c.v.; 12-60 micrograms) significantly increased resting oxygen consumption (VO2 by approximately 15-20%) in conscious rats, without apparent effects on physical activity. Small increases (5-7%) in VO2 were also observed following peripheral injections of aspartate or glycine (20 mg/kg) but not taurine, whilst central injections of tyrosine or leucine (15-18 micrograms) significantly increased VO2 by 15%. We have previously reported that the thermogenic and anorexic actions of 5-HT are mediated by corticotropin-releasing factor (CRF). In the present study, the thermogenic actions of 5-HTP, like those of 5-HT, were significantly reduced by pretreatment (5 min before) with the CRF antagonist alpha-helical CRF9-41 (25 micrograms, i.c.v.) or a polyclonal antibody to CRF. However, the thermogenic actions of tryptophan were not significantly modified by pretreatment with either the 5-HT antagonist, methysergide (20 micrograms, i.c.v.) or with the CRF antagonist or antibody and thus appear to act through different mechanisms to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗
PubMed1992

Use of the nirB promoter to direct the stable expression of heterologous antigens in Salmonella oral vaccine strains: development of a single-dose oral tetanus vaccine.

Plasmid pTETnir15, which directs the expression of the non-toxic immunogenic fragment C of tetanus toxin from the anaerobically inducible nirB promoter, was introduced into the Salmonella typhimurium aroA aroD live oral vaccine strain BRD509. The resulting strain, designated BRD847, was used to vaccinate orally BALB/c mice and was tested for plasmid stability and its ability to protect against a lethal tetanus toxin challenge. pTETnir15 was stably inherited by bacteria growing or persisting in the tissues of immunized mice whereas another BRD509 derivative, designated BRD753, harboring plasmid pTET85 which directs fragment C expression from the tac promoter, was highly unstable. Mice immunized with a single oral dose of BRD847 developed high levels of circulating anti-fragment C antibodies and were solidly protected against tetanus toxin challenge. Mice immunized with a single oral dose of BRD753 developed no detectable anti-fragment C antibodies. After boosting, antibodies were detected, but the mice were only partially protected against tetanus toxin challenge. Thus the use of an in vivo inducible promoter such as nirB may be a generally applicable approach to obtaining the stable in vivo expression of heterologous antigens in Salmonella vaccine strains.

Anaerobiosis↗
PubMed1992

Influence of cardiopulmonary bypass on water balance hormones in children.

OBJECTIVE: To determine the changes in the endocrine mechanisms of fluid balance after cardiopulmonary bypass in children. DESIGN: Prospective study; analysis of numbered plasma samples performed blind with respect to clinical data. SETTING: Regional paediatric cardiothoracic unit. PATIENTS: Nine patients, median age 4, range 2 to 9 years, five males. Patients under the age of 1 year were excluded because of the frequent blood sampling involved. MAIN OUTCOME MEASURES: Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin, plasma renin activity, aldosterone, noradrenaline and adrenaline, and urinary concentrations of cyclic guanosine monophosphate (cGMP) as measured by radioimmunoassay. RESULTS: After 30 minutes of cardiopulmonary bypass plasma atrial natriuretic peptide (ANP) decreased from (mean (SEM)) 151 (71) pg/ml to 52 (44) pg/ml (NS), and urinary production of its second messenger cyclic guanosine monophosphate (cGMP) decreased from 1286 (600) pmol/ml to 151 (414) pmol (p < 0.05). Other plasma concentrations of hormones studied did not change significantly although arginine vasopressin, adrenaline, and noradrenaline increased whereas aldosterone and plasma renin activity decreased. After cardiopulmonary bypass stopped there was an immediate and significant rise in plasma ANP, but within the next 24 hours plasma ANP declined significantly (p < 0.05), decreasing from 294 (49) pg/ml to 64 (29) pg/ml at 22 hours. In the postoperative period there was a significant correlation between plasma ANP and both mean fluid balance (r = 0.96, p < 0.001) and mean urine output (r = 0.97, p < 0.001). Plasma aldosterone peaked (p < 0.05) at 22 hours after operation, and argine vasopressin peaked (p < 0.05) at two hours and then declined (p < 0.05) to a trough at 24 hours. Plasma renin activity, adrenaline, noradrenaline, and urinary cGMP concentrations, and mean central venous pressure did not change significantly in the postoperative period. CONCLUSION: The changes documented show the differing pattern of release of water balance hormones invoked by cardiopulmonary bypass. The central role of ANP is shown by its strong correlation with urinary output and its similarly strong relation to fluid balance.

Aldosterone↗
PubMed1991

Ultrastructure of melatonin-responsive cells in the ovine pars tuberalis.

Functional receptors for melatonin have been localized and characterized on the pars tuberalis (PT) of a number of mammalian species, but the cell-type responsive to melatonin is unknown. The ultrastructure of the ovine pars tuberalis has been examined and these findings correlated with the functional response of the gland to melatonin. This study revealed that two secretory cell types predominate in the ovine PT, which differ in the abundance of dense-core granules. The most abundant of the cells are either agranular or very sparsely granulated and represent 90% of the total population, with the remaining 10% being composed of cells with abundant dense-core vesicles. Few follicular cells were observed. This ratio of secretory cell-types persisted in primary culture, with the two types non-separable by Percoll gradient centrifugation. Using forskolin, as a non-specific stimulant of adenylate cyclase, melatonin was shown to inhibit the formation of cyclic AMP by 80-90% in cells both before and after Percoll centrifugation. The results demonstrate that the agranular secretory cells of the ovine pars tuberalis are the melatonin responsive cell-type of this gland.

Animals↗
PubMed1988

Automatic implantable scanning burst pacemakers for recurrent tachyarrhythmias.

Ninety patients (13 patients with supraventricular tachycardia and 72 patients with ventricular tachycardia) underwent electrophysiological study. Six out of 18 patients with supraventricular tachycardia (33%) and one out of 72 patients with ventricular tachycardia (1.4%) were considered suitable candidates for the scanning pacemaker. However, only six of the seven patients underwent implantation. The seventh patient decided not to undergo implantation and continued to have recurrent episodes of supraventricular tachycardia. The scanning pacemaker delivers extrastimuli at preset initial and coupled delay after four cycles of tachycardia. If tachycardia is not terminated, another set of extrastimuli are delivered with a decrement in the coupling cycle. During the follow-up period of 7-25 months (mean, 14.3 months), tachycardia cycle lengths and termination windows changed in four patients. The pacemakers in these patients were reprogrammed multiple times (2 to 6 times with a mean of 3.5) as the previous number of extrastimuli and intervals were ineffective in the termination of tachycardias. The major limitations of the extrastimulus pacemaker were: 1) only a small percentage of patients were suitable candidates for its use; (2) the initially selected termination window in the majority of patients was ineffective during the follow-up period due mainly to the changes in tachycardia cycle length and subsequent termination windows; and (3) the majority (five out of six patients in this series) of patients needed additional pharmacologic therapy to modify their tachycardia rates. However, despite these limitations, the scanning pacemaker may be an additional tool in the management of recurrent tachyarrhythmias in selected patients.

Adult↗