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T Sharp

Publications and source records attributed to T Sharp.

176 records · Page 10Linked to original sources

Biochemical evidence for the regulation of central noradrenergic activity by 5-HT1A and 5-HT2 receptors: microdialysis studies in the awake and anaesthetized rat.

Here we have studied the effect of various 5-HT1A and 5-HT2 receptor-selective drugs on noradrenaline release in the hippocampus on anaesthetized and awake rats using microdialysis. In the anaesthetized rat, administration of the 5-HT1A agonists buspirone, gepirone and ipsapirone increased noradrenaline levels in the microdialysates. However, the common metabolite of these compounds, 1-PP (an alpha-2 adrenoceptor antagonist with low affinity for 5-HT1A receptors), also increased noradrenaline efflux whilst the 5-HT1A receptor agonist 8-OH-DPAT and MDL 73005EF, which are not metabolized to 1-PP, did not. In the awake rat, buspirone but also 8-OH-DPAT increased noradrenaline efflux. A similar effect was observed in response to MDL 73005EF and the 5-HT1A ligand NAN-190. Since the latter two drugs have weak intrinsic activity at the post-versus presynaptic 5-HT1A receptor, a presynaptic mechanism (inhibition of 5-HT release) was implicated. The 5-HT2 receptor may be important to this mechanism as noradrenaline increased following administration of the 5-HT2 receptor antagonists, ritanserin and ICI 170,809. In conclusion, our data indicate that there are clear differences in the effects of 5-HT1A and 5-HT2 receptor-selective drugs on noradrenaline efflux in hippocampus of the anaesthetized versus awake rat. Our findings are reconcilable with the hypothesis that in the awake (but not anaesthetized) rat, release of noradrenaline in hippocampus is influenced by an inhibitory tone mediated via 5-HT2 receptors. If this inhibitory tone is removed, either by decreasing 5-HT release through activation 5-HT1A autoreceptors or by blocking postsynaptic 5-HT2 receptors, noradrenaline release increases.

Anesthesia↗

Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on 5-HT cell firing and release: comparison between dorsal and median raphe 5-HT systems.

It is proposed that 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) is more toxic to 5-HT neurones projecting from the dorsal raphe nucleus (DRN) than to those from the median raphe nucleus (MRN). Since increased 5-HT release has been associated with MDMA-induced neurotoxicity, MDMA may have a DRN-selective 5-HT releasing effect. Here we have compared the effects of acute MDMA on DRN and MRN 5-HT pathways using in vivo electrophysiological and neurochemical techniques. MDMA inhibited the firing of 5-HT neurones in both the DRN and the MRN, and did so with similar potency (ED50 values, 0.589 +/- 0.151 (8) and 0.588 +/- 0.207 (6) mg/kg i.v., respectively). In both nuclei this inhibitory effect was reversed by the selective 5-HT1A receptor antagonist, WAY 100635 (0.1 mg/kg i.v.). Microdialysis measurements were made in the frontal cortex and dorsal hippocampus, regions which receive a DRN- and an MRN-selective 5-HT innervation, respectively. A dose of 1 mg/kg i.v. MDMA increased extracellular 5-HT 3-fold in both the frontal cortex and dorsal hippocampus. A higher dose (3 mg/kg i.v.) increased 5-HT levels 8-fold in both regions. Overall, our data suggest that MDMA releases 5-HT from the cell body and terminal regions of both DRN and MRN 5-HT pathways, and does so in a qualitatively and quantitatively similar fashion. We conclude that any DRN-selectivity in the neurotoxic effects of MDMA is not due to a DRN-selective, acute 5-HT releasing action of the drug.

Chromatography, High Pressure Liquid↗

Handling complaints in a constructive way.

This article offers advice on dealing with specific complaints and looks at the nurse's role and responsibilities in handling and resolving them.

Hospital-Patient Relations↗

Listening to carers.

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Caregivers↗

Whose problem?

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Attitude of Health Personnel↗

Functional MR imaging of the porcine kidney: physiologic changes of prolonged pneumoperitoneum.

BACKGROUND: Increased intraabdominal pressure (IPA) during laparoscopy has been associated with decreased urine output. The purpose of this study was to use a noninvasive MRI technique to measure renal vessel flow velocity and change in differential renal medulla and cortex perfusion during pneumoperitoneum. STUDY DESIGN: Six female farm pigs underwent general endotracheal anesthesia and dynamic imaging following left ventricular (LV) injection of Gd-DTPA, utilizing a dual echo gradient echo sequence. MRI was repeated after three hours of continuous 15 mm Hg pneumoperitoneum in three study pigs and after three hours of monitored general anesthesia without pneumoperitoneum in three control pigs. Renal artery and renal vein flow velocities were calculated using cine phase-contrast technique. Renal perfusion was independently measured by LV injection of radiolabelled microspheres. RESULTS: There was a decrease in mean renal vein flow velocity in the pneumoperitoneum group as compared to the control group. During pneumoperitoneum there was a similar percentage reduction in the perfusion of the cortex (-28%) and medulla (-31%); this corresponded with a decreased urine output. In addition, radiolabelled microspheres corroborated the similar decrease in both cortical and medullary perfusion rates during pneumoperitoneum. CONCLUSIONS: Prolonged IAP is associated with a decrease in renal vein flow velocity and urine output. There is a similar decrease in the renal medulla and cortex perfusion rates during pneumoperitoneum of 15 mm Hg.

Animals↗