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Biomedical subjects

A Reid

Publications and source records attributed to A Reid.

At least 19 recordsLinked to original sources
PubMed1992

Noradrenergic mediation of spinal antinociception by 5-hydroxytryptamine: characterization of receptor subtypes.

The present study examined the involvement of spinal noradrenergic mechanisms in spinal antinociception by the 5-hydroxy-tryptamine (5-HT) receptor-selective agonists CGS 12066B (5-HT1B; 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline), TFMPP (5-HT1C; M-trifluoromethylphenyl-piperazine) and DOI (5-HT2; 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) using the rat hot plate test. Effects of alpha-adrenoreceptor antagonists (phentolamine, yohimbine), the adrenergic neurotoxin 6-hydroxydopamine, and the selective noradrenergic uptake blocker desipramine were determined. CGS 12066B, TFMPP and DOI produced dose-related antinociception. The antinociceptive effect of each agent was reduced by pretreatment with both phentolamine and yohimbine (15-60 micrograms). Pretreatment with 6-hydroxydopamine (100 micrograms, intrathecal) for 7-10 days, which reduced spinal cord levels of noradrenaline by 87%, inhibited the action of TFMPP (and 5-HT), but not CGS 12066B or DOI. Pretreatment with desipramine (25 mg/kg, systemic) potentiated the action of TFMPP but not CGS 12066B or DOI (or 2-methyl-5-HT). These results suggest that antinociception by TFMPP is dependent on release of endogenous noradrenaline from the spinal cord, while that produced by CGS 12066B and DOI is not. As TFMPP exhibits a close similarity to 5-HT in these experiments, the 5-HT receptor subtype being activated to induce noradrenaline release may either be a 5-HT1C or a 5-HT1S subtype. Other mechanisms account for the observed blockade of the action of CGS 12066B and DOI by alpha-adrenoreceptor antagonists.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Noradrenergic and purinergic involvement in spinal antinociception by 5-hydroxytryptamine and 2-methyl-5-hydroxytryptamine.

The adrenergic involvement in spinal antinociception by 5-hydroxytryptamine (5-HT) and 2-methyl-5-hydroxytryptamine (2-Me-5-HT) was examined using the alpha-adrenoceptor antagonists phentolamine, yohimbine and prazosin, and the neurotoxin 6-hydroxydopamine. Intrathecal pretreatment with phentolamine and yohimbine (7.5-30 micrograms), but not prazosin (30 micrograms), reduced the action of 5-HT and 2-Me-5-HT in both the tail flick and hot plate tests. Pretreatment with 6-hydroxydopamine (100 micrograms) reduced (5-HT) or increased (2-Me-5-HT) antinociception in the hot plate test, while tail flick responses were largely unaffected. In other experiments, 8-phenyltheophylline, an adenosine receptor antagonist, reduced the action of 5-HT, but not 2-Me-5-HT, in both tests. These results indicate that (a) antinociception by both 5-HT and 2-Me-5-HT involves some form of interaction with spinal alpha 2-adrenoceptors, but the nature of the interaction for these two agents is different because only 5-HT is dependent on endogenous noradrenaline, (b) release of adenosine from the spinal cord contributes to spinal antinociception by 5-HT but not by 2-Me-5-HT.

Analgesics↗
PubMed1991

Spinal antinociception by adenosine analogs and morphine after intrathecal administration of the neurotoxins capsaicin, 6-hydroxydopamine and 5,7-dihydroxytryptamine.

The effects of intrathecal pretreatment with the neurotoxins capsaicin, 6-hydroxydopamine and 5,7-dihydroxytryptamine on spinal antinociception by adenosine analogs (NECA, 5'-N-ethylcarboxamido adenosine and CHA, N6-cyclohexyl adenosine) and morphine were examined using the rat tail flick and hot plate tests. Pretreatment with 50 micrograms capsaicin for 7 to 11 days (which reduced substance P immunoreactivity in the superficial layers of the dorsal spinal cord) produced a slight increase in the action of NECA and CHA, and reduced the action on morphine in the hot plate test but not in the tail flick test. Pretreatment with 50 to 100 micrograms 6-hydroxydopamine for 7 to 14 days (which reduced spinal cord noradrenaline levels by 54-65%) reduced spinal antinociception by NECA and CHA but not that by morphine. Pretreatment with 50 micrograms 5,7-dihydroxytryptamine (which reduced spinal cord serotonin levels by 74-89%) had no effect on any agent. Acute pretreatment with 7.5-30 micrograms phentolamine reduced the spinal antinociceptive action of noradrenaline, NECA and CHA, primarily in the hot plate test. Phentolamine (30 micrograms) also reduced the action of morphine (hot plate greater than tail flick), but did not affect the action of L-baclofen. These results suggest that spinal antinociception by adenosine analogs: 1) occurs primarily at a postsynaptic site of action (capsaicin results), and 2) is dependent on release of endogenous noradrenaline and activation of spinal adrenergic receptors (6-hydroxydopamine and phentolamine results). The reduction in the effect of morphine by capsaicin (removes a source of adenosine release) and phentolamine (antagonizes the action of endogenously released adenosine) can be explained in terms of the adenosine release hypothesis of morphine action within the spinal cord.

5,7-Dihydroxytryptamine↗
PubMed1991

8-Phenyltheophylline reverses the antinociceptive action of morphine in the periaqueductal gray.

Morphine was injected into the periaqueductal gray region of the rat and 8-phenyltheophylline, an adenosine receptor antagonist, was injected intrathecally 15 or 30 min later, to determine whether supraspinally-administered morphine activated descending mechanisms to release adenosine (or a nucleotide which is metabolized to adenosine) from the spinal cord. 8-Phenyltheophylline (10 micrograms) reversed the antinociceptive action of morphine in the hot plate but not the tail-flick test. A combination of methysergide/phentolamine (15 micrograms each) reversed the action of morphine in both tests. 8-Phenyltheophylline retained the ability to reverse the action of morphine in the hot plate test in rats pretreated with 6-hydroxydopamine (to induce degeneration of descending noradrenergic pathways) but reversal was no longer observed in rats pretreated with 5,7-dihydroxytryptamine (after pretreatment with desipramine, to induce degeneration of descending serotonergic pathways). These results indicate that a component of the supraspinal antinociceptive action of morphine is due to release of adenosine or nucleotide, within the spinal cord and this release is dependent on intact serotonergic pathways.

5,7-Dihydroxytryptamine↗
PubMed1991

Effects of forskolin and phosphodiesterase inhibitors on spinal antinociception by morphine.

The effect of intrathecal pretreatment with forskolin and the phosphodiesterase inhibitors Ro 20-1724, rolipram and 3-isobutyl-1-methylxanthine (IBMX) on the antinociceptive action of morphine administered intrathecally was examined using the rat tail-flick test to determine whether inhibition of adenylate cyclase contributed to spinal antinociception. Intrathecal pretreatment with forskolin (10 micrograms), Ro 20-1724 (15 micrograms) and IBMX (10 micrograms) inhibited the action of morphine in the tail-flick test. However, pretreatment with Ro 20-1724 (30 micrograms), rolipram (10 and 30 micrograms) and IBMX (30 micrograms) increased the action of morphine. These agents were devoid of intrinsic antinociceptive activity. Inhibition of spinal antinociception by morphine with agents which increase cyclic AMP levels in biochemical experiments is consistent with the hypothesis that some opiate actions are due to inhibition of adenylate cyclase. However, in view of the consistent increase in the effect of morphine with phosphodiesterase inhibitors at higher doses, this hypothesis may be insufficient to account for opiate interactions with the adenylate cyclase system in the spinal cord. Some effects on spinal antinociception also may be due to additional pharmacological actions of the agents used.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Survival of cancer of the larynx related to treatment.

Analysis of 3445 cases of cancer of the larynx has been made with reference to primary (first) and secondary treatments. It is easy to confirm that while radiotherapy is inferior to laryngectomy in the cure of larger glottic tumours, it is preferable in many cases because salvage surgery is possible and successful. Salvage surgery cannot be shown to be successful in larger supraglottic tumours, which should be considered for primary surgery. Radiotherapy appears better than surgery for small tumours.

Carcinoma, Squamous Cell↗
PubMed1991

Isochronic mapping: a preliminary report of a new technique.

A new technique which we have named 'isochronic mapping' is described. The conventional technique of plotting isopotential maps shows little or no contrast for far-field potentials such as the auditory brainstem response (ABR). However, by modifications to the mapping software, the latency values of a peak can be plotted and lines of equal time or isochronic maps can be produced. Data from a normal subject has been obtained for both the compound and derived ABRs and are described in detail. The data are clear but the time delays between earliest and latest projections of a peak are hard to interpret. For monaural click stimulation, wave JV of the ABR projects first to the contralateral side of the head then moves towards the stimulated ear arriving some 0.3 ms later. Possible interpretations of this finding are discussed but further experimentation is needed to develop our understanding of these data.

Acoustic Stimulation↗
PubMed1991

Labeling by [3H]1,3-di(2-tolyl)guanidine of two high affinity binding sites in guinea pig brain: evidence for allosteric regulation by calcium channel antagonists and pseudoallosteric modulation by sigma ligands.

Equilibrium binding studies with the sigma receptor ligand [3H]1,3-di(2-tolyl)guanidine ([3H]DTG) demonstrated two high affinity binding sites in membranes prepared from guinea pig brain. The apparent Kd values of DTG for sites 1 and 2 were 11.9 and 37.6 nM, respectively. The corresponding Bmax values were 1045 and 1423 fmol/mg of protein. Site 1 had high affinity for (+)-pentazocine, haloperidol, (R)-(+)-PPP, carbepentane, and other sigma ligands, suggesting a similarity with the dextromethorphan/sigma 1 binding site described by Musacchio et al. [Life Sci. 45:1721-1732 (1989)]. Site 2 had high affinity for DTG and haloperidol (Ki = 36.1 nM) and low affinity for most other sigma ligands. Kinetic experiments demonstrated that [3H]DTG dissociated in a biphasic manner from both site 1 and site 2. DTG and haloperidol increased the dissociation rate of [3H]DTG from site 1 and site 2, demonstrating the presence of pseudoallosteric interactions. Inorganic calcium channel blockers such as Cd2+ selectively increased the dissociation rate of [3H]DTG from site 2, suggesting an association of this binding site with calcium channels.

Animals↗
PubMed1991

Inner ear deafness in Wegener's granulomatosis.

Autoimmune deafness represents a heterogeneous group of disorders in which there is though to be inner ear and/or middle ear damage mediated by various immunological abnormalities. We describe a patient with Wegener's granulomatosis in whom there was evidence of significant inner ear damage caused by vasculitis, which was completely reversed by cyclophosphamide and prednisolone. We propose that Wegener's granulomatosis is a cause of autoimmune deafness.

Adult↗
PubMed1991

Effect of repeated intraperitoneal chemotherapy with epirubicin on the hepatic transport of bile acids and their enterohepatic circulation.

The effect of repeated intraperitoneal perfusion with epirubicin on the clearance of 14C-taurocholate by the liver and the enterohepatic circulation of the synthetic bile acid 75-SeHCAT were investigated using a rat model. After six treatments there was no significant difference in the transport rate constants (plasma to liver, liver to bile and liver to plasma) between and within the saline and epirubicin groups. Similarly, there were no differences detected between the groups for the parameters derived from these transport rate constants. Thus the initial plasma clearance after six perfusions was 39 +/- 9, and 36 +/- 11 ml/min/kg in the epirubicin and saline groups respectively. The excretory efficiency of the liver at this stage was identical: 67 +/- 10% in the epirubicin treated animals and 67 +/- 6% in the saline controls. A deterioration in the SeHCAT retention was observed after repeated intraperitoneal perfusion in both groups. This was significant only in the cytotoxic group, between the first and sixth epirubicin perfusion: 59 +/- 9% vs 48 +/- 9% at 24 h (P = 0.03), 31 +/- 8% vs 22 +/- 5% at 48 h (P = 0.019) and was not cumulative beyond this stage. These findings indicate that repeated intraperitoneal perfusion chemotherapy with epirubicin does not impair bile acid clearance by the hepatocyte. The decrease in the retention of SeHCAT is unlikely to be the result of epirubicin-induced ileal mucosal damage since the reduction was not cumulative beyond 48 h of administration of the compound.

Animals↗
PubMed1990

Adenosine mediates calcium-induced antinociception and potentiation of noradrenergic antinociception in the spinal cord.

Intrathecal (i.t.) coadministration of calcium (Ca2+), 50 micrograms potentiates the spinal antinociceptive action of morphine and noradrenaline (NA) but not cyclohexyladenosine, 5'-N-ethylcarboxamido adenosine or 5-hydroxytryptamine in the rat tail flick test. This dose of Ca2+ has no intrinsic effect in this test. Higher doses of Ca2+ (200-400 micrograms) produce antinociception in the tail flick and hot plate tests, which is completely blocked by pretreatment with the adenosine receptor antagonists theophylline, 50 micrograms and 8-phenyltheophylline, 3 micrograms. 8-Phenyltheophylline also eliminates potentiation of the antinociceptive action of NA by 50 micrograms Ca2+. The intrinsic antinociceptive effect of Ca2+ is blocked by i.t. pretreatment with the neurotoxins capsaicin, 50 micrograms and 6-hydroxydopamine, 50 micrograms but not 5,7-dihydroxytryptamine, 50 micrograms. Antinociception also is blocked by pretreatment with phentolamine but not by methysergide. These results suggest that the antinociceptive action of high doses of Ca2+ is due to release of adenosine (or a nucleotide which is metabolized to adenosine) from the spinal cord. At lower doses, the release of adenosine is insufficient to cause antinociception, but potentiates the action of NA. Adenosine appears to originate from capsaicin-sensitive small diameter primary afferent nerve terminals. A subsequent interaction of adenosine with spinal adrenergic receptors contributes to antinociception.

5,7-Dihydroxytryptamine↗
PubMed1990

Supersensitivity to intrathecal 5-hydroxytryptamine, but not noradrenaline, following depletion of spinal 5-hydroxytryptamine by 5,7-dihydroxytryptamine administered into various sites.

The present study was conducted (a) to determine if cross-supersensitivity at spinal noradrenergic receptors could be demonstrated in antinociceptive tests following depletion of spinal cord 5-hydroxytryptamine (5HT) by the intrathecal (i.t.) and intracerebroventricular (i.c.v.) administration of 5,7-dihydroxytryptamine (5,7DHT), and (b) to compare the pattern of supersensitivity at spinal 5HT receptors following these manipulations and 5,7DHT microinjected into the ventral raphe (VR) region and the nucleus raphe magnus (NRM). Both i.t. and i.c.v. administration of 5,7DHT produced a marked depletion of spinal cord 5HT (greater than 75%) and supersensitivity to the i.t. injection of 5HT in the tail flick and hot plate tests. No supersensitivity to the i.t. injection of noradrenaline (NA) was observed. Microinjection of 5,7DHT into the VR and NRM produced less depletion of spinal cord 5HT (40-57%), and supersensitivity to the i.t. injection of 5HT was observed only in the hot plate test following microinjection of 5,7DHT into the VR. An increased incidence of signs of the 5HT behavioural syndrome, particularly tremor and Straub tail, was observed in all 5,7DHT-pretreated groups. These results indicate that cross-supersensitivity to spinal NA receptors does not occur following depletion of spinal cord 5HT. In addition, responses mediated by 5HT receptors show a differential pattern of development of supersensitivity. Thus, the 5HT behavioural syndrome (presumably mediated by 5HT1A receptors) more readily reflects the development of supersensitivity than the tail flick test (presumably mediated by 5HT2 receptors), while the hot plate test (uncharacterized subtype) shows an intermediate development of supersensitivity.

5,7-Dihydroxytryptamine↗
PubMed1990

Cochlear and cerebrospinal fluid pressure: their inter-relationship and control mechanisms.

The patency of the cochlear aqueduct is a key factor in intra-cochlear hydromechanics. If patent, the cerebrospinal fluid (CSF) provides the reference pressure for the perilymph and also to a large extent the endolymph, since Reissner's membrane can only withstand a relatively small pressure differential. The aqueduct often becomes sealed as a natural process of ageing. In this instance the reference pressure is from a source, its position unknown, within the boundaries of the cochlea itself. Relatively large and rapid changes in the cerebrospinal fluid pressure may result from everyday events such as coughing (ca. 175 mm saline) and sneezing (ca. 250 mm saline). The resistive nature of the cochlear aqueduct and the mechanical compliance of the cochlear windows are probably important factors in limiting the amount of stress, and therefore possible damage, which may occur to the cochlea and cochlear windows for a given pressure change within the CSF system. A narrow aqueduct and compliant cochlear windows reduce the risk of structural damage. In practice, this should mean that the risk of structural damage will be increased by any process which reduces the compliance of one or both of the cochlear windows, for example, extremes of middle ear pressure perhaps brought about by Eustachian tube dysfunction or rapid barometric pressure changes. Techniques are now available which provide non-invasive indirect measures of perilymphatic pressure and CSF-perilymphatic pressure transfer. The tympanic membrane displacement measurement technique has been used to provide reliable measures of perilymphatic pressure and CSF-perilymphatic pressure transfer on an individual subject basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗