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Biomedical subjects

A Doble

Publications and source records attributed to A Doble.

At least 73 records · Page 4Linked to original sources
PubMed1992

Pharmacological characterization of RP 62203, a novel 5-hydroxytryptamine 5-HT2 receptor antagonist.

1. RP 62203 (2-[3-(4-(4-fluorophenyl)-piperazinyl)propyl]naphto[1,8- ca]isothiazole-1,1-dioxide) is a novel naphtosultam derivative which shows very high affinity for 5-HT2 receptors in the rat cerebral cortex (Ki = 50.0 pM). 2. RP 62203 is relatively selective for this sub-type of 5-hydroxytryptamine (5-HT) receptor, having lower affinity for the 5-HT1A receptor and very low affinity for the 5-HT, receptor. RP 62203 displayed low to moderate affinity for alpha 1-adrenoceptors, dopamine D2 receptors and histamine H1 receptors. 3. In vivo binding experiments demonstrated that oral administration of low doses of RP 62203 led to a long-lasting (greater than 6 h) occupation of cortical 5-HT2 receptors (ID50 = 0.39 mgkg-1). 4. In cortical slices from the neonatal rat, RP 62203 potently inhibited inositol phosphate formation evoked by 5-HT, with an IC50 of 7.76 nM. 5. The activity of neurones in the raphé and their responses to microiontophoretically applied 5-HT were studied with extracellular recording electrodes in the anaesthetized rat. RP 62203 potently and dose-dependently blocked excitations evoked by 5-HT when administered at doses of 0.5-4.0 mg kg-1, i.p. In contrast, neither 5-HT-evoked depressions nor glutamate-evoked excitations of raphé neuronal firing were blocked by RP 62203 at doses as high as 8.0 mg kg-1, i.p. 6. Head twitches induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) could be abolished by low doses of RP 62203 in mice (ED50 = 0.44 mg kg-1, p.o.) and in rats (ED50 = 1.54 p.o.). Similar results were obtained with mescaline and 5-hydroxytryptophan (5-HTP). 7. The potency of RP 62203 was compared with that of three other 5-HT2 receptor antagonists, ritanserin, ICI 169,369 and ICI 170,809. In all models, RP 62203 showed similar activity to ritanserin, whilst either ICI 169,369 or ICI 170,809 was several fold less active. 8. It is concluded that RP 62203 is a potent and selective antagonist at 5-HT2 receptors in the rodent central nervous system.

Action Potentials↗
PubMed1992

A rapid filtration assay for the glycine binding site on the NMDA receptor in rat cortical membranes using [3H]dichlorokynurenic acid.

A filtration binding assay using [3H]dichlorokynurenic acid to label the glycine binding site on the N-methyl-D-aspartic acid receptor has been evaluated on rat cortical membranes. This ligand binds to a single population of binding sites following mass action kinetics with a KD of 29 nM and a capacity of 5.73 pmol (mg protein)-1. The pharmacological specificity of the binding site is identical to that previously reported for this binding site using [3H]glycine as a radioligand. Agonists showed lower affinity and antagonists higher affinity when [3H]dichlorokynurenic acid was used compared with [3H]glycine. The higher affinity of [3H]dichlorokynurenic acid compared with [3H]glycine make it the more suitable compound with which to label the glycine site.

Animals↗
PubMed1992

Potassium markedly potentiates the effect of veratridine on dopamine release from rat superfused striatal ribbons.

The effects of veratridine-induced depolarization on [3H]dopamine ([3H]DA) release in the presence of a physiological (5 mM) or a depolarizing (25 mM) concentration of K+ were studied in-vitro in rat superfused striatal ribbons. A combination of the two depolarizing agents induced a marked potentiation in the overflow of [3H]DA, giving an overall 3- to 5-fold increase in veratridine activity. This potentiation was completely antagonized by tetrodotoxin (100 nM). These studies indicated that K(+)-induced depolarization can increase the potency of veratridine in releasing dopamine from terminals.

Animals↗
PubMed1991

Possible involvement of nitric oxide in long-term potentiation.

Long-term potentiation (LTP) in the hippocampus is known to involve NMDA (N-methyl-D-aspartate) receptors. Since activation of NMDA receptors in the cerebellum results in the formation of nitric oxide (NO), we studied the possible involvement of this messenger in hippocampal synaptic plasticity. We report here that the NO-synthase inhibitor, L-N omega-nitro-arginine, blocks LTP and that sodium nitroprusside, which releases NO, produces a long-lasting enhancement in synaptic efficacy which is not additive with tetanus-induced LTP.

Animals↗
PubMed1991

Prostatodynia and herpes simplex virus infection.

The etiology of chronic abacterial prostatitis remains obscure, although viral agents have been postulated. Herpes simplex virus was isolated from the prostatic fluid of a patient with symptoms of prostatitis and the implications are reviewed.

Adult↗
PubMed1991

Naphthosultam derivatives: a new class of potent and selective 5-HT2 antagonists.

A series of 2-(aminoalkyl)naphth[1,8-cd]isothiazole 1,1-dioxides was synthesized and examined in various receptor binding tests. Most compounds demonstrated high affinity for the 5-HT2 receptor with moderate to high selectivity. A member of this series, compound 24 (RP 62203), displays high 5-HT2 receptor affinity (Ki = 0.26 nM), which is respectively more than 100 and 1000 times higher than its affinity for alpha 1 (Ki = 38 nM) and D2 (Ki greater than 1000 nM) receptors. This compound is a potent orally effective and long lasting 5-HT2 antagonist in the mescaline-induced head-twitches test in mice and rats.

Animals↗
PubMed1991

Differential effects of potassium channel blockers on dopamine release from rat striatal slices.

The effects of different potassium channel blockers on tritiated dopamine [( 3H]DA) release were investigated in rat striatal slices in the presence of pargyline and nomifensine (10 microM each). 4-Aminopyridine (4-AP; 10 and 30 microM) and 3,4-diaminopyridine (3,4-DAP; 30 microM) markedly increased the basal tritium outflow, whereas tetraethylammonium (TEA; 100-1000 microM) was without effect. The facilitating effect of 4-AP (10 microM) on spontaneous release was Ca(2+)- and K(+)-dependent. Moreover, the 4-AP-induced increase in spontaneous release was abolished in the presence of tetrodotoxin, indicating that voltage-dependent Na+ channels were involved in the release mechanism. 4-AP (10 and 30 microM) induced a dose-dependent decrease in K(+)-evoked [3H]DA release. This effect was confirmed with 3,4-DAP (30 microM). When striatal slices were depolarized with veratridine (5 microM), these two aminopyridines increased the evoked release of [3H]DA. TEA increased both K(+)- and veratridine-evoked [3H]DA release. These biochemical results are consistent with electrophysiological differences between the mechanism of action of aminopyridines and that of TEA.

4-Aminopyridine↗
PubMed1991

A comparative study between Michel and Proximate clips for the closure of neck incisions.

A prospective study comparing two types of surgical clip, the Proximate II (Ethicon) staple and the Michel clip, was performed on 30 thyroidectomy (horizontal) and 50 carotid endarterectomy (vertical) incisions with reference to their ease of handling, patient comfort, complication rate, cosmetic result and cost. In each patient half of the wound was approximated with one type of clip and half with the other. The Proximate II staple was more comfortable for the patient in the vertical wounds (P less than 0.02), easier to remove as judged by the nurse in both horizontal (P less than 0.001) and vertical (P less than 0.02) wounds, and by the patient in the horizontal wounds (P less than 0.02) only. The incidence of inflammation was significantly higher with the Michel clip (P less than 0.001). In both the horizontal (P less than 0.05) and the vertical (P less than 0.001) wounds, when the scar was assessed at the time of discharge from hospital, the Proximate II staple achieved a significantly better result. However, assessment of the wounds by patient and researcher 6 weeks postoperatively, revealed no significant difference between the wounds with regard to cosmetic outcome. The Proximate II design, however, costs between seven and ten times more than the Michel clip depending on the size of the dispenser used, and since the late cosmetic result offers no advantage over the latter design, we feel these financial variables deserve consideration.

Adult↗
PubMed1990

Intraprostatic antibody deposition in chronic abacterial prostatitis.

Sixty patients with chronic abacterial prostatitis and 21 men without prostatitis were studied. Transperineal prostatic biopsies taken under transrectal ultrasound control were examined for antibody, complement (C3) and fibrinogen deposition using a direct immunofluorescence (IF) technique; 34 patients (57%) had prostatic tissue that displayed IF staining compared with only 1 (5%) in the non-prostatitis group. IF staining for IgM was found in 85%, for C3 in 44%, for IgA in 35% and for fibrinogen in 24%, but the IgG subclass was not detected. Antibody deposition was mainly periglandular and glandular and in the wall of vessels. Five symptoms, particularly poor urinary flow, irritative voiding and urgency, were significantly correlated with IgM and C3 deposition and, to a lesser extent, fibrinogen deposition. The aetiology of chronic abacterial prostatitis remains obscure but several possible mechanisms are discussed. The link between symptomatology and immunology could rest with functional outflow obstruction causing intraprostatic reflux of urine, this in turn inciting an immunological response, the inducing antigens being organism remnants or products, urinary constituents or autoantibodies.

Adult↗
PubMed1990

Preferential decrease in dopamine utilization in prefrontal cortex by zopiclone, diazepam and zolpidem in unstressed rats.

This study has compared the effects of a cyclopyrrolone, zopiclone, a benzodiazepine, diazepam, and an imidazopyridine, zolpidem, on dopamine (DA) and DOPAC levels, and DA utilization (DOPAC/DA ratio) in rat striatum and prefrontal cortex. The endogenous levels of DA were significantly increased by both zopiclone (2.5, 10 and 40 mg kg-1 p.o.) and diazepam (10 and 40 mg kg-1 p.o.) in the prefrontal cortex, whereas striatal DA content was significantly increased only with the highest dose of diazepam (40 mg kg-1 p.o.). Diazepam (10 and 40 mg kg-1 p.o.) decreased cortical level of DOPAC more markedly than striatal levels, whereas zopiclone (40 mg kg-1 p.o.) only slightly decreased striatal DOPAC levels. Zopiclone and diazepam dose-dependently decreased DA utilization, an effect which was more marked in prefrontal cortex than in striatum. This result was confirmed with zolpidem, another benzodiazepine ligand. Zopiclone was most potent at decreasing DA utilization at the cortical level. The diazepam-induced decreases in DA metabolism and utilization were antagonized by Ro 15-1788, suggesting that the effects seen were mediated by specific benzodiazepine receptors. Thus, our results clearly show that ligands acting on the benzodiazepine receptor GABA receptor chloride ionophore complex can decrease the utilization of dopamine in unstressed rats. The preferential decrease in cortical DA utilization induced by benzodiazepine ligands may be compared to the well-known activation by stress of the mesocortical DAergic system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Ibotenic acid stimulates D-[3H]aspartate release from cultured cerebellar granule cells.

The release of D-[3H]aspartate from cultured cerebellar granule cells can be evoked by potassium depolarization or by superfusion with the excitatory amino acids glutamic and aspartic acids. The latter phenomenon is not mediated by N-methyl-D-aspartate (NMDA)-, kainate- or quisqualate-preferring receptors, but is stimulated by ibotenic acid. Excitatory amino acid-stimulated D-[3H]aspartate release is antagonised by L-serine-O-phosphate and riluzole. These compounds did not block potassium-stimulated D-[3H]aspartate release. This pharmacology resembles an excitatory amino acid receptor coupled to inositol phosphate (PI) turnover.

Amino Acids↗
PubMed1989

The role of Chlamydia trachomatis in chronic abacterial prostatitis: a study using ultrasound guided biopsy.

We studied 50 patients with chronic abacterial prostatitis as defined by the Stamey procedure via transrectal prostatic ultrasound and subsequent transperineal biopsy of the abnormal areas of the prostate to ascertain the role of Chlamydia trachomatis organisms (chlamydiae) in this condition. Chlamydiae were detected by an immunofluorescence technique in the urethra of 1 patient (2 per cent) but they were not recovered in McCoy cell culture from the prostatic tissue of any patient nor were they detected in the tissue by immunofluorescence. In addition, serum antibody to Chlamydia trachomatis was not found even in moderate titer. The approach in this study has overcome the problem of urethral contamination in the assessment of prostatic specimens from patients with chronic abacterial prostatitis. There is no evidence that chlamydiae are directly implicated in the disease, although the possibility of an earlier active role cannot be excluded.

Adult↗
PubMed1989

Acute epididymitis: a microbiological and ultrasonographic study.

In a prospective study of 24 men (mean age 28.3 years) with acute epididymitis who underwent epididymal aspiration, micro-organisms were detected in 15 (62.5%). Chlamydia trachomatis accounted for 10 (42%) of the cases, being located in both the urethra and epididymis in 5 individuals. Chlamydial serology supported the diagnosis of chlamydial infection, there being a strong correlation between the detection of C. trachomatis and elevated titres of both chlamydial IgG and IgM antibodies. In 4 patients (mean age 55.5 years), Escherichia coli was cultured from both mid-stream urine and epididymal aspirate. Transrectal ultrasound revealed abnormal prostatic scans in 19 patients (79%). These data confirm the aetiological role of C. trachomatis, support the notion that micro-organisms spread intra-canalicularly and suggest that the prostate is also involved in the inflammatory process in acute epididymitis.

Acute Disease↗
PubMed1989

A search for infectious agents in chronic abacterial prostatitis using ultrasound guided biopsy.

A series of 60 patients with a diagnosis of chronic abacterial prostatitis, as defined by the Stamey procedure, was studied by transrectal prostatic ultrasound and subsequent transperineal biopsy of the abnormal areas of the prostate in order to ascertain the role of micro-organisms in this condition. Histological assessment revealed a chronic inflammatory infiltrate, generally of low grade, in 53 patients (88%). Organisms were isolated from the prostatic tissue of only 9 patients (15%) and were considered to be contaminants from the perineal skin, since treatment with an appropriate antimicrobial agent failed to alter symptoms or affect the leucocyte count in the urine or prostatic fluid. Chronic abacterial prostatitis may be a non-organismal inflammatory process.

Adult↗
PubMed1989

Ultrasonographic findings in prostatitis.

Transrectal prostatic ultrasound is a minimally invasive, painless investigation that provides objective data on the topography of the prostate. Prostatitis is a condition difficult to diagnose in view of its varied symptomatology and lack of physical signs. The diagnosis currently rests on the finding of excessive numbers of leukocytes in the prostatic secretion obtained during the Stamey localization procedure. Seven ultrasound features having a significant correlation with a diagnosis of prostatitis have been identified: high-density and mid-range echoes, echo-lucent zones, capsular irregularity and thickening, ejaculatory duct echoes, and periurethral-zone irregularity. Ultrasonography confirms the focal nature and frequent peripheral-zone location of inflammatory prostate disease. Follow-up ultrasound studies over a short period showed that the echo-lucent zones may resolve to normal, mid-range, or high-density echoes in conjunction with a fall in the leukocyte count in expressed prostatic secretions. The ability to place a biopsy needle accurately under ultrasound control has enabled histologic assessment of the parenchymal features. The high-density echoes represent corpora amylacea; the mid-range echoes, inflammation, fibrosis, or both; and the echo-lucent zones, inflammation. The low specificity of mid-range and high-density echoes (51.9 and 40.7 per cent) and the low sensitivity (range 30.8 to 62.3 per cent) of the remaining five ultrasound features of prostatitis preclude identification of any one feature as being diagnostic of this condition. A possible exception may be the finding of echo-lucent zones, which may also prove useful in the monitoring of response to treatment. The detection of several signs within an individual's prostate suggests a diagnosis of chronic prostatitis, whereas a normal scan in a patient with symptoms of prostatitis is highly suggestive of prostatodynia.

Adult↗