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  • 1
    ISSN: 1432-2072
    Keywords: Electroconvulsive shock ; Corticosterone ; Muscarinic agonists ; Serotoninergic agonists ; α-Adrenoceptor agonists ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of repeated and single electroconvulsive shocks (ECS) on the corticosterone response to pharmacological stimuli has been studied in male rats. Plasma corticosterone concentrations are elevated by oxotremorine, a muscarinic agonist, and by 5-hydroxy-l-tryptophan, a precursor of serotonin. Both these agonists probably stimulate corticotrophinreleasing-factor release from the hypothalamus. The log dose-response curves of the corticosterone response to oxotremorine and to 5-hydroxy-l-tryptophan are shifted to the left after a single ECS given daily for 10 days compared with sham-shocked controls. Plasma corticosterone concentrations are elevated by treatment with α-methyl-p-tyrosine methyl ester (400 mg/kg IP). This rise is suppressed by clonidine. The log dose-response curve for the corticosterone response to clonidine after α-methyl-p-tyrosine methyl ester is also shifted to the left by repeated ECS, compared with controls. There is no difference in the corticosterone response of ECS and sham-treated groups given vasopressin, which is thought to act directly on the pituitary to release ACTH. A single ECS produces a slight enhancement of the response to 5-hydroxy-l-tryptophan, a slight decrease in the response to oxotremorine and no change in the response to clonidine after α-methyl-p-tyrosine. The disappearance of the difference in response between ECS and sham-treated animals was also studied 1,3, and 6 days after a series of ten ECS or sham procedures. Significant differences in the corticosterone responses to oxotremorine, 5-hydroxy-l-tryptophan and clonidine after α-methyl-p-tyrosine between ECS and sham-treated animas were found 24 h after the last ECS or sham shock. These differences were in decline 3 days after the last procedure and had completely disappeared by day 6. The decline was largely due to an increase in plasma corticosterone responsiveness to pharmacological stimuli of the shamshocked controls. Responses in the ECS-treated groups remained constant. It is apparent that the anaesthetic procedure suppresses the effect of oxotremorine, 5-hydroxy-l-tryptophan and clonidine after α-methyl-p-tyrosine on corticosterone concentrations in plasma. This effect is spontaneously reversible. Repeated ECS reverses the effect of the anaesthetic procedure but produces no reversible enhancement of its own.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Corticosterone ; Muscarinic agonists ; Serotoninergic agonists ; α-Adrenoceptor agonists ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A method is described for demonstrating the hypothalamic control of corticosterone in the intact rat. Oxotremorine 0.01–0.05 mg/kg IP and 5-hydroxy-l-tryptophan 1–50 mg/kg IP raise plasma corticosterone levels in dose-related fashion. The oxotremorine response is blocked by atropine 1 mg/kg SC and the 5-hydroxy-l-tryptophan response by mianserin 10 mg/kg IP. α-Methylparatyrosine methyl ester 400 mg/kg IP raises plasma corticosterone levels 14–16 h later. This rise can be suppressed by clonidine 0.01–0.05 mg/kg IP and this suppression is antogonized by piperoxane 5–50 mg/kg IP. Apomorphine 5 mg/kg IP does not lower plasma corticosterone levels in rats pre-treated with α-methylparatyrosine. The response to oxotremorine cannot be blocked by atropine methylbromide or by mianserin. The response to 5-hydroxy-l-tryptophan is unaffected by benserazide or atropine sulphate. These data suggest separate cholinergic and serotoninergic facilitation of corticosterone release in the intact rat. The stimulating drugs used appear to be acting centrally. The data also support the presence of a noradrenergic inhibitory system mediated by α-adrenoceptors. Dopaminergic receptors appear to play no part in the central control of corticosterone secretion after pre-treatment with α-methylparatyrosine.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1434-9949
    Keywords: Kidney ; NSAID ; Tenoxicam ; Osteoarthritis ; Rheumatoid Arthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fifty-eight patients, aged 48–87 years, with impaired renal function and mean initial creatinine clearance of 52.1 mls/min were recruited to a 12-week open study of tenoxicam 20 mg/day for osteoarthrosis or rheumatoid arthritis. Renal function was mea sured before and after a brief run-in period when patients discontinued all nonsteroidal anti-inflammatory drugs, taking paracetamol alone, prior to monthly monitoring thereafter. Fifty-four% of patients completed the study, the others being withdrawn from lack of efficacy (17%), adverse events (24%) or both (5%). During the run-in period the mean creatinine clearance of 28 patients completing the trial improved to 64.7 mls/min and then dropped to 57.9 mls/min during the course of 12 weeks treatment with tenoxicam. Serial analysis of haematological and biochemical safety parameters showed no drug-induced change of significance. Twenty-three% of patients felt worse and 45% better at the end of treatment. Seventeen patients withdrew because of adverse events. These were normally gastrointestinal and always unrelated to further deterioration in renal function. Tenoxicam, 20 mg/day, can be given safely for a period of at least three months in patients with mild or moderate renal impairment.
    Type of Medium: Electronic Resource
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