36 resultados para cox 2-3 spacer


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Postmenopausal Caucasian women aged less than 80 years (n = 99) with one or more atraumatic vertebral fracture and no hip fractures, were treated by cyclical administration of enteric coated sodium fluoride (NaF) or no NaF for 27 months, with precautions to prevent excessive stimulation of bone turnover. In the first study 65 women, unexposed to estrogen (-E study), age 70.8 +/- 0.8 years (mean SEM) were all treated with calcium (Ca) 1.0-1.2 g daily and ergocalciferol (D) 0.25 mg per 25 kg once weekly and were randomly assigned to cyclical NaF (6 months on. 3 months off, initial dose 60 mg/day; group F CaD, n = 34) or no NaF (group CaD, n = 3 1). In the second study 34 patients. age 65.5 +/- 1.2 years, on hormone replacement therapy (E) at baseline, had this standardized, and were all treated with Ca and D and similarly randomized (FE CaD, n = 17, E CaD, n = 17) (+E study). The patients were stratified according to E status and subsequently assigned randomly to NaF. Seventy-five patients completed the trial. Both groups treated with NaF showed an increase in lumbar spinal density (by DXA) above baseline by 27 months: FE CaD + 16.2% and F CaD +9.3% (both p = 0.0001). In neither group CaD nor E CaD did lumbar spinal density increase. Peripheral bone loss occurred at most sites in the F CaD group at 27 months: tibia/fibula shaft -7.3% (p = 0.005); femoral shaft -7.1% (p = 0.004); distal forearm -4.0% (p = 0.004); total hip -4.1% (p = 0. 003); and femoral neck -3.5% (p = 0.006). No significant loss occurred in group FE CaD. Differences between the two NaF groups were greatest at the total hip at 27 months but were not significant [p < 0.05; in view of the multiple bone mineral density (BMD) sites, an alpha of 0.01 was employed to denote significance in BMD changes throughout this paper]. Using Cox's proportional hazards model, in the -E study there were significantly more patients with first fresh vertebral fractures in those treated with NaF than in those not so treated (RR = 24.2, p = 0.008, 95% CI 2.3-255). Patients developing first fresh fractures in the first 9 months were markedly different between groups: -23% of F CaD, 0 of CaD, 29% of FE CaD and 0 of E CaD. The incidence of incomplete (stress) fractures was similar in the two NaF-treated groups. Complete nonvertebral fractures did not occur in the two +E groups, there were no differences between groups F CaD and CaD. Baseline BMD (spine and femoral neck) was related to incident vertebral fractures in the control groups (no NaF), but not in the two NaF groups. Our results and a literature review indicate that fluoride salts. if used, should be at low dosage, with pretreatment and co-treatment with a bone resorption inhibitor.

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In humans, hydromorphone (HMOR) is metabolised principally by conjugation with glucuronic acid to form hydromorphone-3-glucuronide (H3G), a close structural analogue of morphine-3-glucuronide (M3G), the major metabolite of morphine. In a previous study we described the biochemical synthesis of H3G together with a preliminary evaluation of its pharmacology which revealed that it is a neuro-excitant in rats in a manner analogous to M3G. Thus the aims of the current study were to quantify the neuro-excitatory behaviours evoked by intracerebroventricular (icv) H3G in the rat and to define its potency relative to M3G. Groups of adult male Sprague-Dawley rats received icy injections (1 muL) of H3G (1 - 3 mug), M3G (2 - 7 mug) or vehicle via a stainless steel guide cannula that had been implanted stereotaxically seven days prior to drug administration. Behavioural excitation was monitored by scoring fifteen different behaviours (myoclonic jerks, chewing, wet-dog-shakes, rearing, tonic-clonic-convulsions, explosive motor behaviour, grooming, exploring, general activity, eating, staring, ataxia, righting reflex, body posture, touch evoked agitation) immediately prior to icy injection and at the following post-dosing times: 5, 15, 25, 35, 50, 65 and 80 min. H3G produced dose-dependent behavioural excitation in a manner analogous to that reported previously for M3G by our laboratory and reproduced herein. H3G was found to be approximately 2.5-fold more potent than M3G, such that the mean (+/- S.D.) ED50 values were 2.3 (+/- 0.1) mug and 6.1 (+/- 0.6) mug respectively. Thus, our data clearly imply that if H3G crosses the BBB with equivalent efficiency to M3G, then the myoclonus, allodynia and seizures observed in some patients dosed chronically with large systemic doses of HMOR, are almost certainly due to the accumulation of sufficient H3G in the central nervous system, to evoke behavioural excitation. (C) 2001 Elsevier Science Inc. All rights reserved.

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Quinolizine-2,4-diones 11 are obtained by ash vacuum thermolysis (FVT) of 3-acyl-1,2,3-triazolo[1,5-a]pyridines 7. The reaction takes place via methyl- and phenyl(2-pyridyl)ketenes 10, which are directly observable by infrared spectroscopy in low temperature matrices. FVT of 11 regenerates the ketenes 10.

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Flying foxes are commonly thought of as highly social mammals, yet little is known about the dynamics of their social interactions at a day roost. The aim of the present study was to examine the nature of the seasonal activities of territoriality and courtship amongst wild flying foxes in Australia. Focal observations were conducted at two permanent roosts of black flying foxes Pteropus alecto during periods of peak social interaction in the summers of 1999 and 2000 in urban Brisbane, Queensland. Observations of male territoriality were conducted at dawn and began eight weeks prior to the commencement of mating. The majority of defense bouts (87%) consisted of ritualised pursuit, while 13% of bouts involved physical contact expressed as either wrestling or hooking. One male with an unusually large territory took significantly longer to defend it than other males with less territory to defend. Observations of courtship revealed repetitive courtship sequences, including pre-copulatory approaches by the males, copulation attempts and grooming/resting periods. Thirty-four complete courtship sequences incorporating 135 copulation attempts were recorded over two seasons. Females actively resisted courtship approaches by males, forcing males to display a continuous determination to mate over time where determination can be considered an indicator of 'fitness'. The courtship bout length of females with suckling young was significantly longer ((x) over bar +/- SE; 230.9 +/- 22.16 s) than that of females unencumbered by large pups (158.5 +/- 9.69 s), although the length of copulations within those courtships was not (45.6 +/- 5.19 versus 36.2 +/- 3.43 s).

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Background: The heavy usage of coxibs in Australia far outstrips the predicted usage that was based on the treatment of patients with risk factors for upper gastro-intestinal adverse events from conventional anti--inflammatory agents. This raises questions regarding the appropriateness of prescribing. Aims: To determine: (i) the relationship between prescriptions for cyclooxygenase 2 (COX-2) inhibitors and objective evidence of inflammatory arthritis, (ii) prior experience with paracetamol and/or conventional non-steroidal anti-inflammatory drugs (NSAIDs), and (iii) contraindications to the use of NSAIDs. Methods: Drug utilization evaluation and rheumato-logical assessment was conducted on 70 consecutive patients admitted on COX-2 inhibitors to a 480-bed metropolitan hospital. The main outcome measures were: the indication for COX-2 inhibitor; objective -evidence of inflammatory arthritis; previous trial of -paracetamol or conventional NSAIDs; and patient -satisfaction. Results: Only 11 patients (16%) had symptoms or signs of an inflammatory arthropathy, and met Pharmaceut-ical Benefits Schedule criteria for prescribing a COX-2 inhibitor. Fifty-nine patients (84%) had chronic osteo-arthritis, degenerative spinal disease, injury or malignancy, without overt active inflammation. Fourteen patients (20%) had trialled regular paracetamol prior to using any NSAID treatment. Conventional NSAIDs had been previously used by 51 patients (73%). Eleven patients (16%) reported previous adverse gastrointestinal effects from conventional NSAIDs. On the basis of significant renal impairment (creatinine clearance 5/10). Conclusions: Drug utilization data indicate that COX-2 inhibitors are frequently used first line for degenerative osteoarthritis in the absence of overt inflammation, without prior adequate trial of paracetamol and with disregard for the cautions and contraindications of these agents. These findings may explain the unprecedented Pharmaceutical Benefits Schedule expenditure on COX-2 inhibitors in Australia.

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Matrix photolysis of 3-methoxycarbonyl-1,2,3-triazolo[1,5-a]pyridine (12) affords s-E-2-pyridylketene (4), but flash vacuum thermolysis of 12 gives methoxy(2-pyridyl)ketene (15), predominantly in the s-Z-conformation. Matrix photolysis of 15 affords 2-acetylpyridine. Copyright (C) 2003 John Wiley Sons, Ltd.