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71.
A Choppin I Irwin L Lach MG McDonald AE Rettie L Shao C Becker MP Palme X Paliard S Bowersox DM Dennis P Druzgala 《British journal of pharmacology》2009,158(6):1536-1547
Background and purpose:
Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.Experimental approach:
Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).Key results:
Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K1 treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.Conclusions and implications:
Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients. 相似文献72.
Heart failure is a syndrome of huge and growing importance worldwide. It is widely accepted that the energy status of the myocardium in heart failure is impaired, irrespective of etiology. Agents which modify cardiac substrate utilisation have the potential to ameliorate this energy deficiency by increasing cardiac mechanical efficiency. This may represent a new therapeutic paradigm in heart failure. In this review we discuss existing and new agents that alter cardiac substrate use and summarise the data on clinical efficacy. 相似文献
73.
Development of the Manchester framework for the evaluation of emergency department pharmacy services
Greenwood D Tully MP Martin S Steinke D 《International journal of clinical pharmacy》2022,44(4):930-938
International Journal of Clinical Pharmacy - Many countries, including the United Kingdom, have established Emergency Department (ED) pharmacy services where some ED pharmacists now work as... 相似文献
74.
Treatment of vitiligo with topical imiquimod 总被引:1,自引:0,他引:1
75.
76.
T Canedo MP De Almeida T Cuzzi M Ramos‐e‐Silva 《Journal of the European Academy of Dermatology and Venereology》2010,24(2):178-185
Background Some adnexal tumours have many controversies about their histogenesis. Objectives To evaluate the eccrine and/or apocrine differentiation phenotype in cases of cylindroma and clear cell hidradenoma with CD15 and p63 antibodies. Methodology Slides and blocks of six cases of cylindroma and seven cases of nodular hidradenoma (clear cells) were analyzed by the technique of immunohistochemistry with CD15 and p63 antibodies. Results In all cases of cylindroma we obtained negative results for CD15 antibody and positive for p63 antibody. In five of seven cases of nodular hidradenoma (clear cell), we could easily observe clear cells between 20% and 50% of tumour cells. In the two other cases, cystic lesions were present and occasional clear cells could be seen. The reaction with CD15 antibody was positive in granular and cytoplasmic pattern in six of seven cases, especially in cells with suggestive clear cytoplasm in lower proportion than this clear cells could be seen in haematoxylin and eosin. The positivity for p63 antibody, nuclear pattern, was observed in six of seven cases, in the major part of tumour cells. In only one case, the positivity was in 20% of cells. Limitation Samples are in small number because these are relatively rare tumours. Conclusions The present study suggests eccrine origin for both tumours: cylindroma and clear cell hidradenoma. 相似文献
77.
78.
MA Vieira-Coelho MP Serr?o J Afonso CE Pinto E Moura 《British journal of pharmacology》2009,158(3):726-737
Background and purpose:
This study investigates the role of α2-adrenoceptor subtypes, α2A, α2B and α2C, on catecholamine synthesis and catabolism in the central nervous system of mice.Experimental approach:
Activities of the main catecholamine synthetic and catabolic enzymes were determined in whole brains obtained from α2A-, α2B- and α2C-adrenoceptor knockout (KO) and C56Bl\7 wild-type (WT) mice.Key results:
Although no significant differences were found in tyrosine hydroxylase activity and expression, brain tissue levels of 3,4-dihydroxyphenylalanine were threefold higher in α2A- and α2C-adrenoceptor KO mice. Brain tissue levels of dopamine and noradrenaline were significantly higher in α2A and α2CKOs compared with WT [WT: 2.8 ± 0.5, 1.1 ± 0.1; α2AKO: 6.9 ± 0.7, 1.9 ± 0.1; α2BKO: 2.3 ± 0.2, 1.0 ± 0.1; α2CKO: 4.6 ± 0.8, 1.5 ± 0.2 nmol·(g tissue)−1, for dopamine and noradrenaline respectively]. Aromatic L-amino acid decarboxylase activity was significantly higher in α2A and α2CKO [WT: 40 ± 1; α2A: 77 ± 2; α2B: 40 ± 1; α2C: 50 ± 1, maximum velocity (Vmax) in nmol·(mg protein)−1·h−1], but no significant differences were found in dopamine β-hydroxylase. Of the catabolic enzymes, catechol-O-methyltransferase enzyme activity was significantly higher in all three α2KO mice [WT: 2.0 ± 0.0; α2A: 2.4 ± 0.1; α2B: 2.2 ± 0.0; α2C: 2.2 ± 0.0 nmol·(mg protein)−1·h−1], but no significant differences were found in monoamine oxidase activity between all α2KOs and WT mice.Conclusions and implications:
In mouse brain, deletion of α2A- or α2C-adrenoceptors increased cerebral aromatic L-amino acid decarboxylase activity and catecholamine tissue levels. Deletion of any α2-adrenoceptor subtypes resulted in increased activity of catechol-O-methyltransferase. Higher 3,4-dihydroxyphenylalanine tissue levels in α2A and α2CKO mice could be explained by increased 3,4-dihydroxyphenylalanine transport. 相似文献79.
80.
F Gallardo MP García-Muret O Servitje T Estrach I Bielsa A Salar E Abella C Barranco RM Pujol 《Journal of the European Academy of Dermatology and Venereology》2009,23(6):639-647
Background The presence of a prominent granulomatous tissue reaction in skin biopsies from primary cutaneous or systemic malignant lymphomas with secondary cutaneous involvement is a rare but well-known phenomenon.
Objective This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component.
Patients and methods The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30+ cutaneous T-cell lymphoma (2 patients), CD4+ small/medium pleomorphic cutaneous T-cell lymphoma (1 patient), primary cutaneous B-cell lymphoma (3 patients) and peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement (4 patients) were reviewed.
Results The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established.
Conclusion The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.
None declared. 相似文献
Objective This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component.
Patients and methods The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30
Results The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established.
Conclusion The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.
Conflicts of interest
None declared. 相似文献