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61.
62.
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63.
64.
65.
Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr- labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP. 相似文献
66.
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MG Pacheco-Tovar E Avalos-Díaz E Vega-Memije JJ Bollain-y-Goytia E López-Robles MT Hojyo-Tomoka L Domínguez-Soto R Herrera-Esparza 《Journal of the European Academy of Dermatology and Venereology》2009,23(6):697-701
Background Pemphigus is an autoimmune disease characterized by the formation of intra-epidermal blisters. Patients develop auto-antibodies against desmoglein 1 and 3 proteins and induce acantholysis.
Objective This work addresses the issue of whether the Fas pathway mediates acantholysis. Furthermore, the possible suppliers of the Fas pathway were investigated.
Methods Seventeen biopsies of pemphigus patients were studied by haematoxylin and eosin staining, and apoptosis was defined by TUNEL. The expression of Fas, FasL and caspase 3 was studied by in situ hybridization and immunohistochemistry. Cell infiltrates were studied by immunofluorescence with monoclonal anti-CD3, CD4, CD8, CD19 and CD69.
Results All of the biopsies showed intra-epidermal blisters, acantholytic cells and inflammatory infiltrates. The blisters expressed Fas, FasL and caspase 3. Cell infiltrates were composed of CD8 and a few CD4+ CD69+ cells. Additionally, CD19+ cells were detected. Interestingly, the Fas expression was increased in acantholytic cells and perilesional keratinocytes. Incidentally, these cells exhibited apoptotic features. Interestingly, the CD8 cells expressed FasL.
Conclusion This paper presents the morphological evidence that apoptosis and acantholysis are linked. Therefore, the Fas pathway is associated with CD8 cells in pemphigus lesions.
None declared. 相似文献
Objective This work addresses the issue of whether the Fas pathway mediates acantholysis. Furthermore, the possible suppliers of the Fas pathway were investigated.
Methods Seventeen biopsies of pemphigus patients were studied by haematoxylin and eosin staining, and apoptosis was defined by TUNEL. The expression of Fas, FasL and caspase 3 was studied by in situ hybridization and immunohistochemistry. Cell infiltrates were studied by immunofluorescence with monoclonal anti-CD3, CD4, CD8, CD19 and CD69.
Results All of the biopsies showed intra-epidermal blisters, acantholytic cells and inflammatory infiltrates. The blisters expressed Fas, FasL and caspase 3. Cell infiltrates were composed of CD8 and a few CD4
Conclusion This paper presents the morphological evidence that apoptosis and acantholysis are linked. Therefore, the Fas pathway is associated with CD8 cells in pemphigus lesions.
Conflicts of interest
None declared. 相似文献
68.
69.
M G Schoon W J Van der Walt J Fourie H Kruger 《International journal of gynaecology and obstetrics》1990,33(2):111-114
In a retrospective study, the antenatal records of 241 consecutive patients were analyzed. Maternal gravidity, age, blood pressure recordings, and fetal gestational age at birth, weight and perinatal deaths were recorded. Blood pressure recordings were done by the clinic staff with the patient in the supine position tilted 15 degrees to the right. Hypertension was defined as a diastolic pressure (Korotkoff phase 4) of 90 mmHg or more. Forty-one percent were classified as hypertensive. Hypertension before 33 weeks had a perinatal mortality of 264/1000. 相似文献
70.
Surgical treatment of toxic megacolon 总被引:1,自引:0,他引:1
L P Leenen E Schoon W Stuifbergen C van der Werken 《Nederlands tijdschrift voor geneeskunde》1991,135(22):992-996
From 1978 to 1989, 11 patients suffering from toxic megacolon were treated. In eight patients it was based on ulcerative colitis, while Crohns' disease, infectious colitis and pseudomembranous colitis were seen once each. Patients were initially treated with intravenous fluids and corticosteroids. They were closely followed both clinically and radiologically. The plain abdominal X-ray was of great help. Conservative regimen was successful in 3 patients, the remaining had to be operated on in due course. Three patients proved to have a perforation of the bowel at the time of operation. The initial operations performed were one proctocolectomy, four times a subtotal colectomy, twice a partial colectomy and in one instance a diverting colostomy. Two patients had to undergo an additional colon resection. Postoperative complications consisted mainly of intra-abdominal abscesses. Two of the operated patients died. Follow-up is between 2 and 9 years. None of the patients had a recurrence of the toxic megacolon. Four patients had a recurrence of their underlying disease, which however could be resolved in most cases by medical means. In one patient total colectomy is being considered. 相似文献