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71.
BACKGROUND: Rupatadine is an oral active antihistamine for the management of diseases with allergic inflammatory conditions, such as perennial and seasonal rhinitis and chronic idiopathic urticaria. Oral rupatadine has been approved for the treatment of allergic rhinitis and chronic urticaria in adults and adolescents in several European countries. OBJECTIVE: The purpose of this study was to describe the effect of the concomitant intake of food on the pharmacokinetic profile and bioavailability of a single dose of rupatadine. METHODS: This was a single-dose, randomized, open-label, 2-way crossover study in which healthy male and female volunteers received a single, 20-mg oral dose of rupatadine under fed and fasting conditions. Blood samples were collected and plasma concentrations of rupatadine and its active metabolites desloratadine and 3-hydroxydesloratadine were determined by liquid chromatography tandem mass spectrometry. Tolerability was based on the recording of adverse events (AEs), physical examinations, electrocardiograms, and laboratory tolerability tests immediately before each treatment period and at the final visit of the study. RESULTS: Twenty-four volunteers (12 males; mean [SD] age, 25.4 [5.3] years [range, 18-34 years]; mean [SD] weight, 71.2 [4.3] kg [range, 64-77 kg]; 12 females; mean [SD] age, 26.8 [6.5] years [range, 18-38 years]; mean [SD] weight, 58.4 [6.8] kg, [range 50-69 kg]) were enrolled and randomized with equal distribution of sex. A significant increase in AUC from drug administration to the final quantifiable sample (AUC(0-t)) and AUC from drug administration to infinity (AUC(0-infinity)) values of rupatadine was seen under fed conditions without affecting C(max). The ratios (90% CI) of the mean log-transformed AUC(0-t) and AUC(0-infinity) for rupatadine revealed a significant increase in AUC(0-t) (ratio 131%; 90% CI, 111%-154%) and AUC(0-infinity) (ratio 133%; 90% CI, 113%-156%), whereas C(max) remained unaltered (ratio 97%; 90% CI, 80%-116%). Plasma concentration-time profiles of desloratadine and 3-hydroxydesloratadine were similar with and without food, and no differences were seen for AUC(0-t), AUC(0-infinity), or C(max). Seven (28%) subjects reported > or =1 AE. All AEs were mild, resolved spontaneously, and did not affect the outcome of the study. CONCLUSIONS: The results of this study indicate that concomitant intake of food with a single 20-mg oral dose of rupatadine exhibits a significant increase in rupatadine bioavailability. Despite the absence of bioequivalence, the drug was well tolerated under fed and fasting conditions, and no major changes in severity and/or prevalence of AEs were reported. 相似文献
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Down-regulation of annexin A1 and A2 protein expression in intestinal-type sinonasal adenocarcinomas
Rodrigo JP García-Pedrero JM Llorente JL Fresno MF Allonca E Suarez C Hermsen M 《Human pathology》2011,42(1):88-94
Annexins are a structurally related family of calcium- and phospholipid-binding proteins that have been implicated in a broad range of molecular and cellular processes. The altered expression of individual annexins has been implicated in tumor development and progression. In this study the expression of annexin A1 and annexin A2 was studied by immunohistochemistry in intestinal-type sinonasal adenocarcinoma using a study set of 57 intestinal-type sinonasal adenocarcinomas represented on an intestinal-type sinonasal adenocarcinoma tissue microarray to assess its potential role in the pathogenesis of these tumors. Our results showed that annexin A1 expression was consistently lost in 52 (91%) intestinal-type sinonasal adenocarcinomas, as compared with the normal epithelium. The expression of annexin A2 was more heterogeneous, and only 19 (33%) cases showed annexin A2 negative expression. Annexin A2 expression was correlated with the histopathological type, being lower in the mucinous type (P = .022). The loss of annexin A2 expression correlated with a reduced survival in univariate analysis (P = .004). However, the impact of annexin A2 expression on patient survival could be an indirect consequence of its association with the histopathological type, since annexin A2 expression was not found to be an independent predictor in multivariate analyses. These results suggest that annexin A1 expression is frequently and commonly lost in intestinal-type sinonasal adenocarcinoma development. Annexin A2 expression is also reduced in intestinal-type sinonasal adenocarcinoma, and this loss of expression is associated to the more aggressive histopathological types. 相似文献
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Rocha L Lorigados-Pedre L Orozco-Suárez S Morales-Chacón L Alonso-Vanegas M García-Maeso I Villeda-Hernández J Osorio-Rico L Estupiñán B Quintana C 《Progress in neuro-psychopharmacology & biological psychiatry》2007,31(6):1208-1218
The main goal of the present study was to evaluate binding to serotonin in the neocortex surrounding the epileptic focus of patients with mesial temporal lobe epilepsy (MTLE). Binding to 5-HT, 5-HT(1A), 5-HT(4), 5-HT(7) receptors and serotonin transporter (5-HTT) in T1-T2 gyri of 15 patients with MTLE and their correlations with clinical data, neuronal count and volume were determined. Autopsy material acquired from subjects without epilepsy (n=6) was used as control. The neocortex from MTLE patients demonstrated decreased cell count in layers III-IV (21%). No significant changes were detected on the neuronal volume. Autoradiography experiments showed the following results: reduced 5-HT and 5-HT(1A) binding in layers I-II (24% and 92%, respectively); enhanced 5-HT(4) binding in layers V-VI (32%); no significant changes in 5-HT(7) binding; reduced 5-HTT binding in all layers (I-II, 90.3%; III-IV, 90.3%, V-VI, 86.9%). Significant correlations were found between binding to 5-HT(4) and 5-HT(7) receptors and age of seizure onset, duration of epilepsy and duration of antiepileptic treatment. The present results support an impaired serotoninergic transmission in the neocortex surrounding the epileptic focus of patients with MTLE, a situation that could be involved in the initiation and propagation of seizure activity. 相似文献
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In the central nervous system, transferrin (Tf) is produced by oligodendroglial cells (OLGcs) and is essential for their development. Recently, using the complete cDNA of the human Tf gene, we obtained clones overexpressing Tf in two OLGc lines, N19 and N20.1, which represent different stages of differentiation. We showed that the overexpression of this glycoprotein promotes the maturation and myelinogenic capacity of both cell lines. In this work, using cDNA array technology, we examined changes induced by Tf in 1,176 genes. We found 41 genes differentially expressed in both cell lines, all of them involved in OLGc development. In the less mature cells (N19) overexpressing Tf, there was a significant increase in key enzymes of neurosteroid metabolism, such as cholesterol side chain cleavage cytochrome P450, 3beta-hydroxysteroid dehydrogenase and 5alpha-reductase type 1. In the more mature cell line (N20.1), Tf overexpression produced an induction of several mRNAs of the GABA(A) receptor subunits, of thyroid hormone receptors and of proteins involved in axon-glia interactions such as F3/contactin. In addition, in both cell lines, Tf overexpression induced an increase in the expression of different isoforms of transforming growth factor beta receptors and in several genes related to mitochondrial function and to complex lipid metabolism, crucial steps in myelin synthesis. Differentiation produced by Tf in both cell lines seems to occur by modulation of different genes depending on the maturational stage of the cells. Our findings provide new insights into the molecular basis of OLGc differentiation and on the role played by Tf in this process. 相似文献
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The prevalence of child sexual abuse in community and student samples: A meta-analysis 总被引:4,自引:0,他引:4