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3.
Neuroradiology ; 64(9): 1781-1794, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35420310

RESUMO

PURPOSE: Vessel wall MRI (VW-MRI) can be used to evaluate the nature of intracranial atherosclerosis (ICAS) plaque in vivo. Phosphodiesterase 4D (PDE4D) participates in stroke development. This study aims to explore the value of VW-MRI findings and the PDE4D gene variant in predicting stroke recurrence in patients with ICAS. METHODS: We prospectively recruited 324 symptomatic ICAS patients. VW-MRI was performed to determine luminal and wall changes. PDE4D gene single-nucleotide polymorphisms (SNPs)-namely, SNP32, SNP83, and SNP87-were determined by direct sequencing. The risk factors of stroke recurrence were analyzed using the multivariate Cox proportional hazards model. RESULTS: Of the 324 subjects, 97 (29.9%) experienced recurrent ischemic stroke during the follow-up period. A total of 254 patients (78.4%) showed plaque enhancement; 87 of these patients experienced stroke recurrence. The CT/CC genotype frequencies of PDE4D83 were significantly higher in participants with recurrent stroke than in patients without stroke recurrence (p = 0.019 and p < 0.001, respectively). However, the PDE4D32 and PDE4D87 variants were not correlated with recurrent stroke. Multivariate analysis showed that plaque enhancement from VW-MRI (HR 4.52, 95% CI 2.35-8.73, p < 0.001) and the PDE4D83 variant (HR 7.43, 95% CI 1.75-31.87, p = 0.005) were independently correlated with stroke recurrence. Kaplan-Meier curves showed significant differences in stroke recurrence rates between the plaque-enhanced group and the non-enhanced group (p < 0.001) and between the PDE4D83 variant carriers and noncarriers (p = 0.002). CONCLUSION: Plaque enhancement on VW-MRI and the presence of the PDE4D83 variant are associated with ischemic stroke recurrence in subjects with symptomatic ICAS.


Assuntos
Arteriosclerose Intracraniana , AVC Isquêmico , Placa Aterosclerótica , Acidente Vascular Cerebral , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/genética , Imageamento por Ressonância Magnética , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/genética
4.
Am J Transl Res ; 13(5): 4422-4436, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150024

RESUMO

This study aimed to analyze the association between background parenchymal enhancement (BPE) in the contralateral breast tissue on magnetic resonance imaging (MRI) and clinicopathologic parameters in patients with unilateral breast carcinoma and to investigate its potential prognostic significance. A total of 467 patients who were pathologically confirmed to have unilateral breast cancer and underwent breast MRI were recruited to participate in this cohort study. BPE was assessed in the healthy contralateral breast. Minimal and mild levels were classified as low BPE, whereas moderate and marked levels were classified as high BPE. The effects of BPE on clinicopathologic parameters, overall survival (OS), and invasive disease-free survival (IDFS) were determined. Among the 467 patients, 327 cases were classified into the low-BPE group, whereas 140 cases were classified into the high-BPE group. The high-BPE pattern markedly correlated with age at diagnosis, menopausal status, histologic grading, and estrogen receptor status. BPE pattern did not correlate with OS and IDFS in the entire breast cancer cohort, regardless of whether adjuvant chemotherapy was received. Notably, BPE in the healthy contralateral breast on MRI is markedly related to OS and IDFS in triple-negative breast cancer (TNBC) cases who received chemotherapy. High BPE is related to chemotherapeutic benefits and can be an independent favorable prognostic factor for TNBC patients. Thus, our observations suggest that high BPE pattern can potentially be used as an imaging biomarker for relatively favorable prognosis in TNBC cases receiving chemotherapy. However, the findings need to be verified in a large-scale study.

5.
Poult Sci ; 95(9): 2129-35, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27118859

RESUMO

P-glycoprotein ( P-GP: , encoding gene Abcb1) and Breast Cancer Resistance Protein ( BCRP: , encoding gene Abcg2) are transport proteins that play a major role in modulating the bioavailability of oral drugs in humans and rodents. It has been shown that rifampicin is the typical inducer of P-gp in rodents by activating the nuclear receptor. However, its effect on Abcb1, Abcg2, CYP3A, and chicken xenobiotic-sensing orphan nuclear receptor ( CXR: ) mRNA expression in broilers is poorly understood. This study explored the effect of rifampicin on mRNA expression of Abcb1, Abcg2, CYP3A37, CXR as well as its effect on the pharmacokinetics of enrofloxacin in broilers. The mRNA levels of Abcb1, Abcg2, CYP3A37, and CXR were significantly increased in the liver (except Abcg2), kidney, jejunum, and ileum (P < 0.05) but not significantly changed in the duodenum (P > 0.05) after treated with rifampicin. Further analysis revealed that the variation tendencies of Abcb1, Abcg2, and CYP3A37 expression levels were significantly correlated with CXR mRNA expression levels in liver, kidney, jejunum, and ileum. Coadministration of rifampicin significantly changed the pharmacokinetic behavior of enrofloxacin orally administered by showing clearly lower AUC0-∞, AUC0-t, and Cmax as well as longer Tmax. The bioavailability of orally administered enrofloxacin was decreased from 72.5% to 24.8% by rifampicin. However, rifampicin did not significantly change the pharmacokinetics of enrofloxacin following intravenous administration. Our study shows that rifampicin up-regulated the small intestinal level of P-gp and BCRP and suggests that P-gp and BCRP are key factors that affected pharmacokinetic behavior of orally administered enrofloxacin by limiting its absorption from the intestine in broilers.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Proteínas Aviárias/genética , Galinhas/genética , Galinhas/metabolismo , Rifampina/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacocinética , Hidrocarboneto de Aril Hidroxilases/genética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Proteínas Aviárias/metabolismo , Disponibilidade Biológica , Família 3 do Citocromo P450/genética , Família 3 do Citocromo P450/metabolismo , Enrofloxacina , Feminino , Fluoroquinolonas/metabolismo , Expressão Gênica , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo
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