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1.
J Cardiovasc Pharmacol ; 82(2): 148-156, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37295072

RESUMO

PURPOSE: This study evaluated the association among the plasma concentration of ticagrelor, ARC124910XX, aspirin, and salicylic acid with the risk of recent bleeding in patients with the acute coronary syndrome. To this end, we developed an accurate model to predict bleeding. METHODS: A total of 84 patients included in this study cohort between May 2021 and November 2021. The risk factors were identified by univariate and multivariate analyses, and statistically significant risk factors identified in the multivariate analysis were included in the nomogram. We used the calibration curve and the receiver operating characteristic curve to verify the accuracy of the prediction model. RESULTS: Multivariable logistic analysis showed that ticagrelor concentration (odds ratio [OR]: 2.47, 95% confidence interval [CI], 1.51-4.75, P = 0.002), ST-segment elevation acute myocardial infarction (OR: 32.2, 95% CI, 2.37-780, P = 0.016), and lipid-lowering drugs (OR: 11.52, 95% CI, 1.91-110, P = 0.015) were positively correlated with bleeding. However, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (OR: 0.04, 95% CI, 0.004-0.213, P < 0.001) was negatively correlated with bleeding. The receiver operating characteristic curve analysis showed that ticagrelor concentration and these factors together predict the occurrence of bleeding (area under receiver operating characteristic curve = 0.945, 95% CI, 0.896-0.994) and that ticagrelor concentration >694.90 ng/mL is the threshold of bleeding concentration (area under receiver operating characteristic curve = 0.696, 95% CI, 0.558-0.834). CONCLUSION: In patients with acute coronary syndrome treated with dual antiplatelet therapy, ticagrelor concentration >694.90 ng/mL was an independent risk factor for bleeding (OR: 2.47, 95% CI, 1.51-4.75, P = 0.002), but ARC124910XX and salicylic acid concentration did not affect bleeding risk ( P > 0.05).


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Ticagrelor/efeitos adversos , Aspirina , Inibidores da Agregação Plaquetária , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , População do Leste Asiático , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Ácido Salicílico/uso terapêutico , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento
2.
BMC Plant Biol ; 19(1): 191, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31072335

RESUMO

BACKGROUND: BRASSINAZOLE-RESISTANT (BZR) family genes encode plant-specific transcription factors (TFs) that participate in brassinosteroid signal transduction. BZR TFs have vital roles in plant growth, including cell elongation. However, little is known about BZR genes in sugar beet (Beta vulgaris L.). RESULTS: Therefore, we performed a genome-wide investigation of BvBZR genes in sugar beet. Through an analysis of the BES1_N conserved domain, six BvBZR gene family members were identified in the sugar beet genome, which clustered into three subgroups according to a phylogenetic analysis. Each clade was well defined by the conserved motifs, implying that close genetic relationships could be identified among the members of each subfamily. According to chromosomal distribution mapping, 2, 1, 1, 1, and 1 genes were located on chromosomes 1, 4, 5, 6, and 8, respectively. The cis-acting elements related to taproot growth were randomly distributed in the promoter sequences of the BvBZR genes. Tissue-specific expression analyses indicated that all BvBZR genes were expressed in all three major tissue types (roots, stems, and leaves), with significantly higher expression in leaves. Subcellular localization analysis revealed that Bv1_fxre and Bv6_nyuw are localized in the nuclei, consistent with the prediction of Wolf PSORT. CONCLUSION: These findings offer a basis to predict the functions of BZR genes in sugar beet, and lay a foundation for further research of the biological functions of BZR genes in sugar beet.


Assuntos
Beta vulgaris/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Fatores de Transcrição/genética , Motivos de Aminoácidos , Beta vulgaris/efeitos dos fármacos , Cromossomos de Plantas/genética , Sequência Conservada/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Proteínas de Fluorescência Verde/metabolismo , Motivos de Nucleotídeos/genética , Filogenia , Reguladores de Crescimento de Plantas/farmacologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo
3.
Drug Des Devel Ther ; 12: 2017-2024, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30013321

RESUMO

BACKGROUND: Nocturnal symptoms are common in Parkinson's disease (PD), which greatly affect the quality of life but are often overlooked in clinical settings. Treatment strategies that provide sustained dopaminergic stimulation may have sleep benefits. OBJECTIVE: To investigate the treatment effects of pramipexole (PPX) sustained release (SR) versus PPX immediate release (IR) on nocturnal symptoms in advanced PD patients with sleep disturbances. MATERIALS AND METHODS: In this study, the PPX clinical trial (NCT00466167) was retrospectively analyzed for PD Sleep Scale (PDSS) total and domain scores in patients with advanced idiopathic PD receiving either PPX SR or PPX IR, who experienced motor fluctuations while on stable levodopa with a baseline PDSS total score of <90, indicating sleep disturbances. Analysis of covariance test was used to compare the adjusted mean changes at week 18 from baseline between treatment groups, after adjusting for pooled country and baseline scores. RESULTS: A total of 119 patients with PD reported sleep disturbances at baseline (PDSS <90; SR, n=59; IR, n=60). At week 18, patients receiving PPX SR reported numerically greater improvement of sleep disturbance than those receiving PPX IR, although the difference of 6.8 points was not statistically significant (adjusted mean changes in PDSS total score, SR=28.5 versus IR=21.7 points, P=0.165). Patients receiving PPX SR observed a numerically greater adjusted mean change in all PDSS domains compared with PPX IR. The overall proportions of patients with any adverse event were similar between both PPX SR and IR groups (62.7% versus 70.0%). CONCLUSION: Both the PPX formulations showed improvements in nocturnal symptoms in advanced PD patients with sleep disturbances and were generally well tolerated. Given the known pharmacokinetic profile of an SR formulation and numerical advantage in PDSS mean change over IR formulation, these preliminary evidences support future prospectively designed studies to investigate the effects of PPX SR for improved sleep.


Assuntos
Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/uso terapêutico , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Pramipexol/administração & dosagem , Pramipexol/uso terapêutico , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Método Duplo-Cego , Composição de Medicamentos , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Pramipexol/efeitos adversos , Sono/efeitos dos fármacos , Software
4.
PLoS One ; 12(4): e0175454, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28406933

RESUMO

In sugar beet (Beta vulgaris L.), taproot weight and sucrose content are the important determinants of yield and quality. However, high yield and low sucrose content are two tightly bound agronomic traits. The advances in next-generation sequencing technology and the publication of sugar beet genome have provided a method for the study of molecular mechanism underlying the regulation of these two agronomic traits. In this work, we performed comparative transcriptomic analyses in the high taproot yield cultivar SD13829 and the high sucrose content cultivar BS02 at five developmental stages. More than 50,000,000 pair-end clean reads for each library were generated. When taproot turned into the rapid growth stage at the growth stage of 82 days after emergence (DAE), eighteen enriched gene ontology (GO) terms, including cell wall, cytoskeleton, and enzyme linked receptor protein signaling pathway, occurred in both cultivars. Differentially expressed genes (DEGs) of paired comparison in both cultivars were enriched in the cell wall GO term. For pathway enrichment analyses of DEGs that were respectively generated at 82 DAE compared to 59 DAE (the earlier developmental stage before taproot turning into the rapid growth stage), plant hormone signal transduction pathway was enriched. At 82 DAE, the rapid enlarging stage of taproot, several transcription factor family members were up-regulated in both cultivars. An antagonistic expression of brassinosteroid- and auxin-related genes was also detected. In SD13829, the growth strategy was relatively focused on cell enlargement promoted by brassinosteroid signaling, whereas in BS02, it was relatively focused on secondarily cambial cell division regulated by cytokinin, auxin and brassinosteroid signaling. Taken together, our data demonstrate that the weight and sucrose content of taproot rely on its growth strategy, which is controlled by brassinosteroid, auxin, cytokinin, and gibberellin.


Assuntos
Beta vulgaris/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas de Plantas/biossíntese , Raízes de Plantas/crescimento & desenvolvimento , Sacarose/metabolismo , Transcriptoma/fisiologia , Câmbio/metabolismo , Perfilação da Expressão Gênica
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