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1.
Lasers Med Sci ; 32(8): 1819-1823, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28699044

RESUMEN

UVA1 phototherapy, a new therapeutic approach, has recently been shown good efficacy in the treatment of palmoplantar pustulosis (PPP). The purpose of this study was to compare the efficacy of UVA1 and narrowband UVB (NB-UVB) therapy in the treatment of PPP. Patients with PPP were randomly assigned to either UVA1 or NB-UVB therapy according to a left-right randomization table. Both treatments were performed three times weekly for up to 30 sessions. Clinical evaluation was based on the Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI) score. Totally 64 patients completed the study. Both UVA1 and NB-UVB therapy showed a statistically significant reduction of PPPASI score compared with the baseline value at the end of the treatment period (P < 0.05). There was a significantly greater mean reduction of PPPASI score in the UVA1 treated group when compared to the NB-UVB treated patients at 30 sessions (6.0 ± 2.4 vs. 4.4 ± 1.4, P < 0.05). No phototoxic reaction or bullous changes were observed in either group. Both NB-UVB and UVA1 phototherapy of PPP resulted in significant improvement. UVA1 phototherapy was more effective than NB-UVB irradiation in the treatment of PPP.


Asunto(s)
Psoriasis/radioterapia , Terapia Ultravioleta/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del Tratamiento , Rayos Ultravioleta
2.
Arterioscler Thromb Vasc Biol ; 35(1): 71-8, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25359865

RESUMEN

OBJECTIVE: Homocysteine can accelerate the senescence of endothelial progenitor cells or endothelial cells (ECs) via telomerase inactivation and length shortening. However, the underlying mechanism is unclear. Here, we investigated whether homocysteine promotes endothelial senescence by reducing the expression and activity of human telomerase reverse transcriptase (hTERT) by DNA methylation to reduce ECs telomerase activity. APPROACH AND RESULTS: When compared with primary human umbilical vein endothelial cells grown under standard conditions, ECs with chronic homocysteine treatment showed accelerated upregulation of p16, p21, and p53, markers of cellular senescence, during 6 to 10 passages. Interestingly, homocysteine-stimulated but not angiotensin II-stimulated ECs senescence could be reversed by hypermethylation induced by folic acid or s-adenosylmethionine supplementation. Meanwhile, homocysteine promoted the shortening of telomere length specifically related to restoration of hTERT transcriptional expression and CCCTC-binding factor binding sites with hTERT promoter hypomethylation, as detected by quantitative real-time polymerase chain reaction, Western blot, methylation-specific polymerase chain reaction, and bisulfite sequencing assay. Electrophoretic mobility shift assay and chromatin immunoprecipitation results showed that homocysteine-reduced telomere activity and homocysteine-induced EC senescence might contribute to hTERT promoter demethylation by increasing CCCTC-binding factor repression and interfering in the SP1 binding to the demethylated hTERT promoter, which might relate with reduced of DNA methyltransferase 1. Furthermore, the CCCTC-binding factor-dependent mechanism of homocysteine-reduced hTERT expression via DNA demethylation was confirmed in aortic endothelia of mice with hyperhomocysteine levels. CONCLUSIONS: CCCTC-binding factor and SP1 cross talk may contribute to homocysteine-reduced hTERT DNA methylation and expression in endothelial senescence.


Asunto(s)
Senescencia Celular/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Homocisteína/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Telomerasa/metabolismo , Telómero/efectos de los fármacos , Angiotensina II/metabolismo , Animales , Sitios de Unión , Factor de Unión a CCCTC , Células Cultivadas , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Modelos Animales de Enfermedad , Ácido Fólico/farmacología , Regulación Enzimológica de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/enzimología , Humanos , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/enzimología , Hiperhomocisteinemia/genética , Masculino , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas , Interferencia de ARN , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , S-Adenosilmetionina/farmacología , Factor de Transcripción Sp1/genética , Factor de Transcripción Sp1/metabolismo , Telomerasa/genética , Telómero/metabolismo , Acortamiento del Telómero/efectos de los fármacos , Factores de Tiempo , Transfección , Proteína p53 Supresora de Tumor/metabolismo
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