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Métodos Terapéuticos y Terapias MTCI
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1.
PLoS One ; 14(9): e0214037, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31518346

RESUMEN

Linezolid is an oxazolidinone antibiotic that effectively treats methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Since rifampicin induces other antibiotic effects, it is combined with linezolid in therapeutic regimes. However, linezolid blood concentrations are reduced by this combination, which increases the risk of the emergence of antibiotic-resistant bacteria. We herein demonstrated that the combination of linezolid with rifampicin inhibited its absorption and promoted its elimination, but not through microsomal enzymes. Our results indicate that the combination of linezolid with rifampicin reduces linezolid blood concentrations via metabolic enzymes.


Asunto(s)
Antibióticos Antituberculosos/farmacología , Linezolid/farmacocinética , Rifampin/farmacología , Animales , Antibióticos Antituberculosos/farmacocinética , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Interacciones Farmacológicas , Humanos , Hígado/metabolismo , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología
2.
Cancer Res ; 77(23): 6603-6613, 2017 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-29038345

RESUMEN

Clock genes encoding transcription factors that regulate circadian rhythms may inform chronomodulated chemotherapy, where time-dependent dose alterations might affect drug efficacy and reduce side effects. For example, inhibiting the essential cystine transporter xCT with sulfasalazine induces growth arrest in cancer cells. Although the anticancer effects of sulfasalazine have been studied extensively, its effects on transcriptional control of xCT expression have not been studied. Here, we show that sulfasalazine administration during the period of increased xCT expression improves its anticancer effects and that the Clock gene itself induces xCT expression and regulates its circadian rhythm. Our findings highlight the clinical potential of chronomodulated chemotherapy and the importance of xCT-mediated transcriptional regulation in the utility of such strategies. Cancer Res; 77(23); 6603-13. ©2017 AACR.


Asunto(s)
Factores de Transcripción ARNTL/genética , Sistema de Transporte de Aminoácidos y+/antagonistas & inhibidores , Antineoplásicos/farmacología , Relojes Circadianos/fisiología , Cronoterapia de Medicamentos , Sulfasalazina/farmacología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación de la Expresión Génica , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos ICR , Compuestos Organoplatinos/farmacología , Oxaliplatino , Interferencia de ARN , ARN Interferente Pequeño/genética , Transcripción Genética/genética
4.
Int J Infect Dis ; 17(12): e1234-6, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23791858

RESUMEN

In recent years, carbapenem-resistant Acinetobacter baumannii infections have been responsible for outbreaks in medical facilities. A 35-year-old Japanese woman developed a skin and soft tissue infection due to carbapenem-resistant A. baumannii. The isolate was resistant to antibiotics other than ampicillin-sulbactam and colistin, suggesting drug resistance due to carbapenemase production by OXA-23. We selected a combination therapy consisting of intravenous ampicillin-sulbactam and meropenem. No changes were observed in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, or serum creatinine during therapy, and carbapenem-resistant A. baumannii was not detected in wound exudates 3 days after therapy initiation. In our patient's case, combination therapy with ampicillin-sulbactam and meropenem was successful. Thus, combination therapy with ampicillin-sulbactam and meropenem is effective against skin and soft tissue infection due to carbapenem-resistant A. baumannii. Combination therapy with intravenous ampicillin-sulbactam and meropenem may be an option for skin and soft tissue infections due to carbapenem-resistant A. baumannii.


Asunto(s)
Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter baumannii , Antibacterianos/uso terapéutico , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/microbiología , Tienamicinas/uso terapéutico , Infecciones por Acinetobacter/diagnóstico , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , Adulto , Ampicilina/farmacología , Ampicilina/uso terapéutico , Antibacterianos/farmacología , Carbapenémicos/farmacología , Quimioterapia Combinada , Femenino , Humanos , Meropenem , Pruebas de Sensibilidad Microbiana , Enfermedades Cutáneas Bacterianas/diagnóstico , Infecciones de los Tejidos Blandos/diagnóstico , Sulbactam/farmacología , Sulbactam/uso terapéutico , Tienamicinas/farmacología , Resultado del Tratamiento , Resistencia betalactámica
5.
Chronobiol Int ; 28(3): 267-74, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21452922

RESUMEN

Methotrexate (MTX) is the most important drug for treating rheumatoid arthritis (RA). It has been stated that cytokines play an important role in the pathogenesis of RA, and that cytokine levels increase and show 24-h rhythms in RA patients. Previously, we found that arthritis was relieved after the administration of MTX at specific times in synchronization with the 24-h rhythm of tumor necrosis factor (TNF)-α in collagen-induced arthritis (CIA) animals. Based on our findings in an earlier study of the dosing time-dependent effects of MTX in MRL/lpr mice, which develop autoimmune disorders that share similarities with human RA, we examined here the utility of MTX chronotherapy in Japanese RA patients. In an initial animal modeling study, we collected blood from MRL/lpr mice at different times (2, 6, 10, 14, 18, or 22 hours after the light was turned on [HALO]), and we measured TNF-α mRNA expression in leukocytes. MTX was administered to the mice at two different dosing times (6 or 18 HALO), and various blood parameters were measured to estimate arthritis activity. TNF-α mRNA levels showed a clear 24-h rhythm with a peak at 22 HALO and a trough at 18 HALO after RA had developed. In these MRL/lpr mice, inflammation and TNF-α were markedly reduced when the MTX dosing time was matched to the time (18 HALO) when the TNF-α level began to increase. We then applied these findings to Japanese RA patients by switching them from the standard MTX three times/wk (day 1: after breakfast and supper; day 2: after breakfast schedule), to chronotherapy, in which the dose and number of doses/wk were not changed but MTX was administered once-a-day at bedtime. Disease Activity Score (DAS)28, modified health assessment questionnaire (MHAQ), and adverse effects were assessed. With MTX chronotherapy, DAS28, which is commonly used to quantitatively assess RA symptoms, was significantly improved at all follow-up clinical visit times compared with the baseline (vs. 1 mo: p = .0197, 2 mos: p = .0107, 3 mos: p = .0087). Significant symptom recovery was observed in 41.2% of patients, and 23.5% of patients achieved clinical remission during the 3 mos of follow-up. Functional capacity of RA patients, as indicated by the MHAQ, was markedly improved by chronotherapy. There were no severe adverse effects. Thus, we demonstrated (i) inflammation and plasma TNF-α concentrations were significantly reduced in MRL/lpr mice treated with MTX at 18 HALO, the time when TNF-α mRNA level began to increase; and (ii) MTX bedtime chronotherapy was safe, markedly reduced disease activity, and improved the functional capacity of RA patients. The findings on RA patients show that bedtime MTX chronotherapy can improve RA symptoms compared to the current standard dosing methods.


Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Cronoterapia de Medicamentos , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Adulto , Animales , Cronoterapia , Ritmo Circadiano , Humanos , Inmunoglobulina G , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Leucocitos/metabolismo , Masculino , Ratones , Ratones Endogámicos MRL lpr , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor Reumatoide , Proteína Amiloide A Sérica/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Adulto Joven
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