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1.
Indian J Crit Care Med ; 21(11): 779-782, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29279640

RESUMEN

OBJECTIVE: The aim was to analyze the impact of education and training of nurses on the incidence of ventilator-associated pneumonia (VAP) and central line-associated bloodstream infection (CLABSI). PATIENTS AND METHODS: A prospective observational study at a tertiary care hospital included adult patients with Intensive Care Unit stay >48 h. The study was done in three phases: in Phase 1, baseline VAP and CLABSI incidence was calculated; in Phase 2, education and training of nurses; and in Phase 3, data were recollected for the incidence of VAP and CLABSI. RESULTS: The baseline incidence of VAP in Phase 1 was 28.86/1000 ventilator days and that of CLABSI was 7.89/1000 central-line days. In Phase 3, the incidence of VAP increased to 35.06 and that of CLABSI decreased significantly, 1.73. CONCLUSION: Intensive education and training sessions with feedback from nurses over a period of 6 months led to significant reduction in the incidence of CLABSI; however, the incidence of VAP increased.

2.
Carcinogenesis ; 34(9): 2039-49, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23629419

RESUMEN

Polyphenolic phytochemicals present in fruits and vegetables indisputably confer anticancer benefits upon regular consumption. Recently, we demonstrated the growth-inhibitory and apoptosis-inducing properties of polyphenol-rich sweet potato greens extract (SPGE) in cell culture and in vivo prostate cancer xenograft models. However, the bioactive constituents remain elusive. Here, we report a bioactivity-guided fractionation of SPGE based upon differential solvent polarity using chromatographic techniques that led to the identification of a remarkably active polyphenol-enriched fraction, F5, which was ~100-fold more potent than the parent extract as shown by IC50 measurements in human prostate cancer cells. High-performance liquid chromatography-ultraviolet and mass spectrometric analyses of the seven SPGE fractions suggested varying abundance of the major phenols, quinic acid (QA), caffeic acid, its ester chlorogenic acid, and isochlorogenic acids, 4,5-di-CQA, 3,5-di-CQA and 3,4-di-CQA, with a distinct composition of the most active fraction, F5. Subfractionation of F5 resulted in loss of bioactivity, suggesting synergistic interactions among the constituent phytochemicals. Quantitative analyses revealed a ~2.6- and ~3.6-fold enrichment of QA and chlorogenic acid, respectively, in F5 and a definitive ratiometric relationship between the isochlorogenic acids. Daily oral administration of 400mg/kg body wt of F5 inhibited growth and progression of prostate tumor xenografts by ~75% in nude mice, as evidenced by tumor volume measurements and non-invasive real-time bioluminescence imaging. These data generate compelling grounds to further examine the chemopreventive efficacy of the most active fraction of SPGE and suggest its potential usefulness as a dietary supplement for prostate cancer management.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Ipomoea batatas/química , Extractos Vegetales/administración & dosificación , Polifenoles/administración & dosificación , Neoplasias de la Próstata/dietoterapia , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Suplementos Dietéticos , Sinergismo Farmacológico , Humanos , Masculino , Ratones , Extractos Vegetales/química , Polifenoles/química , Neoplasias de la Próstata/patología , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Carcinogenesis ; 34(7): 1558-66, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23430955

RESUMEN

Plant extracts, a concoction of bioactive non-nutrient phytochemicals, have long served as the most significant source of new leads for anticancer drug development. Explored for their unique medicinal properties, the leaves of Piper betel, an evergreen perennial vine, are a reservoir of phenolics with antimutagenic, antitumor and antioxidant activities. Here, we show that oral feeding of betel leaf extract (BLE) significantly inhibited the growth of human prostate xenografts implanted in nude mice compared with vehicle-fed controls. To gain insights into the 'active principles', we performed a bioactivity-guided fractionation of methanolic BLE employing solvents of different polarity strengths using classical column chromatography. This approach yielded 15 fractions, which were then pooled to 10 using similar retention factors on thin-layer chromatographs. Bioactivity assays demonstrated that one fraction in particular, F2, displayed a 3-fold better in vitro efficacy to inhibit proliferation of prostate cancer cells than the parent BLE. The presence of phenols, hydroxychavicol (HC) and chavibetol (CHV), was confirmed in F2 by nuclear magnetic resonance, high-performance liquid chromatography and mass spectroscopy. Further, the HC containing F2 subfraction was found to be ~8-fold more potent than the F2 subfraction that contained CHV, in human prostate cancer PC-3 cells as evaluated by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay. Removing CHV from F2 remarkably decreased the IC50 of this fraction, indicating that HC is perhaps the major bioactive constituent, which is present to an extent of 26.59% in BLE. These data provide evidence that HC is a potential candidate for prostate cancer management and warrants further preclinical evaluation.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Piper/química , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Antineoplásicos Fitogénicos/química , Apoptosis , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Fraccionamiento Químico , Cromatografía Líquida de Alta Presión , Eugenol/análogos & derivados , Eugenol/química , Eugenol/aislamiento & purificación , Eugenol/uso terapéutico , Humanos , Inmunohistoquímica , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Masculino , Metanol/química , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fitoterapia , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Solventes/química , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Eur J Med Chem ; 45(9): 3709-18, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20627471

RESUMEN

A series of novel dibenzo[b,d]furan mono-carboxylic acid derivatives were synthesized, characterized and evaluated for their ability to inhibit Protein Tyrosine Phosphatase 1B (PTP1B) in vitro in order to use them as potential anti-diabetic agents. Structure-activity relationship study led to the identification of potent compound 5 E which inhibited PTP1B with IC(50) value of 82+/-0.43 nM. Compound 5 E was screened in vivo as drug candidate for anti-diabetic activity using rosiglitazone maleate as the standard. Compound 5 E showed significant reduction in body weight, fed-state whole blood glucose (WBG), fasting WBG, plasma glucose and plasma cholesterol levels and non-significant reduction in fasting plasma triglyceride levels in ob/ob mice.


Asunto(s)
Ácidos Carboxílicos/síntesis química , Ácidos Carboxílicos/farmacología , Furanos/química , Hipoglucemiantes/síntesis química , Hipoglucemiantes/farmacología , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Ácidos Carboxílicos/química , Dominio Catalítico , Colesterol/sangre , Descubrimiento de Drogas , Hipoglucemiantes/química , Concentración 50 Inhibidora , Masculino , Ratones , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 1/química , Especificidad por Sustrato , Triglicéridos/sangre
5.
Eur J Med Chem ; 44(8): 3147-57, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19349096

RESUMEN

A series of novel isochroman mono-carboxylic acid derivatives were synthesized, characterized and evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B) in vitro in order to use them as potential anti-diabetic agents. Analysis of structure-activity relationships led to the identification of potent compound 4n which inhibited PTP1B with IC(50) value of 51.63+/-0.91 nM. In general, high potency was associated with a dithiolane ring with a spacer of five carbons to the isochroman ring. Compound 4n has been selected for in vivo evaluation as drug candidate for anti-diabetic activity.


Asunto(s)
Ácidos Carboxílicos/síntesis química , Ácidos Carboxílicos/farmacología , Diseño de Fármacos , Hipoglucemiantes/síntesis química , Hipoglucemiantes/farmacología , Animales , Ácidos Carboxílicos/química , Hipoglucemiantes/química , Concentración 50 Inhibidora , Masculino , Ratones , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Estereoisomerismo , Relación Estructura-Actividad
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