RESUMO
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.
RESUMO
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.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Piper/química , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Neoplasias da Próstata/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fracionamento Químico , Cromatografia Líquida de Alta Pressão , Eugenol/análogos & derivados , Eugenol/química , Eugenol/isolamento & purificação , Eugenol/uso terapêutico , Humanos , Imuno-Histoquímica , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Masculino , Metanol/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Solventes/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
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.
Assuntos
Proliferação de Células/efeitos dos fármacos , Ipomoea batatas/química , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Neoplasias da Próstata/dietoterapia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais , Sinergismo Farmacológico , Humanos , Masculino , Camundongos , Extratos Vegetais/química , Polifenóis/química , Neoplasias da Próstata/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
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.
Assuntos
Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/farmacologia , Furanos/química , Hipoglicemiantes/síntese química , Hipoglicemiantes/farmacologia , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Ácidos Carboxílicos/química , Domínio Catalítico , Colesterol/sangue , Descoberta de Drogas , Hipoglicemiantes/química , Concentração Inibidora 50 , Masculino , Camundongos , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/química , Especificidade por Substrato , Triglicerídeos/sangueRESUMO
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.