RESUMEN
BACKGROUND: Empyema is a rare but important complication among patients with end-stage renal disease (ESRD). However, a nationwide, propensity-matched cohort study has never been performed. METHODS: We conducted a retrospective cohort study using data from the National Health Insurance Research Database of Taiwan. The ESRD group consisted of 82 765 patients diagnosed between 2000 and 2008. The comparison group consisted of individuals without kidney disease selected at a 1:1 ratio matched by propensity score estimated with age, gender, year of diagnosis and comorbidities. The occurrence of empyema was monitored until the end of 2011. The hazard ratios (HRs) of empyema were estimated using the Cox proportional hazards model. RESULTS: The incidence of empyema was 2.76-fold higher in the ESRD group than in the comparison group (23.7 vs. 8.19/10 000 person-years, P <0.001), with an adjusted HR of 3.01 [95% confidence interval (CI) = 2.67-3.39]. There was no difference of the incidence of empyema between hemodialysis (HD) and peritoneal dialysis (PD) (adjusted HR = 0.96, 95% CI = 0.75-1.23). In addition, 30-day mortality rate since empyema diagnosis was significantly higher in ESRD group than the comparison group (15.9% vs. 10.9%), with an adjusted OR of 1.69 (95% CI = 1.17-2.44). CONCLUSION: The risk of empyema was significantly higher in patients with ESRD than in those without kidney disease. The occurrence of empyema was without difference in patients undergoing HD compared to those undergoing PD. The 30-day mortality rate since empyema diagnosis was also significantly higher in patients with ESRD.
Asunto(s)
Empiema/epidemiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Adulto , Distribución por Edad , Anciano , Comorbilidad , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Taiwán/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Previous studies have suggested that mycobacterial infections could trigger autoimmune diseases, including rheumatoid arthritis (RA). OBJECTIVE: To explore the association between previous tuberculosis (TB) and RA. METHODS: We conducted a case-control study using data obtained from the National Health Insurance (NHI) system of Taiwan. We identified 26 535 adults with RA from 2002 to 2011, with the date of diagnosis as the index date. This number was randomly selected and frequency-matched four times by age, sex and the year of index date from among non-RA individuals. Odds ratios (ORs) of RA were calculated for associations with TB. RESULTS: Compared with controls, RA patients had a crude OR of 1.77 for TB (95%CI 1.61-1.94). The strength of the association between RA and TB remained at the same level after controlling for other potential risk factors (adjusted OR 1.73, 95%CI 1.57-1.90), although RA patients tended to have a higher prevalence of hypertension, coronary artery disease and kidney disease. CONCLUSION: TB was much more prevalent in RA patients than in control subjects. Prospective cohort studies are required to establish a causal relationship between previous TB and RA.
Asunto(s)
Artritis Reumatoide/complicaciones , Tuberculosis/epidemiología , Adulto , Anciano , Estudios de Casos y Controles , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Taiwán/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The relationship between tuberculosis (TB) and subsequent chronic kidney disease (CKD) remains unclear. Therefore, we examined the risk of CKD among patients with TB in a nationwide study. METHODS: We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan. The cohort included 8735 patients who were newly diagnosed with TB. Patients were recruited between 1998 and 2002, and the date of diagnosis was defined as the index date. Each patient was randomly matched with four people from the general population without TB, according to age, gender and the index year. The occurrence of CKD was followed up until the end of 2011. The relative risks of CKD were estimated using the Cox proportional hazard model after adjusting for age, gender, index year and comorbidities. RESULTS: The overall incidence of CKD was 1.27-fold greater in the TB cohort than in the non-TB cohort. The adjusted hazard ratio (HR) of CKD associated with TB was higher in women (1.72; 95% confidence interval [CI]: 1.33-2.22), those aged <50 years (1.67; 95% CI: 1.15-2.41) and those without comorbidities (1.39; 95% CI: 1.06-1.83). In addition, patients with more comorbidities among hypertension, diabetes and hyperlipidemia have a greater risk of developing CKD in both cohorts, and the adjusted HRs were higher in the TB cohort than in the non-TB cohort. CONCLUSION: TB patients had a significantly higher risk of developing CKD than the general population. The detailed mechanisms need further investigation.
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Insuficiencia Renal Crónica/epidemiología , Tuberculosis/complicaciones , Adulto , Anciano , Comorbilidad , Complicaciones de la Diabetes , Femenino , Humanos , Hiperlipidemias/complicaciones , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología , Tuberculosis/epidemiologíaAsunto(s)
Infarto Encefálico/inducido químicamente , Técnicas Cosméticas/efectos adversos , Ácido Hialurónico/efectos adversos , Oclusión de la Arteria Retiniana/inducido químicamente , Viscosuplementos/efectos adversos , Adulto , Ceguera/inducido químicamente , Femenino , Humanos , Imagen por Resonancia Magnética , NarizRESUMEN
BACKGROUND: Figitumumab (CP-751,871) is a fully human IgG2 monoclonal antibody that inhibits the insulin-like growth factor 1 receptor. This multicenter, randomized, phase III study investigated the efficacy of figitumumab plus erlotinib compared with erlotinib alone in patients with pretreated, nonsmall-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients (stage IIIB/IV or recurrent disease with nonadenocarcinoma histology) who had previously received at least one platinum-based regimen were randomized to receive open-label figitumumab (20 mg/kg) plus erlotinib 150 mg/day or erlotinib alone every 3 weeks. The primary end point was overall survival (OS). RESULTS: Of 583 patients randomized, 579 received treatment. The study was closed early by an independent data safety monitoring committee due to results crossing the prespecified futility boundary. At the final analysis, median OS was 5.7 months for figitumumab plus erlotinib and 6.2 months for erlotinib alone [hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.91-1.31; P = 0.35]. Median progression-free survival was 2.1 months for figitumumab plus erlotinib and 2.6 months for erlotinib alone (HR 1.08; 95% CI 0.90-1.29; P = 0.43). Treatment-related nonfatal serious adverse events occurred in 18% and 5% of patients in the figitumumab arm or erlotinib alone arm, respectively. There were nine treatment-related deaths (three related to both drugs, four related to erlotinib alone and two related to figitumumab). CONCLUSIONS: The addition of figitumumab to erlotinib did not improve OS in patients with advanced, pretreated, nonadenocarcinoma NSCLC. Clinical development of figitumumab has been discontinued. CLINICAL TRIAL ID: NCT00673049.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Clorhidrato de Erlotinib/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: The role of autoimmune pathology in development and progression of chronic obstructive pulmonary disease (COPD) is becoming increasingly popular. Our aim was to assess the association between patients with rheumatoid arthritis (RA) and subsequent COPD risk in a nationwide population. METHOD: We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan. The RA cohort included patients who were newly diagnosed and recruited between 1998 and 2008. Each patient was randomly frequency-matched for age, sex and the year of index date with people without RA from the general population. The newly diagnosed COPD was followed up until the end of 2010. The relative risks of COPD were estimated using Cox proportional hazard models after adjusting for age, sex, index year and comorbidities. RESULT: The overall incidence rate of COPD was 1.74-fold higher in the RA cohort than in the non-RA cohort (5.25 vs. 3.01 per 1000 person-years, 95% confidence interval (CI) = 1.68-1.81). Age-related risk analysis showed an increased incidence of COPD with age in both RA and non-RA cohorts. However, adjusted hazard ratio (HR) maximum was witnessed in the age range of 20-34 years (adjusted HR: 7.67, 95% CI=1.94-30.3), whereas adjusted HR minimum was observed in the oldest age group (>65 years). CONCLUSION: Patients with RA have a significantly higher risk of developing COPD than that of the control population. Further, age-related risk analysis indicated much higher adjusted HR in younger patients although COPD incidence increased with age. It can be hypothesized that in addition to cigarette smoke, RA may be a determining factor for COPD incidence and/or facilitates shortening of the time course for developing COPD. However, further investigation is needed to corroborate this hypothesis.
Asunto(s)
Artritis Reumatoide/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/etiología , Adulto , Distribución por Edad , Anciano , Artritis Reumatoide/epidemiología , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Retrospectivos , Medición de Riesgo/métodos , Distribución por Sexo , Taiwán/epidemiología , Adulto JovenRESUMEN
BACKGROUND: This preplanned subset analysis of the phase III MONET1 study aimed to determine whether motesanib combined with carboplatin/paclitaxel (C/P) would result in improved overall survival (OS) versus chemotherapy alone, in a subset of Asian patients with nonsquamous nonsmall-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with nonsquamous NSCLC (stage IIIB/IV or recurrent) and no prior systemic therapy for advanced disease were randomized to IV carboplatin (AUC, 6 mg/ml min) and paclitaxel (200 mg/m2) for up to six 3-week cycles, plus either oral motesanib 125 mg q.d. or placebo. Primary end point was OS; secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. RESULTS: Two hundred twenty-seven Asian patients from MONET1 were included in this descriptive analysis. Median OS was 20.9 months in the motesanib plus C/P arm and 14.5 months in the placebo plus C/P arm (P=0.0223); median PFS was 7.0 and 5.3 months, respectively, (P=0.0004); and ORR was 62% and 27%, respectively, (P<0.0001). Grade≥3 adverse events were more common in the motesanib plus C/P arm versus placebo plus C/P (79% versus 61%). CONCLUSION: In this preplanned subset analysis of Asian patients with nonsquamous NSCLC, motesanib plus C/P significantly improved OS, PFS, and ORR versus placebo plus C/P. CLINICAL TRIAL NUMBER: NCT00460317.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Pueblo Asiatico , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Diarrea/inducido químicamente , Supervivencia sin Enfermedad , Método Doble Ciego , Femenino , Humanos , Indoles/administración & dosificación , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Oligonucleótidos , Paclitaxel/administración & dosificación , Modelos de Riesgos Proporcionales , Resultado del Tratamiento , Adulto JovenRESUMEN
In this paper, experimental studies of a decentralized neural network control scheme of the reference compensation technique applied to control a 2-degrees-of-freedom (2-DOF) inverted pendulum on an x - y plane are presented. Each axis is controlled by two separate neural network controllers to have a decoupled control structure. Neural network controllers are applied not only to balance the angle of pendulum, but also to control the position tracking of the cart. The decoupled control structure can compensate for uncertainties and cancel coupling effects. Especially, a circular trajectory tracking task is tested for position tracking control of the cart while maintaining the angle of the pendulum. Experimental result shows that position control of the inverted pendulum and cart is successful.
Asunto(s)
Algoritmos , Técnicas de Apoyo para la Decisión , Modelos Teóricos , Redes Neurales de la Computación , Reconocimiento de Normas Patrones Automatizadas/métodos , Simulación por Computador , Sistemas de Computación , Retroalimentación , InvestigaciónRESUMEN
To evaluate the question of whether or not paclitaxel affects the distribution and metabolism of chemical carcinogens such as 2-aminofluorene (AF) on Sprague-Dawley rats were examined. The AF, acetylated AF and AF metabolites were determined and examined by using high performance liquid chromatography. After having received AF only, AF with paclitaxel at the same time and paclitaxel pretreated for 24 h then treated with AF for 24 h, urine, stool and tissues such as liver, kidneys, stomach, colon, bladder and blood were collected and assayed for AF and its metabolites. Compared to the control group, paclitaxel caused an increase of the metabolites excreted in urine and stool. The major metabolite excreted in urine and stool was 9-OH-AAF. The liver is the major metabolism center and the major residual metabolite of AF in the liver was also 9-OH-AAF.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinógenos/farmacocinética , Fluorenos/farmacocinética , Paclitaxel/farmacología , Fitoterapia , Acetilación , Administración Oral , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Cromatografía Líquida de Alta Presión , Interacciones Farmacológicas , Heces/química , Fluorenos/sangre , Fluorenos/metabolismo , Fluorenos/orina , Hígado/metabolismo , Masculino , Paclitaxel/administración & dosificación , Ratas , Ratas Sprague-Dawley , Distribución TisularRESUMEN
In this study, we evaluated the potential apoptosis effects of baicalein on human promyelocytic leukemia HL-60 cells in vitro. Apoptosis induction, cell viability, morphology and caspase-3 activity were then performed to determine by flow cytometric assay, DNA gel electrophoresis, anti-ADP-ribose stain and determination of caspase-3 activity. There is a significant difference in cell death of HL-60 cells that was detected between baicalein-treated and untreated groups. Furthermore, there was a further significant increase in apoptosis induction when cells were treated with baicalein compared to without baicalein treated groups. Flow cytometric assays and DNA fragmentation gel electrophoresis also confirmed baicalein induced apoptosis in HL-60 cells. Baicalein also promoted caspase-3 activity then leading to cleavage of poly-ADP-ribose polymerase finally leading to DNA fragmentation occurrence. Furthermore, the baicalein-induced apoptosis was markedly blocked by the broad-spectrum caspase inhibitor, z-VAD-fmk. Taken together, these results suggest that treatment of human leukemia HL-60 cells with baicalein induced apoptosis through activation of caspase-3 activity.
Asunto(s)
Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Caspasas/biosíntesis , Flavanonas , Flavonoides/farmacología , Clorometilcetonas de Aminoácidos/farmacología , Anticuerpos Monoclonales , Inhibidores de Caspasas , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Citometría de Flujo , Células HL-60 , Humanos , Indicadores y Reactivos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Azul de TripanoRESUMEN
Despite advances in morphological imaging, some patients with non-small cell lung cancer (NSCLC) are found to have non-resectable disease at surgery or die of recurrence within a year of surgery. At present, metastatic bone involvement is usually assessed using conventional technetium-99m methylene diophosphate (Tc-99m MDP) whole body bone scan (bone scan), which has a high sensitivity but a poor specificity. We have attempted to evaluate the usefulness of whole body positron emission tomography with 18F-2-deoxyglucose (FDG-PET) for the detection of malignant bone metastases of NSCLC, and to compare FDG-PET results with Bone Scan findings. Forty-eight patients with biopsy-proven NSCLC and suspected to have stage IV disease underwent whole body bone scan and FDG-PET to detect bone metastases. The final diagnoses of bone metastases were established by operative, histopathological findings or clinical follow-up longer than 1 year by additional radiographs or following FDG-PET/Tc-99m MDP bone scan findings showing progressively and extensively widespread bone lesions. A total of 138 bone lesions found on either FDG-PET or Tc-99m MDP bone scan were evaluated. Among the 106 metastatic and 32 benign bone lesions, FDG-PET and Tc-99m MDP bone scan could accurately diagnose 99 and 98, as well as 30 and 2 metastatic and benign bone lesions, respectively. Diagnostic sensitivity and accuracy of FDG-PET and Tc-99m MDP bone scan were 93.4% and 92.5%, as well as 93.5% and 72.5%, respectively. In conclusion, our data suggest that FDG-PET with the same sensitivity and a better accuracy than those of Tc-99m MDP bone scan to detect metastatic bone lesions in patients with biopsy-proven NSCLC and suspected to have stage IV disease.
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Neoplasias Óseas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Neoplasias Pulmonares/patología , Radiofármacos , Medronato de Tecnecio Tc 99m , Tomografía Computarizada de Emisión/métodos , Adulto , Anciano , Neoplasias Óseas/secundario , Carcinoma de Pulmón de Células no Pequeñas/secundario , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Irradiación Corporal Total/métodosRESUMEN
The resistance of small cell lung cancer (SCLC) to anticancer drugs is a serious clinical problem often encountered during chemotherapy. Therefore, how to prevent this drug resistance need to be investigated. Multidrug resistance 1 (MDR1) gene and multidrug resistance-related protein (MRP) gene, two genes known to be associated with the development of drug resistance, are very common in SCLC. The purpose of this study was to evaluate retrospectively the relationship between chemotherapy responses to MDR1 gene encodes 170 kDa P-glycoprotein (Pgp) expression or MRP gene encodes 190 kDa MRP expression in SCLC. Before chemotherapy, multiple nonconsecutive sections of the bronchoscopy biopsy specimens of SCLC from 50 patients were analyzed immunohistochemically to detect Pgp and MRP expressions. Chemotherapy responses of the 50 patients were evaluated in the third month after completion of treatment by clinical and radiological methods. Of the 23 SCLC patients with poor response to chemotherapy, 11 had positive Pgp and MRP expressions, 2 had positive Pgp but negative MRP expressions, 6 had positive MRP but negative Pgp expressions, and 4 patients had negative Pgp and MRP expressions. All 27 SCLC patients with good response had negative Pgp and MRP expression. Immunohistochemical analyses of Pgp or MRP expression are potential tools for predicting patients' chemotherapy response in SCLC.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/biosíntesis , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
In this study, paclitaxel was used to determine inhibition of arylamine N-acetyltransferase (NAT) activity, gene expression and 2-aminofluorene-DNA adduct formation in a human lung tumor cell line (A549). The activity of NAT was measured by HPLC assaying for the amounts of N-acetyl-2-aminofluorene (2-AAF) and remaining 2-aminofluorene (2-AF). Human lung tumor cell cytosols and intact cells were used for examining NAT activity and carcinogen-DNA adduct formation. The results demonstrated that NAT activity, gene expression (NAT1 mRNA) and 2-AF-DNA adduct formation in human lung tumor cells were inhibited and decreased by paclitaxel in a dose-dependent manner. The effects of paclitaxel on the values of the apparent Km and Vmax of NAT from human lung tumor cells were also determined in both examined systems. The result also indicated that paclitaxel decreased the apparent values of Km and Vmax from human lung tumor cells in both cytosol and intact cells. Thus, paclitaxel is an uncompetitive inhibitor to NAT enzyme.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Arilamina N-Acetiltransferasa/metabolismo , Carcinógenos/química , Aductos de ADN/efectos de los fármacos , Fluorenos/química , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Paclitaxel/farmacología , Acetilación , Arilamina N-Acetiltransferasa/genética , Citosol/enzimología , Citosol/metabolismo , Depresión Química , Relación Dosis-Respuesta a Droga , Humanos , Cinética , Neoplasias Pulmonares/enzimología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
N-Acetylation is recognized as the first step in arylamine metabolism. The enzyme responsible for N-acetylation is called arylamine N-acetyltransferase (NAT),which uses acetyl coenzyme A as the acetyl group donor. Paclitaxel has been shown to exhibit antineoplastic and anticancer activity. In this study, paclitaxel was selected to determine the inhibition of arylamine N-acetyltransferase activity, gene expression (NAT mRNA) and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cell line. Paclitaxel (0.01-l microM) did decrease the level of NAT mRNA in a dose-dependent manner. The results demonstrated that paclitaxel inhibited NAT activity and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cells in a dose-dependent manner. Using standard steady-state kinetic analysis, it was demonstrated that paclitaxel was a possible uncompetitive inhibitor to NAT activity in cytosols based on the decrease in apparent values of K(m) and V(max). This report is the first demonstration that paclitaxel affected human leukemia HL-60 cells NAT activity and DNA-2-aminofluorene adduct formation.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Arilamina N-Acetiltransferasa/metabolismo , Carcinógenos/química , Aductos de ADN/efectos de los fármacos , Fluorenos/química , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Leucemia/enzimología , Leucemia/genética , Paclitaxel/farmacología , Acetilación , Animales , Arilamina N-Acetiltransferasa/genética , Citosol/enzimología , Citosol/metabolismo , Depresión Química , Relación Dosis-Respuesta a Droga , Células HL-60 , Humanos , Cinética , Ratones , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Helicobacter pylori is now recognized as an important cause of type B gastritis, which is strongly associated with gastric and duodenal ulcer disease. H. pylori may be a causative factor in patients with gastric cancer. The growth inhibition and N-acetylation of 2-Aminofluorene (AF) or P-aminobenzoic acid (PABA) by arylamine N-acetyltransferase (NAT) in H. pylori were inhibited by luteolin, a component in herbal medicine. The growth inhibition was based on the changes of optical density (OD) by using a spectrophotometer. The N-acetylation of AF or PABA by NAT from H. pylori were assayed by the amounts of acetylated and non-acetylated AF or PABA in cytosols and intact bacteria of H. pylori by using HPLC. An inhibition of growth on H. pylori demonstrated that luteolin elicited a dose-dependent growth inhibition in the H. pylori cultures. Cytosols and suspensions of H. pylori with or without specific concentrations of luteolin co-treatment showed different percentages of AF or PABA acetylation. The data indicated that there was decreased NAT activity associated with increased levels of luteolin in H. pylori cytosols and suspensions. Using standard steady-state kinetic analysis, it was demonstrated that luteolin was a possible uncompetitive inhibitor to NAT enzyme in H. pylori. This report is the first demonstration to show that luteolin can inhibit H. pylori growth and NAT activity.
Asunto(s)
Arilamina N-Acetiltransferasa/metabolismo , Citosol/enzimología , Flavonoides/farmacología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/enzimología , Úlcera Péptica/microbiología , Ácido 4-Aminobenzoico/metabolismo , Acetilación/efectos de los fármacos , Supervivencia Celular , Cromatografía Líquida de Alta Presión , Citosol/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Fluorenos/metabolismo , Fluorenos/farmacocinética , Gastritis/microbiología , Helicobacter pylori/crecimiento & desarrollo , Humanos , Cinética , Luteolina , Pruebas de Sensibilidad Microbiana , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
The fact that vitamin C (ascorbic acid) exhibits a protective effect in certain types of cancer is well documented. Our previous studies demonstrated that human bladder tumor cell line (T24) has N-acetyltransferase (NAT) activity in cytosols and intact cells. The present studies examined the inhibition of arylamine NAT activity and carcinogen (2-aminofluorene)-DNA adduct formation by ellagic acid (EA) in human bladder tumor cell lines (T24 and TSGH 8301). Two assay systems were performed, one with cellular cytosols (9,000 g supernatant), the other with intact bladder tumor cell suspensions. NAT activity and 2-aminofluorene-DNA adduct formation in T24 and TSGH 8301 cells was inhibited by EA in a dose-dependent manner in both systems, i.e.. the greater the concentration of EA in the reaction the greater the inhibition of NAT activity (dose- and time-course dependent effects). The data also indicated that EA decreased the apparent Km and Vmax of NAT enzymes from T24 and TSGH 8301 cells in cytosols. NAT activity and 2-aminofluorene-DNA adducts in T24 is higher than in TSGH 8301. This report is the first to demonstrate that EA affects human bladder tumor cell NAT activity.
Asunto(s)
2-Acetilaminofluoreno/análogos & derivados , Arilamina N-Acetiltransferasa/antagonistas & inhibidores , Aductos de ADN/metabolismo , Ácido Elágico/farmacología , Inhibidores Enzimáticos/farmacología , Flavonoides , Fenoles/farmacología , Polímeros/farmacología , Neoplasias de la Vejiga Urinaria , 2-Acetilaminofluoreno/metabolismo , Ácido 4-Aminobenzoico/metabolismo , Antineoplásicos Fitogénicos/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Polifenoles , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismoRESUMEN
Genetic regulation of acetyl coenzyme A-dependent N-acetyltransferase (NAT)and O-acetyltransferase (OAT) activities may play an important role in the metabolic activation of arylamine chemicals and carcinogens. N-acetylation is thought to be the first step in arylamine metabolism. The enzyme responsible for N-acetylation is called NAT. In this study, synthetic non-steroidal antiestrogen tamoxifen was selected for determining the inhibition of arylamine NAT activity, gene expression (NAT mRNA) and DNA-2-aminofluorene adduct formation in human leukemia HL-60 cell line. The results demonstrated that tamoxifen did not affect the level of NAT mRNA in HL-60 cells. But the results also showed that NAT activity and 2-Aminofluorene-DNA adduct formation in HL-60 cells were inhibited and decreased by tamoxifen in a dose-dependent manner when the doses of tamoxifen up to 100 micro M. We also examined the standard steady-state kinetic analysis, and the data showed that tamoxifen may be an uncompetitive inhibitor to NAT activity in cytosols based on the decrease apparent values of Km and Vmax. This report is the first finding that tamoxifen inhibited human leukemia HL-60 cells NAT activity and DNA-2-aminofluorene on adduct formation.
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2-Acetilaminofluoreno/toxicidad , Arilamina N-Acetiltransferasa/metabolismo , Aductos de ADN/genética , Células HL-60/efectos de los fármacos , Tamoxifeno/toxicidad , Arilamina N-Acetiltransferasa/antagonistas & inhibidores , Carcinógenos , Relación Dosis-Respuesta a Droga , Células HL-60/enzimología , HumanosRESUMEN
We evaluated experimentally the optical quality of poly(methyl methacrylate) (PMMA) (Storz 68UV, AMO PC58) and silicone (AMO SI19, Adatomed 90D) intraocular lenses (IOLs) and compared the results with our clinical data. We measured surface and image quality using the Zygo laser interferometer and modulation transfer function (MTF) using the Ealing EROS MTF analyzer. Contrast acuity was tested clinically with glare and without glare (Regan charts); AMO PC58, n = 18; AMO SI19, n = 7; Adatomed 90D, n = 18). Modulation transfer function and image quality were slightly better with PMMA IOLs but the reduction of MTF with silicone lenses was within the 1/8 diopter defocus range. Surface quality of silicone IOLs was superior to that of PMMA IOLs. Contrast acuity measured clinically was also slightly better with PMMA IOLs at low contrast and with glare but differences were not significant. Our results suggest that optical and visual quality of silicone IOLs is slightly lower than with PMMA IOLs. Experimental and clinical results correlated closely. However, the small differences observed are unlikely to be significant clinically.