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1.
Medicine (Baltimore) ; 99(11): e19186, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176045

RESUMEN

Obese individuals are apt to develop Stanford A acute aortic dissection (AAD) complicated with acute lung injury (ALI), but the mechanism is still not well defined. We aim to investigate whether oxidative stress and inflammatory are involved in the aortic dissection lung injury caused by obesity.Seventy-nine patients were categorized into AAD with obesity group (n = 17) and AAD without obesity group (n = 62) according to body mass index (BMI). Inflammatory reactions including interleukin 1ß (IL-1ß), tumor necrosis factor-α (TNF-α), IL-6, C-reactive protein (CRP) and white blood cell (WBC) count, and oxidative stress including malondialdehyde (MDA), superoxide dismutase were determined using enzyme-linked immunosorbent assays and chemiluminescence. All the patients received ascending aorta replacement combined with total arch replacement and stented elephant trunk. The postoperative complications were recorded.The incidence of preoperative hypoxemia (94.1% vs 35.5%, P < .01) and postoperative ALI (88.2% vs 40.3%, P < .01) in obese patients was significantly higher than that in non-obese patients. Besides, the ICU stay (119.2 ±â€Š59.2 vs 87.8 ±â€Š31.2 h, P < .01) and hospitalization duration (18.8 ±â€Š8.5 vs 14.3 ±â€Š8.1d, P = .048) were increased in the obese patients with AAD. The expression of IL-1ß, TNF-α, IL-6, CRP, and WBC was remarkably increased (P < .01) in obese group compared with non-obese group.Oxidative stress and inflammatory response may be involved in the process of ALI of aortic dissection caused by obesity, which provides new ideas for the treatment of ALI of the aortic dissection.


Asunto(s)
Lesión Pulmonar Aguda/cirugía , Aneurisma Disecante/cirugía , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Hipoxia/etiología , Obesidad/complicaciones , Lesión Pulmonar Aguda/diagnóstico por imagen , Adulto , Anciano , Aneurisma Disecante/diagnóstico por imagen , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Implantación de Prótesis Vascular/métodos , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Hospitales Universitarios , Humanos , Hipoxia/fisiopatología , Modelos Lineales , Masculino , Persona de Mediana Edad , Obesidad/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Cuidados Preoperatorios , Pronóstico , Valores de Referencia , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
2.
Medicine (Baltimore) ; 99(11): e19284, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176052

RESUMEN

High levels of albuminuria have been demonstrated to associate with hearing loss in non-diabetic people, while the clinical impact of low-grade albuminuria has attracted less attention. This cross-sectional population-based study aimed to examine whether hearing loss in non-diabetic United States (US) adults is independently associated with low-grade albuminuria or reduced estimated glomeruli filtration rate (eGFR).A total of 2518 participants aged 20 to 69 years were selected from the US National Health and Nutritional Examination Survey database. Participants with diabetes or high-grade albuminuria were excluded. Hearing loss was assessed using low-frequency pure-tone average (LFPTA) thresholds (0.5, 1.0, 2.0 kHz) and high-frequency pure-tone average (HFPTA) thresholds (3.0, 4.0, 6.0, 8.0 kHz). Logistic and linear regression analyses were used to evaluate associations between renal function indicators and hearing loss.The median age of included participants was 37.4 years, and 55% of them were female. Multivariate analysis revealed that participants with urinary albumin-to-creatinine ratio (UACR) in the highest tertile had a significantly higher risk of hearing loss (OR, 1.79; 95% CI, 1.01-3.19) and higher HFPTA thresholds (ß: 2.23; SE: 0.77). Participants with eGFR <60 mL/min/1.73 m had higher LFPTA thresholds (ß: 4.31; SE: 1.79). After stratification by sex, a significant risk remained only for males in the highest UACR tertile, with 2.18 times the risk of hearing loss (95% CI, 1.06-4.48).Non-diabetic US males with low-grade albuminuria are at increased risk of hearing loss, independent of eGFR.


Asunto(s)
Albuminuria/complicaciones , Albuminuria/diagnóstico , Comorbilidad , Pérdida Auditiva/epidemiología , Pérdida Auditiva/etiología , Adulto , Distribución por Edad , Anciano , Audiometría/métodos , Glucemia/análisis , Estudios Transversales , Diabetes Mellitus , Tasa de Filtración Glomerular , Pérdida Auditiva/diagnóstico , Humanos , Incidencia , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Encuestas Nutricionales , Valores de Referencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estados Unidos , Urinálisis/métodos
3.
Rev Bras Epidemiol ; 23: e200002, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32130391

RESUMEN

OBJECTIVES: To estimate the magnitude of gender differences in disability among adults aged 60 and older and to evaluate whether they can be associated with social gender inequality and socioeconomic contextual factors at the level of Brazilian federative units. METHODS: This is a multilevel study that used data from 23,575 older adults of 27 federative units who participated in the 2013 Brazilian Health Survey. The activity limitation index was developed from the item response theory, using activities of daily living and instrumental activities of daily living variables. The association of individual and contextual variables with disability was estimated by assessing the magnitude of differences between genders, using cross-level interaction effects in multilevel generalized linear models, including only the variables that were statistically significant in the final model. RESULTS: The prevalence of disability was higher among women (37.6%) than among men (26.5%), totaling 32.7% of the older adults. In the adjusted multilevel analysis, disability was influenced by income inequality (γgini = 0.022, p < 0.001) among federative units. In addition, gender differences in disability were associated with social gender inequalities (γmgiiXsex = 0.020, p = 0.004). CONCLUSION: Women had higher disability disadvantages compared to men, and those differences were associated with social gender inequalities among the Brazilian federative units influenced by income inequality.


Asunto(s)
Evaluación de la Discapacidad , Personas con Discapacidad/estadística & datos numéricos , Encuestas Epidemiológicas/estadística & datos numéricos , Renta/estadística & datos numéricos , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Estudios Transversales , Femenino , Disparidades en el Estado de Salud , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multinivel , Distribución por Sexo , Factores Sexuales , Factores Socioeconómicos
4.
Rev Bras Epidemiol ; 23: e200004, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32130393

RESUMEN

INTRODUCTION: Epidemiological studies have shown associations between placental measurements and perinatal and later life outcomes. OBJECTIVES: To report placental measurements and evaluate their association with birth weight in a Brazilian birth cohort. METHODS: Retrospective cohort study with 958 mothers, placentas, and newborns delivered at the Ribeirão Preto Medical School Hospital, Universidade de São Paulo, Brazil, in 2010 and 2011. The information was collected from interviews, medical records, and pathology reports. The placental measurements were: weight, largest and smallest diameters, eccentricity, thickness, shape, area, and birth weight/placental weight and placental weight/birth weight ratios. We analyzed the associations between birth weight and placental measurements using multiple linear regression. RESULTS: Placental weight alone accounted for 48% of birth weight variability (p < 0.001), whereas placental measurements combined (placental weight, largest and smallest diameters, and thickness) were responsible for 50% (p < 0.001). When adjusted for maternal and neonatal characteristics, placental measurements explained 74% of birth weight variability (p < 0.001). CONCLUSION: Placental measurements are powerful independent predictors of birth weight. Placental weight is the most predictive of them, followed by the smallest diameter.


Asunto(s)
Peso al Nacer/fisiología , Placenta/anatomía & histología , Adulto , Índice de Masa Corporal , Brasil , Femenino , Edad Gestacional , Humanos , Recién Nacido , Modelos Lineales , Masculino , Análisis Multivariante , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
5.
Rev Bras Epidemiol ; 23: e200008, 2020.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-32130397

RESUMEN

INTRODUCTION: Sedentary behavior has been associated with several health indicators. This study aims to describe this outcome in elderly people living in rural areas. METHODOLOGY: A cross-sectional study was carried out with elderly people from the rural area in the city of Rio Grande/RS, in 2017. Data were collected using an electronic questionnaire. Sedentary behavior was evaluated by eight aspects: watching television/videos/DVDs, using computer/internet, reading, socializing with friends and/or family, driving or riding a car/bike/taking public transport, practicing a hobby, working, and other activities. The analysis was composed by the description of aspects and multivariable (linear regression) analysis to test associations between the outcome and socioeconomic, demographic and physical activity characteristics. Association of the excess of sedentary behavior and time watching television within the independent variables was also verified. RESULTS: The mean of sedentary behavior was 274.9 minutes/day (n = 1,030), but watching television represented almost half (130.5 minutes/ day). Age was inversely associated with sedentary behavior, while income and schooling presented a direct relation. Income had a positive association with excessive sedentary behavior and time watching television. CONCLUSION: The mean sedentary behavior was lower when compared with the literature for the elderly. We suggest that actions to encourage healthy habits aim especially at reducing the time spent watching television.


Asunto(s)
Población Rural/estadística & datos numéricos , Conducta Sedentaria , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Estudios Transversales , Ejercicio , Femenino , Humanos , Actividades Recreativas , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores Socioeconómicos , Encuestas y Cuestionarios , Televisión , Factores de Tiempo
6.
J Sports Sci ; 38(6): 676-681, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32028853

RESUMEN

The aim of this study was to assess if tactical and technical performance indicators (PIs) could be used in combination to model match outcomes in Australian Football (AF). A database of 101 technical PIs and 14 tactical PIs from every match in the 2009-2016 Australian Football League (AFL) seasons was merged. Two outcome measures Win-loss and Score margin were used as dependent variables. The top 45 ranked technical and tactical PIs from a feature selection process were used to model match outcome using decision tree and Generalised Linear Models (GLMs). Of the top 45 selected features, this included seven tactical PIs. The Win-loss-based Decision tree model achieved a classification accuracy of 89.0% and GLM 93.2%. A Score margin-based GLM achieved a root mean squared error (RMSE) of 6.9 points. A combined approach to the classification of match outcomes provided no improvement in model accuracy compared with previous literature. However, this study has established the relative importance of technical and tactical measures of performance in relation to successful team performance in AF.


Asunto(s)
Rendimiento Atlético/fisiología , Conducta Competitiva/fisiología , Árboles de Decisión , Modelos Lineales , Fútbol/fisiología , Australia , Humanos , Análisis y Desempeño de Tareas
7.
Braz Oral Res ; 34: e002, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32049107

RESUMEN

Oral potentially malignant disorders (OPMD) possess significant chances of malignancy conversion. In order to develop an early diagnostic tool, the present study evaluated the expression of miRNA-21 and 31 as salivary markers. The case-control study was carried out in 36 healthy participants as controls and in 36 patients who were newly diagnosed as OPMD having four different lesions including leucoplakia, oral sub mucous fibrosis (OSMF)궱, oral lichen planus, and (OSMF)궱 with leucoplakia. The samples were also classified as non-dysplastic, or with mild, moderate, and severe dysplasia according to their histopathological reports. The salivary miRNA-21 and 31 expressions were studied using real-time PCR. The statistical analysis was carried out using SPSS version 22. Salivary miRNA-21 (p-value = 0.02) and 31 (p-value = 0.01) were significantly upregulated in severe dysplasia compared with control. Among the different lesions, leucoplakia had significant upregulation of miRNA-21 and 31. miRNA-21 can be used as a diagnostic marker with specificity of 66% and sensitivity of 69%. The area under the ROC curve was 0.820 for miRNA-21 and 0.5 for miRNA-31, which proved that miRNA-21 is a better diagnostic marker than miRNA-31 for OPMD.


Asunto(s)
MicroARNs/análisis , Neoplasias de la Boca/patología , Lesiones Precancerosas/patología , Saliva/química , Análisis de Varianza , Biomarcadores de Tumor/análisis , Estudios de Casos y Controles , Humanos , Leucoplasia Bucal/patología , Liquen Plano Oral/patología , Modelos Lineales , Neoplasias de la Boca/química , Fibrosis de la Submucosa Bucal/patología , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Valores de Referencia , Índice de Severidad de la Enfermedad
8.
Medicine (Baltimore) ; 99(3): e18598, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32011439

RESUMEN

A large interarm and interleg systolic blood pressure (SBP) difference and ankle-brachial index (ABI) <0.9 were associated with peripheral artery disease and left ventricular hypertrophy. These 3 parameters were derived from 4-limb SBP data. However, there is no study to assess clinical significance of SBP heterogeneity in 4 limbs. The aim of this study was to evaluate the association of 4-limb SBP standard deviation (SD) with peripheral vascular parameters and echocardiographic data in patients with or without clinical findings of peripheral artery disease.A total of 1240 patients were included, of whom 1020 had no clinical evidence of overt peripheral artery disease. The 4-limb blood pressures, brachial-ankle pulse wave velocity, and ABI were measured simultaneously by an ABI-form device.In the multivariable linear regression analysis, increased left ventricular mass index (LVMI), ABI < 0.9, interarm SBP difference >10 mm Hg, and interleg SBP difference >15 mm Hg (P ≤ .030) were associated with increased 4-limb SBP SD. Additionally, a subgroup multivariable linear regression analysis in 1020 patients without ABI < 0.9, interarm SBP difference >10 mm Hg, and interleg SBP difference >15 mm Hg found 4-limb SBP SD still had a positive correlation with LVMI (P < .001).In addition to significant association with ABI < 0.9, interarm SBP difference >10 mm Hg, and interleg SBP difference >15 mm Hg, 4-limb SBP SD was positively correlated with LVMI in the multivariable linear regression analysis in all study patients. Furthermore, in the subgroup of patients without clinical evidence of peripheral artery disease, 4-limb SBP SD still had a positive correlation with LVMI. Hence, assessment of 4-limb SBP heterogeneity is useful in identification of high-risk group of peripheral artery disease and/or increased LVMI, irrespective of the presence of overt peripheral artery disease.


Asunto(s)
Presión Sanguínea/fisiología , Ecocardiografía/métodos , Extremidades/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Enfermedad Arterial Periférica/fisiopatología , Índice Tobillo Braquial , Femenino , Humanos , Modelos Lineales , Masculino , Enfermedad Arterial Periférica/diagnóstico , Análisis de la Onda del Pulso
9.
Medicine (Baltimore) ; 99(6): e19105, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32028437

RESUMEN

This study is to explore the quality of life (QoL) of the rural poor elderly in central China (Anhui province) and the influencing factors.A multi-stage random sampling method was used to extract 3352 effective samples of the rural elderly in Anhui, including 1206 poor and 2146 non-poor elderly subjects. Euro QoL 5-dimension questionnaire (EQ-5D) was used for the measurement of QoL. Descriptive statistics and χ test were used to compare and analyze the sociodemographic characteristics and QoL scores between poor and non-poor elderly. Multiple linear regression was used to assess the influencing factors of QoL.There were significant differences in gender, age, education levels, professions, chronic diseases, physical discomfort within 2 weeks, hospitalization within 1 year, economic sources, and migrant workers between the rural poor and non-poor elderly groups. The QoL of rural poor elderly scored significantly higher than the non-poor elderly, in all these five dimensions. The average EuroQol Visual Analogue Scale (EQ-VAS) of poor elderly was 65.689, lower than the non-poor elderly (71.039). After controlling the confounding factors, there was a significant statistical difference in the total utility score of EQ-5D between the poor and non-poor elderly groups.The QoL of poor elderly in central China is lower than non-poor elderly, with the worst dimension of pain/discomfort. The QoL of rural poor elderly in this area could be affected by many factors, to which more attention should be paid.


Asunto(s)
Pobreza , Calidad de Vida , Población Rural , Factores de Edad , Anciano , Anciano de 80 o más Años , China , Femenino , Estado de Salud , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Pobreza/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Factores Socioeconómicos , Encuestas y Cuestionarios
10.
Bioresour Technol ; 303: 122926, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32035386

RESUMEN

Vermicomposting is one of the best technologies for nutrient recovery from solid waste. This study aims to assess the efficiency of Artificial Neural Network (ANN) and Multiple Linear Regression (MLR) models in predicting nutrient recovery from solid waste under different vermicompost treatments. Seven chemical and biological indices were studied as input variables to predict total nitrogen (TN) and total phosphorus (TP) recovery. The developed ANN and MLR models were compared by statistical analysis including R-squared (R2), Adjusted-R2, Root Mean Square Error and Absolute Average Deviation. The results showed that vermicomposting increased TN and TP proportions in final products by 1.5 and 16 times. The ANN models provided better prediction for TN and TP with R2 of 0.9983 and 0.9991 respectively, compared with MLR models with R2 of 0.834 and 0.729. TN and C/N ratio were key factors for TP and TN prediction by ANN with percentages of 17.76 and 18.33.


Asunto(s)
Fósforo , Modelos Lineales , Análisis Multivariante , Nutrientes
11.
Medicine (Baltimore) ; 99(7): e19103, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32049818

RESUMEN

Bioelectrical impedance analysis (BIA) is currently the most commonly used method in clinical practice to measure body composition. However, the bioelectrical impedance analyzer is not designed according to different countries, races, and elderly populations. Because different races may have different body compositions, a prediction model for the elderly population in Taiwan should be developed to avoid population bias, thereby improving the accuracy of community evaluation surveys.Dual energy X-ray absorptiometry (DXA) was used as a standard method for comparison, and impedance analysis was used for the development of a highly accurate predictive model that is suitable for assessing the body composition of elderly people.This study employed a cross-sectional design and recruited 438 elderly people who were undergoing health examinations at the health management center in the Tri-Service General Hospital as study subjects. Basic demographic variables and impedance analysis values were used in four predictive models, namely, linear regression, random forest, support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost) models, to predict DXA body composition. The data from 354 study subjects were used to develop the predictive model, while the data from 84 study subjects were used to validate the accuracy of the predictive model.The body composition of elderly people as estimated by InBody 720 was highly correlated with that estimated by DXA. The correlation coefficient between InBody 720 and DXA for muscle mass was 0.969, and that for fat mass was 0.935. Consistency analysis results showed that InBody 720 tends to underestimate muscle mass and fat mass. A comparison of the accuracy of the linear regression, random forest, SVM, and XGBoost models showed that the linear regression has the highest accuracy. The correlation coefficient between the new model and DXA for muscle mass and fat mass were 0.977 and 0.978, respectively.The new predictive model can be used to monitor the nutrition status of elderly people and identify people with sarcopenia in the community.


Asunto(s)
Absorciometría de Fotón/métodos , Composición Corporal , Impedancia Eléctrica , Anciano , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Masculino , Valor Predictivo de las Pruebas , Taiwán
12.
Artículo en Inglés | MEDLINE | ID: mdl-32062366

RESUMEN

Albendazole (ABZ) is the first-line drug in treating echinococcosis, which is recommended by WHO. To address the poor bioavailability of albendazole, liposomal albendazole was formulated and is available in our hospital for many years. In this study, a sensitive, reliable and accurate UPLC-Q-TOF-MS method was developed and validated for the determination of albendazole and its metabolites, albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO2) and albendazole-2-aminosulfone (ABZSO2NH2) in naturally echinococcus granulosus (E. granulosus) infected sheep plasma and tissues with mebendazole (MBZ) as the internal standard (IS). Plasma and tissues samples were prepared by protein precipitation method. The separation was performed on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 µm) with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at 0.4 mL/min. The detection was performed on a quadrupole time-of-flight (Q-TOF) high-resolution mass spectrometer using positive electrospray ionization (ESI) source with a chromatographic run time of 6.0 min. The detection was operated using target ions of [M + H]+ at m/z 266.096 for ABZ, m/z 282.091 for ABZSO, m/z 298.086 for ABZSO2, m/z 240.081 for ABZSO2NH2 and m/z 296.104 for IS in selective ion mode, respectively. This method was validated in terms of selectivity, linearity, precision, accuracy, recovery, matrix effect, dilution effect, carryover effects, stability, calibration curve and LLOQ. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. This method has been successfully applied to the pharmacokinetic study following single and multiple oral dose of 10 mg/kg liposomal albendazole, and tissue distribution study following multiple oral dose of 10 mg/kg, with emulsion albendazole as the reference preparation. The results in the article will provide valuable information for use in clinical applications of liposomal albendazole and also be beneficial for further development of liposomal albendazole in future studies.


Asunto(s)
Albendazol/sangre , Albendazol/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Equinococosis/tratamiento farmacológico , Enfermedades de las Ovejas/tratamiento farmacológico , Albendazol/química , Albendazol/uso terapéutico , Animales , Equinococosis/veterinaria , Echinococcus granulosus , Modelos Lineales , Liposomas , Espectrometría de Masas/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Ovinos , Distribución Tisular
13.
Artículo en Inglés | MEDLINE | ID: mdl-32062367

RESUMEN

Protein-arginine methyltransferases catalyze the methylation of the guanidine (NG) group of proteinic L-arginine (Arg) to produce monomethyl and dimethylarginine proteins. Their proteolysis releases the free amino acids monomethylarginine (MMA), symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA), respectively. MMA, SDMA and ADMA are inhibitors of the nitric oxide synthase (NOS) activity. High circulating and low urinary concentrations of ADMA and SDMA are considered risk factors in the cardiovascular and renal systems, mainly due to their inhibitory action on NOS activity. Identity, biological activity and concentration of NG-methylated proteins are largely unknown. The present study addressed these issues by using GC-MS and LC-MS/MS approaches. GC-MS was used to quantify free ADMA released by classical HCl-catalyzed hydrolysis of three synthetic Arg-vasopressin (V) peptides and of unknown endogenous NG-dimethylated proteins. The cyclic (c) disulfide forms of Arg-vasopressin analogs, i.e., Arg-vasopressin (cV-Arg-Gly-NH2), asymmetrically NG-dimethylated vasopressin (cV-ADMA-Gly-NH2) and symmetrically NG-dimethylated vasopressin (cV-SDMA-Gly-NH2) were used as model peptides in quantitative GC-MS analyses of ADMA, SDMA and other expected amino acids from the hydrolyzed Arg-vasopressin analogs. cV-ADMA-Gly-NH2 and cV-SDMA-Gly-NH2 were discriminated from cV-Arg-Gly-NH2 by LC-MS and LC-MS/MS, yet they were indistinguishable from each other. The same applies to the respective open (o) reduced and di-S-acetamide forms of oV-ADMA-Gly-NH2, oV-SDMA-Gly-NH2 and oV-Arg-Gly-NH2. Our LC-MS and LC-MS/MS studies suggest that the Arg-vasopressin analogs form [(M-H)]+ and [(M-H)+H]+ in the positive ESI mode and undergo in part conversion of their terminal Gly-NH2 (NH2, 16 Da) group to Gly-OH (OH, 17 Da). The product ion mass spectra of the di-S-acetamide forms are complex and contain several intense mass fragments differing by 1 Da. cV-ADMA-Gly-NH2 and cV-SDMA-Gly-NH2 induced platelet aggregation in platelet-rich human plasma with moderately different initial velocity and maximal aggregation rates compared to cV-Arg-Gly-NH2. Previous studies showed that human red blood cells are rich in large (>50 kDa) ADMA-containing proteins of unknown identity. Our LC-MS/MS proteomic study identified several membrane and cytosolic erythrocytic NG-dimethylated proteins, including spectrin-α (280 kDa), spectrin-ß (247 kDa) and protein 4.1 (80 kDa). Being responsible for the stability of the erythrocyte membrane, the newly identified main targets for NG-dimethylation in human erythrocytes should be given a closer look in erythrocytic diseases like hereditary spherocytosis.


Asunto(s)
Arginina Vasopresina , Cromatografía Liquida/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Guanidina/química , Espectrometría de Masas en Tándem/métodos , Arginina/análogos & derivados , Arginina/análisis , Arginina/sangre , Arginina/química , Arginina Vasopresina/análisis , Arginina Vasopresina/sangre , Arginina Vasopresina/química , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/química , Humanos , Modelos Lineales , Masculino , Péptidos/análisis , Péptidos/sangre , Péptidos/química , Proyectos Piloto , Procesamiento Proteico-Postraduccional
14.
Artículo en Inglés | MEDLINE | ID: mdl-32065955

RESUMEN

Developing dissolution testing methods to measure the nicotine release profiles from smokeless tobacco products is valuable for product assessment and product-to-product comparisons. In this work, we developed a robust dissolution method to study the in vitro release of nicotine from smokeless tobacco products using the U.S. Pharmacopeia flow-through cell dissolution apparatus 4 (USP-4). We further developed and validated a sensitive Ultra Performance Liquid Chromatography coupled to Photodiode Array detector (UPLC-PDA) method for the accurate quantitation of the released nicotine into artificial saliva, which is our selected dissolution medium. We have successfully shown the applicability of the validated method by investigating the release profiles of nicotine from various commercial and CORESTA reference smokeless tobacco products [CRP 1.1 (Swedish-style snus pouch), CRP 2.1 (American-style loose moist snuff), CRP 4 (loose-leaf chewing tobacco) and CRP 4.1 (chopped loose-leaf chewing tobacco)]. Nicotine release profiles were analyzed by calculating the difference factor (f1) and similarity factor (f2) by adopting a methodology referenced in the Guidance for Industry from FDA's Center for Drug Evaluation and Research (CDER) and by fitting the release profile curves using a first order kinetic model. Nicotine release was found to be dependent on the form and cut of the smokeless tobacco products, with a slower release observed for snus and loose-leaf, compared to chopped and loose moist snuff smokeless tobacco. This dissolution methodology can be extended to measure and compare release of other constituents from smokeless tobacco products and has the potential for method standardization.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Nicotina/análisis , Tabaco sin Humo/análisis , Técnicas de Química Analítica/instrumentación , Técnicas de Química Analítica/métodos , Diseño de Equipo , Humanos , Límite de Detección , Modelos Lineales , Modelos Biológicos , Nicotina/farmacocinética , Reproducibilidad de los Resultados , Saliva/química
15.
Artículo en Inglés | MEDLINE | ID: mdl-32106061

RESUMEN

A comparative study was conducted to replace the traditional screening method (MFDS#83) with the Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) EN method for the determination of 267 pesticides/metabolites/plant activators/growth regulators in five representative crop matrices (mandarin, pepper, potato, rice, and soybean). In the traditional method, samples were extracted with acetonitrile and salt, and purified with a solid-phase extraction cartridge. In the QuEChERS method, the sample extraction was carried out using acetonitrile and a mixture of salts, and purification was performed using dispersive solid phase extraction. The limit of quantification (LOQ) for the MFDS#83 method was 0.0004 mg/kg, whereas for the QuEChERS EN method, the LOQ varied from 0.002 to 0.006 mg/kg for all analytes in various matrices. A six-point matrix-matched calibration curve was prepared for all analytes in five matrices for both methods. Both the MFDS#83 and QuEChERS EN methods provided excellent linearity, with the coefficients of determination (R2) ≥ 0.99 for most of the compounds. In both cases, the method was validated in terms of recovery and repeatability after the fortification of two different concentrations with three replicates for each of the concentrations. The QuEChERS EN method provided better recovery than the MFDS#83 method for all matrices except mandarin.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Residuos de Plaguicidas/análisis , Espectrometría de Masas en Tándem/métodos , Verduras/química , Límite de Detección , Modelos Lineales , Residuos de Plaguicidas/química , Residuos de Plaguicidas/aislamiento & purificación , Reproducibilidad de los Resultados , Extracción en Fase Sólida/métodos
16.
Artículo en Inglés | MEDLINE | ID: mdl-32109745

RESUMEN

In this study, haptens were designed to produce highly sensitive and specific monoclonal antibodies (mAb) against carbamazepine (CBZ) and its metabolite carbamazepine-10, 11-epoxide (CBZ-EP). According to the results of our competitive enzyme-linked immunosorbent assay (ic-ELISA), the half-maximum inhibitory concentration values for anti-CBZ and anti-CBZ-EP mAb were 0.18 and 0.59 ng/mL, respectively. An immunochromatographic assay (ICA) was developed for the determination of CBZ and CBZ-EP concentrations. This method can provide visible limits of detection ranging from 0.25 to 1 ng/mL, and cut-off limits ranging from 5 to 10 ng/mL, and takes 10 min to evaluate with the naked eye. Importantly, these observations were consistent with those obtained by ic-ELISA and liquid chromatography-mass spectrometry. The ICA assay represented a reliable, fast, and high-throughput method for the determination of CBZ and CBZ-EP in serum samples.


Asunto(s)
Anticuerpos Monoclonales/química , Carbamazepina/análogos & derivados , Carbamazepina/sangre , Inmunoensayo/métodos , Anticuerpos Inmovilizados/química , Anticuerpos Inmovilizados/metabolismo , Anticuerpos Monoclonales/metabolismo , Carbamazepina/aislamiento & purificación , Carbamazepina/metabolismo , Cromatografía Liquida , Humanos , Límite de Detección , Modelos Lineales
17.
Artículo en Inglés | MEDLINE | ID: mdl-32109746

RESUMEN

Polycyclic aromatic hydrocarbons (PAH) are well-established environmental carcinogens likely to be causative agents for some human cancers. Bay-region diol epoxides are ultimate carcinogenic metabolites of multiple PAH. Dihydrodiols are the important intermediate products of this pathway and can be further oxidized to form diol epoxides. We quantified two dihydrodiol metabolites of phenanthrene (Phe), the simplest PAH with a bay-region, in the 6 h urine of smokers (N = 25) and non-smokers (N = 25) using a newly developed and validated analytical method. After hydrolysis by ß-glucuronidase and sulfatase, and solid phase extraction, the sample was silylated and analyzed by gas chromatography-negative ion chemical ionization-tandem mass spectrometry (GC-NICI-MS/MS). Levels (nmol/6h urine) of Phe-1,2-dihydrodiol (Phe-1,2-D) and Phe-3,4-dihydrodiol (Phe-3,4-D) were 2.04 ± 1.52 and 0.51 ± 0.35 , respectively, in smokers, significantly higher than those in non-smokers (1.35 ± 1.11 of Phe-1,2-D, p < 0.05; 0.27 ± 0.25 of Phe-3,4-D, p < 0.005). Cigarette smoking also influenced the regioselective metabolism of Phe, presenting as a significant difference in the urinary distribution pattern of Phe-1,2-D and Phe-3,4-D between smokers and non-smokers: the ratio Phe-3,4-D: Phe-1,2-D increased from 0.20 in non-smokers to 0.28 in smokers (p < 0.01), which can be explained by the induction of the phenanthrene metabolizing enzymes CYP1A2 and CYP1B1 by cigarette smoke. The method described here is the first example of facile quantitation of an intact human dihydrodiol metabolite of any PAH with three or more aromatic rings and will be applicable in clinical and molecular epidemiology studies of PAH metabolism and cancer susceptibility.


Asunto(s)
Cromatografía de Gases y Espectrometría de Masas/métodos , Naftalenos/orina , Fenantrenos/orina , Fumar/orina , Espectrometría de Masas en Tándem/métodos , Femenino , Humanos , Límite de Detección , Modelos Lineales , Masculino , Reproducibilidad de los Resultados , Fumadores
18.
Artículo en Inglés | MEDLINE | ID: mdl-32109748

RESUMEN

The standard approach to detect misuse with testosterone in sport is based on the determination and evaluation of the urinary steroid profile followed by the confirmation of atypical profiles using isotope ratio mass spectrometry. The detection capacity of these methods can be attenuated by confounding factors or testosterone preparations with endogenous isotopic fingerprints. An alternative detection method for misuse of an endogenous steroid in sports is the direct detection of the administered steroid ester present in most preparations. Thus unambiguous proof for doping misuse can be delivered. In this work, the sensitivity of gas chromatography coupled to a triple quadrupole with chemical ionization (GC-CI-MS/MS) is applied to detect trace levels of 10 testosterone and 2 nandrolone esters in plasma for in human doping analysis. The detection method was developed employing a liquid-liquid extraction and HPLC cleanup step before analysis on the GC-CI-MS/MS. The quantitative method was validated in a linear range of 100-2000 pg/ml and proved to be selective, reproducible and very sensitive with limits of detection as low as to 10 pg/ml. A clinical study with the administration of testosterone undecanoate in 3 volunteers was carried out and the compound was detectable up to 86 days after administration.


Asunto(s)
Doping en los Deportes , Cromatografía de Gases y Espectrometría de Masas/métodos , Esteroides/sangre , Espectrometría de Masas en Tándem/métodos , Ésteres , Humanos , Modelos Lineales , Extracción Líquido-Líquido , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Esteroides/química , Esteroides/aislamiento & purificación , Testosterona/análogos & derivados , Testosterona/sangre
19.
Artículo en Inglés | MEDLINE | ID: mdl-32109749

RESUMEN

Obtaining longitudinal endocrinological data from free-ranging animals remains challenging. Steroid hormones can be extracted sequentially from non-invasively sampled biologically inert keratinous tissues, such as feathers, nails, hair and whiskers. However, uncertainty regarding the type and levels of steroids incorporated into such tissues complicates their utility in wildlife studies. Here, we developed a novel, comprehensive method to analyze fourteen C19 and fourteen C21 steroids deposited chronologically along the length of seal whiskers in a single, 6-minute chromatographic step, using ultra-performance convergence chromatography-tandem mass spectrometry. The limits of detection and quantification ranged from 0.01 to 2 ng/mL and from 0.1 to 10 ng/mL, respectively. The accuracy and precision were within acceptable limits for steroids at concentrations ≥2 ng/mL. The recovery (mean = 107.5% at 200 ng/mL), matrix effect and process efficiency of steroids evaluated, using blanked whisker matrix samples, were acceptable. The method was applied to the analysis of steroid hormone levels in adult female whisker segments obtained from southern elephant seals (Mirounga leonina), n = 10, and two fur seal species, Antarctic fur seals (Arctocephalus gazella; n = 5) and subantarctic fur seals (Arctocephalus tropicalis; n = 5), sampled between 2012 and 2017. In the whisker subsamples analyzed (n = 71), the median concentration of steroid hormones detected above the LOQ ranged from 2.0 to 273.7 pg/mg. This was the first extraction of multiple C19 and C21 steroids, including their C11-oxy metabolites, from the whiskers of mammals. Measuring hormones sequentially along the whisker lengths can contribute to our understanding of the impact of stress associated with environmental/climate changes that affect the health, survival of organisms, as well as to delineate the reproductive cycles of free-living mammals with cryptic life stages.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Esteroides/análisis , Espectrometría de Masas en Tándem/métodos , Vibrisas/química , Andrógenos/análisis , Animales , Femenino , Lobos Marinos , Glucocorticoides/análisis , Ensayos Analíticos de Alto Rendimiento , Límite de Detección , Modelos Lineales , Progestinas/análisis , Reproducibilidad de los Resultados
20.
Artículo en Inglés | MEDLINE | ID: mdl-32109750

RESUMEN

Di-n-butyl adipate (DnBA) is an alternative to the anti-androgenic and strictly regulated di-n-butyl phthalate (DnBP) used as a cosmetic ingredient, plasticizer, and in various articles of everyday life. Hence, exposures of the general population have to be expected. Currently, biomarkers of DnBA exposure and methods for their determination are not available. Here, we describe a sensitive, rugged and precise analytical method for the determination of the DnBA monoester metabolite mono-n-butyl adipate (MnBA), as well as its potential downstream metabolites 3-hydroxy-mono-n-butyl adipate (3OH-MnBA) and 3-carboxy-mono-n-propyl adipate (3cx-MnPrA) in human urine. Glucuronic acid conjugates present in urine were deconjugated using a pure ß-glucuronidase. The metabolites were then analyzed by liquid chromatography on a C18 column with superficially porous particles coupled to electrospray ionization-triple quadrupole-tandem mass spectrometry, applying online turbulent flow chromatography for analyte enrichment and matrix depletion (online-SPE-LC-MS/MS). The metabolites were quantified using stable isotope dilution analysis with limits of quantification of 0.05 µg/L (MnBA), 0.1 µg/L (3OH-MnBA), and 0.5 µg/L (3cx-MnPrA). Method imprecision in urinary matrix was below 7% (coefficient of variation) for all analytes. Mean relative recoveries were between 93% and 107%. The suitability of the DnBA metabolites as biomarkers of exposure was demonstrated after dermal application of a commercially available sunscreen containing DnBA. Maximum concentrations were reached 6.5 h after dose (219 µg/L 3cx-MnPrA, 91 µg/L MnBA, and 3.9 µg/L 3OH-MnBA). Elimination kinetics were similar for all three metabolites. We were able to quantify 3cx-MnPrA and MnBA until 4 d after sunscreen application. In a sample set of 35 urine samples from the general German population, 3cx-MnPrA was quantified in 94% (median 2.54 µg/L, maximum 78.3 µg/L) and MnBA in 3% (median < LOQ, maximum 0.18 µg/L) of the samples. The method will be applied in future human metabolism and human biomonitoring population studies.


Asunto(s)
Adipatos/orina , Cromatografía Líquida de Alta Presión/métodos , Extracción en Fase Sólida/métodos , Espectrometría de Masas en Tándem/métodos , Adipatos/aislamiento & purificación , Adulto , Biomarcadores/orina , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto Joven
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