RESUMO
Metformin, a drug frequently used by diabetic patients as the first-line treatment worldwide, is positively charged and is transported into the cell through human organic cation transporter (hOCT 1-3) proteins. We aimed to mimic the cellular uptake of metformin by hOCT1-3 with various bioinformatics methods and tools. 3D structure of OCT1-3 proteins was predicted by considering the structures and function of these proteins. We predicted functional regions (active and ligand binding sites) of OCT1-3 and performed comparative bioinformatics analysis. The predicted structure of hOCT1-3 was then analyzed in the Blind Docking server and the results were confirmed with predicted binding site residues and conserved domain regions. We simulated the OCT1-3 and metformin docking and also validated the docking procedure with other substrates of HOCT1-3 proteins. We selected the best poses of metformin docking simulations as per binding energy (-5.27 to -4.60 kcal/mol). Lastly, we validated the static description of protein-ligand (OCT-Metformin) interactions by performing molecular dynamics simulation. Eventually, we obtained stable simulation of OCT-metformin interaction.
Assuntos
Metformina/metabolismo , Fator 1 de Transcrição de Octâmero/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Transportador 2 de Cátion Orgânico/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Biologia Computacional , Humanos , Metformina/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Fator 1 de Transcrição de Octâmero/química , Proteínas de Transporte de Cátions Orgânicos/química , Transportador 2 de Cátion Orgânico/química , Ligação ProteicaRESUMO
Familial lecithin cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by the appearance of corneal opacity, anemia, proteinuria progressing to chronic renal failure and abnormalities in the composition of plasma lipoproteins. No established therapy currently exists for this condition. We report here a new case of FLD caused by two novel mutations in the LCAT gene in which, for the first time, aggressive therapy with angiotensin II receptor blockers and lipid-lowering drugs showed benefit in blood pressure, lipid abnormalities, proteinuria and also kidney function, probably delaying progression to renal failure.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Deficiência da Lecitina Colesterol Aciltransferase/tratamento farmacológico , Adulto , DNA/genética , Relação Dose-Resposta a Droga , Eletroforese em Gel de Ágar , Seguimentos , Humanos , Deficiência da Lecitina Colesterol Aciltransferase/enzimologia , Deficiência da Lecitina Colesterol Aciltransferase/genética , Masculino , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , Fosfatidilcolina-Esterol O-Aciltransferase/genética , Mutação Puntual , Fatores de TempoRESUMO
La pérdida de heterocigosidad 1p/19q tiene valor pronóstico clÃnico y está fuertemente asociada con caracterÃsticas histológicas clásicas de oligodendroglioma. Objetivos: El presente artÃculo, propone un método molecular para determinar la pérdida de heterocigosidad (LOH por sus siglas en inglés) para 1p/19q y permitir la clasificación de tumores oligodendrogliales. Material y Métodos: Se utilizaron muestras en fresco del Banco de Tejidos Tumorales del Instituto Nacional de Enfermedades Neioplásicas (INEN) y biopsias de tejido embebido en parafina de tumores oligodendrogliales, con diagnóstico patológico de oligodendroglioma y oligoastrocitoma. Los métodos propuestos son PCR Multiplex y amplificación de fragmentos por electroforesis capilar de los productos de PCR, y fueron aplicados a un total de 39 casos que presentaban grado histológico II y III. Resultados: Los resultados obtenidos permiten una adecuada clasificación molecular de los tumores oligodendrogliales.
A heterozygosity loss of 1p/19q has clinical prognostic value and is strongly associated with classical histologic features of oligodendroglioma. Objectives: The present article proposes a molecular method to determine the loss of heterozygosity (LOH) for 1p/19q and to allow the classification of oligodendroglial tumors. Material and Methods: Fresh samples from the National Institute of Neoplastic Diseasesâ Tumor BioBank and paraffin-embedded tissue biopsies of oligodendroglial tumors with pathological diagnosis of oligodendroglioma and oligoastrocytoma were used. The proposed methods are Multiplex PCR and amplification of fragments by capillary electrophoresis of PCR products, and were applied to a total of 39 cases which presented histological grade II and III. Results: The results obtained allow an adequate molecular classification of oligodendroglial tumors.
RESUMO
El objetivo del presente trabajo fue proponer un modelo estructural que delinee la relación que guardan distintas caracterÃsticas psicológicas en su relación con problemas de salud mental por medio de un modelo de ecuaciones estructurales. En una muestra no aleatoria e intencional de N = 231 estudiantes, el modelo especificado demuestra que las variables de ira-rasgo, abnegación y locus de control interno tienen efectos en problemas de salud mental a través de mediadores como la ira contenida, la falta de asertividad y la autoeficacia, y que estos guardan las relaciones teóricas esperadas (X2 = 50.24, gl = 35 y p = 0.04; razón X2/gl = 1.44, CFI = .98, NFI = .93, IFI = .98, RMSEA = .04). Se discuten estos hallazgos en términos de su contribución a la comprensión de los mecanismos de la compleja relación de las caracterÃsticas psicológicas, la personalidad y la salud.
The objective of this study was to propose a structural model that delineates the relationship between different psychological characteristics in relation to mental health problems through a structural equation model. In a non-random, intentional sample of N = 231 students, the specified model demonstrates that anger-trait, self-denial and internal locus of control variables have effects on mental health problems through mediators such as anger-in, lack of assertiveness, and self-efficacy, and that they keep the expected theoretical relationships (X2 = 50.24, gl = 35 and p = 0.04; razón X2/gl = 1.44, CFI = .98, NFI = .93, IFI = .98, RMSEA = .04) These findings are discussed in terms of their contribution to understanding the mechanisms of the complex relationship among psychological characteristics, personality and health.
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Objetivo: Determinar la prevalencia de incisivos en forma de pala y su asociación con el overjet. Material y Métodos: La muestra estuvo conformada por 270 niños de 7 a 11 años de una Institución pública deChilca. Se realizó una evaluación clínica para determinar la presencia o ausencia de los incisivos en pala y de qué tipo se trataba según la clasificación de Hrdlicka. Asimismo, se registró la medida del overjet con una sonda periodontal PCP 11.5B Hu Friedy®. Finalmente, se realizó la prueba de Chi cuadrado para determinar la asociación entre ambasvariables. Resultados: La prevalencia de incisivos en forma de pala fue de 72,60% con mayor frecuencia en el género femenino. Se halló una mayor prevalencia de forma de pala en los incisivos laterales (71,85%) que en los centrales (67,77%). El tipode forma de pala predominante fue el de tipo I en ambos grupos de incisivos (31,85% y 31,48%). No se encontró una asociación estadísticamente significativa entre los incisivos en forma de pala y el overjet. (p=0.075)...
Objective: To determine the prevalence of the shovel-shaped incisors and their association with the overjet. Material and Methods: The sample included 270 children from a Chilcas Public Institution aged from 7 to 11. Aclinical assessment was carried out to determine the presence or absence of the shovel-shaped incisors and whichwas its type according to the Hrdlickas scale. Likewise, the measurement of overjet was registered with only oneperiodontal probe PCP 11.5B Hu Friedy®. Finally, the chi-squared test was carried out to determine the association between both variables. Results: The prevalence of the shovel-shaped incisors was 72,60%, more frequently in females It was found a greaterprevalence of shovel-shaped lateral incisors (71,85%) than shovel-shaped central incisors (67,77%). In both groups ofincisors, the Type I was predominant (31,85% and 31.48%). An association statistically significant between the shovelshaped incisors and overjet was not found. (p=0.075)...
Assuntos
Humanos , Masculino , Feminino , Criança , Anormalidades Dentárias , Incisivo/anormalidades , PrevalênciaRESUMO
La dapsona es una sulfona utilizada en una variedad de enfermedades dermatológicas que incluye el pénfigo, lametahemoglobinemia es un síndrome clínico potencialmente mortal debido a la disminución del aporte de oxígenodesde la sangre hacia los tejidos; la metahemoglobinemia adquirida es la forma más frecuente y es un conocidoefecto adverso del uso de dapsona. Describimos el caso de un varón con pénfigo foliáceo y tratamiento reciente condapsona, que presentó cianosis, disnea y choque circulatorio ante concentraciones elevadas de metahemoglobina(21%); el tratamiento inicial incluyó oxigenoterapia, soporte ventilatorio invasivo, hemodinámico y administraciónde azul de metileno intravenoso, ante la ausencia de respuesta clínica se realizó exanguinotransfusión como terapiade segunda línea con respuesta óptima, el nivel sérico de metahemoglobina fue 2,3% tres horas posteriores alrecambio sanguíneo.
Dapsone is a sulphone used for a variety of dermatologic conditions including pemphigus. Methemoglobinemia isa potentially lethal syndrome due to a diminished supply of oxygen from blood to tissues, the acquired form is themost frequent presentation and it is a recognized adverse effect of dapsone. We report the case of a male patientwith pemphigus treated with dapsone that developed cyanosis, dyspnea and shock in the presence of elevatedconcentrations of methemoglobin (21%). Initial treatment included oxygen, invasive ventilatory support andintravenous administration of methylene blue, but due to lack of response, exchange transfusion was performedwith optimal response, serum level of methemoglobin after the procedure was 2.3%.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Dapsona/uso terapêutico , Metemoglobinemia/terapia , Transfusão Total , Transfusão de SangueRESUMO
El objetivo de la presente investigación fue comparar la jerarquÃa de valores entre estudiantes de secundaria, según tipo de colegio (religioso y laico) y sexo. La muestra estuvo conformada por 250 alumnos de secundaria (60.4 % varones, 52 % colegio religioso). Las edades correspondientes se encuentran en el rango de 14 a 17 años (M = 15.47, DE = 0.63). Se administró el Cuestionario de Valores de Schwartz (2001), cuyo análisis de estructura y consistencia interna resultó satisfactorio. Para comparar la jerarquÃa de valores entre los grupos, se utilizaron correlaciones top down (r td ). De acuerdo a los resultados, se halló mayor asociación (similitud) entre la jerarquÃa de valores según el tipo de colegio (r td = .82) y, en menor grado, según el sexo (r td = .69). Los resultados comparativos por sexo mostraron diferencias significativas, siendo las mujeres quienes presentaron mayores puntajes en Benevolencia, Autodirección, Estimulación y los hombres en Logro. Se discuten las implicancias de los resultados comparativos.
The purpose of this research was to compare the hierarchy of values among high school students, according to type of school (religious and secular) and sex. The sample was composed by 250 high school students (60.4% male, 52% religious school). The ages are in the range of 14 to 17 years (M = 15.47, SD = 0.63). The instrument used was the Portrait Value Questionnaire by Schwartz (2001), whose analysis of structure and internal consistency was satisfactory. To compare the hierarchy of values between the groups, top down correlations (r td >) were used. According to the results, greater association (similarity) was found between the hierarchy of values depending on the type of school (r td = .82) and, to a lesser degree by sex (r td = .69). The comparative results show greater Benevolence, Self-Direction, Stimulation among women and Achievement among men. The implications of the comparative results are discussed.
RESUMO
La importante función homeostática del sistema endocrino se consigue con la participación multifactorial de diversas hormonas, que en orden de jerarquÃa regulan la secreción de una manera precisa e integrada; pero las pertenecientes al grupo de las mineralocorticoides, en especial la aldosterona, son primordiales, pues mantienen el balance hidromineral del cuerpo, de extrema importancia para la conservación del equilibrio del medio interno.
The important homeostatic function of the endocrine system is achieved with the multifactorial participation of diverse hormones which, above or below in rank, regulate the secretion in a precise and integrated way; but those belonging to the mineralocorticoids group, especially aldosterone, are essential because they maintain the hydromineral balance of the body, of extreme importance for the conservation of the inner balance.
Assuntos
Humanos , Masculino , Feminino , Aldosterona , Sistema Endócrino , Homeostase , HormôniosRESUMO
This study reports the data recorded from four patients intoxicated with shellfish during the summer 2002, after consuming ribbed mussels (Aulacomya ater) with paralytic shellfish toxin contents of 8,066 n 61.37 mg/100 gr of tissue. Data associated with clinical variables and paralytic shellfish toxins analysis in plasma and urine of the intoxicated patients are shown. For this purpose, the evolution of respiratory frequency, arterial blood pressure and heart rate of the poisoned patients were followed and recorded. The clinical treatment to reach a clinically stable condition and return to normal physiological parameters was a combination of hydration with saline solution supplemented with Dobutamine (vasoactive drug), Furosemide (diuretic) and Ranitidine (inhibitor of acid secretion). The physiological condition of patients began to improve after four hours of clinical treatment, and a stable condition was reached between 12 to 24 hours. The HPLC-FLD analysis showed only the GTX3/GTX2 epimers in the blood and urine samples. Also, these epimers were the only paralytic shellfish toxins found in the shellfish extract sample.
Assuntos
Humanos , Masculino , Animais , Pessoa de Meia-Idade , Frutos do Mar/análise , Frutos do Mar/microbiologia , Frutos do Mar/toxicidade , Chile/epidemiologia , /etiologia , /microbiologia , Parestesia/etiologia , Parestesia/microbiologia , Toxinas Marinhas/isolamento & purificação , Toxinas Marinhas/análise , Toxinas Marinhas/efeitos adversos , Toxinas Marinhas/farmacologia , Toxinas Marinhas/toxicidadeRESUMO
The study shown here provides the first indisputable evidence that shellfish can be contaminated with Paralytic Shellfish Poisoning (PSP) and Diarrheic Shellfish Poisoning (DSP) toxins during the summer season in the Southern Chilean fjords. Quantitative analysis of the simultaneous presence of PSP and DSP toxins in Mytilus chilensis samples collected in the Chiloe Island are shown. The High Performance Liquid Chromatography (HPLC) analysis with pre-column derivatization method for DSP toxins and the post-column derivatization methods for PSP toxins, both with fluorescent on-line detections, showed that both type of toxins were concentrated by the filter bivalve Mytilus chilensis in amounts above the international safe limits. The phytoplankton analysis showed the presence of both Alexandrium catenella and Dinophysis acuta in the water column. The data shows stratification of the toxic dinoflagellates in the water column, since the lowest amount of both DSP and PSP toxins were measured in the superficial and deeper levels of the water column. Moreover, the highest toxicities of both types of toxins were shown by the shellfish samples collected at a depth of 6 meters with 190 nanograms of DTX-1 / gram of digestive gland and 709.8 mg of PSP toxins / 100 grams of mussel meat.