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Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.
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Descubrimiento de Drogas , Aprendizaje , Humanos , Escolaridad , Brasil , Suplementos DietéticosRESUMEN
Tomato fruit is susceptible to chilling injury (CI) during its postharvest handling at low temperature. The symptoms caused by this physiological disorder have been commonly evaluated by visual inspection at a macro-observation scale on fruit surface; however, the structure at deeper scales is also affected by CI. This work aimed to propose a descriptive model of the CI development in tomato tissue under the micro-scale, micro-nano-scale and nano-scale approaches using fractal analysis. For that, quality and fractal parameters were determined. In this sense, light microscopy, Environmental Scanning Electron Microscopy (ESEM) and Atomic Force Microscopy (AFM) were applied to analyse micro-, micro-nano- and nano-scales, respectively. Results showed that the morphology of tomato tissue at the micro-scale level was properly described by the multifractal behaviour. Also, generalised fractal dimension (Dq=0) and texture fractal dimension (FD) of CI-damaged pericarp and cuticle were higher (1.659, 1.601 and 1.746, respectively) in comparison to non-chilled samples (1.606, 1.578 and 1.644, respectively); however, FD was unsuitable to detect morphological changes at the nano-scale. On the other hand, lacunarity represented an appropriate fractal parameter to detect CI symptoms at the nano-scale due to differences observed between damaged and regular ripe tissue (0.044 and 0.025, respectively). The proposed multi-scale approach could improve the understanding of CI as a complex disorder to the development of novel techniques to avoid this postharvest issue at different observation scales.
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Solanum lycopersicum , Frutas/química , FríoRESUMEN
Screener, a board game supplemented with online resources, was introduced and distributed by the Brazilian Society of Pharmacology and Experimental Therapeutics to postgraduate programs as an instructional tool for the process of drug discovery and development (DDD). In this study, we provided a comprehensive analysis of five critical aspects for evaluating the quality of educational games, namely: 1) description of the intervention; 2) underlying pedagogical theory; 3) identification of local educational gaps; 4) impact on diverse stakeholders; and 5) elucidation of iterative quality enhancement processes. We also present qualitative and quantitative assessments of the effectiveness of this game in 11 postgraduate courses. We employed the MEEGA+ online survey, comprising thirty-three close-ended unipolar items with 5-point Likert-type response scales, to assess student perceptions of the quality and utility of Screener. Based on 115 responses, the results indicated a highly positive outlook among students. In addition, we performed a preliminary evaluation of learning outcomes in two courses involving 28 students. Pre- and post-quizzes were applied, each consisting of 20 True/False questions directly aligned with the game's content. The analysis revealed significant improvement in students' performance following engagement with the game, with scores rising from 8.4 to 13.3 (P<0.0001, paired t-test) and 9.7 to 12.7 (P<0.0001, paired t-test). These findings underscore the utility of Screener as an enjoyable and effective tool for facilitating a positive learning experience in the DDD process. Notably, the game can also reduce the educational disparities across different regions of our continental country.
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El objetivo de este trabajo fue evaluar el efecto de soluciones de irrigación endodónticas solas y combinadas sobre iones calcio y fosfato de la dentina radicular ex vivo. Se emplearon 56 discos de dentina obtenidos del tercio medio radicular de premolares inferiores unirradiculares extraídos por razones ortodóncicas. Los discos se dividieron al azar en 8 grupos (n=7). Grupo I: agua destilada (AD), Grupo II: hipoclorito de sodio (NaClO) 1 %, Grupo III: EDTA 17 %, Grupo IV: ácido maleico (AM) 5 %, Grupo V: ácido acético (AA) 5 %, Grupo VI: EDTA 17 % + NaClO 1 %, Grupo VII: AM 5 % + NaClO 1 %, Grupo VIII: AA 5 % + NaClO 1 %. Los segmentos de dentina permanecieron en contacto a 37° C durante 5 min y 2,5 minutos en cada solución cuando se usaron en forma sucesiva. Se determinó la concentración de iones calcio de las soluciones mediante espectrometría de absorción atómica y la concentración de iones fosfatos mediante colorimetría (Wienner Lab.). Los resultados se expresaron en mg/ml/gr de tejido. Para el análisis estadístico se utilizó ANOVA y Test de Tukey. AA 5 % y EDTA 17 % se comportaron de manera similar utilizados solos durante 5 minutos, NaClO 1 % no mostró diferencias con el AD. AM 5 % eliminó significativamente más calcio y fosfato que todos los grupos. Todas las soluciones desmineralizaron la dentina, pero AM 5 % durante 5 min fue la solución que más afectó el componente inorgánico de la dentina.
The aim of the present study was to evaluate ex vivo irrigating solutions effect under calcium and phosphates dentin ions, using them alone and combined. In this study 56 dentin discs where used. They were obtained from middle third of mandibular single-root premolars extracted for orthodontics reasons. Discs were randomly divided into 8 groups (n:7). Group I: Distilled water (DW), Group II: 1 % sodium hypochlorite (NaOCl), Group III: 17 % EDTA, Group IV: 5 % maleic acid (MA), Group V: 5 % acetic acid (AA), Group VI: 17 % EDTA + 1 % NaOCl, Group VII: 5 % MA + 1 % NaOCl, Group VIII: 5 % AA + 1 % NaOCl. Dentin segments were kept in contact with irrigating solutions at 37°C for 5 minutes, when used alone, or for 2.5 minutes when used combined. After that, calcium ions (using absorption atomic spectrometry) and phosphorus ions (by colorimetry Wienner Lab.) were determined. Results were expressed in mg/ml/g tissue. Statistical analysis was performed by ANOVA and Tukey test. 5 % AA and 17 % EDTA eliminated similar concentrations of calcium and phosphates ions from dentin at 5 minutes exposure time, while 1 % NaOCl did not present statistical differences with control. 5 % MA eliminated significantly more calcium and phosphates ions than the rest of analyzed groups. Every tested solutions demineralized human dentin, but 5 % MA used for 5 minutes did it the most.
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RESUMEN Introducción: La población de adultos mayores está incrementando y se observa la necesidad emergente de implementar estrategias dirigidas a recuperar o conservar su salud para que puedan gozar de una vejez plena. Técnicas como el Tai Chi podrían contribuir, ya que han mostrado tener múltiples beneficios para quien la práctica, tales como mejoras en la concentración, memoria, marcha, equilibrio, reducción del riesgo de caídas, fortalecimiento del sistema cardiovascular, reducción del estrés y la depresión, entre otros beneficios. Objetivo: Analizar la evidencia científica del uso del Tai Chi para conservar la salud del adulto mayor. Desarrollo: Revisión bibliográfica realizada durante el periodo 2013-2019 en distintas bases de datos como: Pubmed, Dialnet, SciELO, LILACS, ScienceDirect y Google Académico. Se utilizaron las palabras Tai Chi Chuan, Tai Ji Quan, Tai Chi. Aplicando los criterios de elegibilidad se seleccionaron 29 artículos. Resultados: Gran porcentaje de los artículos revisados estudian la atención de síntomas físicos que deterioran la movilidad del adulto mayor, sin embargo, también se encontraron investigaciones dirigidas a la parte psicológica, como el estrés, la ansiedad, el insomnio, la depresión y el enfado-tensión, en las cuales la práctica del Tai Chi demostró mejoría. Conclusiones: El Tai Chi es una terapia alternativa para prevenir y conservar la salud del adulto mayor, fácil de aprender y de bajo costo. En la revisión bibliográfica realizada no se reportan reacciones adversas durante ni después de la práctica de la técnica; el profesional de enfermería puede recomendarla ampliamente para ser implementada como un cuidado dirigido al adulto mayor.
ABSTRACT Introduction: The population of older adults is increasing and an emergent need to implement strategies aimed at recovering or maintaining their health is observed. In this sense, techniques such as Tai Chi could contribute because they have demonstrated bringing diverse benefits for those who practice them, including improvements in the concentration, memory, gait, and equilibrium, a reduction in the risk of falls, a strengthening of the cardiovascular system, and a reduction of stress and depression, among other benefits. Objective: To analyze the scientific evidence on the use of Tai Chi as a health promoter and preserver among older adults. Development: This bibliographic review was conducted during 2013-2019 on the Pubmed, Dialnet, SciELO, LILACS, ScienceDirect and Academic Google databases. The keywords used were Tai Chi Chuan, Tai Ji Quan, and Tai Chi. After filtering through the eligibility criteria, 29 articles were selected for the review. Results: An important percentage of the articles were focused on the attention to physical symptoms which impair the mobility of older adults; nevertheless, some studies addressed psychological issues such as stress, anxiety, sleep disorders, depression, and anger-tension, as well. In these studies, the practice of Tai Chi was associated with health improvements among older adults. Conclusions: Tai Chi is an alternative therapy to promote and maintain health among older adults. This technique is easy to learn, and its practice is not expensive. No adverse reactions during or after the practice of this technique were reported in the studies of this literature review. Therefore, the nursing professional can recommend Tai Chi practice to be implemented as a complementary healthcare measure for older adults.
RESUMO Introdução: A população de idosos está aumentando e observa-se a necessidade emergente de implementação de estratégias que visem a recuperação ou preservação da saúde para que possam desfrutar de uma velhice plena. Técnicas como o Tai Chi podem contribuir, dado que têm se mostrado múltiplos benefícios para quem o pratica, tais como melhora na concentração, memória, marcha, equilíbrio, redução do risco de quedas, fortalecimento do sistema cardiovascular, redução de estresse e depressão, entre outros benefícios. Objetivo: Analisar a evidência científica do uso do Tai Chi na preservação da saúde de idosos. Desenvolvimento: Revisão bibliográfica realizada no período 2013-2019 em diferentes bases de dados como: Pubmed, Dialnet, SciELO, LILACS, ScienceDirect e Google Academic. Foram utilizadas as palavras Tai Chi Chuan, Tai Ji Quan, Tai Chi. Aplicando os critérios de elegibilidade, foram selecionados 29 artigos. Resultados: Grande porcentagem dos artigos revisados estuda a atenção aos sintomas físicos que prejudicam a mobilidade do idoso, porém, as pesquisas também foram direcionadas à parte psicológica, como estresse, ansiedade, insônia, depressão e raiva-tensão, em que a prática do Tai Chi demonstrou melhora. Conclusões: O Tai Chi é uma terapia alternativa para prevenir e preservar a saúde do idoso, de fácil aprendizado e de baixo custo. Na revisão bibliográfica realizada, não foram relatadas reações adversas durante ou após a prática da técnica; o profissional de enfermagem pode recomendar veementemente que seja implementada como cuidado ao idoso.
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The two co-authors of the mentioned above article were incorrect. The correct are authors should have been "P. A. Beltrán" instead of "P. A. B. Roa" and "J. F. Diaz-Coto" instead of "L. Diaz Soto".
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Glioblastoma, which is highly invasive and has a poor patient prognosis, is the most common type of brain tumor. Flavonoids have known antiproliferative and antineoplastic effects, such as apoptosis induction and tumor growth inhibition. We investigated the effects of treatment with three flavonoids (BAS-1, BAS-4, and BAS-6) isolated from the Amazon plant Brosimum acutifolium on the proliferation and migration of the C6 glioma cell line. Cytotoxicity was evaluated by MTT assay, and morphological changes were evaluated by phase-contrast microscopy and by transmission electron microscopy. Apoptosis was determined using Annexin V-FITC-propidium iodide (PI) staining. A hemolysis assay was used to evaluate plasma membrane injury. Antiproliferative effects were assessed by wound migration and colony formation assays. Mitochondrial transmembrane potential (ΔΨm) was determined using JC-1 dye and flow cytometry. To identify the flavonoid targets, western blotting was performed. BAS-1 and BAS-4 reduced C6 cell proliferation in a dose-dependent manner. BAS-6 showed no effect. Due to its high toxicity toward primary glial cells and its high hemolytic index, BAS-1 was not used in the remaining experiments. BAS-4 treatment did not induce cytotoxicity in primary glial cells; however, in glioma cells, it suppressed migration and invasion and led to apoptosis through mitochondrial damage, ΔΨm loss, cell cycle arrest, and reduced AKT phosphorylation, which is a component of the main cell survival pathway. We conclude that BAS-4 showed potential activity against glioma by inducing apoptosis mediated by ΔΨm loss and AKT pathway disruption, and future studies should further evaluate BAS-4 as a promising antineoplastic agent against glioblastoma.
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Neoplasias Encefálicas/tratamiento farmacológico , Flavonoides/farmacología , Glioma/tratamiento farmacológico , Moraceae/química , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Encefálicas/patología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Flavonoides/administración & dosificación , Flavonoides/aislamiento & purificación , Citometría de Flujo , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioma/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas WistarRESUMEN
INTRODUCTION: Biologics have improved the treatment of rheumatic diseases, resulting in better outcomes. However, their high cost limits access for many patients in both North America and Latin America. Following patent expiration for biologicals, the availability of biosimilars, which typically are less expensive due to lower development costs, provides additional treatment options for patients with rheumatic diseases. The availability of biosimilars in North American and Latin American countries is evolving, with differing regulations and clinical indications. OBJECTIVE: The objective of the study was to present the consensus statement on biosimilars in rheumatology developed by Pan American League of Associations for Rheumatology (PANLAR). METHODS: Using a modified Delphi process approach, the following topics were addressed: regulation, efficacy and safety, extrapolation of indications, interchangeability, automatic substitution, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. Consensus was achieved when there was agreement among 80% or more of the panel members. Three Delphi rounds were conducted to reach consensus. Questionnaires were sent electronically to panel members and comments about each question were solicited. RESULTS: Eight recommendations were formulated regarding regulation, pharmacovigilance, risk management, naming, traceability, registries, economic aspects, and biomimics. CONCLUSION: The recommendations highlighted that, after receiving regulatory approval, pharmacovigilance is a fundamental strategy to ensure safety of all medications. Registries should be employed to monitor use of biosimilars and to identify potential adverse effects. The price of biosimilars should be significantly lower than that of reference products to enhance patient access. Biomimics are not biosimilars and, if they are to be marketed, they must first be evaluated and approved according to established regulatory pathways for novel biopharmaceuticals. KEY POINTS: ⢠Biologics have improved the treatment of rheumatic diseases. ⢠Their high cost limits access for many patients in both North America and Latin America. ⢠Biosimilars typically are less expensive, providing additional treatment options for patients with rheumatic diseases. ⢠PANLAR presents its consensus on biosimilars in rheumatology.
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Biosimilares Farmacéuticos/uso terapéutico , Enfermedades Reumáticas/tratamiento farmacológico , Biosimilares Farmacéuticos/efectos adversos , Consenso , Medicina Basada en la Evidencia , Humanos , América Latina/epidemiología , América del Norte , Guías de Práctica Clínica como Asunto , Reumatología , Sociedades MédicasRESUMEN
The association between cardiovascular and periodontal diseases is characterized by chronic inflammatory processes, with a high prevalence worldwide and complex genetic-environment interactions. Although apolipoprotein E4 (ApoE4), one of the isoforms coded by a polymorphic APOE gene, has been widely recognized as a risk factor for cardiovascular diseases and as an immunoinflammatory factor, less is known regarding how ApoE4 affects atherosclerosis in periodontitis patients. The aim of this review was to investigate the potential underlying mechanisms related to APOE4 that could increase the risk of periodontal disease and, ultimately, of atherosclerosis. There have only been a few studies addressing apoE polymorphisms in patients with chronic periodontitis. To date, no studies have been performed that have assessed how ApoE4 affects atherosclerotic disease in chronic periodontitis patients. Although clinical studies are warranted, experimental studies have consistently documented the presence of periodontal pathogens, which are usually found in the oral cavity and saliva, in the atherosclerotic plaques of ApoE-deficient mice. In addition, in this review, the potential role of the APOE4 allele as an example of antagonistic pleiotropy during human evolution and its relation to oral health is discussed.
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Apolipoproteínas E/metabolismo , Aterosclerosis/etiología , Enfermedades Periodontales/complicaciones , Animales , Apolipoproteína E3/metabolismo , Apolipoproteína E4 , Apolipoproteínas E/genética , Enfermedades Cardiovasculares/etiología , Pleiotropía Genética , Humanos , Inflamación/etiología , Ratones , Microbiota , Boca , Polimorfismo Genético , Isoformas de Proteínas , Factores de RiesgoRESUMEN
Mercury exposure is considered to be a public health problem due to the generation of toxic effects on human health as a result of environmental and occupational conditions. The inorganic form of mercury (HgCl2) can cause several biological changes in cells and tissues through its cumulative toxic potential, but little has been experimentally proven about the effects of inorganic mercury on salivary glands, an important modulator organ of oral health. This study analyzes the effects of prolonged low dose exposure to HgCl2 on the salivary glands of rats. Adult animals received a dose of 0.375 mg kg-1 day-1 over a period of 45 days. The parotid and submandibular glands were collected for analysis of the mercury levels and evaluation of oxidative stress, histological parameters and immunomodulation for metallothionein I and II (MT-I/II). In this investigation, biochemical and tissue changes in the salivary glands were verified due to the mercury levels, causing reduction in antioxidant capacity against peroxyl radicals, with consequent cellular lipid peroxidation and an increase in nitrite levels, volumetric changes and cytoskeletal damage in the submandibular glands, with less severe damage to the parotid glands. The results also have shown the occurrence of a cytoprotection mechanism due to increased MT-I/II expression, but not enough to avoid the morphology and oxidative damage. This evidence highlights, for the first time, that inorganic mercury is able to alter the morphology and oxidative biochemistry in salivary glands when exposed for a long time in low doses.
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Cloruro de Mercurio/toxicidad , Mercurio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Glándulas Salivales/efectos de los fármacos , Animales , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Metalotioneína/metabolismo , Nitritos/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Ratas Wistar , Glándulas Salivales/anatomía & histología , Glándulas Salivales/metabolismoRESUMEN
BACKGROUND: While 18F-fluorodeoxyglucose and 18F-sodium fluoride with positron emission tomography relate with inflammation and calcification, their role in the assessment of patients with Takayasu arteritis has not yet been studied. METHODS: We present 5 patients with suspected active metabolic disease who underwent PET with 18F-fluorodeoxyglucose and 18F-sodium fluoride in order to explore the locations and correlations of 18F-fluorodeoxyglucose and 18F-sodium fluoride uptakes. Diagnosis of metabolic active disease was based on 18F-fluorodeoxyglucose uptake. RESULTS: We studied 3 female patients and 2 male patients. Median age was 29 years (min: 19 max: 63). In areas with atherosclerotic plaques, we found a negative correlation between 18F-sodium fluoride and 18F-fluorodeoxyglucose uptakes (r = -0.78) (P = .001). Meanwhile, in areas with only metabolic active disease, we found a positive correlation between 18F-sodium fluoride and 18F-fluorodeoxyglucose uptakes (r = 0.94) (P = .019). CONCLUSIONS: In Takayasu arteritis, 18F-sodium fluoride uptake can document different stages of metabolic disease, even in the absence of active metabolic disease or symptoms.
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Radioisótopos de Flúor/farmacocinética , Tomografía de Emisión de Positrones , Fluoruro de Sodio/farmacocinética , Arteritis de Takayasu/diagnóstico por imagen , Adulto , Aorta/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The central dogma of gene therapy relies on the application of novel therapeutic genes to treat or prevent diseases. The main types of vectors used for gene transfer are adenovirus, retrovirus, lentivirus, liposome, and adeno-associated virus vectors. Gene therapy has emerged as a promising alternative for the treatment of inflammatory diseases. The main targets are cytokines, co-stimulatory molecules, and different types of cells from hematological and mesenchymal sources. In this review, we focus on molecules with anti-inflammatory effects used for in vivo gene therapy mediated by adenoviral gene transfer in the treatment of immune-mediated inflammatory diseases, with particular emphasis on autoinflammatory and autoimmune diseases.
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Adenoviridae/inmunología , Antiinflamatorios/uso terapéutico , Enfermedades Autoinmunes/terapia , Modelos Animales de Enfermedad , Terapia Genética/métodos , Vectores Genéticos , Inflamación/terapia , Animales , Enfermedades Autoinmunes/inmunología , Productos Biológicos/uso terapéutico , Inflamación/inmunología , Ratones , Conejos , RatasRESUMEN
A considerable number of single nucleotide polymorphisms (SNPs) are required to elucidate genotype-phenotype associations and determine the molecular basis of important traits. In this work, we carried out de novo SNP discovery accounting for both genome duplication and genetic variation from American and European salmon populations. A total of 9 736 473 nonredundant SNPs were identified across a set of 20 fish by whole-genome sequencing. After applying six bioinformatic filtering steps, 200 K SNPs were selected to develop an Affymetrix Axiom(®) myDesign Custom Array. This array was used to genotype 480 fish representing wild and farmed salmon from Europe, North America and Chile. A total of 159 099 (79.6%) SNPs were validated as high quality based on clustering properties. A total of 151 509 validated SNPs showed a unique position in the genome. When comparing these SNPs against 238 572 markers currently available in two other Atlantic salmon arrays, only 4.6% of the SNP overlapped with the panel developed in this study. This novel high-density SNP panel will be very useful for the dissection of economically and ecologically relevant traits, enhancing breeding programmes through genomic selection as well as supporting genetic studies in both wild and farmed populations of Atlantic salmon using high-resolution genomewide information.
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Genética de Población/métodos , Técnicas de Genotipaje/métodos , Polimorfismo de Nucleótido Simple , Salmo salar/clasificación , Salmo salar/genética , Américas , Animales , Animales Salvajes , Acuicultura , Biología Computacional/métodos , Europa (Continente) , Estudios de Asociación Genética , Análisis de Secuencia de ADNRESUMEN
PURPOSE: To evaluate the utility of Ki67 as a prognostic marker in Luminal B node-negative breast cancer patients. METHODS: We identified 888 patients with invasive breast carcinomas who underwent surgery between 1997 and 2004. Several classical factors were collected: age, tumor size, node involvement, tumor grade, estrogen and progesterone receptors, HER2 and Ki-67 expression. We analyzed if these parameters could be considered as a prognostic factor. In early Luminal B group, we investigated which of the following biological features provide information about bad prognosis: lack of progesterone receptor expression, HER2 overexpression/amplification or high Ki-67 value. RESULTS: The majority of patients were alive and without relapse of tumor at the moment of the analysis (70 %). The prognostic factors founded in multivariate analysis were: tumor size, node involvement, grade 3 and Ki-67 expression. When we stratified the sample by immunohistochemistry (IHC) in tumor subtypes, we assessed 680 patients and we observed 191 Luminal B tumors. The biological parameter related to the worst survival in absence of nodal involvement was Ki-67 value. CONCLUSIONS: Ki-67 represents an additional predictor of survival in Luminal B node negative breast cancer. Conversely, neither Progesterone-receptor nor HER2 status proved prognostic significance in this group in our study.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Antígeno Ki-67/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , Carcinoma Medular/metabolismo , Carcinoma Medular/patología , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
Heavy metals, such as methylmercury, are key environmental pollutants that easily reach human beings by bioaccumulation through the food chain. Several reports have demonstrated that endocrine organs, and especially the pituitary gland, are potential targets for mercury accumulation; however, the effects on the regulation of hormonal release are unclear. It has been suggested that serum prolactin could represent a biomarker of heavy metal exposure. The aim of this study was to evaluate the effect of methylmercury on prolactin release and the role of the nitrergic system using prolactin secretory cells (the mammosomatotroph cell line, GH3B6). Exposure to methylmercury (0-100 µM) was cytotoxic in a time- and concentration-dependent manner, with an LC50 higher than described for cells of neuronal origin, suggesting GH3B6 cells have a relative resistance. Methylmercury (at exposures as low as 1 µM for 2 h) also decreased prolactin release. Interestingly, inhibition of nitric oxide synthase by N-nitro-L-arginine completely prevented the decrease in prolactin release without acute neurotoxic effects of methylmercury. These data indicate that the decrease in prolactin production occurs via activation of the nitrergic system and is an early effect of methylmercury in cells of pituitary origin.
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Compuestos de Metilmercurio/toxicidad , Óxido Nítrico Sintasa/antagonistas & inhibidores , Nitroarginina/toxicidad , Hipófisis/efectos de los fármacos , Prolactina/metabolismo , Animales , Bovinos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Caballos , Humanos , Hipófisis/metabolismo , Neoplasias Hipofisarias , RatasRESUMEN
Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H2O2 but partially prevented lipid peroxidation caused by 0.0025% H2O2 (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2, opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.
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Animales , Ratas , Analgésicos Opioides/farmacología , Glioma/tratamiento farmacológico , Peróxido de Hidrógeno/administración & dosificación , Morfina/farmacología , Estrés Oxidativo/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular , Depuradores de Radicales Libres/farmacología , Glioma/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Modelos Biológicos , Morfina/administración & dosificación , Oxidación-Reducción , Factores Protectores , Compuestos de Sulfhidrilo/análisisRESUMEN
Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 µM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H2O2 but partially prevented lipid peroxidation caused by 0.0025% H2O2 (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2, opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.
Asunto(s)
Analgésicos Opioides/farmacología , Glioma/tratamiento farmacológico , Peróxido de Hidrógeno/administración & dosificación , Morfina/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Línea Celular Tumoral , Supervivencia Celular , Depuradores de Radicales Libres/farmacología , Glioma/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Modelos Biológicos , Morfina/administración & dosificación , Oxidación-Reducción , Factores Protectores , Ratas , Compuestos de Sulfhidrilo/análisisRESUMEN
Mercury is responsible for serious episodes of environmental pollution throughout the world, especially in the Amazon. This toxicity has led regulatory agencies to focus on fish as the target organism for protecting the health of humans and other sensitive organisms. Unfortunately, in the Amazon area, different sampling strategies and the wide variety of sampling areas and fish species make it extremely difficult to determine relationships across geographic regions or over time to ascertain historical trends. Thus, the aim of this work was to achieve three main objectives: a comparative study of mercury contamination in fish of Itaituba (Tapajós, located downstream of the largest gold-mining region in Amazon) and Belém (an area non-exposed to mercury pollution of anthropogenic origin), perform an analysis of inorganic mercury (IHg) versus monomethylmercury (MeHg) contents, and, finally, compare mercury contamination in Tapajós over time. Five piscivorous species were obtained in Itaituba and Belém. Also, four non-piscivorous species were collected in Itaituba. For the first time, mercury speciation showed that (1) current MeHg levels in piscivorous species in Tapajós are higher than those of the non-exposed area, (2) piscivorous species from Itaituba (dourada, filhote, and sarda) contained mercury levels above the World Health Organization safety limit (~17%) and/or above the US Environmental Protection Agency tissue residue criterion (40%), (3) increased MeHg is usually accompanied by increased IHg, and (4) the mean total mercury concentrations for piscivorous species in Itaituba were within the same range and, associated uncertainties as those previously reported, although a remarkable decreasing trend over time was observed for mean total Hg concentrations in non-piscivorous species from Itaituba. The present study supports the importance of continuous monitoring of both populations in the Amazon Rivers. Our results will better assist the development of preventive strategies and governmental actions to confront the problem of mercury contamination in the Amazon.
Asunto(s)
Peces/metabolismo , Mercurio/análisis , Ríos , Contaminantes Químicos del Agua/análisis , Animales , Brasil , Comercio , Monitoreo del Ambiente , Mercurio/metabolismo , Compuestos de Metilmercurio/análisis , Compuestos de Metilmercurio/metabolismo , Contaminantes Químicos del Agua/metabolismoRESUMEN
BACKGROUND: Knee osteoarthritis (OA) is one of the most common and disabling disorders of the musculoskeletal system. It may affect any ethnic group and causes variable degrees of disability. Various risk factors have been associated with the development and progression of this condition, such as: age, genetic and occupational factors, trauma, menopause, diabetes mellitus, obesity, and gender, among others. Distinguishing these factors, whether individually or altogether, is important to prevent or diagnose and treat the disease early on. METHODS: A case-control study was conducted in 260 females in Torre6n, Coahuila, to analyze the relationship between primary knee osteoarthritis and the D-repeat polymorphism in the ASPN gene (asporin). 130 females with knee osteoarthritis and 130 healthy female controls were included. RESULTS: In this study, menopause and the D16 allele variant were found to be significant risk factors for knee osteoarthritis (p = 0.002, OR 2.656, CI 95% 1.412-4.998; p = 0.026, OR 2.418, CI 95% 1.111-5.263, respectively). The D12 variant was found to be a significant protective allele. CONCLUSIONS: As far as we know, this is the first case-control study in Mexican women that suggests that menopause and the D-repeat polymorphism in the ASPN gene are associated with knee OA.
Asunto(s)
Proteínas de la Matriz Extracelular/genética , Osteoartritis de la Rodilla/genética , Polimorfismo Genético , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: Vascular endothelial growth factor (VEGF) gene is an important angiogenesis regulator related to cancer development and progression. We evaluated the association between -2578 C/A (rs699947) VEGF polymorphism and PCa in Mexican subjects, to contribute to knowledge of VEGF role in genetic epidemiology of prostate cancer (PCa). OBJECTIVE: The aim of this study was to evaluate the association between -2578 C/A VEGF variant and PCa in Mexican population. METHODS: A total of 249 men (77 PCa cases and 172 controls) from the Northwestern region of Mexico were screened for the -2578 C/A VEGF variant. The polymorphism was determined by polymerase chain reaction-based restriction analysis. RESULTS: Genotype frequencies for C/C, C/A, and A/A, were 0.48, 0.49, 0.03 for cases and 0.41, 0.45, 0.14 for controls respectively. Genotype A/A of -2578 VEGF variant reduces the risk of PCa in an 84% among studied population (Odds Ratio 0.16; 95% CI: 0.04-0.71, P=0.007). C/C carriers showed an increased PCa risk of 6.1 times among the study population. CONCLUSIONS: Inheritance of -2578 A/A genotype of VEGF gene may modify PCa susceptibility risk in Mexican population.