RESUMEN
Nitrone-containing compounds are commonly employed as spin traps of free radical species in chemical and biological studies. Some molecules as α-phenyl-N-t-butyl nitrone (PBN) and its derivatives have been tested as potential drugs to treat oxidative stress related diseases, as Alzheimer and stroke for example. In this work we report the design and the synthesis of α-aryl-N-aryl nitrones and their cytoprotection profile on human neuroblastoma cells (SH-SY5Y) under induced oxidative stress. All the nine synthesized nitrones showed a significant response at low micromolar concentration. The selected compound 8 (α-phenyl-N-phenyl nitrone) increased the reduced glutathione (GSH) levels by 65% and lowered the necrotic cell death from 25.8% to 3.8%. Based on our data, the designed highly conjugated nitrone double-bond skeleton can be considered as a good scaffold for further studies regarding oxidative stress-related diseases.
Asunto(s)
Compuestos de Anilina/farmacología , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Bases de Schiff/farmacología , Compuestos de Anilina/síntesis química , Compuestos de Anilina/química , Antioxidantes/síntesis química , Antioxidantes/química , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Humanos , Estructura Molecular , Bases de Schiff/síntesis química , Bases de Schiff/química , Relación Estructura-ActividadRESUMEN
The CBFß gene encodes a transcription factor that, in combination with CBFα (also called Runx, runt-related transcription factor) regulates expression of several target genes. CBFß interacts with all Runx family members, such as RUNX2, a regulator of bone-related gene transcription that contains a conserved DNA-binding domain. CBFß stimulates DNA binding of the Runt domain, and is essential for most of the known functions of RUNX2. A comparative analysis of the zebrafish cbfß gene and protein, and of its orthologous identified homologous proteins in different species indicates a highly conserved function. We cloned eleven zebrafish cbfß gene transcripts, one resulting in the known Cbfß protein (with 187 aa), and three additional variants resulting from skipping exon 5a (resulting in a protein with 174 aa) or exon 5b (resulting in a protein with 201 aa), both observed for the first time in zebrafish, and a completely novel isoform containing both exon 5a and 5b (resulting in a protein with 188 aa). Functional analysis of these isoforms provides insight into their role in regulating gene transcription. From the other variants two are premature termination Cbfß forms, while the others show in-frame exon-skipping causing changes in the Cbfß domain that may affect its function.
Asunto(s)
Subunidad beta del Factor de Unión al Sitio Principal/genética , Subunidad beta del Factor de Unión al Sitio Principal/metabolismo , Transcripción Genética , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Secuencia de Aminoácidos , Animales , Cromosomas/genética , Clonación Molecular , Secuencia Conservada , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad beta del Factor de Unión al Sitio Principal/biosíntesis , Subunidad beta del Factor de Unión al Sitio Principal/química , Regulación del Desarrollo de la Expresión Génica , Datos de Secuencia Molecular , Biosíntesis de Proteínas , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Alineación de Secuencia , Pez Cebra/embriología , Pez Cebra/genética , Proteínas de Pez Cebra/biosíntesis , Proteínas de Pez Cebra/químicaRESUMEN
Amaranth has attracted a great deal of interest in recent decades due to its valuable nutritional, functional, and agricultural characteristics. Amaranth seeds can be cooked, popped, roasted, flaked, or extruded for consumption. This study compared the in vitro starch digestibility of processed amaranth seeds to that of white bread. Raw seeds yielded rapidly digestible starch content (RDS) of 30.7% db and predicted glycemic index (pGI) of 87.2, the lowest among the studied products. Cooked, extruded, and popped amaranth seeds had starch digestibility similar to that of white bread (92.4, 91.2, and 101.3, respectively), while flaked and roasted seeds generated a slightly increased glycemic response (106.0 and 105.8, respectively). Cooking and extrusion did not alter the RDS contents of the seeds. No significant differences were observed among popped, flaked, and roasted RDS contents (38.0%, 46.3%, and 42.9%, respectively), which were all lower than RDS content of bread (51.1%). Amaranth seed is a high glycemic food most likely because of its small starch granule size, low resistant starch content (< 1%), and tendency to completely lose its crystalline and granular starch structure during those heat treatments.
Asunto(s)
Amaranthus/química , Carbohidratos de la Dieta/metabolismo , Manipulación de Alimentos/métodos , Índice Glucémico , Almidón/metabolismo , Pan/análisis , Semillas/químicaRESUMEN
Carpal tunnel syndrome (CTS), a cumulative trauma disorder of the hand and wrist, is one of the most common disabling injuries experienced by video-display terminal (VDT) operators. The purpose of this study was to develop a theoretically based operational quantitative predictive model of the risk of work-related CTS among VDT operators. A total of 100 female VDT operators, who performed a variety of office functions, were studied at a major midwestern university. Data were collected on job exposure, anthropometry and posture factors using questionnaires, direct observation and video-recording. Discriminant analysis and logistic regression were performed to develop the operational models. The results of the study indicated the following: (1) percentage of workday working with a VDT was the most significant factor and accounted for 60% of the variance explaining the causation of musculoskeletal discomforts associated with CTS; (2) discriminant function with six variables (i.e. work duration, trunk incline, wrist extension, wrist ulnar deviation, overall anthropometric measure, weighted anthropometric measure) correctly classified 73% of the CTS group and 72% of the non-CTS group; (3) using the logistic regression model, the probabilities associated with changes in the predictive variables as affecting CTS risk are presented such that increasing the daily work duration from 1 h to 4 h increases the probability of CTS risk from 0.45 to 0.92. The results of the study suggest that the main causation of CTS is job design, the secondary (and lesser cause) is posture associated with the workplace design and the least contributing factor to CTS causation is the individual's anthropometric make-up.