Formación del residente en gastroenterología: una propuesta pedagógica para la atención holística endoscópica a pacientes con neoplasias del sistema digestivo / Gastroenterology residents training: a pedagogical proposal for the endoscopic holistic care to patients with digestive system neoplasms

Introducción: En el proceso de formación del residente en Gastroenterología se perciben limitaciones en la atención a pacientes con neoplasias digestivas, las cuales tienen su base en una insuficiente dinámica, en tanto se revela una visible polarización médico-instrumental de la práctica asistencial, orientada más hacia la endoscopia digestiva diagnóstica y terapéutica, en detrimento de lo preventivo, como parte indisoluble de esa formación. Objetivo: Proponer una estrategia para la formación del residente en gastroenterología en la atención holística endoscópica a pacientes con neoplasias del sistema digestivo. Desarrollo: Se propone una estrategia pedagógica para sistematizar la atención holística preventivo-diagnóstico-terapéutica en la formación del residente en gastroenterología, que deviene un instrumento práctico y flexible, contentivo de etapas, subetapas, orientaciones metodológicas y un sistema de evaluación que permite articular los contenidos clínico-endoscópicos, en un movimiento integrador, a través del diagnóstico, elaboración, implementación y evaluación de acciones para la formación del futuro especialista. Conclusiones: Este instrumento práctico se encamina a sistematizar la formación praxiológico-endoscópico-asistencial de este especialista en la atención holística preventivo-diagnóstico-terapéutica a pacientes con neoplasias digestivas, para el desarrollo de la excelencia en la profesión.

Introduction: In the process of the Gastroenterology resident training there are limitations in the care to patients with digestive neoplasms, which have their base in an scarce dynamics, while a visible polarization doctor-tools in the healthcare practice is observed, which is addressed towards the diagnostic and therapeutical digestive endoscopy more than to the preventive digestive endoscopy, as an indispensable part of the training process. Objective: To propose a pedagogical strategy, for the training of the Gastroenterology resident in the holistic and endoscopic care to patients with neoplasms of the digestive system. Development: A pedagogical strategy is proposed to systematize the preventive-diagnostic-therapeutical and holistic care in the training of the gastroenterology resident, which becomes a practical and flexible instrument, that includes stages and substages, methodological orientations and an evaluation system which allows to articulate the clinical and endoscopic contents, in an comprehensive movement, through the diagnosis, elaboration, implementation and evaluation of actions for the training of the future specialist. Conclusions: This practical instrument proposed is aimed at systematizing the praxiological-endoscopic training of these specialists in the holistic, preventive-diagnostic-therapeutic treatment to patients with digestive neoplasms, so as to reach professional excellence in the profession.

Molecular dynamics investigation into substrate binding and identity of the catalytic base in the mechanism of Threonyl-tRNA synthetase.

The structure and nature of the fully bound active site of Threonyl-tRNA Synthetase (ThrRS) for the second half-reaction has been investigated using molecular dynamics simulations. More specifically, we examined the ThrRS active site with both the substrate Threonyl-AMP and the cosubstrate cognate Threonyl-tRNA bound. Furthermore, we also considered the cases in which an active-site histidyl residue (His309) is either neutral or protonated. Moreover, we considered the role a water molecule may play in formation of a viable Michaelis complex. From the results it is found that the most likely role of His309 is in binding and properly orientating the ribose of the Ado76 nucleotidyl residue of the threonyl-tRNA via formation of a direct His309···Ado76 hydrogen bond, i.e., without involvement of a water. In addition, the imidazole of the His309 residue is likely neutral. It was found that upon protonation the positioning of the Ado76-3'-OH was perturbed, leading to a reduced chance for nucleophilic attack of the threonyl's C1 center.

The first branching point in porphyrin biosynthesis: a systematic docking, molecular dynamics and quantum mechanical/molecular mechanical study of substrate binding and mechanism of uroporphyrinogen-III decarboxylase.

In humans, uroporphyrinogen decarboxylase is intimately involved in the synthesis of heme, where the decarboxylation of the uroporphyrinogen-III occurs in a single catalytic site. Several variants of the mechanistic proposal exist; however, the exact mechanism is still debated. Thus, using an ONIOM quantum mechanical/molecular mechanical approach, the mechanism by which uroporphyrinogen decarboxylase decarboxylates ring D of uroporphyrinogen-III has been investigated. From the study performed, it was found that both Arg37 and Arg50 are essential in the decarboxylation of ring D, where experimentally both have been shown to be critical to the catalytic behavior of the enzyme. Overall, the reaction was found to have a barrier of 10.3 kcal mol(-1) at 298.15 K. The rate-limiting step was found to be the initial proton transfer from Arg37 to the substrate before the decarboxylation. In addition, it has been found that several key interactions exist between the substrate carboxylate groups and backbone amides of various active site residues as well as several other functional groups.

Redox mechanism of glycosidic bond hydrolysis catalyzed by 6-phospho-alpha-glucosidase: a DFT study.

Glycosidic bonds are remarkably resistant to cleavage by chemical hydrolysis. Glycoside hydrolases catalyze their selective hydrolysis in oligosaccharides, polysaccharides, and glycoconjugates by following nonredox catalytic pathways or a net redox-neutral catalytic pathway using NAD(+) and divalent metal ions as cofactors. GlvA (6-phospho-alpha-glucosidase) is a glycosidase belonging to family GH4 and follows a regioselective redox-neutral mechanism of glycosidic-bond hydrolysis that favors alpha- over beta-glycosides. Its proposed catalytic mechanism can be divided into two half-reactions: the first one activates the glucopyranose ring by successively forming intermediates that are oxidized at the 3-, 2-, and 1-positions of the ring, which ultimately facilitate the heterolytic deglycosylation. The second half-reaction is essentially the reverse of the first half-reaction, beginning with the pyranose ring hydroxylation at the anomeric carbon, and it is followed by 3-reduction and regeneration of the active forms of the catalytic site and its cofactors. We investigated the NAD(+)-dependent redox mechanism of glycosidic bond hydrolysis as catalyzed by GlvA through the combined application of density functional theory and a self-consistent reaction field to a large active-site model obtained from the crystallographic structure of the enzyme, then we applied natural bond orbital and second-order perturbation analyses to monitor the electron flow and change in oxidation state on each atomic center along the reaction coordinate to rationalize the energetics and regioselectivity of this catalytic mechanism. We find that in GlvA, the redox catalytic mechanism of hydrolysis is driven by the gradual strengthening of the axial endo-anomeric component within the hexose ring along the reaction coordinate to facilitate the heterolytic dissociation of the axial C1-O bond. In addition, the combined influence of specific components of the generalized anomeric effect fully explains the regioselectivity observed in the catalytic activity of GlvA.

A DFT study of nucleobase dealkylation by the DNA repair enzyme AlkB.

Oxidative dealkylation is a unique mechanistic pathway found in the alpha-ketoglutarate-Fe(II)-dependent AlkB family of enzymes to remove the alkylation damage to DNA bases and regenerate nucleobases to their native state. The B3LYP density functional combined with a self-consistent reaction field was used to explore the triplet, quintet, and septet spin-state potential energy surfaces of the multistep catalytic mechanism of AlkB. The mechanism was found to consist of four stages. First, binding of dioxygen to iron in the active-site complex occurs concerted with electron transfer, thereby yielding a ferric-superoxido species. Second, competing initiation for the activation of oxygen to generate the high-valent iron-oxygen intermediates (ferryl-oxo Fe(IV)O and ferric-oxyl Fe(III)O(*) species) was found to occur on the quintet and septet surfaces. Then, conformational reorientation of the activated iron-oxygen ligand was found to be nearly thermoneutral with a barrier of ca. 50 kJ mol(-1). The final stage is the oxidative dealkylation of the damaged nucleobase with the rate-controlling step being the abstraction of a hydrogen atom from the damaging methyl group by the ferryl-oxo ligand. For this step, the calculated barrier of 87.4 kJ mol(-1) is in good agreement with the experimental activation energy of ca. 83 kJ mol(-1) for the enzyme-catalyzed reaction.

Importancia de la fibra dietética para la nutrición humana / Importance of dietary fiber for human nutrition

La inclusión de la fibra dietética en la dieta diaria de los seres humanos parece desempeñar una importante función para la prevención y el tratamiento de algunas enfermedades crónicas. Esta revisión tiene como objetivo brindar una actualización sobre los avances recientes publicados acerca de la utilidad de la fibra dietética en la salud y en las enfermedades. Entre los beneficios que aporta un ingreso adecuado de fibra dietética se encuentran la disminución de la presión arterial, la reducción del riesgo de cáncer colorrectal, el efecto hipocolesterolémico, menor riesgo de enfermedad cardiovascular y un mejor control de la diabetes mellitus tipo II. Aunque se postulan diferentes mecanismos por los cuales se producen los beneficios, aún no hay resultados concluyentes, pero si está establecido que el aumento en el ingreso dietético de cereales, leguminosas, frutas y vegetales favorece la preservación de la salud y el control de algunas enfermedades crónicas

The inclusion of the dietary fiber in the daily diet of human beings seems to play an important role in the prevention and/or treatment of some chronic diseases. The main objective of this paper is to offer an updating of the recent advances published about the usefulness of the dietary fiber in health and illness. Among the benefits of a proper intake of dietary fiber, one may find the lowering of blood pressure, reduction in colorrectal cancer risks, reduced cholesterol levels, less risks of cardiovascular diseases, and a better control of diabetes mellitus type 2. Although different mechanisms are discussed by which the dietary fiber produces these benefits, there is no conclussive results yet; however, it is stated that increased intake of grain, cereal, fruit and vegetable favours health preservation and the control of some chronic diseases

Mecanismos inmunológicos y de escape en la infección por bacterias grampositivas: el estafilococo dorado: papel de las vitaminas y los minerales / Immunogical and escape mechanisms in Gram positive bacteria infection: the Staphylococus aureus: role of vitamins and minerals

Se realizó una revisión de los aspectos microbiológicos inherentes a la infección cutánea por estafilococo dorado y los relacionados con las características biológicas de las bacterias grampositivas, así como algunos aspectos nutricionales relacionados con el grado de suficiencia de la respuesta inmune contra este grupo de bacterias, que pueden estar implicados como factores de riesgo para la infección. Se hizo énfasis en los elementos de la respuesta inmune relacionados con la protección del huésped ante las infecciones por dichos gérmenes, así como los mecanismos de adaptación de las bacterias a la respuesta inmunológica. Se revisó el papel de las vitaminas y minerales antioxidantes en la inmunidad celular, que evidenció la estrecha relación entre la respuesta al estafilococo y los niveles de minerales y vitaminas que propician un funcionamiento adecuado del estallido respiratorio del leucocito polimorfonuclear neutrófilo (PMN), como primera línea de defensa contra el estafilococo patógeno

Separación de hemoglobina A2 y hemoglobina C por cromatografía en carboximetilcelulosa (CM-52) con amortiguador imidazol-HCL-KCN-NaCL / Separation of A2 hemoglobin and C hemoglobin by (CM-52) carbonxymethylcellolose chromatography with damperer iminazole-HCL-KCN_NaCL

Se ensayó una nueva técnica macrocromatográfica en carboximetilcelulosa y amortiguador imidazol-HCl-KCN-NaCl a pH 6,7. La técnica es confiable y exacta para la separación y cuantificación de hemoglobina A2 en individuos portadores de hemoglobina AC, Cb talasemia, hemoglobina AS y hemoglobina SC, lo cual es en muchos casos de interés clínico. También se detectó una variante de hemoglobina A2 en una embarazada portadora de hemoglobina AC y un gen b talasémico en Cis con el gen para la hemoglobina C

Variaciones fenotípicas de las heterocigotos para las hemoglobinas S y C / Phenotypic variations of heterozygotes for hemoglobins S an C

Se estudiaron algunas características cuantitativas sanguíneas en un grupo de heterocigotos AS y AC. Se encontró que cuando la concentración de HbS es menor que el 30%hay cambios cuantitativos en las constantes corpusculares, hemoglobina A2 y hemoglobina fetal con relación al grupo control, lo cual puede estar asociado al número de genes alfa ausentes en el individuo