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Cancer cells have unlimited replicative potential, insensitivity to growth-inhibitory signals, evasion of apoptosis, cellular stress, and sustained angiogenesis, invasiveness and metastatic potential. Cancer cells adequately adapt cell metabolism and integrate several intracellular and redox signaling to promote cell survival in an inflammatory and hypoxic microenvironment in order to maintain/expand tumor phenotype. The administration of tyrosine kinase inhibitor (TKI) constitutes the recommended therapeutic strategy in different malignancies at advanced stages. There are important interrelationships between cell stress, redox status, mitochondrial function, metabolism and cellular signaling pathways leading to cell survival/death. The induction of apoptosis and cell cycle arrest widely related to the antitumoral properties of TKIs result from tightly controlled events involving different cellular compartments and signaling pathways. The aim of the present review is to update the most relevant studies dealing with the impact of TKI treatment on cell function. The induction of endoplasmic reticulum (ER) stress and Ca2+ disturbances, leading to alteration of mitochondrial function, redox status and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways that involve cell metabolism reprogramming in cancer cells will be covered. Emphasis will be given to studies that identify key components of the integrated molecular pattern including receptor tyrosine kinase (RTK) downstream signaling, cell death and mitochondria-related events that appear to be involved in the resistance of cancer cells to TKI treatments., This study was funded by Institute of Health Carlos III (ISCiii) (PI16/00090, PI19/00838 and PI19/01266), Spanish Ministry of Economy and Competitiveness (BFU2016-80006-P), Andalusian Ministry of Economy, Innovation, Science and Employment (BIO-216 and CTS-6264), Andalusian Ministry of Equality, Health and Social Policies (PI-0198-2016) and Valencian Ministry of Education, Culture and Sports (PROMETEO/2019/027). P de la C-O was supported by FPU predoctoral fellowship (FPU17/00026) from Spanish Ministry of Education, Culture and Sports. E N-V was supported by the the predoctoral i-PFIS IIS-enterprise contract in science and technologies in health (IFI18/00014) from ISCiii. We thank the Biomedical Research Network Center for Cardiovascular Diseases (CIBERcv), and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd) founded by the ISCiii and co-financed by European Regional Development Fund (ERDF) "A way to achieve Europe" for their financial support.

Nitric oxide (NO) is a physiopathological messenger generating different reactive nitrogen species (RNS) according to hypoxic, acidic and redox conditions. Recent Advances: RNS and reactive oxygen species (ROS) promote relevant post-translational modifications, such as nitrosation, nitration, and oxidation, in critical components of cell proliferation and death, epithelial-to-mesenchymal transition, and metastasis.The pro- or antitumoral properties of NO are dependent on local concentration, redox state, cellular status, duration of exposure, and compartmentalization of NO generation. The increased expression of NO synthase has been associated with cancer progression. However, the experimental strategies leading to high intratumoral NO generation have been shown to exert antitumoral properties. The effect of NO and ROS on cell signaling is critically altered by factors modulating tumor progression such as oxygen content, metabolism, and inflammatory response. The review describes the alteration of key components involved in cell survival and death, metabolism, and metastasis induced by RNS- and ROS-related post-translational modifications.The identification of the molecular targets affected by nitrosation, nitration, and oxidation, as well as their interactions with other post-translational modifications, will improve the understanding on the complex signaling and cell fate decision in cancer. The therapeutic NO-based strategies have to address the complex crosstalk among NO and ROS with regard to critical components affecting tumor cell survival, metabolism, and metastasis in the progression of cancer, as well as close interaction with ionizing radiation and chemotherapy.

Nuestros pioneros avances permitieron reconocimientos de sitios arqueológicos e itinerarios de altura hacia la vertiente occidental de los Andes. Estos incluyeron excavaciones y estudios de ma teriales de instalaciones que presentan ocupaciones temporales (c. 800 al 1480 ad), registrando la impronta del conspicuo Período Inca (c. 1470 al 1536 ad) y alcanzando su utilización hasta la primera mitad del siglo xix). Nuestra hipótesis, si bien considera posibles las posiciones de colegas que proponen para el derrotero de Almagro un abanico de pasos que van desde Peña Negra a Pircas Negras, con sus desechos y con Comecaballos como paso central, señala a la quebrada del arroyo Peña Negra y al paso de La Ollita con suficiente probabilidad como uno de los pasos transitados, tal vez el más importante. Our pioneering research led to the discovery of archaeological sites and high-altitude routes in the western side of the Andes. This included excavations and studies of settlement materials exhibiting temporary occupations (c. 800 to 1480 ce), with a record from a conspicuous Inca period (c.1470 to 1536 ad) until the first half of the nineteenth century. We hypothesize that the Peña Negra ravine and, particularly, the paso de la Ollita were not only some of the most traveled mountain passes, but also the main ones. We do not rule out, however, other colleagues’ positions that consider a wide range of other mountain passes, from Peña Negra to Pircas Negras, among which Comecaballos was the most important. Fil: Barcena, Joaquin Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentina. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras; Argentina

Dried corn distillers grains with solubles (DDGS) can partially replace grains and forages in diets for ruminants. The objective of this research was to evaluate the effect of replacing grains and soybean meal with DDGS (0%, 15%, 30% and 45%) in the diet of lambs. Thirty-two native lambs were used (initial bodyweight = 28.6 ± 2.19 kg) in a completely randomized design. Initial body weight was a co-variable, and the means were compared with the Tukey test. The dry matter intake was significantly higher in DDGS containing diet than in the control treatment. The daily weight gain was higher in the diets with 15% of DDGS compared with the control. Dry matter digestibility was lower by 7% with 45% of DDGS. The hot and cold carcass weights were significantly higher by 8% in DDGS treatments compared to the control. The inclusion of increasing levels of DDGS in the diet of fattening lambs increased their dry matter intake, improved carcass weight, and did not adversely affect carcass characteristics. Keywords: Carcass, by-products, animal production, ruminant nutrition

The present study analyzes zooarchaeological and palaeoenvironmental trends from an assemblage of small mammals recovered from Agua de la Tinaja (AT), an archaeological site from an intermountain valley of the Andean cordillera (northern Mendoza, Argentina). Small mammal remains recovered from AT, chronologically associated with 900–600 years BP, showed taphonomic traces corresponding to the action of owls and humans. Such results were included and compared within the framework of a resource intensification process suggested for Prehistoric human societies from northern Mendoza in Central Western Argentina. The small mammal assemblage from AT is composed by typical species from highland areas (Abrothrix andina, Microcavia australis, Phyllotis xanthopygus) mixed with some species from the Monte Desert (Calomys musculinus, Ctenomys sp., Eligmodontia sp., Thylamys pallidior) and Abrocoma sp. The co-occurrence of some species with modern allopatric distributions could support a scenario of greater environmental heterogeneity during the late Holocene than in the present. A situation like this could be consistent with a more dense vegetation cover and larger availability of patch resources. Fil: López, José Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentina. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras. Instituto de Arqueología y Etnología; Argentina Fil: Fernández, Fernando Julián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería; Argentina Fil: Teta, Pablo Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina Fil: Rosi, María Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; Argentina Fil: Sironi, Osvaldo Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentina Fil: Bárcena, Joaquín Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Ciencias Humanas, Sociales y Ambientales; Argentina

Respiratory CO 2 response in acute cervical spinal cord injury (CO 2 response in spinal cord injury)

Background: Stress hyperglycaemia is common in the intensive care unit (ICU) setting and has been related to a worst outcome. Objective: The objective was to characterize the association of glucoregulatory hormones, mainly incretins, with the levels of glycaemia, and its relationship with outcome in ICU patients. Methods: We prospectively studied 60 patients. Stress hyperglycaemia was diagnosed when glycaemia was < 115 mg/dL. At ICU admission we determined glycaemia, insulin, glucagon, cortisol, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) plasma levels. Groups were compared using Kruskal-Wallis test. The association between glycaemia levels and glucoregulatory hormones was evaluated using linear regression. Results: Forty-five patients (75%) had hyperglycaemia. We observed no differences in glucoregulatory hormones levels between normo- and hyper- glycaemia groups. Glycaemia levels were not significantly correlated with insulin, glucagon, cortisol or GIP levels, but were correlated with GLP-1 (p = 0.04). GLP-1 was also correlated with cortisol (p = 0.01), but failed to show a significant correlation with insulin, glucagon or GIP levels. Lower levels of plasma GLP-1 were found in patients with stress hyperglycaemia requiring vasoactive support (p = 0.02). Conclusions: Glycaemia levels were correlated with GLP-1 levels in ICU patients. GLP-1 levels were also associated with cortisol. Patients with stress hyperglycaemia who required vasoactive support had lower incretin levels compared with those patients with stress hyperglycaemia who were hemodynamically stables. (ClinicalTrials.gov Identifier: NCT01087372).Antecedentes: La hiperglucemia de estrés es habitual en el contexto de la Unidad de cuidados intensivos (UCI) y se ha relacionado con un peor pronóstico. Objetivo: el objetivo fue caracterizar la asociación de hormonas glucorreguladoras, principalmente las incretinas, con las glucemias y su relación con el pronóstico de los pacientes de UCI. Métodos: Estudiamos de forma prospectiva a 60 pacientes. La hiperglucemia de estrés se diagnosticaba cuando la glucemia era < 115 mg/dl. En el ingreso en la UCI, determinamos la glucemia y las concentraciones plasmáticas de insulina, glucagón, cortisol, polipéptido insulinotropo dependiente de glucosa (GIP) y péptido-1 de tipo glucagón (GLP-1). Se compararon los grupos mediante la prueba de Kruskal-Wallis. La asociación entre las glucemias y las hormonas contrarreguladoras se evaluó mediante regresión linear. Resultados: 45 pacientes (75%) tenían hiperglucemia. No observamos diferencias en las concentraciones de hormonas glucorreguladoras entre los grupos de normo e hiperglucemia. Las glucemias no se correlacionaron de forma significativa con las concentraciones de insulina, glucagón, cortisol o GIP, pero sí con el GLP-1 (p = 0,04). El GLP-1 también se correlacionó con el cortisol (p = 0,01), pero no consiguió mostrar una correlación significativa con las concentraciones de insulina, glucagón o GIP. Se encontraron menores concentraciones plasmáticas de GLP-1 en los pacientes con hiperglucemia de estrés que requerían soporte vasoactivo (p = 0,02). Conclusiones: las glucemias se correlacionaron con las concentraciones de GLP-1 en los pacientes en UCI . Las concentraciones de GLP-1 también se asociaron con el cortisol. Los pacientes con hiperglucemia de estrés que necesitaron soporte vasoactivo tenían menores concentraciones de incretina en comparación con aquellos con hiperglucemia de estrés con estabilidad hemodinámica (ClinicalTrials.gov Identifier: NCT01087372).

Hipótesis: La suplementación endovenosa con el dipéptido N(2)-L-alanil-L-glutamina, en pacientes traumáticos ingresado en la UCI puede ejercer un efecto beneficioso en cuanto a reducción de la incidencia de infecciones, de la estancia en UCI y de la mortalidad, independientemente del tipo de nutrición (enteral o parenteral) administrada. Objetivos: El objetivo principal es medir la eficacia de la suplementación con el dipéptido, administrado de forma endovenosa, en reducir la incidencia de las complicaciones infecciosas, la mortalidad y la estancia en UCI de los pacientes traumáticos ingresados en la UCI. Otros objetivos secundarios son: 1) Evaluar la eficacia de L-alanil-L-glutamina en diferentes grupos de gravedad y en relación con los niveles plasmáticos de glutamina. 2) Recoger los posibles efectos adversos del dipéptido administrado de forma endovenosa. Metodología: Ensayo clínico prospectivo, multicéntrico, aleatorizado y doble ciego, con dos grupos paralelos de tratamiento, para evaluar eficacia frente a placebo. Los pacientes traumáticos ingresados en la UCI que cumplan los criterios de inclusión/no exclusión, serán aleatorizados para recibir L-alanil-L-glutamina o placebo, independientemente del tipo de nutrición que reciba el paciente (enteral o parenteral) El dipéptido será administrado como un farmaconutriente en forma de perfusión continua durante 24 horas y durante 5 días a 0,5 g/kg/día.Hypothesis: the endovenous administration of glutamine, independently of the type of nurtrition received, can reduce the ICU length of stay, the incidence of infections and the mortality in the traumatic patients admitted to the ICU. Objectives: The main objective is to assess the efficacy of glutamine suplementation, given intravenously, to reduce the incidence of infectious complications, mortality and ICU length of stay in the traumatic patients admitted to the ICU. Other objectives are: 1) to assess the efficacy of glutamine in different groups of patients according to the severity and the plasma levels of glutamine. 2) Record all the adverse events due to the intravenous administration of glutamine. Methods: prospective, randomized, doble-blind and multicenter study with two parallel groups: placebo and treatment group. The patients who fulfill the inclusion criteria will receive either glutamine or placebo, independently of the type on nutrition. Glutamine will be administered as a pharmaconutrient at 0.5 g/kg/day during 5 days as a continous perfusion.

Objetivo. Generar el modelo de competencias del profesor para ejercer la docencia de alto nivel en Medicina. Materiales y métodos. Para generar el modelo se analizó la bibliografía, el propósito del plan de estudio por competencias y se utilizó el método Developing a Curriculum (DACUM), con la participación de 35 expertos que integraron mediante consenso el trabajo que debe realizar un docente de medicina para cumplir con éxito el propósito del plan de estudio. Resultados. Se identificaron las funciones básicas de los profesores de medicina, así como las actividades para su cumplimiento. Se conformó el modelo con seis competencias: disciplinaria, de investigación, psicopedagógica, de comunicación, académico-administrativa y humanística. Conclusiones. El modelo pretende guiar las acciones de los profesores que actualmente participan en el programa y aquellos que aspiran a formar parte del proceso educativo; elaborar programas para la formación de profesores que favorezcan el desarrollo de competencias académicas; identificar elementos que se deben considerar para la evaluación del desempeño docente; orientar el diseño de indicadores útiles para otorgar reconocimientos y estímulos a los profesores cuyo desempeño académico sea excepcional; orientar al estudiante, en la relación profesor-alumno, sobre las funciones y actividades que puede esperar del profesor.Aim. To create a competency model for the medical professor in order to exert teaching at its highest level. Materials and methods. To create such model, we analyzed current literature on teaching, the aim of the curricula for competencies and we used the DACUM method whose letters stand for Developing a Curriculum. 35 experts who participated in this project reached a consensus regarding the duties that have to be carried out by a medical professor in order to successfully fulfill the aim of the curricula. Results. We identified the basic functions of medical professors as well as the related duties for its fulfillment. The model comprises six competencies: disciplinary, research, psico-pedagogy, communicative, academic-administrative and humanistic competencies. Conclusion. This model pretends to guide the actions of medical professors who are currently participating in this program and those who want to become part of the education process. It also pretends to create programs favoring the professors´ training benefiting the development of academic competencies; to identify the elements to be considered for the assessment of the professors´ development; to guide the design of useful indicators to grant awards and incentives to those professors whose academic development be exceptional; to guide the student within the professor-student relationship, on the duties and activities that they can expect from the professor.

Nitric oxide (NO) plays relevant roles in signal transduction in physiopathology and its effects are dependent on several environmental factors. NO has both pro-apoptotic and anti-apoptotic functions but the molecular mechanisms responsible for these opposite effects are not fully understood. The action of NO occurs mainly through redox changes in target proteins, particularly by S-nitrosylation of reactive cysteine residues. Thioredoxin (Trx) and glutaredoxin (Grx) systems are the main cellular controllers of the thiolic redox state of proteins exerting controversial effects on apoptosis with consequences for the resistance to or the development of cancer. The aim of this study was to ascertain whether Trx and/or Grx systems mediate the antiproliferative effect of NO on hepatoblastoma cells by modulating the redox-state of key proteins. Proliferation decreased and apoptosis increased in HepG2 cells overexpressing Nitric Oxide Synthase-3 (NOS-3) as a result of multilevel cellular responses to the oxidative environment generated by NO. Enzyme levels and cysteine redox state at several metabolic checkpoints were consistent with prominence of the pentose phosphate pathway to direct the metabolic flux toward NADPH for antioxidant defense and lowering of nucleotide biosynthesis and hence proliferation. Proteins involved in cell survival pathways, proteins of the redoxin systems and phosphorylation of MAPK were all significantly increased accompanied by a shift of the thiolic redox state of Akt1, Trx1 and Grx1 to more oxidized. Silencing of Trx1 and Grx1 neutralized the increases in CD95, Akt1 and pAkt levels induced by NO and produced a marked increase in caspase-3 and -8 activities in both control and NOS-3 overexpressing cells concomitant with a decrease in the number of cells. These results demonstrate that the antiproliferative effect of NO is actually hampered by Trx1 and Grx1 and support the strategy of weakening the thiolic antioxidant defenses when designing new antitumoral therapies., Graphical abstract, Highlights • Endogenous NO induces NADPH and reduces nucleotide biosynthesis in HepG2 cells. • Trx1 and Grx1 have a pro-oxidant action on key proteins under nitrosative conditions. • Trx1 and Grx1 hamper the antiproliferative action of NO in tumoral cells. • Weakening of thiolic antioxidant defenses could help in the design of anti-tumoral therapies.

Glutaredoxins belong to a family of small proteins with glutathione-dependent disulfide oxidoreductase activity involved in cellular defense against oxidative stress. The product of the yeast GRX2 gene is a protein that is localized both in the cytosol and mitochondria. To throw light onto the mechanism responsible for the dual subcellular distribution of Grx2 we analyzed mutant constructs containing different targeting information. By altering amino acid residues around the two in-frame translation initiation start sites of the GRX2 gene, we could demonstrate that the cytosolic isoform of Grx2 was synthesized from the second AUG, lacking an N-terminal extension. Translation from the first AUG resulted in a long isoform carrying a mitochondrial targeting presequence. The mitochondrial targeting properties of the presequence and the influence of the mature part of Grx2 were analyzed by the characterization of the import kinetics of specific fusion proteins. Import of the mitochondrial isoform is relatively inefficient and results in the accumulation of a substantial amount of unprocessed form in the mitochondrial outer membrane. Substitution of Met(35), the second translation start site, to Val resulted in an exclusive targeting to the mitochondrial matrix. Our results show that a plethora of Grx2 subcellular localizations could spread its antioxidant functions all over the cell, but one single A to G [corrected] mutation converts Grx2 into a typical protein of the mitochondrial matrix. The "A" denotes adenine, rather than alanine, and the "G" refers to guanine, not glycine [corrected]

Endocranial hypertension is a frequent complication in severe head trauma appearing up to in 50-75% of cases. At times it is impossible to manage endocranial hypertension despite the treatment, and in these cases mortality reaches 84-100%. External lumbar drainage is a therapeutic option in refractory endocranial hypertension. Although it has been used predominantly in pediatric patients there is also experience in adult patients. The literature shows that this technique frequently controls intracranial pressure and that is associated with a limited incidence of serious complications. We present our experience in the use of external lumbar drainage in four patients admitted because of severe head trauma who showed refractory to the habitual treatment; endocranial hypertension in this case was controlled with external lumbar drainage.

Glutaredoxins (Grx) are small (approximately 12kDa) proteins which catalyze thiol disulfide oxidoreductions involving glutathione (GSH) and disulfides in proteins or small molecules. Here, we present data which demonstrate the ability of glutaredoxins to catalyze the reduction of oxidized glutathione (GSSG) by dihydrolipoamide (DHL), an important biological redox catalyst and synthetic antioxidant. We have designed a new assay method to quantify the rate of reduction of GSSG and other disulfides by reduced lipoamide and have tested a set of eight recombinant Grx from human, rat, yeast, and E. coli. Lipoamide dependent activity is highest with the large atypical E. coli Grx2 (k(cat)=3.235 min(-1)) and lowest for human mitochondrial Grx2a (k(cat)=96 min(-1)) covering a wider range than k(cat) for the standard reduction of hydroxyethyldisulfide (HED) by GSH (290-2.851 min(-1)). The lipoamide/HED activity ratio was highest for yeast Grx2 (1.25) and E. coli Grx2 and lowest for E. coli Grx1 (0.13). These results suggest a new role for Grxs as ancillary proteins that could shunt reducing equivalents from main catabolic pathways to recycling of GSSG via a lipoyl group, thus serving biochemical functions which involve GSH but without NAD(P)H consumption.

El registro arqueológico inka en el centro-oeste argentino, así como la existencia de documentación de los primeros tiempos coloniales hispánicos —con datos acerca de la dominación y de las nuevas relaciones resultantes— brindan grandes posibilidades de investigación. Así, es factible adentrarse en consideraciones sobre el espacio abarcado y el efectivamente controlado por la organización estatal. Del mismo modo, pueden conocerse las formas y funciones del control, las reacciones y ajustes zonales, la continuidad y el cambio en las diversas expresiones disponibles, entre otros.En el presente trabajo se presentará una parte de la infraestructura y de los materiales inkas regionales conocidos. Estos son tratados sobre la base de sus características y funciones, en contraste con los propios de las poblaciones locales. Tales bases se articularán con la documentación de archivos y referencias de los cronistas. De ello se derivará la interpretación de un modelo ad hoc válido para la periferia, en el extremo austral, para la época final de la expansión. Esta será seguida de un modelo, quizás similar, válido para los primeros tiempos de la incidencia hispánica.

Objetivo Revisar la evidencia cientifica existente en la bibliografia respecto al empleo de dosis altas de barbituricos en el traumatismo craneoencefalico grave (TCEG), haciendo especial hincapie en su efecto sobre la mortalidad y el control de la presion intracraneal (PIC). Fuente de datos Se realizo una busqueda bibliografica en Medline de los ultimos 30 anos con las siguientes palabras: barbiturate, pentobarbital, thiopental Resultados El uso de barbituricos en el TCEG se remonta a mas de 6 decadas, aunque es a mediados de los anos setenta cuando se comenzo a publicar series de casos, de los que se puede concluir que los barbituricos tenian un efecto terapeutico al controlar la PIC elevada y que la falta de control de la PIC conllevaba un peor pronostico. Hasta la fecha no se ha publicado ningun estudio que haya demostrado una mejora en la mortalidad de los pacientes con TCEG tratados con altas dosis de barbituricos. El estudio de Eisenberg es un estudio prospectivo, aleatorizado, multicentrico y cruzado en el que en el analisis de regresion logistica, el tratamiento con barbituricos a dosis elevadas tuvo una probabilidad de controlar la PIC 5-6 veces mayor que el tratamiento convencional Conclusiones El empleo de barbituricos a altas dosis en el TCEG puede controlar la PIC cuando otros tratamientos han fracasado. Dicha afirmacion se basa en estudios que son series de casos y en un trabajo prospectivo aleatorizado

Fundamento Estudiar el grado de asociacion entre el patron electrocardiografico de ingreso en el infarto agudo de miocardio, la falta de eficacia de la trombolisis y el mayor riesgo de disfuncion ventricular izquierda Pacientes y metodos Se estudiaron retrospectivamente 150 pacientes ingresados de manera consecutiva por infarto de menos de 6 h de evolucion, que recibieron tratamiento trombolitico. Los pacientes se agruparon segun el patron electrocardiografico, definido por la presencia o ausencia de distorsion de la porcion terminal del complejo QRS. Se consideraron criterios de reperfusion el pico temprano de CK/CKMB, el descenso del segmento ST mayor del 50% y la negativizacion de la onda T a las 2 h postrombolisis. Se realizo un analisis estadistico mediante el test de la t de Student para variables cuantitativas y el de la χ2 para las cualitativas Resultados La edad media de los pacientes, 131 varones y 19 mujeres, fue de 60 anos. Un total de 80 infartos fueron de cara inferior y 59 de pared anterior. No existieron diferencias entre los grupos en cuanto a sexo, tipo y tiempo de inicio de la trombolisis, criterios de reperfusion, resultados de la ergometria y la coronariografia, episodios de angina postinfarto o arritmias malignas y fallecimientos. Los pacientes con distorsion final del complejo QRS presentaron infartos de mayor tamano (CK/CKMB = 3.207[1662]/403 [226] U frente a 2.251[1564]//281[186] U, p = 0,001). Los pacientes con distorsion del complejo QRS presentaron mayor presencia de claves Killip III/IV (OR = 5,44; IC del 95%, 1,01-229,13; p = 0,002) y disfuncion ventricular izquierda severa (OR = 3,2; IC del 95% 1,06-9,66; p = 0,003) Conclusion El patron electrocardiografico del ingreso en el infarto agudo de miocardio tratado con trombolisis no se asocia con la respuesta al tratamiento trombolitico, pero si con el tamano del infarto y la disfuncion ventricular izquierda

Objetivo Analizar la importancia de la sospecha clinica inicial en el diagnostico de la diseccion de aorta toracica y la influencia en su pronostico, revisar los diferentes metodos complementarios utilizados. Material y metodos Se estudiaron retrospectivamente 33 casos de diseccion de aorta toracica entre enero de 1993 y junio de 1998, valorandose parametros clinico-epidemiologicos, diagnosticos de ingreso y pruebas complementarias. Los resultados cualitativos se valoraron mediante χ2. Resultados La sintomatologia tipica de diseccion (dolor toracico, abdominal e interescapular) se aprecio en 19 (58%) casos. La sospecha clinica al ingreso se realizo en 9 (27%) de los pacientes, siendo diagnosticos tardios/casuales 22 (67% ) casos. Se realizo el diagnostico de diseccion a traves de la necropsia en 2 (6%) ocasiones.Diagnosticos erroneos de ingreso fueron: cardiopatia isquemica en 9 casos; isquemia de miembros inferiores en 3. Se realizo el diagnostico de colico hepatico, neumonia, gastroenteritis, sincope, colico nefritico, aneurisma de aorta abdominal, pancreatitis y dolor osteomuscular respectivamente en un caso. El retraso en el diagnostico no influyo significativamente en la mortalidad. La prueba diagnostica que se utiliza en nuestro medio en primer lugar es la tomografia axial computarizada (TAC). La aortografia se utiliza como prueba confirmatoria del diagnostico. Conclusiones No se valoran adecuadamente los datos de la clinica inicial. La mortalidad es mayor en el grupo de pacientes en el cual no hay sospecha clinica inicial de diseccion de aorta.

Retrospective study.The objective of this study was to compare the CO₂ response of acute tetraplegic cervical spinal cord injury (SCI) patients undergoing mechanical ventilation with a control group of critically ill patients ready for weaning of mechanical ventilation and successfully extubated.This study was conducted at the intensive care unit of a University Hospital in Mallorca, Spain.CO₂ response was studied in 12 acute tetraplegic cervical SCI patients at the C4-C7 level and 22 control patients. The control group patients were consecutively selected from a database of patients with mechanical ventilation and who were successfully extubated after a CO₂ response test. To increase the CO₂ , we used the method of re-inhalation of expired air, and we evaluated the hypercapnic ventilatory response, the change in minute ventilation induced by the increase of partial pressure of arterial carbon dioxide (PaCO₂ ), which measures the whole respiratory system (metabolic control, neuromuscular or ventilatory apparatus), and the hypercapnic drive response, the change in the airway occlusion pressure at 100 ms induced by the increase in PaCO2, which measures the chemosensitivity of the respiratory center.Cervical SCI patients were younger than the control group patients (26±7 and 62±12 years, respectively; P0.001). Mean values of the hypercapnic ventilatory response in cervical SCI and control groups were 0.52±0.31 and 0.64±0.33 l min(-1) per mm Hg (P=0.40), respectively, and the hypercapnic drive response was 0.24±0.16 and 0.48±0.23 cm H₂O per mm Hg (P=0.001), respectively.Acute tetraplegic cervical SCI patients had reduced hypercapnic drive response that may contribute to the difficult weaning, without reduction in hypercapnic ventilatory response.

La incidencia de la trombocitopenia inducida por heparina tipo II (TIH-II) es aproximadamente un 1%, pero puede ser mas elevada en pacientes postoperados de cirugia cardiaca. La TIH-II puede ocasionar una elevada morbimortalidad en relacion con sus complicaciones tromboticas, especialmente si no se diagnostica precozmente. Presentamos el caso de una TIH-II desarrollada en el postoperatorio de una anuloplastia mitral. Se revisan sus mecanismos fisiopatologicos, la importancia de la sospecha clinica ante la presencia de trombos resistentes a la terapia anticoagulante habitual y la complejidad del tratamiento.

Specific polyclonal antibodies towards the oxidized form of bovine thioredoxin reductase (TR) have been obtained in rabbits, and purified. The antigenicity was lost upon reduction of TR by NADPH indicating a large conformational change upon reduction of the redox-active disulfide in the enzyme. The antibodies did not cross-react with other bovine NADPH-dependent dehydrogenases. No reactivity was observed with TR from bacteria, yeast or rat and only a slight reaction was obtained with TR from horse. Immunoafinity purified anti-thioredoxin and anti-glutaredoxin antibodies were used to develop competitive indirect ELISA assays that were validated giving very good linearity, reproducibility, sensitivity and parallelism. The glutaredoxin (Grx) immunoassay is the first quantitative method described to measure the protein. When applied to a battery of calf tissues the contents of Grx varied from 7 to 120 μg per gram of fresh tissue. Skeletal and heart muscles gave the lowest values and spleen and salivary glands the highest. However, skeletal muscle showed the highest gluthathione-hydroxyethyl disulfide oxidoreductase specific activity.

Stress hyperglycaemia is common in the intensive care unit (ICU) setting and has been related to a worst outcome.The objective was to characterize the association of glucoregulatory hormones, mainly incretins, with the levels of glycaemia, and its relationship with outcome in ICU patients.We prospectively studied 60 patients. Stress hyperglycaemia was diagnosed when glycaemia was115 mg/dL. At ICU admission we determined glycaemia, insulin, glucagon, cortisol, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) plasma levels. Groups were compared using Kruskal-Wallis test. The association between glycaemia levels and glucoregulatory hormones was evaluated using linear regression.Forty-five patients (75%) had hyperglycaemia. We observed no differences in glucoregulatory hormones levels between normo- and hyper- glycaemia groups. Glycaemia levels were not significantly correlated with insulin, glucagon, cortisol or GIP levels, but were correlated with GLP-1 (p = 0.04). GLP-1 was also correlated with cortisol (p = 0.01), but failed to show a significant correlation with insulin, glucagon or GIP levels. Lower levels of plasma GLP-1 were found in patients with stress hyperglycaemia requiring vasoactive support (p = 0.02).Glycaemia levels were correlated with GLP-1 levels in ICU patients. GLP-1 levels were also associated with cortisol. Patients with stress hyperglycaemia who required vasoactive support had lower incretin levels compared with those patients with stress hyperglycaemia who were hemodynamically stables. (ClinicalTrials.gov Identifier: NCT01087372).

Drainage of cerebrospinal fluid by means of external lumbar drainage (ELD) is controversial in the adult population with traumatic brain injury. We report our experience with ELD in the treatment of post-traumatic high intracranial pressure (ICP) and the results of the long-term follow-up in these patients. We undertook clinical evaluation of 30 patients with traumatic brain injury and high ICP treated with second-tier measures or with first-tier measures if second-tier measures were contraindicated. The study involved a retrospective review of collected data. Outcome at intensive care unit discharge and three to five years after injury were evaluated with the Glasgow Outcome Scale. The mean age of patients was 34.9±12.5 years and 25 (83%) were male. The median (interquartile range) Glasgow Coma score was 8 (7 to 10). ICP before and one hour after ELD placement was 33.7±9.0 and 12.5±4.8 mmHg respectively, a decrease in 21.2±8.3 mmHg (P The use of ELD resulted in a marked decrease in ICP. These patients presented a good outcome in 62% of the cases in the long-term evaluation. Few complications related with ELD use were noted.

Thioredoxin (TRX) and glutaredoxin (GRX) had previously been localized in folliculo-stellatae (FS) cells and in only a fraction of glandular cells of the anterior pituitary (Padilla et al., 1992). Here we report on a double immunolabelling study carried out to determine the correlation between the type of secretory cell and the presence of TRX or GRX. TRX and GRX levels were under the detection limits in gonadotropes, thyrotropes and corticotropes. A considerable proportion of lactotropes contained TRX or GRX; a higher proportion of somatotropes contained TRX and all of them were GRX-positive. The secretory cell types more frequently detected in the epithelium of well-defined follicles lined by TRX-positive FS cells were somatotropes and lactotropes followed by corticotropes; gonadotropes and thyrotropes were scarce in these structures. Regarding the biological functions of glutaredoxin and thioredoxin, these results show that involvement in the processing of secretory proteins is not a general property of these two thiol-disulfide oxidoreductases, not even specifically in the case of cysteine-rich secretory proteins. On the other hand, another type of functional specificity perhaps related to the heterogeneous response of the endocrine cells is discussed.

1. 1. Purification of horse-liver glutathione reductase was obtained by affinity chromatography on N 6 -(6-aminohexyl)-adenosine-1′5′-bisphosphate Sepharose ( N 6 -2′5′-ADP-Sepharose) and Reactive Red-120-Agarose, and chromatography on DEAE-Sephadex and Sephacryl S-300. 2. 2. The final preparation had 248 U/mg specific activity after 11,174-fold purification with 47% final recovery, and was homogeneous by SDS-electrophoresis. It showed charge heterogeneity in non-denaturing electrophoresis and chromatofocusing, with several peaks of pI between 5.7 and 6.7. 3. 3. The enzyme was homodimeric (107,000 native MW), with S 20 w = 6.31 S, and 41.22 A of hydrodynamic radius. It showed absorption peaks at 270, 370 and 462 nm, a characteristic of flavoproteins. 4. 4. When NADPH was substituted by deamino-NADPH or NADH the enzyme showed 69 and 8.5% activity, respectively, while with glutathione-CoA mixed disulfide the enzyme had 23% of the activity shown with GSSG. Apparent K m values of 8.8, 680, 59, and 560 μ M were measured for NADPH, NADH, GSSG and ferrycianide, respectively.

Ein Polytrauma ist eine lebensbedrohliche Situation – nicht nur wegen der Verletzungen an sich, sondern auch wegen der darauf folgenden immunologischen und metabolischen Storungen. Die Beeintrachtigung des Immunsystems begunstigt wiederum Infektionen, eine der haufigsten Todesursachen nach Polytrauma. Glutamin, eine nicht essenzielle Aminosaure bei Gesunden, wird von solchen schwer kranken Patienten nicht mehr in ausreichendem Mas produziert, und einige Arbeiten haben bei Glutaminsupplementation positive Wirkungen auf das Outcome gesehen. Eine spanische Arbeitsgruppe hat das nun genauer betrachtet.

Introduction: Brain cortisol availability has never been evaluated in patients with traumatic brain injury (TBI). Cerebral microdialysis is a well-established technique for monitoring brain metabolism in neurocritically ill patients, which may be used to measure interstitial cortisol. The objective of this preliminary study was to measure brain interstitial cortisol and its correlation with total serum cortisol in patients with TBI. Methods: We prospectively studied 6 patients with severe TBI admitted to the Intensive Care Unit of our tertiary University Hospital in which multimodal neuromonitoring including cerebral microdialysis with a high cut-off of 100 k-Da and 20-mm long membrane was used. Serum and brain interstitial cortisol microdialysis samples were obtained every 8 h and analyzed afterwards. Results: Linear regression analysis of total serum cortisol and brain interstitial cortisol in the whole population showed a moderate correlation (R2=0.538, p

Streptococcus suis serotype 2 is a major Gram-positive swine pathogen, causing also zoonoses. We describe here the immunoprotective activity in an in vivo animal model of a serotype-2 cell wall protein, designated Sat, which was identified by a previously validated proteomics approach consisting of the protease digestion of live bacteria and the selective recovery of exposed domains, followed by LC/MS/MS analysis. Increased survival rate (80%) and decreased bacterial burden were observed in mice immunized with a recombinant Sat fragment, suggesting that this protein is a potential vaccine candidate against serotype-2 infection.

Medical training curricula is a constantly evolving field. The objective of the present study is to analyze the changes the field has undergone. Our sources of information include demographic and health surveys, surveys carried out with students and faculty members and medical school guidelines from prestigious teaching centers. We compared medical curricula offered in Mexico as well as international trends. We analyzed context requirements, current status and future trends in biological, sociomedical and clinical disciplines; research and teaching methods; adequate academic programs. We describe the state of affairs in medical teaching in Mexico and the challenges that academic programs are currently facing. We propose a curricula with horizontal and vertical planning according to skills and competences that focus on health problems to foster scientific reasoning. Teaching strategies that are student-focused and foster significant/long-lasting learning. We suggest the need to include early clinical activities, communication skills and training in technological resources. Finally, there is a need to define a teaching profile that is consistent with training programs, to include experts in technology and modern teaching methods in order to establish permanent monitoring mechanisms, and to offer incentives to academics and administrative personnel.

the postoperative evolution of patients submitted to orthotopic liver transplant (OLT) is frequently associated with the appearance of different types of complications such as renal failure, graft rejection, infections, and neurological disorders. These complications are the most significant causes of early morbidity and mortality in patients undergoing OLT. The purpose of the present study was the identification of factors related to the different postoperative complications after OLT.a prospective study was carried out.seventy-eight variables were analyzed in 32 consecutive patients undergoing OLT. The factors independently associated with the appearance of postoperative complications were identified using a stepwise logistic regression analysis.the multivariate analysis showed that malondialdehyde and creatinine pretransplant serum levels were associated with the development of renal dysfunction. The pretransplant levels of haemoglobin and the units of platelets administered during surgery were prognostic factors of infections. Acute graft rejection was predicted by ?-glutamyl transpeptidase and total bilirubin serum levels. The pretransplant sodium and glutaredoxin levels in serum were associated with neurological complications.we propose these markers for the identification of high-risk patients allowing an early surveillance and/or treatment to improve morbidity and survival in patients submitted to OLT.

Con el apoyo de la ANPCyT (SECYT) y del CONICET mediante subsidios, desarrollamos investigaciones arqueológicas y etnohistóricas sobre la dominación inka en el Centro oeste argentino, extremo austral oriental del Tawantinsuyu. En la actualidad trabajamos en las provincias de La Rioja (Famatina, Laguna Brava, Guandacol, entre otras áreas), San Juan (Reserva de la Biosfera de San Guillermo, Valle Fértil, Paso del Lámar —Jáchal—, entre otros sectores) y Mendoza (Valle de Uspallata, Valle de Uco, entre otras zonas), estudiando la vialidad y los sitios relacionados, excavando varios de éstos. Un abordaje de tal envergadura implica, entre otras, la posibilidad de contrastar semejanzas y diferencias en la implantación territorial, diversidad en las relaciones con las poblaciones locales y sumanifestación en los indicadores arqueológicos y etnohistóricos y permite contrastar los modelos de dominación regional. En este contexto nos referimos, desde la perspectiva del significado, al registro de bienes inka como ser, entre otros, la propia arquitectura o los relacionados con los sitios ceremoniales de alturaWith the support of the ANPCyT (SECYT) and of the CONICET we have undertaken archaeological and ethnohistorical research on the Inka domination in the Argentine centralwest, at the oriental austral extreme of the Tawantinsuyu. Our team is presently working in the provinces of: La Rioja (at Famatina, Laguna Brava,Guandacol, among other areas), San Juan (at the Reserva de la Biosfera de San Guillermo, Valle Fértil and Paso del Lámar -Jáchal-, among other sectors) and,Mendoza (at the Valle deUspallata, Valle deUco, among other zones), studying the net of roads and other related sites, excavating several of the later ones. Such an approach implies, between others, the possibility of contrasting similarities and differences in the territorial implantation, the diversity in relations with the local inhabitants and its manifestation in the archaeological and ethnohistorical indicators, thus allowing for the contrast with the regional domination models. From the perspective of the significance and within such a context,we refer to Inka goods such us the architecture in itself or those goods related to the high ceremonial sites.

Transcranial sonography is a common tool for monitoring neurocritical patients. Transcranial color-coded duplex ultrasonography enables hemodynamic and structural study of the cerebral parenchyma in these patients. Its advantages over conventional ultrasonography are evident and are derived from direct visualization of the vessel to be studied and appropriate adjustment of the sample volume and angle of insonation. The use of ultrasonographic contrast agents enables conclusive findings in practically 100% of cases and allows cerebral perfusion to be studied at the bedside using semiquantitative methods. This review aims to show the applications of transcranial color-coded duplex ultrasonography for monitoring neurocritical patients in intensive care units.