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Background: Quorum sensing (QS) is a cell density dependent mechanism that allows bacteria to regulate the expression of specific genes in response to changes in their population density, thus controlling their activities in order to produce a response as a unit multicellular. These responses include production of virulence factors, formation of biofilm, bioluminescence, sporulation, among other behavior.Objectives: The objective of this work was to obtain pharmacophore models able to filter and identify molecules with possible agonist activity of quorum sensing and to find possible candidates based on calculations of molecular docking Methods: The structure of the receptor was taken from the Protein Data Bank (PDB). The program AutoDock 4.2 was used to perform docking calculations. The 3D structure of the ligand TP1 was extracted from the complex co-crystallized identified with the code PDB 3IX3. The geometries of ligands were optimized using the PM3 semiempirical method. Results: Two pharmacophoric models were designed, the first one was made using the most active compound (TP-1), highlighting the most important chemical characteristics for molecular recognition. The second model was based on the alignment of three of the most active ligands (TP-1, TP-3 and TP-4). These models were used as a filter in a screening on a database of conformations of several compounds with possible agonist activity of the main circuit of QS present in Pseudomona aeruginosa.The pharmacophoric model based on alignment of the most active compounds showed greater capacity to select or identify compounds exhibiting significant structural and chemical characteristics to be considered possible hit. With this model, 22 compounds were identified.These compounds were subjected to a series of calculations of docking. The outcomes of the docking were used to identify interactions making a SAR analysis and were used as support to understand how chemically distinct compounds can be accommodated by a highly selective receptor, and provide the framework for the development of novel quorum-sensing regulators, utilizing the 2-(benzamido)methyl)phenyl benzoate scaffold and to assess the possibility of synthetic routes, considering the structural similarity presenting between these compounds, generating in this way an alternative to find new compounds with modulating activity QS. These two strategies were used to select a list of potential modulators of quorum sensing or new pharmacophoric candidates. Conclusions: The two pharmacophoric models designed in this study, the number 2 (model based on the alignment of the most active compounds) showed greater ability to select or identify compounds that had important structural and chemical characteristics to be considered possible hits. With this model, 22 compounds were identified, which were subsequently subjected to docking calculations. In general, the docking protocol used is adequate, since in validating the conformation of the co-crystallized ligand.

Conventional chromosomal preparations were made of three native mice from Huánuco, Peru: a male and a female of Thomasomys sp., and a male of Akodon orophilus. Thomasomys sp. had a karyotype of 2n = 42, XY (n = 21), meanwhile A. orophilus presented 2n = 22, XY (n = 11). Comparisons between chromosomal pairs from the existent literature indicate that both are new karyotypes. Thomasomys sp. has a distinct sexual Y chromosome, the only metacentric (m) reported for the genus. The chromosomes X and Y of A. orophilus are acrocentrics (a); and the length of chromosome Y (2/3 of the length of X) distinguishes A. orophilus from other congeneric. Because the structural differences between the sexual chromosomes usually generates mechanism of reproductive isolation at intraspecific level and are bigger still in interspecific crosses, we concluded that the karyotypes reported here support the validity of the species A. orophilus and suggest that Thomasomys sp. represents a new species to science.

Objetivos: Avanzar en el conocimiento del origen de las poblaciones peruanas estudiadas en un contexto filogeográfico. Diseño: Estudio genético poblacional. Instituciones: Laboratorio de Genética Humana, Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, e Instituto de Genética y Biología Molecular, Facultad de Medicina, Universidad San Martín de Porras, Lima, Perú. Participantes: Siete poblaciones peruanas. Metodología: Análisis comparativo de los resultados a partir del estudio del mtDNA y el gen nuclear MBL de siete poblaciones peruanas, procesados de manera separada y luego combinados, utilizando el programa PHYLYP 3.65, para obtener valores FST de diferenciación genética y la construcción de árboles de distancias por aplicación del algorritmo UPGMA y el análisis subsecuente de los agrupamientos (clusters) generados. Principales medidas de resultados: Árboles genéticos generados. Resultados: De manera separada, los árboles generados para cada marcador genético tuvieron topologías propias y diferentes entre sí. Procesados de manera combinada, el árbol resultante demostró que los mayores valores de diferenciación genética se hallaron en las Islas del Lago Titicaca (Puno, Perú) conocidas -Taquile, Amantani y Anapia-, que fue calificada como muy alta, porque mostró valores de FST de 0.3113, 0.2949 y 0.3348 respecto de las poblaciones estudiadas, tanto fuera del Departamento de Puno -como Chachapoyas, Pucallpa y Chiclayo, respectivamente-, así como a la de los Uro del mismo Puno y del mismo Lago Titicaca (0.2837). Fuera de Puno, el par de poblaciones Chachapoyas-Pucallpa fue el menos divergente, al alcanzar entre ellas un valor de FST de 0.0108, calificándosele de pequeña. Conclusiones: El árbol obtenido del procesamiento de los marcadores vía una matriz combinada demostró que las poblaciones que habitan las islas de Taquile, Amantani y Anapia, divergen notablemente de las restantes cuatro procesadas del Perú, incluyendo la más próxima a ellas dentro del mismo Lago Titicaca, como es la de los Uro. Explicar estos hallazgos será el siguiente objetivo de nuestras investigaciones, en principio, mediante la ampliación de los marcadores genéticos empleados y del número de poblaciones analizadas a nivel del Perú.

Introducción: en los pacientes con falla cardiaca y cardiopatía isquémica elegibles para la terapia de células progenitoras derivadas de la médula ósea, se ha demostrado la disminución de la variabilidad de la frecuencia cardiaca [medida por la desviación estándar del intervalo RR (NN) SDNN, siglas en inglés], situación que se relaciona con un aumento del riesgo cardiovascular y de eventos arrítmicos, como consecuencia de una disfunción del sistema nervioso autónomo. Métodos: se analizaron los pacientes que recibieron trasplante autólogo derivado de la médula ósea y que tenían enfermedad cardiaca isquémica aguda o crónica con fracción de eyección menor del 45%, susceptibles o no de revascularización quirúrgica y zonas de tejido miocárdico necrótico y viable. Se les realizó monitoreo Holter de 24 horas pre-trasplante, a los dos, seis y doce meses posteriores a la intervención. Resultados: se analizaron los datos de 16 pacientes, en lo referente al promedio de la frecuencia cardiaca máxima, mínima y media, la variabilidad de la frecuencia cardiaca y la aparición de arritmias ventriculares malignas. La terapia con células progenitoras derivadas de la médula ósea, se asoció con una mejoría estadísticamente significativa en la variabilidad de la frecuencia cardiaca (SDNN) pasando de 65,44 ± 27 ms a 102,12 ± 37,88 ms (p= 0,004) y 100,23 ± 42,88 ms (p= 0,013) a los dos y seis meses respectivamente. En cuanto a la clasificación de riesgo cardiovascular de acuerdo con la variabilidad de la frecuencia cardiaca (SDNN), todos los pacientes considerados de alto riesgo (SDNN < 50 ms) antes del procedimiento pasaron a riesgo intermedio o bajo en el seguimiento total de seis meses. Además, no se encontró un riesgo mayor de presentar arritmias ventriculares malignas durante el periodo de seguimiento posterior a la terapia con células progenitoras derivadas de la médula ósea. Conclusión: en los pacientes con cardiopatía isquémica sometidos a un trasplante autólogo de médula ósea para regeneración miocárdica, la variabilidad de la frecuencia cardiaca, medida por la SDNN, aumenta significativamente, lo que conlleva una disminución del riesgo cardiovascular. Además, no se halló un aumento del riesgo de arritmias ventriculares.Introduction: in patients with chronic heart failure and ischemic cardiopathy eligible for therapy with stem cells derived from bone marrow, it has been demonstrated that there is a decrease in Heart Rate Variability (HRV), measured by the standard deviation of RR interval (NN) SDNN, situation related to an increase of cardiovascular risk and arrhythmic events as direct consequence of autonomous nervous system dysfunction. Methods: patients that received autologous transplant derived from bone marrow and that had acute or chronic ischemic heart disease with ejection fraction less than 45% susceptible or not of surgical revascularization and with zones of necrotic and viable myocardial tissue, were analyzed. 24 hours Holter monitoring before transplant and at two, six and twelve months after the intervention was performed. Results: data of 16 patients regarding maximal, minimal and mean heart rate average, variability of heart rate and appearance of malign ventricular arrhythmias were analyzed. Therapy with stem cells derived from bone marrow was associated with a statistically significant improvement of heart rate variability (SDNN) going from 65.44 ± 27 ms. to 102.12 ± 37.88 ms. (p=0.004) and 100.23 ± 42.88 ms. (p=0.013) at 2 and 6 months respectively. With regard to the cardiovascular risk classification according to the variability of heart rate (SDNN), all patients considered at high risk (SDNN

Introducción: estudios recientes demuestran la seguridad y eficacia de la implantación de células progenitoras derivadas de la médula ósea y de la administración del factor estimulante de colonias de granulocito en pacientes con infarto agudo del miocardio con elevación del segmento ST y en cardiopatía isquémica crónica. Se diseñó un estudio prospectivo, abierto de «antes y después» para evaluar la seguridad y eficacia de la terapia celular asociada a la administración del factor de crecimiento. Se reporta la primera experiencia con este tipo de terapia. Metodología: este es el reporte del seguimiento a seis meses, de los pacientes con cardiopatía isquémica aguda y crónica a quienes se les realizó trasplante de células progenitoras derivadas de la médula ósea, movilizadas con factor de crecimiento estimulante de colonias de granulocitos, por vía intracoronaria o epicárdica. Se incluyeron dos grupos de pacientes: 1. Diez pacientes con infarto de pared anterior y 2. Cinco pacientes con cardiopatía isquémica crónica, todos con necrosis extensa demostrada por ausencia de viabilidad miocárdica por medicina nuclear y fracción de eyección menor del 40%. Resultados: se demostró mejoría significativa de la fracción de eyección de 29,44 ± 3,36 a 37,6 ± 5,3 con p< 0,001; disminución del volumen ventricular sistólico y diastólico sin significancia estadística, p= 0,31 y 0,4 respectivamente. La capacidad de ejercicio aumentó en forma significativa evidenciada por incremento en el test de los seis minutos, el tiempo de ejercicio y el número de MET alcanzados. Hubo cambios significativos en el defecto de perfusión desde el segundo mes de seguimiento y no se presentaron complicaciones que se relacionaran directamente con el trasplante de células progenitoras derivadas de la médula ósea o la utilización del factor estimulante de colonias de granulocito. Conclusiones: esta es la primera experiencia con el trasplante de células progenitoras derivadas de la médula ósea para regeneración miocárdica, asociada a la administración de factor estimulante de colonias de granulocito, en la cual se demostró recuperación de la función ventricular izquierda y mejoría en la capacidad de ejercicio y en el defecto de perfusión sin efectos secundarios o complicaciones relacionadas con alguna de las dos terapias.Introduction: recent studies have shown the safety and efficacy of the stem cells derived from bone marrow (BMC) implant with concomitant administration of stimulating factor of granulocyte colonies in patients with acute myocardial infarction with ST segment elevation and in chronic ischemic cardiopathy. An open prospective «before and after» design was made to evaluate the safety and efficacy of cell therapy associated to growth factor administration. The first experience with this kind of therapy is reported. Methodology; this is a 6 months follow-up report of patients with acute and chronic ischemic cardiopathy to whom transplant of stem cells derived from bone marrow mobilized with granulocyte colonies growth stimulating factor via coronary arteries or epicardium was realized. Two groups of patients were included: 1. Ten patients with anterior wall infarct and 2. Five patients with chronic ischemic cardiopathy, all with extensive necrosis demonstrated by absence of myocardial viability through nuclear medicine and ejection fraction of less than 40%. Results: significant improvement of ejection fraction from 29.44 ± 3.36 to 37.6 ± 5.3 with p

Introducción: estudios experimentales y clínicos demuestran que la implantación intramiocárdica de células progenitoras derivadas de la médula ósea, produce angiogénesis y mejora la función cardiaca en pacientes con cardiopatía isquémica crónica. Metodología: este es el reporte del seguimiento a dos meses de un paciente con cardiopatía isquémica crónica no susceptible de revascularización quirúrgica o percutánea, a quien se le realizó ,por vía epicárdica, un implánte de células progenitoras derivadas de médula ósea movilizadas con factor de crecimiento granulocito-macrófago. Resultados: se demostró mejoría significativa en la sintomatología, en la capacidad funcional (1.8 MET a 10 MET), en el estado funcional (IV a I), en el tamaño del defecto de perfusión miocárdica por medicina nuclear, en la fracción de eyección y en la disminución del volumen sistólico final del ventrículo izquierdo, sin observar complicaciones relacionadas con el procedimiento. Conclusión: el trasplante de células progenitoras derivadas de la médula ósea es una terapia efectiva y segura para promover neovascularización y para mejorar la contractilidad y la perfusión miocárdica en los pacientes con cardiopatía isquémica crónica pobres candidatos a cirugía.Introduction: experimental and clinical studies have demonstrated that intramyocardial bone marrow derived stem cells implantation produce angiogenesis and improvement of cardiac function in patients with chronic ischemic cardiopathy. Methodology: this is a two months follow-up report of a patient with chronic ischemic cardiopathy not susceptible of surgical or percutaneous revascularization, to whom bone marrow stem cells mobilized with granulocyte - macrophage growth factor was implanted. Results: significant improvement was demonstrated in symptomatology, functional capacity (1.8 Mets to 10 Mets), functional state (IV to I), size of the myocardial perfusion defect by nuclear medicine, in the ejection fraction and diminution of the final left ventricular systolic volume, without complications related to the procedure. Conclusion: bone marrow derived stem cells transplant is an effective and safe therapy in order to promote neo-vascularization and improve contractility and myocardic perfusion in patients with chronic ischemic cardiopathy considered poor surgical candidates.

ABSTRACT Background: Quorum sensing (QS) is a cell density dependent mechanism that allows bacteria to regulate the expression of specific genes in response to changes in their population density, thus controlling their activities in order to produce a response as a unit multicellular. These responses include production of virulence factors, formation of biofilm, bioluminescence, sporulation, among other behavior. Objectives: The objective of this work was to obtain pharmacophore models able to filter and identify molecules with possible agonist activity of uorum sensing and to find possible candidates based on calculations of molecular docking. Methods: The structure of the receptor was taken from the Protein Data Bank (PDB). The program AutoDock 4.2 was used to perform docking calculations. The 3D structure of the ligand TP1 was extracted from the complex co-crystallized identified with the code PDB 3IX3. The geometries of ligands were optimized using the PM3 semiempirical method. Results: Two pharmacophoric models were designed, the first one was made using the most active compound (TP-1), highlighting the most important chemical characteristics for molecular recognition. The second model was based on the alignment of three of the most active ligands (TP-1, TP-3 and TP-4). These models were used as a filter in a screening on a database of conformations of several compounds with possible agonist activity of the main circuit of QS present in Pseudomonas aeruginosa. The pharmacophoric model based on alignment of the most active compounds showed greater capacity to select or identify compounds exhibiting significant structural and chemical characteristics to be considered possible hit. With this model, 22 compounds were identified. These compounds were subjected to a series of calculations of docking. The outcomes of the docking were used to identify interactions making a SAR analysis and were used as support to understand how chemically distinct compounds can be accommodated by a highly selective receptor, and provide the framework for the development of novel quorum-sensing regulators, utilizing the 2-benzamido(methyl) phenyl benzoate scaffold and to assess the possibility of synthetic routes, considering the structural similarity presenting between these compounds, generating in this way an alternative to find new compounds with modulating activity QS. These two strategies were used to select a list of potential modulators of quorum sensing or new pharmacophoric candidates. Conclusions: The two pharmacophoric models designed in this study, the number 2 (model based on the alignment of the most active compounds) showed greater hability to select or identify compounds that had important structural and chemical characteristics to be considered possible hits. With this model, 22 compounds were identified, which were subsequently subjected to docking calculations. In general, the docking protocol used is adequate, since in validating the conformation of the co-crystallized ligand.

Introduction: Atopic dermatitis (AD) is a frequent disease in infants with diverse clinical evolution. Although multiple studies have assessed inflammatory changes in chronic AD, little is known about the molecular transition from symptomatic stage to clinical remission without pharmacotherapy. Objective: The aim of the study was to evaluate clinical and inflammatory factors and its relationship with AD clinical evolution. Methods: Three groups of participants older than 10 years of age were recruited; 2 AD groups and 1 non-AD group. The AD-remission group (more than 1 year without AD symptoms and without pharmacotherapy), the AD-persistent group (AD symptoms and pharmacotherapy), and 1 non-AD group. We measured eosinophil peroxidase (EPX), eosinophil cationic protein (ECP), IgE autoantibodies against these antigens, and natural moisturizing factor (NMF). Results: Different inflammatory profiles within each group were observed: AD-persistent group is characterized by a high frequency of IgE autoantibodies (55.5%), contrasting with the low occurrence in the non-AD group (2%) and a moderate frequency in the AD-remission group (21.4%). A similar distribution was observed for the other type 2 inflammatory biomarkers (Eosinophils, total IgE, EPX, ECP) and NMF. Conclusion: Patients with AD-remission maintain a minimal T2 inflammation. We identified different potential biomarkers for prognosis of AD evolution. Further studies are necessary to evaluate the mechanisms that allow the coexistence of the inflammatory process without clinical symptoms.

Este artículo da cuenta del proceso y los resultados de una investigación cualitativa con enfoque analítico, titulada: Análisis crítico del discurso multimodal en la caricatura internacional del periódico The Washington Post, desarrollada como tesis de la Maestría en lingüística de la Universidad Pedagó- gica y Tecnológica de Colombia, cuyo propósito es develar los significados contenidos en las caricatu- ras, para reconocer fenómenos socioculturales que se dan a partir del acto comunicativo en mención. El corpus seleccionado para la investigación fue cuatro caricaturas, publicadas en el primer semestre de 2010, de temas relacionados con intervención extranjera; sin embargo, en el presente artículo únicamente se incluye un resumen del análisis hecho a la caricatura titulada: Rebuilding Haiti, or not (Reconstruir Haití, o no). Para abordar el objeto de estudio, se empleo la metodología del Análisis Crítico del Discurso Multimodal, en la que desarrolló una fase descriptiva, una fase interpretativa y una fase propositiva. Como resultado general del análisis, se determinó que es recurrente el fenómeno sociopolítico de exclusión en los discursos de las caricaturas, generado a través de estrategias discursivas como: la acusación, la generalización, la intensificación y la predicación.

Early detection of CSU patients with low probability of a clinical response with antihistamines could undergo prompt initiation of therapeutic alternatives. The aim of the study was to develop and internally validate a model for predicting the clinical response to antihistamines in adult patients with chronic spontaneous urticaria (CSU), who consult allergology and dermatology care centers. A cohort of CSU patients, recruited from four participating centers, were followed up for 12 months. Fifteen candidate variables were selected to be included in the multivariate model and then internal validation was done with bootstrap analysis with 1000 simulations. The outcome variable, clinical response to antihistamines, was evaluated with the UAS (Urticaria Activity Score) scale for seven days: "No response to antihistamines" was defined as UAS7 ≥7 points after at least one month with a maximum dose of antihistamines, while "Response to antiH1" was defined as UAS7 ≤6 points for at least three months with the use of antiH1. A total of 790 patients were included. Among the different models analyzed, the model that included age, angioedema, anxiety/depression, time with the disease, NSAIDs (Non-steroidal anti-inflammatory drugs) intolerance, and UAS7 baseline was considered the one with the best performance (accuracy 0.675, HL 0.87, AUC 0.727). The internal validation analyses demonstrated good consistency of the model. In conclusion, this prediction model identifies the probability of response to antihistamines in patients with chronic spontaneous urticaria. The model could be useful for a personalized therapeutic approach according to individual patient risk.

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Chronic urticaria causes a significant limitation to quality of life. In the literature, various studies can be found that have reviewed several clinical and laboratory markers, but none of these variables alone is sufficient to predict the patient's prognosis. In this study, we present a protocol to develop a prognostic model that can predict the clinical response of urticaria patients to antihistamines. This is a protocol for a bidirectional cohort study. Urticaria data will be routinely collected from a population of patients over 18 years old. A full multivariable logistic regression model will be fitted, following five steps: 1) Selection of predictive variables for the model; 2) Evaluation of the quality of the collected data and control of lost data; 3) Data statistical management; 4) Strategies to select the variables to include at the end of the model; 5) Evaluation of the performance of the different possible models (predictive accuracy) and selection of the best model. The performance and internal validation of the model will be assessed. Some clinical and paraclinical variables will be measured for further exploration.

El Acoplamiento Molecular (Docking) es una técnica de Mecánica Molecular ampliamente utilizada para predecir energías y modos de enlace entre ligandos y proteínas, lo que proporciona información de gran utilidad para el estudio de nuevos compuestos con efectos terapéuticos. No obstante, los resultados obtenidos mediante esta técnica tienden a la subjetividad, debido a que los programas utilizados para llevarla a cabo proporcionan más de un criterio de selección de la mejor pose. En la presente investigación, se aplicó el método semiempírico PM6 a los resultados del acoplamiento, obteniendo con ello mejorarías en el proceso de selección de la mejor pose al observarse finalmente poses con alta probabilidad de unión al sitio activo de su receptor y con energías de unión menores a las reportadas por los criterios de selección ofrecidos por el programa de Docking.

This work deal with the construction of water sorption isotherms for dehydrated mucilage gum powder at two temperatures, 7 and 30 ºC using the gravimetric method of Wink. The saturated solutions were handled in gas tight flasks within a range of water activity from 0,110 to 0,817. The monolayer value was calculated using the BET mathematical model. It was found an inverse relationship with respect to temperature. The experimental curves obtained show the typical shape of compounds with high sugar content and were classified as type III isotherms. The thermodynamic parameters such as the heat of sorption, Gibbs free energy, enthalpy and entropy were maintained nearly constant. They reach maximum values for high humidity content close to the monolayer value, indicating a proportional relationship between the thermodynamic equilibrium of the system and the point of greatest stability of the mucilage, given for the humidity of the monolayer. [ABSTRACT FROM AUTHOR]