Setting course for a translational pharmacology and a predictive toxicology based on the numerical probability of clinical relevance.

For a significant share of the chemicals, current bioassays mispredicted the outcomes in the reference methods they simulate. For any drug or chemical, and depending on the regulatory or corporate situation, three different approaches calculate the numerical probability by which agreement (or discrepancy) can be statistically expected between (1) the result of a predictive bioassay, and (2) the outcome on its reference method. If such concordance is expected with enough confidence based on a sufficient percentage probability, then specific results from that bioassay can be considered as correctly predictive. The statistical approaches analyzed in this article assist in valuable tasks, including (1) a better translation of the clinical relevance (or insignificance) of specific preclinical findings; (2) waiving unnecessary animal testing (or any other unpredictive testing; e.g., a given in vitro bioassay), and (3) in advancing only the most promising candidates in the pharmaceutical, pesticide, or chemical development process.

The numerical probability of carcinogenicity to humans of some antimicrobials: Nitro-monoaromatics (including 5-nitrofurans and 5-nitroimidazoles), quinoxaline-1,4-dioxides (including carbadox), and chloramphenicol.

Many substances are already tested in the long-term rodent bioassay (RCB). Nonetheless, statements such as the following are common in the regulatory literature: "the significance of the carcinogenicity findings in rodents relative to the therapeutic use of drugs in humans is unknown." (U.S. FDA prescribing information for nitrofurantoin). In the absence of epidemiological data, chemicals carcinogenic in RCBs are typically classified as either possibly or probably carcinogenic to humans, particularly without the -numerical probability for the carcinogenicity to humans- (PPV) of the classified substance. Through the biostatistics-based and regulatorily pertinent -predictive values approach- (PVA), the present study investigated the PPV of several antimicrobials relevant to human or veterinary medicine. A combination of structure-activity relationship, mutagenicity, and tumor-related histopathology was used to resolve reliable and pertinent PPVs. For 62 specific antimicrobials (e.g., carbadox), a 97.9% (or more) probability of carcinogenicity to humans was estimated. For nitrofurantoin, a 99.9% probability of carcinogenicity to humans was reckoned. Therefore, a risk-benefit evaluation on the in-force authorization of nitrofurantoin for uncomplicated human urinary infections is needed. A discussion was provided on the involved mechanisms of carcinogenic action and some regulatory implications of the findings. Neither this study nor the PVA aimed to encourage indiscriminate animal testing but the contrary, to reduce unnecessary or redundant in vivo testing by powering the predictivity of nonclinical toxicology.

The numerical probability of carcinogenicity to humans of some pharmaceutical drugs: Alkylating agents, topoisomerase inhibitors or poisons, and DNA intercalators.

The nonclinical branch of regulatory pharmacology has traditionally relied on the sensitivity and specificity of regulatorily recommended bioassays. Nonetheless, any predictive testing (eg, safety pharmacology) with less than 100% sensitivity or 100% specificity is prone to deliver false positive or negative results (namely, outcomes discordant to the clinical gold standard). It was recently suggested that the statistics-based and regulatory pertinent "predictive values approach" (PVA) might help to reach a more predictive use of preclinical testing data. To resolve the associated probability of carcinogenicity to humans, the PVA was applied to 37 pharmaceuticals bearing inadequate epidemiological evidence of carcinogenicity, but identifiable as unequivocal mutagens. According to current knowledge, a 98.9% (or more) probability of carcinogenicity to humans was reckoned for those 37 genotoxic drugs. Accordingly, these pharmaceutical drugs might be either scientifically or regulatorily regarded as "carcinogenic to humans." In the USA, European Union, or Canada as examples, the great majority of these 37 pharmaceuticals are authorized for medical use in humans. From the results of the present appraisal, the following is suggested (1) for the pharmaceuticals listed in this report, to include significant carcinogenicity warnings in their prescribing information; (2) to conduct pharmacoepidemiology studies or risk-benefit analyses (if warranted), and (3) based on the respective risk-benefit analyses, to re-evaluate the authorization of hydralazine and phenoxybenzamine as antihypertensives, oxcarbazepine as an anticonvulsant, and phenazopyridine as a urinary tract antimicrobial or analgesic. For the four latter drugs (eg, phenoxybenzamine), a 99.5% probability of carcinogenicity to humans was estimated.

Applying Bayesian forecasting to predictive toxicology: The probability of innate carcinogenicity to humans of colorants synthesized from benzidine.

The preclinical identification of health hazards relies on the performance (the historic concordance to the respective gold standard) of regulatorily recommended bioassays. However, any testing with less than 100% sensitivity (or 100% specificity) can deliver false results (outcomes discordant to the respective gold standard). Conversely, the predictive values approach (a.k.a. Bayesian forecasting) weighs (1) the performance of the predictive bioassay (battery, or framework) with (2) the prevalence of -positivity to the respective gold standard- in the most representative category to which the test substance can be allocated. Thus, the predictive values approach (PVA) provides the numeric probability for the toxicity to humans of chemicals that, circumstantially, are evaluable only through nonclinical data. Consequently, the PVA improves the predictivity of nonclinical toxicology, and increases the impact of hazard identifications entirely based on preclinical data. This article aimed to introduce the PVA through a worked example. Due to their toxicological homogeneity and public health relevance, the superfamily of colorants synthesized from benzidine (BZ) or some mutagenic congeners was selected (colorings hereafter mentioned as BZ-related-colorants). Through the PVA, the numeric probability of innate carcinogenicity to humans of 259 BZ-related-colorants was either estimated from rodent carcinogenesis bioassays (RCBs) or predicted from methods alternative to the RCB. A discussion was provided on (1) some limitations and implications of the PVA, and (2) the probable significance of the predictive values figured here for 259 BZ-related-colorings.

The 2-year rodent bioassay in drug and chemical carcinogenicity testing: Performance, utility, and configuration for cancer hazard identification.

For several intended uses of chemicals, the 2-year rodent bioassay (RCB) has been the benchmark method to screen the carcinogenicity to humans of substances, according to the hazard identification sphere. Despite the ongoing controversy around this traditional testing, the RCB is in force and being used by stakeholders. After assembling the RCB's ability to forecast the carcinogenicity to humans of substances, the current review aimed to provide a discussion on the RCB's (1) sensitivity and specificity; (2) utility; (3) configuration, and (4) provisional role in the regulatory policy. In general, RCBs conducted at maximum tolerated doses (MTDs) exhibited a functional ability to (1) not missing the great majority of human carcinogens, and to (2) not responding to the large majority of human non-carcinogens. There is citable evidence supporting the use of MTDs to render RCBs as sensitive as possible, particularly provided the ethically-justified small samples used in RCBs. The literature shows that rodent-specific mechanisms of chemical carcinogenesis contribute significant unspecificity to RCBs. Nonetheless, the paradox between a functional sensitivity and a significant unspecificity can be predictively resolved through the application of Bayesian forecasting. In terms of performance to forecast the carcinogenicity to humans of either genotoxic or non-genotoxic substances, 2-species-RCBs added no value over the rat-RCB. Nevertheless, there is preliminary evidence cautioning that 15% of the rodent carcinogens probably carcinogenic to humans could be missed if mouse-RCBs are indiscriminately discontinued. More than thirteen RCB-related issues relevant to regulatory pharmacology and toxicology were discussed and summarized in this review.

Moderating Effect of the Situation of Return or Relocation on the Well-Being and Psychosocial Trauma of Young Victims of the Armed Conflict in Colombia.

Colombia is the second country with the highest number of internally displaced persons. In the last 10 years, more than 400,000 young people carry, in their life experiences, the title of victims. The psychological and social circumstances that determine the lives of displaced young people in the world are not unknown. Fear, the poor resources for social adaptation available to them, and the possible reproduction of the cycle of violence, represent psychosocial risk factors in the young and displaced population. In this context, the Victims Law in Colombia stipulated various measures of repairment, including Relocation (the person or household victim of forced displacement decides to settle in some place, other than the one they were forced to leave) and Return (the person or the household victim of forced displacement decides to return to the place from which they were displaced, in order to settle indefinitely) provided the conditions of voluntariness, security, and dignity are present. A hypothesis that well-being will be better in the returnees was set, since they would strengthen the social support networks between neighbors and other victims in their old spaces of life. To test the hypothesis, the scales of Psychological Well-being, Social Well-being, the Satisfaction with Life Scale, and the Psychosocial Trauma Scale were applied to young returnees (n = 129) and relocated (n = 259) in Colombia. The Exploratory and Confirmatory Factor Analysis was performed to extract the general measure of well-being and psychosocial trauma followed by the comparison between the groups. Significance, power, and effect size indicators were obtained, and finally, the partial correlation between the groups was made in relation to psychosocial trauma and well-being. Results showed that returnees have greater well-being and clearer indicators (d = 0.365, 1-ß = 0.996), with respect to that of relocated. In addition, the well-being of returnees has fewer trauma factors, who in turn are quasi-moderated by the situation of return or relocation.

Glomerulopatía por C3: algoritmo diagnóstico en gestantes

La enfermedad glomerular comprende un grupo heterogéneo de entidades que se caracterizan por la pérdida de la arquitectura o función del glomérulo secundario a proceso inflamatorio del mismo de etiología autoinmune, infecciosa, paraneoplásica, que puede ser identificada con estudios de histopatología. Su reconocimiento durante la gestación representa un reto diagnóstico por la sobreposición de cambios fisiológicos, el debut de enfermedades autoinmunitarias o de enfermedades genéticas, entre otros. La presentación clínica suele encajar en grupos sindromáticos específicos, sin embargo, es frecuente que sean clínicamente indistinguibles o sobrepuestos. El debut de la enfermedad renal con curso clínico de rápida instauración y de evolución desfavorable con respecto a la función renal, hace mandatorio un estudio completo desde el abordaje clínico hasta la interpretación de los hallazgos histopatológicos, encaminado en la distinción de causas primarias y secundarias. Si bien las glomerulonefritis primarias no son las más frecuentes en la gestación, la identificación certera del diagnóstico y su adecuada clasificación permite el manejo dirigido y óptimo de las mismas. Se presentan los casos clínicos de dos gestantes con enfermedad glomerular primaria, con discrepancia en su diagnóstico, enfatizando en sus manifestaciones durante el curso de la gestación, el algoritmo diagnóstico utilizado, el tratamiento inicial y de mantenimiento utilizado. Se resalta la utilidad de la biopsia renal, específicamente la inmunofluorencia para aclarar el mismo.

Glomerular disease involves a heterogeneous group of entities that are characterized by loss of the architecture and function of the glomerulus and this can be caused by immunity, infectious and paraneoplastic etiologies. The aforementioned can be identified in histopathological studies. The recognition of this entity during pregnancy represents a diagnostic challenge due to the superposition of physiological changes, the development of autoimmune diseases and / or genetic disease, among others. Clinical manifestations can be into specific syndromic groups; however we can find indistinguishable manifestations and overlapping of this. When the disease is present its common to find rapidly establishment and unfavorable evolution about renal function. With this it's necessary to complete studies involving the initial clinical approach until histopathological findings with the goal to find primary and secondary causes. As it's known primary glomerulonephritis is not the most frequent in pregnancy, the accuracy in the diagnosis and the proper classification allows the direct and soon management. In this case report we describe 2 pregnant women with primary glomerular disease with discrepancy in their diagnosis. We talk about manifestations during pregnancy, the algorithm used in the diagnosis and finally the initial treatment and the maintenance used in these patients.

Depolarization preconditioning produces cytoprotection against veratridine-induced chromaffin cell death.

The hypothesis that K(+) channels and cell depolarization are involved in neuronal death and neuroprotection was tested in bovine chromaffin cells subjected to two treatment periods: the first period (preconditioning period) lasted 6 to 48 h and consisted of treatment with high K(+) solutions or with tetraethylammonium (TEA), a K(+) channel blocker; the second period consisted of incubation with veratridine for 24 h, to cause cell damage. Preconditioning with high K(+) (20-80 mM) or TEA (10-30 mM) for 24 h caused 20-60% cytoprotection against veratridine-induced cell death in bovine chromaffin cells. The absence of Ca(2+) ions during the first 9 h of an 18-h preconditioning period abolished the cytoprotection. Preconditioning with K(+) or TEA increased by 2.5-fold the expression of brain-derived neurotrophic factor and by nearly 2-fold the expression of the antiapoptotic protein Bcl-2. However, preconditioning did not modify the veratridine-evoked Ca(2+) signal. High K(+) shifted the Em by about 10 mV and TEA evoked a transient burst of action potentials superimposed on a sustained depolarization. We conclude that preconditioning may protect chromaffin cells from death by blocking K(+) channels that depolarize the cell and cause a cytosolic Ca(2+) signal, leading to enhanced expression of BDNF and Bcl-2.

Endothelial hyperpolarizing factor increases acetylcholine-induced vasodilatation in pulmonary hypertensive broilers arterial rings.

Pulmonary arterial hypertension (PAH) develops as result of imbalances between endothelium derived vasoconstrictors and vasodilators. Pulmonary hypertensive broiler chickens (PHBs) are deficient in NO production and endothelin-1 (ET-1) excess. With respect to prostacyclin, it appears that it does not alter vascular pulmonary tone in broilers. However, the role of Endothelium-Derived Hyperpolarizing Factor (EDHF) in PAH in broilers has not been determined. The possible involvement of EDHF in acetylcholine (Ach) induced vasodilatation was studied in pulmonary arterial rings taken from PHB and non-pulmonary hypertensive broilers (NPHBs). Ach induced higher vasodilatation in PHB than in NPHB. This dilatation seems to be directly related to the degree of PAH. Ach derived vasodilatation was inhibited, in PBH but not in NPHB, by blocking EDHF action with K(+) or Apamin plus Charybdotoxin. It is proposed EDHF as an important vasodilator in the pulmonary arteries of PHB, which may play a compensatory role in PAH pathophysiology.

Estudio sobre las estrategias deafrontamiento y el bienestar subjetivo,psicológico y social en mujeres internasen un centro de reclusión femenino delCaribe colombiano (2012) / A study on coping strategies and the subjective, psychological andsocial well-being of female inmates in a women’s detention facilityat the Colombian Caribbean area (2012) / Estudo sobre as estratégias de afrontamento e o bem-estarsubjetivo, psicológico e social em mulheres internas em umcentro de reclusão feminino do Caribe colombiano (2012)

La investigación tuvo como objetivo determinar la relación entre las estrategias de afrontamiento y el bienestar subjetivo, psicológico y social, durante el año 2012, de mujeres internas en un centro de reclusión femenino en el Caribe colombiano. La muestra estipulada para el estudio consistió en un total de 26 internas de ese centro de reclusión. Para la medición se aplicó la adaptación al español, realizada por Blanco & Díaz (2005), de las escalas de: Bienestar Subjetivo de Diener, Bienestar Psicológico de Ryff, Bienestar Social de Keyes y la Escala de Estrategias de Afrontamiento Individual de Londoño et ál. (2006). Los resultados mostraron que el uso de algunas estrategias de afrontamiento por parte de las reclusas está relacionado tanto con el bienestar psicológico como con el social; no obstante, no se encontró tal asociación con el bienestar de tipo subjetivo.

The objective of this research was to determine the relationship between the coping strategies and the subjective, psychological and social well-being of female inmates kept at a women’s detention facility during year 2012 at the Caribbean area in Colombia. The sample being stipulated for this studio consisted of a total of 26 inmates in this internment center. For the outcome measurement, use was made of the adaptation into Spanish made by Blanco & Diaz (2005) of Diener’s Subjective Well-being scale, Ryff’s Psychological Well-being scale, Keyes’ Social Well-being scale, and Londoño et al.'s (2006) Individual Coping scale. The results showed that the use of some coping strategies by the inmates relates to both psychological and social well-being. Nevertheless, this association was not found with well-being of the subjective type.

A investigação teve como objetivo determinar a relação entre as estratégias de afrontamento e bem-estar subjetivo, psicológico e social, durante o ano 2012, de mulheres internas em um centro de reclusão feminino no Caribe colombiano. A amostra estipulada para o estudo consistiu em um total de 26 internas desse centro de reclusão. Para a medição a adaptação ao espanhol foi aplicada, feita por Blanco & Diaz (2005), das escalas de: Bem-estar Subjetivo de Diener, Bem-estar Psicológico de Ryff, Bem-estar Social de Keyes e a Escala das Estratégias de Afrontamento Individual de Londoño (2006). Os resultados mostraram que o uso de algumas estratégias de afrontamento na parte das reclusas está relacionado tanto ao bem-estar psicológico quanto o social; contudo, não houve associação com o bem-estar do tipo subjetivo.

BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources.

Online gene annotation resources are indispensable for analysis of genomics data. However, the landscape of these online resources is highly fragmented, and scientists often visit dozens of these sites for each gene in a candidate gene list. Here, we introduce BioGPS http://biogps.gnf.org, a centralized gene portal for aggregating distributed gene annotation resources. Moreover, BioGPS embraces the principle of community intelligence, enabling any user to easily and directly contribute to the BioGPS platform.

Estrategias de afrontamiento individual y familiar frente a situaciones de estrés psicológico / Individual and family copying strategies when facing psychological stress situations

El artículo presenta el recorrido teórico que sustentan las estrategias de afrontamiento individual y las estrategias de afrontamiento familiar, a partir de una investigación bibliográfica analítica sobre los mismos. Los resultados de esta investigación dan cuenta de la génesis social del afrontamiento, concebido desde un enfoque cognitivo fenomenológico que en coherencia con el interaccionismo simbólico nos explica, a partir de la estrecha relación interactiva entre el individuo y las instituciones a las que pertenece, el uso de dichas estrategias a nivel individual y familiar. Igualmente se destaca en los hallazgos la relación positiva del afrontamiento con la salud y la funcionalidad del sistema familiar.

This paper presents a theoretical summary of individual coping strategies and family coping strategies based on a review of the literature. The results of this study show the social genesis of coping, designed from a cognitive phenomenological approach consistent with the symbolic interactionist which explains, from the close interactive relationship between individuals and institutions to which it belongs, how to use these strategies to individual and family level. Also we highlighted the positive relationship of coping with health and functionality of the family system.

Factores familiares y sociales de alto riesgo asociados al trabajo infantil en ciudades de la Costa Caribe colombiana / High risk family and social factors associated with child labour in cities of the colombian caribbean coast

Se describen los factores familiares y sociales de alto riesgo asociados al trabajo infantil. La muestra, de carácter intencional, estuvo constituida por 835 niños, niñas y adolescentes entre 6 y 17 años (M = 10.6 años y DE = 2.2) de las ciudades de Barranquilla, Santa Marta y Cartagena, que participaron en el proyecto "Edúcame primero, Colombia" durante 2008. Los resultados presentan datos relevantes sobre el estado sociodemográfico de los niños participantes, sus características familiares y condiciones sociales, que permitirán establecer una línea base actualizada y abrir camino para la construcción de estrategias de intervención efectivas sobre un flagelo que azota a los niños, niñas y jóvenes no solo de Colombia, sino del mundo.

The investigation describes the familiar and social factors of high risk associated with child labour. The sample of intentional character, was made up of 835 children and teenagers between 6 and 17 years (average of 10.6 years and DT = 2.2) of the cities of Barranquilla, Santa Marta, and Cartagena, which participated in the project "Educate First Your Colombia "during the year 2008. The results presented relevant data on the State population partner participating children, familiar characteristics and social conditions, to help establish a baseline updated and pave way for the construction of effective intervention strategies on a scourge that flogs the children and young people not only of Colombia but worldwide.

Relación entre redes personales y calidad de vida en individuos desmovilizados del conflicto armado colombiano / Personal networks and quality of life in Colombian individuals demobilized from the armed conflict

El objetivo de este artículo fue identificar la existencia de relaciones significativas entre los indicadores estructurales y funcionales de las redes personales de individuos desmovilizados y sus niveles de calidad de vida física y psicológica. Se evaluaron 37 individuos residentes en una zona de distensión militar en El Caribe colombiano aplicando el SF-36 y el ASSIS en un estudio correlacional. Los datos se examinaron mediante Análisis de Redes Sociales (ARS) y cálculo estadístico con la t de Student y el coeficiente de correlación de Pearson. Se observaron redes pequeñas, con altos niveles de insatisfacción frente al apoyo social y reducidos promedios de calidad de vida. Se registraron diferencias significativas en la percepción general de apoyo de las redes y la obtención objetiva de ayuda (p = 0.000), así como correlaciones entre los niveles de participación social en las redes y la vitalidad psicológica de los individuos.

The Aim of this study was to identify the existence of significant relationships between structural and functional indicators of personal networks of demobilized individuals and their levels of physical and psychological quality of life. We assessed 37 individuals living in an area of military distension in the Colombian Caribbean using the SF-36 and the ASSIS in a correlational study. The data were examined with Social Network Analysis (SNA) and statistical calculation with the Student t and Pearson correlation coefficients. There were small networks, with high levels of dissatisfaction with social support and low indices of quality of life. There were significant differences in the general perception of support networks and obtaining objective help (p = 0.000) and correlations between levels of social participation in networks and psychological vitality of individuals.

Síndrome de disfunción congnitiva del perro como modelo de investigación de las enfermedades neurodegenerativas del humano / Cognitive dysfunction syndrome in dog senior: a suitable model for human neurodegenerative diseases

En humanos y caninos, el proceso de envejecimiento aumenta el riesgo de padecer enfermedades neurodegenerativas tales como la enfermedad de Alzheimer y el síndrome de disfunción cognitiva de perros senior. Estos síndromes demenciales provocan alteraciones patológicas en diferentes áreas cerebrales, generando un evidente déficit cognitivo caracterizado por cambios comportamentales como alteración en los procesos de memoria y aprendizaje. Los efectos deletéreos sobre la calidad de vida en pacientes humanos afectados por la enfermedad de Alzheimer, promueven la necesidad de encontrar patologías similares que afecten a otras especies, haciendo de estas, modelos experimentales útiles para la investigación de los padecimientos humanos. Recientemente ha sido sugerida una estrecha similitud entre varias de las características clínicas, anatómicas y fisiopatológicas propias de la enfermedad de Alzheimer y el síndrome de disfunción cognitiva de perros senior, en las que se incluye la formación y acumulación de placas amiloideas, apoptosis de neuronas colinérgicas con la consiguiente disminución del neurotransmisor Acetil-colina, déficit cognitivo de tipo progresivo y alteraciones en el ciclo sueño-vigilia, entre otras. Así, el avance en el conocimiento de los procesos implicados en la fisiopatología del síndrome de disfunción cognitiva de perros senior, y tras reconocer sus similitudes con los ocurridos durante la enfermedad de Alzheimer, ha facilitado los estudios que tienen como objetivo la comprensión de algunos aspectos que aún no han sido muy bien detallados en las enfermedades neurodegenerativas humanas. Además, al considerar la alta probabilidad de padecer el síndrome de disfunción cognitiva de perros senior, que se identifica en algunas poblaciones caninas, da cabida a la posibilidad de proponer al perro, como un modelo óptimo de experimentación para la investigación de los procesos neurodegenerativos asociados al envejecimiento de los humanos.

Redes personales y dimensiones de apoyo en individuos desmovilizados del conflicto armado / Personal nets and support dimensions in people demobilized from the armed conflict

El objetivo de este estudio fue identificar las características de las redes personales de un grupo de individuos desmovilizados del conflicto armado colombiano. Se evaluaron diez hombres mediante un diseño descriptivo transversal de enfoque cuantitativo con la aplicación del ASSIS para medir las redes y se identificaron seis dimensiones de apoyo social. Las redes personales se visualizaron con el programa Visone 2.3.5, y se detectó que la ayuda material es la dimensión de mayor satisfacción en la muestra. Sobresalen las redes pequeñas, conformadas por familiares y con buen nivel de intimidad personal.

The objective of this study was to identify the personal network characteristics of a group of individuals demobilized of the Colombian armed conflict. Ten men were evaluated using a descriptive cross-sectional design of a quantitative approach to the implementation of ASSIS identifying networks to measure six dimensions of social support. Personal networks were visualized with the program Visone 2.3.5 identifying that material assistance is the dimension of greater satisfaction in the sample program. Outstanding small networks, made up by relatives and with good level of personal privacy are also present.

ITH4012 (ethyl 5-amino-6,7,8,9-tetrahydro-2-methyl-4-phenylbenzol[1,8]naphthyridine-3-carboxylate), a novel acetylcholinesterase inhibitor with "calcium promotor" and neuroprotective properties.

Ethyl 5-amino-6,7,8,9-tetrahydro-2-methyl-4-phenylbenzol[1,8] naphthyridine-3-carboxylate (ITH4012) is a novel tacrine derivative that can reduce cell death induced by various compounds with different mechanisms of action, such as thapsigargin (reticular stress), H2O2 (free radicals), and veratridine (calcium overload), in bovine chromaffin cell. Cell viability, quantified as lactic dehydrogenase release, was significantly reduced by ITH4012 at concentrations ranging from 0.01 to 3 microM. In the human neuroblastoma cell line SH-SY5Y, ITH4012 also reduced amyloid beta25-35-induced apoptosis, determined by flow cytometry. ITH4012 caused a slight elevation in the cytosolic concentration of Ca2+ in fura 2-loaded bovine chromaffin cells, which could be related to the induction of protein synthesis relevant for cell survival. Blockade of protein synthesis by cycloheximide or blockade of Bcl-2's active site with HA14-1 (ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate) reversed the cytoprotective action of ITH4012. Furthermore, exposure of bovine chromaffin cells for 24 or 48 h to neuroprotective concentrations of this compound enhanced, nearly 3-fold, the expression of the antiapoptotic protein Bcl-2. In conclusion, ITH4012 is a tacrine derivative that maintains acetylcholinesterase-inhibiting activity (IC50=0.8 microM) but has the additional property of acting as a calcium promotor, a property leading to neuroprotection through the induction of antiapoptotic proteins.

Bienestar y trauma en personas adultas desplazadas por la violencia política / Well-being and trauma in adults displaced by political violence

La presente investigación ha estudiado el Bienestar psicológico, Subjetivo y Social, el Fatalismo, y el Trauma y Cogniciones Irracionales Postraumáticas, en personas adultas desplazadas por la violencia sociopolítica, radicadas en la ciudad de Barranquilla, Colombia. Los resultados indican que si bien las personas víctimas del desplazamiento forzado, presentan innegables síntomas de trauma con un matiz psicosocial, también se encuentran en ellos elementos asociados a la Salud Mental.

This study studied Subjective and Objective Psychological Well-being, andFatalism, Trauma and Irrational Posttraumatic Cognitions, in adults displaced by socio-political violence, living in Barranquilla, Colombia. Outcomes suggest that people who have been victims of forced displacement exhibit undeniable symptoms of psychosocial trauma, and that they also have elements associated to Mental Health.

Explotación sexual comercial infantil en el distrito turístico y portuario de Santa Marta / Infant exploitation & sexual commerce in the tourist and bay district of Santa Marta

El propósito de esta investigación fue caracterizar la situación actual de niños, niñas y adolescentes víctimas de explotación sexual comercial infantil (ESCI), del agresor y otros actores involucrados para determinar la magnitud del problema en el distrito turístico y portuario de Santa Marta. Se utilizó una metodología descriptiva y la muestra estuvo conformada por 52 menores. Los resultados arrojaron que la totalidad de las menores pertenecen al estrato socioeconómico bajo, convirtiéndose la prostitución en uno de los medios evasivos mediante el cual estas niñas pretenden llenar las sensaciones de vacío que tienen por las circunstancias del entorno sociocultural en las que se desenvuelven, como lo son la austeridad, la precariedad, la violencia intrafamiliar, la deserción escolar y ausencia de valores, entre otros. Convirtiéndose en una problemática que se está extendiendo en la ciudad y se materializa socialmente en la medida en que se percibe como un negocio rentable, incorporando a múltiples actores, escenarios y dinámicas.