A MET Targeting Antibody-Drug Conjugate Overcomes Gemcitabine Resistance in Pancreatic Cancer.

PURPOSE: Pancreatic cancer is an aggressive disease associated with a poor 5-year overall survival. Most patients are ineligible for surgery due to late diagnosis and are treated primarily with chemotherapy with very limited success. Pancreatic cancer is relatively insensitive to chemotherapy due to multiple factors, including reduced bioavailability of drugs to tumor cells. One strategy to improve drug efficacy with reduced toxicity is the development of antibody-drug conjugates (ADC), which have now been used successfully to treat both solid and liquid tumors. Here, we evaluate the efficacy of TR1801-ADC, a newly developed ADC composed of a MET antibody conjugated to the highly potent pyrrolobenzodiazepine toxin-linker, tesirine. EXPERIMENTAL DESIGN: We first evaluated MET expression and subcellular localization in pancreatic cancer cell lines, human tumors, and patient-derived xenografts (PDX). We then tested TR1801-ADC efficacy in vitro in pancreatic cancer cell lines. Preclinical evaluation of TR1801-ADC efficacy was conducted on PDXs selected on the basis of their MET expression level. RESULTS: We show that MET is highly expressed and located at the plasma membrane of pancreatic cancer cells. We found that TR1801-ADC induces a specific cytotoxicity in pancreatic cancer cell lines and a profound tumor growth inhibition, even in a gemcitabine-resistant tumor. We also noted synergism between TR1801-ADC and gemcitabine in vitro and an improved response to the combination in vivo. CONCLUSIONS: Together, these results suggest the promise of agents such as TR1801-ADC as a novel approach to the treatment of pancreatic cancer.

Attitudes among working professionals toward immigrants and refugees living in Ecuador: Impacts on health and well-being.

OBJECTIVE: To explore attitudes toward immigrants and refugees living in Ecuador. DESIGN AND MEASURES: A transnationalism framework informed this qualitative study, which utilized a semi-structured interview guide to elicit responses from participants about their attitudes toward immigrants and refugees. Interviews were conducted in Spanish, audio-taped, transcribed, coded, and analyzed in Spanish to identify emergent themes. Demographic data were analyzed using SPSS. SAMPLE: Participants (n = 50) were recruited from five sectors that interact with refugees: health care, the press, the police, nongovernmental organizations, and education. Fifty interviews were conducted with adults in Quito, Ecuador, in 2017. RESULTS: Participants reported concerns about the health and well-being of immigrants and refugees, expressed a willingness to assist them, but within limits, noted discrimination and bias against refugees, and cited social policies and human rights as factors that influenced their attitudes. CONCLUSIONS: Our findings indicate that immigrants and refugees face challenges which impact their health and well-being, according to participants in the study. Social policies can influence attitudes, but are also affected by rapidly shifting immigration patterns. Migration flows in South America is an under-studied area of research, with opportunity for further public health nursing inquiry.

TR1801-ADC: a highly potent cMet antibody-drug conjugate with high activity in patient-derived xenograft models of solid tumors.

cMet is a well-characterized oncogene that is the target of many drugs including small molecule and biologic pathway inhibitors, and, more recently, antibody-drug conjugates (ADCs). However, the clinical benefit from cMet-targeted therapy has been limited. We developed a novel cMet-targeted 'third-generation' ADC, TR1801-ADC, that was optimized at different levels including specificity, stability, toxin-linker, conjugation site, and in vivo efficacy. Our nonagonistic cMet antibody was site-specifically conjugated to the pyrrolobenzodiazepine (PBD) toxin-linker tesirine and has picomolar activity in cancer cell lines derived from different solid tumors including lung, colorectal, and gastric cancers. The potency of our cMet ADC is independent of MET gene copy number, and its antitumor activity was high not only in high cMet-expressing cell lines but also in medium-to-low cMet cell lines (40 000-90 000 cMet/cell) in which a cMet ADC with tubulin inhibitor payload was considerably less potent. In vivo xenografts with low-medium cMet expression were also very responsive to TR1801-ADC at a single dose, while a cMet ADC using a tubulin inhibitor showed a substantially reduced efficacy. Furthermore, TR1801-ADC had excellent efficacy with significant antitumor activity in 90% of tested patient-derived xenograft models of gastric, colorectal, and head and neck cancers: 7 of 10 gastric models, 4 of 10 colorectal cancer models, and 3 of 10 head and neck cancer models showed complete tumor regression after a single-dose administration. Altogether, TR1801-ADC is a new generation cMet ADC with best-in-class preclinical efficacy and good tolerability in rats.

Decline of General Intelligence in Children Exposed to Manganese from Mining Contamination in Puyango River Basin, Southern Ecuador.

Based on ecosystem approaches to health (Ecohealth), this study sought to identify neurobehavioral disorders in children exposed to several levels of toxic metal pollution from gold mining in the Puyango River Basin, Southern Ecuador. Ninety-three children born or living in the study area participated in the study. A neurobehavioral test battery consisting of 12 tests assessing various functions of the nervous system was applied as well as a questionnaire regarding events of exposure of children's mothers to contaminants during perinatal period. Hair samples were taken from children to determine manganese concentrations. Descriptive and inferential statistics were applied in order to examine possible relationships between exposure events, hair manganese, and neurobehavioral disorders. Having controlled co-variables such as age and educational level, it was found that children with elevated levels of hair manganese (over 2 µg/g) had poor performance in the test of general intelligence (Raven's Progressive Color Matrices Scale PCM). The Ecohealth approach helped to identify that children in the lower Puyango Basin with very elevated levels of manganese in the river water (970 µg/L) are the ones who have the highest levels of hair manganese and the worst performance in the intelligence test.

Sending-country violence and receiving-country discrimination: effects on the health of Colombian refugees in Ecuador.

This study explored factors affecting the health and well being of recent refugees from Colombia in Ecuador. Data collection focused on how sending-country violence and structural violence in a new environment affect immigrant health vulnerability and risk behaviors. A qualitative approach included ethnographic observation, media content analysis, focus groups, and individual interviews with refugees (N = 137). The focus groups (5) provided perspectives on the research domains by sex workers; drug users; male and female refugees; and service providers. Social and economic marginalization are impacting the health and well being of this growing refugee population. Data illustrate how stigma and discrimination affect food and housing security, employment and health services, and shape vulnerabilities and health risks in a new receiving environment. Widespread discrimination in Ecuador reflects fears, misunderstanding, and stereotypes about Colombian refugees. For this displaced population, the sequelae of violence, combined with survival needs and lack of support and protections, shape new risks to health and well-being.

Estandarización de un ensayo inmunoenzimático para la detección de anticuerpos anti-ADN doble cadena en el lupus eritematoso sistémico / Standardization of an immunoenzymatic assay to detect anti-double-stranded DNA antibodies in systemic lupus erythematosus

Introducción: los anticuerpos anti-ADN doble cadena son un marcador serológico diagnóstico de lupus eritematoso sistémico (LES). El ensayo inmunoenzimático en fase sólida es una técnica rápida y rentable para su detección. Objetivo: estandarizar un ELISA que detecte anti ADN doble cadena para el diagnóstico del lupus. Métodos: los pasos que se siguieron para la estandarización incluyeron la preparación de controles, la sensibilización de la fase sólida, la selección de los amortiguadores y conjugado del ensayo, la evaluación de las condiciones de reacción y la determinación del nivel de corte. Además se realizó el estudio de inespecificidades. Se probaron 5 tipos de placas de poliestireno y se compararon ADN plasmádico de E.coli, pUC19 y ADN genómico humano como antígenos de recubrimiento. Se evaluó el efecto de la poli-L-lisina y la irradiación de la placa con luz ultravioleta, en la fijación del antígeno. El valor de corte del ensayo se determinó por el método del valor límite. Resultados: se observó disociación del antígeno cuando no se utilizó poli-L-lisina en el pretratamiento de la placa y la irradiación con luz UV no favoreció la unión del ADN a la fase sólida. No se encontraron diferencias significativas (p=0,710) entre ambos ADN, en el recubrimiento. El valor de corte (K=3) permitió clasificar como positivas 28 muestras (63,6 porciento) de pacientes con LES. Conclusiones: el método estandarizado, con el empleo de ADN plasmádico, permitió la detección de anticuerpos anti-ADN doble cadena en pacientes con lupus(AU)

Introduction: anti-double-stranded DNA antibodies are a diagnostic serological marker for systemic lupus erythematosus (SLE). The solid-phase immunoenzymatic assay is a rapid, cost-effective technique for their detection. Objective: Standardize an ELISA detecting anti-double-stranded DNA for the diagnosis of lupus. Methods: the standardization process included the following steps: preparation of controls, sensitization of the solid phase, selection of buffers and assay conjugate, evaluation of reaction conditions and determination of the cut-off level. A study of unspecificities was also conducted. Five types of polystyrene plates were tested, and a comparison was made of E. coli (pUC19) plasmid DNA and human genomic DNA as coating antigens. An evaluation was conducted of the effect of poly (L-lysine) and irradiation of the plate with ultraviolet light upon antigen fixation. The assay cut-off value was determined by the limit value method. Results: antigen dissociation was observed when poly (L-lysine) was not used in the pretreatment of the plate and UV light irradiation did not foster DNA binding to the solid phase. No significant differences were found (p=0.710) between the two DNA coatings. The cut-off value (K=3) made it possible to classify 28 samples of patients with SLE as positive (63.6 percent). Conclusions: the method standardized with the use of plasmid DNA enabled detection of anti-double-stranded DNA antibodies in patients with lupus(AU)

Estandarización de un ensayo inmunoenzimático para la detección de anticuerpos anti-ADN doble cadena en el lupus eritematoso sistémico / Standardization of an immunoenzymatic assay to detect anti-double-stranded DNA antibodies in systemic lupus erythematosus

Introducción: los anticuerpos anti-ADN doble cadena son un marcador serológico diagnóstico de lupus eritematoso sistémico (LES). El ensayo inmunoenzimático en fase sólida es una técnica rápida y rentable para su detección. Objetivo: estandarizar un ELISA que detecte anti ADN doble cadena para el diagnóstico del lupus. Métodos: los pasos que se siguieron para la estandarización incluyeron la preparación de controles, la sensibilización de la fase sólida, la selección de los amortiguadores y conjugado del ensayo, la evaluación de las condiciones de reacción y la determinación del nivel de corte. Además se realizó el estudio de inespecificidades. Se probaron 5 tipos de placas de poliestireno y se compararon ADN plasmádico de E.coli, pUC19 y ADN genómico humano como antígenos de recubrimiento. Se evaluó el efecto de la poli-L-lisina y la irradiación de la placa con luz ultravioleta, en la fijación del antígeno. El valor de corte del ensayo se determinó por el método del valor límite. Resultados: se observó disociación del antígeno cuando no se utilizó poli-L-lisina en el pretratamiento de la placa y la irradiación con luz UV no favoreció la unión del ADN a la fase sólida. No se encontraron diferencias significativas (p=0,710) entre ambos ADN, en el recubrimiento. El valor de corte (K=3) permitió clasificar como positivas 28 muestras (63,6 porciento) de pacientes con LES. Conclusiones: el método estandarizado, con el empleo de ADN plasmádico, permitió la detección de anticuerpos anti-ADN doble cadena en pacientes con lupus

Introduction: anti-double-stranded DNA antibodies are a diagnostic serological marker for systemic lupus erythematosus (SLE). The solid-phase immunoenzymatic assay is a rapid, cost-effective technique for their detection. Objective: Standardize an ELISA detecting anti-double-stranded DNA for the diagnosis of lupus. Methods: the standardization process included the following steps: preparation of controls, sensitization of the solid phase, selection of buffers and assay conjugate, evaluation of reaction conditions and determination of the cut-off level. A study of unspecificities was also conducted. Five types of polystyrene plates were tested, and a comparison was made of E. coli (pUC19) plasmid DNA and human genomic DNA as coating antigens. An evaluation was conducted of the effect of poly (L-lysine) and irradiation of the plate with ultraviolet light upon antigen fixation. The assay cut-off value was determined by the limit value method. Results: antigen dissociation was observed when poly (L-lysine) was not used in the pretreatment of the plate and UV light irradiation did not foster DNA binding to the solid phase. No significant differences were found (p=0.710) between the two DNA coatings. The cut-off value (K=3) made it possible to classify 28 samples of patients with SLE as positive (63.6 percent). Conclusions: the method standardized with the use of plasmid DNA enabled detection of anti-double-stranded DNA antibodies in patients with lupus

Estabilidad de un suero control multienzimático utilizado como material de referencia en los laboratorios clínicos / Stability of a multienzyme control serum used as reference material in clinical laboratories

Una de las vías fundamentales para garantizar la calidad de los ensayos realizados en los laboratorios clínicos es mediante el uso de materiales de referencia. Una problemática a la que nos enfrentamos es la escasez de estos productos en el mercado nacional dado su alto costo. Objetivo: evaluar la estabilidad de un suero bovino adulto enriquecido con las enzimas alanina aminotransferasa (ALAT/TGP), aspartato aminotransferasa (ASAT/TGP), fosfatasa alcalina (FA) y amilasa. Métodos: se evaluó la estabilidad a tiempo real de la matriz enriquecida con las diferentes enzimas durante 12 meses a 2 temperaturas (refrigeración y congelación). Se evaluó el efecto del glicerol sobre la actividad enzimática de los extractos, así como el efecto de los preservantes propilenglicol y etilenglicol en la estabilidad de las enzimas. Resultados: los extractos enzimáticos obtenidos comenzaron a perder la actividad biológica a partir de los 15 días, independientemente de la temperatura de almacenamiento y de la presencia o no de glicerol. Los resultados del ensayo a tiempo real realizados a la matriz enriquecida, mostraron que la estabilidad varió con el tiempo y con el tipo de enzima, independientemente del preservante ensayado, disminuyendo por debajo de los límites aceptables de actividad enzimática luego de 3 meses de almacenamiento del producto a 4 ºC. Conclusiones: se logró un material de referencia multienzimático estable por un período de 3 meses

A fundamental method to assure the quality of clinical laboratory tests is the use of reference materials. A problem we are faced with is the scarcity of these products in the domestic market, due their high cost. Objective: Evaluate the stability of an adult bovine serum enriched with the enzymes alanine aminotransferase (ALT, GPT), aspartate aminotransferase (AST, GPT), alkaline phosphatase (AP) and amylase. Methods: This enzyme-enriched matrix underwent real-time stability assessment during 12 months at two temperatures (refrigerated and frozen). An evaluation was made of the effect of glycerol on the enzymatic activity of extracts, as well as the effect of the preservatives propylene glycol and ethylene glycol on enzymatic stability. Results: The enzyme extracts obtained began to lose their biological activity at 15 days, irrespective of the storage temperature and the presence or absence of glycerol. The real time assessment of the enriched matrix showed that stability varied with time and enzyme type, irrespective of the preservative tested, and fell below acceptable limits of enzymatic activity after three months of storage at 4 ºC. Conclusions: A multienzyme reference material was obtained which was stable for a period of 3 months

Estabilidad de un suero control multienzimático utilizado como material de referencia en los laboratorios clínicos / Stability of a multienzyme control serum used as reference material in clinical laboratories

Una de las vías fundamentales para garantizar la calidad de los ensayos realizados en los laboratorios clínicos es mediante el uso de materiales de referencia. Una problemática a la que nos enfrentamos es la escasez de estos productos en el mercado nacional dado su alto costo. Objetivo: evaluar la estabilidad de un suero bovino adulto enriquecido con las enzimas alanina aminotransferasa (ALAT/TGP), aspartato aminotransferasa (ASAT/TGP), fosfatasa alcalina (FA) y amilasa. Métodos: se evaluó la estabilidad a tiempo real de la matriz enriquecida con las diferentes enzimas durante 12 meses a 2 temperaturas (refrigeración y congelación). Se evaluó el efecto del glicerol sobre la actividad enzimática de los extractos, así como el efecto de los preservantes propilenglicol y etilenglicol en la estabilidad de las enzimas. Resultados: los extractos enzimáticos obtenidos comenzaron a perder la actividad biológica a partir de los 15 días, independientemente de la temperatura de almacenamiento y de la presencia o no de glicerol. Los resultados del ensayo a tiempo real realizados a la matriz enriquecida, mostraron que la estabilidad varió con el tiempo y con el tipo de enzima, independientemente del preservante ensayado, disminuyendo por debajo de los límites aceptables de actividad enzimática luego de 3 meses de almacenamiento del producto a 4 ºC. Conclusiones: se logró un material de referencia multienzimático estable por un período de 3 meses(AU)

A fundamental method to assure the quality of clinical laboratory tests is the use of reference materials. A problem we are faced with is the scarcity of these products in the domestic market, due their high cost. Objective: Evaluate the stability of an adult bovine serum enriched with the enzymes alanine aminotransferase (ALT, GPT), aspartate aminotransferase (AST, GPT), alkaline phosphatase (AP) and amylase. Methods: This enzyme-enriched matrix underwent real-time stability assessment during 12 months at two temperatures (refrigerated and frozen). An evaluation was made of the effect of glycerol on the enzymatic activity of extracts, as well as the effect of the preservatives propylene glycol and ethylene glycol on enzymatic stability. Results: The enzyme extracts obtained began to lose their biological activity at 15 days, irrespective of the storage temperature and the presence or absence of glycerol. The real time assessment of the enriched matrix showed that stability varied with time and enzyme type, irrespective of the preservative tested, and fell below acceptable limits of enzymatic activity after three months of storage at 4 ºC. Conclusions: A multienzyme reference material was obtained which was stable for a period of 3 months(AU)

Long-range effect of cyanide on mercury methylation in a gold mining area in southern Ecuador.

Small-scale gold mining in Portovelo-Zaruma, Southern Equador, performed by mercury amalgamation and cyanidation, yields 9-10 t of gold/annum, resulting in annual releases of around 0.65 t of inorganic mercury and 6000 t of sodium cyanide in the local river system. The release of sediments, cyanide, mercury, and other metals present in the ore such as lead, manganese and arsenic significantly reduces biodiversity downstream the processing plants and enriches metals in bottom sediments and biota. However, methylmercury concentrations in sediments downstream the mining area were recently found to be one order of magnitude lower than upstream or in small tributaries. In this study we investigated cyanide, bacterial activity in water and sediment and mercury methylation potentials in sediments along the Puyango river watershed, measured respectively by in-situ spectrophotometry and incubation with (3)H-leucine and (203)Hg(2+). Free cyanide was undetectable (<1 µg·L(-1)) upstream mining activities, reached 280 µg·L(-1) a few km downstream the processing plants area and was still detectable about 100 km downstream. At stations with detectable free cyanide in unfiltered water, 50% of it was dissolved and 50% associated to suspended particles. Bacterial activity and mercury methylation in sediment showed a similar spatial pattern, inverse to the one found for free cyanide in water, i.e. with significant values in pristine upstream sampling points (respectively 6.4 to 22 µgC·mg wet weight(-1)·h(-1) and 1.2 to 19% of total (203) Hg·gdry weight(-1)·day(-1)) and undetectable downstream the processing plants, returning to upstream values only in the most distant downstream stations. The data suggest that free cyanide oxidation was slower than would be expected from the high water turbulence, resulting in a long-range inhibition of bacterial activity and hence mercury methylation. The important mercury fluxes resultant from mining activities raise concerns about its biomethylation in coastal areas where many mangrove areas have been converted to shrimp farming.

Salud y seguridad en el trabajo en el Ecuador / Occupational health and safety in Ecuador

El Ecuador, país de enorme biodiversidad, tiene también una amplia gama de actividades laborales, con formas productivasmodernas y ancestrales. Sin embargo, la salud y seguridad en el trabajo han sido descuidadas, reflejo de las débiles políticas yacciones en este campo. El Instituto Ecuatoriano de Seguridad Social, el Ministerio de Trabajo y Relaciones Laborales y unaspocas empresas han hecho esfuerzos para responder a los persistentes problemas de la salud de los trabajadores, pero queda unamplio camino por recorrer. Uno de los vacíos se encuentra en el sistema de registros, razón por la cual no es posible tener unavisión integral y actualizada de las condiciones de trabajo y salud de la población ecuatoriana. En los últimos años ha progresadola formación de recursos humanos con maestrías y diplomaturas. En cuanto a la gestión de los llamados riesgos del trabajo, sehan hecho también interesantes aportaciones, recogidas por el Instrumento Andino de Seguridad y Salud en el Trabajo. Unode los retos es superar los enfoques convencionales de la teoría de los ¨riesgos del trabajo¨, reemplazándolos por otros que recuperenla posibilidad de hacer análisis profundos del ¨proceso de trabajo¨, trascendiendo así una visión puramente negativa delas condiciones de trabajo para identificar los aspectos positivos del trabajo, y superando el énfasis centrado solo en los efectosterminales (accidentes y enfermedades) para poner la mira en las manifestaciones tempranas y en las expresiones saludables(AU)

Ecuador, a country of rich biodiversity, also has a wide range of occupations, combining both ancestral and modern productionprocesses. However, occupational health and safety at work have been neglected, as a result of weak policies andfew interventions. The Ecuadorian Institute of Social Security, the Ministry of Labour and Employment and a few companieshave made efforts to respond to the persistent problems of the health of workers, but there is still a long way to go. Oneof the problems is the lack of accurate injury and illness registries, which prevents a comprehensive view of working conditionsand health of the Ecuadorian population. In recent years, there has been progress in the training of health and safetyprofessionals, through diploma and master’s degree programs. With respect to the management of so called “occupational riskfactors”, a few interesting initiatives have been gathered over the past few years by the Andean Instrument for OccupationalHealth and Safety. One of the challenges is to overcome conventional approaches to the theory of “occupational risk factors”,replacing them with others that allow for a more in-depth analysis of work processes. There is a need to transcend a purelynegative view of working conditions in order to identify their positive aspects and to overcome an emphasis centred solelyon end consequences (injuries and illnesses), in order to shift the focus towards early detection and promotion of health(AU)

Caracterización electroforética y cromatográfica del veneno del alacrán Rhopalurus junceus / Electrophoretic and chromatographic characterization of the Rhopalurus junceus scorpion venom

El veneno del alacrán azul, Rhopalurus junceus es actualmente comercializado con el nombre de Escozul. Este producto natural se emplea en el tratamiento de diferentes patologías, sin embargo en la literatura revisada no aparece información referente a la caracterización bioquímica del extracto de este ejemplar cubano. Objetivo: hacer una caracterización bioquímica preliminar del veneno crudo del alacrán cubano mediante el empleo de dos técnicas destinadas a estos fines. Método: se empleó la electroforesis discontinua de proteínas en gel de poliacrilamida al 15% y la cromatografía de alta presión. Resultados: se identificó un patrón difuso correspondiente a péptidos de talla inferiores a catorce KDa, mientras que por HPLC se determinaron trece picos en el veneno crudo de esta especie. Conclusiones: el veneno del alacrán azul presenta una composición molecular similar a la descrita para otras especies con una mezcla molecular inferior a catorce KDa.

The blue scorpion venom, Rhopalurus junceus is currently marketed with the name of Escozul. This natural product is used in the treatment of different pathologies; however in the revised literature doesn't appear concerning information to the biochemical characterization of the extract of this Cuban specimen. Objective: to make a preliminary biochemical characterization on the crude venom of the Cuban scorpion by means of the employment of two techniques dedicated to these purposes. Method: the discontinuous electrophoresis of proteins was used in polyacrylamide to 15% and the chromatography of high pressure. Results: a diffuse pattern corresponding to inferior size peptides to fourteen KDa was identified, while for HPLC thirteen peaks were determined in the crude venom of this species. Conclusions: the blue scorpion venom presents a similar molecular composition to the one described for other species with an inferior molecular mixture to fourteen KDa.

Caracterización electroforética y cromatográfica del veneno del alacrán Rhopalurus junceus / Electrophoretic and chromatographic characterization of the Rhopalurus junceus scorpion venom

El veneno del alacrán azul, Rhopalurus junceus es actualmente comercializado con el nombre de Escozul. Este producto natural se emplea en el tratamiento de diferentes patologías, sin embargo en la literatura revisada no aparece información referente a la caracterización bioquímica del extracto de este ejemplar cubano. Objetivo: hacer una caracterización bioquímica preliminar del veneno crudo del alacrán cubano mediante el empleo de dos técnicas destinadas a estos fines. Método: se empleó la electroforesis discontinua de proteínas en gel de poliacrilamida al 15% y la cromatografía de alta presión. Resultados: se identificó un patrón difuso correspondiente a péptidos de talla inferiores a catorce KDa, mientras que por HPLC se determinaron trece picos en el veneno crudo de esta especie. Conclusiones: el veneno del alacrán azul presenta una composición molecular similar a la descrita para otras especies con una mezcla molecular inferior a catorce KDa (AU)

The blue scorpion venom, Rhopalurus junceus is currently marketed with the name of Escozul. This natural product is used in the treatment of different pathologies; however in the revised literature doesn't appear concerning information to the biochemical characterization of the extract of this Cuban specimen. Objective: to make a preliminary biochemical characterization on the crude venom of the Cuban scorpion by means of the employment of two techniques dedicated to these purposes. Method: the discontinuous electrophoresis of proteins was used in polyacrylamide to 15% and the chromatography of high pressure. Results: a diffuse pattern corresponding to inferior size peptides to fourteen KDa was identified, while for HPLC thirteen peaks were determined in the crude venom of this species. Conclusions: the blue scorpion venom presents a similar molecular composition to the one described for other species with an inferior molecular mixture to fourteen KDa (AU)

Evaluación de la toxicidad in vitro del veneno del alacrán Rophalurus junceus a través de un ensayo celular / In vitro toxicity assessment caused by Rophalurus junceus scorpion poison though a cellular assay

El veneno del alacrán azul, Rophalurus junceus es comercializado con el nombre de Escozul. Este producto natural se emplea en el tratamiento de diferentes patologías. Este trabajo evaluó el efecto citotóxico in vitro de este producto en las líneas tumorales P3-X63/AG8/653 y Dunning R3327-G provenientes de mieloma murino y próstata de rata, respectivamente. La citotoxicidad fue evaluada mediante la cinética de crecimiento celular y el daño metabólico. Se utilizaron dosis de 1, 10, 20, 50, 100 y 200 mg/mL. El veneno presentó un efecto citostático dependiente de la línea tumoral en cuestión. Las dosis efectivas variaron entre las líneas celulares ensayadas. Se estudió además la estabilidad del producto almacenado durante 30 días a temperaturas de -20 y 4ºC, se evidenció la pérdida de la actividad biológica. El trabajo demostró la citotoxicidad del veneno crudo del alacrán azul en cultivos celulares.

Poison of blue scorpion (Rophalurus junceus) is marketed as Escozul. This natural product is used in treatment of different pathologies. Present paper evaluated the in vitro cytotoxic effect of this product in P3-X63/AG8/653 and Dunning R3327-G tumor lines from murine myeloma and rat prostate, respectively. Cytotoxic effect was evaluated by means of cellular growing kinetics and the metabolic damage. Doses of 1,10, 20, 50, 100, and 200 ìg/mL. Poison had a cytostatic effect dependent of tumor line at issue. Doses effective varied among the cellular lines assessed. We studied also stability of product stored during 30 days at temperatures of -20° and 4° C, evidenced the loss of biological activity. We showed cytotoxic effect of crude poison of blue scorpion in cellular cultures.

Cambio climático y salud en la región andina / Climate change and health in the andean region

Se presentan de manera resumida las causas fundamentales que contribuyen al calentamiento global y una serie de evidencias de la realidad que nos afecta: aumenta la temperatura de la tierra, se derriten los glaciares, sube el nivel de los océanos y se incrementa la frecuencia e intensidad de los eventos meteorológicos; todo ello como producto de la acumulación inusitada de gases de efecto invernadero, provenientes de la actividad humana. Se plantea las implicaciones que, de forma directa o indirecta, el cambio climático tiene para la salud, en particular para los países andinos: trastornos vinculados con la disponibilidad y calidad del agua y los alimentos, afecciones respiratorias, infecciones de transmisión vectorial, cáncer y enfermedades crónico degenerativas, cuadros asociados con desastres climáticos y temperaturas extremas. Finalmente, se revisa las propuestas y cursos de acción.

We present a short summary of the root causes that contribute to global warming and a host of evidence of the reality that affects us; such as: raising the temperature of the earth, melting glaciers, rising ocean level, increases the frequency and intensity of weather events, all as a result of the unusual accumulation of greenhouse gases, as product of human activity. There are implications that directly or indirectly, the climate change has to health in particular for Andean countries; such as: disorders linked to the availability and quality of water and food, respiratory disease, vector-borne infections, cancer and pathologies chronic degenerative tables associated with climatic disasters and extreme temperatures. Finally we review proposals and courses of action.

Evaluación de la toxicidad in vitro del veneno del alacrán Rophalurus junceus a través de un ensayo celular / In vitro toxicity assessment caused by Rophalurus junceus scorpion poison though a cellular assay

El veneno del alacrán azul, Rophalurus junceus es comercializado con el nombre de Escozul. Este producto natural se emplea en el tratamiento de diferentes patologías. Este trabajo evaluó el efecto citotóxico in vitro de este producto en las líneas tumorales P3-X63/AG8/653 y Dunning R3327-G provenientes de mieloma murino y próstata de rata, respectivamente. La citotoxicidad fue evaluada mediante la cinética de crecimiento celular y el daño metabólico. Se utilizaron dosis de 1, 10, 20, 50, 100 y 200 mg/mL. El veneno presentó un efecto citostático dependiente de la línea tumoral en cuestión. Las dosis efectivas variaron entre las líneas celulares ensayadas. Se estudió además la estabilidad del producto almacenado durante 30 días a temperaturas de -20 y 4ºC, se evidenció la pérdida de la actividad biológica. El trabajo demostró la citotoxicidad del veneno crudo del alacrán azul en cultivos celulares(AU)

Poison of blue scorpion (Rophalurus junceus) is marketed as Escozul. This natural product is used in treatment of different pathologies. Present paper evaluated the in vitro cytotoxic effect of this product in P3-X63/AG8/653 and Dunning R3327-G tumor lines from murine myeloma and rat prostate, respectively. Cytotoxic effect was evaluated by means of cellular growing kinetics and the metabolic damage. Doses of 1,10, 20, 50, 100, and 200 ìg/mL. Poison had a cytostatic effect dependent of tumor line at issue. Doses effective varied among the cellular lines assessed. We studied also stability of product stored during 30 days at temperatures of -20° and 4° C, evidenced the loss of biological activity. We showed cytotoxic effect of crude poison of blue scorpion in cellular cultures(AU)

Purificación de ADN genómico humano para el diagnóstico del lupus eritematoso sistémico / Purification of human genomic DNA for the diagnosis of the systemic lupus erythematosus

Fundamento: La molécula de ADN constituye un antígeno necesario en el recubrimiento de un sistema inmunoenzimático destinado al diagnóstico de enfermedades autoinmunes, específicamente del lupus eritomatoso sistémico. Por otra parte, esta molécula se emplea en la obtención de anticuerpos monoclonales anti ADN de doble cadena. Objetivo: Se evaluó la calidad del ADN humano purificado por el método del fenol:cloroformo con fines diagnósticos. La molécula fue obtenida por primera vez en el Centro de Inmunología y Productos Biológicos de Camagüey. Método: El ADN se extrajo a partir de tejido prostático de un paciente con hiperplasia prostática benigna. Se realizó la técnica convencional de fenol: cloroformo/alcohol isoamilico. El tejido fue previamente tratado con Pronasa a 56ºC. La corrida electroforética se realizó en gel de agarosa 0,8 %, y se determinó la relación 260/280nm mediante espectrofotometría, con la finalidad de evaluar la integridad de la macromolécula, así como el grado de pureza de la misma respectivamente. Resultados: No se observó degradación de la molécula de ADN genómico humano, y la relación 260/280 fue de 1,6. La molécula de ADN humana fue ensayada en el recubrimiento de un ELISA destinado al diagnóstico del Lupus, y su comparación con ADN plásmidico no arrojó diferencias significativas (p= 0.710). Conclusiones: El método aquí descrito proporcionó una molécula de ácido nucleico con la calidad requerida para ser utilizada en el sistema inmunoenzimático destinado al diagnóstico del lupus eritematoso sistémico.

Background: The DNA molecule constitutes a necessary antigen in the capping of an immunoenzymatic system dedicated to the diagnosis of autoimmune diseases, specifically of the systemic lupus erythematosus. On the other hand, this molecule is used for obtaining the anti DNA monoclonal antibodies´ of double chain. Objective: The quality of the purified human DNA was evaluated by the phenol method: chloroform with diagnostic purposes. The molecule for the first time was obtained in the Center of Immunology and Biological Products of Camagüey. Method: The DNA was extracted from a patient's prostatic tissue with benign prostatic hyperplasia. The conventional technique of phenol: chloroform / isoamyl alcohol was perfomed. The tissue was previously treated with Pronasa at 56ºC. The agarose gel electrophoresis was performed at 0,8% and the relationship 260/280nm was determined by spectrophotometry, with the purpose of evaluating the integrity of the macromolecule, as well as its grade of purity respectively. Results: It was not observed degradation of the human genomic DNA molecule, and the relationship 260/280 was about 1,6. The human DNA molecule was tested in the capping of an ELISA dedicated to lupus diagnosis, and its comparison with plasmid DNA did not show significant differences (p = 0.710). Conclusions: The described method, provided a nucleic acid molecule with the quality required to be used in the immunoenzymatic system dedicated to the diagnosis of the systemic lupus erythematosus.

Purificación de ADN genómico humano para el diagnóstico del lupus eritematoso sistémico / Purification of human genomic DNA for the diagnosis of the systemic lupus erythematosus

Fundamento: La molécula de ADN constituye un antígeno necesario en el recubrimiento de un sistema inmunoenzimático destinado al diagnóstico de enfermedades autoinmunes, específicamente del lupus eritomatoso sistémico. Por otra parte, esta molécula se emplea en la obtención de anticuerpos monoclonales anti ADN de doble cadena. Objetivo: Se evaluó la calidad del ADN humano purificado por el método del fenol:cloroformo con fines diagnósticos. La molécula fue obtenida por primera vez en el Centro de Inmunología y Productos Biológicos de Camagüey. Método: El ADN se extrajo a partir de tejido prostático de un paciente con hiperplasia prostática benigna. Se realizó la técnica convencional de fenol:cloroformo/alcohol isoamilico. El tejido fue previamente tratado con Pronasa a 56ºC. La corrida electroforética se realizó en gel de agarosa 0,8 %, y se determinó la relación 260/280nm mediante espectrofotometría, con la finalidad de evaluar la integridad de la macromolécula, así como el grado de pureza de la misma respectivamente(AU)

Background: The DNA molecule constitutes a necessary antigen in the capping of an immunoenzymatic system dedicated to the diagnosis of autoimmune diseases, specifically of the systemic lupus erythematosus. On the other hand, this molecule is used for obtaining the anti DNA monoclonal antibodies´ of double chain. Objective: The quality of the purified human DNA was evaluated by the phenol method: chloroform with diagnostic purposes. The molecule for the first time was obtained in the Center of Immunology and Biological Products of Camagüey. Method: The DNA was extracted from a patient's prostatic tissue with benign prostatic hyperplasia. The conventional technique of phenol: chloroform / isoamyl alcohol was perfomed. The tissue was previously treated with Pronasa at 56ºC. The agarose gel electrophoresis was performed at 0,8% and the relationship 260/280nm was determined by spectrophotometry, with the purpose of evaluating the integrity of the macromolecule, as well as its grade of purity respectively(AU)

Superoxide dismutase 1 (SOD1) is essential for H2O2-mediated oxidation and inactivation of phosphatases in growth factor signaling.

Superoxide dismutase 1 (SOD1) is an abundant copper/zinc enzyme found in the cytoplasm that converts superoxide into hydrogen peroxide and molecular oxygen. Tetrathiomolybdate (ATN-224) has been recently identified as an inhibitor of SOD1 that attenuates FGF-2- and VEGF-mediated phosphorylation of ERK1/2 in endothelial cells. However, the mechanism for this inhibition was not elucidated. Growth factor (GF) signaling elicits an increase in reactive oxygen species (ROS), which inactivates protein tyrosine phosphatases (PTP) by oxidizing an essential cysteine residue in the active site. ATN-224-mediated inhibition of SOD1 in tumor and endothelial cells prevents the formation of sufficiently high levels of H(2)O(2), resulting in the protection of PTPs from H(2)O(2)-mediated oxidation. This, in turn, leads to the inhibition of EGF-, IGF-1-, and FGF-2-mediated phosphorylation of ERK1/2. Pretreatment with exogenous H(2)O(2) or with the phosphatase inhibitor vanadate abrogates the inhibition of ERK1/2 phosphorylation induced by ATN-224 or SOD1 siRNA treatments. Furthermore, ATN-224-mediated SOD1 inhibition causes the down-regulation of the PDGF receptor. SOD1 inhibition also increases the steady-state levels of superoxide, which induces protein oxidation in A431 cells but, surprisingly, does not oxidize phosphatases. Thus, SOD1 inhibition in A431 tumor cells results in both prooxidant effects caused by the increase in the levels of superoxide and antioxidant effects caused by lowering the levels of H(2)O(2). These results identify SOD1 as a master regulator of GF signaling and as a therapeutic target for the inhibition of angiogenesis and tumor growth.