The level of exposure affects the arsenic urinary methylation profile of a population of children.

Differences in the As methylation capacity of Argentine children, exposed to different levels of As in drinking water were evaluated, considering the gender and the presence of the As3MT T860C gene polymorphism. Inorganic As (%IAs), monomethylated As (%MMA) and dimethylated As (%DMA), primary methylation index (PMI) and secondary methylation index (SMI) were evaluated and represented the As methylation capacity. Urinary As ranged from 18 to 5106 µg/g creatinine. Comparisons were performed between lowest and highest quartiles of urinary As. The level of exposure was positively related to urinary %MMA and negatively to %DMA and to SMI. Considering the presence of the As3MT T860C polymorphism, the level of exposure increased %MMA, and decreased %DMA and the SMI in carriers of the T/T genotype. SMI OR for T/T carriers was 10.61 (95% CI: 2.16-52.16, p: 0.0036). Regarding the gender, the level of exposure increased %MMA, and decreased %DMA and the SMI in girls and boys. SMI OR for girls was 8.71 (95% CI: 1.48-51.08, p: 0.0165) and for boys, OR: 18.15 (95% CI: 2.03-162.35, p: 0.0095). It was possible to identify the level of exposure as a factor that can modify the influence that other factors have on the methylation of As.

Arsenic in Argentina: Technologies for arsenic removal from groundwater sources, investment costs and waste management practices.

An overview about the presence of arsenic (As) in groundwaters of Argentina, made by a transdisciplinary group of experts is presented. In this second part, the conventional and emerging technologies for As removal, management of wastes, and the initial investment costs of the proposed technologies, with emphasis on developments of local groups are described. Successful examples of real application of conventional and emerging technologies for As removal in waters for human consumption, for medium, small and rural and periurban communities are reported. In the country, the two most applied technologies for arsenic removal at a real scale are reverse osmosis and coagulation-adsorption-filtration processes using iron or aluminum salts or polyelectrolytes as coagulants. A decision tree to evaluate the possible technologies to be applied, based on the population size, the quality of the water and its intended use, is presented, including preliminary and indicative investment costs. Finally, a section discussing the treatment and final disposal of the liquid, semiliquid and solid wastes, generated by the application of the most used technologies, is included. Conclusions and recommendations, especially for isolated rural and periurban regions, have been added.

Arsenic in Argentina: Occurrence, human health, legislation and determination.

An overview about the presence of arsenic (As) in groundwaters of Argentina, made by a transdisciplinary group of experts is presented. Aspects on As occurrence, effects of As on human health, regulations regarding the maximum allowable amount of As in drinking water as well as bottled water, and analytical techniques for As determination are presented. The most affected region in Argentina is the Chaco-Pampean plain, covering around 10 million km2, where approximately 88% of 86 groundwater samples collected in 2007 exceeded the World Health Organization (WHO) guideline value. In the Salí river basin, As concentrations ranged from 11.4 to 1660 µg/L, with 100% of the samples above the WHO guideline value. In the Argentine Altiplano (Puna) and Subandean valleys, 61% of 62 samples collected from surface and groundwaters exceeded the WHO limit. Thus, it can be estimated that, at present, the population at risk in Argentina reaches around four million people. Pathologies derived from the chronic consumption of As, the metabolism of As in the human body and the effects of the different As chemical forms, gathered under the name HACRE (hidroarsenicismo crónico regional endémico in Spanish, for chronic regional endemic hydroarsenicism) are described. Regarding the regulations, the 10 µg/L limit recommended by the WHO and the United States Environmental Protection Agency has been incorporated in the Argentine Food Code, but the application is still on hold. In addition, there is disparity regarding the maximal admitted values in several provinces. Considerations about the As concentrations in bottled water are also presented. A survey indicates that there are several Argentine laboratories with the suitable equipment for As determination at 10 µg/L, although 66% of them are concentrated in Buenos Aires City, and in the Santa Fe, Córdoba and Buenos Aires provinces. Conclusions and recommendations of this first part are provided.

Uso inapropiado de diuréticos: Algunas características no tan conocidas / Diuretic misuse: Some not so well known characteristics

Entre las situaciones asociadas al uso inapropiado de diuréticos se encuentran los intentos por descencer rápidamente de peso, comunes en los desordenes de la alimentación, y los intentos por enmascarar el consumo de otras sustancias, en el caso de las competencias deportivas. El uso sin indicación ni supervisión médica de estos fármacos genera un desbalance electrolítico, que puede manifestarse con hiponatremia, hipocalemia, hipocalcemia e hipomagnesemia, hipercalemia, entre otras alteraciones. El objetivo de este trabajo fue investigar las caracteríscas del uso inapropiado de diuréticos a partir de la casuística del CENATOXA. Se realizó un estudio descriptivo restrospectivo sobre los análisis ingresados al CENATOXA con solicitud de investigación cualitativa de diuréticos en orina, entre los años 2002 y 2016. En dicho período ingresaron al CENATOXA 138 casos, de los cuales el 56 % resultó positivo para algún diurético. Del total de casos con resultado positivo, el 93,5 % fueron mujeres entre 25 y 55 años de edad y predominó la etiología intencional. Los diuréticos mayoritariamente encontrados fueron hidroclorotiazida y furosemida. El perfil de diuréticos hasta el año 2008 (hidroclorotiazida = 68% de los casos positivos) se diferenció del hallado entre 2009 y 2016 (furosemida + hidroclorotiazida = 60% de los casos positivos). Se observó recurrencia en el uso inapropiado en el 8% de los casos. El uso simultáneo de más de un diurético y la recurrencia son factores que pueden contribuir a la aparición de toxicidad. Estos resultados sugieren que el uso inapropiado de diuréticos es una situación que debería ser ob­servada más atentamente para establecer mejor su alcance y sus riesgos.

Among the situations associated with diuretics misuse are the attempts to lose weight fast, frequently observed in eating disorders, and the attempts to mask the consumption of other substances, in the case of sports competitions. The use of these drugs with no medical indication or supervision generates an electrolyte imbalance, leading to hyponatremia, hypokalemia, hypocalcemia and hypomagnesemia, hyperkalemia, among other alterations. The objective of this work was to investigate the characteristics of diuretics misuse from the CENATOXA database, where the qualitative investigation of diuretics in urine is per­formed. A descriptive retrospective study was conducted on the cases admitted to the CENATOXA with a request for qualitative diuretic investigation, between 2002 and 2016. During this period, 138 urine samples were received at the CENATOXA and 56% were positive for at least one diuretic. Of all cases with positive results, 93.5% were women between 25 and 55 years of age, and intentional etiology predominated. The most detected diuretics were hydrochlorothiazide and furosemide. The diuretic misuse pattern detected up to 2008 (hydrochlorothiazide = 68% of positive cases) differed from that detected between 2009 and 2016 (furosemide + hydrochlorothiazide = 60% of positive cases). Recurrence in misuse was observed in 8% of the cases. The simul­taneous misuse of more than one diuretic and the recurrence are factors that can contribute to the onset of toxicity. These results suggest that diuretic misuse is a situation that should be observed more closely to better assess its consequences and its risks.

Hidroarsenicismo: mecanismos de acción asociados a la toxicidad del arsénico / Hydroarsenicism: Mechanisms of action related to arsenic toxicity

La exposición crónica al arsénico (As) inorgánico a través del agua de bebida da lugar al desarrollo de la enfermedad conocida como hidroarsenicismo. Esta enfermedad presenta sintomatología característica, sin embargo, para la mayoría de los efectos tóxicos que produce del As aún no se conoce en detalle el mecanismo de acción tóxica. Los mecanismos moleculares de acción del arsenito (unión a grupos sulfhidrilos) y del arseniato (sustitución del fosfato) están bien identificados, sin embargo, las consecuencias a nivel subcelular, celular, tisular y orgánico de esos mecanismos todavía presentan muchos huecos por llenar. A nivel subcelular y celular, la generación de especies reactivas de oxígeno (ERO) y de nitrógeno (ERN) son los mecanismos de acción tóxica del As más estudiados últimamente. Se los ha vinculado con la diferenciación y proliferación de queratinocitos, con la disfunción endotelial, con la resistencia a la insulina, con la inducción de peroxidación lipídica en hígado, de necrosis tubular renal y con cambios en la expresión del receptor estrogénico. Por último, la respuesta celular a proteínas no plegadas (como consecuencia del estrés del retículo endoplásmico) podría ser un mecanismo para explicar la afectación de la inmunidad humoral y la celular.

Chronic exposure to inorganic arsenic (As) through drinking water leads to the development of the disease known as hydroarsenicism. This disease presents characteristic symptomatology but the mechanisms underlying most of the toxic effects produced by As are not fully understand. The molecular mechanisms of action of arsenite (binding to sulfhydryl groups) and arsenate (phosphate substitution) are well identified, however, the consequences at the subcellular, cellular, tissue and organic levels of these mechanisms still have many gaps to fill. At the subcellular and cellular level, the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the most studied mechanisms of toxic action. They have been linked to the differentiation and proliferation of keratinocytes, endothelial dysfunction, insulin resistance, induction of lipid peroxidation in the liver, renal tubular necrosis and changes in the expression of estrogen receptor. Finally, the cellular response to unfolded proteins (as a consequence of the stress of the endoplasmic reticulum) could be a mechanism to explain the affectation of humoral and cellular immunity.

Exposición a arsénico en agua de bebida y asociación con cáncer y con ERC, genotoxicidad y daño neurocognitivo en Argentina / Exposure to arsenic in drinking water and association with cancer and CKD, genotoxicity and neurocognitive damage in Argentina

Se realizó un estudio ecológico con el objetivo evaluar la asociación entre los niveles de arsénico (As) en agua de bebida con la mortalidad por cáncer de piel, vejiga, pulmón, hígado y riñón y con la IN (IN) y prevalencia (PR) de enfermedad renal crónica de etiología desconocida (ERCd). Se construyó un mapa con datos de As en agua de 167 departamentos de la Argentina. Se analizó la asociación entre los valores de As en agua y las tasas de mortalidad por los distintos cánceres, y la IN y PR de ERCd, mediante la autocorrelación espacial I Moran, el modelo regresión de Poisson, la prueba de Kruskal Wallis y el modelo de regresión lineal. En localidades seleccionadas de dos provincias argentinas (Santa Fe y Jujuy) se realizaron sendos estudios transversales para investigar la asociación entre la exposición a As y el daño genético en adultos (mediante el conteo de micronúcleos y el ensayo cometa), y el daño neurocognitivo (mediante la aplicación de pruebas neuroconductuales) en niños y adultos. No se encontró asociación estadísticamente significativa entre la concentración de As en el agua y las tasas de mortalidad para ninguno de los cánceres estudiados, ni con la IN o la PR de ERCd. Solo para las tasas de mortalidad por cáncer de pulmón se observó una asociación marginal. Tampoco se observaron diferencias significativas entre los grupos control y tratamiento en cuanto al daño genético, ni para el daño neurocognitivo. Se concluye que la ausencia de asociación entre mortalidad por cánceres específicos y ERCd con los valores de As en el agua pudo deberse a que tanto la base de datos de As en agua, como la de la mortalidad por cánceres y la de ERCd no fueron lo suficientemente desagregadas como para encontrar asociación. En cuanto a los estudios transversales se propone profundizar el análisis, aumentando el número de individuos estudiados

Evaluación de la ingesta diaria de cafeína en niños y adolescentes de Argentina / Assessment of caffeine daily intake in children and adolescents from Argentina

. La cafeína (1,3,7 trimetilxantina) es un alcaloide de la familia de las xantinas. Está presente en una gran cantidad de bebidas como café, té, cacao, mate, guaraná, bebidas gaseosas y bebidas energizantes, y alimentos que son consumidos por adultos, adolescentes y niños. A fin de obtener información acerca de la ingesta de cafeína en población infantil y adolescente de Argentina, se plantearon los siguientes objetivos de trabajo: a) estimar la ingesta diaria de cafeína en niños y adolescentes que residen en conglomerados urbanos de Argentina; b) estudiar la asociación de dicha ingesta con distintas variables tales como el género, la edad, el nivel socioeconómico (NSE) y el lugar de residencia; c) estudiar la relación de la ingesta de cafeína con la duración del sueño y d) valorar la contribución de las distintas bebidas a la ingesta diaria de cafeína. Se obtuvieron los datos de consumo de bebidas de 425 participantes de hasta 20 años de edad, residentes de distintas ciudades del país y de diferente NSE. Los resultados mostraron que la ingesta diaria promedio de cafeína (11, 43, 76, 132 y 233 mg/día) aumentó con la franja etaria (menores de 2, de 3 a 5, de 6 a 12, de 13 a 17 y de 18 a 20 años, respectivamente), aunque al relacionarla con el peso corporal (mg/kg/día) el aumento no fue tan marcado. El 50 % de los niños de hasta 2 años evaluados, nunca había consumido bebidas con cafeína. Por el contrario, a partir de 3 años en adelante más del 90 % sí consumieron regularmente por lo menos una bebida con cafeína. Las ingestas promedio calculadas para los niños y adolescentes evaluados resultaron ser superiores a las reportadas por otros autores para otros países. No se encontraron diferencias en la ingesta según el género, el lugar de residencia o el NSE. No se encontró relación entre la ingesta de cafeína y la duración del sueño para ningún grupo etario, a excepción de la franja etaria de 18 a 20 años en la que se observó una disminución significativa en la duración promedio del sueño para el grupo de individuos con ingesta extrema. Las bebidas gaseosas cola se mostraron como principales contribuyentes a la ingesta promedio de cafeína, aunque el mate también se destacó en ese aspecto. Como conclusiones generales de este trabajo se destaca que se logró caracterizar la ingesta de cafeína en niños y adolescentes y establecer la composición de dicha ingesta en cuanto a sus contribuyentes mayoritarios y minoritarios. Por último, si bien se podría clasificar a las ingestas promedio obtenidas en este estudio como elevadas con respecto a las reportadas para otros países, se debe considerar que no se ha definido un valor de ingesta diaria recomendada para niños y adolescentes.

Caffeine (1,3,7 trimethylxanthine) is an naturally occurring alkaloid. It is present in many beverages such as coffee, tea, cocoa, mate, guarana, soft drinks and energy drinks, and foods, widely consumed by adults, adolescents and children. Since information about caffeine intake in children and adolescents in our country is scarce, the aims of the study were set as follows: a) estimate the caffeine daily intake of children and adolescents from Argentina, b) associate the intake to different variables such as gender, age, socioeconomic status (SES) and place of residence; c) study the relationship between caffeine intake and sleep duration, and d) assess the contribution of different beverages to the caffeine daily intake. Information on non alcoholic beverages consumption was obtained from 425 participants up to 20 years old. Participants were from different cities and of different SES all over the country. Results showed that the caffeine mean daily intake increased (11 , 43 , 76 , 132 and 233 mg/day ) with age range (up to 2 , 3 to 5, 6 to 12 , 13 to 17 and 18 20 years old, respectively), but when the intake was related to body weight (mg/ kg/day) the increase was not so marked. Fifty percent of children up to 2 years old had never consumed any caffeinated beverage. However, from ages 3 and up, more than 90% of children regularly consumed at least one caffeinated beverage. The mean daily intakes for the evaluated children and adolescents were higher to those reported by other authors for other countries. When data were analyzed by gender, place of residence or SES, no differences in caffeine intake were observed. No relationship between caffeine intake and sleep duration for any age group was found, except for the age group of 18-20 years, where a significant decrease in average sleep duration for the group of individuals with extreme intake was observed. Soft drinks showed to be main contributors to the mean caffeine daily intake, although mate also highlighted in that aspect. Characterization of the caffeine daily intake and identification of the major and minor contributors to that intake are remarked as achievements of this study. And finally, although caffeine mean daily intake obtained in this study could be considered as elevated when compared with those reported for other countries, it should be noted that a recommended daily intake value for children and adolescents has not already been set.

Evaluación de la ingesta diaria de cafeína en niños y adolescentes de Argentina / Assessment of caffeine daily intake in children and adolescents from Argentina

. La cafeína (1,3,7 trimetilxantina) es un alcaloide de la familia de las xantinas. Está presente en una gran cantidad de bebidas como café, té, cacao, mate, guaraná, bebidas gaseosas y bebidas energizantes, y alimentos que son consumidos por adultos, adolescentes y niños. A fin de obtener información acerca de la ingesta de cafeína en población infantil y adolescente de Argentina, se plantearon los siguientes objetivos de trabajo: a) estimar la ingesta diaria de cafeína en niños y adolescentes que residen en conglomerados urbanos de Argentina; b) estudiar la asociación de dicha ingesta con distintas variables tales como el género, la edad, el nivel socioeconómico (NSE) y el lugar de residencia; c) estudiar la relación de la ingesta de cafeína con la duración del sueño y d) valorar la contribución de las distintas bebidas a la ingesta diaria de cafeína. Se obtuvieron los datos de consumo de bebidas de 425 participantes de hasta 20 años de edad, residentes de distintas ciudades del país y de diferente NSE. Los resultados mostraron que la ingesta diaria promedio de cafeína (11, 43, 76, 132 y 233 mg/día) aumentó con la franja etaria (menores de 2, de 3 a 5, de 6 a 12, de 13 a 17 y de 18 a 20 años, respectivamente), aunque al relacionarla con el peso corporal (mg/kg/día) el aumento no fue tan marcado. El 50 % de los niños de hasta 2 años evaluados, nunca había consumido bebidas con cafeína. Por el contrario, a partir de 3 años en adelante más del 90 % sí consumieron regularmente por lo menos una bebida con cafeína. Las ingestas promedio calculadas para los niños y adolescentes evaluados resultaron ser superiores a las reportadas por otros autores para otros países. No se encontraron diferencias en la ingesta según el género, el lugar de residencia o el NSE. No se encontró relación entre la ingesta de cafeína y la duración del sueño para ningún grupo etario, a excepción de la franja etaria de 18 a 20 años en la que se observó una disminución significativa en la duración promedio del sueño para el grupo de individuos con ingesta extrema. Las bebidas gaseosas cola se mostraron como principales contribuyentes a la ingesta promedio de cafeína, aunque el mate también se destacó en ese aspecto. Como conclusiones generales de este trabajo se destaca que se logró caracterizar la ingesta de cafeína en niños y adolescentes y establecer la composición de dicha ingesta en cuanto a sus contribuyentes mayoritarios y minoritarios. Por último, si bien se podría clasificar a las ingestas promedio obtenidas en este estudio como elevadas con respecto a las reportadas para otros países, se debe considerar que no se ha definido un valor de ingesta diaria recomendada para niños y adolescentes.(AU)

Caffeine (1,3,7 trimethylxanthine) is an naturally occurring alkaloid. It is present in many beverages such as coffee, tea, cocoa, mate, guarana, soft drinks and energy drinks, and foods, widely consumed by adults, adolescents and children. Since information about caffeine intake in children and adolescents in our country is scarce, the aims of the study were set as follows: a) estimate the caffeine daily intake of children and adolescents from Argentina, b) associate the intake to different variables such as gender, age, socioeconomic status (SES) and place of residence; c) study the relationship between caffeine intake and sleep duration, and d) assess the contribution of different beverages to the caffeine daily intake. Information on non alcoholic beverages consumption was obtained from 425 participants up to 20 years old. Participants were from different cities and of different SES all over the country. Results showed that the caffeine mean daily intake increased (11 , 43 , 76 , 132 and 233 mg/day ) with age range (up to 2 , 3 to 5, 6 to 12 , 13 to 17 and 18 20 years old, respectively), but when the intake was related to body weight (mg/ kg/day) the increase was not so marked. Fifty percent of children up to 2 years old had never consumed any caffeinated beverage. However, from ages 3 and up, more than 90% of children regularly consumed at least one caffeinated beverage. The mean daily intakes for the evaluated children and adolescents were higher to those reported by other authors for other countries. When data were analyzed by gender, place of residence or SES, no differences in caffeine intake were observed. No relationship between caffeine intake and sleep duration for any age group was found, except for the age group of 18-20 years, where a significant decrease in average sleep duration for the group of individuals with extreme intake was observed. Soft drinks showed to be main contributors to the mean caffeine daily intake, although mate also highlighted in that aspect. Characterization of the caffeine daily intake and identification of the major and minor contributors to that intake are remarked as achievements of this study. And finally, although caffeine mean daily intake obtained in this study could be considered as elevated when compared with those reported for other countries, it should be noted that a recommended daily intake value for children and adolescents has not already been set.(AU)

Ethnic characterization of a population of children exposed to high doses of arsenic via drinking water and a possible correlation with metabolic processes.

Because the ratio between the two major arsenic metabolites is related to the adverse health effects of arsenic, numerous studies have been performed to establish a relationship between the ability to metabolically detoxify arsenic and other variables, including exposure level, gender, age and ethnicity. Because ethnicity may play a key role and provide relevant information for heterogeneous populations, we characterized a group of 70 children from rural schools in the Argentinean provinces of Chaco and Santiago del Estero who were exposed to high levels of arsenic. We used genetic markers for maternal, paternal and bi-parental ancestry to achieve this goal. Our results demonstrate that the Amerindian maternal linages are present in 100% of the samples, whereas the Amerindian component transmitted through the paternal line is less than 10%. Informative markers for autosomal ancestry show a predominantly European ancestry, in which 37% of the samples contained between 90 and 99% European ancestry. The native American component ranged from 50 to 80% in 15.7% of the samples, and in all but four samples, the African component was less than 10%. Correlation analysis demonstrated that the ethnicity and the ratio of the excreted arsenic metabolites monomethyl arsenic and dimethyl arsenic are not associated, dismissing a relationship between ethnic origin and differential metabolism.

Arsenic exposure in Latin America: biomarkers, risk assessments and related health effects.

In Latin America, several regions have a long history of widespread arsenic (As) contamination from both natural and anthropological sources. Yet, relatively little is known about the extent of As exposure from drinking water and its related health consequences in these countries. It has been estimated that at least 4.5 million people in Latin America are chronically exposed to high levels of As (>50 µg/L), some to as high as 2000 µg/L--200 times higher than the World Health Organization (WHO) provisional standard for drinking water. We conducted a systematic review of 82 peer reviewed papers and reports to fully explore the current understanding of As exposure and its health effects, as well as the influence of genetic factors that modulate those effects in the populations of Latin America. Despite some methodological limitations, these studies suggested important links between the high levels of chronic As exposure and elevated risks of numerous adverse health outcomes in Latin America--including internal and external cancers, reproductive outcomes, and childhood cognitive function. Several studies demonstrated genetic polymorphisms that influence susceptibility to these and other disease states through their modulation of As metabolism, with As methyltransferase (AS3MT), glutathione S-transferase (GST), and genes of one-carbon metabolism being specifically implicated. While the full extent and nature of the health burden are yet to be known in Latin America, these studies have significantly enriched knowledge of As toxicity and led to subsequent research. Targeted future studies will not only yield a better understanding of the public health impact of As in Latin America populations, but also allow for effective and timely mitigation efforts.

Revisión de la toxicocinética y la toxicodinamia del ácido cianhídrico y los cianuros / Review of toxicokinetics and toxicodynamics of cyanides and hydrogen cyanide

El cianuro es uno de los tóxicos más peligrosos por su rápida y potente acción, muchas veces letal. Los diferentes tratamientos de la intoxicación tienen su base o explicación en el conocimiento de la toxicocinética y la toxicodinamia. La revisión de la toxicocinética del cianuro muestra que, si bien la vía de la tiosulfato-cianuro sulfotransferasa (rodanasa) es la principal vía metabólica, el complejo con albúmina sérica sería el primer proceso de detoxificación del cianuro en el metabolismo normal. El efecto protector de formadores de cianhidrinas en casos de intoxicación sigue siendo evaluado a nivel experimental. Los estudios actuales sobre la toxicodinamia del cianuro se enfocan en la afinidad de la unión del cianuro al centro binuclear hemo a3-CuB de la citocromo oxidasa en sus diferentes estados redox y enel mecanismo de inhibición de enzimas antioxidantes. Un mayor y mejor entendimiento de la detoxificación del cianuro así como de los mecanismos de acción tóxica podrían llevar al desarrollo de potenciales antídotos.(AU)

Cyanide is one of the most dangerous poisons because of its rapid and potent toxicity, most times with lethal outcomes. Different poisoning treatments are based on knowledge of cyanides toxicokinetic and toxicodynamic. The review of cyanides toxicokinetics shows that, although thiosulfate-cyanide sulfotransferase (rhodanese) is the major metabolic pathway, binding serum albumin would be the first process of detoxification of cyanide in normal metabolism. The protective effect of cyanohydrin formers in cases of poisoning remains experimentally evaluated. Cyanides binding affinity to the binuclear center heme a3-CuB of cytochrome oxidase within their different redox states and cyanides mechanism of inhibition of antioxidant enzymes are currently still being investigated. More and better understanding of cyanides detoxification pathways and/or mechanisms of toxic action could lead to the development of new potential antidotes.(AU)

Revisión de la toxicocinética y la toxicodinamia del ácido cianhídrico y los cianuros / Review of toxicokinetics and toxicodynamics of cyanides and hydrogen cyanide

El cianuro es uno de los tóxicos más peligrosos por su rápida y potente acción, muchas veces letal. Los diferentes tratamientos de la intoxicación tienen su base o explicación en el conocimiento de la toxicocinética y la toxicodinamia. La revisión de la toxicocinética del cianuro muestra que, si bien la vía de la tiosulfato-cianuro sulfotransferasa (rodanasa) es la principal vía metabólica, el complejo con albúmina sérica sería el primer proceso de detoxificación del cianuro en el metabolismo normal. El efecto protector de formadores de cianhidrinas en casos de intoxicación sigue siendo evaluado a nivel experimental. Los estudios actuales sobre la toxicodinamia del cianuro se enfocan en la afinidad de la unión del cianuro al centro binuclear hemo a3-CuB de la citocromo oxidasa en sus diferentes estados redox y enel mecanismo de inhibición de enzimas antioxidantes. Un mayor y mejor entendimiento de la detoxificación del cianuro así como de los mecanismos de acción tóxica podrían llevar al desarrollo de potenciales antídotos.

Cyanide is one of the most dangerous poisons because of its rapid and potent toxicity, most times with lethal outcomes. Different poisoning treatments are based on knowledge of cyanide’s toxicokinetic and toxicodynamic. The review of cyanide’s toxicokinetics shows that, although thiosulfate-cyanide sulfotransferase (rhodanese) is the major metabolic pathway, binding serum albumin would be the first process of detoxification of cyanide in normal metabolism. The protective effect of cyanohydrin formers in cases of poisoning remains experimentally evaluated. Cyanide’s binding affinity to the binuclear center heme a3-CuB of cytochrome oxidase within their different redox states and cyanide’s mechanism of inhibition of antioxidant enzymes are currently still being investigated. More and better understanding of cyanide’s detoxification pathways and/or mechanisms of toxic action could lead to the development of new potential antidotes.

Brodifacoum poisoning with toxicokinetic data.

The case of a 46-year-old woman who survived after a brodifacoum poisoning is presented. The patient was admitted due to a severe coagulopathy. Initial prothrombin time and activated partial thromboplastin time were both greater than 110 seconds and the patient suffered severe gastric and pulmonary hemorrhage requiring fresh frozen plasma transfusion and parenteral phytonadione administration (up to 100 mg per day). Serum brodifacoum levels were determined by HPLC during seven months. Five days after admission, serum brodifacoum level was 1302 ng/ml. Serum brodifacoum levels decreased till day 209 when became not detectable. Brodifacoum elimination showed a first order kinetic and a 56-day half-life. Investigation of superwarfarin should be considered in any patient with vitamin K dependent coagulation disorder. It would be also useful to obtain periodic brodifacoum levels and build the corresponding elimination curve to help direct phytonadione therapy in poisoned patients.

High-performance liquid chromatography method for urinary trans,trans-muconic acid. Application to environmental exposure to benzene.

This report describes a specific and precise high-performance liquid chromatography (HPLC) method for the quantification of trans,trans-muconic acid in human urine. The procedure involved a highly efficient Bond-Elut SAX extraction with 20% acetic acid elution. The HPLC analysis used a sodium acetate/methanol mobile phase with a C18 reverse phase column and UV detection at 265 nm. The recovery, precision, linearity, and limits of detection and quantification of the method were determined. Mean absolute recoveries were between 97% and 115%. The calibration curve showed a correlation coefficient of 0.9955 and the limit of detection was determined to be 10.8 microg/L. The method is suitable for evaluation of occupational and environmental benzene exposure in humans. The study of urinary trans,trans-muconic acid of two populations of children to evaluate environmental benzene exposure is presented.

Aislamiento e identificación de diuréticos en orina por cromatografía en capa delgada / Isolation and identification of diuretics in urine by TLC

Se investgó mediante cromatografía en capa delgana la presencia de acetazolamida, ácido 4-sulfonamido benzoico, amiloride, bendroflumetiazida, bumetanida, dehídroclorotiazida, espironolactona, fuirosemida y triamtireno en muestras de orina enriquecidas. La fase fija fue silicagel 60 GF 254 y la fase móvil acetato de etilo. El revelado de las máculas fue secuencial- El sistema cromatográfico separó e identificó los nueve diuréticos ensayados con diferente sensibilidad. El amiloride, la bendroflumetiazida, la furosemida y el triamtireno pudieron ser observados a concentraciones de 0,1ug/ml; el ácido 4-sulfonamidop benzoico, la dihidroclorotiazida y la espironolactona a concentraciones de 2 ug/ml y la acetazolamida y bumetanida a concentraciones de 5 ug/ml. Este método es rápido, sencillo y económico para investigar la presencxia de diuréticos en muestras de orina, por lo que resulta adecuado para ser usado en el "screening" de diuréticos en el análisis antidopaje(AU)

Aislamiento e identificación de diuréticos en orina por cromatografía en capa delgada / Isolation and identification of diuretics in urine by TLC

Se investgó mediante cromatografía en capa delgana la presencia de acetazolamida, ácido 4-sulfonamido benzoico, amiloride, bendroflumetiazida, bumetanida, dehídroclorotiazida, espironolactona, fuirosemida y triamtireno en muestras de orina enriquecidas. La fase fija fue silicagel 60 GF 254 y la fase móvil acetato de etilo. El revelado de las máculas fue secuencial- El sistema cromatográfico separó e identificó los nueve diuréticos ensayados con diferente sensibilidad. El amiloride, la bendroflumetiazida, la furosemida y el triamtireno pudieron ser observados a concentraciones de 0,1ug/ml; el ácido 4-sulfonamidop benzoico, la dihidroclorotiazida y la espironolactona a concentraciones de 2 ug/ml y la acetazolamida y bumetanida a concentraciones de 5 ug/ml. Este método es rápido, sencillo y económico para investigar la presencxia de diuréticos en muestras de orina, por lo que resulta adecuado para ser usado en el "screening" de diuréticos en el análisis antidopaje