Residential proximity to pesticide applications in Argentine Patagonia: impact on pregnancy and newborn parameters.

Among residents living close to agricultural fields who are potentially exposed to pesticides, pregnant women and their fetuses are of particular concern for their vulnerability to environmental chemicals. In this collaborative multicenter study, we covered a wide distribution of participants in the most important fruit production zone of north Patagonia (Argentina) to investigate whether maternal residential proximity to fruit croplands with intense pesticide applications (rural group -RG-) is associated with pregnancy complications and alterations in their newborn parameters compared to the urban population (urban group -UG-). A total of 776 pregnant women met the inclusion criteria. The percentage of threatened miscarriage was significantly higher in the RG than in the UG. The percentage of miscarriage, threat of premature labor, intrauterine fetal death, preterm premature rupture of membranes, and intrauterine growth retardation were similar in both groups. Newborn anthropometric parameters were corrected by sex and gestational age prior to statistical analysis. Length at birth and head circumference were lower in the RG than in the UG. Birth weight was similar in both groups. The percentage of head circumference less than the 5th percentile and the ponderal index were greater in the RG than in the UG. Our results suggest that proximity to pesticide applications may increase the risk of pregnancy complications and altered newborn parameters.

Evaluation of endocrine disruption and gestational disorders in women residing in areas with intensive pesticide application: An exploratory study.

The proximity to areas of intensive pesticide application is a risk factor that favors xenobiotic exposure. Pesticides may interfere with hormonal function and cause alterations in the reproductive system, pregnancy complications, and adverse fetal development. We evaluated potential endocrine disruption and the evolution of the third trimester of pregnancy in women residing in a rural area of Argentina with intense pesticide applications, and the characteristics of their newborns. Blood samples were collected from healthy women in the third trimester of pregnancy during the pesticide spraying (SP) (n = 26) and nonspraying (NSP) (n = 27) periods. Plasma cholinesterase activity and cortisol and DHEA-S levels were lower in SP than in NSP. The percentage of preterm premature rupture of membranes was higher in SP than in NSP. Macrosomia at birth was17% in both periods. This study reinforces the importance of preventing potential cases of cumulative toxicity during the perinatal period through monitoring and epidemiological studies.

Susceptibility of placental mitochondria to oxidative stress.

BACKGROUND: Two different mitochondrial fractions (MFs) have been characterized in the human placenta: the "light" and "heavy" fractions (LMF and HMF). Although these organelles are the main source of reactive oxygen species, an imbalance between their production and the rate of detoxification represents a serious threat to mitochondrial homeostasis and, in the case of the placenta, also to the fetus. The aim of this study was to evaluate the antioxidant capacity and susceptibility to oxidative stress in both types of MFs. METHODS: Human MFs were isolated from healthy donors (n = 11) and either incubated or not with H2 O2 . Catalase (CAT) activity, and reduced glutathione (GSH), lipid peroxidation (LP), and protein carbonylation (PC) levels were determined. RESULTS: H2 O2 treatment increased LP and PC levels and decreased CAT activity. GSH levels were similar in control and treated MFs. CONCLUSION: H2 O2 caused oxidative damage in both LMF and HMF and the antioxidant system measured in these two MFs responded similarly. To the best of our knowledge, this is the first partial description of the antioxidant defense in placental HMF and LMF performed in a cell-free assay. The small number of antioxidant system parameters measured did not allow detecting differences between HMF and LMF.

Neonatal, placental, and umbilical cord blood parameters in pregnant women residing in areas with intensive pesticide application.

In rural populations, the proximity to areas with intensive pesticide application represents a risk factor of xenobiotic exposure. Here, we investigated whether newborns born to mothers residing in an area with intensive pesticide application show alterations in placental and neonatal morphometric standards, umbilical cord blood (UCB) biochemical parameters, and/or biomarkers related to oxidative stress and oxidative damage. Samples were collected from 151 healthy pregnant women residing in a rural area (rural group; RG) during the pesticide spraying (SS) and nonspraying (NSS) seasons, as well as from women from an urban population (control group; CG), and grouped according to the delivery type (vaginal or cesarean). In the vaginal delivery group, the placental weight and placental index were higher in the RG groups than in the CG (p = 0.01), whereas in the cesarean delivery group, newborn weight was lower in the RG-SS group than in the CG. In the RG-SS group, UCB erythrocyte osmotic fragility and the DNA damage index (DI) were higher, and superoxide dismutase (SOD) activity was lower than in the RG-NSS group. Acetylcholinesterase and SOD activities were found to be inversely correlated with the DI.

Alteration of syncytiotrophoblast mitochondria function and endothelial nitric oxide synthase expression in the placenta of rural residents.

The impact of environmental organophosphate (OP) pesticide exposure on respiratory complexes, enzymatic antioxidant defense activities, and oxidative damage markers in the syncytiotrophoblast and cytotrophoblast mitochondria was evaluated. Placental progesterone (PG) levels and endothelial nitric oxide synthase (eNOS) expression were studied. Samples from women non-exposed (control group-CG) and women living in a rural area (rural group-RG) were collected during pesticide spraying season (RG-SS) and non-spraying season (RG-NSS). In RG-SS, the exposure biomarker placental carboxylesterase decreased and syncytiotrophoblast cytochrome c oxidase activity increased, while 4-hydroxynonenal levels decreased. PG levels decreased in RG-SS and in the RG. Nitric oxide synthase expression decreased in RG, RG-SS and RG-NSS. No significant changes in mitochondrial antioxidant enzyme activities were found. These results suggest that the alteration of syncytiotrophoblast mitochondrial complex IV activity and steroidogenic function may be associated to pesticide exposure. Reduction in placental PG and eNOS expression may account for low newborn weight in RG.

Exposición ambiental a plaguicidas: biomarcadores en matrices de la tríada madre-placenta-feto / Environmental exposure to pesticides: biomarkers in matrices of the mother-placenta-fetus triad / Exposição ambiental aos agrotóxicos: biomarcadores em matrizes do tríade mãe-placenta-feto

El biomonitoreo tiene un papel fundamental en la evaluación de la salud ambiental de poblaciones expuestas a contaminantes. Este artículo analiza información referente a biomarcadores de exposición y susceptibilidad así como también a biomarcadores de efecto que pueden ser útiles en estrategias diagnósticas y preventivas en la exposición a plaguicidas persistentes (órganoclorados) y a plaguicidas moderadamente persistentes (órganofosforados), en un período de alta vulnerabilidad como el embarazo. También revisa diferentes estudios en los que se ha observado correlación entre biomarcadores de exposición en matrices de la tríada madre-placentafeto y el impacto en el desarrollo del embarazo y el crecimiento intrauterino así como también en la funcionalidad del cerebro en la infancia. Finalmente, este trabajo describe noveles biomarcadores inespecíficos entre los que se incluyen biomarcadores epigenéticos, de estrés oxidativo, de disrupción endocrina y de expresión genética.

Biomonitoring plays a key role in the assessment of environmental health of populations exposed to pollutants. This paper analyzes information regarding biomarkers of exposure and biomarkers of susceptibility as well as biomarkers of effect that may be useful in diagnostic and preventive strategies in the exposure to persistent pesticides (organochlorine) and moderately persistent pesticides (organophosphates) in a period of high vulnerability as pregnancy. It also reviews different studies where correlation between biomarkers of exposure in matrices of the mother-placenta-feto triad and the impact on the course of pregnancy and fetal growth as well as the functionality of the brain in childhood has been observed. Finally, this work describes nonspecific novel biomarkers including epigenetic biomarkers, biomarkers of oxidative stress, endocrine disruption and gene expression.

O biomonitoramento desempenha um papel fundamental na avaliação da saúde ambiental de populações expostas a contaminantes. Este artigo analisa informações sobre biomarcadores de exposição e de susceptibilidade, bem como biomarcadores de efeito, que podem ser úteis em estratégias de diagnóstico e de prevenção na exposição a pesticidas persistentes (organoclorados) e a pesticidas moderadamente persistentes (organofosforados), em um período de alta vulnerabilidade, tal como a gravidez. Ele também revisa vários estudos nos quais tem sido observada correlação entre biomarcadores de exposição em matrizes da tríade mãe-placenta-feto e o impacto no desenvolvimento da gestação e no crescimento intra-uterino, bem como na funcionalidade do cérebro na infância. Finalmente, este artigo descreve biomarcadores inespecíficos nóveis incluindo biomarcadores epigenéticos, de estresse oxidativo, de disrupção endócrina e de expressão gênica.

Exposición ambiental a plaguicidas: biomarcadores en matrices de la tríada madre-placenta-feto / Environmental exposure to pesticides: biomarkers in matrices of the mother-placenta-fetus triad / ExposiþÒo ambiental aos agrotóxicos: biomarcadores em matrizes do tríade mÒe-placenta-feto

El biomonitoreo tiene un papel fundamental en la evaluación de la salud ambiental de poblaciones expuestas a contaminantes. Este artículo analiza información referente a biomarcadores de exposición y susceptibilidad así como también a biomarcadores de efecto que pueden ser útiles en estrategias diagnósticas y preventivas en la exposición a plaguicidas persistentes (órganoclorados) y a plaguicidas moderadamente persistentes (órganofosforados), en un período de alta vulnerabilidad como el embarazo. También revisa diferentes estudios en los que se ha observado correlación entre biomarcadores de exposición en matrices de la tríada madre-placentafeto y el impacto en el desarrollo del embarazo y el crecimiento intrauterino así como también en la funcionalidad del cerebro en la infancia. Finalmente, este trabajo describe noveles biomarcadores inespecíficos entre los que se incluyen biomarcadores epigenéticos, de estrés oxidativo, de disrupción endocrina y de expresión genética.(AU)

Biomonitoring plays a key role in the assessment of environmental health of populations exposed to pollutants. This paper analyzes information regarding biomarkers of exposure and biomarkers of susceptibility as well as biomarkers of effect that may be useful in diagnostic and preventive strategies in the exposure to persistent pesticides (organochlorine) and moderately persistent pesticides (organophosphates) in a period of high vulnerability as pregnancy. It also reviews different studies where correlation between biomarkers of exposure in matrices of the mother-placenta-feto triad and the impact on the course of pregnancy and fetal growth as well as the functionality of the brain in childhood has been observed. Finally, this work describes nonspecific novel biomarkers including epigenetic biomarkers, biomarkers of oxidative stress, endocrine disruption and gene expression.(AU)

O biomonitoramento desempenha um papel fundamental na avaliaþÒo da saúde ambiental de populaþ§es expostas a contaminantes. Este artigo analisa informaþ§es sobre biomarcadores de exposiþÒo e de susceptibilidade, bem como biomarcadores de efeito, que podem ser úteis em estratégias de diagnóstico e de prevenþÒo na exposiþÒo a pesticidas persistentes (organoclorados) e a pesticidas moderadamente persistentes (organofosforados), em um período de alta vulnerabilidade, tal como a gravidez. Ele também revisa vários estudos nos quais tem sido observada correlaþÒo entre biomarcadores de exposiþÒo em matrizes da tríade mÒe-placenta-feto e o impacto no desenvolvimento da gestaþÒo e no crescimento intra-uterino, bem como na funcionalidade do cérebro na infÔncia. Finalmente, este artigo descreve biomarcadores inespecíficos nóveis incluindo biomarcadores epigenéticos, de estresse oxidativo, de disrupþÒo endócrina e de expressÒo gÛnica.(AU)

Placental oxidative status in rural residents environmentally exposed to organophosphates.

The impact of environmental organophosphate pesticide exposure on the placenta oxidative status was assessed. Placental samples were collected from women residing in an agricultural area during pesticide pulverization period, non-pulverization period and from control group. Carboxylesterase activity was significantly decreased in pulverization period group. Enzymatic and non-enzymatic defense system, the oxidative stress biomarkers and the nuclear factor erythroid 2-related factor levels showed no differences among groups. However, in the pulverization period group, an inverse association between catalase activity and placental index, a useful metric for estimating placental inefficiency, was found. This result suggests that catalase may serve as a potential placental biomarker of susceptibility to pesticides. Further studies designed from a gene-environment perspective are needed.

Environmental pesticide exposure modulates cytokines, arginase and ornithine decarboxylase expression in human placenta.

To evaluate the cytokine balance and enzymatic alterations induced by environmental pesticide exposure during pregnancy, this transversal study explored placentas derived from non-exposed women (control group-CG), and from women living in a rural area (rural group-RG), collected during intensive organophosphate (OP) pesticide spraying season (RG-SS) and during non-spraying season (RG-NSS). The exposure biomarkers blood cholinesterase and placental carboxylesterase (CaE) were significantly decreased in RG-SS. Among the cytokines studied IL-8, IL-6, TNFα, IL-10, TGFß and IL-13, the expression frequency of IL-13 increased in RG-SS. Arginase and ornithine decarboxylase (ODC) enzymes were induced in syncytiotrophoblast and endothelial cells. Interestingly, the decrease in CaE activity was associated with arginase and ODC activity induction. These findings suggest that environmental pesticide exposure impacts the placenta by increasing the expression frequency of the anti-inflammatory cytokine IL-13, which may be related to the up-regulation of enzymes implicated in tissue repair.

Plasma cholinesterase and carboxylesterase activities and nuclear and mitochondrial lipid composition of human placenta associated with maternal exposure to pesticides.

Blood cholinesterases and tissue carboxylesterases (CEs) are sensitive indicators of environmental organophosphate pesticides (OPs) exposure. The aim of this pilot study was to assess the impact of OP exposure on placental CE activity and lipid composition. We performed a study of 40 healthy women who live in agricultural farms. Samples were collected during the pulverization period (PP) and recess period (RP). The plasma cholinesterase and placental CE activity decreased in PP, suggesting that women were exposed to OPs and that these pesticides reached the placenta. The cardiolipin content increased and the phosphatidylethanolamine content decreased in the light mitochondrial fraction while total cholesterol and sphingomyelin increased in the nuclear fraction. These changes in lipid profiles suggest repair by hyperplasia of the cytotrophoblast. Decreased CE activity may have clinical and toxicological implications and thus entail potential risks to damage fetal growth and development.

Effects of the organophosphate insecticides phosmet and chlorpyrifos on trophoblast JEG-3 cell death, proliferation and inflammatory molecule production.

Epidemiological data have associated environmental organophosphate insecticide (OP) exposure during pregnancy with fetal growth deficits. To better understand OP injury that may adversely affect pregnancy, we used the JEG-3 choriocarcinoma cell line, which provide a recognized in vitro model to study placental function. The effects of the OP phosmet (Pm) and chlorpyrifos (Cp) on JEG-3 cells viability, proliferation, cell cycle and inflammatory molecule production were evaluated. Both insecticides affected cellular viability in a concentration- and time-dependent manner, inducing apoptosis and decreasing [(3)H]-thymidine incorporation. However, only Pm reduced DNA synthesis independently of cellular death and decreased the cell percentage at the S-phase. Unlike apoptosis, TNFα production varied with the concentration tested, suggesting that other TNFα independent mechanisms might trigger cell death. No induction of the inflammatory molecule nitric oxide was detected. The mRNA levels of pro-inflammatory IL-6, IL-17 and the anti-inflammatory IL-13 cytokines were differentially modulated. These findings show that Pm and Cp generate a specific toxicity signature, altering cell viability and inducing an inflammatory cytokine profile, suggesting that trophoblasts may represent a possible target for OP adverse effects.

Organophosphate pesticide environmental exposure: analysis of salivary cholinesterase and carboxilesterase activities in preschool children and their mothers.

A pilot study was conducted to evaluate the usefulness of salivary cholinesterase and carboxylesterase as biomarkers of exposure to environmental organophosphate pesticides. Ninety samples were obtained from women and 62 samples from their preschool-aged children who live near an agricultural area of the Upper Valley of the Negro River (Patagonia, Argentina) where pesticides are applied 6 months a year. Each participant donated two samples under similar conditions: one in the pre-exposure period and another during the pulverization period. Demographic information, potential confounders, and risk behaviors were registered. Active or passive smoking had no effect on these enzyme activities in either group. During the pulverization period, cholinesterase activity was not detectable in 76% of the children's samples and 23% of the mothers' samples. Comparing samples collected during the pulverization period with respect to the pre-pulverization period, the average mother and child cholinesterase activity decreased by 65.7% (p < 0.001) and 85.8% (p < 0.001), respectively. Also, mother and child carboxylesterase activity decreased by 27.5% (p < 0.001) and 41.9% (p < 0.01), respectively. Child carboxylesterase activity in the pulverization period was associated to the habit of eating dust outdoors (p < 0.01). The most frequent inhibition levels observed for cholinesterase and carboxylesterase activity were between 70-100% and 0-29%, respectively, in both groups studied. This shows that at the same level of exposure, cholinesterase was more sensitive to inhibition than carboxylesterase. Therefore, carboxylesterase might more properly reflect the degree of environmental organophosphate exposure and may have potential as a novel tool for biomonitoring.

Exposición ambiental a plaguicidas: impacto en parámetros moleculares, bioquímicos y morfométricos de la tríada madre-placenta-feto / Environmental exposure to pesticides: impact on molecular, biochemical and morphometric parameters of the mother-placenta-fetus triad

INTRODUCCION:La salud prenatal representa un problema relevante de salud públic, y uno de los temas prioritarios es la exposición ambiental a los plaguicidas.OBJETIVO:Identificar modificaciones en biomarcadores de efecto en la tríada madre-placenta-feto, mecanismos involucrados y asociaciones con el desarrollo "in utero".METODOS:Se realizó un estudio prospectivo con 776 embarazadas del Alto Valle del Río Negro, donde se aplican organofosforados (OF) intensivamente. Se utilizaron criterios de inclusión/exclusión, determinándose parámetros bioquímicos, moleculares y morfométricos en población de comunidades rurales (PoR) en período de pulverizaciones (PP) y de receso (PR) y en grupo control (PoC). Se registraron las alteraciones del embarazo.RESULTADOS:En PP, la Por presentó exposición a OF, y se vieron afectados los niveles de progesterona, cortisol y sulfato de dehidroepiandrosterona séricos durante el embarazo. En sangre de cordón aumentó la actividad de catalasa eritrocitaria. En la placenta se modificaron biomarcadores de estrés oxidativo, de funcionalidad mitocondrial, la expresión de TNFò e IL-13 y el contenido de la proteína Bcl-2. En concordancia, en células JEG-3 expuestas a OF se observó estrés oxidativo, apoptosis y aumento en la expresión de dichas citoquinas. La talla y el perímetro cefálico ajustados por sexo y edad gestacional del neonato fueron menores en PoR que en PoC (p<0,010 y p<0,05, respectivamente), mientras que el porcentaje de neonatos con perímetro cefálico menor al percentilo 5 fue mayor. En PoR se registró un mayor porcentaje de amenaza de aborto. Los niveles maternos de cortisol de primer y segundo trimestre de embarazo de PoR se asociaron negativamente con el peso y el perímetro cefálico.CONCLUSIONES:En PoR se afectaron parámetros de la tríada y del desarrollo intrauterino. El aumento en el nivel de cortisol materno sobreexpondría al feto a esta hormona, afectando la programación del eje hipotalámico-adrenal y la capacidad cognitiva.

INTRODUCTION: Prenatal health represents a relevant problem in public health. Special attention should be given to pesticide environmental exposure.OBJECTIVE: To identify changes in biomarkers of effect in the triad mother-placenta-fetus, mechanisms involved and their association with the in utero development.METHODS: Prospective study of 776 pregnante woman living in the High Valley of Río Negro, where organophosphate pesticides (OP) are intensively applied. The study used inclusion/exclusion criteria. Biochemical, molecular and morphometric parameters were determined in rural residents (RR) in pulverization (PP) and recess periods (RP) and in a control group (CG). Pregnancy alterations were registered.RESULTS: In PP, RR were exposed to OP, while serum progesterone, cortisol and dehydroepiandrosterone sulfate levels were affected during pregnancy. In cord blood, erythrocyte catalase activity was increased. In the placenta, there was a change in stress oxidative biomarkers, mitochondrial function biomarkers, the expression of TNFò and IL-13 and the protein Bcl-2 content. In line with the above, JEG-3 cells exposed to OP showed oxidative stress, apoptosis and increase in these cytokines expression. In RR, the newborn length and heah circumference adjusted by sex and gestational age were lower (p<0.010 and p<0.05, respectively) than in CG. Meanwhile, the percentage of newborns with head circumference lower than percentile 5 was higher. In RR, a higher percentage of threatened abortion was registered. Cortisol blood levels at first and second trimester of pregnancy were negatively associated with newborn weight and head circumference.CONCLUSIONS: Parameters of the triad and intrauterine development were affected in RR. The increase in the level of maternal cortisol would overexpose the fetus to this hormone, affecting the programming of hypothalamic-adrenal axis and the cognitive ability.

Exposición ambiental a plaguicidas: impacto en parámetros moleculares, bioquímicos y morfométricos de la tríada madre-placenta-feto / Environmental exposure to pesticides: impact on molecular, biochemical and morphometric parameters of the mother-placenta-fetus triad

INTRODUCCION:La salud prenatal representa un problema relevante de salud públic, y uno de los temas prioritarios es la exposición ambiental a los plaguicidas.OBJETIVO:Identificar modificaciones en biomarcadores de efecto en la tríada madre-placenta-feto, mecanismos involucrados y asociaciones con el desarrollo "in utero".METODOS:Se realizó un estudio prospectivo con 776 embarazadas del Alto Valle del Río Negro, donde se aplican organofosforados (OF) intensivamente. Se utilizaron criterios de inclusión/exclusión, determinándose parámetros bioquímicos, moleculares y morfométricos en población de comunidades rurales (PoR) en período de pulverizaciones (PP) y de receso (PR) y en grupo control (PoC). Se registraron las alteraciones del embarazo.RESULTADOS:En PP, la Por presentó exposición a OF, y se vieron afectados los niveles de progesterona, cortisol y sulfato de dehidroepiandrosterona séricos durante el embarazo. En sangre de cordón aumentó la actividad de catalasa eritrocitaria. En la placenta se modificaron biomarcadores de estrés oxidativo, de funcionalidad mitocondrial, la expresión de TNFò e IL-13 y el contenido de la proteína Bcl-2. En concordancia, en células JEG-3 expuestas a OF se observó estrés oxidativo, apoptosis y aumento en la expresión de dichas citoquinas. La talla y el perímetro cefálico ajustados por sexo y edad gestacional del neonato fueron menores en PoR que en PoC (p<0,010 y p<0,05, respectivamente), mientras que el porcentaje de neonatos con perímetro cefálico menor al percentilo 5 fue mayor. En PoR se registró un mayor porcentaje de amenaza de aborto. Los niveles maternos de cortisol de primer y segundo trimestre de embarazo de PoR se asociaron negativamente con el peso y el perímetro cefálico.CONCLUSIONES:En PoR se afectaron parámetros de la tríada y del desarrollo intrauterino. El aumento en el nivel de cortisol materno sobreexpondría al feto a esta hormona, afectando la programación del eje hipotalámico-adrenal y la capacidad cognitiva.

INTRODUCTION: Prenatal health represents a relevant problem in public health. Special attention should be given to pesticide environmental exposure.OBJECTIVE: To identify changes in biomarkers of effect in the triad mother-placenta-fetus, mechanisms involved and their association with the in utero development.METHODS: Prospective study of 776 pregnante woman living in the High Valley of Río Negro, where organophosphate pesticides (OP) are intensively applied. The study used inclusion/exclusion criteria. Biochemical, molecular and morphometric parameters were determined in rural residents (RR) in pulverization (PP) and recess periods (RP) and in a control group (CG). Pregnancy alterations were registered.RESULTS: In PP, RR were exposed to OP, while serum progesterone, cortisol and dehydroepiandrosterone sulfate levels were affected during pregnancy. In cord blood, erythrocyte catalase activity was increased. In the placenta, there was a change in stress oxidative biomarkers, mitochondrial function biomarkers, the expression of TNFò and IL-13 and the protein Bcl-2 content. In line with the above, JEG-3 cells exposed to OP showed oxidative stress, apoptosis and increase in these cytokines expression. In RR, the newborn length and heah circumference adjusted by sex and gestational age were lower (p<0.010 and p<0.05, respectively) than in CG. Meanwhile, the percentage of newborns with head circumference lower than percentile 5 was higher. In RR, a higher percentage of threatened abortion was registered. Cortisol blood levels at first and second trimester of pregnancy were negatively associated with newborn weight and head circumference.CONCLUSIONS: Parameters of the triad and intrauterine development were affected in RR. The increase in the level of maternal cortisol would overexpose the fetus to this hormone, affecting the programming of hypothalamic-adrenal axis and the cognitive ability.

El trabajo en pequeños grupos facilita la enseñanza-aprendizaje de Bioquímica / Work in small groups makes easy the Biochemical teaching and learning

El objetivo de este trabajo fue analizar la nueva propuesta de enseñanza de Bioquímica en la carrera de Medicina, que incluyó cambios en las estrategias de enseñanza-aprendizaje y de evaluación. Las clases expositivas fueron reemplazadas por la Discusión en Pequeños Grupos (DPG), en la que diez alumnos discuten situaciones del proceso salud-enfermedad. Los exámenes parciales individuales fueron reemplazados por la Evaluación en Pequeños Grupos (EPG) con la presentación de situaciones problema para la discusión y el análisis grupal. La información del presente estudio, de abordaje cualitativo, se obtuvo a partir de entrevistas semiestructuradas con docentes y alumnos. Los núcleos de análisis fueron: motivación, relaciones interpersonales, trabajo en grupo, construcción de conocimientos, comunicación, integración teórico-práctica y evaluación. La articulación de la DPG con las demás estrategias didácticas, como Clases de Consolidación, Seminarios Científicos, Trabajos Prácticos de Laboratorio y EPG motivó a docentes y alumnos, permitió la recuperación de conocimientos previos, la búsqueda activa de conocimientos e incentivó las relaciones interpersonales colaborativas y la integración conceptual. De esta forma, la incorporación de estrategias problematizadoras en grupos favoreció los procesos de aprendizaje significativo promoviendo las readecuaciones.

The objective of this work was the analysis of the new biochemistry teaching proposal presented in the Medicine Career. This proposal included changes in the teaching-learning and evaluation strategies. Explanatory lessons were replaced for Discussions in Small Groups (DSG) where groups of ten students discuss different issues related to situations in the health-illness process. At the same time, individual mid-term exams were changed for Evaluations in Small Groups (ESG) with presentation of problematic situations for discussion and group analysis. The qualitative information contained herein was obtained from organized meetings with teachers and students. The data analysis was directed by: motivation, interpersonal relationships, group work, knowledge building, communication, theoretical and practical integration and evaluation. The DSG together with other didactic strategies of the department such as Consolidation Lessons, Scientific Seminars, Laboratory Written Assignments and ESG motivated teachers and students, allowed the recovery of previous knowledge and the active search for it, encouraged the interpersonal relationships and the conceptual integration. In this way, the inclusion of this type of strategies benefited the significant learning processes and promoted changes.

O objetivo de este trabalho foi analisar a nova proposta de ensino de Bioquímica na carreira de Medicina, incluindo as mudanças nas estratégias de ensino-aprendizagem e de avaliação. As aulas expositivas foram substituídas pela Discussão em Pequenos Grupos (DPG), em que dez alunos discutem situações do processo saúde-doença. As provas parciais individuais foram substituías pela Avaliação em Pequenos Grupos (APG) com a apresentação de situações problema para a discussão e a análise grupal. As informações para este estudo, de abordagem qualitativa, foram obtidas a partir de entrevistas semi-estruturadas com docentes e alunos. Os núcleos de análise foram: a motivação, as relações interpessoais, o trabalho em grupo, a construção de conhecimentos, a comunicação, a integração teórico-prática e a avaliação. A articulação da DPG com as demais estratégias didáticas, como as Aulas de Consolidação, Seminários Científicos, Trabalhos Práticos de Laboratório e APG motivou docentes e alunos, permitiu a recuperação de conhecimentos prévios, a busca ativa de conhecimentos e incentivou as relações interpessoais colaborativas e a integração conceitual. Desta forma, a incorporação de estratégias problematizadoras em grupos, tem favorecido os processos de aprendizagem significativa promovendo as readequações.

Heptachlor and o-p'DDT effects on protein kinase activities associated with human placenta particulate fractions.

Organochlorine pesticides have been detected in placenta. The ability of heptachlor (HC) and 1,1,1-tricholoro-2-(2-chlorophenyl)-2-4-chlorophenyl)ethane (o-p'DDT) to interfere with protein phosphorylation was evaluated. In vitro incubations of cell-free placental villi homogenates with a concentration range 1-100 microM were performed. In particulate fractions, total serine/threonine kinase activity was increased by 10 microM HC and o-p' DDT (59% and 82%, respectively). Maximum eightfold increase was observed with 10 microM o-p' DDT on protein kinase A activity. By contrast, protein kinase C activity was reduced by 10 microM HC and o-p' DDT (40% and 52%, respectively). Endogenous substrate phosphorylation studies demonstrated that slight but significant increase in 24-kDa band labeling was produced in nuclear samples with 1, 10, and 100 microM HC and 100 microM o-p' DDT. Exposition to 100 microM HC increased 85-kDa band labeling. In mitochondrial fractions, 10 microM HC and o-p' DDT increased 24- and 65-kDa bands' labeling. These data indicate that both pesticides affect protein kinase activities in particulate fraction. Nuclear compartmentalization of these compounds, insertion in membranes, and chemical stress production may be associated to the observed effects, thus suggesting deleterious consequences in signaling pathways.

Biomarcadores para el monitoreo de la exposición intrauterina a plaguicidas en comunidades rurales / Biomarkers for monitoring in utero exposure to pesticides in a rural community

La prevención del daño por exposición acontaminantes ambientales requiere identificar biomarcadores que representen una medida del proceso toxicológico antes de la manifestación de daños irreversibles. Considerando la alta vulnerabilidad del período de gestación, este trabajo fue diseñadopara evaluar el impacto de la exposición in utero a plaguicidas organofosforados (OP) y la utilidad de biomarcadores de exposición/efecto en tejidos fácilmente accesibles. Se entrevistaron 342 embarazadas del área frutícola del Alto Valle de Río Negro y Neuquén donde se alternan períodos de 6 meses de fumigación y receso. Se registraron características, hábitos y lugar de residencia materna, parámetros del neonato y de la placenta a término. Los estudios analíticos incluyeron colinesterasas sanguíneas, hemograma de las embarazadas y enzimas placentarias. Los datos fueron analizados por ANOVA regresión y correlación. La actividad de colinesterasa plasmática en época de fumigación disminuyó significativamente (18 %) y presentó asociacióncon la duración de la exposición. Tanto la actividad de acetilcolinesterasa (AChE) como catalasa (CAT) placentariaaumentaron en dicho período (40%) y la edad gestacional disminuyó en dos semanas. El perímetro cefálico aumentó por la residencia rural materna y por la fumigación en el hogar. Este parámetro se asoció con la actividad de CAT. Estos resultados indican que el uso combinado de la AChE y CAT placentarias, enzimas involucradas en eventos adaptativos, serían herramientas útiles en programas de monitoreo ambiental. Asimismo, corroboran que este tejido, el más accesible de la tríada madre – placenta– feto, muestra efectos acumulativos que reflejan el ambiente intrauterino.

Improvement of children’s health requires preventing environmental exposures and identifying predictive biomarkers that represent the toxicological process before irreversibleinjury appears. Considering the high vulnerability of the intrauterine development, this study was designed to investigate the impact of in utero exposure to organophosphate pesticides and biomarkers of early effects in easily asequible tissues. A cohort of 342 women living in the agricultural area of High Valley of Río Negro and Neuquén, where 6 month spraying and non spraying periods are alternated, were interviewed in order to characterize their demographic characteristics and lifestyle habits. Morphometric information about the offspring and placentas were recorded. The analytical studies included pregnant womenhemogram, blood cholinesterases as well as placental enzymes activities. Data were analyzed by ANOVA, regression and correlation. During spraying season plasma cholinesterase diminished significantly (18%) and was associated to exposure length. Inthis period, placental acetylcholinesterase (AChE) and catalase (CAT) increased in a similar extent (40%) and gestational agediminished in two weeks. An increase in cephalic circumference was observed in newborns from women residents in rural areas and also in ones having indoors fumigation habits. This parameter was associated to CAT activity. These results indicate that the combined use of the placental AChE and CAT, enzymes involved in adaptative events, seems to be a useful tool in environmentalmonitoring programmes. Also, they corroborate that this tissue, the most accessible and available component of the triad mother-infant-placenta shows cumulative effects that reflect the intrauterine environment in which the newborn was developed.

Prevención en salud ambiental para poblaciones expuestas a plaguicidas: Entrevistas en comunidades rurales y taller educativo para agentes multiplicadores / Prevention in environmental health for pesticide exposed populations: Interviews in rural communities and workshop for multiplying agents

La zona frutihortícola del alto Valle de Río Negro, en Argentina, constituye una región de exposición residencial a plaguicidas en razón de la dinámica ambiental de estos compuestos y la situación geográfica de sus comunidades. Considerando que los comportamientos preventivos de la población dependen del nivel educativo, este trabajo se planificó con el objetivo de capacitar al personal de salud del hospital de Cinco Saltos, localidad situada en esta región, como agentes multiplicadores en el fortalecimiento de dichas conductas. Previo a la capacitación, se realizaron entrevistas domiciliarias en un asentamiento rural en el que, si bien el 92% de las mujeres estaba alfabetizada, el 81% desconocía el período anual de fumigaciones y sólo el 12% conocía las vías de incorporación. Se registraron conductas de riesgo para el uso doméstico de plaguicidas y para la exposición residencial. Aunque el 95% identificaba a los niños como el grupo social más vulnerable y el 58% estimaba que la exposición materna afecta al feto, solamente el 56 % tomaba precauciones durante el período de fumigación y el 92% utilizaba plaguicidas en el hogar. La encuesta diagnóstica aplicada al personal de salud reveló un importante grado de desconocimiento sobre la exposición indirecta. En base a la información recabada en ambas actividades se dictó un Taller sobre toxicología de plaguicidas cuya acreditación incluyó el diseño de un plan de trabajo para la transferencia hacia las comunidades de riesgo. También se llevaron a cabo acciones para la difusión de esta problemática en medios locales.

In Argentina, the agricultural area of High Valley of Río Negro and Neuquén, is a region of pesticide residential exposition in view of the environmental dynamics of these compounds and the geographic situation of their communities. Considering that people prevention behavior depends on their educational level, this work was designed with the purpose of preparing health workers of Cinco Saltos Hospital, location settled in this area, as multiplying agents to strengthen those conducts. Previously to this preparation, interviews were performed in a rural community where, though 92% of the women were alphabetized, 81% ignored the time covered by the annual fumigation period and only the 12% knew about pesticides routes of absorption. Risk behaviors were registered for domestic use of pesticides and for residential exposure. Although children were identified (95%) as the most vulnerable social group and 58% estimated that maternal exposition affects the fetus, only 56 % took cares during fumigation period and 92% used pesticides at home. A diagnostic poll performed with the health workers revealed an important lack of knowledge about indirect exposition. According to the information obtained in both activities a Workshop about pesticides toxicology was organized, whose approval included the design of a work plan to be carried out with the communities under risk. Additionally, actions were performed to diffuse this theme in local media.