Effects of 3,3′,4,4′,5-pentachlorobiphenyl on human Kv1.3 and Kv1.5 channels

Among the environmental chemicals that may be able to disrupt the endocrine systems of animals and humans are polychlorinated biphenyls (PCBs), a chemical class of considerable concern. PCB consists of two six-carbon rings linked by a single carbon bond, and theoretically, 209 congeners can form, depending on the number of chlorines and their location on the biphenyl rings. Furthermore, 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) exposure also increases nitric oxide production and nuclear factor kappa-light-chain-enhancer of activated B cells binding activity in chondrocytes, thus contributing as an initiator of chondrocyte apoptosis and resulting in thymic atrophy and immunosuppression. This study identified whether cardiac and immune abnormalities from PCB126 were caused by the Kv1.3 and Kv1.5 channels. PCB126 did not affect either the steady-state current or peak current of the Kv1.3 and Kv1.5 channels. However, PCB126 right-shifted the steady-state activation curves of human Kv1.3 channels. These results suggest that PCBs can affect the heart in a way that does not block voltage-dependent potassium channels including Kv1.3 and Kv1.5 directly.

Determinación de Bifenilos policlorados (PCB's) en trabajadores de una empresa del sector eléctrico. Barranquilla - Atlántico, 2017 / Determination of polychlorinated biphenyls (PCB's) in workers of a company in the electricity sector. Barranquilla - Atlantic, 2017

Resumen Introducción: Se determinó Bifenilos Policlorados (PCB's) en sangre y pruebas de función orgánica para evaluación de la salud en trabajadores de una empresa del sector eléctrico. Métodos: Fueron seleccionados 61 trabajadores de la empresa Electricaribe S.A de Barranquilla, 30 expuestos al PCB's y 31 no expuestos, mayores de 18 años, sin patología establecida y que firmaron el consentimiento informado. Se analizó: glicemia, perfil lipidico, creatinina, nitrógeno ureico (BUN), bilirrubinas, fosfatasa alcalina, transaminasas pirúvica y oxaloacética, gamma-glutamil transpeptidasa, T3, T4 hormona estimulante de la tiroides (TSH). Para la detección de PCB's, se utilizó un cromatógrafo de gases HP 5890 series II (Hewlett Packard), detector de captura de electrones (EDC) y columna DB-5 (30m x 0.25mm x 0.25μm). Los datos fueron procesados con el software Minitab 15, nivel de confianza 95%. Resultados: Se encontró que el 100% de trabajadores examinados presentaron cifras de PCB's inferiores al valor límite mínimo de detección del método cromatográfico utilizado: 4 μg/L de PCB's, y evaluaciones clínicas negativas para cualquier daño orgánico. Conclusiones: No se encontró diferencia significativa en los resultados obtenidos entre trabajadores expuestos y no expuestos al PCB's.

Abstract Introduction: Polychlorinated Biphenyls (PCB's) in blood and tests of organic function for evaluation of the health in workers of a company of the electrical sector were determined. Methods: We selected 61 company employees Electricaribe S.A. of Barranquilla, 30 exposed to PCB's and 31 unexposed, over 18 years without established pathology and that signed the informed consent. It was analyzed: glycemia, lipid profile, creatinine, blood urea nitrogen (BUN), bilirrubin, alkaline phosphatase, pyruvic and oxaloacetic transaminase, gamma-glutamyl transpeptidase, T3, T4, thyroid stimulating hormone (TSH). For detection of PCB's, a chromatograph HP 5890 series II gas (Hewlett Packard), electron capture detector (EDC) and DB-5 column (30 m x 0.25 mm x 0.25 μm) was used. The data were processed with Minitab 15 software, 95% confidence level. Results: It was found that 100% of workers examined showed PCB's values lower than the minimum limit value of detection of the chromatographic method used: 4 μg/L of PCB's, and negative clinical evaluations for any organic damage. Conclusions: No significant difference in the results between exposed and unexposed to the PCB's workers.

Descripción de casos registrados en el Centro Nacional de Toxicología (MSPyBS) por exposición debida a incendio de transformadores fuera de uso / Description of cases registered at the National Toxicology Center (MSPyBS) for exposure due to a fire of discarded transformers

En octubre de 2015 el depósito de transformadores fuera de uso de la Administración Nacional de Electricidad (ANDE) ubicado en San Lorenzo (Paraguay), sufrió un incendio de gran magnitud, con destrucción de transformadores, condensadores, y otros materiales que pudieron contener bifenilopoliclorados (PCBs), considerados compuestos orgánicos persistentes, de baja toxicidad aguda, clasificados como cancerígenos (Grupo1) por la Agencia Internacional para la Investigación sobre el cáncer (IARC). Niveles de PCBs en plasma son considerados biomarcadores de exposición al agente químico. El objetivo del trabajo fue describir los casos toxicológicos por exposición al incendio de transformadores fuera de uso, según síntomas manifestados, actividades relacionadas al incendio y resultados del biomarcador de exposición. En este estudio observacional descriptivo de corte transversal, se estudiaron 190 historias clínicas del Centro Nacional de Toxicología (CNTox), hasta 29 días posteriores al incendio, que contaban con resultados del biomarcador determinado por GC/MS. Se detectó el biomarcador hasta 13 días después del incendio. Se observaron niveles plasmáticos de PCBs: <1 ng/ml en 86,84% (165/190) y ≥1 ng/ml 13,16% (25/190). No se registraron casos de cloracné. Pacientes asintomáticos constituyeron 48,94% (93/190), con detección del biomarcador en 56% (14/25). Pacientes con síntomas constituyeron 51,06% (97/190) con detección del biomarcador en 44% (11/25). Teniendo en cuenta la actividad de los pacientes con PCB detectado en plasma fueron bomberos 88% (22/25). Pacientes asintomáticos con niveles detectables de PCBs en plasma como biomarcador de exposición, describe la complementación de datos clínicos con los laboratoriales(AU)

Environmental Pollution and Diabetes / 임상당뇨병

Endocrine disrupting chemicals (EDCs) are exogenous chemicals contained in industrial substances and plasticizers commonly utilized worldwide. Human exposure to such chemicals, particularly at low-doses, is omnipresent, persistent, and occurs in complex mixtures. EDCs include bisphenol A, phthalates, pesticides, and persistent organic pollutants such as polychlorinated biphenyls. Burgeoning epidemiological, animal, and cellular data link environmental EDCs to metabolic dysfunction. In the last three decades, the number of diabetic patients has drastically increased worldwide, with current statistics suggesting that the number will double in the next two decades. There is epidemiological and experimental evidence linking background exposure to a selection of environmental EDCs with diabetes and impaired glucose metabolism. EDC may be related to increased risk of diabetes.

Early-life exposure to endocrine disrupting chemicals associates with childhood obesity

Increasing prevalence of childhood obesity poses threats to the global health burden. Because this rising prevalence cannot be fully explained by traditional risk factors such as unhealthy diet and physical inactivity, early-life exposure to endocrine disrupting chemicals (EDCs) is recognized as emerging novel risk factors for childhood obesity. EDCs can disrupt the hormone-mediated metabolic pathways, affect children’s growth and mediate the development of childhood obesity. Many organic pollutants are recently classified to be EDCs. In this review, we summarized the epidemiological and laboratory evidence related to EDCs and childhood obesity, and discussed the possible mechanisms underpinning childhood obesity and early-life exposure to non-persistent organic pollutants (phthalates, bisphenol A, triclosan) and persistent organic pollutants (dichlorodiphenyltrichloroethane, polychlorinated biphenyls, polybrominated diphenyl ethers, per- and polyfluoroalkyl substances). Understanding the relationship between EDCs and childhood obesity helps to raise public awareness and formulate public health policy to protect the youth from exposure to the harmful effects of EDCs.

Validación de una metodología analítica para determinar bifenilos policlorados en muestras de plasma sanguíneo / Validation of an analytical methodology to determine polychlorinated biphenyls in samples from blood plasma

Resumen Introducción. Los bifenilos policlorados se encuentran entre los cinco contaminantes orgánicos persistentes más tóxicos para los organismos vivos, según la Agency for Toxic Substances and Disease Registry (ATSDR) de los Estados Unidos. Objetivo. Estandarizar y validar un método analítico para la determinación y cuantificación de los bifenilos policlorados indicadores en muestras de plasma sanguíneo, mediante cromatografía de gases acoplada a espectrometría de masas. Materiales y métodos. Se fortificó un pool de plasma para hacer los ensayos en la matriz. Además, se utilizó el material de referencia NIST SRM ® 1958 (Organic Contaminants in Fortified Human Serum, Freeze-Dried) para los ensayos de veracidad y precisión intermedia. Resultados. Los porcentajes de recuperación obtenidos con la metodología estuvieron entre 88,4 y 97,5 %, y el sesgo fue menor del 20 %. Los límites de detección y cuantificación de los bifenilos policlorados indicadores policlorados fueron de 0,04 µg/L y 0,10 µg/L, respectivamente. La linealidad representada por el coeficiente de determinación (R2) varió entre 0,9866 y 0,9886. La precisión expresada como desviación estándar relativa fue menor del 20 % en todo el rango lineal de trabajo (0,5-500 µg/L). Por último, se analizaron 115 muestras de población colombiana de diferentes zonas del país y se encontraron 65 muestras positivas, de las cuales dos estuvieron por encima de los valores de control biológico en humanos (Human Biomonitoring Values, HBM- II): 7,0 µg/L, 2XΣPCB 138, 153, 180 , y otras dos, por encima del HBM-I: 3,5 µg/L, 2XΣPCB 138, 153, 180. Conclusión. El método desarrollado resultó ser preciso para el análisis de los bifenilos policlorados en muestras de plasma sanguíneo y se puede utilizar para el control biológico de estos contaminantes en población colombiana.

Abstract Introduction: Polychlorinated biphenyls are among the five most toxic persistent contaminants for living organisms according to the Agency for Toxic Substances and Disease Registry (ATSDR). Objective: To standardize and validate an analytical method to determine and quantify polychlorinated biphenyl indicators in samples from blood plasma by means of gas chromatography-mass spectrometry. Materials and methods: We fortified a plasma pool to do the matrix assays. Additionally, we used the NIST SRM® 1958 reference material for the veracity and intermediate accuracy assays. Results: Methodology recovery percentages ranged between 88.4 and 97.5%, and the bias was less than 20%. Detection and quantification limits were 0.04 µg/L and 0.10 µg/L, respectively, for all polychlorinated biphenyl indicators. The linearity represented by the determination coefficient (R2 ) varied between 0.9866 and 0.9886. Accuracy, expressed as relative standard deviation was less than 20% in all the linear work range (0.5-500 µg/L). Finally, we analyzed 115 samples from Colombian population in various zones of the country and we found 65 positive samples, from which two samples were above HBM-II (7.0 µg/L, 2XΣPCB 138, 153, 180), and two, above HBM-I (3.5 µg/L, 2XΣPCB 138, 153, 180 ). Conclusion: The method we developed is accurate for PCB analysis in blood plasma samples and could be used for biological surveillance of these contaminants in the Colombian population.

Toxicidade equivalente da atmosfera por dioxinas, furanos e bifenilas policloradas,com uso de duas técnicas de coleta, passiva e ativa / Equivalent toxicity of the atmosphere for dioxins, furans and polychlorinated biphenyls, using two air sampling techniques, passive and active

Introdução: Dioxinas, furanos e bifenilas policloradas são poluentes tóxicos para a saúde humana incluindo riscos de incidência de cânceres, efeitos de neurodesenvolvimento, lesões dérmicas, cloroacne. Estes compostos são poluentes orgânicos persistentes (POPs) que podem ser transportados de longas distâncias da fonte de emissão e se bioacumular em ecossistemas. A atmosfera poluída foi recentemente classificada como carcinogênica para os seres humanos pela Organização Mundial da Saúde, mostrando a importância de sua caracterização, principalmente para compostos tóxicos. Entretanto, técnica de coleta ativa tem custo elevado para POPs, e existem poucos estudos de calibração que validem a substituição. Objetivos: Avaliar a toxicidade equivalente da atmosfera por dioxinas, furanos e bifenilas cloradas, utilizando técnicas de coleta ativa e passiva, e verificar gradiente de concentração nos ambientes urbano, urbano/industrial e de background. Método: Amostras de ar foram coletadas, utilizando coletores ativos e passivos, durante dois períodos consecutivos de quatro meses: de setembro a dezembro de 2014 (período 1) e de maio a agosto de 2015 (período 2) em três cidades de São Paulo, SP, em ambientes urbano, urbano/industrial e de background. Todas as amostras foram extraídas com solução de tolueno:acetona (9:1) em Soxhlet por 24 h e padrões marcados (13C12-PCDD/Fs e 13C12-PCBs) foram adicionados em cada amostra antes do processo de extração. Os extratos foram purificados em coluna de sílica mista (40 por cento H2SO4 e 10 por cento AgNO3) seguida por coluna de alumina. O procedimento analítico foi realizado utilizando HRGC/HRMS (High Resolution Gas Chromatograph/High Resolution Mass Spectrometer) operando em ionização de impacto de elétrons com energia de 35 eV no modo SIM (Select Ion Monitoring) e resolução de 10.000. Resultados mostraram que: (1) existe variação sazonal para concentrações de PCDD/Fs no ar entre os períodos 1 e 2 (p=0,03), enquanto as concentrações de dl-PCBs não foram estatisticamente diferentes nestes períodos (p=0,52); (2) existe gradiente de concentração de PCDD/Fs e dl- PCBs que aumenta na seguinte ordem: background

Introduction: Dioxins, furans and polychlorinated biphenyls are toxic pollutants for human health including risks of cancer incidence, neurodevelopmental effects, dermal lesions, chloracne. These compounds are persistent organic pollutants (POPs) that can be transported to long distances from the emission source and they are bioaccumulated in ecosystems. Recently, the outdoor air pollution were classified as carcinogenic to humans by the World Health Organization, showing the importance of its characterization for toxic compounds. However, active air monitoring has a high cost for POPs, and there is a few calibration studies which support that substitution. Objective: To assess the equivalent toxicity of the atmosphere regarding the measurement of dioxins, furans and polychlorinated biphenyls, using active and passive air samplers, and to evatuate the contrasting concentrations at urban, urban/industrial and background sites. Method: Air samples were collected, using active and passive samplers, over two consecutive periods of four months: from September to December 2014 (period 1) and from May to August 2015 (period 2) at three cities in São Paulo, SP, covering urban, urban/industrial and background sites. All samples were extracted with toluene:acetone (9:1) in a Soxhlet apparatus for 24 hours and surrogate standards (13C12-PCDD/F and 13C12-PCBs) were spiked on each sample media prior to extraction procedure. The extracts were purified on an silica column (40 per cent H2SO4 and 10 per cent AgNO3) followed by an alumina column. The analytical procedure was carried out using HRGC/HRMS (High Resolution Gas Chromatograph/High Resolution Mass Spectrometer) operating in electron impact ionization with an energy of 35 eV in SIM (selected ion monitoring) mode and 10.000 resolution power. Results show that (1) there are seasonal variations for PCDD/F concentrations in air between period 1 and 2 (p=0.03), whereas dl-PCB levels were not statistically different (p=0.52) in those periods. (2) PCDD/F and dl-PCB air levels are in the following order: background

Aislamiento e Identificación de Hongos filamentosos tolerantes a aceites dieléctricos usados y los Bifenilos Policlorados (PCBs) de suelos contaminados / Isolation and Identification of Filamentous Fungi Tolerant to Used Dielectric Oils and Contaminated Soil Polychlorinated biphenyls (PCBs)

Los PCBs por sus propiedades físicas y químicas son usados en diferentes sectores industriales; sus productos de desechos y su almacenamiento inadecuado han contaminado ambientes como suelos y aguas poniendo en peligro la supervivencia en los ecosistemas. Sin embargo, algunos seres vivos son capaces de adaptarse. Los bifenilos policlorados (PCBs) son compuestos orgánicos de hidrocarburos sintéticos formados por dos anillos de benceno unidos por un enlace de carbono; comprenden una clase de 209 compuestos individuales, isómeros y congéneres. Su objetivo fue aislar e identificar hongos filamentosos capaces de tolerar y adaptarse para sobrevivir en condiciones adversas en el ecosistema suelo contaminado por el xenobiótico PCBs, presente en aceites dieléctricos usados (ADU) en un sector industrial de Barranquilla. Los hongos aislados de los géneros Aspergillus sp, Alternaría sp, Phoma sp, Rhizopus sp. sobrevivieron a concentraciones de ADU 20 %, y a 200 ppm de PCBs

PCBs for their physical and chemical properties are used in different industrial sectors; waste products and inadequate storage have polluted environments such as soils and water that endanger ecosystem survival. However, some living beings are able to adapt. Polychlorinated biphenyls (PCBs) are organic synthetic hydrocarbon compounds formed by two benzene rings bonded by a carbon bond, comprise a class of 209 individual compounds, isomers and congeners. Its objective was the isolation and identification of filamentous fungi capable of tolerating and adapting to survive in adverse conditions in the soil ecosystem contaminated by the xenobiotic PCBs, present in used dielectric oils (ADU) in an industrial sector of Barranquilla. The isolated fungi of the genus Aspergillus sp, Alternaria sp, Phoma sp, Rhizopus sp. survived concentrations of 20% ADU, and 200 ppm of PCBs.

The Relationship between the Blood Level of Persistent Organic Pollutants and Common Gastrointestinal Symptoms / 가정의학회지

BACKGROUND: Persistent organic pollutants (POPs) are toxic materials that cannot be broken down naturally and that easily accumulate in the body. Although several studies have attempted to uncover the effects of POPs on the endocrine and nervous systems and on cancer, few focus on the relationship between low-dose POPs and public health. Here, we attempt to determine the relationship between the level of POPs and common gastrointestinal symptoms, including abdominal discomfort, diarrhea, and constipation. METHODS: We recruited 121 subjects who visited Kyungpook National University Medical Center for health screening. Plasma concentrations were evaluated for 40 kinds of POPs including 17 types of polychlorinated biphenyls (PCBs) and 23 types of organochlorine pesticides (OCP). Furthermore, the Korean version of the Rome III criteria was used to identify gastrointestinal symptoms. RESULTS: Based on our results, abdominal discomfort showed an inverse relationship with several PCBs and an inverted U-shaped relationship with several other OCPs including pp-DDD and pp-DDT. The effects of pp-DDD and pp-DDT on abdominal discomfort were similar to those of OCPs on obesity and metabolic syndrome. CONCLUSION: Our results suggest that mild and unspecified gastrointestinal symptoms with no clear causes could be related to POP levels.

The Relationship between the Blood Level of Persistent Organic Pollutants and Common Gastrointestinal Symptoms / 가정의학회지

BACKGROUND: Persistent organic pollutants (POPs) are toxic materials that cannot be broken down naturally and that easily accumulate in the body. Although several studies have attempted to uncover the effects of POPs on the endocrine and nervous systems and on cancer, few focus on the relationship between low-dose POPs and public health. Here, we attempt to determine the relationship between the level of POPs and common gastrointestinal symptoms, including abdominal discomfort, diarrhea, and constipation. METHODS: We recruited 121 subjects who visited Kyungpook National University Medical Center for health screening. Plasma concentrations were evaluated for 40 kinds of POPs including 17 types of polychlorinated biphenyls (PCBs) and 23 types of organochlorine pesticides (OCP). Furthermore, the Korean version of the Rome III criteria was used to identify gastrointestinal symptoms. RESULTS: Based on our results, abdominal discomfort showed an inverse relationship with several PCBs and an inverted U-shaped relationship with several other OCPs including pp-DDD and pp-DDT. The effects of pp-DDD and pp-DDT on abdominal discomfort were similar to those of OCPs on obesity and metabolic syndrome. CONCLUSION: Our results suggest that mild and unspecified gastrointestinal symptoms with no clear causes could be related to POP levels.

Regional analysis of potential polychlorinated biphenyl degrading bacterial strains from China

ABSTRACT Polychlorinated biphenyls (PCBs), the chlorinated derivatives of biphenyl, are one of the most prevalent, highly toxic and persistent groups of contaminants in the environment. The objective of this study was to investigate the biodegradation of PCBs in northeastern (Heilongjiang Province), northern (Shanxi Province) and eastern China (Shanghai municipality). From these areas, nine soil samples were screened for PCB-degrading bacteria using a functional complementarity method. The genomic 16S rDNA locus was amplified and the products were sequenced to identify the bacterial genera. Seven Pseudomonas strains were selected to compare the capacity of bacteria from different regions to degrade biphenyl by HPLC. Compared to the biphenyl content in controls of 100%, the biphenyl content went down to 3.7% for strain P9-324, 36.3% for P2-11, and 20.0% for the other five strains. These results indicate that a longer processing time led to more degradation of biphenyl. PCB-degrading bacterial strains are distributed differently in different regions of China.

Harmful Environmental Factors Leading to Attention-Deficit Hyperactivity Disorder

Attention-deficit hyperactivity disorder (ADHD) is a common, childhood-onset, neuropsychiatric disorder with an estimated prevalence of 2–7.6% in Korean children. Although the etiology of ADHD is not well understood, evidence from genetic factor and environmental factor studies suggests that ADHD results from a gene environmental interaction. In the current study, we reviewed the evidence for and clinical implications of the hypothetical roles of organophosphate pesticides, organochlorine pesticides, polychlorinated biphenyls, phthalate, bisphenol, polyfluoroalkyl chemicals, polycyclic aromatic hydrocarbons, mercury, lead, arsenic, cadmium, manganese, tobacco, alcohol as harmful risk factors in the development of ADHD.

The Relationship between the Blood Level of Persistent Organic Pollutants and Common Gastrointestinal Symptoms / 가정의학회지

BACKGROUND: Persistent organic pollutants (POPs) are toxic materials that cannot be broken down naturally and that easily accumulate in the body. Although several studies have attempted to reveal the effects of POPs on the endocrine and nervous system and on cancer, few studies focus on the relationship between low-dose POPs and public health. We attempted to find a relationship between the level of POPs and common gastrointestinal symptoms, including abdominal discomfort, diarrhea, and constipation. METHODS: We recruited 121 subjects who visited Kyungpook National University Hospital for a health screening. Plasma concentrations were evaluated for 40 kinds of POPs including 17 types of polychlorinated biphenyls and 23 types of organochlorine pesticides. Furthermore, the Korean version of the Rome III criteria was used to identify gastrointestinal symptoms. RESULTS: Our results showed that abdominal discomfort had an inverse relationship with several polychlorinated biphenyls. Moreover, an inverted U-shaped relationship was observed between abdominal discomfort and several other organochlorine pesticides including p,p'-dichlorodiphenyldichloroethane and p,p'-dichlorodiphenyltrichloroethane, and the effects of these pesticides on abdominal discomfort were similar to that of organochlorine pesticides on obesity and metabolic syndrome. CONCLUSION: Our results suggest that mild and unspecified gastrointestinal symptoms with no clear cause could be related to POPs levels.

Efeitos citotóxicos, genotóxicos e epigenéticos do Bisfenol A em células HL-60, MCF-7 e em ratos / Cytotoxic, genotoxic and epigenetics effects of Bisphenol A on HL-60, MCF-7 cells and rats

Bisfenol A (BPA) é um insumo largamente utilizado na produção de plástico policarbonato e amplamente difundido no meio ambiente, levando o ser humano à exposição crônica desde o período intrauterino. A literatura aponta a possibilidade de BPA aumentar o risco de diversos tipos de câncer, mas são necessários estudos que possibilitem o entendimento de mecanismos pelos quais isso pode ocorrer. Neste trabalho foram investigados os efeitos do BPA ou nitro-BPA em células HL-60, MCF-7 e tecidos de ratos. Células HL-60 foram expostas ao BPA ou nitro-BPA nas concentrações de 25, 100 e 250 µM (0,1 % DMSO v/v) por 2, 24 ou 48 horas na presença ou ausência de H2O2 (40 nmol/5 x 104 células). Células MCF-7 foram expostas da mesma forma, sem o uso de H2O2, mas na presença e ausência de agonista (PCB) de receptor Ah. Ratos Sprague-Dawley machos receberam BPA diariamente ao longo de 4 semanas (50 mg/kg de peso corpóreo) por gavagem, na vigência e ausência de diabetes, com subsequente coleta de urina, fígado, rins, medula óssea e sangue. Nos experimentos com as células, a viabilidade, ciclo celular, fragmentação do DNA e a produção intracelular de espécies reativas de oxigênio (ROs) foram avaliadas por citometria de fluxo, a atividade da cadeia respiratória mitocondrial pelo ensaio do XTT, e a atividade de MPO de células HL-60 por ensaio de fluorescência, bem como a produção de •NO. A metilação e hidroximetilação global do DNA e os adutos 8-oxodG, CEdG, 1,N6-εdA, 1,N2-εdG e BPA-Gua no DNA das células, tecidos, meio de cultura e urina foram analisados por HPLC-ESI-MS/MS. O hemograma e mielograma dos animais foram obtidos no Laboratório de Hematologia Experimental da FCF USP. Observou-se que tanto BPA quanto nitro-BPA induziram a geração de ROS em células HL-60 logo após 2h de incubação. BPA levou subsequentemente à perda de atividade da cadeia respiratória mitocondrial, aumento da permeabilidade da membrana plasmática, fragmentação do DNA, parada na fase G2/M do ciclo celular e hipermetilação acompanhada de hipohidroximetilação global do DNA. A citotoxicidade induzida pelas mesmas concentrações de nitro-BPA em células HL-60 foi menos pronunciada, sem perda de atividade da cadeia respiratória mitocondrial, com pouca fragmentação do DNA, mas com parada na fase G0/G1 do ciclo celular e indução de hipohidroximetilação global do DNA na presença de H2O2. Não foi observada a indução de adutos de DNA nas células HL-60 incubadas com BPA, mas sim de CEdG nas células incubadas com nitro-BPA. Os dados obtidos a partir da exposição das células HL-60 a BPA e nitro-BPA nos indicam que as duas moléculas provocam alterações metabólicas distintas nesse tipo celular, independentes da via estrogênica, que levam a alterações predominantemente epigenéticas (BPA) ou genéticas e epigenéticas (nitro-BPA), que podem ter consequências fenotípicas, como progressão maligna, que precisam ser investigadas. Foi observado que as células MCF-7 são mais resistentes que as células HL-60 à citotoxicidade induzida por BPA e nitro-BPA. Como resultado da exposição das células MCF-7 a BPA, houve pequeno aumento da permeabilidade da membrana plasmática (250 µM), indução dos níveis de ROS após 24 h (25 µM) e aumento da população de células em sub G1, ou seja, com DNA fragmentado (100 µM e 250 µM), mas sem alteração do ciclo celular. No caso de nitro-BPA, foi observada parada do ciclo celular em G2/M (25 µM, 100 µM e 250 µM), assim como aumento de permeabilidade da membrana plasmática após 24 h de incubação (25 µM, 250 µM), sem indução de ROS ou aumento de células em sub G1. Entretanto, observou-se aumento dos níveis de CEdG e 8-oxodG no DNA das células incubadas com BPA (100 µM, 250 µM) sem a ativação prévia de receptores Ah. A ativação dos receptores Ah com PCB levou a menor aumento do nível das lesões após as incubações com BPA. A maior resistência das células MCF-7 aos efeitos citotóxicos do BPA está provavelmente relacionada à ação estrogênica desse xenobiótico. A sinalização estrogênica juntamente com o aumento dos níveis de lesões no DNA aumenta a chance de mutações e de transformação maligna. Nas células com ativação do receptor Ah, BPA levou ainda ao aumento da hidroximetilação global, sem alteração da metilação global do DNA. Os animais não diabéticos expostos ao BPA apresentaram quantidades diminuídas de promielócitos, blastos e bastonetes na medula óssea (aplasia medular), sem alteração no hemograma. Houve aumento dos níveis de CEdG no fígado, da metilação e hidroximetilação global do DNA hepático, e não foi observada alteração das marcas epigenéticas e adutos de DNA no rim ou na urina. Os animais diabéticos expostos ao BPA apresentaram aumento do número de eosinófilos e linfócitos na medula óssea, podendo-se sugerir a indução de um estado inflamatório alérgico, e aumento do número total de hemácias circulantes e do hematócrito. Houve aumento dos níveis de CEdG, da metilação e hidroximetilação global do DNA hepático, aumento dos níveis de 8-oxodG no DNA renal, sem alteração das marcas epigenéticas no rim, e não foi observada alteração dos adutos de DNA na urina. Os dados obtidos apontam para a geração de ROS como uma importante via de cito- e genotoxicidade induzidas por BPA. Sua biotransformação para BPA-3,4- quinona nos modelos utilizados parece ter menor importância para os efeitos, uma vez que não foi detectada a lesão BPA-Gua em nenhuma amostra de DNA, meio de cultura das células ou urina dos animais. Alterações metabólicas induzidas por BPA e ROS podem favorecer as alterações das marcas epigenéticas observadas no DNA das células HL-60, MCF-7 e fígado dos animais. Todas essas alterações podem contribuir para a transformação maligna de células expostas ao BPA

Bisphenol A (BPA) is a compound widely used in polycarbonate plastic production and widespread in the environment, humans are chronic exposed to BPA in intrauterine period and entire life. The literature suggests the possibility of BPA increase the risk of developing cancers, but studies are required to enable the understanding of mechanisms by which this can occur. HL -60 cells were exposed to BPA or nitro-BPA at concentrations of 25, 100 and 250 uM (0.1% DMSO v/v) for 2, 24 or 48 hours in presence or absence of H2O2 (40 nmol/5x104 cells), MCF-7 cells followed a similar profile of exposure without the use of H2O2, but in presence or absence of Ah agonist receptor (PCB126). Male Sprague-Dawley rats received BPA daily over 4 weeks (50 mg/kg body weight) by gavage in presence and absence of diabetes, with subsequent collection of urine, liver, kidney, bone marrow and circulating blood. The viability, cell cycle, DNA fragmentation and the intracellular production of reactive oxygen species (ROS) was evaluated by flow cytometry, MPO activity and NO production was evaluated by fluorescence assay for HL- 60 cells, mitochondrial activity by XTT assay, and the global DNA methylation was checked by HPLC-PDA. DNA adducts 8-oxodG, CEdG, 1,N6-εdA, 1,N6-εdG and BPA-Gua were quantified by HPLC- ESI-MS/MS in DNA of cells, culture medium, urine and tissue collected from Sprague-Dawley rats. Blood count and bone marrow examination were obtained in collaboration with Experimental Hematology Laboratory of University of Sao Paulo We observed that both BPA and BPANO2 induced ROS generation in HL- 60 cells after 2 hours of incubation. BPA subsequently led to failure of mitochondrial respiratory chain activity, increased permeability of the plasma membrane, DNA fragmentation, arrest in G2/M phase of cell cycle, DNA hypermethylation with global hipohydroxymethylation. We saw low cytotoxicity in HL-60 cells induced by nitro-bpa n the same concentration, without loss of mitochondrial respiratory chain activity, discrete DNA fragmentation, but leading cell cycle to stopping at G0/G1 phase, and induction of DNA global hypermethylation. No lesions were observed in the DNA of HL-60 cells.The results obtained from the exposure of HL-60 cells to BPA and nitro-BPA indicate that these two molecules induce different metabolic abnormalities in this cell line, independent of estrogen pathway, leading to changes in epigenetic (BPA) or genetic and epigenetic (nitro-BPA) profile, that can induce phenotypic consequences such as malignant progression. It was observed along the study that MCF-7 cells are more resistant than HL-60 cells to cell damage induced by BPA and nitro-BPA. As a result of MCF-7 cells exposure to BPA, we saw a slight increase in membrane permeability (250 mM), ROS generation after 24h (25 mM) and increase in cell population in sub G1, so we had DNA fragmentation (100 uM and 250 uM), but with no effect on cell cycle. However, we observed increased levels of CEdG and 8-oxodG on DNA of cells incubated with BPA (100 uM, 250 mM) without prior activation of Ah receptors. The activation of Ah receptors with PCB took a small increase in the level of DNA lesions after incubations with BPA. MCF-7 cells resistance to the cytotoxic effects of BPA is probably related to estrogen action of this compound. Estrogen signaling in addition with the increased levels of DNA damage increases the chance of mutations and malignant transformation. In cells with Ah receptor activation, BPA also led to increased DNA global hydroxymethylation, without changing the global DNA methylation. Nondiabetic animals exposed to BPA had decreased amounts of promyelocytes, blasts and rods in the bone marrow, with any change in blood count. There were an increase of CEdG levels in liver, methylation and global hydroxymethylation on hepatic DNA, and was observed any alteration on epigenetic markers and DNA adducts in kidney or urine. On the other hand diabetic animals exposed to BPA showed increased numbers of eosinophils and lymphocytes in bone marrow, suggesting the induction of an allergic inflammatory state. There were increased levels of CEdG, methylation and global hydroxymethylation on hepatic DNA, increased 8-oxodG levels on kidney DNA without changing epigenetic markers, was not observed DNA adducts in urine. The data obtained indicate that the generation of ROS could be the major route of cytotoxic and genotoxic induced by BPA exposure. BPA biotransformation to BPA-3,4-quinone used in the models seem to have poor effects, since we was not detected BPA-Gua lesion in any DNA sample, culture medium of cells or urine of the animals. Metabolic changes induced by BPA and ROS can enable changes in epigenetic markers observed in the DNA of HL-60 cells, MCF-7 and liver tissue. All these changes may contribute to malignant transformation of cells that were exposed to BPA

Bioleaching of gold, copper and nickel from waste cellular phone PCBs and computer goldfinger motherboards by two Aspergillus nigerstrains

In an effort to develop alternate techniques to recover metals from waste electrical and electronic equipment (WEEE), this research evaluated the bioleaching efficiency of gold (Au), copper (Cu) and nickel (Ni) by two strains of Aspergillus niger in the presence of gold-plated finger integrated circuits found in computer motherboards (GFICMs) and cellular phone printed circuit boards (PCBs). These three metals were analyzed for their commercial value and their diverse applications in the industry. Au-bioleaching ranged from 42 to 1% for Aspergillus niger strain MXPE6; with the combination of Aspergillus niger MXPE6 + Aspergillus niger MX7, the Au-bioleaching was 87 and 28% for PCBs and GFICMs, respectively. In contrast, the bioleaching of Cu by Aspergillus niger MXPE6 was 24 and 5%; using the combination of both strains, the values were 0.2 and 29% for PCBs and GFICMs, respectively. Fungal Ni-leaching was only found for PCBs, but with no significant differences among treatments. Improvement of the metal recovery efficiency by means of fungal metabolism is also discussed.

Effectiveness of Limberg and Karydakis flap in recurrent pilonidal sinus disease

OBJECTIVE: Sacrococcygeal pilonidal sinus is common in young men and may recur over time after surgery. We investigated whether a factor exists that can aid in the determination of the preferred technique between the early Limberg flap and Karydakis flap techniques for treating recurrent pilonidal sinus. MATERIALS AND METHODS: This prospective and randomized study enrolled 71 patients with recurrent pilonidal sinus in whom the Limberg flap or Karydakis flap techniques were applied for reconstruction after excision. Patients were divided into two groups as follows: 37 patients were treated with the Limberg flap technique and 34 patients were treated with the Karydakis flap technique. Fluid collection, wound infection, flap edema, hematoma, partial wound separation, return to daily activities, pain score, complete healing time, painless seating and patient satisfaction were compared between the groups. ClinicalTrial.gov: NCT02287935. RESULTS: The development rates of total fluid collection, wound infection, flap edema, hematoma, and partial wound separation were 9.8%, 16%, 7%, 15% and 4.2%, respectively; total flap necrosis was not observed in any patient (p<0.001). During the average follow-up of 28 months, no patients (0%) developed recurrent disease. The two groups differed with respect to early surgical complications (p<0.001). CONCLUSION: In this study, use of the Limberg flap was associated with lower complication rates, shorter length of hospital stay, early return to work, low pain score, high patient satisfaction and better complete healing duration. Therefore, we recommend the Limberg flap for treatment of recurrent pilonidal sinus. .

The reduction of serum aminotransferase levels is proportional to the decline of the glomerular filtration rate in patients with chronic kidney disease

OBJECTIVE: This study sought to determine the serum aminotransferase levels of patients with predialysis chronic kidney disease and establish their relationships with serum creatinine levels and glomerular filtration rate. METHODS: Patients with chronic kidney disease were evaluated between September 2011 and May 2012. Aminotransferase and creatinine serum levels were measured using an automated kinetic method, and glomerular filtration rates were estimated using the Cockroft-Gault and Modification of Diet in Renal Disease formulas to classify patients into chronic kidney disease stages. RESULTS: Exactly 142 patients were evaluated (mean age: 64±16 years). The mean creatinine serum level and glomerular filtration rate were 3.3±1.2 mg/dL and 29.1±13 mL/min/1.73 m2, respectively. Patients were distributed according to their chronic kidney disease stages as follows: 3 (2.1%) patients were Stage 2; 54 (38%) were Stage 3; 70 (49.3%) were Stage 4; and 15 (10.5%) were Stage 5. The mean aspartate aminotransferase and alanine aminotransferase serum levels showed a reduction in proportion to the increase in creatinine levels (p=0.001 and p=0.05, respectively) and the decrease in glomerular filtration rate (p=0.007 and p=0.028, respectively). Alanine aminotransferase and aspartate aminotransferase serum levels tended to be higher among patients classified as stage 2 or 3 compared with those classified as stage 4 or 5 (p=0.08 and p=0.06, respectively). CONCLUSIONS: The aspartate aminotransferase and alanine aminotransferase serum levels of patients with predialysis chronic kidney disease decreased in proportion to the progression of the disease; they were negatively correlated with creatinine levels and directly correlated with glomerular filtration rate. .

Organochlorine compound levels in fertile and infertile women from Rio de Janeiro, Brazil / Níveis de substâncias organocloradas em mulheres férteis e inférteis do Rio de Janeiro, Brasil

OBJECTIVE: The aim of the study was quantify organochlorine compounds in women seeking for infertility treatment (n = 15) and in spontaneously pregnant ones (n = 21). MATERIALS AND METHODS: A questionnaire was applied regarding lifestyle, occupational and reproductive history. Blood samples were collected from both groups. RESULTS: From the pesticides studied, pp'DDE was detected in 100% of infertile women, at higher mean levels than in pregnant women (3.02 mcg/L vs. 0.88 mcg/L; p = 0.001; power of 69%), without correlation with the etiology of infertility. Levels of the polychlorinated biphenyls (PCBs) were low, with positive samples in 100% in the infertile women for PCBs 138, 153, 180, while in pregnant women, they were 85.7% for congeners 138 and 153. Only PCB180 showed significance, with frequency of 71.4% (p = 0.019). CONCLUSIONS: The risk factors for female infertility were: age, consumption of untreated water and of canned foods. Exposure to the most prevalent organochlorine compounds described in literature was confirmed in the study, indicating that pp'DDE may adversely influence female fertility.

OBJETIVO: O estudo teve como objetivo quantificar as substâncias organocloradas em mulheres buscando tratamento para infertilidade (n = 15) e que espontaneamente engravidaram (n = 21). MATERIAIS E MÉTODOS: Foi aplicado questionário considerando estilo de vida, história ocupacional e reprodutiva. Amostras de sangue foram obtidas em ambos os grupos. RESULTADOS: Dos pesticidas, pp'DDE foi detectado em 100% das inférteis, com níveis maiores que nas grávidas (3,02 mcg/L vs. 0,88 mcg/L; p = 0,001; poder 69%), sem correlação na etiologia da infertilidade. Os níveis de detecção das bifenilas policloradas (PCBs) foram baixos, com 100% de positividade das amostras nas inférteis para os PCBs 138, 153, 180, e de 85,7% nas grávidas para os congêneres 138 e 153. Apenas PCB180 mostrou significância na frequência de 71,4% (p = 0,019). CONCLUSÕES: Os fatores de risco para infertilidade feminina foram: idade, consumo de água não tratada e alimentos enlatados. A exposição aos organoclorados mais prevalentes descritos na literatura foi confirmada no estudo, indicando que pp'DDE pode influenciar adversamente a fertilidade feminina.

Tóxicos ambientales y su efecto sobre el neurodesarrollo / [Environmental toxic and its effect on neurodevelopment].

Neurodevelopmental disorders are the result of a disturbance of brain function. They are frequent, with varied symptomatology, manifest themselves at different times of life and tend to be persistent with impact at the individual, family and social level. The association of these disorders with genetic entities is low. Although the research supports a mode of genetic inheritance, epigenetic factors and environmental factors can play an important role. In recent years there was a striking increase of these disorders especially attention deficit hyperactivity disorders and pervasive development disorder. Environmental factors such as the intoxication of the fetus by especially heavy metals lead and mercury are to blame in some children, of these disorders. Other substances of wide use, little degradation and maintenance in the food chain as pesticides, polychlorinated biphenyls and now the recycling of electronic waste put especially infants and children at risk, and even more so in the developing countries.

The effect of the structure of polychlorinated biphenyls on their hydroxylation, oxidation, and glutathionyl conjugation reactions / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To compare the nature of the metabolites formed from the phase I metabolism (hydroxylation and oxidation) and phase II metabolism (glutathionyl conjugation) of PCBs that have different chlorine substitution patterns. To discuss the structure-activity relationships and metabolic mechanisms of PCBs.</p><p><b>METHODS</b>4-Cl-biphenyl (PCB3), 4,4'-Cl-biphenyl (PCB15), 3,4,3',4'-Cl-biphenyl (PCB77) were used for in vitro metabolic study. LC/MS and UV-Vis studies were performed for metabolites identification.</p><p><b>RESULTS</b>The cytochrome P-450 catalyzed hydroxylation rate decreased as the number of chlorine substitutions increased. In this reaction, PCB3 was fully metabolized, approximately half of the PCB15 was metabolized and PCB77 was not metabolized at all. The oxidation rate of PCB15-HQ was higher than that of PCB3-HQ under various oxidation conditions. The LC/MS and UV-Vis data suggest that in the conjugation reaction of PCB15-Q and GSH, the Michael addition reaction occurs preferentially over the displacement reaction.</p><p><b>CONCLUSION</b>The metabolic profiles of polychlorinated biphenyls (PCBs) are dramatically affected by chlorine substitution patterns. It is suggested that the metabolic profiles of PCBs are related to their chlorine substitution patterns, which may have implications for the toxicity of PCB exposure.</p>