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1.
Crit Rev Oncol Hematol ; 150: 102950, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32339980

RESUMO

Incidence and mortality of thyroid cancer are increasing, thus making mandatory to improve the knowledge of disease etiology. The hypothesis of a role for anthropogenic chemicals is raising wide consideration. A series of occupational studies revealed that job exposures with high risk of chemical contamination were usually more prone to thyroid cancer development. These include shoe manufacture, preserving industry, building activities, pulp/papermaker industry and the wood processing, agricultural activities, and other work categories characterized by contact with chemicals, such as chemists and pharmacists. However, such epidemiological analyses cannot define a causal relationship. Thyroid-disrupting activity has emerged for a broad set of anthropogenic chemicals, with the best evidence being gained for polychlorinated biphenyls, polybrominated diphenyl ethers, dioxins, bisphenols, phthalates, pesticides, and heavy metals. A series of case-control studies, assessing exposure to thyroid-disrupting agents, as measured on biological matrices, have been recently performed providing the following insights: a) positive relationship with thyroid cancer was found for phthalates, bisphenols, the heavy metals cadmium, copper, and lead; b) polybrominated diphenyl ethers exposure showed no relationship with thyroid cancer c) controversial results were reported for polychlorinated biphenyls and pesticides. However, such studies cannot demonstrate the causal link with disease occurrence, as exposure is assessed after tumour development. Studies with different methodological approach are therefore required for defining the role of anthropogenic environmental chemicals in thyroid carcinogenesis.


Assuntos
Dioxinas/efeitos adversos , Poluentes Ambientais/efeitos adversos , Praguicidas/efeitos adversos , Bifenil Polibromatos/efeitos adversos , Bifenilos Policlorados/efeitos adversos , Glândula Tireoide/efeitos dos fármacos , Neoplasias da Glândula Tireoide/induzido quimicamente , Monitoramento Ambiental , Poluentes Ambientais/metabolismo , Éteres Difenil Halogenados , Humanos , Praguicidas/metabolismo , Fenóis/toxicidade , Éteres Fenílicos/efeitos adversos , Glândula Tireoide/fisiologia
2.
BMC Public Health ; 20(1): 64, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941472

RESUMO

BACKGROUND: Health risks linked with dioxin in fish remain a complex policy issue. Fatty Baltic fish contain persistent pollutants, but they are otherwise healthy food. We studied the health benefits and risks associated with Baltic herring and salmon in four countries to identify critical uncertainties and to facilitate an evidence-based discussion. METHODS: We performed an online survey investigating consumers' fish consumption and its motivation in Denmark, Estonia, Finland, and Sweden. Dioxin and methylmercury concentrations were estimated based on Finnish studies. Exposure-response functions for several health endpoints were evaluated and quantified based on the scientific literature. We also quantified the infertility risk of men based on a recent European risk assessment estimating childhood dioxin exposure and its effect on sperm concentration later in life. RESULTS: Baltic herring and salmon contain omega-3 fatty acids and vitamin D, and the beneficial impact of these fishes on cardiovascular diseases, mortality, and the risk of depression and cancer clearly outweighs risks of dioxins and methylmercury in people older than 45 years of age and in young men. Young women may expose their children to pollutants during pregnancy and breast feeding. This study suggests that even in this critical subgroup, the risks are small and the health benefits are greater than or at least similar to the health risks. Value of information analysis demonstrated that the remaining scientific uncertainties are not large. In contrast, there are several critical uncertainties that are inherently value judgements, such as whether exceeding the tolerable weekly intake is an adverse outcome as such; and whether or not subgroup-specific restrictions are problematic. CONCLUSIONS: The potential health risks attributable to dioxins in Baltic fish have more than halved in the past 10 years. The new risk assessment issued by the European Food Safety Authority clearly increases the fraction of the population exceeding the tolerable dioxin intake, but nonetheless, quantitative estimates of net health impacts change only marginally. Increased use of small herring (which have less pollutants) is a no-regret option. A more relevant value-based policy discussion rather than research is needed to clarify official recommendations related to dioxins in fish.


Assuntos
Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/análise , Peixes , Contaminação de Alimentos/análise , Alimentos Marinhos/análise , Adulto , Animais , Criança , Dioxinas/efeitos adversos , Dioxinas/análise , Estudos de Avaliação como Assunto , Feminino , Humanos , Recém-Nascido , Infertilidade Masculina/induzido quimicamente , Masculino , Compostos de Metilmercúrio/efeitos adversos , Compostos de Metilmercúrio/análise , Valor Nutritivo , Gravidez , Medição de Risco , Salmão , Países Escandinavos e Nórdicos , Doenças Dentárias/induzido quimicamente
3.
Toxicol Lett ; 320: 58-63, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31805342

RESUMO

The current study uses the metabolic probe, antipyrine, and AhRR transcript expression (qRT-PCR) to examine the impact of the AhRR (565C > G or Pro185Ala, rs2292596) genetic polymorphism upon CYP1A2 inducibility in an established cohort of male firefighters with exposure to dioxin-like chemicals. The lipid adjusted concentrations of 29 dioxin and dioxin-like congeners were measured in serum. Possession of the G allele (CG and GG genotypes) was correlated with high expression AhRR transcript and lower CYP1A2 induction than found in individuals homozygous for CC. The induction of CYP1A2 was dioxin-dependent among carriers of the G allele. Multivariate models indicated that CYP1A2 activity, detected as urinary 3-hydroxymethylantipyrine, was significantly correlated with cotinine concentration and for those currently working as firefighters, dioxin body burden (ß = 0.54, p = 0.041). The efficacy of the AhRR in regulating the AhR signaling pathway is influenced by the AhRR (565C > G) polymorphism. Our study of firefighters using the induction of CYP1A2 as an indicator suggest that G allele proteins have variable AhR repressor activity which is manifested in a dioxin-dependent manner. These results provide evidence of metabolic differences that may affect susceptibility to dioxin-mediated health effects.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Indutores do Citocromo P-450 CYP1A2/efeitos adversos , Citocromo P-450 CYP1A2/biossíntese , Dioxinas/efeitos adversos , Bombeiros , Exposição Ocupacional/efeitos adversos , Polimorfismo Genético , Proteínas Repressoras/genética , Antipirina/análogos & derivados , Antipirina/urina , Indução Enzimática , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
4.
Int J Mol Sci ; 20(12)2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31212893

RESUMO

Dioxins are ubiquitous and persistent environmental contaminants whose background levels are still reason for concern. There is mounting evidence from both epidemiological and experimental studies that paternal exposure to the most potent congener of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), can lower the male/female ratio of offspring. Moreover, in laboratory rodents and zebrafish, TCDD exposure of parent animals has been reported to result in reduced reproductive performance along with other adverse effects in subsequent generations, foremost through the paternal but also via the maternal germline. These impacts have been accompanied by epigenetic alterations in placenta and/or sperm cells, including changes in methylation patterns of imprinted genes. Here, we review recent key studies in this field with an attempt to provide an up-to-date picture of the present state of knowledge to the reader. These studies provide biological plausibility for the potential of dioxin exposure at a critical time-window to induce epigenetic alterations across multiple generations and the significance of aryl hydrocarbon receptor (AHR) in mediating these effects. Currently available data do not allow to accurately estimate the human health implications of these findings, although epidemiological evidence on lowered male/female ratio suggests that this effect may take place at realistic human exposure levels.


Assuntos
Dioxinas/efeitos adversos , Poluentes Ambientais/efeitos adversos , Exposição Materna/efeitos adversos , Herança Materna , Herança Paterna , Efeitos Tardios da Exposição Pré-Natal , Animais , Biomarcadores , Dioxinas/metabolismo , Poluentes Ambientais/metabolismo , Poluição Ambiental , Epigênese Genética , Feminino , Humanos , Masculino , Gravidez
5.
Acta Biochim Pol ; 66(2): 123-127, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31125391

RESUMO

The notion of 'civilization diseases' is used to describe certain ailments whose aetiology is difficult to explain based on the knowledge about the functioning of the body and its metabolism. Only studies at the cellular level, on biochemical changes shed light on the causes of some diseases described as civilization diseases (cancers, cardiovascular and respiratory diseases, obesity, psychomotor disorders in children and an increase in the frequency of malformations). The factors whose incontestable influence on the increase in the frequency of occurrence of various 'civilization diseases' has been proved are persistent organic pollutants, among others belonging to the group of organohalogen compounds. Among organohalogen pollutants one needs to distinguish organochlorine compounds, which have been used as pesticides, and pollution emitted by various industries such as dioxins and furans, polychlorinated biphenyls, and polybrominated organic compounds used as flame retardants and perfluoroalkylated substances, which are characterized by high chemical and thermal stability as well as high surface activity due to which they may be widely used as oleophobic and hydrophobic factors.


Assuntos
Exposição Ambiental/efeitos adversos , Neoplasias/etiologia , Obesidade/etiologia , Aleitamento Materno/efeitos adversos , Pré-Escolar , Dioxinas/efeitos adversos , Dioxinas/sangue , Feminino , Retardadores de Chama/efeitos adversos , Retardadores de Chama/análise , Furanos/efeitos adversos , Furanos/sangue , Humanos , Hidrocarbonetos Clorados/efeitos adversos , Hidrocarbonetos Clorados/análise , Lactente , Recém-Nascido , Masculino , Praguicidas/efeitos adversos , Praguicidas/análise , Bifenilos Policlorados/efeitos adversos , Bifenilos Policlorados/sangue
6.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(4): 365-370, 2019 Apr 06.
Artigo em Chinês | MEDLINE | ID: mdl-30982269

RESUMO

Objective: To study the pollution status of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCB), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in cord blood of newborns in an e-waste dismantling area of Guangdong Province. Methods: We recruited 20 eligible mothers and newborns who could meet the inclusion criteria in local hospitals of Guiyu in 2007. The inclusion criteria included directly engaged in dismantling e-waste during pregnancy and within 1 year before pregnancy; living in the e-waste dismantling workshops or the distance between living place and the e-waste dismantling areas was ≤200 m; the father of newborn was directly engaged in electronic waste dismantling for more than 1 year; the frequency of visiting the e-waste dismantling workshop during pregnancy was ≥3 times in a week. Questionnaires and physical examinations were performed on maternal and neonatal, and cord blood was collected from newborns to detect PCDD/Fs, PCB and PBDE. The concentration level of organic pollutants was corrected by the blood lipid content, and the total toxicity equivalent was calculated. The correlation between three compounds was analyzed by Spearman correlation. Results: The mothers of the 20 newborns were (23.45±3.27) years old and lived for more than 5 years. The number of one parent engaged in e-waste dismantling, the mother or father smoking, and parent engaged in e-waste dismantling work were 3, 13, 15 and 19, respectively. The weight of newborns ranged from 2.5 to 3.6 kilogram and the Apgar score was 10 points. No adverse birth outcomes such as preterm birth, malformation or stillbirth were found. The median (maximum, minimum) concentration of PCBs, PCDD/Fs and PBDEs in cord blood were 263.22 (328.29, 244.19), 38.42 (147.49, 12.68), 39.33 (265.11, 14.81) pg/g lipid, respectively. The median (maximum, minimum) of toxic equivalence concentrations of PCDD/Fs and PCB were 3.94 (9.24, 2.69) and 15.95 (26.64, 9.28) pg TEQ/g lipid. PBDE, the proportion of PBDE, PCB and PCDD/Fs in cord blood was 50.41%, 49.25% and 0.34%, respectively. PCBs and PBDEs were positively correlated (r=0.733, P=0.039). Conclusion: The high concentrations of PCDD/Fs, PCB, and PBDE were detected in the e-waste dismantling area. It is recommended that the risk of such substances on the health of local people should be assessed in a timely manner.


Assuntos
Dioxinas/sangue , Resíduo Eletrônico , Exposição Ambiental , Poluentes Ambientais/sangue , Sangue Fetal/metabolismo , Bifenilos Policlorados/sangue , Dibenzodioxinas Policloradas/sangue , Reciclagem , Adulto , Dioxinas/efeitos adversos , Feminino , Humanos , Recém-Nascido , Exposição Materna , Gravidez , Inquéritos e Questionários , Adulto Jovem
7.
Artigo em Japonês | MEDLINE | ID: mdl-30787254

RESUMO

There is mounting concern about the effects of early-life exposure to chemical substances on children's health and development. We summarize the past and ongoing birth cohort studies carried out worldwide on the association between environmental exposure and children's health. Our PubMed search with the keywords 'birth cohort' revealed that the number of articles jumped from 200-300 in the 1980s to over 1,000 in the 1990s. Many of these articles reported elevated risks to children's health posed by chemical exposure owing their vulnerability. At the same time, policies implemented to reduce exposure to lead and dioxins were successful in the past few decades. Research also demonstrated that intervention to reduce exposure to certain chemicals whose exposure routes were well documented was also successful. We summarize the effects of early-life exposure to chemical substances on children's health and development. Our findings will hopefully help safeguard the environment in which future generations grow and live.


Assuntos
Desenvolvimento Infantil , Saúde da Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/prevenção & controle , Substâncias Perigosas/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Dioxinas/efeitos adversos , Dioxinas/sangue , Monitoramento Ambiental , Feminino , Saúde Global , Humanos , Lactente , Recém-Nascido , Chumbo/efeitos adversos , Chumbo/sangue , Masculino , Metanálise como Assunto , Gravidez , PubMed , Risco , Fatores de Tempo
8.
Chimia (Aarau) ; 72(10): 690-696, 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-30376917

RESUMO

Polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) summarized as dioxins, as well as polychlorinated biphenyls (PCBs) are persistent, bio-accumulative and toxic environmental contaminants. Over 95% of human exposure to these problematic chemicals occurs via the ingestion of fatty rich food like meat and meat products, fatty fish, as well as milk and dairy products. Several major food and feed contamination incidents in Europe during the years 1997 and 2010 revealed the necessity of establishing food and feed monitoring programs for dioxins and PCBs. Various monitoring programs carried out by the Federal Office of Public Health (FOPH) and the Federal Food Safety and Veterinary Office (FSVO), suggest that cattle from extensive farming (suckler cow husbandry) exhibited higher levels of dioxin-like PCBs (dl-PCBs) and exceeded with higher frequency the permitted maximum levels (ML) when compared to conventional raised cattle. The reasons for the higher levels are possibly due to higher levels of PCBs in green fodder (pasture, silage, and hay) when compared to the concentrated feed used in conventional farming. Additionally, an increased uptake of soil, which is known to be a risk matrix for the uptake of dioxins and PCBs in grazing animals, leads to elevated contaminant levels in the suckler cows and hence their calves. Furthermore, PCB point sources present on a farm from older building and construction materials (e.g. PCB-containing wall paints) might result in very high contamination of the animals and the meat produced from them.


Assuntos
Dioxinas/análise , Contaminação de Alimentos/análise , Carne/análise , Bifenilos Policlorados/análise , Agricultura , Ração Animal/análise , Animais , Bovinos , Dioxinas/efeitos adversos , Humanos , Carne/efeitos adversos , Bifenilos Policlorados/efeitos adversos
9.
Environ Int ; 121(Pt 1): 71-84, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30179766

RESUMO

A 1976 chemical factory explosion near Seveso, Italy exposed residents to high levels of 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD or dioxin). Dioxin is a known human carcinogen and potent endocrine disruptor. It is highly lipophilic and has a long half-life in humans. Much of what we know and can learn about the risks of dioxin exposure on human health arose from the tragic circumstances of Seveso. This review aims to describe the Seveso accident, summarize the results of 40 years of research on the health of the Seveso population since the accident, and discuss next-stage research on the health of Seveso residents, their children, and grandchildren.


Assuntos
Dioxinas , Exposição Ambiental , Vazamento Acidental em Seveso , Animais , Dioxinas/efeitos adversos , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Itália , Troca Materno-Fetal , Gravidez , Pesquisa
10.
BMC Pediatr ; 18(1): 213, 2018 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-29976197

RESUMO

BACKGROUND: We previously reported that perinatal dioxin exposure increased autistic traits in children living in dioxin-contaminated areas of Vietnam. In the present study, we investigated the impact of dioxin exposure on children's eating behavior, which is often altered in those with developmental disorders. METHODS: A total of 185 mother-and-child pairs previously enrolled in a birth cohort in dioxin-contaminated areas participated in this survey, conducted when the children reached 3 years of age. Perinatal dioxin exposure levels in the children were estimated using dioxin levels in maternal breast milk after birth. Mothers were interviewed using the Children's Eating Behaviour Questionnaire (CEBQ). A multiple linear regression model was used to analyze the association between dioxin exposure and CEBQ scores, after controlling for covariates such as location, parity, maternal age, maternal education, maternal body mass index, family income, children's gestational age at delivery, and children's age at the time of the survey. A general linear model was used to analyze the effects of sex and dioxin exposure on CEBQ scores. RESULTS: There was no significant association between most dioxin congeners or toxic equivalencies of polychlorinated dibenzo-p-dioxins/furans (TEQ-PCDDs/Fs) and CEBQ scores in boys, although significant associations between some eating behavior sub-scores and 1,2,3,4,6,7,8,9-octachlorodibenzofuran were observed. In girls, there was a significant inverse association between levels of TEQ-PCDFs and enjoyment of food scores and between levels of TEQ-PCDFs and TEQ-PCDDs/Fs and desire to drink scores. Two pentachlorodibenzofuran congeners and 1,2,3,6,7,8-hexachlorodibenzofuran were associated with a decreased enjoyment of food score, and seven PCDF congeners were associated with a decreased desire to drink score. The adjusted mean enjoyment of food score was significantly lower in children of both sexes exposed to high levels of TEQ-PCDFs. There was, however, a significant interaction between sex and TEQ-PCDF exposure in their effect on desire to drink scores, especially in girls. CONCLUSIONS: Perinatal exposure to dioxin can influence eating behavior in children and particularly in girls. A longer follow-up study would be required to assess whether emotional development that affects eating styles and behaviors is related to dioxin exposure.


Assuntos
Dioxinas/efeitos adversos , Poluentes Ambientais/efeitos adversos , Comportamento Alimentar/efeitos dos fármacos , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal , Adulto , Animais , Apetite/efeitos dos fármacos , Pré-Escolar , Deficiências do Desenvolvimento/induzido quimicamente , Dioxinas/análise , Feminino , Seguimentos , Herbicidas/efeitos adversos , Herbicidas/análise , Humanos , Leite Humano/química , Gravidez , Fatores Sexuais , Inquéritos e Questionários , Paladar/efeitos dos fármacos , Vietnã
11.
Hum Mutat ; 39(10): 1384-1392, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29969170

RESUMO

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) or dioxin, is commonly considered the most toxic man-made substance. Dioxin exposure impacts human health and diseases, birth defects and teratogenesis were frequently observed in children of persons who have been exposed to dioxin. However, the impact of dioxin on human mutation rate in trios has not yet been elucidated at the whole genome level. To identify and characterize the genetic alterations in the individuals exposed to dioxin, we performed whole genome sequencing (WGS) of nine Vietnamese trios whose fathers were exposed to dioxin. In total, 846 de novo point mutations, 26 de novo insertions and deletions, 4 de novo structural variations, and 1 de novo copy number variation were identified. The number of point mutations and dioxin concentrations were positively correlated (P-value < 0.05). Considering the substitution pattern, the number of A > T/T > A mutation and the dioxin concentration was positively correlated (P-value < 0.05). Our analysis also identified one possible disease-related mutation in LAMA5 in one trio. These findings suggested that dioxin exposure might affect father genomes of trios leading to de novo mutations in their children. Further analysis with larger sample sizes would be required to better clarify mutation rates and substitution patterns in trios caused by dioxin.


Assuntos
Dioxinas/efeitos adversos , Estudo de Associação Genômica Ampla , Mutação , Exposição Paterna/efeitos adversos , Sequenciamento Completo do Genoma , Alelos , Criança , Dioxinas/sangue , Feminino , Células Germinativas/metabolismo , Mutação em Linhagem Germinativa , Humanos , Masculino , Espectrometria de Massas , Taxa de Mutação , Polimorfismo de Nucleotídeo Único , Veteranos
12.
Nihon Eiseigaku Zasshi ; 73(2): 110-114, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-29848860

RESUMO

The brain and mind are not only determined genetically but are also nurtured by environmental stimuli in early life. However, the relationship between early life environment and phenotypes in adulthood remains elusive. Using the IntelliCage-based competition task for group-housed mice, we previously found that maternal exposure to a low dose of an environmental pollutant, dioxin, resulted in abnormal social behavior, that is, low competitive dominance, which is defined by decreased occupancy of limited resource sites under highly competitive circumstances. Although we were unable to identify which behavioral phenotype applies to abnormalities such as "human social nature", we found signs of hypoactivation of the medial prefrontal cortex, as seen in patients with autism spectrum disorder. In addition, another model of environmental factors, repeated isolation during development, and that of genetic factors including mice with neuronal heterotopia, which refers to brain malformations resulting from deficits of neuronal migration, showed low competitive dominance. These results indicate that a constitutive approach to capture the neural network of the whole brain is necessary especially in cases where the temporal gap of causal relationships is large such as DOHaD.


Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Exposição Materna/efeitos adversos , Comportamento Social , Meio Social , Animais , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/fisiopatologia , Comportamento Animal , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Comportamento Competitivo , Dioxinas/efeitos adversos , Poluentes Ambientais/efeitos adversos , Feminino , Humanos , Camundongos , Modelos Animais , Rede Nervosa/fisiologia
13.
Nihon Eiseigaku Zasshi ; 73(2): 164-177, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-29848869

RESUMO

Since "Our Stolen Future" by Theo Colborn was published in 1996, global interest on the impact of chemical substances, such as the endocrine-disrupting action of chemicals, has increased. In Japan, "The Hokkaido Study on Environment and Children's Health: Malformation, Development and Allergy" was launched in 2001. It was a model of Japan Environment and Children's Study of the Ministry of the Environment. In a large-scale, Hokkaido cohort, we obtained the consent of 20,926 mothers at the organogenesis stage with the cooperation of 37 obstetrics clinics in Hokkaido. We tracked the effects of endocrine disruptors on developmental disorders. In a small-scale Sapporo cohort, we observed in detail the neuropsychiatric development of children with the consent of 514 mothers in their late pregnancy. We examined how prenatal exposure to low concentrations of environmental chemicals affect the development of organs and the postnatal development of children. Maternal exposure to POPs, such as PCB/dioxins and perfluorinated alkyl substances, has affected not only children's birth size, thyroid functions, and sex hormone levels, but also postnatal neurodevelopment, infection, and allergy among others. The associations of short-half-life substances, such as DEHP and BPA, with obesity, ASD, and ADHD have been investigated. Gene-environment interactions have been found for smoking, caffeine, folic acid, and PCB/dioxin. In 2015, our center was officially designated as the WHO Collaborating Centre for Environmental Health and Prevention of Chemical Hazards, and we continue to the contribute to the global perspectives of child health.


Assuntos
Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Dioxinas/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversos , Exposição Materna/efeitos adversos , Bifenilos Policlorados/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental/prevenção & controle , Saúde Ambiental , Feminino , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Organização Mundial da Saúde
14.
J Eur Acad Dermatol Venereol ; 32(8): 1368-1372, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29575357

RESUMO

BACKGROUND: Patients treated with vemurafenib for metastatic melanoma often develop skin lesions similar to those observed after exposure to dioxin-like compounds. We previously called these lesions MADISH (metabolizing acquired dioxin-induced skin hamartoma) when analysing a case of acute dioxin poisoning. OBJECTIVE: We performed a clinical trial aimed at comparing the skin lesions observed under vemurafenib treatment with MADISH in order to bring to light a possible crosstalk between vemurafenib and dioxin pathways. METHODS: In this case series study, we explored the histological aspect of skin lesions in 10 cases treated with vemurafenib for malignant melanoma. We also analysed the ability of vemurafenib and tyrosine kinase inhibitors to induce dioxin-AhR pathway. RESULTS: All patients had skin lesions diagnosed as 'non-inflammatory acneiform eruption' by dermatologists. These were predominantly facial with notable retroauricular involvement and clinically compatible with chloracne/MADISH when assessed by dioxin expert. Histological analysis showed mostly comedone-like lesions and dermal cysts containing epithelial wall with basal or lateral epithelial projections and lamellar keratinization and alterations of remaining sebaceous glands. The expression of CYP1A1, a gene highly induced following dioxin exposure, was not observed in these lesions. Vemurafenib and the tyrosine kinase inhibitors erlotinib and gefitinib did not induce CYP1A1 activity. DISCUSSION: Although the skin lesions under vemurafenib treatment were morphologically similar to MADISH, the absence of CYP1A1 expression in dermal cysts of patients and the absence of CYP1A1 activation by vemurafenib led us consider that these skin lesions were different from true MADISH and not mediated by a crosstalk of AhR signalling, but rather to a hyperactivation of PI3K-Akt pathway as a consequence of vemurafenib treatment. A strong expression of CYP1A1 in the epithelial wall of dermal cysts must be required, parallel to the morphology of the lesions, to make the diagnosis of MADISH, the hallmark of an exposure to dioxin-like/chloracnegen compounds.


Assuntos
Antineoplásicos/efeitos adversos , Cloracne/patologia , Cisto Epidérmico/metabolismo , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Vemurafenib/efeitos adversos , Antineoplásicos/farmacologia , Cloracne/etiologia , Cloracne/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Dioxinas/efeitos adversos , Erupção por Droga/etiologia , Erupção por Droga/metabolismo , Erupção por Droga/patologia , Ativação Enzimática/efeitos dos fármacos , Cisto Epidérmico/induzido quimicamente , Cloridrato de Erlotinib/farmacologia , Feminino , Gefitinibe/farmacologia , Células Hep G2 , Humanos , Masculino , Inibidores de Proteínas Quinases/farmacologia , Vemurafenib/farmacologia
15.
Adv Clin Exp Med ; 27(1): 5-14, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29521038

RESUMO

BACKGROUND: Dioxins contribute to neurological disorders in humans and animals, causing also neurological disorders in offspring during prenatal and postnatal periods. These compounds significantly affect the development of the central nervous system (CNS) structures, which results in behavioral changes. Tocopherol (TCP) and acetylsalicylic acid (ASA) may provide protective measures to reduce the inflammatory effects in the CNS associated with free radicals generated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), thus contributing to the reduction of the negative effects of dioxin. OBJECTIVES: The main objective of this study was to determine the influence of dioxin on rats and their behavioral functions, and to ascertain whether a combined administration of TCP and ASA to rats treated with TCDD shows the possibility of potential protective effect on the functioning of the CNS. MATERIAL AND METHODS: Experiments were performed on 75 female and 12 male Buffalo strain rats, which are offspring of females from particular study groups. TCDD was used in the experiments, TCP and ASA were administered orally every day for 3 weeks. Animals were subjected to behavioral testing: the tail and swimming tests. RESULTS: During the observation of the offspring of both sexes born to females exposed to TCDD, males did not demonstrate any attempt to swim, whereas in females, the immobility time was significantly extended. Assessing the response times from the tail test in the animals treated with dioxins in relation to the control group, it was demonstrated that the response time was extended in the 3rd measurement in both females and males. CONCLUSIONS: Dioxin is characterized by neurotoxic effect causing behavioral disorders associated with prolonged response times. The use of TCP after the administration of dioxins causes a significant reduction and improvement of reflex response times. In contrast, ASA reduces the reflex response times also in the offspring of females exposed to TCDD and ASA.


Assuntos
Aspirina/farmacologia , Comportamento Animal/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Dioxinas/efeitos adversos , Tocoferóis/farmacologia , Animais , Animais Recém-Nascidos/metabolismo , Aspirina/administração & dosagem , Encéfalo/efeitos dos fármacos , Dioxinas/uso terapêutico , Feminino , Masculino , Dibenzodioxinas Policloradas , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Substâncias Protetoras/farmacologia , Ratos , Tocoferóis/administração & dosagem
16.
Poult Sci ; 97(2): 607-619, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29161444

RESUMO

Differences in risk perceptions of public health and food safety hazards in various poultry husbandry systems by various stakeholder groups, may affect the acceptability of those husbandry systems. Therefore, the objective was to gain insight into risk perceptions of citizens, poultry farmers, and poultry veterinarians regarding food safety and public health hazards in poultry husbandry systems, and into factors explaining these risk perceptions. We surveyed risk perceptions of Campylobacter contamination of broiler meat, avian influenza introduction in laying hens, and altered dioxin levels in eggs for the most commonly used broiler and laying hen husbandry systems in Dutch citizens (n = 2,259), poultry farmers (n = 100), and poultry veterinarians (n = 41). Citizens perceived the risks of the three hazards in the indoor systems higher and in the outdoor systems lower than did the professionals. Citizens reported higher concerns regarding aspects reflecting underlying psychological factors of risk perception compared to professionals. Professionals indicated a relatively low level of personal control, which might imply risk denial. Of the socio-demographic characteristics, gender and childhood residence were associated with risk perceptions. The influence of other factors of risks perception are discussed. It is suggested that risk perceptions of all stakeholder groups are influenced by affect, stigma, and underlying values. To adapt current or new husbandry systems that can count on societal support, views of key stakeholders and multiple aspects such as animal welfare, public health, food safety, and underlying values should be considered integrally. When trade-offs, such as between animal welfare and public health have to be made, insight into underlying values might help to find consensus among stakeholders.


Assuntos
Infecções por Campylobacter/psicologia , Fazendeiros/psicologia , Influenza Aviária/psicologia , Percepção , Doenças das Aves Domésticas/psicologia , Opinião Pública , Risco , Médicos Veterinários/psicologia , Criação de Animais Domésticos , Animais , Campylobacter/fisiologia , Galinhas , Dioxinas/efeitos adversos , Ovos/análise , Feminino , Microbiologia de Alimentos , Inocuidade dos Alimentos , Conhecimentos, Atitudes e Prática em Saúde , Carne/microbiologia , Países Baixos , Saúde Pública
17.
Sci Total Environ ; 610-611: 191-199, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28803196

RESUMO

INTRODUCTION: In utero exposure to dioxin-like compounds (DLCs) may cause imbalance of immune development in early infancy. However, there are few epidemiological studies into the effects of in utero exposure to DLCs on allergies and infections during childhood. This study evaluates associations between concentrations of maternal DLCs and cord blood immunoglobulin (Ig) E, as well as allergies and infections during childhood. METHOD: We recruited 514 pregnant women in a maternity hospital in Sapporo, Japan, and measured concentrations of DLCs in 426 maternal blood samples using high-resolution gas chromatography/high-resolution mass spectrometry. We examined the relationship between concentrations of maternal DLCs and cord blood IgE at birth (n=239), as well as for allergies and infections in children at 3.5 (n=327) and 7 (n=264) years, using regression analysis adjusted for confounding variables. RESULTS: We found a positive association between maternal DLC concentrations and frequency of wheezing in children aged up to 7years [odds ratio (OR); 7.81 (95% confidence interval (CI), 1.42 to 42.9)]. At 3.5years, boys showed inverse associations between maternal DLC concentrations and cord blood IgE [partial regression coefficient; -0.87 (95% CI), -1.68 to -0.06], and frequency of wheezing [OR; 0.03 (95% CI), 0.00 to 0.94] but girls did not. DISCUSSION: As one reason for the significant association observed at 7 but absent at 3.5years, we suggest that allergic symptoms are more obvious in older children due to matured immune function. CONCLUSION: The findings suggest that prenatal exposure to DLCs may modify offspring immune responses and result in increased risk of allergy among children of school age.


Assuntos
Dioxinas/efeitos adversos , Imunoglobulina E/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Sons Respiratórios/etiologia , Criança , Pré-Escolar , Feminino , Sangue Fetal/química , Humanos , Japão , Masculino , Gravidez
18.
Yakugaku Zasshi ; 137(11): 1373-1379, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-29093374

RESUMO

Dioxins, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), are responsible for producing serious toxic effects in the next generation, such as sexual immaturity. Our laboratory found that treating pregnant rats on gestational day 15 with TCDD (1 µg/kg orally) targets pituitary luteinizing hormone (LH) to attenuate testicular steroidogenesis in fetuses. Because sex steroids during a short window ("the critical period") in the perinatal stage stimulate brain differentiation closely linked to sexual maturation, it is likely that TCDD imprints sexual immaturity on the offspring due to the lowered expression of LH during the fetal period. To address this hypothesis, we first investigated the effect of supplementation of equine chorionic gonadotropin (eCG), an LH-mimicking hormone, in fetuses exposed to TCDD. The result showed that eCG ameliorated defects in sexual behavior in adulthood as well as in steroidogenesis during the fetal stage. We also found that maternal exposure to TCDD induced the pituitary expression of histone deacetylases (HDACs) in fetuses. In agreement with this, TCDD deacetylated the histones wrapped around the LHß gene, and valproic acid, an HDAC inhibitor, blocked the reduced level of LHß caused by TCDD. These observations strongly suggest that TCDD induces the expression of HDACs to attenuate fetal LH production. Finally, such a transient reduction in steroidogenesis of the pituitary-gonadal axis causes a decrease in the expression of hypothalamic gonadotropin-releasing hormone, resulting in defects in sexual behavior in adulthood. This review increases our understanding of the developmental toxicities caused by endocrine disruptors including dioxins.


Assuntos
Dioxinas/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Exposição Materna/efeitos adversos , Troca Materno-Fetal , Efeitos Tardios da Exposição Pré-Natal , Maturidade Sexual/efeitos dos fármacos , Maturidade Sexual/genética , Animais , Dioxinas/toxicidade , Disruptores Endócrinos/toxicidade , Feminino , Idade Gestacional , Hormônios Esteroides Gonadais/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Histona Desacetilases/metabolismo , Humanos , Hipotálamo/metabolismo , Recém-Nascido , Hormônio Luteinizante/metabolismo , Masculino , Hipófise/metabolismo , Gravidez , Ratos , Testículo/metabolismo
19.
Sci Total Environ ; 607-608: 32-41, 2017 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-28686893

RESUMO

Over the past decades, southern Vietnam has been burdened by dioxins from contaminated herbicides sprayed during the Vietnam War. In a previous study, we found that dioxin exposure decreased levels of salivary dehydroepiandrosterone (DHEA), an adrenal androgen, in 3-year-old children. In present study, to assess the relationship between adrenal hormones disruption in lactating mothers and in children, we compared mother-child pairs from dioxin- and nondioxin-contaminated regions. In 2010 and 2011, mother-child pairs from a dioxin hotspot region (n=37) and a non-contaminated region (n=47) were recruited and donated breast milk and serum samples for dioxin and steroid hormones determination. Mothers were 20-30years old and had given birth to their first child between 4 and 16weeks previously. One year later, saliva samples were collected from the children. Dioxin levels in breast milk were determined by gas chromatography/high-resolution mass spectrometry. Salivary DHEA, cortisol in children and androstenedione (A-dione), estradiol, cortisol, and DHEA in maternal serum were analyzed by liquid chromatography/tandem mass spectrometry. Concentrations of dioxin congeners in the hotspot region were 2- to 5-fold higher than in samples from the non-contaminated region. Salivary DHEA levels in children and serum A-dione levels in mothers were significantly higher in the hotspot region; no difference was found in the levels of other hormones. Moreover, there was a significant positive correlation between the elevated hormone levels in mothers and children (r=0.62, p<0.001). Several dioxin congeners exhibited strong significant dose-response relationships with salivary DHEA and serum A-dione levels. Our findings suggest that dioxin disrupts adrenal androgens in mothers and breastfeeding children through the same mechanism.


Assuntos
Androstenodiona/sangue , Desidroepiandrosterona/análise , Dioxinas/efeitos adversos , Exposição Ambiental/efeitos adversos , Leite Humano/química , Saliva/química , Adulto , Desidroepiandrosterona/sangue , Estradiol/sangue , Feminino , Humanos , Hidrocortisona/sangue , Lactente , Lactação , Masculino , Mães , Vietnã , Adulto Jovem
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