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1.
Int J Hyg Environ Health ; 257: 114326, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38295493

RESUMO

BACKGROUND: Nearly six million people residing in the United States do not have access to safely managed sanitation. Housed populations may lack access to centralized wastewater treatment systems or functioning onsite wastewater treatment systems, which subsequently places them at higher risk for adverse health outcomes associated with unsafe sanitation. OBJECTIVES: We sought to understand the various social barriers that impact access to safe sanitation in the United States. METHODS: We included peer-reviewed studies published between January 2000 and March 2023. The publication search was conducted using Scopus, ProQuest Social Science Database, and HeinOnline. We extracted data on social barriers and physical factors associated with access to sanitation. RESULTS: Twenty publications met the inclusion criteria, and data relating to 11 social barriers and two physical factors were extracted. The social barriers to safe sanitation access mentioned most frequently were found to be socioeconomic status and race-based discrimination. Studies discussed sanitation in communities in five states. DISCUSSION: Barriers pertained to lack of access to centralized wastewater treatment system, inadequate repair or replacement of septic systems, and lack of safely managed onsite sanitation systems. We discuss the intersectionality of the barriers, the underlying policy and history that leads to them, and make recommendations to address inequitable access to safe sanitation. Legislation and policy must be critically reviewed at national, state, and local levels to limit or eliminate ability for utilities to be extended on the basis of a community's income and property values or racial makeup. Policy recommendations also include additional community engagement, onsite sanitation system monitoring, and knowledge dissemination and education of septic system users. More geographically diverse research and research on sanitation in specific communities such as those of migrant farmworkers, undocumented persons, and tenants are recommended.


Assuntos
Saneamento , Purificação da Água , Humanos , Estados Unidos , Habitação , Renda
2.
Artigo em Inglês | MEDLINE | ID: mdl-37569064

RESUMO

Landfills pose an important public health risk, especially in historically disenfranchised communities that are disproportionately sited for landfills and in rural areas where private wells may be impacted. Landfills are major sources of perfluoroalkyl substances (PFAS) that migrate into the surrounding environment. This study characterized PFAS in surface waters adjacent to two landfills, one in Sampson County (SC) and one in Orange County (OC) in North Carolina. In addition to municipal solid waste and construction and demolition waste, the landfill in SC accepts industrial sludge from a chemical plant that produces proprietary PFAS. Over four months, 35 surface water samples were collected at upstream, landfill-adjacent, and downstream/downgradient sites. Thirty-four PFAS were analyzed using liquid chromatography with tandem mass spectroscopy. Of those, six novel and six legacy PFAS were detected. Legacy PFAS were detected in surface water near both landfills, with the highest concentrations adjacent to the landfill. Novel PFAS were only detected in surface water near the SC landfill and showed the highest concentrations adjacent to the landfill, indicating offsite migration of PFAS. These findings support the need for more comprehensive and frequent monitoring of groundwater and surface water wells near landfills and stricter regulation regarding the landfilling of industrial materials.


Assuntos
Fluorocarbonos , Água Subterrânea , Eliminação de Resíduos , Poluentes Químicos da Água , Eliminação de Resíduos/métodos , North Carolina , Poluentes Químicos da Água/análise , Água Subterrânea/química , Instalações de Eliminação de Resíduos , Fluorocarbonos/análise
3.
Artigo em Inglês | MEDLINE | ID: mdl-37174182

RESUMO

Rural communities of color in the southeastern U.S. experience a high burden of environmental hazards from concentrated industry placement. Community-engaged research and qualitative methods can improve our understanding of meaning-making in a community impacted by polluting facilities. This study applies the photovoice method to assess how a predominantly African American community in rural North Carolina, impacted by a landfill and confined animal feeding operations (CAFOs), perceives their health-related quality of life (HRQoL). Two research questions were developed with community-based partners: (a) How do environmental health concerns in this community influence residents' perceptions of their HRQoL? and (b) How do community and county factors facilitate or inhibit community organizing around these concerns? Three photo assignment sessions were held to engage participants in discussions related to the research questions. Researchers analyzed discussion audio recordings and identified themes related to concerns about the following issues: health and quality of life, the landfill industry's influence on community cohesion and self-determination, and actions to address environmental injustice in Sampson County. Photovoice benefits community-engaged researchers by providing a process for assessing the research interests of a community. Photovoice also serves community organizers by providing residents with a structured way to discuss their lived experiences and strategize ways to reduce hazard exposure.


Assuntos
População Rural , Qualidade da Água , Humanos , Qualidade de Vida , North Carolina
4.
Environ Epidemiol ; 7(2): e241, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37064422

RESUMO

Coal-fired power plants (CFPP) are major contributors of air pollution, including the majority of anthropogenic sulfur dioxide (SO2) emissions, which have been associated with preterm birth (PTB). To address a 2002 North Carolina (NC) policy, 14 of the largest NC CFPPs either installed desulfurization equipment (scrubbers) or retired coal units, resulting in substantial reductions of SO2 air emissions. We investigated whether SO2 air emission reduction strategies at CFPPs in NC were associated with changes in prevalence of PTB in nearby communities. Methods: We used US EPA Air Markets Program Data to track SO2 emissions and determine the implementation dates of intervention at CFPPs and geocoded 2003-2015 NC singleton live births. We conducted a difference-in-difference analysis to estimate change in PTB associated with change in SO2 reduction strategies for populations living 0-<4 and 4-<10 miles from CFPPs pre- and postintervention, with a comparison of those living 10-<15 miles from CFPPs. Results: With the spatial-temporal exposure restrictions applied, 42,231 and 41,218 births were within 15 miles of CFPP-scrubbers and CFPP-retired groups, respectively. For residents within 4-<10 miles from a CFPP, we estimated that the absolute prevalence of PTB decreased by -1.5% [95% confidence interval (CI): -2.6, -0.4] associated with scrubber installation and -0.5% (95% CI: -1.6, 0.6) associated with the retirement of coal units at CFPPs. Our findings were imprecise and generally null-to-positive among those living within 0-<4 miles regardless of the intervention type. Conclusions: Results suggest a reduction of PTB among residents 4-<10 miles of the CFPPs that installed scrubbers.

5.
N C Med J ; 83(4): 304-310, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35817451

RESUMO

BACKGROUND Coal combustion releases a number of airborne toxins. The North Carolina Clean Smokestacks Act (CSA) of 2002 required North Carolina coal-fired power plants (CFPP) to reduce nitrogen oxides (NOX) emissions by 2009 and sulfur dioxide (SO2) emissions to 2 benchmarks by 2009 and 2013.METHODS We utilized publicly available databases from the Energy Information Administration and the Environmental Protection Agency to characterize North Carolina's electricity generation profile from 2000 until 2019 and evaluate corresponding NOx and SO2 emissions by sector over the same time period.RESULTS Between 2000 and 2008 in North Carolina, approximately 60% of electric power was generated by CFPPs. Since then, North Carolina's electric power generation has transformed from predominant dependence on coal to approximately equal dependence on natural gas and nuclear power (each at ~ 30%), with coal close behind (~ 25%). Renewables have increased, although marginally relative to the rapid increase in natural gas. Despite the stark drop in reliance on CFPPs for energy in North Carolina and subsequent drop in emissions, CFPPs still contribute ~ 60% of SO2 air pollution as of 2017.LIMITATIONS This analysis relies upon electricity generation and emissions data self-reported by utilities and publicly available from federal agenciesCONCLUSION North Carolina's electric utilities met the 2009 and 2013 regulatory benchmarks set by the CSA, which resulted in substantial reductions in SO2 emissions from the fuel combustion electric generation sector. Still, CFPPs remain the primary utility-related and overall anthropogenic contributor of SO2 air pollution in North Carolina.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/prevenção & controle , Carvão Mineral , Humanos , Gás Natural , North Carolina , Centrais Elétricas
7.
Dis Model Mech ; 14(8)2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34378773

RESUMO

Clinically pertinent electrocardiogram (ECG) data from model systems, such as zebrafish, are crucial for illuminating factors contributing to human cardiac electrophysiological abnormalities and disease. Current zebrafish ECG collection strategies have not adequately addressed the consistent acquisition of high-quality traces or sources of phenotypic variation that could obscure data interpretation. Thus, we developed a novel platform to ensure high-quality recording of in vivo subdermal adult zebrafish ECGs and zebrafish ECG reading GUI (zERG), a program to acquire measurements from traces that commercial software cannot examine owing to erroneous peak calling. We evaluate normal ECG trait variation, revealing highly reproducible intervals and wave amplitude variation largely driven by recording artifacts, and identify sex and body size as potential confounders to PR, QRS and QT intervals. With this framework, we characterize the effect of the class I anti-arrhythmic drug flecainide acetate on adults, provide support for the impact of a Long QT syndrome model, and establish power calculations for this and other studies. These results highlight our pipeline as a robust approach to evaluate zebrafish models of human cardiac electrophysiological phenotypes.


Assuntos
Síndrome do QT Longo , Peixe-Zebra , Animais , Eletrocardiografia/métodos , Peixe-Zebra/genética
8.
J Pediatr Adolesc Gynecol ; 33(5): 574-576, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32574600

RESUMO

BACKGROUND: Pyometra is an uncommon but serious condition that is generally diagnosed in postmenopausal women. It rarely occurs in premenopausal patients, particularly adolescents. CASE: A 16-year-old girl with multiple comorbidities including severe intellectual disability, neurogenic bladder, and recurrent urinary tract infection presented with fever, abdominal pain, and vaginal discharge after prolonged treatment with depot medroxyprogesterone acetate. Ultrasound imaging showed an intrauterine fluid collection consistent with hematometra; however, hysteroscopic evaluation confirmed pyometra, which was evacuated using a suction curette. Despite postoperative antibiotic therapy, she re-presented with similar findings requiring additional hysteroscopic evaluation and evacuation. After a third evacuation, an intrauterine catheter was placed to aid in drainage. This was not tolerated by the patient, and she ultimately required total laparoscopic hysterectomy for definitive management, which was performed without incident. SUMMARY AND CONCLUSION: Pyometra is a rare occurrence that typically presents after menopause; however, it should be considered in patients with poor genitourinary hygiene and medically induced endometrial atrophy. In severe cases, hysterectomy might be required for definitive management.


Assuntos
Piometra/diagnóstico , Adolescente , Drenagem/efeitos adversos , Feminino , Humanos , Histerectomia/métodos , Piometra/patologia , Piometra/cirurgia , Ultrassonografia
9.
Int J Mol Sci ; 21(9)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32353937

RESUMO

Bisphenol A (BPA) is the most common environmental endocrine disrupting chemical. Studies suggest a link between perinatal BPA exposure and increased breast cancer risk, but the underlying mechanisms remain unclear. This study aims to investigate the effects of in utero BPA exposure on mammary tumorigenesis in MMTV-erbB2 transgenic mice. Pregnant mice were subcutaneously injected with BPA (0, 50, 500 ng/kg and 250 µg/kg BW) daily between gestational days 11-19. Female offspring were examined for mammary tumorigenesis, puberty onset, mammary morphogenesis, and signaling in ER and erbB2 pathways. In utero exposure to low dose BPA (500 ng/kg) induced mammary tumorigenesis, earlier puberty onset, increased terminal end buds, and prolonged estrus phase, which was accompanied by proliferative mammary morphogenesis. CD24/49f-based FACS analysis showed that in utero exposure to 500 ng/kg BPA induced expansion of luminal and basal/myoepithelial cell subpopulations at PND 35. Molecular analysis of mammary tissues at PND 70 showed that in utero exposure to low doses of BPA induced upregulation of ERα, p-ERα, cyclin D1, and c-myc, concurrent activation of erbB2, EGFR, erbB-3, Erk1/2, and Akt, and upregulation of growth factors/ligands. Our results demonstrate that in utero exposure to low dose BPA promotes mammary tumorigenesis in MMTV-erbB2 mice through induction of ER-erbB2 crosstalk and mammary epithelial reprogramming, which advance our understanding of the mechanism associated with in utero exposure to BPA-induced breast cancer risk. The studies also support using MMTV-erbB2 mouse model for relevant studies.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Neoplasias Mamárias Experimentais/patologia , Fenóis/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/patologia , Transdução de Sinais/efeitos dos fármacos , Animais , Compostos Benzidrílicos/administração & dosagem , Reprogramação Celular , Disruptores Endócrinos/administração & dosagem , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Idade Gestacional , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/genética , Vírus do Tumor Mamário do Camundongo/patogenicidade , Exposição Materna , Camundongos , Camundongos Transgênicos , Fenóis/administração & dosagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Maturidade Sexual/efeitos dos fármacos
10.
Toxicol In Vitro ; 64: 104463, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31628012

RESUMO

In this paper, we evaluate the PPARα signaling network in rats, examining transcriptional responses in primary hepatocytes exposed to a PPARα specific ligand, GW7647. These transcriptomic studies were complemented with ChIP-seq studies of PPARα binding and transcription binding motif identification for PPARα responsive genes. We also conducted a limited study of GW7647 dosing the in intact rat to examine differences in transcriptional responses for primary hepatocytes in vitro and in the intact liver. The rat network has a much larger number of down-regulated genes and pathways than we had found in the human and the PPARα binding motifs in rat differed for upregulated and down regulated genes. Based on these results and comparison with our previous work with the human PPARα signaling network, we identified qualitative differences in the transcriptional networks controlled by PPARα activation in the two species that provide an explanation of the interspecies differences in the responses of humans and rodents to GW7647 and likely to other PPARα agonists. These studies also allow some observations on the manner in which in vitro, fit-for-purpose assays in human hepatocytes could form the basis for risk assessment without recourse to in-life studies in rodents or other test species.


Assuntos
Hepatócitos/metabolismo , PPAR alfa/metabolismo , Medição de Risco/métodos , Animais , Butiratos/farmacologia , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Humanos , Masculino , PPAR alfa/agonistas , PPAR alfa/genética , Compostos de Fenilureia/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
11.
Artigo em Inglês | MEDLINE | ID: mdl-30857258

RESUMO

Lower back musculoskeletal disorders (MSDs) are an important public health problem and the leading cause of disability worldwide, but with yet unknown prevalence among shellfish gatherers. To investigate the prevalence and work-related factors associated with lower back MSD in a population of female shellfish gatherers, an epidemiological cross-sectional study was carried out in Saubara, Bahia-Brazil, in 2013. The Brazilian version of the Job Content Questionnaire (JCQ) and the Nordic Musculoskeletal Questionnaire (NMQ), in addition to a questionnaire containing the physical demands adapted to the artisanal work, were applied to a random sample of 209 female shellfish gatherers. The prevalence of lower back MSD was 72.7%. Using multivariate logistic regression, the shellfish gatherers who had worked for more than 26 years in the activity showed a prevalence of 1.22 (95% CI: 1.04⁻1.44) times higher compared to those unexposed. Lower back MSD was 1.24 (95% CI: 1.08⁻1.42) times higher among those more exposed to work sitting with trunk flexion. Those performed manual handling and muscle force with the arms had a prevalence ratio of 1.18 (95% CI: 1.01⁻1.39). These results show the need for greater awareness of health and social welfare factors impacting workers in small-scale fisheries and will promote the elaboration of health care policies for this occupational class.


Assuntos
Dor Lombar/epidemiologia , Doenças Musculoesqueléticas/epidemiologia , Doenças Profissionais/epidemiologia , Adulto , Brasil/epidemiologia , Estudos Transversais , Feminino , Pesqueiros , Humanos , Modelos Logísticos , Prevalência , Fatores de Risco , Alimentos Marinhos , Frutos do Mar , Inquéritos e Questionários
12.
Nat Genet ; 51(1): 42-50, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30455415

RESUMO

Bicuspid aortic valve (BAV) is a common congenital heart defect (population incidence, 1-2%)1-3 that frequently presents with ascending aortic aneurysm (AscAA)4. BAV/AscAA shows autosomal dominant inheritance with incomplete penetrance and male predominance. Causative gene mutations (for example, NOTCH1, SMAD6) are known for ≤1% of nonsyndromic BAV cases with and without AscAA5-8, impeding mechanistic insight and development of therapeutic strategies. Here, we report the identification of variants in ROBO4 (which encodes a factor known to contribute to endothelial performance) that segregate with disease in two families. Targeted sequencing of ROBO4 showed enrichment for rare variants in BAV/AscAA probands compared with controls. Targeted silencing of ROBO4 or mutant ROBO4 expression in endothelial cell lines results in impaired barrier function and a synthetic repertoire suggestive of endothelial-to-mesenchymal transition. This is consistent with BAV/AscAA-associated findings in patients and in animal models deficient for ROBO4. These data identify a novel endothelial etiology for this common human disease phenotype.


Assuntos
Aneurisma da Aorta Torácica/genética , Valva Aórtica/anormalidades , Doenças das Valvas Cardíacas/genética , Mutação/genética , Receptores de Superfície Celular/genética , Animais , Doença da Válvula Aórtica Bicúspide , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Peixe-Zebra
13.
N C Med J ; 79(5): 324-328, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30228142

RESUMO

Environmental justice means equal access to a healthful environment for all. In North Carolina, many sources of pollution disproportionately affect low-income communities and communities of color. Clinicians who recognize effects of environmental injustices can improve patient care and community health. As an example, we present the effects of industrial-scale hog operations in North Carolina.


Assuntos
Ração Animal , Saúde Ambiental , Indústria Alimentícia , Saúde Pública , Justiça Social , Suínos , Animais , Humanos , North Carolina
14.
Cien Saude Colet ; 22(11): 3635-3644, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29211169

RESUMO

The aim is to analyze upper limb functioning and disability, and its association with health-related quality of life among artisanal fisherwomen from Bahia, Brazil. Cross-sectional epidemiological study was conducted with a sample of 209 fisherwomen. Structured questionnaires were used for socio-demographic and comorbidity information, as well as the instruments Disabilities of the Arm, Shoulder and Hand (DASH) and Short-Form Healthy Survey (SF-36) respectively, to evaluate the upper limbs and health-related quality of life. The results demonstrated that the presence of musculoskeletal disorders in the upper limbs directly affects the values of the DASH instrument and the SF-36v01 questionnaire scores, while also generating a negative correlation between the DASH and SF-36v01. The varying functioning abilities, pain and social aspects negatively affect upper limb function, and the daily activities and work of fisherwomen. The presence of chronic disease and the absence of intervention and rehabilitation for these professionals, that could produces, in a long-term, cases of disability.


Assuntos
Pessoas com Deficiência , Doenças Musculoesqueléticas/epidemiologia , Doenças Profissionais/epidemiologia , Qualidade de Vida , Atividades Cotidianas , Adulto , Animais , Brasil/epidemiologia , Doença Crônica , Estudos Transversais , Avaliação da Deficiência , Feminino , Peixes , Inquéritos Epidemiológicos , Humanos , Pessoa de Meia-Idade , Frutos do Mar , Extremidade Superior , Adulto Jovem
15.
Ciênc. Saúde Colet. (Impr.) ; 22(11): 3635-3644, Nov. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-890202

RESUMO

Abstract The aim is to analyze upper limb functioning and disability, and its association with health-related quality of life among artisanal fisherwomen from Bahia, Brazil. Cross-sectional epidemiological study was conducted with a sample of 209 fisherwomen. Structured questionnaires were used for socio-demographic and comorbidity information, as well as the instruments Disabilities of the Arm, Shoulder and Hand (DASH) and Short-Form Healthy Survey (SF-36) respectively, to evaluate the upper limbs and health-related quality of life. The results demonstrated that the presence of musculoskeletal disorders in the upper limbs directly affects the values of the DASH instrument and the SF-36v01 questionnaire scores, while also generating a negative correlation between the DASH and SF-36v01. The varying functioning abilities, pain and social aspects negatively affect upper limb function, and the daily activities and work of fisherwomen. The presence of chronic disease and the absence of intervention and rehabilitation for these professionals, that could produces, in a long-term, cases of disability.


Resumo O objetivo foi analisar a incapacidade e a funcionalidade de membros superiores e verificar sua associação com a qualidade de vida relacionada com a saúde de pescadoras artesanais da Bahia, Brasil. Estudo epidemiológico, de corte transversal, envolvendo uma amostra de 209 pescadoras artesanais. Foram utilizados questionários estruturados para informações sociodemográficas e comorbidades e os instrumentos Disabilities of the Arm, Shoulder and Hand (DASH) e Medical Outcomes Study 36-Item Short-Form Healthy Survey (SF-36), para, respectivamente, avaliação dos membros superiores e qualidade de vida relacionada com a saúde. Os resultados encontrados demonstram que a presença de distúrbios musculoesqueléticos (DME) em membros superiores afeta diretamente os valores do instrumento DASH e os escores do SF-36v01, bem como a correlação negativa encontrada entre o DASH e os domínios do SF-36v01. As variáveis capacidade funcional, dor e aspectos sociais afetam negativamente a funcionalidade de membros superiores e as atividades do cotidiano e do trabalho de pescadoras artesanais. A presença de doença crônica e a ausência de intervenção e reabilitação desses profissionais geram, a longo prazo, casos de incapacidade.


Assuntos
Humanos , Animais , Feminino , Adulto , Adulto Jovem , Qualidade de Vida , Doenças Musculoesqueléticas/epidemiologia , Doenças Profissionais/epidemiologia , Frutos do Mar , Brasil/epidemiologia , Atividades Cotidianas , Doença Crônica , Estudos Transversais , Inquéritos Epidemiológicos , Pessoas com Deficiência , Extremidade Superior , Avaliação da Deficiência , Peixes , Pessoa de Meia-Idade
17.
Artigo em Inglês | MEDLINE | ID: mdl-27164118

RESUMO

Quality of life is an indicator of how well one perceives that he/she is functioning physically and mentally. The aim of this paper is to determine the health-related quality of life (HRQOL) of artisanal fisherwomen/shellfish gatherers from the Saubara municipality in Bahia, Brazil in comparison to the general population. A structured questionnaire was administered to a sample of 209 artisanal fisherwomen selected at random. The HRQOL questionnaire, known as the 36-Item Short-Form Health Survey version 1 (SF-36v01), was also used, having been translated and verified cross-culturally for the Brazilian population. Sociodemographic, lifestyle and comorbidity information was also collected. Chronic diseases and indicators of musculoskeletal disorders (MSDs) were self-reported. The study population consisted primarily of individuals between 30 and 45 years of age (78%), of self-classified races black or brown (96.2%), with no more than an elementary school education (77%) and married (64.6%). In all the SF-36v01 dimensions, the values in the sample were lower than in the general population of Brazil, which was used as the reference population. In the "Physical Health" domain (Physical Functioning; Physical Role Limitations; Bodily Pain; General Health Perception) a tendency toward a lower health-related quality of life was observed among those who were older, had a lower education level, and had a prevalence of MSDs, hypertension or arthritis. The interference of health conditions linked to the fisherwomen's work activities may contribute to lower HRQOL in all analyzed aspects, in comparison to the general population. In light of these findings, public health policies must consider these informal workers who contribute greatly to Brazil's economy and food system.


Assuntos
Pesqueiros , Inquéritos Epidemiológicos , Doenças Musculoesqueléticas/epidemiologia , Doenças Profissionais/epidemiologia , Saúde Ocupacional/estatística & dados numéricos , Qualidade de Vida , Adulto , Idoso , Animais , Brasil/epidemiologia , Doença Crônica/epidemiologia , Doença Crônica/psicologia , Comorbidade , Estudos Transversais , Escolaridade , Feminino , Peixes , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/etiologia , Doenças Musculoesqueléticas/psicologia , Doenças Profissionais/etiologia , Doenças Profissionais/psicologia , Prevalência , Alimentos Marinhos , Autorrelato , Frutos do Mar , Recursos Humanos , Adulto Jovem
18.
Chem Biol Interact ; 209: 14-24, 2014 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-24269660

RESUMO

Nuclear receptor activation in liver leads to coordinated alteration of the expression of multiple gene products with attendant phenotypic changes of hepatocytes. Peroxisome proliferators including endogenous fatty acids, environmental chemicals, and drugs induce a multi-enzyme metabolic response that affects lipid and fatty acid processing. We studied the signaling network for the peroxisome proliferator-associated receptor alpha (PPARα) in primary human hepatocytes using the selective PPARα ligand, GW7647. We measured gene expression over multiple concentrations and times and conducted ChIP-seq studies at 2 and 24h to assess genomic binding of PPARα. Over all treatments there were 192 genes differentially expressed. Of these only 51% showed evidence of PPARα binding-either directly at PPARα response elements or via alternative mechanisms. Almost half of regulated genes had no PPARα binding. We then developed two novel bioinformatics methods to visualize the dose-dependent activation of both the transcription factor circuitry for PPARα and the downstream metabolic network in relation to functional annotation categories. Available databases identified several key transcription factors involved with the non-genomic targets after GW7647 treatment, including SP1, STAT1, ETS1, ERα, and HNF4α. The linkage from PPARα binding through gene expression likely requires intermediate protein kinases to activate these transcription factors. We found enrichment of functional annotation categories for organic acid metabolism and cell lipid metabolism among the differentially expressed genes. Lipid transport processes showed enrichment at the highest concentration of GW7647 (10 µM). While our strategy for mapping transcriptional networks is evolving, these approaches are necessary in moving from toxicogenomic methods that derive signatures of activity to methods that establish pathway structure, showing the coordination of the activated nuclear receptor with other signaling pathways.


Assuntos
Biologia Computacional , Relação Dose-Resposta a Droga , Hepatócitos/fisiologia , PPAR alfa/genética , Sítios de Ligação , Mapeamento Cromossômico , Regulação para Baixo , Humanos , Análise em Microsséries , PPAR alfa/química , PPAR alfa/metabolismo , Transdução de Sinais , Transcrição Gênica , Regulação para Cima
19.
Pharm Res ; 30(9): 2248-59, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23468051

RESUMO

PURPOSE: Oxidative stress is implicated in pancreatic ß-cell dysfunction, yet clinical outcomes of antioxidant therapies on diabetes are inconclusive. Since reactive oxygen species (ROS) can function as signaling intermediates for glucose-stimulated insulin secretion (GSIS), we hypothesize that exogenously boosting cellular antioxidant capacity dampens signaling ROS and GSIS. METHODS: To test the hypothesis, we formulated a mathematical model of redox homeostatic control circuit comprising known feedback and feedforward loops and validated model predictions with plant-derived antioxidant sulforaphane (SFN). RESULTS: SFN acutely (30-min treatment) stimulated basal insulin secretion in INS-1(832/13) cells and cultured mouse islets, which could be attributed to SFN-elicited ROS as N-acetylcysteine or glutathione ethyl ester suppressed SFN-stimulated insulin secretion. The mathematical model predicted an adapted redox state characteristic of strong induction of endogenous antioxidants but marginally increased ROS under prolonged SFN exposure, a state that attenuates rather than facilitates glucose-stimulated ROS and GSIS. We validated the prediction by demonstrating that although 24-h treatment of INS-1(832/13) cells with low, non-cytotoxic concentrations of SFN (2-10 µM) protected the cells from cytotoxicity by oxidative insult, it markedly suppressed insulin secretion stimulated by 20 mM glucose. CONCLUSIONS: Our study indicates that adaptive induction of endogenous antioxidants by exogenous antioxidants, albeit cytoprotective, inhibits GSIS in ß-cells.


Assuntos
Antioxidantes/farmacologia , Glucose/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Isotiocianatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Humanos , Células Secretoras de Insulina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , Sulfóxidos
20.
Diabetes ; 62(3): 845-54, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23238296

RESUMO

Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that functions as a master regulator of the cellular adaptive response to oxidative stress. Our previous studies showed that Nrf2 plays a critical role in adipogenesis by regulating expression of CCAAT/enhancer-binding protein ß and peroxisome proliferator-activated receptor γ. To determine the role of Nrf2 in the development of obesity and associated metabolic disorders, the incidence of metabolic syndrome was assessed in whole-body or adipocyte-specific Nrf2-knockout mice on a leptin-deficient ob/ob background, a model with an extremely positive energy balance. On the ob/ob background, ablation of Nrf2, globally or specifically in adipocytes, led to reduced white adipose tissue (WAT) mass, but resulted in an even more severe metabolic syndrome with aggravated insulin resistance, hyperglycemia, and hypertriglyceridemia. Compared with wild-type mice, WAT of ob/ob mice expressed substantially higher levels of many genes related to antioxidant response, inflammation, adipogenesis, lipogenesis, glucose uptake, and lipid transport. Absence of Nrf2 in WAT resulted in reduced expression of most of these factors at mRNA or protein levels. Our findings support a novel role for Nrf2 in regulating adipose development and function, by which Nrf2 controls the capacity of WAT expansion and insulin sensitivity and maintains glucose and lipid homeostasis.


Assuntos
Tecido Adiposo Branco/metabolismo , Adiposidade , Regulação da Expressão Gênica , Síndrome Metabólica/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Obesidade/complicações , Adipogenia , Tecido Adiposo Branco/patologia , Animais , Cruzamentos Genéticos , Feminino , Perfilação da Expressão Gênica , Hiperglicemia/etiologia , Hipertrigliceridemia/etiologia , Resistência à Insulina , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/patologia , Síndrome Metabólica/fisiopatologia , Camundongos , Camundongos Knockout , Camundongos Obesos , Fator 2 Relacionado a NF-E2/genética , Especificidade de Órgãos , Estresse Oxidativo , RNA Mensageiro/metabolismo , Índice de Gravidade de Doença
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