RESUMO
BACKGROUND: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects and is a potential early biomarker of lung damage. The CC16 single nucleotide polymorphism (SNP) rs3741240 risk allele (A) has been inconsistently linked to asthma; other tagging SNPs in the gene have not been explored. The aim was to determine whether CC16 tagging polymorphisms are associated with adult asthma, asthma subtypes or asthma control in the Agricultural Lung Health Study (ALHS). METHODS: The ALHS is an asthma case-control study nested in the Agricultural Health Study cohort. Asthma cases were individuals with current doctor diagnosed asthma, likely undiagnosed asthma, or asthma-COPD overlap defined by questionnaire. We also examined asthma subtypes and asthma control. Five CC16 tagging SNPs were imputed to 1000 Genomes Integrated phase 1 reference panel. Logistic regression was used to estimate associations between CC16 SNPs and asthma outcomes adjusted for covariates. RESULTS: The sample included 1120 asthma cases and 1926 controls of European ancestry, with a mean age of 63 years. The frequency of the risk genotype (AA) for rs3741240 was 12.5% (n = 382). CC16 rs3741240 was not associated with adult asthma outcomes. A tagging SNP in the CC16 gene, rs12270961 was associated with uncontrolled asthma (n = 208, ORadj= 1.4, 95% CI 1.0, 1.9; p = 0.03). CONCLUSION: This study, the largest study to investigate associations between CC16 tagging SNPs and asthma phenotypes in adults, did not confirm an association of rs3741240 with adult asthma. A tagging SNP in CC16 suggests a potential relationship with asthma control.
Assuntos
Asma , Uteroglobina , Humanos , Asma/diagnóstico , Asma/epidemiologia , Asma/genética , Estudos de Casos e Controles , Pulmão , Polimorfismo de Nucleotídeo Único/genética , Uteroglobina/genética , AdultoRESUMO
BACKGROUND: Sensitization to food allergens and food allergic reactions are mostly caused by ingesting the allergen, but can also occur from exposure via the respiratory tract or the skin. Little is known about exposure to food allergens in the home environment. OBJECTIVE: The objective of this study was firstly to describe the frequency of detection of allergens from fish, egg, milk, and peanut in mattress dust collected from homes of 13-year-old adolescents and secondly to identify home characteristics associated with the presence of food allergen contamination in dust. METHODS: Food allergens were measured by dot blot analysis in mattress dust from 143 homes in Oslo, Norway. We analysed associations between home characteristics (collected by parental questionnaires and study technicians) and food allergens by multivariate regression models. RESULTS: Fish allergen was detected in 46%, peanut in 41%, milk in 39%, and egg allergen in 22% of the mattress dust samples; only three samples contained none of these allergens. All four food allergens were more frequently detected in mattresses in small dwellings (< 100 m(2)) than larger dwellings (≥ 130 m(2)); 63-71% of the small dwellings (n = 24) had milk, peanut, and fish allergens in the samples compared with 33-44% of the larger dwellings (n = 95). Milk, peanut, and egg allergens were more frequently detected in homes with bedroom and kitchen on the same floor as compared with different floors, with odds ratios of 2.5 (95% confidence interval (CI): 1.1, 5.6) for milk, 2.4 (95% CI: 1.0, 6.1) for peanut, and 3.1 (95% CI: 1.3, 7.5) for egg allergens. CONCLUSIONS AND CLINICAL RELEVANCE: Food allergens occurred frequently in beds in Norwegian homes, with dwelling size and proximity of kitchen and bedroom as the most important determinants. Due to the amount of time children spent in the bedroom, mattress dust may be an important source of exposure to food allergens.
Assuntos
Alérgenos/imunologia , Leitos/efeitos adversos , Poeira/imunologia , Exposição Ambiental , Hipersensibilidade Alimentar/imunologia , Alimentos/efeitos adversos , Criança , Feminino , Seguimentos , Humanos , Masculino , Noruega , Fatores de TempoRESUMO
BACKGROUND: Exposure to the synthetic antimicrobial chemical, triclosan, used in personal care products, has been hypothesized to lead to allergic disease. We investigated whether triclosan exposure was associated with allergic sensitization and symptoms in 10-year-old Norwegian children. METHODS: Urinary concentrations of triclosan were measured in one first morning void from 623 children, collected during 2001-2004. Logistic regression models, controlling for urine specific gravity, parental allergic disease, maternal education, and household income, were fitted for allergic sensitization (either skin prick test positivity or serum-specific IgE ≥ 0.35 kU/l to at least one of 15 evaluated inhalant and food allergens), current rhinitis, and current asthma (questionnaire and exercise challenge test). RESULTS: The adjusted odds ratio (aOR) for allergic sensitization among those in the fourth quartile of triclosan concentration was 2.0 [95% confidence interval (CI): 1.1, 3.4] compared with the reference group (Assuntos
Alérgenos/imunologia
, Hipersensibilidade/imunologia
, Triclosan/imunologia
, Asma/diagnóstico
, Asma/imunologia
, Criança
, Exposição Ambiental/efeitos adversos
, Feminino
, Humanos
, Hipersensibilidade/diagnóstico
, Imunoglobulina E/sangue
, Imunoglobulina E/imunologia
, Masculino
, Rinite/diagnóstico
, Rinite/imunologia
, Triclosan/urina
RESUMO
CONTEXT: Endothelial function is abnormal in chronic obstructive pulmonary disease (COPD); whether endothelial dysfunction causes COPD is unknown. OBJECTIVE: Test associations of endothelial biomarkers with FEV1 using instrumental variables. METHODS: Among 26 907 participants with spirometry, ICAM-1, P-selectin, E-selectin and endothelin-1 were measured in subsets. RESULTS: ICAM-1 and P-selectin were inversely associated with FEV1 among European-Americans (-29 mL and -34 mL per standard deviation of log-transformed biomarker, p < 0.001), as was endothelin-1 among African-Americans (-22 mL, p = 0.008). Genetically-estimated ICAM-1 and P-selectin were not significantly associated with FEV1. The instrumental variable for endothelin-1 was non-informative. CONCLUSION: Although ICAM-1, P-selectin and endothelin-1 were inversely associated with FEV1, associations for ICAM-1 and P-selectin do not appear causal.
Assuntos
Endotélio Vascular/metabolismo , Expressão Gênica , Pulmão/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Biomarcadores/metabolismo , População Negra , Estudos de Coortes , Selectina E/genética , Selectina E/metabolismo , Endotelina-1/genética , Endotelina-1/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Selectina-P/genética , Selectina-P/metabolismo , Doença Pulmonar Obstrutiva Crônica/etnologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Testes de Função Respiratória , Espirometria , População BrancaRESUMO
INTRODUCTION: The American Dental Association (ADA) defines evidence-based dentistry (EBD) as "an approach to oral healthcare that requires the judicious integration of systematic assessments of clinically relevant scientific evidence, relating to the oral and medical condition and history, with the dentist's clinical expertise and the patient's treatment needs and preferences." Clinical practice guidelines (CPGs) are statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options. Therefore, ADA CPGs are the most rigorous examples of EBD to inform clinical practice. CPGs should be of the highest level of quality to ensure the appropriateness and timeliness of clinical recommendations. OBJECTIVES: The aim of this study was to measure the methodological rigor and transparency of the ADA CPGs. METHODS: Each ADA CPG was appraised by 4 independent assessors using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Quantitative quality scores were obtained for 6 domains and overall quality. In addition, assessors provided a qualitative analysis by providing comments for each item and an appraisal of the full recommendation. RESULTS: A quality score of 75% was used as the threshold for high-quality guidelines. Using this metric, 6 of the current 10 current ADA CPGs were considered to be of high quality, 1 was slightly below the quality threshold, and 3 were considered marginal. Even among those evaluated to be high quality in overall assessment, certain domains did not reach the quality threshold of 75%. CONCLUSION: Overall, the ADA CPGs collectively provide high-quality guidance for the clinician. While the AGREE appraisal guidelines have been used in CPG development since 2016, there is still room for improvement in certain domains (i.e., stakeholder involvement, rigor of development, applicability, and editorial independence). KNOWLEDGE TRANSFER STATEMENT: The results of this study summarize the methodological rigor and transparency of the 10 current ADA clinical practice guidelines. Since adoption of AGREE standards (2016), CPGs have been uniformly of high quality. The quality of older CPGs was somewhat lower but overall deemed acceptable. Thus, ADA CPGs may be used with confidence to inform practitioners of treatment options supported by rigorous evidence-based dentistry standards. However, there is still room for improvement in methodological quality.
Assuntos
American Dental Association , Instalações de Saúde , Estados Unidos , Humanos , Conhecimento , Processos MentaisRESUMO
In this report we have shown that reovirus 1/L is an effective mucosal immunogen capable of generating a cytotoxic T cell (CTL) and associated helper T cell response to the nominal antigens associated with reovirus 1/L. The effectors that mediate reovirus-specific cytotoxicity are Thy-1+, Lyt-2+, and major histocompatibility complex (MHC)-restricted in their recognition of reovirus antigens, and can therefore be classified as CTLs. Frequency analysis of precursor CTLs occurring in Peyer's patches (PP) and peripheral lymph nodes (PLN) 6 d and 6 mo after intraduodenal stimulation have demonstrated that a persistent gradient of precursors is established, with higher frequencies present in PP. The generation of a CTL response in PP may be important in preferentially repopulating mucosal tissues with effector CTLs that could result in the local containment of infections in the gut. We also found that reovirus 1/L generates a virus-specific B cell response that is dominated by IgA memory cells after intraduodenal immunization. We hypothesize that the efficacy of reovirus 1/L at stimulating T and B cells in the gut mucosa is related to its ability to selectively enter PP via microfold (M) cells after enteric application. In this study we have also demonstrated that PP cells, upon in vitro culture and unrelated to prior reovirus priming, can generate natural killer-like (NK) cytotoxic activity. This may be an in vitro correlate of the in vivo generation of effectors that may populate mucosal tissues (i.e., the intestinal epithelium) with NK-like effector cells.
Assuntos
Linfócitos B/imunologia , Imunoglobulina A/imunologia , Mucosa Intestinal/imunologia , Reoviridae/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Antígenos Virais/imunologia , Linhagem Celular , Antígenos H-2/imunologia , Imunização , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Nódulos Linfáticos Agregados/imunologia , Linfócitos T Auxiliares-Indutores/imunologiaRESUMO
AIM: To explore the associations between acute otitis media in early childhood and prenatal and postnatal tobacco smoke exposure. METHODS: Subjects were 32 077 children born between 2000 and 2005 in the Norwegian Mother and Child Study with questionnaire data on tobacco smoke exposure and acute otitis media up to 18 months of age. Multivariate regression models were used to obtain adjusted relative risks for acute otitis media. RESULTS: Acute otitis media was slightly more common in children exposed to parental smoking. The incidence from 0 to 6 months was 4.7% in unexposed children and 6.0% in children exposed both prenatally and postnatally. After adjusting for postnatal exposure and covariates, the relative risk for acute otitis media 0-6 months when exposed to maternal smoking in pregnancy was 1.34, 95% confidence interval: 1.06-1.69. Maternal smoking in pregnancy was associated with acute otitis media up to 12 months of age. Compared with non-exposed children, there was a slightly increased risk of recurrent acute otitis media for children exposed both prenatally and postnatally with a relative risk of 1.24, 95% confidence interval: 1.01-1.52. CONCLUSION: Even in a cohort with relatively low exposure levels of parental smoking, maternal smoking in pregnancy was associated with an increased risk of acute otitis media in early childhood.
Assuntos
Otite Média/etiologia , Efeitos Tardios da Exposição Pré-Natal , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Doença Aguda , Adulto , Estudos de Coortes , Feminino , Humanos , Incidência , Lactente , Masculino , Análise Multivariada , Noruega/epidemiologia , Otite Média/epidemiologia , Pais , Gravidez , Análise de Regressão , Medição de Risco , Fumar/epidemiologia , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: In recent years, Asia has experienced rapid economic growth and a deteriorating environment caused by the increasing use of fossil fuels. Although the deleterious effects of air pollution from fossil-fuel combustion have been demonstrated in many Western nations, few comparable studies have been conducted in Asia. Time-series studies of daily mortality in Asian cities can contribute important new information to the existing body of knowledge about air pollution and health. Not only can these studies verify important health effects of air pollution in local regions in Asia, they can also help determine the relevance of existing air pollution studies to mortality and morbidity for policymaking and environmental controls. In addition, the studies can help identify factors that might modify associations between air pollution and health effects in various populations and environmental conditions. Collaborative multicity studies in Asia-especially when designed, conducted, and analyzed using a common protocol-will provide more robust air pollution effect estimates for the region as well as relevant, supportable estimates of local adverse health effects needed by environmental and public-health policymakers. SPECIFIC OBJECTIVES: The Public Health and Air Pollution in Asia (PAPA*) project, sponsored by the Health Effects Institute, consisted of four studies designed to assess the effects of air pollution on mortality in four large Asian cities, namely Bangkok, in Thailand, and Hong Kong, Shanghai, and Wuhan, in China. In the PAPA project, a Common Protocol was developed based on methods developed and tested in NMMAPS, APHEA, and time-series studies in the literature to help ensure that the four studies could be compared with each other and with previous studies by following an established protocol. The Common Protocol (found at the end of this volume) is a set of prescriptive instructions developed for the studies and used by the investigators in each city. It is flexible enough to allow for adjustments in methods to optimize the fit of health-effects models to each city's data set. It provides the basis for generating reproducible results in each city and for meta-estimates from combined data. By establishing a common methodology, factors that might influence the differences in results from previous studies can more easily be explored. Administrative support was provided to ensure that the highest quality data were used in the analysis. It is anticipated that the PAPA results will contribute to the international scientific discussion of how to conduct and interpret time-series studies of air pollution and will stimulate the development of high-quality routine systems for recording daily deaths and hospital admissions for time-series analysis. METHODS: Mortality data were retrieved from routine databases with underlying causes of death coded using the World Health Organization (WHO) International Classification of Diseases, 9th revision or 10th revision (ICD-9, ICD-10). Air quality measurements included nitrogen dioxide (NO2), sulfur dioxide (SO2), particulate matter with aerodynamic diameter < or = 10 microm (PM10), and ozone (O3) and were obtained from several fixed-site air monitoring stations that were located throughout the metropolitan areas of the four cities and that met the standards of procedures for quality assurance and quality control carried out by local government units in each city. Using the Common Protocol, an optimized core model was established for each city to assess the effects of each of the four air pollutants on daily mortality using generalized linear modeling with adjustments for time trend, seasonality, and other time-varying covariates by means of a natural-spline smoothing function. The models were adjusted to suit local situations by correcting for influenza activity, autocorrelation, and special weather conditions. Researchers in Hong Kong, for example, used influenza activity based on frequency of respiratory mortality; researchers in Hong Kong and Shanghai used autoregressive terms for daily outcomes at lag days; and researchers in Wuhan used additional smoothing for periods with extreme weather conditions. RESULTS AND DISCUSSION: For mortality due to all natural (nonaccidental) causes at all ages, the effects of air pollutants per 10-microg/m3 increase in concentration was found to be higher in Bangkok than in the three Chinese cities, with the exception of the effect of NO2 in Wuhan. The magnitude of the effects for cardiovascular and respiratory mortality were generally higher than for all natural mortality at all ages. In addition, the effects associated with PM10 and O3 in all natural, cardiovascular; and respiratory mortality were found to be higher in Bangkok than in the three Chinese cities. The explanation for these three findings might be related to consistently higher daily mean temperatures in Bangkok, variations in average time spent outdoors by the susceptible populations, and the fact that less air conditioning is available and used in Bangkok than in the other cities. However, when pollutant concentrations were incorporated into the excess risk estimates through the use of interquartile range (IQR), the excess risk was more comparable across the four cities. We found that the increases in effects among older age groups were greater in Bangkok than in the other three cities. After excluding data on extremely high concentrations of PM10 in Bangkok, the effect estimate associated with PM10 concentrations decreased in Bangkok (suggesting a convex relationship between risk and PM10, where risk levels off at high concentrations) instead of increasing, as it did in the other cities. This leveling off of effect estimates at high concentrations might be related to differences in vulnerability and exposure of the population to air pollution as well as to the sources of the air pollutant. IMPLICATIONS OF THE STUDY: The PAPA project is the first coordinated Asian multicity air pollution study ever published; this signifies the beginning of an era of cooperation and collaboration in Asia, with the development of a common protocol for coordination, data management, and analysis. The results of the study demonstrated that air pollution in Asia is a significant public health burden, especially given the high concentrations of pollutants and high-density populations in major cities. When compared with the effect estimates reported in the research literature of North America and Western Europe, the study's effect estimates for PM10 were generally similar and the effect estimates for gaseous pollutants were relatively higher. In Bangkok, however, a tropical city where total exposures to outdoor pollution might be higher than in most other cities, the observed effects were greater than those reported in the previous (i.e., Western) studies. In general, the results suggested that, even though social and environmental conditions across Asia might vary, it is still generally appropriate to apply to Asia the effect estimates for other health outcomes from previous studies in the West. The results also strongly support the adoption of the global air quality guidelines recently announced by WHO.
Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Doenças Cardiovasculares/mortalidade , Saúde Pública , Doenças Respiratórias/mortalidade , Idoso , Ásia/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Ozônio/análise , Ozônio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , Doenças Respiratórias/induzido quimicamente , Dióxido de Enxofre/análise , Dióxido de Enxofre/toxicidade , Fatores de TempoRESUMO
Government and nongovernmental organizations need national and global estimates on the descriptive epidemiology of common oral conditions for policy planning and evaluation. The aim of this component of the Global Burden of Disease study was to produce estimates on prevalence, incidence, and years lived with disability for oral conditions from 1990 to 2017 by sex, age, and countries. In addition, this study reports the global socioeconomic pattern in burden of oral conditions by the standard World Bank classification of economies as well as the Global Burden of Disease Socio-demographic Index. The findings show that oral conditions remain a substantial population health challenge. Globally, there were 3.5 billion cases (95% uncertainty interval [95% UI], 3.2 to 3.7 billion) of oral conditions, of which 2.3 billion (95% UI, 2.1 to 2.5 billion) had untreated caries in permanent teeth, 796 million (95% UI, 671 to 930 million) had severe periodontitis, 532 million (95% UI, 443 to 622 million) had untreated caries in deciduous teeth, 267 million (95% UI, 235 to 300 million) had total tooth loss, and 139 million (95% UI, 133 to 146 million) had other oral conditions in 2017. Several patterns emerged when the World Bank's classification of economies and the Socio-demographic Index were used as indicators of economic development. In general, more economically developed countries have the lowest burden of untreated dental caries and severe periodontitis and the highest burden of total tooth loss. The findings offer an opportunity for policy makers to identify successful oral health strategies and strengthen them; introduce and monitor different approaches where oral diseases are increasing; plan integration of oral health in the agenda for prevention of noncommunicable diseases; and estimate the cost of providing universal coverage for dental care.
Assuntos
Cárie Dentária , Doenças da Boca , Cárie Dentária/epidemiologia , Carga Global da Doença , Saúde Global , Humanos , Incidência , Doenças da Boca/epidemiologia , Prevalência , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Although specific pesticides have been associated with wheeze in farmers, little is known about pesticides and asthma. Data from 19,704 male farmers in the Agricultural Health Study were used to evaluate lifetime use of 48 pesticides and prevalent adult-onset asthma, defined as doctor-diagnosed asthma after the age of 20 yrs. Asthma cases were categorised as allergic (n = 127) and nonallergic (n = 314) based on their history of eczema or hay fever. Polytomous logistic regression, controlling for age, state, smoking and body mass, was used to assess pesticide associations. High pesticide exposure events were associated with a doubling of both allergic and nonallergic asthma. For ever-use, 12 individual pesticides were associated with allergic asthma and four with nonallergic asthma. For allergic asthma, coumaphos (OR 2.34; 95% CI 1.49-3.70), heptachlor (OR 2.01; 95% CI 1.30-3.11), parathion (OR 2.05; 95% CI 1.21-3.46), 80/20 mix (carbon tetrachloride/carbon disulfide) (OR 2.15; 95% CI 1.23-3.76) and ethylene dibromide (OR 2.07; 95% CI 1.02-4.20) all showed ORs of >2.0 and significant exposure-response trends. For nonallergic asthma, DDT (dichlorodiphenyltrichloroethane) showed the strongest association (OR 1.41; 95% CI 1.09-1.84), but with little evidence of increasing asthma with increasing use. Current animal handling and farm activities did not confound these results. There was little evidence that allergy alone was driving these associations. In conclusion, pesticides may be an overlooked contributor to asthma risk among farmers.
Assuntos
Doenças dos Trabalhadores Agrícolas/etiologia , Asma/etiologia , Praguicidas/toxicidade , Adulto , Idoso , Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Agricultura , Asma/induzido quimicamente , Dissulfeto de Carbono/toxicidade , Tetracloreto de Carbono/toxicidade , DDT/toxicidade , Dibrometo de Etileno/toxicidade , Humanos , Iowa , Masculino , Pessoa de Meia-Idade , North Carolina , Exposição Ocupacional , Paration/toxicidade , Estudos Prospectivos , Fumar , Inquéritos e QuestionáriosRESUMO
BACKGROUND: A genome-wide association study identified ORM1-like 3 (orosomucoid 1-like 3, ORMDL3) as an asthma candidate gene. Single nucleotide polymorphisms (SNPs) in the region including ORMDL3 on chromosome 17q21 were related to childhood asthma risk and ORMDL3 expression levels in Europeans. OBJECTIVE: We examined whether polymorphisms in ORMDL3 and the adjacent gasdermin-like (GSDML) gene associated with asthma in the genome-wide association study are related to childhood asthma and atopy in a Mexico City population. METHODS: We genotyped rs4378650 in ORMDL3 and rs7216389 in GSDML in 615 nuclear families consisting of asthmatic children aged 4-17 years and their parents. Atopy was determined by skin prick tests to 25 aeroallergens. RESULTS: Individuals carrying the C allele of rs4378650 or the T allele of rs7216389 had increased risk of asthma [relative risk (RR) = 1.73, 95% confidence interval (CI) 1.19-2.53, P = 0.003 for one or two copies of rs4378650 C, and RR = 1.64, 95% CI 1.12-2.38, P = 0.009 for one or two copies of rs7216389 T). Linkage disequilibrium between the two SNPs was high (r(2) = 0.92). Neither of the SNPs was associated with the degree of atopy. A meta-analysis of five published studies on rs7216389 in nine populations gave an odds ratio for asthma of 1.44 (95% CI, 1.35-1.54, P < 0.00001). CONCLUSIONS: Our results and the meta-analysis provide evidence to confirm the finding from a recent genome-wide association study that polymorphisms in ORMDL3 and the adjacent GSDML may contribute to childhood asthma.
Assuntos
Asma/genética , Predisposição Genética para Doença , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Adolescente , Adulto , Criança , Pré-Escolar , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Hipersensibilidade Imediata , Desequilíbrio de Ligação , Pais , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: Viral hepatitis is known to cause xerostomia in humans, but this has not been reported in an animal model. We report a severe, acute, highly reproducible saliva deficiency occurring in BALB/c mice as a result of experimental viral hepatitis. MATERIALS AND METHODS: BALB/c mice, splenectomized or carrying genetic mutations to detect immunological contributions to the saliva deficiency syndrome, were infected intraperitoneally with a non-lethal dose of murine cytomegalovirus. Pilocarpine-stimulated saliva volumes were determined between 0 and 15 days after infection. Salivary gland, liver, spleen, and sera were analyzed for the presence of virus, cytokines, inflammatory infiltrates, and tissue damage. RESULTS: Saliva deficiency was detectable 2 days after cytomegalovirus infection, peaked at 88% below normal by day 7, and resolved partially in all mice by 15 days postinfection as sialoadenitis increased. Neither salivary gland viral titers, sialoadenitis, splenectomy, nor systemic inflammatory markers correlated with hyposalivation severity. Elevated liver enzymes did correlate with hyposalivation, and mice genetically resistant to murine cytomegalovirus-induced hepatitis were significantly protected. CONCLUSIONS: Murine cytomegalovirus-induced salivary gland dysfunction is biphasic, with an acute hepatitis-associated phase and a later sialoadenitis-associated phase. Acute murine cytomegalovirus infection of BALB/c mice may provide a model for investigation of hepatitis-associated xerostomia.
Assuntos
Hepatite Viral Animal/complicações , Infecções por Herpesviridae/complicações , Muromegalovirus/patogenicidade , Xerostomia/complicações , Análise de Variância , Animais , Aquaporina 5/metabolismo , Modelos Animais de Doenças , Feminino , Hepatite Viral Animal/virologia , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Mutantes , Salivação/fisiologia , Estatísticas não Paramétricas , Xerostomia/metabolismo , Xerostomia/patologia , Xerostomia/virologiaRESUMO
Smoking impacts DNA methylation genome-wide in blood of newborns from maternal smoking during pregnancy and adults from personal smoking. We compared smoking-related DNA methylation in lung adenocarcinoma (61 never smokers, 91 current smokers, and 238 former smokers) quantified with the Illumina450k BeadArray in The Cancer Genome Atlas with published large consortium meta-analyses of newborn and adult blood. We assessed whether CpG sites related to smoking in blood from newborns and adults were enriched in the lung adenocarcinoma methylation signal. Testing CpGs differentially methylated by smoke exposure, we identified 296 in lung adenocarcinoma meeting a P < 10-4 cutoff, while previous meta-analyses identified 3,042 in newborn blood, and 8,898 in adult blood meeting the same P < 10-4 cutoff. Lung signals were highly enriched for those seen in newborn (24 overlapping CpGs, Penrichment = 1.2 × 10-18) and adult blood (66 overlapping CpGs, Penrichment = 1.2 × 10-48). The 105 genes annotated to CpGs differentially methylated in lung tumors, but not blood, were enriched for RNA processing ontologies. Some epigenetic alterations associated with cigarette smoke exposure are tissue specific, but others are common across tissues. These findings support the value of blood-based methylation biomarkers for assessing exposure effects in target tissues.
Assuntos
Metilação de DNA , Suscetibilidade a Doenças , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/etiologia , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal , Fumar/efeitos adversos , Adulto , Biomarcadores , Biologia Computacional , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Masculino , Gravidez , Vigilância em Saúde PúblicaRESUMO
INTRODUCTION: Prenatal exposure to perfluoroalkyl substances (PFASs) has been inconsistently associated with asthma and allergic diseases and increased number of infections in early childhood. We examined the association of PFASs measured in pregnancy with childhood asthma, allergies and common infectious diseases in a prospective pregnancy cohort followed to age 7â¯years. MATERIAL AND METHODS: Six PFASs (out of 19 measured) with at least 80% of measurements above the limit of quantification (LOQ) in maternal plasma during pregnancy in two subcohorts of the Norwegian Mother and Child Cohort Study (MoBa) were analyzed in relation to health outcomes: perfluorooctane sulfonic acid (PFOS), acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluoroheptane sulfonic acid (PFHpS). Follow-up questionnaires were completed at 3â¯years by 1270 women and at 7â¯years by 972 women among the 1943 with pregnancy questionnaire and PFAS measures. Health outcomes included parent reports of child's symptoms or doctor diagnosed asthma and allergic conditions at age 7â¯years and parent-reported frequency of various infections at 3 and 7â¯years of age. Logistic and Poisson regression were used. The false discovery rate was controlled at 5%. Sensitivity analyses on gender were performed. RESULTS: Among the allergy and asthma outcomes, a statistically significant inverse association was seen between PFUnDA concentrations and ever having atopic eczema in girls. PFUnDA also tended to be inversely associated with both wheeze and asthma. For infections from 0 to 3 and 6 to 7â¯years, 11 significant positive associations were seen between PFASs and airways infections (bronchitis/pneumonia, throat infection, pseudocroup), ear infection and gastric flu/diarrhea; whereas 6 inverse associations were seen for pseudocroup, ear infections and urinary tract infections. The majority of the findings with respect to infectious diseases were found in girls only. DISCUSSION: With the exception of an inverse association between PFUnDA and eczema, and a tendency of a similar association for wheeze and asthma, maternal PFAS levels during pregnancy showed little association with asthma or allergy related outcomes. Findings from the present study suggest immunosuppressive effects of PFASs on airways infections, such as bronchitis/pneumonia and throat infections, as well as diarrhea/gastric flu. Our results indicate a possible role of gender in the PFAS-health outcome associations.
Assuntos
Asma/etiologia , Poluentes Ambientais/toxicidade , Fluorocarbonos/toxicidade , Hipersensibilidade/etiologia , Mães , Adulto , Asma/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fluorocarbonos/sangue , Humanos , Hipersensibilidade/epidemiologia , Masculino , Noruega/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Estudos Prospectivos , Adulto JovemRESUMO
G-protein-coupled receptor for asthma susceptibility (GPRA or GPR154) was identified as an asthma and atopy candidate gene by positional cloning. Some subsequent studies suggest associations of GPRA single nucleotide polymorphisms (SNPs) and haplotypes with asthma or atopy susceptibility. However, the associated SNPs or haplotypes vary among studies. The role of GPRA genetic variation in asthma and atopy remains unsolved. Published data on GRPA variants and asthma come exclusively from Caucasian and Asian populations. We examined whether GPRA SNPs and haplotypes are associated with asthma and atopy in a Mexican population. We genotyped and analyzed 27 GPRA SNPs in 589 nuclear families consisting of asthmatic children aged 4-17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests to 25 aeroallergens. The 27 SNPs examined provided excellent coverage of the GPRA gene. GPRA SNPs and haplotypes were not associated with childhood asthma and the degree of atopy to aeroallergens in a Mexican population. Our review of studies of GPRA variants in relation to asthma phenotypes shows considerable heterogeneity. Accordingly, our results suggest that GPRA variants are not an important contributor to childhood asthma and atopy susceptibility in a Mexican population.
Assuntos
Asma/genética , Predisposição Genética para Doença/genética , Variação Genética , Hipersensibilidade Imediata/genética , Receptores Acoplados a Proteínas G/genética , Adolescente , Criança , Pré-Escolar , Clonagem Molecular , Genótipo , Haplótipos/genética , Humanos , México , Polimorfismo de Nucleotídeo Único/genéticaAssuntos
Protocolos Clínicos/normas , Determinismo Genético , Predisposição Genética para Doença/genética , Pesquisa em Genética , Genética Comportamental , Genética Médica/normas , Experimentação Humana , Alelos , Criança , Revelação , Ética Médica , Governo Federal , Guias como Assunto , Humanos , Consentimento Livre e Esclarecido , Menores de Idade , National Institutes of Health (U.S.) , Formulação de Políticas , Projetos de Pesquisa , Sujeitos da Pesquisa , Estados UnidosRESUMO
There is new evidence that the brain of developing songbirds can synthesize estradiol de novo. In males, this neurally derived estrogen might masculinize a connection within the neural song system. These results challenge traditional concepts about mechanisms of brain sexual differentiation and reveal a significant function for neurosteroids.
Assuntos
Química Encefálica/fisiologia , Estradiol/fisiologia , Diferenciação Sexual , Animais , Feminino , Masculino , Aves CanorasRESUMO
BACKGROUND: Glutathione S-transferase M1 (GSTM1) is active in the detoxication of a number of carcinogens, including polyaromatic hydrocarbons, such as those present in cigarette smoke. In about 30%-55% of individuals, depending on the ethnic group, there is a virtual absence of GSTM1 enzyme activity due to deletion of both copies of the GSTM1 gene (GSTM1 null genotype). This genetic polymorphism of the GSTM1 gene locus has been proposed as a risk factor for lung cancer. However, results across studies are inconsistent. PURPOSE: We conducted a case-control study of patients with incident lung cancer and population control subjects to examine the association between homozygous deletion of the GSTM1 gene and lung cancer risk among African-Americans and Caucasians. METHODS: At 35 hospitals in Los Angeles County, California, we identified patients with a first diagnosis of lung cancer between September 1, 1990, and January 6, 1994. Of the 859 potentially eligible case patients, 207 had died by the time their physicians had received our request for permission to contact them. We enrolled 356 eligible case patients (167 African-Americans and 189 Caucasians) and 731 eligible control subjects (258 African-Americans and 473 Caucasians, all residents of Los Angeles County). Samples of white blood cell DNA sufficient for determination of the GSTM1 genotype by a polymerase chain reaction-based assay were obtained from 342 case patients and 716 control subjects. The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1 gene, in total and after stratification by a number of relevant characteristics, were estimated by logistic regression analysis. RESULTS: For patients with all lung cancers combined, the GSTM1 null genotype was associated with an OR of 1.29 (95% CI = 0.94-1.77). The OR was similar among African-Americans (OR = 1.20; 95% CI = 0.72-2.00) and Caucasians (OR = 1.37; 95% CI = 0.91-2.06). The association was strongest for squamous cell carcinoma (OR = 1.57; 95% CI = 0.93-2.63). We observed an OR of 1.77 (95% CI = 1.11-2.82) for the GSTM1 null genotype in relation to lung cancer risk among smokers of less than 40 pack-years, but no association among heavier smokers (OR = 0.90; 95% CI = 0.56-1.44). CONCLUSIONS: Our data do not support a substantial association between homozygous deletion of the GSTM1 gene and the risk of lung cancer overall in this population. However, our data do suggest an elevated risk for lighter smokers with this genotype. IMPLICATIONS: Because the power of our analyses within strata of lifetime smoking history was limited, larger studies will be needed to confirm these findings.
Assuntos
População Negra/genética , Glutationa Transferase/genética , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Polimorfismo Genético , População Branca/genética , Idoso , Antioxidantes/administração & dosagem , Amianto/efeitos adversos , California , Estudos de Casos e Controles , Exposição Ambiental , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Fatores de Risco , Fumar/efeitos adversos , Vitaminas/administração & dosagemRESUMO
In 1976, 117,557 women in the United States aged 30-55 years and without a history of cancer provided detailed information on current smoking habits. By 1986, 1,788 cases of breast cancer had been documented during 1,133,682 person-years. There was no association between current smoking and risk of breast cancer (multivariate-adjusted relative risk for smokers of greater than or equal to 25 cigarettes/day compared to nonsmokers: 1.02, 95% confidence interval, 0.96-1.22). Past smoking also was unrelated to breast cancer risk (relative risk, 1.08; 95% confidence interval, 0.96-1.20). The results did not differ by menopausal status. Tumor size and the presence of nodal metastases were unrelated to smoking. Smoking was weakly associated with estrogen receptor-positive tumors (relative risk for smokers of greater than or equal to 25 cigarettes/day compared with never smokers, 1.38; 95% confidence interval, 1.04-1.84), but there was no dose-response relationship across categories of current smoking. These results suggest that smoking and breast cancer are not materially related.