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1.
Reprod Toxicol ; 119: 108413, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37236408

RESUMO

Analyses were conducted of reproductive outcomes for conceptions of participants of the Air Force Heath Study. Participants were male Air Force veterans of the Vietnam War. Conceptions were categorized into conceived before and after the start of the participant's Vietnam War service. Analyses accounted for correlation between outcomes for multiple conceptions for each participant. For each of three non-sparsely occurring outcomes, including not live born, miscarriage, and preterm, the probability of occurrence increased substantially when conceived after compared to before the start of Vietnam War service. These results support the conclusion of an adverse effect due to Vietnam War service on these reproductive outcomes. Data for conceptions after the start of Vietnam War service for participants with measured dioxin values were used to estimate dose-response curves for the effect of dioxin exposure on the occurrence of each of the three non-sparsely occurring outcomes. These curves were assumed to be constant up to a threshold and then monotonic after that threshold. For each of the three non-sparsely occurring outcomes, the estimated dose-response curves increased nonlinearly after associated thresholds. These results support the conclusion that the adverse effect due to conception after the start of Vietnam War service is attributable to high enough exposures to dioxin, a toxic contaminant of Agent Orange used for herbicide spraying in the Vietnam War. Sensitivity analyses supported the conclusion that dioxin results were not substantially affected by the assumption of monotonicity, decay due to elapsed time from exposure to measurement, and available covariates.


Assuntos
Desfolhantes Químicos , Dioxinas , Dibenzodioxinas Policloradas , Recém-Nascido , Humanos , Masculino , Feminino , Ácido 2,4-Diclorofenoxiacético , Ácido 2,4,5-Triclorofenoxiacético/efeitos adversos , Desfolhantes Químicos/efeitos adversos , Desfolhantes Químicos/análise , Exposição Ambiental , Dibenzodioxinas Policloradas/toxicidade
2.
Molecules ; 27(3)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35163979

RESUMO

The aim of this study was to determine the effects of defoliation performed in the Babica red grape variety on the volatile compounds in produced wine. Three treatments were performed during 2017 and 2018: the removal of six leaves before flowering (FL) and at the end of veraison (VER), as well as control (C). Volatile compounds were analyzed using a gas chromatograph coupled to a mass spectrophotometric detector. Results were statistically evaluated by analysis of variance (ANOVA at the p = 0.05 level) and principal component analysis (PCA). Defoliation treatments were affected by the concentration of several compounds, but only in one year. The VER2017 treatment significantly increased the concentration of three aliphatic esters up to 8 C atoms and octanoic acid ethyl ester. The FL2017 treatment increased the concentration of three aliphatic alcohols. The FL2018 treatment has significantly enhanced the concentration ethyl cinnamate but decreased the concentrations of eugenol and dihydro-2-methyl-3(2H)-thiophenone. Both defoliation treatments reduced the concentration of γ-decanolactone in 2017. Aldehydes, monoterpenoles, and monoterpenes remained unaffected by the defoliation treatments. Vintage was found to be the largest source of variability for most volatile compounds under investigation, which was confirmed by PCA. The effect of defoliation in the mild-Mediterranean climate was found to mostly depend on seasonal weather conditions.


Assuntos
Desfolhantes Químicos/efeitos adversos , Vitis/química , Vitis/metabolismo , Compostos Orgânicos Voláteis/análise , Cromatografia Gasosa/métodos , Clima , Frutas/química , Odorantes/análise , Folhas de Planta/química , Análise de Componente Principal , Compostos Orgânicos Voláteis/química , Tempo (Meteorologia) , Vinho/análise
3.
J Environ Manage ; 299: 113599, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34492437

RESUMO

The Danang airport in Vietnam was used heavily by US forces in the 1960s and 1970s. In 2018, the remediation of dioxin contamination at the airport resulting from Agent Orange use and management was completed by the US government. Generation of reliable, defensible, and cost-effective confirmation sampling data over large areas and for large volumes was a significant challenge. Traditional discrete and composite sampling methods were utilized to assess dioxin concentrations and the extent of contamination present at the airport prior to remediation. Confirmation sampling was performed after excavation of contaminated soil and sediment across the entire 28-ha site to demonstrate that remaining concentrations met the Vietnamese standards for the airport site. The volume of excavated soil and sediment was 162,567 m3. Incremental Sampling Methodology (ISM) was used for confirmation sampling to provide a defensible estimate of the mean concentration of dioxin remaining after excavation. The use of ISM revealed that traditional methods underestimated the volume of material requiring treatment. ISM also decreased sampling variability dramatically and provided more reliable estimates of true mean concentrations in an area when compared with traditional methods. The use of ISM: 1) better captured distributional heterogeneity and decreased variability between samples from the same DU by 64%; 2) resulted in low variability between duplicate analyses of the same sample (12%), indicating a reduction in compositional heterogeneity; 3) did not underestimate contaminant levels; and, 4) increased the frequency that excavation boundaries met project goals by 61%, when compared with traditional sampling.


Assuntos
Desfolhantes Químicos , Dioxinas , Ácido 2,4,5-Triclorofenoxiacético , Ácido 2,4-Diclorofenoxiacético , Agente Laranja , Desfolhantes Químicos/análise , Solo , Vietnã
4.
PLoS One ; 16(8): e0256942, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34464415

RESUMO

Under inadequate chilling conditions, hydrogen cyanamide (HC) is often used to promote budbreak and improve earliness of Southern highbush blueberry (Vaccinium corymbosum L. interspecific hybrids). However, HC is strictly regulated or even banned in some countries because of its high hazardous properties. Development of safer and effective alternatives to HC is critical to sustainable subtropical blueberry production. In this study, we examined the efficacy of HC and defoliants as bud dormancy-breaking agents for 'Emerald' blueberry. First, we compared water control, 1.0% HC (9.35 L ha-1), and three defoliants [potassium thiosulfate (KTS), urea, and zinc sulfate (ZS)] applied at 6.0% (28 kg ha-1). Model fitting analysis revealed that only HC and ZS advanced both defoliation and budbreak compared with the water control. HC-induced budbreak showed an exponential plateau function with a rapid phase occurring from 0 to 22 days after treatment (DAT), whereas ZS-induced budbreak showed a sigmoidal function with a rapid phase occurring from 15 to 44 DAT. The final budbreak percentage was similar in all treatments (71.7%-83.7%). Compared with the water control, HC and ZS increased yield by up to 171% and 41%, respectively, but the yield increase was statistically significant only for HC. Phytohormone profiling was performed for water-, HC- and ZS-treated flower buds. Both chemicals did not increase gibberellin 4 and indole-3-acetic acid production, but they caused a steady increase in jasmonic acid (JA) during budbreak. Compared with ZS, HC increased JA production to a greater extent and was the only chemical that reduced abscisic acid (ABA) concentrations during budbreak. A follow-up experiment tested ZS at six different rates (0-187 kg ha-1) but detected no significant dose-response on budbreak. These results collectively suggest that defoliants are not effective alternatives to HC, and that HC and ZS have different modes of action in budbreak induction. The high efficacy of HC as a dormancy-breaking agent could be due to its ability to reduce ABA concentrations in buds. Our results also suggest that JA accumulation is involved in budbreak induction in blueberry.


Assuntos
Mirtilos Azuis (Planta)/crescimento & desenvolvimento , Cianamida/farmacologia , Desfolhantes Químicos/farmacologia , Flores/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas/fisiologia , Mirtilos Azuis (Planta)/efeitos dos fármacos , Mirtilos Azuis (Planta)/fisiologia , Flores/fisiologia , Frutas/crescimento & desenvolvimento , Dormência de Plantas/efeitos dos fármacos , Dormência de Plantas/fisiologia
5.
Sci Rep ; 11(1): 15054, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301993

RESUMO

The increasing severity and frequency of natural disturbances requires a better understanding of their effects on all compartments of biodiversity. In Northern Fennoscandia, recent large-scale moth outbreaks have led to an abrupt change in plant communities from birch forests dominated by dwarf shrubs to grass-dominated systems. However, the indirect effects on the belowground compartment remained unclear. Here, we combined eDNA surveys of multiple trophic groups with network analyses to demonstrate that moth defoliation has far-reaching consequences on soil food webs. Following this disturbance, diversity and relative abundance of certain trophic groups declined (e.g., ectomycorrhizal fungi), while many others expanded (e.g., bacterivores and omnivores) making soil food webs more diverse and structurally different. Overall, the direct and indirect consequences of moth outbreaks increased belowground diversity at different trophic levels. Our results highlight that a holistic view of ecosystems improves our understanding of cascading effects of major disturbances on soil food webs.


Assuntos
Biodiversidade , Ecossistema , Cadeia Alimentar , Mariposas/efeitos dos fármacos , Animais , Betula/efeitos dos fármacos , Desfolhantes Químicos/efeitos adversos , Poluição Ambiental/efeitos adversos , Micorrizas/efeitos dos fármacos , Poaceae/efeitos dos fármacos
6.
Environ Health ; 20(1): 43, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849548

RESUMO

BACKGROUND: Between 1962 and 1971, the US Air Force sprayed Agent Orange across Vietnam, exposing many soldiers to this dioxin-containing herbicide. Several negative health outcomes have been linked to Agent Orange exposure, but data is lacking on the effects this chemical has on the genome. Therefore, we sought to characterize the impact of Agent Orange exposure on DNA methylation in the whole blood and adipose tissue of veterans enrolled in the Air Force Health Study (AFHS). METHODS: We received adipose tissue (n = 37) and whole blood (n = 42) from veterans in the AFHS. Study participants were grouped as having low, moderate, or high TCDD body burden based on their previously measured serum levels of dioxin. DNA methylation was assessed using the Illumina 450 K platform. RESULTS: Epigenome-wide analysis indicated that there were no FDR-significantly methylated CpGs in either tissue with TCDD burden. However, 3 CpGs in the adipose tissue (contained within SLC9A3, LYNX1, and TNRC18) were marginally significantly (q < 0.1) hypomethylated, and 1 CpG in whole blood (contained within PTPRN2) was marginally significantly (q < 0.1) hypermethylated with high TCDD burden. Analysis for differentially methylated DNA regions yielded SLC9A3, among other regions in adipose tissue, to be significantly differentially methylated with higher TCDD burden. Comparing whole blood data to a study of dioxin exposed adults from Alabama identified a CpG within the gene SMO that was hypomethylated with dioxin exposure in both studies. CONCLUSION: We found limited evidence of dioxin associated DNA methylation in adipose tissue and whole blood in this pilot study of Vietnam War veterans. Nevertheless, loci in the genes of SLC9A3 in adipose tissue, and PTPRN2 and SMO in whole blood, should be included in future exposure analyses.


Assuntos
Tecido Adiposo/metabolismo , Agente Laranja , Substâncias para a Guerra Química , Metilação de DNA , Desfolhantes Químicos , Veteranos , Guerra do Vietnã , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Idoso de 80 Anos ou mais , Ilhas de CpG , Exposição Ambiental , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Dibenzodioxinas Policloradas/sangue , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/genética , Trocador 3 de Sódio-Hidrogênio/genética
7.
J Chem Ecol ; 47(3): 313-321, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33683546

RESUMO

Climate warming can influence interactions between plants and associated organisms by altering levels of plant secondary metabolites. In contrast to studies of elevated temperature on aboveground phytochemistry, the consequences of warming on root chemistry have received little attention. Herein, we investigated the effects of elevated temperature, defoliation, and genotype on root biomass and phenolic compounds in trembling aspen (Populus tremuloides). We grew saplings of three aspen genotypes under ambient or elevated temperatures (+4-6 °C), and defoliated (by 75%) half of the trees in each treatment. After 4 months, we harvested roots and determined their condensed tannin and salicinoid (phenolic glycoside) concentrations. Defoliation reduced root biomass, with a slightly larger impact under elevated, relative to ambient, temperature. Elevated temperature decreased condensed tannin concentrations by 21-43% across the various treatment combinations. Warming alone did not alter salicinoid concentrations but eliminated a small negative impact of defoliation on those compounds. Graphical vector analysis suggests that effects of warming and defoliation on condensed tannins and salicinoids were predominantly due to reduced biosynthesis of these metabolites in roots, rather than to changes in root biomass. In general, genotypes did not differ in their responses to temperature or temperature by defoliation interactions. Collectively, our results suggest that future climate warming will alter root phytochemistry, and that effects will vary among different classes of secondary metabolites and be influenced by concurrent ecological interactions such as herbivory. Temperature- and herbivory-mediated changes in root chemistry have the potential to influence belowground trophic interactions and soil nutrient dynamics.


Assuntos
Desfolhantes Químicos/química , Extratos Vegetais/análise , Folhas de Planta/química , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Populus/química , Populus/metabolismo , Animais , Biomassa , Mudança Climática , Desfolhantes Químicos/metabolismo , Genótipo , Glicosídeos/química , Glicosídeos/metabolismo , Herbivoria , Larva/efeitos dos fármacos , Mariposas , Fenóis/química , Fenóis/metabolismo , Folhas de Planta/metabolismo , Proantocianidinas/química , Proantocianidinas/metabolismo , Metabolismo Secundário , Solo , Temperatura
8.
JAMA Neurol ; 78(4): 473-477, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33492338

RESUMO

Importance: Agent Orange is a powerful herbicide that contains dioxin and was used during the Vietnam War. Although prior studies have found that Agent Orange exposure is associated with increased risk of a wide range of conditions, including neurologic disorders (eg, Parkinson disease), metabolic disorders (eg, type 2 diabetes), and systemic amyloidosis, the association between Agent Orange and dementia remains unclear. Objective: To examine the association between Agent Orange exposure and incident dementia diagnosis in US veterans of the Vietnam era. Design, Setting, and Participants: This cohort study included Veterans Health Administration data from October 1, 2001, and September 30, 2015, with up to 14 years of follow-up. Analyses were performed from July 2018 to October 2020. A 2% random sample of US veterans of the Vietnam era who received inpatient or outpatient Veterans Health Administration care, excluding those with dementia at baseline, those without follow-up visits, and those with unclear Agent Orange exposure status. Exposures: Presumed Agent Orange exposure documented in electronic health record. Main Outcomes and Measures: Fine-Gray competing risk models were used to compare the time to dementia diagnosis (with age as the time scale) for veterans with vs without presumed Agent Orange exposure (as per medical records), adjusting for demographic variables and medical and psychiatric comorbidities. Results: The total sample was 511 189 individuals; after exclusions, 316 351 were included in analyses. Veterans were mostly male (n = 309 889 [98.0%]) and had a mean (SD) age of 62 (6.6) years; 38 121 (12.1%) had presumed Agent Orange exposure. Prevalence of most conditions, including Parkinson disease, diabetes, and amyloidosis, was similar at baseline among veterans with and without Agent Orange exposure. After adjusting for demographic variables and comorbidities, veterans exposed to Agent Orange were nearly twice as likely as those not exposed to receive a dementia diagnosis over a mean (SD) of 5.5 (3.8) years of follow-up (1918 of 38 121 [5.0%] vs 6886 of 278 230 [2.5%]; adjusted hazard ratio: 1.68 [95% CI, 1.59-1.77]). Veterans with Agent Orange exposure developed dementia at a mean of 1.25 years earlier (at a mean [SD] age of 67.5 [7.0] vs 68.8 [8.0] years). Conclusions and Relevance: Veterans with Agent Orange exposure were nearly twice as likely to be diagnosed with dementia, even after adjusting for the competing risk of death, demographic variables, and medical and psychiatric comorbidities. Additional studies are needed to examine potential mechanisms underlying the association between Agent Orange exposure and dementia.


Assuntos
Agente Laranja/efeitos adversos , Demência/induzido quimicamente , Demência/diagnóstico , Exposição Ambiental/efeitos adversos , Veteranos , Guerra do Vietnã , Idoso , Estudos de Coortes , Desfolhantes Químicos/efeitos adversos , Demência/psicologia , Registros Eletrônicos de Saúde/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Veteranos/psicologia , Serviços de Saúde para Veteranos Militares/tendências
9.
Int J Mol Sci ; 21(8)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32326540

RESUMO

Chemical defoliation is an important part of cotton mechanical harvesting, which can effectively reduce the impurity content. Thidiazuron (TDZ) is the most used chemical defoliant on cotton. To better clarify the mechanism of TDZ promoting cotton leaf abscission, a greenhouse experiment was conducted on two cotton cultivars (CRI 12 and CRI 49) by using 100 mg L-1 TDZ at the eight-true-leaf stage. Results showed that TDZ significantly promoted the formation of leaf abscission zone and leaf abscission. Although the antioxidant enzyme activities were improved, the reactive oxygen species and malondialdehyde (MDA) contents of TDZ increased significantly compared with CK (water). The photosynthesis system was destroyed as net photosynthesis (Pn), transpiration rate (Tr), and stomatal conductance (Gs) decreased dramatically by TDZ. Furthermore, comparative RNA-seq analysis of the leaves showed that all of the photosynthetic related genes were downregulated and the oxidation-reduction process participated in leaf shedding caused by TDZ. Consequently, a hypothesis involving possible cross-talk between ROS metabolism and photosynthesis jointly regulating cotton leaf abscission is proposed. Our findings not only provide important insights into leaf shedding-associated changes induced by TDZ in cotton, but also highlight the possibility that the ROS and photosynthesis may play a critical role in the organ shedding process in other crops.


Assuntos
Desfolhantes Químicos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Gossypium/metabolismo , Compostos de Fenilureia/farmacologia , Fotossíntese/efeitos dos fármacos , Folhas de Planta/metabolismo , Tiadiazóis/farmacologia , Carboidratos/análise , Clorofila/análise , Fibra de Algodão , Desfolhantes Químicos/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , Ontologia Genética , Gossypium/efeitos dos fármacos , Gossypium/genética , Malondialdeído/análise , Microscopia Eletrônica de Varredura , Epiderme Vegetal/anatomia & histologia , Epiderme Vegetal/efeitos dos fármacos , Epiderme Vegetal/ultraestrutura , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/ultraestrutura , Estômatos de Plantas/efeitos dos fármacos , Estômatos de Plantas/fisiologia , RNA-Seq , Espécies Reativas de Oxigênio/metabolismo , Plântula/anatomia & histologia , Plântula/crescimento & desenvolvimento
11.
J Exp Bot ; 70(5): 1525-1538, 2019 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-30715415

RESUMO

Abscission is a process that allows plants to shed tissues or organs via cell separation, and occurs throughout the life cycle. Removal of leaves through the use of chemical defoliants is very important for mechanical harvesting of cotton (Gossypium hirsutum). However, our knowledge of the molecular mechanisms of the defoliation response involved is limited. In this study, RNA-seq was conducted in order to profile the differentially expressed genes (DEGs) between cultivars X50 (sensitive to chemical defoliants) and X33 (relatively insensitive) at different time points after treatment with thidiazuron and ethephon (TE). A total of 2434 DEGs were identified between the two cultivars across the different time-points. Functional categories according to GO and KEGG analyses revealed that plant hormone signal transduction and zeatin biosynthesis were involved in the response to TE. Cytokinin oxidase/dehydrogenase (CKX) genes and ethylene-related genes were up-regulated following TE treatment, and were associated with increased level of ethylene, especially in cultivar X50. Down-regulation of GhCKX3 resulted in delayed defoliation and a reduced ethylene response. The results show that crosstalk between cytokinin and ethylene regulates cotton defoliation, and provide new insights into the molecular mechanisms underlying the mode of action of defoliants in cotton.


Assuntos
Citocininas/metabolismo , Desfolhantes Químicos/administração & dosagem , Etilenos/metabolismo , Gossypium/fisiologia , Folhas de Planta/crescimento & desenvolvimento , Gossypium/efeitos dos fármacos , Gossypium/genética , Compostos Organofosforados/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tiadiazóis/administração & dosagem
12.
J Urol ; 201(4): 742-750, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30321553

RESUMO

PURPOSE: In this study we explored the effect of Agent Orange exposure on prostate cancer survival in VA (Veterans Affairs) patients receiving androgen deprivation therapy for advanced prostate cancer. MATERIALS AND METHODS: We retrospectively examined the association between Agent Orange exposure in men with prostate cancer in national VA databases who were being treated with androgen deprivation therapy. Patients were diagnosed with prostate cancer from 2000 to 2008 with followup through May 2016. Clinical, pathological and demographic variables were compared by Agent Orange exposure. Associations of Agent Orange with overall survival, skeletal related events and cancer specific survival were performed using adjusted Cox proportional hazard models after IPSW (inverse propensity score weighted) adjustment. RESULTS: Overall 87,344 patients were identified. The 3,475 Agent Orange exposed patients were younger (p <0.001), had lower prostate specific antigen (p = 0.002) and were more likely to receive local therapy and chemotherapy (p <0.001) than the 83,869 nonexposed patients. The Charlson comorbidity index was similar in the groups (p = 0.40). After IPSW adjustment Agent Orange exposure was associated with improved overall survival (HR 0.84, 95% CI 0.73-0.97, p = 0.02). However, no difference was observed in the risk of skeletal related events (HR 1.04, 95% CI 0.80-1.35, p = 0.77) or cancer specific survival (HR 0.79, 95% CI 0.60-1.03, p = 0.08). CONCLUSIONS: Agent Orange exposure was associated with a decreased risk of death in men receiving androgen deprivation therapy for advanced prostate cancer. It does not appear to be associated with worse oncologic outcomes.


Assuntos
Agente Laranja/toxicidade , Desfolhantes Químicos/toxicidade , Neoplasias da Próstata/mortalidade , Saúde dos Veteranos , Idoso , Antagonistas de Receptores de Andrógenos/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Taxa de Sobrevida
13.
Environ Pollut ; 242(Pt A): 976-985, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30373043

RESUMO

During the Vietnam War, the United States military sprayed over 74 million litres of Agent Orange (AO) to destroy forest cover as a counterinsurgency tactic in Vietnam, Laos and Cambodia. The main ingredient was contaminated by 2,3,7,8-tetrachlorodibenzo-paradioxin (TCDD). DNA methylation (DNAm) differences are potential biomarker of environmental toxicants exposure. The aim of this study was to perform a preliminary investigation of the DNAm levels from peripheral blood of the present-day Vietnamese population, including individuals whose parents, according to historical data, were exposed to AO/TCDD during the war. 94 individuals from heavily sprayed areas (cases) and 94 individuals from non-sprayed areas (controls) were studied, and historical data on alleged exposure of parents collected. 94 cases were analysed considering those whose father/parents participated in the war (N = 29) and considering the place of residence of both parents (64 living in sprayed areas versus 30 in non-contaminated areas). DNAm levels in CYP1A1 and IGF2 genes were measured (MALDI-TOF technology). The analyses showed that: 1) one CpG site in the CYP1A1 and one in the IGF2 gene showed significant differences in DNAm levels between cases and controls; 2) the CYP1A1 region resulted to be hypomethylated (in 9 out of 16 sites/units; p-val<0.01) in 29 individuals whose father/parents participated in the war in the spray zones; 3) we showed that the place of residence of both parents influenced methylation levels of the CYP1A1 and IGF2 genes (p-val<0.05). In conclusion this study indicates that past environmental exposure to dioxin (AO/TCDD) shapes the DNAm profile of CYP1A1 and that the place of living for parents in former spray zones influences DNAm of CYP1A1 and IGF2 genes. These results open the way to new applications of DNAm as potential biomarker(s) of past human exposure to dioxin.


Assuntos
Citocromo P-450 CYP1A1/genética , Metilação de DNA , Dioxinas/toxicidade , Exposição Ambiental/estatística & dados numéricos , Fator de Crescimento Insulin-Like II/genética , Ácido 2,4,5-Triclorofenoxiacético , Ácido 2,4-Diclorofenoxiacético , Agente Laranja , Camboja , Desfolhantes Químicos , Dioxinas/análise , Exposição Ambiental/análise , Feminino , Humanos , Militares , Dibenzodioxinas Policloradas/análise , Vietnã
14.
Medicine (Baltimore) ; 97(19): e0662, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29742706

RESUMO

During the Vietnam War, the US military sprayed almost 20 million gallons of Agent Orange (AO), an herbicide contaminated with dioxin, over Vietnam. Approximately, 2.7 million US military personnel may have been exposed to AO during their deployment. Ordinarily, veterans who can demonstrate a nexus between a diagnosed condition and military service are eligible for Department of Veterans Affairs (VA) service-connected disability compensation. Vietnam Veterans have had difficulty, however, establishing a nexus between AO exposure and certain medical conditions that developed many years after the war. In response, VA has designated certain conditions as "presumed service connected" for Vietnam Veterans who were present and possibly exposed. Veterans with any of these designated conditions do not have to document AO exposure, making it easier for them to access the VA disability system. The extent to which VA healthcare utilization patterns reflect easier access afforded those with diagnosed presumptive conditions remains unknown. In this cross-sectional study, we hypothesized that Vietnam Veterans with diagnosed presumptive conditions would be heavier users of the VA healthcare system than those without these conditions. In our analysis of 85,699 Vietnam Veterans, we used binary and cumulative logit multivariable regression to assess associations between diagnosed presumptive conditions and VA healthcare utilization in 2013. We found that diagnosed presumptive conditions were associated with higher odds of 5+ VHA primary care visits (OR = 2.01, 95% CI: 1.93-2.07), 5+ specialty care visits (OR = 2.11, 95% CI: 2.04-2.18), emergency department use (OR = 1.22, 95% CI: 1.11-1.34), and hospitalization (OR = 1.23, 95% CI: 1.17-1.29). Consistent with legislative intent, presumptive policies appear to facilitate greater VA system utilization for Vietnam Veterans who may have been exposed to AO.


Assuntos
Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Ajuda a Veteranos Incapacitados/legislação & jurisprudência , Veteranos/estatística & dados numéricos , Guerra do Vietnã , Agente Laranja/toxicidade , Estudos Transversais , Desfolhantes Químicos/toxicidade , Hospitais de Veteranos/estatística & dados numéricos , Humanos , Atenção Primária à Saúde/estatística & dados numéricos , Estados Unidos , United States Department of Veterans Affairs , Revisão da Utilização de Recursos de Saúde , Exposição à Guerra
15.
Hum Exp Toxicol ; 37(11): 1131-1160, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29569487

RESUMO

Diquat (1,1'-ethylene-2,2'-bipyridinium ion; DQ) is a nonselective quick-acting herbicide, which is used as contact and preharvest desiccant to control terrestrial and aquatic vegetation. Several cases of human poisoning were reported worldwide mainly due to intentional ingestion of the liquid formulations. Its toxic potential results from its ability to produce reactive oxygen and nitrogen species through redox cycling processes that can lead to oxidative stress and potentially cell death. Kidney is the main target organ due to DQ toxicokinetics and redox cycling. There is no antidote against DQ intoxications, and the efficacy of treatments currently applied is still unsatisfactory. The aim of this work was to review the most relevant human and experimental findings related to DQ, characterizing its chemistry, activity as herbicide, mechanisms of toxicity, consequences of poisoning, and potential therapeutic approaches taking into account previous experience in developing antidotes for paraquat, a more toxic bipyridinium herbicide.


Assuntos
Desfolhantes Químicos/envenenamento , Diquat/envenenamento , Estresse Oxidativo/efeitos dos fármacos , Intoxicação/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Desfolhantes Químicos/farmacocinética , Diquat/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Intoxicação/diagnóstico , Intoxicação/metabolismo , Intoxicação/mortalidade , Medição de Risco , Toxicocinética , Resultado do Tratamento , Adulto Jovem
16.
Urol Oncol ; 35(11): 633-639, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28947305

RESUMO

Agent Orange is an herbicide sprayed widely in Vietnam that is linked to a variety of malignancies in as early as 1991.Since then, there has been concern for, and subsequent interest in studying, the potential connection between Agent Orange and other malignancies. In the past 2 decades, there have been significant changes in the opinion of the National Academy of Science regarding Agent Orange and certain genitourinary malignancies. Herein, we review the literature regarding the potential link between Agent Orange and various urological cancers, including prostate, bladder, testicular, and renal cancers.


Assuntos
Agente Laranja/envenenamento , Neoplasias Renais/diagnóstico , Dibenzodioxinas Policloradas/envenenamento , Neoplasias da Próstata/diagnóstico , Neoplasias Testiculares/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Agente Laranja/química , Desfolhantes Químicos/química , Desfolhantes Químicos/envenenamento , Humanos , Neoplasias Renais/induzido quimicamente , Masculino , Neoplasias da Próstata/induzido quimicamente , Fatores de Risco , Neoplasias Testiculares/induzido quimicamente , Neoplasias da Bexiga Urinária/induzido quimicamente
17.
Mol Nutr Food Res ; 61(11)2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28759161

RESUMO

SCOPE: Serine lies at the central node linking biosynthetic flux from glycolysis to glutathione synthesis and one-carbon metabolic cycle which are closely related to antioxidant capacity. The present study was conducted to determine the effects of serine supplementation on oxidative stress and its relative mechanisms. METHODS AND RESULTS: Diquat treatment was performed to induce oxidative stress in mice and primary hepatocytes. The results showed that hepatic glutathione anti-oxidant systems were impaired and reactive oxygen species and homocysteine were increased in diquat-induced mice and hepatocytes, while such disadvantageous changes were diminished by serine supplementation both in vivo and in vitro. However, when cystathionine ß-synthase expression was inhibited by interference RNA in hepatocytes, the effects of serine supplementation on the improvement of glutathione synthesis and the alleviation of oxidative stress were diminished. Moreover, when hepatocytes were treated with cycloleucine, an inhibitor of methionine adenosyltransferase, the effects of serine supplementation on the improvement of methionine cycle and the alleviation of DNA hypomethylation and oxidative stress were also diminished. CONCLUSION: Our results indicated that serine supplementation alleviated oxidative stress via supporting glutathione synthesis and methionine cycle, mostly by condensing with homocysteine to synthesize cysteine and providing one-carbon units for homocysteine remethylation.


Assuntos
Antioxidantes/uso terapêutico , Suplementos Nutricionais , Glutationa/metabolismo , Hepatócitos/metabolismo , Metionina/metabolismo , Estresse Oxidativo , Serina/uso terapêutico , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cicloleucina/farmacologia , Cistationina beta-Sintase/antagonistas & inibidores , Cistationina beta-Sintase/genética , Cistationina beta-Sintase/metabolismo , Metilação de DNA/efeitos dos fármacos , Desfolhantes Químicos/antagonistas & inibidores , Desfolhantes Químicos/toxicidade , Diquat/antagonistas & inibidores , Diquat/toxicidade , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Homocisteína/metabolismo , Masculino , Metionina Adenosiltransferase/antagonistas & inibidores , Metionina Adenosiltransferase/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Interferência de RNA , Distribuição Aleatória , Serina/antagonistas & inibidores , Serina/metabolismo , Organismos Livres de Patógenos Específicos
18.
Urol Oncol ; 35(11): 627-632, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28826703

RESUMO

BACKGROUND: During the Vietnam War, many veterans were exposed to Agent Orange (AO), a chemical defoliant containing varying levels of the carcinogen dioxin. The health effects of AO exposure have been widely studied in the VA population. Here we review and interpret data regarding the association between AO exposure and bladder cancer (BC) mortality. MAIN FINDINGS: Data evaluating the association between AO and BC is limited. Methods characterizing exposure have become more sophisticated over time. Several studies support the link between AO exposure and increased mortality due to BC, including the Korean Veterans Health Study. CONCLUSIONS: Available data suggest an association with exposure to AO and increased mortality due to BC. In patients exposed to AO, increased frequency of cystoscopic surveillance and potentially more aggressive therapy for those with BC may be warranted but utility of these strategies remains to be proven. Additional research is required to better understand the relationship between AO and BC.


Assuntos
Agente Laranja/envenenamento , Exposição Ambiental/análise , Dibenzodioxinas Policloradas/envenenamento , Neoplasias da Bexiga Urinária/diagnóstico , Agente Laranja/química , Desfolhantes Químicos/envenenamento , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/envenenamento , Humanos , Fatores de Risco , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/mortalidade , Veteranos/estatística & dados numéricos , Guerra do Vietnã
19.
BMJ Case Rep ; 20162016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27908921

RESUMO

Wartime toxin exposures have been implicated in the genesis of malignancy in war veterans. Agent Orange, one toxin among many, has been linked to malignancy and the subcomponent phenoxyacetic acid has been associated with soft tissue sarcomas (STSs). This case demonstrates the association between a wartime toxin exposure (Agent Orange) and subsequent cancer development. Ultimately, we aim to highlight the importance of simple, specific questions in the patient history to account for previous wartime toxin exposures.


Assuntos
Ácido 2,4,5-Triclorofenoxiacético/envenenamento , Ácido 2,4-Diclorofenoxiacético/envenenamento , Guerra Química , Desfolhantes Químicos/envenenamento , Exposição Ambiental/efeitos adversos , Anamnese , Dibenzodioxinas Policloradas/envenenamento , Sarcoma/induzido quimicamente , Veteranos , Guerra do Vietnã , Administração Cutânea , Agente Laranja , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco
20.
Med Confl Surviv ; 32(2): 138-152, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27748632

RESUMO

Attempts through the US courts to hold the corporations responsible for the production of dioxin-contaminated herbicides used by the US military in the 1960s and early 1970s liable for their ongoing health consequences have failed. This article scrutinizes the most recent judgement - that of the United States District Court for the Eastern District of New York handed down in 2005 following a lawsuit brought by the Vietnam Association of Victims of Agent Orange/dioxin (VAVA). It is argued that despite this judgement there is the potential to bring a further legal case, with some prospect of success, on the basis of: (i) debatable legal judgements in the 2005 decision; (ii) new scientific evidence on the health effects of exposure to Agent Orange; and (iii) cases brought in other jurisdictions. The article concludes by noting the underfunding of ongoing remediation efforts, especially for the provision of assistance to affected individuals, and argues that it is desirable to oblige the producers of the herbicides to contribute financially to these efforts.


Assuntos
Ácido 2,4,5-Triclorofenoxiacético/efeitos adversos , Ácido 2,4-Diclorofenoxiacético/efeitos adversos , Indústria Química/legislação & jurisprudência , Desfolhantes Químicos/efeitos adversos , Responsabilidade Legal , Dibenzodioxinas Policloradas/efeitos adversos , Agente Laranja , Causalidade , Humanos , Direito Internacional , Estados Unidos , Veteranos/legislação & jurisprudência , Guerra do Vietnã
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