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1.
ACS Chem Neurosci ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32078767

RESUMO

The photodynamic process requires three elements: light, oxygen, and photosensitizer. The process involves the formation of singlet oxygen which is the molecular oxygen in excited electronic states. Previously, we reported that heterologously expressed hyperpolarization-activated cAMP-gated (HCN) channels in excised membrane patches are sensitive to photodynamic modification (PDM). Here we extend this study to native HCN channels expressed in thalamocortical (TC) neurons in the ventrobasal (VB) complex of the thalamus and dopaminergic neurons (DA) of the ventral tegmental area (VTA). To do this we introduced the photosensitizer FITC-cAMP into TCs or DAs of rodent brain slices via a whole-cell patch-clamp recording pipette. After illumination with blue light pulses, we observed an increase in the voltage-insensitive, instantaneous Iinst component, accompanied by a long-lasting decrease in the hyperpolarization-dependent Ih component. Both Ih and the increased Iinst after PDM could be blocked by the HCN blockers Cs+ and ZD7288. When FITC and cAMP were dissociated and loaded into neurons as two separate chemicals, light application did not result in any long-lasting changes of the HCN currents. In contrast, light pulses applied to HCN2-/- neurons loaded with FITC-cAMP generated a much greater reduction in the Iinst component compared to that of WT neurons. Next, we investigated the impact of the long-lasting increases in Iinst after PDM on the cellular physiology of VB neurons. Consistent with an upregulation of HCN channel function, PDM elicited a depolarization of the resting membrane potential (RMP). Importantly, Trolox-C, an effective quencher for singlet oxygen, could block the PDM-dependent increase in Iinst and depolarization of the RMP. We propose that PDM of native HCN channels under physiological conditions may provide a photodynamic approach to alleviate HCN channelopathy in certain pathological conditions.

2.
Biomed Pharmacother ; 118: 109344, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545246

RESUMO

Background Acute respiratory distress syndrome (ARDS), which is the severest form of pulmonary injury, is the leading cause of death in critical care. At present, the mortality remains high in ARDS. Partial liquid ventilation (PLV) using perfluorocarbon (PFC) has been proven to improve gas exchange and respiratory dynamics of the lungs during ARDS. However, PLV has not been shown to reduce the mortality of ARDS. Some studies have shown that mild hypothermia therapy can reduce lung injuries in animal models of ARDS by reducing inflammatory cytokine levels in lung tissues. However, hypothermia cannot produce a lung protection effect alone, and it may have a synergistic effect with other protective measures. To explore the possible role of PLV combined with mild hypothermia in the treatment of ARDS, in this study, we used PFC liquid ventilation to induce mild hypothermia in dogs suffering from ARDS and analyzed the effects of PFC liquid ventilation-induced mild hypothermia on the levels of inflammatory factors and lung histopathology in dogs with ARDS. The experimental dogs were randomly divided into conventional mechanical ventilation (CMV), normal temperature PFC liquid ventilation (NPLV), hypothermic PFC liquid ventilation (HPLV), and mechanical ventilation (MV) groups. After induction of ARDS, the CMV group was treated with CMV for respiratory support, the HPLV group was treated with PLV-induced mild hypothermia using 15 °C PFC and maintained the rectal temperature at 34-36 °C, the NPLV group was treated with PLV using 36 °C PFC and maintained the rectal temperature at 36-38 °C. The MV group served as the control group. Analyses of the pulmonary pathology, partial pressure of oxygen in the blood, and lung wet-dry weight ratio (W/T) of each dog revealed that PLV-induced mild hypothermia significantly increased the PaO2 values and attenuated lung injury, and there were no adverse effects on hemodynamics. Furthermore, treatment with PLV-induced mild hypothermia significantly increased the expression of the anti-inflammatory factor IL-10 in bronchoalveolar lavage fluid (BALF) and attenuated the expression of interleukin (IL-6) and tumor necrosis factor-α (TNF-α) in peripheral blood and in lung BALF. Moreover, the results showed that the expression of myeloperoxidase (MPO) and NF-κB p65 in lung tissues was significantly decreased by PLV-induced mild hypothermia compared with NPLV and CMV. Our results indicated that PLV combined with mild hypothermia can provide protection against oleic acid-induced ARDS in dogs.

3.
ACS Omega ; 4(8): 12995-13004, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31460426

RESUMO

Silicalite-1-type zeolites with unique intracrystal holes or cracks were successfully prepared using a cellulose nanofiber (CNF) as an additional mediating material, and their vapor phase adsorption properties toward methyl tert-butyl ether (MTBE) and n-nitrosodimethylamine (NDMA) were examined. It was found that the mixing protocol of CNF and structure-directing agents (SDAs), the addition amount of CNF, and the CNF/SDAs amount ratio play important roles in forming the holed silicalite-1. The synthesis route that preliminarily mixes CNF with SDAs in a series of controlled conditions is particularly beneficial for the formation of the holed silicalite-1 with mesoporosity and larger pores because the CNF-SDAs composite structure benefits the zeolite growth closely encompassing CNF inside the crystal structure. It also promotes the preferential formation of the orthorhombic phase vicinal to the CNF surface, namely, the surface of the formed internal holes or cracks, with the twin-type crystal size reduced as compared to the non-CNF-templated sample. On the contrary, the synthesis route that mixes CNF with SDAs-silicate composite ions tends to modify the twin-type crystal shape at the same time to form small but uniform well-crystallized particles with less holes or cracks and a dominative monoclinic phase. It was considered that both the inter-subunit structural defect and silanol defect whose content is increased with CNF addition influence the adsorptivity of MTBE and NDMA. Owing to the small twin-type crystal size, the smaller crystal subunits, and the favored short path from the surface of internal holes or cracks, the holed silicalite-1 derived from the CNF and SDA premixture assures the easiest access of adsorbate molecules to the most energetically favored sites and is most appropriate for the adsorption of both MTBE and NDMA among the examined zeolites.

4.
Sci Total Environ ; 688: 742-750, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31255812

RESUMO

This study aimed to evaluate internal biomarkers and external estimation of exposure to polycyclic aromatic hydrocarbons (PAH) in a high cancer mortality area in southeast China and identify which of these showed a stronger association of PAH with cancer mortality. A retrospective death survey was conducted to determine the mortality rate of cancer. Cumulative and aggregate external exposures to PAHs of local residents were estimated by field sampling. Three regions in southwest China with gradient PAH exposure levels from high to low (H, M, and L) were selected in this study. Research participants were selected from these three regions using a statistical sampling method. To determine the internal exposure, urinary OH-PAHs were measured using the first morning urine samples. From the retrospective death survey, the highest age-standardized lung cancer mortality rate occurred in Region H (78 per 100,000 person-years), followed by that in Regions M (33 per 100,000 person-years) and L (15 per 100,000 person-years), and the rate was nearly four times China's national mortality rate (20 per 100,000 person-years). Residents estimated daily aggregate exposure doses per unit body weight to carcinogenic benzo(a)pyrene equivalent concentration were 159 ±â€¯14 ng-kg-1-day-1, 7.41 ±â€¯2.76 ng-kg-1-day-1, and 6.13 ±â€¯2.89 ng-kg-1-day-1 in Region H, M, and L, respectively. The participants in Region M had the greatest urinary OH-PAH concentration (9.10 ±â€¯4.92 µg-g-1 crt), followed by Region H (8.01 ±â€¯4.22 µg-g-1 crt) and L (7.12 ±â€¯3.10 µg-g-1 crt). The spatial difference in the total OH-PAHs was not statistically significant. Aggregate and cumulative exposure to 16 PAHs from external routes were found, and external exposure had a stringer relationship with lung cancer mortality than internal exposure.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluição Ambiental/estatística & dados numéricos , Neoplasias/epidemiologia , Hidrocarbonetos Policíclicos Aromáticos/análise , Adulto , Biomarcadores/metabolismo , China/epidemiologia , Poluição Ambiental/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Environ Mol Mutagen ; 60(7): 617-623, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30942501

RESUMO

We previously reported that bacterial diversity in sputum samples from never-smoking women in rural China varied by lung cancer status and household air pollution (HAP) exposure type. Here, we expand on our associations between environmental exposures and respiratory tract microbiota with an additional 90 never-smoking women from Xuanwei, China. DNA from sputum samples of cases (n = 45) and controls (n = 45) was extracted using a multistep enzymatic and physical lysis, followed by a standardized clean up. V1-V2 regions of 16S rRNA genes were Polymerase chain reaction (PCR) amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high-quality sequences were evaluated for diversity and taxonomic membership. In our population of never-smokers, increased risk of lung cancer was associated with lower alpha diversity compared to higher alpha diversity (Shannon: ORhigh = 1.00 [reference], ORmedium = 3.84 [1.02-14.48], ORlow = 3.78 [1.03-13.82]; observed species: ORhigh = 1.00 [reference], ORmedium = 2.37 [0.67-8.48], ORlow = 2.01 [0.58-6.97]; Phylogenetic Diversity (PD) whole tree: ORhigh = 1.00 [reference], ORmedium = 3.04 [0.85-10.92], ORlow = 2.53 [0.72-8.96]), as well as a decreased relative abundance of Fusobacteria (ORhigh = 1.00 [reference], ORmedium = 1.24 [0.42-3.66], ORlow = 2.01 [0.63-6.44], ptrend = 0.03). Increasing alpha diversity was associated with smoky coal use compared to clean fuel use among all subjects (observed species, P = 0.001; PD whole tree, P = 0.006; Shannon, P = 0.0002), as well as cases (observed species, P = 0.02; PD whole tree, P = 0.03; Shannon, P = 0.03) and controls (observed species, P = 0.01; PD whole tree, P = 0.05; Shannon, P = 0.002). Increased diversity was also associated with presence of livestock (observed species, P = 0.02; PD whole tree, P = 0.02; Shannon, P = 0.03) in the home for cases. Our study is the first to report that decreased microbial diversity is associated with risk of lung cancer. Larger studies are necessary to elucidate the direct and indirect effects attributed to the disease-specific, HAP-specific, and animal-specific associations. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.


Assuntos
Exposição Ambiental/efeitos adversos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/microbiologia , Sistema Respiratório/microbiologia , Adulto , Idoso , Poluição do Ar/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , Bactérias/genética , Estudos de Casos e Controles , China , Carvão Mineral/efeitos adversos , Feminino , Humanos , Microbiota/genética , Pessoa de Meia-Idade , Filogenia , RNA Ribossômico 16S/genética , Fatores de Risco , Fumaça/efeitos adversos , Fumar/efeitos adversos
6.
Sci Total Environ ; 649: 731-738, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30176483

RESUMO

This study was designed to test whether the dietary intake of polycyclic aromatic hydrocarbons (PAHs) is a potential exposure source relating to the high cancer incidence area in southwest China. Duplicate plate method was used to collect food samples in rural and urban sites in the region. Questionnaire surveys were conducted among 300 local residents to obtain their dietary habits and 50 subjects were chosen to collect the samples. The 16 priority PAHs (PAH16) in composite food samples for each individual subject were measured, and non-carcinogenic and carcinogenic risks were analyzed based on the results of Monte Carlo method. The average concentration of the PAH16 in food samples was 12.04 ±â€¯8.52 ng g-1. The life time average daily benzo(a)pyrene equivalent (BaPeq) exposure dose was 6.07 × 10-6 mg kg-1 day-1. Although non-carcinogenic risk was found to be within a controllable range, the average incremental lifetime cancer risk (ILCR) was 3.7 × 10-5 for rural subjects and 6.1 × 10-5 for urban subjects, which is comparable with other regions in China. The serious risk level of 10-4 was exceeded by 10.7% of urban residents and 2.1% of rural residents. This study implies that dietary exposure to PAHs is a potential exposure source to the high cancer in the region, and further cancer risk control strategies need to be formulated.


Assuntos
Exposição Dietética/análise , Poluentes Ambientais/análise , Contaminação de Alimentos/análise , Neoplasias/epidemiologia , Hidrocarbonetos Policíclicos Aromáticos/análise , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/induzido quimicamente , Medição de Risco , Fatores de Risco , Adulto Jovem
7.
Sci Total Environ ; 643: 559-568, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945090

RESUMO

Synthetic phenolic antioxidants (SPAs) have gained high concerns due to their extensive usages and unintended environmental release via various routes. Their contamination in water system could pose potential threat to aquatic organisms, therefore, the studies on the aquatic toxicology of this kind of chemicals are of high importance. In this research, the developmental toxicities of four commonly used SPAs, including butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butyl hydroquinone (TBHQ), and 2,2'-methylenebis (6-tert-butyl-4-methylphenol) (AO2246) were investigated using the zebrafish embryo toxicity test (ZFET). The results showed that these four SPAs exerted different acute toxicities to zebrafish, and the toxic order, based on their 96 h LC50 values, was AO2246 > TBHQ > BHA > BHT, and decreased hatching rates were induced for the embryos in BHA, TBHQ and AO2246 exposure groups. Non-lethal exposures of BHA (≤20 µM), TBHQ (≤20 µM), BHT (≤200 µM) and AO2246 (≤2 µM) decreased the heart rates and body lengths of zebrafish in exposure concentration-dependent manners. Diverse morphological deformities, including uninflated swim bladder, pericardial edema, spinal curvature, severe yolk deformation, or abnormal pigmentation, were induced in zebrafish larvae upon SPA treatments. The transcriptional levels of the related genes, examined by quantitative PCR, indicated that the interferences of SPAs with hypothalamic-pituitary-thyroid axis (HPT axis), GH/PRL synthesis and Hedgehog (hh) pathway contributed to their developmental toxicities in zebrafish. The up-regulation of pluripotency biomarker, Oct4, caused the developmental retardation during the early stages of zebrafish embryos in BHA and TBHQ exposure groups. The results obtained herein provided important information on the developmental toxicity of SPAs, which could be very helpful in guiding the risk assessment on their aquatic toxicology.


Assuntos
Antioxidantes/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Hidroxianisol Butilado/toxicidade , Hidroxitolueno Butilado/toxicidade , Fenóis/toxicidade , Testes de Toxicidade , Peixe-Zebra
8.
J Physiol ; 596(7): 1259-1276, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29327340

RESUMO

KEY POINTS: Shank3 increases the HCN channel surface expression in heterologous expression systems. Shank3Δ13-16 deficiency causes significant reduction in HCN2 expression and Ih current amplitude in thalamocortical (TC) neurons. Shank3Δ13-16 - but not Shank3Δ4-9 -deficient TC neurons share changes in basic electrical properties which are comparable to those of HCN2-/- TC neurons. HCN channelopathy may critically mediate events downstream from Shank3 deficiency. ABSTRACT: SHANK3 is a scaffolding protein that is highly enriched in excitatory synapses. Mutations in the SHANK3 gene have been linked to neuropsychiatric disorders especially the autism spectrum disorders. SHANK3 deficiency is known to cause impairments in synaptic transmission, but its effects on basic neuronal electrical properties that are more localized to the soma and proximal dendrites remain unclear. Here we confirmed that in heterologous expression systems two different mouse Shank3 isoforms, Shank3A and Shank3C, significantly increase the surface expression of the mouse hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channel. In Shank3Δ13-16 knockout mice, which lack exons 13-16 in the Shank3 gene (both Shank3A and Shank3C are removed) and display a severe behavioural phenotype, the expression of HCN2 is reduced to an undetectable level. The thalamocortical (TC) neurons from the ventrobasal (VB) complex of Shank3Δ13-16 mice demonstrate reduced Ih current amplitude and correspondingly increased input resistance, negatively shifted resting membrane potential, and abnormal spike firing in both tonic and burst modes. Impressively, these changes closely resemble those of HCN2-/- TC neurons but not of the TC neurons from Shank3Δ4-9 mice, which lack exons 4-9 in the Shank3 gene (Shank3C still exists) and demonstrate moderate behavioural phenotypes. Additionally, Shank3 deficiency increases the ratio of excitatory/inhibitory balance in VB neurons but has a limited impact on the electrical properties of connected thalamic reticular (RTN) neurons. These results provide new understanding about the role of HCN channelopathy in mediating detrimental effects downstream from Shank3 deficiency.


Assuntos
Potenciais de Ação , Córtex Cerebral/patologia , Canalopatias/patologia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neurônios/patologia , Canais de Potássio/fisiologia , Tálamo/patologia , Animais , Córtex Cerebral/metabolismo , Canalopatias/genética , Canalopatias/metabolismo , Potenciais da Membrana , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Tálamo/metabolismo , Xenopus laevis
9.
Carcinogenesis ; 38(9): 893-899, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911003

RESUMO

Households in Xuanwei and Fuyuan, China, possess hazardous levels of fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) from coal combustion. Previous studies found that increased exposure to PM2.5 and benzo[a]pyrene (BaP; a PAH) were associated with decreased mitochondrial DNA copy number (mtDNAcn), a marker of oxidative stress. We further evaluated these associations in a cross-sectional study of 148 healthy non-smoking women from Xuanwei and Fuyuan. Personal exposure to PM2.5 and BaP was measured using portable devices. MtDNAcn was measured using qPCR amplification of leukocyte DNA that was collected after air measurements. Linear regression models were used to estimate the associations between personal exposure to PM2.5 and BaP, and mtDNAcn adjusted for age, body mass index (BMI) and fuel type. We found inverse associations between exposure to PM2.5 and BaP, and mtDNAcn. Each incremental log-µg/m3 increase in PM2.5 was associated with a significant decrease in mtDNAcn of -10.3 copies per cell [95% confidence interval (95% CI): -18.6, -2.0; P = 0.02]. Additionally, each log-ng/m3 increase in BaP was associated with a significant decrease in mtDNAcn of -5.4 copies per cell (95% CI: -9.9, -0.8, P = 0.02). Age, BMI, fuel type and coal mine type were not significantly associated with mtDNAcn. Exposure to PM2.5 and BaP may alter mitochondrial dynamics in non-smoking Chinese women. MtDNAcn may be a potential mediator of indoor air pollution on chronic disease development.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Benzo(a)pireno/efeitos adversos , Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Exposição Ambiental , Mitocôndrias/metabolismo , Material Particulado/efeitos adversos , Adulto , Idoso , Biomarcadores , China/epidemiologia , Estudos Transversais , DNA Mitocondrial/sangue , Demografia , Doença Ambiental/etiologia , Feminino , Humanos , Leucócitos/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo
10.
Medicine (Baltimore) ; 96(38): e8093, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28930850

RESUMO

The aim of this study was to evaluate the safety of acute normovolemic hemodilution (ANH) for patients undergoing intracranial meningioma resection.Eighty patients (aged 48-65 years) with American Society of Anesthesiologists physical status I-II undergoing intracranial meningioma resection were included in this prospective observational study. The patients were randomly divided into group A (ANH group), which underwent a combination of ANH and intraoperative cell salvage (ICS), and group B (control group), which underwent ICS alone. The study parameters were recorded as baseline values before blood drainage (T0), after blood drainage (T1), and before (T2) and after (T3) retransfusion in group A. Whereas in group B, the same parameters were measured 10 minutes after anesthesia induction (T0), before surgery (T1), and before (T2) and after (T3) transfusion of autologous blood.When intraoperative blood loss was <2000 mL, the mean volume of homologous blood transfused in group A patients was 100.8 ±â€Š82.3 mL, compared with the 190.0 ±â€Š91.8 mL in group B. Reduction in homologous blood used in group A was statistically significant (P < .05). In group B, 15.1% patients received homologous blood, whereas only 5.9% patients received homologous blood in group A. The difference in heart rate between both groups at different time points was statistically nonsignificant (P > .05). The mean hemoglobin and hematocrit levels at T1 and T2 in group A were lower than in group B (P < .05). The prothrombin time and activated partial thromboplastin time in both groups were prolonged significantly after T2 (all P < .05), but were all within normal range. There were no significant differences in postoperative hospital stay, mortality, and postoperative infection between the 2 groups.For patients undergoing excision of intracranial meningioma, ANH is an effective procedure to reduce the need for allogeneic transfusions.


Assuntos
Hemodiluição/métodos , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Idoso , Perda Sanguínea Cirúrgica , Transfusão de Sangue , Feminino , Hematócrito , Hemodiluição/efeitos adversos , Hemodinâmica , Hemoglobinometria , Humanos , Masculino , Neoplasias Meníngeas/fisiopatologia , Meningioma/fisiopatologia , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Estudos Prospectivos , Tempo de Protrombina
11.
Chemosphere ; 184: 866-878, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28646769

RESUMO

The metal(loid) pollution still is a great concern due to the effects from urbanization and industrialization. While, the health risks from the toxic metal(loid)s could decrease if strict pollution control measures were adopted. However, few studies to date investigate the health risks of heavy metal(loid)s in a systematic river basin for the dependent residents, after taking pollution control measures. Thus, the contents of metal(loid)s (Cu, Pb, Zn, Cd, Mn, As) in surface water along a typical river basin were investigated in this study, and the potential non-carcinogenic and carcinogenic health risks posed to the residents were assessed. Although the soluble contents of Cu, Pb, Zn and Cd exceeded the respective thresholds in two sites located downstream the mine area, they were greatly decreased in comparison with previous contamination levels, and the soluble concentrations of all the metal(loid)s were within the relevant thresholds in the sites far away from the mining area. Moreover, the closer to the mining area, the higher the pollution levels of metal(loid)s. The total hazard index for non-carcinogenic risks of metal(loid)s were basically lower than the threshold (1) for the local population. Whereas, although the content of metal(loid)s were low (such as As), they could pose relative higher non-carcinogenic health risks. The result illustrated that pollution levels, toxicity of the contaminants and exposure behavior patterns all could contribute to the potential detrimental health risks. Additionally, the non-carcinogenic and carcinogenic risks from ingestion exposure were ∼2-∼4 orders of magnitude higher than those from dermal contact. The total carcinogenic risks were basically lower than the maximum tolerable levels (1.0 × 10-4), indicating carcinogenic risks from most areas of the river could also be accepted. Among different population groups, heavy metal(loid)s posed relative higher non-carcinogenic and carcinogenic risks to the children in 0-5 years old. Fortunately, the surface water in most area of this basin is safe in usage for the local population and the health risks were basically acceptable in case exposed to the target metal(loid)s, after the river basin was in the charge of strict pollution control measures.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluição Ambiental/estatística & dados numéricos , Mineração , Criança , China , Exposição Ambiental/análise , Exposição Ambiental/prevenção & controle , Monitoramento Ambiental , Poluição Ambiental/análise , Poluição Ambiental/prevenção & controle , Intoxicação por Metais Pesados , Humanos , Metaloides , Metais Pesados/análise , Envenenamento , Medição de Risco , Rios
12.
Environ Pollut ; 221: 318-325, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27939206

RESUMO

Exposure to crystalline silica (quartz) has been implicated as a potential cause of the high lung cancer rates in the neighbouring counties of Xuanwei and Fuyuan, China, where the domestic combustion of locally sourced "smoky" coal (a bituminous coal) is responsible for some of the highest lung cancer rates in the nation, irrespective of gender or smoking status. Previous studies have shown that smoky coal contains approximately twice as much quartz when compared to alternative fuels in the area, although it is unclear how the quartz in coal relates to household air pollution. Samples of ash and fine particulate matter (PM2.5) were collected from 163 households and analysed for quartz content by Fourier transformed infrared spectroscopy (FT-IR). Additionally, air samples from 12 further households, were analysed by scanning electron microscopy (SEM) to evaluate particle structure and silica content. The majority (89%) of household air samples had undetectable quartz levels (<0.2 µg/m3) with no clear differences by fuel-type. SEM analyses indicated that there were higher amounts of silica in the smoke of smoky coal than smokeless coal (0.27 µg/m3 vs. 0.03 µg/m3). We also identified fibre-like particles in a higher concentration within the smoke of smoky coal than smokeless coal (5800 fibres/m3 vs. 550 fibres/m3). Ash analysis suggested that the bulk of the quartz in smoky coal went on to form part of the ash. These findings indicate that the quartz within smoky coal does not become adequately airborne during the combustion process to cause significant lung cancer risk, instead going on to form part of the ash. The identification of fibre-like particles in air samples is an interesting finding, although the clinical relevance of this finding remains unclear.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Cinza de Carvão/análise , Exposição por Inalação/estatística & dados numéricos , Neoplasias Pulmonares/epidemiologia , Material Particulado/análise , Quartzo/análise , China/epidemiologia , Carvão Mineral/análise , Cinza de Carvão/química , Monitoramento Ambiental , Humanos , Incidência , Fumaça/análise , Espectroscopia de Infravermelho com Transformada de Fourier
13.
Chemosphere ; 147: 404-11, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26774306

RESUMO

Rapid development of industrialization and urbanization results in serious environmental contamination by metal(loid)s, which would consequently cause deleterious health effects to the exposed people through multi-pathways. Therefore, total health risk assessment for the population in urban environment is very important. Unfortunately, few studies to date investigate the cumulative health risks of metal(loid)s through aggregative pathways in Children who are often susceptible population. 12 metal(loid)s including Lead(Pb), Cadmium(Cd), Arsenic(As), Chromium(Cr), Zinc(Zn), Copper(Cu), Nickel(Ni), Manganese(Mn), Cobalt(Co), Selenium(Se), Antimony(Se) and Vanadium(V), were analyzed in PM10, drinking water, food, soil and indoor dust in this study. The cumulative and aggregative risks of these metal(loid)s among the local children were then evaluated on a field sampling and questionnaire-survey basis. The results showed that the environments were heavily polluted by metal(loid)s. For most metal(loid)s, food ingestion accounted for more than 80% of the total daily exposure dose. The non-cancer risks were up to 30 times higher than the acceptable level due to the food ingestion via Pb, Cr, Cu, Zn, As, Se, Cd and Sb, and the PM10 inhalation via Cr and Mn. While, the cancer risks were mainly attributed to Cr via food ingestion and As via food and dust ingestion, and approximately 100 times of the maximum acceptable level of 1.0 × 10(-4). The study highlights the cumulative and aggregative exposure assessment, instead of pollutant investigation to evaluate the potential health risks and emphasizes concerns to improve indoor hygienic and environmental quality and to decrease the potential harmful health effects of children living in urban area.


Assuntos
Arsênico/análise , Exposição Ambiental/análise , Metais/análise , Poluição do Ar em Ambientes Fechados/análise , Criança , Pré-Escolar , China , Cidades , Água Potável/análise , Poeira/análise , Feminino , Contaminação de Alimentos/análise , Humanos , Masculino , Material Particulado/análise , Medição de Risco , Poluentes do Solo/análise , Poluentes Químicos da Água/análise
14.
Chemosphere ; 144: 2469-75, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26619312

RESUMO

Dietary intake is one of the major exposure pathways of polycyclic aromatic hydrocarbons (PAHs), especially in Chinese people because foods are often prepared with grilling and/or frying that would produce high levels of PAHs. In this paper, we assessed daily dietary intakes (DDI) of PAHs, using a "duplicate plate method", among 100 Chinese urban residents. The DDI of benzo(a)pyrene ranged from 0.06 µg per day to 13.5 µg per day with a median of 0.69 µg per day, varying largely across subjects. The median Incremental Lifetime Cancer Risk (ILCR) attributable to PAH dietary intake was 6.65 × 10(-5) (4.41 × 10(-5) to 1.02 × 10(-4) as inter-quartile range). The contribution of several high-PAH containing foods like barbecued, smoked or deep-fried meats to the overall DDIs was about 13%. The use of raw foods may underestimate dietary intake of PAHs and associated exposure risk considerably. Results from foods sampled in different seasons suggested that seasonal variability within an individual may contribute notably to overall variability measured in a population and more future studies with longer-term investigation on food ingestion and pollutant exposure are needed. The study indicates that measuring actually consumed foods is more appropriate for dietary intake exposure assessment, and intra-individual variance should be taken into account during study design and data analysis.


Assuntos
Exposição Ambiental , Poluentes Ambientais/análise , Contaminação de Alimentos/análise , Exposição por Inalação , Neoplasias/epidemiologia , Hidrocarbonetos Policíclicos Aromáticos/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos de Coortes , Monitoramento Ambiental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Medição de Risco , Estações do Ano , População Urbana , Adulto Jovem
15.
Environ Pollut ; 208(Pt B): 506-11, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26552516

RESUMO

Cytochrome P450 1A2 (CYP1A2) is an enzyme involved in the metabolic activation of certain carcinogens, and inducible by toxic substrates. To date, few studies have investigated in vivo CYP1A2 induction in humans and its relationship to polycylic aromatic hydrocarbons (PAHs) like benzo(a)pyrene (BaP). Non-smoking healthy male coke-oven workers (n = 30) were recruited as 'exposure' group, and non-smoking healthy office workers in the same city (n = 10) were selected as 'control' group, to test whether high inhalation exposure to PAHs can induce CYP1A2 activity in human livers. Significantly higher inhalation exposure of PAHs were found among the exposure group compared to the control. Inhalation BaP exposure concentration in the exposure group was more than 30 times higher than the control group (p < 0.001). However, the exposure group did not exhale significant higher levels of (13)CO2/(12)CO2 in breath samples (p = 0.81), and no significant relationship was found between the inhaled BaP concentration and the (13)CO2/(12)CO2 ratio (p = 0.91). A significant association was found between the (13)CO2/(12)CO2 exhalation and dietary BaP intake level. Hepatic CYP1A2 activity/induction level was not effected by inhaled BaP but was altered by ingestion of BaP.


Assuntos
Poluentes Atmosféricos/toxicidade , Benzo(a)pireno/toxicidade , Citocromo P-450 CYP1A2/metabolismo , Exposição por Inalação/análise , Adulto , Poluentes Atmosféricos/metabolismo , Benzo(a)pireno/metabolismo , Testes Respiratórios , Carcinógenos/toxicidade , Coque , Monitoramento Ambiental , Humanos , Isótopos , Fígado/metabolismo , Masculino , Exposição Ocupacional/análise
16.
Carcinogenesis ; 36(12): 1494-501, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26468118

RESUMO

In China's rural counties of Xuanwei and Fuyuan, lung cancer rates are among the highest in the world. While the elevated disease risk in this population has been linked to the usage of smoky (bituminous) coal as compared to smokeless (anthracite) coal, the underlying molecular changes associated with this exposure remains unclear. To understand the physiologic effects of smoky coal exposure, we analyzed the genome-wide gene-expression profiles in buccal epithelial cells collected from healthy, non-smoking female residents of Xuanwei and Fuyuan who burn smoky (n = 26) and smokeless (n = 9) coal. Gene-expression was profiled via microarrays, and changes associated with coal type were correlated to household levels of fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs). Expression levels of 282 genes were altered with smoky versus smokeless coal exposure (P < 0.005), including the 2-fold increase of proinflammatory IL8 and decrease of proapoptotic CASP3. This signature was more correlated with carcinogenic PAHs (e.g. Benzo[a]pyrene; r = 0.41) than with non-carcinogenic PAHs (e.g. Fluorene; r = 0.08) or PM2.5 (r = 0.05). Genes altered with smoky coal exposure were concordantly enriched with tobacco exposure in previously profiled buccal biopsies of smokers and non-smokers (GSEA, q < 0.05). This is the first study to identify a signature of buccal epithelial gene-expression that is associated with smoky coal exposure, which in part is similar to the molecular response to tobacco smoke, thereby lending biologic plausibility to prior epidemiological studies that have linked this exposure to lung cancer risk.


Assuntos
Poluição do Ar em Ambientes Fechados , Carvão Mineral , Exposição por Inalação , Mucosa Bucal/metabolismo , Fumaça , Transcriptoma , Adulto , Idoso , Feminino , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Família Multigênica
17.
Environ Pollut ; 200: 16-23, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25686884

RESUMO

Manufacture of lead-acid batteries is of widespread interest because of its emissions of heavy metals and metalloids into environment, harming environmental quality and consequently causing detrimental effects on human health. In this study, exposure pathways and health risks of children to heavy metal(loid)s (Pb, Cd, As, etc) were investigated based on field sampling and questionnaire. Pb was one of the most abundant elements in children's blood, with an elevated blood lead level of 12.45 µg dL(-1). Soil/dust and food were heavily polluted by targeted metal(loid)s. Food ingestion accounted for more than 80% of the total exposure for most metal(loid)s. The non-cancer risks to children were 3-10 times higher than the acceptable level of 1, while the cancer risks were 5-200 times higher than the maximum acceptable level of 1.0 × 10(-4). The study emphasized the significance of effective environmental management, particularly to ensure food security near battery facilities.


Assuntos
Fontes de Energia Elétrica , Exposição Ambiental/estatística & dados numéricos , Metaloides/análise , Poluentes do Solo/análise , Criança , China , Poeira/análise , Poluição Ambiental/estatística & dados numéricos , Humanos , Resíduos Industriais/análise , Resíduos Industriais/estatística & dados numéricos , Chumbo , Metais/análise , Medição de Risco , Solo
18.
Environ Pollut ; 199: 18-25, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25617855

RESUMO

As a highly toxic heavy metal, the pollution and exposure risks of lead are of widespread concern for human health. However, the collection of blood samples for use as an indicator of lead pollution is not always feasible in most cohort or longitudinal studies, especially those involving children health. To evaluate the potential use of urinary lead as an indicator of exposure levels and source apportionment, accompanying with environmental media samples, lead concentrations and isotopic measurements (expressed as (207)Pb/(206)Pb, (208)Pb/(206)Pb and (204)Pb/(206)Pb) were investigated and compared between blood and urine from children living in the vicinities of a typical coking plant and lead-acid battery factory. The results showed urinary lead might not be a preferable proxy for estimating blood lead levels. Fortunately, urinary lead isotopic measurements could be used as an alternative for identifying the sources of children's lead exposure, which coincided well with the blood lead isotope ratio analysis.


Assuntos
Exposição Ambiental/análise , Poluição Ambiental/estatística & dados numéricos , Intoxicação por Chumbo/urina , Chumbo/urina , Criança , Coque , Exposição Ambiental/estatística & dados numéricos , Poluição Ambiental/análise , Humanos , Isótopos/análise , Chumbo/análise
19.
Int J Cancer ; 137(2): 311-9, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25516442

RESUMO

Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.


Assuntos
Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Telômero/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , China , Feminino , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Hong Kong , Humanos , Japão , Neoplasias Pulmonares/etnologia , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , República da Coreia , Fatores de Risco , Singapura , Fumar , Taiwan , Homeostase do Telômero/genética
20.
Environ Sci Technol ; 48(24): 14632-41, 2014 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-25393345

RESUMO

Exposure to polycyclic aromatic hydrocarbons (PAHs) from burning "smoky" (bituminous) coal has been implicated as a cause of the high lung cancer incidence in the counties of Xuanwei and Fuyuan, China. Little is known about variations in PAH exposure from throughout the region nor how fuel source and stove design affects exposure. Indoor and personal PAH exposure resulting from solid fuel combustion in Xuanwei and Fuyuan was investigated using repeated 24 h particle bound and gas-phase PAH measurements, which were collected from 163 female residents of Xuanwei and Fuyuan. 549 particle bound (283 indoor and 266 personal) and 193 gas phase (all personal) PAH measurements were collected. Mixed effect models indicated that PAH exposure was up to 6 times higher when burning smoky coal than smokeless coal and varied by up to a factor of 3 between different smoky coal geographic sources. PAH measurements from unventilated firepits were up to 5 times that of ventilated stoves. Exposure also varied between different room sizes and season of measurement. These findings indicate that PAH exposure is modulated by a variety of factors, including fuel type, coal source, and stove design. These findings may provide valuable insight into potential causes of lung cancer in the area.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Carvão Mineral , Hidrocarbonetos Policíclicos Aromáticos/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Poluição do Ar em Ambientes Fechados/efeitos adversos , China/epidemiologia , Culinária/instrumentação , Estudos Transversais , Análise Fatorial , Características da Família , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Pessoa de Meia-Idade , Modelos Teóricos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Fatores de Risco
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