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1.
Artigo em Inglês | MEDLINE | ID: mdl-32785185

RESUMO

The concentrations, chemical availability, distribution, and sources of potentially toxic elements (PTEs) in the soil of Xiangjiang Basin in Hunan Province, China were investigated at 85 sites. The highest mean concentrations of Cd, Cu, Zn, As, and Pb were observed in Hengyang, whereas those for Mn, Co, and Hg were observed in Changde. The pollution index values followed the order: Cd > Hg > Cu > Zn > As > Pb; the mean geo-accumulation index values were in the order: Cd > Hg > Pb > Cu > Zn > As > Co > Mn. Cd was associated with moderate contaminated level, Hg and Pb were associated with moderate contaminated to uncontaminated level, and Cu, Zn, As, Co, and Mn were associated with uncontaminated level of pollution. Furthermore, 64.5% of Cd was water-soluble and exhibited exchangeable fractions; its chemical availability posed a risk to the ecosystem. Spatial analysis, principal component analysis, and a positive matrix factorization model were used to assess the PTE sources. Four principal components contributed to 88.8% of the 8 PTEs concentrations. Mining, smelting, industrial, and agricultural activities, alongside sewage irrigation, the use of agrochemicals, and vehicular emissions are the possible anthropogenic sources that pollute agricultural products and threaten human health in the Xiangjiang Basin.

2.
Ann Palliat Med ; 9(4): 2141-2151, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32762228

RESUMO

BACKGROUND: Acute lung injury (ALI) is the damage of alveolar epithelial cells and capillary endothelial cells caused by various direct and indirect injury factors, resulting in diffuse pulmonary interstitial and alveolar edema, resulting in acute hypoxic respiratory insufficiency. This study aimed to investigate the effects of hypothermia induced by partial fluid ventilation on dogs with ALI. METHODS: The experimental dogs were randomly divided into a conventional mechanical ventilation group (CMV) group, a normal temperature perfluorocarbon liquid ventilation group (NPLV) group, and a hypothermic perfluorocarbon liquid ventilation group (HPLV) group. After induction of ALI, the dogs of the CMV group was treated with CMV for respiratory support, the HPLV group was given a 15 °C low-temperature perfluorocarbon partial liquid ventilation (PLV), and the NPLV group was given partial fluid permeation of perfluorocarbon (PFC) at a room temperature of 37 °C. Anesthesia was stable at 0.5 h (T0), and successful modeling (T1), at 1 h (T2), 2 h (T3), 3 h (T4) and 4 h (T5) was completed. Blood gas analysis was performed, and rectum temperature, peak airway pressure (PIP), and lung compliance were measured. We performed enzyme-linked immunosorbent assay (ELISA) for peripheral blood and postoperative bronchoalveolar lavage fluid (BALF), calculation of lung tissue wet weight/dry weight ratio, and Western blot detection of NF-κB p65. RESULTS: In the HPLV group, the blood gas index of dogs with ALI was close to normal. In T2¬-T5, the rectal temperature of the HPLV group was significantly lower than that of the NPLV group and the CMV group the lung compliance in the HPLV group and the NPLV group was lower than that in the CMV group at the T2-T5 time point, while the CLst value was significantly increased. The detection of peripheral blood and BALF in dogs showed that interleukin-10 (IL-10) was significantly increased and TNF-α was significantly decreased in the HPLV group compared with the CMV group and NPLV group. Compared with CMV group, the wet/dry ratio of lung tissue in the BALF of HPLV group was decreased. CONCLUSIONS: The results indicate that mild hypothermia caused by partial fluid ventilation can increase oxygenation capacity, oxygen partial pressure, the expression of anti-inflammatory factor IL-10 and improve lung compliance in dogs with ALI.

3.
Sci Rep ; 10(1): 11335, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647370

RESUMO

Outdoor air pollution is a growing public health concern, particularly in urban settings. However, there are limited epidemiological data on outdoor air pollution in rural areas with substantial levels of air pollution attributed to solid fuel burning for household cooking and heating. Xuanwei and Fuyuan are rural counties in China where the domestic combustion of locally sourced bituminous ("smoky") coal has been associated with the highest lung cancer rates in China. We previously assessed indoor and personal air pollution exposures in this area; however, the influence of indoor coal combustion and household ventilation on outdoor air pollution has not been assessed. Therefore, we measured outdoor fine particulate matter (PM2.5), species of polycyclic aromatic hydrocarbons (PAHs) including naphthalene (NAP) and the known carcinogen benzo(a)pyrene (BaP), sulfur dioxide (SO2), and nitrogen dioxide (NO2) over two consecutive 24-h sampling periods in 29 villages. Just over half of the villages were revisited two to nine months after the initial sampling period to repeat all measurements. The overall geometric mean (GM) of outdoor PM2.5, BaP, NAP, and NO2 were 45.3 µg/m3, 9.7 ng/m3, 707.7 ng/m3, and 91.5 µg/m3, respectively. Using linear mixed effects models, we found that burning smoky coal was associated with higher outdoor BaP concentrations [GM ratio (GMR) = 2.79] and lower outdoor SO2 detection rates (GMR = 0.43), compared to areas burning smokeless coal. Areas with predominantly ventilated stoves (> 50% of stoves) had higher outdoor BaP (GMR = 1.49) compared to areas with fewer ventilated stoves. These results show that outdoor air pollution in a rural region of China was associated with the type of coal used for cooking and heating indoors and the presence of stove ventilation. Our findings suggest that efforts of household stove improvement to reduce indoor air pollution have resulted in higher outdoor air pollution levels. Further reducing adverse health effects in rural villages from household coal combustion will require the use of cleaner fuel types.

4.
Indoor Air ; 30(5): 872-884, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32347976

RESUMO

Contamination of metals in household dust remains a concern for human health. However, few studies to date have been conducted on the contribution of both indoor and outdoor environments to the health risks posed by metals. This study was carried out to assess the potential health risks from both indoor and outdoor household dust and the respective contribution to the health risks for children. The results showed that household dusts were heavily polluted by metal(loid)s, which were up to 30 times higher than the relative background level, and were attributed to smelting activity. However, there are other pollution sources in indoor environments, since the I/O ratio values of Pb, Cd, and As were significantly higher than 1. HI values of Pb and As exceeded the threshold of (1) and accounted for approximately 60% and 24% to the HIt, respectively. The HIts of Zn, Cr, Mn, Hg, and Cu were mainly attributable to indoor dust exposure, particularly for Hg (73.44%), indicating non-carcinogenic health risks could be attributed more to the indoor dust exposure. This study highlights the potential risks of metal contamination in household environment, particularly indoor environment, on the health of children who live in the vicinity of smelting activity.

5.
Environ Res ; 185: 109478, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32276165

RESUMO

As important pollution gases and represented precursors of both ozone and second organic aerosol (SOA), the component characteristics, source origins, environmental health and emission control of volatile organic compounds (VOCs), are gaining more and more attention in Chinese megacities. In order to understand the concentration, composition and temporal and spatial distribution characteristics of VOCs in the atmosphere of Chengdu, a megacity located in Sichuan basin in southwest China, the offline sampling measurements of VOCs were carried out at 28 different field sites covering all the districts and counties of Chengdu during special periods from May 2016 to January 2017. Speciated VOCs measurement was performed by the GC-FID/MS, and 99 species were identified. The averaged total VOC mixing ratios of each sampling site were in the range from 35.03 to 180.57 ppbv. Based on these observational data, the distribution characteristics of VOCs in different months and different regions of Chengdu were clarified. The VOCs data were used to estimate the potential amount of ozone, secondary aerosol formation and health risk assessment in Chengdu. Furthermore, the positive matrix factorization (PMF) model was used to identify the dominant emission sources and evaluate their contribution to VOCs in the city. The two main sources of VOCs in Chengdu were motor vehicle exhaust and solvent utilization. These accounted for 43% of all emission sources. In the summertime, due to higher temperatures and stronger sunlight, the contribution of natural sources and secondary emissions were also relatively high, which were supported by the regional emission inventories. Finally, the controlling direction of VOCs and O3 pollution in Chengdu was discussed, and the VOCs pollution control strategy was proposed for the near future.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Cidades , Monitoramento Ambiental , Ozônio/análise , Compostos Orgânicos Voláteis/análise
6.
ACS Chem Neurosci ; 11(6): 851-863, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32078767

RESUMO

The photodynamic process requires three elements: light, oxygen, and photosensitizer, and involves the formation of singlet oxygen, 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.

7.
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.


Assuntos
Hipotermia Induzida , Inflamação/complicações , Inflamação/terapia , Ventilação Líquida , Pulmão/fisiopatologia , /terapia , Animais , Artérias/patologia , Gasometria , Líquido da Lavagem Broncoalveolar , Cães , Hemodinâmica , Inflamação/sangue , Inflamação/patologia , Interleucina-6/sangue , Pulmão/patologia , Masculino , Pressão Parcial , Peroxidase/metabolismo , /patologia , Temperatura , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/sangue
8.
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.

9.
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
10.
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
11.
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
12.
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
13.
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 , Proteínas dos Microfilamentos , Neurônios/metabolismo , Tálamo/metabolismo , Xenopus laevis
14.
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
15.
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
16.
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
17.
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
18.
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
19.
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
20.
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
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