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1.
Sci Total Environ ; 711: 134745, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31822400

RESUMO

In the Northern China Plain (NCP), extreme haze events with high concentrations of fine particles occur frequently during the winter but rarely occur in autumn. In this study, we present a synthetic analysis of particulate constituents during the historically polluted transition period of autumn-winter in 2018, revealing that mixed-type haze episodes are the result of regional transport, homogeneous/heterogeneous conversion, and sandstorm influences. The hydrolysis process of N2O5 at higher relative humidity levels (>70%), which feature an enhanced nitrate oxidation ratio (0.30-0.70) and NO3- concentration (>60 µg m-3), was the driving factor for high PM2.5 mass concentrations during the observation periods. The long-distance transport of sandstorms, characterized by decreasing PM2.5/PM10 ratios (<30%) from the north/northwest, is the most important factor for the explosive growth of PM10 concentration. These results can help us gain a comprehensive understanding of haze formation and highlight the importance of nitrate chemistry in the aqueous phase. The results suggest that persistent NOx emission reduction measures must be made to better achieve air quality standards in Beijing and the NCP region.

2.
Biochimie ; 166: 203-213, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518617

RESUMO

Influenza A virus (IAV) is one of the most common infectious pathogen and associated with significant morbidity and mortality. Although processing the IAV hemagglutinin (HA) envelope glycoprotein precursor is a pre-requisite for viral membrane fusion activity, viral entry and transmission, HA-processing protease is not encoded in the IAV genome and thus the cellular trypsin-type serine HA-processing proteases determine viral infectious tropism and viral pathogenicity. The initial process of IAV infection of the airway is followed by marked upregulation of ectopic trypsin in various organs and endothelial cells through the induction of various proinflammatory cytokines, and this process has been termed the "influenza virus-cytokine-trypsin" cycle. In the advanced stage of IAV infection, the cytokine storm induces disorders of glucose and lipid metabolism and the "metabolic disorders-cytokine" cycle is then linked with the "influenza virus-cytokine-trypsin" cycle, to advance the pathogenic process into energy crisis and multiple organ failure. Application of protease inhibitors and treatment of metabolic disorders that break these cycles and their interconnection is therefore a promising therapeutic approach against influenza. This review discusses IAV pathogenicity on trypsin type serine HA-processing proteases, cytokines, metabolites and therapeutic options.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A , Influenza Humana , Serina Proteases/fisiologia , Internalização do Vírus/efeitos dos fármacos , Animais , Galinhas/virologia , Citocinas/metabolismo , Humanos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/patogenicidade , Influenza Aviária/tratamento farmacológico , Influenza Aviária/virologia , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Orthomyxoviridae/efeitos dos fármacos , Orthomyxoviridae/patogenicidade , Tripsina/metabolismo
3.
Environ Pollut ; 253: 377-383, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325882

RESUMO

Changzhou, an industrial city in the Yangtze River Delta, has been experiencing serious haze pollution, particularly in winter. However, studies pertaining to the haze in Changzhou are very limited, which makes it difficult to understand the characteristics and formation of winter haze in this area, and develop effective control measures. In this study, we carried out continuous online observation of particulate matter, chemical components, and meteorology in Changzhou in February 2017. Our results showed that haze pollution occurred frequently in Changzhou winter and exhibited two patterns: dry haze with low relative humidity (RH) and wet haze with high RH. Water-soluble inorganic ions (SO42-, NO3-, and NH4+) accounted for ∼52.2% of the PM2.5 mass, of which sulfate was dominant in wet haze periods while nitrate was dominant in other periods. With the deterioration of haze pollution, the proportion of nitrate in PM2.5 increased, while sulfate proportion increased under wet haze and decreased under dry haze. Dry haze and wet haze appeared under slow north wind and south wind, respectively, and strong north wind or sea breeze scavenged pollution. We found that formation of nitrate occurred rapidly in daytime with high concentrations of odd oxygen (Ox = O3 + NO2), whereas formation of sulfate occurred rapidly during nighttime with high RH, indicating that photochemistry and heterogeneous reaction were the major formation mechanisms for nitrate and sulfate, respectively. Through the cluster analysis of 36-h backward trajectories, five sources of air masses from three directions were identified. High PM2.5 concentrations (84.1 µg m-3 on average) usually occurred under the influence of two clusters (46%) from the northwest, indicating that regional transport from northern China aggravated the winter haze pollution in Changzhou. Emission reduction, particularly the mobile sources, and regional joint prevention and control can help to mitigate the winter haze in Changzhou.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Material Particulado/análise , Aerossóis/análise , China , Cidades , Umidade , Meteorologia , Nitratos/análise , Óxidos de Nitrogênio/análise , Rios , Estações do Ano , Sulfatos/análise , Vento
4.
Environ Pollut ; 244: 84-92, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30326389

RESUMO

Organic aerosol (OA) are always the most abundant species in terms of relative proportion to PM2.5 concentration in Beijing, while in previous studies, poor link between carbonaceous particles and their gaseous precursors were established based on field observation results. Through this study, we provided a comprehensive analysis of critical carbonaceous species in the atmosphere. The concentrations, diurnal variations, conversions, and gas-particle partitioning (F-factor) of 8 carbonaceous species, carbon dioxide (CO2), carbon monoxide (CO), methane (CH4), volatile organic compounds (VOCs), non-methane hydrocarbon (NMHC), organic carbon (OC), elemental carbon (EC), and water soluble organic compounds (WSOCs), in Beijing were analyzed synthetically. Carbonaceous gases (CO, CO2, VOCs, and CH4) and OC/EC ratios exhibited double-peak diurnal patterns with a pronounced midnight peak, especially in winter. High correlation between VOCs and OC during winter nighttime indicated that OC was formed from VOCs precursors via an unknown mechanism at relative humidity greater than 50% and 80%, thereby promoting WSOC formation in PM1 and PM2.5 respectively. The established F-factor method was effective to describe gas-to-particle transformation of carbonaceous species and was a good indicator for haze events since high F-factors corresponded with enhanced PM2.5 level. Moreover, higher F-factors in winter indicated carbonaceous species were more likely to exist as particles in Beijing. These results can help gain a comprehensive understanding of carbon cycle and formation of secondary organic aerosols from gaseous precursors in the atmosphere.


Assuntos
Poluentes Atmosféricos/análise , Carbono/análise , Monitoramento Ambiental/métodos , Umidade , Compostos Orgânicos/análise , Material Particulado/análise , Estações do Ano , Aerossóis/análise , Poluição do Ar , Atmosfera/análise , Pequim , Ciclo do Carbono , Dióxido de Carbono/análise , Monóxido de Carbono/análise , China , Metano/análise , Tamanho da Partícula , Compostos Orgânicos Voláteis/análise , Água/análise
5.
Vaccine ; 37(4): 612-622, 2019 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-30553569

RESUMO

We reported previously that a synthetic mucosal adjuvant SF-10, which mimics human pulmonary surfactant, delivers antigen to mucosal dendritic cells in the nasal cavity and promotes induction of humoral and cellular immunity. The aim of the present study was to determine the effects of oral administration of antigen combined with SF-10 (antigen-SF-10) on systemic and local immunity. Oral administration of ovalbumin, a model antigen, combined with SF-10 enhanced ovalbumin uptake into intestinal antigen presenting MHC II+CD11c+ cells and their CD11b+CD103+ and CD11b+CD103- subtype dendritic cells, which are the major antigen presenting subsets of the intestinal tract, more efficiently compared to without SF-10. Oral vaccination with influenza hemagglutinin vaccine (HAv)-SF-10 induced HAv-specific IgA and IgG in the serum, and HAv-specific secretory IgA and IgG in bronchoalveolar lavage fluid, nasal washes, gastric extracts and fecal material; their levels were significantly higher than those induced by subcutaneous HAv or intranasal HAv and HAv-SF-10 vaccinations. Enzyme-linked immunospot assay showed high numbers of HAv-specific IgA and IgG antibody secreting cells in the gastrointestinal and respiratory mucosal lymphoid tissues after oral vaccination with HAv-SF-10, but no or very low induction following oral vaccination with HAv alone. Oral vaccination with HAv-SF-10 provided protective immunity against severe influenza A virus infection, which was significantly higher than that induced by HAv combined with cholera toxin. Oral vaccination with HAv-SF-10 was associated with unique cytokine production patterns in the spleen after HAv stimulation; including marked induction of HAv-responsive Th17 cytokines (e.g., IL-17A and IL-22), high induction of Th1 cytokines (e.g., IL-2 and IFN-γ) and moderate induction of Th2 cytokines (e.g., IL-4 and IL-5). These results indicate that oral vaccination with HAv-SF-10 induces more efficient systemic and local immunity than nasal or subcutaneous vaccination with characteristically high levels of secretory HAv-specific IgA in various mucosal organs and protective immunity.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Imunidade nas Mucosas , Infecções por Orthomyxoviridae/prevenção & controle , Surfactantes Pulmonares/administração & dosagem , Surfactantes Pulmonares/imunologia , Administração Intranasal , Administração Oral , Animais , Anticorpos Antivirais/sangue , Citocinas/imunologia , Feminino , Humanos , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/virologia , Surfactantes Pulmonares/química , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Vacinação/métodos
6.
Environ Pollut ; 242(Pt A): 544-554, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30007265

RESUMO

Continuous haze monitoring was conducted from 12:00 3 April to 12:00 8 April 2016 in Beijing, China to develop a more detailed understanding of spring haze characteristics. The PM2.5 concentration ranged from 6.30 to 165 µg m-3 with an average of 63.8 µg m-3. Nitrate was the most abundant species, accounting for 36.4% of PM2.5, followed by organic carbon (21.5%), NH4+ (19.3%), SO42- (18.8%), and elemental carbon (4.10%), indicating the key role of nitrate in this haze event. Species contribution varied based on the phase of the haze event. For example, sulfate concentration was high during the haze formation phase, nitrate was high during the haze, and secondary organic carbon (SOC) had the highest contribution during the scavenging phase. The secondary transition of sulfate was influenced by SO2, followed by relative humidity (RH) and Ox (O3+NO2). Nitrate formation occurred in two stages: through NO2 oxidation, which was vulnerable to Ox; and by the partitioning of N (+5) which was susceptible to RH and temperature. SOC tended to form when Ox and RH were balanced. According to hourly species behavior, sulfate and nitrate were enriched during haze formation when the mixed layer height decreased. However, SOC accumulated prior to the haze event and during formation, which demonstrated the strong contribution of secondary inorganic aerosols, and the limiting contribution of SOC to this haze case. Investigating backward trajectories showed that high speed northwestern air masses following a straight path corresponded to the clear periods, while southwesterly air masses which traversed heavily polluted regions brought abundant pollutants to Beijing and stimulated the occurrence of haze pollution. Results indicate that the control of NO2 needs to be addressed to reduce spring haze. Finally, the correlation between air mass trajectories and pollution conditions in Beijing reinforce the necessity of inter-regional cooperation and control.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Material Particulado/análise , Aerossóis/análise , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Pequim , Carbono , China , Nitratos/análise , Estações do Ano , Sulfatos/análise , Transportes
7.
Artigo em Inglês | MEDLINE | ID: mdl-29406285

RESUMO

The influenza A virus (IAV)-cytokine-trypsin/matrix metalloproteinase-9 (MMP-9) cycle is one of the important mechanisms of multiple organ failure in severe influenza. Clarithromycin, a macrolide antibiotic, has immune modulatory and anti-inflammatory effects. We analyzed the effects of clarithromycin on the induction of chemokines, cytokines, MMP-9, trypsin, vascular hyper-permeability and inflammatory aggravation in mice with IAV infection. IAV/Puerto Rico/8/34(H1N1) infection increased the levels of monocyte chemoattractant protein-1 (MCP-1) and cytokines in serum, and MMP-9 and trypsin in serum and/or the lungs and heart. Clarithromycin significantly suppressed the induction of serum MCP-1 and MMP-9 and vascular hyperpermeability in these organs in the early phase of infection, but did not suppress the induction of trypsin, IL-6 or IFN-γ. Histopathological examination showed that clarithromycin tended to reduce inflammatory cell accumulation in the lungs and heart. These results suggest that clarithromycin suppresses infection-related inflammation and reduces vascular hyperpermeability by suppressing the induction of MCP-1 and MMP-9.


Assuntos
Antibacterianos/uso terapêutico , Quimiocina CCL2/metabolismo , Claritromicina/uso terapêutico , Vírus da Influenza A , Pulmão/patologia , Metaloproteinase 9 da Matriz/metabolismo , Miocárdio/patologia , Infecções por Orthomyxoviridae/tratamento farmacológico , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia
8.
PLoS One ; 13(1): e0191133, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29370185

RESUMO

We reported previously that intranasal instillation of a synthetic human pulmonary surfactant with a carboxy vinyl polymer as a viscosity improver, named SF-10, shows potent adjuvanticity for humoral immunity in mice and cynomolgus monkeys. SF-10 effectively induces influenza hemagglutinin vaccine (HAv)-specific IgA in nasal and lung washes and IgG in sera with their neutralizing activities. Since CD8+ T cell-mediated protection is an important requirement for adaptive immunity, we investigated in this study the effects of SF-10 with antigen on local and systemic cell-mediated immunity. Nasal instillation of ovalbumin, a model antigen, combined with SF-10 efficiently delivered antigen to mucosal dendritic and epithelial cells and promoted cross-presentation in antigen presenting cells, yielding a high percentage of ovalbumin-specific cytotoxic T lymphocytes in the nasal mucosa, compared with ovalbumin alone. Nasal immunization of HAv-SF-10 also induced HAv-specific cytotoxic T lymphocytes and upregulated granzyme B expression in splenic CD8+ T cells with their high cytotoxicity against target cells pulsed with HA peptide. Furthermore, nasal vaccination of HAv-SF-10 significantly induced higher cytotoxic T lymphocytes-mediated cytotoxicity in the lungs and cervical lymph nodes in the early phase of influenza virus infection compared with HAv alone. Protective immunity induced by HAv-SF-10 against lethal influenza virus infection was partially and predominantly suppressed after depletion of CD8+ and CD4+ T cells (induced by intraperitoneal injection of the corresponding antibodies), respectively, suggesting that CD4+ T cells predominantly and CD8+ T cells partially contribute to the protective immunity in the advanced stage of influenza virus infection. These results suggest that SF-10 promotes effective antigen delivery to antigen presenting cells, activates CD8+ T cells via cross-presentation, and induces cell-mediated immune responses against antigen.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Hemaglutinação por Vírus/imunologia , Imunidade Celular , Vacinas contra Influenza/administração & dosagem , Mimetismo Molecular , Surfactantes Pulmonares/química , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Vacinas contra Influenza/imunologia , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mucosa Nasal/imunologia
9.
Environ Pollut ; 229: 339-349, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28609735

RESUMO

Heavy haze pollution occurs frequently in northern China, most critically in the Beijing-Tianjin-Hebei area (BTH). Zibo, an industrial city located in Shandong province, is often listed as one of the top ten most polluted cities in China, particularly in winter. However, no studies of haze in Zibo have been conducted, which limits the understanding of the source and formation of haze pollution in this area, as well as mutual effects with the BTH area. We carried out online and continuous integrated field observation of particulate matter in winter, from 11 to 25 January 2015. SO42-, NO3-, and NH4+ (SIA) and organics were the main constituents of PM2.5, contributing 59.4% and 33.6%, respectively. With the increasing severity of pollution, the contribution of SIA increased while that of organics decreased. Meteorological conditions play an important role in haze formation; high relative humidity (RH) and low wind speed increased both the accumulation of pollutants and the secondary transition from gas precursors (gas-particle phase partitioning). Since RH and the presence of O3 can indicate heterogeneous and photochemistry processes, respectively, we carried out correlation analysis and linear regression to identify their relative importance to the three main secondary species (sulfate, nitrate, and secondary organic carbon (SOC)). We found that the impact of RH is in the order of SO42- > NO3- > SOC, while the impact of O3 is reversed, in the order of SOC > NO3- > SO42-, indicating different effect of these factors on the secondary formation of main species in winter. Cluster analysis of backward trajectories showed that, during the observation period, six directional sources of air masses were identified, and more than 90% came from highly industrialized areas, indicating that regional transport from industrialized areas aggravates the haze pollution in Zibo. Inter-regional joint prevention and control is necessary to prevent further deterioration of the air quality.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental , Material Particulado/análise , Aerossóis/análise , Poluição do Ar/análise , Pequim , China , Cidades , Poluição Ambiental , Umidade , Meteorologia , Nitratos/análise , Estações do Ano , Sulfatos/análise , Vento
10.
Environ Pollut ; 227: 296-305, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28477554

RESUMO

Four haze episodes (EPs) were observed in October 2014 in Beijing, China. For better understanding of the characteristics and the formation mechanisms of PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 µm), especially secondary water-soluble inorganic species in these haze events, hourly concentrations of PM2.5, sulfate, nitrate, and ammonium (SNA) were measured in this study. Concentrations of gaseous pollutants and meteorological parameters were also measured. The average concentration of PM2.5 was 106.6 ± 83.5 µg m-3, which accounted for around 53% of PM10 (particulate matter with an aerodynamic diameter ≤ 10 µm) mass. Nitrogen dioxide (NO2) concentration was much higher than that of sulfur dioxide (SO2) since October is a non-heating month. SNA is the most abundant secondary water-soluble inorganic species and contributed to 33% of PM2.5 mass concentration. Sulfur oxidation ratio (SOR) was much higher than nitrogen oxidation ratio (NOR). NOR and SOR increased with elevated PM2.5 levels and heterogeneous processes seemed to be the most plausible explanation of this increase. Relative humidity (RH), which is of great influence on aerosol liquid water content (ALWC), played a considerable role in the formation of secondary inorganic aerosols, accelerated the secondary transformation of gaseous precursors, and further aggravated haze pollution. The positive feedback loop associated with high aerosol levels and low planetary boundary layer (PBL) height led to the evolution and exacerbation of heavy haze pollution. Fire maps and 48-h air mass backward trajectories supported the significant impact of biomass burning activities and regional transport on haze formation over Beijing in October 2014.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Material Particulado/análise , Aerossóis/análise , Pequim , China , Meteorologia , Nitratos/análise , Dióxido de Nitrogênio , Estações do Ano , Solubilidade , Sulfatos/análise , Dióxido de Enxofre , Água
11.
Anal Sci ; 33(4): 477-479, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28392524

RESUMO

Infrared waveguide spectroscopy using a sapphire rod coated with an amorphous fluoropolymer (Cytop, Asahi Glass Co., ltd, Japan) has been developed in order to directly observe CO2 in aqueous solutions. Since the amorphous fluoropolymer has a relatively high gas-permeability and hydrophobic feature, the aqueous CO2 transmits into the amorphous fluoropolymer coating film, but water cannot penetrate into the film. Good linearity of calibration curves for CO2 in the gas and the aqueous solution were obtained.

12.
Clin Exp Rheumatol ; 34(6 Suppl 102): 111-114, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27791954

RESUMO

OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD. METHODS: The study involved a large-scale interview survey of Japanese patients with BD at 21 institutes of ophthalmology; 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA). RESULTS: Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD. CONCLUSIONS: Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.


Assuntos
Síndrome de Behçet/epidemiologia , Oftalmopatias/epidemiologia , Hipersensibilidade/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/imunologia , Comorbidade , Oftalmopatias/diagnóstico , Oftalmopatias/imunologia , Feminino , Inquéritos Epidemiológicos , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
13.
Respir Investig ; 54(5): 312-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27566378

RESUMO

Severe influenza is characterized by cytokine storm and multiorgan failure. Influenza patients with underlying diseases show a rapid progression in disease severity. The major mechanism that underlies multiorgan failure during the progressive stage of infection, particularly in patients with underlying risk factors, is mitochondrial energy crisis. The relationship between the factors that determine infection severity, such as influenza virus, cytokines, cellular trypsin as a hemagglutinin processing protease for viral multiplication, accumulation of metabolic intermediates and ATP crisis in mitochondria, is termed the "influenza virus-cytokine-trypsin" cycle. This occurs during the initial stages of infection, and is interconnected with the "metabolic disorders-cytokine" cycle in the middle to late phase of infection. Experiments using animal models have highlighted the complex relationship between these two cycles. New treatment options have been proposed that target the ATP crisis and multiorgan failure during the late phase of infection, rather than antiviral treatments with neuraminidase inhibitors that work during the initial phase. These options are (i) restoration of glucose oxidation in mitochondria by diisopropylamine dichloroacetate, which inhibits infection-induced pyruvate dehydrogenase kinase 4 activity, and (ii) restoration of long-chain fatty acid oxidation in mitochondria by l-carnitine and bezafibrate, an agonist of peroxisome proliferation-activated receptors-ß/δ, which transcriptionally upregulates carnitine palmitoyltransferase II. The latter is particularly effective in patients with influenza-associated encephalopathy who have thermolabile and short half-life compound variants of carnitine palmitoyltransferase II.


Assuntos
Influenza Humana/complicações , Doenças Metabólicas/complicações , Animais , Metabolismo Energético , Humanos , Vírus da Influenza A , Influenza Humana/terapia , Camundongos , Fatores de Risco
14.
Environ Sci Technol ; 50(9): 4632-41, 2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27050081

RESUMO

Haze episodes occurred in Beijing repeatedly in 2013, resulting in 189 polluted days. These episodes differed in terms of sources, formation processes, and chemical composition and thus required different control policies. Therefore, an overview of the similarities and differences among these episodes is needed. For this purpose, we conducted one-year online observations and developed a program that can simultaneously divide haze episodes and identify their shapes. A total of 73 episodes were identified, and their shapes were linked with synoptic conditions. Pure-haze events dominated in wintertime, whereas mixed haze-dust (PM2.5/PM10 < 60%) and mixed haze-fog (Aerosol Water/PM2.5 ∼ 0.3) events dominated in spring and summer-autumn, respectively. For all types, increase of ratio of PM2.5 in PM10 was typically achieved before PM2.5 reached ∼150 µg/m(3). In all PM2.5 species observed, organic matter (OM) was always the most abundant component (18-60%), but it was rarely the driving factor: its relative contribution usually decreased as the pollution level increased. The only OM-driven episode observed was associated with intensive biomass-burning activities. In comparison, haze evolution generally coincided with increasing sulfur and nitrogen oxidation ratios (SOR and NOR), indicating the enhanced production of secondary inorganic species. Applicability of these conclusions required further tests with simultaneously multisite observations.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Aerossóis , Pequim , China
15.
Vaccine ; 34(16): 1881-8, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-26954466

RESUMO

Induction of systemic and mucosal immunity and maintenance of its memory was investigated in 12 young male cynomolgus monkeys after intranasal instillation of flu vaccine using a new mucosal adjuvant SF-10 derived from pulmonary surfactant constituents. Split-product of influenza virus A/California/7/2009(H1N1)pdm hemagglutinin vaccine (HAv) at 15 µg with or without SF-10 and the adjuvant alone were instilled intranasally three times every 2 weeks. SF-10-adjuvanted HAv (SF-10-HAv) elicited significantly higher HAv-specific IgG and hemagglutinin inhibition (HI) titers in serum and HAv-specific secretory IgA and its neutralizing activities in nasal washes compared with HAv antigen and SF-10 alone. Significant cross-neutralizing activities of nasal washes after the third vaccination to several other H1N1 and H3N2 strains were observed. HI titers in serum and neutralizing activities in nasal washes reached peak levels at 6 weeks after initial vaccination, then gradually decreased after 10 weeks and returned to the baseline levels at 36 weeks. A single intranasal revaccination of SF-10-HAv at 36 weeks rapidly and significantly increased both immunity in serum and nasal washes compared with naïve monkeys. Revaccination by one or two doses achieved almost maximal immunity at 2 or 4 weeks after instillation. Statistically significant adverse effects (e.g., body weight loss, elevated body temperature, nasal discharge, change in peripheral blood leukocyte and platelet counts) were not observed for 2 weeks after vaccination of SF-10-HAv, HAv or SF-10 and also during the experimental period. These results in young monkey model suggest the potential of clinical use SF-10 for intranasal flu vaccine.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Imunidade nas Mucosas , Memória Imunológica , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Surfactantes Pulmonares/imunologia , Administração Intranasal , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Proteção Cruzada , Testes de Inibição da Hemaglutinação , Imunoglobulina A Secretora/imunologia , Imunoglobulina G/sangue , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza/administração & dosagem , Macaca fascicularis , Masculino , Testes de Neutralização , Vacinação/métodos
16.
PLoS One ; 10(4): e0125737, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25874989

RESUMO

UbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a significant role in vitamin K2 (MK-4) synthesis. We investigated the enzymological properties of UBIAD1 using microsomal fractions from Sf9 cells expressing UBIAD1 by analysing MK-4 biosynthetic activity. With regard to UBIAD1 enzyme reaction conditions, highest MK-4 synthetic activity was demonstrated under basic conditions at a pH between 8.5 and 9.0, with a DTT ≥0.1 mM. In addition, we found that geranyl pyrophosphate and farnesyl pyrophosphate were also recognized as a side-chain source and served as a substrate for prenylation. Furthermore, lipophilic statins were found to directly inhibit the enzymatic activity of UBIAD1. We analysed the aminoacid sequences homologies across the menA and UbiA families to identify conserved structural features of UBIAD1 proteins and focused on four highly conserved domains. We prepared protein mutants deficient in the four conserved domains to evaluate enzyme activity. Because no enzyme activity was detected in the mutants deficient in the UBIAD1 conserved domains, these four domains were considered to play an essential role in enzymatic activity. We also measured enzyme activities using point mutants of the highly conserved aminoacids in these domains to elucidate their respective functions. We found that the conserved domain I is a substrate recognition site that undergoes a structural change after substrate binding. The conserved domain II is a redox domain site containing a CxxC motif. The conserved domain III is a hinge region important as a catalytic site for the UBIAD1 enzyme. The conserved domain IV is a binding site for Mg2+/isoprenyl side-chain. In this study, we provide a molecular mapping of the enzymological properties of UBIAD1.


Assuntos
Dimetilaliltranstransferase/metabolismo , Vitamina K 2/metabolismo , Sequência de Aminoácidos , Animais , Vias Biossintéticas , Linhagem Celular , Colesterol/metabolismo , Dimetilaliltranstransferase/análise , Dimetilaliltranstransferase/genética , Expressão Gênica , Humanos , Insetos , Ácido Mevalônico/metabolismo , Microssomos/enzimologia , Microssomos/metabolismo , Dados de Sequência Molecular , Mutação Puntual , Prenilação de Proteína , Estrutura Terciária de Proteína , Alinhamento de Sequência
17.
Influenza Other Respir Viruses ; 7(6): 1218-26, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23710832

RESUMO

BACKGROUND: We found previously that bovine pulmonary Surfacten® used in newborns with acute respiratory distress syndrome is a safe and efficacious antigen vehicle for intranasal vaccination. OBJECTIVES: The objective of this study was to industrially produce a synthetic adjuvant mimicking Surfacten® for clinical use without risk of bovine spongiform encephalopathy. METHODS: We selected three Surfacten lipids and surfactant protein (SP)-C as essential constituents for adjuvanticity. For replacement of the hydrophobic SP-C, we synthesized SP-related peptides and analyzed their adjuvanticity. We evaluated lyophilization to replace sonication for the binding of influenza virus hemagglutinin (HA) to the synthetic adjuvant. We also added a carboxy vinyl polymer (CVP) to the synthetic adjuvant and named the mixture as SF-10 adjuvant. HA combined with SF-10 was administered intranasally to mice, and induction of nasal-wash HA-specific secretory IgA (s-IgA) and serum IgG with Th1-/Th2-type cytokine responses in nasal cavity and virus challenge test were assessed. RESULTS AND CONCLUSIONS: Intranasal immunization with HA-SF-10 induced significantly higher levels of anti-HA-specific nasal-wash s-IgA and serum IgG than those induced by HA-poly(I:C), a reported potent mucosal vaccine, and provided highly efficient protection against lethal doses of virus challenge in mice. Anti-HA-specific serum IgG levels induced by HA-SF-10 were almost equivalent to those induced by subcutaneous immunization of HA twice. Intranasal administration of HA-SF-10 induced balanced anti-HA-specific IgG1 and IgG2a in sera and IFN-γ- and IL-4-producing lymphocytes in nasal cavity without any induction of anti-HA IgE. The results suggest that HA-SF-10 is a promising nasal influenza vaccine and that SF-10 can be supplied in large quantities commercially.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacinas contra Influenza/imunologia , Vacinação/métodos , Administração Intranasal , Animais , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Sangue/imunologia , Citocinas/metabolismo , Feminino , Imunoglobulina A/análise , Imunoglobulina G/sangue , Vacinas contra Influenza/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Nasal/imunologia , Linfócitos T/imunologia
18.
Influenza Other Respir Viruses ; 6(6): 396-403, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22226319

RESUMO

OBJECTIVES: To determine the induction and changes in anti-influenza virus secretory IgA (s-IgA) levels in nasal washes and serum IgG levels in patients with influenza. METHODS: The study recruited 16 patients with influenza aged 35.6 ± 9.6 years in 2007/2008 and 2008/2009 seasons. Nasal washes and serum were obtained throughout the first year. Anti-viral s-IgA levels and neutralization activities in nasal washes, and serum anti-viral IgG levels and hemagglutination inhibition (HI) titers were measured. RESULTS: Anti-viral(H1N1) s-IgA to total IgA ratio and neutralizing antibody titer were low in nasal washes of all patients, whereas serum levels of anti-viral IgG and HI titers varied widely at day 1.4 ± 1.0 postinfection. Both nasal s-IgA and serum IgG levels later increased significantly, reaching peak levels at day 9.6 ± 3.3 postinfection. The induced nasal s-IgA then returned toward the initial levels within 300 days, although the levels at day 143 ± 70 were 3.03-fold of the initial. Individual serum IgG levels also returned toward the initial levels within 300 days, although the mean levels remained high probably because of re-infection in a subgroup of patients. Although influenza A (H3N2) was a minor epidemic subtype in both flu seasons, a significant rise in nasal anti-viral (H3N2) s-IgA levels and a slightly increase in serum IgG levels were noted. CONCLUSION: Low levels of nasal anti-viral s-IgA and neutralizing antibody were noted compared with a wide range of serum anti-viral IgG and HI titers at the onset of infection. Elevated s-IgA and IgG returned toward the initial levels within 300 days of infection with minor exceptions.


Assuntos
Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Imunoglobulina A Secretora/análise , Imunoglobulina G/sangue , Influenza Humana/imunologia , Orthomyxoviridae/imunologia , Adulto , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Testes de Neutralização , Estudos Retrospectivos , Soro/imunologia , Adulto Jovem
19.
Vaccine ; 29(33): 5368-78, 2011 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-21669246

RESUMO

We have reported that Surfacten(®) (St), a bovine pulmonary surfactant free of antigenic c-type lectins, is a useful mucosal adjuvant for nasal vaccination. To prepare ample supplies a synthetic adjuvant that mimics St, we analyzed essential constituents of St for mucosal adjuvanticity. Intranasal inoculation of influenza virus hemagglutinin (HA) vaccine combined with St free of surfactant protein (SP)-C resulted in failure of HA vaccine delivery to dendritic cells and loss of local and systemic immune responses. Naïve bovine SP-C, synthetic human or bovine SP-C peptide reconstituted with three major St lipids restored delivery activity and local and systemic immune responses to levels similar to those of St and provided almost complete protection against lethal doses of influenza virus challenge in mice. The delivery of fluoresceinated HA vaccine to cultured dendritic cells was significantly enhanced by co-administration of St or synthetic adjuvant, and moderately stimulated the expression of MHC class II and CD86. In addition, both St and synthetic adjuvant markedly sustained HA vaccine and achieved a wide antigen distribution in murine nasal cavity. These results suggest that synthetic mucosal adjuvant reconstituted with SP-C peptide and major St lipids is useful for ample supply of the potent mucosal adjuvant as an antigen delivery vehicle for intranasal vaccination.


Assuntos
Adjuvantes Imunológicos/farmacologia , Produtos Biológicos/farmacologia , Imunidade nas Mucosas/efeitos dos fármacos , Vacinas contra Influenza/imunologia , Lipopeptídeos/farmacologia , Peptídeos Cíclicos/farmacologia , Administração Intranasal , Animais , Antígeno B7-2/biossíntese , Modelos Animais de Doenças , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Antígenos de Histocompatibilidade Classe II/biossíntese , Vacinas contra Influenza/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Doenças dos Roedores/prevenção & controle , Doenças dos Roedores/virologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/imunologia
20.
Anal Sci ; 26(6): 709-13, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20543505

RESUMO

The open-cell titration of seawater was studied for alkalinity measurements by colorimetry. 1) The colorimetric pH of free hydrogen ion concentration, pH(F(ind)), was calculated from the ratio of the absorbances at 436 and 590 nm (R = (590nm)A/(436nm)A), along with the molar absorption coefficient ratios (e(1), e(2) and e(3)/e(2)) and a tentative acid dissociation constant value (pK(a(2))). 2) The perturbation of hydrogen ion was evaluated from the change in titration mass (Deltam). The total hydrogen ion concentration at m + Deltam, pH(T(at m+Deltam)), was calculated using pH(F(ind)) for a mass m and constants for sulfate (S(T)) and fluoride (F(T)). 3) The alkalinity (A(T)) was computed from the titrant mass (m + Deltam) and the corresponding pH(T(at m+Deltam)) through a non-linear least-squares approach using the pK(a(2)) value as a variable parameter. Seawater sample at 2000 m depth from the West Pacific was analyzed. The resulting A(T) (2420.92 +/- 3.35 micromol kg(-1)) was in good agreement with the A(T) measured by potentiometric electric force (2420.46 +/- 1.54 micromol kg(-1)). The resulting pK(a(2)) was 3.7037, in close proximity to that reported by King et al. (pK(a(2)) = 3.695).

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