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The KamLAND-Zen experiment has provided stringent constraints on the neutrinoless double-beta (0νßß) decay half-life in ^{136}Xe using a xenon-loaded liquid scintillator. We report an improved search using an upgraded detector with almost double the amount of xenon and an ultralow radioactivity container, corresponding to an exposure of 970 kg yr of ^{136}Xe. These new data provide valuable insight into backgrounds, especially from cosmic muon spallation of xenon, and have required the use of novel background rejection techniques. We obtain a lower limit for the 0νßß decay half-life of T_{1/2}^{0ν}>2.3×10^{26} yr at 90% C.L., corresponding to upper limits on the effective Majorana neutrino mass of 36-156 meV using commonly adopted nuclear matrix element calculations.
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Abrasion of the brake lining of automobiles is one of the main antimony (Sb) sources on the road. Therefore, the road effluent possibly supplies Sb to the combined sewer collection system. However, Sb in road-sewer systems has attracted little concern, although heavy metals such as copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) in sewer water have been studied by many previous authors. We investigated the effect of road effluent on Sb in the combined sewer water by collecting road effluent, road dust, and sewer water under rainy and dry weather conditions. Sb in road effluent showed a significantly higher concentration than the other types of samples, and the Sb concentration in sewer during wet weather was significantly higher than that during dry weather. Furthermore, the Sb concentration in sewer water decreased with time during a wash-off event. Clear positive relationships between Sb and Cu and between Sb and Ba in both road effluent and road dust extract indicate the effect of brake abrasion because the brake lining contains Cu, Sb, and Ba in high concentrations. Approximately 42% of Sb load occurred during the wash-off event, while the loads of Cu and Ba were much less. Unlike Cu and Ba, we conclude that Sb in combined sewer water largely depends on road effluent in wet weather due to the wash-off of road dust, which is probably associated with brake lining abrasion.
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Poeira , Metais Pesados , Antimônio , Poeira/análise , Monitoramento Ambiental , Metais Pesados/análise , ChuvaRESUMO
We present a precision analysis of the ^{136}Xe two-neutrino ßß electron spectrum above 0.8 MeV, based on high-statistics data obtained with the KamLAND-Zen experiment. An improved formalism for the two-neutrino ßß rate allows us to measure the ratio of the leading and subleading 2νßß nuclear matrix elements (NMEs), ξ_{31}^{2ν}=-0.26_{-0.25}^{+0.31}. Theoretical predictions from the nuclear shell model and the majority of the quasiparticle random-phase approximation (QRPA) calculations are consistent with the experimental limit. However, part of the ξ_{31}^{2ν} range allowed by the QRPA is excluded by the present measurement at the 90% confidence level. Our analysis reveals that predicted ξ_{31}^{2ν} values are sensitive to the quenching of NMEs and the competing contributions from low- and high-energy states in the intermediate nucleus. Because these aspects are also at play in neutrinoless ßß decay, ξ_{31}^{2ν} provides new insights toward reliable neutrinoless ßß NMEs.
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This corrects the article DOI: 10.1103/PhysRevLett.117.082503.
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We present an improved search for neutrinoless double-beta (0νßß) decay of ^{136}Xe in the KamLAND-Zen experiment. Owing to purification of the xenon-loaded liquid scintillator, we achieved a significant reduction of the ^{110m}Ag contaminant identified in previous searches. Combining the results from the first and second phase, we obtain a lower limit for the 0νßß decay half-life of T_{1/2}^{0ν}>1.07×10^{26} yr at 90% C.L., an almost sixfold improvement over previous limits. Using commonly adopted nuclear matrix element calculations, the corresponding upper limits on the effective Majorana neutrino mass are in the range 61-165 meV. For the most optimistic nuclear matrix elements, this limit reaches the bottom of the quasidegenerate neutrino mass region.
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Perfluorooctanoic acid (PFOA) is very persistent in the environment and widely detected in the water environment. Only some advanced methods with extreme reaction conditions are shown to be capable of degrading the compound efficiently, and almost all the earlier investigations used very high PFOA concentrations. The compound is detected normally at very low concentrations in the water environment, while mild reaction conditions for its degradation are preferable. This article aimed to elucidate photodegradation of PFOA in dilute aqueous solutions by combined UV wavelengths (185 nm+254 nm) and 254 nm using a newly designed UV jacket. PFOA degradation was greatly enhanced with the combined wavelengths with almost one hundred percent PFOA removals in four-hour reaction. The removals were well described by the first-order reaction kinetic. The removal efficiencies and rate values significantly decreased with smaller initial PFOA concentrations. But defluorination was greatly enhanced with smaller PFOA concentrations possibly due to accelerated decomposition of fluorinated intermediates of PFOA. Formic acid and acetic acid were two tentatively identified intermediates of PFOA photolysis while the former was a major intermediate predominantly controlling solution pH during the oxidation. The results demonstrated that PFOA photolysis by the combined wavelengths with mild reaction conditions can be greatly enhanced by proper design of UV jacket and reactor system.
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Caprilatos/efeitos da radiação , Fluorocarbonos/efeitos da radiação , Fotólise/efeitos da radiação , Raios Ultravioleta , Água/química , Ácidos Carboxílicos/análise , Cromatografia por Troca Iônica , Fluoretos/análise , Meia-Vida , Halogenação/efeitos da radiação , Concentração de Íons de Hidrogênio/efeitos da radiação , Cinética , SoluçõesRESUMO
The widespread detection of perfluorinated compounds (PFCs) in the water environment has been a concern for the last several years, while effluents from wastewater treatment facilities are the major sources of these compounds. Even advanced oxidation technologies (AOTs) are not useful for mineralization of the compounds due to their very high stability. Photochemical techniques using particularly vacuum UV (VUV) have been found to be very promising in this regard. But the use of VUV in UV-based AOTs has still not progressed much. Moreover, the impact of water quality on PFCs photomineralization is unknown. This investigation aimed to assess photomineralization potentials of perfluorooctanoic acid (PFOA) in ultrapure water (UPW), tap water (TW), surface water and treated wastewater effluent using a reactor setup enabling maximum utilization of VUV emission of low pressure lamp in laboratory batch experiments. Neya River water (NRW) and the Nakahama Wastewater Treatment Plant Effluent (NWWTPE) represented surface water and treated wastewater effluent respectively. Also, tests were carried out in 50% diluted NRW and NWWTPE. PFOA photomineralization in terms of PFOA removal, defluorination and total organic carbon (TOC) removal are discussed. The usefulness of the method for PFOA mineralization in organic-rich wastewaters, and further research needs are also highlighted.
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Caprilatos/análise , Fluorocarbonos/análise , Raios Ultravioleta , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Qualidade da Água/normas , Japão , FotóliseRESUMO
Presence of chlorinated organic compounds in water bodies has become a concern among governments, health authorities and general public. Oxidation of organic compounds in water under high temperature and pressure is considered as a promising technique, but usefulness of the technique to mineralize 2,4-dichlorophenoxyacetic acid (2,4-D) is not well understood. This article aimed to elucidate degradation characteristics of 2,4-D in both subcritical and supercritical waters by laboratory batch experiments. 2,4-D degradation, total organic carbon (TOC) removal and dechlorination increased with increasing reaction time and temperature especially in subcritical waters, while dechlorination was a major step. 2,4-dichlorophenol (2,4-DCP) and acetic acid were the main degradation intermediates both in subcritical and supercritical waters. Though 2,4-D disappeared almost completely in subcritical waters near critical region ( approximately 99%), significant amounts of TOC and organic chlorine still remained as 2,4-DCP and acetic acid. But TOC removal and dechlorination were significantly enhanced ( approximately 95 and 91% respectively) in supercritical waters. Complete mineralization of 2,4-D in subcritical waters required a considerably longer reaction period, while the mineralization was almost complete within a short reaction period in supercritical waters. This is an important information of practical significance for oxidative degradation of chlorinated pesticides similar to 2,4-D.
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Ácido 2,4-Diclorofenoxiacético/química , Herbicidas/química , Poluentes Químicos da Água/química , Água/química , Oxirredução , Pressão , Temperatura , Purificação da ÁguaRESUMO
Acute lung injury has a range of causes, and occasionally leads to lethal respiratory failure. Despite advances in treatment, acute lung injury continues to have a high mortality rate, and thus a new therapeutic approach is needed. ST2 is an interleukin (IL)-1 receptor-related protein, and its expression is induced by various inflammatory responses. Recently, ST2 has been speculated to exert anti-inflammatory effects; therefore, we investigated the role of the ST2 in the murine model of acute lung injury. To elucidate the function of ST2 in vivo, mice that transiently overexpressed ST2 protein were prepared using the hydrodynamic gene transfer method, and lung injury was induced by intratracheal administration of bleomycin. In bleomycin-treated ST2-overexpressing mice, the increase of neutrophils in the bronchoalveolar lavage fluid (BALF) was markedly suppressed. Additionally, the levels of tumour necrosis factor-alpha and IL-6, as well as the concentration of albumin, in BALF were reduced compared with those of controls. Furthermore, the pulmonary architecture in ST2-overexpressing mice remained almost normal, and the survival rate was significantly improved. From these results, we concluded that ST2 has the potential to suppress the initial stage of acute lung injury, and therefore it may be a useful reagent for the treatment of acute lung injury.
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Lesão Pulmonar Aguda/fisiopatologia , Receptores de Interleucina/fisiologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Albuminas/metabolismo , Análise de Variância , Animais , Bleomicina/toxicidade , Líquido da Lavagem Broncoalveolar/química , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Técnicas de Transferência de Genes , Vetores Genéticos , Interleucina-1/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-33 , Interleucina-6/metabolismo , Interleucinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plasmídeos , Receptores de Interleucina-1/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/metabolismo , beta-Galactosidase/metabolismoRESUMO
At tight junctions (TJs), claudins with four transmembrane domains are incorporated into TJ strands. Junctional adhesion molecule (JAM), which belongs to the immunoglobulin superfamily, is also localized at TJs, but it remains unclear how JAM is integrated into TJs. Immunoreplica electron microscopy revealed that JAM showed an intimate spatial relationship with TJ strands in epithelial cells. In L fibroblasts expressing exogenous JAM, JAM was concentrated at cell-cell adhesion sites, where there were no strand-like structures, but rather characteristic membrane domains free of intramembranous particles were detected. These domains were specifically labeled with anti-JAM polyclonal antibody, suggesting that JAM forms planar aggregates through their lateral self-association. Immunofluorescence microscopy and in vitro binding assays revealed that ZO-1 directly binds to the COOH termini of claudins and JAM at its PDZ1 and PDZ3 domains, respectively. Furthermore, another PDZ-containing polarity-related protein, PAR-3, was directly bound to the COOH terminus of JAM, but not to that of claudins. These findings led to a molecular architectural model for TJs: small aggregates of JAM are tethered to claudin-based strands through ZO-1, and these JAM aggregates recruit PAR-3 to TJs. We also discuss the importance of this model from the perspective of the general molecular mechanisms behind the recruitment of PAR proteins to plasma membranes.
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Moléculas de Adesão Celular/metabolismo , Receptores de Trombina/metabolismo , Junções Íntimas/metabolismo , Animais , Adesão Celular/fisiologia , Moléculas de Adesão Celular/genética , Polaridade Celular/fisiologia , Células Cultivadas , Claudina-1 , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Fibroblastos/citologia , Fibroblastos/fisiologia , Técnica de Fratura por Congelamento , Moléculas de Adesão Juncional , Proteínas de Membrana/química , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Mutagênese/fisiologia , Fosfoproteínas/química , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Ligação Proteica/fisiologia , Estrutura Terciária de Proteína , Receptores de Trombina/genética , Transdução de Sinais/fisiologia , Junções Íntimas/ultraestrutura , Transfecção , Proteína da Zônula de Oclusão-1RESUMO
The electronic density of states and magnetic properties were investigated by tunneling spectroscopy and SQUID, respectively, for a series of 3d transition-metal (Mn, Fe, Co)-doped ZnO. By tunneling spectroscopy an additional density of states was observed in Mn- and Co-doped ZnO adjacent to the top of the valence band of the host ZnO. Instead, in the Fe-doped sample, a band of density of states was observed across the Fermi level in the mid-gap. The magnetization curve (M versus H) obtained by SQUID showed a ferromagnetic hysteresis at room temperature for the Fe-doped sample, whereas for the Mn- and Co-doped samples, the M versus H curve showed only a linear characteristic without hysteresis. From the comparison of the density of states and the magnetization characteristics, it is strongly suggested that the ferromagnetism in Fe-doped ZnO at room temperature originates from the half-filled Fe 3d band in the mid-gap of the host ZnO.
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This study aimed to investigate the effects of a gradually decreasing intensity training from that corresponding to maximal anaerobic power (MAnP) to that of near maximal oxygen uptake ([Formula: see text]) (decrescent intensity training) on MAnP, maximal accumulated oxygen deficit (MAOD), and [Formula: see text] in untrained young men. Seventeen untrained young men were randomly divided into either a training (TR; n = 9) group or a control (CON; n = 8) group. The TR group performed the decrescent intensity training, whereas the CON group did not perform any exercises. The mean training time per session throughout the training period was 275 ± 135 s. There was a Group × Time interaction for both absolute and relative (p < 0.01) values of [Formula: see text], MAOD, and MAnP. The TR group had significantly increased values for all variables after the 8-week training program, and the relative values of all variables were significantly higher in the TR group than in the CON group. Muscle thicknesses in the anterior and posterior aspects of the thigh and maximal isokinetic knee extension and flexion strengths improved only in the TR group (p < 0.05). A single-exercise training with gradually decreasing intensity from that corresponding to the MAnP to that of approximately 100% [Formula: see text] improves MAnP, MAOD, and [Formula: see text] concurrently, despite the short training time per session.
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Limiar Anaeróbio/fisiologia , Anaerobiose/fisiologia , Exercício Físico/fisiologia , Consumo de Oxigênio/fisiologia , Aptidão Física/fisiologia , Adulto , Teste de Esforço/métodos , Terapia por Exercício/métodos , Humanos , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Oxigênio/metabolismo , Corrida/fisiologia , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: We have recently reported that phytosteryl ferulates isolated from rice bran inhibit nuclear factor-kappaB (NF-kappaB) activity in macrophages. In the present study, we investigated the effect of gamma-oryzanol (gamma-ORZ), a mixture of phytosteryl ferulates, cycloartenyl ferulate (CAF), one of the components of gamma-ORZ, and ferulic acid (FA), a possible metabolite of gamma-ORZ in vivo, on a model of colitis in mice. EXPERIMENTAL APPROACH: We induced colitis with dextran sulphate sodium (DSS) in mice and monitored disease activity index (DAI), histopathology score, tissue myeloperoxidase (MPO) activity, mRNA expressions of cytokines and COX-2, colon length, antioxidant potency and NF-kappaB activity in colitis tissue. KEY RESULTS: Both DAI and histopathology score revealed that DSS induced a severe mucosal colitis, with a marked increase in the thickness of the muscle layer, distortion and loss of crypts, depletion of goblet cells and infiltration of macrophages, granulocytes and lymphocytes. MPO activity, pro-inflammatory cytokines and COX-2 levels, NF-kappaB p65 nuclear translocation and inhibitory protein of nuclear factor-kappaB-alpha degradation levels were significantly increased in DSS-induced colitis tissues. gamma-ORZ (50 mg kg(-1) day(-1) p.o.) markedly inhibited these inflammatory reactions and CAF had a similar potency. In vitro assay demonstrated that gamma-ORZ and CAF had strong antioxidant effects comparable to those of alpha-tocopherol. CONCLUSIONS AND IMPLICATIONS: Phytosteryl ferulates could be new potential therapeutic and/or preventive agents for gastrointestinal inflammatory diseases. Their anti-inflammatory effect could be mediated by inhibition of NF-kappaB activity, which was at least partly due to the antioxidant effect of the FA moiety in the structure of phytosteryl ferulates.
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Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Ácidos Cumáricos/farmacologia , Fenilpropionatos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Colite/induzido quimicamente , Ácidos Cumáricos/isolamento & purificação , Sulfato de Dextrana , Modelos Animais de Doenças , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Oryza/química , Fenilpropionatos/química , Fenilpropionatos/isolamento & purificação , Fitosteróis/isolamento & purificação , Fitosteróis/farmacologia , alfa-Tocoferol/farmacologiaRESUMO
The effects of dietary taurine on the experimental colitis induced by dextran sulfate sodium (DSS) in mice were evaluated. C57BL/6 female mice were given 3% DSS in drinking water for 5 d to induce acute colitis. Taurine at 2% was added to the drinking water 5 d before and during the DSS-treatment to investigate its preventive effect. Taurine supplementation significantly attenuated the weight decrease, diarrhea severity, colon shortening, and the increase in the colonic tissue myeloperoxidase activity induced by DSS. Taurine also significantly inhibited the increase in the expression of a pro-inflammatory chemokine, macrophage inflammatory protein 2 (MIP-2), but not of interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha mRNA. Furthermore, taurine significantly protected the intestinal Caco-2 cell monolayers from the damage by macrophage-like THP-1 cells in an in vitro coculture system. These results suggest that taurine prevented DSS-induced colitis partly in association with (1) its inhibitory effects on the secretion of MIP-2 from the intestinal epithelial cells and on the infiltration of such inflammatory cells as neutrophils and (2) its cytoprotective functions on the epithelial barrier from the direct toxicity of DSS and from the inflammatory cell-induced injury.
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Colite/prevenção & controle , Sulfato de Dextrana/toxicidade , Suplementos Nutricionais , Taurina/farmacologia , Animais , Células CACO-2 , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Diarreia/induzido quimicamente , Diarreia/metabolismo , Diarreia/patologia , Diarreia/prevenção & controle , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Neutrófilos/metabolismo , Neutrófilos/patologiaRESUMO
Photocatalytic ozonation (O(3)/UV/TiO2) is an emerging oxidation method for recalcitrant organic contaminants in water. However, immobilised TiO2 catalysts suffer from reduced photonic efficiency. Therefore, TiO2 catalysts with excellent mechanical and thermal properties and enhanced photonic efficiencies are sought. This paper aimed to elucidate the mineralisation of low concentration 2,4-D (45.0 microM) by O(3)/UV/TiO2 using the world's first high-strength TiO2 fibre in laboratory batch experiments. 2,4-D degradation and TOC removal followed pseudo first-order reaction kinetic. The removal rates for 2,4-D and TOC in O(3)/UV/TiO2 were 1.5 and 2.4-fold larger than the summation of the values for ozonation (O3)) and photocatalysis (UV/TiO2), respectively. O(3)/UV/TiO2 was characterised by few aromatic intermediates with low abundance, fast degradations of aliphatic intermediates and dechlorination as a major step. The significantly enhanced 2,4-D mineralisation in O(3)/UV/TiO2 was attributed to increased ozone dissolution and decomposition, and reduced electron-hole recombination resulting in large number of hydroxyl radical (*OH) formation from more than one parallel path. The discrepancies in the organic carbon mass budget were attributed to few apparently major unidentified intermediates, while chlorine mass balance was reasonably acceptable. The mineralisation efficiency of O(3)/UV/TiO2 with the TiO2 fibre can further be enhanced by optimisation of experimental design parameters. The new TiO2 fibre is very promising to overcome the problem of reduced efficiency of TiO2 catalyst in an immobilised state.
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Ozônio , Titânio/química , Ácido 2,4-Diclorofenoxiacético/isolamento & purificação , Catálise , Cinética , Oxirredução , Fotoquímica , Soluções , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodosRESUMO
This paper aims to elucidate retention characteristics of some pharmaceuticals and personal care products (PPCPs), and endocrine disrupting chemicals (EDCs), by two polyamide low pressure reverse osmosis (LPRO) membranes. Feed solution pH did not have an influence on rejections of undissociated solutes, which was most likely governed by adsorption, size exclusion and diffusion simultaneously. Size exclusion was presumably dominant, especially with tight membranes (UTC-70U). Rejections of the solutes with low dipole moment (<1.0 debye) decreased with increasing octanol-water partition coefficient (K(ow)). The solutes with large K(ow) values were most likely adsorbed on membrane and subsequently passed through it resulting in larger diffusion coefficient (D(p)). The rejections decreased with increasing D(p) values irrespective of their dipole moments. Rejections of solutes with comparatively larger dipole moments might be dominated by diffusion and/or convection rather than their hydrophobicity. However, rejections of solutes with hydroxyl and carboxyl functional groups by UTC-60 increased with solution pH. More than 80% rejections were obtained for degree of dissociation (alpha)>0.5. Electrostatic repulsion played a key role for rejection of dissociated solutes, especially by loose LPRO membranes. Therefore, assessing the dissociation degree at desired pH values can be a key step to obtain an insight of rejection mechanisms by polyamide membranes.
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Disruptores Endócrinos/isolamento & purificação , Preparações Farmacêuticas/isolamento & purificação , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , Adsorção , Cromatografia em Gel , Desenho de Equipamento , Produtos Domésticos/análise , Humanos , Concentração de Íons de Hidrogênio , Potenciais da Membrana , Osmose , Ultrafiltração/métodos , População Urbana , Eliminação de Resíduos Líquidos/instrumentação , Poluentes Químicos da Água/isolamento & purificação , Abastecimento de Água/normasRESUMO
To evaluate the virulence of avian pathogenic Escherichia coli (APEC) isolates obtained from colibacillosis cases associated with pericarditis, perihepatitis, and salpingitis, the embryo lethality assay and experimental infection model in chicks were used in this study. According to the established criteria based on mortality in the embryo lethality assay for evaluating the virulence of E. coli isolates, 23 of the 26 APEC isolates associated with pericarditis and perihepatitis and 8 of the 20 isolates associated with salpingitis were found to be virulent. Isolate D137, which had been obtained from a case with pericarditis and perihepatitis and had an embryo mortality of 92%, and isolate D445, which had been obtained from a case with pericarditis and perihepatitis and had an embryo mortality of 17%, were used for the experimental infection. Four of the five 11-day-old chickens inoculated through the air sac with isolate D137 died 1 day postinoculation, and the challenge strain was recovered from the air sac, pericardial sac, or liver; however, colibacillosis lesions were found in only one of the five birds postmortem. All five chicks inoculated with isolate D445 survived for 7 days postinoculation and exhibited airsacculitis or pericarditis lesions at 7 days postinoculation; the challenge strain was not recovered from the lesions postmortem. The results obtained in this study suggest that the different APEC isolates tested cause illness in chickens through distinct pathogenesis.
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Infecções por Chlamydia/veterinária , Infecções por Escherichia coli/veterinária , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Doença Inflamatória Pélvica/veterinária , Pericardite/veterinária , Peritonite/veterinária , Doenças das Aves Domésticas/microbiologia , Salpingite/veterinária , Animais , Embrião de Galinha , Galinhas , Infecções por Chlamydia/microbiologia , Infecções por Escherichia coli/microbiologia , Feminino , Hepatite/microbiologia , Doença Inflamatória Pélvica/microbiologia , Pericardite/microbiologia , Peritonite/microbiologia , Salpingite/microbiologia , VirulênciaRESUMO
BACKGROUND: Interstitial cells of Cajal (ICC) serve as intestinal pacemakers. Postoperative ileus (POI) is a gastrointestinal motility disorder that occurs following abdominal surgery, which is caused by inflammation-induced dysfunction of smooth muscles and enteric neurons. However, the participation of ICC in POI is not well understood. In this study, we investigated the functional changes of ICC in a mouse model of POI. METHODS: Intestinal manipulation (IM) was performed to induce POI. At 24 h or 48 h after IM, the field potential of the intestinal tunica muscularis was investigated. Tissues were also examined by immunohistochemistry and electron microscopic analysis. KEY RESULTS: Gastrointestinal transit was significantly decreased with intestinal tunica muscularis inflammation at 24 h after IM, which was ameliorated at 48 h after IM. The generation and propagation of pacemaker potentials were disrupted at 24 h after IM and recovered to the control level at 48 h after IM. ICC networks, detected by c-Kit immunoreactivity, were remarkably disrupted at 24 h after IM. Electron microscopic analysis revealed abnormal vacuoles in the ICC cytoplasm. Interestingly, the ICC networks recovered at 48 h after IM. Administration of aminoguanidine, an inducible nitric oxide synthase inhibitor, suppressed the disruption of ICC networks. Ileal smooth muscle tissue cultured in the presence of nitric oxide donor, showed disrupted ICC networks. CONCLUSIONS AND INFERENCES: The generation and propagation of pacemaker potentials by ICC are disrupted via nitric oxide after IM, and this disruption may contribute to POI. When inflammation is ameliorated, ICC can recover their pacemaker function.
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BACKGROUND AND PURPOSE: Hepatic stellate cells play an important role in liver fibrosis but little is known about liver myofibroblasts located around the central vein and in the portal area. In this study, intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured to assess the response to endothelin-1 (ET-1), platelet derived growth factor (PDGF) and ATP in rat liver myofibroblasts. EXPERIMENTAL APPROACH: Rat liver myofibroblasts were compared in 'quiescent' (cultured on Matrigel-coated dishes) and 'activated' (cultured on non-coated plastic dishes) conditions. [Ca(2+)](i) was measured with the fluorescent dye fura-2 and mRNA for ET-1, PDGF and their receptors by RT-PCR. KEY RESULTS: ET-1 increased [Ca(2+)](i) in quiescent cells but not in activated cells, whereas PDGF-BB increased [Ca(2+)](i) in activated cells but not in quiescent cells. However, there was no difference between responses to ATP in quiescent or activated cells. ET-1 (in quiescent cells), PDGF-BB (in activated cells) and ATP (in both cells) all induced transient increases in [Ca(2+)](i) in the absence of extracellular Ca(2+) (with EGTA), indicating the involvement of Ca(2+) release from intracellular Ca(2+) stores. The sustained increase in [Ca(2+)](i) in the presence of external Ca(2+) in activated cells (ATP and PDGF) was significantly reduced by nicardipine, a L-type Ca(2+) channel blocker, but not in quiescent cells (ATP and ET-1). CONCLUSIONS AND IMPLICATIONS: The different pharmacological profiles of [Ca(2+)](i)-response in quiescent and activated myofibroblasts suggest that ET-1 and PDGF contribute differently to myofibroblast activation during the process of liver fibrosis.
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Cálcio/metabolismo , Diferenciação Celular/fisiologia , Endotelina-1/fisiologia , Cirrose Hepática/fisiopatologia , Fígado/metabolismo , Fator de Crescimento Derivado de Plaquetas/fisiologia , Trifosfato de Adenosina/fisiologia , Animais , Becaplermina , Sinalização do Cálcio , Células Cultivadas , Fibroblastos/metabolismo , Fígado/citologia , Masculino , Proteínas Proto-Oncogênicas c-sis , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The mechanism of gastrointestinal dysmotility in inflammatory bowel disease has not been clarified. In this study, we examined the mechanism involved in the inflamed distal colon isolated from a mouse model of dextran sodium sulphate-induced ulcerative colitis (DSS-treated mouse). Although substance P-induced contraction was not changed, carbachol-induced contraction was reduced in the DSS-treated mouse colon. Pre-incubation with the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) or the cyclooxygenase inhibitor indomethacin did not reverse the carbachol-induced contraction in the DSS-treated mouse colon. In semi-quantitative reverse transcription-polymerase chain reaction experiments and Western blot analysis, muscarinic M3 receptor expressions were not changed. The Ca2+ -sensitization of contractile elements induced by carbachol with GTP or GTPgammaS was reduced in the beta-escin-permeabilized DSS-treated mouse colon. Although the expression of proteins such as rhoA, ROCK1, ROCK2 or MYPT1 in smooth muscles was not changed, the expression of CPI-17, the functional protein involved in smooth muscle Ca2+ -sensitization, was significantly decreased in the DSS-treated mouse colon. These results suggest that the suppression of carbachol-induced contraction in mice with colitis is attributable at least partially to the increased activity of myosin phosphatase following the downregulation of CPI-17.