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1.
Toxicol Lett ; 319: 49-57, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31693926

RESUMO

Blast lung injury is associated with high morbidity and mortality. Vaporized perfluorocarbon (PFC) inhalation has been reported to attenuate acute respiratory distress syndrome in humans and animal models. However, the effect of vaporized PFC on blast lung injury is still unknown. In this study, we investigated the protective effects and potential underlying mechanisms of action of vaporized PFC on blast lung injury in a canine model. This was a prospective, controlled, animal study in adult male hybrid dogs randomized to sham, blast (B), blast plus mechanical ventilation (B + M), and blast plus PFC (B + P) groups. All groups except for the sham were exposed to blast wave. The B + P group was treated with vaporized PFC for 1.5 h followed by 5.5 h mechanical ventilation. B + M group received 7.5 h mechanical ventilation and B group was observed for 7.5 h. Blast lung injury was induced using a shock tube. Blood gas, inflammatory cytokines, and oxidative stress were measured. Expression of nuclear factor (NF)-κB activation, mitogen-activated protein kinase (MAPK) and nuclear factor, erythroid 2 like 2 (Nrf2) were measured using western blot. Lung injury observed after blast exposure was marked by increased histopathological scores, ratio of lung wet to dry weight. PFC treatment attenuated blast lung injury as indicated by histopathological scores and ratio of lung wet to dry weight. PFC treatment downregulated interleukin (IL)-6, tumor necrosis factor (TNF)-α, and malondialdehyde (MDA), and upregulated superoxide dismutase (SOD) activity. PFC also suppressed expression of MAPK/NF-κB and Nrf2 protein levels. Our results suggest that PFC attenuated blast-induced acute lung injury by inhibiting MAPK/NF-κB activation and inducing Nrf2 expression in dogs.


Assuntos
Traumatismos por Explosões/tratamento farmacológico , Fluorcarbonetos/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Administração por Inalação , Animais , Traumatismos por Explosões/patologia , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Cães , Fluorcarbonetos/administração & dosagem , Pulmão/patologia , Lesão Pulmonar/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos
2.
PLoS One ; 12(3): e0173884, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28323898

RESUMO

BACKGROUND AND OBJECTIVE: Blast lung injury is a common type of blast injury and has very high mortality. Therefore, research to identify medical therapies for blast injury is important. Perfluorocarbon (PFC) is used to improve gas exchange in diseased lungs and has anti-inflammatory functions in vitro and in vivo. The aim of this study was to determine whether PFC reduces damage to A549 cells caused by blast injury and to elucidate its possible mechanisms of action. STUDY DESIGN AND METHODS: A549 alveolar epithelial cells exposed to blast waves were treated with and without PFC. Morphological changes and apoptosis of A549 cells were recorded. PCR and enzyme-linked immunosorbent assay (ELISA) were used to measure the mRNA or protein levels of IL-1ß, IL-6 and TNF-α. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels were detected. Western blot was used to quantify the expression of NF-κB, Bax, Bcl-2, cleaved caspase-3 and MAPK cell signaling proteins. RESULTS: A549 cells exposed to blast wave shrank, with less cell-cell contact. The morphological change of A549 cells exposed to blast waves were alleviated by PFC. PFC significantly inhibited the apoptosis of A549 cells exposed to blast waves. IL-1ß, IL-6 and TNF-α cytokine and mRNA expression levels were significantly inhibited by PFC. PFC significantly increased MDA levels and decreased SOD activity levels. Further studies indicated that NF-κB, Bax, caspase-3, phospho-p38, phosphor-ERK and phosphor-JNK proteins were also suppressed by PFC. The quantity of Bcl-2 protein was increased by PFC. CONCLUSION: Our research showed that PFC reduced A549 cell damage caused by blast injury. The potential mechanism may be associated with the following signaling pathways: 1) the signaling pathways of NF-κB and MAPK, which inhibit inflammation and reactive oxygen species (ROS); and 2) the signaling pathways of Bcl-2/Bax and caspase-3, which inhibit apoptosis.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Traumatismos por Explosões/tratamento farmacológico , Traumatismos por Explosões/metabolismo , Fluorcarbonetos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Lesão Pulmonar Aguda/patologia , Apoptose/efeitos dos fármacos , Traumatismos por Explosões/patologia , Caspase 3/metabolismo , Forma Celular/efeitos dos fármacos , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Modelos Biológicos , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo
3.
Exp Physiol ; 100(3): 331-40, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25480159

RESUMO

NEW FINDINGS: What is the central question of this study? It is not known whether treatment with interleukin-10 (IL-10) attenuates hyperoxia-induced acute lung injury in mice. What is the main finding and its importance? Our results showed that exogenous IL-10 treatment alleviated hyperoxia-induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases. Lung injury caused by breathing air enriched with oxygen continues to be a major problem in clinical medicine. Here, we investigated the therapeutic role of interleukin-10 (IL-10) in hyperoxia-induced acute lung injury in mice. In the first experiment, mice were exposed to room air or 95% O2 and treated with IL-10 simultaneously. In the second experiment, wild-type mice and IL-10(-/-) mice were exposed to room air or 95% O2 . Exogenous IL-10 treatment attenuated hyperoxia-induced acute lung injury, evidenced by a reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, cell numbers and protein content in bronchoalveolar lavage fluid and cell death. Interleukin-10 treatment markedly prolonged the survival of mice during oxygen exposure. Interleukin-10 treatment reduced the activity of myeloperoxidase and mRNA levels of interleukin-6, tumour necrosis factor-α and macrophage inflammatory protein 2, suppressed nuclear factor-κB activation and decreased inducible nitric oxide synthnase expression and nitric oxide formation in lungs of mice exposed to hyperoxia. Interleukin-10 treatment suppressed activities of matrix metalloproteinase 2 and matrix metalloproteinase 9 and reduced lung permeability in mice during oxygen exposure. Furthermore, absence of IL-10 aggravated hyperoxia-induced acute lung injury and reduced the duration of survival of mice during oxygen exposure, which was attenuated by treatment with IL-10. In conclusion, our results show that exogenous IL-10 treatment alleviates hyperoxia-induced acute lung injury in mice, possibly by regulating neutrophil recruitment and the subsequent generation of cytokines, nitric oxide and matrix metalloproteinases. This suggests that IL-10 treatment may be a promising therapeutic strategy to reduce lung injury in patients exposed to hyperoxia.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Hiperóxia/complicações , Interleucina-10/farmacologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/fisiopatologia , Animais , Peso Corporal/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar , Morte Celular/efeitos dos fármacos , Quimiocina CXCL2/metabolismo , Modelos Animais de Doenças , Hiperóxia/metabolismo , Hiperóxia/fisiopatologia , Interleucina-6/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Oxigênio/metabolismo , Peroxidase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
4.
Exp Ther Med ; 7(2): 501-507, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24396434

RESUMO

Linezolid is an oxazolidinone antibiotic agent, active against gram-positive bacteria that are resistant to traditional antibiotics, including glycopeptides. Linezolid is generally well tolerated, but has been associated with hematologic adverse effects such as thrombocytopenia. The primary objective of this study was to compare the incidence of thrombocytopenia between patients receiving linezolid or glycopeptides in different age groups. The secondary objective was to assess the association between the time-to-event and occurrence of thrombocytopenia. This retrospective study reviewed the medical records of patients who were treated with linezolid or glycopeptides (vancomycin or teicoplanin) between January 2010 and June 2013 in a respiratory intensive care unit. Data were extracted from the patients' electronic medical records, which were obtained from a central database in the hospital, and multivariate analyses were performed. In total, the study included 225 patients who received linezolid or glycopeptides. The cumulative probability of thrombocytopenia was higher in the patients receiving linezolid than in those receiving glycopeptides (P<0.05), however the cumulative probability of thrombocytopenia did not differ significantly between patients receiving linezolid or glycopeptides in the subgroup whose age was <65 years (P>0.05). With a treatment duration of ≥7 days, the incidence of thrombocytopenia and the mean platelet count reduction in the patients receiving linezolid was significantly higher than in those receiving glycopeptides (P<0.05). No significant difference was identified in the mean platelet counts between the patients receiving linezolid and those receiving glycopeptides. In conclusion, it was identified that patients in a respiratory intensive care unit, aged ≥65 years or with a treatment duration of ≥7 days who were treated with linezolid were more likely to develop thrombocytopenia than patients of the same subgroup who were treated with glycopeptides.

5.
J Aerosol Med Pulm Drug Deliv ; 27(3): 219-27, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23905575

RESUMO

BACKGROUND: The incorrect handling of Diskus inhalers in Chinese patients with chronic obstructive pulmonary disease (COPD) is not well documented. OBJECTIVE: The present study was conducted to evaluate in detail the handling errors related to the Diskus device, and to elucidate the importance of educating COPD patients on the proper use of the device. METHODS: A total of 384 COPD patients from a pulmonary clinic in China over a period of 5 years were included in the study. The compliance of COPD patients to the 13 discrete steps of Diskus usage were scored and analyzed by three measures: (1) On day 0, patients were given only a package insert on Diskus, and the handling error rate was assessed. Then the patients were given instruction on the 13-step Diskus procedure until they could demonstrate the proper technique. (2) On days 1, 2, and 3, the observation group was continuously educated on a 13-step procedure, and the percentage of patients who scored 100% for each step was recorded. The control group had no such training. (3) On days 10, 20, and 30, the percentage of all subjects correctly performing the Diskus 13-step inhalation procedure was assessed. RESULTS: Incorrect handling techniques on Diskus usage were widely distributed among Chinese COPD patients. Step 8 ("Inhale forcefully from the beginning, slowly, deeply, and uniformly during the inspiratory phase until the lungs are full") was the most commonly mishandled step (93.8%). The total score and individual step scores of the patients from the observation group were significantly improved during 3-day continuous education. There was also a significantly higher percentage of correctly performed steps in the observation group than in the control group upon assessment on day 10 (96.24% vs. 85.63%, respectively; p<0.01), day 20 (97.31% vs. 86.09%, respectively; p<0.01), and day 30 (98.19% vs. 87.39%, respectively; p<0.01). CONCLUSION: Handling errors of the Diskus 13-step inhalation procedure were commonly observed in Chinese COPD patients. Continuous educational interventions and regular supervision by health-care providers are therefore crucial for the optimum use of the Diskus inhaler.


Assuntos
Grupo com Ancestrais do Continente Asiático/psicologia , Inaladores de Pó Seco , Comportamentos Relacionados com a Saúde/etnologia , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , China , Desenho de Equipamento , Feminino , Volume Expiratório Forçado , Humanos , Inalação , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/etnologia , Educação de Pacientes como Assunto , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/etnologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/psicologia , Análise e Desempenho de Tarefas , Capacidade Vital
6.
J Bone Miner Metab ; 32(5): 494-504, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24196871

RESUMO

The bone protective effects of the hydrogen molecule (H2) have been demonstrated in several osteoporosis models while the underlying molecular mechanism has remained unclear. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. In this work, we evaluated the effects of incubation with H2 on receptor activator of NFκB ligand (RANKL)-induced osteoclast differentiation. We found that treatment with H2 prevented RANKL-induced osteoclast differentiation in RAW264.7 cells and BMMs. Treatment with H2 inhibits the ability to form resorption pits of BMMs stimulated by RANKL. Treatment with H2 reduced mRNA levels of osteoclast-specific markers including tartrate resistant acid phosphatase, calcitonin receptor, cathepsin K, metalloproteinase-9, carbonic anhydrase typeII, and vacuolar-type H(+)-ATPase. Treatment with H2 decreased intracellular reactive oxygen species (ROS) formation, suppressed NADPH oxidase activity, down-regulated Rac1 activity and Nox1 expression, reduced mitochondrial ROS formation, and enhanced nuclear factor E2-related factor 2 nuclear translocation and heme oxygenase-1 activity. In addition, treatment with H2 suppressed RANKL-induced expression of nuclear factor of activated T cells c1 and c-Fos. Furthermore, treatment with H2 suppressed NF-κB activation and reduced phosphorylation of p38, extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and protein kinases B (AKT) stimulated with RANKL. In conclusion, hydrogen molecules prevented RANKL-induced osteoclast differentiation associated with inhibition of reactive oxygen species formation and inactivation of NF-κB, mitogen-activated protein kinase and AKT pathways.


Assuntos
Hidrogênio/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Osteoclastos/citologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Ativação Enzimática/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Fatores de Transcrição NFATC/metabolismo , Óxido Nítrico/metabolismo , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais
7.
PLoS One ; 8(1): e55220, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23372839

RESUMO

Western Bahr el Ghazal State is located in northwestern South Sudan, which is a tropical area subject to Plasmodium falciparum malaria epidemics. The aim of this study is to explore the epidemiological and clinical features of Plasmodium falciparum malaria in United Nations personnel stationed in this area. From July 2006 to June 2009, epidemiological data and medical records of 678 patients with Plasmodium falciparum malaria at the U.N. level 2 hospital were analyzed. The U.N. personnel were divided into individuals not immune to Plasmodium falciparum and individuals semi-immune to Plasmodium falciparum. The patients were divided into a chemoprophylaxis group (non-immune individuals who complied with the chemoprophylaxis regimen, 582 cases) and a no/incomplete chemoprophylaxis group (non-immune individuals who either did not fully comply with chemoprophylaxis or did not use it at all and semi-immune individuals who did not use chemoprophylaxis, 96 cases). Overall morbidity was about 11.3%. There was a significant difference in the morbidity of semi-immune and non-immune individuals (1.3% vs. 15.1%, P<0.001). Out of the total, 82.9% of cases occurred during the rainy season. The incidence of fever in the chemoprophylaxis group was significantly lower than in the no/incomplete chemoprophylaxis group (36.8% vs. 96.9%, P<0.001). Significant differences were observed between the two groups with respect to all other malaria-like symptoms except gastrointestinal symptoms, serum glucose level, platelet count, and alanine aminotransferase level. The incidence of complications was 1.2% (chemoprophylaxis group) and 44.8% (no/incomplete chemoprophylaxis group).The most common complication was thrombocytopenia, which was seen in 40.6% of the no/incomplete chemoprophylaxis group. In summary, Plasmodium falciparum malaria mainly occurred in rainy season. Gastrointestinal symptoms are an important precursor of malaria. Blood smears and rapid diagnostic tests should be performed after the onset of gastrointestinal symptoms. Appropriate chemoprophylaxis is necessary for reducing the severity of malaria.


Assuntos
Pessoal de Saúde , Malária Falciparum/diagnóstico , Malária Falciparum/epidemiologia , Nações Unidas , Adulto , Antimaláricos/uso terapêutico , Feminino , Humanos , Malária Falciparum/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prevalência , Resultado do Tratamento , Adulto Jovem
8.
Eur J Appl Physiol ; 113(6): 1555-63, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23307012

RESUMO

The aim of this work was to test the effect of treatment with hydrogen sulfide (H2S) on hyperoxia-induced acute lung injury in mice. Mice were exposed to room air or 95 % O2, and treated with NaHS (intraperitoneal injection of 0.1 ml/kg/day of 0.56 mol/l NaHS). Treatment with H2S partly restored the reduced H2S levels in plasma and lungs of mice exposed to hyperoxia. Treatment with H2S attenuated hyperoxia-induced acute lung injury marked by reduced ratio of lung weight to body weight, ratio of lung wet weight to dry weight, and cell numbers and protein content in bronchoalveolar lavage (BAL) and decreased apoptosis. Treatment with H2S markedly prolonged the survival of mice under oxygen exposure. Treatment with H2S abated hyperoxia-induced oxidative stress marked by reduced malondialdehyde and peroxynitrite formation, reduced NADPH oxidase activity, enhanced translocation of nuclear factor E2-related factor (Nrf2) into nucleus and increased activity of HO-1. Treatment with H2S decreased IL-1ß, MCP-1, and MIP-2, and increased IL-10 expression in lungs of mice exposed to hyperoxia. Treatment with H2S decreased NFκB activity and iNOS expression in lungs, and reduced NOx content in BAL of mice exposed to hyperoxia. Treatment with H2S reduced lung permeability and suppressed VEGF release and VEGFR2 expression in lungs of mice under oxygen exposure. Treatment with exogenous H2S attenuated hyperoxia-induced acute lung injury through abating oxidative stress, suppressing inflammation, and reducing lung permeability in mice.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Sulfeto de Hidrogênio/uso terapêutico , Hiperóxia/complicações , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Animais , Interleucinas/genética , Interleucinas/metabolismo , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidases/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Ácido Peroxinitroso/metabolismo , Receptores CCR2/genética , Receptores CCR2/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
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