Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27.738
Filtrar
1.
N Engl J Med ; 382(6): 525-533, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32023372

RESUMO

BACKGROUND: We previously reported the results of a trial of prenatal vitamin D supplementation to prevent asthma and recurrent wheeze in young children, which suggested that supplementation provided a protective effect at the age of 3 years. We followed the children through the age of 6 years to determine the course of asthma and recurrent wheeze. METHODS: In this follow-up study, investigators and participants remained unaware of the treatment assignments through the children's sixth birthday. We aimed to determine whether, when maternal levels of 25-hydroxyvitamin D were taken into account, children born to mothers who had received 4400 IU of vitamin D3 per day during pregnancy (vitamin D group) would have a lower incidence of asthma and recurrent wheeze at the age of 6 years than would those born to mothers who had received 400 IU of vitamin D3 per day (control group). Time-to-event methods were used to compare the treatment groups with respect to time to the onset of asthma or recurrent wheeze. Multivariate methods were used to compare longitudinal measures of lung function between the treatment groups. RESULTS: There was no effect of maternal vitamin D supplementation on asthma and recurrent wheeze in either an intention-to-treat analysis or an analysis with stratification according to the maternal 25-hydroxyvitamin D level during pregnancy. There was no effect of prenatal vitamin D supplementation on most of the prespecified secondary outcomes. We found no effects of prenatal supplementation on spirometric indexes. Although there was a very small effect on airway resistance as measured by impulse oscillometry, this finding was of uncertain significance. CONCLUSIONS: Vitamin D supplementation during the prenatal period alone did not influence the 6-year incidence of asthma and recurrent wheeze among children who were at risk for asthma. (Funded by the National Heart, Lung, and Blood Institute; VDAART ClinicalTrials.gov number, NCT00920621.).


Assuntos
Resistência das Vias Respiratórias/efeitos dos fármacos , Asma/prevenção & controle , Suplementos Nutricionais , Cuidado Pré-Natal , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Asma/epidemiologia , Criança , Feminino , Seguimentos , Humanos , Incidência , Análise de Intenção de Tratamento , Pulmão/efeitos dos fármacos , Pulmão/embriologia , Gravidez , Sons Respiratórios/efeitos dos fármacos , Espirometria , Vitamina D/análogos & derivados , Vitamina D/sangue
2.
Toxicol Lett ; 322: 58-65, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31962155

RESUMO

High-level concentrations of chlorine (Cl2) can cause life-threatening lung injuries and the objective in this study was to understand the pathogenesis of short-term sequelae of Cl2-induced lung injury and to evaluate whether pre-treatment with the antioxidant N-acetyl cysteine (NAC) could counteract these injuries using Cl2-exposed precision-cut lung slices (PCLS). The lungs of Sprague-Dawley rats were filled with agarose solution and cut into 250 µm-thick slices that were exposed to Cl2 (20-600 ppm) and incubated for 30 min. The tissue slices were pre-treated with NAC (5-25 mM) before exposure to Cl2. Toxicological responses were analyzed after 5 h by measurement of LDH, WST-1 and inflammatory mediators (IL-1ß, IL-6 and CINC-1) in medium or lung tissue homogenate. Exposure to Cl2 induced a concentration-dependent cytotoxicity (LDH/WST-1) and IL-1ß release in medium. Similar cytokine response was detected in tissue homogenate. Contraction of larger airways was measured using electric-field-stimulation method, 200 ppm and control slices had similar contraction level (39 ± 5%) but in the 400 ppm Cl2 group, the evoked contraction was smaller (7 ± 3%) possibly due to tissue damage. NAC-treatment improved cell viability and reduced tissue damage and the contraction was similar to control levels (50 ± 11%) in the NAC treated Cl2-exposed slices. In conclusion, Cl2 induced a concentration-dependent lung tissue damage that was effectively prevented with pre-treatment with NAC. There is a great need to improve the medical treatment of acute lung injury and this PCLS method offers a way to identify and to test new concepts of treatment of Cl2-induced lung injuries.


Assuntos
Acetilcisteína/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cloro/toxicidade , Mediadores da Inflamação/metabolismo , Lesão Pulmonar/prevenção & controle , Pulmão/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL1/metabolismo , Citoproteção , Relação Dose-Resposta a Droga , Feminino , Técnicas In Vitro , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Ratos Sprague-Dawley
3.
Toxicol Lett ; 321: 103-113, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31706003

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no effective medication. Andrographolide (Andro), extracted from Chinese herbal Andrographis paniculata, could attenuate bleomycin (BLM)-induced pulmonary fibrosis via inhibition of inflammation and oxidative stress, however, the anti-fibrotic mechanisms have not been clarified. Myofibroblasts are the primary cell types responsible for the accumulation of extracellular matrix (ECM) in fibrotic diseases, and targeting fibroblast proliferation and differentiation is an important therapeutic strategy for the treatment of IPF. Hence, this study aimed to investigate the effects of Andro on the fibroblast proliferation and differentiation in the in vivo and in vitro models. The results showed that Andro improved pulmonary function and inhibited BLM-induced fibroblast proliferation and differentiation and ECM deposition in the lungs. In vitro, Andro inhibited proliferation and induced apoptosis of TGF-ß1-stimulated NIH 3T3 fibroblasts and primary lung fibroblasts (PLFs). Andro also inhibited TGF-ß1-induced myofibroblast differentiation and ECM deposition in both cells. We also found that Andro suppressed TGF-ß1-induced Smad2/3 and Erk1/2 activation, suggesting that Smad2/3 and Erk1/2 inactivation mediates Andro-induced effects on TGF-ß1-induced fibroblast proliferation and differentiation. These results indicated that Andro has novel and potent anti-fibrotic effects in lung fibroblasts via inhibition of the proliferation and myofibroblast differentiation of fibroblasts and subsequent ECM deposition, which are modulated by TGF-ß1-mediated Smad-dependent and -independent pathways.


Assuntos
Bleomicina , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diterpenos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibrose Pulmonar Idiopática/prevenção & controle , Pulmão/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Células NIH 3T3 , Ratos Sprague-Dawley , Transdução de Sinais
4.
Toxicol Lett ; 321: 146-154, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31836503

RESUMO

BACKGROUND: Exposure to particulate matters (PMs) can lead to an acute exacerbation of allergic airway diseases, increasing the severity of symptoms and mortality. However, little is known about the underlying molecular mechanism. This study aimed to investigate the effects of PMs on acute exacerbation of allergic airway inflammation and seek potential therapeutic targets. METHODS: Non-allergic control and ovalbumin (OVA)-allergic wide-type (WT) and Toll-like receptor 2 knockout (Tlr2-/-) mice were exposed to 100 µg of PM (diameter 5.85 µm) or saline by the oropharyngeal instillation. The responses were examined three days after exposure. In the RAW264.7 macrophage cell line, Tlr2 was knocked down by small-interfering RNA or the NF-κB inhibitor JSH-23 was used, and then the cells were stimulated with PMs for 12 h before comparison of the inflammatory responses. RESULTS: PM exposure led to increased inflammatory cell recruitment and airway intensity of PAS + staining in OVA-allergic WT mice, accompanied with an accumulation of inflammatory cells and elevated inflammatory cytokines, such as IL-6 and IL-18, in the bronchoalveolar lavage fluid (BALF). Furthermore, the protein levels of TLR2 and the NLRP3 inflammasome were elevated concomitantly with the airway inflammation post-OVA/PMs challenge. Tlr2 deficiency effectively inhibited the airway inflammation, including pulmonary inflammatory cell recruitment, mucus secretion, serum OVA-specific immunoglobulin E (IgE), and BALF inflammatory cytokine production. Additionally, the P-induced NLRP3 activation in the RAW 264.7 cell line was diminished by the knockdown of Tlr2 or JSH-23 treatment in vitro. CONCLUSION: Our results indicated that PMs exacerbate the allergic airway inflammation mediated by the TLR2/ NF-κB/NLRP3 signaling pathway. Inhibition of NF-κB seems to be a possible treatment.


Assuntos
Pulmão/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Material Particulado/toxicidade , Hipersensibilidade Respiratória/induzido quimicamente , Receptor 2 Toll-Like/metabolismo , Alérgenos , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Pulmão/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina , Tamanho da Partícula , Células RAW 264.7 , Hipersensibilidade Respiratória/genética , Hipersensibilidade Respiratória/metabolismo , Transdução de Sinais , Receptor 2 Toll-Like/deficiência , Receptor 2 Toll-Like/genética
5.
Environ Toxicol ; 35(1): 37-46, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31456356

RESUMO

Phenanthrene (Phe) female rat model was established to explore the effects of Phe on oxidative stress and inflammation. The rats were randomly divided into three groups including control (C), low (L), and high (H) group. Phe was supplied to L and H groups at the dosage of 180 mg/kg and 900 mg/kg orally at first day, and with the dose 90 mg/kg and 450 mg/kg by intraperitoneal injection at the last 2 days. The C group was enriched with the same volume of corn oil. The blood, lung, and liver tissues were collected. The superoxide dismutase (SOD), malonaldehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were detected to evaluate oxidative stress. The protein and mRNA expressions of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), and interleukin 10 (IL-10) were detected to evaluate inflammation. Further, the forkhead box transcription factor 3 (Foxp3) was analyzed to hint the injury mechanism of inflammation. The results showed SOD and MDA in lung and liver, and serum 8-OHdG elevated significantly in H groups (P < .05). Meanwhile, there were significant increases in the protein and mRNA expression of TNF-α and IL-6 in lung and liver of H groups (P < .05). In addition, the protein and mRNA expressions of TGF-ß and Foxp3 were all decreased significantly in both lung and liver of H groups (P < .05). Results demonstrated that an obvious change of Phe exposure could induce oxidative stress and inflammation in female rats. This is a first pilot study to explore the association between Phe exposure and oxidative stress and inflammation using a female rat model.


Assuntos
Poluentes Atmosféricos/toxicidade , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Fenantrenos/toxicidade , Animais , Citocinas/sangue , Citocinas/imunologia , Relação Dose-Resposta a Droga , Feminino , Fígado/imunologia , Fígado/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Projetos Piloto , Distribuição Aleatória , Ratos , Ratos Wistar
6.
Environ Toxicol ; 35(1): 27-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31498972

RESUMO

In 2011, a link between humidifier disinfectants and patients with idiopathic pulmonary fibrosis was identified in Korea, and Kathon was suggested as one of the causative agents. In this study, Kathon induced apoptotic cell death along with membrane damage at 24 h post-exposure. Additionally, on day 14 after a single instillation with Kathon, the total number of pulmonary cells and the levels of TNF-α, IL-5, IL-13, MIP-1α, and MCP-1α clearly increased in the lung of mice. The proportion of natural killer cells and eosinophils were significantly elevated in the spleen and the bloodstream, respectively, and the level of immunoglobulin (Ig) A, but not IgG, IgM, and IgE, dose-dependently increased. Therefore, we suggest that inhaled Kathon may induce eosinophilia-mediated disease in the lung by disrupting homeostasis of pulmonary surfactants. Considering that eosinophilia is closely related to cancer and fibrosis, further studies are needed to understand the relationship between them.


Assuntos
Desinfetantes/toxicidade , Eosinofilia/induzido quimicamente , Pulmão/efeitos dos fármacos , Surfactantes Pulmonares/metabolismo , Tiazóis/toxicidade , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Citocinas/imunologia , Eosinofilia/sangue , Eosinofilia/imunologia , Eosinófilos/citologia , Humanos , Imunoglobulina A/sangue , Exposição por Inalação/efeitos adversos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR
7.
Sci Total Environ ; 699: 134397, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31677469

RESUMO

Children are vulnerable to air pollution-induced lung function deficits, and the prevalence of obesity has been increasing in children. To evaluate the joint effects of long-term PM1 (particulate matter with an aerodynamic diameter ≤ 1.0 µm) exposure and obesity on children's lung function, a cross-sectional sample of 6740 children (aged 7-14 years) was enrolled across seven northeastern Chinese cities from 2012 to 2013. Weight and lung function, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF), were measured according to standardized protocols. Average PM1, PM2.5, PM10 and nitrogen dioxide (NO2) exposure levels were estimated using a spatiotemporal model, and sulphur dioxide (SO2) and ozone (O3) exposure were estimated using data from municipal air monitoring stations. Two-level logistic regression and general linear models were used to analyze the joint effects of body mass index (BMI) and air pollutants. The results showed that long-term air pollution exposure was associated with lung function impairment and there were significant interactions with BMI. Associations were stronger among obese and overweight than normal weight participants (the adjusted odds ratios (95% confidence intervals) for PM1 and lung function impairments in three increasing BMI categories were 1.50 (1.07-2.11) to 2.55 (1.59-4.07) for FVC < 85% predicted, 1.44 (1.03-2.01) to 2.51 (1.53-4.11) for FEV1 < 85% predicted, 1.34 (0.97-1.84) to 2.04 (1.24-3.35) for PEF < 75% predicted, and 1.34 (1.01-1.78) to 1.93 (1.26-2.95) for MMEF < 75% predicted). Consistent results were detected in linear regression models for PM1, PM2.5 and SO2 on FVC and FEV1 impairments (PInteraction < 0.05). These modification effects were stronger among females and older participants. These results can provide policy makers with more comprehensive information for to develop strategies for preventing air pollution induced children's lung function deficits among children.


Assuntos
Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Obesidade/epidemiologia , Adolescente , Poluentes Atmosféricos/análise , Criança , China/epidemiologia , Cidades , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/efeitos dos fármacos , Masculino , Dióxido de Nitrogênio/análise , Sobrepeso , Ozônio/análise , Material Particulado/análise , Testes de Função Respiratória , Dióxido de Enxofre , Capacidade Vital
8.
J Surg Res ; 245: 273-280, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421373

RESUMO

BACKGROUND: Transplantation of lungs procured after donation after circulatory death (DCD) is challenging because postmortem metabolic degradation may engender susceptibility to ischemia-reperfusion (IR) injury. Because oxidative mitochondrial DNA (mtDNA) damage has been linked to endothelial barrier disruption in other models of IR injury, here we used a fusion protein construct targeting the DNA repair 8-oxoguanine DNA glycosylase-1 (OGG1) to mitochondria (mtOGG1) to determine if enhanced repair of mtDNA damage attenuates endothelial barrier dysfunction after IR injury in a rat model of lung procurement after DCD. MATERIALS AND METHODS: Lungs excised from donor rats 1 h after cardiac death were cold stored for 2 h after which they were perfused ex vivo in the absence and presence of mt-OGG1 or an inactive mt-OGG1 mutant. Lung endothelial barrier function and mtDNA integrity were determined during and at the end of perfusion, respectively. RESULTS AND CONCLUSIONS: Mitochondria-targeted OGG1 attenuated indices of lung endothelial dysfunction incurred after a 1h post-mortem period. Oxidative lung tissue mtDNA damage as well as accumulation of proinflammatory mtDNA fragments in lung perfusate, but not nuclear DNA fragments, also were reduced by mitochondria-targeted OGG1. A repair-deficient mt-OGG1 mutant failed to protect lungs from the adverse effects of DCD procurement. CONCLUSIONS: These findings suggest that endothelial barrier dysfunction in lungs procured after DCD is driven by mtDNA damage and point to strategies to enhance mtDNA repair in concert with EVLP as a means of alleviating DCD-related lung IR injury.


Assuntos
DNA Glicosilases/administração & dosagem , Endotélio Vascular/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteínas Recombinantes de Fusão/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Aloenxertos/irrigação sanguínea , Aloenxertos/citologia , Aloenxertos/efeitos dos fármacos , Animais , DNA Glicosilases/genética , Reparo do DNA/efeitos dos fármacos , DNA Mitocondrial/efeitos dos fármacos , DNA Mitocondrial/genética , Modelos Animais de Doenças , Endotélio Vascular/citologia , Endotélio Vascular/patologia , Humanos , Pulmão/irrigação sanguínea , Pulmão/citologia , Pulmão/efeitos dos fármacos , Transplante de Pulmão , Masculino , Mitocôndrias/genética , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Perfusão/métodos , Ratos , Proteínas Recombinantes de Fusão/genética , Traumatismo por Reperfusão/patologia , Coleta de Tecidos e Órgãos/métodos
9.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 37(11): 815-819, 2019 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-31826544

RESUMO

Objective: To investigate the effects of simulated-thermobaric explosive gas on the respiration and nervous system in rats. Methods: 70 of SPF SD rats were randomly divided into four thermobaric explosive gas groups, two restoration observation groups and control group from April to August in 2018. The exposure time of in four thermobaric explosive gas groups were 3.75, 7.5, 15.0 and 30 min, respectively. The restoration observation groups were designed to observe for 30 and 120 min after exposure thermobaric explosive gas 30 min. The bloods were collected and analyzed at the end of exposure and recovery observation. The endogenous carbon monoxide (CO) , nitric oxide (NO) , glutamic acid (GLU) , acetylcholinesterase (AchE) and dopamine (DA) were detected in brain tissues, respectively. Results: The blood gas index (pH, PCO(2), PO(2), COHb, O(2)Hb, MeHbt) and blood electrolytes (Na(+), K(+), Ca(2+) and Cl(-)) in exposure groups have significant differences with these in control (P<0.05) . The pH value decreased with the exposure time longer. However, it basically returned to normal level when terminating exposure for 120 min. The concentration of PCO(2), MeHb and CoHb increased first and then decreased with the exposure time extension. Conversely, The PO(2) and O(2)Hb decreased first and then increased with the exposure time longer. The concentration of endogenous CO, GLU, and AchE decreased and NO increased in exposure group 4 and the restoration observation group 1 compared with those in control (P<0.01) . In addition, there were pathological changes in lung and brain tissue of exposure group, such as inflammatory cell infiltration and edema. Conclusion: The blood gas index, electrolytes, neurotransmitter, histopathology of lung and brain were changed to various degrees by thermobaric bomb gas exposure. These findings would provide some beneficial support for evaluating the damage effect of thermobaric bomb gas on organisms.


Assuntos
Bombas (Dispositivos Explosivos) , Combustíveis Fósseis , Sistema Nervoso , Sistema Respiratório , Animais , Encéfalo/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Combustíveis Fósseis/toxicidade , Concentração de Íons de Hidrogênio , Pulmão/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sistema Respiratório/efeitos dos fármacos , Fatores de Tempo
10.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 37(11): 855-857, 2019 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-31826555

RESUMO

Objective: To analyze the clinical characteristics caused by acute poisoning by inhalation of hydrogen chloride (HCl) and to raise awareness and treatment level of the disease. Methods: The clinical manifestations, imaging features, diagnosis, treatment and prognosis of 5 patients with acute HCl poisoning were analyzed retrospectively. Results: Among the 5 cases of HCl poisoning, 2 cases were severe poisoning, 3 cases were moderate poisoning. All patients were treated with corticosteroids and symptomatic treatment, one of them was treated with venovenous extracorporeal membrane oxygenation (VV-ECMO) . All patients were recovered and discharged from hospital. Conclusion: The lung damage of acute poisoning by inhalation of HCl is rapidly progressing, early detection and timely medical treatment can obtain a better prognosis.


Assuntos
Ácido Clorídrico , Pulmão , Envenenamento , Oxigenação por Membrana Extracorpórea , Humanos , Ácido Clorídrico/envenenamento , Pulmão/efeitos dos fármacos , Envenenamento/diagnóstico , Envenenamento/terapia , Prognóstico
11.
Handb Exp Pharmacol ; 260: 143-159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31792683

RESUMO

Inhalation therapy is one of the oldest approaches to the therapy of diseases of the respiratory tract. It is well recognised today that the most effective and safe means of treating the lungs is to deliver drugs directly to the airways. Surprisingly, the delivery of therapeutic aerosols has a rich history dating back more than 2,000 years to Ayurvedic medicine in India, but in many respects, the introduction of the first pressurised metered-dose inhaler (pMDI) in 1956 marked the beginning of the modern pharmaceutical aerosol industry. The pMDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 to reduce the use of CFCs as propellants for aerosols led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern pMDIs, dry powder inhalers and nebuliser systems. There is also great interest in tailoring particle size to deliver drugs to treat specific areas of the respiratory tract. One challenge that has been present since antiquity still exists, however, and that is ensuring that the patient has access to the medication and understands how to use it effectively. In this article, we will provide a summary of therapeutic aerosol delivery systems from ancient times to the present along with a look to the future.


Assuntos
Sistemas de Liberação de Medicamentos/história , Pulmão/efeitos dos fármacos , Inaladores Dosimetrados , Nebulizadores e Vaporizadores , Administração por Inalação , Aerossóis , História do Século XX , História do Século XXI , Humanos
12.
An Acad Bras Cienc ; 91(4): e20190434, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800708

RESUMO

Sepsis is a life-threatening organ dysfunction induced by a disrupted host response to infecting pathogens. Inflammation and oxidative stress are intrinsically related to sepsis progression and organ failure. Vitamin B6 is an important cellular cofactor for metabolic processes and has anti-inflammatory and antioxidant properties. We aimed at evaluating the effect of vit B6 on inflammation and oxidative stress markers in the liver and lung of rats subjected to a relevant animal model of polymicrobial sepsis. Adult male Wistar rats were submitted to cecal ligation and perforation model and immediately after sepsis induction, vit B6 was administered as a single dose (600 mg/kg, subcutaneous). Twenty-four hours later, the lung and liver were harvest for neutrophil infiltration, oxidative markers to lipids and protein and antioxidant activity of endogenous enzyme. Vitamin B6 diminished neutrophil infiltration in both organs, oxidative markers in the liver and restored catalase activity levels in the lung of septic animals. Vitamin B6 exerts anti-inflammatory and antioxidant effects in peripheral organs after polymicrobial sepsis.


Assuntos
Antioxidantes/farmacologia , Inflamação/prevenção & controle , Fígado/patologia , Pulmão/patologia , Estresse Oxidativo/efeitos dos fármacos , Sepse/complicações , Vitamina B 6/farmacologia , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Ratos , Ratos Wistar , Sepse/patologia
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(10): 1232-1238, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31801723

RESUMO

OBJECTIVE: To investigate the effect of ulinastatin on the inflammatory mediators and their signaling pathways miR-146a/TLR4/NF-κB in rats with hemorrhagic shock. METHODS: Seventy-two SD rats were randomly assigned into shock without resuscitation group (SR group, n=24), acetated Ringer's solution resuscitation group (AR group, n=24) and ulinastatin treatment group (n=24). In all the 3 groups hemorrhagic shock models were established by femoral artery bleeding (with the mean arterial pressure maintained at 30-40 mmHg) without resuscitation (in SR group) or with resuscitation (in AR and ulinastatin groups) using acetated Ringer's solution for 30 min at 60 min after the onset of shock. At 1, 4, and 6 h after the shock onset or immediately after shock if the rats died, the lung tissues were taken for measurement of mRNA expressions of miR-146a, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-4, IL-6 and IL-10 using real-time quantitative PCR and the protein expressions of TLR4, MyD88, IκB-α, p-IκB-α, NF-κB p65, IRAK4, p-IRAK4 (Thr345, Ser346), p-IRAK4 (Thr342) and TRAF6 using Western blotting. The lung histopathology of the rats was examined under optical microscope with HE staining. RESULTS: Compared with the SR group, the rats in the AR group showed slightly alleviated inflammatory infiltration in the lung tissues with significantly increased mRNA levels of miR-146a, IL-4 and IL-10 (P < 0.05) and protein expressions of IκB-α, p-IRAK4 (Thr342) and p-IRAK4 (Thr345, ser346) (P < 0.05), and decreased mRNA levels of TNF-α, IL-1 and IL-6 (P < 0.05) and protein expressions of TLR4, MyD88, NF-κB p65, p-IκB-α, IRAK-4 and TRAF6 (P < 0.05). Compared with those in AR group, the rats in ulinastatin group showed further alleviation of inflammatory lung tissue injury, with increased mRNA levels of miR-146a, IL-4 and IL-10 (P < 0.01) and protein expressions of IκB-α, p-IRAK4 and p-IRAK4 (P < 0.01) and decreased mRNA levels of TNF-α, IL-1 and IL-6 (P < 0.01) and protein expressions of TLR4, MyD88, NF-κB p65, p-IκB-α, IRAK-4 and TRAF6 (P < 0.01). CONCLUSIONS: Ulinastatin combined with acetated Ringer's solution resuscitation alleviates lung inflammations in rats with hemorrhagic shock possibly by enhancing miR-146a expression to regulate TLR4/NF-κB signaling pathway through a negative feedback mechanism and thus modulate the balance of pro-inflammatory and anti-inflammatory factors.


Assuntos
Glicoproteínas/farmacologia , Inflamação/tratamento farmacológico , Pulmão/patologia , Choque Hemorrágico/tratamento farmacológico , Transdução de Sinais , Animais , Citocinas/metabolismo , Pulmão/efeitos dos fármacos , MicroRNAs/genética , NF-kappa B/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/complicações , Receptor 4 Toll-Like/metabolismo
14.
Ann Agric Environ Med ; 26(4): 672-673, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31885245

RESUMO

INTRODUCTION: Thiram, a fungicides, is widely used on seeds and as foliar agent on turf, vegetables and fruit. It is also used in the rubber industry as a vulcanization accelerator. When absorbed through the respiratory system, it is rapidly metabolised to dimethylthiocarbamate and carbon disulphide, causing noxious effects. A brief review is presented of the literature, centering on the interesting case of a 45-year-old woman admitted to the hospital suffering from acute respiratory failure. RESULTS: Computer tomography in angiographic option (angio-CT) showed an extensive, irregular area of ground glass in both upper lobes and apical segments of the lower lobes of the lungs. A significant enlargement of both atria was also described. There was no improvement after cardiac treatment and patient was transferred to the pulmonary department where she was succesfully treated with systemic glucocortycosteroids. The patient remains under the supervision of the pulmonary out-patient department.


Assuntos
Fungicidas Industriais/toxicidade , Exposição por Inalação/efeitos adversos , Lesão Pulmonar/etiologia , Tiram/toxicidade , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/efeitos dos fármacos , Lesão Pulmonar/diagnóstico por imagem , Pessoa de Meia-Idade
15.
Medicine (Baltimore) ; 98(48): e18051, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770219

RESUMO

BACKGROUND: Evaluating the efficacy and safety of low molecular weight heparin (LMWH) for patients with chronic obstructive pulmonary disease (COPD) and respiratory failure (RF) is a major purpose of this study. METHODS: The following electronic databases will be comprehensively retrieved from the inception to July 1, 2019: Cochrane Library, PUBMED, EMBASE, Google Scholar, Web of Science, Allied and Complementary Medicine Database, WANGFANG, and China National Knowledge Infrastructure without language restrictions. All randomized controlled trials related to LMWH for COPD and RF will be included. Two authors will carry out study selection, data collection, and risk of bias assessment independently. RESULTS: This study will systematically explore the efficacy and safety of LMWH for COPD and RF. The primary outcome is lung function. The secondary outcomes are severity of dyspnea on exertion, quality of life, body mass index, airflow obstruction; and any expected and unexpected adverse events. CONCLUSION: The findings of this study will provide evidence to judge whether LMWH is an effective treatment for patients with COPD and RF. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019 139631.


Assuntos
Heparina de Baixo Peso Molecular/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Insuficiência Respiratória/tratamento farmacológico , Índice de Massa Corporal , Dispneia/tratamento farmacológico , Dispneia/etiologia , Humanos , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/complicações , Ventilação Pulmonar/efeitos dos fármacos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Insuficiência Respiratória/complicações , Revisão Sistemática como Assunto , Resultado do Tratamento
16.
Eur. j. anat ; 23(6): 405-413, nov. 2019. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-185083

RESUMO

Nicotine exposure during pregnancy is linked to multiple obstetrical, fetal, and developmental complications. Parsley (Petroselinum crispum) is an aromatic herb, which has well-known potent anti-inflammatory and anti-oxidative effects. The purpose of this study was to investigate, for the first time, the protective effect of parsley extract on alveolar stage of lung development in rats exposed to perinatal nicotine. Thirty Sprague-Dawley adult female rats were randomly divided into five main groups after being pregnant: control, sham control, parsley-treated (5mg /kg/day), nicotine-treated group (1mg /kg/day), and protected (nicotine + parsley extract) groups. Nicotine was injected subcutaneously, while parsley extract was given orally by gastric tube from the 7th day of pregnancy until the 21st day postnatally. At the end of the experiment, lungs of 21-day-old male offspring were subjected to biochemical, histological, and immuno-histochemical analyses. Our results revealed toxic effects of nicotine on alveolar stage of rat lung development. These were indicated by histopathological alterations, including poorly developed primary and secondary septa; interstitial tissue infiltration with inflammatory cells, atypical features appeared in some cells of bronchioles and blood vessels. In addition, a reduction in elastic fibers contents and in alpha smooth muscle expression, an increase in surfactant protein B expression, and changes of oxidative stress indices and tumor necrosis factor alpha level in lung tissue were detected. Co-administration of parsley extract ameliorated nicotine induced toxic alterations on the development of the lung. Therefore, parsley can be a promising candidate for the prevention of nicotine-induced toxicity in the developing lung


No disponible


Assuntos
Animais , Petroselinum/efeitos dos fármacos , Pulmão/anatomia & histologia , Pulmão/efeitos dos fármacos , Nicotina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Nicotina/efeitos adversos , Ratos Sprague-Dawley , Imuno-Histoquímica , Projetos de Pesquisa , Análise de Variância , Fator de Necrose Tumoral alfa
17.
Int J Nanomedicine ; 14: 6465-6480, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616140

RESUMO

Purpose: Multiwalled carbon nanotubes (MWCNTs) have been known to enter the circulatory system via the lungs from inhalation exposure; however, its carcinogenicity and subsequent accumulation in other organs have not been adequately reported in the literature. Moreover, the safety of MWCNTs as a biomaterial has remained a matter of debate, particularly when the material enters the circulatory system. To address these problems, we used carcinogenic rasH2 transgenic mice to intravenously administer highly dispersed MWCNTs and to evaluate their carcinogenicity and accumulation in the organs. Methods: Two types of MWCNTs (thin- and thick-MWCNTs) were intravenously administered at a high dose (approximately 0.7 mg per kg body weight) and low dose (approximately 0.07 mg per kg body weight). Results: MWCNTs showed pancreatic accumulation in 3.2% of mice administered with MWCNTs, but there was no accumulation in other organs. In addition, there was no significant difference in the incidence of tumor among the four MWCNTs-administered groups compared to the vehicle group without MWCNTs administration. Blood tests revealed elevated levels in mean red blood cell volume and mean red blood cell hemoglobin level for the MWCNTs-administered group, in addition to an increase in eotaxin. Conclusion: The present study demonstrated that the use of current technology to sufficiently disperse MWCNTs resulted in minimal organ accumulation with no evidence of carcinogenicity.


Assuntos
Carcinógenos/toxicidade , Nanotubos de Carbono/toxicidade , Administração Intravenosa , Animais , Peso Corporal , Carcinogênese/patologia , Citocinas/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos Transgênicos , Nanotubos de Carbono/ultraestrutura , Análise de Sobrevida , Distribuição Tecidual/efeitos dos fármacos
18.
Postepy Biochem ; 65(3): 224-230, 2019 10 01.
Artigo em Polonês | MEDLINE | ID: mdl-31643170

RESUMO

Berberine (BRB) is a compound belonging to the group of isoquinoline alkaloids of plant origin that has long been used in traditional chinese medicine (TMC). Due to, among others anti-inflammatory properties BRB is a potential therapeutic in the treatment of acute pancreatitis (OZT). In a study in the mouse model of L-arginine-induced acute pancreatitis, we showed that BRB administered by the intravenous route at 0.1 and 0.5 mg / kg body weight significantly reduces the level of myeloperoxidase activity (an indicator of inflammation) in the pancreas and lungs. Promising results point to the need for larger, randomized studies to assess the long-term efficacy and side effects of BRB therapy.


Assuntos
Berberina/uso terapêutico , Pancreatite/tratamento farmacológico , Doença Aguda/terapia , Animais , Berberina/farmacologia , Modelos Animais de Doenças , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pâncreas/efeitos dos fármacos , Pâncreas/patologia
19.
Vet Microbiol ; 238: 108431, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31648725

RESUMO

The infection by porcine reproductive and respiratory syndrome virus (PRRSV) has a severe impact on the world swine industry. However, commercially available vaccines provide only incomplete protection against this disease. Thus, novel approaches to control PRRSV infection are essential for the robust and sustainable swine industry. In our previous study, Xanthohumol (Xn), a prenylated flavonoid extracted for hops (Humulus lupulus L), was screened from 386 natural products to inhibit PRRSV proliferation and alleviate oxidative stress induced by PRRSV via the Nrf2-HMOX1 axis in Marc-145 cells. In this study, we furtherly found that Xn could inhibit PRRSV different sub-genotype strains infection with a low IC50 value in porcine primary alveolar macrophages (PAMs). In addition, it caused decreased expression of interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α in PAMs infected with PRRSV or treated with lipopolysaccharide. Animal challenge experiments showed that Xn effectively alleviated clinical signs, lung pathology, and inflammatory responses in lung tissues of pigs induced by highly pathogenic PRRSV infection. The results demonstrate that Xn is a promising therapeutic agent to combat PRRSV infections.


Assuntos
Flavonoides/farmacologia , Flavonoides/uso terapêutico , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Vírus da Síndrome Respiratória e Reprodutiva Suína/efeitos dos fármacos , Propiofenonas/farmacologia , Propiofenonas/uso terapêutico , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Produtos Biológicos/farmacologia , Citocinas/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Genótipo , Concentração Inibidora 50 , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/virologia , Suínos
20.
Ecotoxicol Environ Saf ; 186: 109770, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606643

RESUMO

Cultured human lung epithelial cells, particularly A549 cells, are commonly used as the in vitro model to evaluate the inhalational toxicity of nanoparticles (NPs). However, A549 cells are cancer cells that might not reflect the response of normal tissues to NP exposure. In addition, the possible influence of pulmonary surfactant also should be considered. This study used silica NPs as model NPs, and evaluated the toxicity of silica NPs to both 16HBE human bronchial epithelial cells and A549 adenocarcinomic cells, with or without the presence of pulmonary surfactant component dipalmitoyl phosphatidylcholine (DPPC). We found that silica NPs induced cytotoxicity at the concentration of 128 µg/mL in 16HBE cells but not A5490 cells, and the cytotoxicity of silica NPs to 16HBE cells was inhibited by DPPC. Intracellular reactive oxygen species (ROS) was only induced in 16HBE cells, accompanying with decreased thiol levels. Moreover, 16HBE cells internalized more silica NPs compared with A549 cells, and the internalization was reduced with the presence of DPPC in both types of cells. The retention of ABC transporter substrate Calcein was only significantly induced by silica NPs at high concentrations in 16HBE cells, and was partially reduced due to the presence of DPPC. In addition, ABC transporter inhibitor MK571 increased the toxicity of silica NPs to both types of cells, with 16HBE cells being more sensitive. Our data revealed that the cell types and pulmonary surfactant components could influence the toxicological consequences of silica NPs to human lung cells. Therefore, it is recommended that in vitro studies should carefully select suitable models to evaluate the inhalational toxicity of NPs.


Assuntos
1,2-Dipalmitoilfosfatidilcolina/metabolismo , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Nanopartículas/toxicidade , Surfactantes Pulmonares/metabolismo , Dióxido de Silício/toxicidade , 1,2-Dipalmitoilfosfatidilcolina/análogos & derivados , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Pulmão/metabolismo , Espécies Reativas de Oxigênio/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA