Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.436
Filtrar
1.
J Environ Pathol Toxicol Oncol ; 38(3): 229-238, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679310

RESUMO

Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.


Assuntos
Antiasmáticos/farmacologia , Antioxidantes/metabolismo , Asma/tratamento farmacológico , Citocinas/imunologia , Inflamação/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Xantofilas/farmacologia , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar/química , Citocinas/efeitos dos fármacos , Inflamação/induzido quimicamente , Masculino , Camundongos , Ovalbumina/toxicidade
2.
Georgian Med News ; (294): 98-103, 2019 Sep.
Artigo em Russo | MEDLINE | ID: mdl-31687958

RESUMO

The article reveals the modern aspects of IPF pathogenesis in with an emphasis on the main proposed prognostic biomarkers. IPF remains the leader among diseases with unknown etiology, the diagnosis and management of which are not very successful, despite the obvious progress in molecular medicine. There is presented analysis of the significance of IPF potential biomarkers and their concentrations in the blood and bronchoalveolar lavage fluids (BAL): endothelin-1, CC-chemokine ligand 18, interleukin-1, surfactant protein SP-D in the review. The role of their changing levels in the blood and BAL for assessing the course of the IPF and its prognosis, as well as the prevailing importance of the polymorphism of the genes encoding them, is shown. Obviously, the progressive accumulation of fibroblast-myofibroblast cells in the lungs IPF patients worsens the prognosis of disease, forms its own environment with a set of cytokines, growth factors, collagen, fibronectin in the extracellular matrix of fibrous lungs. The insufficient amount of studies in the face of the rarity of the disease leaves a lot of controversial issues for solution in the future. Obviously, to assess the prognosis of IPF mortality, it is necessary to include a very large number of patients, to extend the observation period, which increases their cost and reduces the opportunities and desire of pharmaceutical companies to participate in these studies.


Assuntos
Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/química , Fibrose Pulmonar Idiopática/diagnóstico , Pulmão/metabolismo , Biomarcadores/análise , Quimiocinas CC , Endotelina-1 , Humanos , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/mortalidade , Interleucina-1 , Pulmão/fisiopatologia , Prognóstico , Proteína D Associada a Surfactante Pulmonar/análise , Proteína D Associada a Surfactante Pulmonar/sangue , Surfactantes Pulmonares/análise , Surfactantes Pulmonares/sangue
3.
MMWR Morb Mortal Wkly Rep ; 68(45): 1040-1041, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31725707

RESUMO

CDC, the Food and Drug Administration (FDA), state and local health departments, and multiple public health and clinical partners are investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). Based on data collected as of October 15, 2019, 86% of 867 EVALI patients reported using tetrahydrocannabinol (THC)-containing products in the 3 months preceding symptom onset (1). Analyses of THC-containing product samples by FDA and state public health laboratories have identified potentially harmful constituents in these products, such as vitamin E acetate, medium chain triglyceride oil (MCT oil), and other lipids (2,3) (personal communication, D.T. Heitkemper, FDA Forensic Chemistry Center, November 2019). Vitamin E acetate, in particular, might be used as an additive in the production of e-cigarette, or vaping, products; it also can be used as a thickening agent in THC products (4). Inhalation of vitamin E acetate might impair lung function (5-7).


Assuntos
Líquido da Lavagem Broncoalveolar/química , Surtos de Doenças , Lesão Pulmonar/epidemiologia , Vaping/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
4.
Acta Cir Bras ; 34(9): e201900902, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778524

RESUMO

PURPOSE: To investigate the role of vagus nerve activation in the protective effects of hypercapnia in ventilator-induced lung injury (VILI) rats. METHODS: Male Sprague-Dawley rats were randomized to either high-tidal volume or low-tidal volume ventilation (control) and monitored for 4h. The high-tidal volume group was further divided into either a vagotomy or sham-operated group and each surgery group was further divided into two subgroups: normocapnia and hypercapnia. Injuries were assessed hourly through hemodynamics, respiratory mechanics and gas exchange. Protein concentration, cell count and cytokines (TNF-α and IL-8) in bronchoalveolar lavage fluid (BALF), lung wet-to-dry weight and pathological changes were examined. Vagus nerve activity was recorded for 1h. RESULTS: Compared to the control group, injurious ventilation resulted in a decrease in PaO2/FiO2 and greater lung static compliance, MPO activity, enhanced BALF cytokines, protein concentration, cell count, and histology injury score. Conversely, hypercapnia significantly improved VILI by decreasing the above injury parameters. However, vagotomy abolished the protective effect of hypercapnia on VILI. In addition, hypercapnia enhanced efferent vagus nerve activity compared to normocapnia. CONCLUSION: These results indicate that the vagus nerve plays an important role in mediating the anti-inflammatory effect of hypercapnia on VILI.


Assuntos
Líquido da Lavagem Broncoalveolar/química , Hipercapnia , Nervo Vago/cirurgia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Animais , Citocinas/análise , Modelos Animais de Doenças , Interleucina-8/análise , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/análise , Vagotomia
5.
J Med Microbiol ; 68(12): 1766-1770, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31746725

RESUMO

Introduction. Evidence for the clinical utility of bronchoalveolar lavage (BAL) galactomannan in the management of fungal disease outside of haemato-oncology patients is limited.Aim. To determine how the introduction of BAL galactomannan testing impacted on the diagnosis and management of invasive aspergillosis and other fungal diseases in non-haemato-oncology patients.Methodology. Retrospective review of all adult patients (age ≥16 years) without a diagnosis of haematological malignancy who had a positive BAL galactomannan from 1 November 2014 to 30 April 2018. Using electronic patient records we obtained demographic data, clinical details, laboratory investigations, relevant radiology and antimicrobial history for each case.Results. In total, 121 episodes with a galactomannan OD index of ≥0.500 were included in the study; 29 cases (24 %) were felt to reflect fungal disease. Antifungal therapy was commenced as a direct consequence of a positive BAL galactomannan result in 13 patients where the ultimate diagnosis was subsequently considered to be non-mycological: associated medication-related side-effects in this group included deranged liver function tests (n=3), rash (n=1) and fever (n=1), related to amphotericin B (n=1) and voriconazole (n=4).Conclusion. We show that vigilance is required when interpreting galactomannan results in non-haematology patients to avoid potentially harmful overtreatment.


Assuntos
Antifúngicos/uso terapêutico , Líquido da Lavagem Broncoalveolar/química , Mananas/análise , Sobremedicalização , Micoses/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Estudos Retrospectivos , Adulto Jovem
6.
Sheng Li Xue Bao ; 71(5): 689-697, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31646322

RESUMO

The aim of the present study was to investigate the role of ferroptosis in acute lung injury (ALI) mouse model induced by oleic acid (OA). ALI was induced in the mice via the lateral tail vein injection of pure OA. The histopathological score of lung, lung wet-dry weight ratio and the protein content of bronchoalveolar lavage fluid (BALF) were used as the evaluation indexes of ALI. Iron concentration, glutathione (GSH) and malondialdehyde (MDA) contents in the lung tissues were measured using corresponding assay kits. The ultrastructure of pulmonary cells was observed by transmission electron microscope (TEM), and the expression level of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA was detected by quantitative polymerase chain reaction (q-PCR). Protein expression levels of glutathione peroxidase 4 (GPX4), ferritin and transferrin receptor 1 (TfR1) in lung tissues were determined by Western blot. The results showed that histopathological scores of lung tissues, lung wet-dry weight ratio and protein in BALF in the OA group were higher than those of the control group. In the OA group, the mitochondria of pulmonary cells were shrunken, and the mitochondrial membrane was ruptured. The expression level of PTGS2 mRNA in the OA group was seven folds over that in the control group. Iron overload, GSH depletion and accumulation of MDA were observed in the OA group. Compared with the control group, the protein expression levels of GPX4 and ferritin in lung tissue were down-regulated in the OA group. These results suggest that ferroptosis plays a potential role in the pathogenesis of ALI in our mouse model, which may provide new insights for development of new drugs for ALI.


Assuntos
Lesão Pulmonar Aguda/patologia , Apoptose , Ácido Oleico , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Líquido da Lavagem Broncoalveolar/química , Ciclo-Oxigenase 2/metabolismo , Ferritinas/metabolismo , Glutationa/análise , Glutationa Peroxidase/metabolismo , Ferro/análise , Sobrecarga de Ferro/fisiopatologia , Pulmão/citologia , Pulmão/patologia , Malondialdeído/análise , Camundongos , Microscopia Eletrônica de Transmissão , Membranas Mitocondriais/ultraestrutura
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(3): 317-322, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31631596

RESUMO

Objective: To explore the molecular mechanism of ventilation induced lung injury (VILI) formation based on Keap1/Nfr2/ARE signaling pathway. Methods: The VILI model was established by excessive mechanical ventilation in SD rats. HE staining was used to detect the pathological changes of lung tissue in the control group, normal tidal volume (VT) group and large VT group (VT 40 mL/kg). The wet weight of lung tissue was detected in each group. Dry weight (W/D) ratio change; BCA method was used to detect the changes of total protein in bronchoalveolar lavage fluid (BALF) of each group; ELISA was used to detect interleukin-1ß (IL-1ß) and leukocyte in BALF and serum of each group. The content of 8-OHdG in the lung tissue was detected by IL-8 and the content of malondialdehyde (MDA) in the lung tissue was detected by TBA method. The NLRP3, ASC and caspase-1 proteins in macrophages were detected by Western blot. The changes of Keap1 and Nrf2 proteins in lung tissues were detected by RT-PCR. The expressions of SOD mRNA and HO-1 mRNA in lung tissues of each group were detected by RT-PCR. Results: Excessive mechanical ventilation could damage lung tissue, leading to alveolar rupture, inflammatory cell infiltration and erythrocytosis. Compared with the control group and normal VT group, the W/D value, 8-OHdG and MDA content in the large VT group, and total BALF, the contents of IL-1ß and IL-18 in protein, IL-1ß, IL-18 in serum increased significantly ( P<0.05). Compared with the control group and normal VT group, NLRP3, ASC, in macrophage of large VT group, the content of Keap1 protein in caspase-1 protein and lung tissue increased significantly ( P<0.05). The expression of Nrf2 protein, SOD mRNA and HO-1 mRNA in lung tissue decreased significantly. Conclusions: Large VT ventilation can cause acute inflammatory injury in lung tissue and lead to the occurrence of VILI. Inflammatory bodies of NLRP3 in alveolar macrophages are involved in this process, and the mechanism of NLRP3 inflammatory bodies is caused by hyperventilation in addition to mechanical injury. Decreased Keap1/Nrf2-ARE pathway inhibition and ROS clearance may also cause macrophage production of NLRP3 inflammatory bodies.


Assuntos
Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Heme Oxigenase (Desciclizante)/metabolismo , Interleucina-18/análise , Interleucina-1beta/análise , Pulmão , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
8.
Life Sci ; 236: 116864, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31518607

RESUMO

AIMS: To elucidate the role of alveolar macrophages (AM) in the pathogenesis of hypoxic pulmonary hypertension (HPH), we tested the effects of sustained hypoxia on AM polarization and on the formation of superoxide by AM in vivo and in vitro. MAIN METHODS: Rat AM were obtained by bronchoalveolar lavage. 4-day exposure to hypoxia (10% O2) was carried out in vivo (rats in isobaric hypoxic chamber, controls kept in air) or in vitro (control AM in 21% O2 and 5% CO2). Superoxide production was measured by luminol-orthovanadate chemiluminescence, AM polarization was detected immunocytochemically. To ascertain the effect of substances contained in the alveolar environment, we cultivated cells also in the presence of non-cellular components of the bronchoalveolar lavage fluid (BALF) either from controls or from rats exposed to 4 days of hypoxia. KEY FINDINGS: In vivo, but not in vitro, hypoxia increased AM superoxide production. Both types of hypoxia polarized AM into M2 (pro-proliferative) type. While the presence of control BALF attenuated superoxide production in AM cultivated in normoxia, BALF from the hypoxia-exposed rats had no effect. In AM cultivated in hypoxia, superoxide production was not altered by control BALF and elevated by BALF obtained from hypoxic rats. SIGNIFICANCE: Hypoxia does not influence superoxide production by AM directly but rather by modulating their milieu and their sensitivity to external influences.


Assuntos
Hipóxia/fisiopatologia , Macrófagos Alveolares/patologia , Superóxidos/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Células Cultivadas , Macrófagos Alveolares/metabolismo , Masculino , Ratos , Ratos Wistar
9.
Int J Mol Sci ; 20(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480246

RESUMO

High surface tension at the alveolar air-liquid interface is a typical feature of acute and chronic lung injury. However, the manner in which high surface tension contributes to lung injury is not well understood. This study investigated the relationship between abnormal alveolar micromechanics, alveolar epithelial injury, intra-alveolar fluid properties and remodeling in the conditional surfactant protein B (SP-B) knockout mouse model. Measurements of pulmonary mechanics, broncho-alveolar lavage fluid (BAL), and design-based stereology were performed as a function of time of SP-B deficiency. After one day of SP-B deficiency the volume of alveolar fluid V(alvfluid,par) as well as BAL protein and albumin levels were normal while the surface area of injured alveolar epithelium S(AEinjure,sep) was significantly increased. Alveoli and alveolar surface area could be recruited by increasing the air inflation pressure. Quasi-static pressure-volume loops were characterized by an increased hysteresis while the inspiratory capacity was reduced. After 3 days, an increase in V(alvfluid,par) as well as BAL protein and albumin levels were linked with a failure of both alveolar recruitment and airway pressure-dependent redistribution of alveolar fluid. Over time, V(alvfluid,par) increased exponentially with S(AEinjure,sep). In conclusion, high surface tension induces alveolar epithelial injury prior to edema formation. After passing a threshold, epithelial injury results in vascular leakage and exponential accumulation of alveolar fluid critically hampering alveolar recruitability.


Assuntos
Células Epiteliais Alveolares/patologia , Líquido da Lavagem Broncoalveolar/química , Proteína B Associada a Surfactante Pulmonar/deficiência , Células Acinares/patologia , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/ultraestrutura , Animais , Fenômenos Biomecânicos , Doxiciclina/farmacologia , Feminino , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pulmão/ultraestrutura , Camundongos Knockout , Modelos Biológicos , Proteína B Associada a Surfactante Pulmonar/metabolismo , Relação Estrutura-Atividade , Tensão Superficial
10.
Vet J ; 251: 105352, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31492391

RESUMO

Pneumonia is one of the potential complications of general anaesthesia in horses. Anaesthesia is known to increase neutrophils in bronchoalveolar lavage fluid (BALF) of horses after lateral recumbency, but studies after dorsal recumbency are lacking. Our primary aim was to determine when lung inflammation reaches its maximum and how rapidly BALF cytology returns to baseline after anaesthesia in dorsal recumbency. A secondary aim was to investigate the possible effect of vatinoxan, a novel drug, on the BALF cytology results. Six healthy experimental horses were enrolled in this observational crossover study. The horses were subject to repeated BALF and blood sampling for 7 days after general anaesthesia with two treatment protocols, and without anaesthesia (control). During the two treatments, the horses received either medetomidine-vatinoxan or medetomidine-placebo as premedication, and anaesthesia was induced with ketamine-midazolam and maintained with isoflurane for 1h in dorsal recumbency. The differences in BALF and blood variables between the two anaesthesia protocols and control were analysed with repeated measures analysis of variance models. In this study, anaesthesia in dorsal recumbency resulted in no clinically relevant changes in airway cytology that could be differentiated from the effect of repeated BALF sampling. No differences in BALF matrix metalloproteinase gelatinolytic activity could be detected between the two treatments or the control series. Marked increase in serum amyloid A was detected in some animals. Vatinoxan as premedication did not consistently affect lung cytology or blood inflammatory markers after anaesthesia.


Assuntos
Anestesia Geral/veterinária , Líquido da Lavagem Broncoalveolar/citologia , Cavalos/fisiologia , Quinolizinas/farmacologia , Anestesia Geral/efeitos adversos , Anestésicos Inalatórios/farmacologia , Animais , Líquido da Lavagem Broncoalveolar/química , Estudos Cross-Over , Hipnóticos e Sedativos/farmacologia , Inflamação , Isoflurano/farmacologia , Medetomidina/farmacologia , Postura/fisiologia , Proteína Amiloide A Sérica
11.
Int J Mol Sci ; 20(14)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31373289

RESUMO

The pathogenic mechanisms of acute lung injury due to direct and indirect pulmonary insults are incompletely understood. Using an unbiased, discovery and quantitative proteomic approach, we examined bronchoalveolar lavage fluid (BALF) proteome following lipopolysaccharide (LPS)-induced direct and indirect lung injury in mice. A total of 1017 proteins were both identified and quantitated in BALF from control, intratracheal (I.T., direct) and intraperitoneal (I.P., indirect) LPS-treated mice. The two LPS groups shared 13 up-regulated and 22 down-regulated proteins compared to the control group. Ingenuity pathway analysis revealed that acute-phase response signaling was activated by both I.T. and I.P. LPS; however, the magnitude of activation was much greater in the I.T. LPS group. Intriguingly, two canonical signaling pathways, liver X receptor/retinoid X receptor activation, and the production of nitric oxide and reactive oxygen species in macrophages, were activated by I.T. but suppressed by I.P. LPS. Cxcl15 (also known as lungkine) was also up-regulated by I.T. but down-regulated by I.P. LPS. In conclusion, our quantitative discovery-based proteomic approach identified commonalities, as well as significant differences in BALF protein expression profiles between LPS-induced direct and indirect lung injury, and importantly, LPS-induced indirect lung injury resulted in suppression of select components of lung innate immunity.


Assuntos
Lesão Pulmonar Aguda/patologia , Líquido da Lavagem Broncoalveolar/química , Lipopolissacarídeos/efeitos adversos , Pulmão/patologia , Proteoma/análise , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Quimiocinas CXC/biossíntese , Escherichia coli/patogenicidade , Perfilação da Expressão Gênica , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Receptores X do Fígado/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo
12.
Int J Pharm ; 569: 118562, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31351178

RESUMO

The purpose of this study was to explore the influence of stabilizer type and concentration on the properties of spray dried nanosuspension-in-microparticles (NS-in-MPs) for inhalation. Taking resveratrol (RES) as a Biopharmaceutical Classification System II (BCS II) model drug, the RES containing nanosuspensions were fabricated by high pressure homogenization method with different stabilizers including sodium dodecyl sulphate (SDS), sodium alginate (SA), chitosan (CS) and polyvinyl alcohol (PVA). Then, the nanosuspensions were spray dried with mannitol to obtain inhalable NS-in-MPs. The particle size, morphology, drug existing state, in vitro aerodynamic performance, in vitro release behavior, lung retention and pharmacokinetic behaviors were characterized. It was found that the morphology, lung deposition as well as in vitro drug release from the microparticles were significantly influenced by stabilizer type, with 1% PVA as stabilizer presenting the highest fine particle fraction (FPF). Meanwhile, taking PVA as an example, it was found stabilizer concentration could alter morphology and flowability of the microparticles, and the FPF value decreased with the increase of stabilizer concentration. Further drug retention and in vivo pharmacokinetic studies demonstrated that the positively charged stabilizer CS could facilitate drug retention and minimize drug expose to the systemic circulation. In conclusion, the deposition and lung retention behavior of NS-in-MPs could be well tuned by selecting different type or concentration of stabilizers, which could facilitate local lung diseases therapy.


Assuntos
Pulmão/metabolismo , Nanopartículas/administração & dosagem , Resveratrol/administração & dosagem , Alginatos/administração & dosagem , Alginatos/química , Animais , Líquido da Lavagem Broncoalveolar/química , Quitosana/administração & dosagem , Quitosana/química , Dessecação , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Masculino , Nanopartículas/química , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/química , Ratos Sprague-Dawley , Resveratrol/química , Resveratrol/farmacocinética , Dodecilsulfato de Sódio/administração & dosagem , Dodecilsulfato de Sódio/química , Suspensões
13.
Mycoses ; 62(10): 945-948, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31313395

RESUMO

BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains a life-threatening opportunistic infection, but can be difficult to diagnose. New biomarkers are therefore needed. Gliotoxin (GT), a secondary metabolite of Aspergillus fumigatus, and bis(methylthio)gliotoxin (bmGT), a degradation product of GT, have been proposed as potential biomarkers. However, these findings have yet to be confirmed. OBJECTIVES: To identify the diagnostic potential of GT and bmGT in serum and bronchoalveolar lavage fluid (BALf) in haematology patients compared to galactomannan (GM). MATERIALS AND METHODS: We prospectively collected culture supernatant, serum and BALf from patients with culture-positive IPA and measured GT and bmGT concentrations using ultra high-performance liquid chromatography-quadrupole time of flight mass spectrometry. Galactomannan was detected using a commercially available enzyme immunoassay. RESULTS: We included 18 patients with proven (n = 6) and probable (n = 12) IPA, all with positive cultures for Aspergillus fumigatus. BmGT was only detected in serum from one patient (5.6%), whereas GM was positive (optical density ≥ 0.5) in 11/18 patients (61.1%, P = 0.002). We could not find GT in any serum sample. In BALf, bmGT was detected in 8/18 patients (44.4%) and GT in 9/18 patients (50%), compared to GM (optical density ≥ 1.0) in all patients (100%). CONCLUSIONS: Gliotoxin and bis(methylthio)gliotoxin had a very poor performance for diagnosing IPA. As other biomarkers are more sensitive and easier to detect, we would not recommend serum or BALf GT/bmGT to be used in the diagnosis of IPA.


Assuntos
Biomarcadores/sangue , Testes Diagnósticos de Rotina/métodos , Gliotoxina/sangue , Aspergilose Pulmonar Invasiva/diagnóstico , Líquido da Lavagem Broncoalveolar/química , Humanos , Mananas/sangue , Estudos Prospectivos , Soro/química
14.
J Immunol Res ; 2019: 9708769, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355298

RESUMO

Myeloid-derived suppressor cells (MDSCs) are present in the human lung microenvironment, and they may be involved in the local inflammatory process in chronic obstructive pulmonary disease (COPD). Chronic inflammation in COPD may induce immunogenic cell death of structural airway cells, causing the release of damage-associated molecular patterns (DAMPs). DAMPs may activate the innate and adaptive immune system. The relationship between MDSCs and DAMPs in COPD is poorly described in the available literature. Objectives. (1) Assessment of MDSC percentage and DAMP concentration in bronchoalveolar lavage fluid (BALF) and peripheral blood. (2) Analysis of the relationship between MDSC percentage and chosen DAMPs. Patients and Methods. 30 COPD patients were included. Using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry, MDSCs were assessed in BALF and peripheral blood. The concentration of DAMPs was estimated using sandwich ELISA. Using the Bradford method, the total protein concentrations were evaluated. Results. The percentage of MDSCs among MC in BALF correlated well with the concentration of defensin and heat shock protein 27. Assessing the percentage of MDSCs among all leukocytes in BALF, we revealed a significant correlation with the concentration of defensin, hyaluronic acid, and surfactant protein A. No dependencies occurred between DAMPs and MDSCs in peripheral blood. Conclusion. MDSCs and DAMPs occur in the COPD patient lung microenvironment. Significant correlations between them found in BALF may indicate their influence on the local inflammatory process in COPD. These relationships allow better understanding of the inflammatory process in COPD.


Assuntos
Líquido da Lavagem Broncoalveolar/imunologia , Pulmão/metabolismo , Células Supressoras Mieloides/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Idoso , Líquido da Lavagem Broncoalveolar/química , Defensinas/metabolismo , Feminino , Proteínas de Choque Térmico/metabolismo , Humanos , Ácido Hialurônico/metabolismo , Inflamação/fisiopatologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares/metabolismo , Células Supressoras Mieloides/química , Células Supressoras Mieloides/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Proteína A Associada a Surfactante Pulmonar/metabolismo
15.
Int Immunopharmacol ; 73: 414-423, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152979

RESUMO

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants and is mainly caused by hyperoxia exposure and mechanical ventilation. Alveolar simplification, pulmonary vascular abnormalities and pulmonary inflammation are the main pathological changes in hyperoxic lung injury animals. Lipoxin A4 (LXA4) is an important endogenous lipid that can mediate the regression of inflammation and plays a role in acute lung injury and asthma. The purpose of this study was to evaluate the effects of LXA4 on inflammation and lung function in neonatal rats with hyperoxic lung injury and to explore the mechanism of the PINK1 pathway. After 85% oxygen exposure in newborn rats for 7 days, the BPD model was established. We found that LXA4 could significantly reduce cell and protein infiltration and oxidative stress in rat lungs, improve pulmonary function and alveolar simplification, and promote weight gain. LXA4 inhibited the expression of TNF-α, MCP-1 and IL-1ß in serum and BALF from hyperoxic rats. Moreover, we found that LXA4 could reduce the expression of the PINK1 gene and down-regulate the expression of PINK1, Parkin, BNIP3L/Nix and the autophagic protein LC3B.These protective effects of LXA4 could be partially reversed by addition of BOC-2.Thus, we concluded that LXA4 can alleviate the airway inflammatory response, reduce the severity of lung injury and improve lung function in a hyperoxic rat model of BPD partly through the PINK1 signaling pathway.


Assuntos
Anti-Inflamatórios/uso terapêutico , Hiperóxia/tratamento farmacológico , Lipoxinas/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Proteínas Quinases/metabolismo , Animais , Animais Recém-Nascidos , Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Hiperóxia/metabolismo , Hiperóxia/patologia , Hiperóxia/fisiopatologia , Lipoxinas/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/fisiopatologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
16.
Int J Mol Sci ; 20(11)2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31181746

RESUMO

Exposure to ultrafine particles (UFPs) leads to adverse effects on health caused by an unbalanced ratio between UFPs deposition and clearance efficacy. Since air pollution toxicity is first direct to cardiorespiratory system, we compared the acute and sub-acute effects of diesel exhaust particles (DEP) and biomass burning-derived particles (BB) on bronchoalveolar Lavage Fluid (BALf), lung and heart parenchyma. Markers of cytotoxicity, oxidative stress and inflammation were analysed in male BALB/c mice submitted to single and repeated intra-tracheal instillations of 50 µg UFPs. This in-vivo study showed the activation of inflammatory response (COX-2 and MPO) after exposure to UFPs, both in respiratory and cardiovascular systems. Exposure to DEP results also in pro- and anti-oxidant (HO-1, iNOS, Cyp1b1, Hsp70) protein levels increase, although, stress persist only in cardiac tissue under repeated instillations. Statistical correlations suggest that stress marker variation was probably due to soluble components and/or mediators translocation of from first deposition site. This mechanism, appears more important after repeated instillations, since inflammation and oxidative stress endure only in heart. In summary, chemical composition of UFPs influenced the activation of different responses mediated by their components or pro-inflammatory and pro-oxidative molecules, indicating DEP as the most damaging pollutant in the comparison.


Assuntos
Exposição por Inalação/efeitos adversos , Material Particulado/toxicidade , Emissões de Veículos/toxicidade , Animais , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Ciclo-Oxigenase 2/análise , Citocromo P-450 CYP1B1/análise , Proteínas de Choque Térmico HSP70/análise , Heme Oxigenase-1/análise , Inflamação/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/análise
17.
Cell Mol Biol Lett ; 24: 35, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31160894

RESUMO

Background: Pulmonary edema is one of the pathological characteristics of acute respiratory distress syndrome (ARDS). The epithelial sodium channel (ENaC) is thought to be the rate-limiting factor for alveolar fluid clearance (AFC) during pulmonary edema. The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone was shown to stimulate ENaC-mediated salt absorption in the kidney. However, its role in the lung remains unclear. Here, we investigated the role of the PPARγ agonist in the lung to find out whether it can regulate AFC during acute lung injury (ALI). We also attempted to elucidate the mechanism for this. Methods: Our ALI model was established through intratracheal instillation of lipopolysaccharide (LPS) in C57BL/6 J mice. The mice were randomly divided into 4 groups of 10. The control group underwent a sham operation and received an equal quantity of saline. The three experimental groups underwent intratracheal instillation of 5 mg/kg LPS, followed by intraperitoneal injection of 4 mg/kg rosiglitazone, 4 mg/kg rosiglitazone plus 1 mg/kg GW9662, or only equal quantity of saline. The histological morphology of the lung, the levels of TNF-α and IL-1ß in the bronchoalveolar lavage fluid (BALF), the level of AFC, and the expressions of αENaC and serum and glucocorticoid-induced kinase-1 (SGK1) were determined. Type 2 alveolar (AT II) cells were incubated with rosiglitazone (15 µM) with or without GW9662 (10 µM). The expressions of αENaC and SGK1 were determined 24 h later. Results: A mouse model of ALI was successfully established. Rosiglitazone significantly ameliorated the lung injury, decreasing the TNF-α and IL-1ß levels in the BALF, enhancing AFC, and promoting the expressions of αENaC and SGK1 in ALI mice, which were abolished by the specific PPARγ blocker GW9662. In vitro, rosiglitazone increased the expressions of αENaC and SGK1. This increase was prevented by GW9662. Conclusions: Rosiglitazone ameliorated the lung injury and promoted ENaC-mediated AFC via a PPARγ/SGK1-dependent signaling pathway, alleviating pulmonary edema in a mouse model of ALI.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Líquido da Lavagem Broncoalveolar/química , Canais Epiteliais de Sódio/metabolismo , PPAR gama/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Rosiglitazona/farmacologia , Transdução de Sinais , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Animais , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
18.
J Vet Med Sci ; 81(7): 1043-1046, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31189765

RESUMO

The aim of this study was to investigate the relationship between the endotoxin activity in plasma and that in bronchoalveolar lavage fluid (BALF) in bronchopneumonia. Thirty-three calves were included in this study (17 healthy calves and 16 calves with respiratory disease). In the calves with bronchopneumonia, the median endotoxin activity in plasma (0.437 EU/ml, P<0.001) and BALF (29.45 EU/ml, P<0.001) was significantly higher than in the control calves. Plasma endotoxin activity was significantly and positively correlated with that in BALF (r2=0.900, P<0.001). Based on the receiver operating characteristics curves, we propose a diagnostic cutoff point for plasma endotoxin activity (0.104 EU/ml, AUC=0.914, P<0.001, Se 81.3% and Sp 82.4%) for identification of bronchopneumonia in calves which could die within a week.


Assuntos
Líquido da Lavagem Broncoalveolar/química , Broncopneumonia/veterinária , Doenças dos Bovinos/diagnóstico , Endotoxinas/análise , Endotoxinas/sangue , Animais , Broncopneumonia/diagnóstico , Estudos de Casos e Controles , Bovinos , Doenças dos Bovinos/sangue , Feminino , Masculino , Infecções por Mycoplasma/veterinária , Mycoplasma bovis/isolamento & purificação , Sensibilidade e Especificidade
19.
BMC Complement Altern Med ; 19(1): 124, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182097

RESUMO

BACKGROUND: Troxerutin (TRX), a naturally occurring flavonoid in various fruits, has been reported to exhibit numerous pharmacological and biological activities in vitro and in vivo. However, the molecular mechanisms underlying TRX as a treatment for disease are poorly understood. METHODS: Using pharmacophore mapping and inverse docking, a set of potential TRX target proteins that have been associated with multiple forms of diseases was obtained. Bioinformatic analyses were performed using the Enrichr and STRING servers to analyse the related biological processes and protein-protein networks. Furthermore, we investigated the potential protective effect of TRX against lipopolysaccharide-induced acute lung injury (ALI) using a mouse model. Morphological changes in the lungs were assessed using haematoxylin and eosin staining. Inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6 and IL-10 were investigated using ELISA. Activation of MAPK and NF-κB was detected using western blotting. RESULTS: Our network pharmacology analysis revealed the existence of multiple TRX-related chemical-target interactions and the related biological processes. We found that pretreatment with TRX protected against histological changes and obviously regulated the inflammatory cell counts and inflammatory cytokine levels in bronchoalveolar lavage fluid. Based on bioinformatic and western blot analyses, TRX may exert a protective effect against ALI by inhibiting MAPK and NF-κB signalling. CONCLUSIONS: TRX can ameliorate pulmonary injury by inhibiting the MAPK and NF-κB signalling pathways and has a potential protective effect against ALI. This study may be helpful for understanding the mechanisms underlying TRX action and for discovering new drugs from plants for the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Hidroxietilrutosídeo/análogos & derivados , Lesão Pulmonar Aguda/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Simulação por Computador , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Ontologia Genética , Hidroxietilrutosídeo/farmacologia , Hidroxietilrutosídeo/uso terapêutico , Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos Endogâmicos BALB C , Terapia de Alvo Molecular , NF-kappa B/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Edema Pulmonar/prevenção & controle
20.
BMC Pulm Med ; 19(1): 110, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221118

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening disease; however, its treatment has not yet been fully established. The progression of ARDS is considered to be mediated by altered intercellular communication between immune and structural cells in the lung. One of several factors involved in intercellular communication is the extracellular vesicle (EV). They act as carriers of functional content such as RNA molecules, proteins, and lipids and deliver cargo from donor to recipient cells. EVs have been reported to regulate the nucleotide-binding oligomerization like receptor 3 (NLRP3) inflammasome. This has been identified as the cellular machinery responsible for activating inflammatory processes, a key component responsible for the pathogenesis of ARDS. METHODS: Here, we provide comprehensive genetic analysis of microRNAs (miRNAs) in EVs, demonstrating increased expression of the miRNA-466 family in the bronchoalveolar lavage fluid of a mouse ARDS model. RESULTS: Transfection of bone marrow-derived macrophages (BMDMs) with miRNA-466 g and 466 m-5p resulted in increased interleukin-1 beta (IL-1ß) release after LPS and ATP treatment, which is an established in vitro model of NLRP3 inflammasome activation. Moreover, LPS-induced pro-IL-1ß expression was accelerated by miRNA-466 g and 466 m-5p in BMDMs. CONCLUSIONS: These findings imply that miRNA-466 family molecules are secreted via EVs into the airways in an ARDS model, and this exacerbates inflammation through the NLRP3 inflammasome. Our results suggest that the NLRP3 inflammasome pathway, regulated by extracellular vesicle miRNA, could act as a therapeutic target for ARDS.


Assuntos
Vesículas Extracelulares/metabolismo , Inflamassomos/metabolismo , MicroRNAs/metabolismo , Síndrome do Desconforto Respiratório do Adulto/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Modelos Animais de Doenças , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fatores Desencadeantes , Síndrome do Desconforto Respiratório do Adulto/induzido quimicamente
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA