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1.
Life Sci ; 239: 117017, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678284

RESUMO

Saxagliptin (Saxa), a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, is widely used for the treatment of type 2 diabetes mellitus. It has been documented to have immunomodulatory and anti-inflammatory actions. Our objective was to delineate the protective effect and the underlying mechanism of Saxa-in comparison with Dexamethasone (Dexa) - in airway inflammation induced by ovalbumin (OVA) in mice. METHODS: Mice were OVA-sensitized and challenged for the induction of acute asthma. Mice were orally administrated Saxa or Dexa. Total and differential cell counts, lactate dehydrogenase (LDH) and total protein concentrations were assessed in bronchoalveolar lavage fluid (BALF). The toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-kB), reduced glutathione (GSH), and total nitrate/nitrite products (NOx) levels as well as myeloperoxidase (MPO) activity in lung tissues were measured. Histopathological examination of the lung specimens was carried out using the hematoxylin and eosin (H & E) staining. RESULTS: Histopathological examination revealed that both Saxa and Dexa ameliorated OVA-induced inflammatory changes and significantly reduced total and differential leukocyte counts, LDH and total protein level in BALF upon comparison with OVA group. In addition, both treatments significantly mitigated OVA-induced oxidative stress as evidenced by diminished lung NOx level and MPO activity and elevated GSH level. The elevation of TLR4 and NF-kB levels in lung tissue were ameliorated by Saxa and Dexa administration. CONCLUSION: Saxa had marked antiasthmatic effect in OVA-induced allergic asthma through modulation of TLR4 and NF-κB signaling. Also, Saxa may represent a promising therapeutic agent for acute allergic asthma.


Assuntos
Adamantano/análogos & derivados , Asma/tratamento farmacológico , Dipeptídeos/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , NF-kappa B/efeitos dos fármacos , Receptor 4 Toll-Like/efeitos dos fármacos , Doença Aguda , Adamantano/uso terapêutico , Animais , Asma/induzido quimicamente , Asma/patologia , Líquido da Lavagem Broncoalveolar/citologia , Dexametasona/uso terapêutico , L-Lactato Desidrogenase/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Óxido Nítrico/metabolismo , Ovalbumina , Peroxidase/metabolismo
2.
Am J Case Rep ; 20: 1440-1445, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31564716

RESUMO

BACKGROUND Herein, we describe a case of eosinophilic pneumonia that was likely to have been induced by vancomycin. CASE REPORT A 65-year-old man on maintenance hemodialysis presented with chest pain and dyspnea. He subsequently developed methicillin-resistant Staphylococcus aureus-positive acute pleural empyema in an evacuated right-sided pneumothorax. Surgical thoracoscopic curettage was ultimately performed, but dyspnea recurred postoperatively. Computed tomography depicted widespread reticular shadowing of the left lung, and peripheral eosinophilia was detected. The proportion of eosinophils found in bronchoalveolar lavage fluid was also remarkable (43%). All symptoms and the results of laboratory tests immediately improved after the discontinuation of vancomycin and initiation of prednisolone therapy. CONCLUSIONS We attribute this case of eosinophilic pneumonia to vancomycin, because all other candidate causes were ruled out, and only vancomycin fulfilled the criteria of both drug-induced eosinophilic pneumonia and drug-induced lung injury. If confirmed, this constitutes the first reported case of vancomycin-induced eosinophilic pneumonia.


Assuntos
Antibacterianos/efeitos adversos , Eosinofilia Pulmonar/induzido quimicamente , Vancomicina/efeitos adversos , Idoso , Líquido da Lavagem Broncoalveolar/citologia , Eosinófilos/metabolismo , Humanos , Masculino
3.
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
4.
Immunohorizons ; 3(8): 368-377, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31603851

RESUMO

The hallmark features of allergic asthma are type 2 (eosinophilic) inflammation and airways hyperresponsiveness (AHR). Although these features often comanifest in mouse lungs in vivo, we demonstrate in this study that the serine protease Alp1 from the ubiquitous mold and allergen, Aspergillus fumigatus, can induce AHR in mice unable to generate eosinophilic inflammation. Strikingly, Alp1 induced AHR in mice devoid of protease-activated receptor 2/F2 trypsin-like receptor 1 (PAR2/F2RL1), a receptor expressed in lung epithelium that is critical for allergic responses to protease-containing allergens. Instead, using precision-cut lung slices and human airway smooth muscle cells, we demonstrate that Alp1 directly increased contractile force. Taken together, these findings suggest that Alp1 induces bronchoconstriction through mechanisms that are largely independent of allergic inflammation and point to a new target for direct intervention of fungal-associated asthma.


Assuntos
Aspergillus fumigatus/imunologia , Asma/imunologia , Asma/microbiologia , Proteínas Fúngicas/imunologia , Serina Endopeptidases/imunologia , Alérgenos/imunologia , Animais , Aspergillus fumigatus/enzimologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Broncoconstrição/efeitos dos fármacos , Broncoconstrição/imunologia , Células Cultivadas , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Humanos , Inflamação/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos de Músculo Liso/imunologia , Receptor PAR-2/genética , Receptor PAR-2/imunologia
5.
Clin Lab ; 65(9)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31532092

RESUMO

BACKGROUND: The profile of leukocytes in bronchoalveolar lavage (BAL) fluid provides important information for diagnosing various lung diseases. A differential cell count of BAL is conventionally performed by evaluating centrifuged samples under a light microscope and enumerating the stained cells. Another rarely used method to identify BAL leukocytes is flow cytometry (FCM). However, there are no guidelines for standardizing this method and related literature is limited. This study aimed to evaluate the accuracy of FCM for identifying BAL leukocytes. METHODS: The BAL samples accepted to the hematology laboratory between 2014 - 2018 were retrospectively evaluated via light microscopy (LM) by a hematologist; while flow cytometric analyses with a monoclonal antibody panel composed of CD45/CD14/CD16 were noted by another doctor. The percentages of macrophages, lymphocytes, neutrophils and eosinophils determined by both methods were recorded for analysis. Correlations between the results from LM and FCM were investigated. In addition, compatibility between LM and FCM for denoting pathological values for each cell type was checked. RESULTS: Among 140 reviewed BAL samples, 76 were included for further analysis. Comparisons revealed strong correlations between FCM and LM for identifying macrophages, lymphocytes, neutrophils, and eosinophils. In addition, regarding the normal cutoff values for each leukocyte type, FCM and LM were similar in the identification of pathological changes of all cell types except eosinophils. CONCLUSIONS: Flow cytometry was found to be feasible for use instead of LM and might become a more widely used technique to analyze BAL fluid in the future.


Assuntos
Anticorpos Monoclonais/análise , Líquido da Lavagem Broncoalveolar/citologia , Citometria de Fluxo/métodos , Pneumopatias/diagnóstico , Neoplasias Pulmonares/diagnóstico , Anticorpos Monoclonais/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Eosinófilos/citologia , Eosinófilos/imunologia , Estudos de Viabilidade , Feminino , Humanos , Contagem de Leucócitos , Leucócitos/citologia , Leucócitos/imunologia , Macrófagos/citologia , Macrófagos/imunologia , Masculino , Microscopia/métodos , Pessoa de Meia-Idade , Neutrófilos/citologia , Neutrófilos/imunologia , Patologia Clínica/instrumentação , Patologia Clínica/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
6.
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
7.
J Vet Intern Med ; 33(5): 2319-2326, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31397944

RESUMO

BACKGROUND: Public pressure exists in the United States to eliminate race-day furosemide administration despite its efficacy in decreasing the severity of equine exercise pulmonary hemorrhage (EIPH). No effective alternative prophylaxis strategies have been identified. OBJECTIVE: To investigate alternative protocols to race-day furosemide that might mitigate EIPH. ANIMALS: Seven fit Thoroughbreds with recent EIPH. METHODS: Double-blinded placebo-controlled Latin square crossover using a treadmill followed by a blinded placebo-controlled crossover study at a racetrack. First, horses exercised supramaximally to fatigue 24 hours after initiating 5 EIPH prophylaxis protocols: 0.5 and 1.0 mg/kg furosemide IV 24 hours pre-exercise with and without controlled access to water, and 24 hour controlled access to water. Effects were compared to those measured after giving a placebo 24 hours pre-exercise, and 0.5 mg/kg furosemide IV 4 hours pre-exercise. Bronchoalveolar lavage (BAL) erythrocyte count was determined 45-60 minutes postexercise after endoscopy to assign an EIPH score. Data were analyzed using linear mixed effects models. The most promising protocol from the treadmill study was further evaluated in 6 horses using endoscopy and BAL after 1100 m simulated races. RESULTS: Intravenous furosemide (0.5 mg/kg) administered 24 hours pre-exercise combined with controlled access to water decreased the severity of EIPH on the treadmill and at the racetrack. CONCLUSION AND CLINICAL IMPORTANCE: Administering 0.5 mg/kg furosemide 24 hours pre-racing combined with controlling water intake may be a strategy to replace race-day furosemide administration for the management of EIPH. A larger study is indicated to further evaluate whether this protocol significantly mitigates EIPH severity.


Assuntos
Furosemida/farmacologia , Hemorragia/veterinária , Doenças dos Cavalos/prevenção & controle , Animais , Líquido da Lavagem Broncoalveolar/citologia , Estudos Cross-Over , Diuréticos/administração & dosagem , Diuréticos/farmacologia , Contagem de Eritrócitos , Feminino , Furosemida/administração & dosagem , Hemorragia/prevenção & controle , Cavalos , Pneumopatias/prevenção & controle , Pneumopatias/veterinária , Masculino
8.
Med Sci Monit ; 25: 6255-6263, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429423

RESUMO

BACKGROUND Acute lung injury (ALI) is one of major causes of death in newborns, making it urgent to improve therapy. Administration of low dose carbon monoxide (CO) plays a protective role in ALI but the mechanisms are not fully understood. This study was designed to test the therapeutic effect of monoxide-releasing molecule 3 (MORM3) in lipopolysaccharide (LPS) induced neonatal ALI and the possibly associated molecular mechanisms. MATERIAL AND METHODS For this study, 3- to 8-day old Newborn Sprague-Dawley rats were subjected to intraperitoneal injection of 3 mg/kg LPS to induce ALI. Then animals received intraperitoneal injection of carbon monoxide-releasing molecules 3 (CORM3) (8 mg/kg) or inactive CORM3 (iCORM3) for 7 consecutive days. Lung tissues were collected for histological examination and total cell counts and protein content in bronchoalveolar lavage fluid (BALF) were measured. Expression of Cx43 and necroptosis-related markers were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. RESULTS LPS exposure induced significant lung injury indicated by histological damage, increased lung wet/dry weight ratio (W/D) and increased total cell counts and protein concentration in BALF. These changes were significantly ameliorated by administration of CORM3 but not iCORM3. LPS also increased necroptosis-related markers RIP1, RIP3, and MLKL and their elevation was blocked by CORM3. CORM3 administration ameliorated LPS induced elevation of Cx43 expression and adenoviral overexpression of Cx43 abolished lung protective effect of CORM3. CORM3 administration attenuated LPS induced activation of extracellular-signal-regulated kinase (ERK) and its protection against necroptosis was abolished by ERK inhibitor U0126. CONCLUSIONS CORM3 attenuates LPS-Induced ALI in neonatal rats and its lung protective effect might be through downregulation of Cx43 to attenuate ERK signaling and ameliorate necroptosis, suggesting CORM3 as a potential therapeutic drug for ALI in neonates.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Monóxido de Carbono/administração & dosagem , Conexina 43/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Animais , Animais Recém-Nascidos , Líquido da Lavagem Broncoalveolar/citologia , Monóxido de Carbono/metabolismo , Regulação para Baixo/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
9.
J Vet Intern Med ; 33(5): 2217-2226, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31468629

RESUMO

BACKGROUND: Eosinophilic lung disease is a poorly understood inflammatory airway disease that results in substantial morbidity. OBJECTIVE: To describe clinical findings in dogs with eosinophilic lung disease defined on the basis of radiographic, bronchoscopic, and bronchoalveolar lavage fluid (BAL) analysis. Categories included eosinophilic bronchitis (EB), eosinophilic granuloma (EG), and eosinophilic bronchopneumopathy (EBP). ANIMALS: Seventy-five client owned dogs. METHODS: Medical records were retrospectively reviewed for dogs with idiopathic BAL fluid eosinophilia. Information abstracted included duration and nature of clinical signs, bronchoscopic findings, and laboratory data. Thoracic radiographs were evaluated for the pattern of infiltrate, bronchiectasis, and lymphadenomegaly. RESULTS: Thoracic radiographs were normal or demonstrated a bronchial pattern in 31 dogs assigned a diagnosis of EB. Nine dogs had intraluminal mass lesions and were bronchoscopically diagnosed with EG. The remaining 35 dogs were categorized as having EBP based on radiographic changes, yellow green mucus in the airways, mucosal changes, and airway collapse. Age and duration of cough did not differ among groups. Dogs with EB were less likely to have bronchiectasis or peripheral eosinophilia, had lower total nucleated cell count in BAL fluid, and lower percentage of eosinophils in BAL fluid compared to dogs in the other 2 groups. In contrast to previous reports, prolonged survival (>55 months) was documented in dogs with EG. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with eosinophilic lung disease can be categorized based on imaging, bronchoscopic and BAL fluid cytologic findings. Further studies are needed to establish response to treatment in these groups.


Assuntos
Bronquite Crônica/veterinária , Doenças do Cão/patologia , Eosinofilia/veterinária , Granuloma Eosinófilo/veterinária , Eosinofilia Pulmonar/veterinária , Animais , Bronquiectasia/veterinária , Bronquite Crônica/diagnóstico por imagem , Bronquite Crônica/patologia , Líquido da Lavagem Broncoalveolar/citologia , Broncoscopia/veterinária , Doenças do Cão/diagnóstico por imagem , Cães , Granuloma Eosinófilo/diagnóstico por imagem , Granuloma Eosinófilo/patologia , Feminino , Masculino , Eosinofilia Pulmonar/diagnóstico por imagem , Eosinofilia Pulmonar/patologia , Radiografia Torácica/veterinária , Estudos Retrospectivos
10.
Medicine (Baltimore) ; 98(32): e16518, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393354

RESUMO

BACKGROUND: The main objective was to evaluate and compare the local genotoxicity of sevoflurane and desflurane in bronchoalveolar cells, while the secondary outcome was to detect systemic oxidative DNA damage. To our knowledge, our study is the first one to evaluate the local effects of inhalation anesthetics in human bronchoalveolar cells in patients. METHODS: American Society of Anesthesiologists group I-II patients scheduled for lumbar discectomy surgery were enrolled in this randomized prospective study. Patients were randomized to sevoflurane or desflurane for anesthesia maintenance. Bronchoalveolar lavage samples and peripheral blood samples were taken at 2-time points: the first point (baseline, T1); and the second point (postexposure, T2). Final number of 48 samples were the sevoflurane (n = 22) and desflurane (n = 26) groups. Comet assay was applied to examine genotoxic properties. Oxidative DNA damage in plasma was measured with 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: T2 values were higher than baseline values in both the desflurane group (tail-length: 66 ±â€Š24, %DNA in tail: 72 ±â€Š60, tail moment: 47.52 ±â€Š14.4; P = .001, P = .005, P = .001, respectively) and the sevoflurane group (tail-length: 58 ±â€Š33, %DNA in tail: 88 ±â€Š80, tail moment: 51.04 ±â€Š26.4; P = .001, P = .012, P = .001, respectively). T2 plasma 8-OHdG levels were also higher than baseline levels in the desflurane group (3.91 ±â€Š0.19 ng/ml vs 1.32 ±â€Š0.20 ng/ml, P = .001) and sevoflurane group (3.98 ±â€Š0.18 ng/ml vs 1.31 ±â€Š0.11 ng/ml, P = .001). There were no differences between the 2 groups in comet parameters and 8-OHdG levels. CONCLUSION: Our results indicate that both inhalation agents cause DNA damage in the bronchoalveolar cells. Also, we detected increases in plasma 8-OHdG concentrations. Local genotoxicity and systemic oxidized DNA damage were similar in both groups.


Assuntos
Anestésicos Inalatórios/efeitos adversos , Anestésicos Inalatórios/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Dano ao DNA/efeitos dos fármacos , Adulto , Idoso , Ensaio Cometa , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Desflurano/efeitos adversos , Desflurano/farmacologia , Discotomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Sevoflurano/administração & dosagem , Sevoflurano/farmacologia
11.
Aust Vet J ; 97(9): 343-350, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31286483

RESUMO

OBJECTIVE: To investigate the relationship between bronchoalveolar lavage fluid cytology, particularly mast cells, and airway hyper-reactivity in athletic horses presented for poor performance that included a respiratory tract evaluation in two disparate locations in Australia. DESIGN: Multi-centre, retrospective and prospective cross-sectional study METHODS: Eighty four adult horses underwent both pulmonary function testing and histamine bronchoprovocation with a commercial flowmetric plethysmography system. A bronchoalveolar lavage was performed four to twelve hours later. Bronchoalveolar lavage fluid cytology was categorised using two differing classification systems to define mild equine asthma. Statistical analysis was used to assess associations between bronchoalveolar lavage fluid relative inflammatory cell percentages, and airway hyper-reactivity and their associated categorisations. RESULTS: Sixty four percent (54/84) of horses displayed airway hyper-reactivity, as defined by PC35 < 6 mg/ml of histamine. A relative mastocytosis was the most common bronchoalveolar lavage fluid cytological abnormality. Horses with a sole mast cell response of ≥ 5% within their bronchoalveolar lavage fluid displayed airway hyper-reactivity at a lower dose of nebulized histamine than horses with normal bronchoalveolar lavage fluid cytology. Horses with mixed cell responses (relative mast cell percentage > 2% and/or relative neutrophil percentage > 5% and/or eosinophil relative cell percentage ≥ 1%) displayed airway hyper-reactivity at a lower dose of nebulized histamine than horses with normal bronchoalveolar lavage fluid cytology. CONCLUSION: In the Australian context, recently revised increased bronchoalveolar lavage fluid cytology relative cell percentage cut offs appear appropriate for sole mast cell responses. The historical lower cut offs appear to be appropriate for mixed inflammatory cell responses.


Assuntos
Asma/veterinária , Líquido da Lavagem Broncoalveolar/citologia , Doenças dos Cavalos/fisiopatologia , Animais , Asma/epidemiologia , Asma/fisiopatologia , Desempenho Atlético/fisiologia , Austrália/epidemiologia , Lavagem Broncoalveolar , Estudos Transversais , Doenças dos Cavalos/epidemiologia , Cavalos , Testes de Função Respiratória/veterinária , Hipersensibilidade Respiratória/epidemiologia , Hipersensibilidade Respiratória/fisiopatologia , Hipersensibilidade Respiratória/veterinária
12.
Vet Microbiol ; 235: 101-109, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31282367

RESUMO

Highly virulent porcine reproductive and respiratory syndrome virus (PRRSV) strains have increasingly overwhelmed Asia and Europe in recent years. This study aims to compare the clinical signs, gross and microscopic findings as well as the expression of CD163 within live pulmonary alveolar macrophages (PAMs) from bronchoalveolar lavage fluid (BALF) of pigs experimentally infected with two PRRSV strains of different virulence. Pigs were infected with either a subtype 1 PRRSV-1 3249 strain or a subtype 3 PRRSV-1 Lena strain and consecutively euthanized at 1, 3, 6, 8 and 13 days post-inoculation. Clinical signs were reported daily and BALF and lung tissue samples were collected at the different time-points and accordingly processed for their analysis. Pigs infected with Lena strain exhibited greater clinical signs as well as gross and microscopic lung scores compared to 3249-infected pigs. A decreased frequency of PAMs from BALF was observed early in pigs infected with Lena strain. Moreover, the frequency and median fluorescence intensity (MFI) of CD163 within PAMs were much lower in Lena-infected pigs than in 3249-infected pigs. This downregulation in CD163 was also observed in lung sections after the assessment of macrophages expressing CD163 by means of immunohistochemistry. This outcome may result from the effect of PRRSV replication, PRRSV-induced inflammation, the influx of immature macrophages to restore lung homeostasis and/or the evidence of CD163low cells after CD163+ cells decrease in BALF.


Assuntos
Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Broncopneumonia/veterinária , Macrófagos Alveolares/imunologia , Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Receptores de Superfície Celular/genética , Animais , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Broncopneumonia/virologia , Regulação para Baixo , Feminino , Pulmão/citologia , Pulmão/virologia , Macrófagos Alveolares/virologia , Masculino , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Receptores de Superfície Celular/imunologia , Suínos , Virulência
13.
Environ Sci Pollut Res Int ; 26(26): 27444-27456, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31327144

RESUMO

Air pollution represents a major health problem in megacities, bringing about 8 million deaths every year. The aim of the study was to evaluate in vivo the ocular and respiratory mucosa biological response after chronic exposure to urban air particles from Buenos Aires (UAP-BA). BALB/c mice were exposed to UAP-BA or filtered air for 1, 6, 9, and 12 months. After exposure, histology, histomorphometry, and IL-6 proinflammatory cytokine level were evaluated in the respiratory and ocular mucosa. Total cell number and differential cell count were determined in the brochoalveolar lavage fluid. In the lung, chronic exposure to UAP-BA induced reduction of the alveolar space, polymorhonuclear cell recruitment, and goblet cell hyperplasia. In the ocular surface, UAP-BA induced an initial mucin positive cells rise followed by a decline through time, while IL-6 level increased at the latest point-time assayed. Our results showed that the respiratory and the ocular mucosas respond differently to UAP-BA. Being that lung and ocular mucosa diseases may be triggered and/or exacerbated by chronic exposure to urban air PM, the inhabitants of Buenos Aires whom are chronically exposed to environmental urban air pollution may be considered a subpopulation at risk. Based on our results, we propose the ocular mucosa as a reliable and more accessible surrogate for pulmonary mucosa environmental toxicity that might also serve as an earlier biomarker for air pollution adverse impact on health.


Assuntos
Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Olho/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Membrana Mucosa/efeitos dos fármacos , Poluição do Ar/análise , Animais , Argentina , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/citologia , Olho/patologia , Feminino , Interleucina-6/análise , Interleucina-6/genética , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Material Particulado/efeitos adversos , Material Particulado/análise , Material Particulado/química , Testes de Toxicidade Crônica , Urbanização
14.
Inflammation ; 42(5): 1857-1868, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31332661

RESUMO

Pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, has been reported to have anti-inflammatory properties, but the effects of PF11 on acute lung inflammation were unknown. The present study aimed to investigate the protective effects and potential mechanisms of PF11 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in male BALB/c mice. After being treated with PF11 (3, 10, and 30 mg/kg, intravenous) once a day for 3 consecutive days, the mice were challenged by intratracheal instillation of LPS, and then their lung tissues and bronchoalveolar lavage fluid (BALF) were collected for further analysis. The results showed that PF11 attenuated LPS-induced ALI, with alleviated histopathological damage, decreased lung wet/dry weight ratio, and reduced protein concentration and inflammatory cells number in BALF. Moreover, PF11 reversed the LPS-induced increases of mRNA expression and protein levels of interleukin-6, tumor necrosis factor-α, and interleukin-1ß. Meanwhile, PF11 decreased LPS-induced myeloperoxidase activity and neutrophil infiltration in lung tissue by reducing the expression of macrophage inflammatory protein-2 and intercellular adhesion molecule-1, as well as enhanced neutrophil clearance by accelerating neutrophils apoptosis and their phagocytosis by alveolar macrophages. In conclusion, these results indicated that PF11 significantly attenuated LPS-induced ALI through suppressing neutrophil infiltration and accelerating neutrophil clearance, suggesting its potential in the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Movimento Celular/efeitos dos fármacos , Ginsenosídeos/farmacologia , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/metabolismo , Ginsenosídeos/uso terapêutico , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
15.
Immunohorizons ; 3(7): 274-281, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31356157

RESUMO

A number of pulmonary diseases occur with upper lobe predominance, including cystic fibrosis and smoking-related chronic obstructive pulmonary disease. In the healthy lung, several physiologic and metabolic factors exhibit disparity when comparing the upper lobe of the lung to lower lobe, including differences in oxygenation, ventilation, lymphatic flow, pH, and blood flow. In this study, we asked whether these regional differences in the lung are associated with DNA methylation changes in lung macrophages that could potentially lead to altered cell responsiveness upon subsequent environmental challenge. All analyses were performed using primary lung macrophages collected via bronchoalveolar lavage from healthy human subjects with normal pulmonary function. Epigenome-wide DNA methylation was examined via Infinium MethylationEPIC (850K) array and validated by targeted next-generation bisulfite sequencing. We observed 95 CpG loci with significant differential methylation in lung macrophages, comparing upper lobe to lower lobe (all false discovery rate < 0.05). Several of these genes, including CLIP4, HSH2D, NR4A1, SNX10, and TYK2, have been implicated as participants in inflammatory/immune-related biological processes. Functionally, we identified phenotypic differences in oxygen use, comparing upper versus lower lung macrophages. Our results support a hypothesis that epigenetic changes, specifically DNA methylation, at a multitude of gene loci in lung macrophages are associated with metabolic differences regionally in lung.


Assuntos
Metilação de DNA , Pulmão/citologia , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Consumo de Oxigênio/fisiologia , Adulto , Algoritmos , Líquido da Lavagem Broncoalveolar/citologia , Respiração Celular/fisiologia , Ilhas de CpG/genética , Epigênese Genética , Feminino , Loci Gênicos , Voluntários Saudáveis , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Macrófagos Alveolares/citologia , Masculino , Fenótipo , Adulto Jovem
16.
Int Immunopharmacol ; 75: 105749, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31306981

RESUMO

Acute lung injury (ALI) is a pulmonary diffuse dysfunction disease caused by immoderate inflammatory response breaking the coordination of physiological structures and functions, and there are very few effective treatments to reduce high morbidity of ALI in critical patients. Glycitin is a natural ingredient derived from the seeds of leguminous plants and may have potent anti-inflammation features. The purpose of this study was to investigate the anti-inflammation effect of glycitin on LPS-induced ALI in mice and elucidate its possible anti-inflammatory mechanisms. The results of histopathological changes, the wet/dry weight ratio as well as the myeloperoxidase (MPO) activity indicated that glycitin obviously alleviated the lung injury induced by LPS. In addition, qPCR and ELISA results found that glycitin could dose-dependently decrease the expressions of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. Western blotting was performed to revealed that glycitin inhibited the activation of NF-κB and MAPKs signaling pathways by suppressing the expression of TLR4 protein and the phosphorylation of IKKß, IκBα, p65, p38, ERK, and JNK. All data indicated that glycitin could protect lung tissues from LPS-induced inflammation via inhibiting TLR4-mediated NF-κB and MAPKs signaling pathways.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Isoflavonas/uso terapêutico , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/genética , Citocinas/imunologia , Células HEK293 , Humanos , Isoflavonas/farmacologia , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/imunologia , Neutrófilos/imunologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética
17.
Part Fibre Toxicol ; 16(1): 23, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31182125

RESUMO

BACKGROUND: Little is known about the exposure levels and adverse health effects of occupational exposure to airplane emissions. Diesel exhaust particles are classified as carcinogenic to humans and jet engines produce potentially similar soot particles. Here, we evaluated the potential occupational exposure risk by analyzing particles from a non-commercial airfield and from the apron of a commercial airport. Toxicity of the collected particles was evaluated alongside NIST standard reference diesel exhaust particles (NIST2975) in terms of acute phase response, pulmonary inflammation, and genotoxicity after single intratracheal instillation in mice. RESULTS: Particle exposure levels were up to 1 mg/m3 at the non-commercial airfield. Particulate matter from the non-commercial airfield air consisted of primary and aggregated soot particles, whereas commercial airport sampling resulted in a more heterogeneous mixture of organic compounds including salt, pollen and soot, reflecting the complex occupational exposure at an apron. The particle contents of polycyclic aromatic hydrocarbons and metals were similar to the content in NIST2975. Mice were exposed to doses 6, 18 and 54 µg alongside carbon black (Printex 90) and NIST2975 and euthanized after 1, 28 or 90 days. Dose-dependent increases in total number of cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid were observed on day 1 post-exposure for all particles. Lymphocytes were increased for all four particle types on 28 days post-exposure as well as for neutrophil influx for jet engine particles and carbon black nanoparticles. Increased Saa3 mRNA levels in lung tissue and increased SAA3 protein levels in plasma were observed on day 1 post-exposure. Increased levels of DNA strand breaks in bronchoalveolar lavage cells and liver tissue were observed for both particles, at single dose levels across doses and time points. CONCLUSIONS: Pulmonary exposure of mice to particles collected at two airports induced acute phase response, inflammation, and genotoxicity similar to standard diesel exhaust particles and carbon black nanoparticles, suggesting similar physicochemical properties and toxicity of jet engine particles and diesel exhaust particles. Given this resemblance as well as the dose-response relationship between diesel exhaust exposure and lung cancer, occupational exposure to jet engine emissions at the two airports should be minimized.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Aeroportos , Dano ao DNA , Pulmão/efeitos dos fármacos , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Ocupacionais do Ar/análise , Poluentes Ocupacionais do Ar/farmacocinética , Animais , Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/citologia , Feminino , Pulmão/metabolismo , Pulmão/ultraestrutura , Camundongos Endogâmicos C57BL , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Material Particulado/análise , Material Particulado/farmacocinética , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/farmacocinética , Proteína Amiloide A Sérica/análise , Fatores de Tempo , Distribuição Tecidual
18.
Int Immunopharmacol ; 73: 581-589, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31234092

RESUMO

Inhaled terbutaline is commercially available ß2-agonist which consists of equivalent amount of R- and S-enantiomer. In this study, we aimed to investigate the effects of single enantiomers of terbutaline and its racemate in an ovalbumin (OVA)-induced mouse model of asthma via. seven days inhalation and the potential mechanisms involved. In a standard experimental asthma model, BALB/c mice were sensitized and challenged with OVA. R-terbutaline (R-ter), S-terbutaline (S-ter) or racemic terbutaline (rac-ter) was given via. nose-only inhalation for one week. Airway responsiveness to methacholine was measured by the plethysmography in conscious mice. Eosinophils counts in blood and bronchoalveolar (BAL) fluid were determined. The OVA-sIgE in plasma and inflammatory cytokines and mediators in BAL fluid or lung tissue were analyzed by ELISA, qRT-PCR or western blotting. Airway inflammation and remodeling were evaluated with hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson staining. Drug distribution and deposition after inhalation were determined by LC-MS/MS. Our data showed that R-ter efficiently ameliorated asthma responses, including airway hyperresponsiveness, eosinophils influx and IL-5 in BALF, plasma OVA-sIgE and significantly reduced pulmonary inflammation, peribronchial smooth muscle layer thickness, goblet cell hyperplasia, and deposition of collagen fibers, as well as downregulation of p38 MAPK phosphorylation and NF-κB expression. Racemic mixture exhibited diminished effects while S-ter enhanced airway responsiveness to methacholine and exerted pro-asthmatic effects.


Assuntos
Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Terbutalina/uso terapêutico , Administração por Inalação , Animais , Asma/imunologia , Asma/patologia , Asma/fisiopatologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Broncoconstrição/efeitos dos fármacos , Broncodilatadores/farmacologia , Citocinas/imunologia , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Imunoglobulina E/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , NF-kappa B/imunologia , Ovalbumina , Estereoisomerismo , Terbutalina/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
20.
Int Immunopharmacol ; 73: 568-574, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203114

RESUMO

PIM kinase is involved in the cellular processes of growth, differentiation and apoptosis. However, the role of PIM1 in lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains largely unknown. A trend of PIM1 in the lung tissue of LPS-induced ALI at different time points was detected. Histology, wet/dry (W/D) ratio, inflammatory cells in the bronchoalveolar lavage fluid (BALF) and survival rate analyses were performed when mice received the PIM1 inhibitor SMI-4a intratracheally 3 h before LPS administration. Cytokine production in vivo and in vitro was measured after SMI-4a pretreatment. NF-κB subunit p65 expression in nuclei and phosphorylation at Ser276 in lung tissues or cells were detected by Western blot analysis. The results showed that PIM1 mRNA and protein were upregulated in the lung tissue of LPS-induced ALI. The PIM1 inhibitor SMI-4a markedly improved the survival rate after lethal LPS administration, reduced the severity of lung edema, attenuated the histologic injuries of the lung tissue and reduced the counts of infiltrated inflammatory cells in the BALF. The PIM1 inhibitor SMI-4a suppressed the production of cytokines in LPS-treated RAW264.7 cell supernatants and BALF. Furthermore, LPS administration upregulated the levels of nuclear p65 and phosphorylated p65 (p-p65) at Ser276, whereas pretreatment with the PIM1 inhibitor SMI-4a reduced p65 upregulation in the nucleus and p-p65 at Ser276. Taken together, these data indicate that the PIM1 inhibitor SMI-4a may serve as a promising therapeutic strategy for LPS-induced ALI by suppressing macrophage production of cytokines via a reduction of p65 activities.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Compostos de Benzilideno/uso terapêutico , Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores , Tiazolidinedionas/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/farmacologia , Compostos de Benzilideno/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Lipopolissacarídeos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Tiazolidinedionas/farmacologia , Fator de Transcrição RelA/imunologia
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