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1.
Medicine (Baltimore) ; 100(21): e26149, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032770

RESUMO

RATIONALE: Lung pleomorphic carcinoma (LPC) is generally resistant to chemotherapy or radiotherapy. However, a combination of immune checkpoint inhibitors and radiotherapy has a remarkable efficacy against LPC. PATIENT CONCERNS AND DIAGNOSES: Here, we report the case of a 50-year old man diagnosed with progressive LPC. The tumor invaded the carina and predominantly obstructed the right main bronchus; therefore, a combination of palliative chemoradiotherapy and atezolizumab was initiated. However the trachea was gradually obstructed. INTERVENTION AND OUTCOME: Argon plasma coagulation (APC) was performed to prevent tumor invasion. After three APC sessions, the tumor showed a necrotic change and was easily excised using biopsy forceps. LESSONS: A combination of chemoradiotherapy, atezolizumab, and APC showed a good efficacy, and the patient had a good response to atezolizumab maintenance therapy. Multidisciplinary treatments, such as a combination of immune checkpoint inhibitors and APC, could have synergistic efficacy in lung cancer.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Inibidores de Checkpoint Imunológico/uso terapêutico , Fotocoagulação a Laser , Lasers de Gás/uso terapêutico , Neoplasias Pulmonares/terapia , Brônquios/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Traqueia/patologia , Resultado do Tratamento
2.
J Vis Exp ; (169)2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33749675

RESUMO

Intratracheal (IT) drug delivery allows the direct delivery of pharmaceutical substances to the lung, maximizing potential pulmonary benefit and minimizing systemic drug exposure. The transcutaneous technique is simple and allows for the IT delivery of substances to the lung of prematurely born rabbits shortly after birth. Newborn pups are anesthetized with inhaled Isoflurane before being placed in a supine position with the neck extended. The larynx is identified and stabilized before transcutaneous placement of a 26-gauge (G) catheter into the trachea. Following catheterization of the trachea, a 30 G blunt needle attached to a Hamilton syringe is introduced into the IT catheter and is used for delivering a precise volume into the trachea during spontaneous respiration. After the IT injection is completed, the needle and catheter are withdrawn, and the pup is allowed to recover from anesthesia. Transcutaneous IT injection delivers a large proportion of the injected substance to the lung, with the majority remaining in the lung 3 hours after the intervention. The injections are well tolerated from the day of birth and can be repeated for multiple consecutive days without influencing survival. This technique can be used to investigate the effect of pharmaceutical agents on lung development and in the prevention of neonatal lung injury in preterm rabbits.


Assuntos
Sistemas de Liberação de Medicamentos , Nascimento Prematuro/patologia , Traqueia/patologia , Administração Cutânea , Anestesia , Animais , Animais Recém-Nascidos , Injeções , Coelhos , Distribuição Tecidual
3.
Poult Sci ; 100(2): 685-696, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518122

RESUMO

Ammonia (NH3) is a known harmful gas and exists in haze, forming secondary organic aerosols. Exposure to ambient ammonia correlates with the respiratory tract infection, and microbiota in the upper respiratory tract is an emerging crucial player in the homeostatic regulation of respiratory tract infection, and microbiota perturbation is usually accompanied by the inflammatory reactions; however, the effects of different levels of ammonia exposure on tracheal microbiota and inflammation are unclear. A total of 288 22-day-old male Arbor Acres broilers were chosen and divided into 4 groups with 6 replicates of 12 chickens, and respectively exposed to ammonia at 0, 15, 25, and 35 ppm for 21-d trial period. Cytokines (interleukin (IL)-1ß, IL-6, and IL-10) in the trachea were measured at the 21 d of exposure to NH3. Tracheal microbiota at the 21 d was analyzed by the 16S rRNA gene analysis. The results showed that an increase in ammonia levels, even in 15 ppm, significantly decreased the alpha diversity and changed the bacterial community structure. Six genera (Faecalibacterium, Ruminococcus]_torques_group, unclassified_f__Lachnospiraceae, Ruminococcaceae_UCG-014, Streptococcus, Blautia) significantly increased, whereas Lactobacillus significantly decreased under different levels of ammonia exposure. We also observed positive associations of Faecalibacterium, Blautia, g__Ruminococcaceae_UCG-014, unclassified_f__Lachnospiraceae and Ruminococcus]_torques_group abundances with tracheal IL-1ß concentration. Moreover, an increase in ammonia levels, even in 15 ppm, caused respiratory tract inflammatory injury. The results indicated that 15 ppm ammonia exposure changed the composition of tracheal microbiota that caused the tracheal injury possibly through increasing the IL-1ß, which might make the broiler more sensitive to the changes of environment and pathogenic micro-organisms in the poultry house, and may be also a critical value that needs high alertness. Herein, the present experiment also suggested that the standard limit of ammonia concentration in adult poultry house is 15 ppm. This research provides an insight into the relationship between the upper respiratory tract microbiota and inflammation under ammonia exposure.


Assuntos
Amônia/toxicidade , Bactérias/crescimento & desenvolvimento , Galinhas , Microbiota , Doenças das Aves Domésticas/induzido quimicamente , Traqueíte/veterinária , Amônia/administração & dosagem , Animais , Bactérias/classificação , Bactérias/genética , Masculino , Doenças das Aves Domésticas/microbiologia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/isolamento & purificação , Traqueia/microbiologia , Traqueia/patologia , Traqueíte/induzido quimicamente , Traqueíte/microbiologia
4.
Khirurgiia (Mosk) ; (2): 32-39, 2021.
Artigo em Russo | MEDLINE | ID: mdl-33570352

RESUMO

OBJECTIVE: To assess the tracheal elasticity and tracheal anastomosis tension for prevention of anastomosis-related complications and estimation of the maximum length of resection. MATERIAL AND METHODS: At the first stage, 20 patients with cicatricial tracheal stenosis underwent tracheoscopy in usual position, under maximum flexion and extension of the head for the period from September 2017 to December 2019. We measured the total length of trachea and length of stenotic segment. Tracheal extensibility was assessed considering the difference in measurements. At the second stage, anastomosis tension was intraoperatively measured using a dynamometer in normal head position, as well as at maximum flexion in 22 patients who underwent tracheal resection. Unlike multiple other studies, we studied tissue tension intraoperatively. RESULTS: Mean length of trachea was 12.8 cm, extensibility - 1.3 cm. Tracheal elasticity was greater in patients with a longer trachea and in patients under 40 years old. Mean length of resection was 3.9 cm (30% of mean length of trachea), anastomosis tension - 2.7 H or 270 g. Head flexion was followed by tension decrease by 0.7 H (26.9%), i.e. 70 g. This approach is less effective in case of resection of more than 30% of trachea length in a particular patient. CONCLUSION: Further experience in measurement of tracheal extensibility and anastomosis tension will make it possible to establish clinical significance of these indicators for prevention of complications.


Assuntos
Anastomose Cirúrgica/efeitos adversos , Elasticidade , Traqueia , Estenose Traqueal , Adulto , Cicatriz/patologia , Cicatriz/cirurgia , Constrição Patológica/patologia , Constrição Patológica/cirurgia , Endoscopia , Humanos , Tamanho do Órgão , Amplitude de Movimento Articular , Traqueia/patologia , Traqueia/cirurgia , Estenose Traqueal/diagnóstico , Estenose Traqueal/etiologia , Estenose Traqueal/cirurgia
5.
Pediatr Surg Int ; 37(2): 257-260, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33388965

RESUMO

PURPOSE: Congenital tracheal stenosis is a disease in which complete tracheal cartilage rings (CTCR) cause airway narrowing. Although tracheal cartilage malformation has been suggested as a cause of CTCR, no histological studies have been performed. Here, we report a comparison of the tissues from CTCR and normal tracheal cartilage. METHODS: Thirty-one infants who underwent slide tracheoplasty at our institution from May 2016 to August 2019 were included. Tissues from ten autopsy cases without tracheal lesions were used as controls. The survey items were tracheal cartilage cell density, cartilage thickness, and chondrocyte findings. RESULTS: The median cartilage cell density from cases was 23/125 × 125 µm2 and from controls was 23.5/125 × 125 µm2 (p = 0.90). The median cartilage thickness from cases was 689 µm and from controls was 840 µm (p = 0.11). Comparing the ventral and dorsal sides of the CTCR tissues, the cell density was significantly different (median ventral 23/125 × 125 µm2; median dorsal 19.5/125 × 125 µm2; p = 0.034). There were no significant findings in the chondrocytes of the CTCR tissues. CONCLUSION: CTCR tissues did not differ in cartilage density and thickness from normal tracheal cartilage.


Assuntos
Traqueia/patologia , Estenose Traqueal/patologia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Procedimentos Cirúrgicos Reconstrutivos/métodos , Traqueia/anormalidades , Traqueia/cirurgia , Estenose Traqueal/congênito , Estenose Traqueal/cirurgia , Resultado do Tratamento
6.
Am J Physiol Lung Cell Mol Physiol ; 320(4): L545-L556, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33501891

RESUMO

Obesity increases incidence and severity of asthma but the molecular mechanisms are not completely understood. Hyperinsulinemia potentiates vagally induced bronchoconstriction in obese rats. Since bronchoconstriction results from airway smooth muscle contraction, we tested whether insulin changed agonist-induced airway smooth muscle contraction. Obesity-prone and resistant rats were fed a low-fat diet for 5 wk and treated with insulin (Lantus, 3 units/rat sc) 16 h before vagally induced bronchoconstriction was measured. Ex vivo, contractile responses to methacholine were measured in isolated rat tracheal rings and human airway smooth muscle strips before and after incubation (0.5-2 h) with 100 nM insulin or 13.1 nM insulin like growth factor-1 (IGF-1). M2 and M3 muscarinic receptor mRNA expression was quantified by qRT-PCR and changes in intracellular calcium were measured in response to methacholine or serotonin in isolated rat tracheal smooth muscle cells treated with 1 µM insulin. Insulin, administered to animals 16 h prior, potentiated vagally induced bronchoconstriction in both obese-prone and resistant rats. Insulin, not IGF-1, significantly increased methacholine-induced contraction of rat and human isolated airway smooth muscle. In cultured rat tracheal smooth muscle cells, insulin significantly increased M2, not M3, mRNA expression and enhanced methacholine- and serotonin-induced increase in intracellular calcium. Insulin alone did not cause an immediate increase in intracellular calcium. Thus, insulin acutely potentiated agonist-induced increase in intracellular calcium and airway smooth muscle contraction. These findings may explain why obese individuals with hyperinsulinemia are prone to airway hyperreactivity and give insights into future targets for asthma treatment.


Assuntos
Hiper-Reatividade Brônquica/patologia , Broncoconstrição , Hiperinsulinismo/complicações , Insulina/efeitos adversos , Cloreto de Metacolina/farmacologia , Contração Muscular , Músculo Liso/patologia , Animais , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/metabolismo , Cálcio/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Agonistas Muscarínicos/farmacologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Obesidade/complicações , Ratos , Ratos Sprague-Dawley , Receptores Muscarínicos/metabolismo , Traqueia/efeitos dos fármacos , Traqueia/patologia , Nervo Vago/fisiopatologia
7.
Ecotoxicol Environ Saf ; 210: 111870, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33440271

RESUMO

Ammonia is the main harmful gas in livestock houses. However, the toxic mechanism of ammonia is still unclear. Therefore, we examined the effects of ammonia exposure on different tissues of fattening pigs by histological analysis and transcriptome techniques in this study. The results showed that there were varying degrees of pathological changes in liver, kidney, hypothalamus, jejunum, lungs, spleen, heart and trachea of fattening pigs under ammonia exposure. Notably, the extent of damage in liver, kidney, jejunum, lungs, hypothalamus and trachea was more severe than that in heart and spleen. Transcriptome results showed that ammonia exposure caused changes in 349, 335, 340, 229, 120, 578, 407 and 115 differentially expressed genes in liver, kidney, spleen, lung, trachea, hypothalamus, jejunum and heart, respectively. Interestingly, the changes in solute vector (SLC) family genes were found in all 8 tissues, and the verified gene results (SLC11A1, SLC17A7, SLC17A6, SLC6A4, SLC22A7, SLC25A3, SLC28A3, SLC7A2, SLC6A6, SLC38A5, SLC22A12, SLC34A1, SLC26A1, SLC26A6, SLC27A5, SLC22A8 and SLC44A4) were consistent with qRT-PCR results. In conclusion, ammonia exposure can cause pathological changes in many tissues and organs of fattening pigs and changes in the SCL family gene network. Importantly, the SCL family is involved in the toxic mechanism of ammonia. Our findings will provide a new insight for better assessing the mechanism of ammonia toxicity.


Assuntos
Amônia/toxicidade , Proteínas de Membrana Transportadoras/genética , Animais , Feminino , Redes Reguladoras de Genes/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Hipotálamo/patologia , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Jejuno/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Miocárdio/patologia , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Suínos , Traqueia/efeitos dos fármacos , Traqueia/metabolismo , Traqueia/patologia , Transcriptoma/efeitos dos fármacos
9.
Medicine (Baltimore) ; 99(50): e23586, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327320

RESUMO

RATIONALE: Tracheobronchial injury from acid ingestion is a less reported clinical presentation than injury of the gastrointestinal tract, but it can occur due to direct exposure from acid aspiration and cause fatal complications. PATIENT CONCERNS: A 43-year-old man presented to the emergency department after ingesting nitric acid complaining of chest pain and dyspnea. DIAGNOSES: The initial chest computed tomography (CT) images revealed an acute lung injury related to acid aspiration. The follow-up chest CT showed acute and late tracheobronchial injures. INTERVENTIONS: Bronchoscopy showed deep caustic airway injuries consisting of hemorrhage, sloughing of the mucosa, and ulceration of the trachea and left-side bronchial tree. OUTCOMES: Progressive narrowing of the left main bronchus with total collapse of the left lung occurred as a late complication of acid ingestion. LESSONS: Tracheobronchial injury should be considered in cases of aspiration pneumonia after acid ingestion; chest CT can be used to detect and assess acute and late complications of tracheobronchial injuries.


Assuntos
Brônquios/lesões , Queimaduras Químicas/diagnóstico , Ácido Nítrico/toxicidade , Tentativa de Suicídio , Traqueia/lesões , Adulto , Brônquios/patologia , Broncoscopia , Queimaduras Químicas/complicações , Queimaduras Químicas/diagnóstico por imagem , Dor no Peito/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Tomografia Computadorizada por Raios X , Traqueia/patologia
10.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(11): 947-952, 2020 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-33137861

RESUMO

Objective: To explore the clinical characteristics of non-tuberculous mycobacterium(NTM) pulmonary disease complicated with tracheobronchial lesions. Methods: From January 2014 to December 2018, there were 1 006 patients who were admitted to Guangzhou Chest Hospital for the first time and received examination by bronchoscopy. A total of 89 patients with complete data were selected, including 40 males and 49 females, aged 20 to 85 years, with 46 patients (52%) aged 60 years or older. The clinical symptoms and signs of the patients were analyzed with chest imaging, bronchoscopy and pathological examination results. Comparisons between groups were made by Chi-square test and t test. Results: The number of patients with NTM complicated with tracheobronchial lesions accounted for 8.9%(89/1 006) of those hospitalized with NTM and received bronchoscopy during the same period. Clinical symptoms included cough and sputum (89/89), different degrees of hemoptysis or blood sputum (52/89), and shortness of breath (50/89). Chest CT showed that 72 cases (72/89, 81%) had lung lesions involving more than 3 lung fields, and 83 cases (93%) had bronchiectasis and 63 cases (63/89, 71%) with cavities. Pulmonary atelectasis was shown in 45 cases (45/89, 51%). By bronchoscopy, 39 cases (39/89, 44%) were diagnosed as tuberculous lesions involving bilateral upper bronchi, while lesions of the right lower bronchus was found in 27 cases (27/89, 30%).The percentage of patients with multilobar bronchial involvement was 50.6%(45/89). The morphological characteristics of the bronchial lesions included scar stenosis or atresia in 63 cases (63/89, 71%), hyperemia and edema in 46 cases (46/89, 52%), and multiple types of lesions in 48 cases (48/89, 54%). Conclusions: Patients with NTM lung disease complicated with tracheobronchial inflammatory lesions did not have specific manifestations clinically. Lung lesions are extensive, often accompanied by bronchiectasis and cavity formation. Endoscopic changes were mostly manifested as multilobar tracheobronchial involvement characterized by scar stenosis, congestion and edema, mainly involving bilateral upper bronchi and the right lower bronchus.


Assuntos
Brônquios/patologia , Infecções por Mycobacterium não Tuberculosas/patologia , Traqueia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Brônquios/diagnóstico por imagem , Broncoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micobactérias não Tuberculosas , Traqueia/diagnóstico por imagem , Adulto Jovem
11.
Medicine (Baltimore) ; 99(43): e22351, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120736

RESUMO

Asthma is a chronic inflammatory and multifactorial respiratory tract disease. It affects over 18 million adults and 6 million children in the USA with Puerto Ricans showing the highest prevalence (12%-19%). This airways illness can be triggered by an environmental stimulus such as grass pollen, fungi spores, cockroaches allergens, dust mites metabolic compounds, and importantly, by environmental proteases such as trypsin and tryptase. Because of the pivotal role of proteases in the onset of asthma pathophysiology, we focused this study on the serine Protease Activated Receptor-2 (PAR-2), a G-protein-coupled receptor widely expressed in cells across the respiratory tract. Herein, we measured the activation of PAR-2 on primary pulmonary bronchial/tracheal epithelial cells, human small airway epithelial cells, lung bronchial smooth muscle cells (with and without asthma). We tested human-derived eosinophils from 61 Puerto Rican participants (33 asthmatic and 28 non-asthmatic). As surrogate of PAR-2 activation or inhibition we used intracellular calcium mobilization assay. We hypothesized that following exposure of the PAR-2 agonist (AC264613), the studied human primary cell types will increase the mobilization of intracellular calcium levels. In contrast, we expected a decrease of the intracellular calcium levels upon exposure to a PAR-2 antagonist (FSLLRY-NH2). The Puerto Rican-derived eosinophils were analyzed for the proinflammatory markers MAPK/PI3K using flow cytometry (n = 8). As expected, the PAR-2 agonist significantly increased the activation of PAR-2 on the bronchial/tracheal epithelial cells, bronchial smooth muscle cells and human small airway epithelial cells (P = .01). The PAR-2 antagonist significantly decreased the intracellular calcium levels of these lung primary down to undetectable levels (P = .01). Remarkably, the asthmatic-derived eosinophils showed a striking 300% increase of intracellular calcium mobilization suggesting a severe response to the PAR-2 agonist stimuli in asthmatics. In contrast, there were no significant changes between groups after adding the PAR-2 antagonist. Our outcomes revealed that PAR-2 antagonist effectively inhibited the studied primary cells, expecting to decrease the immune response of eosinophils. Most importantly, our results reveal a promising role for the PAR-2 antagonist in targeting bronchial/tracheal epithelial cells, human small airway epithelial cells and bronchial smooth muscle cells with the potential to oblige an asthma adjuvant therapy.


Assuntos
Asma/tratamento farmacológico , Receptor PAR-2/antagonistas & inibidores , Asma/metabolismo , Biomarcadores/metabolismo , Brônquios/patologia , Cálcio/metabolismo , Sinalização do Cálcio , Células Cultivadas , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Citometria de Fluxo , Humanos , Pulmão/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Músculo Liso/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Receptor PAR-2/agonistas , Receptor PAR-2/metabolismo , Transdução de Sinais , Traqueia/patologia
12.
Khirurgiia (Mosk) ; (10): 5-10, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33047580

RESUMO

Currently, a single classification of cicatricial tracheal stenosis is absent in national and world surgical practice. This issue is actual considering anatomical variability of tracheal structure in people with different constitutional features and previous complications. The proposed classification ensures individualized approach in surgical treatment of patients with cicatricial tracheal stenosis considering anatomical features in a particular patient.


Assuntos
Traqueia/anatomia & histologia , Traqueia/patologia , Estenose Traqueal/classificação , Cicatriz/patologia , Cicatriz/cirurgia , Constrição Patológica/patologia , Constrição Patológica/cirurgia , Humanos , Estenose Traqueal/cirurgia
13.
Can J Vet Res ; 84(3): 163-171, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32801450

RESUMO

Bovine respiratory disease complex is etiologically complex and usually involves co-infection by several agents, including bovine parainfluenza virus-3 (BPIV-3), bovine respiratory syncytial virus (BRSV), and bovine coronavirus (BCoV). Traditionally, vaccines have been tested in seronegative calves infected with a single in vitro-passaged agent, often with little disease, resulting in unvaccinated subjects. To overcome the potential problem of attenuation coincident with in vitro culture of the viruses, cocktails of field isolates of BPIV-3s and BCoVs were passaged in the lungs of neonatal colostrum-deprived calves. Lung lavage fluids were used as inocula, alone and in combination with in-vivo passaged BRSV, and aerosolized into a trailer containing conventionally reared 9-week-old weaned Holstein calves with decayed, but still measurable, maternal antibodies. Calves developed acute respiratory disease of variable severity. Upon necropsy, there were characteristic gross and histologic lesions in the respiratory tract, associated immunohistochemically with BPIV-3, BRSV, and BCoV. In-vivo passage of viruses is an alternative to in vitro culture to produce inocula to better study the pathogenesis of infection and more rigorously and relevantly assess vaccine efficacy.


Assuntos
Doenças dos Bovinos/virologia , Infecções por Coronavirus/veterinária , Coronavirus Bovino/patogenicidade , Vírus da Parainfluenza 3 Bovina/patogenicidade , Infecções por Vírus Respiratório Sincicial/veterinária , Infecções por Respirovirus/veterinária , Animais , Anticorpos Antivirais/sangue , Antígenos Virais/isolamento & purificação , Bovinos , Doenças dos Bovinos/patologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Coronavirus Bovino/isolamento & purificação , Imuno-Histoquímica/veterinária , Pulmão/patologia , Pulmão/virologia , Vírus da Parainfluenza 3 Bovina/imunologia , Vírus da Parainfluenza 3 Bovina/isolamento & purificação , Atelectasia Pulmonar/patologia , Atelectasia Pulmonar/veterinária , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Vírus Sinciciais Respiratórios/patogenicidade , Infecções por Respirovirus/complicações , Infecções por Respirovirus/patologia , Infecções por Respirovirus/virologia , Traqueia/patologia , Traqueia/virologia
14.
Lancet ; 396(10247): 320-332, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682491

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism. METHODS: In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR. FINDINGS: The median age of our cohort was 73·5 years (range 42-84; IQR 67·5-77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue. INTERPRETATION: The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination. FUNDING: None.


Assuntos
Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/ultraestrutura , Células Epiteliais Alveolares/virologia , Autopsia , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Feminino , Trato Gastrointestinal/patologia , Trato Gastrointestinal/ultraestrutura , Trato Gastrointestinal/virologia , Coração/virologia , Humanos , Rim/patologia , Rim/ultraestrutura , Rim/virologia , Fígado/patologia , Fígado/ultraestrutura , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Miocárdio/ultraestrutura , Pandemias , Pneumonia Viral/epidemiologia , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/ultraestrutura , Mucosa Respiratória/patologia , Mucosa Respiratória/ultraestrutura , Mucosa Respiratória/virologia , Baço/patologia , Baço/ultraestrutura , Baço/virologia , Trombose/patologia , Traqueia/patologia , Traqueia/ultraestrutura , Traqueia/virologia , Washington/epidemiologia
15.
Nanotoxicology ; 14(7): 908-928, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32574512

RESUMO

Silver nanoparticles (AgNP) are used in multiple applications but primarily in the manufacturing of antimicrobial products. Previous studies have identified AgNP toxicity in airway epithelial cells, but no in vitro studies to date have used organotypic cultures as a high-content in vitro model of the conducting airway to characterize the effects of interactions between host genetic and acquired factors, or gene × phenotype interactions (G × P), on AgNP toxicity. In the present study, we derived organotypic cultures from primary murine tracheal epithelial cells (MTEC) to characterize nominal and dosimetric dose-response relationships for AgNPs with a gold core on barrier dysfunction, glutathione (GSH) depletion, reactive oxygen species (ROS) production, lipid peroxidation, and cytotoxicity across two genotypes (A/J and C57BL/6J mice), two phenotypes ('Normal' and 'Type 2 [T2]-Skewed'), and two exposures (an acute exposure of 24 h and a subacute exposure of 4 h, every other day, over 5 days [5 × 4 h]). We characterized the 'T2-Skewed' phenotype as an in vitro model of chronic respiratory diseases, which was marked by increased sensitivity to AgNP-induced barrier dysfunction, GSH depletion, ROS production, lipid peroxidation, and cytotoxicity, suggesting that asthmatics are a sensitive population to AgNP exposures in occupational settings. This also suggests that exposure limits, which should be based upon the most sensitive population, should be derived using in vitro and in vivo models of chronic respiratory diseases. This study highlights the importance of considering dosimetry as well as G × P effects when screening and prioritizing potential respiratory toxicants. Such in vitro studies can be used to inform regulatory policy aimed at special protections for all populations.


Assuntos
Antibacterianos/toxicidade , Células Epiteliais/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Traqueia/efeitos dos fármacos , Animais , Antibacterianos/química , Técnicas de Cultura de Células , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Genótipo , Glutationa/metabolismo , Ouro/química , Ouro/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Espécies Reativas de Oxigênio/metabolismo , Prata/química , Propriedades de Superfície , Traqueia/metabolismo , Traqueia/patologia
16.
Arq. bras. med. vet. zootec. (Online) ; 72(3): 799-806, May-June, 2020. ilus, tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1129181

RESUMO

The purpose of this study was to verify the applicability of the compressive radiographic technique (pressures of 5, 10, 15 and 20mmHg) in the diagnosis of tracheal collapse in small breed dogs, in lateral cervicothoracic radiography. Out of the 50 dogs evaluated, 25 presented tracheal collapse (TG group), 23 did not present tracheal collapse (CG) and two were excluded because they did not tolerate a pressure of 20 mmHg. The TG group presented a smaller internal diameter of the trachea in the region of the fourth cervical vertebra (D4) and at the entrance of the thorax (TDE) compared to the CG group, in all the radiographic projections performed, as well as within the TG group where the compressive technique differed from conventional. Furthermore, there was a correlation between the clinical sign of coughing during cervical collar use and the presence of radiographic tracheal collapse at a pressure of 20 mmHg. It was concluded that the compressive radiographic technique was feasible and efficient in confirming the diagnosis of tracheal collapse in dogs, especially in the pressure of 20 mmHg, where it was associated with clinical signs, and can be used in isolation or complementary to the conventional technique.(AU)


O objetivo deste trabalho foi verificar a aplicabilidade da técnica radiográfica compressiva no diagnóstico do colapso de traqueia em cães de raças pequenas, por meio da comparação do diâmetro da traqueia durante a radiografia cervicotorácica lateral convencional e sobre influência da compressão externa com pressões de 5, 10, 15 e 20mmHg (técnica compressiva). Dos 50 cães avaliados, 25 apresentaram colapso de traqueia (grupo TG), 23 não apresentaram o colabamento traqueal (grupo controle - CG) e dois foram excluídos por não tolerarem a pressão de 20mmHg. Os diâmetros internos da traqueia na região da quarta vértebra cervical (D4) e na entrada do tórax (DET) foram menores no grupo TG em relação ao CG, em todas as projeções radiográficas realizadas, bem como dentro do grupo TG, no qual a técnica compressiva diferiu da convencional. Houve correlação entre o sinal clínico de tosse durante o uso de coleira cervical e a presença do colapso de traqueia radiográfico, na pressão de 20mmHg. Concluiu-se que a técnica radiográfica compressiva foi exequível e eficiente na confirmação do diagnóstico do colapso de traqueia em cães, especialmente na pressão de 20mmHg, em que houve associação com sinais clínicos, podendo ser utilizada de forma isolada ou complementar à técnica convencional.(AU)


Assuntos
Animais , Cães , Traqueia/patologia , Traqueia/diagnóstico por imagem , Tosse/veterinária , Radiografia/métodos , Radiografia Torácica/veterinária , Medula Cervical/diagnóstico por imagem
17.
Heart Lung ; 49(6): 855-857, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425272

RESUMO

A 51-year-old man known to be affected by Mounier-Kuhn syndrome (MKS). presented to Accident & Emergecy (A&E) with fever, dyspnea and deterioration of his chronic coughs. Increased diameters of his trachea (39 mm), right (30 mm) and left (26 mm) main bronchi were revealed by chest computerized tomography (CT) scan. CT scan showed also ground-glass opacities (GGO) and bronchiectasis in the mid and lower zones of both lungs. COIVD-19 infection was eventually confirmed by RT-PCR. A severe form of COVID-19 could occur even in the early stages of the disease in presence of underlying co-morbidities including MKS, which increases the susceptibility to more recurrent and severe respiratory infections.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Traqueobroncomegalia/complicações , Dispneia/etiologia , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Tomografia Computadorizada por Raios X , Traqueia/patologia
18.
Immunity ; 52(4): 683-699.e11, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32294408

RESUMO

Mucociliary clearance through coordinated ciliary beating is a major innate defense removing pathogens from the lower airways, but the pathogen sensing and downstream signaling mechanisms remain unclear. We identified virulence-associated formylated bacterial peptides that potently stimulated ciliary-driven transport in the mouse trachea. This innate response was independent of formyl peptide and taste receptors but depended on key taste transduction genes. Tracheal cholinergic chemosensory cells expressed these genes, and genetic ablation of these cells abrogated peptide-driven stimulation of mucociliary clearance. Trpm5-deficient mice were more susceptible to infection with a natural pathogen, and formylated bacterial peptides were detected in patients with chronic obstructive pulmonary disease. Optogenetics and peptide stimulation revealed that ciliary beating was driven by paracrine cholinergic signaling from chemosensory to ciliated cells operating through muscarinic M3 receptors independently of nerves. We provide a cellular and molecular framework that defines how tracheal chemosensory cells integrate chemosensation with innate defense.


Assuntos
Acetilcolina/imunologia , Proteínas de Bactérias/farmacologia , Cílios/imunologia , Depuração Mucociliar/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Canais de Cátion TRPM/imunologia , Traqueia/imunologia , Acetilcolina/metabolismo , Animais , Proteínas de Bactérias/imunologia , Transporte Biológico , Cílios/efeitos dos fármacos , Cílios/metabolismo , Feminino , Formiatos/metabolismo , Expressão Gênica , Humanos , Imunidade Inata , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Optogenética/métodos , Comunicação Parácrina/imunologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Receptor Muscarínico M3/genética , Receptor Muscarínico M3/imunologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/imunologia , Canais de Cátion TRPM/deficiência , Canais de Cátion TRPM/genética , Papilas Gustativas/imunologia , Papilas Gustativas/metabolismo , Traqueia/efeitos dos fármacos , Traqueia/patologia , Virulência
19.
Microbiol Immunol ; 64(6): 469-475, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32227523

RESUMO

We performed RNA sequencing on Bordetella pertussis, the causative agent of whooping cough, and identified nine novel small RNAs (sRNAs) that were transcribed during the bacterial colonization of murine tracheas. Among them, four sRNAs were more strongly expressed in vivo than in vitro. Moreover, the expression of eight sRNAs was not regulated by the BvgAS two-component system, which is the master regulator for the expression of genes contributing to the bacterial infection. The present results suggest a BvgAS-independent gene regulatory system involving the sRNAs that is active during B. pertussis infection.


Assuntos
Bordetella pertussis , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética , Traqueia/microbiologia , Coqueluche/microbiologia , Animais , Proteínas de Bactérias/genética , Bordetella pertussis/genética , Bordetella pertussis/patogenicidade , Regulação Bacteriana da Expressão Gênica/genética , Genes Reguladores/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traqueia/patologia , Fatores de Transcrição/genética , Virulência/genética , Fatores de Virulência de Bordetella/genética
20.
Int J Pediatr Otorhinolaryngol ; 134: 110020, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32251974

RESUMO

OBJECTIVES: To determine the relationship between body mass index and tracheal airway size in children. METHODS: Retrospective case series. CT or MRI images of the neck of 171 pediatric patients obtained from 2000 to 2010 at a tertiary pediatric hospital were analyzed. Age, gender, height, weight, BMI and CDC weight classification for each patient were compared with axial CT measurements (AP diameter and width) and calculated cross-sectional airway area. Linear regression models were performed to identify factors predictive of airway size. RESULTS: Age ranged from 2 to 20 years. Weight was the most significant predictor of tracheal AP diameter (P = 0.029), with height also approaching statistical significance (P = 0.051). Tracheal width was best predicted by height (P = 0.09). Weight was the only statistically significant predictor of cross-sectional tracheal area (P = 0.002). Body mass index was not a statistically significant predictor of airway size in any dimension; however, there was an obvious trend towards decreasing tracheal width and cross-sectional area in patients with BMI of 25 or greater. CONCLUSION: In pediatric patients, estimation of endotracheal or tracheostomy tube size should take into account height, weight and BMI in addition to the patient's age. Patients with elevated BMI may have smaller tracheal sizes in various dimensions than normal or low-weight patients.


Assuntos
Intubação Intratraqueal/instrumentação , Tamanho do Órgão , Traqueia/patologia , Traqueostomia/instrumentação , Adolescente , Índice de Massa Corporal , Peso Corporal , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Traqueia/diagnóstico por imagem , Adulto Jovem
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