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1.
Khirurgiia (Mosk) ; (5): 49-57, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32500689

RESUMO

OBJECTIVE: To evaluate an effectiveness of endobronchial valve treatment of patients with bronchopleural fistulas and prolonged air leakage. MATERIAL AND METHODS: Endobronchial valve treatment was analyzed in 115 patients with bronchopleural fistulas or postoperative air leakage. All patients were divided into 5 groups depending on disease: bullous emphysema, acute purulent lung diseases, chronic purulent lung and pleural diseases, bullous emphysema complicated by pneumothorax with failed pleural cavity, other lung diseases associated with prolonged postoperative air leakage. RESULTS: Endobronchial valve treatment was effective in more than 70% patients. There were no intraoperative and postoperative complications. CONCLUSION: Endobronchial valve treatment is a highly effective minimally invasive method for treating patients with bronchopleural fistulas and postoperative air leakage.


Assuntos
Fístula Anastomótica/cirurgia , Fístula Brônquica/cirurgia , Broncoscopia/métodos , Pneumopatias/cirurgia , Doenças Pleurais/cirurgia , Fístula Anastomótica/etiologia , Brônquios/cirurgia , Fístula Brônquica/etiologia , Humanos , Pneumopatias/etiologia , Doenças Pleurais/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fístula do Sistema Respiratório/etiologia , Fístula do Sistema Respiratório/cirurgia , Supuração/etiologia , Supuração/cirurgia
2.
Medicine (Baltimore) ; 99(22): e20246, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481391

RESUMO

RATIONALE: Left bronchial isomerism is generally associated with abnormal arrangement of the atrium and abdominal viscera; therefore, its diagnosis is confirmed in early childhood. PATIENT CONCERNS: Here we report a rare case involving a 36-year-old man with isolated left bronchial isomerism that presented as an asymptomatic severe obstructive ventilatory disturbance during pulmonary function tests performed as part of routine assessments for an orbital wall fracture. The patient was a current smoker and did not show any respiratory symptoms. DIAGNOSIS: Chest computed tomography revealed left bronchial isomerism, and further tests showed that there was no involvement of other organs. INTERVENTIONS: We recommended smoking cessation and the long-term use of an inhaled long-acting bronchodilator. OUTCOMES: The findings from this case highlight the causative role of left bronchial isomerism in asymptomatic adults with chronic obstructive pulmonary disease. LESSONS: Physicians should consider this condition as a cause of obstructive ventilatory disturbances in asymptomatic adult patients.


Assuntos
Doenças Assintomáticas , Brônquios/anormalidades , Achados Incidentais , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Adulto , Brônquios/diagnóstico por imagem , Humanos , Masculino , Testes de Função Respiratória , Tomografia Computadorizada por Raios X
3.
Medicine (Baltimore) ; 99(22): e20480, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481458

RESUMO

Foreign body (FB) aspiration is a common and serious problem in childhood as it requires early recognition and treatment to avoid potentially lethal consequences. This study aimed to characterize the clinical and epidemiological features of airway FBs in a pediatric Chinese population.A retrospective review of medical records of children aged 0 to 14 years who attended with a diagnosis of FB aspiration the Shanghai Children's Hospital between January 2013 and December 2017 was carried out. Descriptive analysis was used to assess patient's demographics, clinical, radiographic, bronchoscopic findings, time to presentation, and characteristics of the FBs.Among the 200 patients included in the study, 92% were under 3 years of age, with a peak incidence of FB aspiration occurring between 1 and 2 years old. The male to female ratio was about 2.6:1. Twenty-three percent of the patients were admitted within 24 hours of the event, 40% within 1 week, 30% within 1 month, and 7% more than 1 month after aspiration. The most common presenting symptoms of laryngotracheal FBs were cough, dyspnea, and wheezing; those of bronchial FBs were cough, decreased air entry, and wheezing. Chest X-ray was normal in four-fifths of the children with laryngotracheal FBs, whereas most common abnormal X-ray findings in children with bronchial FBs were mediastinal shift, obstructive emphysema, and pneumonia. There was a trend that in children younger than 2 years FBs were more frequently found in the left bronchus, whereas in older children FBs were more frequently found in the right bronchus. Ninety-three percent of the removed FBs were organic materials such as food items and the most frequently aspirated FBs were peanuts. Flexible bronchoscopy was performed in 82.5% of the patients, while rigid bronchoscopy or direct laryngoscopy in 17.5% of the patients. Four patients were subjected to thoracic surgery and 1 died during rigid bronchoscopy due to acute respiratory failure.FBs is a frequent pathology among Chinese children. Tracheobronchial FBs should be strongly suspected in young children who have sudden onset of cough and wheezing episode, even when physical and radiographic evidence is absent.


Assuntos
Corpos Estranhos/diagnóstico , Aspiração Respiratória/diagnóstico , Adolescente , Brônquios , Broncoscopia , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Corpos Estranhos/epidemiologia , Corpos Estranhos/terapia , Humanos , Incidência , Lactente , Recém-Nascido , Laringoscopia , Masculino , Aspiração Respiratória/epidemiologia , Aspiração Respiratória/terapia , Estudos Retrospectivos , Traqueia
4.
J Renin Angiotensin Aldosterone Syst ; 21(2): 1470320320928872, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32490715

RESUMO

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin-angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV. METHODS: Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set. RESULTS: The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours were analyzed, and a total of 15 RAS family and 29 immune genes were found to be highly correlated with the exposure time to the virus in the studied groups. CONCLUSION: RAS genes are important at the initiation of the infections caused by coronavirus family members and may have a strong relationship with the exchange of immune genes in due course following the infection.


Assuntos
Betacoronavirus/fisiologia , Brônquios/patologia , Infecções por Coronavirus/genética , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Inflamação/genética , Pneumonia Viral/genética , Sistema Renina-Angiotensina/genética , Análise por Conglomerados , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Genoma Humano , Humanos , Inflamação/patologia , Modelos Lineares , Pandemias , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
5.
Respir Res ; 21(1): 125, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448391

RESUMO

BACKGROUND: A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia were discharged from hospitals in Wuhan, China. We aimed to determine the cumulative percentage of complete radiological resolution at each time point, to explore the relevant affecting factors, and to describe the chest CT findings at different time points after hospital discharge. METHODS: Patients with COVID-19 pneumonia confirmed by RT-PCR who were discharged consecutively from the hospital between 5 February 2020 and 10 March 2020 and who underwent serial chest CT scans on schedule were enrolled. The radiological characteristics of all patients were collected and analysed. The total CT score was the sum of non-GGO involvement determined at discharge. Afterwards, all patients underwent chest CT scans during the 1st, 2nd, and 3rd weeks after discharge. Imaging features and distributions were analysed across different time points. RESULTS: A total of 149 patients who completed all CT scans were evaluated; there were 67 (45.0%) men and 82 (55.0%) women, with a median age of 43 years old (IQR 36-56). The cumulative percentage of complete radiological resolution was 8.1% (12 patients), 41.6% (62), 50.3% (75), and 53.0% (79) at discharge and during the 1st, 2nd, and 3rd weeks after discharge, respectively. Patients ≤44 years old showed a significantly higher cumulative percentage of complete radiological resolution than patients > 44 years old at the 3-week follow-up. The predominant patterns of abnormalities observed at discharge were ground-glass opacity (GGO) (125 [83.9%]), fibrous stripe (81 [54.4%]), and thickening of the adjacent pleura (33 [22.1%]). The positive count of GGO, fibrous stripe and thickening of the adjacent pleura gradually decreased, while GGO and fibrous stripe showed obvious resolution during the first week and the third week after discharge, respectively. "Tinted" sign and bronchovascular bundle distortion as two special features were discovered during the evolution. CONCLUSION: Lung lesions in COVID-19 pneumonia patients can be absorbed completely during short-term follow-up with no sequelae. Two weeks after discharge might be the optimal time point for early radiological estimation.


Assuntos
Infecções por Coronavirus/complicações , Pneumopatias/etiologia , Pneumopatias/terapia , Pulmão/diagnóstico por imagem , Pneumonia Viral/complicações , Adulto , Fatores Etários , Brônquios/diagnóstico por imagem , Infecções por Coronavirus/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Pneumopatias/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Alta do Paciente , Pleura/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
7.
EMBO J ; 39(10): e105114, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32246845

RESUMO

The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis.


Assuntos
Brônquios/citologia , Expressão Gênica , Pulmão/citologia , Peptidil Dipeptidase A/genética , Serina Endopeptidases/genética , Análise de Célula Única , Adulto , Envelhecimento , Brônquios/metabolismo , Células Cultivadas , Doença Crônica/epidemiologia , Infecções por Coronavirus/genética , Células Epiteliais/metabolismo , Feminino , Perfilação da Expressão Gênica , Alemanha , Células Caliciformes/metabolismo , Humanos , Pulmão/metabolismo , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/genética , Padrões de Referência , Análise de Sequência de RNA , Caracteres Sexuais , Fumar , Bancos de Tecidos
8.
Med Sci Monit ; 26: e922149, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32284524

RESUMO

BACKGROUND Leonurine is an active component of the traditional Chinese medicine Leonurus japonicus. This study aimed to investigate the effects of overexpressed CYP450s on the metabolic activity of leonurine. MATERIAL AND METHODS BEAS-2B cells stably expressing CYP1A1, 1A2, 2A13, 2B6, and 3A4 were constructed. CYP450s expression was identified using reverse-transcription PCR and Western blot assay. CCK-8 assay was used to evaluate the effect of leonurine on cell activity. Leonurine was incubated in vitro with CYP1A1, 1A2, 2A13, 2B6, and 3A4 metabolic enzymes to evaluate the clearance rate of CYP450 enzymes for leonurine. UPLC-MS was used to detect changes of drug concentration and discover the main metabolic enzymes affecting leonurine. RESULTS BEAS-2B cells stably expressing CYP1A1, 1A2, 2A13, 2B6, and 3A4 were successfully constructed. According to primary mass spectra and secondary mass spectra of leonurine, the main metabolic enzymes were 312.1550 [H+] and 181.0484. Compared to the control group, residue of leonurine in CYP2A13 group was significantly reduced (F=5.307, p=0.024). Compared to the 0-min group, the clearance rate of leonurine in the CYP2A13-treated group was significantly decreased at 120 min after treatment (F=7.273, p=0.007). CCK-8 results also showed that activity of BEAS-2B cells that overexpress CYP2A13 gradually decreased with increased concentration of leonurine. Although CYP2A13 demonstrated good metabolic activity for leonurine, we found that CYP1A1, 1A2, 2B6, and 3A4 had no metabolic effects on leonurine. CONCLUSIONS Leonurine can be effectively activated through CYP2A13 enzyme metabolism, and further inhibits activity of human lung epithelial cells (BEAS-2B). Therefore, CYP2A13 is a main metabolic enzyme for leonurine in BEAS-2B cells.


Assuntos
Hidrocarboneto de Aril Hidroxilases/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Ácido Gálico/análogos & derivados , Brônquios/citologia , Linhagem Celular , Ácido Gálico/farmacologia , Humanos , Inativação Metabólica
9.
Zhonghua Shao Shang Za Zhi ; 36(4): 252-259, 2020 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-32340414

RESUMO

Objective: To explore the clinical effects of fiberoptic bronchoscopy airway lavage (FBAL) in the treatment of extremely severe burn patients with severe inhalation injury. Methods: From January 2015 to January 2019, 47 extremely severe burn patients with severe inhalation injury who were hospitalized in Tongren Hospital of Wuhan University & Wuhan Third Hospital, meeting the inclusion criteria, were recruited in this retrospective cohort study. According to whether or not they were treated with FBAL, the patients were divided into fiberoptic bronchoscopy group (23 cases, 19 males and 4 females) and routine group (24 cases, 20 males and 4 females), with the age of (44±11) and (49±9) years, and the admission time of 4 (3, 4) h and 4 (3, 5) h respectively. The patients in routine group were given routine comprehensive treatment, and the patients in fiberoptic bronchoscopy group were treated with FBAL on the basis of routine comprehensive treatment. The pH value, arterial partial pressure of oxygen (PaO(2)), arterial partial pressure of carbon dioxide (PaCO(2)), arterial oxygen saturation (SaO(2)), oxygenation index, white blood cell count (WBC), neutrophils, blood lactic acid, and procalcitonin (PCT) at admission and on post injury day (PID) 3, 5, 7, and 10, the time of mechanical ventilation, the day of intensive care unit (ICU) stay, the incidence of complications and death within PID 28 were compared between the two study groups. The occurrences of bronchospasm and asphyxia of patients in fiberoptic bronchoscopy group were monitored. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, Bonferroni correction, chi-square test, and Fisher's exact probability test. Results: (1) At admission, the values of pH, PaO(2), PaCO(2), SaO(2), and oxygenation index of patients in the two groups were similar (Z=-0.118, -0.320, -0.362, -2.416, -0.234, P>0.05). On PID 3, 5, 7, and 10, the values of pH, PaO(2), SaO(2), and oxygenation index of patients in fiberoptic bronchoscopy group were significantly higher than those of routine group (Z(3 d)=-4.711, -4.161, -5.525, -2.661; Z(5 d)=-3.489, -4.678, -5.875, -3.599; Z(7 d)=-5.104, -4.619, -5.876, -4.844; Z(10 d)=-4.026, -5.698, -5.877, -4.716; P<0.05 or P<0.01). The PaCO(2) values of patients in fiberoptic bronchoscopy group were significantly lower than those of routine group (Z=-2.895, -3.162, -3.407, -2.831, P<0.05 or P<0.01). (2) At admission and on PID 3, 5, and 7, the values of WBC, blood lactic acid, and PCT of patients in the two groups were similar (Z=-0.830, -0.915, -0.458, -0.648, -1.714, -1.479; -0.330, -0.128, -1.766, -0.494, -1.396, -1.522, P>0.05). On PID 10, the values of WBC, blood lactic acid, and PCT of patients in fiberoptic bronchoscopy group were significantly lower than those of routine group (Z=-3.502, -2.630, -2.662, P<0.05 or P<0.01). At admission, the value of neutrophils of patients in fiberoptic bronchoscopy group was 0.887 (0.862, 0.912), which was similar to 0.887 (0.856, 0.897) in routine group (Z=-0.404, P>0.05). On PID 3, 5, 7, and 10, the values of neutrophils of patients in fiberoptic bronchoscopy group were respectively 0.848 (0.802, 0.867), 0.831 (0.815, 0.849), 0.798 (0.771, 0.849), 0.796 (0.751, 0.869), which were significantly lower than those of routine group [0.882 (0.820, 0.906), 0.871 (0.835, 0.903), 0.845 (0.819, 0.905), 0.881 (0.819, 0.916), Z=-2.756, -2.810, -2.618, -3.033, P<0.05]. (3) The time of mechanical ventilation and the days of ICU stay of patients were shorter in fiberoptic bronchoscopy group than those in routine group (Z=-2.199, t=2.368, P<0.05). Within PID 28, the number of patients with complications was significantly less in fiberoptic bronchoscopy group than in routine group (χ(2)=5.436, P<0.05), while the incidence of death within PID 28 in fiberoptic bronchoscopy group was similar to that of routine group (P>0.05). The airway lavage procedures of patients in fiberoptic bronchoscopy group went well with no bronchospasm or asphyxia occurred. Conclusions: FBAL is effective in treating extremely severe burn patients combined with severe inhalation injury. It can improve the oxygenation status of the lung, reduce the systemic inflammatory reaction of patients, shorten the time of mechanical ventilation and ICU stay, and reduce the incidence of complications.


Assuntos
Broncoscopia , Queimaduras , Adulto , Brônquios , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Irrigação Terapêutica
10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(2): 171-177, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32220184

RESUMO

Objective: To investigate the effects of dihydroartemis (DHA) on influenza A virus (IAV) A/PR/8/34 (H1N1) induces the pro-inflammatory factor and protein of extracellular signal regulated kinase (ERK) signaling pathway expression in bronchial epithelial cells. Methods: The BEAS-2B cells were treated with different concentrations of DHA (i.e.,0, 12.5, 25,50 and 100 µmol/L) for 24 h and the effect of DHA on the viability of BEAS-2B cells were measure by CCK8 method. The BEAS-2B cells were absorbed with IAV for 1 h, and then were treated with different concentrations of DHA (i.e., 12.5, 25 and 50 µmol/L) for 24 h, meanwhile, the normal control group and IAV group were established. The mRNA and protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin (IL-6) were measured by real time quantitative PCR (RT-qPCR) and enzyme linked immunosorbent assay (ELISA), the expression levels of phospho-ERK (p-ERK) proteins were tested by Western blot (WB). Then, an ERK agonist (20 ng/mL) was used to treat BEAS-2B cells (the groups were divided into normal control group, DHA group, DHA+IAV group, ERK agonist group and DHA+IAV+ERK agonist group) for 24 h, and to observe the effect of DHA on inhibiting IAV induce the TNF-α, IL-6 and p-ERK expression in the BEAS-2B cells. Results: The BEAS-2B cells viability was not significantly different from that of the normal control group after treatment with DHA (i.e., 12.5, 25, and 50 µmol/L). The expression levels of TNF-α, IL-6 mRNA and TNF-α, IL-6, p-ERK protein in IAV group were significantly up-regulated compared with that in the normal control group ( P<0.05), meanwhile, compared with the IAV group, the expression levels of TNF-α, IL-6 mRNA and TNF-α, IL-6, p-ERK protein showed dose-dependent decrease in IAV+DHA group ( P<0.05). However, ERK agonists attenuated the DHA inhibit IAV induced the proinflammatory factors TNF-α, IL-6 secretion and the p-ERK protein expression of ERK signaling pathway in BEAS-2B cells. Conclusion: These data suggest that DHA can inhibit IAV induces the TNF-α and IL-6 expression in BEAS-2B cells through ERK signaling pathway.


Assuntos
Antivirais/farmacologia , Artemisininas/farmacologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Brônquios , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/virologia , Humanos , Fator de Transcrição STAT1
11.
Toxicol Lett ; 326: 61-69, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32169443

RESUMO

Notch-1 intervenes in the reparative processes of mucosa by controlling cell proliferation, differentiation and stem cell maintenance. Cigarette smoke alters airway epithelial homeostasis. The present study explored whether: Smokers showed altered Notch-1 expression; and whether in bronchial epithelial cells (16HBE): a) cigarette smoke extracts (CSE) altered the expression of Notch-1, of its ligand Jagged-1 (Jag-1) and the nuclear translocation of Notch-1; b) Notch-1 signaling activation as well as CSE modified Ki67, PCNA, p21, IL-33 expression, cell proliferation and repair processes. Notch-1 expression was assessed in the epithelium from large airway surgical samples from non-smoker and smoker subjects by immunohistochemistry.16HBE were cultured with/without CSE and Jag-1. A Notch-1 inhibitor (DAPT) was used as control. The expression of Notch-1, Jag-1, Ki67, PCNA, p21, IL-33 and cell proliferation (by CFSE) were all assessed by flow cytometry. Notch-1 nuclear expression was evaluated by immunofluorescence and western blot analysis. Repair processes were assessed by wound assay. Smokers had cytoplasmic but not nuclear Notch-1 expression. Although CSE increased Notch-1 expression, it counteracted Notch-1 signaling activation since it reduced Jag-1 expression and Notch-1 nuclear translocation. Notch-1 signaling activation by Jag-1 increased Ki67, PCNA and repair processes but reduced intracellular IL-33 and p21 expression without affecting cell proliferation. DAPT counteracted the effects of Notch-1 activation on PCNA and IL-33. CSE increased Ki67, PCNA, p21 and IL-33 expression but reduced cell proliferation and repair processes. In conclusion, cigarette smoke exposure, limiting Notch-1 signaling activation and hindering repair processes, amplifies injury processes in bronchial epithelial cells.


Assuntos
Apoptose/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Receptores Notch/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Poluição por Fumaça de Tabaco/efeitos adversos , Humanos
12.
Toxicol Lett ; 325: 25-33, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32112875

RESUMO

RATIONALE: Diacetyl (DA; 2,3-butanedione) is a chemical found commonly in foods and e-cigarettes. When inhaled, DA causes epithelial injury, though the mechanism of repair remain poorly understood. The objective of this study was to evaluate airway basal cell repair after DA vapor exposure. METHODS: Primary human bronchial epithelial cells were exposed to DA or PBS for 1 h. Lactate dehydrogenase, cleaved caspase 3/7 and trans-epithelial electrical resistance were measured prior to and following exposure. Exposed cultures were analyzed for the airway basal cell markers keratin 5 and p63 as well as ubiquitin and proteasome activity. Cultures were also treated with a proteasome inhibitor (MG132). RESULTS: DA vapor exposure caused a transient decrease in trans-epithelial electrical resistance in all DA-exposed cultures. Supernatant lactate dehydrogenase and cleaved caspase 3/7 increased significantly at the highest DA concentration but not at lower DA concentrations. Increased keratin 5 ubiquitination occurred after DA exposure but resolved by day 3. Damage to airway basal cells persisted at day 3 in the presence of MG132. CONCLUSIONS: Diacetyl exposure results in airway basal cell injury with keratin 5 ubiquitination and decreased p63 expression. The ubiquitin-proteasome-pathway partially mediates airway basal cell repair after acute DA exposure.


Assuntos
Diacetil/toxicidade , Mucosa Respiratória/patologia , Biomarcadores , Brônquios/citologia , Brônquios/patologia , Caspases/metabolismo , Diacetil/administração & dosagem , Impedância Elétrica , Sistemas Eletrônicos de Liberação de Nicotina , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Humanos , Exposição por Inalação , Queratina-5/metabolismo , L-Lactato Desidrogenase/metabolismo , Leupeptinas/farmacologia , Proteínas de Membrana , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Ubiquitinação/efeitos dos fármacos
13.
PLoS One ; 15(2): e0228603, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32040483

RESUMO

The onset and development of many airway pathologies affect sound propagation throughout the respiratory system; changes in respiratory sounds are detected primarily by auscultation, which is highly skill dependent. The aim of the present study was to compare healthy and asthmatic pulmonary acoustics by applying a 1D model of wave propagation on CT-based patient-specific geometries. High-resolution CT lung images were acquired in five healthy volunteers and five asthmatic patients at total lung capacity (TLC) and functional residual capacity (FRC). Tracheobronchial trees were reconstructed from CT images. Acoustic pressure, impedance and wall radial velocity were measured by simulating acoustic wave propagation of two external, acoustic pressure waves (1 Pa, 200 and 600 Hz) from the trachea level to the 4th generation. In asthmatic patients, acoustic pressure averaged across the last three generations showed a reduction equal to 29.7% (p<0.01) at FRC, at 200 Hz; input and terminal impedance were 34.5% (p<0.05) higher both at FRC and TLC; wall radial velocity was more than 80% (p<0.05) lower in higher generations both at FRC and TLC. Airway differences in asthma alter acoustic parameters at FRC and TLC, with the greatest difference at FRC and 200 Hz. Acoustic wave propagation analysis represents a quantitative approach that has potential to objectively characterize airway differences in individuals with diseases such as asthma.


Assuntos
Asma/diagnóstico por imagem , Asma/fisiopatologia , Auscultação , Brônquios/diagnóstico por imagem , Brônquios/fisiopatologia , Acústica , Adulto , Estudos de Casos e Controles , Simulação por Computador , Feminino , Capacidade Residual Funcional , Humanos , Processamento de Imagem Assistida por Computador , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Som , Tomografia Computadorizada por Raios X , Capacidade Pulmonar Total , Adulto Jovem
14.
PLoS One ; 15(2): e0229238, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32106233

RESUMO

BACKGROUND: Airway obstruction due to decreased airway diameter and increased incidence of mucus plugs has not been directly observed in asthma exacerbation. We studied the changes in the inner diameter of the airway (Din) and the frequency of mucus plugs by airway generation in patients with asthma exacerbation. We compared these patients to those in a stable phase using high-resolution computed tomography (HRCT). METHODS AND FINDINGS: Thirteen patients with asthma were studied by HRCT during asthma exacerbation and in a stable period. The HRCT study was performed on patients who could safely hold their breath for a short while in a supine position 1 hour after initial treatment for asthma exacerbation. Using a curved multiplanar reconstruction (MPR) software, we reconstructed the longitudinal airway images and the images exactly perpendicular to the airway axis to measure the Din and mucus plugs from the second- (segmental) to sixth-generation bronchi in all segments of the lungs.The ratios of Din (exacerbation/stable) were 0.91(P = 0.016), 0.88 (P = 0.002), 0.83 (P = 0.001), 0.80 (P = 0.001), and 0.87 (NS) in the second-, third-, fourth-, fifth-, and sixth-generation bronchi, respectively. The percentages of airway obstruction due to mucus plugs were notably higher in the fourth- and fifth-generation bronchi (17.9%/18.1% in stable phase and 43.2%/45.9% in the exacerbation phase, respectively) than in the other generations of bronchi. CONCLUSIONS: Among the bronchi examined, the fourth- and fifth-generation bronchi were significantly obstructed during asthma exacerbation compared with the stable phase in terms of a decreased airway diameter and mucus plugs.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Asma/complicações , Brônquios/patologia , Muco/metabolismo , Obstrução das Vias Respiratórias/diagnóstico por imagem , Obstrução das Vias Respiratórias/patologia , Asma/diagnóstico por imagem , Brônquios/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Muco/química , Muco/diagnóstico por imagem , Prognóstico , Tomografia Computadorizada por Raios X/métodos
15.
Korean J Radiol ; 21(3): 365-368, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32056397

RESUMO

Since the 2019 novel coronavirus (2019-nCoV or officially named by the World Health Organization as COVID-19) outbreak in Wuhan, Hubei Province, China in 2019, there have been a few reports of its imaging findings. Here, we report two confirmed cases of 2019-nCoV pneumonia with chest computed tomography findings of multiple regions of patchy consolidation and ground-glass opacities in both lungs. These findings were characteristically located along the bronchial bundle or subpleural lungs.


Assuntos
Brônquios/diagnóstico por imagem , Infecções por Coronavirus/diagnóstico por imagem , Surtos de Doenças , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , China , Infecções por Coronavirus/patologia , Febre/etiologia , Humanos , Masculino , Pneumonia Viral/patologia , Radiografia Torácica , Organização Mundial da Saúde
16.
Nat Med ; 26(2): 259-269, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32042191

RESUMO

Developmental processes underlying normal tissue regeneration have been implicated in cancer, but the degree of their enactment during tumor progression and under the selective pressures of immune surveillance, remain unknown. Here we show that human primary lung adenocarcinomas are characterized by the emergence of regenerative cell types, typically seen in response to lung injury, and by striking infidelity among transcription factors specifying most alveolar and bronchial epithelial lineages. In contrast, metastases are enriched for key endoderm and lung-specifying transcription factors, SOX2 and SOX9, and recapitulate more primitive transcriptional programs spanning stem-like to regenerative pulmonary epithelial progenitor states. This developmental continuum mirrors the progressive stages of spontaneous outbreak from metastatic dormancy in a mouse model and exhibits SOX9-dependent resistance to natural killer cells. Loss of developmental stage-specific constraint in macrometastases triggered by natural killer cell depletion suggests a dynamic interplay between developmental plasticity and immune-mediated pruning during metastasis.


Assuntos
Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Sistema Imunitário/fisiologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Animais , Brônquios/metabolismo , Diferenciação Celular , Linhagem da Célula , Análise por Conglomerados , Bases de Dados Genéticas , Progressão da Doença , Endoderma/metabolismo , Feminino , Humanos , Hidrogéis/química , Células Matadoras Naturais/metabolismo , Pulmão/patologia , Camundongos , Fenótipo , Alvéolos Pulmonares/metabolismo , Regeneração , Transdução de Sinais
17.
Nature ; 578(7796): 621-626, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32051585

RESUMO

The mechanics of the cellular microenvironment continuously modulates cell functions such as growth, survival, apoptosis, differentiation and morphogenesis via cytoskeletal remodelling and actomyosin contractility1-3. Although all of these processes consume energy4,5, it is unknown whether and how cells adapt their metabolic activity to variable mechanical cues. Here we report that the transfer of human bronchial epithelial cells from stiff to soft substrates causes a downregulation of glycolysis via proteasomal degradation of the rate-limiting metabolic enzyme phosphofructokinase (PFK). PFK degradation is triggered by the disassembly of stress fibres, which releases the PFK-targeting E3 ubiquitin ligase tripartite motif (TRIM)-containing protein 21 (TRIM21). Transformed non-small-cell lung cancer cells, which maintain high glycolytic rates regardless of changing environmental mechanics, retain PFK expression by downregulating TRIM21, and by sequestering residual TRIM21 on a stress-fibre subset that is insensitive to substrate stiffness. Our data reveal a mechanism by which glycolysis responds to architectural features of the actomyosin cytoskeleton, thus coupling cell metabolism to the mechanical properties of the surrounding tissue. These processes enable normal cells to tune energy production in variable microenvironments, whereas the resistance of the cytoskeleton in response to mechanical cues enables the persistence of high glycolytic rates in cancer cells despite constant alterations of the tumour tissue.


Assuntos
Microambiente Celular , Citoesqueleto/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Glucose/metabolismo , Glicólise , Dureza , Actinas/metabolismo , Actomiosina/metabolismo , Animais , Brônquios/citologia , Bovinos , Diferenciação Celular , Linhagem Celular , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Fosfofrutoquinases/química , Fosfofrutoquinases/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ribonucleoproteínas/metabolismo , Fibras de Estresse/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
18.
Chemosphere ; 243: 125440, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31995888

RESUMO

To date no study has been able to clearly attribute the observed toxicological effects of atmospheric particles (PM) to a specific class of components. The toxicity of both the organic extractable matter (OEM2.5-0.3) and non-extractable matter (NEM2.5-0.3) of fine particles (PM2.5-0.3) was compared to that of PM2.5-0.3 in its entirety on normal human epithelial bronchial BEAS-2B cells in culture. The specific effect of the quasi-ultrafine fraction (PM0.3) was assessed, by comparing the responses of cells exposed to the PM2.5-0.3 and PM0.3 organic extractable matter, OEM2.5-0.3 and OEM0.3 respectively. Chemically, PAH, O-PAH, and N-PAH were respectively 43, 17, and 4 times more concentrated in PM0.3 than in PM2.5-0.3, suggesting thereby a predominant influence of anthropogenic activities and combustion sources. BEAS-2B cells exposed to PM2.5-0.3, NEM2.5-0.3, EOM2.5-0.3 and OEM0.3 lead to different profiles of expression of selected genes and proteins involved in the metabolic activation of PAH, O-PAH, and N-PAH, and in the genotoxicity pathways. Specifically, OEM0.3 was the most inducer for phase I and phase II enzymes implicated in the metabolic activation of PAH (AHR, AHRR, ARNT, CYP1A1, CYP1B1, EPHX-1, GSTA-4) thereby producing the highest DNA damage, felt by ATR and, thereafter, a cascade of protein phosphorylation (CHK1/CHK2/MDM2) closely related to the cell cycle arrest (P21 and P53 induction). This study underlined the crucial role played by the organic chemicals present in PM0.3. These results should be considered in any future study looking for the main chemical determinants responsible for the toxicity of ambient fine PM.


Assuntos
Poluentes Atmosféricos/toxicidade , Células Epiteliais/efeitos dos fármacos , Material Particulado/toxicidade , Poluentes Atmosféricos/análise , Brônquios/citologia , Linhagem Celular , Dano ao DNA , Humanos , Compostos Orgânicos/toxicidade , Tamanho da Partícula , Material Particulado/análise
19.
Medicine (Baltimore) ; 99(1): e18647, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895828

RESUMO

RATIONALE: Influenza is an infection caused by the influenza virus, and its symptoms are mostly mild and self-limiting. However, influenza can cause severe or fatal complications in high-risk patients. Although tracheobronchitis is one of the common complications of influenza, necrotizing tracheobronchitis is very rare. Herein, we describe a case of necrotizing tracheobronchitis causing airway obstruction complicated by pandemic 2009 H1N1 influenza. PATIENT CONCERNS: A 60-year-old man presented with fever and dyspnea. On arrival at the emergency room (ER), the patient received oxygen 4 L/minute via a nasal prolong owing to mild hypoxemia. And invasive mechanical ventilation was needed 5 hours after arrival at the ER due to progressive hypoxemia. DIAGNOSES: Fiberoptic bronchoscopy was performed owing to bloody secretion in the endotracheal tube and revealed diffuse tracheobronchitis with necrotic and hemorrhagic materials obstructing the trachea and bronchus. The pandemic 2009 H1N1 influenza virus was detected from the bronchial washing sample; no other microorganism was detected. INTERVENTION: He received peramivir plus oseltamivir and broad-spectrum antibiotics. OUTCOMES: The bloody secretion continued. He developed cardiac arrest due to airway obstruction on the 6th day of admission. After cardiac arrest, his condition progressed to multi-organ failure, and the patient died on the 10th day of admission. LESSONS: We suggest that necrotizing tracheobronchitis be considered in patients with influenza who present with unexplained hypoxemia.


Assuntos
Obstrução das Vias Respiratórias/virologia , Bronquite/virologia , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Doenças da Traqueia/virologia , Brônquios/diagnóstico por imagem , Brônquios/patologia , Bronquite/complicações , Bronquite/diagnóstico por imagem , Bronquite/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Doenças da Traqueia/complicações , Doenças da Traqueia/diagnóstico por imagem , Doenças da Traqueia/patologia
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