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1.
Respir Res ; 20(1): 247, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699094

RESUMO

Chemical pleurodesis is a therapeutic procedure applied to create the symphysis between the parietal and visceral pleura by intrapleural administration of various chemical agents (e.g. talk, tetracycline, iodopovidone, etc.). The two major clinical conditions treated with chemical pleurodesis are recurrent pleural effusion (PE) and recurrent spontaneous pneumothorax. Although the history of chemical pleurodesis began over a century ago, detailed data on the mechanisms of action of sclerosing agents are highly incomplete. The following article aims to present the state of knowledge on this subject.It is believed that mesothelial cells are the main structural axis of pleurodesis. In response to sclerosing agents they secrete a variety of mediators including chemokines such as interleukin 8 (IL-8) and monocyte chemoattractant protein (MCP-1), as well as growth factors - vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) and transforming growth factor- ß (TGF-ß). Numerous data suggest that intact mesothelial cells and the above cytokines play a crucial role in the initiation and maintenance of different pathways of pleural inflammation and pleural space obliteration.It seems that the process of pleurodesis is largely nonspecific to the sclerosant and involves the same ultimate pathways including activation of pleural cells, coagulation cascade, fibrin chain formation, fibroblast proliferation and production of collagen and extracellular matrix components. Of these processes, the coagulation cascade with decreased fibrinolytic activity and increased fibrinogenesis probably plays a pivotal role, at least during the early response to sclerosant administration.A better understanding of various pathways involved in pleurodesis may be a prerequisite for more effective and safe use of various sclerosants and for the development of new, perhaps more personalized therapeutic approaches.


Assuntos
Pleura/efeitos dos fármacos , Pleurodese , Soluções Esclerosantes/administração & dosagem , Talco/administração & dosagem , Animais , Fibrinólise , Fibrose , Humanos , Pleura/metabolismo , Pleura/patologia , Pleurodese/efeitos adversos , Soluções Esclerosantes/efeitos adversos , Transdução de Sinais , Talco/efeitos adversos , Resultado do Tratamento
2.
Clin Respir J ; 13(11): 700-707, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31424623

RESUMO

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB)-guided pleural dye marking is useful to localize small peripheral pulmonary nodules for sublobar resection. OBJECTIVE: To report findings on the use of ENB-guided dye marking among participants in the NAVIGATE study. METHODS: NAVIGATE is a prospective, multicentre, global and observational cohort study of ENB use in patients with lung lesions. The current subgroup report is a prespecified 1-month interim analysis of ENB-guided pleural dye marking in the NAVIGATE United States cohort. RESULTS: The full United States cohort includes 1215 subjects from 29 sites (April 2015 to August 2016). Among those, 23 subjects (24 lesions) from seven sites underwent dye marking in preparation for surgical resection. ENB was conducted for dye marking alone in nine subjects while 14 underwent dye marking concurrent with lung lesion biopsy, lymph node biopsy and/or fiducial marker placement. The median nodule size was 10 mm (range 4-22) and 83.3% were <20 mm in diameter. Most lesions (95.5%) were located in the peripheral third of the lung, at a median of 3.0 mm from the pleura. The median ENB-specific procedure time was 11.5 minutes (range 4-38). The median time from dye marking to resection was 0.5 hours (range 0.3-24). Dye marking was adequate for surgical resection in 91.3%. Surgical biopsies were malignant in 75% (18/24). CONCLUSION: In this study, ENB-guided dye marking to localize lung lesions for surgery was safe, accurate and versatile. More information is needed about surgical practice patterns and the utility of localization procedures.


Assuntos
Broncoscopia/métodos , Corantes/administração & dosagem , Campos Eletromagnéticos/efeitos adversos , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Biópsia , Broncoscopia/tendências , Fenômenos Eletromagnéticos , Feminino , Marcadores Fiduciais , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Pleura/metabolismo , Pleura/patologia , Estudos Prospectivos , Cirurgia Torácica Vídeoassistida/métodos , Estados Unidos/epidemiologia
3.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414757

RESUMO

BACKGROUND: Detection of carcinoembryonic Antigen (CEA) in pleural effusion has good clinical application value in differentiating benign and malignant pleural effusion, but sometimes CEA provides limited help. We report a case of a patient with left lung neoplasms combined with bilateral pleural effusion with increased CEA in the pleural effusion whose thoracoscopy pleural biopsy pathology was negative, mimicking lung carcinoma and ultimately confirmed as pulmonary sarcomatoid carcinoma by CT-guided percutaneous lung biopsy. METHODS: The chest computed tomography (CT) scan, thoracoscopy pleural biopsy, and CT-guided percutaneous lung biopsy were arranged to explore the etiology of pleural effusion. RESULTS: The chest CT scan showed bilateral pleural effusion with left lung neoplasms, pulmonary atelectasis, and left hilar enlargement. Pathology of thoracoscopy biopsy showed pleural inflammation with infiltration of inflammatory cells. Pathology of CT-guided percutaneous lung biopsy confirmed pulmonary sarcomatoid carcinoma. CONCLUSIONS: Elevated pleural effusion CEA is not a specific index of lung cancer. CT-guided percutaneous lung biopsy is appropriate for patients presenting with pleural diseases with lung neoplasms, especially when thoracoscopy pleural biopsy result was negative.


Assuntos
Antígeno Carcinoembrionário/metabolismo , Carcinoma/diagnóstico , Erros de Diagnóstico , Neoplasias Pulmonares/diagnóstico , Pleura/metabolismo , Derrame Pleural/diagnóstico , Idoso , Biópsia , Carcinoma/diagnóstico por imagem , Carcinoma/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pleura/diagnóstico por imagem , Pleura/patologia , Derrame Pleural/metabolismo , Derrame Pleural/patologia , Toracoscopia/métodos , Tomógrafos Computadorizados
4.
Medicina (Kaunas) ; 55(6)2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31212858

RESUMO

Background and objectives: Malignant pleural mesothelioma (MPM) is a devastating malignancy with poor prognosis. Reliable biomarkers for MPM diagnosis, monitoring, and prognosis are needed. The aim of this study was to identify genes associated with wound healing processes whose expression could serve as a prognostic factor in MPM patients. Materials and Methods: We used data mining techniques and transcriptomic analysis so as to assess the differential transcriptional expression of wound-healing-associated genes in MPM. Moreover, we investigated the potential prognostic value as well as the functional enrichments of gene ontologies relative to microRNAs (miRNAs) of the significantly differentially expressed wound-healing-related genes in MPM. Results: Out of the 82 wound-healing-associated genes analyzed, 30 were found significantly deregulated in MPM. Kaplan-Meier analysis revealed that low ITGAV gene expression could serve as a prognostic factor favoring survival of MPM patients. Finally, gene ontology annotation enrichment analysis pointed to the members of the hsa-miR-143, hsa-miR-223, and the hsa-miR-29 miRNA family members as important regulators of the deregulated wound healing genes. Conclusions: 30 wound-healing-related genes were significantly deregulated in MPM, which are potential targets of hsa-miR-143, hsa-miR-223, and the hsa-miR-29 miRNA family members. Out of those genes, ITGAV gene expression was a prognostic factor of overall survival in MPM. Our results highlight the role of impaired tissue repair in MPM development and should be further validated experimentally.


Assuntos
Neoplasias Pulmonares/genética , Mesotelioma/genética , Cicatrização/genética , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/análise , MicroRNAs/genética , Pessoa de Meia-Idade , Pleura/anormalidades , Pleura/metabolismo , Pleura/fisiopatologia , Prognóstico , Cicatrização/fisiologia
5.
Biomed Res Int ; 2019: 5028512, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949501

RESUMO

Objective: As cell-free DNA levels in the pleural fluid and serum of parapneumonic pleural effusion (PPE) patients have not been thoroughly explored, we evaluated their diagnostic potential. Methods: Twenty-two PPE and 16 non-PPE patients were evaluated. Serum and pleural fluids were collected, and cell-free DNA was quantified. All biomarkers were assessed for correlation with days after admission. Receiver operating characteristic (ROC) curve analysis was used to determine diagnostic accuracy and optimal cut-off point. Results: Nuclear and mitochondrial DNA levels in the pleural fluid and nuclear DNA levels in serum of PPE patients were significantly higher than in those of the non-PPE patients. However, only cell-free DNA levels in pleural fluid correlated with days after admission among PPE patients (r= 0.464, 0.538, respectively). ROC curve analysis showed that nuclear and mitochondrial DNA in pleural fluid had AUCs of 0.945 and 0.889, respectively. With cut-off values of 134.9 and 17.8 ng/ml for nuclear and mitochondrial DNA in pleural fluid, respectively, 96% sensitivity and 81% specificity were observed for PPE diagnosis. Conclusion: Nuclear and mitochondrial DNA in pleural fluid possess PPE diagnostic potential and correlated with disease severity. Serum nuclear DNA could also be used to distinguish freshly admitted PPE patients (Day 1) from non-PPE patients, but with less accuracy.


Assuntos
Ácidos Nucleicos Livres/sangue , DNA Mitocondrial/sangue , Pleura/metabolismo , Derrame Pleural , Pneumonia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/sangue , Derrame Pleural/diagnóstico , Pneumonia/sangue , Pneumonia/diagnóstico
6.
Cell Physiol Biochem ; 52(4): 869-878, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30958661

RESUMO

BACKGROUND/AIMS: Cell volume regulation is a critical mechanism for cell homeostasis and depends on the osmotic water permeability (Pf) of the cell plasma membrane. The Pf of human mesothelial cells is unknown although they contribute to serosal fluid turnover. METHODS: In this study we measured the osmotic water permeability of benign human mesothelial cells (MeT-5A) and of epithelioid (M14K) and sarcomatoid (ZL34) malignant pleural mesothelioma (MPM) cells in response to acute hyperosmotic stress. We also assessed the changes in their Pf after preconditioning with 4% glucose for 24 hours. In both cases we also assessed the role of AQP1 inhibition (0.1 mM HgCl2) on the Pf. Finally, we assessed corresponding changes in the AQP1 plasma membrane availability by immunofluorescence. RESULTS: We report that MeT-5A cells have a significantly higher Pf as compared to M14K and ZL34 MPM cells [4.85E-03±2.37E-03 cm/sec (n=17) versus 2.74E-03±0.74E-03 cm/sec (n=11) and 2.86E-03±0.11E-03 cm/sec (n=11)]. AQP1 inhibition significantly decreased the Pf in all cells lines (p<0.001 in all cases). High glucose preconditioning for 24 hours significantly increased MeT-5A Pf (p<0.001), did not influence M14K Pf (p=0.19) and significantly reduced ZL34 Pf (p=0.02). Comparing cell lines after high glucose preconditioning, MeT-5A Pf was significantly higher than that of M14K and ZL34 MPM cells and the AQP1 inhibition effect was significant in MeT-5A and M14K cells. These results were corroborated by AQP1 immunofluorescence. CONCLUSION: We provide evidence for a differential regulation of Pf in benign and MPM cells that require further mechanistic investigation.


Assuntos
Aquaporina 1/metabolismo , Mesotelioma/metabolismo , Proteínas de Neoplasias/metabolismo , Pressão Osmótica , Pleura/metabolismo , Neoplasias Pleurais/metabolismo , Linhagem Celular Tumoral , Humanos , Mesotelioma/patologia , Permeabilidade , Pleura/patologia , Neoplasias Pleurais/patologia
7.
Am J Case Rep ; 20: 447-452, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30944296

RESUMO

BACKGROUND Pseudomesotheliomatous carcinomas are rare tumors that develop like malignant pleural mesothelioma (MPM). These tumors have similar features, and thus pseudomesotheliomatous carcinomas can sometimes be misdiagnosed as MPM. Most pseudomesotheliomatous carcinomas develop from primary lung cancers, although there have been some reports involving other malignancies; however, there has been no report describing a pseudomesotheliomatous carcinoma developing from an esophageal squamous cell carcinoma (ESCC). To the best of our knowledge, this is the first case report describing pseudomesotheliomatous carcinoma originating from primary ESCC. CASE REPORT A 65-year-old man was admitted to our hospital because of persistent cough and right chest pain. Radiological examination suggested MPM, and a high concentration of pleural hyaluronic acid was also observed. Cytological examination of pleural effusion confirmed metastatic squamous cell carcinoma, and ESCC was confirmed by upper-gastrointestinal endoscopy. The patient received cisplatin and 5-FU combination chemotherapy as first-line treatment, and docetaxel chemotherapy as second-line treatment. However, the patient's condition deteriorated, and he died 6 months after the diagnosis was established. We performed an autopsy and found that ESCC had invaded the lung, pleura, peritoneum, liver, stomach, ureter, bladder, spine, and lymph nodes. CONCLUSIONS We demonstrated that primary ESCC can give rise to a pseudomesotheliomatous carcinoma. This report describes the clinical features and outcome of such a patient, with an emphasis on differential diagnosis of MPM.


Assuntos
Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/secundário , Neoplasias Pulmonares/secundário , Idoso , Evolução Fatal , Humanos , Ácido Hialurônico/metabolismo , Masculino , Pleura/metabolismo
8.
Biopreserv Biobank ; 17(2): 163-170, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30707601

RESUMO

During pulmonary resections, removal of visceral pleura is frequently required, resulting in lung air leakage (LAL) and bleeding. Especially persistent LAL after pulmonary surgery has negative consequences. Current surgical procedures are ineffective in closing these visceral pleural injuries. Previously, the authors' laboratory has developed a novel and effective LAL sealant using tissue-engineered cell sheets harvested from temperature-responsive culture dishes. The clinical application of fresh fibroblast sheets (FSs) is limited by several problems related to the cell culture period, mass production, preservation, and transportation. Therefore, cryopreservation of FSs and feasibility of off-the-shelf FSs for repairing visceral pleural defects were investigated. Over 3 to 6 months, harvested skin-derived FSs in Dulbecco's modified Eagle's medium supplemented with 10% dimethyl sulfoxide were stored in an atmosphere of liquid nitrogen. The amounts of cytokines (basic fibroblast growth factor [bFGF] and vascular endothelial growth factor) released from frozen-thawed FSs were determined. bFGF levels were significantly elevated in frozen-thawed FSs compared with fresh FSs. After a visceral pleural injury model was created, a frozen-thawed skin-derived FS was transplanted directly to the defect. One month after transplantation, the frozen-thawed FS remained on the pleural surface, resulting in permanent closure, suggesting that cells in the off-the-shelf FS had the ability to proliferate and release various cytokines. Frozen-thawed FSs were useful for closing LALs during pulmonary surgery as an off-the-shelf technique and would be used as a pleural substitute.


Assuntos
Fibroblastos , Pleura , Transplante de Tecidos , Animais , Células Cultivadas , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibroblastos/transplante , Xenoenxertos , Humanos , Masculino , Pleura/lesões , Pleura/metabolismo , Pleura/patologia , Pleura/cirurgia , Ratos Endogâmicos F344 , Ratos Nus
9.
Am J Respir Cell Mol Biol ; 61(1): 86-96, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30605348

RESUMO

Pleural fibrosis is characterized by severe inflammation of the pleural space and pleural reorganization. Subsequent thickening of the visceral pleura contributes to lung stiffness and impaired lung function. Pleural mesothelial cells (PMCs) can become myofibroblasts via mesothelial-mesenchymal transition (MesoMT) and contribute to pleural organization, fibrosis, and rind formation. However, the mechanisms that underlie MesoMT remain unclear. Here, we investigated the role of myocardin in the induction of MesoMT. Transforming growth factor ß (TGF-ß) and thrombin induced MesoMT and markedly upregulated the expression of myocardin, but not myocardin-related transcription factor A (MRTF-A) or MRTF-B, in human PMCs (HPMCs). TGF-ß stimulation notably induced the nuclear translocation of myocardin in HPMCs, whereas nuclear translocation of MRTF-A and MRTF-B was not observed. Several genes under the control of myocardin were upregulated in cells undergoing MesoMT, an effect that was accompanied by a dramatic cytoskeletal reorganization of HPMCs consistent with a migratory phenotype. Myocardin gene silencing blocked TGF-ß- and thrombin-induced MesoMT. Although myocardin upregulation was blocked, MRTF-A and MRTF-B were unchanged. Myocardin, α-SMA, calponin, and smooth muscle myosin were notably upregulated in the thickened pleura of carbon black/bleomycin and empyema mouse models of fibrosing pleural injury. Similar results were observed in human nonspecific pleuritis. In a TGF-ß mouse model of pleural fibrosis, PMC-specific knockout of myocardin protected against decrements in lung function. Further, TGF-ß-induced pleural thickening was abolished by PMC-specific myocardin knockout, which was accompanied by a marked reduction of myocardin, calponin, and α-SMA expression compared with floxed-myocardin controls. These novel results show that myocardin participates in the development of MesoMT in HPMCs and contributes to the pathogenesis of pleural organization and fibrosis.


Assuntos
Núcleo Celular/metabolismo , Empiema Pleural/metabolismo , Miofibroblastos/metabolismo , Proteínas Nucleares/metabolismo , Pleura/metabolismo , Transativadores/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Bleomicina/efeitos adversos , Bleomicina/farmacologia , Núcleo Celular/patologia , Modelos Animais de Doenças , Empiema Pleural/induzido quimicamente , Empiema Pleural/patologia , Feminino , Fibrose , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Miofibroblastos/patologia , Pleura/patologia , Fuligem/toxicidade , Fator de Crescimento Transformador beta/metabolismo
10.
Toxicol Appl Pharmacol ; 361: 81-88, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30563646

RESUMO

Human autopsied lung sections from a resident in the Quebec asbestos region were examined. The study utilized high resolution transmission electron microscopy, scanning transmission electron microscopy (HRTEM/STEM) with the analytical capabilities of electron energy loss spectroscopy (EELS) and energy dispersive spectroscopy (EDS) detectors. We report the first analytical ultrastructural characteristics of EMPs, detailing chemical concentration gradients inside the iron-protein coatings and lateral elemental gradients in the local tissue regions. It is shown that the EMPs are subjected to bioprocessing which involves physicochemical transformations and also an elemental transport mechanism that alters the inhaled EMP as well as the surrounding cellular matrix. At high resolution imaging the iron-rich coating around the EMP was observed to have a distinct channel-like nanostructure with some parallel aligned nanofibrils that are reminiscent of tooth enamel which consists of biomineralized nanocomposites with alternating organic/inorganic matrices.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Exposição por Inalação/efeitos adversos , Pulmão/metabolismo , Minerais/toxicidade , Material Particulado/toxicidade , Poluentes Ocupacionais do Ar/metabolismo , Autopsia , Humanos , Pulmão/patologia , Pulmão/ultraestrutura , Microscopia Eletrônica de Transmissão , Minerais/metabolismo , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Material Particulado/metabolismo , Pleura/metabolismo , Fibrose Pulmonar/patologia , Espectrometria por Raios X
11.
ACS Nano ; 12(11): 10867-10879, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30380828

RESUMO

The qualitative and quantitative evaluation of the physicochemical parameters associated with the pathogenicity of high-aspect-ratio nanomaterials is important for comprehensive regulation efforts and safety-by-design approaches. Here, we report quantitative data on the correlations between the rigidity of these nanomaterials and toxicity endpoints in vitro and in vivo. As measured by new ISO standards published in 2017, rigidity shows a strong positive correlation with inflammogenic potential, as indicated by inflammatory cell counts and IL-1ß (a biomarker for frustrated phagocytosis) levels in both the acute and chronic phases. In vitro experiments using differentiated THP-1 cells find that only highly rigid multiwalled carbon nanotubes (MWCNTs) and asbestos fibers lead to piercing and frustrated phagocytosis. Thus, this study suggests a bending ratio of 0.97 and a static bending persistence length of 1.08 as threshold rigidity values for asbestos-like pathogenicity. However, additional research using MWCNTs with rigidity values that lie between those of non-inflammogenic ( Db = 0.66 and SBPL = 0.87) and inflammogenic fibers ( Db = 0.97 and SBPL = 1.09) is required to identify more accurate threshold values, which would be useful for comprehensive regulation and safety-by-design approaches based on MWCNTs.


Assuntos
Asbestos/química , Modelos Animais de Doenças , Inflamação/metabolismo , Nanotubos de Carbono/química , Pleura/metabolismo , Virulência , Animais , Feminino , Humanos , Inflamação/patologia , Camundongos , Camundongos Endogâmicos ICR , Tamanho da Partícula , Fagocitose , Pleura/patologia , Células THP-1
12.
Chem Res Toxicol ; 31(10): 1025-1031, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30212183

RESUMO

Translocation of multiwalled carbon nanotubes (MWCNTs) from the lung to the pleural cavity, deposition of the fibers in the pleural tissue, induction of pleural fibrosis, and mesothelial proliferation have been found in rodents administered MWCNTs by different pulmonary exposure methods. However, whether the translocation and deposition and the subsequent pleural inflammation are associated with the pleural lesions is unclear. In the present study, male F344 rats were given 250 µg of two types of MWCNTs, with crocidolite as a positive control, 2 times/week for 4 weeks by intratracheal spraying. At 24 h and at 3 months after the last spraying, the rats were sacrificed for histological examination of the lung and chest wall; pleural cavity lavage was also collected at sacrifice for observation of pleural inflammatory reactions. The results indicated that intratracheally sprayed MWCNTs, like crocidolite fibers, translocated into the pleural cavity, deposited in the pleura, and induced persistent infiltration of immune cells into the pleural cavity, persistent pleural fibrosis, and mesothelial proliferation. The number of MWCNT fibers detected in the pleural cavity lavage was parallel to the number of infiltrating immune cells, which were mainly composed of macrophages. Analysis of cytokines in the fluids of the pleural cavity lavages by suspension array indicated that levels of IL-2, IL-18, and IP-10 were significantly increased both at 24 h and at 3 months after the last spraying. In vitro proliferation assays revealed that a mixture of IL-2, IL-18, and IP-10, but not any of these cytokines alone, promoted cell proliferation of human fibroblasts and mesothelial cells. These results suggest that translocated and deposited MWCNTs induce subsequent pleural inflammation and that increased IL-2, IL-18, and IP-10 synergistically promote the development of pleural fibrosis and mesothelial proliferation.


Assuntos
Inflamação , Nanotubos de Carbono/toxicidade , Pleura/efeitos dos fármacos , Animais , Asbesto Crocidolita/toxicidade , Líquido da Lavagem Broncoalveolar/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Citocinas/análise , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fibrose , Humanos , Inflamação/etiologia , Masculino , Nanotubos de Carbono/química , Pleura/metabolismo , Pleura/patologia , Ratos , Ratos Endogâmicos F344
13.
Clin Respir J ; 12(8): 2309-2320, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30005142

RESUMO

OBJECTIVES: Pleural infection is a condition commonly encountered by the respiratory physician. This review aims to provide the reader with an update on the most recent data regarding the epidemiology, microbiology, and the management of pleural infection. DATA SOURCE: Medline was searched for articles related to pleural infection using the terms "pleural infection," "empyema," and "parapneumonic." The search was limited to the years 1997-2017. Only human studies and reports in English were included. RESULTS: A rise in the incidence of pleural infection is seen worldwide. Despite the improvement in healthcare practices, the mortality from pleural infection remains high. The role of oral microflora in the etiology of pleural infection is firmly established. A concise review of the recent insights on the pathogenesis of pleural infections is presented. A particular focus is made on the role of tPA, DNAse and similar substances and their interaction with inflammatory cells and how this affects the pathogenesis and treatment of pleural infection. CONCLUSION: Pleural infection is a common disease with significant morbidity and mortality, as well as a considerable economic burden. The role of medical management is expanding thanks to the widespread use of newer treatments.


Assuntos
Empiema Pleural/microbiologia , Pleura/microbiologia , Derrame Pleural/metabolismo , Derrame Pleural/microbiologia , Efeitos Psicossociais da Doença , Empiema Pleural/epidemiologia , Empiema Pleural/mortalidade , Empiema Pleural/patologia , Microbioma Gastrointestinal/fisiologia , Humanos , Incidência , Pleura/diagnóstico por imagem , Pleura/metabolismo , Pleura/cirurgia , Toracoscopia/métodos , Terapia Trombolítica/métodos , Tomografia Computadorizada por Raios X/métodos
14.
Biochim Biophys Acta Mol Cell Res ; 1865(9): 1201-1210, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29842893

RESUMO

Pleural fibrosis is barely reversible and the underlying mechanisms are poorly understood. Pleural mesothelial cells (PMCs) which have apical-basal polarity play a key role in pleural fibrosis. Loss of cell polarity is involved in the development of fibrotic diseases. Partition defective protein (PAR) complex is a key regulator of cell polarity. However, changes of PMC polarity and PAR complex in pleural fibrosis are still unknown. In this study, we observed that PMC polarity was lost in fibrotic pleura. Next we found increased Lethal (2) giant larvae (Lgl) bound with aPKC and PAR-6B competing against PAR-3A in PAR complex, which led to cell polarity loss. Then we demonstrated that Lgl1 siRNA prevented cell polarity loss in PMCs, and Lgl1 conditional knockout (ER-Cre+/-Lgl1flox/flox) attenuated pleural fibrosis in a mouse model. Our data indicated that Lgl1 regulates cell polarity of PMCs, inhibition of Lgl1 and maintenance of cell polarity in PMCs could be a potential therapeutic treatment approach for pleural fibrosis.


Assuntos
Células Epiteliais/citologia , Glicoproteínas/genética , Glicoproteínas/metabolismo , Pleura/patologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular , Polaridade Celular , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Feminino , Fibrose , Técnicas de Inativação de Genes , Humanos , Masculino , Camundongos , Pleura/metabolismo , Proteína Quinase C/metabolismo , Ratos
15.
Clin Respir J ; 12(3): 986-990, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28127951

RESUMO

OBJECTIVE: To explore the diagnostic value of joint detection of soluble B7-H4 (sB7-H4) and carcinoembryonic antigen (CEA) in identifying malignant pleural effusion (MPE) from benign pleural effusion (BPE). METHODS: A total of 97 patients with pleural effusion specimens were enrolled from The First Affiliated Hospital of Zhengzhou University between June 2014 and December 2015. All cases were categorized into malignant pleural effusion group (n = 55) and benign pleural effusion group (n = 42) according to etiologies. Enzyme-linked immunosorbent assay was applied to examine the levels of sB7-H4 in pleural effusion and meanwhile CEA concentrations were detected by electro-chemiluminescence immunoassays. Receiver operating characteristic (ROC) curve was established to assess the diagnostic value of sB7-H4 and CEA in pleural effusion. The correlation between sB7-H4 and CEA levels was analyzed by Pearson's product-moment. RESULTS: The concentrations of sB7-H4 and CEA in MPE exhibited obviously higher than those of BPE ([60.08 ± 35.04] vs. [27.26 ± 9.55] ng/ml, P = .000; [41.49 ± 37.16] vs. [2.41 ± 0.94] ng/ml, P = .000). The AUC area under ROC curve of sB7-H4 and CEA was 0.884 and 0.954, respectively. Two cutoff values by ROC curve analysis of sB7-H4 36.5 ng/ml and CEA 4.18 ng/ml were obtained, with a corresponding sensitivity (81.82%, 87.28%), specificity (90.48%, 95.24%), accuracy (85.57%, 90.72%), positive predictive value (PPV) (91.84%, 96.0%), negative predictive value (NPV) (79.17%, 85.11%), positive likelihood ratio (PLR) (8.614, 18.327), and negative likelihood ratio (NLR) (0.201, 0.134). When sB7-H4 and CEA were combined to detect pleural effusion, it obtained a higher sensitivity 90.91% and specificity 97.62%. Furthermore, correlation analysis result showed that the level of sB7-H4 was correlated with CEA level (r = .770, P = .000). CONCLUSIONS: sB7-H4 was a potentially valuable tumor marker in the differentiation between BPE and MPE. The combined detection of sB7-H4 and CEA could improve the diagnostic sensitivity and specificity for MPE.


Assuntos
Antígeno Carcinoembrionário/metabolismo , Pleura/metabolismo , Derrame Pleural Maligno/metabolismo , Derrame Pleural/metabolismo , Inibidor 1 da Ativação de Células T com Domínio V-Set/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pleura/patologia , Derrame Pleural/patologia , Derrame Pleural Maligno/patologia , Valor Preditivo dos Testes
16.
Surg Today ; 48(4): 462-472, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29027010

RESUMO

PURPOSE: The pleural covering technique, i.e., wrapping a part of or the entire surface of the lung with oxidized regenerative cellulose (ORC), reinforces visceral pleura through pleural thickening for patients with pneumothorax and cystic lung diseases. However, it remains undetermined how ORC induces pleural thickening. METHODS: A histopathological examination was performed for lung specimens from patients who had recurrent pneumothoraces after pleural covering and re-operation (n = 5). To evaluate the influence of ORC on the pleura in vitro, we used MeT-5A cells (a human pleural mesothelial cell line). RESULTS: Pleural thickening was confirmed in all lung specimens examined. Three months after covering, the thickened pleura showed inflammatory cell infiltration, proliferation of myofibroblasts, and expression of fibronectin and TGF-ß. However, after 1 year, those findings virtually disappeared, and the thickened pleura was composed mainly of abundant collagen. When MeT-5A cells were cultured in ORC-immersed medium, their morphology changed from a cobblestone to spindle-shaped appearance. The expression of E-cadherin decreased, whereas that of N-cadherin, α-smooth muscle actin, and fibronectin increased, suggesting mesothelial-mesenchymal transition (Meso-MT). CONCLUSIONS: Our results suggest that Meso-MT may be involved as a mechanism of pleural thickening induced by pleural covering with ORC.


Assuntos
Celulose Oxidada , Transição Epitelial-Mesenquimal , Pleura/patologia , Pneumotórax/cirurgia , Telas Cirúrgicas , Procedimentos Cirúrgicos Torácicos/métodos , Actinas/metabolismo , Adolescente , Adulto , Caderinas/metabolismo , Linhagem Celular , Meios de Cultura , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fibronectinas/metabolismo , Humanos , Masculino , Pleura/citologia , Pleura/metabolismo , Recidiva , Reoperação , Estudos Retrospectivos , Adulto Jovem
17.
Tissue Eng Part A ; 24(9-10): 695-702, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28920559

RESUMO

Pleural injury and associated air leaks are a major influence on patient morbidity and healthcare costs after lung surgery. Pectin, a plant-derived heteropolysaccharide, has recently demonstrated potential as an adhesive binding to the glycocalyx of visceral mesothelium. Since bioadhesion is a process likely involving the interpenetration of the pectin-based polymer with the glycocalyx, we predicted that the pectin-based polymer may also be an effective sealant for pleural injury. To explore the potential role of an equal (weight%) mixture of high-methoxyl pectin and carboxymethylcellulose as a pleural sealant, we compared the yield strength of the pectin-based polymer to commonly available surgical products. The pectin-based polymer demonstrated significantly greater adhesion to the lung pleura than the comparison products (p < 0.001). In a 25 g needle-induced lung injury model, pleural injury resulted in an air leak and a loss of airway pressures. After application of the pectin-based polymer, there was a restoration of airway pressure and no measurable air leak. Despite the application of large sheets (50 mm2) of the pectin-based polymer, multifrequency lung impedance studies demonstrated no significant increase in tissue damping (G) or hysteresivity (η)(p > 0.05). In 7-day survival experiments, the application of the pectin-based polymer after pleural injury was associated with no observable toxicity, 100% survival (N = 5), and restored lung function. We conclude that this pectin-based polymer is a strong and nontoxic bioadhesive with the potential for clinical application in the treatment of pleural injuries.


Assuntos
Lesão Pulmonar/cirurgia , Pectinas/química , Pleura/metabolismo , Pleura/cirurgia , Adesivos Teciduais/química , Adesivos Teciduais/metabolismo , Animais , Epitélio/metabolismo , Epitélio/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura
18.
Food Funct ; 8(12): 4459-4468, 2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29090709

RESUMO

The present study seeks to investigate the effect of rutin, a flavonoid compound in rat models of acute inflammation induced by carrageenan (CAR). Twenty-four female Wistar rats weighing 222-247 g received saline or 2% λ-carrageenan in the pleural cavity and treatment with rutin (80 mg kg-1) or saline by oral gavage for 21 days prior to the intrapleural induction of CAR. After 4 h of induction, the rats were euthanized, the plasma was prepared from the blood for the analysis of haematological parameters and the pleural exudate was obtained for the analysis of the total cell count, cell viability, reactive oxygen species (ROS) production, apoptosis and cell cycle. The result revealed that rutin exhibited anti-inflammatory effects by modulating the ROS level, apoptosis and cell cycle. This study indicates that rutin may exert a protective effect against ROS-mediated oxidative damage associated with an anti-inflammatory activity in rat models of acute inflammation.


Assuntos
Anti-Inflamatórios/administração & dosagem , Apoptose/efeitos dos fármacos , Pneumopatias/tratamento farmacológico , Pleura/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Rutina/administração & dosagem , Animais , Carragenina/efeitos adversos , Ciclo Celular/efeitos dos fármacos , Feminino , Humanos , Pneumopatias/imunologia , Pneumopatias/metabolismo , Pneumopatias/fisiopatologia , Pleura/citologia , Pleura/metabolismo , Ratos , Ratos Wistar
19.
Biochem Biophys Res Commun ; 492(2): 218-223, 2017 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-28823918

RESUMO

Exposure to nanoparticles such as carbon nanotubes has been shown to cause pleural mesothelioma similar to that caused by asbestos, and has become an environmental health issue. Not only is the percutaneous absorption of nano-size titanium dioxide particles frequently considered problematic, but the possibility of absorption into the body through the pulmonary route is also a concern. Nevertheless, there are few reports of nano-size titanium dioxide particles on respiratory organ exposure and dynamics or on the mechanism of toxicity. In this study, we focused on the morphology as well as the size of titanium dioxide particles. In comparing the effects between nano-size anatase and rutile titanium dioxide on human-derived pleural mesothelial cells, the anatase form was shown to be actively absorbed into cells, producing reactive oxygen species and causing oxidative damage to DNA. In contrast, we showed for the first time that the rutile form is not easily absorbed by cells and, therefore, does not cause oxidative DNA damage and is significantly less damaging to cells. These results suggest that with respect to the toxicity of titanium dioxide particles on human-derived mesothelial cells, the crystal form rather than the particle size has a greater effect on cellular absorption. Also, it was indicated that the difference in absorption is the primary cause of the difference in the toxicity against mesothelial cells.


Assuntos
Dano ao DNA/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Nanoestruturas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Titânio/toxicidade , Linhagem Celular , Cristalização , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Tamanho da Partícula , Pleura/citologia , Pleura/efeitos dos fármacos , Pleura/metabolismo , Pleura/patologia , Espécies Reativas de Oxigênio/metabolismo
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