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1.
Int J Mol Sci ; 24(9)2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37175936

RESUMO

The effects of the administration of mesenchymal stromal cells (MSC) may vary according to the source. We hypothesized that MSC-derived extracellular vesicles (EVs) obtained from bone marrow (BM), adipose (AD), or lung (L) tissues may also lead to different effects in sepsis. We profiled the proteome from EVs as a first step toward understanding their mechanisms of action. Polymicrobial sepsis was induced in C57BL/6 mice by cecal ligation and puncture (SEPSIS) and SHAM (control) animals only underwent laparotomy. Twenty-four hours after surgery, animals in the SEPSIS group were randomized to receive saline or 3 × 106 MSC-derived EVs from BM, AD, or L. The diffuse alveolar damage was decreased with EVs from all three sources. In kidneys, BM-, AD-, and L-EVs reduced edema and expression of interleukin-18. Kidney injury molecule-1 expression decreased only in BM- and L-EVs groups. In the liver, only BM-EVs reduced congestion and cell infiltration. The size and number of EVs from different sources were not different, but the proteome of the EVs differed. BM-EVs were enriched for anti-inflammatory proteins compared with AD-EVs and L-EVs. In conclusion, BM-EVs were associated with less organ damage compared with the other sources of EVs, which may be related to differences detected in their proteome.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Sepse , Animais , Camundongos , Vesículas Extracelulares/metabolismo , Pulmão , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , Proteoma/metabolismo , Sepse/metabolismo
2.
Crit Care Med ; 49(1): 140-150, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33060501

RESUMO

OBJECTIVES: We hypothesized that a time-controlled adaptive ventilation strategy would open and stabilize alveoli by controlling inspiratory and expiratory duration. Time-controlled adaptive ventilation was compared with volume-controlled ventilation at the same levels of mean airway pressure and positive end-release pressure (time-controlled adaptive ventilation)/positive end-expiratory pressure (volume-controlled ventilation) in a Pseudomonas aeruginosa-induced pneumonia model. DESIGN: Animal study. SETTING: Laboratory investigation. SUBJECTS: Twenty-one Wistar rats. INTERVENTIONS: Twenty-four hours after pneumonia induction, Wistar rats (n = 7) were ventilated with time-controlled adaptive ventilation (tidal volume = 8 mL/kg, airway pressure release ventilation for a Thigh = 0.75-0.85 s, release pressure (Plow) set at 0 cm H2O, and generating a positive end-release pressure = 1.6 cm H2O applied for Tlow = 0.11-0.14 s). The expiratory flow was terminated at 75% of the expiratory flow peak. An additional 14 animals were ventilated using volume-controlled ventilation, maintaining similar time-controlled adaptive ventilation levels of positive end-release pressure (positive end-expiratory pressure=1.6 cm H2O) and mean airway pressure = 10 cm H2O. Additional nonventilated animals (n = 7) were used for analysis of molecular biology markers. MEASUREMENTS AND MAIN RESULTS: After 1 hour of mechanical ventilation, the heterogeneity score, the expression of pro-inflammatory biomarkers interleukin-6 and cytokine-induced neutrophil chemoattractant-1 in lung tissue were significantly lower in the time-controlled adaptive ventilation than volume-controlled ventilation with similar mean airway pressure groups (p = 0.008, p = 0.011, and p = 0.011, respectively). Epithelial cell integrity, measured by E-cadherin tissue expression, was higher in time-controlled adaptive ventilation than volume-controlled ventilation with similar mean airway pressure (p = 0.004). Time-controlled adaptive ventilation animals had bacteremia counts lower than volume-controlled ventilation with similar mean airway pressure animals, while time-controlled adaptive ventilation and volume-controlled ventilation with similar positive end-release pressure animals had similar colony-forming unit counts. In addition, lung edema and cytokine-induced neutrophil chemoattractant-1 gene expression were more reduced in time-controlled adaptive ventilation than volume-controlled ventilation with similar positive end-release pressure groups. CONCLUSIONS: In the model of pneumonia used herein, at the same tidal volume and mean airway pressure, time-controlled adaptive ventilation, compared with volume-controlled ventilation, was associated with less lung damage and bacteremia and reduced gene expression of mediators associated with inflammation.


Assuntos
Pneumonia Bacteriana/terapia , Respiração Artificial/métodos , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Resultado do Tratamento
3.
Respir Res ; 22(1): 214, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330283

RESUMO

BACKGROUND: We evaluated the effects of abrupt versus gradual PEEP decrease, combined with standard versus high-volume fluid administration, on cardiac function, as well as lung and kidney damage in an established model of mild-moderate acute respiratory distress syndrome (ARDS). METHODS: Wistar rats received endotoxin intratracheally. After 24 h, they were treated with Ringer's lactate at standard (10 mL/kg/h) or high (30 mL/kg/h) dose. For 30 min, all animals were mechanically ventilated with tidal volume = 6 mL/kg and PEEP = 9 cmH2O (to keep alveoli open), then randomized to undergo abrupt or gradual (0.2 cmH2O/min for 30 min) PEEP decrease from 9 to 3 cmH2O. Animals were then further ventilated for 10 min at PEEP = 3 cmH2O, euthanized, and their lungs and kidneys removed for molecular biology analysis. RESULTS: At the end of the experiment, left and right ventricular end-diastolic areas were greater in animals treated with high compared to standard fluid administration, regardless of PEEP decrease rate. However, pulmonary arterial pressure, indicated by the pulmonary acceleration time (PAT)/pulmonary ejection time (PET) ratio, was higher in abrupt compared to gradual PEEP decrease, independent of fluid status. Animals treated with high fluids and abrupt PEEP decrease exhibited greater diffuse alveolar damage and higher expression of interleukin-6 (a pro-inflammatory marker) and vascular endothelial growth factor (a marker of endothelial cell damage) compared to the other groups. The combination of standard fluid administration and gradual PEEP decrease increased zonula occludens-1 expression, suggesting epithelial cell preservation. Expression of club cell-16 protein, an alveolar epithelial cell damage marker, was higher in abrupt compared to gradual PEEP decrease groups, regardless of fluid status. Acute kidney injury score and gene expression of kidney injury molecule-1 were higher in the high versus standard fluid administration groups, regardless of PEEP decrease rate. CONCLUSION: In the ARDS model used herein, decreasing PEEP abruptly increased pulmonary arterial hypertension, independent of fluid status. The combination of abrupt PEEP decrease and high fluid administration led to greater lung and kidney damage. This information adds to the growing body of evidence that supports gradual transitioning of ventilatory patterns and warrants directing additional investigative effort into vascular and deflation issues that impact lung protection.


Assuntos
Coração/fisiopatologia , Rim/fisiopatologia , Pulmão/fisiopatologia , Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório/fisiopatologia , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Coração/efeitos dos fármacos , Infusões Intravenosas , Rim/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/terapia , Lactato de Ringer/administração & dosagem , Lactato de Ringer/toxicidade , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
4.
Anesthesiology ; 132(2): 307-320, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31939846

RESUMO

BACKGROUND: Pressure-support ventilation may worsen lung damage due to increased dynamic transpulmonary driving pressure. The authors hypothesized that, at the same tidal volume (VT) and dynamic transpulmonary driving pressure, pressure-support and pressure-controlled ventilation would yield comparable lung damage in mild lung injury. METHODS: Male Wistar rats received endotoxin intratracheally and, after 24 h, were ventilated in pressure-support mode. Rats were then randomized to 2 h of pressure-controlled ventilation with VT, dynamic transpulmonary driving pressure, dynamic transpulmonary driving pressure, and inspiratory time similar to those of pressure-support ventilation. The primary outcome was the difference in dynamic transpulmonary driving pressure between pressure-support and pressure-controlled ventilation at similar VT; secondary outcomes were lung and diaphragm damage. RESULTS: At VT = 6 ml/kg, dynamic transpulmonary driving pressure was higher in pressure-support than pressure-controlled ventilation (12.0 ± 2.2 vs. 8.0 ± 1.8 cm H2O), whereas static transpulmonary driving pressure did not differ (6.7 ± 0.6 vs. 7.0 ± 0.3 cm H2O). Diffuse alveolar damage score and gene expression of markers associated with lung inflammation (interleukin-6), alveolar-stretch (amphiregulin), epithelial cell damage (club cell protein 16), and fibrogenesis (metalloproteinase-9 and type III procollagen), as well as diaphragm inflammation (tumor necrosis factor-α) and proteolysis (muscle RING-finger-1) were comparable between groups. At similar dynamic transpulmonary driving pressure, as well as dynamic transpulmonary driving pressure and inspiratory time, pressure-controlled ventilation increased VT, static transpulmonary driving pressure, diffuse alveolar damage score, and gene expression of markers of lung inflammation, alveolar stretch, fibrogenesis, diaphragm inflammation, and proteolysis compared to pressure-support ventilation. CONCLUSIONS: In the mild lung injury model use herein, at the same VT, pressure-support compared to pressure-controlled ventilation did not affect biologic markers. However, pressure-support ventilation was associated with a major difference between static and dynamic transpulmonary driving pressure; when the same dynamic transpulmonary driving pressure and inspiratory time were used for pressure-controlled ventilation, greater lung and diaphragm injury occurred compared to pressure-support ventilation.


Assuntos
Diafragma/lesões , Diafragma/fisiopatologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/fisiopatologia , Respiração com Pressão Positiva/efeitos adversos , Respiração com Pressão Positiva/métodos , Animais , Masculino , Respiração com Pressão Positiva/normas , Ratos , Ratos Wistar , Mecânica Respiratória/fisiologia , Volume de Ventilação Pulmonar/fisiologia
5.
Am J Physiol Lung Cell Mol Physiol ; 317(6): L823-L831, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31553626

RESUMO

Mesenchymal stromal (stem) cells (MSCs) are increasingly demonstrated to ameliorate experimentally induced lung injuries through disease-specific anti-inflammatory actions, thus suggesting that different in vivo inflammatory environments can influence MSC actions. To determine the effects of different representative inflammatory lung conditions, human bone marrow-derived MSCs (hMSCs) were exposed to in vitro culture conditions from bronchoalveolar lavage fluid (BALF) samples obtained from patients with either the acute respiratory distress syndrome (ARDS) or with other lung diseases including acute respiratory exacerbations of cystic fibrosis (CF) (non-ARDS). hMSCs were subsequently assessed for time- and BALF concentration-dependent effects on mRNA expression of selected pro- and anti-inflammatory mediators, and for overall patterns of gene and mRNA expression. Both common and disease-specific patterns were observed in gene expression of different hMSC mediators, notably interleukin (IL)-6. Conditioned media obtained from non-ARDS BALF-exposed hMSCs was more effective in promoting an anti-inflammatory phenotype in monocytes than was conditioned media from ARDS BALF-exposed hMSCs. Neutralizing IL-6 in the conditioned media promoted generation of anti-inflammatory monocyte phenotype. This proof of concept study suggest that different lung inflammatory environments potentially can alter hMSC behaviors. Further identification of these interactions and the driving mechanisms may influence clinical use of MSCs for treating lung diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar/química , Meios de Cultivo Condicionados/farmacologia , Fibrose Cística/terapia , Células-Tronco Mesenquimais/citologia , Pneumonia/terapia , Síndrome do Desconforto Respiratório/terapia , Fibrose Cística/imunologia , Fibrose Cística/patologia , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Pneumonia/imunologia , Pneumonia/patologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/patologia
6.
J Sci Food Agric ; 97(2): 411-419, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27106744

RESUMO

BACKGROUND: Biodegradable films of native or acetylated starches with different concentrations of cellulose fibers (0%, 10% and 20%) were prepared. The films were characterized by morphological, mechanical, barrier, and thermal properties. RESULT: The tensile strength of the acetylated starch film was lower than those of the native starch film, without fibers. The addition of fibers increased the tensile strength and decreased the elongation and the moisture of native and acetylated starches films. The acetylated starch film showed higher water solubility when compared to native starch film. The addition of cellulose fibers reduced the water solubility of the acetylated starch film. The films reinforced with cellulose fiber exhibited a higher initial decomposition temperature and thermal stability. CONCLUSION: The mechanical, barrier, solubility, and thermal properties are factors which direct the type of the film application in packaging for food products. The films elaborated with acetylated starches of low degree of substitution were not effective in a reduction of the water vapor permeability. The addition of the cellulose fiber in acetylated and native starches films can contribute to the development of more resistant films to be applied in food systems that need to maintain their integrity. © 2016 Society of Chemical Industry.


Assuntos
Plásticos Biodegradáveis/química , Celulose/química , Embalagem de Alimentos/métodos , Hordeum/química , Amido/química , Vapor , Resistência à Tração , Acetilação , Indústria Alimentícia , Humanos , Permeabilidade , Sementes/química , Solubilidade , Temperatura , Água
7.
Rev Port Cir Cardiotorac Vasc ; 24(3-4): 139, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29701371

RESUMO

INTRODUCTION: In the 1930-50s, before the introduction of antimicrobial drugs and development of techniques of pulmonary resssection, collapse therapy was the mainstream of treatment for cavitary pulmonary tuberculosis. The methods to achieve the collapse included artificial pneumothorax with air refills, phrenic nerve crush, thoracoplasty and extrapleural plombage. The plombage involves creating a cavity surgically under the ribs in the upper chest wall and filling the space with inert material, such fat, paraffin wax, rubber ballons, oil and methyl-methacrylate (Lucite) balls. The theory behind Plombage treatment is that collapse of the lung promote de healing process and limit the spread of tuberculous infection to other areas of the lung. However, with time, the presence of these materials for a prolonged period of time resulted in complications, such as erosion of major vessels, respiratory insufficiency, infection and migration. METHODS: We present a clinical case of one patient presented with a late complication of lucite ball plombage after 55 years. RESULTS: An 78-year-old man with a history of pulmonary tuberculosis treated with plombage in 1962, ischemic heart disease, hypertension and diabetes mellitus, was admitted to hospital for axillary swelling and pleurocutaneous fistula. The x-ray of the chest and computed tomography showed the apex of the left hemithorax filled with multiple lucite balls, each approximately 2,5cm in diameter, and extrusion of a ball into the axillary fistuluous tract. In this context, the patient complied with multiple antibiotic regimens without success. So, the patient was submitted to surgical extraction of 21 lucite balls, pleurocutaneous drainage and thoracoplasty (7 ribs and the tip of the scapula was remove). The cultures turned out to be negative and the patient made an uneventful recovery with discharge on the 19th postoperative day. Pathologic examination revealed active chronic inflammatory process and negative microorganism screening. CONCLUSION: Despite the rapid decline in collapse therapy since the appearance of antitubercular chemotherapy, there are still such elderly patients who remain asymptomatic while carrying residual plombage material. There is no need for routine ablation of any this material, however if any foreign material becames a source of complication should be extracted without delay. As the number of living patients treated by plombage is attenuating rapidly, fewer and fewer will be seen in the future, and no one is likely to accumulate considerable experience with this problem.


Assuntos
Colapsoterapia , Corpos Estranhos , Toracoplastia , Tuberculose Pulmonar , Idoso , Humanos , Masculino , Polimetil Metacrilato , Tuberculose Pulmonar/terapia
8.
Rev Port Cir Cardiotorac Vasc ; 24(3-4): 144, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29701375

RESUMO

INTRODUCTION: Non-small cell lung cancer is a very common disease in the elderly population and its incidence in this particular population is expected to increase further, because of the ageing of the Western population. Pulmonary resection is often not recommended in the elderly, even though they have no medical contraindications to surgery. Such patients are postulated to have a limited life expectancy, the rate of complications and perioperative death is considered to be higher than younger population. However, decision making is extremely difficult, since this group in under- represented in clinical trials. METHODS: This study aim to do a retrospective analysis of comorbidity, surgical procedures and pos- operative complications for surgery in patients older than 70 years of age who underwent a pulmonary resection for lung cancer. We analysed the clinical records of all patients with Non-small cell lung cancer submitted to surgery during the period 2012 to 2016 in our department and divide them in 2 groups: elderly group (more than 70 years old) and group control. RESULTS: In the five years study period, our department performed pulmonary resection in 601 patients with NSCLC, of whom 209 (34,8%) were 70 years and older. The mean age was 74,6 years old in the elderly group and 58,6 in the control group. Preoperative comorbidities such as cardiac and previous neoplasic diseases were more frequent in the elderly group, and the percentage of smokers was higher in the control group (80,1% vs 61,7%). A segmentar or wedge resection was performed more frequent for the elderly group (16,7%) than in the control group (6,6%), whereas pneumonectomies and lobectomies were performed more frequently. The ratio of pos-operative complications, especially cardiac complications, was higher in the elderly patients (12,9% vs 8,2%), however, there was no significant difference in prevalence of pulmonary/ respiratory complications, such pulmonary leakage, pneumonia or empyema between the 2 groups. There was no operative or hospital death in any of the groups. CONCLUSION: Advanced age alone is not a contraindication to surgical resection on NSCLC. Elderly patients should be offered the best treatment possible, considering surgical risk on an individualized basis, and keeping in mind that surgery offers the best results when the disease is resectable.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fatores Etários , Idoso , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento
9.
Rev Port Cir Cardiotorac Vasc ; 24(3-4): 140, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29701372

RESUMO

INTRODUCTION: 55 years old, male patient. History of heavy smoking (65 UMA) and COPD. Admitted to hospital due to a left pneumonia. Thoracic CT and PET-Scan, showed left lower lobe mass measuring 92x89 mm (SUVmax 49). Several mediastinal node groups presented increased uptake of FDG. A fiberoptic bronchoscopy was performed. Citology of the bronchoalveolar lavage suggested a squamous carcinoma. EBUS of node stations 4R, 4L e 7 without evidence of malignancy. METHODS: The case was taken to a multidisciplinary meeting staged as IIIA (T3N2M0). Neoadjuvant therapy (four cycles cysplatine and gemcitabine) was decided based on station 5, suspected disease. A left lower lobectomy was performed after a cervical mediastinoscopy excluded metastasis of node stations 4R and 4L. Histology of the specimen was compatible with inflammatory myofibroblastic tumor (IMT). No lymph node involvement was reported. It was restaged as IIB (ypT3N0M0). RESULTS: Three months after surgery one de novo nodule in the lingula with 12,7 of SUVmax was reported. The nodule was removed confirming a IMT metastasis. Four months after the nodule ressection a CT showed new lung and liver nodules. A total oclusion of the left main bronchus was documented and bronchoscopic debulking of the endobronchial mass again revealed IMT. Paliative radiotherapy was decided in the multidisciplinar group targeting the left main bronchus (five sessions of radiotherapy on a dose of 20Gy in 4Gy daily fractions). Ten months after surgery due to the onset of back pain, a CT revealed a sacrum lesion whose needle biopsy was suspicious for multiple myeloma. The patient was referred to another oncological center where previous non-surgical cases had been sent in the past. The patient is now proposed for histology reassessment and discussion by the hematology and pneumology medical teams. CONCLUSION: Inflammatory myofibrobastic tumors are considered benign or low-grade malignant tumors. The size of the tumour (cut-off of 3 cm) and secure surgical resection with free margins are the major determinants for recurrence and survival. There are some cases reported in the literature of distant metastasis and sarcomatous transformation after multiple recurrences. In our patient, the lesion was bigger than 3 cm and he underwent a complete resection. Nothing could foresee this aggressive metastatic behavior, especially when the recurrence did not show a sarcomatous transformation.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Masculino , Mediastinoscopia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias
10.
BMC Pulm Med ; 15: 85, 2015 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-26264367

RESUMO

BACKGROUND: Previously, we showed that treatment with the Rho-kinase inhibitor Y-27632 was able to control airway responsiveness, inflammation, remodeling, and oxidative stress in an animal model of asthma, suggesting that this drug is beneficial in asthma. However, studies evaluating the effects of these inhibitors in conjunction with corticosteroids on chronic pulmonary inflammation have not been conducted. Therefore, we evaluated the effects of treatment with the Rho-kinase inhibitor Y-27632, with or without concurrent dexamethasone treatment, on airway and lung tissue mechanical responses, inflammation, extracellular matrix remodeling, and oxidative stress in guinea pigs with chronic allergic inflammation. METHODS: The guinea pigs were subjected to seven ovalbumin or saline inhalation exposures. Treatment with Y-27632 (1 mM) and dexamethasone (2 mg/kg) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the pulmonary mechanics were evaluated and exhaled nitric oxide (ENO) levels were determined. The lungs were removed and histological analysis was performed using morphometry. RESULTS: The treatment of guinea pigs with the Rho-kinase inhibitor and dexamethasone (ORC group) decreased ENO, the maximal mechanical responses after antigen challenge, inflammation, extracellular matrix remodeling and oxidative stress in the lungs. This therapeutic strategy reduced the levels of collagen and IFN-γ in the airway walls, as well as IL-2, IFN-γ, 8-iso-PGF2α and NF-κB in the distal parenchyma, when compared to isolated treatment with corticosteroid or Rho-kinase inhibitor (P < 0.05) and reduced the number of TIMP-1-positive cells and eosinophils in the alveolar septa compared to corticosteroid-treated animals (P < 0.05). The combined treatment with the Rho-kinase inhibitor and the corticosteroid provided maximal control over the remodeling response and inflammation in the airways and parenchyma. CONCLUSIONS: Rho-kinase inhibition, alone or in combination with corticosteroids, can be considered a future pharmacological tool for the control of asthma.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Amidas/farmacologia , Asma/tratamento farmacológico , Glucocorticoides/farmacologia , Inflamação/tratamento farmacológico , Piridinas/farmacologia , Animais , Asma/patologia , Asma/fisiopatologia , Doença Crônica , Modelos Animais de Doenças , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Cobaias , Inflamação/patologia , Inflamação/fisiopatologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia
11.
J Cell Biochem ; 115(6): 1023-32, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24515922

RESUMO

All adult tissues, including the lung, have some capacity to self-repair or regenerate through the replication and differentiation of stem cells resident within these organs. While lung resident stem cells are an obvious candidate cell therapy for lung diseases, limitations exist regarding our knowledge of the biology of these cells. In contrast, there is considerable interest in the therapeutic potential of exogenous cells, particularly mesenchymal stem/stromal cells (MSCs), for lung diseases. Bone marrow derived-MSCs are the most studied cell therapy for these diseases. Preclinical studies demonstrate promising results using MSCs for diverse lung disorders, including emphysema, bronchopulmonary dysplasia, fibrosis, and acute respiratory distress syndrome. This mini-review will summarize ongoing clinical trials using MSCs in lung diseases, critically examine the data supporting their use for this purpose, and discuss the next steps in the translational pathway for MSC therapy of lung diseases.


Assuntos
Ensaios Clínicos como Assunto , Pneumopatias/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Adulto , Animais , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Pneumopatias/metabolismo , Modelos Biológicos
12.
Respir Res ; 15: 118, 2014 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-25272959

RESUMO

We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route. Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month. After the last elastase instillation, saline or MSCs (1×105), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT. After 1 week, mice were euthanized. Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor-ß levels in lung tissue. In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (BM-MSC) and collagen fiber content (BM-MSC and L-MSC). Intravenous administration of BM- and AD-MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor. Only BM-MSCs (IV > IT) increased the number of M2 macrophages. In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2.


Assuntos
Células da Medula Óssea/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Enfisema Pulmonar/patologia , Enfisema Pulmonar/terapia , Animais , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Resultado do Tratamento
14.
J Thorac Dis ; 16(2): 1087-1096, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38505031

RESUMO

Background: Due to advances in screening and treatment of lung cancer, there has been increased interest in long-term lung cancer survivors (LTLCS). The aim of this study was to evaluate the prevalence of LTLCS, their characteristics and patient-reported outcomes (PROs) of LTLCS. Methods: Cross-sectional study that included patients diagnosed with primary lung cancer between Jan 2012 and Dec 2016 whose overall survival (OS) was greater than 5 years. A self-administered questionnaire was applied, including European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30), Patient Health Questionnaire-4 (PHQ-4) and two open questions regarding quality of life (QoL) and suggestions for improvements. Factors potentially related to QoL were analysed. Results: Of 767 lung cancer patients, 158 (20.6%) were LTLCS and LTLCS' proportion increased yearly. Most patients were male (70.9%) with median age of 65 [interquartile range (IQR), 56-71] years. Fifty-seven percent had adenocarcinoma, 66.2% were diagnosed at early stages but 8.9% were at stage IV. During follow-up, 77.1% quitted smoking, 31.8% had disease progression/relapse and 15.2% developed other tumours. Of all living LTLCS, 100 (85%) patients answered the PROs questionnaire. The median Global Health score was 66.67 (IQR, 50-83), social functioning had the best score and emotional functioning the worst. Pain and fatigue were the symptoms with the worst impact on QoL. PHQ-4 identified mental distress in 36% and patients with a lower QoL were more likely to present anxiety (35.3% vs. 9.4%, P=0.007) or depression (27.9% vs. 3%, P=0.006). In the open questions, patients reported pain (17%), lack of familiar/financial support (16%), dyspnoea (14%), depression (8%), concern for the future (8%) and limitations performing daily activities (8%) as the aspects with most impact in QoL. The most suggested measures were improvement of care provided by health institutions (25%) and better social support (16%). Conclusions: Prevalence of LTLCS is increasing and survivors may experience a high prevalence of anxiety and depression as well as a high disease burden affecting QoL. Therefore, it's important to provide multidisciplinary continuous patient-centred care and a careful follow-up for all lung cancer patients, including LTLCS.

15.
Port J Card Thorac Vasc Surg ; 31(1): 23-28, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38743523

RESUMO

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune, neurologic disease that causes a wide range of symptoms. While the transsternal, transcervical and thoracotomy approaches are accepted as effective, there is still debate regarding the VATS approach. MATERIALS AND METHODS: We analyzed our center's surgical experience with thymectomy for myasthenia gravis, comparing the results of patients operated on using VATS and more invasive approaches, over a period of 10 years. A search of the department's surgical database for myasthenia gravis cases between January 2010 and January 2021, revealed a total of 40 cases. Twenty-four patients were included in the final analysis and were distributed into two groups: the VATS procedure group (group A) and the open procedure group (group B). The latter included sternotomy, thoracotomy, transcervical and hemiclamshell approaches. Only radical thymectomies were included. The established outcomes were clinical improvement defined as asymptomatic remission, reduction, or discontinuation of the medication necessary to achieve optimal symptom control. RESULTS: The median follow-up time was 27 months (ranging from 4 to 75 months). Videothoracoscopy radical thymectomy was performed on 12 patients. Complete remission with no medication was achieved in 1 case (8.3%), while 2 patients (16.7%) became asymptomatic with reduced medication. An improvement (reduced symptoms or decreased medication) was observed in 8 cases (66.6%). No change in clinical outcome was noted in 1 patient (8.3%). None of the patients reported worsening symptoms. Open thymectomy was performed on 12 patients. Complete remission with no medication was achieved in 1 case (8.3%), while 2 patients (16.7%) became asymptomatic with reduced medication. An improvement was noted in 6 cases (50%). No change in clinical outcome was observed in 3 patients (25%) whereas 2 of them (16.7%) experienced slightly better symptom control but with a significant increase in medication. One patient (8.3%) described the clinical results as without any significant change. None of the patients reported worsening symptoms. CONCLUSION: The videotoracoscopic approach in the treatment of myasthenia gravis is non-inferior compared to the open approach and effective in a long-term follow-up, offering all the additional benefits of less invasive surgery.


Assuntos
Miastenia Gravis , Cirurgia Torácica Vídeoassistida , Timectomia , Humanos , Miastenia Gravis/cirurgia , Timectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Resultado do Tratamento , Idoso , Toracotomia/métodos , Toracotomia/efeitos adversos , Adulto Jovem
16.
Cell Physiol Biochem ; 32(6): 1681-94, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24356399

RESUMO

BACKGROUND/AIMS: Bone marrow-derived cells (BMDCs) reduced mechanical and histologic changes in the lung in a murine model of silicosis, but these beneficial effects did not persist in the course of lung injury. We hypothesized that repeated administration of BMDCs may decrease lung inflammation and remodeling thus preventing disease progression. METHODS: One hundred and two C57BL/6 mice were randomly divided into SIL (silica, 20 mg intratracheally [IT]) and control (C) groups (saline, IT). C and SIL groups were further randomized to receive BMDCs (2×10(6) cells) or saline IT 15 and 30 days after the start of the protocol. RESULTS: By day 60, BMDCs had decreased the fractional area of granuloma and the number of polymorphonuclear cells, macrophages (total and M1 phenotype), apoptotic cells, the level of transforming growth factor (TGF)-ß' and types I and III collagen fiber content in the granuloma. In the alveolar septa, BMDCs reduced the amount of collagen and elastic fibers, TGF-ß, and the number of M1 and apoptotic cells. Furthermore, interleukin (IL)-1ß, IL-1R1, caspase-3 mRNA levels decreased and the level of IL-1RN mRNA increased. Lung mechanics improved after BMDC therapy. The presence of male donor cells in lung tissue was not observed using detection of Y chromosome DNA. CONCLUSION: repeated administration of BMDCs reduced inflammation, fibrogenesis, and elastogenesis, thus improving lung mechanics through the release of paracrine factors.


Assuntos
Células da Medula Óssea/citologia , Transplante de Medula Óssea , Silicose/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Citocinas/genética , Citocinas/metabolismo , Progressão da Doença , Feminino , Granuloma/metabolismo , Granuloma/patologia , Pulmão/metabolismo , Pulmão/patologia , Macrófagos/citologia , Macrófagos/imunologia , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/metabolismo , Dióxido de Silício/toxicidade , Silicose/etiologia , Silicose/cirurgia
17.
J Surg Case Rep ; 2023(3): rjad084, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36896161

RESUMO

A 49-year-old female patient, without previous medical history, underwent a thoracic CT due to SARS-CoV2 infection. This exam revealed a heterogeneous mass in the anterior mediastinum with 11 × 8.8 cm in close contact with main thoracic vessels and pericardium. Surgical biopsy documented a B2 thymoma. This clinical case reminds the importance of a systematic and global look of the imaging scans. Years before the thymoma diagnosis, the patient underwent a shoulder X-ray due to musculoskeletal pain, where an irregular shape of the aortic arch was visible, probably related to the growing mediastinal mass. An earlier diagnosis would allow a complete mass resection without such extensive surgery and less morbidity.

18.
Tissue Cell ; 81: 102008, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36638647

RESUMO

Studies on the morphology of the reproductive system are essential for understanding the reproduction processes of species or even within genera or families. The present study aimed to describe the functional morphology of the male reproductive system, spermatophore formation, and sperm count of Macrobrachium brasiliense. The anatomy of the reproductive system consists of a pair of testes from which the vasa deferentia (VD) starts, extending to the fifth pair of pereopods. The VD is divided into three regions: proximal (PVD), middle (MVD), and distal (DVD). In the PVD, there is a prominent fold, the typhlosole, formed by columnar cells. The typhlosole disappears in the MVD, being incorporated into one of the faces of the VD wall, identified by its simple columnar epithelium while the remainder of the vessel wall is formed by squamous or simple cubic epithelium. Columnar cells produce type-II and III secretion. The epithelium in the DVD is made up only of cubic cells. Low sperm concentration was observed when compared to other species of the genus Macrobrachium. In conclusion, the typhlosole and columnar epithelium are responsible for the asymmetric spermatophore, which seems the pattern of Macrobrachium that is probably shared with other caridean shrimps.


Assuntos
Decápodes , Palaemonidae , Humanos , Animais , Masculino , Palaemonidae/anatomia & histologia , Espermatogônias , Contagem de Espermatozoides , Sêmen , Espermatozoides , Genitália Masculina/anatomia & histologia , Água Doce
19.
Port J Card Thorac Vasc Surg ; 30(3): 81-84, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-38499031

RESUMO

The need for complete resection of chest wall tumors creates a huge challenge in terms of reconstructing the complex dynamics of the thorax. We are reporting a case of a low-grade fibromyxoid sarcoma (LGFMS) diagnosed in a young male, where the complete resection of the mass, sternum and parcially the pericardium was performed. Subsequently, a composite porous high-density polyethylene StarPore® prosthesis of the sternum and costal arches was used and the latissimus dorsi muscle free flap with skin graft was implanted over the sternum.


Assuntos
Membros Artificiais , Fibrossarcoma , Mixossarcoma , Parede Torácica , Masculino , Humanos , Parede Torácica/diagnóstico por imagem , Fibrossarcoma/diagnóstico por imagem , Retalhos Cirúrgicos/patologia , Impressão Tridimensional
20.
Port J Card Thorac Vasc Surg ; 30(3): 93, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-38499028

RESUMO

We report a case of a 67-years old non-smoking female diagnosed with hypertension when 24-years-old and complicated with chronic kidney and hypertensive heart diseases. On CT-Chest an incidental discovery of a lesion (16x14x23mm) adjacent to the abdominal aorta was made. Initially suspected to be paraganglioma, a hypothesis which the subsequent MRI did not exclude. Urine analysis showed normal Metanephrine with slightly elevated Chromogranin-A levels. During VATs-procedure "bulging" below the adventitial layer of the descending aorta at the level of the diaphragmatic gutter was identified. By opening the adventitia, a lipomatous lesion with a nodular, consistent center was identified and excised. Final histopathological report confirmed the diagnosis of lymph node not suggestive of neoplasia. Currently, 12 months after the surgery, the patient's condition is good being under surveillance in the Thoracosurgical Outpatient Clinic. Despite not having identified any neuroendocrine component, the patient had clinical signs of clear improvement of arterial hypertension.


Assuntos
Hipertensão , Paraganglioma , Idoso , Feminino , Humanos , Aorta Abdominal , Hipertensão/complicações , Linfonodos , Metanefrina , Paraganglioma/diagnóstico
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