Navegando por Palavras-chave "Nasal polyps"
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- ItemAcesso aberto (Open Access)Comparação das características in vitro e perfil de expressão gênica entre células-tronco mesenquimais derivadas de pólipos nasais e da medula óssea(Universidade Federal de São Paulo (UNIFESP), 2018-11-07) Oliveira, Pedro Wey Barbosa De [UNIFESP]; Gregorio, Luis Carlos [UNIFESP]; http://lattes.cnpq.br/0512614520137100; http://lattes.cnpq.br/6030505570897126; Universidade Federal de São Paulo (UNIFESP)Introduction: Chronic rhinosinusitis (CRS) is clinically defined as persistent inflammation of the nasal mucosa and paranasal sinuses lasting at least 12 weeks;; Chronic rhinosinusitis with nasal polyposis is a disease with its pathophysiological mechanism not yet fully known;; it is believed that nasal polyps are formed by an imbalance in the inflammatory response and an imbalance of tissue remodeling. Classically, we observe a decrease in TGF beta and Treg determining a low immune response and an intense inflammatory response, especially an eosinophilic TH2 response. At the same time, we have an altered tissue repair mechanism with decreased fibrosis formation and intense mucosal edema, resulting in an altered extracellular matrix with elevation of hydrostatic pressure and possibly the formation of polyps. Mesenchymal stem cells (MSCs) are progenitor adult stem cells with the primary goal of supporting the tissue function in which they are in, but they also exhibit immunomodulation and tissue repair characteristics in the healing process. Therefore, we believe that it is fundamental to understand the behavior of the MSCs, especially the the MSC of the nasal polyp, in an attempt to elucidate the mechanism of its formation. Objective: To compare the in vitro characteristics and gene expression profile of mesenchymal stem cells of the nasal polyp (PO-MSC) with the mesenchymal stem cells of the bone marrow (BM-MSC). Materials and methods: We isolated the PO-MSC and BM-MSC and submitted the two groups to in vitro cell differentiation, immunophenotyping, proliferation and co-culture with lymphocytes and finally gene expression profile analysis of the two groups. Results and Discussion: The two groups showed fibroblastoid morphology and a similar potential for osteogenic / adipogenic differentiation, immunophenotyping showed that CTM-PN had a lack of molecules associated with the immune system. Co-cultures of peripheral blood and CTMs also showed a lower ability of CTM-PN to modulate the immune response. We detected in CTM-PN a distinct gene expression profile compared to CTM-MO. CTM- PN expressed higher levels of specific markers of progenitor stem cells (eg, CD133 and ABCB1), whereas the CTM-MO showed high expression of cytokines and growth factors (eg, FGF10, KDR and GDF6). Gene ontology analysis showed that the most expressed genes in the CTM-PN were related to the matrix remodeling process, hexose and glucose transport. CTM-MO showed highly expressed genes related to a distinct biological behavior such as angiogenesis, blood vessel morphogenesis, cell-cell signaling, and regulation of response to external stimuli. Conclusion: CTM-PN and CTM-MO are different sub-populations of CTMs, with distinct transcription profiles that reflect specific biological properties, compatible with the anatomical location of the tissue from which they were extracted. CTM-PN clearly has a lower immunomodulation capacity when compared to CTM-MO;; resulting in a reduced ability to control the local inflammatory process. The genes most significantly expressed in the CTM-PN are partially related to the process of tissue remodeling, extracellular matrix metabolism and tissue regeneration process;; physiopathological basis of RSCcPN. CTM-PN plays an important role in the development of nasal polyps.
- ItemAcesso aberto (Open Access)Convergence of two major pathophysiologic mechanisms in nasal polyposis: immune response to Staphylococcus aureus and airway remodeling(Biomed Central Ltd, 2013-03-28) Pezato, Rogerio [UNIFESP]; Balsalobre, Leonardo [UNIFESP]; Lima, Milena; Bezerra, Thiago F. P.; Voegels, Richard L.; Gregório, Luis Carlos [UNIFESP]; Stamm, Aldo Cassol [UNIFESP]; van Zele, Thibaut; Universidade Federal de São Paulo (UNIFESP); Univ Ghent; Mil Police Hosp; Universidade de São Paulo (USP)This review is addressed two pathophysiologic mechanisms implicated in the pathogenesis of nasal polyposis: the unique remodeling process found in nasal polyp tissue and the immune response of patients with nasal polyposis to Staphylococcus aureus.These two theories converge to the same direction in different aspects, including decreased extracellular matrix production, impaired T regulation and favoring of a Th2 immune response.In patients with nasal polyposis, an exaggerated immune response to Staphylococcus aureus may aggravate the airway remodeling process.
- ItemAcesso aberto (Open Access)Demonstração experimental de um novo mecanismo biofísico envolvido no desenvolvimento da polipose nasal(Universidade Federal de São Paulo (UNIFESP), 2016-02-08) Pezato, Rogerio [UNIFESP]; Gregório, Luiz Carlos [UNIFESP]; http://lattes.cnpq.br/3121718741179338; http://lattes.cnpq.br/8850675385685321; Universidade Federal de São Paulo (UNIFESP)We evaluate biological factors that could influence the remodeling process in the mucosa of nasal polyposis and the biophysical consequences of this abnormal remodeling process. Initially, we evaluate the Staphylococcus aureus invasion limits in the nasal mucosa, we did not demonstrate the bone as possible reservoir for this bacterium, contrary to what is described for the nasal mucosa. We also studied the impact of mesenchymal stem cells on the inflammatory environment of the nasal polyp tissue. In this study we demonstrated the ability of these cells to mitigate the inflammatory process in the nasal polyp tissue. We end the thesis studying the mechanical properties of normal nasal mucosa and nasal polyp tissue. We found that the nasal mucosa of patients with nasal polyposis has lower increase of interstitial hydrostatic pressure than normal nasal mucosa. Using the same methodology we demonstrated that there are differences in the mechanical properties of the nasal mucosa of the inferior turbinate with the middle turbinate. In conclusion, we suggest that the imbalance between the oncotic pressure and hydrostatic pressure contributes to the formation of edema in nasal polyposis.
- ItemAcesso aberto (Open Access)Epithelium and stroma from nasal polyp mucosa exhibits inverse expression of TGF- beta(1) as compared with healthy nasal mucosa(Biomed Central Ltd, 2013-04-15) Balsalobre, Leonardo [UNIFESP]; Pezato, Rogerio [UNIFESP]; Perez-Novo, Claudina; Alves, Maria Teresa S. [UNIFESP]; Santos, Rodrigo P. [UNIFESP]; Bachert, Claus; Weckx, Luc L. M. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ GhentObjective: To evaluate TGF-beta(1) expression in polypoid mucosa (epithelium and stroma) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP).Methods: Cross-sectional study with two groups: 17 patients with nasal polyposis and 11 controls. Polyps and normal nasal mucosa were processed by immunohistochemical methods for TGF-beta 1 visualization. Then, the percentage of TGF-beta 1 expression in stroma and epithelium was objectively quantified using UT Morph software.Results: A lower percentage of positive expression was found in the epithelium of CRSwNP patients (32.44%) versus normal controls (55.91%) (p < 0.05), and a higher percentage of positive expression in the stroma of CRSwNP patients (23.24%) versus controls (5.88%) (p < 0.05).Conclusion: the lower percentage of TGF-beta(1) expression in the nasal epithelium of CRSwNP patients may have an impact on epithelium-directed topical treatments employed in this patient population.
- ItemSomente MetadadadosThe expression of dendritic cell subsets in severe chronic rhinosinusitis with nasal polyps is altered(Elsevier B.V., 2014-09-01) Pezato, Rogerio [UNIFESP]; Perez-Novo, Claudina A.; Holtappels, Gabriele; De Ruyck, Natalie; Van Crombruggen, Koen; De Vos, Geert; Bachert, Claus; Derycke, Lara; Univ Ghent; Universidade Federal de São Paulo (UNIFESP); AZ ST Lucas HospBackground: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized as a Th2-driven disease.Activated dendritic cells (DCs) are the main T-cell activators; their role in the chronic inflammatory process of nasal polyposis is still unclear.Methods: the regulation of DC subsets was analyzed in nasal polyp tissue from CRSwNP patients and compared to inferior turbinate tissue from healthy subjects. Tissue localization and expression of both plasmacytoid and myeloid DCs were assayed by means of immunohistochemistry and flow cytometry. Plasmacytoid DCs were also assayed by PCR, and tissue homogenates were assayed for various inflammatory markers.Results: the number of plasmacytoid (pDCs) and myeloid (mDCs) dendritic cells was significantly increased in nasal polyp tissue when compared to non-inflamed nasal mucosa. the number of pDCs, but not mDCs, was down-regulated in more severe cases (nasal polyps with asthma) and varied with the cytokine milieu. the amount of pDCs was significantly decreased in IL5+IFN gamma - nasal polyp tissue compared to tissues with high IFN gamma levels (IL5+IFN gamma+). Furthermore, levels of indoleamine 2,3-dioxygenase were increased in nasal polyp compared to inferior turbinate tissue and correlated negatively with the number of pDCs.Conclusions: There is an altered balance of pDC and mDC numbers in nasal polyp tissue. pDCs seem to be more susceptible to an inflammatory cytokine milieu and may play a crucial role in disease severity. (C) 2014 Elsevier GmbH. All rights reserved.
- ItemAcesso aberto (Open Access)A fibrose e a remodelação na rinossinusite crônica(Universidade Federal de São Paulo (UNIFESP), 2018-05-24) Gregorio, Luciano Lobato [UNIFESP]; Kosugi, Eduardo Macoto [UNIFESP]; Pezato, Rogério; http://lattes.cnpq.br/8850675385685321; http://lattes.cnpq.br/9771826548166046; http://lattes.cnpq.br/5139361443351453; Universidade Federal de São Paulo (UNIFESP)Introduction: Tissue remodeling is considered a key aspect in distinguishing between chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP), due to its purported central role in polyp formation. Objective: To evaluate the role of fibrosis and remodeling of the nasal mucosa, whether through biomechanical or molecular mechanisms, in CRS. Methods: Three studies were carried out. The first evaluated biomechanical mechanisms in the nasal mucosa. The behavior of interstitial hydrostatic pressure (IHP) was analyzed by recording a continuous infusion of saline solution into the nasal mucosa of patients with CRS, in nasal synechiae, and in control mucosa of individuals without sinonasal disease. Twenty participants (N=20) were examined, at different sites in the nasal cavity. Analysis of the infusion produced a plot of tissue pressure vs. volume infused, which would correspond to IHP, or, in a simplified manner, to mucosal compliance. For the second study, considering the essential role of TGF-β in mucosal remodeling, the existence of a subgroup of patients with CRSwNP who exhibit an exacerbated systemic inflammatory response, and in vitro studies demonstrating a potential relationship between pro- and anti-inflammatory factors, we decided to evaluate the direct influence of administration of a leukotriene receptor antagonist (montelukast) on the systemic production of TGF-β1 in CRS. Serum levels of TGF-β1 were measured in patients with CRSwNP (from different subgroups) and in controls, before and after administration of montelukast. Finally, the third study evaluated the possible variation of tissue levels of TGF-β1 in different regions of the nasal cavity and its relationship with serum levels in healthy controls and in individuals with sinonasal disease. Results: The experimental model of continuous saline injection in the nasal mucosa revealed mechanical dysfunction. IHP increased less in tissue from individuals with CRSwNP when compared to fibrotic tissue (nasal synechiae) and to control tissue. There was no significant difference between the latter two groups. In the control group, a statistically significant difference was found in the IHP reached in the middle and inferior turbinate sites. Regarding analysis of TGF-β1 levels before and after administration of an antileukotriene agent, no statistically significant differences were found, whether in the control group or in subgroups of patients with CRSwNP. Controls showed a trend toward lower serum levels of TGF-β1 in relation to the CRSwNP group. Comparison of tissue levels of TGF-β1 between different nasal sites did not reveal statistically significant differences. Samples taken from the middle meatus of patients with CRSwNP exhibited a numerically lower cytokine concentration in relation to the control and CRSsNP groups. A possible inverse pattern of TGF-β1 levels in the middle meatus/inferior turbinate of the CRSwNP group was found in comparison to the control and CRSsNP groups. Conclusion: These studies confirmed biomechanical involvement of the mucosa in patients with CRSwNP, with evidence of increased mucosal compliance, which might facilitate polyp formation. Montelukast administration had no appreciable impact on systemic TGF-β1 production in patients with CRSwNP, suggesting that use of this agent with a view to altering the remodeling process is a questionable practice. There was no significant difference in tissue levels of TGF-β1 at different sites of the nasal cavity in patients with CRS.
- ItemAcesso aberto (Open Access)The human leukocyte antigen G molecule (HLA-G) expression in patients with nasal polyposis(Associação Brasileira de Otorrinolaringologia e Cirurgia Cervicofacial, 2014-06-01) Avelino, Melissa Ameloti Gomes [UNIFESP]; Wastowski, Isabela Jubé; Ferri, Ricardo Gimenes [UNIFESP]; Elias, Thaís Gomes Abrahão; Lima, Ana Paula Lindoso; Marinho, Larissa Cardoso [UNIFESP]; Pignatari, Shirley Shizue Nagata [UNIFESP]; Universidade Federal de Goiás; Universidade Estadual de Goiás; Pontifícia Universidade Católica de Goiás; Universidade Federal de São Paulo (UNIFESP)INTRODUCTION:Sinonasal polyposis (NP) is a chronic inflammatory pathology of the nasal/paranasal cavities which affects from 1%-4% of the population. Although polyps seem to be a manifestation of chronic inflammation in both allergic and non-allergic subjects, the pathogenesis of nasal polyposis remains unknown. HLA-G molecules are a kind of no classic class I antigen with anti-inflammatory and tolerogenic properties. Little attention has been paid to the role of HLA-G chronic inflammatory disorders.OBJECTIVE:The aim of this study is to investigate the expression of HLA-G in the NP.MATERIALS AND METHODS:Prospective study involving samples of patients presenting with nasal polyposis that were subjected to the immunohistochemistry technique. After a skin prick test, all patients were divided into atopic and nonatopic groups and classified as asthmatic or non-asthmatic.RESULTS:Immunohistochemical staining demonstrated a higher expression of the HLA-G molecule in samples from nonatopic than in those from atopic patients, and was significantly lower in the non-asthmatic patients.CONCLUSION:These results indicate that HLA-G may play an important role in the pathology of nasal polyposis. Considering the anti-inflammatory properties of HLA-G, this study suggests that it could reduce susceptibility to atopy and asthma.
- ItemAcesso aberto (Open Access)Topical therapy with high-volume budesonide nasal irrigations in difficult-to-treat chronic rhinosinusitis(Assoc Brasileira Otorrinolaringologia & Cirurgia Cervicofacial, 2016) Kosugi, Eduardo Macoto [UNIFESP]; Moussalem, Guilherme Figner [UNIFESP]; Simoes, Juliana Caminha [UNIFESP]; Felici de Souza, Rafael de Paula e Silva [UNIFESP]; Chen, Vitor Guo [UNIFESP]; Neto, Paulo Saraceni [UNIFESP]; Mendes Neto, Jose Arruda [UNIFESP]Introduction: Chronic rhinosinusitis (CRS) is termed difficult-to-treat when patients do not reach acceptable level of control despite adequate surgery, intranasal corticosteroid treatment and up to 2 short courses of systemic antibiotics or corticosteroids in the preceding year. Recently, high-volume corticosteroid nasal irrigations have been recommended for CRS treatment. Objective: To assess high-volume budesonide nasal irrigations for difficult-to-treat CRS. Methods: Prospective uncontrolled intervention trial. Participants were assessed before- and 3 months after nasal irrigation with 1 mg of budesonide in 500 mL of saline solution daily for 2 days. Subjective (satisfactory clinical improvement) and objective (SNOT-22 questionnaire and Lund-Kennedy endoscopic scores) assessments were performed. Results: Sixteen patients were included, and 13 (81.3%) described satisfactory clinical improvement. SNOT-22 mean scores (50.2-29.6; p = 0.006) and Lund-Kennedy mean scores (8.8-5.1; p=0.01) improved significantly. Individually, 75% of patients improved SNOT-22 scores, and 75% improved Lund-Kennedy scores after high volume budesonide nasal irrigations. Conclusion: High-volume corticosteroid nasal irrigations are a good option in difficult-to-treat CRS control of disease, reaching 81.3% success control and significant improvement of SNOT-22 and Lund-Kennedy scores. (C) 2015 Associacao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial. Published by Elsevier Editora Ltda.