EDWIN ROGER PARRA CUENTAS
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conferenceObject Collagen V activation and matrix extracellular remodeling mediated pulmonary fibrosis in experimental models of bleomycin and 3-5-di-tert-4-hidroxitoluene(2013) LOPES, Deborah; MARTINS, Vanessa; TEODORO, Walcy; ROGER, Edwin; CAPELOZZI, Vera Luiza- Preservation of Alpha-3 Neuronal Nicotinic Acetylcholine Receptor Expression in Sympathetic Ganglia After Brain Death(2012) MOURA JUNIOR, Nabor Bezerra de; DAS-NEVES-PEREIRA, Joao Carlos; CAMPOS, Jose Ribas Milanez de; OLIVEIRA, Flavio Roberto Garbelini de; WOLOSKER, Nelson; PARRA, Edwin Roger; CAPELOZZI, Vera Luiza; JATENE, Fabio BiscegliThe goal of this study was to evaluate if the immunohistochemical expression of alpha-3 neuronal nicotinic acetylcholine receptor subunit in sympathetic ganglia remains stable after brain death, determining the possible use of sympathetic thoracic ganglia from subjects after brain death as study group. The third left sympathetic ganglion was resected from patients divided in two groups: BD-organ donors after brain death and CON-patients submitted to sympathectomy for hyperhidrosis (control group). Immunohistochemical staining for alpha-3 neuronal nicotinic acetylcholine receptor subunit was performed; strong and weak expression areas were quantified in both groups. The BD group showed strong alpha-3 neuronal nicotinic acetylcholine receptor expression in 6.55% of the total area, whereas the CON group showed strong expression in 5.91% (p = 0.78). Weak expression was found in 6.47% of brain-dead subjects and in 7.23% of control subjects (p = 0.31). Brain death did not affect the results of the immunohistochemical analysis of sympathetic ganglia, and its use as study group is feasible.
- Usual interstitial pneumonia and smoking-related interstitial fibrosis display epithelial to mesenchymal transition in fibroblastic foci(2014) FABRO, Alexandre Todorovic; MINATEL, Igor Otavio; RANGEL, Maristela Peres; HALBWEDL, Iris; PARRA, Edwin Roger; CAPELOZZI, Vera Luiza; POPPER, HelmutBackground: Fibroblastic foci (FF) are a major histological feature of usual interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis (IPF) and collagen vascular diseases (non-IPF). In addition, FF are occasionally associated with smoking-related interstitial fibrosis (SRIF). Recent studies have suggested a role for epithelial to mesenchymal transition (EMT) in pulmonary fibrogenesis. Methods: Here, we investigated whether EMT was present in patients with IPF (n = 19), non-IPF (n = 17), and SRIF (n = 16) using morphometric immunohistochemistry, electron microscopy, and confocal microscopy. All patients had received lung biopsies or lobectomies for lung cancer. Results: IPF and non-IPF patients displayed restrictive lung function patterns, whereas those with SRIF presented mixed patterns. Cells within FF presented high number of alpha-smooth muscle actin (alpha SMA)-staining cells; however, the foci of IPF patients showed comparatively lower number. Moreover, colocalization of thyroid transcription factor-1 (TTF1) and alpha SMA within FF showed low number of staining cells for IPF and SRIF in comparison to non-IPF (p < 0.01). Nevertheless, all groups displayed colocalization of high rate of TTF1(+)-cells and low rate of alpha SMA(+)-cells within hyperplastic epithelioid cells in FF. Also, we observed areas with low proportion of TTF1(+) cells and alpha SMA(+) cells, which were present in SRIF and non-IPF more often than IPF (p < 0.001). Electron microscopy revealed small breaks in the alveolar basal lamina, which allowed epithelioid cells to directly contact the collagenous matrix and fibroblasts. Three-dimensional reconstruction revealed intense alpha SMA staining within some epithelioid cells, suggesting that they had gained a mesenchymal phenotype. Conclusions: These findings constitute the first report of EMT in SRIF and suggest that EMT occurs more prominently in SRIF and non-IPF than IPF.
- Avaliação imuno-histoquímica e morfométrica de COX-1 e COX-2 no remodelamento pulmonar na fibrose pulmonar idiopática e na esclerose sistêmica(2013) PARRA, Edwin Roger; LIN, Flavia; MARTINS, Vanessa; RANGEL, Maristela Peres; CAPELOZZI, Vera LuizaObjective: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (1PF) patients, correlating that expression with patient survival. Methods: We examined open lung biopsy specimens from 24 SSc patients and 301PF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NS1P) in SSc patients and usual interstitial pneumonia (UP) in 1PF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. Results: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in 1PF-U1P and SSc-NS1P lung tissue than in the control tissue. No difference was found between 1PF-UIP and SSc-NS1P tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, 1PF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NS1P), and low COX-1 expression in alveolar septa. Conclusions: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on 1PF. However, prospective randomized clinical trials are needed in order to confirm
- Early type I collagen deposition is associated with prognosis in biliary atresia(2016) LONGO-SANTOS, Luis Ricardo; TEODORO, Walcy Rosolia; MELLO, Evandro Sobroza de; VELOSA, Ana Paula Pereira; PARRA, Edwin Roger; CAPELOZZI, Vera Luiza; TANNURI, UenisBackground: Biliary atresia (BA) is a cholestatic liver disease of children that progresses to hepatic fibrosis. BA is the main indication of pediatric liver transplantation (LTx). Histopathological markers in liver biopsies could be useful for predicting progression to end-stage disease. Objective: To establish histopathological or immunohistochemical markers in liver biopsies of BA patients and correlate those markers with prognosis. Method: Histological analysis of biliary alterations and morphometric assessment of liver fibrosis were performed, in addition to indirect immunofluorescence assays (IF) for type I, III, IV and V collagens in initial and final liver biopsies of 36 patients with BA who underwent Kasai hepatoportoenterostomy (KPE) and LTx in the last 20 years at a single center. Results: Histopathologicalmarkers had no correlation with evolutive time until LTx. The perisinusoidal deposition of type III and V collagens was more prominent in the initial biopsies (p < 0.01), whereas deposition of type I and IV collagens indicated progression (p < 0.01). Patients with large amounts of perisinusoidal type I collagen in the initial biopsies had worse progression time curves until LTx (p = 0.04). Conclusion: Morphometric assessment of perisinusoidal deposition of type I collagen by IF in the initial biopsy can correlate with progression time to LTx in post-surgical BA.
conferenceObject Epithelial mesenchymal transition in fibroblastic foci of different fibrosing lung diseases: Repair or remodeling?(2013) FABRO, Alexandre Todorovic; HALBWEDL, Iris; PARRAS, Edwin Roger; CAPELOZZI, Vera Luiza; POPPER, Helmut- Effects of cilostazol in kidney and skeletal striated muscle of Wistar rats submitted to acute ischemia and reperfusion of hind limbs(2012) MOREIRA NETO, Antonio Augusto; SOUZA JUNIOR, Sylvio Sebastiao de; CAPELOZZI, Vera Luiza; PARRA-CUENTAS, Edwin Roger; SCHMIDT JUNIOR, Aurelino Fernandes; NETO, Acacio Francisco; RODRIGUES, Olavo RibeiroPURPOSE: To investigate the effect of cilostazol, in kidney and skeletal muscle of rats submitted to acute ischemia and reperfusion. METHODS: Fourty three animals were randomized and divided into two groups. Group I received a solution of cilostazol (10 mg/Kg) and group II received saline solution 0.9% (SS) by orogastric tube after ligature of the abdominal aorta. After four hours of ischemia the animals were divided into four subgroups: group IA (Cilostazol): two hours of reperfusion. Group IIA (SS): two hours of reperfusion. Group IB (Cilostazol): six hours of reperfusion. Group IIB (SS) six hours of reperfusion. After reperfusion, a left nephrectomy was performed and removal of the muscles of the hind limb. The histological parameters were studied. In kidney cylinders of myoglobin, vacuolar degeneration and acute tubular necrosis. In muscle interstitial edema, inflammatory infiltrate, hypereosinophilia fiber, cariopicnose and necrosis. Apoptosis was assessed by immunohistochemistry for cleaved caspase-3 and TUNEL. RESULTS: There was no statistically significant difference between groups. CONCLUSION: Cilostazol had no protective effect on the kidney and the skeletal striated muscle in rats submitted to acute ischemia and reperfusion in this model.
- Increased fibroblast telomerase expression precedes myofibroblast alpha-smooth muscle actin expression in idiopathic pulmonary fibrosis(2012) WAISBERG, Daniel Reis; PARRA, Edwin Roger; BARBAS-FILHO, Joao Valente; FERNEZLIAN, Sandra; CAPELOZZI, Vera LuizaOBJECTIVE: This study sought to identify the relationship between fibroblast telomerase expression, myofibroblasts, and telomerase-mediated regulatory signals in idiopathic pulmonary fibrosis. METHODS: Thirty-four surgical lung biopsies, which had been obtained from patients with idiopathic pulmonary fibrosis and histologically classified as usual interstitial pneumonia, were examined. Immunohistochemistry was used to evaluate fibroblast telomerase expression, myofibroblast alpha-smooth muscle actin expression and the tissue expression of interleukin-4, transforming growth factor-beta, and basic fibroblast growth factor. The point-counting technique was used to quantify the expression of these markers in unaffected, collapsed, mural fibrosis, and honeycombing areas. The results were correlated to patient survival. RESULTS: Fibroblast telomerase expression and basic fibroblast growth factor tissue expression were higher in collapsed areas, whereas myofibroblast expression and interleukine-4 tissue expression were higher in areas of mural fibrosis. Transforming growth factor-beta expression was higher in collapsed, mural fibrosis and honeycombing areas in comparison to unaffected areas. Positive correlations were found between basic fibroblast growth factor tissue expression and fibroblast telomerase expression and between interleukin-4 tissue expression and myofibroblast alpha-smooth muscle actin expression. Negative correlations were observed between interleukin-4 expression and basic fibroblast growth factor tissue expression in areas of mural fibrosis. Myofibroblast alpha-smooth muscle actin expression and interleukin-4 tissue expression in areas of mural fibrosis were negatively associated with patient survival. CONCLUSION: Fibroblast telomerase expression is higher in areas of early remodeling in lung tissues demonstrating typical interstitial pneumonia, whereas myofibroblast alpha-smooth muscle actin expression predominates in areas of late remodeling. These events seem to be regulated by basic fibroblast growth factor and interleukin-4 tissue expression, respectively.
- Impact of Bacillus Calmette-Guerin Moreau vaccine on lung remodeling in experimental asthma(2013) SAMARY, Cynthia dos Santos; ANTUNES, Mariana Alves; SILVA, Johnatas Dutra; SILVA, Adriana Lopes da; ARAUJO, Carla Cristina de; BAKKER-ABREU, Ilka; DIAZ, Bruno Lourenco; FERNEZLIAN, Sandra; PARRA, Edwin Roger; CAPELOZZI, Vera Luiza; SILVA, Pedro Leme; SILVA, Jose Roberto Lapa e; ROCCO, Patricia Rieken MacedoWe analyzed the effects of different administration routes and application times of the BCG-Moreau strain on airway and lung inflammation and remodeling in a murine model of allergic asthma. BALB/c mice (n = 168) were divided into two groups. The first group received BCC-Moreau strain while the second group received saline using the same protocol. BCG or saline were intradermally or intranasally injected one or two months before the induction of asthma. Mice were further sensitized and challenged with ovalbumin or received saline. Twenty-four hours after the last challenge, BCG prevented the triggering of pro-inflammatory cytokines, probably by increasing Foxp3 and interleukin (IL)-10, modulating eosinophil infiltration and collagen fiber deposition, thus reducing airway hyperresponsiveness. In conclusion, BCG-Moreau prevented lung remodeling in the present model of allergic asthma, regardless of administration route and time of vaccination. These beneficial effects may be related to the increase in regulatory T cells and to IL-10 production in tandem with decreased Th2 cytokines (IL-4, IL-5, and IL-13).
conferenceObject IL-17+cells immunoexpression in systemic sclerosis pulmonary fibrosis(2014) VELOSA, Ana Paula Pereira; PAIVA, Michelle Abdo; ANDRADE, Priscila Cristina; CHRISTMANN, Romy Beatriz; EHER, Esmeralda Miristeni; FERNEZLIAN, Sandra Morais; PARRA, Edwin Roger; TEODORO, Walcy Rosolia; CAPELOZZI, Vera Luiza