EDWIN ROGER PARRA CUENTAS
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- A long-term prospective randomized controlled study of non-specific interstitial pneumonia (NSIP) treatment in scleroderma(2011) DOMICIANO, Diogo S.; BONFA, Eloisa; BORGES, Claudia T. L.; KAIRALLA, Ronaldo A.; CAPELOZZI, Vera L.; PARRA, Edwin; CHRISTMANN, Romy BeatrizThe association of cyclophosphamide (CYC) and prednisone (PRED) for the treatment of lung fibrosis in systemic sclerosis (SSc) was only evaluated in uncontrolled studies, although in idiopathic interstitial lung disease (ILD) this association seems to be beneficial in patients with non-specific interstitial pneumonia (NSIP). Objectives: To treat SSc-ILD in a prospective open-label controlled study based on lung pattern during 12 months of treatment. Methods: A 3-year analysis was also performed. Twenty-four consecutive patients with SSc and ILD were submitted to an open lung biopsy. Eighteen patients (NSIP) were randomized in two groups: CYC versus CYC + PRED during 12 months. Lung function tests (diffusion lung capacity of monoxide carbone corrected for hemoglobin concentration (DLCO-Hb), forced vital capacity (FVC), total lung capacity) and Modified Rodnan Skin Score (MRSS) were performed before, after one of treatment and after 3 years from the end of the treatment. Results: Pulmonary function tests were similar in both groups on baseline. After 1 year of treatment, FVC% was comparable between CYC groups (p = 0.72) and in CYC + PRED (p = 0.40). Three years after the end of treatment, FVC% values (p = 0.39 in group CYC and p = 0.61 in CYC + PRED and p = 0.22 in CYC + PRED) and DLCO-Hb (p = 0.54 in CYC and p = 0.28 in CYC + PRED) were similar compared to 1 year of treatment. We observed a reduction of the MRSS in the CYC + PRED group after 1 year of treatment (p = 0.02); although after 3 years, MRSS values remained stable in both groups. Conclusions: CYC was effective to stabilize lung function parameters in NSIP lung pattern of SSc disease for 3 years after the end of a 1-year therapy.
- Expression of Acetylcholine and Its Receptor in Human Sympathetic Ganglia in Primary Hyperhidrosis(2013) MOURA JUNIOR, Nabor B. de; DAS-NEVES-PEREIRA, Joao C.; OLIVEIRA, Flavio R. G. de; JATENE, Fabio B.; PARRA, Edwin R.; CAPELOZZI, Vera L.; WOLOSKER, Nelson; CAMPOS, Jose R. M. deBackground. The pathophysiologic characteristics of primary hyperhidrosis are not well understood and seem to be related to a sympathetic nervous system dysfunction. The resection of thoracic sympathetic chain ganglia is the most effective treatment for hyperhidrosis; however sympathetic ganglia function in normal individuals and in patients with hyperhidrosis is unknown. Methods. A cross-sectional study, in which 2 groups of 20 subjects were analyzed: the hyperhidrosis group (HYP), comprised of patients with hyperhidrosis who were eligible for thoracic sympathectomy, and the control group (CON) comprised of brain-dead organ donors without a history of hyperhidrosis. For each subject, the following were performed: resection of the third left sympathetic ganglion, measurement of the ganglion's diameter, and immunohistochemical evaluation by quantification of strong and weak expression areas of primary antibodies against acetylcholine and alpha-7 neuronal nicotinic receptor subunit. Results. The presence of a strong alpha-7 subunit expression area was 4.85% in patients with primary hyperhidrosis and 2.34% in controls (p < 0.001), whereas the presence of a weak expression area was 11.48% in the HYP group and 4.59% in the CON group (p < 0.001). Strong acetylcholine expression was found in 4.95% of the total area in the HYP group and in 1.19% in the CON group (p < 0.001), whereas weak expression was found in 18.55% and 6.77% of the HYP and CON groups, respectively (p < 0.001). Furthermore, diameter of the ganglia was 0.71 cm in the HYP group and 0.53 cm in the CON group (p < 0.001). Conclusions. There is a higher expression of acetylcholine and alpha-7 neuronal nicotinic receptor subunit in the sympathetic ganglia of patients with hyperhidrosis. Furthermore, the diameter of the thoracic sympathetic chain ganglia is larger in such patients. (Ann Thorac Surg 2013;95:465-71) (c) 2013 by The Society of Thoracic Surgeons
- Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis(2013) PARRA, E. R.; AGUIAR, A. C. Junior; SILVA, L. O.; SOUZA, H. S. P.; ESPINOZA, J. D.; CAPELOZZI, V. L.Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc- NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.
- Morphometric Analysis of Thoracic Ganglion Neurons in Subjects with and without Primary Palmar Hyperhidrosis(2014) OLIVEIRA, Flavio Roberto Garbelini de; MOURA JR., Nabor B.; CAMPOS, Jose Ribas M. de; WOLOSKER, Nelson; PARRA, Edwin R.; CAPELOZZI, Vera L.; PEGO-FERNANDES, PauloBackground: Hyperhidrosis (HH) is a disease whose physiopathology remains poorly understood and that adversely affects quality of life. There is no morphologic study that includes an adequate control group that allows for comparison of the ganglion of HH to those of normal individuals. The purpose of study was to analyze morphologic and morphometric characteristics of the ganglion from patients with HH and normal individuals (organ donators). Methods: This was a transversal study. The sympathetic thoracic ganglia were obtained from 2 groups of patients. Group PH (palmar hyperhidrosis), 40 patients with palmar HH submitted to surgery by video-assisted thoracoscopy, and group C (control group), 14 deceased individuals (control group of organ donators) without any history of HH. The third left sympathetic thoracic ganglion was resected in all patients. Results: We observed higher number of cells in the PH group than in the control group (14.25 + 3.81 vs. 10.65 + 4.93) with P = 0.007; the mean percentage of ganglion cells stained by caspases-3 in the PH group was significantly greater than that of the C group (2.37 + 0.79 vs. 0.77 + 0.28) with P < 0.001; the mean value of area of collagen in the PH group was 0.80 IQ (0.08-1.87), and in the control group it was 2.36 IQ (0.49-5.98) with P = 0.061. Conclusions: Subjects with primary palmar HH have a higher number of ganglion cells within the ganglion and a higher number of cells in apoptosis. Also, the subjects of PH group have less collagen in the sympathetic ganglion when compared with the control group, but not statistically significant.
- 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.
- Id-1, Id-2, and Id-3co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy(2016) ANTONANGELO, Leila; TUMA, Taila; FABRO, Alexandre; ACENCIO, Milena; TERRA, Ricardo; PARRA, Edwin; VARGAS, Francisco; TAKAGAKI, Teresa; CAPELOZZI, VeraInhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T1-stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P = 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P = 0.04). Furthermore, high MVD-CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P = 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC.
- 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.