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 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.
- Impact of obesity on airway and lung parenchyma remodeling in experimental chronic allergic asthma(2011) SARAIVA, Simone A.; SILVA, Adriana L.; XISTO, Debora G.; ABREU, Soraia C.; SILVA, Johnatas D.; SILVA, Pedro L.; TEIXEIRA, Tatiana P. F.; PARRA, Edwin R.; CARVALHO, Ana Laura N.; ANNONI, Raquel; MAUAD, Thais; CAPELOZZI, Vera L.; SILVA, Patricia M. R.; MARTINS, Marco A.; ROCCO, Patricia R. M.The impact of obesity on the inflammatory process has been described in asthma, however little is known about the influence of diet-induced obesity on lung remodeling. For this purpose, 56 recently weaned A/J mice were randomly divided into 2 groups. In the C group, mice were fed a standard chow diet, while OB animals received isocaloric high-fat diet to reach 1.5 of the mean body weight of C. After 12 weeks, each group was further randomized to be sensitized and challenged with ovalbumin (OVA) or saline. Twenty-four hours after the last challenge, collagen fiber content in airways and lung parenchyma, the volume proportion of smooth muscle-specific actin in alveolar ducts and terminal bronchiole, and the number of eosinophils in bronchoalveolar lavage fluid were higher in OB-OVA than C-OVA. In conclusion, diet-induced obesity enhanced lung remodeling resulting in higher airway responsiveness in the present experimental chronic allergic asthma.
article 39 Citação(ões) na Scopus Experimental diabetes modulates collagen remodelling of joints in rats(2012) ATAYDE, Sandra A.; YOSHINARI, Natalino H.; NASCIMENTO, Dafne P.; CATANOZI, Sergio; ANDRADE, Priscila C.; VELOSA, Ana Paula P.; PARRA, Edwin R.; PASSARELLI, Marisa; NAKANDAKARE, Edna R.; CAPELOZZI, Vera L.; TEODORO, Walcy R.The aim of this study was to evaluate extracellular matrix components in articular cartilage, ligaments and synovia in an experimental model of diabetes. Young Wistar rats were divided into a streptozotocin-induced (STZ; 35 mg/kg) diabetic group (DG; n=15) and a control group (CG; n=15). Weight, blood glucose and plasma anti-carboxymethyllysine were measured 70 days after STZ infusions. Knee joints, patellar ligaments, and lateral and medial collateral ligaments were isolated and stained with hematoxylineosin and Picrosirius. The total collagen content was determined by morphometry. Immunofluorescence was employed to evaluate types I, III, and V collagen in ligaments and synovial tissues and types II and XI collagen in cartilage. Results: Higher blood glucose levels and plasma anti-carboxymethyllysine were observed in DG rats when compared to those in CG rats. The final weight was significantly lower in the DG rats than in the CG rats. Histomorphometric evaluation depicted a small quantity of collagen fibers in ligaments and articular cartilage in DG rats, as well as increased collagen in synovial tissue. There was a decrease in cartilage proteoglycans in DG rats when compared with CG rats. Immunofluorescence staining revealed an increase of collagen III and V in ligaments, collagen XI in cartilage, and collagen I in synovial tissue of DG rats compared with CG rats. Conclusion: The ligaments, cartilage and synovia are highly affected following STZ-induced diabetes in rats, due the remodeling of collagen types in these tissues. This process may promote the degradation of the extracellular matrix, thus compromising joint function. Our data may help to better understand the pathogenesis of joint involvement related to diabetes.conferenceObject NEW POTENTIAL MARKER FOR THE DIAGNOSIS OF LUNG CANCER: HYALURONAN.(2013) RANGEL, Maristela P.; SA, Vanessa K. De; PARRA, Edwin R.; CAPELOZZI, Vera L.- miR-155 in the progression of lung fibrosis in systemic sclerosis(2016) CHRISTMANN, Romy B.; WOOTEN, Alicia; SAMPAIO-BARROS, Percival; BORGES, Claudia L.; CARVALHO, Carlos R. R.; KAIRALLA, Ronaldo A.; FEGHALI-BOSTWICK, Carol; ZIEMEK, Jessica; MEI, Yu; GOUMMIH, Salma; TAN, Jiangning; ALVAREZ, Diana; KASS, Daniel J.; ROJAS, Mauricio; MATTOS, Thiago Lemos de; PARRA, Edwin; STIFANO, Giuseppina; CAPELOZZI, Vera L.; SIMMS, Robert W.; LAFYATIS, RobertBackground: MicroRNA (miRNA) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from patients with SSc-ILD. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 patients with SSc-ILD and 5 controls. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and peripheral blood mononuclear cells (PBMC) were isolated from healthy controls and patients with SSc-ILD. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DNA Intelligent Analysis (DIANA)-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q < 0.25). DIANA-miRPath revealed 57 Kyoto Encyclopedia of Genes and Genomes pathways related to the most dysregulated miRNA. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts only mildly expressed miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNA are dysregulated in the lungs and PBMC of patients with SSc-ILD. Based on mRNA-miRNA interaction analysis and pathway tools, miRNA may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD.
conferenceObject Abnormal Collagen Fibers Deposition In The Synovial Joints Is a Characteristic Of The Temporal Evolution Of The Diabetic rats' Model Induced By Streptozotocin(2013) ANDRADE, Priscila C.; VELOSA, Ana Paula P.; MORAIS, Jymenez; PARRA, Edwin R.; GOLDEINSTEIN-SCHAINBERG, Claudia; CAPELOZZI, Vera L.; TEODORO, Walcy R.- The Th17 pathway in the peripheral lung microenvironment interacts with expression of collagen V in the late state of experimental pulmonary fibrosis(2015) FABRO, Alexandre T.; SILVA, Pedro H. R. Q. da; ZOCOLARO, William S.; ALMEIDA, Mozar S. de; RANGEL, Maristela P.; OLIVEIRA, Cristiano C. de; MINATEL, Igor O.; PRANDO, Erika d. C.; RAINHO, Claudia A.; TEODORO, Walcy R.; VELOSA, Ana P. P.; SABER, Alexandre M. A.; PARRA-CUENTAS, Edwin R.; POPPER, Helmut H.; CAPELOZZI, Vera L.Background: Myofibroblasts derived from fibroblasts in the pathogenesis of pulmonary fibrosis causes excessive and disordered deposition of matrix proteins, including collagen V, which can cause a Th17-mediated immune response and lead to apoptosis. However, whether the intrinsic ability of lung FBs to produce the matrix depends on their site-specific variations is not known. Aim: To investigate the link between Th17 and collagen V that maintains pulmonary remodeling in the peripheral lung microenvironment during the late stage of experimental pulmonary fibrosis. Methods: Young male mice including wild Balb/c mice (BALB, n = 10), wild C57 Black/6J mice (C57, n = 10) and IL-17 receptor A knockout mice (KO, n = 8), were sacrificed 21 days after treatment with bleomycin. Picrosirius red staining, immunohistochemistry for IL-17-related markers and ""in situ"" detection of apoptosis, immunofluorescence for collagen types I and V, primary cell cultures from tissue lung explants for RT-PCR and electron microscopy were used. Results: The peripheral deposition of extracellular matrix components by myofibroblasts during the late stage is maintained in C57 mice compared with that in Balb mice and is not changed in the absence of IL-17 receptor A; however, the absence of IL-17 receptor A induces overexpression of type V collagen, amplifies the peripheral expression of IL-17 and IL-17-related cytokines and reduces peripheral lung fibroblast apoptosis. Conclusion: A positive feedback loop between the expression patterns of collagen V and IL-17 may coordinate the maintenance of peripheral collagen I in the absence of IL-17 receptor A in fibrosis-susceptible strains in a site-specific manner.
conferenceObject PEQUI FRUIT (CARYOCAR BRASILIENSE CAMB) PULP OIL, A NATURAL SOURCE OF ANTIOXIDANTS, REDUCE THE OXIDATIVE STRESS STATUS AND DNA DAMAGE IN EXPERIMENTAL LUNG CANCER(2012) COLOMBO, Natalia B. R.; PARRA, Edwin R.; GRISOLIA, Cesar K.; GELAIN, Daniel P.; HAGE, Marcia; SCHNORR, Carlos E.; KOLLING, Eduardo; BARBEIRO, Denise F.; CAPELOZZI, Vera L.Background: It is well known that the endogenous antioxidant enzyme defense as well as an adequate ingestion of exogenous sources of antioxidants prevents the oxidative damage caused by reactive species (ROS),including DNA damage, and can reduce the risk of cancer, atherosclerosis and other degenerative diseases. The pulp of Caryocar brasiliense Camb, most known as pequi, is a Brazilian fruit that has high levels of antioxidants properties, such as vitamin C, carotenoids, phenolic compounds like flavonoids, saponins and tannins, and essential oils. The aim of this study was to estimate and to evaluate the antioxidant enzyme activities of catalase (CAT) and superoxide dismutase (SOD), as well as the ratio between then, and the antioxidant activity of the pequi oil, measuring lipid peroxidation and DNA damage in experimental model of lung cancer induced by urethane. Methods: The study was performed in 18 male BALB/c mice: 14 animals received by gavage 0,5μL/mg/day of pequi oil (PI0601631-6) (Control+CBCoil = 4) during 75 days. After 15 days of the beginning of the gavage, 10 of these mices received two doses of 1,5g/kg intraperitoneal of urethane (Urethane+CBC oil=10). The other 4 animals were only submitted to two doses of 1,5g/kg intraperitoneal of urethane (Urethane group=4). After 75 days, the three groups were sacrificed. The antioxidant activity of pequi oil was evaluated in the lung tissues by the biochemical TBARS (Thiobarbituric acidreactive substances), CAT and SOD test. The DNA damage was estimated by the comet test method. Results and Conclusion: The lung parenchyma from the Urethane groups without oil and with oil showed neoplasic formations induced by the chemical carcinogenesis in contrast with Control + CBC oil group. The results of the TBARS test showed a significant decreased of the lipid peroxidation in the Urethane + CBC oil, similar as values of the Control+CBC oil, when compared with Urethane group. The CAT and SOD test, as well as the ratio between then, didn’t show a significant difference. The image analysis of the comet assay showed a statistical significant decreased of the DNA damage cells in the Urethane + CBC oil group when compared with urethane group (p=0.001). The decreased DNA damage was very similar that we obtained in the Control + CBC oil group. We conclude that the different natural antioxidant components found in the pequi oil are efficient to diminish the oxidative stress status and the DNA damage in chemical carcinogenesis induced by urethane experimental lung cancer, suggesting that this type of strategies may have a greater impact in lung cancer treatment.