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FG-3019 is a fully human monoclonal antibody that interferes with the action of connective tissue growth factor, a central mediator in the pathogenesis of fibrosis.This open-label phase 2 trial evaluated the safety and efficacy of two doses of FG-3019 administered by intravenous infusion every 3 weeks for 45 weeks in patients with idiopathic pulmonary fibrosis (IPF). Subjects had a diagnosis of IPF within the prior 5 years defined by either usual interstitial pneumonia (UIP) pattern on a recent high-resolution computed tomography (HRCT) scan, or a possible UIP pattern on HRCT scan and a recent surgical lung biopsy showing UIP pattern. Pulmonary function tests were performed every 12 weeks, and changes in the extent of pulmonary fibrosis were measured by quantitative HRCT scans performed at baseline and every 24 weeks.FG-3019 was safe and well-tolerated in IPF patients participating in the study. Changes in fibrosis were correlated with changes in pulmonary function.Further investigation of FG-3019 in IPF with a placebo-controlled clinical trial is warranted and is underway.

The Pulmonary Biospecimen Repository (PBR) at the University of Alabama at Birmingham (UAB) was launched in 2009. The purpose of the UAB PBR is to provide investigators within the pulmonary community at UAB and elsewhere with clinical samples derived from multiple lung diseases, including transplant recipients, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, cystic fibrosis, and asthma. Cell and fluid samples isolated from bronchoalveolar lavage (BAL), plasma, and serum are collected and stored; samples are assessed routinely for viability. Each sample is linked directly with the respective patient information via the Pulmonary Translational Research and Clinical Database, a Health Insurance Portability and Accountability Act compliant database that includes detailed information allowing for the study of specific patient cohorts. To access samples, investigators must complete a request form, which is reviewed by the UAB PBR Steering Committee. To date, more than 800 patients have provided approximately 7,000 BAL, serum and plasma fluid, and cell samples. Over the past 4 years, nearly 800 of these samples have been distributed to investigators at UAB and elsewhere. Future plans for the UAB PBR include expanding sample collection to additional pulmonary diseases, such as mycobacterial infections, increasing the number of sample users and obtaining external funding to ensure its continued sustainability.

Objective Interstitial lung disease (ILD) is a variably progressive lung disorder resulting in impaired gas-exchange and respiratory failure with significant morbidity. Oxidative stress has been shown to play a role in the pathobiology of ILD, and we have previously shown that the oxidant-mediated tyrosine modification, o,o’-dityrosine, is increased within proteins in circulating plasma of ILD patients. This study sought to elucidate a protein target of o,o’-dityrosine cross-linking in plasma. Therefore, we tested the hypothesis that fibronectin (FN), a tyrosine-rich extracellular matrix protein shown to play a role in the fibrotic response of ILD, is modified by o,o’-dityrosine cross-linking and is increased in plasma of ILD patients. Methods Fibronectin was immunoprecipitated from age- and sex-matched healthy control (n=20) and ILD patient (n=16) plasma and o,o’-dityrosine levels were quantified by tandem mass-spectrometry (MS/MS). The study was approved by the University of Alabama at Birmingham and the University of Michigan Institutional Review Board. Data were analyzed by unpaired t test with Welch’s correction (mean ± SEM, p Results Fibronectin o,o’-dityrosine cross-linking was observed in plasma of human subjects. Furthermore, fibronectin-associated o,o’-dityrosine levels were significantly increased by 10.95 fold (14.34 ± 5.01 vs. 1.20 ± 0.16) in ILD patients when compared to healthy controls. The o,o’-dityrosine cross-linking of fibronectin was recapitulated in in vitro systems utilizing human lung fibroblasts. Conclusions These data support the idea that tyrosine residues within fibronectin are susceptible to o,o’-dityrosine cross-linking, and this modification of fibronectin is increased in the plasma of ILD patients. This covalent modification of fibronectin could alter protein function, stability, and/or create alternative breakdown products. Further understanding the role of fibronectin o,o’-dityrosine cross-linking in ILD pathophysiology could provide insight leading to identification of novel treatments for the disease. Funding: P01 HL114470, R01 AG046210, R01 HL0942230 and T32 GM008361

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown cause characterized by progressive scarring of the lung parenchyma and relentless loss of lung function. The diagnosis depends on close collaboration between clinicians, radiologists, and pathologists. No therapies approved by the Food and Drug Administration are available for IPF, and an analysis of completed clinical trials has demonstrated that the clinical course of IPF is largely unpredictable. Until therapies that improve survival become available, measures to preserve function and quality of life should be considered, and gastroesophageal reflux should be treated aggressively.

This study investigated nitration and chlorination of epithelial lining fluid (ELF) proteins in patients (n = 29) who had undergone lung allotransplantation. We assayed lung lavage nitrotyrosine (NT) and chlorotyrosine (CT) by HPLC. We measured NT, nitrate (NO(3)(-)), and nitrate (NO(2)(-)) in bronchoalveolar lavage fluid (BALF) and total nitrite (NO(2)(-) + NO(3)(-)) in serum of another group of lung transplant patients (n = 82). In the first group (n = 29), percent nitration of tyrosines (Tyr) (NT/total Tyr x 100) in BALF proteins was: patients, 0.01 (0.00-0.12)%; median (25th-75th% confidence interval), and control subjects 0.01 (0.00-0.02)%. CT (CT/ total Tyr x 100) occurred only in the patients' BALF: 0.01 (0. 00- 0.02)%. In the second group (n = 82), nitrotyrosine (NT) was detected by ELISA in the BALF of patients: 9 (0-41) pmol/mg pro and control subjects: 28 (26-33). Total nitrite (NO(2)(-) + NO(3)(-)) in BALF of the patients: 3.3 (1.9-5.1) microM significantly exceeded that in control subjects: 1.3 (0.8-1.3) microM; p = 0.0133. Serum nitrite also was significantly higher in patients: 37 (26-55) microM than control subjects: 19 (17-20) microM; p = 0.0037. Airway inflammation in transbronchial biopsies (B score) correlated with NT in BALF (p = 0.0369). Lung transplants have increased airway concentrations of reactive nitrogen species (RNS) metabolites. NT, a marker of peroxynitrite (ONOO(-)), is related to the degree of airway inflammation in lung transplants.

Este artigo aborda a relacao entre memoria e midia, a partir do longa-metragem, de ficcao, A Proxima Vitima (1983), de Joao Batista de Andrade, partindo da ideia de que um artefato cultural e um suporte de memoria. Se um filme, mesmo de modo ficcional, encena aspectos do presente do periodo no qual e realizado, constitui registros que lhe conferem tal lugar de memoria. O filme de Andrade, concebido no inicio dos anos 1980 e herdeiro da trajetoria profissional do diretor, tanto no cinema quanto na televisao, entra nos embates de memoria, como testemunho do periodo de transicao democratica no Brasil (1974-1989), seja por sua datacao, seja pelo que artificiosamente constroi. No texto, situamos, incialmente, questoes que sobressaem na chave memoria e midia; em seguida, passamos pela cinematografia do cineasta, no que se conecta ao filme em questao; a chegada e o filme como memoria da transicao. Palavras-chave: Cinema e Historia. Memoria. Brasil-Historia- 1974-1989.

"Aos 3 dias do mes de fevereiro do ano do nascimento de Nosso Senhor Jesus Cristo de 1874, nesta Imperial cidade de Sao Paulo, na casa destinada para os trabalhos da Relacao da mesma cidade, presentes os senhores Desembargadores Excelentissimo Conselheiro Tristao de Alencar Araripe, Presidente da mesma Relacao, Joao Jose de Andrade Pinto, Procurador da Coroa e Promotor de Justica, Jose Norberto dos Santos, Frederico Augusto Xavier de Brito, Olegario Herculano de Aquino e Castro, Antonio de Cerqueira Lima e Agostinho Luis da Gama, comigo Secretario abaixo assinado, ai, pelas 11 horas da manha, depois da bencao do edificio, praticadas as solenidades religiosas pelo Reverendissimo Monsenhor Arcediago Dr. Joaquim Manuel Goncalves de Andrade, compareceu o Excelentissimo Senhor Presidente da Provincia, dr. Joao Teodoro Xavier, o qual foi recebido a porta do salao das conferencias do Tribunal por uma comissao composta dos dois mais modernos Desembargadores e de mim Secretario e dirigindo-se todos a mesa colocada no mesmo salao, o Exmo. Conselheiro Presidente da Relacao deu assento na cabeceira da dita mesa em cadeira de espaldar ao mesmo Excelentissimo Senhor Presidente da Provincia e ocupou a sua sede a mesma cabeceira da mesa, sentando-se os demais Senhores Desembargadores nas suas sedes conforme a ordem de suas antiguidades.