Altered expression of adhesion molecules and epithelial-mesenchymal transition in silica-induced rat lung carcinogenesis

Loss of the epithelial phenotype and disruption of adhesion molecules is a hallmark in the epithelial-mesenchymal transition (EMT) reported in several types of cancer. Most of the studies about the relevance of adhesion and junction molecules in lung cancer have been performed using established tumors or in vitro models. The sequential molecular events leading to EMT during lung cancer progression are still not well understood. We have used a rat model for multistep lung carcinogenesis to study the status of adherens and tight junction proteins and mesenchymal markers during EMT. After silica-induced chronic inflammation, rats sequentially develop epithelial hyperplasia, preneoplastic lesions, and tumors such as adenocarcinomas and squamous cell carcinomas. In comparison with normal and hyperplastic bronchiolar epithelium and with hyperplastic alveolar type II cells, the expression levels of E-cadherin, alpha-catenin and beta-catenin were significantly reduced in adenomatoid preneoplastic lesions and in late tumors. The loss of E-cadherin in tumors was associated with its promoter hypermethylation. alpha- and beta-catenin dysregulation lead to cytoplasmic accumulation in some carcinomas. No nuclear beta-catenin localization was found at any stage of any preneoplastic or neoplastic lesion. Zonula occludens protein-1 was markedly decreased in 66% of adenocarcinomas and in 100% squamous cell carcinomas. The mesenchymal-associated proteins N-cadherin and vimentin were analyzed as markers for EMT. N-cadherin was de novo expressed in 32% of adenocarcinomas and 33% of squamous cell carcinomas. Vimentin-positive tumor cells were found in 35% of adenocarcinomas and 88% of squamous cell carcinomas. Mesenchymal markers were absent in precursor lesions, both hyperplastic and adenomatoid. The present results show that silica-induced rat lung carcinogenesis is a good model to study EMT in vivo, and also provide in vivo evidence suggesting that the changes in cell-cell adhesion molecules are an early event in lung carcinogenesis, while EMT occurs at a later stage

Evaluation Of Gasometric Parameters In Trauma Patients During Mobile Prehospital Care [avaliação Dos Parâmetros Gasométricos Dos Traumatizados Durante O Atendimento Pré-hospitalar Móvel]

Objective: To evaluate gasometric differences of severe trauma patients requiring intubation in prehospital care. Methods: Patients requiring airway management were submitted to collection of arterial blood samples at the beginning of pre-hospital care and at arrival at the Emergency Room. We analyzed: Glasgow Coma Scale, respiratory rate, arterial pH, arterial partial pressure of CO2 (PaCO2), arterial partial pressure of O2 (PaO2), base excess (BE), hemoglobin O2 saturation (SpO2) and the relation of PaO2 and inspired O2 (PaO2/FiO2). Results: There was statistical significance of the mean differences between the data collected at the site of the accident and at the entrance of the ER as for respiratory rate (p = 0.0181), Glasgow Coma Scale (p = 0.0084), PaO2 (p <0.0001) and SpO2 (p = 0.0018). Conclusion: tracheal intubation changes the parameters PaO2 and SpO2. There was no difference in metabolic parameters (pH, bicarbonate and base excess). In the analysis of blood gas parameters between survivors and non-survivors there was statistical difference between PaO2, hemoglobin oxygen saturation and base excess.404293299Gonsaga, R.A., Brugugnolli, I.D., Fraga, G.P., Comparison between two mobile pre-hospital care services for trauma patients (2012) Word J Emerg Surg., 7 (SUPPL. 1), pp. S6Pereira Júnior, G.A., Carvalho, J.B., Ponte Filho, A.D., Malzone, D.A., Pedersoli, C.E., Transporte intra-hospitalar do paciente crítico (2007) Medicina., 40 (4), pp. 500-508Kue, R., Brown, P., Ness, C., Scheulen, J., Adverse clinical events during intrahospital transport by a specialized team: A preliminary report (2011) Am J Crit Care., 20 (2), pp. 153-161Lima Junior, N.A., Bacelar, S.C., Japiassú, A.M., Cader, S.A., Lima, R.C.F., Dantas, E.H.M., Gasometria arterial em dois diferentes métodos de transporte intra-hospitalar no pós-operatório imediato de cirurgia cardíaca (2012) Rev bras ter intensiva., 24 (2), pp. 162-166Waydhas, C., Schneck, G., Duswald, K.H., Deterioration of respiratory function after intra-hospital transport of critically ill surgical patients (1995) Intensive Care Med., 21 (10), pp. 784-789Zuchelo, L.T.S., Chiavone, P.A., Transporte intra-hospitalar de pacientes sob ventilação invasiva: Repercussões cardiorrespiratórias e eventos adversos (2009) J bras pneumol., 35 (4), pp. 367-374Gervais, H.W., Eberle, B., Konietzke, D., Hennes, H.J., Dick, W., Comparison of blood gases of ventilated patients during transport (1987) Crit Care Med., 15 (8), pp. 761-763Wildner, G., Pauker, N., Archan, S., Gemes, G., Rigaud, M., Pocivalnik, M., Arterial line in prehospital emergency settings-A feasibility study in four physician-staffed emergency medical systems (2011) Resuscitation., 82 (9), pp. 1198-1201Schmelzer, T.M., Perron, A.D., Thomason, M.H., Sing, R.F., A comparison of central venous and arterial base deficit as a predictor of survival in acute trauma (2008) Am J Emerg Med., 26 (2), pp. 119-123Bilello, J.F., Davis, J.W., Lemaster, D., Townsend, R.N., Parks, S.N., Sue, L.P., Prehospital hypotension in blunt trauma: Identifying the "crump factor" (2011) J Trauma., 70 (5), pp. 1038-1042(2012) Atendimento pré-hospitalar ao traumatizado, PHTLS / NAEMT, , Tradução do original Prehospital trauma life support, por Renata Scavone, et al. 7a ed. Rio de Janeiro: ElsevierFraga, G.P., Mantovani, M., Magna, L.A., Índices de trauma em pacientes submetidos à laparotomia (2004) Rev Col Bras Cir., 31 (5), pp. 299-306Barros, M.D.A., Ximenes, R., Lima, M.L.C., Mortalidade por causas externas em crianças e adolescentes: Tendência de 1979 a 1995 (2001) Rev Saúde Pública., 35 (2), pp. 142-149Gonsaga, R.A.T., Rimoli, C.F., Pires, E.A., Zogheib, F.S., Fujino, M.V.T., Cunha, M.B., Avaliação da mortalidade por causas externas (2012) Rev Col Bras Cir., 39 (4), pp. 263-267Batista, S.E.A., Baccani, J.G., Silva, R.A.P., Gualda, K.P.F., Vianna Junior, R.J.A., Análise comparativa entre os mecanismos de trauma, as lesões e o perfil de gravidade das vítimas, em Catanduva-SP (2006) Rev Col Bras Cir., 33 (1), pp. 6-10Carrasco, C.E., Godinho, M., Berti de Azevedo Barros, M., Rizoli, S., Fraga, G.P., Fatal motorcycle crashes: A serious public health problem in Brazil (2012) World J Emerg Surg., 7 (SUPPL. 1), pp. S5Marín-León, L., Belon, A.P., Barros, M.B.A., Almeida, S.D.M., Restitutti, M.C., Tendênica dos acidentes de trânsito em Campinas, São paulo, Brasil: Importância crescente dos motociclistas (2012) Cad Saúde Pública., 28 (1), pp. 39-51Jousi, M., Reitala, J., Lund, V., Katila, A., Leppäniemi, A., The role of prehospital blood gas analysis in trauma resuscitation (2010) World J Emerg Surg., 5, p. 10Martin, M., Oh, J., Currier, H., Tai, N., Beekley, A., Eckert, M., An analysis of in-hospital deaths at a modern combat support hospital (2009) J Trauma., 66 (4 SUPPL.), pp. S51-S60. , discussion S60-1Ouellet, J.F., Roberts, D.J., Tiruta, C., Kirkpatrick, A.W., Mercado, M., Trottier, V., Admission base deficit and lactate levels in Canadian patients with blunt trauma: Are they useful markers of mortality? (2012) J Trauma Acute Care Surg., 72 (6), pp. 1532-1535Darlington, D.N., Kheirabadi, B.S., Delgado, A.V., Scherer, M.R., Martini, W.Z., Dubick, M.A., Coagulation changes to systemic acidosis and bicarbonate correction in swine (2011) J Trauma., 71 (5), pp. 1271-1277Rudkin, S.E., Kahn, C.A., Oman, J.A., Dolich, M.O., Lotfipour, S., Lush, S., Prospective correlation of arterial vs venous blood gas measurements in trauma patients (2012) Am J Emerg Med., 30 (8), pp. 1371-1377Hussmann, B., Lefering, R., Waydhas, C., Ruchholtz, S., Wafaisade, A., Kauther, M.D., Prehospital intubation of the moderately injured patient: A cause of morbidity? A matched-pairs analysis of 1,200 patients from the DGU Trauma Registry (2011) Crit Care., 15 (5), pp. R207Park, M., Costa, E.L.V., McIel, A.T., Hirota, A.S., Vasconcelos, E., Azevedo, L.C.P., Alterações hemodinâmicas, respiratórias e metabólicas agudas após o contato do sangue com o circuito extracorpóreo da ECMO: Estudo experimental (2012) Rev bras ter intensiva., 24 (2), pp. 137-14

Humoral response to SARS-CoV-2 infection among liver transplant recipients

Objective Immunosuppressive agents are known to interfere with T and/or B lymphocytes, which are required to mount an adequate serologic response. Therefore, we aim to investigate the antibody response to SARS-CoV-2 in liver transplant (LT) recipients after COVID-19. Design Prospective multicentre case-control study, analysing antibodies against the nucleocapsid protein, spike (S) protein of SARS-CoV-2 and their neutralising activity in LT recipients with confirmed SARS-CoV-2 infection (COVID-19-LT) compared with immunocompetent patients (COVID-19-immunocompetent) and LT recipients without COVID-19 symptoms (non-COVID-19-LT). Results Overall, 35 LT recipients were included in the COVID-19-LT cohort. 35 and 70 subjects fulfilling the matching criteria were assigned to the COVID-19-immunocompetent and non-COVID-19-LT cohorts, respectively. We showed that LT recipients, despite immunosuppression and less symptoms, mounted a detectable antinucleocapsid antibody titre in 80% of the cases, although significantly lower compared with the COVID-19-immunocompetent cohort (3.73 vs 7.36 index level, p<0.001). When analysing anti-S antibody response, no difference in positivity rate was found between the COVID-19-LT and COVID-19-immunocompetent cohorts (97.1% vs 100%, p=0.314). Functional antibody testing showed neutralising activity in 82.9% of LT recipients (vs 100% in COVID-19-immunocompetent cohort, p=0.024). Conclusions Our findings suggest that the humoral response of LT recipients is only slightly lower than expected, compared with COVID-19 immunocompetent controls. Testing for anti-S antibodies alone can lead to an overestimation of the neutralising ability in LT recipients. Altogether, routine antibody testing against separate SARS-CoV-2 antigens and functional testing show that the far majority of LT patients are capable of mounting an adequate antibody response with neutralising ability.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program

Altres ajuts: This work was supported by the Obra Social "La Caixa" (to M. Esteller).Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease