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Membrane and Subcellular Muscle Injury Are Induced by Single or Multiple Exposure to Cigarette Smoke

Open Journal of Pathology 2014年第3期4卷 125-137页

作者： Ana Maria Fleig-Mayer alba ramirez-sarmiento Amanda Iglesias Montserrat Morla Carlos Coronell Diego Rodríguez Simona Pichinni Josep Lloreta Piergiorgio Zuccaro Xavier Busquets Joaquim Gea Jose R.Jardim Mauricio Orozco-Levi Centro Universitario do Triangulo(UNITRI) Avenida nicomedes Alves Dos Santos4545-GaveaUberlandiaPulmonary Rehabilitation CenterRespiratory DivisionFederal University of Sao PauloSao PauloBrazil Group of Research in Injury Immune Response and Function(LIF)Municipal Institute of Medical Research(IMIM)Carrer Dr.Aiguader 88BarcelonaE-08003Spain Servei de Pneumologia Hospital del MarPasseig Maritim 25BarcelonaE-08003Spain Centro en Red de Investigacion de Enfermedades Respiratorias(CIBERES) Recinto Hospital Joan March Carretera Soller Km.1207110BunyolaMallorcaIlles BalearsSpain Institut Universitari d’Investigacio en Ciencies de la Salut(IUNICS)and Department de Biologia Universitat Illes Balears(UIB)Cra de ValldemossaKm 7.5PalmaIlles BalearsSpain Laboratorio Di Biochimica Clinica Istituto Superiore Di Sanita.Viale Regina Elena 29900161RomaItaly Respiratory Department Fundacion Cardiovascular de ColombiaCalle 155A 23-58FloridablancaSantanderColombia Servei d’Anatomia Patologica Hospital del MarPasseig Maritim 25BarcelonaE-08003Spain

Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD). Diaphragm injury is observed in patients with COPD. However, the potential role of smoking in triggering or perpetuating muscle injury is unknown. The present study was aimed at evaluating the potential role of commercial tobacco smoke as a direct cause of skeletal muscle injury in experimental conditions. Seventy Wistar rats (170 - 250 g) were assigned to smoking (n = 49) or non-smoking (n = 21) groups. The smoking groups were submitted to a single or multiple (i.e., five or thirty) daily sessions of cigarette smoking in an inhalatory chamber (time length: 2 h each session). The level of exposure was constant and assessed by CO concentrations (50 ppm) and serum cotinine analysis. Animals submitted to a single smoke exposure and the corresponding controls were euthanized in groups at 0 h, 2 h, 4 h, 24 h or 48 h after completing the exposure. Animals submitted to multiple exposures were euthanized at 0 h after smoking. Samples from vastus lateralis muscle were obtained and processed for assessing cell injury and selected protein expression. Monoclonal anti-albumin antibodies were used to identify muscle fibers with sarcolemmal (membrane) injury. Subcellular muscle injury was assessed using transmission electron microscopy (EM). MyoD, myogenin and α-tubulin were immunodetected using western blot techniques. Exposure to cigarette smoke associated with significant membrane damage (mean relative difference (MRD) with controls: +181%, p = 0.004) and sarcomere disruptions (MRD: +226%, p = 0.001). Expression of MyoD and myogenin (normalized to α-tubulin) were significantly increased at 4 h and remained increased at 48 h post-exposure. We conclude that not only a single but also consecutive exposure to tobacco smoke have acute deleterious effects on peripheral muscle structure. A rapid induction of subrogate markers of skeletal muscle stress and repair processes associates to sarcolemmal and

关键词： Skeletal Muscle Muscle Injury Muscle Regeneration Quadriceps Cigarette Smoking

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Lack of MICA Expression Predicts a Worse Prognosis in Patients with Bladder Cancer

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Open Journal of Pathology 2013年第1期3卷 41-50页

作者： Mauricio Orozco-Levi alba Ramírez-sarmiento Michael Borchers Cristiane Murta-Nascimento Francesc Macià Beatriz Casado Maeba Polo Andrea Caballero-Benitez Fredy Diaz-Quijano Antoni Gelabert American Organization for the Promotion of Health Research (OLFIS) Bucaramanga Colombia Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CibeRes) Instituto de Salud Carlos III Ministerio de Ciencia y Tecnología Spain Consorcio de Investigación Biomédica de Epidemiología y Salud Pública (CIBERESP) Spain Department of Environmental Health University of Cincinnati College of Medicine Cincinnati USA Epidemiology and Health Services Evaluation Department Hospital del Mar-Parc de Salut Mar Barcelona Spain Group of Research in Injury Immune Response and Lung Function (LIF) Hospital del Mar Research Institute (IMIM) Urology Department Group of Research in Solid Tumors Universidad Autónoma de Barcelona Barcelona Spain

Background: Bladder and lung cancer are among the ten most common cancers in both genders. The NKG2D receptor and one of its ligands, MICA, are associated with smoking and susceptibility to both chronic obstructive pulmonary disease and lung cancer. Objective: We hypothesized that NKG2D-MICA system was associated with other smoking-related epithelial cancers such as bladder cancer. Design, Setting, and Participants: 70 cases of primary non-muscle invasive bladder cancer were screened for the MICA expression and CD8+, CD4+ and NK cell infiltration. Most patients (n = 55, 78.6%) were current or former smokers. Measurements: Tissue microarray (TMA) technology was chosen to evaluate MICA and tumor infiltrating lymphocytes in samples with confirmed bladder cancer. Kaplan-Meier curves and univariate Cox analysis was used to assess relapse, all-cancer mortality and specific bladder cancer mortality. Results and Limitations: MICA was expressed in most cancer specimens examined (i.e., 70%). Relapse of bladder cancer was not associated with the status of MICA expression (log rank p = 0.1123). Nevertheless, a significant association existed between high MICA expression and bladder cancer mortality (HR = 0.25;CI95% = 0.06 - 0.97). Tumor infiltrating CD4+ and CD8+ lymphocytes were found in the majority (64%) of samples. Cells expressing the NKG2D receptor were found in only 3% of the samples. There was no linear function between NKG2D+ cells and number or ratio of CD4+ and CD8+ TIL. Conclusions: MICA is expressed in a significant proportion of bladder carcinomas. MICA expression associates with significant survival advantages in the face of both all-cancer and bladder cancer. The NKG2D-MICA system could represent a common mechanism involved in the immunopathology and natural history of bladder neoplasms.

关键词： Bladder Cancer NKG2D Ligands MICA Survival Prognosis

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