RESUMO
The pathogenic mechanisms underlying the progression of non-alcoholic fatty liver disease (NAFLD) are not fully understood. In this study, we aimed to assess the relationship between endoplasmic reticulum (ER) stress and autophagy in human and mouse hepatocytes during NAFLD. ER stress and autophagy markers were analyzed in livers from patients with biopsy-proven non-alcoholic steatosis (NAS) or non-alcoholic steatohepatitis (NASH) compared with livers from subjects with histologically normal liver, in livers from mice fed with chow diet (CHD) compared with mice fed with high fat diet (HFD) or methionine-choline-deficient (MCD) diet and in primary and Huh7 human hepatocytes loaded with palmitic acid (PA). In NASH patients, significant increases in hepatic messenger RNA levels of markers of ER stress (activating transcription factor 4 (ATF4), glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP)) and autophagy (BCN1) were found compared with NAS patients. Likewise, protein levels of GRP78, CHOP and p62/SQSTM1 (p62) autophagic substrate were significantly elevated in NASH compared with NAS patients. In livers from mice fed with HFD or MCD, ER stress-mediated signaling was parallel to the blockade of the autophagic flux assessed by increases in p62, microtubule-associated protein 2 light chain 3 (LC3-II)/LC3-I ratio and accumulation of autophagosomes compared with CHD fed mice. In Huh7 hepatic cells, treatment with PA for 8 h triggered activation of both unfolding protein response and the autophagic flux. Conversely, prolonged treatment with PA (24 h) induced ER stress and cell death together with a blockade of the autophagic flux. Under these conditions, cotreatment with rapamycin or CHOP silencing ameliorated these effects and decreased apoptosis. Our results demonstrated that the autophagic flux is impaired in the liver from both NAFLD patients and murine models of NAFLD, as well as in lipid-overloaded human hepatocytes, and it could be due to elevated ER stress leading to apoptosis. Consequently, therapies aimed to restore the autophagic flux might attenuate or prevent the progression of NAFLD.
Assuntos
Autofagia , Estresse do Retículo Endoplasmático , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Demografia , Dieta Hiperlipídica , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Comportamento Alimentar , Feminino , Inativação Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Ácido Palmítico/farmacologia , Fagossomos/efeitos dos fármacos , Fagossomos/metabolismo , Sirolimo/farmacologia , Fator de Transcrição CHOP/metabolismoAssuntos
Infecções Oportunistas Relacionadas com a AIDS , Síndrome da Imunodeficiência Adquirida/complicações , Colite/parasitologia , Criptosporidiose/complicações , Cryptosporidium/isolamento & purificação , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/parasitologia , Adulto , Animais , Colite/diagnóstico , Criptosporidiose/diagnóstico , Humanos , MasculinoRESUMO
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Assuntos
Masculino , Adulto , Animais , Humanos , Infecções Oportunistas Relacionadas com a AIDS , Síndrome da Imunodeficiência Adquirida/complicações , Colite/parasitologia , Criptosporidiose/complicações , Cryptosporidium/isolamento & purificação , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/parasitologia , Colite/diagnóstico , Criptosporidiose/diagnósticoRESUMO
BACKGROUND: Cytologic evaluation of abnormal nipple secretion is a well-established method for the rapid diagnosis of breast carcinoma in females. However, less attention has been focused on male patients presenting with nipple discharge. CASE: A case of intraductal carcinoma of the male breast was diagnosed by nipple discharge cytology alone. CONCLUSION: This report illustrates the usefulness of nipple discharge cytology in the diagnosis of early breast carcinoma in males.
Assuntos
Líquidos Corporais/citologia , Neoplasias da Mama Masculina/patologia , Carcinoma in Situ/patologia , Carcinoma Intraductal não Infiltrante/patologia , Células-Tronco Neoplásicas/ultraestrutura , Mamilos , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/cirurgia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/metabolismo , Carcinoma in Situ/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/cirurgia , Diagnóstico Diferencial , Humanos , Masculino , Mastectomia Simples , Pessoa de Meia-IdadeRESUMO
We studied 156 fine needle aspiration biopsies of tumors from various locations with electron microscopy and, after processing, obtained evaluable material in 99 (63%) cases. Ultrastructural study elicited highly significant or essential findings in 39 patients (39% of the evaluable samples). In the cases requiring urgent treatment we were able to obtain an ultrastructural diagnosis in seven hours.
Assuntos
Biópsia por Agulha/métodos , Neoplasias/ultraestrutura , Adulto , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Neoplasias/diagnósticoRESUMO
We report the case of a patient suffering from acquired immunodeficiency syndrome and hepatitis B and D virus-related cirrhosis of the liver who was diagnosed as subclinical Crohn's disease. We attribute this clinical course to abnormality of intestinal immune system induced by the human immunodeficiency virus. Concomitant hepatitis B and D virus infection may have contributed. This observation supports the hypothesis of helper-inducer T cells (CD4 T cells) having a critical role in the immunopathogenesis of Crohn's disease and its clinical expression.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Doença de Crohn/complicações , Adulto , Humanos , MasculinoRESUMO
A case of gastrointestinal autonomic nerve tumour with light microscopic, immunohistochemical and ultrastructural examination is reported. The tumour was composed of spindle cells or large cells with clear cytoplasm and showed intense staining for vimentin and focal staining for neuron-specific enolase, chromogranin, synaptophysin, gastrin, P substance and S-100 protein. Ultrastructural examination showed long processes with dense core granules and the absence of features characteristic of other gastrointestinal stromal tumours. In addition we noted small traces of basal lamina and the absence of synaptic vesicles. It seems that the biological behaviour of gastrointestinal autonomic nerve tumours is aggressive but there are too few reports on which to conclude anything about their prognosis. Our findings suggest that tumour has a neuroectodermal differentiation.