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key word unitermos abstractThe detection of hepatic nodules by imaging techniques in cirrhotic patients has increased and the growing consensus that these lesions may be premalignant increases their clinical importance and demands precise diagnostic criteria. The prevalence of macroscopic suspect hepatic nodule (MSHN) in cirrhotic livers was analyzed to identify macroregenerative nodule (MRN), dysplastic nodule and hepatocellular carcinoma (HCC) and to evaluate an association between MSHN and HCC. Hepatic nodules larger than 1cm and different from the surrounding nodules of the cirrhosis in color and texture were considered MSHN. Sixty-one cirrhotic liver explants were serially sectioned into 0.5 to 0.7cm slices and MSHN and protocol samples were examined histologically. Ninety-four MSHN were identified in 26 livers (histologically 11 were cirrhotic nodules, 61 MRN, 12 dysplastic nodules, and ten HCC). HCC was identified macroscopically in one liver and by light microscopy within MSHN in six other livers. The relation between HCC and MSHN, specifically MRN, was statistically significant. These findings suggest an association between MRN and MSHN with HCC in cirrhotic livers and reinforce the practical importance of histological classification of hepatic nodules in cirrhosis in order to guide the management of patients who are waiting for liver transplant or surgical treatment. Cirrhotic liver explants Macroregenerative nodule Dysplasia Hepatocellular carcinoma resumo A detecção de nódulos hepáticos por técnicas de imagem em pacientes com cirrose tem aumentado, e o consenso de que essas lesões podem ser pré-malignas aumenta sua importância clínica e demanda critério diagnóstico preciso. A prevalência de nódulos hepáticos macroscopicamente suspeitos (NHMS) em fígados com cirrose foi analisada para identificar macronódulo regenerativo (MNR), nódulo displásico e carcinoma hepatocelular (CHC) e para avaliar a associação de NHMS e CHC. Nódulos hepáticos maiores que 1cm com cor e textura diferentes dos demais nódulos da cirrose em cada peça foram definidos como NHMS. Sessenta e um fígados explantados por cirrose foram seccionados em fatias de 0,5 a 0,7cm e NHMS e amostras de áreas aleatórias do fígado foram examinadas histologicamente. Noventa e quatro NHMS foram identificados em 26 fígados (à histologia
key word unitermos abstractThe detection of hepatic nodules by imaging techniques in cirrhotic patients has increased and the growing consensus that these lesions may be premalignant increases their clinical importance and demands precise diagnostic criteria. The prevalence of macroscopic suspect hepatic nodule (MSHN) in cirrhotic livers was analyzed to identify macroregenerative nodule (MRN), dysplastic nodule and hepatocellular carcinoma (HCC) and to evaluate an association between MSHN and HCC. Hepatic nodules larger than 1cm and different from the surrounding nodules of the cirrhosis in color and texture were considered MSHN. Sixty-one cirrhotic liver explants were serially sectioned into 0.5 to 0.7cm slices and MSHN and protocol samples were examined histologically. Ninety-four MSHN were identified in 26 livers (histologically 11 were cirrhotic nodules, 61 MRN, 12 dysplastic nodules, and ten HCC). HCC was identified macroscopically in one liver and by light microscopy within MSHN in six other livers. The relation between HCC and MSHN, specifically MRN, was statistically significant. These findings suggest an association between MRN and MSHN with HCC in cirrhotic livers and reinforce the practical importance of histological classification of hepatic nodules in cirrhosis in order to guide the management of patients who are waiting for liver transplant or surgical treatment. Cirrhotic liver explants Macroregenerative nodule Dysplasia Hepatocellular carcinoma resumo A detecção de nódulos hepáticos por técnicas de imagem em pacientes com cirrose tem aumentado, e o consenso de que essas lesões podem ser pré-malignas aumenta sua importância clínica e demanda critério diagnóstico preciso. A prevalência de nódulos hepáticos macroscopicamente suspeitos (NHMS) em fígados com cirrose foi analisada para identificar macronódulo regenerativo (MNR), nódulo displásico e carcinoma hepatocelular (CHC) e para avaliar a associação de NHMS e CHC. Nódulos hepáticos maiores que 1cm com cor e textura diferentes dos demais nódulos da cirrose em cada peça foram definidos como NHMS. Sessenta e um fígados explantados por cirrose foram seccionados em fatias de 0,5 a 0,7cm e NHMS e amostras de áreas aleatórias do fígado foram examinadas histologicamente. Noventa e quatro NHMS foram identificados em 26 fígados (à histologia
Toxoplasma gondii is a protozoan pathogen of birds and mammals, including humans. The infective stage, the bradyzoite, lives within cysts, which occur predominantly in cells of the central nervous system and skeletal and cardiac muscles, characterizing the chronic phase of toxoplasmosis. In the present study, we employed for the first time primary mouse culture of skeletal muscle cells (SkMC) infected with bradyzoites, as a cellular model for cystogenesis. The interconversion of bradyzoite and tachyzoite was analyzed by immunofluorescence using 2 stage-specific antibodies, i.e., anti-bradyzoite (anti-BAG1) and anti-tachyzoite (anti-SAG1). After 24 hr of interaction only bradyzoites were multiplying, as revealed by anti-BAG1 incubation; interconversion to tachyzoites was not observed. After 48 hr of infection, 2 types of vacuoles were seen, i.e., BAG1+ and SAG1+, indicating the presence of bradyzoites as well as their interconversion to tachyzoites. After 96 hr of infection, BAG1+ vacuoles presented a higher number of parasites when compared to 48 hr, indicating multiplication of bradyzoites without interconversion. Using ultrastructural analysis, bradyzoites were found to adhere to the cell membranes via both the apical and posterior regions or were associated with SkMC membrane expansions. During bradyzoite invasion of SkMC, migration of the rough endoplasmic reticulum (RER) profiles to the parasite invasion site was observed. Later, RER profiles were localized between the mitochondria and parasitophorous vacuole membrane (PVM) that contained the parasite. After 31 days of parasite-host cell infection, RER profiles and mitochondria were not observed in association with the cyst wall. Alterations of the PVM, including increased thickness and electrondensity gain on its inner membrane face, were observed 48 hr after infection. Cystogenesis was complete 96 hr after infection, resulting in the formation of the cyst wall, which displayed numerous membrane invaginations. In addition, an electron-dense granular region enriched with vesicles and tubules was present, as well as numerous intracystic bradyzoites. These results show that the in vitro T. gondii model and SkMC are potential tools for both the study of cystogenesis using molecular approaches and the drug screening action on tissue cysts and bradyzoites.
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