Hepatocyte metaplasia in experimental chagasic pancreatitis: preliminary report

Beginning the study of chronic pathologic changes in pancreas of hamsters experimentally infected with Trypanosoma cruzi Vic strain, hepatocyte metaplasia was observed in one animal from infected group. This is the first report of oncocytes in Chagas' disease, which could be due to aberrant regenerative response to pancreas inflammatory process.

Rat hepatocyte invasion by Listeria monocytogenes and analysis of TNF-alpha role in apoptosis

Listeria monocytogenes, etiological agent of severe human foodborne infection, uses sophisticated mechanisms of entry into host cytoplasm and manipulation of the cellular cytoskeleton, resulting in cell death. The host cells and bacteria interaction may result in cytokine production as Tumor Necrosis Factor (TNF) alpha. Hepatocytes have potential to produce pro-inflammatory cytokines as TNF-alpha when invaded by bacteria. In the present work we showed the behavior of hepatocytes invaded by L. monocytogenes by microscopic analysis, determination of TNF-alpha production by bioassay and analysis of the apoptosis through TUNEL technique. The presence of bacterium, in ratios that ranged from 5 to 50,000 bacteria per cell, induced the rupture of cellular monolayers. We observed the presence of internalized bacteria in the first hour of incubation by electronic microscopy. The levels of TNF-alpha increased from first hour of incubation to sixth hour, ranging from 0 to 3749 pg/mL. After seven and eight hours of incubation non-significant TNF-alpha levels decrease occurred, indicating possible saturation of cellular receptors. Thus, the quantity of TNF-alpha produced by hepatocytes was dependent of the incubation time, as well as of the proportion between bacteria and cells. The apoptosis rate increased in direct form with the incubation time (1 h to 8 + 24 h), ranging from 0 to 43%, as well as with the bacteria : cells ratio. These results show the ability of hepatocyte invasion by non-hemolytic L. monocytogenes, and the main consequences of this phenomenon were the release of TNF-alpha by hepatocytes and the induction of apoptosis. We speculate that hepatocytes use apoptosis induced by TNF-alpha for release bacteria to extracellular medium. This phenomenon may facilitate the bacteria destruction by the immune system.

Cholestasis in a murine experimental model: lesions include hepatocyte ischemic necrosis

OBJECTIVE: To establish a murine experimental model of bile duct obstruction that would enable controlled observations of the acute and subacute phases of cholestasis. METHODOLOGY: Adult male isogenic BALB/c mice underwent a bile duct ligation (22 animals) or a sham operation (10 animals). Fifteen days after surgery, or immediately after the animal's death, macroscopic findings were noted and histological study of the liver, biliary tree, and pancreas was performed (hematoxylin-eosin and Masson trichromic staining). RESULTS: Beginning 24 hours after surgery, all animals from the bile duct ligation group presented progressive generalized malaise. All animals presented jaundice in the parietal and visceral peritoneum, turgid and enlarged liver, and accentuated dilatation of gallbladder and common bile duct. Microscopic findings included marked dilatation and proliferation of bile ducts with accentuated collagen deposits, frequent areas of ischemic necrosis, hepatic microabscesses, and purulent cholangitis. Animals from the sham operation group presented no alterations. CONCLUSION: We established a murine experimental model of induced cholestasis, which made it possible to study acute and subacute tissue lesions. Our data suggests that in cholestasis, hepatic functional ischemia plays an important role in inducing hepatic lesions, and it also suggests that the infectious process is an important factor in morbidity and mortality.

Metaplasia mieloide do baço na Ancilostomose

Pesquizamos, no figado e baço de dez casos puros de ancilostomose, elementos hemocitopoieticos; verificamos o peso do baço em 23 casos de individuos com idades compreendidas entre 3 e 60 anos; não encontramos, em nenhum caso, celulas hemoformadoras no figado. Em sete casos, encontramos, no baço, elementos da série vermelha em adiantado estado de evolução (eritroblastos ortocromaticos de nucleo picnotico). Em alguns destes casos observamos megacariocitos e numerosos mielocitos eosinofilos. Os tres casos que não apresentavam metaplasia mieloide no baço, eram os de individuos acima de 50 anos de idade. Entretanto, em outro caso de um individuo com 59 anos esta metaplasia foi verificada. Em individuos acima de 20 anos, o peso médio do baço, em nove casos, mostrou-se igual ao peso normal. Em 14 casos, compreendidos entre 3 e 14 anos, o peso deste orgão foi sempre sensivelmente mais elevado que nos normais de idade correspondente. Estes resultados sugerem a possibilidade de ser a metaplasia mieloide responsavel pelos aumentos de pezo nos baços de individuos jovens, vitimados pela anemia ancilostomica. A notavel proliferação dos eritroblastos ortocromaticos mostra que o grão e a rapidez da regeneração sanguinea, após a administração de ferro, são devidos, essencialmente, á grande quantidade de hemoglobina já preformada no baço e na medula ossea dos organismos ancilostomados.

Myeloid Metaplasia of Spleen in Hookworm Disease

We investigated, in the liver and the spleen of ten pures cases of ankylostomiasis haemocytopoietic elements. We verified the weight of spleen in 23 cases of individuals from 3 to 60 years old. In no case did we meet with haemopoietic cells in liver. In seven cases we found in spleen elements of the red series at an advanced evolutional stage (orthochromatic erythroblasts with pyknotic nucleus). In some of these cases we observed megakaryocytes and numerous eosinophilous myelocytes.The three cases which did not show any myeloid metaplasia in spleen were from individuals of over 50 years. Nevertheless, in another case of an individual 59 years old this metaplasia was verified. In individuals of over 20 years, the average weight of spleen in nine cases appeared to be equal to the normal weight. In 14 other cases, between 3 and 14 years of age, the weight of this organ was always sensibly higher than in normal individuals of the corresponding age. These results suggest the possibility of the myeloid metaplasia being the fact responsible for the weight increase of spleen in young individuals victimatized by hookworm anaemia. The remarkable proliferation of orthochromatic erythroblasts shows that the degree and quickness of blood regeneration after iron administration are due, essentially, to the great quantity of haemoglobin previously formed in the spleen and bone marrow of ankylostomized organisms.

Esôfago de Barrett: aspectos fisiopatológicos e moleculares da seqüência metaplasia-displasia-adenocarcinoma - artigo de revisão

The Barrett's esophagus (BE) is defined as endoscopically visible columnar mucosa at the distal esophagus, of any extension, proved to harbor intestinal metaplasia on biopsy, highlighted by the presence of goblet cells. BE denotes long-standing gastroesophageal reflux disease (GERD) and is an important risk factor for the development of esophageal adenocarcinoma (EAC). Therefore, these patients must be on follow-up, in order to diagnose cancer early. BE patients have frequent alterations in esophageal physiologyc studies. Alkaline duodenogastroesophageal reflux seems to have important role. The development BE occurs in steps, initially with formation of cardiac type mucosa subsequent intestinalization. Futher progression can follow a sequence, from low grade dysplasia, to high grade dysplasia and esophageal adenocarcinoma. Current follow-up is based on the presence of dysplasia. It has limitations, grouping patients heterogeneously. Different steps of carcinogenesis have been studied looking for an ideal prognostic marker. Uncontrolled proliferative activity, apoptosis inhibition, angiogenesis, tissue invasion and metastases formation are all implicated in cancer origin. Some cycle cell molecules have been studied in BE, such as retinoblastoma protein, ciclins, kinase dependent ciclins and cell cycle inhibitors. The P53 protein is one of the most investigated in the metaplasia-adenocarcinoma progression. Growth Factors, apoptotic proteins, telomers and DNA ploidy have also been searched. Increased proliferative activity has been implicated in Barrett's carcinogenesis and the Ki-67 antigen, through imunohistochemical analysis, has become the the method of choice. Present in the nucleus, it is found in proliferative cells only. Some studies suport association between Ki-67 activity and the metaplasia-dysplasia-adenocarcinoma sequence.The results, however, are inconclusive and research should follow this way.

Metaplasia óssea e esterilidade primária

A metaplasia óssea do endométrio é uma condição rara e pode ser explicada por uma neoformação no endométrio, com deposição de sais de cálcio. Entretanto, a situação mais comum é a história prévia de abortamento com permanência de ossículos na cavidade uterina. Foi relatado um caso de ossificação endometrial em uma mulher de 31 anos, sem gravidez prévia ou história de aborto, apresentando dismenorréia e infertilidade. A ultra-sonografia pélvica mostrou área hiperecóica no fundo da cavidade uterina. A histeroscopia foi realizada e uma imagem sugestiva de tecido ósseo foi encontrada. Este tecido foi retirado e a histopatologia confirmou a ossificação endometrial.

Metaplasia óssea endometrial: quadro clínico e seguimento após tratamento

OBJETIVO: apresentar o quadro clínico das pacientes com metaplasia óssea e avaliar os fatores de risco, as mudanças dos sinais e sintomas após a retirada do fragmento ósseo. MÉTODOS: foi realizado um estudo transversal com 16 pacientes diagnosticadas com fragmentos ósseos na cavidade uterina no período de julho de 2006 a janeiro de 2009. O critério de inclusão foi o achado de fragmento ósseo retirado da cavidade uterina. Todas as pacientes tiveram confirmação histológica de presença de tecido ósseo na cavidade endometrial. Obtivemos os dados de todas as pacientes antes e depois da retirada por meio de um questionário para avaliar o efeito da retirada sobre a sintomatologia das pacientes, além da pesquisa de possíveis fatores relacionados ao aparecimento da doença. RESULTADOS: metade das pacientes (8/16) tinha sintomas hemorrágicos e um terço (6/16) apresentava infertilidade. A retirada dos fragmentos foi efetiva na melhora das queixas, havendo desaparecimento dos sintomas em todos os casos de menorragia e dor pélvica. CONCLUSÃO: A retirada do fragmento ósseo pode restaurar a fertilidade em pacientes selecionadas e que tenham como causa a metaplasia óssea, além de ser bastante efetiva em proporcionar melhora nos casos que cursam com dor pélvica e menorragia.

Duodenal gastric metaplasia and Helicobacter pylori infection in patients with diffuse nodular duodenitis

Whether the regression of gastric metaplasia in the duodenum can be achieved after eradication of Helicobacter pylori is not clear. The aim of the present study was to investigate the relationship between H. pylori infection and gastric metaplasia in patients with endoscopic diffuse nodular duodenitis. Eighty-six patients with endoscopically confirmed nodular duodenitis and 40 control patients with normal duodenal appearance were investigated. The H. pylori-positive patients with duodenitis received anti-H. pylori triple therapy (20 mg omeprazole plus 250 mg clarithromycin and 400 mg metronidazole, all twice daily) for one week. A control endoscopy was performed 6 months after H. pylori treatment. The H. pylori-negative patients with duodenitis received 20 mg omeprazole once daily for 6 months and a control endoscopy was performed 2 weeks after treatment. The prevalence of H. pylori infection was 58.1%, and the prevalence of gastric metaplasia was 57.0%. Seventy-six patients underwent endoscopy again. No influence on the endoscopic appearance of nodular duodenitis was found after eradication of H. pylori or acid suppression therapy. However, gastric metaplasia significantly decreased and complete regression was achieved in 15/28 patients (53.6%) 6 months after eradication of H. pylori, accompanied by significant improvement of other histological alterations. Only mild chronic inflammation, but not gastric metaplasia, was found in the control group, none with H. pylori infection in the duodenal bulb. Therefore, H. pylori infection is related to the extent of gastric metaplasia in the duodenum, but not to the presence of diffuse nodular duodenitis.

Effect of hepatocyte growth factor and angiotensin II on rat cardiomyocyte hypertrophy

Angiotensin II (Ang II) plays an important role in cardiomyocyte hypertrophy. The combined effect of hepatocyte growth factor (HGF) and Ang II on cardiomyocytes is unknown. The present study was designed to determine the effect of HGF on cardiomyocyte hypertrophy and to explore the combined effect of HGF and Ang II on cardiomyocyte hypertrophy. Primary cardiomyocytes were isolated from neonatal rat hearts and cultured in vitro. Cells were treated with Ang II (1 µM) alone, HGF (10 ng/mL) alone, and Ang II (1 µM) plus HGF (10 ng/mL) for 24, 48, and 72 h. The amount of [³H]-leucine incorporation was then measured to evaluate protein synthesis. The mRNA levels of β-myosin heavy chain and atrial natriuretic factor were determined by real-time PCR to evaluate the presence of fetal phenotypes of gene expression. The cell size of cardiomyocytes was also studied. Ang II (1 µM) increased cardiomyocyte hypertrophy. Similar to Ang II, treatment with 1 µM HGF promoted cardiomyocyte hypertrophy. Moreover, the combination of 1 µM Ang II and 10 ng/mL HGF clearly induced a combined pro-hypertrophy effect on cardiomyocytes. The present study demonstrates for the first time a novel, combined effect of HGF and Ang II in promoting cardiomyocyte hypertrophy.

Efeitos da inalação passiva da fumaça de cigarro sobre as pregas vocais de ratos

Poucos estudos demonstram as reações patológicas devidas à inalação de fumaça pelas vias aéreas de ratos. OBJETIVO: Estudar e analisar os possíveis efeitos histopatologicos produzidos pela inalação crônica de fumaça de cigarro nas pregas vocais de ratos. DESENHO DE ESTUDO: Experimental. MATERIAL E MÉTODOS: 36 ratos masculinos (Rattus norvergicus Wistar), de 60 dias de idade, foram mantidos em gaiolas e expostos à inalação da fumaça produzida por 10 cigarros, 3 vezes ao dia, 7 dias por semana, para períodos de 25, 50 e 75 dias, e os controles respectivos. Os animais foram sacrificados e as suas laringes dissecadas e submetidas a análise histológica com coloração de Hematoxilina e Eosina e analisados através de microscopia simples. RESULTADOS: Os ratos expostos ao cigarro exibiram menor (p <0,05) massa corporal que o grupo controle. Havia hiperplasia e metaplasia escamosa na extremidade livre da prega vocal e hiperplasia escamosa na porção mediana da prega vocal em todos os 3 períodos de estudo. Além disso, o grupo de 50 dias revelou metaplasia com queratinização nesta área. Não foram observadas alterações morfológicas em outras áreas da laringe e reação inflamatória da lâmina propria. CONCLUSÃO: Foi concluído que a inalação passiva de fumaça de cigarro rende mudanças morfológicas importantes no epitélio da prega vocal que podem, eventualmente, progredir para neoplasia.

Histological alterations in liver and testis of Astyanax aff. bimaculatus caused by acute exposition to zinc

This study investigated the effect of acute exposition to zinc (Zn) on histology of the liver and testes of yellow tail lambari (Astyanax aff. bimaculatus). The exposure consisted of six concentrations of Zn (0, 3, 5, 10, 15, and 20 mg/L) for 96 hours of exposure. Fragments of liver and testis were routinely processed and embedded in plastic resin based on glycol methacrylate. Fragments of bones, muscles, liver and testis were dehydrated and digested to quantify the absorption levels of Zn in the tissue. Acute exposure to concentrations above 10mg/L has produced structural changes in the liver and gonads. The changes found in the liver were vascular congestion; decrease of cellular volume; displacement of the hepatocyte nucleus; necrosis; disarrangement of cordon structure; leukocyte infiltrate and vacuolization. The changes found in the gonads were ruptured cyst, delayed development of germ cells, pyknotic nucleus, cell cluster, displacement of cyst wall and vacuolization. The histological changes observed were compatible with the increasing concentration of zinc in environment, compromising liver and reproductive functions, because there was an increase in relative frequency of hepatocytes and reduced sperm production

A case-control study on the association of hepatitis B virus infection and hepatocellular carcinoma in Northeast Brazil

Hepatitis B virus (HBV) serological markers were investigated in 40 incident cases of hepatocellular carcinoma (HCC) and in two age and sex matched control groups, comprising 40 patients with other cancers and 80 healthy individuals, resident in Bahia, Brazil. Serologic tests were done by radioimmunoassay. The study observed high proportion of seropositivity to HBsAg (42.5%) and of those presenting HBsAg or antiHBc (65.0%) among HCC cases, higher in men than women and in those aged 17 to 30 years old. HBsAg seropositivity among HCC patients was greater than in the control group with other cancers (7.5%) and in healthy controls (2.5%), corresponding to odds ratio estimates of 15.0 (95% CI 3.29, 68.30) and 33.0 (95% CI 9.13, 119.28), both statistically significant. HBeAg was not observed and antiHBe was present in 41.2% of cases, suggesting the absence of viral replication, possibly with viral DNA intergration into the hepatocyte genome. The presence of cirrhosis was associated with HBsAg seropositivity among HCC cases. A history of chronic alcoholism is shown to be more frequently related to those cases with cirrhosis. This study highlights the relevant association between HCC and HBV in Northeast Brazil, particularly for young individuals, and the high risk of development of HCC for HBsAg carriers.

Hepatobiliary alterations in massive biliary ascariasis: histopathological aspects of an autopsy case

Hepatobiliary alterations found in an autopsy case of massive Biliary Ascariasis, are reported on histological grounds. Severe cholangitis was the main finding, but other changes were also detected, such as pyloric and intestinal metaplasia, hyperplasia of the epithelial lining, with intraductal papillomas and adenomatous proliferation. Remnants of the worm were observed tightly adhered to the epithelium, forming microscopic intrahepatic calculi. Mucopolysaccharides, especially acid, showed to be strongly positive on the luminal border, and in proliferated glands around the ducts. The authors discuss the similarity between such findings and Oriental Cholangiohepatitis, and suggest that inflammation and the presence of the parasitic remnants are responsible for the hyperplastic and metaplastic changes, similarly with what occurs in chlonorchiasis, fascioliasis and schistosomiasis.