NASH and metabolic syndrome

Visceral obesity and insulin resistance are typical clinical features of nonalcoholic steatohepatitis (NASH) characterized by zone 3-dominant hepatic steatosis with ballooned hepatocytes and Mallory bodies, zone 3 pericellular and perivenular fibrosis with or without bridging fibrosis, and lobular inflammatory cell infiltration. Indeed, 90% of NASH revealed to be complicated with visceral obesity, and two thirds of NASH patients fulfill the criteria of metabolic syndrome. Therefore, NASH could be regarded as the hepatic manifestation of metabolic syndrome, and a variety of life-style related diseases such as obesity, hypertension, hyperlipidemia and diabetes mellitus could be used for detecting     

Drug-induced NASH

Steatohepatitis is pathologically characterized by zone 3-dominant hepatic steatosis with ballooned hepatocytes and Mallory bodies, zone 3 pericellular and perivenular fibrosis with or without bridging fibrosis, and lobular inflammatory cell infiltration. Alcoholic hepatitis is a prototype of this syndrome, but a variety of diseases such as obesity, diabetes mellitus, Wilson disease and hepatitis C could reveal very similar pathological changes in some occasions. Therefore, well defined diseases need to be excluded in the process of differential diagnosis of steatohepatitis. Pathways possibly involved in the development of drug-induced steatohepatitis were categorized into four and outlines of the possible mechanisms involved in the development of this syndrome were proposed in this article.     

Effects of Eriobotrya japonica seed extract on oxidative stress in rats with non‐alcoholic steatohepatitis

Objectives Non‐alcoholic steatohepatitis is associated with the deposition of lipid droplets in the liver, and is characterised histologically by the infiltration of inflammatory cells, hepatocellular degeneration and liver fibrosis. Oxidative stress may play an important role in the onset and deterioration of non‐alcoholic steatohepatitis. We previously reported that an Eriobotrya japonica seed extract, extracted in 70% ethanol, exhibited antioxidant actions in vitro and in vivo. In this study, we examined the effect of this extract in a rat model of non‐alcoholic steatohepatitis. Methods The seed extract was given in the drinking water to fats being fed a methionine‐choline‐deficient diet for 15 weeks. Key findings Increases in alanine aminotransferase and aspartate aminotransferase levels were significantly inhibited in rats fed the seed extract compared with the group on the diet alone. Formation of fatty droplets in the liver was also inhibited. Antioxidant enzyme activity in liver tissue was higher than in the diet‐only group and lipid peroxidation was reduced compared with rats that also received the extract. Expression of 8‐hydroxy‐2′‐deoxyguanosine and 4‐hydroxy‐2‐nonenal was lower in the rats given the seed extract than in the diet‐only group. In the former, liver tissue levels of transforming growth factor‐β and collagen were also decreased. Conclusions Thus, the E. japonica seed extract inhibited fatty liver, inflammation and fibrosis, suggesting its usefulness in the treatment of non‐alcoholic steatohepatitis.     

Thyroid Adenoma with Extensive Extracellular Mucin Deposition: Report of a Case

A thyroid tumor with extensive extracellular mucin deposition is extremely rare. We herein describe a case of a thyroid adenoma with prominent myxoid stroma. A 63-year-old man presented with a mass in his right anterior neck. Radiological examinations showed this mass to be a thyroid tumor with a cystic component. The histopathological findings showed the stroma of this tumor to consist of abundant myxoid materials which stained gray-bluish for hematoxylin-eosin. The myxoid material was positive for alcian blue, whereas periodic acid-Schiff did not stain this material. No intracytoplasmic mucin was identified. In an immunohistochemical study, the tumor cells were negative for cytokeratin 19. Furthermore, positive staining was observed for thyroglobulin while a negative finding was seen for calcitonin.     

Endoscopic Findings and Clinical Manifestation of Gastric Anisakiasis

Objectives : To identify the endoscopic findings and clinical manifestations of anisakiasis, we studied 87 cases of gastric anisakiasis. Methods : Patient information was analyzed by means of patient records. The interval between the day of intake of Anisakis and endoscopic examination was determined in 86 cases. Then the endoscopic findings of each interval were elucidated. Results : Moderate to severe gastric mucosal edema tends to occur within 1 or 2 days after Anisakis infection, accompanied by leukocytosis. As to the sites of penetration of Anisakis, 55 % of cases were found in the greater curvature with severe mucosal edema. Among 87 cases, four patients experienced anisakiasis twice during the interval examined, and six patients had past histories of anisakiasis before the investigated interval. Conclusions : Gastric anisakiasis may be caused by an allergic reaction to the Anisakis antigen. There is a classic relationship between clinical and endoscopic findings and the interval after Anisakis administration. Anisakis usually is found in the greater curvature.     

Deleterious effects of lymphocytes at the early stage of neurodegeneration in an animal model of amyotrophic lateral sclerosis

Background  

Non-neuronal cells, such as microglia and lymphocytes, are thought to be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Previous studies have demonstrated neuroprotective effects of lymphocytes at the end stage of ALS, partly through induction of alternatively activated microglia (M2 microglia), which are neuroprotective. In this study, we investigated the role of lymphocytes in the early stage of the disease using an animal model of inherited ALS.     

Intranuclear immunolocalization of 14-3-3 protein isoforms in brains with spinocerebellar ataxia type 1

Immunolocalization of 14-3-3 protein isoforms, one of the interacters with ataxin 1, was investigated in spinocerebellar ataxia type 1 (SCA 1) brains using isoform-specific antibodies. Samples from the pons and from the cerebellum of four SCA1 cases and three controls were studied. The intensity of the immunoreactivity (IR) and its subcellular topography were analyzed. In control subjects, granular immunoreactivity for an epitope common to all known isoforms of 14-3-3 proteins (14-3-3 COM) found in the cytoplasm of some pontine and dentate nucleus neurons was weak. It was observed in some Purkinje cells, while its intensity varied. Many nuclei of those neurons and Purkinje cells of SCA1 were intensely immunopositive for 14-3-3 COM, while it was less in their cytoplasm. Expanded polyglutamine epitope was colocalized to 14-3-3 COM epitope in some pontine neurons, sometimes accumulated in intranuclear inclusion-like structures. This findings support previous reports that 14-3-3 proteins stabilize mutant ataxin 1 in nucleus and possibly lead to neurodegeneration. However, nuclear localization of 14-3-3 proteins in SCA1 brains was dependent on its isoforms, i.e. pontine neurons intensely positive for beta, Purkinje cells for tau and dentate nucleus neurons for both, while all of those neurons were consistently positive for zeta isoform, although sigma isoform tended to be located in the cytoplasm. Nuclear accumulation and isoform- and region-dependent subcellular localizations of 14-3-3 proteins may be related to SCA1 pathology, which exhibits marked regional variability.