Great progress has been made in understanding the development of non-alcoholic fatty liver disease (NAFLD) but less is known about the mechanisms underlying the progress from steatosis to steatohepatitis (NASH). Our aim was to evaluate if the amount and type of storage of fat in hepatocytes is of importance for hepatocyte injury. We also wanted to show if not only the innate immunity but also the adaptive immunity is involved in NASH. Thirty-one patients with NASH or borderline NASH and 18 non-NASH patients were investigated. Liver biopsies were scored for NASH according to Kleiner et al. Paraffin-embedded liver biopsies were stained with antibodies against CD3, TLR4, CD68, Cleaved Caspase-3, ICAM1, Foxp3 and ApopTag by immunohistochemistry. Serum soluble ICAM-1 (sICAM-1) were analysed by ELISA. The volume density of fat was 59% in the NASH patients and microvesicular fat, increased in high NAS score patients. ICAM-1 positive hepatocytes were seen in NASH patients and were localized in areas with microvesicular fat. Non-NASH biopsies were negative for ICAM-1 positive hepatocytes. The sICAM-1 were significantly higher in NASH-patients (339.8 ± 34.07) than in non-NASH patients (229.5 ± 12.14), p = 0.0015. Patients with NAS score over four had higher area of CD68 positive cells p = 0.0011 and Foxp3 positive cells (p = 0.024) than non-NASH patients. In liver tissue with NASH, hepatocytes with microvesicular steatosis seem to be expressing more inflammatory markers, and in this liver tissue an increased number of CD68 cells and regulatory T-cells (Tregs, e.g. Foxp3+ cells) were seen, indicating an involvement of, both the innate and the adaptive immunity.
TNF-alpha protects rat hepatocytes from normal but not iron-loaded rats from oxidative stress. The protection may be due to an induction of the ferritin synthesis.
C h a r p y nahm als wesentlichen Grund für die durch Vit. D2 erzielbaren Heilerfolge bei. Hauttuberkulose die Entstehung und Unterhaltung einer G e w e b s a z i d o s e an, während sich das humorale System im Gleichgewicht befände. Später stellte er die Hypothese einer Aktivierung der D a r m p h o s p h a t a s e n in den Vordergrund. R a a b fand im Kulturversuch einen direkten Einfluß des Vitamin D auf das Tb-Bazillenwachstum. M e e r s e m a n n u. Mitarbeiter glauben, eine Hemmung der Keime im Meerschweinchenversuch nachweisen zu können. Rost machte erneut auf die bekannte anti-allergische Wirkung des Vitamin D aufmerksam. Diese wurde von D a in o w experimentell untersucht und bestätigt. K a 1 k o f f sieht das wesentliche Merkmal in einer peripheren Terrainänderung, die sich nach E h r j n g auch kapillarmikroskopisch nachweisen läßt. K e i n j n g und B r e t t haben auf die Veränderungen im Mineralhaushalt hingewiesen, wodurch letztlich eine Parallele zur kochsalzfreien Diättherapie wahrscheinlich gemacht wurde. Mit Hilfe des Vitamin D2 lassen sich bekanntlich erhebliche Veränderungen im intermediären Stoffwechsel hervorrufen, Hier inter-1 In Gemeinschaft mit Dr. K o p 1 o w. Hyg. Institut Mainz (Direktor: Prof. Kliewe).
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