The Effect of Cyclophilin D Depletion on Liver Regeneration Following Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy

AIM: Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a modification of two-stage hepatectomy profitable for patients with inoperable hepatic tumors by standard techniques. Unfortunately, initially poor postoperative outcome was associated with ALPPS, in which mitochondrial dysfunction played an essential role. Inhibition of cyclophilins has been already proposed to be efficient as a mitochondrial therapy in liver diseases. To investigate the effect of Cyclophilin D (CypD) depletion on mitochondrial function, biogenesis and liver regeneration following ALPPS a CypD knockout (KO) mice model was created. METHODS: Male wild type (WT) (n = 30) and CypD KO (n = 30) mice underwent ALPPS procedure. Animals were terminated pre-operatively and 24, 48, 72 or 168 h after the operation. Mitochondrial functional studies and proteomic analysis were performed. Regeneration rate and mitotic activity were assessed. RESULTS: The CypD KO group displayed improved mitochondrial function, as both ATP production (P < 0.001) and oxygen consumption (P < 0.05) were increased compared to the WT group. The level of mitochondrial biogenesis coordinator peroxisome proliferator-activated receptor γ co-activator 1-α (PGC1-α) was also elevated in the CypD KO group (P < 0.001), which resulted in the induction of the mitochondrial oxidative phosphorylation system. Liver growth increased in the CypD KO group compared to the WT group (P < 0.001). CONCLUSIONS: Our study demonstrates the beneficial effect of CypD depletion on the mitochondrial vulnerability following ALPPS. Based on our results we propose that CypD inhibition should be further investigated as a possible mitochondrial therapy following ALPPS

Cost accounting in Hungarian public higher education institutions

This paper aims to present the area of cost accounting in the general government sector, more precisely, in higher education, its relationship with managerial accounting. A special emphasis is the question of the application (applicability) and necessity of cost accounting in this sector. The performance, competitiveness, and last but not least, the rate of overall social satisfaction are highly dependent on the capacity, and the quality, effectiveness and efficiency of the operation of financial actors and different public institutions. The efficiency and effectiveness of public services can only be measured and determined in the knowledge of net costs. Our aim is to explore the issue of cost accounting in higher education and to identify the related problems

Collateral circulation of the rat lower limb and its significance in ischemia-reperfusion studies

PURPOSE: Rats are the most commonly used animal model for studies of acute lower limb ischemia-reperfusion. The ischemia induced by arterial clamping may cause milder damage than the application of a tourniquet if the presence of a possible collateral system is considered. METHODS: Male Wistar rats were randomized into three groups: in group A, the muscle weight affected by ischemia was measured; in group B, the severity of muscle damage caused by the application of a tourniquet and by infrarenal aortic occlusion was examined. Blood and muscle samples were taken from group B to assess the serum necroenzyme, potassium and TNF-alpha levels, as well as the muscle fiber viability and for histological examinations. In group C, the identification of the lower limb collateral system was performed using corrosion casting. RESULTS: Tourniquet application affected the lower muscle mass and resulted in significantly more severe injury compared to infrarenal aortic occlusion. This difference was reflected in the serum necroenzyme, potassium and TNF-alpha levels. The histological examination and viability assay confirmed these findings. The corrosion casts showed several anastomoses capable of supplying the lower limb. CONCLUSION: Tourniquet application proved to be capable of inducing absolute lower limb ischemia, in contrast to infrarenal aortic ligation, where a rich collateral system is considered to help mitigate the injury

Increased Expression of Claudin-1 and Claudin-7 in Liver Cirrhosis and Hepatocellular Carcinoma.

Claudins have been reported to be differentially regulated in malignancies and implicated in the process of carcinogenesis and tumor progression. Claudin-1 has been described as key factor in the entry of hepatitis C virus (HCV) into hepatocytes and as promoter of epithelial-mesenchymal transition in liver cells. The objective of the current study was to characterize claudin expression in hepatocellular carcinoma (HCC) as well as HCC-surrounding and normal liver samples with respect to cirrhosis and HCV infection. Expression of claudin-1, -2, -3, -4, and -7 was measured by morphometric analysis of immunohistochemistry, and Western blotting in 30 HCCs with 30 corresponding non-tumorous tissues and 6 normal livers. Claudin-1 and -7 protein expression was found significantly elevated in cirrhosis when compared with non-cirrhotic liver. HCCs developed in cirrhotic livers showed even higher expression of claudin-1 contrary to decreased claudin-7 expression when compared with cirrhosis. With reference to HCV status, HCCs or surrounding livers of HCV-infected samples did not show significant alterations in claudin expression when compared with HCV-negative specimens. Cirrhotic transformation associates with elevated claudin-1 and -7 expressions in both non-tumorous liver and HCC. The fact that no significant differences in claudin expression were found regarding HCV-positivity in our sample set suggests that HCV infection alone does not induce a major increase in the total amount of its entry co-factor claudin-1. Increased expression of claudin-1 seems to be a consequence of cirrhotic transformation and might contribute to a more effective HCV entry and malignant transformation