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BackgroundMitochondrial dysfunction has been shown to play an important role in the development of atherosclerosis and nonalcoholic fatty liver disease (NAFLD). Mitochondrial aldehyde dehydrogenase (ALDH2), an enzyme responsible for the detoxification of reactive aldehydes, is considered to exert protective function in mitochondria. We investigated the influence of Alda‐1, an activator of ALDH2, on atherogenesis and on the liver steatosis in apolipoprotein E knockout (apoE−/−) mice.Methods and ResultsAlda‐1 caused decrease of atherosclerotic lesions approximately 25% as estimated by “en face” and “cross‐section” methods without influence on plasma lipid profile, atherosclerosis‐related markers of inflammation, and macrophage and smooth muscle content in the plaques. Plaque nitrotyrosine was not changed upon Alda‐1 treatment, and there were no changes in aortic mRNA levels of factors involved in antioxidative defense, regulation of apoptosis, mitogenesis, and autophagy. Hematoxylin/eosin staining showed decrease of steatotic changes in liver of Alda‐1‐treated apoE−/− mice. Alda‐1 attenuated formation of 4‐hydroxy‐2‐nonenal (4‐HNE) protein adducts and decreased triglyceride content in liver tissue. Two‐dimensional electrophoresis coupled with mass spectrometry identified 20 differentially expressed mitochondrial proteins upon Alda‐1 treatment in liver of apoE−/− mice, mostly proteins related to metabolism and oxidative stress. The most up‐regulated were the proteins that participated in beta oxidation of fatty acids.ConclusionsCollectively, Alda‐1 inhibited atherosclerosis and attenuated NAFLD in apoE−/− mice. The pattern of changes suggests a beneficial effect of Alda‐1 in NAFLD; however, the exact liver functional consequences of the revealed alterations as well as the mechanism(s) of antiatherosclerotic Alda‐1 action require further investigation.

Nicotinamide N-methyltransferase (NNMT), which converts nicotinamide (NA) to 1-methylnicotinamide (MNA), is up-regulated in the cirrhotic liver. Because MNA displays PGI(2)-dependent anti-inflammatory effects, the up-regulation of NNMT may play a regulatory role in liver inflammation. In the present work, we analyzed changes in NNMT activity in the liver and concomitant changes in the concentration of endogenous MNA in plasma in T-cell dependent hepatitis induced by concanavalin A (ConA) in BALB/c mice. Furthermore, we tested whether exogenous MNA possessed a protective effect against ConA-induced hepatitis. Development of liver injury induced by ConA (10 mg/kg, iv) was characterized by measurements of plasma concentration of alanine aminotransaminase (ALT), inflammatory cytokines (INF gamma and TNFalpha) and by histopathological examination. ConA-induced hepatitis was characterized by an early activation of inflammatory cytokines (IFN gamma; from below 0.05 ng/ml to 23.72 +/- 8.80 ng/ml; TNFalpha;from 0.07 +/- 0.01 ng/ml to 0.71 +/- 0.12 ng/ml, 2 h after ConA), an elevation of ALT (from 40.65 +/- 3.2 U/l to 5,092.20 +/- 1,129.05 U/l, 8 h after ConA) and by morphological signs of severe liver inflammation and injury (24 h after ConA). In mice injected with ConA, NNMT activity in the liver was up-regulated approximately 2-fold to 3-fold, 8-24 h after ConA injection. The concentration of MNA and its metabolites (Met-2PY and Met-4PY) in plasma were elevated approximately 2-fold 8 h after ConA injection. Exogenous MNA (100 mg/kg, iv) diminished ConA-induced liver injury, and this effect was reversed by an antagonist of the prostacyclin receptor, RO 3244794 (10 mg/kg, po). In conclusion, the present study demonstrated that hepatic NNMT activity and MNA concentration in plasma significantly increased during the progression of ConA-induced hepatitis in mice. This response may play a hepatoprotective role compatible with the PGI(2)-releasing properties of MNA.

The results of laparoscopic adrenalectomy depend not only on the experience of the single surgeon, but on the whole team involved in perioperative care. In high volume centers with extensive experience in surgery of adrenals, this technique may provide an alternative to open surgery, also in selected cases of malignant tumours.

IntroductionLaparoscopic adrenalectomy is the gold standard for the treatment of benign adrenal tumors. However, some authors raise the problem of differences in surgery for pheochromocytoma in comparison to other lesions.AimTo compare laparoscopic adrenalectomy for pheochromocytoma and for other tumors.Material and methodsFour hundred and thirty-seven patients with adrenal tumors were included in the retrospective analysis. Patients were divided into two groups: 1 (124 patients treated for pheochromocytoma) and 2 (313 patients with other types of tumor). The two groups were compared with respect to mean operative time, intraoperative blood loss, conversion rate, complication rate and the relationship of tumor size with operative time.ResultsThe mean operative time in group 1 was 91 min, and in group 2 it was 82 min (p = 0.016). In both groups 1 and 2, tumor size correlated with operative time (p < 0.0001 and p = 0.0003, respectively). The mean blood loss in groups 1 and 2 was 117 ml and 54 ml, respectively (p = 0.0011). The complication rate in groups 1 and 2 was 4% and 4.2%, respectively (p = 0.9542). In groups 1 and 2, conversion was necessary in 2 (1.6%) and 5 (1.6%) cases, respectively (p = 0.9925).ConclusionsLonger operative time and higher blood loss after laparoscopic adrenalectomy for pheochromocytoma indicate its greater difficulty. However, despite these drawbacks, minimally invasive surgery still seems to be an effective and safe method.