Soluble Klotho and Brain Atrophy in Alcoholism.

AIM: Fibroblast growth factor (FGF-23) and α-Klotho (Klotho) levels may be altered in inflammatory conditions, possibly as compensatory mechanisms. Klotho exerts a protective effect on neurodegeneration and improves learning and cognition. No data exist about the association of Klotho and FGF-23 levels with brain atrophy observed in alcoholics. The aim of this study is to explore these relationships. SHORT SUMMARY: FGF-23 and Klotho levels are altered in inflammation, possibly as compensatory mechanisms. Klotho enhances learning, but its role in ethanol-mediated brain atrophy is unknown. We found higher FGF-23 and lower Klotho levels in 131 alcoholics compared with 41 controls. Among cirrhotics, Klotho was higher and inversely related to brain atrophy. METHODS: The study was performed on 131 alcoholic patients (54 cirrhotics) and 41 age- and sex-matched controls, in whom a brain computed tomography (CT) was performed and several indices were calculated. RESULTS: Marked brain atrophy was observed among patients when compared with controls. Patients also showed higher FGF-23 and lower Klotho values. However, among cirrhotics, Klotho values were higher. Klotho was inversely related to brain atrophy (for instance, ventricular index (ρ = -0.23, P = 0.008)), especially in cirrhotics. Klotho was also directly related to tumor necrosis factor (TNF) alpha (ρ = 0.22; P = 0.026) and inversely to transforming growth factor (TGF)-ß (ρ = -0.34; P = 0.002), but not to C-reactive protein (CRP) or malondialdehyde levels. FGF-23 was also higher among cirrhotics but showed no association with CT indices. CONCLUSIONS: Klotho showed higher values among cirrhotics, and was inversely related to brain atrophy. FGF-23, although high among patients, especially cirrhotics, did not show any association with brain atrophy. Some inflammatory markers or cytokines, such as CRP or TGF-ß were related to brain atrophy.

Antioxidant vitamins and brain dysfunction in alcoholics.

AIMS: Alcohol induces cytokine secretion by Kupffer cells, which may exert also deleterious effects on distant organs, mediated in part by cytokine-derived increased production of reactive oxygen species (ROS). It is therefore important to assess antioxidant levels. The objective of this study is to analyse the relation of antioxidant vitamins with brain atrophy and cognitive dysfunction. METHODS: In 77 alcoholic patients admitted for withdrawal syndrome, subjected to brain computed tomography (CT), and 19 controls, we determined antioxidant vitamin levels and analysed their relationships with data of brain atrophy and dysfunction. Searching for causes of altered vitamin levels, we also assessed liver function, nutritional status, eating habits, alcohol intake, proinflammatory cytokine (TNF-α, IL-6, IL-8) levels and malondialdehyde (MDA) levels. RESULTS: Both retinol (vitamin A) and tocopherol (vitamin E) levels were decreased in alcoholics, the former in relation with liver failure, and the latter in relation with triglyceride levels and fat mass. Both were related to data of brain atrophy and cerebellar shrinkage (to which also IL-6 was significantly related). CONCLUSION: Among alcoholics, liver function impairment leads to altered serum vitamin A levels, which are related to brain alterations. Vitamin E levels are also decreased, but although in relation with liver function impairment, its decrease seems to be more dependent on nutritional status and irregular eating habits. Both vitamins are lower in patients with cerebellar atrophy and other features related to brain atrophy.

Serum sclerostin in hepatitis C virus infected patients.

BACKGROUND: Sclerostin inhibits osteoblast functions, differentiations, and survival rates. As an endogenous inhibitor of the Wnt/ß-catenin pathway, the sclerostin should be related to decreased bone masses, although several studies indicate opposite results. In addition, it may be related to insulin resistances and carbohydrate metabolisms, a relation shared with other markers of bone metabolisms, such as osteocalcin. Hepatitis C virus (HCV) infected patients may present osteoporosis, and frequently show liver steatosis, which is a consequence of insulin resistance. The behaviour of sclerostin in these patients is yet unknown. The aim of this work is to analyse the relationships between serum sclerostin and osteocalcin levels and bone mineral density (BMD), liver functions, the intensity of liver steatosis and biochemical markers of bone homeostasis and insulin resistance in HCV-infected patients. METHODS: Forty HCV patients with 20 years of age and gender-matching controls were included in this study and underwent bone densitometry. Serum sclerostin, osteocalcin, collagen telopeptide, adiponectin, leptin, insulin, resistin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were determined. Liver fat was histomorphometrically assessed. RESULTS: Sclerostin levels were slightly higher in patients than in controls, and were directly related to BMD at different parts of the skeleton, also to the serum telopeptide, and to the liver steatosis and TNF-α. On the contrary, osteocalcin showed a significant direct relationship with serum adiponectin, and an inverse one with IL-6. CONCLUSIONS: Serum sclerostin levels were within the normal range in HCV patients, and correlated directly with BMD and serum telopeptide. In addition, the relationships of sclerostin and osteocalcin with variables associated with insulin resistance suggested the role of bones for intermediary metabolisms.