Skeletal muscle mass increases after viral eradication with direct-acting antivirals in patients with chronic hepatitis C: A longitudinal study.

BACKGROUND: Results of studies evaluating the effect of viral eradication following direct-acting antiviral (DDA) therapy on skeletal muscle mass of patients with chronic hepatitis C (CHC) are scarce. AIM: To assess the components of sarcopenia (low muscle mass, low muscle strength and low physical performance) in a cohort of CHC individuals before and after DAA therapy. METHODS: We performed a longitudinal study of patients with CHC who underwent body composition assessment before (T0), and at 12 (T1) and 48 (T2) weeks after DDA therapy. Bioelectrical Impedance Analysis was used to assess skeletal mass muscle (SM) and phase angle (PhA). SM index (SMI) was calculated by dividing the SM by squared height. Muscle function was evaluated by hand grip strength (HGS) and timed up-and-go (TUG) test. Mixed-effects linear regression models were fitted to SMI, HGS and physical performance and were used to test the effect of HCV eradication by DAA. RESULTS: 62 outpatients (mean age, 58.6 ± 10.8 years; 58% with compensated cirrhosis) were included. Significant decreases in liver fibrosis markers and an increase of 0.20 and 0.22 kg/m2 in the SMI were observed at T1 and T2. Following DAA therapy, an increase of one unit of PhA was associated with a reduction of 0.38 min in TUG. CONCLUSION: HCV eradication with DAA therapy was associated with a dynamic reduction of non-invasive markers of liver fibrosis and increased muscle mass in 62 patients with CHC who had an undetectable HCV load at 12 weeks after completion of antiviral treatment.

Neurochemical abnormalities in the hippocampus of male rats displaying audiogenic seizures, a genetic model of epilepsy.

BACKGROUND: Epilepsy is a disorder characterized by recurrent seizures that affects 1% of the population. However, the neurochemical alterations observed in epilepsy are not fully understood. There are different animal models of epilepsy, such as genetic or drug induced. In the present study, we utilize Wistar Audiogenic Rats (WAR), a murine strain that develops seizures in response to high intensity audio stimulation, in order to investigate abnormalities in glutamatergic and GABAergic systems. METHODS: Synaptosomes and glial plasmalemmal vesicles were prepared from hippocampus and cortex, respectively. Glutamate and GABA release and uptake were assayed by monitoring the fluorescence and using L-[3H]-radiolabeled compounds. Glutamate and calcium concentration in the synaptosomes were also measured. The expression of neuronal calcium sensor 1 (NCS-1) was determined by western blot. RESULTS: Glutamate and GABA release evoked by KCl was decreased in WAR compared to control Wistar rats. Calcium independent release was not considerably different in both groups. The total amount of glutamate of synaptosomes, as well as glutamate uptake by synaptosomes and GPV were also decreased in WAR in comparison with the controls. In addition, [Ca2+]i of hippocampal synaptosomes, as well as NCS-1 expression in the hippocampus, were increased in WAR in comparison with controls. CONCLUSION: In conclusion, our results suggest that WAR have important alterations in the glutamatergic and GABAergic pathways, as well as an increased expression of NCS-1 in the hippocampus and inferior colliculus. These alterations may be linked to the spreading of hyperexcitability and recruitment of various brain regions.

Disease-specific expression of the serotonin-receptor 5-HT(2C) in natural killer cells in Alzheimer's dementia.

Alzheimer's dementia (AD) is a degenerative brain disorder characterized mainly by cholinergic failure, but other neuro-transmitters are also deficient especially at late stages of the disease. Misfolded ß-amyloid peptide has been identified as a causative agent, however inflammatory changes also play a pivotal role. Even though the most prominent pathology is seen in the cognitive functions, specific abnormalities of the central nervous system (CNS) are also reflected in the periphery, particularly in the immune responses of the body. The aim of this study was to characterize the dopaminergic and serotonergic systems in AD, which are also markedly disrupted along with the hallmark acetyl-choline dysfunction. Peripheral blood mono-nuclear cells (PBMCs) from demented patients were judged against comparison groups including individuals with late-onset depression (LOD), as well as non-demented and non-depressed subjects. Cellular sub-populations were evaluated by mono-clonal antibodies against various cell surface receptors: CD4/CD8 (T-lymphocytes), CD19 (B-lymphocytes), CD14 (monocytes), and CD56 (natural-killer (NK)-cells). The expressions of dopamine D(3) and D(4), as well as serotonin 5-HT(1A), 5-HT(2A), 5-HT(2B) and 5-HT(2C) were also assessed. There were no significant differences among the study groups with respect to the frequency of the cellular sub-types, however a unique profound increase in 5-HT(2C) receptor exclusively in NK-cells was observed in AD. The disease-specific expression of 5-HT(2C), as well as the NK-cell cyto-toxicity, has been linked with cognitive derangement in dementia. These changes not only corroborate the existence of bi-directional communication between the immune system and the CNS, but also elucidate the role of inflammatory activity in AD pathology, and may serve as potential biomarkers for less invasive and early diagnostic purposes as well.

Ascorbic acid, alpha-tocopherol, and beta-carotene reduce oxidative stress and proinflammatory cytokines in mononuclear cells of Alzheimer's disease patients.

OBJECTIVES: The in vitro effect of a vitamin complex in generating and reducing oxidative species in peripheral blood mononuclear cells (PBMNC) and plasma of patients with Alzheimer's disease (AD) and healthy subjects (HS) was evaluated. METHODS: Two concentrations of a vitamin complex ([A] and [20A]) with ascorbic acid, alpha-tocopherol, and beta-carotene were incubated with either mononuclear cells or plasma. The generation of oxidizing species was measured in a luminol-dependent chemiluminescence assay and the reducing response by the MTT dye reduction assay. The levels of cytokines (interleukin [IL]-1ß, IL-6, and IL-4) were measured by sandwich enzyme-linked immunosorbent assay. RESULTS: Our results demonstrated that the increase in the vitamin complex concentration reduced the reactive oxygen species (ROS) production and enhanced cellular reduction capacity in cells of AD patients in concentration [20A]. Plasma reduction capacity rose significantly for both groups (AD and HS). Concentration [A] did not alter the IL-1ß production, increased IL-4 production in both groups and lowered IL-6 production in AD cells. Concentration [20A] increased pro-inflammatory cytokines (IL-1ß and IL-6) and decreased IL-4 production by PBMNC of HS leading to a pro-inflammatory status. DISCUSSION: The antioxidant vitamin complex was effective in reducing oxidative stress in PBMNC of AD patients by lowering ROS production, improving cellular antioxidant capacities and modifying cytokine induced inflammation.