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Immunohistochemistry and electron microscopy analysis were used to detect amyloid β-(Aβ 1-42 ) and hyperphosphorylated tau (AT8) accumulation and ultrastructural changes in the brain. Memory decline was time-(≤3 months/acute, ≥3 months/progressive) and STZ-icv dosedependent. Morphological changes were manifested as thinning of parietal cortex (≥1 month) and corpus callosum (9 months), and were more pronounced in the 3 mg/kg STZ group. Early neurofibrillary changes (AT8) were detected from 1 month onward in the neocortex, and progressed after 3 months to the hippocampus. Intracellular Aβ 1-42 accumulation was found in the neocortex at 3 months following STZ-icv treatment, while diffuse Aβ 1-42 -positive plaque-like formations were found after 6 months in the neocortex and hippocampus. Ultrastructural changes revealed enlargement of Golgi apparatus, pyknotic nuclei, and timedependent increase in lysosome size, number, and density. Our data provide a staging of cognitive, structural/ultrastructural, and neuropathological markers in the STZ-icv rat model that in many aspects seems to be generally comparable to stages seen in human sAD.

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AimTo determine the prognostic value of baseline red blood cell distribution width (RDW) in diffuse large B cell lymphoma (DLBCL) patients.MethodsData from 81 DLBCL patients diagnosed from 2006 to 2013 at the University Hospital Center Osijek, Osijek, Croatia, were reviewed. We evaluated disease outcome, overall survival (OS) and event-free survival (EFS), and demographic, clinical and laboratory factors affecting outcome. Univariate analysis and Cox regression analysis were used.ResultsMedian age of patients was 64 years, 29 were men (35.8%). Higher RDW levels (%) were found in patients with advanced Ann Arbor clinical stage (14.94 ± 1.82 vs 13.55 ± 1.54, P = 0.001) and in those with poor response to therapy (14.94 ± 1.82 vs 13.55 ± 1.54, P = 0.001). Patients with RDW>15% (cut-off was calculated by receiver operating characteristics) had significantly worse OS (median [range], 33 months [20-46] vs 74 months [65-82], P < 0.001) and EFS (27 months [15-40] vs 68 months [59-77], P < 0.001). Cox regression analysis showed that RDW>15% was an independent prognostic factor for OS (HR 3.654, 95% CI 1.128-11.836) and EFS (HR 2.611, 95% CI 1.012-6-739).ConclusionHigh baseline RDW is an independent prognostic marker of poor outcome in patients with DLBCL. RDW could be an easily available and inexpensive marker for the risk stratification in patients with DLBCL.

Scope: Galactose, a ubiquitous monosaccharide with incompletely understood physiology is often exploited for inducing oxidative-stress mediated aging in animals. Recent research demonstrates that galactose can conserve cellular function during periods of starvation and prevent/alleviate cognitive deficits in a rat model of sporadic Alzheimer's disease. The present aim is to examine the acute effects of oral galactose on the redox regulatory network (RRN). Methods and Results: Rat plasma and hippocampal RRNs are analyzed upon acute orogastric gavage of galactose (200 mg kg -1 ). No systemic RRN disbalance is observed; however, a mild pro-oxidative shift accompanied by a paradoxical increment in tissue reductive capacity suggesting overcompensation of endogenous antioxidant systems is observed in the hippocampus. Galactose-induced increment of reductive capacity is accompanied by inflation of the hippocampal pool of nicotinamide adenine dinucleotide phosphates indicating ROS detoxification through disinhibition of the oxidative pentose phosphate pathway flux, reduced neuronal activity, and upregulation of Leloir pathway gatekeeper enzyme galactokinase-1. Conclusion: Based on the observed findings, and in the context of previous work on galactose, a hormetic hypothesis of galactose is proposed suggesting that the protective effects may be inseparable from its pro-oxidative action at the biochemical level.

The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer’s disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model.

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