52 research outputs found

    PP2A ligand ITH12246 protects against memory impairment and focal cerebral ischemia in mice

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    ITH12246 (ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8] naphthyridine-3-carboxylate) is a 1,8-naphthyridine described to feature an interesting neuroprotective profile in in vitro models of Alzheimer's disease. These effects were proposed to be due in part to a regulatory action on protein phosphatase 2A inhibition, as it prevented binding of its inhibitor okadaic acid. We decided to investigate the pharmacological properties of ITH12246, evaluating its ability to counteract the memory impairment evoked by scopolamine, a muscarinic antagonist described to promote memory loss, as well as to reduce the infarct volume in mice suffering phototrombosis. Prior to conducting these experiments, we confirmed its in vitro neuroprotective activity against both oxidative stress and Ca2+ overload-derived excitotoxicity, using SH-SY5Y neuroblastoma cells and rat hippocampal slices. Using a predictive model of blood-brain barrier crossing, it seems that the passage of ITH12246 is not hindered. Its potential hepatotoxicity was observed only at very high concentrations, from 0.1 mM. ITH12246, at the concentration of 10 mg/kg i.p., was able to improve the memory index of mice treated with scopolamine, from 0.22 to 0.35, in a similar fashion to the well-known Alzheimer's disease drug galantamine 2.5 mg/kg. On the other hand, ITH12246, at the concentration of 2.5 mg/kg, reduced the phototrombosis-triggered infarct volume by 67%. In the same experimental conditions, 15 mg/kg melatonin, used as control standard, reduced the infarct volume by 30%. All of these findings allow us to consider ITH12246 as a new potential drug for the treatment of neurodegenerative diseases, which would act as a multifactorial neuroprotectant.Peer Reviewe

    Bioinorganic Chemistry of Alzheimer’s Disease

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    Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population: a nationwide observational, cross-sectional study

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    The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold

    In vitro corrosion resistance of titanium in fluorinated environment

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    The aim of this study was to evaluate the resistance to initial and ongoing corrosion of titanium samples in a fluorinated environment, according to specification G5/95 of the American Society for Testing and Materials (A.S.T.M.). Commercially pure titanium was used in the experimental tests. This was a grade 4 titanium in accordance with A.S.T.M. F67-89 Gd 4 (Fe 0.20, O 0.34, C 0.01, N 0.012, H 0.0006, Ti 99.4374). Three cylindrical samples with 6.35 \ub1 0.003 mm diameter and 20.00 \ub1 1 mm length were utilized in every solution. The potentiodynamic cyclic polarization tests were performed in two different solutions: 1) Fusayama artificial saliva 2) fluorinate solution with 0.5% NaF. The \u201cex novo\u201d prepared solutions before each measurement were preserved at 37.5\ub0 C temperature and deaerated through azote gurgling, 24 hours before the experiment. 1 hour before polarization the samples were immersed in the electrolyte for recording and stabilizing corrosion potential. This operation simulates potentiometric test to measure the loss potential of the examined material. Afterwards, potentiometric tests, according A.S.T.M. G5/95 rule, were performed. The results indicate that the titanium resting potential becomes anodic in fluorinated environment and in such solution corrosive phenomena of titanium are facilitated. The exposure of titanium in artificial saliva with 0.5% NaF determines a radical reduction of breakdown and repassivation potential of titanium, making it more easily exposed to beginning and spreading of the pitting and crevice corrosion
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