Enhancing reductive cleavage of aromatic carboxamides

[GRAPHICS] A set of aromatic and especially heteroaromatic N-benzyl carboxamides, derived from naphthalene, pyridine, pyrazine, and quinoline, and the corresponding tert-butyl acylcarbamates have been synthesized and studied by cyclic voltammetry with respect to facilitated reduction. The latter undergo regiospecific cleavage of their C(O)-N bonds under very mild reductive conditions with formation of Boc-protected (benzyl)amine in most cases in nearly quantitative yields, Examples of preparative cleavage by controlled potential electrolysis, activated aluminum, and NaBH4 are given

Awareness of cognitive decline trajectories in asymptomatic individuals at risk for AD

Background: Lack of awareness of cognitive decline (ACD) is common in late-stage Alzheimer’s disease (AD). Recent studies showed that ACD can also be reduced in the early stages. Methods: We described different trends of evolution of ACD over 3 years in a cohort of memory-complainers and their association to amyloid burden and brain metabolism. We studied the impact of ACD at baseline on cognitive scores’ evolution and the association between longitudinal changes in ACD and in cognitive score. Results: 76.8% of subjects constantly had an accurate ACD (reference class). 18.95% showed a steadily heightened ACD and were comparable to those with accurate ACD in terms of demographic characteristics and AD biomarkers. 4.25% constantly showed low ACD, had significantly higher amyloid burden than the reference class, and were mostly men. We found no overall effect of baseline ACD on cognitive scores’ evolution and no association between longitudinal changes in ACD and in cognitive scores. Conclusions: ACD begins to decrease during the preclinical phase in a group of individuals, who are of great interest and need to be further characterized. Trial registration: The present study was conducted as part of the INSIGHT-PreAD study. The identification number of INSIGHT-PreAD study (ID-RCB) is 2012-A01731-42

Low Cognitive Awareness, but Not Complaint, is a Good Marker of Preclinical Alzheimer's Disease

Subjective cognitive decline (SCD) may result from many conditions, including Alzheimer's disease (AD)

Resistance of nosocomial bacterial strains to commonly used antibiotics and their sensitivity to some Cameroonian Medicinal Plant preparations

No Abstract.Journal of the Cameroon Academy of Sciences Vol. 6 (3) 2006: pp. 139-14

Evaluation of the anti-ulcer and toxicity profile of Aloe buettneri in laboratory animals

The anti-ulcerogenic potential of the leaf methanol extract of Aloe buettneri A. Berger was investigated using three methods of gastric lesion induction in experimental Wistar rats (150-200 g) and mice (20-25 g): 1. HCl/ethanol-induced gastic lesions, 2. Indomethacin-HCl/ethanol-induced gastric lesions, and 3, Pylorus ligation-induced gastric lesions. Mice were used in acute and sub acute toxicity tests. Oral administration of the extract of Aloe buettneri to the rats and mice (500-1000 mg/kg) dose-dependently prevented the formation of acute gastric lesions induced using the three experimental techniques. The dose-dependent reduction of lesion formation was accompanied by a significant increase in gastric mucus production in mice. Inhibition of lesion formation was 22 and 54 % in mice, 25 and 77% in rats for the doses of 500 and 1000 mg/kg when the HCl/ethanol mixture was given. Pre-treatment, by oral route, with indomethacin significantly reduced the ability of the extract to inhibit the formation of HCl/ethanol-induced lesions, inhibition dropping to 11% for the dose of 1000 mg/kg. When the rats were subjected to pylorus ligation, the level of lesion inhibition was 36 and 68% for the two doses of extract. Gastric acid secretion reduced to 88 and 79mEq/l compared with105 mEq/l for the controls. Acute toxicity studies did not reveal toxic effects up to the dose of 10 g/kg. However, sub acute studies revealed toxicity effects in heart (pericarditis), lung (diffuse alveolar disease) and liver (chronic active hepatitis) tissue. These results confirm the ethnomedical use of Aloe buettneri in the management of gastroduodenal ulcer disease and suggest that toxic effects may result from prolonged intake of high doses of the extract. Keywords: Aloe buettneri, antiulcer activity, toxicity profile African Journal of Traditional, Complementary and Alternative Medicines Vol. 3(2) 2006: 8-2

Aptamarker prediction of brain amyloid-β status in cognitively normal individuals at risk for Alzheimer’s disease

The traditional approach to biomarker discovery for any pathology has been through hypothesis-based research one candidate at a time. The objective of this study was to develop an agnostic approach for the simultaneous screening of plasma for consistent molecular differences between a group of individuals exhibiting a pathology and a group of healthy individuals. To achieve this, we focused on developing a predictive tool based on plasma for the amount of brain amyloid-β deposition as observed in PET scans. The accumulation of brain amyloid-β (Aβ) plaques is a key risk factor for the development of Alzheimer’s disease. A contrast was established between cognitively normal individuals above the age of 70 that differed for the amount of brain amyloid-β observed in PET scans (INSIGHT study group). Positive selection was performed against a pool of plasma from individuals with high brain amyloid and negative selection against a pool of plasma from individuals with low brain amyloid This enriched, selected library was then applied to plasma samples from 11 individuals with high levels of brain amyloid and 11 individuals with low levels of brain Aβ accumulation. Each of these individually selected libraries was then characterized by next generation sequencing, and the relative frequency of 10,000 aptamer sequences that were observed in each selection was screened for ability to explain variation in brain amyloid using sparse partial least squares discriminant analysis. From this analysis a subset of 44 aptamers was defined, and the individual aptamers were synthesized. This subset was applied to plasma samples from 70 cognitively normal individuals all above the age of 70 that differed for brain amyloid deposition. 54 individuals were used as a training set, and 15 as a test set. Three of the 15 individuals in the test set were mis-classified resulting in an overall accuracy of 80% with 86% sensitivity and 75% specificity. The aptamers included in the subset serve directly as biomarkers, thus we have named them Aptamarkers. There are two potential applications of these results: extending the predictive capacity of these aptamers across a broader range of individuals, and/or using the individual aptamers to identify targets through covariance analysis and reverse omics approaches. We are currently expanding applications of the Aptamarker platform to other diseases and target matrices. © 2021 Penner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited