23 research outputs found
The identification of proteoglycans and glycosaminoglycans in archaeological human bones and teeth
Bone tissue is mineralized dense connective tissue consisting mainly of a mineral component (hydroxyapatite) and an organic matrix comprised of collagens, non-collagenous proteins and proteoglycans (PGs). Extracellular matrix proteins and PGs bind tightly to hydroxyapatite which would protect these molecules from the destructive effects of temperature and chemical agents after death. DNA and proteins have been successfully extracted from archaeological skeletons from which valuable information has been obtained; however, to date neither PGs nor glycosaminoglycan (GAG) chains have been studied in archaeological skeletons. PGs and GAGs play a major role in bone morphogenesis, homeostasis and degenerative bone disease. The ability to isolate and characterize PG and GAG content from archaeological skeletons would unveil valuable paleontological information. We therefore optimized methods for the extraction of both PGs and GAGs from archaeological human skeleto ns. PGs and GAGs were successfully extracted from both archaeological human bones and teeth, and characterized by their electrophoretic mobility in agarose gel, degradation by specific enzymes and HPLC. The GAG populations isolated were chondroitin sulfate (CS) and hyaluronic acid (HA). In addition, a CSPG was detected. The localization of CS, HA, three small leucine rich PGs (biglycan, decorin and fibromodulin) and glypican was analyzed in archaeological human bone slices. Staining patterns were different for juvenile and adult bones, whilst adolescent bones had a similar staining pattern to adult bones. The finding that significant quantities of PGs and GAGs persist in archaeological bones and teeth opens novel venues for the field of Paleontology
Analysis of sulfates on low molecular weight heparin using mass spectrometry: structural characterization of enoxaparin
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No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies.
IntroductionObservational studies show reduced incidence of Alzheimer dementia (AD) in users of nonsteroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as selective A beta(42)-lowering agents (SALAs) is responsible for this apparent reduction in AD risk.MethodsWe pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs.ResultsOf 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6%) showed reduced risk of AD (adjusted hazard ratio [aHR] 0.77, 95% CI 0.65-0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72-1.04) and non-SALAs (aHR 0.75, CI 0.56-1.01). Because 573 NSAID users (14.5%) reported taking both a SALA and non-SALA, we examined their use alone and in combination. Resulting aHRs were 0.82 (CI 0.67-0.99) for SALA only, 0.60 (CI 0.40-0.90) for non-SALA only, and 0.87 (CI 0.57-1.33) for both NSAIDs (Wald test for differences, p = 0.32). The 40.7% of participants who used aspirin also showed reduced risk of AD, even when they used no other NSAIDs (aHR 0.78, CI 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76-1.13).ConclusionsIn this pooled dataset, nonsteroidal anti-inflammatory drug (NSAID) use reduced the risk of Alzheimer dementia (AD). However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower A beta(42), suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans