Age-related changes in plasma levels of BDNF in Down syndrome patients

<p>Abstract</p> <p>Background</p> <p>The prevalence of coronary artery diseases is low among Down Syndrome (DS) patients and they rarely die of atherosclerotic complications. Histopathological investigations showed no increase in atherosclerosis, or even a total lack of atherosclerotic changes, in DS</p> <p>Aim</p> <p>The aim of our study is to investigate the relationship between age and brain-derived neurotrophic factor (BDNF) levels in Down Syndrome (DS).</p> <p>Subjects and methods</p> <p>Three groups of DS patients were studied: the first consisted of 23 children (age 2-14 years); the second of 14 adults (age 20-50 years), the third group of 13 elderly persons (>60 years) and a controls group of 20 healthy patients (age 15-60 years).</p> <p>The analytes of interest were quantified using a biochip array analyzer (Evidence^®, Randox Ltd., Crumlin, UK).</p> <p>Results</p> <p>Plasma BDNF was higher in DS patients than in controls and there was a significant age-related increase. Serum levels of IL-6 and MCP-1 were also higher in DS children and adults, but not in older patients, than in healthy control. High levels of circulating BDNF may protect DS patients from the clinical complications of atherosclerosis. However, the striking drop in peripheral BDNF levels with age might predispose these patients to clinical manifestations of dementia in later life.</p

LDL receptor expression on T lymphocytes in old patients with Down syndrome

BACKGROUND: In Down syndrome patients several metabolic abnormalities have been reported, some involving the lipid metabolism. The level of LDL in plasma is the major determinant of the risk of vascular disease. There appear to be no studies on the LDL receptor in Down syndrome patients. METHODS: Flow cytometric methods for measuring the LDL receptor in peripheral blood mononuclear cells (PBMC) can identify patients with hypercholesterolemia. We applied this method in 19 old patients with Down syndrome and 23 healthy controls. RESULTS: Down syndrome patients had high levels of triglycerides and low levels of HDL, and high levels of CRP. We also found a down-regulation of LDL receptor expression. CONCLUSIONS: Down syndrome patients show no increase in the frequency of cardiovascular disease. The low incidence in cardiovascular disease despite the low level of HDL, high levels of CRP and reduction of LDL receptor expression lead to the conclusion that either these are not risk factors in these patients or that other risks factors – not yet identified – are considerably lower

Natural zeolites chabazite/phillipsite/analcime increase blood levels of antioxidant enzymes

Imbalance between reactive oxygen species generation and antioxidant capacity induces a condition known as oxidative stress which is implicated in numerous pathological processes. In this study we evaluated whether natural zeolites chabazite/phillipsite/analcime may affect the levels of different antioxidant enzymes (gluthatione peroxidase, superoxide dismutase, gluthatione reductase), total antioxidant status and oxidative stress in 25 clinically healthy men, both non-smokers and smokers. Measurements were performed on whole blood or on plasma samples before (T0) and after 4-weeks zeolites intake (T1). At T1, gluthatione peroxidase, superoxide dismutase and gluthatione reductase increased compared to T0 levels, both considering all subjects as joint and after subdivision in non-smokers and smokers. Differently, a reduction in total antioxidant status was observed at T1. Anyway, total antioxidant status resulted higher than the reference values in both groups at each time point. A decrease in lipid peroxidation, a major indicator of oxidative stress assessed by monitoring thiobarbituric acid reactive substances, was also observed in all subjects at T1. Our results suggested that chabazite/phillipsite/analcime may help to counteract oxidative stress in apparently healthy subjects exposed to different oxidative stress risk factors, such as smoking, thus representing a particular kind of food with potential antioxidant properties

Serum neutrophil gelatinase-B associated lipocalin (NGAL) levels in Down’s syndrome patients

Neutrophil gelatinase-associated lipocalin (NGAL) is a group of proteins with different functions

Neutrophil gelatinase-associated lipocalin and acute kidney injury in endovascular aneurysm repair or open aortic repair: a pilot study

Introduction: Acute kidney injury (AKI) occurs frequently after abdominal aortic surgery and there is currently no effective marker able to detect early onset. The aim of this study is to evaluate the ability of neutrophil gelatinase-associated lipocalin (NGAL) to early identify the development of acute renal damage in patients undergoing endovascular aneurysm repair (EVAR) or open aortic repair (OAR). Materials and methods: Serial samples of blood and urine were obtained from 25 patients undergoing both EVAR and OAR. Seven male subjects with AKI and 18 subjects with no-AKI (17 males, 1 female) were included in the study. We determined concentrations of serum creatinine (sCr) and urinary, serum and whole blood NGAL (uNGAL, sNGAL, bNGAL) collected at baseline, and after 4 and 18 hours. AKI was defined according to the RIFLE criteria (risk, injury, failure, loss of kidney function, and end-stage kidney disease): increase by 50% in sCr or reduction of at least 25% of estimated glomerular filtration rate (eGFR) from baseline. Results: Seven patients developed AKI in the stage Risk. There was no significant difference in sNGAL concentrations in the AKI group as compared to no-AKI group. However, the uNGAL/uCreatinine ratio and bNGAL concentrations were significantly higher after 18 hours in the AKI group (no-AKI 1.69 (0.91 - 2.47) vs AKI 3.2 (2.08 - 5.92) ng/mg for uNGAL/uCreatinine ratio, P = 0.036; and no-AKI 83 (59 - 131) vs AKI 164 (126 – 263) ng/mL for bNGAL, P = 0.029). Conclusions: Our results suggest that uNGAL, sNGAL and bNGAL, after abdominal aortic surgery, are not suitable as early biomarkers of AKI

Expression of AMPA and NMDA receptor subunits in the cervical spinal cord of wobbler mice

BACKGROUND: The localisation of AMPA and NMDA receptor subunits was studied in a model of degeneration of cervical spinal motoneurons, the wobbler mouse. Cervical regions from early or late symptomatic wobbler mice (4 or 12 weeks of age) were compared to lumbar tracts (unaffected) and to those of healthy mice. RESULTS: No differences were found in the distribution of AMPA and NMDA receptor subunits at both ages. Western blots analysis showed a trend of reduction in AMPA and NMDA receptor subunits, mainly GluR1 and NR2A, exclusively in the cervical region of late symptomatic mice in the triton-insoluble post-synaptic fraction but not whole homogenates. Colocalisation experiments evidenced the expression of GluR1 and NR2A receptors in activated astrocytes from the cervical spinal cord of wobbler mice, GluR2 did not colocalise with GFAP positive cells. No differences were found in the expression of AMPA and NMDA receptor subunits in the lumbar tract of wobbler mice, where neither motoneuron loss nor reactive gliosis occurs. CONCLUSION: In late symptomatic wobbler mice altered levels of GluR1 and NR2A receptor subunits may be a consequence of motoneuron loss rather than an early feature of motoneuron vulnerability

Impairment of circulating endothelial progenitors in Down syndrome

<p>Abstract</p> <p>Background</p> <p>Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome.</p> <p>Methods</p> <p>Circulating endothelial progenitors of Down syndrome affected individuals were isolated, <it>in vitro </it>cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of <it>CXCL12 </it>gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis.</p> <p>Results</p> <p>We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells.</p> <p>Conclusions</p> <p>Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.</p

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands