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

Effects of Vitamin E-Stabilized Ultra High Molecular Weight Polyethylene on Oxidative Stress Response and Osteoimmunological Response in Human Osteoblast

High Crosslink process was introduced in the development of joint prosthetic devices, in order to decrease the wear rate of ultrahigh molecular weight polyethylene (UHMWPE), but it also triggers the formation of free radicals and oxidative stress, which affects the physiological bone remodeling, leading to osteolysis. Vitamin E stabilization of UHMWPE was proposed to provide oxidation resistance without affecting mechanical properties and fatigue strength. The aim of this study is to evaluate the antioxidant effect of vitamin E added to UHMWPE on oxidative stress induced osteolysis, focusing in particular on the oxidative stress response in correlation with the production of osteoimmunological markers, Sclerostin and DKK-1, and the RANKL/OPG ratio compared to conventional UHMWPE wear debris. Human osteoblastic cell line SaOS2 were incubated for 96 h with wear particles derived from crosslinked and not crosslinked Vitamin E-stabilized, UHMWPE without Vitamin E, and growth medium as control. Cellular response to oxidative stress, compared to not treat cells, was evaluated in terms of proteins O-GlcNAcylation, cellular levels of OGA, and OGT proteins by immunoblotting. O-GlcNAcylation and its positive regulator OGT levels are increased in the presence of Vitamin E blended UHMWPE, in particular with not crosslinked Vit E stabilized UHMWPE. Conversely, the negative regulator OGA increased in the presence of UHMWPE not blended with Vitamin E. Vitamin E-stabilized UHMWPE induced a decrease of RANKL/OPG ratio compared to UHMWPE without Vitamin E, and the same effect was observed for Sclerostin, while DKK-1 was not significantly affected. In conclusion, Vitamin E stabilization of UHMWPE increased osteoblast response to oxidative stress, inducing a cellular mechanism aimed at cell survival. Vitamin E antioxidant effect influences the secretion of osteoimmunological factors, shifting the bone turnover balance toward bone protection stimuli. This suggests that Vitamin E-Stabilization of UHMWPE could contribute to reduction of oxidation-induced osteolysis and the consequent loosening of the prosthetic devices, therefore improving the longevity of total joint replacements

Understanding the Role of Surface Modification of Randomized Trabecular Titanium Structures in Bone Tissue Regeneration: An Experimental Study

Background and Objectives: Three-dimensional (3D) metallic trabecular structures made by additive manufacturing (AM) technologies promote new bone formation and osteointegration. Surface modifications by chemical treatments can improve the osteoconductive properties of metallic structures. An in vivo study in sheep was conducted to assess the bone response to randomized trabecular titanium structures that underwent a surface modification by chemical treatment compared to the bone response to the untreated specimens. Material and Methods: Sixteen specimens with a randomized trabecular titanium structure were implanted in the spongious bone of the distal femur and proximal tibia and the cortical bone of the tibial diaphysis of two sheep. Of them, eight implants had undergone a chemical treatment (treated) and were compared to eight implants with the same structure but native surfaces (native). The sheep were sacrificed at 6 weeks. Surface features of the lattice structures (native and treated) were analyzed using a 3D non-contact profilometer. Compression tests of 18 lattice cubes were performed to investigate the mechanical properties of the two structures. Excellent biocompatibility for the trabecular structures was demonstrated in vitro using a cell mouse fibroblast culture. Histomorphometric analysis was performed to evaluate bone implant contact and bone ingrowth. Results: A compression test of lattice cubic specimens revealed a comparable maximum compressive strength value between the two tested groups (5099 N for native surfaces; 5558 N for treated surfaces; p > 0.05). Compared to native surfaces, a homogenous formation of micropores was observed on the surface of most trabeculae that increased the surface roughness of the treated specimens (4.3 versus 3.2 µm). The cellular viability of cells seeded on three-dimensional structure surfaces increased over time compared to that on plastic surfaces. The histomorphometric data revealed a similar behavior and response in spongious and cortical bone formation. The percentage of the implant surface in direct contact with the regenerated bone matrix (BIC) was not significantly different between the two groups either in the spongious bone (BIC: 27% for treated specimens versus 30% for native samples) or in the cortical bone (BIC: 75% for treated specimens versus 77% for native samples). Conclusions: The results of this study reveal rapid osseointegration and excellent biocompatibility for the trabecular structure regardless of surface treatment using AM technologies. The application of implant surfaces can be optimized to achieve a strong press-fit and stability, overcoming the demand for additional chemical surface treatments

Immunohistochemical and molecular analysis of bone remodelling pattern in alveolar socket

Following tooth extraction, the alveolar bone remodelling process starts. Bundle bone and buccal wall resorption occur early with horizontal and vertical bone crest reduction [1]. The use of bone substitutes has been proposed to limit bone resorption, thus allowing further dental rehabilitation [2]. Aim of this project was to characterize by a molecular and morphological approach the physiological remodelling of post-extractive alveolar socket and to compare it with the bone remodelling occurring after alveolar bone reconstruction with an alloplastic material. Thirty-six patients needing tooth extraction were enrolled and equally divided into three groups: A) baseline, B) spontaneous healing, C) biomaterial. In each group, 2 biopsies per site were harvested during tooth extraction (group A) or 4-6 months after tooth extraction (groups B and C). In group B, patients recovered spontaneously, while in group C the alveolar socket was filled with a magnesium-enriched hydroxyapatite. One biopsy was processed for immunohistochemistry to localise TNF-α, IL-6, RANK, RANKL and OPG. The second biopsy underwent a Real-Time PCR analysis for the same biomarkers in order to evaluate gene expression. In groups B and C, a third biopsy was retrieved and processed for ground section aiming to assess tissue composition. Differences between the three groups were investigated using Kruskal Wallis test (p&lt;0,05) followed by post-hoc tests. All samples showed a normal structure without inflammatory infiltrate. At immunohistochemical analysis, all biomarkers except for OPG had increased. Significant differences were found between the three groups for TNF-α (p&lt; 0,05), IL-6 (p&lt;0,001), RANK (p&lt; 0,01) and RANKL (p&lt;0,001), between groups A and C for IL-6 (p≤ 0,001), RANK (p≤ 0,01), RANKL (p≤ 0,001) and between B and C for IL-6 (p≤ 0,01). Gene expression did not show statistical differences. Crumbles of biomaterial surrounded by regenerated bone were evident. A higher percentage of mineral component was obtained in group B than in C. The biomarkers selected in the current study were involved in the alveolar remodelling and the biomaterial used for socket preservation did not influence the process

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

Histomorphometrical evaluation of cells and tissues in contact with a new anti-wear dental implant surface: Bioloy® coating

Dental implants rehabilitation of edentulous patients is the current accepted treatment to increase prosthetic stabilization. Various implant surface modifications have been tried to enhance osseointegration and to reduce the spread of detrimental metallic ions toward host tissues [1]. The aim of this preliminary study was to investigate in vitro the viability, proliferation and adhesion of a Bioloy® (B®) coating compared to machined and sandblasted surfaces and to assess histologically in vivo the bone response to customized mini-implants coated with B® () placed in the mandible of patients. B® is a titanium niobium nitride coating applied on surface by physical vapor deposition (Permedica Spa). It is a thin ceramic monolayer, extremely hard and with high resistance against wear, scratches and corrosion [2] Viability and adhesion was tested at 24, 48 and 72 hours after seeding of SAOS-2 on customised scaffold. Cell viability (2x104 cells) was evaluated by AlamarBlue® assay [3] and it resulted statistically higher on B® than in the other 2 groups (48 and 72 hours, p-valu

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81&nbsp;years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

New Molecular Mechanisms and Markers in Inflammatory Disorders

Inflammation is the primary response of different disorders, and these encompass a wide range of conditions in various tissues and organs [...

Osteomyelitis, Oxidative Stress and Related Biomarkers

Bone is a very dynamic tissue, subject to continuous renewal to maintain homeostasis through bone remodeling, a process promoted by two cell types: osteoblasts, of mesenchymal derivation, are responsible for the deposition of new material, and osteoclasts, which are hematopoietic cells, responsible for bone resorption. Osteomyelitis (OM) is an invasive infectious process, with several etiological agents, the most common being Staphylococcus aureus, affecting bone or bone marrow, and severely impairing bone homeostasis, resulting in osteolysis. One of the characteristic features of OM is a strong state of oxidative stress (OS) with severe consequences on the delicate balance between osteoblastogenesis and osteoclastogenesis. Here we describe this, analyzing the effects of OS in bone remodeling and discussing the need for new, easy-to-measure and widely available OS biomarkers that will provide valid support in the management of the disease

SCD14-ST and New Generation Inflammatory Biomarkers in the Prediction of COVID-19 Outcome

Since no definitive cure for COVID-19 is available so far, one of the challenges against the disease is understanding the clinical features and the laboratory inflammatory markers that can differentiate among different severity grades of the disease. The aim of the present study is a comprehensive and longitudinal evaluation of SCD14-ST and other new inflammatory markers, as well as cytokine storm molecules and current inflammatory parameters, in order to define a panel of biomarkers that could be useful for a better prognostic prediction of COVID-19 mortality. SCD14-ST, as well as the inflammatory markers IL-6, IL-10, SuPAR and sRAGE, were measured in plasma-EDTA of ICU COVID-19 positive patients. In this longitudinal study, SCD14-ST resulted significantly higher in patients who eventually died compared to those who were discharged from the ICU. The results suggest that the new infection biomarker SCD14-ST, in addition to new generation inflammatory biomarkers, such as SuPAR, sRAGE and the cytokines IL-6 and IL-10, can be a useful prognostic tool associated with canonical inflammatory parameters, such as CRP, to predict SARS-CoV-2 outcome in ICU patients