Extracellular Nucleotides Regulate Arterial Calcification by Activating Both Independent and Dependent Purinergic Receptor Signaling Pathways

Arterial calcification, the deposition of calcium-phosphate crystals in the extracellular matrix, resembles physiological bone mineralization. It is well-known that extracellular nucleotides regulate bone homeostasis raising an emerging interest in the role of these molecules on arterial calcification. The purinergic independent pathway involves the enzymes ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs), ecto-nucleoside triphosphate diphosphohydrolases (NTPDases), 5′-nucleotidase and alkaline phosphatase. These regulate the production and breakdown of the calcification inhibitor—pyrophosphate and the calcification stimulator—inorganic phosphate, from extracellular nucleotides. Maintaining ecto-nucleotidase activities in a well-defined range is indispensable as enzymatic hyper- and hypo-expression has been linked to arterial calcification. The purinergic signaling dependent pathway focusses on the activation of purinergic receptors (P1, P2X and P2Y) by extracellular nucleotides. These receptors influence arterial calcification by interfering with the key molecular mechanisms underlying this pathology, including the osteogenic switch and apoptosis of vascular cells and possibly, by favoring the phenotypic switch of vascular cells towards an adipogenic phenotype, a recent, novel hypothesis explaining the systemic prevention of arterial calcification. Selective compounds influencing the activity of ecto-nucleotidases and purinergic receptors, have recently been developed to treat arterial calcification. However, adverse side-effects on bone mineralization are possible as these compounds reasonably could interfere with physiological bone mineralization

Management of hyperphosphatemia in patients with end-stage renal disease: focus on lanthanum carbonate

Elevated serum phosphate levels as a consequence of chronic kidney disease (CKD) contribute to the increased cardiovascular risk observed in dialysis patients. Protein restriction and dialysis fail to adequately prevent hyperphosphatemia, and in general treatment with oral phosphate binding agents is necessary in patients with advanced CKD. Phosphate plays a pivotal role in the development of vascular calcification, one of the factors contributing to increased cardiovascular risk in CKD patients. Treatment of hyperphosphatemia with standard calcium-based phosphate binders and vitamin D compounds can induce hypercalcemic episodes, increase the Ca × PO4 product and thus add to the risk of ectopic mineralization. In this review, recent clinical as well as experimental data on lanthanum carbonate, a novel, non-calcium, non-resin phosphate binding agent are summarized. Although lanthanum is a metal cation no aluminium-like toxicity is observed since the bioavailability of lanthanum is extremely low and its metabolism differs from that of aluminium. Clinical studies now document the absence of toxic effects of lanthanum for up to 6 years of follow-up. The effects of lanthanum on bone, vasculature and brain are discussed and put in perspective with lanthanum pharmacokinetics

Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures

The basic mechanisms by which strontium ranelate acts on bone are still unclear. We show that an important action of strontium salts is to block calcification in cultures of osteoblasts, the bone-forming cells. These results suggest that strontium treatment could have previously overlooked effects on bone

Potential release of aluminum and other metals by food-grade aluminum foil used for skin allograft cryo preservation

Since 1991, the skin bank of the Queen Astrid Military Hospital uses food-grade aluminum foil as a primary support for storing cryo preserved human donor skin (511 donors). The possible release of heavy metals into the cryo preservation media (30% (v/v) glycerol in physiological water) and the possible impact this release could have on the quality of the cryo preserved donor skin was evaluated. Aluminum was the principal detection target. Possible contaminants of the aluminum foil as such (arsenic, cadmium, chromium and lead) were also investigated. The evaluation was set up after a Belgian Competent Authority inspection remark. Aluminum was detected at a concentration of 1.4 mg/l, arsenic and lead were not detected, while cadmium and chromium were detected in trace element quantities. An histological analysis revealed no differences between cryo preserved and fresh donor skin. No adverse reactions in patients, related to the presence of aluminum or heavy metal traces, were reported since the introduction of the cryo preserved donor skin in our burn wound centre

Diversity of Phylogenetic Information According to the Locus and the Taxonomic Level: An Example from a Parasitic Mesostigmatid Mite Genus

Molecular markers for cladistic analyses may perform differently according to the taxonomic group considered and the historical level under investigation. Here we evaluate the phylogenetic potential of five different markers for resolving evolutionary relationships within the ectoparasitic genus Dermanyssus at the species level, and their ability to address questions about the evolution of specialization. COI provided 9–18% divergence between species (up to 9% within species), 16S rRNA 10–16% (up to 4% within species), ITS1 and 2 2–9% (up to 1% within species) and Tropomyosin intron n 8–20% (up to 6% within species). EF-1α revealed different non-orthologous copies within individuals of Dermanyssus and Ornithonyssus. Tropomyosin intron n was shown containing consistent phylogenetic signal at the specific level within Dermanyssus and represents a promising marker for future prospects in phylogenetics of Acari. Phylogenetic analyses revealed that the generalist condition is apomorphic and D. gallinae might represent a complex of hybridized lineages. The split into hirsutus-group and gallinae-group in Dermanyssus does not seem to be appropriate based upon these results and D. longipes appears to be composed of two different entities

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when “at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication.” The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist

A cross-sectional study examining predictors of visit frequency to local green space and the impact this has on physical activity levels

Background Lack of physical activity (PA) is a growing public health concern. There is a growing body of literature that suggests a positive relationship may exist between the amount of local green space near one?s home and PA levels. For instance, park proximity has been shown to predict PA levels amongst certain populations. However, there is little evidence for the role of relatedness towards nature and perceptions of local green space on this relationship. The aim of this study was to examine, in a National UK sample, whether subjective indices associated with local green space were better predictors of visit frequency to local green space and PA levels compared to objectively measured quantity of local green space. Methods A cross-sectional survey was designed. From a random sample, 2079 working age adults responded to an online survey in September 2011. Demographics, self-reported PA, objective measures of the local environment (including local green space, road coverage, and environmental deprivation), were assessed in conjunction with perceptions of local green space and nature relatedness. Quantity of local green space was assessed by cross-referencing respondents? home postcodes with general land use databases. Regression models were conducted to assess which of our independent variables best predicted visit frequency to local green space and/or meeting PA guidelines. In addition, an ordinal regression was run to examine the relationship between visit frequency to local green space and the likelihood of meeting national PA guidelines. Results Nature relatedness was the strongest predictor for both visit frequency to local green space and meeting PA guidelines. Results show that perceived quality is a better predictor of visit frequency to local green space than objective quantity of local green space. The odds of achieving the recommended amount of PA was over four times greater for people who visited local green space once per week compared to never going (OR 4.151; 95 % CI, 2.40 to 7.17). Conclusions These results suggest that perceptions of local green space and nature relatedness play an important role in the relationship between local green space and PA. Considering the known health benefits of PA, our results are potentially important for public health interventions, policy making and environmental planning