Acute effects of hypouricemia on endothelium, oxidative stress, and arterial stiffness: A randomized, double-blind, crossover study.

We hypothesized acute moderate and drastic reductions in uric acid concentration exert different effects on arterial function in healthy normotensive and hypertensive adults. Thirty-six adults (aged 58 [55;63] years) with or without primary hypertension participated in a three-way, randomized, double-blind, crossover study in which [placebo] and [febuxostat] and [febuxostat and rasburicase] were administered. Febuxostat and rasburicase reduce the uric acid concentration by xanthine oxidoreductase inhibition and uric acid degradation into allantoin, respectively.

Severe Hypouricemia Impairs Endothelium-Dependent Vasodilatation and Reduces Blood Pressure in Healthy Young Men: A Randomized, Placebo-Controlled, and Crossover Study.

Background Uric acid (UA) is a plasmatic antioxidant that has possible effects on blood pressure. The effects of UA on endothelial function are unclear. We hypothesize that endothelial function is not impaired unless significant UA depletion is achieved through selective xanthine oxidase inhibition with febuxostat and recombinant uricase (rasburicase).

Multimodal imaging Gd-nanoparticles functionalized with Pittsburgh compound B or a nanobody for amyloid plaques targeting.

Aim: Gadolinium-based nanoparticles were functionalized with either the Pittsburgh compound B or a nanobody (B10AP) in order to create multimodal tools for an early diagnosis of amyloidoses.

Materials & Methods: The ability of the functionalized nanoparticles to target amyloid fibrils made of β-amyloid peptide, amylin or Val30Met-mutated transthyretin formed in vitro or from pathological tissues was investigated by a range of spectroscopic and biophysics techniques including fluorescence microscopy.

Results: Nanoparticles functionalized by both probes efficiently interacted with the three types of amyloid fibrils, with K values in 10 micromolar and 10 nanomolar range for, respectively, Pittsburgh compound B and B10AP nanoparticles.

Prevalence of non-infectious comorbidities in the HIV-positive population in Belgium: a multicenter, retrospective study.

Objectives: In Belgium, eleven AIDS Reference Centers (ARCs) and seven AIDS Reference Laboratories diagnose and treat HIV-positive individuals and track patients under care. As AIDS-related deaths are avoided and the HIV-positive population ages, non-infectious comorbidities (NICMs), such as cardiovascular disease, renal disease and certain cancers, play a larger role in the quality and length of patients' lives. This study aims to characterize the HIV-positive population in Belgium in terms of the prevalence of key NICMs.

Gd-nanoparticles functionalization with specific peptides for ß-amyloid plaques targeting.

Background: Amyloidoses are characterized by the extracellular deposition of insoluble fibrillar proteinaceous aggregates highly organized into cross-β structure and referred to as amyloid fibrils. Nowadays, the diagnosis of these diseases remains tedious and involves multiple examinations while an early and accurate protein typing is crucial for the patients' treatment. Routinely used neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) using Pittsburgh compound B, [(11)C]PIB, provide structural information and allow to assess the amyloid burden, respectively, but cannot discriminate between different amyloid deposits.

An immunological method to combine the measurement of active and total myeloperoxidase on the same biological fluid, and its application in finding inhibitors which interact directly with the enzyme.

Myeloperoxidase (MPO) is a pro-oxidant enzyme involved in inflammation, and the measurement of its activity in biological samples has emerged essential for laboratory and clinical investigations. We will describe a new method which combines the SIEFED (specific immunological extraction followed by enzymatic detection) and ELISA (ELISAcb) techniques to measure the active and total amounts of MPO on the same human sample and with the same calibration curve, as well as to define an accurate ratio between both the active and total forms of the enzyme. The SIEFED/ELISAcb method consists of the MPO extraction from aqueous or biological samples by immobilized anti-MPO antibodies coated onto microplate wells.

A role for APPL1 in TLR3/4-dependent TBK1 and IKKε activation in macrophages.

Endosomes have important roles in intracellular signal transduction as a sorting platform. Signaling cascades from TLR engagement to IRF3-dependent gene transcription rely on endosomes, yet the proteins that specifically recruit IRF3-activating molecules to them are poorly defined. We show that adaptor protein containing a pleckstrin-homology domain, a phosphotyrosine-binding domain, and a leucine zipper motif (APPL)1, an early endosomal protein, is required for both TRIF- and retinoic acid-inducible gene 1-dependent signaling cascades to induce IRF3 activation.

Nuclear and mitochondrial genetic structure in the Eurasian beaver (Castor fiber) - implications for future reintroductions.

Many reintroduction projects for conservation fail, and there are a large number of factors that may contribute to failure. Genetic analysis can be used to help stack the odds of a reintroduction in favour of success, by conducting assessment of source populations to evaluate the possibility of inbreeding and outbreeding depression and by conducting postrelease monitoring. In this study, we use a panel of 306 SNP (single nucleotide polymorphism) markers and 487-489 base pairs of mitochondrial DNA control region sequence data to examine 321 individuals from possible source populations of the Eurasian beaver for a reintroduction to Scotland.

A new role for histone deacetylase 5 in the maintenance of long telomeres.

Telomeres are major regulators of genome stability and cell proliferation. A detailed understanding of the mechanisms involved in their maintenance is of foremost importance. Of those, telomere chromatin remodeling is probably the least studied; thus, we intended to explore the role of a specific histone deacetylase on telomere maintenance.

Effects of light on cognitive brain responses depend on circadian phase and sleep homeostasis.

Light is a powerful modulator of cognition through its long-term effects on circadian rhythmicity and direct effects on brain function as identified by neuroimaging. How the direct impact of light on brain function varies with wavelength of light, circadian phase, and sleep homeostasis, and how this differs between individuals, is a largely unexplored area. Using functional MRI, we compared the effects of 1 minute of low-intensity blue (473 nm) and green light (527 nm) exposures on brain responses to an auditory working memory task while varying circadian phase and status of the sleep homeostat.

Exforge (amlodipine/valsartan combination) in hypertension: the evidence of its therapeutic impact.

Introduction: Hypertension is an important risk factor for cardiovascular disease and its management requires improvement. New treatment strategies are needed.

Aims: This review analyses one of these strategies, which is the development of effective and safe combination therapy.

Some facts about sleep relevant for Landau-Kleffner syndrome.

Our understanding of the neural mechanisms of non-rapid eye movement sleep (NREM) is steadily increasing. Given the intriguing activation of paroxysmal activity during NREM sleep in patients with Landau-Kleffner syndrome (LKS), a thorough characterization of commonalities and differences between the neural correlates of LKS paroxysms and normal sleep oscillations might provide useful information on the neural underpinning of this disorder. Especially, given the suspected role of sleep in brain plasticity, this type of information is needed to assess the link between cognitive deterioration and electroencephalography (EEG) paroxysms during sleep.

Synthesis of eight- and star-shaped poly(epsilon-caprolactone)s and their amphiphilic derivatives.

Spirocyclic tin dialkoxides are unique initiators for the ring-expansion polymerization of lactones leading to complex, but well-defined macromolecular architectures. In a first example, epsilon-caprolactone (epsilon CL) was polymerized, followed by the resumption of polymerization of a mixture of epsilon CL and epsilon CL alpha-substituted by a chloride (alpha Cl epsilon CL), so leading to "living" eight-shaped chains. Upon hydrolysis of the alkoxides, a four-arm star-shaped copolyester was formed, whose each arm was grafted by conversion of the chloride units into azides, followed by the Huisgen's [3+2] cycloaddition of alkyne end-capped poly(ethylene oxide) (PEO) onto the azide substituents.

Inhibitory effect of curcuminoids and tetrahydrocurcuminoids on equine activated neutrophils and myeloperoxidase activity.

In the horse, the inflammation response to various pathologies (intestinal strangulations, laminitis, etc.) involves an excessive stimulation of the polymorphonuclear neutrophils releasing reactive oxygen species (ROS) and myeloperoxidase (MPO). The aim of the present work was to study the effect of natural polyphenols, curcuminoids and tetrahydrocurcuminoids (THC) on isolated stimulated equine neutrophils and on the activity of purified MPO.

Neuroimaging in sleep medicine.

The development of neuroimaging techniques has made possible the characterization of cerebral function throughout the sleep-wake cycle in normal human subjects. Indeed, human brain activity during sleep is segregated within specific cortical and subcortical areas in relation to the sleep stage, sleep physiological events and previous waking activity. This approach has allowed sleep physiological theories developed from animal data to be confirmed, but has also introduced original concepts about the neurobiological mechanisms of sleep, dreams and memory in humans.

Implicit oculomotor sequence learning in humans: Time course of offline processing.

Studies of manual and digital sequence learning indicate that motor memories continue to be processed after training has ended, following a succession of identifiable steps. However, it is not known whether this offline memory processing constitutes a basic feature of motor learning and generalizes to the implicit learning of a sequence of eye movements. To assess this hypothesis, we have created the serial oculomotor reaction time task (SORT).

Structure and energetics of two- and three-dimensional neutral, cationic, and anionic gold clusters Au(5< or = n < or =9)Z (Z=0,+/-1).

Low-energy structures are found on the potential energy surfaces of the neutral, cationic, and anionic gold clusters Au(5< or = n < or =9)Z (Z=0,+/-1) and on the neutral potential energy surface of Au(9). These structures provide insights on the two to three dimensional (2D-->3D) transition in small neutral and charged gold clusters. It is demonstrated that the size threshold for the 2D-3D coexistence is lower for cationic than neutral gold clusters: the 2D-3D coexistence develops for Au(5) (+) and Au(7) (+) on the cationic potential energy surfaces while only for Au(9) on the neutral.

Cuttings of the non-rooting rac tobacco mutant overaccumulate phenolic compounds.

The auxin and phenolic contents, as well as phenylalanine ammonia-lyase (PAL) activity, were determined in in vitro cultured shoots of the recalcitrant-to-root rac mutant of tobacco, and compared with wild-type shoots. The mutant and wild-type shoots showed similar auxin changes during the culture cycle, but with higher contents for the mutant. A transient peak of auxin (corresponding to the achievement of the rooting inductive phase) occurred at day 14 in both types of shoots, but earlier in the basal parts of the wild-type stems.

Core-Shell-Corona Micelles with a Responsive Shell.

A reactor for the synthesis of gold nanoparticles is one of the uses of a poly(styrene)-block-poly(2-vinylpyridine)-block-poly(ethylene oxide) triblock copolymer (PS-b-P2VP-b-PEO) which forms core-shell-corona micelles in water. Very low polydispersity spherical micelles are observed that consist of a PS core surrounded by a pH-sensitive P2VP shell and a corona of PEO chains end-capped by a hydroxyl group. The corona can act as a site for attaching responsive or sensing molecules.

Inhibitory effect of oxytocin on corticotrope function in humans: are vasopressin and oxytocin ying-yang neurohormones?

Oxytocin (OT) and vasopressin (VP) are very similar neurohypophyseal peptides. While VP is known as an ACTH stimulating factor synergistic to CRF since two decades, the inhibiting activity of OT, first demonstrated in the human, is now confirmed in various species including mouse and rat!It is likely that endogenous oxytocinergic system which can be activated by physiological and/or pharmacological manipulation can "buffer" the stress activated vasopressin-ACTH-cortisol action. Since VP and OT share also opposite action on cognitive function, those two "sister" neuropeptides might be considered as "ago-antagonist" or "ying-yang" neurohormones!

CBP and histone deacetylase inhibition enhance the transactivation potential of the HOXB7 homeodomain-containing protein.

Homeodomain-containing proteins are transcription factors regulating the coordinated expression of multiple target genes involved in development, differentiation and cellular transformation. In this study, we demonstrated that HOXB7, one member of this family, behaved as a transactivator in breast cancer cells. Deletion of either the HOXB7 N-terminal domain or the C-terminal acidic tail abolished this transcriptional effect, suggesting a combination of distinct functional transactivating domains.

Cytological comparison of leaves and stems of Prunus avium L. shoots cultured on a solid medium with agar or gelrite.

An axillary proliferating clone of Prunus avium L. was subcultured every four weeks on solid MS medium with agar as the gelling agent. Vitrification (hyperhydricity) of shoots was induced in one four week cycle with the same medium except that agar was replaced by gelrite.

Multiple ways to cellular immune tolerance.

Both central and peripheral pathways leading to T-cell tolerance were discussed at a recent meeting. The mechanisms that maintain self tolerance, as well as the conditions in which self-reactive T cells launch an autoaggressive attack, were specially emphasized.