Redox regulation of cellular stress response in multiple sclerosis

Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease with characteristic foci of inflammatory demyelination in the brain, spinal cord, and optic nerves. Recent studies have demonstrated not only that axonal damage and neuronal loss are significant pathologic components of MS, but that this neuronal damage is thought to cause the permanent neurologic disability often seen in MS patients. Emerging finding suggests that altered redox homeostasis and increased oxidative stress, primarily implicated in the pathogenesis of MS, are a trigger for activation of a brain stress response. Relevant to maintenance of redox homeostasis, integrated mechanisms controlled by vitagenes operate in brain in preserving neuronal survival during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. In the present study we assess stress response mechanisms in the CSF, plasma and lymphocytes of control patients compared to MS patients. We found that the levels of vitagenes Hsp72, Hsc70, HO-1, as well as oxidative stress markers carbonyls and hydroxynonenals were significantly higher in the blood and CSF of MS patients than in control patients. In addition, an increased expression of Trx and sirtuin 1, together with a decrease in the expression of TrxR were observed. Our data strongly support a pivotal role for redox homeostasis disruption in the pathogenesis of MS and, consistently with the notion that new therapies that prevent neurodegeneration through nonimmunomodulatory mechanisms can have a tremendous potential to work synergistically with current MS therapies, unravel important targets for new cytoprotective strategies

Diffuse light and galaxy interactions in the core of nearby clusters

The kinematics of the diffuse light in the densest regions of the nearby clusters can be unmasked using the planetary nebulae (PNs) as probes of the stellar motions. The position-velocity diagrams around the brightest cluster galaxies (BCGs) identify the relative contributions from the outer halos and the intracluster light (ICL), defined as the light radiated by the stars floating in the cluster potential. The kinematics of the ICL can then be used to asses the dynamical status of the nearby cluster cores and to infer their formation histories. The cores of the Virgo and Coma are observed to be far from equilibrium, with mergers currently on-going, while the ICL properties in the Fornax and Hydra clusters show the presence of sub-components being accreted in their cores, but superposed to an otherwise relaxed population of stars. Finally the comparison of the observed ICL properties with those predicted from Lambda-CDM simulations indicates a qualitative agreement and provides insights on the ICL formation. Both observations and simulations indicate that BCG halos and ICL are physically distinct components, with the ``hotter" ICL dominating at large radial distances from the BCGs halos as the latter become progressively fainter.Comment: 14 pages, 5 figures. Invited review to appear in the proceedings of "Galaxies and their masks" eds. Block, D.L., Freeman, K.C. and Puerari, I., 2010, Springer (New York

New Technologies in Endourology and Laser Lithotripsy: The Need for Evidence in Comprehensive Clinical Settings

Flexible ureteroscopy (fURS) with laser lithotripsy is currently the gold standard surgical treatment for ureteral and kidney stones with a maximum diameter of 2 cm [...]

Global Variations in the Mineral Content of Bottled Still and Sparkling Water and a Description of the Possible Impact on Nephrological and Urological Diseases

Kidney stone disease (KSD) is a complex disease. Besides the high risk of recurrence, its association with systemic disorders contributes to the burden of disease. Sufficient water intake is crucial for prevention of KSD, however, the mineral content of water might influence stone formation, bone health and cardiovascular (CVD) risk. This study aims to analyse the variations in mineral content of bottled drinking water worldwide to evaluate the differences and describes the possible impact on nephrological and urological diseases. The information regarding mineral composition (mg/L) on calcium, bicarbonate, magnesium, sodium and sulphates was read from the ingredients label on water bottles by visiting the supermarket or consulting the online shop. The bottled waters in two main supermarkets in 21 countries were included. The evaluation shows that on a global level the mineral composition of bottled drinkable water varies enormously. Median bicarbonate levels varied by factors of 12.6 and 57.3 for still and sparkling water, respectively. Median calcium levels varied by factors of 18.7 and 7.4 for still and sparkling water, respectively. As the mineral content of bottled drinking water varies enormously worldwide and mineral intake through water might influence stone formation, bone health and CVD risk, urologists and nephrologists should counsel their patients on an individual level regarding water intake

Global Variations in the Mineral Content of Bottled Still and Sparkling Water and a Description of the Possible Impact on Nephrological and Urological Diseases

Kidney stone disease (KSD) is a complex disease. Besides the high risk of recurrence, its association with systemic disorders contributes to the burden of disease. Sufficient water intake is crucial for prevention of KSD, however, the mineral content of water might influence stone formation, bone health and cardiovascular (CVD) risk. This study aims to analyse the variations in mineral content of bottled drinking water worldwide to evaluate the differences and describes the possible impact on nephrological and urological diseases. The information regarding mineral composition (mg/L) on calcium, bicarbonate, magnesium, sodium and sulphates was read from the ingredients label on water bottles by visiting the supermarket or consulting the online shop. The bottled waters in two main supermarkets in 21 countries were included. The evaluation shows that on a global level the mineral composition of bottled drinkable water varies enormously. Median bicarbonate levels varied by factors of 12.6 and 57.3 for still and sparkling water, respectively. Median calcium levels varied by factors of 18.7 and 7.4 for still and sparkling water, respectively. As the mineral content of bottled drinking water varies enormously worldwide and mineral intake through water might influence stone formation, bone health and CVD risk, urologists and nephrologists should counsel their patients on an individual level regarding water intake

Short-Term Striatal Gene Expression Responses to Brain-Derived Neurotrophic Factor Are Dependent on MEK and ERK Activation

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is believed to be an important regulator of striatal neuron survival, differentiation, and plasticity. Moreover, reduction of BDNF delivery to the striatum has been implicated in the pathophysiology of Huntington's disease. Nevertheless, many essential aspects of BDNF responses in striatal neurons remain to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we assessed the relative contributions of multipartite intracellular signaling pathways to the short-term induction of striatal gene expression by BDNF. To identify genes regulated by BDNF in these GABAergic cells, we first used DNA microarrays to quantify their transcriptomic responses following 3 h of BDNF exposure. The signal transduction pathways underlying gene induction were subsequently dissected using pharmacological agents and quantitative real-time PCR. Gene expression responses to BDNF were abolished by inhibitors of TrkB (K252a) and calcium (chelator BAPTA-AM and transient receptor potential cation channel [TRPC] antagonist SKF-96365). Interestingly, inhibitors of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2) and extracellular signal-regulated kinase ERK also blocked the BDNF-mediated induction of all tested BDNF-responsive genes. In contrast, inhibitors of nitric oxide synthase (NOS), phosphotidylinositol-3-kinase (PI3K), and CAMK exhibited less prevalent, gene-specific effects on BDNF-induced RNA expression. At the nuclear level, the activation of both Elk-1 and CREB showed MEK dependence. Importantly, MEK-dependent activation of transcription was shown to be required for BDNF-induced striatal neurite outgrowth, providing evidence for its contribution to striatal neuron plasticity. CONCLUSIONS: These results show that the MEK/ERK pathway is a major mediator of neuronal plasticity and other important BDNF-dependent striatal functions that are fulfilled through the positive regulation of gene expression

Optimization of the Zr-loading on siliceous support catalysts leads to a suitable Lewis/Bronsted acid sites ratio to produce high yields to gamma-valerolactone from furfural in one-pot

The study for the production of gamma-valerolactone from furfural in one-pot has been carried out using ZrO2 supported on silica spheres. The catalysts synthesized were characterized by XRD, UV-vis, HR-TEM, N-2 adsorption, IR, pyridine adsorption-IR and NH3-TPD in order to determine their physicochemical characteristics. Both, Lewis and Bronsted acid sites are necessary to produce gamma-valerolactone from furfural, because they are involved in different steps of the reaction. Accordingly, a reaction mechanism has been proposed. Lewis acid sites of ZrO2 interacting with the -OH surface groups of the siliceous spheres can generate Bronsted acid sites in the supported Zr catalysts, which are absent in both pure ZrO2 and the silica spheres. Then, by controlling the amount of Zr in the supported catalysts, the relative amount of Lewis and Bronsted acid sites can be optimized to obtain the highest yields to gamma-valerolactone. The Zr-loading of the optimal supported catalyst was ca. 7 wt% Zr, which reached a gamma-valerolactone yield of 72.4 % after 8 h at 180 C using 2-propanol as a solvent and hydrogen donor