Impact of the L-arginine-Nitric Oxide Pathway and Oxidative Stress on the Pathogenesis of the Metabolic Syndrome

The discovery of the physiological roles of nitric oxide has revolutionized the understanding of regulation of vascular tone, platelet adhesion and aggregation, and immune activation. Perhaps the most intriguing aspect of nitric oxide (NO) is that it is a gas that, in the absence of receptors, can regulate both normal physiological events and mediate cytotoxicity under pathological conditions. NO is produced from L-arginine by NO synthases (NOS), yielding L-citrulline and NO. The regulation of L-arginine pathway activity occurs at the level of NO production. The metabolic syndrome is a cluster of insulin resistance, elevated blood pressure, and atherogenic dyslipidemia, a common basis of cardiovascular disease. It occurs in genetically susceptible individuals with environmental influences and has serious economic and social consequences. Pharmacological and non-pharmacological therapies should be individualized and targeted to normalize its alterations of blood pressure, HDL cholesterol, triglycerides and glucose values. Despite the increasing prevalence of the metabolic syndrome in the last decades, there has been little progress in the understanding of the precise mechanisms involved in the pathogenesis of this syndrome and its complications. Emerging evidence is available that NO, inflammation and oxidative stress play important roles in the physiopathology of this syndrome. This review summarizes and evaluates the participation of the L-arginine-NO pathway and oxidative stress in the physiopathology of the metabolic syndrome and cardiovascular events at the systemic level, as well as the effects of exercise on this syndrome

The DNA damage response is developmentally regulated in the African trypanosome

Genomes are affected by a wide range of damage, which has resulted in the evolution of a number of widely conserved DNA repair pathways. Most of these repair reactions have been described in the African trypanosome Trypanosoma brucei, which is a genetically tractable eukaryotic microbe and important human and animal parasite, but little work has considered how the DNA damage response operates throughout the T. brucei life cycle. Using quantitative PCR we have assessed damage induction and repair in both the nuclear and mitochondrial genomes of the parasite. We show differing kinetics of repair for three forms of DNA damage, and dramatic differences in repair between replicative life cycle forms found in the testse fly midgut and the mammal. We find that mammal-infective T. brucei cells repair oxidative and crosslink-induced DNA damage more efficiently than tsetse-infective cells and, moreover, very distinct patterns of induction and repair of DNA alkylating damage in the two life cycle forms. We also reveal robust repair of DNA lesions in the highly unusual T. brucei mitochondrial genome (the kinetoplast). By examining mutants we show that nuclear alkylation damage is repaired by the concerted action of two repair pathways, and that Rad51 acts in kinetoplast repair. Finally, we correlate repair with cell cycle arrest and cell growth, revealing that induced DNA damage has strikingly differing effects on the two life cycle stages, with distinct timing of alkylation-induced cell cycle arrest and higher levels of damage induced death in mammal-infective cells. Our data reveal that T. brucei regulates the DNA damage response during its life cycle, a capacity that may be shared by many microbial pathogens that exist in variant environments during growth and transmission

Running coupling constant and propagators in SU(2) Landau gauge

We present a numerical study of the running coupling constant and of the gluon and ghost propagators in minimal Landau gauge. Simulations are done in pure SU(2) lattice gauge theory for several values of beta and lattice sizes. We use two different lattice setups.Comment: 3 pages and 5 figures; talk presented by A. Cucchieri at Lattice2002(topology), Cambridge MA, USA, June 24-29, 2002 Minor typos correcte

New bounds for Tsallis parameter in a noncommutative phase-space entropic gravity and nonextensive Friedmann equations

In this paper, we have analyzed the nonextensive Tsallis statistical mechanics in the light of Verlinde's formalism. We have obtained, with the aid of a noncommutative phase-space entropic gravity, a new bound for Tsallis nonextensive (NE) parameter (TNP) that is clearly different from the ones present in the current literature. We derived the Friedmann equations in a NE scenario. We also obtained here a relation between the gravitational constant and the TNP.Comment: 15 pages. Final version to appear in Physica

Experimental periodontitis promotes transient vascular inflammation and endothelial dysfunction

AbstractObjectivesThis study aimed to evaluate the systemic inflammatory response and cardiovascular changes induced by experimental periodontitis in rats.DesignExperimental periodontitis was induced by placing a cotton ligature around the cervix of both sides of mandibular first molars and maxillary second molars in each male rat. Sham-operated rats had the ligature removed immediately after the procedure. Seven, 14 or 28 days after procedure, the effects of acetylcholine, sodium nitroprusside and phenylephrine were evaluated on blood pressure, aortic rings and isolated and perfused mesenteric bed. The blood was obtained for plasma Interleukin-6 (IL-6), C-reactive protein (CRP) and lipid evaluation. The mesenteric vessels were obtained to evaluate superoxide production and nitric oxide synthase 3 (NOS-3) expression.ResultsLigature induced periodontitis reduced endothelium-dependent vasodilatation, a hallmark of endothelial dysfunction. This effect was associated with an increase in systemic inflammatory markers (IL-6 and CRP), worsens on lipid profile, increased vascular superoxide production and reduced NOS-3 expression. It is interesting to note that many of these effects were transitory.ConclusionPeriodontitis induced a transient systemic and vascular inflammation which leads to endothelial dysfunction, an initial step for cardiovascular diseases. Moreover, the animal model of periodontitis used here may represent a valuable tool for studying the relationship between periodontitis and endothelial dysfunction

The initial months of antiretroviral therapy and its influence on AGEs, HMGB1, and sRAGE levels in asymptomatic HIV-infected individuals

The development of the typical comorbidities of aging which currently affects people living with HIV/AIDS (PLWHA) can be partially ascribed to the persistent immune activation and chronic inflammation characterizing these individuals. The aim of this study was to analyze the effect exerted by combined antiretroviral therapy (cART) administration on plasma levels of HMGB1 (high mobility group box protein-1), AGEs (advanced glycation end products), their soluble receptor sRAGE, cytokines, C-reactive protein (CRP), and some metabolic markers in asymptomatic PLWHA. Analyses were performed longitudinally in 30 PLWHA, before and about 6\u201312 months after cART initiation. We observed that lower levels of AGEs in post-cART group were accompanied by an increase of CRP and triglyceride levels already in the early months of therapy. Because of the current ever-earlier recommendations to start cART and its prolonged use, these and other markers should be investigated in order to monitor and postpone the appearance of non-AIDS comorbidities in PLWHA

Recent results on multiplicative noise

Recent developments in the analysis of Langevin equations with multiplicative noise (MN) are reported. In particular, we: (i) present numerical simulations in three dimensions showing that the MN equation exhibits, like the Kardar-Parisi-Zhang (KPZ) equation both a weak coupling fixed point and a strong coupling phase, supporting the proposed relation between MN and KPZ; (ii) present dimensional, and mean field analysis of the MN equation to compute critical exponents; (iii) show that the phenomenon of the noise induced ordering transition associated with the MN equation appears only in the Stratonovich representation and not in the Ito one, and (iv) report the presence of a new first-order like phase transition at zero spatial coupling, supporting the fact that this is the minimum model for noise induced ordering transitions.Comment: Some improvements respect to the first versio

Accelerated forgetting of real-life events in Transient Epileptic Amnesia.

addresses: Cognitive and Behavioural Neurology, Peninsula Medical School, University of Exeter, Exeter, UK.types: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2010 Elsevier. NOTICE: This is the author’s version of a work accepted for publication by Elsevier. Changes resulting from the publishing process, including peer review, editing, corrections, structural formatting and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuropsychologia, 2010, Vol. 48, Issue 11, pp. 3235 – 3244 DOI: http://dx.doi.org/10.1016/j.neuropsychologia.2010.07.001Transient Epileptic Amnesia (TEA) is a form of temporal lobe epilepsy associated with ictal and interictal memory disturbance. Some patients with TEA exhibit Accelerated Long-term Forgetting (ALF), in which memory for verbal and non-verbal material is retained normally over short delays but fades at an unusually rapid rate over days to weeks. This study addresses three questions about ALF in TEA: (i) whether real-life events undergo ALF in a similar fashion to laboratory-based stimuli; (ii) whether ALF can be detected within 24h; (iii) whether procedural memories are susceptible to ALF. Eleven patients with TEA and eleven matched healthy controls wore a novel, automatic camera, SenseCam, while visiting a local attraction. Memory for images of events was assessed on the same day and after delays of one day, one week, and three weeks. Forgetting of real-life events was compared with forgetting of a word list and with performance on a procedural memory task. On the day of their excursion, patients and controls recalled similar numbers of primary events, associated secondary details (contiguous events, thoughts and sensory information) and items from the word list. In contrast, patients showed ALF for primary events over three weeks, with ALF for contiguous events, thoughts and words over the first day. Retention on the procedural memory task was normal over three weeks. The results indicate that accelerated forgetting in TEA: (i) affects memory for real-life events as well as laboratory stimuli; (ii) is maximal over the first day; and (iii) is specific to declarative memories

Validation of standard and alternative satellite ocean-color chlorophyll products off Western Iberia

Chlorophyll a concentration (Chl) product validation off theWestern Iberian coast is here undertaken by directly comparing remote sensing data with in situ surface reference values. Both standard and recently developed alternative algorithms are considered for match-up data analysis. The investigated standard products are those produced by the MERIS (algal 1 and algal 2) and MODIS (OC3M) algorithms. The alternative data products include those generatedwithin the CoastColour Project and Ocean Color Climate Change Initiative (OC-CCI) funded by ESA, as well as a neural net model trained with field measurements collected in the Atlantic off Portugal (MLPATLP). Statistical analyses showed that satellite Chl estimates tend to be larger than in situ reference values. The study also revealed that a non-uniform Chl distribution in the water column can be a concurring factor to the documented overestimation tendency when considering larger optical depth match-up stations. Among standard remote sensing products, MODIS OC3M and MERIS algal 2 yield the best agreement with in situ data. The performance of MLPATLP highlights the capability of regional solutions to further improve Chl retrieval by accounting for environmental specificities. Results also demonstrate the relevance of oceanographic regions such as the Nazaré area to evaluate how complex hydrodynamic conditions can influence the quality of Chl products.This studywas performed in the framework of HabSpot FCT Project, PTDC/MAR/100348/2008 and European Space Agency projects DUE CoastColour (ESRIN/AO/1-6141/09/l-EC) and Climate Change Iniciative — Ocean Color (AO-1/6207/09/I-LG). The work has been also partially supported by the European Space Agency within the framework of the MERIS Validation Activities under contract n. 12595/09/I-OL, and sampling activities benefited from European projects HERMES (GOCE-CT-2005-511234) and Hermione (EC contract 226354) support. We would like to thank NASA OBPG for the MODIS data and ESA Project AOPT-2423 for providing MERIS full resolution images. Ana C. Brito was funded by a Portuguese Post-doc grant from FCT (BPD/63017/2009) and by the Investigador FCT Program (IF/00331/2013). Davide D'Alimonte was funded by Investigador FCT Program (IF/00541/2013).info:eu-repo/semantics/publishedVersio

Planck 2015 results. XXVII. The Second Planck Catalogue of Sunyaev-Zeldovich Sources

We present the all-sky Planck catalogue of Sunyaev-Zeldovich (SZ) sources detected from the 29 month full-mission data. The catalogue (PSZ2) is the largest SZ-selected sample of galaxy clusters yet produced and the deepest all-sky catalogue of galaxy clusters. It contains 1653 detections, of which 1203 are confirmed clusters with identified counterparts in external data-sets, and is the first SZ-selected cluster survey containing > $10^3$ confirmed clusters. We present a detailed analysis of the survey selection function in terms of its completeness and statistical reliability, placing a lower limit of 83% on the purity. Using simulations, we find that the Y5R500 estimates are robust to pressure-profile variation and beam systematics, but accurate conversion to Y500 requires. the use of prior information on the cluster extent. We describe the multi-wavelength search for counterparts in ancillary data, which makes use of radio, microwave, infra-red, optical and X-ray data-sets, and which places emphasis on the robustness of the counterpart match. We discuss the physical properties of the new sample and identify a population of low-redshift X-ray under- luminous clusters revealed by SZ selection. These objects appear in optical and SZ surveys with consistent properties for their mass, but are almost absent from ROSAT X-ray selected samples