5,082 research outputs found
Biosynthesis of H2S is impaired in non-obese diabetic (NOD) mice
Hydrogen sulphide (H2S) has been involved in cardiovascular homoeostasis but data about its role in animal models of diabetic pathology are still lacking. Here, we have analysed H2S signalling in a genetic model of diabetes, the non-obese diabetic (NOD) mice.
NOD mice exhibit a progressive endothelial dysfunction characterized by a reduced reactivity of blood vessels as diabetes develops. NOD mice were divided into three groups according to different glycosuria values: NOD I, NOD II and NOD III. Age-matched non-obese resistant (NOR) mice were used as controls. H(2)S levels in plasma and aortic tissue were measured. Functional studies in aorta were carried out in isolated organ baths using both an exogenous source of H2S (NaHS) and the metabolic precursor (L-cysteine). Real time PCR and western blot analysis were also carried out on aortic tissues.
NOD mice exhibited a progressive reduction of H2S plasma levels, which paralleled disease severity. L-cysteine-induced H2S production by aortic tissues was also progressively reduced. L-cysteine-induced vasorelaxation was significantly reduced in NOD mice while NaHS-induced relaxation was unaffected. ODQ (guanylate cyclase inhibitor), L-NAME (NO synthase inhibitor) or PAG, an inhibitor of cystathionine-gamma-lyase (CSE) inhibited H2S production induced by L-cysteine.
In NOD mice, endogenous H2S production is significantly impaired. Also, the ability of isolated aorta to respond to exogenous H2S is enhanced and endothelium-derived NO appears to be involved in the enzymatic conversion of L-cysteine into H2S
Sphingosine-1-phosphate modulates vascular permeability and cell recruitment inacute inflammation in vivo.
The sphingosine kinase (SPK)/sphingosine-1-phosphate (S1P) pathway recently has been associated with a variety of inflammatory-based diseases. The majority of these studies have been performed in vitro. Here, we have addressed the relevance of the SPK/S1P pathway in the acute inflammatory response in vivo by using different well known preclinical animal models. The study has been performed by operating a pharmacological modulation using 1) L-cycloserine and DL-threo-dihydrosphingosine (DTD), S1P synthesis inhibitors or 2) 2-undecyl-thiazolidine-4-carboxylic acid (BML-241) and N-(2,6-dichloro-4-pyridinyl)-2-[1,3-dimethyl-4-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-hydrazinecarboxamide (JTE-013), specific S1P(2) and S1P(3) receptor antagonists. After local injection of carrageenan in mouse paw S1P release significantly increases locally and decreases during the resolution phase. Expression of SPKs and S1P(2) and S1P(3) receptors is increased in inflamed tissues. Administration of L-cycloserine or DTD caused a significant anti-inflammatory effect. By using different animal models we have also demonstrated that the SPK/S1P pathway contributes to changes in vascular permeability and promotes cell recruitment. The S1P effect on cell recruitment results is receptor-mediated because both JTE-013 and BML-241 inhibited zymosan-induced cell chemotaxis without effect on vascular leakage. Conversely, changes in vascular permeability involve mainly SPK activity, because compound 48/80-induced vascular leakage was significantly inhibited by DTD. In conclusion, the SPK/S1P pathway is involved in acute inflammation and could represent a valuable therapeutic target for developing a new class of anti-inflammatory drugs
New Eco-gas mixtures for the Extreme Energy Events MRPCs: results and plans
The Extreme Energy Events observatory is an extended muon telescope array,
covering more than 10 degrees both in latitude and longitude. Its 59 muon
telescopes are equipped with tracking detectors based on Multigap Resistive
Plate Chamber technology with time resolution of the order of a few hundred
picoseconds. The recent restrictions on greenhouse gases demand studies for new
gas mixtures in compliance with the relative requirements. Tetrafluoropropene
is one of the candidates for tetrafluoroethane substitution, since it is
characterized by a Global Warming Power around 300 times lower than the gas
mixtures used up to now. Several mixtures have been tested, measuring
efficiency curves, charge distributions, streamer fractions and time
resolutions. Results are presented for the whole set of mixtures and operating
conditions, %. A set of tests on a real EEE telescope, with cosmic muons, are
being performed at the CERN-01 EEE telescope. The tests are focusing on
identifying a mixture with good performance at the low rates typical of an EEE
telescope.Comment: 8 pages, 6 figures, proceedings for the "XIV Workshop on Resistive
Plate Chambers and Related Detectors" (19-23 February 2018), Puerto Vallarta,
Jalisco State, Mexic
A simulation tool for MRPC telescopes of the EEE project
The Extreme Energy Events (EEE) Project is mainly devoted to the study of the
secondary cosmic ray radiation by using muon tracker telescopes made of three
Multigap Resistive Plate Chambers (MRPC) each. The experiment consists of a
telescope network mainly distributed across Italy, hosted in different building
structures pertaining to high schools, universities and research centers.
Therefore, the possibility to take into account the effects of these structures
on collected data is important for the large physics programme of the project.
A simulation tool, based on GEANT4 and using GEMC framework, has been
implemented to take into account the muon interaction with EEE telescopes and
to estimate the effects on data of the structures surrounding the experimental
apparata.A dedicated event generator producing realistic muon distributions,
detailed geometry and microscopic behavior of MRPCs have been included to
produce experimental-like data. The comparison between simulated and
experimental data, and the estimation of detector resolutions is here presented
and discussed
The Extreme Energy Events HECR array: status and perspectives
The Extreme Energy Events Project is a synchronous sparse array of 52
tracking detectors for studying High Energy Cosmic Rays (HECR) and Cosmic
Rays-related phenomena. The observatory is also meant to address Long Distance
Correlation (LDC) phenomena: the network is deployed over a broad area covering
10 degrees in latitude and 11 in longitude. An overview of a set of preliminary
results is given, extending from the study of local muon flux dependance on
solar activity to the investigation of the upward-going component of muon flux
traversing the EEE stations; from the search for anisotropies at the sub-TeV
scale to the hints for observations of km-scale Extensive Air Shower (EAS).Comment: XXV ECRS 2016 Proceedings - eConf C16-09-04.
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Risk Factors for Symptomatic Hyperlactatemia and Lactic Acidosis Among Combination Antiretroviral Therapy-Treated Adults in Botswana: Results from a Clinical Trial
Nucleoside analogue reverse transcriptase inhibitors are an integral component of combination antiretroviral treatment regimens. However, their ability to inhibit polymerase-γ has been associated with several mitochondrial toxicities, including potentially life-threatening lactic acidosis. A total of 650 antiretroviral-naive adults (69% female) initiated combination antiretroviral therapy (cART) and were intensively screened for toxicities including lactic acidosis as part of a 3-year clinical trial in Botswana. Patients were categorized as no lactic acidosis symptoms, minor symptoms but lactate <4.4 mmol/liter, and symptoms with lactate ≥ 4.4 mmol/liter [moderate to severe symptomatic hyperlactatemia (SH) or lactic acidosis (LA)]. Of 650 participants 111 (17.1%) developed symptoms and/or laboratory results suggestive of lactic acidosis and had a serum lactate drawn; 97 (87.4%) of these were female. There were 20 events, 13 having SH and 7 with LA; all 20 (100%) were female (p<0.001). Cox proportional hazard analysis limited to the 451 females revealed that having a higher baseline BMI was predictive for the development of SH/LA [aHR=1.17 per one-unit increase (1.08-1.25), p<0.0001]. Ordered logistic regression performed among all 650 patients revealed that having a lower baseline hemoglobin [aOR=1.28 per one-unit decrease (1.1-1.49), p=0.002] and being randomized to d4T/3TC-based cART [aOR=1.76 relative to ZDV/3TC (1.03-3.01), p=0.04] were predictive of the symptoms and/or the development of SH/LA. cART-treated women in sub-Saharan Africa, especially those having higher body mass indices, should receive additional monitoring for SH/LA. Women presently receiving d4T/3TC-based cART in such settings also warrant more intensive monitoring
INFN What Next: Ultra-relativistic Heavy-Ion Collisions
This document was prepared by the community that is active in Italy, within
INFN (Istituto Nazionale di Fisica Nucleare), in the field of
ultra-relativistic heavy-ion collisions. The experimental study of the phase
diagram of strongly-interacting matter and of the Quark-Gluon Plasma (QGP)
deconfined state will proceed, in the next 10-15 years, along two directions:
the high-energy regime at RHIC and at the LHC, and the low-energy regime at
FAIR, NICA, SPS and RHIC. The Italian community is strongly involved in the
present and future programme of the ALICE experiment, the upgrade of which will
open, in the 2020s, a new phase of high-precision characterisation of the QGP
properties at the LHC. As a complement of this main activity, there is a
growing interest in a possible future experiment at the SPS, which would target
the search for the onset of deconfinement using dimuon measurements. On a
longer timescale, the community looks with interest at the ongoing studies and
discussions on a possible fixed-target programme using the LHC ion beams and on
the Future Circular Collider.Comment: 99 pages, 56 figure
Multiplicity Studies and Effective Energy in ALICE at the LHC
In this work we explore the possibility to perform ``effective energy''
studies in very high energy collisions at the CERN Large Hadron Collider (LHC).
In particular, we focus on the possibility to measure in collisions the
average charged multiplicity as a function of the effective energy with the
ALICE experiment, using its capability to measure the energy of the leading
baryons with the Zero Degree Calorimeters. Analyses of this kind have been done
at lower centre--of--mass energies and have shown that, once the appropriate
kinematic variables are chosen, particle production is characterized by
universal properties: no matter the nature of the interacting particles, the
final states have identical features. Assuming that this universality picture
can be extended to {\it ion--ion} collisions, as suggested by recent results
from RHIC experiments, a novel approach based on the scaling hypothesis for
limiting fragmentation has been used to derive the expected charged event
multiplicity in interactions at LHC. This leads to scenarios where the
multiplicity is significantly lower compared to most of the predictions from
the models currently used to describe high energy collisions. A mean
charged multiplicity of about 1000-2000 per rapidity unit (at ) is
expected for the most central collisions at .Comment: 12 pages, 19 figures. In memory of A. Smirnitski
A new approach in modeling the response of RPC detectors
The response of RPC detectors is highly sensitive to environmental variables.
A novel approach is presented to model the response of RPC detectors in a
variety of experimental conditions. The algorithm, based on Artificial Neural
Networks, has been developed and tested on the CMS RPC gas gain monitoring
system during commissioning
Charge separation relative to the reaction plane in Pb-Pb collisions at TeV
Measurements of charge dependent azimuthal correlations with the ALICE
detector at the LHC are reported for Pb-Pb collisions at TeV. Two- and three-particle charge-dependent azimuthal correlations in
the pseudo-rapidity range are presented as a function of the
collision centrality, particle separation in pseudo-rapidity, and transverse
momentum. A clear signal compatible with a charge-dependent separation relative
to the reaction plane is observed, which shows little or no collision energy
dependence when compared to measurements at RHIC energies. This provides a new
insight for understanding the nature of the charge dependent azimuthal
correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286
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