Inclusion Complex Of S(-) Bupivacaine And 2-hydroxypropyl- β-cyclodextrin: Study Of Morphology And Cytotoxicity

Local anesthetics (LA) belong to a class of pharmacological compounds that attenuate or eliminate pain by binding to the sodium channel of excitable membranes, blocking the influx of sodium ions and the propagation of the nerve impulse. S (-) bupivacaine (S(-) bvc) is a local anesthetic of amino-amide type, widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. This article focuses on the characterization of an inclusion complex of S(-) bvc in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). Differential scanning calorimetry, scanning electron microscopy and X-Ray diffraction analysis showed structural changes in the complex. In preliminary toxicity studies, the cell viability tests revealed that the inclusion complex decreased the toxic effect (p<0.001) produced by S(-) bvc. These results suggest that the S(-) bvc:HP-β-CD inclusion complex represents a promising agent for the treatment of regional pain.273207212Araújo, D.R., Cereda, C.M., Brunetto, G.B., Pinto, L.M.A., Santana, M.H., de Paula, E., Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice (2004) Can J Anaesth, 51, pp. 566-572Araújo, D.R., Fraceto, L.F., Braga, A.F.A., de Paula, E., Drug-delivery systems for racemic bupivacaine (S50-R50) and bupivacaine enantiomeric mixture (S75-R25):cyclodextrins complexation effects on sciatic nerve blockade in mice (2005) Rev Bras Anestesiol, 55, pp. 316-328Araújo, D.R., Moraes, C.M., Fraceto, L.F., Braga, A.F.A., de Paula, E., Cyclodextrin-bupivacaine enantiomeric mixture (S75-R25) inclusion complex and intrathecal anesthesia in rats (2006) Rev Bras Anestesiol, 56, pp. 495-506Bibby, D., Davies, N.M., Tueker, I.G., Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems (2000) Int J Pharm, 197, pp. 1-11Covino, B.G., Vassalo, H.G., (1976) Local anesthetics: Mechanisms of action and clinical use, , New York: Grune and Stratton;, 255pFoster, R.H., Markham, A., Levobupivacaine. A review of its pharmacology and use as a local anaesthetic (2000) Drugs, 59, pp. 551-579Grant, G.J., Bansinath, M., Liposomal delivery systems for local anesthetics (2001) Reg Anesth Pain Med, 26, pp. 61-63Gristwood, R.W., Cardiac and CNS toxicity of levobupivacaine: Strengths of evidence for advantage over bupivacaine (2002) Drug Saf, 25, pp. 153-163Hirayama, F., Uekama, K., Cyclodextrin-based controlled drug release system (1999) Adv Drug Deliv Rev, 36, pp. 125-141Huang, Y.F., Pryor, M.E., Mather, L.E., Veering, B.T., Cardiovascular and central nervous system effects of intravenous S-bupivacaine and bupivacaine in sheep (1998) Anesth Analg, 86, pp. 797-804Jong, R.H., (1994) Local anesthetics, , Springfield: CC. Thomas;, 325pKohata, S., Jyodi, K., Ohyoshi, A., Thermal decomposition of cyclodextrins (α -, β-, γ, and modified β-CyD) and of metal-(β-CyD) complex in the solid phase (1993) Thermochim Acta, 217, pp. 187-198Loftsson, T., Brewster, M.E., Pharmaceutical application of Cyclodextrin. 1. Drug solubilization and stabilization (1996) J Pharm Sci, 85, pp. 1017-1025Loukas, Y.L., Vraka, V., Gregoriadis, G., Novel non-acidic formulations of haloperidol complexed with beta-cyclodextrin derivatives (1997) J Pharm Biomed Anal, 16, pp. 263-268Mather, L.E., McCall, P., McNicol, P.L., Bupivacaine enantiomer pharmacokinetics after intercostal neural blockade in liver transplant patients (1995) Anesth Analg, 80, pp. 328-335Michaud, M., Icart, S., Determination of the substitution of hydroxypropylbetadex using fourier transform infrared spectrophotometry (2001) PharmEuropa, 13, pp. 714-716Naidu, N.B., Chowdary, K.P.R., Murthy, K.V.R., Satyanarayana, V., Hayman, A.R., Becket, G., Physicochemical characterization and dissolution properties of meloxicam-cyclodextrin binary systems (2004) J Pharm Biomed Anal, 35, pp. 75-86Pinto, L.M.A., Fraceto, L.F., Santana, M.H.A., Pertinhez, T.A., Oyama, S., de Paula, E., Physico-chemical characterization of benzocaine-β-cyclodextrin inclusion complexes (2005) J Pharm Biomed Anal, 39, pp. 956-963Ren, X., Xue, Y., Liu, J., Zhang, K., Zheng, J., Lou, G., Gou, C., Shen, J., A novel cyclodextrin-deri ved tellurium compound with glutathione peroxidase (2002) Chembiochem, 3, pp. 363-365Rose, J.S., Neal, J.M., Kopacz, D.J., Extended-duration analgesia: Update on microspheres and liposomes (2005) Reg Anesth Pain Med, 30, pp. 275-285Strichartz, G.R., Ritchie, J.M., (1987) Local anesthetics: Handbook of experimental pharmacology, , Berlin: Springer-Verlag;, 445pThompson, D.O., Cyclodextrin-enabling excipients: Their present and future use in pharmaceuticals (1997) Crit Rev Ther Drug Carrier Syst, 14, pp. 1-10

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

EpiReumaPt- the study of rheumatic and musculoskeletal diseases in Portugal: a detailed view of the methodology

Rheumatic and musculoskeletal diseases (RMD) are prevalent and leading causes of disability and consumption of healthcare and social resources. EpiReumaPt is a national population-based survey developed by the Portuguese Society of Rheumatology that aimed to estimate the prevalence of RMDs and determine their impact on function, quality of life, mental health and use of healthcare resources. This article describes in detail the design, methodology and planned analyses of EpiReumaPt. Recruitment started in September 2011 and finished in December 2013. This study involved a three-stage approach. The first step was a face-to-face survey performed by trained interviewers at the household of 10,661 subjects who where randomly selected by a stratified multistage sampling. A highly sensitive screening questionnaire for RMDs was used. Secondly, participants who screened positive (64%) for at least one RMD as well as 20% of individuals with a negative screening were invited for assessment by a rheumatologist. In total, 3,877 subjects participated in this second phase, where they were also invited to donate a blood sample to be stored at the Biobanco-IMM. History and physical examination, followed by appropriate laboratory and imaging tests were performed. At the end of the visit, the rheumatologist established a diagnosis. Finally, a team of three experienced rheumatologists reviewed all the clinical data and defined the diagnoses according to previously validated criteria. The EpiReumaPt dataset, containing data from several questionnaires, various clinical measurements and information from laboratory and imaging tests, comprises an invaluable asset for research. The large amount of information collected from each participant and the large number of participants, with a wide age range covering and being representative of the adults from the entire country, makes EpiReumaPt the largest study of RMDs performed in Portugal

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements

A search for resonances decaying into a Higgs boson and a new particle X in the XH → qqbb final state with the ATLAS detector

A search for heavy resonances decaying into a Higgs boson (H) and a new particle (X) is reported, utilizing 36.1 fb−1 of proton–proton collision data at collected during 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. The particle X is assumed to decay to a pair of light quarks, and the fully hadronic final state is analysed. The search considers the regime of high XH resonance masses, where the X and H bosons are both highly Lorentz-boosted and are each reconstructed using a single jet with large radius parameter. A two-dimensional phase space of XH mass versus X mass is scanned for evidence of a signal, over a range of XH resonance mass values between 1 TeV and 4 TeV, and for X particles with masses from 50 GeV to 1000 GeV. All search results are consistent with the expectations for the background due to Standard Model processes, and 95% CL upper limits are set, as a function of XH and X masses, on the production cross-section of the resonance

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

Fiducial and differential cross sections of Higgs boson production measured in the four-lepton decay channel in pp collisions at √s = 8 TeV with the ATLAS detector

Measurements of fiducial and differential cross sections of Higgs boson production in the H→ZZ∗ → 4ℓ decay channel are presented. The cross sections are determined within a fiducial phase space and corrected for detection efficiency and resolution effects. They are based on 20.3 fb−¹ of pp collision data, produced at √s = 8 TeV centre-of-mass energy at the LHC and recorded by the ATLAS detector. The differential measurements are performed in bins of transverse momentum and rapidity of the four-lepton system, the invariant mass of the subleading lepton pair and the decay angle of the leading lepton pair with respect to the beam line in the four-lepton rest frame, as well as the number of jets and the transverse momentum of the leading jet. The measured cross sections are compared to selected theoretical calculations of the Standard Model expectations. No significant deviation from any of the tested predictions is found

Search for dark matter produced in association with a hadronically decaying vector boson in pp collisions at sqrt (s) = 13 TeV with the ATLAS detector

A search is presented for dark matter produced in association with a hadronically decaying W or Z boson using 3.2 fb−1 of pp collisions at View the MathML sources=13 TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with a hadronic jet compatible with a W or Z boson and with large missing transverse momentum are analysed. The data are consistent with the Standard Model predictions and are interpreted in terms of both an effective field theory and a simplified model containing dark matter

Search for TeV-scale gravity signatures in high-mass final states with leptons and jets with the ATLAS detector at sqrt [ s ] = 13TeV

A search for physics beyond the Standard Model, in final states with at least one high transverse momentum charged lepton (electron or muon) and two additional high transverse momentum leptons or jets, is performed using 3.2 fb−1 of proton–proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2015 at √s = 13 TeV. The upper end of the distribution of the scalar sum of the transverse momenta of leptons and jets is sensitive to the production of high-mass objects. No excess of events beyond Standard Model predictions is observed. Exclusion limits are set for models of microscopic black holes with two to six extra dimensions