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

Compliance, persistence, costs and quality of life in young patients treated with antipsychotic drugs: Results from the COMETA study

Background: Little data is available on the real-world socio-economic burden and outcomes in schizophrenia. This study aimed to assess persistence, compliance, costs and Health-Related Quality-of-Life (HRQoL) in young patients undergoing antipsychotic treatment according to clinical practice.Methods: A naturalistic, longitudinal, multicentre cohort study was conducted: we involved 637 patients aged 18-40 years, with schizophrenia or schizophreniform disorder diagnosed ≤10 years before, enrolled in 86 Italian Mental Health Centres and followed-up for 1 year. Comparisons were conducted between naïve (i.e., patients visiting the centre for the first time and starting a new treatment regimen) and non naïve patients.Results: At enrolment, 84% of patients were taking atypical drugs, 3.7% typical, 10% a combination of the two classes, and 2% were untreated. During follow-up, 23% of patients switched at least once to a different class of treatment, a combination or no treatment. The mean Drug-Attitude-Inventory score was 43.4, with 94.3% of the patients considered compliant by the clinicians. On average, medical costs at baseline were 390.93€/patient-month, mostly for drug treatment (29.5%), psychotherapy (29.2%), and hospitalizations (27.1%). Patients and caregivers lost 3.5 days/patient-month of productivity. During follow-up, attitude toward treatment remained fairly similar, medical costs were generally stable, while productivity, clinical statusand HRQoL significantly improved. While no significantly different overall direct costs trends were found between naïve and non naïve patients, naïve patients showed generally a significant mean higher improvement of clinical outcomes, HRQoL and indirect costs, compared to the others.Conclusions: Our results suggest how tailoring the treatment strategy according to the complex and specific patient needs make it possible to achieve benefits and to allocate more efficiently resources. This study can also provide information on the most relevant items to be considered when conducting cost-effectiveness studies comparing specific alternatives for the treatment of target patients

Brane Inflation, Solitons and Cosmological Solutions: I

In this paper we study various cosmological solutions for a D3/D7 system directly from M-theory with fluxes and M2-branes. In M-theory, these solutions exist only if we incorporate higher derivative corrections from the curvatures as well as G-fluxes. We take these corrections into account and study a number of toy cosmologies, including one with a novel background for the D3/D7 system whose supergravity solution can be completely determined. This new background preserves all the good properties of the original model and opens up avenues to investigate cosmological effects from wrapped branes and brane-antibrane annihilation, to name a few. We also discuss in some detail semilocal defects with higher global symmetries, for example exceptional ones, that could occur in a slightly different regime of our D3/D7 model. We show that the D3/D7 system does have the required ingredients to realise these configurations as non-topological solitons of the theory. These constructions also allow us to give a physical meaning to the existence of certain underlying homogeneous quaternionic Kahler manifolds.Comment: Harvmac, 115 pages, 9 .eps figures; v2: typos corrected, references added and the last section expanded; v3: Few minor typos corrected and references added. Final version to appear in JHE

Vaccinia Virus Infection in Monkeys, Brazilian Amazon

To detect orthopoxvirus in the Brazilian Amazon, we conducted a serosurvey of 344 wild animals. Neutralizing antibodies against orthopoxvirus were detected by plaque-reduction neutralizing tests in 84 serum samples. Amplicons from 6 monkey samples were sequenced. These amplicons identified vaccinia virus genetically similar to strains from bovine vaccinia outbreaks in Brazil

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

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio