Glutathione And S-nitrosoglutathione In Alginate/chitosan Nanoparticles: Cytotoxicity

Nitric oxide (NO) is involved in several physiological processes, such as the control of vascular tone, the immune response and the wound healing process. Thus, there is a great interest in the development of NO-releasing drugs and in matrices which are able to stabilize and release NO locally in different tissues. Thiols, such as glutathione (GSH), are ready nitrosated to form the NO donors S-nitrosothiols (RSNOs). In this work, GSH, a precursor of the NO donor S-nitrosoglutathione (GSNO), was encapsulated into a mucoadhesive combination of alginate/chitosan nanoparticles. The encapsulated GSH was nitrosated in the alginate/chitosan nanoparticles by adding sodium nitrite, leading to the formation of encapsulated GSNO. The cytotoxicity characterization of the nanoparticles containing either GSH or GSNO showed that these materials were completely non cytotoxic to cellular viability. These results show that this novel nanostructure biomaterial has a great potential to be use in biomedical applications where NO has a therapeutical effect.3041Seabra, A.B., Fitzpatrick, A., Paul, J., De Oliveira, M.G., Weller, R., (2004) Br. J. Dermatol., 151, p. 977Seabra, A.B., Pankotai, E., Fehér, M., Somlai, A., Kiss, L., Bíró, L., Szabó, C., Lacza, Z., (2007) Br. J. Dermatol., 156, p. 814Moore, C., Tymvios, C., Emerson, M., (2010) Thromb. Haemost., 104, p. 342Amadeu, T.P., Seabra, A.B., De Oliveira, M.G., Costa, A.M.A., (2007) J. Eur. Acad. Dermatol. Venereol., 21, p. 629Amadeu, T.P., Seabra, A.B., De Oliveira, M.G., Costa, A.M.A., (2008) J. Surg Res., 149, p. 84Nahrevanian, H., Amini, M., (2008) Iranian J. Basic Med. Sci., 11, p. 197Seabra, A.B., Durán, N., (2010) J. Mater. Chem., 20, p. 1624Kapadia, M.R., Chow, L.W., Tsihlis, N.D., Ahanchi, S.S., Eng, J.W., Murar, J., Martinez, J., Kibbe, M.R., (2008) J. Vasc. Surg., 47, p. 173De Oliveira, M.G., Shishido, S.M., Seabra, A.B., Morgon, M.H., (2002) J. Phys. Chem., 106, p. 8963Hogg, N., Singh, R.J., Kalyanaraman, B., (1996) FEBS Lett., 382, p. 223Seabra, A.B., Da Silva, R., De Souza, G.F.P., De Oliveira, M.G., (2008) Artif. Organs, 32, p. 262Seabra, A.B., Martins, D., Simes, M.M.S.G., Da Silva, R., Brocchi, M., De Oliveira, M.G., (2010) Artif. Organs, 34, p. 204Seabra, A.B., De Souza, G.F.P., Da Rocha, L.L., Eberlin, M.N., De Oliveira, M.G., (2004) Nitric Oxide, 11, p. 263Seabra, A.B., Da Silva, R., De Oliveira, M.G., (2005) Biomacromolecules, 6, p. 2512Frost, M.C., Reynolds, M., Meyerhoff, M.E., (2005) Biomaterials, 26, p. 1685Fortenberry, J.D., Owens, M.L., Brown, L.A.S., (1999) Am. J. Physiol. Lung Cell Mol. Physiol., 276, p. 435Douglas, K.L., Piccirillo, C.A., Tabrizian, M., (2006) J. Control. Release, 115, p. 354Correa, D.H.A., Melo, P.S., De Carvalho, C.A.A., De Azevedo, M.B.M., Durán, N., Haun, M., (2005) Eur. J. Pharmacol., 510, p. 17De Conti, R., Oliveira, D.A., Fernandes, A.M.A.P., Melo, P.S., Rodriguez, J.A., Haun, M., Castro, S.L., Durán, N., (1998) In Vitro Mol. Toxicol, 11, p. 153Borefreund, E., Puerner, J.A., (1984) J. Tissue Cult. Methods, 9, p. 7Denizot, F., Lang, R., (1986) J. Immunol. Methods, 89, p. 27

Nanoparticles In Treatment Of Thermal Injured Rats: Is It Safe?

The aim of this study was to assess whether thermal trauma induced oxidative stress altered the balance between oxidant and antioxidant systems in the blood of burn wound rats in the absence and presence of silver nanoparticles and S-nitrosoglutathione, GSNO. Free silver nanoparticles, free GSNO and silver nanoparticles + GSNO had no cytotoxic effects. Under anesthesia, the shaved dorsum of the rats was exposed to 90°C (burn group) water bath. Studied compounds were administered topically immediately and at 28 days after the burn injury, four times a day. Silver nanoparticles and silver nanoparticles + GSNO were no toxic in vitro and in vivo. There were no significant differences in the levels of urea, creatinine, aminotransferases and hematological parameters, in control-burn groups (free silver nanoparticles) and treated-burn groups (free GSNO or silver nanoparticles + GSNO). There were no differences in lipid peroxidation and in the levels of protein carbonyls and glutathione, used as oxidative stress markers. A little inflammatory cell response, papillary dermis vascularization, fibroblasts differentiated into contractile myofibroblasts and the presence of a large amount of extracellular matrix were evidenced in treated groups following skin injury. These results indicate that silver nanoparticles and GSNO may provide an effective action on wound healing.3041Tian, J., Wong, K.K.Y., Ho, C.M., Lok, C.N., Yu, W.Y., Che, C.M., Chiu, J.F., Tam, P.K.H., (2007) J. Chem. Med. Chem., 2, p. 129Teli, M.K., Mutalik, S., Rajanikant, G.K., (2010) Cur. Pharm. Design., 16, p. 1882Schaller, M., Laude, J., Bodewaldt, H., Hamm, G., Korting, H.C., (2004) Skin Pharmacol. Physiol., 17, p. 31Seabra, A.B., Da Silva, R., De Souza, G.F.P., De Oliveira, M.G., (2008) Artif. Organs, 32, p. 262Seabra, A.B., Pankotai, E., Fehér, M., Somlai, A., Kiss, L., Bíró, L., Szabó, C., Lacza, Z., (2007) Br. J. Dermatol., 156, p. 814Seabra, A.B., Martins, D., Simes, M.M.S.G., Da Silva, R., Brocchi, M., De Oliveira, M.G., (2010) Artif. Organs, 34, p. 204Durán, N., Marcato, P.D., Alves, O.L., De Souza, G.I.H., Esposito, E., (2005) J. Nanobiotechnol., 3, p. 1Durán, N., Marcato, P.D., De Souza, G.I.H., Alves, O.L., Esposito, E., (2007) J. Biomed. Nanotechnol., 3, p. 203Amadeu, T.P., Seabra, A.B., De Oliveira, M.G., Costa, A.M.A., (2007) J. Eur. Acad. Dermatol. Venereol., 21, p. 629Amadeu, T.P., Seabra, A.B., De Oliveira, M.G., Costa, A.M.A., (2008) J. Surg Res., 149, p. 84Correa, D.H.A., Melo, P.S., De Carvalho, C.A.A., De Azevedo, M.B.M., Durán, N., Haun, M., (2005) Eur. J. Pharmacol., 510, p. 17De Conti, R., Oliveira, D.A., Fernandes, A.M.A.P., Melo, P.S., Rodriguez, J.A., Haun, M., Castro, S.L., Durán, N., (1998) Vitro Mol. Toxicol, 11, p. 153Borefreund, E., Puerner, J.A., (1984) J. Tissue Cult. Methods, 9, p. 7Denizot, F., Lang, R., (1986) J. Immunol. Methods, 89, p. 271Michailidis, Y., Jamurta, A.Z., Nikolaidis, M.G., Fatouros, I.G., Koutedakis, Y., Papassotiriou, I., (2007) Med. Sci. Sport Exerc., 39, p. 1107Davis, T.A., Amare, M., Naik, S., Kovalchuk, A.L., Tadaki, D., (2007) Wound Repair Regen., 15, p. 57

Evolution of costs of inflammatory bowel disease over two years of follow-up

Background: With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. Methods and Findings: In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of € 7,835 in CD and € 3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02-3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61-13.86)). Conclusions: BD-related costs remained stable over two years. However, the proportion of anti-TNFrelated healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC

Study of Tau-pair Production in Photon-Photon Collisions at LEP and Limits on the Anomalous Electromagnetic Moments of the Tau Lepton

Tau-pair production in the process e+e- -> e+e-tau+tau- was studied using data collected by the DELPHI experiment at LEP2 during the years 1997 - 2000. The corresponding integrated luminosity is 650 pb^{-1}. The values of the cross-section obtained are found to be in agreement with QED predictions. Limits on the anomalous magnetic and electric dipole moments of the tau lepton are deduced.Comment: 20 pages, 9 figures, Accepted by Eur. Phys. J.

Evidence for an Excess of Soft Photons in Hadronic Decays of Z^0

Soft photons inside hadronic jets converted in front of the DELPHI main tracker (TPC) in events of qqbar disintegrations of the Z^0 were studied in the kinematic range 0.2 < E_gamma < 1 GeV and transverse momentum with respect to the closest jet direction p_T < 80 MeV/c. A clear excess of photons in the experimental data as compared to the Monte Carlo predictions is observed. This excess (uncorrected for the photon detection efficiency) is (1.17 +/- 0.06 +/- 0.27) x 10^{-3} gamma/jet in the specified kinematic region, while the expected level of the inner hadronic bremsstrahlung (which is not included in the Monte Carlo) is (0.340 +/- 0.001 +/- 0.038) x 10^{-3} gamma/jet. The ratio of the excess to the predicted bremsstrahlung rate is then (3.4 +/- 0.2 +/- 0.8), which is similar in strength to the anomalous soft photon signal observed in fixed target experiments with hadronic beams.Comment: 37 pages, 9 figures, Accepted by Eur. Phys. J.

Study of Inclusive J/psi Production in Two-Photon Collisions at LEP II with the DELPHI Detector

Inclusive J/psi production in photon-photon collisions has been observed at LEP II beam energies. A clear signal from the reaction gamma gamma -> J/psi+X is seen. The number of observed N(J/psi -> mu+mu-) events is 36 +/- 7 for an integrated luminosity of 617 pb^{-1}, yielding a cross-section of sigma(J/psi+X) = 45 +/- 9 (stat) +/- 17 (syst) pb. Based on a study of the event shapes of different types of gamma gamma processes in the PYTHIA program, we conclude that (74 +/- 22)% of the observed J/psi events are due to `resolved' photons, the dominant contribution of which is most probably due to the gluon content of the photon.Comment: 13 pages, 8 figures, Accepted by Phys. Lett.

CP asymmetry in B→ϕKSB \to \phi K_S in a general two-Higgs-doublet model with fourth-generation quarks

We discuss the time-dependent CP asymmetry of decay $B \to \phi K_S$ in an extension of the Standard Model with both two Higgs doublets and additional fourth-generation quarks. We show that although the Standard Model with two-Higgs-doublet and the Standard model with fourth generation quarks alone are not likely to largely change the effective $\sin 2 \beta$ from the decay of $B \to \phi K_S$, the model with both additional Higgs doublet and fourth-generation quarks can easily account for the possible large negative value of $\sin 2 \beta$ without conflicting with other experimental constraints. In this model, additional large CP violating effects may arise from the flavor changing Yukawa interactions between neutral Higgs bosons and the heavy fourth generation down type quark, which can modify the QCD penguin contributions. With the constraints obtained from $b \to s \bar{s} s$ processes such as $B \to X_s \gamma$ and $\Delta m_{B_s^0}$, this model can lead to the effective $\sin 2 \beta$ to be as large as $- 0.4$ in the CP asymmetry of $B \to \phi K_S$.Comment: 13 pages, 5 figures, references added, to appear in Eur.Phys.J.

Energy dependence of Cronin momentum in saturation model for p+Ap+A and A+AA+A collisions

We calculate $\sqrt{s}$ dependence of Cronin momentum for $p+A$ and $A+A$ collisions in saturation model. We show that this dependence is consistent with expectation from formula which was obtained using simple dimentional consideration. This can be used to test validity of saturation model (and distinguish among its variants) and measure $x$ dependence of saturation momentum from experimental data.Comment: LaTeX2e, 12 pages, 8 figure

A Precise Measurement of the Tau Lifetime

The tau lepton lifetime has been measured with the e+e- -> tau+tau- events collected by the DELPHI detector at LEP in the years 1991-1995. Three different methods have been exploited, using both one-prong and three-prong tau decay channels. Two measurements have been made using events in which both taus decay to a single charged particle. Combining these measurements gave tau_tau (1 prong) = 291.8 +/- 2.3 (stat) +/- 1.5 (sys) fs. A third measurement using taus which decayed to three charged particles yielded tau_tau (3 prong) = 288.6 +/- 2.4 (stat) +/- 1.3 (sys) fs. These were combined with previous DELPHI results to measure the tau lifetime, using the full LEP1 data sample, to be tau_tau = 290.9 +/- 1.4 (stat) +/- 1.0 (sys) fs.Comment: 27 pages, 7 figure