Anti-inflammatory effect of chitosan oligomers

info:eu-repo/semantics/acceptedVersio

Inovação e gestão tecnológica em organizações de P&D: um modelo integrador.

Modelos são representações da realidade que têm se revelado úteis para o avanço do conhecimento em inúmeras áreas. Este artigo busca apresentar um modelo de inovação tecnológica em que esse fenômeno seja concebido como sendo: a) sistêmico; b) multinível; c) organizacional, d) multideterminado; e) passível de mensuração; f) de intervenção. A literatura sobre modelos de inovação apresenta propostas em que dois elementos estão sempre presentes: a) o processo de P&D, em suas diversas etapas; b) determinantes dessas etapas, ou fatores originados nos contextos macro, meso ou micro do processo de inovação. A literatura sobre gestão tecnológica apresenta modelos de gestão, enfatizando variáveis relativas à gestão de portfólio e gestão de pesquisa em rede, como as mais relevantes para os modelos de gestão de última geração. A proposta apresentada neste trabalho integra essas duas literaturas, procurando enfatizar a relevância de variáveis de gestão tecnológica como determinantes importantes, ao longo do processo de inovação tecnológica. O artigo conclui com uma discussão de áreas beneficiadas com a utilização do modelo

Prospective evaluation of glutamine and phospholipids levels in first degree relatives of patients with Type 1 Diabetes from a multiethnic population

A dysregulation in the metabolism of lipids may be an early marker of autoimmunity in Type 1 Diabetes (T1D). It would be of general importance to identify metabolic patterns that would predict the risk for T1D later in life. The aim of this study was to perform a prospective evaluation of glutamine and phospholipids levels in Brazilian first degree relatives (FDR) of patients with T1D in a mean interval of 5 years

Synthesis And Evaluation Of New β-carboline-3-(4-benzylidene)- 4h-oxazol-5-one Derivatives As Antitumor Agents

In the present work, we report the synthesis and in vitro anticancer and antimicrobial activity evaluation of a new series of 1-substituted-β- carboline derivatives bearing a 4-benzylidene-4H-oxazol-5-one unity at C-3. The compound 2-[1-(4- methoxyphenyl)-9H-β-carbolin-3-yl]-4-(benzylidene)-4H- oxazol-5-one (11) was the most active derivative, exhibiting a potent cytotoxic activity against glioma (U251), prostate (PC-3) and ovarian (OVCAR-03) cancer cell lines with IC 50 values of 0.48, 1.50 and 1.07 μM, respectively. An in silico study of the ADME properties of the novel synthesized β-carboline derivatives was also performed. © 2012 by the Authors.17561006113Cao, R., Peng, W., Wang, Z., Xu, A., B-carboline alkaloids: Biochemical and pharmacological functions (2007) Curr. Med. Chem., 14, pp. 479-500Yao, K., Zhao, M., Zhang, X., Wang, Y., Li, L., Zheng, M., Peng, S., A class of oral n-[(1s,3s)-1- methyl-1,2,3,4-tetrahydro-β-carboline- 3-carbonyl]-n-(amino-acid-acyl) hydrazine: Discovery, synthesis, in vitro anti-platelet aggregation/in vivo anti-thrombotic evaluation and 3d qsar analysis (2011) Eur. J. Med. Chem., 46, pp. 3237-3249Bi, W., Bi, Y., Xue, P., Zhang, Y., Gao, X., Wang, Z., Li, M., Gibson, M.K., A new class of β-carboline alkaloid-peptide conjugates with therapeutic efficacy in acute limb ischemia/reperfusion injury (2011) Eur. J. Med. Chem., 46, pp. 1453-1462Liu, J., Jiang, X., Zhao, M., Zhang, X., Zheng, M., Peng, L., Peng, S., A class of 3s-2- aminoacyltetrahydro-b-carboline-3-carboxylic acids: Their facile synthesis, inhibition for platelet activation, and high in vivo anti-thrombotic potency (2010) J. Med. Chem., 53, pp. 3106-3116Costa, E.V., Pinheiro, M.L.B., De Souza, A.D.L., Barison, A., Campos, F.R., Valdez, R.H., Ueda-Nakamura, T., Nakamura, C.V., Trypanocidal activity of oxoaporphine and pyrimidine-b-carboline alkaloids from the branches of annona foetida mart. (annonaceae (2011) Molecules, 16, pp. 9714-9720Polanski, W., Reichmann, H., Gille, G., Stimulation protection and regeneration of dopaminergic neurons by 9-methyl-b-carboline: A new anti-parkinson drug? (2011) Expert Rev. Neurother., 11, pp. 845-860Valdez, R.H., Tonin, L.T.D., Ueda-Nakamura, T., Silva, S.O., Dias, B.P., Kaneshima, E.N., Yamada-Ogatta, S.F., Nakamura, C.V., In vitro and in vivo trypanocidal synergistic activity of n-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-b- carboline-3-carboxamide) associated with benznidazole (2012) Antimicrob. Agents Chemother., 56, pp. 507-512Ikeda, R., Kurosawa, M., Okabayashi, T., Takei, A., Yoshiwara, M., Kumakura, T., Sakai, N., Ikekita, M., 3-(3-phenoxybenzyl)amino-b-carboline: A novel antitumor drug targeting a-tubulin (2011) Bioorg. Med. Chem. Lett., 21, pp. 4784-4787Shen, L., Park, E.-J., Kondratyuk, P., Guendisch, D., Marler, L., Pezzuto, J.M., Wright, A.D., Sun, D., Design synthesis, and biological evaluation of callophycin a and analogues as potential chemopreventive and anticancer agents (2011) Bioorg. Med. Chem., 19, pp. 6182-6195Chen, Z., Cao, R., Shi, B., Guo, L., Sun, J., Ma, Q., Fan, W., Song, H., Synthesis and biological evaluation of 1,9-disubstituted b-carbolines as potent dna intercalating and cytotoxic agents (2011) Eur. J. Med. Chem., 46, pp. 5127-5137Zhang, X., Yang, Y., Zhao, M., Liu, L., Zheng, M., Wang, Y., Wu, J., Peng, S., A class of trp-trp-aa-obzl: Synthesis, in vitro anti-proliferation/in vivo anti-tumor evaluation, intercalationmechanism investigation and 3d qsar analysis (2011) Eur. J. Med. Chem., 46, pp. 3410-3419Chen, Z., Cao, R., Shi, B., Yi, W., Yu, L., Song, H., Ren, Z., Synthesis and biological evaluation of novel b-carbolines as potent cytotoxic and dna intercalating agents (2010) Chem. Pharm. Bull., 58, pp. 901-907Ma, C., Cao, R., Shi, B., Zhou, X., Ma, Q., Sun, J., Guo, L., Song, H., Synthesis and cytotoxic evaluation of 1-carboxamide and 1-amino side chain substituted b-carbolines (2010) Eur. J. Med. Chem., 45, pp. 5513-5519Chen, Z., Cao, R., Yu, L., Shi, B., Sun, J., Guo, L., Ma, Q., Song, H., Synthesis, cytotoxic activities and dna binding properties of b-carboline derivatives (2010) Eur. J. Med. Chem., 45, pp. 4740-4745Cao, R., Guan, X., Shi, B., Chen, Z., Ren, Z., Peng, W., Song, H., Design synthesis and 3d-qsar of b-carboline derivatives as potent antitumor agents (2010) Eur. J. Med. Chem., 45, pp. 2503-2515Wu, J., Li, C., Zhao, M., Wang, W., Wang, Y., Peng, S., A class of novel carboline intercalators: Their synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and 3d qsar analysis (2010) Bioorg. Med. Chem., 18, pp. 6220-6229Formagio, A.S.N., Tonin, L.T.D., Foglio, M.A., Madjarof, C., De Carvalho, J.E., Da Costa, W.F., Cardoso, F.P., Sarragiotto, M.H., Synthesis and antitumoral activity of novel 3-(2-substituted- 1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) b-carboline derivatives (2008) Bioorg. Med. Chem., 16, pp. 9660-9667Savariz, F.C., Formagio, A.S.N., Barbosa, V.A., Foglio, M.A., De Carvalho, J.E., Duarte, M.C.T., Filho, B.P.D., Sarragiotto, M.H., Synthesis, antitumor and antimicrobial activity of novel 1-substituted phenyl-3-[3-alkylamino(methyl)-2-thioxo-1,3,4-oxadiazol-5-yl] b-carboline derivatives (2010) J. Braz. Chem. Soc., 21, pp. 288-298Barbosa, V.A., Formagio, A.S.N., Savariz, F.C., Foglio, M.A., Spindola, H.M., De Carvalho, J.E., Meyer, E., Sarragiotto, M.H., Synthesis and antitumor activity of b-carboline 3- (substitutedcarbohydrazide) derivatives (2011) Bioorg. Med. Chem., 19, pp. 6400-6408Wu, S., Fu, Y., Yan, R., Wu, Y., Lei, X., Ye, S., Synthesis of neamine-carboline conjugates for rna binding and their antibacterial activities (2010) Tetrahedron, 66, pp. 3433-3440Schupp, P., Poehner, T., Edrada, R., Ebel, R., Berg, A., Wray, V., Proksch, P., Eudistomins w and x, two new b-carbolines from the micronesian tunicate eudistoma sp (2003) J. Nat. Prod., 66, pp. 272-275Desai, N.C., Bhavsar, A.M., Baldaniya, B.B., Synthesis and antimicrobial activity of 5-imidazolinone derivatives (2009) Indian J. Pharm. Sci., 71, pp. 90-94Argade, N.D., Kalrale, B.K., Gill, C.H., Microwave assisted improved method for the synthesis of pyrazole containing 2,4,-disubstitute oxazole-5-one and their antimicrobial activity (2008) Eur. J. Chem., 5, pp. 120-129Salgin-Goken, U., Gokhan-Kelekçi, N., Goktas, O., Koysal, Y., Kilic, E., Isik, S., Aktay, G., Ozalp, M., 1-Acylthiosemicarbazides, 1,2,4-triazole-5(4H)-thiones, 1,3,4-thiadiazoles and hydrazones containing 5-methyl-2-benzoxazolinones: Synthesis, analgesic, anti-inflammatory and antimicrobial activities (2007) Bioorg. Med. Chem., 15, pp. 5738-5751Siddiqui, I.R., Singh, P.K., Srivastava, V., Singh, J., Facile synthesis of acyclic analogues of carbocyclic nucleoside as potential anti-hiv pro-drug (2010) Indian J. Chem., 49 B, pp. 512-520Perron-Sierra, F.M., Pierré, A., Burbridge, M., Guilbaud, N., Novel bicyclic oxazolone derivatives as anti-angiogenic agents (2002) Bioorg. Med. Chem. Lett., 12, pp. 1463-1466Khan, K.M., Mughal, U.R., Khan, M.T.H., Zia-Ullah, Perveen, S., Choudhary, M.I., Oxazolones new tyrosinase inhibitorssynthesis and their structure-activity relationships (2006) Bioorg. Med. Chem., 14, pp. 6027-6033Mesaik, M.A., Rahat, S., Khan, K.M., Zia-Ullah Choudhary, M.I., Murad, S., Ismail, Z., Atta-Ur-Rahman Ahmad, A., Synthesis and immunomodulatory properties of selected oxazolone derivatives (2004) Bioorg. Med. Chem., 12, pp. 2049-2057Bala, S., Saini, M., Kamboj, S., Methods for synthesis of oxazolones: A review (2011) Int. J. ChemTech Res., 3, pp. 1102-1118Tikdari, A.M., Fozooni, S., Hamidian, H., Dodecatungstophosphoric acid (h3pw12o40), samarium and ruthenium (iii) chloride catalyzed synthesis of unsaturated 2-phenyl-5(4h)-oxazolone derivatives under solvent-free conditions (2008) Molecules, 13, pp. 3246-3252Cleary, T., Rawalpally, T., Kennedy, N., Chavez, F., Catalyzing the erlenmeyer plöchl reaction: Organic bases versus sodium acetate (2010) Tetrahedron Lett., 51, pp. 1533-1536Ma, C., Cao, R., Shi, B., Li, S., Chen, Z., Yi, W., Peng, W., Song, H., Synthesis and cytotoxic evaluation of n2-benzylated quaternary b-carboline amino acid ester conjugates (2010) Eur. J. Med. Chem., 45, pp. 1515-1523Lipinski, C.A., Lombardo, F., Dominy, B.W., Feeney, P.J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings (1997) Adv. Drug Deliv. Rev., 23, pp. 3-25Ertl, P., (2012) Calculation of Molecular Properties and Bioactivity Score, , http://www.molinspiration.com, Available online: accessed on 31 JanuarySander, T., (2012) Molecular Property Explorer, , http://www.organic-chemistry.org/prog/peo, Available online: accessed on 31 JanuaryMonks, A., Scudiero, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D., Hose, C., Vaigro-Wolff, A., Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines (1991) J. Natl. Cancer Inst., 83, pp. 757-766Shoemaker, R.H., The nci60 human tumour cell line anticancer drug screen (2006) Nat. Rev. Cancer, 6, pp. 813-823(2003) Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically Approved Standard, , NCCLS, 6th Ed.NCCLS document M7-A6NCCLS: Wayne, MI, USA(2002) Methods for Broth Dilution Antifungal Susceptibility Testing of Yeasts, , NCCLS. Approved standard, 2nd Ed.NCCLS document M27-ANCCLS: Wayne, MI, US

Plantio direto, adubação verde e suplementação com esterco de aves na produção orgânica de berinjela.

Sob manejo orgânico, foram avaliados, em Seropédica, RJ, os sistemas de plantio direto da berinjela(Solanum melongena) nas palhadas de Crotalaria juncea (crotalária), Pennisetum glaucum (milheto, cv. BRS 1501)e vegetação espontânea (pousio), em comparação com o plantio convencional (aração e gradagem ou enxada rotativa). Simultaneamente, foram avaliados três tipos de cultivo: berinjela em monocultura, em consórcio com crotalária e em consórcio com caupi (Vigna unguiculata, cv. Mauá). Não houve diferença entre os sistemas de plantio direto e convencional quanto à produção comercial da berinjela. A palhada da crotalária foi mais eficiente que a do milheto e do pousio para cobertura morta do solo e conseqüentemente o controle de plantas espontâneas foi maior. O cultivo simultâneo com as leguminosas não acarretou redução da produtividade da berinjela.Em um segundo estudo, foram comparados plantio direto (palhadas de crotalária e da vegetação espontânea) e plantio convencional, combinados com doses crescentes de cama de aviário (0, 100, 200 e 400 kg ha-1 de N)aplicada em cobertura. Em termos de aporte de biomassa, a crotalária foi novamente superior à vegetação espontânea.A berinjela respondeu à adubação orgânica, com produtividade máxima de 50,6 t ha-1 , correspondendo à maior dose empregada, contra 36,9 t ha-1 referentes ao controle

Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease

Background:Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection.Methods:Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of São Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) cluster analysis based on the expression of the quantified cytokines was applied to identify groups of patients with similar cytokine profiles. Markers of microbial translocation were linked to groups with similar clinical disease severity and clusters with similar cytokine profiles.Results:Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease.Conclusions:The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis