CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / INTRODUCTION: The radiation-induced oral mucisitis (OM) is the most important acute toxicity and the most impacting dose-limiting factor in head and neck cancer patients. Despite its major incidence, the pathogenesis is not well known. OBJECTIVES: Evaluate the role of the cytokines and the nitric oxide (NO) in the pathogenesis of the experimental radiation-induced oral mucisitis (OM) as well as indicate possible protector agents. METHODS: The OM was induced with only one fraction of megavoltage radiation (RT) in hamsters. The animals were treated with: cytokines inhibitors (PTX 15 mg/Kg), nitric oxide synthase inhibitor (NOSi), amineguanidine (AG 10, 30 and 90 mg/Kg) or saline solution (0.5 ml) just one hour before RT and daily until the animalsâ sacrifice (13th day). Another group of animals were treated with two different phytotherapy using: Myracrodruon urundeava (Aroeira-do-sertao) topical gel 5, 10 and 20% or Aloe barbadensis Miller (Aloe vera) topical gel 25, 50 and 100%. The control group received biologically inert topical gel. The animals were treated just one hour before RT and twice daily until their sacrifice (13th day). For the evaluation of the results, the following parameters were used: histopathology analysis of the oral mucosa (macro and microscopically), MPO and NOSi activity, nitrite and cytokines (TNF-α, IL-1 and IL-10) tissue levels, cytokines and NOSi immunochemistry as well as NOSi expression by Western blot. RESULTS: The animals with radiation-induced OM showed increased inflammatory parameters: on histopathology, myeloperoxidase activity, cytokines and nitrite levels and intense NOSi immune expression when compared to the control group. AG significantly reduced in a dose-dependent effect the macro and microscopically parameters in animals with OM as well as the neutrophil infiltration and nitrite and cytokines (TNF-α, IL-1) levels. AG also reduced the NOSi activity and the cytokines and NOSi immune expression. The PTX treatment significantly reduced the inflammatory parameters (on histopathology, MPO activity, and cytokines tissue levels) and the cytokines and NOSi immune expression. The Aroeira, despite of inhibiting the nitrite and tissue TNF-α production, did not reduce the micro and macroscopically parameters of OM. On the other hand, the Aloe vera 100%, significantly inhibited the inflammatory parameters (on histopathology, MPO activity, tissue cytokines, TNF-α, IL-1 and nitrite levels). CONCLUSIONS: The data suggested that TNF-α and IL-1 by NOSi activation and consequently NO production seem to play an important role in the pathogenesis of the experimental radiation-induced OM. PTX, AG and Aloe vera 100% were able to significantly reduce the OM. / INTRODUÃÃO: A mucosite oral (MO) radioinduzida à o principal efeito colateral agudo e o mais impactante fator dose limitante da radioterapia (RXT) de pacientes em tratamento para tumores de cabeÃa e pescoÃo. à despeito da importante incidÃncia, sua patogÃnese ainda nÃo està completamente esclarecida. OBJETIVOS: Avaliar o envolvimento de citocinas e do Ãxido nÃtrico (NO) na patogÃnese da MO experimental induzida por RXT, assim como estudar possÃveis agentes protetores. MÃTODOS: A MO foi induzida por RXT de megavoltagem em hamsters. Os animais foram tratados com inibidor de citocinas (pentoxifilina-15mg/kg), inibidor da Ãxido nÃtrico sintase induzida (NOSi), aminoguanidina (AG), nas doses de 10, 30 e 90 mg/kg), ou salina (0,5ml/kg), uma hora antes da RXT e diariamente, atà o sacrifÃcio, no 13 dia. Em outro grupo experimental, os animais foram tratados com dois fitoterÃpicos: Myracrodruon urundeava (Aoreira-do-sertÃo) na forma de gel nas concentraÃÃes de 5, 10 e 20% e Aloe barbadensis Miller (Aloe vera) na forma de gel nas concentraÃÃes de 25, 50 e 100%, ou receberam gel inerte atravÃs de aplicaÃÃo tÃpica, uma hora antes da RXT, e duas vezes ao dia, atà o sacrifÃcio, no 13 dia. Para avaliaÃÃo de resultados foram utilizados os seguintes parÃmetros: anÃlises macro e microscÃpicas das mucosas jugais, atividade de mieloperoxidase e de NOSi, dosagens teciduais de nitrito e de citocinas (TNF-α, IL-1 e IL-10), imunohistoquÃmica para citocinas e NOSi, assim como, expressÃo de NOSi por western blot. RESULTADOS: Os animais com MO induzida por RXT apresentaram aumento significativo dos seguintes parÃmetros inflamatÃrios: histopatolÃgico, atividade de mieloperoxidase, dosagem de citocinas e de nitrito e intensa imunoexpressÃo de NOSi quando comparado com grupos controles. AG reduziu de forma significativa e dose-dependente os parÃmetros macro e microscÃpicos nos animais com MO, bem como a infiltraÃÃo de neutrÃfilos e a dosagem de nitrito e de citocinas (TNF-α, IL-1). Reduziu tambÃm a atividade da NOSi e imunomarcaÃÃo para citocinas e NOSi. O tratamento com PTX atenuou significativamente os parÃmetros inflamatÃrios (histopatolÃgico, atividade de MPO, nÃveis teciduais de citocinas), e a imunoexpressÃo de NOSi e de citocinas. A Aroeira, à despeito de ter inibido a produÃÃo de nitrito e de TNF-α tecidual, nÃo foi capaz de atenuar os parÃmetros macro e microscÃpicos da MO. Por outro lado, o Aloe vera, na concentraÃÃo de 100% inibiu de forma significativa os parÃmetros inflamatÃrios (histopatolÃgico, atividade de MPO, nÃveis teciduais das citocinas TNF-α e IL-1 e dosagem de nitrito). CONCLUSÃES: Os dados permitiram concluir que: TNF-α e IL-1 via ativaÃÃo de NOSi e consequente produÃÃo de NO parecem desempenhar um papel importante na patogÃnese da MO experimental induzida por RXT de megavoltagem. PTX, AG e Aloe vera (na concentraÃÃo de 100%) foram capazes de inibir de forma significativa a MO induzida por RX

O presente estudo teve como objetivo avaliar e comparar, morfologicamente, a resposta do tecido subcutâneo de ratos frente ao de hidróxido de cálcio associado a diferentes substâncias, sendo elas: clorexidina 0,2% em propilenoglicol, clorexidina 0,4% em propilenoglicol, Casearia sylvestris Sw (Guaçatonga) em propilenoglicol e propilenoglicol (que serviu como grupo controle). Para isso, foram utilizados 72 ratos Wistar. As pastas foram preparadas e colocadas em tubos de polietileno, que foram implantados no tecido subcutâneo do dorso de cada animal. Os períodos experimentais foram de 7, 14 e 30 dias após o procedimento cirúrgico, quando então, os animais foram mortos. As amostras coletadas passaram por processamento histotécnico e foram feitos cortes de 5µm de espessura e coloração com Hematoxilina e Eosina (H.E.). A avaliação das respostas do tecido conjuntivo em contato com as pastas testadas foirealizada de forma descritiva e quantitativa subjetiva.Os dados obtidos após análise quantitativa foram submetidos ao teste estatístico de Kruskal-Wallis e Dunn com nível de significância p<0,05. Os resultados mostraram que a clorexidina 0,4%, de modo geral, se mostrou mais irritante que os demais grupos. O extrato de Casearia sylvestris Sw apresentou comportamento satisfatório em relação à intensidade da reação inflamatória, igualando-se aos grupos 1 e 4. Com base na metodologia aplicada, foi possível concluir que aos 30 dias todos os grupos mostraram não interferir no processo de reparo e que todas as substâncias experimentais (clorexidina a 0,4%, a 0,2% e o extrato de Casearia sylvestris Sw) podem ser associadas ao hidróxido de cálcio. / This study aimed to evaluate the response of rat subcutaneous tissue against calcium hydroxide associated with different substances: chlorhexidine 0.2% in propylene glycol, 0,4% chlorhexidine in propylene glycol, Casearia sylvestris (guaçatonga) in propylene glycol and propylene glycol (control group). The pastes were prepared and placed in polyethylene tubes, which were implanted in the dorsum of each animal (N=18). The experimental periods were 7, 14 and 30 days after surgery, at which time the animals were killed. The samples were histologically processed and stained with hematoxylin and eosin. The evaluation of the responses of connective tissue in contact with the pastes was performed using descriptive and quantitative analyses. The data obtained after the quantitative analysis were subjected to statistical test of Kruskal-Wallis and Dunn with significance level p <0.05. In overall, chlorhexidine 0,4%/calcium hydroxide showed the more intense inflamatory reaction in comparison to the other groups. The extract of Casearia sylvestris showed satisfactory performance in relation to the intensity of the inflammatory reaction, similar to groups 1 and 4. Based on the methodology, it was concluded that at 30 days all the materials do not to interfere with the repair process and that all experimental substances (chlorhexidine 0.4%, 0.2% and the extract of Casearia sylvestris) can be associated with calcium hydroxide.

Thesis (Masters of Science)--Curtin University of Technology, 2003. / Title from PDF t.p. (viewed Mar. 3, 2007). "November 2003." Includes bibliographical references.

According to data of research company „IMS Health“ the pharmacy market in Lithuania increases year by year, and sales of non-prescribed medicine increase significantly. A part of those sales is comprised of herbal medicine preparations. Analysis of competitive environment, analysis of available preparations portfolio and possibilities of the company‘s development are compulsory seeking to stay competitive. During the last years we observed an increasing interest of consumers in herbal medicine preparations, therefore, the topic chosen is relevant for the Master‘s Degree thesis. Aim of the study: to evaluate possibilities of development of „Bionorica AG“ company on Lithuanian market. Objectives: Review of market of herbal preparations, evaluation of external environment, analysis of portfolio of the company‘s preparations, possibilities and analysis of the company‘s development on the market. Methods – model of M. Porter, with the help of which competitive analysis was performed. Survey of drugstores. Questionnaire data of surveys were entered, processed and analyzed with the use of statistics data analysis program SPSS. Analysis of the products‘ portfolio was performed with the use of matrix model of Boston consulting group (BCG). Possibilities of the company‘s development are analyzed in the paper with the use of forecasting method - trend model. Results: Many large companies, which follow each others‘ actions in order to know the means that are necesary to be assumed... [to full text]

Thesis (doctoral)--Universität Basel, 1999. / Includes bibliographical references and index.

Thesis (doctoral)--Universität Basel, 1999. / Includes bibliographical references and index.

Zugl.: Braunschweig, Techn. Univ., Diss., 2009 / Includes bibliographical references.

1 Abstract Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy Student: Olga Krupová Supervisor: PharmDr. Tomáš Siatka, CSc. Title of diploma thesis: Modern phytotherapy - revision of usage of medicinal plants according to clinical trials Key words: phytotherapy, medicinal plants, liver diseases, painful joints, nervousness and insomnia, clinical trials The aim of diploma thesis was to review the said effects of the herbs, to make a list of herbs used in popular traditional medicine of selected diseases and to verify their use by giving documented evidence. This thesis addresses in detail three ranges of problems in which the use of herbal therapy could be considered. Following three ranges of problems were selected: liver diseases, painful joints, nervousness and insomnia. Clinical studies were explored to substantiate the effects of individual herbs or their substances. Preclinical studies were used in case of deficiency in clinical studies. The outcome of this thesis was to approve or - on the contrary - to disapprove the effects quoted by the use of folk medicine herbs. From the result of this thesis it emerges, that not all popular quoted herbal indications are verified by sufficient evidence. However, for a considerable part of the quoted herbs their effects were...

Submitted by GUILHERME RODRIGUES TEODORO null (guilhermerte@uol.com.br) on 2016-03-18T16:38:35Z No. of bitstreams: 1 Tese versao final guilherme em pdf.pdf: 1687373 bytes, checksum: 7ecfd9e5312d17f5c4885c915efc1671 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-03-21T20:00:16Z (GMT) No. of bitstreams: 1 teodoro_gr_dr_sjc.pdf: 1687373 bytes, checksum: 7ecfd9e5312d17f5c4885c915efc1671 (MD5) / Made available in DSpace on 2016-03-21T20:00:16Z (GMT). No. of bitstreams: 1 teodoro_gr_dr_sjc.pdf: 1687373 bytes, checksum: 7ecfd9e5312d17f5c4885c915efc1671 (MD5) Previous issue date: 2016-02-04 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O objetivo deste estudo foi avaliar a efetividade frente a Candida albicans da fração enriquecida em fenólicos (FE) das folhas de Buchenavia tomentosa além das substâncias ácido gálico (AG), corilagina, kaempferol e vitexina, substâncias fenólicas que foram previamente detectadas no extrato aquoso de B. tomentosa livres ou encapsuladas em ciclodextrinas. Para tal, foi realizado teste de microdiluição com cepas padrão e isolados clínicos e análise química da FE por espectrometria de massa (ESI-MS). Detectou-se que o extrato acetônico foi a FE e AG foi a substância fenólica mais eficiente contra C. albicans. O efeito de FE e AG contra os fatores de virulência de C. albicans foram analisados. FE e AG foram encapsulados em 2-hidroxipropil-beta-ciclodextrina e tiveram sua análise química realizada. As CIMs e CFMs dos encapsulados foram determinadas, porém apenas o AG encapsulado teve sua ação anti-biofilme e in vivo verificadas. A citotoxicidade de AG e FE livres e encapsulados foi determinada. As CIMs variaram de 5,0 e 0,625 mg/ml para o ácido gálico e 2,5 e 0,019 mg/ml para FE. AG e as outras moléculas foram encontradas na FE. Não foram encontrados CFMs. Os fenólicos estudados também foram encontrados em FE por ESI/MS. Tanto FE quanto AG tiveram efeito direto nos fatores de virulência de C. albicans, exceto sobre a secreção de exoenzimas. Não houve diferença na CIM entre as substâncias livres e encapsuladas. AG encapsulado teve melhor ação anti-biofilme do sua forma livre. Foi verificada melhora clínica de lesões eritematosas no palato de ratos, porém não foi possível. A citotoxicidade das substâncias livres ou encapsuladas variou de moderava a leve para FE e foi moderada para AG. Após as análises, observou-se o efeito anti-C. albicans de FE e AG. AG encapsulado apresentou promissor efeito anti-biofilme e aparente melhora clínica nas lesões sugestivas de candidose eritematosa na mucosa palatar dos ratos. / The aim of this study was to evaluate the effectiveness against Candida albicans of fraction enriched in phenolic (FE) of Buchenavia leaves tomentosa beyond substances gallic acid (GA), corilagin, kaempferol and vitexin, phenolic substances previously detected in the aqueous extract of B. tomentosa, free or encapsulated in cyclodextrins. Microdilution test with standard strains and clinical isolates besides the chemical analysis of FE by mass spectrometry (ESI-MS) were carried out. The acetone extract was the FE and AG was the most efficient phenolic substance against C. albicans. The effect of FE and AG against the virulence factors of C. albicans was also analyzed. FE and AG were encapsulated into 2-hydroxypropyl-beta-cyclodextrin (HP-β-CD) and had their chemical analyses made. MICs and MFCs of encapsulated have been determined. Solely the GA encapsulated had its anti-biofilm and in vivo action verified. Cytotoxicity of free and encapsulated GA and FE were determined. The MIC ranged from 5,0 to 0,625 mg/ml for GA and 2,5 and 0,019 mg/ml for FE. MFCs values were not found. All phenolics molecules were found in FE by ESI/MS. AG and FE had a direct effect on virulence factors of C. albicans, except on the secretion of exoenzymes. There was no difference in the CIM between free and encapsulated substances. The anti-biofilm effect was better in GA encapsuladed than its free form. A clinical improvement of sugestives erythematous lesions on the palate of rats was observed, although the hyphaes were not found in the palatar mucosa. The cytotoxicity for all substances was moderated. After the analysis, we observed the anti-C. albicans effect of GA and FE. AG encapsulated showed promising anti-biofilm effect and apparent clinical improvement in lesions suggestive of erythematous candidiasis in palatar mucosa of rats. / FAPESP: 2012/16805-5 / FAPESP: 2013/00037-1 / CAPES - PDSE: 99999.000217/2014-00

Submitted by LUCAS DE PAULA RAMOS null (lucas93paula@hotmail.com.br) on 2017-01-20T14:09:20Z No. of bitstreams: 1 Dissertação (correções biblioteca).pdf: 4172563 bytes, checksum: 3cfab803e9b5a294021bdd02082d4128 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2017-01-24T17:04:02Z (GMT) No. of bitstreams: 1 ramos_lp_me_sjc.pdf: 4172563 bytes, checksum: 3cfab803e9b5a294021bdd02082d4128 (MD5) / Made available in DSpace on 2017-01-24T17:04:02Z (GMT). No. of bitstreams: 1 ramos_lp_me_sjc.pdf: 4172563 bytes, checksum: 3cfab803e9b5a294021bdd02082d4128 (MD5) Previous issue date: 2016-12-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo do trabalho foi investigar se os extratos de Pfaffia paniculata K. e Juglans regia L. possuem ação antifúngica, antibacteriana e toxicidade celular, com testes in vitro. Para os testes antifúngicos foram utilizadas cepas ATCC de Candida spp., e para os testes antibacterianos foram utilizadas cepas ATCC de Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans e Pseudomonas aeruginosa. Para a atividade antimicrobiana primeiramente foram determinados os valores da Concentração Inibitória Mínima (CIM) e da Concentração Microbicida Mínima (CMM) dos extratos pelo método de microdiluição em caldo, segundo Clinical and Laboratory Standards Institute (CLSI). Os micro-organismos que apresentaram CMM foram selecionados para os testes em biofilme, no qual foi preparado em fundo de placa com 96 poços, por 48 h. Após os biofilmes foram tratados por 5 min. utilizando as concentrações de 200, 100 e 50 mg dos extratos. Para mensuração da biomassa foi utilizado o teste de Cristal violeta (CV), e para avaliar a atividade metabólica foi utilizado o teste de MTT. A citotoxicidade foi avaliada sobre fibroblastos gengivais humanos (FMM-1) utilizando os mesmos parâmetros de tratamento utilizados para os testes em biofilmes. Foram avaliadas a viabilidade celular pelos testes de MTT, vermelho neutro e cristal violeta. Os dados obtiveram distribuição normal e foram analisados por ANOVA e teste de Tukey, com significância de 5% (p<0.05%). O extrato de P. paniculata demostrou ação antifúngica em biofilmes, com reduções médias de 29,4 e 42,7% nos testes de CV e MTT. Já a ação antibacteriana foi restrita a S. mutans e P. aeruginosa com reduções médias de 15,7 e 28,6% nos respectivos testes. O extrato de J. regia também demostrou ação antifúngica com redução média de 22,2% na biomassa e 31,4% na atividade metabólica. A ação antimicrobiana ficou restrita a P. aeruginosa com reduções médias de 17,7 e 15,6%, indicados pelos testes de CV e MTT. Quanto a citotoxicidade, a média entre os três testes realizados, indicou que após exposição ao extrato de P. paniculata 58,8% das células continuaram viáveis e para J. regia a viabilidade foi de 65,1%. Conclui-se queo extrato de P. paniculata demostrou ação antifúngica sobre todas as cepas de Candida spp. testadas e demostrou ação antibacteriana para P. aeruginosa e S. mutans. As concentrações de 200, 100 e 50 mg do extrato demostraram ser citotóxicas conforme nova diretriz de toxicidade. J. regia demostrou ação antifúngica sobre todas as cepas de Candida spp. testadas e demostrou ação antibacteriana sobre P. aeruginosa. Apenas a concentração de 200 mg do extrato se mostrou tóxica a FMM-1. / The aim of this study was to investigate whether extracts of Pfaffia paniculata K. and Juglans regia L. have antifungal, antibacterial and cellular toxicity, with in vitro tests. ATCC strains of Candida spp. Were used for antifungal tests, and ATCC strains of Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans and Pseudomonas aeruginosa were used for the antibacterial tests. For the antimicrobial activity, the values of the Minimum Inhibitory Concentration (MIC) and the Minimal Microbicidal Concentration (CMM) of the extracts were determined by the microdilution method in broth, according to Clinical and Laboratory Standards Institute (CLSI). The microorganisms that presented CMM were selected for the biofilm tests, in which it was prepared on a 96-well plate bottom for 48 h. After the biofilms were treated for 5 min. Using the concentrations of 200, 100 and 50 mg of the extracts. To measure the biomass, the Violet Crystal test (CV) was used, and the MTT test was used to evaluate the metabolic activity. Cytotoxicity was assessed on human gingival fibroblasts (FMM-1) using the same treatment parameters used for biofilm tests. Cell viability was evaluated by the MTT, neutral red and violet crystal tests. The data obtained normal distribution and were analyzed by ANOVA and Tukey test, with significance of 5%. The extract of P. paniculata showed antifungal action in biofilms, with average reductions of 29.4 and 42.7% in CV and MTT tests; The antibacterial action was restricted to S. mutans and P. aeruginosa with mean reductions of 15.7 and 28.6% in the respective tests. The extract of J. regia also demonstrated antifungal action with an average reduction of 22.2% in biomass and 31.4% in metabolic activity. The antimicrobial action was restricted to P. aeruginosa with mean reductions of 17.7 and 15.6%, indicated by CV and MTT tests. As for cytotoxicity, the mean of the three tests carried out indicated that after exposure to P. paniculata extract 58.8% of the cells remained viable and for viability the viability was 65.1%. In conclusion the extract of P. paniculata showed antifungal action on all strains of Candida spp. Tested and demonstrated antibacterial action for P. aeruginosa and S. mutans. The concentrations of 200, 100 and 50 mg of the extract proved to be cytotoxic according to the new toxicity guideline. J. regia demonstrated antifungal action on all strains of Candida spp. Tested and demonstrated antibacterial action on P. aeruginosa. Only the 200 mg concentration of the extract was shown to be toxic to FMM-1.