Thesis (M.S.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains viii, 52 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 45-47).

Thesis (Ph. D.)--University of Nevada, Reno, 2008. / "August 2008." Includes bibliographical references. Online version available on the World Wide Web.

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Orientador: Carlos Frederico de Oliveira Graeff / Banca: Wendel Andrade Alves / Banca: Francisco Carlos Lavarda / O Programa de Pós-Graduação em Ciência e Tecnologia de Materiais, PosMat, tem carater institucional e integra as atividades de pesquisa em materiais de diversos campi da Unesp / Resumo: O óxido nítrico (NO) é um radical livre com inúmeras funções fisiológicas, tais como regulação da pressão sanguínea e sistema nervoso. O desenvolvimento de Sistemas de Liberação Controlada (SLC) de NO no organismo são de grande importância em tratamentos de diversas patologias, bem como para a indústria farmacêutica. A espectroscopia de ressonância paramagnética (RPE) foi utilizada para detecção e caracterização da taxa de liberação de NO. Esta é uma técnica amplamente utilizada no estudo de entes paramagnéticos existentes em sistemas biológicos. Os SLCs de NO foram desenvolvidos a partir da incorporação do agente aprisionador de NO, FeDETC, nas matrizes biocompatíveis de látex e siloxanopoli(oxipropileno) (PPO). O foco deste trabalho é obter membranas para liberação controlada de NO que sejam capazes de liberar NO localmente através de estímulos externos. A matriz de PPO apresentou forte sinal de NO, resistência mecânica e estabilidade igual às melhores matrizes sólidas já obtidas em nosso laboratório. Mantendo a matriz de PPO em ambiente sem iluminação e à temperatura ambiente, o NO permanece aprisionado ao FeDETC por até 45 dias nas primeiras sínteses e 33 dias nas últimas sínteses. Em experimentos feitos com a matriz de látex foi observado que o NO permanece complexado ao FeDETC até 61 dias e 45 dias para amostras estocadas no escuro à temperatura ambiente e sob temperatura de 50C. Em ambas matrizes, foi observado que a taxa de liberação de NO do sistema pode também ser acelerada através da aplicação de um campo magnético ou através do aumento de temperatura. Estas características fazem do PPO e látex , matrizes ideais para construção de SLCs de NO. / Abstract: Nitric oxide (NO) is a free radical species with multiples physiological functions, such as the regulation of blood pressure and nervous system. The development of drug delivery systems (DDS) of NO in the body are of great importante in the treatment of varios diseases, as well as for the pharmaceutical industry. Electron Paramagnetic Resonance (EPR) technique, was used for NO detection and characterization of the NO delivery kinetics. This is a technique widely used in the study of paramagnetic entities existing in biological systems. NO DDSs were developed based in trap FeDETC incorporated in siloxane-poly(oxypropylene) (PPO) and latex biocompatible matrix. The focus of this work is to obtain membranes for controlled release of NO that are able to release NO locally by external stimuli. The PPO400 and PPO2000 DDS presents a stronger EPR signal, strength and highest stability, equal to the best solid matrices already obtained in our laboratory, e. g. latex matrix. Keeping the matrix in PPO enviromment without lighting and temperature, the NO remains trapped in FeDETC for up to 45 days in the first synthesis and summaries for the last 33 days. In experiments made with the latex matrix was observed that NO remains trapped in FeDETC until 61 or 45 days for samples stored in the dark at room temperature and samples left at the greenhouse 50C. In both matrices was observed that the kinetics of NO release of NO release of the system can also be accelerated by applying modulated magnetic field of 40G or by increasing temperature. These characteristics make the PPO and latex, matrices ideal for building DDS NO. / Mestre

Made available in DSpace on 2014-06-11T19:23:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-06-14Bitstream added on 2014-06-13T18:20:00Z : No. of bitstreams: 1 croce_gb_me_botfmvz.pdf: 1461373 bytes, checksum: 7de79400775b5c3b2032c8bc6d2c33c4 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Lesões pré-neoplásicas da próstata humana foram descritas como neoplasia intraepitelial prostática (PIN) e atrofia inflamatória proliferativa (PIA) e são importantes no diagnóstico precoce do câncer. Nos caninos a PIN foi descrita pela primeira vez por Waters & Bostwick (1997) e nosso grupo de estudo de próstata canina reconheceu a alta freqüência de PIA. A relação funcional entre inflamação e câncer não é nova. O estresse oxidativo crônico resulta em peroxidação de lipídeos e geração de outros produtos com potencial de dano ao DNA. Este trabalho teve por objetivo avaliar a expressão de óxido nítrico (iNOS-2) agente envolvido no desenvolvimento de atipias no epitélio prostático, correlacionando-o com a imunomarcação dos genes “protetores” como p53 e GSTP-1, para tal, foram coletadas próstatas de cães encaminhados ao Serviço de Patologia Veterinária da FMVZ – UNESP, Botucatu e da Escola de Veterinária, UFG, Goiânia, GO, tendo sido estas pesadas, medidas, clivadas, processadas, coradas pelo método de Hematoxilina e eosina, submetidas à técnica de imunoistoquímica, para os anticorpos iNOS-2, GSTP-1 e p53. Os cinco grupos de diagnósticos foram estabelecidos sendo: Grupo I: Animais com próstatas normais; Grupo II: Animais com hiperplasia prostática; Grupo III: Animais com PIN; Grupo IV: Animais com PIA, Grupo V: Animais com prostatite; Grupo VI: Animais com adenocarcinoma prostático. Os resultados foram tabulados por grupo diagnóstico e submetidos ao teste estatístico de Tuckey. Os objetivos do presente trabalho consistem em avaliar o papel de óxido nítrico como causador de lesão genotóxica no epitélio prostático atípico, neoplásico, normal e hiperplásico e sua correlação com genes protetores como o p53 e GSTP-1, avaliar e quantificar a imunomarcação do óxido nítrico nas hiperplasias prostáticas, neoplasia intra-epitelial... / Preneoplastic lesions of human prostate were described as prostatic intraepithelial neoplasia (PIN) and proliferative inflammatory atrophy (PIA) and are very important in early diagnosis of cancer. PIN in dogs was first described by Waters & Bostwick (1997) and our study group of canine prostate recognized the high incidence of PIA. A relação funcional entre inflamação e câncer não é nova. The functional relationship between inflammation and cancer is not new. The chronic oxidative stress results in lipid peroxidation and generation of products with potential for DNA damage. This study aimed to evaluate the expression of nitric oxide (iNOS-2) agent involved in the development of atypical epithelium in the prostate, correlating it with the immunostaining of protectors genes as p53 and GSTP-1, for this purpose were collected prostates from dogs sent to the Department of Veterinary Pathology of FMVZ - UNESP, Botucatu and the School of Veterinary Medicine, UFG, Goiânia, GO, they were weighed, measured, cleaved, processed and stained with hematoxylin and eosin, subjected to immunohistochemistry for the iNOS antibody-2, GSTP-1 and p53. Five groups of diagnoses were established: Group I: animals with normal prostates, Group II: Animals prostatic hyperplasia, Group III: Animals with PIN, Group IV: Animals with PIA, Group V: Animals with prostatitis, Group VI: Animals with prostatic adenocarcinoma. The results were tabulated by diagnostic group and subjected to statistical analysis (Tuckey Test). The purpose of this study are to assess role of nitric oxide to cause genotoxic damage in prostatic epithelial atypical neoplastic, normal and hyperplastic and its correlation with protective genes such as p53, and GSTP-1, evaluate and quantify the immunostaining of nitric oxide in prostatic hyperplasia, prostatic intraepithelial neoplasia (PIN), proliferative inflammatory atrophy (PIA)... (Complete abstract click electronic access below)

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Estudos recentes, realizados no LFE da UFC, mostraram que o extrato aquoso da planta Alpinia zerumbet (Pers.) Burtt. et Smith (EaAz), conhecida popularmente como colÃnia, causa atividade vasodilatadora na aorta torÃcica isolada de rato. Objetivando encontrar o principio ativo desta planta, o EaAz foi fracionado com diferentes solventes e a atividade vasodilatadora das fraÃÃes foi avaliada em anÃis da aorta torÃcica isolada de rato. AlÃm disso, o mecanismo de aÃÃo da fraÃÃo acetato de etila obtida a partir do EaAz foi caracterizado. Ratos machos Wistar (250 a 300 g), oriundos do biotÃrio da UFC, foram sacrificados por deslocamento cervical e a aorta torÃcica removida e dissecada. Montaram-se os anÃis da aorta (4 a 5 mm) em cÃmeras orgÃnicas, contendo soluÃÃo de Krebs, aeradas com carbogÃnio e mantidas a 37ÂC, para a medida de variaÃÃes na tensÃo isomÃtrica. A integridade do endotÃlio foi avaliada utilizando-se a acetilcolina (ACh; 10-5 M) e, posteriormente, o EaAz e as fraÃÃes obtidas do EaAz, hexÃnica (FHxAz), acetato de etila (FAmAz), diclorometano (FDmAz) (0,15; 0,5; 1,5; 5; 15 e 50 g/mL) foram testados em preparaÃÃes contraÃdas com fenilefrina (Phe; 10-8 â 3x10-8 M). A fraÃÃo FAmAz, ACh e nitroprussiato de sÃdio foram testados em preparaÃÃes desprovidas de endotÃlio e tratadas com L-NAME (100 M), caribdotoxina (CTX; 100nM) mais apamina (100 nM), ODQ (30 M), catalase (500 U/mL), superÃxido dismutase (SOD; 500 U/mL) e PEG-catalase (500 U/mL). O EaAz e as fraÃÃes FHxAz e FAmAz foram capazes de relaxar, significativamente, a aorta torÃcica isolada de rato, apresentando os respectivos EC50 19,73, 11,15 e 9,08 (n = 5, 5 e 7, respectivamente, para cada grupo). Contudo, a fraÃÃo FDmAz nÃo apresentou atividade vasodilatadora. Depois, caracterizou-se a resposta vasodilatadora da fraÃÃo FamAz, resposta essa que foi abolida em preparaÃÃes desprovidas de endotÃlio e tratadas com L-NAME (n = 5), ODQ (n = 6) e PEG-Catalase (n = 2). Contudo, o efeito vasodilatador da fraÃÃo FAmAz permaneceu inalterado apÃs tratamento com CTX mais apamina, catalase e SOD na aorta torÃcica de rato (n = 5, 6 e 6, respectivamente, para cada grupo). Segundo nossos resultados, as fraÃÃes FAmAz e FHxAz apresentaram uma maior potÃncia na sua atividade vasodilatadora comparada ao EaAz. Este dado sugere que estas fraÃÃes, possivelmente, contÃm os princÃpios ativos responsÃveis pela atividade vasodilatadora do EaAZ. AlÃm disso, concluiu-se que a atividade vasodilatadora produzida pela FAmAz na aorta torÃcica de rato à dependente do endotÃlio e via NO-GMPc, talvez contando com a participaÃÃo das espÃcies reativas do oxigÃnio ao nÃvel intracelular / Recent studies conducted at the LFE showed that the aqueous extract from Alpinia zerumbet (Pers.) Burtt. et Smith (EaAz), popularly known as ColÃnia, causes vasodilation on isolated rat aortic rings. In order to find the active compound, the EaAz was diluted with different solvents and the vasodilator effect from the different fractions was analyzed on isolated rings of rat aorta. Additionally, the mechanism of action of the ethyl acetate fraction obtained from EaAz was characterized. Male rats Wistar (250 to 300g), provided by the vivarium of UFC, were terminated by cervical dislocation and the thoracic aorta was removed and dissected. The aortic rings (4 to 5 mm) were placed in chambers, which contained Krebs solution and carbogen and were kept at 37o C, in order to measure isometric tension variation. The endothelium integrity was assessed with acetylcholine (ACh; 10-5 M). Afterwards, the EaAz and the other fractions obtained from EaAz, hexane (FHxAz), ethyl acetate (FAmAz), dichloromethane (FDmAz) (0,15; 0,5; 1,5; 5; 15 and 50 g/mL) were tested in preparations that contained phenylephrine (Phe; 10-8 â 3x10-8 M). The FAmAz fraction, ACh and sodium nitroprussiate (SNP; 10-8 M) were tested in preparations without endothelium and treated with L-NAME (100 M), charybdotoxin (CTX; 100nM) plus apamine (100 nM), ODQ (30 M), catalase (500 U/mL), superoxide dismutase (SOD; 500 U/mL) and PEG-catalase (500 U/mL). The EaAz and the FHxAz and FAmAz fractions were able to relax significantly the isolated rat aortic rings, and EC50 was respectively 19,73, 11,15 and 9,08 (n = 5, 5 and 7, respectively, for each group). However, the FDmAz fraction did not present vasodilator activity. The vasodilatory effect of the FAmAz fraction was characterized. The vasodilator activity of the FAmAz fraction was impaired in preparation without endothelium and previously treated with L-NAME (n = 5), ODQ (n = 6) and PEG-Catalase (n = 2). However, the vasodilator activity of the FAmAz fraction remained unchanged after treatment with CTX plus apamin, catalase and SOD on the isolated rat aortic rings (n = 5, 6 and 6, respectively, for each group). The FAmAz and FHxAz fractions presented higher potency in their activity when compared to EaAz. This phenomenon suggests that these fractions possibly contain the active compound responsible for the EaAZ vasodilator effect. In addition, it was concluded that the vasodilator effect caused by the FAmAz fraction on the isolated rat aortic ring is endothelium-dependent and via NO-cGMP. We also believe that the intracellular reactive oxygen species play an important role on the vasodilator mechanism

Orientador: Antonio Condino Neto / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T16:31:53Z (GMT). No. of bitstreams: 1 OliveiraJunior_EdgarBorgesde_M.pdf: 512340 bytes, checksum: d83efc345a2ad7f2aecfc60038e38380 (MD5) Previous issue date: 2006 / Resumo: Investigamos os efeitos do BAY 41-2272 (5-cyclopropyl-2- [1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine) sobre a atividade do sistema NADPH (nicotinamide adenine dinucleotide phosphate) oxidase e expressão do gene CYBB que codifica seu componente principal, a proteína gp91-phox , simultaneamente aos níveis intracelulares de GMPc (cyclic guanosine-3', 5'-monophosphate) e AMPc (cyclic adenosine-3', 5'-monophosphate) em células mielomonocíticas humanas THP-1. ... Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da dissertação digital / Abstract: We investigated the effects of the BAY 41-2272 (5-cyclopropyl-2- [1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b] pyridin-3-yl]-pyrimidin-4-ylamine) on the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase system, gene expression of gp91-phox, cGMP (cyclic guanosine-3', 5'-monophosphate) levels, and cAMP (cyclic adenosine-3', 5'-monophosphate) levels, in the human myelomonocytic THP-1 cells. ... Note: The complete abstract is available with the full electronic digital dissertation / Mestrado / Mestre em Farmacologia

Background: Inhaled Nitric Oxide (iNO) functions as a selective pulmonary vasodilator. It is an expensive treatment that is often employed as rescue therapy for refractory hypoxaemia in acute respiratory distress syndrome (ARDS) and pulmonary hypertension (PHT) following cardiac surgery. Objectives: To describe the response to treatment with iNO. Secondary observations were deaths, comorbidities of the patients treated, lengths of treatment and admission, and the cost of treatment. Methods: A retrospective descriptive study of all patients treated with iNO in the Paediatric Intensive Care Unit (PICU) at Red Cross War Memorial Children’s Hospital (RCWMCH) from 2011- 2015. Results: A total of 140 patients were treated with iNO during this time period, 82 were for PHT following cardiac surgery, 53 for ARDS and 5 for PPHN. A response to treatment was observed in 64% of the cohort as a whole, 80% of those with PPHN, 67% of those with PHT post-cardiac surgery, and 64% of those with ARDS. A longer duration of ICU and hospital admission, and higher in hospital mortality (53%) was seen in the group with ARDS, in particular those with adenoviral infection (63%), when compared to patients treated for PHT (18%) and for PPHN (20%). There is no protocol in place guiding the use of iNO in our unit, and it was found that response to treatment was not being objectively measured and documented and that practise varied between clinicians. Conclusions: Considering the cost of treatment and lack of evidence to support beneficial effects of iNO therapy, its continued use in our resource poor setting should be guided by protocol.

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