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Id: biblio-972053
Autor: Campelo, Marcio Wilker Soares.
Título: Efeitos do nitrosil rutênio na lesão cerebral induzida porisquemia e reperfusão em ratos.
Fonte: Fortaleza; s.n; 2016. 69 p. ilus.
Idioma: pt.
Tese: Apresentada a Universidade Federal do Ceará para obtenção do grau de Mestre.
Resumo: Efeitos do nitrosil rutênio na lesão cerebral induzida por isquemia e reperfusão em ratos. MARCIO WILKER SOARES CAMPELO. Pós-Graduação Stricto Sensu do Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Ceará (Grau de Mestre em Cirurgia). Novembro, 2009. Orientador: Prof. Dr. Paulo Roberto Leitão de Vasconcelos. Introdução e objetivo: Doadores de NO podem diminuir a lesão neuronal durante a isquemia e reperfusão cerebral (I/R) por aumento do fluxo sanguíneo cerebral. O objetivo deste estudo é avaliar se um novo complexo de nitrosilo complexo de rutênio (Rut-bpy) capaz liberar NO direto na musculatura lisa vascular apresenta algum efeito durante I/R. Método: Foram utilizados 96 ratos machos, da linhagem Wistar, com peso médio de 290.27 g, distribuídos em 2 fases com 8 grupos cada: Fase de isquemia 4 grupos sham (SF, Rut-bpy,L-NAME e L-NAME+Rut-bpy) e 4 grupos isquemia (SF, Rut-bpy,L-NAME e L-NAME+Rut-bpy); da mesma forma foi dividido a fase de reperfusão ( 4 grupos sham e 4 grupos isquemia/reperfusão) com as mesmas drogas teste da fase de isquemia. Foi utilizado um modelo de isquemia cerebral global incompleta, com oclusão da artéria carótida comum bilateral e administração do SF, Rut-bpy e L-NAME via intraperitoneal. No final do experimento os animais foram decapitados e o cérebro fatiado para ser avaliado à área de lesão por histoquímica. Durante todo o experimento a PAM dos animais foi monitorizada...

Effects of nitrosyl ruthenium in injury brain induced by ischemia and reperfusion of rats.MARCIO WILKER SOARES CAMPELO. Stricto SensuPost-graduation. Department of Surgery, Medicine School, Federal University of Ceará (Degree of Master of Surgery). November, 2009. Advisor: Prof. Dr. Paulo Roberto Leitão de Vasconcelos. Background and purpose - Nitric oxide (NO) donors are known to reduce neuronal damage during brain ischemia and reperfusion by increasing the blood flow. Rut-bpy is a novel nitrosyl-ruthenium complex releasing NO directly into the vascular smooth musculature. The objective of the study was to evaluate the effect of Rut-bpy on a rat model of brain ischemia and reperfusion. Methods - Ninety-six male Wistar rats weighing approximately 290g were randomly assigned to 16 groups. Four groups and their respective sham groups were submitted to ischemia (Stage 1), while four groups and their respective sham groups were submitted to ischemia + reperfusion (Stage 2). At each stage of the experiment the groups were treated pairwise with saline solution (SS), Rut-bpy, L-NAME and L-NAME+Rut-bpy, respectively. The study was based on an incomplete global brain ischemia model with occlusion of the common bilateral carotid arteries and intraperitoneal administration of the study drugs. Following the experiment the animals were decapitated and the brain was sectioned for histochemical evaluation of the area of damage. The mean arterial blood pressure (MABP) was monitored throughout the experiment...
Descritores: Isquemia Encefálica
Estresse Oxidativo
Óxido Nítrico
Compostos de Rutênio
Limites: Humanos
Responsável: BR6.1 - BCS - Biblioteca de Ciências da Saúde
BR6.1


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Id: biblio-847714
Autor: Costa, Iguatinã de Melo.
Título: Estudo de propriedades físico-químicas de metalofármacos de dirutênio com anti-inflamatórios não esteroides / Study of physico-chemical properties of diruthenium metallodrugs with non-steroidal anti-inflammatory drugs.
Fonte: São Paulo; s.n; 2014. 127p p. tab, graf, ilus.
Idioma: pt.
Tese: Apresentada a Universidade de São Paulo. Instituto de Química para obtenção do grau de Doutor.
Resumo: Complexos de rutênio, em razão da menor toxicidade e por poderem exibir atividade citotóxica ou antimetastática, tem sido considerados como alternativas potencialmente promissoras aos complexos de platina para tratamento de câncer. Nosso grupo de pesquisa tem investigado a interação de íons metálicos com fármacos anti-inflamatórios não esteroides (FAINEs) e já obteve sucesso na preparação de metalofármacos de dirutênio(II,III)-FAINEs, os quais se mostraram promissores com relação à atividade frente a modelos de glioma. Com a finalidade de contribuir para o entendimento das propriedades físico-químicas desses complexos, o presente trabalho teve como principal objetivo analisar propriedades consideradas particularmente essenciais a um potencial candidato a fármaco, tais como, estabilidade no estado sólido, lipofilicidade, solubilidade aquosa e dissolução intrínseca. Um complexo inédito de fórmula [Ru2Cl(feno)4], em que feno = fenoprofenato, foi sintetizado e caracterizado por meio de análise elementar, espectroscopia eletrônica, espectroscopia vibracional, difratometria de raios X, análise térmica e espectrometria de massas. Os complexos já testados anteriormente para atividade biológica, [Ru2Cl(ibp)4], ibp = ibuprofenato, e [Ru2(cet)4Cl], cet = cetoprofenato, foram analisados quanto à estabilidade no estado sólido por meio da determinação isotérmica de variação de massa. As lipofilicidades desses dois complexos, juntamente com a dos fármacos de origem e a do precursor sintético [Ru2(O2CH3)4Cl], foram avaliadas pelo método shake flask, e suas solubilidade aquosas foram investigadas em presença de co-solventes alcoólicos. Investigou-se ainda a velocidade de dissolução intrínseca do [Ru2Cl(ibp)4] que se encontra em estágio avançado de estudos biológicos. Os resultados obtidos trazem novas informações sobre o comportamento térmico dos complexos e sobre suas características biofarmacêutica

Ruthenium complexes, mainly due to the lower toxicity and the cytotoxic and anti-metastatic activities, have been considered as potentially promising alternatives to platinum drugs for cancer treatment. Our research group has investigated the interactions of diruthenium metal cores with anti-inflammatory non-steroidal drugs (NSAIDs) and succeeded in preparing diruthenium(II,III)-NSAIDs metallodrugs which show promising activity against glioma models. With the aim of elucidating the physico-chemical properties of these complexes, the major objective of the present work was to investigate properties which are considered as essential for a potential candidate to drug, e.g., stability in the solid state, lipophilicity, aqueous solubility and intrinsic dissolution. A new complex of formula [Ru2Cl(feno)4], where feno = fenoprofen, was synthesized and characterized by elemental analysis, electronic spectroscopy, vibrational spectroscopy, X-rays difractommetry, thermal analysis and mass spectrometry. The complexes previously tested for biological properties, [Ru2Cl(ibp)4], ibp = ibuprofenate, and [Ru2(cet)4Cl], cet = cetoprofenate, were inv estigated for the stability in the solid state by isothermal thermogravimetry. The lipophilicity of the se complexes, as well as those of the parent drugs and of the precursor [Ru2(O2CH3)4Cl], was evaluated by the shake flask method, and their aqueous solubility in the presence of alcohol co-solvents was investigated. In addition, the intrinsic dissolution rate was determined for [Ru2Cl(ibp)4], which is undergoing advanced biological studies. The results provide important new information on the thermal behavior of the complexes and also on their biopharmaceutical propertie
Descritores: Anti-Inflamatórios não Esteroides/efeitos adversos
-Análise Diferencial Térmica/métodos
Dissolução/análise
Propriedades Físicas e Químicas
Compostos de Rutênio/análise
Rutênio/análise
Solubilidade
Responsável: BR40.1 - DBD - Divisão de Biblioteca e Documentacão do Conjunto das Químicas
BR40.1; T546, C837e. 30100025344-Q


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Moraes, Maria Elisabete Amaral de
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Id: lil-655997
Autor: Cerqueira, João Batista Gadelha de; Gonzaga-Silva, Lúcio Flávio; Silva, Francisco Ordelei Nascimento da; Cerqueira, João Victor Medeiros de; Oliveira, Ricardo Reges Maia; Moraes, Maria Elisabete Amaral de; Nascimento, Nilberto Robson Falcão do.
Título: Identification of mechanisms involved in the relaxation of rabbit cavernous smooth muscle by a new nitric oxide donor ruthenium compound
Fonte: Int. braz. j. urol;38(5):687-694, Sept.-Oct. 2012. ilus.
Idioma: en.
Resumo: PURPOSE: The aim of this study was to evaluate the relaxation in vitro of cavernous smooth muscle induced by a new NO donor of the complex nitrosil-ruthenium, named trans-[Ru(NH3)4(caffeine)(NO)]C13 (Rut-Caf) and sodium nitroprusside (SNP). MATERIALS AND METHODS: The tissues, immersed in isolated bath systems, were pre-contracted with phenilephrine (PE) (1 µM) and then concentration-response curves (10-12 - 10-4 M) were obtained. To clarify the mechanism of action involved, it was added to the baths ODQ (10 µM, 30 µM), oxyhemoglobin (10 µM), L-cysteine (100 µM), hydroxicobalamine (100 µM), glibenclamide, iberotoxin and apamine. Tissue samples were frozen in liquid nitrogen to measure the amount of cGMP and cAMP produced. RESULTS: The substances provoked significant relaxation of the cavernous smooth muscle. Both Rut-Caf and SNP determined dose-dependent relaxation with similar potency (pEC50) and maximum effect (Emax). The substances showed activity through activation of the soluble guanylyl cyclase (sGC), because the relaxations were inhibited by ODQ. Oxyhemoglobin significantly diminished the relaxation effect of the substances. L-cysteine failed to modify the relaxations caused by the agents. Hydroxicobalamine significantly diminished the relaxation effect of Rut-Caf. Glibenclamide significantly increased the efficacy of Rut-Caf (pEC50 4.09 x 7.09). There were no alterations of potency or maximum effect of the substances with the addition of the other ion channel blockers. Rut-Caf induced production of significant amounts of cGMP and cAMP during the relaxation process. CONCLUSIONS: In conclusion, Rut-Caf causes relaxation of smooth muscle of corpus cavernosum by means of activation of sGC with intracellular production of cGMP and cAMP; and also by release of NO in the intracellular environment. Rut-Caf releases the NO free radical and it does not act directly on the potassium ion channels.
Descritores: Relaxamento Muscular/fisiologia
Músculo Liso/efeitos dos fármacos
Doadores de Óxido Nítrico/farmacologia
Nitroprussiato/farmacologia
Compostos de Rutênio/farmacologia
-GMP Cíclico/biossíntese
GMP Cíclico/química
Cisteína/farmacologia
Guanosina Monofosfato/biossíntese
Guanosina Monofosfato/química
Músculo Liso/fisiologia
Doadores de Óxido Nítrico/química
Nitroprussiato/química
Canais de Potássio/química
Compostos de Rutênio/química
Fatores de Tempo
Limites: Animais
Masculino
Coelhos
Responsável: BR1.1 - BIREME


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Id: lil-599673
Autor: Pereira, A. C; Paulo, M; Araújo, A. V; Rodrigues, G. J; Bendhack, L. M.
Título: Nitric oxide synthesis and biological functions of nitric oxide released from ruthenium compounds
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;44(9):947-957, Sept. 2011. ilus.
Idioma: en.
Conferência: Apresentado em: XV Simpósio Brasileiro de Fisiologia Cardiovascular, São Paulo, February 2-5, 2011.
Resumo: During three decades, an enormous number of studies have demonstrated the critical role of nitric oxide (NO) as a second messenger engaged in the activation of many systems including vascular smooth muscle relaxation. The underlying cellular mechanisms involved in vasodilatation are essentially due to soluble guanylyl-cyclase (sGC) modulation in the cytoplasm of vascular smooth cells. sGC activation culminates in cyclic GMP (cGMP) production, which in turn leads to protein kinase G (PKG) activation. NO binds to the sGC heme moiety, thereby activating this enzyme. Activation of the NO-sGC-cGMP-PKG pathway entails Ca2+ signaling reduction and vasodilatation. Endothelium dysfunction leads to decreased production or bioavailability of endogenous NO that could contribute to vascular diseases. Nitrosyl ruthenium complexes have been studied as a new class of NO donors with potential therapeutic use in order to supply the NO deficiency. In this context, this article shall provide a brief review of the effects exerted by the NO that is enzymatically produced via endothelial NO-synthase (eNOS) activation and by the NO released from NO donor compounds in the vascular smooth muscle cells on both conduit and resistance arteries, as well as veins. In addition, the involvement of the nitrite molecule as an endogenous NO reservoir engaged in vasodilatation will be described.
Descritores: Células Endoteliais/metabolismo
Doadores de Óxido Nítrico/metabolismo
Óxido Nítrico Sintase Tipo III/metabolismo
Óxido Nítrico/biossíntese
Compostos de Rutênio/metabolismo
-Endotélio Vascular/metabolismo
Hipertensão/fisiopatologia
Músculo Liso Vascular/metabolismo
Óxido Nítrico/farmacologia
Vasodilatação/fisiologia
Limites: Animais
Humanos
Ratos
Tipo de Publ: Research Support, Non-U.S. Gov't
Revisão
Responsável: BR1.1 - BIREME


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Id: lil-500400
Autor: Cerqueira, Joao B. G; Silva, Lucio F. G; Lopes, Luis G. F; Moraes, Maria E. A; Nascimento, Nilberto R. F.
Título: Relaxation of rabbit corpus cavernosum smooth muscle and aortic vascular endothelium induced by new nitric oxide donor substances of the nitrosyl-ruthenium complex
Fonte: Int. braz. j. urol;34(5):638-646, Sept.-Oct. 2008. graf.
Idioma: en.
Resumo: INTRODUCTION: Endothelial dysfunction characterized by endogenous nitric oxide (NO) deficiency made 56 percent of patients affected with erectile dysfunction decline treatment with PDE-5 inhibitors. New forms of treatment are currently being developed for this group of patients. MATERIALS AND METHODS: The study compared the effect of sodium nitroprusside (SNP) and two substances of the nitrosyl-ruthenium complex, cis-[Ru(bpy)2(SO3)(NO)]PF-6-9 ("FONO1”) and trans-[Ru(NH3)4(caffeine)(NO)]C13 ("LLNO1”) on relaxation of rabbit corpus cavernosum smooth muscle and aortic vascular endothelium. The samples were immersed in isolated baths and precontracted with 0.1 µM phenylephrine (PE) and the corresponding relaxation concentration/response curves were plotted. In order to investigate the relaxation mechanisms involved, 100 µM ODQ (a soluble guanylate cyclase-specific inhibitor), 3 µM or 10 µM oxyhemoglobin (an extracellular NO scavenger) or 1 mM L-cysteine (a nitrosyl anion-specific scavenger) was added to the samples. RESULTS: All the NO donors tested produced a significant level of relaxation in the vascular endothelium. In corpus cavernosum samples, FONO1 produced no significant effect, but LLNO1 and SNP induced dose-dependent relaxation with comparable potency (pEC50 = 6.14 ± 0.08 and 6.4 ± 0.14, respectively) and maximum effect (Emax = 82 percent vs. 100 percent, respectively). All NO donors were found to activate soluble guanylate cyclase, since the addition of the corresponding inhibitor (100 µM ODQ) completely neutralized the relaxation effect observed. The addition of oxyhemoglobin reduced the relaxation effect, but did not inhibit it completely. In aortic vascular endothelium 3 µM oxyhemoglobin decreased the relaxation effect by 26 percent on the average, while 10 µM oxyhemoglobin reduced it by over 52 percent. The addition of 100 µM L-cysteine produced no significant inhibiting effect. CONCLUSIONS: These results suggest that LLNO1...
Descritores: Aorta Torácica/efeitos dos fármacos
Músculo Liso/efeitos dos fármacos
Doadores de Óxido Nítrico/farmacologia
Nitroprussiato/farmacologia
Pênis/efeitos dos fármacos
Compostos de Rutênio/farmacologia
-Endotélio Vascular/efeitos dos fármacos
Relaxamento Muscular
Limites: Animais
Masculino
Coelhos
Tipo de Publ: Estudo Comparativo
Responsável: BR1.1 - BIREME


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Azzellini, Gianluca Camillo
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Id: lil-259475
Autor: Azzellini, Gianluca Camillo.
Título: Supramolecular effects in dentritic systems containing photoactive groups
Fonte: An. acad. bras. ciênc;72(1):34-7, mar. 2000.
Idioma: en.
Resumo: In this article are described dendritic structures containing photoactive groups at the surface or in the core. The observed supramolecular effects can be attributed to the nature of the photoactive group and their location in the dendritic architecture. The peripheric azobenzene groups in these dendrimeric compounds can be regarded as single residues that retain the spectroscopic and photochemical properties of free azobenzene moiety. The E and Z forms of higher generation dendrimer, functionalized with azobenzene groups, show different host ability towards eosin dye, suggesting the possibility of using such dendrimer in photocontrolled host-guest systems. The photophysical properties of many dendritic-bipyridine ruthenium complexes have been investigated. Particularly in aerated medium more intense emission and a longer excited-state lifetime are observed as compared to the parent unsubstituted bipyridine ruthenium complexes. These differences can be attributed to a shielding effect towards dioxygen quenching originated by the dendritic branches
Descritores: Compostos Azo/química
Dendritos/química
Compostos de Rutênio/química
-Dendritos/fisiologia
Fotoquímica
Tipo de Publ: Revisão
Responsável: BR1.1 - BIREME


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Araki, Koiti
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Id: lil-259474
Autor: Araki, Koiti; Lima, Simone de Souza; Winnischofer, Herbert.
Título: Thin molecular films of supramolecular porphyrins
Fonte: An. acad. bras. ciênc;72(1):27-32, mar. 2000.
Idioma: en.
Resumo: A relevant series of symmetric supramolecular porphyrins has been obtained by attaching four [RuII(bipy)2Cl] groups to the pyridyl substituents of meso-tetra(4-pyridyl)porphyrin and its metallated derivatives. These compounds display a rich electrochemistry and versatile catalytic, electrocatalytic and photochemical properties, associated with the ruthenium-bipyridine and the porphyrin complexes. These properties can be transferred to the electrodes by attaching thin molecular films of the compounds, by dip-coating, electrostatic assembly or electropolymerization. In this way, the interesting properties of those supermolecules and supramolecular assemblies can be used to prepare molecular devices and sensors
Descritores: Técnicas Biossensoriais/métodos
Porfirinas/química
-Técnicas Biossensoriais/métodos
Eletroquímica/métodos
Substâncias Macromoleculares
Espectrometria de Massas
Compostos de Rutênio/química
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME



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