Planejamento e estudo da viabilidade de obtenção do pró-fármaco recíproco nitrofural-alendronato potencialmente antichagásico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Síntese e avaliação biológica de bioisósteros de nitrofural ativos contra Leishmania amazonensis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Reação do tecido conjuntivo subcutâneo e de feridas incisas em contacto com gaze furacinada: estudo histológico

Strips of gauze and furacin gauze were implanted into the subcutaneous space and employed as dressing of dorsal incisions of albino rats. The animals were sacrificed after 24 hours, 2, 5, and 7 post-operative days. The pieces were processed for histological examination. It is possible to conclude that furacin gauze provokes more severe inflammatory reactions and does not favour connective neoformation and epithelization. Furacin gauze should be utilized only as a germicidal aim.

Advances in prodrug design

The background of prodrug design is presented herein as the basis for introducing new and advanced latent systems, taking into account mainly the versatility of polymers and other macromolecules as carriers. PDEPT (Polymer-Directed Enzyme Prodrug Therapy); PELT (Polymer-Enzyme Liposome Therapy); CDS (Chemical Delivery System); ADEPT(Antibody-Directed Enzyme Prodrug Therapy); GDEPT/VDEPT (Gene-Directed Enzyme Prodrug Therapy/Virus-Directed Enzyme Prodrug Therapy); ODDS (Osteotropic Drug Delivery System) and LEAPT (Lectin-directed enzyme-activated prodrug therapy) are briefly described and some examples are given. © 2005 Bentham Science Publishers Ltd.

Arthrodesis tarsocrural or tarsometatarsal in 2 dogs using circular external skeletal fixator

An external fixation technique, using a circular fixator, to obtain arthrodesis was evaluated in 2 dogs with infected open lesions and soft tissue damage. In both cases, articular cartilage was curetted, and devitalized bone and necrotic soft tissue were removed. No bone graft was used. The wounds were maintained open and the dogs received postoperative antibiotic therapy. The arthrodesis site was compressed progressively as needed. Infection was eradicated and bony union was obtained in both dogs. It was concluded that the use of a circular fixator is an effective method to achieve arthrodesis.

Preparação e caracterização inicial de complexo de inclusão entre nitrofurazona e 2-hidroxipropil-β-ciclodextrina

Nitrofurazone (NF), 5-nitro-2-furaldehyde semicarbazone, a broad-spectrum antibiotic, has reported toxic effects and low solubility in water. It would be of great interest to form inclusion complexes between NF and a cyclodextrin, to develop more effective and safer antibiotic formulations. This paper focuses on the preparation of inclusion complexes of NF with 2-hydroxypropyl-β- cyclodextrin (HP-β-CD) and their initial characterization by evaluating rates of complex formation, photostability, solubility isotherms, release rate profiles, stoichiometry of the complexes and their morphology, as revealed by scanning electron microscopy. The kinetic tests of complex formation revealed that 17,3 h is enough for stabilization of the NF-cyclodextrin complex. The solubility isotherm studies showed that the isotherm changes from type A to type B, as a function of temperature. The photostability experiments showed that the insertion of the NF in the HP-β-CD cavity protects the drug from photodecomposition. The release kinetic tests showed that the profile of NF release from the complex is altered by the presence of HP-β-CD in the medium. A Job's plot indicated that the stoichiometry of the complex was 1:1 NF:HP-β-CD. The scanning electron micrographs showed changes in the crystal structure of NF in the complex. This study focused on the physicochemical properties of drug-delivery formulations that could potentially be developed into a novel type of therapy with NF.

Toxicidade de fármacos nitrofurânicos

During the structural designing of new drugs, it is possible predict the influence of specific chemical groups on pharmacological activity. Among these, the nitro group has potential antiparasitic activity, being present in many antimicrobial drugs, such as metronidazole, nitrofurazone, furazolidone, oxamniquine and chloramphenicol. Also, the introduction of the nitro group into a molecule can modify the physicochemical and electronic properties of the substance. Besides antimicrobial drugs, this group is also found in other drug classes, such as antiulcer, anti-inflamatory and anxiolytic. However, the use of the nitro group in drug design has encountered restrictions, due to the associated toxicity. This article is a review of the toxicity of nitrofuran compounds, as well the possible mechanisms involved and the strategy of latentiation by molecular modification to decrease their toxicity.

Farmacocinética pré-clínica do hidroximetilnitrofural (NFOH) – potencial pró-fármaco antichagásico

Pós-graduação em Ciências Farmacêuticas - FCFAR

Avaliação da presença do grupo nitro na atividade antichagásica e mutagênica do candidato a fármaco hidroximetilnitrofural (NFOH)

Pós-graduação em Ciências Farmacêuticas - FCFAR

Preparação e determinação da atividade toxicológica do pró-fármaco hidroximetilnitrofural, potencialmente antichagásico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Planejamento, sintese e avaliação biológica de derivados furoxânicos e benzofuroxânicos potencialmente antichagásicos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conversão in vitro e in vivo do pró-fármaco hidroximetilnitrofural, candidato a fármaco antichagásico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação comparativa da segurança hepática e cardíaca do potencial fármaco antichagásico hidroximetilnitrofural (NFOH) com nitrofurazona (NF) em coelhos

A tripanossomíase americana – Doença de Chagas – é uma parasitose típica de países tropicais e subdesenvolvidos. Devido a grande abrangência da doença, somada a dificuldade encontrada pelos pacientes para adquirir os medicamentos, Chung et al. (1996) sintetizaram o pró-fármaco hidroximetilnitrofural (NFOH). Esse derivado do nitrofural (NF), em estudos preliminares, apresentou resultados significativamente superiores aos observados com benznidazol e nitrofural, disponíveis para a terapia convencional. O presente estudo teve como objetivo a avaliação preliminar do potencial de hepatotoxicidade e cardiotoxicidade do NFOH quando administrado a coelhos albinos. O protocolo experimental se deu através da avaliação da atividade sérica dos biomarcadores hepáticos AST, ALT, GGT e bilirrubina, e do cardíaco CK-MB. Os animais foram divididos em três grupos (n=5), que receberam NFOH, NF e o veículo DMSO duas vezes ao dia, durante 24 dias. Para realização das análises foram coletadas amostras de sangue a cada seis dias. Os testes foram realizados através de kits bioquímicos para diagnóstico (Labtest®). Os níveis de AST e ALT dos grupos expostos aos fármacos apresentaram significativa diminuição com relação ao grupo controle, a bilirrubina não apresentou alterações significativas, e a atividade sérica da GGT apresentou-se elevada tanto nos grupos NFOH e NF quanto no grupo controle. Foi observada alta mortalidade entre os animais expostos ao NF e os valores de CK-MB foram significativamente superiores aos valores de referência descritos em literatura, sugerindo dano cardíaco. Tendo como base tais resultados, concluímos que o pró-fármaco não originou prejuízos relacionados ao tecido hepático, porém com relação à cardiotoxicidade há necessidade de estudos posteriores.

Síntese e avaliação biológica de novos compostos das séries LAPDESF FUR-PQ E LAPDESF FUR-TS contra Trypanosoma cruzi

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Síntese e avaliação biológica de novos compostos das séries LAPDESF FUR-PQ E LAPDESF FUR-TS contra Trypanosoma cruzi

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)