Assessment of DNA damage induced by extracts, fractions and isolated compounds of Davilla nitida and Davilla elliptica (Dilleniaceae)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of isocoumarins isolated from Paepalanthus bromelioides on mitochondria: Uncoupling, and induction/inhibition of mitochondrial permeability transition

Isolated mitochondria may undergo uncoupling, and in presence of Ca2+ at different conditions, a mitochondrial permeability transition (MPT) linked to protein,thiol oxidation, and demonstrated by CsA-sensitive mitochondrial swelling; these processes may cause cell death either by necrosis or by apoptosis. Isocoumarins isolated from the Brazilian plant Paepalanthus bromelioides (Eriocaulaceae) paepalantine (9,10-dihydroxy-5,7-dimethoxy-1H-naptho(2,3c)pyran-1-one), 8,8'-paepalantine dimer, and vioxanthin were assayed at 1-50 mu M on isolated rat liver mitochondria, for respiration, MPT, protein thiol oxidation, and interaction with the mitochondrial membrane using 1,6-diphenyl-1,3,5-hexatriene (DPH). The isocoumarins did not significantly affect state 3 respiration of succinate-energized mitochondria; they did however, stimulate 4 respiration, indicating mitochondrial uncoupling. Induction of MPT and protein thiol oxidation were assessed in succinate-energized mitochondria exposed to 10 mu M Ca2+; inhibition of these processes was assessed in non-energized organelles in the presence of 300 mu M t-butyl hydroperoxide plus 500 mu M Ca2+. Only paepalantine was an effective MPT/protein thiol oxidation inducer, also releasing cytochrome c from mitochondria; the protein thiol oxidation, unlike mitochondrial swelling, was neither inhibited by CsA nor dependent on the presence of Ca2+. Vioxanthin was an effective inhibitor of MPT/protein thiol oxidation. All isocoumarins inserted deeply into the mitochondrial membrane, but only paepalantine dimer and vioxantin decreased the membrane's fluidity. A direct reaction with mitochondrial membrane protein thiols, involving an oxidation of these groups, is proposed to account for MPT induction by paepalantine, while a restriction of oxidation of these same thiol groups imposed by the decrease of membrane fluidity, is proposed to account for MPT inhibition by vioxanthin. (c) 2006 Published by Elsevier B.V..

Preparation and characterisation of Dextran-70 hydrogel for controlled release of praziquantel

Um hidrogel foi desenvolvido a partir de dextrano 70 kDa (DEX-70) e praziquantel incorporado (PZQ) como fármaco modelo. Propriedades biofarmacêuticas, como solubilidade e velocidade de dissolução, foram analisadas no desenvolvimento do hidrogel. Além disso, o hidrogel também foi caracterizado por espectroscopia na região do infravermelho e calorimetria diferencial exploratória (DSC). Testes da taxa de intumescimento mostraram que o hidrogel intumesce lentamente, embora tenha sido mais rápido do que a taxa do polímero livre. Nos testes de dissolução, o hidrogel liberou o fármaco lenta e continuamente. Esta liberação lenta foi semelhante a observada nos testes de intumescimento e resultou em uma liberação controlada do fármaco. Assim, o dextrano 70 kDa é um polímero adequado para o desenvolvimento de hidrogéis como veículos para a liberação controlada de fármacos.

Alginate-chitosan systems: In vitro controlled release of triamcinolone and in vivo gastrointestinal transit

The aim of this study was to develop multiparticulate therapeutic systems of alginate (AL) and chitosan (CS) containing triamcinolone (TC) to colonic drug delivery. Multiparticulate systems of AL-CS, prepared by a complex coacervation/ionotropic gelation method, were characterized for morphological and size aspects, swelling degree, encapsulation content and efficiency, in vitro release profile in different environments simulating the gastrointestinal tract (GIT) and in vivo gastrointestinal transit. The systems showed suitable morphological characteristics with particle diameters of approximately 1.6 mm. In simulated gastric environment, at pH 1.2, the capsules presented low degree of swelling and in vitro release of drug. A higher swelling degree was observed in simulated enteric environment, pH 7.5, followed by erosion. Practically all the drug was released after 6 h of in vitro assay. The in vivo analysis of gastrointestinal transit, carried out in rats, showed that the systems passed practically intact through the stomach and did not show the same profile of swelling observed in the in vitro tests. It was possible to verify the presence of capsules in the colonic region of GIT. The results indicate that AL-CS multiparticulate systems can be used as an adjuvant for the preparation of therapeutic systems to colonic delivery of drugs. (C) 2010 Elsevier Ltd. All rights reserved.

In vitro drug permeation from chitosan pellets

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Modeling a system of phosphated cross-linked high amylose for controlled drug release. Part 2: Physical parameters, cross-linking degrees and drug delivery relationships

High amylose cross-linked to different degrees with sodium trimetaphosphate by varying base strength (2% or 4%) and contact time (0.5-4 h) was evaluated as non-compacted systems for sodium diclophenac controlled release. The physical properties and the performance of these products for sodium diclophenac controlled release from non-compacted systems were related to the structures generated at each cross-linking degree. For samples at 2% until 2 h the swelling ability, G' and eta* values increased with the cross-linking degree, because the longer polymer chains became progressively more entangled and linked. This increases water uptake and holding, favoring the swelling and resulting in systems with higher viscosities. Additionally, the increase of cross-linking degree should contribute for a more elastic structure. The shorter chains with more inter-linkages formed at higher cross-linking degrees (2%4h and 4%) make water caption and holding difficult, decreasing the swelling, viscosity and elasticity. For 2% samples, the longer drug release time exhibited for 2%4h sample indicates that the increase of swelling and viscosity contribute for a more sustained drug release, but the mesh size of the polymeric network seems to be determinant for the attachment of drug molecules. For the 4% samples, smaller meshes size should determine less sustained release of drug. (C) 2008 Elsevier B.V. All rights reserved.

In vitro characterization of coevaporates containing chitosan for colonic drug delivery

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Chitosan-pectin multiparticulate systems associated with enteric polymers for colonic drug delivery

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effect of the doping medium on blends of polyurethane and polyaniline

Flexible and free-standing films from blends of polyurethane, based on castor oil, and polyaniline were obtained with various compositions by casting. Significant increase on conductivity followed by a considerable decrease on doping time was obtained by doping the films in N,N-dimethylformamide (DMF) solution with p-toluene sulphonic acid (TSA) or HCl instead of the conventional doping in aqueous solution. This doping efficiency is proposed to be due to an improved swelling of the blend structure caused by the solvent. The electrical conductivity increases significantly upon polyaniline content increase reaching 10(-2) S/cm for a polyaniline content of about 10% (w/w).

Investigação do processo de absorção de água de hidrogéis de polissacarídeo: efeito da carga iônica, presença de sais, concentrações de monômero e polissacarídeo

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

Aneurysm of the Superior Labial Artery

This is a case report of a true and dissecting aneurysm of the superior labial artery in a 51-year-old patient without risk factors for vascular pathology. The patient complained of swelling of the upper lip, mostly on the left side. A Doppler ultrasonography was used in the diagnosis. The definitive treatment was surgical resection, and the histopathological analysis confirmed the diagnosis. The progress of the patient was satisfactory, leaving a slight change in sensitivity in the area. This seems to be the first reported case of true and dissecting aneurysm of the superior labial artery in the medical literature.

Beta-carotene supplementation attenuates cardiac remodeling induced by one-month tobacco-smoke exposure in rats

Objective: the objectives were to analyze the cardiac effects of exposure to tobacco smoke (ETS), for a period of 30 days, alone and in combination with beta-carotene supplementation (BC). Research methods and procedures: Rats were allocated into: Air (control, n = 13); Air + BC (n = 11); ETS (n = 11); and BC + ETS (n = 9). In Air + BC and BC + ETS, 500 mg of BC were added to the diet. After three months of randomization, cardiac structure and function were assessed by echocardiogram. After that, animals were euthanized and morphological data were analyzed post-morten. One-way and two-way ANOVA were used to assess the effects of ETS, BC and the interaction between ETS and BC on the variables. Results: ETS presented smaller cardiac output (0.087 +/- 0.001 vs. 0.105 +/- 0.004 l/min; p = 0.007), higher left ventricular diastolic diameter (19.6 +/- 0.5 vs. 18.0 +/- 0.5 mm/kg; p = 0.024), higher left ventricular (2.02 +/- 0.05 vs. 1.70 +/- 0.03 g/kg; p < 0.001) and atrium (0.24 +/- 0.01 vs. 0.19 +/- 0.01 g/kg; p = 0.003) weight, adjusted to body weight of animals, and higher values of hepatic lipid hydroperoxide (5.32 +/- 0.1 vs. 4.84 +/- 0.1 nmol/g tissue; p = 0.031) than Air. However, considering those variables, there were no differences between Air and BC + ETS (0.099 +/- 0.004 l/min; 19.0 +/- 0.5 mm/kg; 1.83 +/- 0.04 g/kg; 0.19 +/- 0.01 g/kg; 4.88 +/- 0.1 nmol/g tissue, respectively; p > 0.05). Ultrastructural alterations were found in ETS: disorganization or loss of myofilaments, plasmatic membrane infolding, sarcoplasm reticulum dilatation, polymorphic mitochondria with swelling and decreased cristae. In BC + ETS, most fibers showed normal morphological aspects. Conclusion: One-month tobacco-smoke exposure induces functional and morphological cardiac alterations and BC supplementation attenuates this ventricular remodeling process.

Xantogranuloma órbito-palpebral: relato de caso

Xantogranuloma é doença histiocítica, caracterizada por lesões amareladas na pele ou na derme, acompanhadas ou não de alterações hematológicas ou neoplasias. O objetivo deste é relatar o caso de uma mulher de 39 anos, com queixa de inchaço progressivo nas pálpebras superiores, há 6 anos, indolor, sem alterações sistêmicas. O exame histológico mostrou infiltração maciça da pele, tecido muscular e gordura orbitária por histiócitos xantomatosos e abundantes células gigantes do tipo Touton. O diagnóstico foi de xantogranuloma do adulto. Os autores comentam os diagnósticos diferenciais, assim como a necessidade de exames periódicos, devido ao risco de associação com doenças sistêmicas malignas.

Cell-free antigens from precocious Paracoccidioides brasiliensis culture induce a typical delayed-type hypersensitivity reaction

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Clinical presentation and salivary gland histopathology of paediatric primary Sjogren's syndrome

ObjectiveExplore the presentation, diagnostic criteria and exocrine gland histopathology of paediatric primary Sjogren's syndrome (PPSjS).MethodsA case series of 8 children is reported and American-European Consensus Group (AECG-2002) criteria were examined, as well as minor labial salivary and lachrymal gland biopsies, which were scored by a pathologist blinded to outcome. For all cases, connective tissue diseases and parotid-related infectious disease were excluded.ResultsAge at onset varied from 5-13 years old; 6 were females, all followed from diagnosis up to the last visit (1-10 years). The main features at presentation were recurrent tender parotid swelling and sialectasis imaging, with decreased salivary function assessed by Tc-99 scintigraphy. Mild sicca symptoms were observed in 4/8 cases. Systemic features, including fatigue, myalgia, arthritis, tenosynovitis, joint contractures, transient Raynaud's and high ESR, were recorded at onset. Autoantibody profile was unremarkable for diagnosis, while lymphocytic infiltration of labial salivary glands and sialectasis were observed in all biopsies (8/8). In lachrymal glands, massive lymphocytic infiltration and lymphocytic gastritis were observed during complementary assessment. Flares were treated with low dose steroids and long-term use of hydroxychloroquine (5/8), although only 318 fulfilled AECG-2002 diagnostic criteria, throughout the disease course.ConclusionPPSjS is rare, slowly progressive and its early presentation is variable. Standardised diagnostic algorithms should include recurrent parotid swelling and early diagnosis should rely mostly on salivary and lachrymal gland histopathology in this age group.