Comparação de efeitos dos extratos de Hypericum perforatum (Hipérico) e de Mentha crispa (Hortelã) em diferentes modelos experiemtais

Several clinic evaluations have been possible with radiobiocomplexes labeled with technetium-99m (99mTc). Some natural and synthetic drugs are capable of to interfere on the labeling of blood constituents with 99mTc, as well as on the biodistribution of radiobiocomplexes. Authors have also reported about the toxicity of several natural products. The aim of this study was to compare the effects of the Mentha crispa (hortelã) and of the Hypericum perforatum (hipérico) in different experimental models. On the labeling of red blood cells (RBC) and plasma and cellular proteins with 99mTc, both extracts were capable of to decrease the radioactivity percentage on the cellular compartment and on the fixation on plasma and cellular proteins. On the morphometry of the RBC, only the hortelã was capable to alter the shape and the perimeter/area ratio of the RBC. On the biodistribution of the radiobiocomplex sodium pertechnetate (Na99mTcO4), the hortelã increased the Na99mTcO4 distribution in the kidney, spleen, liver and thyroid, meanwhile the hipérico decreased the Na99mTcO4 distribution in the bone, stomach, lungs and thyroid, and increased the Na99mTcO4 distribution in the pancreas. On the bacterial cultures survival, the hipérico was capable of to protect the bacteria against the stannous chloride (SnCl2) effect. The hipérico did not alter the topology of plasmidial DNA and did not protect the plasmidial DNA against the SnCl2 action. Probably, the effects presented by both extracts could be due to chemical compounds of the extracts that could alter the morphology of the RBC and the plasma membrane ions transport, and/or by phytocomplexes that could be formed with different effects dependent on the biological system considered

Desenvolvimento de uma formulação cólon específica visando o tratamento da colite ulcerativa

Micro and nanoparticulate systems as drug delivery carriers have achieved successful therapeutic use by enhancing efficacy and reducing toxicity of potent drugs. The improvement of pharmaceutical grade polymers has allowed the development of such therapeutic systems. Microencapsulation is a process in which very thin coatings of inert natural or synthetic polymeric materials are deposited around microsized particles of solids or around droplets. Products thus formed are known as microparticles. Xylan is a natural polymer abundantly found in nature. It is the most common hemicellulose, representing more than 60% of the polysaccharides existing in the cell walls of corn cobs, and is normally degraded by the bacterial enzymes present in the colon of the human body. Therefore, this polymer is an eligible material to produce colon-specific drug carriers. The aim of this study was to evaluate the technological potential of xylan for the development of colon delivery systems for the treatment of inflammatory bowel diseases. First, coacervation was evaluated as a feasible method to produce xylan microcapsules. Afterwards, interfacial cross-linking polymerization was studied as a method to produce microcapsules with hydrophilic core. Additionally, magnetic xylan-coated microcapsules were prepared in order to investigate the ability of producing gastroresistant systems. Besides, the influence of the external phase composition on the production and mean diameter of microcapsules produced by interfacial cross-linking polymerization was investigated. Also, technological properties of xylan were determined in order to predict its possible application in other pharmaceutical dosage forms

Sistemas microemulsionados como carreador lipídico para fármacos insolúveis

Several pharmaceutical products have been developed in recent years aiming to enhance the treatment of diseases by increasing the effectiveness of drugs. Many of these new products are based on new drug delivery systems. Among these, microemulsions, which were first studied in 1943 by Hoar and Schulman, is of great interest. Microemulsion can be defined as a thermodynamically stable, isotropic, translucent and transparent system of two immiscible liquids stabilized by a surfactant film located in the oil / water interface. The aim os this work was the incorporation of Amphotericin B and Simvasatin to a microemulsion system and analyzes its physicochemical properties and their therapeutical activity when incorporated into this system. Some very promising results were achieved as the reduction of the toxicity and maintenance of the efficacy of the Amphotericin B incorpored into a microemulsion, which was demonstrated in the in vitro pharmacotoxicological study. As for the incorporation of Simvastatin in microemulsion, it was observed a significant improvement in the potential antiinflammatory and anti-infective properties when the system was use to treat infected wounds (simvastatin pleiotropic effects). Therefore, it can be concluded that the incorporation of these drugs into microemulsion system reveal the potential of microemulsions as a promising and novel dosage form, qualifying them for future trials in order to make them available in the pharmaceutical market

Avaliação do potencial de mutagenicidade e toxidade da lectina hipoglicemiante de folha de Bauhinia monandra (pata-de-vaca)

Medicinal plants have been used since antiquity to treat various human diseases. The leaves of Bauhinia monandra are widely used in Brazil as herbal remedies in the treatment of Diabetes Mellitus. From the leaves of B. monandra was purified a galactose-specific lectin, called BmoLL, which also showed a significant hypoglycemic capacity. Following the proposed rules by decree No 116 of 1996/08/08 of the Ministry of Health of Brazil, the study aimed to evaluate the potential for toxicity and mutagenicity of BmoLL from the use of tests with Escherichia coli strain CC104 (Forward mutagenesis assay) with Salmonella typhimurium strain TA (Kado test), with plasmid pBCKS (Break occurrences in plasmid DNA) and enzyme exonuclease III (Search of abasic sites). The results demonstrated that the lectin was unable to increase the frequency of reverse mutation of strains of S. typhimurium, with and without metabolic activity. However, a significant decrease in the frequency of spontaneous mutation was observed in strains of E. coli, especially in poor repair (CC104mutMmutY), indicating an antioxidant potential of the lectin. BmoLL is unable to generate genotoxic and cytotoxic damage, based on the concentrations and the tests performed

Ecotoxicological assessment of sediments from the Santos and São Vicente estuarine system- Brazil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ecotoxicological assessment of sediments from the Port of Santos and the disposal sites of dredged material

A dragagem dos sedimentos do Canal de Santos é necessária para permitir o trânsito de navios que operam no Porto de Santos. As áreas de disposição do material dragado estão situadas na zona costeira, em frente à Baía de Santos. Este estudo visou avaliar a qualidade dos sedimentos do Canal de Santos e das áreas de disposição atuais e antigas, utilizando testes de toxicidade de sedimento integral com anfípodos e de toxicidade de elutriatos com embriões de ouriço do mar. As amostras do Canal de Santos foram consideradas as mais tóxicas: todas as amostras dessa área foram consideradas significativamente tóxicas. Além disso, algumas amostras das áreas de disposição exibiram toxicidade. Os resultados mostraram, portanto, que os sedimentos apresentam evidências de degradação em sua qualidade, porém novos estudos devem ser conduzidos visando determinar as relações entre contaminação e toxicidade. Os resultados sugerem ainda que a disposição dos sedimentos dragados deva ser reavaliada.

Desenvolvimento e caracterização de um sistema microemulsionado contendo anfotericina b para uso oftalmológico

Universidade Federal do Rio Grande do Norte

A simple approach to integrate the ecotoxicological and chemical data for the establishment of environmental risk levels

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

Acute and chronic toxicity of sediment samples from Guanabara Bay (RJ) during the rainy period

A Baía de Guanabara é um ambiente marinho-estuarino de grande relevância ecológica e sócio-econômica, e sujeita a uma ampla gama de impactos ambientais. O sedimento é o principal destino para a maioria das substâncias introduzidas nos corpos d'água, podendo fornecer uma medida integrada da qualidade ambiental, a qual pode ser avaliada por várias abordagens. Neste projeto, a qualidade de sedimentos da Baía de Guanabara foi por uma abordagem ecotoxicológica, por meio de testes de toxicidade aguda de sedimento integral, utilizando Tiburonella viscana, e testes de toxicidade crônica de água intersticial, elutriato e interface sedimento-água, utilizando embriões de Lytechinus variegatus. Os sedimentos foram coletados em 14 estações de amostragem. Nos testes crônicos houve efeitos significativos na maioria das amostras, enquanto os sedimentos coletados nas estações 1, 2, 3, 6, 8, 10, 11, 12 e 15 apresentaram também toxicidade aguda. Houve grande concordância entre os resultados dos diferentes testes, e sua integração mostrou que os sedimentos analisados encontram-se inadequados à vida aquática, indicando degradação ambiental na baía da Guanabara. Nesse contexto, o controle das fontes poluidoras e o gerenciamento dos múltiplos usos da baía devem ser implementados, no sentido da melhora da qualidade ambiental.

Efeito de um extrato de Ganoderma lucidum (Reishi) na marcação de constituintes sanguíneos com tecnécio-99M e na sobrevivência de Escherichia coli

Clinical evaluations have been made possible with radiobiocomplexes marked with tecnecium-99m (99mTc). Natural or synthetic drugs are able to interfere in the marking of blood structures with 99m Tc. Also, the toxicity of several natural products has been described. The aim of this study was evaluating the effect of an extract of Ganoderma lucidum (Reishi) in the marking of blood constituents with 98m Tc and in the survival of Escherichia coli. Blood samples from Wistar rats were treated with reishi extract. Radiomarking procedure was performed. Samples of plasma (P), blood cells (CS), and insoluble (FI) and soluble (FS) fractions of P and CS were separated and the radioactivity was counted to determine radioactivity percentages (%ATI). Escherichia coli AB1157 cultures were treated with stannous chloride in the presence and absence of the reishi extract. Blood samples and bacterial cultures treated with NaCl 0.9% were used as controls. Data indicated that the reishi extract has significantly altered (p<0,05) the %ATI of P, CS, FI-P, FS-P, FI-CS e FS-CS, as well as it has increased survival of bacterial cultures treated with stannous chloride. Our results suggest that the Reishi extract would be able to present a redox/ chelant action by altering blood constituent marking with 99mTc and by protecting bacterial cultures against stannous chloride-induced oxydating lesions. The study had a multidisciplinary character, with the participation of the following areas of knowledge: Biophysics, Radiobiology, Botanics, Phytotherapy, and Hematology

Emulsões de óleo de copaíba: determinação do equilíbrio hidrófilo-lipófilo crítico (EHLC), propriedades e estabilidade físico-químicas

Durante as últimas décadas, as indústrias farmacêuticas têm despertado grande interesse em óleos vegetais e vários extratos de planta por causa da sua baixa toxicidade e alta biodegrabilidade. O óleo de copaíba (Cop) é usado in natura na medicina popular como anti-inflamatório e antimicrobiano para tratar várias doenças, tais como inflamação da garganta, úlceras e infecções urinárias e pulmonares. Emulsões são sistemas dispersos termodinamicamente instáveis que consistem em dispersões de gotículas microscópicas em outro líquido imiscível. O objetivo deste trabalho foi preparar diferentes emulsões de Cop, determinar o EHL crítico deste óleo e avaliar a sua estabilidade, além de realizar estudos comparativos entre diferentes métodos de construção de diagramas de fases. As emulsões foram preparadas pelo método de inversão de fases variando as proporções de EHL de 4,7 a 16,7. A estabilidade foi determinada por vários métodos e os diagramas de fases foram produzidos pelo método de titulação usando diferentes procedimentos de agitação. As emulsões a base de Cop com EHL entre 12,7 e 15,7 foram as mais estáveis. As emulsões apresentaram boa estabilidade em curto e longo prazo, aspecto leitoso e baixos valores de índice de cremagem. Diferentes sistemas coloidais foram produzidos a partir dos diagramas de fases dependendo do processo de agitação. Baseado nesses métodos, o valor determinado de EHL do Cop foi 14,8, as emulsões permaneceram estáveis por mais de um ano e estes resultados indicam que o estudo das emulsões de Cop pode ser um promissor veículo de liberação tópica de fármacos e ativos cosméticos

Anfotericina b pré-aquecida: um novo sistema terapêutico para infecções fúngicas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Estudo do efeito dos metabólitos do benzeno e tolueno sobre as mitocôndris cerebrais e hepáticas de ratos

Aim: The aim of this work was to investigate the hypothesis that catechol and 3MC inhibit FADH2-linked basal respiration in mitochondria isolated from rat liver and brain homogenates. Moreover, catechol ability to induce DNA damage in rat brain cells through the comet assay (alkaline single-cell gel electrophoresis assay) was also observed. Methods: Two different catechols were evaluated: pirocatechol (derived from benzene) and 3-methylcatechol (derived from toluene); rat liver and brain homogenates were incubated with 1mM catechol at pH 7.4 for up to 30 minutes. After that, mitochondrial fractions were isolated by differential centrifugation. Basal oxygen uptake was measured using a Clark-type electrode after the addition of 10 mM sodium succinate for a period of 12 minutes. In additional experiments, rat brain cells were treated with 1, 5 and 10mM pirocatechol for up to 20 minutes at 37º C, and submitted to electrophoresis. Results: Catechols (pirocatechol and 3methylcatechol) induced a time-dependent partial inhibition of FADH2-linked basal mitochondrial respiration. Indeed, pirocatechol was able to produce a dosedependent DNA oxidative damage in rat brain cells by 2 and 4 injury levels. These results suggest that reactive oxygen species generated by the oxidation of catechols, induced an impairment on mitochondrial respiration and a DNA damage, which might be related to their citotoxicity. Conclusion: Catechols produced an inhibition of basal respiration associated to FADH2 in isolated liver and brain mitochondria; 3-methylcatechol, at the same concentration, produced similar toxicity in the mitochondrial model. Indeed, pirocatechol induced a DNA damage in rat brain cells, mainly observed in comets formation and consequent DNA degradation

Análise das mutações C282Y e H63D no gene da proteína HFE em pacientes com hiperferritinemia

Hereditary Hemochromatosis (HH) is a genetic disease caused by high iron absorption and deposition in several organs. This accumulation results in clinical disturbances such as cirrhosis, arthritis, cardiopathies, diabetes, sexual disorders and skin darkening. The H63D and C282Y mutations are well defined in the hemochromatosis etiology. The aim of this paper was that of identifying the H63D and C282Y genetical mutations in the hemochromatosis gene and the frequency assessment of these mutations in the HFE protein gene in patients with hyperferritin which are sent to the DNA Center laboratory in Natal, state of Rio Grande do Norte. This paper also evaluates the HH H63D and C282Y gene mutations genotype correlation with the serum ferritin concentration, glucose, alanine aminotransferasis, aspartato aminotransferasis, gama glutamil transferasis and with the clinical complications and also the interrelation with life habits including alcoholism and iron overload. The biochemical dosages and molecule analyses are done respectively by the enzymatic method and PCR with enzymatic restriction. Out of the 183 patients investigated, 51,4% showed no mutation and 48,6% showed some type of mutation: 5,0% were C282Y heterozygous mutation; 1,1%, C282Y homozygous mutation; 31%, H63D heterozygous mutation; 8,7%, H63D homozygous mutation; and 3,3%, heterozygous for the mutation in both genes. As to gender, we observed a greater percentage of cases with molecular alteration in men in relation to women in the two evaluated mutations. The individuals with negative results showed clinical and lab signs which indicate hemochromatosis that other genes could be involved in the iron metabolism. Due to the high prevalence of hemochromatosis and taking into account that hemochromatosis is considered a public health matter, its gravity being preventable and the loss treatment toxicity, the early genetic diagnosis is indicated, especially in patients with high ferritin, and this way it avoids serious clinical manifestations and increases patients' life expectation. Our findings show the importance of doing such genetic studies in individuals suspected of hereditary hemochromatosis due to the high incidence of such a hereditary disease in our region

Controle de qualidade físico-químico e biodisponibilidade relativa em ratos de suspensões orais de naproxeno sódico obtidas de farmácias de manipulação na cidade do Natal RN

Compounded medicines have been reported by the ANVISA due to decreased of the therapeutic response or toxicity of these formulations. The aim of this work was to investigate the physicochemical quality control among naproxen sodium oral suspensions 25 mg/mL obtained from six compounding pharmacies (A, B, C, D, E and F) and the manufactured suspension (R). In the quality control test, the tests of pH, content, homogeneity, volume and physical and organoleptic characteristics were performed according to the Brazilian Pharmacopoeia. The analytical method for determination of naproxen in suspensions was validate. This method showed excellent precision, accuracy, linearity and specificity. In the content test the suspensions B, C and E showed lower value and the F suspension showed a high value of the content. The products C and E were disapproved in the description of the physical and organoleptic characteristics test. In the pH test, three suspensions were outside specifications (C, E and F). Only the products R, A and D showed satisfactory results in these tests and therefore they were approved for relative bioavailability test. The R, A and D suspensions were orally administered to Wistar rats and the blood samples were taken at time intervals of 10, 20, 40, 60 min, 3, 4, 6, 24 and 48 h. The plasma samples were immediately stored at 80 ºC until analysis of HPLC. The bioanalytical method validation showed specificity, linearity (R2 0.9987), precision, accuracy, good recovery and stability. The chromatographic conditions were: flow rate of 1.2 mL.min-1 with a mobile phase of acetonitrile : sodium phosphate buffer pH 4.0 (50:50, v/v) at 280 nm, using a C18 column. The confidence interval of 90% for the Cmax and AUCt ratio was within the range of 80 - 125% proposed by the FDA. Only one suspension, obtained from the compounding pharmacy D, was considered bioequivalent to the rate of absorption under the conditions proposed by this study. Thus, the results indicate the need for strict supervision from the relevant authorities to ensure the patient safety and the quality of compounded drugs by pharmacies