Effects of the extract and glycoalkaloids of Solanum lycocarpum St. Hill on Giardia lamblia trophozoites.

BACKGROUND: Solanum lycocarpum has great importance for food and medicinal traditional use. Recently, it was also evidenced that extracts of S. lycocarpum St. Hill (Solanaceae) and its glycoalkaloids, solamargine (Sg) and solasonine (Sn), are active against flagellated protozoa. OBJECTIVE: The aim was to assess the effects of the extract of S. lycocarpum and its glycoalkaloids, Sn, and Sg, on Giardia lamblia trophozoites. MATERIALS AND METHODS: A crude extract (96%ethanol) (EB) of fruits of S. lycocarpum was prepared and fractionated by partition with 40%ethanol and n-hexane: Ethyl acetate. Glycoalkaloids, Sn, and Sg were recognized in the ethanol fraction (EF) and further isolated by column chromatography. EB, EF, the isolated Sn and Sg and a mixture (1:1) of both glycoalkaloids were tested on cultures of G. lamblia trophozoites and macrophages. RESULTS: EB, EF and glycoalkaloids of S. lycocarpum showed activity against Giardia (95.0 < Inhibitory concentration 50 [IC50] ≤120.3 µg/mL). The mixture of glycoalkaloids (1:1) was more active (IC50 = 13.23 µg/mL) than each one individually, suggesting a synergic effect. Moreover, the mixture is nontoxic to macrophage cells. CONCLUSION: Results are optimistic concerning the anti-Giardia potential of the mixture Sn + Sg. Further studies, in vitro and in vivo, will be required to consolidate the usefulness of the mixture of Sn + Sg in view of a new therapeutic strategy for giardiasis.

In vitro trypanocidal activity of solamargine and extracts from Solanum palinacanthum and Solanum lycocarpum of Brazilian cerrado.

The present investigation was to evaluate the potential trypanocidal activity of crude ethanolic extract of the fruits of Solanum palinacanthum, Solanum lycocarpum and the glycoalcaloid, solamargine. S. palinacanthum and S. lycocarpum fruit powders were submitted to exhaustively extraction with 96% ethanol and solamargine were isolated from the extract of S. palinacanthum. Both extracts and solamargine were analysed for trypanocidal activity by using MTT colorimetric assay. Extracts of S. palinacanthum showed to be more active (IC50 = 175.9 µg.ml-1) than S. lycocarpum (IC50 = 194.7 µg.ml-1). Solamargine presented a strong activity (IC50 = 15.3 µg.ml-1), which can explain the better activity of the both extracts. Benznidazol (IC50 = 9.0 µg.ml-1) is the only drug used to treat Chagas' disease. These findings demonstrate for the first time that ethanol extracts obtained from both fruits of S. palinacanthum and S. lycocarpum and also solamargine have a potential anti-trypanosomal activity.

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

A hydrogel was developed from 70 kDa dextran (DEX-70) and praziquantel (PZQ) incorporated as a model drug. Biopharmaceutical properties, such as solubility and dissolution rate, were analysed in the design of the hydrogel. Furthermore, the hydrogel was also characterized by IR spectroscopy and DSC. Tests of the swelling rate showed that the hydrogel swelled slowly, albeit faster than the rate for the free polymer. In dissolution tests, the hydrogel released the drug slowly and continuously. This slow release was similar to that observed in the swelling tests and resulted in controlled release of the drug. Thus, this dextran is a suitable polymer for the development of hydrogels as vehicles for the controlled release of drugs.

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.

Chemical and bioactive quality traits during fruit ripening in eggplant (S. melongena L.) and allied species.

A chemical and bioactive quality evaluation of phytochemicals content of 10 eggplant lines and three allied species (S. sodomaeum, S. aethiopicum and S. integrifolium) was performed. The eggplant lines were divided into the two subgroups of delphinidin-3-rutinoside (D3R) and nasunin (NAS) typologies, on the basis of the anthocyanin detected in their fruit skin. The allied species had higher glycoalkaloids content, lower soluble solids and PPO activity and absence of anthocyanins compared to the eggplant lines; S. sodomaeum stood out for high phenols content. Orthogonal contrast revealed a higher sugar content and low PPO activity in NAS- compared to D3R-typologies, whereas higher chlorogenic acid and anthocyanin contents were present in D3R-typologies. The main effect of the ripening was a decrease in phenols and in the PPO activity, not evidenced in S. sodomaeum, and an increase of glycoalkaloids in overripe fruits. A good relationship was found between superoxide anion scavenging capacity and chlorogenic acid. This study highlighted the pattern of accumulation, also evidencing variations, of several phytochemicals during the eggplant fruit development and ripening.

A discriminating dissolution method for glimepiride polymorphs.

Glimepiride, an oral antidiabetic drug, is practically insoluble in water and exists in two polymorphic forms, I and II, of which form II has higher solubility in water. Because the dissolution rate of drugs can depend on the crystal form, there is a need to develop discriminating dissolution methods that are sensitive to changes in polymorphic forms. In this work, a dissolution method for the assessment of 4 mg glimepiride tablets was developed and validated. The optimal dissolution conditions were 1000 mL of phosphate buffer (pH 6.8) containing 0.1% (w/v) of sodium dodecyl sulfate as the dissolution medium and a stirring speed of 50 rpm using a paddle apparatus. The results demonstrated that all the data meet the validation acceptance criteria. Subsequently, tablets containing forms I and II of glimepiride were prepared and subjected to dissolution testing. A significant influence of polymorphism on the dissolution properties of glimepiride tablets was observed. These results suggested that the raw material used to produce glimepiride tablets must be strictly controlled because they may produce undesirable and unpredictable effects.

Mutagenic and genotoxic effect of hydroxyurea.

The hydroxyurea, a cytotoxic drug, is the mainly available therapeutical strategy for the treatment of sickle cell disease. This study aimed to evaluate the mutagenic and genotoxic potential of the hydroxyurea through the Salmonella/Microsome assay and micronucleus test in peripheral blood of mice. The doses were evaluated at 29.25-468 µmol/plate in Salmonella/Microsome assay in presence and absence of metabolic activation the drug. In the micronucleus test the doses were evaluated at 12.5; 25; 50; 75 and 100 mg/kg. The results show that hydroxyurea present mutagenic activity in TA98 and TA100 in doses above 117 µmol/plate and 234 µmol/plate respectively. The drug induced a significant increase in the frequency of micronuclei in reticulocytes of mice at concentrations of 50, 75 and 100 mg/kg, compared to negative control (water). These results demonstrated the mutagenic and genotoxic potential of hydroxyurea.

Síntese e atividade biológica do derivado 6-formil-oxamniquina / Synthesis and biological activity of 6-formyl-oxamniquine derivative

A esquistossomose, uma importante doença no Brasil, é causada por trematódeo pertencente ao gênero Schistosoma, atingindo milhões de pessoas, numa das maiores regiões endêmicas dessa doença em todo globo. O principal objetivo desse trabalho foi sintetizar o derivado 6-formil-oxamniquina e avaliar sua atividade biológica. O derivado 6-formil- oxamniquina foi obtido por oxidação da oxamniquina com dióxido de manganês empregando diclorometano como solvente, à temperatura ambiente, por 24 horas. Sua obtenção foi confirmada por espectrometria na região de infravermelho e espectroscopia de RMN 13C e ÕH, apresentando atividade similar quando comparada à oxamniquina comercial (Mansil®).

Schistosomiasis, an important disease in Brazil, is caused by a trematode of the genus Schistosoma, reaching millions of person in one of the most endemic region of this disease in the whole globe. The main goal of this work was to syntetize the 6-formyl-oxamniquine derivative and evaluate its biological activity. The 6-formyl-oxamniquine derivative was obtained by the oxidation of oxamniquine with MnO2, applying CH2Cl2 as solvent at room temperature for 24 hours. The obtaintion of 6-formyl-oxamniquine derivative compound was confirmed by IR spectroscopy and 13C NMR and ÕH NMR, presenting similar activity when compared to the commercial oxamniquine (Mansil®).

Prodrugs for the treatment of neglected diseases.

Recently, World Health Organization (WHO) and Medicins San Frontieres (MSF) proposed a classification of diseases as global, neglected and extremely neglected. Global diseases, such as cancer, cardiovascular and mental (CNS) diseases represent the targets of the majority of the R&D efforts of pharmaceutical companies. Neglected diseases affect millions of people in the world yet existing drug therapy is limited and often inappropriate. Furthermore, extremely neglected diseases affect people living under miserable conditions who barely have access to the bare necessities for survival. Most of these diseases are excluded from the goals of the R&D programs in the pharmaceutical industry and therefore fall outside the pharmaceutical market. About 14 million people,mainly in developing countries, die each year from infectious diseases. From 1975 to 1999,1393 new drugs were approved yet only 1% were for the treatment of neglected diseases[3]. These numbers have not changed until now, so in those countries there is an urgent need for the design and synthesis of new drugs and in this area the prodrug approach is a very interesting field. It provides, among other effects, activity improvements and toxicity decreases for current and new drugs, improving market availability. It is worth noting that it is essential in drug design to save time and money, and prodrug approaches can be considered of high interest in this respect. The present review covers 20 years of research on the design of prodrugs for the treatment of neglected and extremely neglected diseases such as Chagas' disease (American trypanosomiasis), sleeping sickness (African trypanosomiasis), malaria, sickle cell disease, tuberculosis, leishmaniasis and schistosomiasis.

Estudo da camada de fibras nervosas da retina em pacientes com esquistossomose mansônica: análise com GDxTM / Study of retinal nerve fiber layer in patients with schistosomiasis mansoni: analysis with GDX TM

OBJETIVO: Estudar a camada de fibras nervosas da retina de portadores de esquistossomose mansônica hepatoesplênica. MÉTODOS: Foram submetidos ao exame com o GDx Scanning Laser System, 23 portadores de esquistossomose na forma hepatoesplênica que tinham sido submetidos, quando crianças, a esplenectomia, ligadura da veia gástrica esquerda e auto-implante de tecido esplênico no omento maior. Todos apresentaram pressão intra-ocular menor que 21 mmHg. No grupo controle foram estudados 23 indivíduos com idade e condição socioeconômico-geográfica similar, sem esquistossomose. RESULTADOS: Em apenas um paciente do grupo portador de esquistossomose foram observadas alterações em quatro parâmetros: superior nasal, média superior, média da espessura e número de fibra. Todos os indivíduos do grupo controle apresentaram GDx com parâmetros dentro da normalidade. CONCLUSÃO: No estudo realizado não foi encontrado diferença significante entre os dois grupos. Apenas um paciente mostrou redução da camada de fibras nervosas.

PURPOSE: To study the retinal nerve fiber layer in young patients suffering from hepatosplenic schistosomiasis mansoni. METHODS: Twenty-three patients with hepatosplenic schistosomiasis mansoni who were submitted, when children, to splenectomy, ligature of the left gastric vein and auto-implantation of spleen tissue in the major omentum underwent GDx Scanning Laser System evaluations. All patients presented with intraocular pressure below 21 mmHg. RESULTS: Only one patient suffering from hepatosplenic schistosomiasis mansoni showed abnormalities on the GDx examination. There were no abnormalities on GDx examination in the control group. CONCLUSION: There was no significant difference between the two groups of this study. Only one patient showed retinal nerve fiber layer reduction.

[Study of retinal nerve fiber layer in patients with schistosomiasis mansoni: analysis with GDX]. / Estudo da camada de fibras nervosas da retina em pacientes com esquistossomose mansônica: análise com GDx.

PURPOSE: To study the retinal nerve fiber layer in young patients suffering from hepatosplenic schistosomiasis mansoni. METHODS: Twenty-three patients with hepatosplenic schistosomiasis mansoni who were submitted, when children, to splenectomy, ligature of the left gastric vein and auto-implantation of spleen tissue in the major omentum underwent GDx Scanning Laser System evaluations. All patients presented with intraocular pressure below 21 mmHg. RESULTS: Only one patient suffering from hepatosplenic schistosomiasis mansoni showed abnormalities on the GDx examination. There were no abnormalities on GDx examination in the control group. CONCLUSION: There was no significant difference between the two groups of this study. Only one patient showed retinal nerve fiber layer reduction.

Achados oftalmológicos em pacientes com a forma hepatoesplênica da esquistossomose na cidade de Timbaúba-PE / Ophthalmologic findings of patients with the hepatosplenic form of schistosommiasis mansoni in the city of Timbaúba-PE, Brasil

O objetivo do trabalho foi descrever os achados oftalmológicos dos portadores de esquistossomose na forma hepatoesplênica (EHE). Foi realizado um estudo de campo com 464 indivíduos, em agosto de 2003, ma cidade de Timbaúba-PE, os quais foram submetidos a exame oftalmológico completo no ônibos Clínico da Fundação Altino Ventura. Desses, 72 (15,5por cento) indivíduos apresentavam esquistossomose hepatoesplênica(EHE). A presença de EHE, nos pacientes avaliados, esteve significantemente associada a: pior acuidade visual com e sem correção; maior freqüência de alterações à biomicroscopia; maior freqüência de pressão intra-ocular acima de 17mmHg; maior escavação papilar; maior freqüência de alterações fundoscópicas, sobretudo nas manifestações vasculares. Os resultados emprestam suporte ao conceito de que a EHE contribuiu para deterioração da saúde ocuilar de seus portadores

Fatores envolvidos no trauma ocular ocupacional / Factors related to ocular ocupacional trauma

Objetivos: Analisar o trauma ocular ocupacional em um hospital de emergência em Pernambuco, Brasil. Local: Fundação Altino Ventura, Recife, Pernambuco. Métodos: Foram analisados os casos de traumatismo ocular ocupacional atendidos no serviço de emergência oftalmológica do Hospital da Restauração, no período de junho a outubro de 2000. Resultados: Do total (314/100,0 por cento) de traumatismo oculares atendidos no período em estudo, 187 (59,5 por cento) corresponderam a trauma ocular no ambiente de trabalho. O tipo de lesão mais encontrado foi o corpo estranho corneano (61,0 por cento / n = 108), sendo o metálico o mais freqüente. As profissões mais acometidas foram os serralheiros e mecânicos, sendo que 44,1 por cento (n = 64) eram reincidentes. Apesar de 73,7 por cento (n = 98) afirmarem estar naquele ramo de serviço há mais de um ano, apenas 26,0 por cento (n = 38) relataram usar equipamentos de proteção no momento do acidente, embora estes estivessem disponíveis para uso no local de trabalho em 72,9 por cento (n = 105) dos casos. Conclusões: Houve predomínio de traumatismos oculares ocorridos no ambiente de trabalho, demonstrando a importância de sua prevenção uma vez que é notória a falta de conscientização e/ou negligência de fiscalização por parte de empresas e empregados quanto ao uso de equipamentos de proteção individual.