Increased bioavailability of primaquine using poly(ethylene oxide) matrix extended-release tablets administered to beagle dogs.

Primaquine (PQ) is used for the radical cure of Plasmodium vivax malaria and can cause serious side effects in some individuals. The development of an extended-release dosage with poly(ethylene oxide) as a hydrophilic polymer has been investigated to improve drug efficacy and tolerability. The aim of this study was to evaluate in vivo a new extended-release formulation of PQ (60 mg). The formulation was administered to beagle dogs and plasma PQ concentrations were compared to a conventional immediate-release formulation of PQ (60 mg). The evaluation was carried out using a validated high-performance liquid chromatography method using solid-phase extraction. Total PQ exposure in beagle dogs was 2.2 times higher (area under curve of 12 193 versus 5678 ng h/ml) and the elimination half-life of PQ was a 19-fold greater (12.95 hours versus 0.68 hours) with the extended-release tablets compared with the immediate-release tablets. These findings suggest that the extended-release formulation of PQ merits further evaluation for the treatment of P. vivax malaria and/or chemoprophylaxis.

Development, validation and stability study of pediatric atenolol syrup.

Atenolol [4-(2-hydroxy-isopropylaminopropoxy)-phenylacetamide], is a cardioselective beta1-adrenergic receptor blocking agent prescribed for treatment of hypertension, angina pectoris and cardiac arrhythmias. However, most of these medicines are not formulated for easy or accurate administration to children. Atenolol is unstable in solutions and therefore the development of a liquid dosage form is a significant challenge. Studies showed that the degradation rate of atenolol is dependent on the temperature, indicating higher stability at 4 degrees C. Atenolol syrup is stable for 9 days, with acceptable apearance. A second order model adequately described atenolol decomposition when stored as syrup. A stability-indicating method was developed and validated in order to evaluate these studies.

Magnetoelectric effects in the spiral magnets CuCl2 and CuBr2.

The nature and symmetry of transition mechanisms in the spin-spiral copper halides CuCl2 and CuBr2 are analyzed theoretically. The magnetoelectric effects observed in the two multiferroic compounds are described and their phase diagram at zero and applied magnetic fields are worked out. The emergence of the electric polarization at zero field below the paramagnetic phase is shown to result from the coupling of two distinct spin-density waves and to be only partly related to the Dzialoshinskii-Moriya interactions. Applying a magnetic field along the two-fold monoclinic axis of CuCl2 yields a decoupling of the spin-density waves modifying the symmetry of the phase and the spin-spiral orientation. The remarkable periodic dependences of the magnetic susceptibility and polarization, on rotating the field in the monoclinic plane, are described theoretically.

Histomorphologic characterization of the hepatopancreas of freshwater prawn Macrobrachium rosenbergii (De Man, 1879) / Caracterização histomorfológica do hepatopâncreas do camarão-de-água-doce Macrobrachium rosenbergii (De Man, 1879)

This study aimed to describe the Macrobrachium rosenbergii hepatopancreas histomorphology. The hepatopancreas is constituted by a set of blind end tubules, divided into proximal, middle, and distal regions, with the epithelium formed by E, F, B, R, and M cells differently of other species. Measurements of the length and width of the tubules were 419.64+69.09µm and 117.42+16.99µm, respectively. The percentage of each cell type per region was: proximal region (40%B, 20%F, 6.7%M, 33.3%R), middle region (45.4%B, 18.2%F, 9.1%M, and 27.3%R) and distal region (36.4%E, 27.2%B, 18.2%F, 9.1%M, 9.1%R). Cell B that stores glycogen and lipids, is the most commonly found cell in proximal and middle regions. In the distal region, the E, responsible for the mitosis, is the most prominent. M, responsible by nutrient storage, is numerically constant among the portions differently in the Macrobrachium amazonicum. The study for the first time also suggests that in addition to digestive enzymes, the F cell produces protective mucus. The present study generated for the first time a morphometric profile of M. rosenbergii hepatopancreas, demonstrating differences from other species, and can be an important tool for new studies in nutrition, reproduction, and production with the species.(AU)

O objetivo do presente estudo foi descrever a histomorfologia do hepatopâncreas do camarão-de-água-doce Macrobrachium rosenbergii. Observou-se que ele é constituído por um conjunto de túbulos de fundo cego, sendo cada túbulo dividido em regiões proximal, média e distal, com o epitélio formado por cinco tipos de células (E, F, B, R, M), diferentemente de outras espécies. As medidas de comprimento e largura dos túbulos foram de 419,64+69,09µm e 117,42+16,99µm, respectivamente. A porcentagem de cada tipo celular por região foi: região proximal (40%B, 20%F, 6,7%M, 33,3%R), região média (45,4%B, 18,2%F, 9,1%M e 27,3%R) e região distal (36,4%E, 27,2%B, 18,2%F, 9,1%M, 9,1%R). Assim, a B, que armazena glicogênio e lipídeos, é a célula mais encontrada nas regiões proximal e média. Na região distal, a célula E, responsável pela mitose, é a mais encontrada. A célula M, responsável pelo acúmulo de nutrientes, tem um número constante de células nas porções do túbulo, diferentemente do Macrobrachium amazonicum. O estudo também sugere, pela primeira vez, que a célula F produz, além de enzimas digestivas, um muco protetor para o túbulo hepatopancreático. O presente estudo foi o primeiro a gerar um perfil morfométrico do hepatopâncreas do M. rosenbergii e demonstrou diferenças em relação a outras espécies, bem como serviu de importante ferramenta para novos estudos que abranjam a produção, a nutrição e a reprodução para a espécie.(AU)

Resultados da aplicação tópica do extrato de própolis na redução da progressão da doença periodontal / Results of topical application of propolis extracts in reducing progression of periodontal disease

RESUMO Agentes químicos têm sido usados para auxiliar na inibição da formação do biofilme e impedir desenvolvimento da doença periodontal (DP). O objetivo deste estudo foi avaliar radiograficamente a ação do extrato de própolis na progressão da DP induzida em ratos. Foram utilizados 48 ratos Wistar, divididos em 4 grupos (n=12): Controle, Pincel, Própolis e Clorexidina. Os grupos foram subdivididos para análise aos 7 e 21 dias. A progressão da DP foi avaliada radiograficamente pela distância entre a junção cemento-esmalte e a crista óssea alveolar na face mesial do 1º molar inferior. A perda óssea foi significativamente menor nos animais do grupo própolis em ambos os períodos (p ≤ 0,01). Concluiu-se por análise radiográfica que a aplicação tópica do extrato de própolis interfere reduzindo a progressão da doença periodontal induzida por ligadura em ratos, demonstrando a importância desse composto como substância auxiliar no tratamento periodontal.

ABSTRACT Chemical agents have been used to assist on inhibiting biofilm formation and on preventing the development of periodontal disease (PD). The aim of this study was to radiographically evaluate the action of propolis extract on the progression of PD induced in rats. 48 Wistar rats were divided into 4 groups (n = 12): Control, Brush, Propolis and Chlorhexidine. The groups were subdivided for analysis at 7 and 21 days. The progression of the periodontal disease was radiographically assessed by the distance between the cement-enamel junction and the alveolar bone crest mesial of the 1st molar. Bone loss was significantly lower in the Propolis group in both periods (p ≤ 0.01). By radiographic analysis, it is concluded that the topical application of propolis extract interferes by reducing the progression of ligature-induced periodontal disease in rats, demonstrating the importance of this compound as an auxiliary substance in periodontal treatment.

Avaliação da qualidade e equivalência farmacêutica de comprimidos contendo 10mg de sinvastatina / Assessment of quality and pharmaceutical equivalence of 10 mg simvastatin tablets

A sinvastatina, pertencente à classe das estatinas, é um importante fármaco redutor do colesterol e é encontrada comercialmente como medicamentos referência, genéricos e similares em diferentes dosagens, sendo a de 10 mg a mais comum. Este trabalho tem como objetivo avaliar a qualidade e a equivalência entre comprimidos de sinvastatina 10 mg comercializados no mercado brasileiro. Foram selecionados dois medicamentos similares, um genérico e referência. Os ensaios de controle de qualidade aplicados foram: determinação do peso médio, dureza, friabilidade, desintegração, teor de princípio ativo, uniformidade de conteúdo e dissolução in vitro. Para tanto, foi necessário desenvolvimento e validação de metodologia por espectrofotometria na região do ultravioleta (UV). As formulações apresentaram-se dentro dos limites preconizados para todas as análises. No entanto, quando analisou-se estatisticamente os perfis de dissolução, verificou-se a não equivalência entre os medicamentos similares e o de referência. Porém, através dos resultados obtidos, podemos evidenciar a equivalência entre o genérico e o de referência, sugerindo sua intercambialidade...

Simvastatin, a well-known medicine of the statin class, is used therapeutically for the reduction of cholesterol and is commercially available in reference, similar and generic forms, in various doses, the tablet of 10 mg being the commonest in prescriptions. The purpose of this study was to test the quality and the pharmaceutical equivalence of tablets containing 10 mg of simvastatin available on the Brazilian market. One generic, one reference and two similar dosage forms were selected. The quality-control variables used were: weight variation, hardness, friability, disintegration, content of the active principle, content uniformity and dissolution in vitro. A UV-spectrophotometric method was developed and validated. All formulations were approved in the quality analysis. By using mathematical and statistical models, it was observed that the dissolution profiles of the similar dosage forms were not equivalent to that of the reference. On the other hand, when the generic medicine was compared with the reference, their interchangeability was confirmed...

Effect of binders on 500mg metformin hydrochloride tablets produced by wet granulation

Metformin hydrochloride (MH) is an oral hypoglycemic agent and a high-dose drug that has poor flow and compression properties. In this study, the feasibility of developing adequate, low cost 500mg tablets of metformin hydrochloride by wet granulation was tested with several binders (Starch / PVP K30®; Starch1500® /PVP K30®, PVP K30® and PVP K90®) in a simple tablet press of the type used in small pharmaceutical laboratories. The drug powder was tested for ability to flow, by determining Carr?s Index (CI) and the Hausner ratio (HR). Differential scanning calorimetry and thermogravimetric analysis were carried out on isolated MH and 1:1 (w/w) binary mixtures with the excipients. The size distribution, friability, flow properties and drug content of the granules were analyzed, as were the hardness, friability, disintegration, dissolution and uniformity of the dosage form. The drug powder showed CI > 22% and HR > 1.25, characteristic of a poor flow powder, and no significant incompatibilities with the excipients. All the granules showed adequate flow properties and were suitable for pressing into tablets, all of which complied with pharmacopeial specifications. The starch /PVP K30® and starch 1500®/PVP K30® mixtures were best for producing 500 mg MH tablets.

Cloridrato de metformina é um fármaco hipoglicemiante oral que apresenta propriedades pobres de fluxo e compressibilidade. Este trabalho teve como objetivo o desenvolvimento de comprimidos de baixo custo,após granulação por via úmida, contendo 500 mg de cloridrato de metformina e diferentes aglutinantes (F1-amido / PVP K30®; F2- Starch 1500® / PVP K30®, F3-PVP K30®, F4- PVP K90®) em máquinas de compressão de baixo desempenho usadas em laboratórios farmacêuticos de pequeno porte. As propriedades defluxo do fármaco foram analisadas através do índice de Carr (IC) e fator de Hausner (FH). Cloridrato de metformina e suas misturas binárias com os excipientes na relação 1:1 (m/m) foram analisadas por calorimetria diferencial por varredura e análise termogravimétrica. Os granulados foram analisados quanto a distribuição granulométrica, friabilidade, propriedades de fluxo e teor e os comprimidos em relação à dureza, friabilidade, desintegração, dissolução e uniformidade de conteúdo.O cloridrato de metformina apresentou IC > 22% e FH> 1,25, característicos de fluxo pobre e não apresentou incompatibilidades com os outros excipientes. Todos os granulados demonstraram adequadas propriedades de fluxo e facilidade no processo de compressão. Os comprimidos apresentaram conformidade com as especificações farmacopeicas. As misturas amido / PVPK30® e Starch 1500® / PVP K30® foram mais adequadas para produzir comprimidos de cloridrato de metformina 500 mg.

Transcriptome characterization of the dimorphic and pathogenic fungus Paracoccidioides brasiliensis by EST analysis.

Paracoccidioides brasiliensis is a pathogenic fungus that undergoes a temperature-dependent cell morphology change from mycelium (22 degrees C) to yeast (36 degrees C). It is assumed that this morphological transition correlates with the infection of the human host. Our goal was to identify genes expressed in the mycelium (M) and yeast (Y) forms by EST sequencing in order to generate a partial map of the fungus transcriptome. Individual EST sequences were clustered by the CAP3 program and annotated using Blastx similarity analysis and InterPro Scan. Three different databases, GenBank nr, COG (clusters of orthologous groups) and GO (gene ontology) were used for annotation. A total of 3,938 (Y = 1,654 and M = 2,274) ESTs were sequenced and clustered into 597 contigs and 1,563 singlets, making up a total of 2,160 genes, which possibly represent one-quarter of the complete gene repertoire in P. brasiliensis. From this total, 1,040 were successfully annotated and 894 could be classified in 18 functional COG categories as follows: cellular metabolism (44%); information storage and processing (25%); cellular processes-cell division, posttranslational modifications, among others (19%); and genes of unknown functions (12%). Computer analysis enabled us to identify some genes potentially involved in the dimorphic transition and drug resistance. Furthermore, computer subtraction analysis revealed several genes possibly expressed in stage-specific forms of P. brasiliensis. Further analysis of these genes may provide new insights into the pathology and differentiation of P. brasiliensis.

Concentraçäo mínima inibitória de dez antimicrobianos para amostras de Staphylococcus aureus isoladas de infecçäo intramamária bovina / Minimum inhibitory concentrations for ten antimicrobial agents against Staphylococcus aureus from bovine intramammary infection

Determinou-se a concentraçäo mínima inibitória (CMI) de ampicilina, cefalotina, eritromicina, gentamicina, neomicina, norfloxacina, oxacilina, penicilina G, tetraciclina e tilosina para 112 amostras de Staphylococcus aureus isoladas de infecçöes intramamárias bovina, em 33 rebanhos leiteiros da Zona da Mata do Estado de Minas Gerais. Foram isoladas 24 amostras de infecçäo clínica, 66 de subclínica e 22 de infecçäo crônica. As amostras de infecçäo crônica foram isoladas repetidas vezes dos mesmos quartos mamários de nove vacas de um rebanho, no período de 13 meses. A CMI foi realizada em ágar Mueller Hinton, com concentraçöes entre 0,015 e 128µgml elevado a -1 de cada antimicrobiano. As amostras da American Type Culture Collection (ATCC) recomendadas para controle de qualidade S. aureus ATCC 29213, Escherichia coli ATCC 25922 e Pseudomonas aeruginosa ATCC 27853, foram incluídas em cada teste. Cem por cento das amostras foram susceptíveis à cefalotina, eritromicina, gentamicina, norfloxacina e oxacilina, 91 por cento à tetraciclina (CMI50 (subscrito): 0,5µgml elevado a -1) e à tilosina (CMI50 (subscrito): 2,0µgml elevado a -1), 65 por cento à ampicilina (CMI50 (subscrito): 0,125µgml elevado a -1) e à penicilina G (CMI50 (subscrito): 0,06µgml elevado a -1). Todas foram susceptíveis neomicina (CMI50 (subscrito): 0,5µgml elevado a -1) exceto uma amostra que apresentou um padräo intermediário. O nível de resistência para ampicilina e penicilina foi maior nas amostras isoladas de casos clínicos e nas de infecçäo subclínica com escores positivos no CMT (P<0,02). Nas isoladas de infecçäo clínica, o nível de resistência à tilosina foi maior (P<0,02). As amostras que apresentaram CMI>=0,125µgm1 elevado a -1 para penicilina foram positivas para produçäo de ß-lactamase

Quantitative and descriptive analysis of the meniscotibial ligament in human corpses

The meniscotibial ligaments (LMT) of humans are capsular fibers with proximal origin in the lateral border of the menisci and distal insertion in the lateral border of the tibial condyle, also called coronary ligament of the knee. However, few studies describe the presence, course and anatomical variations of this ligament. Our objective was to evaluate the LMT through quantitative and descriptive methods. Eighty-five knees were examined(42 right knees [RK] and 43 left knees [LK]), dissected, evaluated, catalogued and photographed by four examiners. Twenty knees (23.53%) presented LMT, 6 (30%) in RK and 14 (70%) in LK. In two RKs, the LMT presented proximal insertion in the medial menisci and distal insertion in medial tibial condyle; in the other ones, the LMT presented proximal insertion in the lateral menisci and distal insertion in the lateral tibial condyle. In the LK, four LMT presented proximal insertion in the medial menisci and distal insertion in the medial tibial condyle, while the other ones presented proximal insertion in the lateral menisci and distal insertionin the lateral tibial condyle. One LMT in the LK presented proximal and distal insertion in both menisci and tibial condyle. The analysis of human corpses in our study suggests that the presence of the LMT is much more common in the LK than in the RK, with more frequent insertion in the proximal region of the lateral menisci and distal insertion in the lateral tibial condyle.