Historic of therapeutic efficacy of albendazol sulphoxide administered in different routes, dosages and treatment schemes, against Taenia saginata in cattle experimentally infected

The present study aimed to notify the history of albendazole sulphoxide (ALB-SO) and albendazole (ALBZ) efficacy against Taenia saginata cysticercus (Cysticercus bovis) parasitizing experimentally infected bovines. A total of 11 efficacy trials were performed between the years of 2002 and 2010. In order to perform these trials, animals were individually inoculated with 2 x 104 eggs of T. saginata in each study's day zero (DO). For every trial, a positive control group (untreated infected animals) and a negative control group (animals that were neither infected nor treated) were used. ALB-SO or ALB were administered in the different dosages, in different days of treatments. In a last study with this formulation, this active principle was administered orally, mixed with the mineral supplement, on the 60th DPI, in a dosage of 30 mg/kg. In all trials, on the 100th DPI, all animals were euthanized and submitted to the sequenced slicing of 26 anatomical segments (fragments of approximately five millimeters) for the survey of T. saginata cysticercus. With the obtained results it is possible to verify that in the first trials, conducted in 2002, ALB-SO reached, independently of dosage and treatment scheme, efficacies superior to 98% (arithmetic means). The trials conducted in 2005 (2.5 mg/kg on the 30th, 60th, and 90th DPI) obtained values of efficacy all inferior to 60%. In 2008, the trials with 2.5 and 7.7 mg/kg demonstrated efficacy values inferior to 40%, for both dosages and treatment schemes (30th/60th/90th DPI and 60th DPI). When this formulation was administered orally on the dosage of 30 mg/kg on the 60th DPI, the efficacy against T. saginata cysticercus reached 88.28%. ALB administered orally showed efficacy values of 0.0%, 29.88% and 28.64% in the dosages of 5, 10 and 15 mg/kg, respectively, using the treatment schemes described above for each dosage. Based on the results of these trials, conducted in an eight year period (2002-2010) using the sequenced slicing method for evaluating the efficacy of the aforementioned formulations against T. saginata cysticercus, it is possible to observe that, amongst the few molecules used in the chemotherapic treatment against T. saginata larvae, ALB-SO, administered in varied routes, dosages and treatment schemes, the studies conducted in 2008, 2009, and 2010, have a low therapeutic efficacy against C bovis in Brazil, while ALBZ had insignificant efficacy values against T. saginata larvae parasitizing experimentally infected bovines. However, future studies using molecular biology will be necessary to assess whether the difference on the efficacy of the ALB-SO can be related to strain or another specific factor. (C) 2013 Elsevier Inc. All rights reserved.

Histopathological study of ovaries of Rhipicephalus sanguineus (Acari: Ixodidae) exposed to different thymol concentrations

Thymol is a monoterpene with proven acaricide action for several tick species. In addition to killing these ectoparasites, thymol can also reduce oviposition and egg hatch rate. However, the effects of thymol on the morphophysiology of tick ovaries are still unknown. Thus, the aim of this study was to evaluate the morphophysiological changes caused by this active principle in ovaries of Rhipicephalus sanguineus after a 6-day feeding period, through the application of morphohistochemical techniques. After the feeding period, a total of 50 females were divided into five groups and immersed in the following solutions: (I) distilled water (control), (II) 30 % ethanol (control), (III) 1.25 mg/mL thymol, (IV) 2.5 mg/mL thymol, and (V) 5.0 mg/mL thymol. The experimental groups were kept in a climatic chamber (27 +/- 1 A degrees C; RH 80 A +/- 10 %) for 5 days. After this period, morphological (hematoxylin/eosin) and histochemical (von Kossa) techniques were applied after remotion of the ovaries. The morphological results revealed large vacuoles in germ cells at different developmental stages and invaginations that represent deformations in the chorionic membrane. From the results obtained in this study, it was concluded that thymol interfered with the development of oocytes, which showed degeneration signs. The treatment containing 5.0 mg/mL thymol affected more accentuately the morphological development. Moreover, thymol also altered the calcium content of yolk granules, which generally showed an intense staining for this element.

Perfil da farmacoterapia utilizada por idosos institucionalizados: uma análise dos problemas relacionados ao uso de medicamentos em instituições de longa permanência para idosos

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

Notificações espontâneas de eventos adversos a medicamentos hospitalares: estudo piloto

Introduction: Post-marketing surveillance of drugs aims to detect problems related to safety, effectiveness and quality. The identification of adverse drug events (ADE) is made, mainly, by health professionals´ spontaneous reporting. This method allows risk communication in pharmacovigilance and contributes for market regulation. Objective: To estimate the prevalence of adverse drug reaction (ADR) and the suspicions of therapeutic failure (TF) reported by health professionals; to verify the active principle and type of drugs related to ADE, seriousness, causality, production mechanism and clinical manifestation of the events identified. METHODS: A cross-sectional study was performed in a teaching and public hospital which integrates the Sentinel Hospital Network, in 2008. ADR seriousness was classified according to intensity (mild, moderate, serious and lethal); drugs associated with ADE were categorized according to type (brand name drugs and non-brand name drugs); causality was imputed with Naranjo algorithm and the mechanism of occurrence was analyzed according to Rawlins e Thompson definitions (A or B). Results: There were 103 ADE reports in the period, of which 39 comprised TF and 64 ADR. Nurses reported the most ADE (53.4%). The majority of ADR were classified as type A (82.8%), mild (81.3%), possible (57.8%), according to causality assessment, and related to brand name drugs (20/35). Human immunoglobulin, docetaxel and paclitaxel were the drugs frequently associated with ADR. TF arising from no-brand name drugs (26/29), regarding, mainly, midazolam and ganciclovir. Conclusion: The results of the ADE report contribute for proposition of trigger tools for intensive monitoring of drug safety, as well as for the supplier qualification and for the improvement of quality products.

Processo de produção de composto orgânico derivado de resíduos industriais com aplicação no cultivo de alface

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação fitoquímica e microbiológica da espécia Artemisia annua L. submetida a tratamentos de armazenamento e condições de ambiente

The species Artemisia annua L. (Asteraceae) is native to China and has artemisinin as its main active component, substance that is considered a potent antimalarial drug. With the increased interest in natural active principles, studies related to post-harvest and storage of vegetable material become important for better conservation of its phytotherapic properties. Therefore, the present study had as objectivedefine the best storage conditions to preserve and keep the quality of phytotherapic drugs. Leaves of A. annua dried were stored for six months in polyethylene bags wrapped in Kraft paper and packed in four treatments: at ambient condition, refrigerated at 4 ± 2 oC, using normal packing, and using vacuum packing. Samples were taken for microbiological, moisture content, and level of artemisinin analyses before the experiment begun and at 30, 90, 120 and 180 days. The results of microbiological tests showed no significant contamination, as well as the moisture content of the stored (biological) material, which remain between 5% and 10%, keeping within acceptable parameters. The ambient without vacuum treatment (SVA) was the treatment that better maintained the sample stability during 180 days, however, the refrigerated without vacuum (SVR) showed greater efficiency to conserve the content of artemisinin.

Exogenous Administration of 15d-PGJ(2)-Loaded Nanocapsules Inhibits Bone Resorption in a Mouse Periodontitis Model

The 15-deoxy-(Delta 12,14)-PG J(2) (15d-PGJ(2)) has demonstrated excellent anti-inflammatory results in different experimental models. It can be used with a polymeric nanostructure system for modified drug release, which can change the therapeutic properties of the active principle, leading to increased stability and slower/prolonged release. The aim of the current study was to test a nano-technological formulation as a carrier for 15d-PGJ(2), and to investigate the immunomodulatory effects of this formulation in a mouse periodontitis model. Poly (D, L-lactide-coglycolide) nanocapsules (NC) were used to encapsulate 15d-PGJ(2). BALB/c mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 5) that were treated daily during 15 d with 1, 3, or 10 mu g/kg 15d-PGJ(2)-NC. The animals were sacrificed, the submandibular lymph nodes were removed for FACS analysis, and the jaws were analyzed for bone resorption by morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by reverse transcriptase-quantitative PCR, Western blotting, or ELISA. Infected animals treated with the 15d-PGJ(2)-NC presented lower bone resorption than infected animals without treatment (p < 0.05). Furthermore, infected animals treated with 10 mu g/kg 15d-PGJ(2)-NC had a reduction of CD4(+)CD25(+)FOXP3(+) cells and CD4/CD8 ratio in the submandibular lymph node (p < 0.05). Moreover, CD55 was upregulated, whereas RANKL was downregulated in the gingival tissue of the 10 mu g/kg treated group (p < 0.05). Several proinflammatory cytokines were decreased in the group treated with 10 mu g/kg 15d-PGJ(2)-NC, and high amounts of 15d-PGJ(2) were observed in the gingiva. In conclusion, the 15d-PGJ(2)-NC formulation presented immunomodulatory effects, decreasing bone resorption and inflammatory responses in a periodontitis mouse model. The Journal of Immunology, 2012, 189: 1043-1052.

Novel retinoic acid receptor ligands in Xenopus embryos.

Retinoids are a large family of natural and synthetic compounds related to vitamin A that have pleiotropic effects on body physiology, reproduction, immunity, and embryonic development. The diverse activities of retinoids are primarily mediated by two families of nuclear retinoic acid receptors, the RARs and RXRs. Retinoic acids are thought to be the only natural ligands for these receptors and are widely assumed to be the active principle of vitamin A. However, during an unbiased, bioactivity-guided fractionation of Xenopus embryos, we were unable to detect significant levels of all-trans or 9-cis retinoic acids. Instead, we found that the major bioactive retinoid in the Xenopus egg and early embryo is 4-oxoretinaldehyde, which is capable of binding to and transactivating RARs. In addition to its inherent activity, 4-oxoretinaldehyde appears to be a metabolic precursor of two other RAR ligands, 4-oxoretinoic acid and 4-oxoretinol. The remarkable increase in activity of retinaldehyde and retinol as a consequence of 4-oxo derivatization suggests that this metabolic step could serve a critical regulatory function during embryogenesis.

Potentiation of the bioavailability of daidzin by an extract of Radix puerariae.

The dose effect of pure daidzin on the suppression of ethanol intake in Syrian golden hamsters was compared with that of crude daidzin contained in a methanol extract of Radix puerariae (RP). EC50 values estimated from the graded dose-response curves for pure daidzin and RP extract daidzin are 23 and 2.3 mg per hamster per day, respectively. Apparently the antidipsotropic activity of the RP extract cannot be accounted for solely by its daidzin content (22 mg/g). In addition to daidzin, six other isoflavones were identified in the RP extract and quantified--namely, puerarin (160 mg per g of extract), genistin (3.7 mg/g), daidzein (2.6 mg/g), daidzein-4',7-diglucoside (1.2 mg/g), genistein (0.2 mg/g), and formononetin (0.16 mg/g). None of these, administered either alone or combined, contributes in any significant way to the antidipsotropic activity of the extract. Plasma daidzin concentration-time curves determined in hamsters administered various doses of pure daidzin or RP extract by i.p.injection indicate that the crude extract daidzin has approximately 10 times greater bioavailability than the pure compound. Reconstruction of the dose-response effects for pure and crude daidzin using bioavailable daidzin rather than administered dose gives a single curve. Synthetic daidzin added to the RP extract acquires the bioavailability of the endogenous daidzin that exists naturally in the extract. These results show that (i) daidzin is the major active principle in methanol extracts of RP, and (ii) additional constituents in the methanol extract of RP assist uptake of daidzin in golden hamsters.

Development of plasmid dna formulations for application as microspheric dna vaccines

The advent of DNA vaccines has heralded a new technology allowing the design and elicitation of immune responses more adequate for a wider range of pathogens. The formulation of these vaccines into the desired dosage forms extends their capability in terms of stability, routes of administration and efficacy. This thesis describes an investigation into the fabrication of plasmid DNA, the active principle of DNA vaccines, into microspheres, based on the tenet of an increased cellular uptake of microparticulate matter by phagocytic cells. The formulation of plasmid DNA into microspheres using two methods, is presented. Formulation of microspheric plasmid DNA using the double emulsion solvent evaporation method and a spray-drying method was explored. The former approach involves formation of a double emulsion, by homogenisation. This method produced microspheres of uniform size and smooth morphology, but had a detrimental effect on the formulated DNA. The spray-drying method resulted in microspheres with an improved preservation of DNA stability. The use of polyethylenimine (PEI) and stearylamine (SA) as agents in the microspheric formulation of plasmid DNA is a novel approach to DNA vaccine design. Using these molecules as model positively-charged agents, their influence on the characteristics of the microspheric formulations was investigated. PEI improved the entrapment efficiency of the plasmid DNA in microspheres, and has minimal effect on either the surface charge, morphology or size distribution of the formulations. Stearylamine effected an increase in the entrapment efficiency and stability of the plasmid DNA and its effect on the micropshere morphology was dependent on the method of preparation. The differences in the effects of the two molecules on microsphere formulations may be attributable to their dissimilar physico-chemical properties. PEI is water-soluble and highly-branched, while SA is hydrophobic and amphipathic. The positive charge of both molecules is imparted by amine functional groups. Preliminary data on the in vivo application of formulated DNA vaccine, using hepatitis B plasmid, showed superior humoral responses to the formulated antigen, compared with free (unformulated) antigen.

Chemoenzymatic routes to enantiopure hydroxytetrahydrofurans: muscarine and its analogues

Muscarine was identified as an active principle of the poisonous mushroom Amanita muscaria over 170 years ago and has been identified as an agonist of acetylcholine. The synthesis of all stereoisomers of muscarine have been accomplished at this stage by chemical methods and the biological activity of these compounds tested. A number of synthetic routes to enantiomerically pure muscarine and its analogues have been published. In this work, we are focussed on the use of a novel biotransformation strategy to access these compounds. Asymmetric synthesis involves targeting a synthetic pathway leading to one enantiomer of a compound and biocatalysis is one strategy used in asymmetric synthesis. Chapter 1 consists of a review of the relevant literature pertaining to the synthesis and stereoselective transformations of 3-hydroxytetrahydrofuranss. A review of synthetic routes to these compounds is presented, with a particular focus on routes to the natural product muscarine and its analogues. Chapter 2 discusses the preparative routes to the 3-hydroxytetrahydrofurans via 3(2H)- furanones. Steps amongst which include Rh(II) mediate cyclisation and kinetic resolution via baker’s yeast mediated carbonyl reduction, resulting in enantioenriched 3- hydroxytetrahydrofuran derivatives. Finally, application of this methodology to the preparation of all four enantiomers of an analogue of desmethylmuscarine and the synthesis of epimuscarine is described. Chapter 3 consists of a detailed experimental section outlining the synthetic procedures employed.

Estudo da influência da morfologia de nanopartículas de sílica mesoporosa na liberação do anticancerígeno indol-3-carbinol

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ceilândia, Programa de Pós-graduação em Ciências e Tecnologias em Saúde, 2015.

Exogenous Administration of 15d-PGJ(2)-Loaded Nanocapsules Inhibits Bone Resorption in a Mouse Periodontitis Model

The 15-deoxy-(Delta 12,14)-PG J(2) (15d-PGJ(2)) has demonstrated excellent anti-inflammatory results in different experimental models. It can be used with a polymeric nanostructure system for modified drug release, which can change the therapeutic properties of the active principle, leading to increased stability and slower/prolonged release. The aim of the current study was to test a nano-technological formulation as a carrier for 15d-PGJ(2), and to investigate the immunomodulatory effects of this formulation in a mouse periodontitis model. Poly (D, L-lactide-coglycolide) nanocapsules (NC) were used to encapsulate 15d-PGJ(2). BALB/c mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 5) that were treated daily during 15 d with 1, 3, or 10 mu g/kg 15d-PGJ(2)-NC. The animals were sacrificed, the submandibular lymph nodes were removed for FACS analysis, and the jaws were analyzed for bone resorption by morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by reverse transcriptase-quantitative PCR, Western blotting, or ELISA. Infected animals treated with the 15d-PGJ(2)-NC presented lower bone resorption than infected animals without treatment (p < 0.05). Furthermore, infected animals treated with 10 mu g/kg 15d-PGJ(2)-NC had a reduction of CD4(+)CD25(+)FOXP3(+) cells and CD4/CD8 ratio in the submandibular lymph node (p < 0.05). Moreover, CD55 was upregulated, whereas RANKL was downregulated in the gingival tissue of the 10 mu g/kg treated group (p < 0.05). Several proinflammatory cytokines were decreased in the group treated with 10 mu g/kg 15d-PGJ(2)-NC, and high amounts of 15d-PGJ(2) were observed in the gingiva. In conclusion, the 15d-PGJ(2)-NC formulation presented immunomodulatory effects, decreasing bone resorption and inflammatory responses in a periodontitis mouse model. The Journal of Immunology, 2012, 189: 1043-1052.

Deconjugated Bile Salts Produced by Extracellular Bile-Salt Hydrolase-Like Activities from the Probiotic Lactobacillus johnsonii La1 Inhibit Giardia duodenalis In vitro Growth

Giardiasis, currently considered a neglected disease, is caused by the intestinal protozoan parasite Giardia duodenalis and is widely spread in human as well as domestic and wild animals. The lack of appropriate medications and the spread of resistant parasite strains urgently call for the development of novel therapeutic strategies. Host microbiota or certain probiotic strains have the capacity to provide some protection against giardiasis. By combining biological and biochemical approaches, we have been able to decipher a molecular mechanism used by the probiotic strain Lactobacillus johnsonii La1 to prevent Giardia growth in vitro. We provide evidence that the supernatant of this strain contains active principle(s) not directly toxic to Giardia but able to convert non-toxic components of bile into components highly toxic to Giardia. By using bile acid profiling, these components were identified as deconjugated bile-salts. A bacterial bile-salt-hydrolase of commercial origin was able to mimic the properties of the supernatant. Mass spectrometric analysis of the bacterial supernatant identified two of the three bile-salt-hydrolases encoded in the genome of this probiotic strain. These observations document a possible mechanism by which L. johnsonii La1, by secreting, or releasing BSH-like activity(ies) in the vicinity of replicating Giardia in an environment where bile is present and abundant, can fight this parasite. This discovery has both fundamental and applied outcomes to fight giardiasis, based on local delivery of deconjugated bile salts, enzyme deconjugation of bile components, or natural or recombinant probiotic strains that secrete or release such deconjugating activities in a compartment where both bile salts and Giardia are present.

Road segment delineation using active testing principle and an edge-based post-processing strategy

This paper presents a semi-automated method for extracting road segments from medium-resolution images based on active testing and edge analysis. The method is based on two sequential and independent stages. Firstly, an active testing method is used to extract an approximated road centreline which is based on a sequential and local exploitation of the image. Secondly, an iterative strategy based on edge analysis and the approximated centreline is used to measure precisely the road centreline. Based on the results obtained using medium-resolution test images, the method seems to be very promising. In general, the method proved to be very accurate whenever the roads are characterized by two well-defined anti-parallel edges and robust even in the presence of larger obstacles such as trees and shadows.