Instituto Aggeu Magalhaes

Recife, Brazil

Instituto Aggeu Magalhaes

Recife, Brazil

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Queto T.,Laboratorio Of Fisiopatologia Humana | Xavier-Elsas P.,Federal University of Rio de Janeiro | Gardel M.A.,Laboratorio Of Fisiopatologia Humana | De Luca B.,Laboratorio Of Fisiopatologia Humana | And 7 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010

Rationale: The mechanism of action of diethylcarbamazine (DEC), an antifilarial drug effective against tropical pulmonary eosinophilia, remains controversial. DEC effects on microfilariae depend on inducible NO synthase (iNOS). In eosinophilic pulmonary inflammation, its therapeutic mechanism has not been established. We previously described the rapid up-regulation of bone marrow eosinophilopoiesis in ovalbumin (OVA)-sensitized mice by airway allergen challenge, and further evidenced the down-regulation of eosinophilopoiesis by iNOS- and CD95L-dependent mechanisms. Objectives:We investigated whether: (1) DEC can prevent the effects of airway challenge of sensitized mice on lungs and bone marrow, and (2) its effectiveness depends on iNOS/CD95L. Methods: OVA-sensitized BALB/c mice were intranasally challenged for 3 consecutive days, withDECadministered over a 12-, 3-, or 2-day period, ending at the day of the last challenge. We evaluated: (1) airway resistance, cytokine (IFN-γ, IL-4, IL-5, and eotaxin) production, and pulmonary eosinophil accumulation; and (2) bone marrow eosinophil numbers in vivo and eosinophil differentiation ex vivo. Measurements and Main Results: DEC effectively prevented the effects of subsequent challenges on: (1) airway resistance, Th1/Th2 cytokine production, and pulmonary eosinophil accumulation; and (2) eosinophilopoiesis in vivo and ex vivo. Recovery from unprotected challenges included full responses to DEC during renewed challenges. DEC directly suppressed IL-5-dependent eosinophilopoiesis in naive bone marrow. DEC was ineffective in CD95L-deficient gld mice and in mice lacking iNOS activity because of gene targeting or pharmacological blockade. Conclusions: DEC has a strong impact on pulmonary eosinophilic inflammation in allergic mice, as well as on the underlying hemopoietic response, suppressing the eosinophil lineage by an iNOS/ CD95L-dependent mechanism.


Ribeiro E.L.,Federal University of Pernambuco | Ribeiro E.L.,Instituto Aggeu Magalhaes | Barbosa K.P.D.S.,Federal University of Pernambuco | Fragoso I.T.,Federal University of Pernambuco | And 7 more authors.
Mediators of Inflammation | Year: 2014

Diethylcarbamazine (DEC) is an antifilarial drug with potent anti-inflammatory properties as a result of its interference with the metabolism of arachidonic acid. The aim of the present study was to evaluate the anti-inflammatory activity of DEC in a mouse model of acute inflammation (carrageenan-induced pleurisy). The injection of carrageenan into the pleural cavity induced the accumulation of fluid containing a large number of polymorphonuclear cells (PMNs) as well as infiltration of PMNs in lung tissues and increased production of nitrite and tumor necrosis factor-α and increased expression of interleukin-1β, cyclooxygenase (COX-2), and inducible nitric oxide synthase. Carrageenan also induced the expression of nuclear factor-B. The oral administration of DEC (50 mg/Kg) three days prior to the carrageenan challenge led to a significant reduction in all inflammation markers. The present findings demonstrate that DEC is a potential drug for the treatment of acute lung inflammation. © 2014 Edlene Lima Ribeiro et al.


Dos Santos Gomes F.O.,Federal University of Pernambuco | De Melo C.M.L.,Instituto Aggeu Magalhaes | Peixoto C.A.,Instituto Aggeu Magalhaes | De Lima M.D.C.A.,Federal University of Pernambuco | And 3 more authors.
Parasitology Research | Year: 2012

Imidazolidine derivatives are key components for the development of bioactive compounds for the treatment of many diseases, especially Chagas. In fact, others studies showed that the imidazolidine-2,4-dione has stood out by presenting a wide spectrum of pharmacological activities including anticonvulsants, antiarrhythmic, and antiparasitic. In the present study, we investigated themorphological alterations induced by imidazolidine derivates LPSF/NN-52 and LPSF/ NN-100 on trypomastigotes forms of Trypanosoma cruzi through ultrastructural analysis by electron microscopy. Many concentrations were used to measure the antiparasitic propriety promoted by imidazolidine derivatives, and our study indicates that parasites treated with 13 μgmL -1 of the imidazolidine derivates for 24 h revealed severe damage to the parasite's mitochondrial complex. Beyond that, also observed in treated parasites were the following: myelin bodies, enlargement of cytoplasm vacuole, fragmentation of endoplasmic reticulum, and some treated samples clearly showed signs of necrosis. To confirm the ultrastructural results, some assays were performed for knowledge cellular death induction promoted by imidazolidine derivates against immune spleen cells. The induction of the necrotic process through derivatives LPSF/NN-52 and LPSF/NN-100 showed similar results in relation to nifurtimox and benznidazole. In the last assays, it was demonstrated that NN-100 was efficient against epimastigotes and trypomastigotes forms and these results reinforce the mechanisms of action of both new imidazolidine derivatives against T. cruzi. © Springer-Verlag 2012.


PubMed | Instituto Aggeu Magalhaes, Federal Rural University of Pernambuco and Federal University of Pernambuco
Type: | Journal: Mediators of inflammation | Year: 2014

Diethylcarbamazine (DEC) is an antifilarial drug with potent anti-inflammatory properties as a result of its interference with the metabolism of arachidonic acid. The aim of the present study was to evaluate the anti-inflammatory activity of DEC in a mouse model of acute inflammation (carrageenan-induced pleurisy). The injection of carrageenan into the pleural cavity induced the accumulation of fluid containing a large number of polymorphonuclear cells (PMNs) as well as infiltration of PMNs in lung tissues and increased production of nitrite and tumor necrosis factor- and increased expression of interleukin-1, cyclooxygenase (COX-2), and inducible nitric oxide synthase. Carrageenan also induced the expression of nuclear factor-B. The oral administration of DEC (50mg/Kg) three days prior to the carrageenan challenge led to a significant reduction in all inflammation markers. The present findings demonstrate that DEC is a potential drug for the treatment of acute lung inflammation.


Donalisio M.R.,University of Campinas | Peterson A.T.,University of Kansas | Costa P.L.,Instituto Aggeu Magalhaes | Da Silva F.J.,Instituto Aggeu Magalhaes | And 3 more authors.
Journal of Tropical Medicine | Year: 2012

The purpose of this study is to analyze the spatial distribution and population trends through time of Lutzomyia species in a long-term focus of cutaneous leishmaniasis transmission in an Atlantic Forest area, northeastern Brazil. Sand fly populations of different ecological niches were monitored spatiotemporally in 2009. To summarize vegetation characteristics and phenology, we calculated the Normalized Difference Vegetation Index from Landsat images. Using niche modeling approaches, we assessed suites of environmental factors to identify areas of transmission risk. Although 12 species were detected, L. whitmani was the most abundant and broadly distributed across the area, particularly in peridomiciliary locations, and associated negatively with denser vegetation areas. On the other hand, L. complexa, L. sordelli, and L. tupynambai were found almost exclusively in forested areas (P < 0.05), and associated positively with denser vegetation. Lutzomyia species' occurrences are related to specific environmental combinations (with contrast among species) in the region. Copyright © 2012 Maria Rita Donalisio et al.


Parrilha G.L.,Federal University of Minas Gerais | Dias R.P.,Federal University of Minas Gerais | Rocha W.R.,Federal University of Minas Gerais | Mendes I.C.,Federal University of Minas Gerais | And 8 more authors.
Polyhedron | Year: 2012

Complexes [Sb(2Ac4oClPh)Cl2] (1), [Sb(2Ac4oFPh)Cl2] (2), [Sb(2Ac4oNO2Ph)Cl2] (3), [Sb(2Bz4oClPh)Cl 2] (4), [Sb(2Bz4oFPh)Cl2] (5) and [Sb(2Bz4oNO 2Ph)Cl2] (6) were obtained with 2-acetylpyridine-N(4)- ortho-chlorophenyl thiosemicarbazone (H2Ac4oClPh) and its N(4)-ortho-fluor (H2Ac4oFPh) and N(4)-ortho-nitro (H2Ac4oNO2Ph) analogues, and with the corresponding 2-benzoylpyridine-derived thiosemicarbazones (H2Bz4oClPh, H2Bz4oFPh, H2Bz4oNO2Ph). The studied compounds are excellent inhibitors of Trypanosoma cruzi growth. H2Bz4oClPh and complexes (4) and (1) were the most trypanosomicidal. Upon coordination of H2Ac4oClPh to antimony(III) in 1, the therapeutic index (TI) goes from 10.58 to 14.35. However, the best values of TI were found for H2Bz4oClPh (TI = 1240) and H2Ac4oNO2Ph (TI = 773). Structure-activity relationship (SAR) studies did not allow the establishment of correlations between the anti-trypanosomal activity and physico-chemical parameters, but correlations were found between the cytotoxicities and physico-chemical properties. © 2011 Elsevier Ltd. All rights reserved.


Jordao L.M.R.,Federal University of Goais | Vasconcelos D.N.,Federal University of Goais | Moreira R.S.,Instituto Aggeu Magalhaes | Freire M.C.M.,Federal University of Goais
Brazilian Oral Research | Year: 2015

The aim of this study was to describe malocclusion prevalence and its association with individual and contextual factors among Brazilian 12-year-old schoolchildren. This cross-sectional study included data from an oral health survey carried out in Goiânia, Brazil (n = 2,075), and data from the files of the local health authority. The data were collected through oral clinical examinations. The Dental Aesthetic Index (DAI) was used to assess occlusion. The presence of malocclusion (DAI > 25) was used as the dependent variable. The individual independent variables consisted of adolescents' sex and race and their mothers' level of schooling. The clinical variables were caries experience and presence of adverse periodontal condition (calculus and/or gingival bleeding). The contextual variables included type of school and the location of schools in the city's health districts. The Rao-Scott test and multilevel logistic regression were performed. The prevalence of malocclusion was 40.1%. In the final model, significantly higher rates of malocclusion were found among those who attended schools located in less affluent health districts and whose mothers had fewer years of education. Rates were also higher among those presenting calculus and/or gingival bleeding. Malocclusion demonstrated a high prevalence rate and the inequalities in its distribution were determined by individual and contextual factors.


PubMed | Federal University of Goais and Instituto Aggeu Magalhaes
Type: | Journal: Brazilian oral research | Year: 2015

The aim of this study was to describe malocclusion prevalence and its association with individual and contextual factors among Brazilian 12-year-old schoolchildren. This cross-sectional study included data from an oral health survey carried out in Goinia, Brazil (n = 2,075), and data from the files of the local health authority. The data were collected through oral clinical examinations. The Dental Aesthetic Index (DAI) was used to assess occlusion. The presence of malocclusion (DAI > 25) was used as the dependent variable. The individual independent variables consisted of adolescents sex and race and their mothers level of schooling. The clinical variables were caries experience and presence of adverse periodontal condition (calculus and/or gingival bleeding). The contextual variables included type of school and the location of schools in the citys health districts. The Rao-Scott test and multilevel logistic regression were performed. The prevalence of malocclusion was 40.1%. In the final model, significantly higher rates of malocclusion were found among those who attended schools located in less affluent health districts and whose mothers had fewer years of education. Rates were also higher among those presenting calculus and/or gingival bleeding. Malocclusion demonstrated a high prevalence rate and the inequalities in its distribution were determined by individual and contextual factors.


PubMed | Instituto Aggeu Magalhaes
Type: Journal Article | Journal: Tissue & cell | Year: 2015

Sildenafil is an important phosphodiesterase inhibitor used to treat a range of diseases, including cardiovascular disease, prostatic hyperplasia and pulmonary hypertension. Its main mechanism of action is the inhibition of phosphodiesterase 5, leading to increased intracellular cyclic guanosine 3,5-monophosphate. This second messenger plays an interesting role in the reproductive tract. The aim of the present study was to evaluate the effect of Sildenafil on folliculogenesis and fertility in mice. To do so, C57BL/6 wild-type mice and inducible nitric oxide synthase knockout (iNOS(-/-)) mice were treated with Sildenafil, and reproductive variables were evaluated. The treated and control animals underwent estrous cycle and fertility assay. Lipid profile, serum nitric oxide levels and the expression of endothelial nitric oxide synthase, inducible nitric oxide synthase and guanylate cyclase were evaluated. Additionally, ovaries were submitted to histological and morphological analysis. The findings demonstrated that chronic treatment with Sildenafil had no effect on folliculogenesis or fertility in C57BL/6 mice, suggesting that this drug can be safely used by women of childbearing age.


PubMed | Instituto Aggeu Magalhaes
Type: Journal Article | Journal: European journal of pharmacology | Year: 2013

A number of studies have demonstrated the biological activities of peroxisome proliferator-activated receptors. However, few studies have addressed the effects of the agonists of these receptors on lung diseases. The aim of the present study was to evaluate the anti-inflammatory action of a novel synthetic thiazolidine derivative (5Z)-3-benzyl-5-(1H-indol-3-ylmethylene)-thiazolidine-2,4-dione (LPSF/RA-4) on acute lung inflammation (pleurisy) induced by carrageenan. Forty mice were randomly allocated to the following groups: (I) saline control group (sham); (II) carrageenan (CAR) group; (III) CAR+LPSF/RA-4 group treated with LPSF/RA-4 (60 mol/kg); and (IV) INDO group treated with indometacin (5mg/kg). Total cell counts and the measure of nitric oxide (NO) were performed in pleural exudates. Lung fragments were processed for light microscopy, transmission electron microscopy, immunohistochemistry and Western blotting. The influx of leucocytes and NO levels were significantly reduced following treatment with LPSF/RA-4 and INDO. Histopathological and ultrastructural analyses of the CAR group revealed evident tissue alterations, such as oedema, infiltrates of inflammatory cells and emphysema. These alterations were significantly reduced in the groups treated with LPSF/RA-4 or INDO. Immunohistochemistry revealed an increase in inflammatory markers (COX-2, iNOS, TNF- and IL-1) in the lung tissue of the CAR group, whereas the groups treated with LPSF/RA-4 and INDO exhibited significant reductions in such immunomarkers. Western blot analysis revealed an increased expression of COX-2 and IL-1 in the CAR group, which was reduced by treatment with LPSF/RA-4. The present findings demonstrate the potent anti-inflammatory action of the novel derivative thiazolidinedione LPSF/RA-4 in acute lung injury induced by carrageenan.

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