Fiocruz
no Portal
neste Site
Fundação Oswaldo Cruz
Página Principal

Área de PDI em Pesquisa, Desenvolvimento e Inovação em Farmacologia, Fisiopatologia, Inovações Terapêuticas e Bioprodutos 2013

Veja, abaixo, a relação de artigos científicos publicados pelo IOC, na referida Área Temática, organizados em ordem alfabética crescente:

Total: 0
Amancio RT, Japiassu AM, Gomes RN, Mesquita EC, Assis EF, Medeiros DM, Grinsztejn B, Bozza PT, Neto HCCF and Bozza FA (2013), "The Innate Immune Response in HIV/AIDS Septic Shock Patients: A Comparative Study", Plos One., July, 2013. Vol. 8(7), pp. e68730. Public Library Science.
Abstract: Introduction: In recent years, the incidence of sepsis has increased in critically ill HIV/AIDS patients, and the presence of severe sepsis emerged as a major determinant of outcomes in this population. The inflammatory response and deregulated cytokine production play key roles in the pathophysiology of sepsis; however, these mechanisms have not been fully characterized in HIV/AIDS septic patients. Methods: We conducted a prospective cohort study that included HIV/AIDS and non-HIV patients with septic shock. We measured clinical parameters and biomarkers (C-reactive protein and cytokine levels) on the first day of septic shock and compared these parameters between HIV/AIDS and non-HIV patients. Results: We included 30 HIV/AIDS septic shock patients and 30 non-HIV septic shock patients. The HIV/AIDS patients presented low CD4 cell counts (72 [7-268] cells/mm(3)), and 17 (57%) patients were on HAART before hospital admission. Both groups were similar according to the acute severity scores and hospital mortality. The IL-6, IL-10 and G-CSF levels were associated with hospital mortality in the HIV/AIDS septic group; however, the CRP levels and the surrogates of innate immune activation (cytokines) were similar among HIV/AIDS and non-HIV septic patients. Age (odds ratio 1.05, CI 95% 1.02-1.09, p=0.002) and the IL-6 levels (odds ratio 1.00, CI 95% 1.00-1.01, p=0.05) were independent risk factors for hospital mortality. Conclusions: IL-6, IL-10 and G-CSF are biomarkers that can be used to predict prognosis and outcomes in HIV/AIDS septic patients. Although HIV/AIDS patients are immunocompromised, an innate immune response can be activated in these patients, which is similar to that in the non-HIV septic population. In addition, age and the IL-6 levels are independent risk factors for hospital mortality irrespective of HIV/AIDS disease.
BibTeX:
 @article{Amancio2013, author = {Amancio, R. T. and Japiassu, A. M. and Gomes, R. N. and Mesquita, E. C. and Assis, E. F. and Medeiros, D. M. and Grinsztejn, B. and Bozza, P. T. and Neto, H. C. C. F. and Bozza, F. A.}, title = {The Innate Immune Response in HIV/AIDS Septic Shock Patients: A Comparative Study}, journal = {Plos One}, publisher = {Public Library Science}, year = {2013}, volume = {8}, number = {7}, pages = {e68730}, doi = {10.1371/journal.pone.0068730} } 
Amaral JJ, Antunes LCM, de Macedo CS, Mattos KA, Han J, Pan JX, Candea ALP, Henriques MDMO, Ribeiro-Alves M, Borchers CH, Sarno EN, Bozza PT, Finlay BB and Pessolani MCV (2013), "Metabonomics Reveals Drastic Changes in Anti-Inflammatory/Pro-Resolving Polyunsaturated Fatty Acids-Derived Lipid Mediators in Leprosy Disease", Plos Neglected Tropical Diseases., August, 2013. Vol. 7(8), pp. e2381. Public Library Science.
Abstract: Despite considerable efforts over the last decades, our understanding of leprosy pathogenesis remains limited. The complex interplay between pathogens and hosts has profound effects on host metabolism. To explore the metabolic perturbations associated with leprosy, we analyzed the serum metabolome of leprosy patients. Samples collected from lepromatous and tuberculoid patients before and immediately after the conclusion of multidrug therapy (MDT) were subjected to high-throughput metabolic profiling. Our results show marked metabolic alterations during leprosy that subside at the conclusion of MDT. Pathways showing the highest modulation were related to polyunsaturated fatty acid (PUFA) metabolism, with emphasis on anti-inflammatory, pro-resolving omega-3 fatty acids. These results were confirmed by eicosanoid measurements through enzyme-linked immunoassays. Corroborating the repertoire of metabolites altered in sera, metabonomic analysis of skin specimens revealed alterations in the levels of lipids derived from lipase activity, including PUFAs, suggesting a high lipid turnover in highly-infected lesions. Our data suggest that omega-6 and omega-3, PUFA-derived, pro-resolving lipid mediators contribute to reduced tissue damage irrespectively of pathogen burden during leprosy disease. Our results demonstrate the utility of a comprehensive metabonomic approach for identifying potential contributors to disease pathology that may facilitate the development of more targeted treatments for leprosy and other inflammatory diseases.
BibTeX:
 @article{Amaral2013, author = {Amaral, J. J. and Antunes, L. C. M. and de Macedo, C. S. and Mattos, K. A. and Han, J. and Pan, J. X. and Candea, A. L. P. and Henriques, M. D. M. O. and Ribeiro-Alves, M. and Borchers, C. H. and Sarno, E. N. and Bozza, P. T. and Finlay, B. B. and Pessolani, M. C. V.}, title = {Metabonomics Reveals Drastic Changes in Anti-Inflammatory/Pro-Resolving Polyunsaturated Fatty Acids-Derived Lipid Mediators in Leprosy Disease}, journal = {Plos Neglected Tropical Diseases}, publisher = {Public Library Science}, year = {2013}, volume = {7}, number = {8}, pages = {e2381}, doi = {10.1371/journal.pntd.0002381} } 
de Arruda VAS, Pereira AAS, de Freitas AS, Barth OM and de Almeida-Muradian LB (2013), "Dried bee pollen: B complex vitamins, physicochemical and botanical composition", Journal of Food Composition and Analysis., March, 2013. Vol. 29(2), pp. 100-105. Academic Press Inc Elsevier Science.
Abstract: We investigated the concentration of B complex vitamins (B-1, B-2, B-6 and PP) including their vitamers, physicochemical composition and botanical origin of dried bee pollen samples from the State of Sao Paulo, Brazil. The possible influence of pollen types on the proximate composition and vitamin content was also verified. Vitamins, after simultaneous extraction, were quantified by HPLC, with fluorescence detection. The results showed a great concentration difference of B complex vitamins in the samples analyzed. The variations were (dry basis): 0.59-1.09 mg/100 g for vitamin B-1; 1.73-2.56 mg/100 g for vitamin B-2; 6.43-15.34 mg/100 g for vitamin PP and 0.33-0.68 mg/100 g for vitamin B-6. All samples were considered sources of vitamin By. For the proximate composition, this was not observed, and the results were: 3.47 +/- 0.30% for moisture; 2.98 +/- 0.18% for ash; 539 +/- 0.60% for lipids and 23.38 +/- 1.24% for protein. The frequency of the plant families presented showed a total of 10 significant pollen types: Arecaceae, Cecropia, Cestrum, Cyperaceae, Eucalyptus, Ilex, Myrcia, Piper, Vernonia and Trema. The data analyzed served as an indication of the nutritional quality and value for commercial dried bee pollen. (C) 2013 Published by Elsevier Inc.
BibTeX:
 @article{Arruda2013, author = {de Arruda, V. A. S. and Pereira, A. A. S. and de Freitas, A. S. and Barth, O. M. and de Almeida-Muradian, L. B.}, title = {Dried bee pollen: B complex vitamins, physicochemical and botanical composition}, journal = {Journal of Food Composition and Analysis}, publisher = {Academic Press Inc Elsevier Science}, year = {2013}, volume = {29}, number = {2}, pages = {100--105}, doi = {10.1016/j.jfca.2012.11.004} } 
Bargut TCL, Ferreira TPT, Daleprane JB, Martins MA, Silva PMR and Aguila MB (2013), "Fish oil has beneficial effects on allergen-induced airway inflammation and hyperreactivity in mice.", PLoS One. Vol. 8(9), pp. e75059.
Abstract: Fish oil (FO) is rich in n-3 polyunsaturated fatty acids (PUFA), which have been suggested to be anti-inflammatory and are associated with improvement of several inflammatory diseases. In this study, we investigated the influence of FO on allergen-induced lung inflammation and airway hyperreactivity in mice.Male A/J mice were fed either a standard-chow (SC) or a FO diet (FO) for 8 weeks. After 4 weeks, each group was further randomized for ovalbumin (SC-OVA and FO-OVA) or saline (SC-SAL and FO-SAL) challenge. Resistance and elastance were measured at baseline and after aerosolized methacholine, 24h after the last challenge. Bronchoalveolar lavage (BAL) was performed for leukocyte counts. Lung tissue mucus deposition, peribronchiolar matrix deposition and eosinophil infiltration were quantified. Serum immunoglobulin E (IgE) and IgG1 (ref 2.2), lung IL-4, IL-5, IL-10, IL-13, IL-17, INFγ and eotaxin-1 and 2 were detected by ELISA and nuclear factor kappa B (NFκB), GATA-3 and peroxisome proliferator-activated receptor gamma (PPARγ) expression was measured by Western blot.Levels of serum IgE and IgG1 were significantly higher in OVA sensitized mice. OVA challenge resulted in increased eosinophil infiltration, increased inflammatory cytokine production, peribronchiolar matrix and mucus deposition and airway hyperreactivity to aerosolized methacholine. Elevated lung NFκB and GATA-3 expression was noted in OVA-challenged mice. These changes were attenuated in mice fed with FO diet. Higher PPARγ expression was also detected in the lungs from the FO-fed groups.Our results demonstrate that FO intake attenuated classical asthma features by suppressing the systemic sensitization, thus providing evidence that FO might be a prophylactic alternative for asthma prevention.
BibTeX:
 @article{Bargut2013, author = {Bargut, Thereza Cristina Lonzetti and Ferreira, Tatiana Paula Teixeira and Daleprane, Julio Beltrame and Martins, Marco Aurélio and Silva, Patrícia Machado Rodrigues and Aguila, Marcia Barbosa}, title = {Fish oil has beneficial effects on allergen-induced airway inflammation and hyperreactivity in mice.}, journal = {PLoS One}, year = {2013}, volume = {8}, number = {9}, pages = {e75059}, url = {http://dx.doi.org/10.1371/journal.pone.0075059}, doi = {10.1371/journal.pone.0075059} } 
Barth OM, De Freitas AD, Matsuda AH and De Almeida-Muradian LB (2013), "Botanical origin and Artepillin-C content of Brazilian propolis samples", Grana., June, 2013. Vol. 52(2), pp. 129-135. Taylor & Francis As.
Abstract: Propolis quality depends on its botanical origin and the producing bee species. Twenty-one propolis samples from northeast, southeast and southern Brazil were investigated using palynological and physicochemical techniques. The aim of the present study was to understand Artepillin-C concentration in the propolis samples in relation to the pollen spectrum and its phytogeographical origin. The propolis obtained from Baccharis (Asteraceae), occurring mainly in mountain regions of the southern part of the state of Minas Gerais to the northern part of the state of Parana, presents a high content of Artepillin-C and is the most valuable. Nevertheless, Artepillin-C was detected in the propolis samples from localities where Baccharis plants are growing. It is expected that other plant species of the Asteraceae family, such as Eupatorium, may contribute to the production of propolis containing a high content of flavonoids.
BibTeX:
 @article{Barth2013a, author = {Barth, O. M. and De Freitas, A. D. and Matsuda, A. H. and De Almeida-Muradian, L. B.}, title = {Botanical origin and Artepillin-C content of Brazilian propolis samples}, journal = {Grana}, publisher = {Taylor & Francis As}, year = {2013}, volume = {52}, number = {2}, pages = {129--135}, doi = {10.1080/00173134.2012.747561} } 
Barth OM, Freitas AS, Sousa GL and Almeida-Muradian LB (2013), "POLLEN AND PHYSICOCHEMICAL ANALYSIS OF Apis AND Tetragonisca (APIDAE) HONEY", Interciencia., April, 2013. Vol. 38(4), pp. 280-285. Interciencia.
Abstract: Pollen and physicochemical analyses of honey were carried out in order to distinguish between trophic resources and nutritional preferences of Apis mellifera (honeybees) and Tetragonisca angustula ('jatai' bees). Honey samples from both bee species were obtained on the same day in each apiary. Six apiaries, localized in different regions of the State of Sao Paulo, Brazil, contributed, in different days, to the experiment. No bee species was more generalist than the other. Eucalyptus and Citrus, two introduced plant genera in Brazil, were very attractive to honeybees. The preference of fatal bees was directed to plants of the native flora. The assemblage, of plant species visited during the flowering period by Apis and Tetragonisca was not the same. Physicochemical analyses showed differences between all analyzed parameters, except for color determination. Jatai honeys presented higher values of humidity, acidity, diastase, ashes, sucrose and electric conductivity, and Apis honeys of fructose and glucose. No correspondence between physicochemical and monofloral honey properties was observed.
BibTeX:
 @article{Barth2013, author = {Barth, O. M. and Freitas, A. S. and Sousa, G. L. and Almeida-Muradian, L. B.}, title = {POLLEN AND PHYSICOCHEMICAL ANALYSIS OF Apis AND Tetragonisca (APIDAE) HONEY}, journal = {Interciencia}, publisher = {Interciencia}, year = {2013}, volume = {38}, number = {4}, pages = {280--285} } 
Carvalho V, Fernandes L, Conde T, Zamith H, Silva R, Surrage A, Frutuoso V, Castro-Faria-Neto H and Amendoeira F (2013), "Antinociceptive Activity of Stephanolepis hispidus Skin Aqueous Extract Depends Partly on Opioid System Activation", Marine Drugs., April, 2013. Vol. 11(4), pp. 1221-1234. Mdpi Ag.
Abstract: Stephanolepis hispidus is one of the most common filefish species in Brazil. Its skin is traditionally used as a complementary treatment for inflammatory disorders. However, there are very few studies on chemical and pharmacological properties using the skin of this fish. This study was undertaken in order to investigate the effect of aqueous crude extract of S. hispidus skin (SAE) in different nociception models. Here, we report that intraperitoneal administration of SAE inhibited the abdominal constrictions induced by acetic acid in mice. In addition to the effect seen in the abdominal constriction model, SAE was also able to inhibit the hyperalgesia induced by carrageenan and prostaglandin E2 (PGE2) in mice. This potent antinociceptive effect was observed in the hot plate model too, but not in tail-flick test. Naloxone, an opioid receptor antagonist, was able to block the antinociceptive effect of SAE in the abdominal constriction and hot plate models. In addition, SAE did not present cytotoxic or genotoxic effect in human peripheral blood cells. Our results suggest that aqueous crude extract from S. hispidus skin has antinociceptive activity in close relationship with the partial activation of opioid receptors in the nervous system. Moreover, aqueous crude extract from S. hispidus skin does not present toxicity and is therefore endowed with the potential for pharmacological control of pain.
BibTeX:
 @article{Carvalho2013, author = {Carvalho, V. and Fernandes, L. and Conde, T. and Zamith, H. and Silva, R. and Surrage, A. and Frutuoso, V. and Castro-Faria-Neto, H. and Amendoeira, F.}, title = {Antinociceptive Activity of Stephanolepis hispidus Skin Aqueous Extract Depends Partly on Opioid System Activation}, journal = {Marine Drugs}, publisher = {Mdpi Ag}, year = {2013}, volume = {11}, number = {4}, pages = {1221--1234}, doi = {10.3390/md11041221} } 
Colares AV, Almeida-Souza F, Taniwaki NN, Souza CDF, da Costa JGM, Calabrese KD and Abreu-Silva AL (2013), "In Vitro Antileishmanial Activity of Essential Oil of Vanillosmopsis arborea (Asteraceae) Baker", Evidence-based Complementary and Alternative Medicine. , pp. 727042. Hindawi Publishing Corporation.
Abstract: The search for new immunopharmacological chemical agents to treat various diseases caused by bacteria, fungi, and protozoa, such as leishmaniasis, for example, has led to the exploration of potential products from plant species and their main active ingredients. Antimonial drugs are the current treatment for leishmaniasis. These drugs cause major side effects and frequent discontinuation of treatment. In this study, we evaluated the in vitro leishmanicidal activity of essential oil of Vanillosmopsis arborea (VAEO) and its major compound alpha-bisabolol against Leishmania amazonensis. The essential oil and alpha-bisabolol showed activity against promastigotes (IC50 7.35 and 4.95 mu g/mL resp.) and intracellular amastigotes (IC50 12.58 and 10.70 mu g/mL, resp.). Neither product showed any cytotoxicity on treated macrophages. The ultrastructural analysis of promastigotes incubated with VAEO or alpha-bisabolol at 30 mu g/mL, showed morphological changes with the accumulation of vesicles electrodense lipid inclusions. The results give evidence that both VAEO and alpha-bisabolol have potential as new therapeutic agents against leishmaniasis.
BibTeX:
 @article{Colares2013, author = {Colares, A. V. and Almeida-Souza, F. and Taniwaki, N. N. and Souza, C. D. F. and da Costa, J. G. M. and Calabrese, K. D. and Abreu-Silva, A. L.}, title = {In Vitro Antileishmanial Activity of Essential Oil of Vanillosmopsis arborea (Asteraceae) Baker}, journal = {Evidence-based Complementary and Alternative Medicine}, publisher = {Hindawi Publishing Corporation}, year = {2013}, pages = {727042}, doi = {10.1155/2013/727042} } 
de Almeida CJG, Jasmin J-F, Del Galdo F and Lisanti MP (2013), "Genetic ablation of caveolin-2 sensitizes mice to bleomycin-induced injury.", Cell Cycle., Jul, 2013. Vol. 12(14), pp. 2248-2254.
Abstract: Caveolar domains act as platforms for the organization of molecular complexes involved in signal transduction. Caveolin proteins, the principal structural components of caveolae, have been involved in many cellular processes. Caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are highly expressed in the lung. Cav-1-deficient mice (Cav-1(-/-)) and Cav-2-deficient mice (Cav-2(-/-)) exhibit severe lung dysfunction attributed to a lack of Cav-2 expression. Recently, Cav-1 has been shown to regulate lung fibrosis in different models. Here, we show that Cav-2 is also involved in modulation of the fibrotic response, but through distinct mechanisms. Treatment of wild-type mice with the pulmonary fibrosis-inducer bleomycin reduced the expression of Cav-2 and its phosphorylation at tyrosine 19. Importantly, Cav-2(-/-) mice, but not Cav-1(-/-) mice, were more sensitive to bleomycin-induced lung injury in comparison to wild-type mice. Bleomycin-induced lung injury was characterized by alveolar thickening, increase in cell density, and extracellular matrix deposition. The lung injury observed in bleomycin-treated Cav-2(-/-) mice was not associated with alterations in the TGF-β signaling pathway and/or in the ability to produce collagen. However, apoptosis and proliferation were more prominent in lungs of bleomycin-treated Cav-2(-/-) mice. Since Cav-1(-/-) mice also lack Cav-2 expression and show a different outcome after bleomycin treatment, we conclude that Cav-1 and Cav-2 have distinct roles in bleomycin induced-lung fibrosis, and that the balance of both proteins determines the development of the fibrotic process.
BibTeX:
 @article{deAlmeida2013, author = {de Almeida, Cecilia J G. and Jasmin, Jean-François and Del Galdo, Francesco and Lisanti, Michael P.}, title = {Genetic ablation of caveolin-2 sensitizes mice to bleomycin-induced injury.}, journal = {Cell Cycle}, year = {2013}, volume = {12}, number = {14}, pages = {2248--2254}, url = {http://dx.doi.org/10.4161/cc.25335}, doi = {10.4161/cc.25335} } 
De Almeida-Muradian LB, Stramm KM, Horita A, Barth OM, de Freitas AD and Estevinho LM (2013), "Comparative study of the physicochemical and palynological characteristics of honey from Melipona subnitida and Apis mellifera", International Journal of Food Science and Technology., August, 2013. Vol. 48(8), pp. 1698-1706. Wiley-blackwell.
Abstract: Twenty-four samples of Apis mellifera honey and twenty-four samples of Melipona subnitida (Jandaira) honey were collected in the northeast of Brazil. Moisture, hydroxymethylfurfural, free acidity, insoluble solids in water, diastase activity, ashes, electrical conductivity, proteins, lipids, total carbohydrates, energy and sugars were the parameters analysed. The efficiency of the qualitative tests (Fiehe's test, Lugol's reaction, Lund's reaction) was tested. Pollen types and the corresponding plant species were identified in all samples (3 in Apis and 1 in Melipona). Apis mellifera honey samples demonstrated parameters in accordance with the Brazilian Legislation, while the Melipona subnitida honey samples displayed moisture (24.80%) and diastase activity (null) in discordance with the established by the regulation for Apis mellifera honeys. Apis honey samples presented higher values of electric conductivity (284.00 mu S cm(-1)) than the obtained from the Jandaira honey samples (102.77 mu S cm(-1)) as well as a darker colour (26.67 mmPfund) when compared with Jandaira honey (7.00 mmPfund). The concentration of the glucose, fructose and sucrose was higher in the Apis honeys than in the Jandaira honey. The characteristics of the two types of honey were very different, highlighting the need of developing specific legislation for stingless bees' honey.
BibTeX:
 @article{Almeida-Muradian2013, author = {De Almeida-Muradian, L. B. and Stramm, K. M. and Horita, A. and Barth, O. M. and de Freitas, A. D. and Estevinho, L. M.}, title = {Comparative study of the physicochemical and palynological characteristics of honey from Melipona subnitida and Apis mellifera}, journal = {International Journal of Food Science and Technology}, publisher = {Wiley-blackwell}, year = {2013}, volume = {48}, number = {8}, pages = {1698--1706}, doi = {10.1111/ijfs.12140} } 
De Castro SL, Emery FS and da Silva Júnior EN (2013), "Synthesis of quinoidal molecules: Strategies towards bioactive compounds with an emphasis on lapachones.", Eur J Med Chem., Sep, 2013. Vol. 69C, pp. 678-700.
Abstract: Naphthoquinoidal compounds are of great interest in medicinal chemistry. In recent years, several synthetic routes have been developed to obtain bioactive molecules derived from lapachones. In this mini-review, we focus on the synthetic aspects and strategies used to design these compounds and on the biological activities of these substances for the development of drugs against the neglected diseases leishmaniasis and Chagas disease as well as malaria, tuberculosis and cancer. Three strategies used to develop bioactive naphthoquinoidal compounds are discussed: (i) C-ring modification, (ii) redox centre modification and (iii) A-ring modification. Among these strategies, reactions such as copper-catalysed azide-alkyne cycloaddition (click chemistry), palladium-catalysed cross couplings, and heterocyclisations will be discussed for the development of naphthoquinoidal compounds against Trypanosoma cruzi, Leishmania and cancer. The aim of derivatisation is the generation of novel molecules that inhibit cellular organelles/processes, generate reactive oxygen species (ROS) and increase lipophilicity to enhance penetration through the plasma membrane. Modified lapachones have emerged as promising prototypes for the development of drugs against neglected diseases and cancer.
BibTeX:
 @article{deCastro2013, author = {De Castro, Solange L. and Emery, Flavio S. and da Silva Júnior, Eufrânio N.}, title = {Synthesis of quinoidal molecules: Strategies towards bioactive compounds with an emphasis on lapachones.}, journal = {Eur J Med Chem}, year = {2013}, volume = {69C}, pages = {678--700}, url = {http://dx.doi.org/10.1016/j.ejmech.2013.07.057}, doi = {10.1016/j.ejmech.2013.07.057} } 
Floyd RA, Neto HCCF, Zimmerman GA, Hensley K and Towner RA (2013), "Nitrone-based therapeutics for neurodegenerative diseases: Their use alone or in combination with lanthionines", Free Radical Biology and Medicine., September, 2013. Vol. 62, pp. 145-156. Elsevier Science Inc.
Abstract: The possibility of free radical reactions occurring in biological processes led to the development and employment of novel methods and techniques focused on determining their existence and importance in normal and pathological conditions. For this reason the use of nitrones for spin trapping free radicals became widespread in the 1970s and 1980s, when surprisingly the first evidence of their potent biological properties was noted. Since then widespread exploration and demonstration of the potent biological properties of phenyl-tert-butylnitrone (PBN) and its derivatives took place in preclinical models of septic shock and then in experimental stroke. The most extensive commercial effort made to capitalize on the potent properties of the PBN-nitrones was for acute ischemic stroke. This occurred during 1993-2006, when the 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, was shown to be safe in humans and was taken all the way through clinical phase 3 trials and then was deemed to be ineffective. As summarized in this review, because of its excellent human safety profile, 2,4-disulfonylphenyl PEN, now called OKN-007 in the cancer studies, was tested as an anti-cancer agent in several preclinical glioma models and shown to be very effective. Based on these studies this compound is now scheduled to enter into early clinical trials for astrocytoma/glioblastoma multiforme this year. The potential use of OKN-007 in combination with neurotropic compounds such as the lanthionine ketamine esters is discussed for glioblastoma multiforme as well as for various other indications leading to dementia, such as aging, septic shock, and malaria infections. There is much more research and development activity ongoing for various indications with the nitrones, alone or in combination with other active compounds, as briefly noted in this review. (C) 2013 Elsevier Inc. All rights reserved.
BibTeX:
 @article{Floyd2013, author = {Floyd, R. A. and Neto, H. C. C. F. and Zimmerman, G. A. and Hensley, K. and Towner, R. A.}, title = {Nitrone-based therapeutics for neurodegenerative diseases: Their use alone or in combination with lanthionines}, journal = {Free Radical Biology and Medicine}, publisher = {Elsevier Science Inc}, year = {2013}, volume = {62}, pages = {145--156}, doi = {10.1016/j.freeradbiomed.2013.01.033} } 
Freitas F, Estato V, Carvalho VF, Torres RC, Lessa MA and Tibiriçá E (2013), "Cardiac microvascular rarefaction in hyperthyroidism-induced left ventricle dysfunction.", Microcirculation., Oct, 2013. Vol. 20(7), pp. 590-598.
Abstract: The pathophysiology underlying hyperthyroidism-induced left ventricle (LV) dysfunction and hypertrophy directly involves the heart and indirectly involves the neuroendocrine systems. The effects of hyperthyroidism on the microcirculation are still controversial in experimental models. We investigated the effects of hyperthyroidism on the cardiac function and microcirculation of an experimental rat model.Male Wistar rats (170-250 g) were divided into two groups: the euthyroid group (n = 10), which was treated with 0.9% saline solution, and the hyperthyroid group (n = 10), which was treated with l-thyroxine (600 μg/kg/day, i.p.) during 14 days. An echocardiographic study was performed to evaluate the alterations in cardiac function, structure and geometry. The structural capillary density and the expression of angiotensin II AT1 receptor in the LV were analyzed using histochemistry and immunohistochemistry, respectively.Hyperthyroidism was found to induce profound cardiovascular alterations, such as systolic hypertension, tachycardia, LV dysfunction, cardiac hypertrophy, and myocardial fibrosis. This study demonstrates the existence of structural capillary rarefaction and the down-regulation of the cardiac angiotensin II AT1 receptor in the myocardium of hyperthyroid rats in comparison with euthyroid rats.Microvascular rarefaction may be involved in the pathophysiology of hyperthyroidism-induced cardiovascular alterations.
BibTeX:
 @article{Freitas2013, author = {Freitas, Felipe and Estato, Vanessa and Carvalho, Vinícius Frias and Torres, Rafael Carvalho and Lessa, Marcos Adriano and Tibiriçá, Eduardo}, title = {Cardiac microvascular rarefaction in hyperthyroidism-induced left ventricle dysfunction.}, journal = {Microcirculation}, year = {2013}, volume = {20}, number = {7}, pages = {590--598}, url = {http://dx.doi.org/10.1111/micc.12057}, doi = {10.1111/micc.12057} } 
Lourenco WR, Giupponi APL and Leguin EA (2013), "Description of three more new species of the genus Ananteris Thorell, 1891 (Scorpiones, Buthidae) from Brazil", Anais Da Academia Brasileira De Ciencias., June, 2013. Vol. 85(2), pp. 709-725. Acad Brasileira De Ciencias.
Abstract: Three new species of the genus Ananteris Thorell have been discovered in Brazil. Ananteris desiderio sp. n., Ananteris camacan sp. n. and Ananteris infuscata sp. n. are respectively described from specimens collected in the regions of Sao Desiderio, Camaca, Rebio UNA and Jequie in the state of Bahia, and Grao Mogol and Novo Horizonte in the state of Minas Gerais, Brazil. New records are also proposed for Ananteris luciae Lourenco, Ananteris mauryi Lourenco and Ananteris franckei Lourenco. The number of known Ananteris species known in the scorpion fauna of Brazil is now raised to 24.
BibTeX:
 @article{Lourenco2013, author = {Lourenco, W. R. and Giupponi, A. P. L. and Leguin, E. A.}, title = {Description of three more new species of the genus Ananteris Thorell, 1891 (Scorpiones, Buthidae) from Brazil}, journal = {Anais Da Academia Brasileira De Ciencias}, publisher = {Acad Brasileira De Ciencias}, year = {2013}, volume = {85}, number = {2}, pages = {709--725}, doi = {10.1590/S0001-37652013000200016} } 
Lucena SA, Moraes CS, Costa SG, de Souza W, Azambuja P, Garcia ES and Genta FA (2013), "Miniaturization of hydrolase assays in thermocyclers", Analytical Biochemistry., March, 2013. Vol. 434(1), pp. 39-43. Academic Press Inc Elsevier Science.
Abstract: We adapted the protocols of reducing sugar measurements with dinitrosalicylic acid and bicinchoninic acid for thermocyclers and their use in enzymatic assays for hydrolases such as amylase and beta-1,3-glucanase. The use of thermocyclers for these enzymatic assays resulted in a 10 times reduction in the amount of reagent and volume of the sample needed when compared with conventional microplate protocols. We standardized absorbance readings from the polymerase chain reaction plates, which allowed us to make direct readings of the techniques above, and a -glycosidase assay was also established under the same conditions. Standardization of the enzymatic reaction in thermocyclers resulted in less time-consuming temperature calibrations and without loss of volume through leakage or evaporation from the microplate. Kinetic parameters were successfully obtained, and the use of the thermocycler allowed the measurement of enzymatic activities in biological samples from the field with a limited amount of protein. (C) 2012 Elsevier Inc. All rights reserved.
BibTeX:
 @article{Lucena2013, author = {Lucena, S. A. and Moraes, C. S. and Costa, S. G. and de Souza, W. and Azambuja, P. and Garcia, E. S. and Genta, F. A.}, title = {Miniaturization of hydrolase assays in thermocyclers}, journal = {Analytical Biochemistry}, publisher = {Academic Press Inc Elsevier Science}, year = {2013}, volume = {434}, number = {1}, pages = {39--43}, doi = {10.1016/j.ab.2012.10.032} } 
Luna-Gomes T, Bozza PT and Bandeira-Melo C (2013), "Eosinophil recruitment and activation: the role of lipid mediators.", Front Pharmacol. Vol. 4, pp. 27.
Abstract: Eosinophils are effector cells that migrate toward several mediators released at inflammatory sites to perform their multiple functions. The mechanisms driving eosinophil selective accumulation in sites of allergic inflammation are well-established and involve several steps controlled by adhesion molecules, priming agents, chemotactic, and surviving factors. Even though the majority of studies focused on role of protein mediators like IL-5 and eotaxins, lipid mediators also participate in eosinophil recruitment and activation. Among the lipid mediators with distinguish eosinophil recruitment and activation capabilities are platelet activating factor and the eicosanoids, including leukotriene B4, cysteinyl leukotrienes, and prostaglandin D2. In this review, we focused on the role of these four lipid mediators in eosinophil recruitment and activation, since they are recognized as key mediators of eosinophilic inflammatory responses.
BibTeX:
 @article{Luna-Gomes2013, author = {Luna-Gomes, Tatiana and Bozza, Patrícia T. and Bandeira-Melo, Christianne}, title = {Eosinophil recruitment and activation: the role of lipid mediators.}, journal = {Front Pharmacol}, year = {2013}, volume = {4}, pages = {27}, url = {http://dx.doi.org/10.3389/fphar.2013.00027}, doi = {10.3389/fphar.2013.00027} } 
Magalhaes GS, Caporrino MC, Della-Casa MS, Kimura LF, Prezotto-Neto JP, Fukuda DA, Portes JA, Neves-Ferreira AGC, Santoro ML and Barbaro KC (2013), "Cloning, expression and characterization of a phospholipase D from Loxosceles gaucho venom gland", Biochimie., September, 2013. Vol. 95(9), pp. 1773-1783. Elsevier France-editions Scientifiques Medicales Elsevier.
Abstract: Loxosceles venom comprises a mixture of diverse toxins that induces intense local inflammatory reaction, dermonecrotic injury, platelet aggregation, hemolytic anemia and acute renal failure. Among several toxins in the venom, phospholipases D (PLDs), also called dermonecrotic toxins, are the most important and best studied, since they account for the main effects observed in loxoscelism. Despite their importance, biological analysis of PLDs is hampered by the minute amounts normally purified from the venom, and therefore many efforts have been made to clone those toxins. However, to date, no PLD from Loxosceles gaucho has been obtained in a heterologous system. Thus, in this work we show the cloning of a PLD from L gaucho venom gland, named LgRec1, which was successfully expressed in a bacterial system. LgRec1 evoked local reaction (edema, erythema, ecchymosis, and paleness), dermonecrosis and hemolysis. It was also able to hydrolyze sphingomyelin and promote platelet aggregation. ELISA and Western blot analysis showed that LgRec1 was recognized by an anti-L gaucho venom serum, a commercial arachnidic antivenom as well as a monoclonal antibody raised against the dermonecrotic fraction of L gaucho venom. In addition, LgRec1 demonstrated to be highly immunogenic and antibodies raised against this recombinant toxin inhibited local reaction (similar to 65%) and dermonecrosis (similar to 100%) elicited by L gaucho whole venom. Since PLDs are considered the major components accounting for the local and systemic envenomation effects caused by spiders from genus Loxosceles, the information provided here may help to understand the mechanisms behind clinical symptomatology. (C) 2013 Elsevier Masson SAS. All rights reserved.
BibTeX:
 @article{Magalhaes2013, author = {Magalhaes, G. S. and Caporrino, M. C. and Della-Casa, M. S. and Kimura, L. F. and Prezotto-Neto, J. P. and Fukuda, D. A. and Portes, J. A. and Neves-Ferreira, A. G. C. and Santoro, M. L. and Barbaro, K. C.}, title = {Cloning, expression and characterization of a phospholipase D from Loxosceles gaucho venom gland}, journal = {Biochimie}, publisher = {Elsevier France-editions Scientifiques Medicales Elsevier}, year = {2013}, volume = {95}, number = {9}, pages = {1773--1783}, doi = {10.1016/j.biochi.2013.06.002} } 
Neves AP, Pereira MXG, Peterson EJ, Kipping R, Vargas MD, Silva FP, Carneiro JWM and Farrell NP (2013), "Exploring the DNA binding/cleavage, cellular accumulation and topoisomerase inhibition of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases and their platinum(II) complexes", Journal of Inorganic Biochemistry., February, 2013. Vol. 119, pp. 54-64. Elsevier Science Inc.
Abstract: Several chlorido and amino Pt2+ complexes of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases HL exhibiting moderate to high cytotoxicity against cancer cell lines were studied in order to investigate their modes of DNA binding, in vitro DNA strand breaks, mechanism of topoisomerase (Topo I) inhibition and cellular accumulation. DNA model base studies have shown that complex la [Pt(HL1)Cl-2] was capable of binding covalently to 9-ethylguanine (9-EtG) and 5'-GMP. H-1 NMR and mass spectrometry studies have shown that both chlorides were substituted by 9-EtG ligands, whereas 5'-GMP was able to replace only one chlorido ligand, due to steric hindrance. The chlorido Pt2+ complexes [Pt(HL)Cl-2] highly accumulate in prostate (PC-3) and melanoma (MDA-MB-435) cell lines, being able to induce DNA strand breaks in vitro and inhibit Topo I by a catalytic mode. On the other hand, the free 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones HL and the amino Pt2+ complexes [Pt(L-)(NH3)(2)]NO3 neither cause DNA strand breakage nor exhibit strong DNA interaction, nevertheless the latter were also found to be catalytic inhibitors of Topo I at 100 mu M. Thus, coordination of the Mannich bases HL to the "PtCl2" fragment substantially affects the chemical and biophysical properties of the pro-ligands, leading to an improvement of their DNA binding properties and generating compounds that cleave DNA and catalytically inhibit Topo I. Finally, the high cytotoxicity exhibited by the free (uncomplexed) 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones might be associated with their decomposition in solution, which is not observed for the Pt2+ complexes. (C) 2012 Elsevier Inc. All rights reserved.
BibTeX:
 @article{Neves2013, author = {Neves, A. P. and Pereira, M. X. G. and Peterson, E. J. and Kipping, R. and Vargas, M. D. and Silva, F. P. and Carneiro, J. W. M. and Farrell, N. P.}, title = {Exploring the DNA binding/cleavage, cellular accumulation and topoisomerase inhibition of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases and their platinum(II) complexes}, journal = {Journal of Inorganic Biochemistry}, publisher = {Elsevier Science Inc}, year = {2013}, volume = {119}, pages = {54--64}, doi = {10.1016/j.jinorgbio.2012.10.007} } 
Pratt-Riccio LR, Chehuan YF, Siqueira MJ, Alecrim MG, Bianco C, Druilhe P, Brasseur P, Ferreira-Da-Cruz MF, Carvalho LJM and Daniel-Ribeiro CT (2013), "Use of a colorimetric (DELI) test for the evaluation of chemoresistance of Plasmodium falciparum and Plasmodium vivax to commonly used anti-plasmodial drugs in the Brazilian Amazon", Malaria Journal., August, 2013. Vol. 12, pp. 294. Biomed Central Ltd.
Abstract: Background: The emergence and spread of Plasmodium falciparum and Plasmodium vivax resistance to available anti-malarial drugs represents a major drawback in the control of malaria and its associated morbidity and mortality. The aim of this study was to evaluate the chemoresistance profile of P. falciparum and P. vivax to commonly used anti-plasmodial drugs in a malaria-endemic area in the Brazilian Amazon. Methods: The study was carried out in Manaus (Amazonas state), in the Brazilian Amazon. A total of 88 P. falciparum and 178 P. vivax isolates was collected from 2004 to 2007. The sensitivity of P. falciparum isolates was determined to chloroquine, quinine, mefloquine and artesunate and the sensitivity of P. vivax isolates was determined to chloroquine and mefloquine, by using the colorimetric DELI test. Results: As expected, a high prevalence of P. falciparum isolates resistant to chloroquine (78.1%) was observed. The prevalence of isolates with profile of resistance or decreased sensitivity for quinine, mefloquine and artesunate was 12.7, 21.2 and 11.7%, respectively. In the case of P. vivax, the prevalence of isolates with profile of resistance for chloroquine and mefloquine was 9.8 and 28%, respectively. No differences in the frequencies of isolates with profile of resistance or geometric mean IC50s were seen when comparing the data obtained in 2004, 2005, 2006 and 2007, for all tested anti-malarials. Conclusions: The great majority of P. falciparum isolates in the Brazilian malaria-endemic area remain resistant to chloroquine, and the decreased sensitivity to quinine, mefloquine and artesunate observed in 10-20% of the isolates must be taken with concern, especially for artesunate. Plasmodium vivax isolates also showed a significant proportion of isolates with decreased sensitivity to chloroquine (first-line drug) and mainly to mefloquine. The data presented here also confirm the usefulness of the DELI test to generate results able to impact on public health policies.
BibTeX:
 @article{Pratt-Riccio2013, author = {Pratt-Riccio, L. R. and Chehuan, Y. F. and Siqueira, M. J. and Alecrim, M. G. and Bianco, C. and Druilhe, P. and Brasseur, P. and Ferreira-Da-Cruz, M. F. and Carvalho, L. J. M. and Daniel-Ribeiro, C. T.}, title = {Use of a colorimetric (DELI) test for the evaluation of chemoresistance of Plasmodium falciparum and Plasmodium vivax to commonly used anti-plasmodial drugs in the Brazilian Amazon}, journal = {Malaria Journal}, publisher = {Biomed Central Ltd}, year = {2013}, volume = {12}, pages = {294}, doi = {10.1186/1475-2875-12-281} } 
Ribeiro-Filho J, Calheiros AS, Vieira-de-Abreu A, de Carvalho KIM, da Silva Mendes D, Melo CB, Martins MA, da Silva Dias C, Piuvezam MR and Bozza PT (2013), "Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma.", Toxicol Appl Pharmacol., Nov, 2013. Vol. 273(1), pp. 19-26.
Abstract: Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca(++) influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs.
BibTeX:
 @article{Ribeiro-Filho2013, author = {Ribeiro-Filho, Jaime and Calheiros, Andrea Surrage and Vieira-de-Abreu, Adriana and de Carvalho, Katharinne Ingrid Moraes and da Silva Mendes, Diego and Melo, Christianne Bandeira and Martins, Marco Aurélio and da Silva Dias, Celidarque and Piuvezam, Márcia Regina and Bozza, Patrícia T.}, title = {Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma.}, journal = {Toxicol Appl Pharmacol}, year = {2013}, volume = {273}, number = {1}, pages = {19--26}, url = {http://dx.doi.org/10.1016/j.taap.2013.08.015}, doi = {10.1016/j.taap.2013.08.015} } 
Soares DC, Calegari-Silva TC, Lopes UG, Teixeira VL, Paixao ICND, Cirne-Santos C, Bou-Habib DC and Saraiva EM (2012), "Dolabelladienetriol, a Compound from Dictyota pfaffii Algae, Inhibits the Infection by Leishmania amazonensis", Plos Neglected Tropical Diseases., September, 2012. Vol. 6(9), pp. e1787. Public Library Science.
Abstract: Background: Chemotherapy for leishmaniasis, a disease caused by Leishmania parasites, is expensive and causes side effects. Furthermore, parasite resistance constitutes an increasing problem, and new drugs against this disease are needed. In this study, we examine the effect of the compound 8,10,18-trihydroxy-2,6-dolabelladiene (Dolabelladienetriol), on Leishmania growth in macrophages. The ability of this compound to modulate macrophage function is also described. Methodology/Principal Findings: Leishmania-infected macrophages were treated with Dolabelladienetriol, and parasite growth was measured using an infectivity index. Nitric oxide (NO), TNF-alpha and TGF-beta production were assayed in macrophages using specific assays. NF-kappa B nuclear translocation was analyzed by western blot. Dolabelladienetriol inhibited Leishmania in a dose-dependent manner; the IC50 was 44 mu M. Dolabelladienetriol diminished NO, TNF-alpha and TGF-beta production in uninfected and Leishmania-infected macrophages and reduced NF-kappa B nuclear translocation. Dolabelladienetriol inhibited Leishmania infection even when the parasite growth was exacerbated by either IL-10 or TGF-beta. In addition, Dolabelladienetriol inhibited Leishmania growth in HIV-1-co-infected human macrophages. Conclusion: Our results indicate that Dolabelladienetriol significantly inhibits Leishmania in macrophages even in the presence of factors that exacerbate parasite growth, such as IL-10, TGF-beta and HIV-1 co-infection. Our results suggest that Dolabelladienetriol is a promising candidate for future studies regarding treatment of leishmaniasis, associated or not with HIV-1 infection.
BibTeX:
 @article{Soares2012, author = {Soares, D. C. and Calegari-Silva, T. C. and Lopes, U. G. and Teixeira, V. L. and Paixao, I. C. N. D. and Cirne-Santos, C. and Bou-Habib, D. C. and Saraiva, E. M.}, title = {Dolabelladienetriol, a Compound from Dictyota pfaffii Algae, Inhibits the Infection by Leishmania amazonensis}, journal = {Plos Neglected Tropical Diseases}, publisher = {Public Library Science}, year = {2012}, volume = {6}, number = {9}, pages = {e1787}, doi = {10.1371/journal.pntd.0001787} } 
Soares-Bezerra RJ, Calheiros AS, da Silva Ferreira NC, da Silva Frutuoso V and Alves LA (2013), "Natural Products as a Source for New Anti-Inflammatory and Analgesic Compounds through the Inhibition of Purinergic P2X Receptors.", Pharmaceuticals (Basel). Vol. 6(5), pp. 650-658.
Abstract: Natural products have reemerged in traditional medicine as a potential source of new molecules or phytomedicines to help with health disorders. It has been established that members of the P2X subfamily, ATP-gated ion channels, are crucial to the inflammatory process and pain signalization. As such, several preclinical studies have demonstrated that P2X2R, P2X3R, P2X4R and P2X7R are promising pharmacological targets to control inflammatory and pain disorders. Several studies have indicated that natural products could be a good source of the new specific molecules needed for the treatment of diseases linked to inflammation and pain disorders through the regulation of these receptors. Herein, we discuss and give an overview of the applicability of natural products as a source to obtain P2X receptors (P2XR) selective antagonists for use in clinical treatment, which require further investigation.
BibTeX:
 @article{Soares-Bezerra2013a, author = {Soares-Bezerra, Rômulo José and Calheiros, Andrea Surrage and da Silva Ferreira, Natiele Carla and da Silva Frutuoso, Valber and Alves, Luiz Anastacio}, title = {Natural Products as a Source for New Anti-Inflammatory and Analgesic Compounds through the Inhibition of Purinergic P2X Receptors.}, journal = {Pharmaceuticals (Basel)}, year = {2013}, volume = {6}, number = {5}, pages = {650--658}, url = {http://dx.doi.org/10.3390/ph6050650}, doi = {10.3390/ph6050650} } 
Soares-Bezerra RJ, Leon LL, Echevarria A, Reis CM, Gomes-Silva L, Agostinho CG, Fernandes RA, Canto-Cavalheiro MM and Genestra MS (2013), "In vitro evaluation of 4-phenyl-5-(4 '-X-phenyl)-1,3,4-thiadiazolium-2-phenylaminide chlorides and 3[N-4 '-X-phenyl]-1,2,3-oxadiazolium-5-olate derivatives on nitric oxide synthase and arginase activities of Leishmania amazonensis", Experimental Parasitology., September, 2013. Vol. 135(1), pp. 50-54. Academic Press Inc Elsevier Science.
Abstract: Leishmaniasis is a spectrum of infectious diseases caused by Leishmania protozoan parasites. The purpose of this study was to perform, in vitro, a comparative analysis of the activity amastigotes. Results showed excellent efficacy of all compounds against axenic amastigotes, compared to pentamidine isethionate, the reference drug used. The cytotoxic effect of these mesoionic compounds of six mesoionic compounds (three 1,3,4-thiadiazolium-2-aminide and three 1,2,3-oxadiazolium-5-olate class compounds) was evaluated in mouse peritoneal macrophages using MTT assay, low toxicity (similar to 10%) for these mammalian cells being observed. In an attempt to define a potential drug target, the activities of nitric oxide synthase (NOS) and arginase of the parasites treated with the mesoionic derivatives were evaluated. NOS was purified from a cell-free extract of infective promastigotes and axenic amastigotes and all derivatives tested were able to inhibit the enzyme as monitored by the decrease of NADPH consumption. Arginase activity from both stages of the parasite was measured using urea production and none of the compounds inhibited the enzyme activity of axenic amastigotes. On the other hand, when tested with promastigotes, those compounds without and substituents inhibited arginase activity. (C) 2013 Elsevier Inc. All rights reserved.
BibTeX:
 @article{Soares-Bezerra2013, author = {Soares-Bezerra, R. J. and Leon, L. L. and Echevarria, A. and Reis, C. M. and Gomes-Silva, L. and Agostinho, C. G. and Fernandes, R. A. and Canto-Cavalheiro, M. M. and Genestra, M. S.}, title = {In vitro evaluation of 4-phenyl-5-(4 '-X-phenyl)-1,3,4-thiadiazolium-2-phenylaminide chlorides and 3[N-4 '-X-phenyl]-1,2,3-oxadiazolium-5-olate derivatives on nitric oxide synthase and arginase activities of Leishmania amazonensis}, journal = {Experimental Parasitology}, publisher = {Academic Press Inc Elsevier Science}, year = {2013}, volume = {135}, number = {1}, pages = {50--54}, doi = {10.1016/j.exppara.2013.05.008} } 
Towner RA, Garteiser P, Bozza F, Smith N, Saunders D, D Avila JCP, Magno F, Oliveira MF, Ehrenshaft M, Lupu F, Silasi-Mansat R, Ramirez DC, Gomez-Mejiba SE, Mason RP and Castro Faria-Neto HC (2013), "In vivo detection of free radicals in mouse septic encephalopathy using molecular MRI and immuno-spin trapping.", Free Radic Biol Med., Aug, 2013. Vol. 65C, pp. 828-837.
Abstract: Free radicals are known to play a major role in sepsis. Combined immuno-spin trapping and molecular magnetic resonance imaging (MRI) was used to detect in vivo and in situ levels of free radicals in murine septic encephalopathy after cecal ligation and puncture (CLP). DMPO (5,5-dimethyl pyrroline N-oxide) was injected over 6h after CLP, before administration of an anti-DMPO probe (anti-DMPO antibody bound to albumin-gadolinium-diethylene triamine pentaacetic acid-biotin MRI targeting contrast agent). In vitro assessment of the anti-DMPO probe in oxidatively stressed mouse astrocytes significantly decreased T1 relaxation (p < 0.0001) compared to controls. MRI detected the presence of anti-DMPO adducts via a substantial decrease in change within the hippocampus, striatum, occipital, and medial cortex brain regions (p < 0.01 for all) in septic animals compared to shams, which was sustained for over 60min (p < 0.05 for all). Fluorescently labeled streptavidin was used to target the anti-DMPO probe biotin, which was elevated in septic brain, liver, and lungs compared to sham. Ex vivo DMPO adducts (qualitative) and oxidative products, including 4-hydroxynonenal and 3-nitrotyrosine (quantitative, p < 0.05 for both), were elevated in septic brains compared to shams. This is the first study that has reported on the detection of in vivo and in situ levels of free radicals in murine septic encephalopathy.
BibTeX:
 @article{Towner2013, author = {Towner, Rheal A. and Garteiser, Philippe and Bozza, Fernando and Smith, Nataliya and Saunders, Debra and D Avila, Joana C P. and Magno, Flora and Oliveira, Marcus F. and Ehrenshaft, Marilyn and Lupu, Florea and Silasi-Mansat, Robert and Ramirez, Dario C. and Gomez-Mejiba, Sandra E. and Mason, Ronald P. and Castro Faria-Neto, Hugo C.}, title = {In vivo detection of free radicals in mouse septic encephalopathy using molecular MRI and immuno-spin trapping.}, journal = {Free Radic Biol Med}, year = {2013}, volume = {65C}, pages = {828--837}, url = {http://dx.doi.org/10.1016/j.freeradbiomed.2013.08.172}, doi = {10.1016/j.freeradbiomed.2013.08.172} } 
Vieira AB, Coelho LP, Insuela DBR, Carvalho VF, dos Santos MH, Silva PMR and Martins MA (2013), "Mangiferin Prevents Guinea Pig Tracheal Contraction via Activation of the Nitric Oxide-Cyclic GMP Pathway", Plos One., August, 2013. Vol. 8(8), pp. e71759. Public Library Science.
Abstract: Previous studies have described the antispasmodic effect of mangiferin, a natural glucoside xanthone (2-C-beta-Dglucopyranosyl-1,3,6,7-tetrahydroxyxanthone) that is present in mango trees and other plants, but its mechanism of action remains unknown. The aim of this study was to examine the potential contribution of the nitric oxide-cyclic GMP pathway to the antispasmodic effect of mangiferin on isolated tracheal rings preparations. The functional effect of mangiferin on allergic and non-allergic contraction of guinea pig tracheal rings was assessed in conventional organ baths. Cultured tracheal rings were exposed to mangiferin or vehicle, and nitric oxide synthase (NOS) 3 and cyclic GMP (cGMP) levels were quantified using western blotting and enzyme immunoassays, respectively. Mangiferin (0.1-10 mu M) inhibited tracheal contractions induced by distinct stimuli, such as allergen, histamine, 5-hydroxytryptamine or carbachol, in a concentration-dependent manner. Mangiferin also caused marked relaxation of tracheal rings that were precontracted by carbachol, suggesting that it has both anti-contraction and relaxant properties that are prevented by removing the epithelium. The effect of mangiferin was inhibited by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME) (100 mu M), and the soluble guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 mu M), but not the adenylate cyclase inhibitor, 9-(tetrahydro-2-furyl)adenine (SQ22536) (100 mu M). The antispasmodic effect of mangiferin was also sensitive to K+ channel blockers, such as tetraethylammonium (TEA), glibenclamide and apamin. Furthermore, mangiferin inhibited Ca2+-induced contractions in K+ (60 mM)-depolarised tracheal rings preparations. In addition, mangiferin increased NOS3 protein levels and cGMP intracellular levels in cultured tracheal rings. Finally, mangiferin-induced increase in cGMP levels was abrogated by co-incubation with either ODQ or L-NAME. These data suggest that the antispasmodic effect of mangiferin is mediated by epithelium-nitric oxide- and cGMP-dependent mechanisms.
BibTeX:
 @article{Vieira2013, author = {Vieira, A. B. and Coelho, L. P. and Insuela, D. B. R. and Carvalho, V. F. and dos Santos, M. H. and Silva, P. M. R. and Martins, M. A.}, title = {Mangiferin Prevents Guinea Pig Tracheal Contraction via Activation of the Nitric Oxide-Cyclic GMP Pathway}, journal = {Plos One}, publisher = {Public Library Science}, year = {2013}, volume = {8}, number = {8}, pages = {e71759}, doi = {10.1371/journal.pone.0071759} } 
Voltan AR, Sardi JDO, Soares CP, Machado MP, Almeida AMF and Mendes-Giannini MJS (2013), "Early Endosome Antigen 1 (EEA1) decreases in macrophages infected with Paracoccidioides brasiliensis", Medical Mycology., October, 2013. Vol. 51(7), pp. 759-764. Informa Healthcare.
Abstract: Paracoccidioidomycosis (PCM) is a chronic granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis, endemic in Latin America. P. brasiliensis has been observed in epithelial cells in vivo and in vitro, as well as within the macrophages. The identification of the mechanism by which it survives within the host cell is fertile ground for the discovery of its pathogenesis since this organism has the ability to induce its own endocytosis in epithelial cells and most likely in macrophages. The study of the expression of endocytic proteins pathway and co-localization of microorganisms enable detection of the mechanism by which microorganisms survive within the host cell. The aim of this study was to evaluate the expression of the endocytic protein EEA1 (early endosome antigen 1) in macrophages infected with P. brasiliensis. For detection of EEA1, three different techniques were employed: immunofluorescence, real-time polymerase chain reaction (PCR) and immunoblotting. In the present study, decreased expression of EEA1 as well as the rearrangement of the actin was observed when the fungus was internalized, confirming that the input mechanism of the fungus in macrophages occurs through phagocytosis.
BibTeX:
 @article{Voltan2013, author = {Voltan, A. R. and Sardi, J. D. O. and Soares, C. P. and Machado, M. P. and Almeida, A. M. F. and Mendes-Giannini, M. J. S.}, title = {Early Endosome Antigen 1 (EEA1) decreases in macrophages infected with Paracoccidioides brasiliensis}, journal = {Medical Mycology}, publisher = {Informa Healthcare}, year = {2013}, volume = {51}, number = {7}, pages = {759--764}, doi = {10.3109/13693786.2013.777859} } 

Instituto Oswaldo Cruz /IOC /FIOCRUZ - Av. Brasil, 4365 - Tel: (21) 2598-4220 | INTRANET IOC| EXPEDIENTE
Manguinhos - Rio de Janeiro - RJ - Brasil CEP: 21040-360

Logos