Theranostic applications of phage display to control leishmaniasis: Selection of biomarkers for serodiagnostics, vaccination, and immunotherapy

© 2015, Sociedade Brasileira de Medicina Tropical. All rights reserved. Phage display is a high-throughput subtractive proteomic technology used for the generation and screening of large peptide and antibody libraries. It is based on the selection of phage-fused surface-exposed peptides that recognize specific ligands and demonstrate desired functionality for diagnostic and therapeutic purposes. Phage display has provided unmatched tools for controlling viral, bacterial, fungal, and parasitic infections, and allowed identification of new therapeutic targets to treat cancer, metabolic diseases, and other chronic conditions. This review presents recent advancements in serodiagnostics and prevention of leishmaniasis -an important tropical parasitic disease- achieved using phage display for the identification of novel antigens with improved sensitivity and specificity. Our focus is on theranostics of visceral leishmaniasis with the aim to develop biomarker candidates exhibiting both diagnostic and therapeutic potential to fight this important, yet neglected, tropical disease.Peer Reviewe

Tambaqui, Colossoma macropomum, fisheries with focus on an area on middle Amazon River, Amazonas state, Brazil

This study evaluates the importance of tambaqui (Colossoma macropomum) in fisheries of the Orinoco and Amazon River basins, through the analysis of published data and new data from the fishing fleet of Tefé, a city in the middle Solimões River. Data were collected between 1991 and 1995 in Tefe\'s market and between 1994 and 1995 on board commercial fishing boats. The relative importance of this species can reach 21% of catches in some landing places of the Orinoco basin, in Venezuela; around 8% in the Peruvian Amazonia; and 35% in Bolivian Amazonia. In Brazil, catches of tambaqui increased in the Madeira River region from 10% in 1977 to 32% between 1984 and 1989. In Manaus, this species composed up to 40% of the landed fish in the past. In the 80\'s and 90\'s, the proportion of tambaqui in landed fish has suffered a drastic reduction, declining to as little as 2,5%. In the middle Solimões, which is the main area of fisheries for this species, catches are made with various fishing gears and in different habitats, accordingly with water level fluctuations. In this region, tambaqui fisheries concentrate inside lakes, where the main gears used are gillnet and purse seine, and the catch is composed of the young fish (<55 cm). The habitats created by river bank collapse enseada-pausada") are important for the catch of larger individuals.Este trabalho avalia a importância da pesca do tambaqui (Colossoma macropomum) nas bacias dos rios Amazonas e Orinoco e, mais especificamente, na região do médio Solimões. As análises foram baseadas em dados de literatura e da pesca praticada pela frota de Tefé no médio Solimões, coletados no mercado de Tefé, entre 1991 e 1995, e a bordo de embarcações da frota pesqueira comercial, entre 1994 e 1995. A importância relativa da espécie pode alcançar 21% da produção de pescado em alguns centros urbanos da bacia do Orinoco, na Venezuela; 8% da Amazônia peruana; e 35% da Amazônia boliviana. No Brasil, na região do rio Madeira, a importância relativa do tambaqui subiu de 10% em 1977 para 32% entre 1984 e 1989. Em Manaus, a espécie já respondeu por 44% do pescado desembarcado. Porém, a proporção de tambaqui desembarcado nesta cidade sofreu uma grande diminuição nos anos 80 e 90, chegando a representar apenas 2,5% do total desembarcado. No médio Solimões, região apontada como a principal área de pesca para esta espécie, são utilizados diversos tipos de aparelhos e explorados diferentes habitats, de acordo com a flutuação do nível da água dos rios. A pesca do tambaqui nesta região é realizada principalmente em lagos, através de malhadeira e rede de cerco, incidindo sobre peixes jovens (<55 cm). O ambiente formado pela caída de terras nos meandros do rio enseada-pausada") é importante para a captura de indivíduos de maior porte

Myofibroma of the oral cavity. A rare spindle cell neoplasm

Myofibroma is an uncommon spindle cell neoplasm rarely found in oral cavity. Typically, this lesion is seen in neonates and infants with few cases reported in adults patients. In the oral cavity, myofibroma occurs within the submucosal or intramuscular tissue and has a predilection by the tongue, buccal mucosa and lips. Microscopically, a typical biphasic pattern can be observed. Misdiagnosis included benign and malignant spindle cell lesions of nerve tissue or smooth muscle origin, such as neurofibroma, leiomyoma and sarcomas. Thus, immunohistochemical staining is a useful tool to identify the nature of neoplastic cells and to reach an accurate diagnosis. An immunohistochemical panel consisting of antibodies to vimentin, SMA, HHF-35, S-100p and desmin must be achieved. In most cases, positivity for vimentin, SMA and HHF-25 can be observed. Our report describes a solitary myofibroma of the tongue of a 23-year-old man with emphasis in clinical, histopathological and immunohistochemical features of this lesion

Development and validation of a simple and rapid capillary zone electrophoresis method for determination of nnrti nevirapine in pharmaceutical formulations

A simple and fast capillary zone electrophoresis (CZE) method has been developed and validated for quantification of a non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine, in pharmaceuticals. The analysis was optimized using 10 mmol L-1 sodium phosphate buffer pH 2.5, +25 kV applied voltage, hydrodynamic injection 0.5 psi for 5 s and direct UV detection at 200 µm. Diazepam (50.0 µg mL-1) was used as internal standard. Under these conditions, nevirapine was analyzed in approximately less than 2.5 min. The analytical curve presented a coefficient of correlation of 0.9994. Limits of detection and quantification were 1.4 µg mL-1 and 4.3 µg mL-1, respectively. Intra- and inter-day precision expressed as relative standard deviations were 1.4% and 1.3%, respectively and the mean recovery was 100.81%. The active pharmaceutical ingredient was subjected to hydrolysis (acid, basic and neutral) and oxidative stress conditions. No interference of degradation products and tablet excipients were observed. This method showed to be rapid, simple, precise, accurate and economical for determination of nevirapine in pharmaceuticals and it is suitable for routine quality control analysis since CE offers benefits in terms of quicker method development and significantly reduced operating costs.Um método simples e rápido por eletroforese capilar foi desenvolvido e validado para a quantificação do inibidor não nucleosídeo da transcritase reversa (NNRTI) nevirapina, em medicamentos. A análise foi otimizada utilizando tampão fosfato de sódio 10 mmol L-1, pH 2,5, voltagem aplicada de +25 kV, injeção hidrodinâmica a 0,5 psi por 5 s e detecção UV em 200 µm. Diazepam (50,0 µg mL-1) foi usado como padrão interno. Sob estas condições, nevirapina foi analisada em aproximadamente menos de 2,5 min. A curva analítica apresentou um coeficiente de correlação de 0,9994. Os limites de detecção e quantificação foram 1,4 µg mL-1 e 4,3 µg mL-1, respectivamente. Precisões intra e inter-dia expressas como desvio padrão relativo foram 1,4% e 1,3%, respectivamente e a recuperação média foi de 100,81%. O fármaco foi submetido a testes de hidrólises (ácida, básica e neutra) e a estresse oxidativo. Não foi observada interferência por parte dos produtos de degradação, nem dos excipients na análise da nevirapina. Este método mostrou ser rápido, simples, preciso, exato e econômico para a determinação de nevirapina em produtos farmacêuticos e é apropriado para o controle de qualidade em análise de rotina uma vez que a eletroforese capilar oferece benefícios em termos de desenvolvimento rápido dos métodos e custos muito reduzidos de operação.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The Tully-Fisher Relation and H_not

The use of the Tully-Fisher (TF) relation for the determination of the Hubble Constant relies on the availability of an adequate template TF relation and of reliable primary distances. Here we use a TF template relation with the best available kinematical zero-point, obtained from a sample of 24 clusters of galaxies extending to cz ~ 9,000 km/s, and the most recent set of Cepheid distances for galaxies fit for TF use. The combination of these two ingredients yields H_not = 69+/-5 km/(s Mpc). The approach is significantly more accurate than the more common application with single cluster (e.g. Virgo, Coma) samples.Comment: 10 pages, including 2 figures and 1 table; uses AAS LaTex. Submitted to ApJ Letter

Cluster vs. Field Elliptical Galaxies and Clues on their Formation

Using new observations for a sample of 931 early-type galaxies we investigate whether the \mg2--\so relation shows any dependence on the local environment. The galaxies have been assigned to three different environments depending on the local overdensity: clusters, groups, and field, having used our completeredshift database to guide the assignment of galaxies. It is found that cluster, group and field early-type galaxies follow almost identical \mg2--\so\ relations, with the largest \mg2 zero-point difference (clusters minus field) being only $0.007\pm 0.002$ mag. No correlation of the residuals is found with the morphological type or the bulge to disk ratio. Using stellar population models in a differential fashion, this small zero-point difference implies a luminosity-weighted age difference of only $\sim 1$ Gyr between the corresponding stellar populations, with field galaxies being younger. The mass-weighted age difference could be significantly smaller, if minor events of late star formation took place preferentially in field galaxies. We combine these results with the existing evidence for the bulk of stars in cluster early-type galaxies having formed at very high redshift, and conclude that the bulk of stars in galactic spheroids had to form at high redshifts (z\gsim 3), no matter whether such spheroids now reside in low or high density regions. The cosmological implications of these findings are briefly discussed.Comment: 16 pages, 2 figures, accepted for publication in the ApJ.

Family Health Strategy and More Doctors Program in Rural Area of Porto Velho, Brazil: A Qualitative Analysis under the Nurse’s Perspective

The Family Health Strategy (FHS) together with the implementation of the More Doctors Program (MDP) has an effective contribution to the strengthening of Primary Health Care (PHC) and the consolidation of the Unified Health System (SUS), which has intended to meet the health needs of the population in need of care less complex. Thus, this study aims to analyze the Family Health Strategy and the Program More Doctors implanted in the Rural Municipality of Porto Velho, Rondônia, from the perspective of nurses. This is a qualitative research, descriptive exploratory performed in the field, based on the assessment the perspective of nurses working in the FHS, which are favored by the MDP. The data collection was carried out through a questionnaire,Primary Care Assessment Tool (PCA Tool), in its version validated in Brazil entitled PCA Tool- Brazil (BRAZIL, 2010). This instrument is widely used by national research that evaluates the quality of primary care. For the construction of the database was used Microsoft Word software. For qualitative data, the collection was carried out through interviews recorded by a script containing open questions. The response were discussed based on the content analysis technique proposed by Bardin (2011). The results achieved indicate that the MDM enabled the structuring of teams that were incomplete in the rural area of the town, however presents numerous challenges in the organization of the work process and the understanding of program objectives

Omega-3 intake is associated with attenuated inflammatory response and cardiac remodeling after myocardial infarction

Myocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether -3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling. ST-elevation MI (STEMI) patients (n=421) underwent clinical, biochemical, nutritional, 3D echocardiogram, Cardiac Magnetic Resonance imaging (CMRi) at 30 days and 3D echocardiogram imaging at six months after the MI. Blood tests were performed at day one (D1) and day five (D5) of hospitalization. Changes in inflammatory markers (D5-D1) were calculated. A validated food frequency questionnaire estimated the nutritional consumption and -3 intake in the last 3months before admission. The intake of -3 below the median (<1.7g/day) was associated with a short-term increase in hs-C-reactive protein [OR:1.96(1.24-3.10); p=0.004], Interleukin-2 [OR:2.46(1.20-5.04); p=0.014], brain-type natriuretic peptide [OR:2.66(1.30-5.44); p=0.007], left-ventricle end-diastolic volume [OR:5.12(1.11-23.52)]; p=0.036] and decreases in left-ventricle ejection fraction [OR:2.86(1.47-6.88); p=0.017] after adjustment for covariates. No differences were observed in the extension of infarcted mass obtained by CMRi. These findings suggest that a reduced daily intake of -3 may intensify outcome-determining mechanisms after STEMI, such as acute inflammatory response and late left ventricular remodeling.18CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ308550/2010-