Structural studies of BmooMP alpha-I, a non-hemorrhagic metalloproteinase from Bothrops moojeni venom

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The Venomics of Bothrops alternatus is a Pool of Acidic Proteins with Predominant Hemorrhagic and Coagulopathic Activities

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

Optimal and sub-optimal control in Dengue epidemics

This work concerns the application of the optimal control theory to Dengue epidemics. The dynamics of this insect-borne disease is modelled as a set of non-linear ordinary differential equations including the effect of educational campaigns organized to motivate the population to break the reproduction cycle of the mosquitoes by avoiding the accumulation of still water in open-air recipients. The cost functional is such that it reflects a compromise between actual financial spending (in insecticides and educational campaigns) and the population health (which can be objectively measured in terms of, for instance, treatment costs and loss of productivity). The optimal control problem is solved numerically using a multiple shooting method. However, the optimal control policy is difficult to implement by the health authorities because it is not practical to adjust the investment rate continuously in time. Therefore, a suboptimal control policy is computed assuming, as the admissible set, only those controls which are piecewise constant. The performance achieved by the optimal control and the sub-optimal control policies are compared with the cases of control using only insecticides when Breteau Index is greater or equal to 5 and the case of no-control. The results show that the sub-optimal policy yields a substantial reduction in the cost, in terms of the proposed functional, and is only slightly inferior to the optimal control policy. Copyright (C) 2001 John Wiley & Sons, Ltd.

Explaining the high number of infected people by dengue in Rio de Janeiro in 2008 using a susceptible-infective-recovered model

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Spatial distribution of dengue in the city of Cruzeiro, São Paulo State, Brazil: use of geoprocessing tools

Este artigo tem por objetivo identificar padrões na distribuição espacial dos casos de dengue ocorridos no município de Cruzeiro/SP, no ano de 2006. Trata-se de um estudo ecológico e exploratório que utiliza as ferramentas de análise espacial na elaboração de mapas temáticos, com dados obtidos do SinanNet. Foi feita uma análise por área, tomando-se como unidade o setor censitário do IBGE; a análise considerou quatro meses do ano de 2006 que mostra a ocorrência da doença no município. Os mapas temáticos foram construídos pelo programa computacional TerraView 3.3.1; assim como os valores dos índices de Moran Global (I M) mês a mês e o estimador de Kernel. Foram georreferenciados 691 casos de dengue (taxa de 864,2 casos/100.000 habitantes); os Índices de Moran e p-valores obtidos foram I M = 0,080 (março) p = 0,11; I M = 0,285 (abril) p = 0,01; I M = 0,201 (maio) p = 0,01 e I M = 0,002 (junho) p = 0,57. Os primeiros casos foram identificados na região nordeste e central e os últimos casos, na região norte, nordeste e central. Foi possível identificar os setores censitários onde a epidemia teve início e como ocorreu têmporo-espacialmente no município.

Education in primary school as a strategy to control dengue

A proliferação do Aedes aegypti é propiciada pelo habito de permitir a formação de criadouros em vários tipos de recipientes. Uma das formas de controla-lo é a disseminação do conhecimento sobre o vetor, por conduzir a conscientização e a tomada de medidas contra a sua proliferação. Para avaliar um método de ensino sobre o vetor e a dengue, foram comparando alunos de 5ª e 6ª séries antes e após a intervenção didática. Os alunos com intervenção foram mais aptos em reconhecerem as fases do ciclo e tiveram um discernimento maior sobre a importância dos mosquitos para a saúde. Eles também foram mais aptos em reconhecerem quais medidas de controle são mais eficientes e viáveis, repercutindo em suas residências que apresentaram duas vezes menos criadouros em relação aos que não tiveram intervenção.

LESION OF THE ANTEROVENTRAL 3RD VENTRICLE REGION IMPAIRS THE RECOVERY OF ARTERIAL-PRESSURE INDUCED BY HYPERTONIC SALINE IN RATS SUBMITTED TO HEMORRHAGIC-SHOCK

The effect of intravenous infusion of hypertonic saline (HS, 7.5% NaCl) on the recovery of mean arteria pressure (MAP) after hemorrhage was studied in sham-operated rats and in rats with electrolytic lesion of the anteroventral third ventricle (AV3V) region (4 h, 4 and 20 days). Rats anesthetized with thiopental sodium were bled (about 2.8 ml/100 g) until the MAP was stabilized at the level of 60 mmHg for 30 min. In sham-lesioned rats, MAP increased to 90 mmHg and became stable near this level after intravenous infusion of 7.5% NaCl (4 ml/kg b.wt.). In AV3V-lesioned rats, the same infusion induced a smaller increase in MAP (80 mmHg) and the MAP returned to pre-infusion levels within 30 min. These results show that the AV3V region plays an important role in the recovery of arterial pressure induced by hypertonic saline in rats submitted to hemorrhagic shock.

Neo-clerodane diterpenoid, a new metalloprotease snake venom inhibitor from Baccharis trimera (Asteraceae): anti-proteolytic and anti-hemorrhagic properties

Many plants are used in traditional medicine as active agents against various effects induced by snakebite. Few attempts have been made however to identify the nature of plain natural products with anti-ophidian properties. Baccharis trimera (Less) DC (Asteraceae), known in Brazil as carqueja. has been popularly used to treat liver diseases. rheumatism. diabetes, as well as digestive, hepatic and renal disorders. The active component was identified as 7alpha-hydroxy-3,13-clerodadiene-16,15:18,19-diolide, C20H28O5, (clerodane diterpenoid, Bt-CD). We report now the anti-proteolytic and anti-hemorrhagic propenies against snake venoms of a Bt-CD inhibitor from B. trimera. Bt-CD exhibited full inhibition of hemorrhage and proteolytic activity caused by Bothrops snake venoms. The inhibitor was able to neutralize the hemorrhagic, fibrinogenolytic and caseinolytic activities of class P-I and III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. No inhibition of the coagulant activity was observed. Bt-CD also partially inhibited the edema induced by other crude venoms, metallopronteases, basic and acidic phospholipases A(2). To further elucidate the inhibitory specificity of Bt-CD against metalloproteases isolated from snake venoms, a deeper understanding of its Structure and function is necessary. Furthermore, the potential use of these inhibitors to complement anti-venom as an alternative treatment of snakebite envenomations needs to be evaluated in future Studies. (C) 2004 Elsevier B.V.. All rights reserved.

A disposable chitosan-modified carbon fiber electrode for dengue virus envelope protein detection

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Continuous measurement of cerebral oxygen saturation (rSO 2) for assessment of cardiovascular status during hemorrhagic shock in a swine model

Background: Early trauma care is dependent on subjective assessments and sporadic vital sign assessments. We hypothesized that near-infrared spectroscopy-measured cerebral oxygenation (regional oxygen saturation [rSO 2]) would provide a tool to detect cardiovascular compromise during active hemorrhage. We compared rSO 2 with invasively measured mixed venous oxygen saturation (SvO2), mean arterial pressure (MAP), cardiac output, heart rate, and calculated pulse pressure. Methods: Six propofol-anesthetized instrumented swine were subjected to a fixed-rate hemorrhage until cardiovascular collapse. rSO 2 was monitored with noninvasively measured cerebral oximetry; SvO2 was measured with a fiber optic pulmonary arterial catheter. As an assessment of the time responsiveness of each variable, we recorded minutes from start of the hemorrhage for each variable achieving a 5%, 10%, 15%, and 20% change compared with baseline. Results: Mean time to cardiovascular collapse was 35 minutes ± 11 minutes (54 ± 17% total blood volume). Cerebral rSO 2 began a steady decline at an average MAP of 78 mm Hg ± 17 mm Hg, well above the expected autoregulatory threshold of cerebral blood flow. The 5%, 10%, and 15% decreases in rSO 2 during hemorrhage occurred at a similar times to SvO2, but rSO 2 lagged 6 minutes behind the equivalent percentage decreases in MAP. There was a higher correlation between rSO 2 versus MAP (R =0.72) than SvO2 versus MAP (R =0.55). Conclusions: Near-infrared spectroscopy- measured rSO 2 provided reproducible decreases during hemorrhage that were similar in time course to invasively measured cardiac output and SvO2 but delayed 5 to 9 minutes compared with MAP and pulse pressure. rSO 2 may provide an earlier warning of worsening hemorrhagic shock for prompt interventions in patients with trauma when continuous arterial BP measurements are unavailable. © 2012 Lippincott Williams & Wilkins.

High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses

Dengue virus is a mosquito-borne flavivirus that has a large impact in global health. It is considered as one of the medically important arboviruses, and developing a preventive or therapeutic solution remains a top priority in the medical and scientific community. Drug discovery programs for potential dengue antivirals have increased dramatically over the last decade, largely in part to the introduction of high-throughput assays. In this study, we have developed an image-based dengue high-throughput/high-content assay (HT/HCA) using an innovative computer vision approach to screen a kinase-focused library for anti-dengue compounds. Using this dengue HT/HCA, we identified a group of compounds with a 4-(1-aminoethyl)-N-methylthiazol-2-amine as a common core structure that inhibits dengue viral infection in a human liver-derived cell line (Huh-7.5 cells). Compounds CND1201, CND1203 and CND1243 exhibited strong antiviral activities against all four dengue serotypes. Plaque reduction and time-of-addition assays suggests that these compounds interfere with the late stage of viral infection cycle. These findings demonstrate that our image-based dengue HT/HCA is a reliable tool that can be used to screen various chemical libraries for potential dengue antiviral candidates. © 2013 Cruz et al.

Circulation of Different Lineages of Dengue Virus 2, Genotype American/Asian in Brazil: Dynamics and Molecular and Phylogenetic Characterization

The American/Asian genotype of Dengue virus type 2 (DENV-2) was introduced into the Americas in the 80′s. Although there is no data showing when this genotype was first introduced into Brazil, it was first detected in Brazil in 1990. After which the virus spread throughout the country and major epidemics occurred in 1998, 2007/08 and 2010. In this study we sequenced 12 DENV-2 genomes obtained from serum samples of patients with dengue fever residing in São José do Rio Preto, São Paulo (SJRP/SP), Brazil, in 2008. The whole open reading frame or envelope sequences were used to perform phylogenetic, phylogeographic and evolutionary analyses. Isolates from SJRP/SP were grouped within one lineage (BR3) close to isolates from Rio de Janeiro, Brazil. Isolates from SJRP were probably introduced there at least in 2007, prior to its detection in the 2008 outbreak. DENV-2 circulation in Brazil is characterized by the introduction, displacement and circulation of three well-defined lineages in different times, most probably from the Caribbean. Thirty-seven unique amino acid substitutions were observed among the lineages, including seven amino acid differences in domains I to III of the envelope protein. Moreover, we dated here, for the first time, the introduction of American/Asian genotype into Brazil (lineage BR1) to 1988/89, followed by the introduction of lineages BR2 (1998-2000) and BR3 (2003-05). Our results show a delay between the introduction and detection of DENV-2 lineages in Brazil, reinforcing the importance and need for surveillance programs to detect and trace the evolution of these viruses. Additionally, Brazilian DENV-2 differed in genetic diversity, date of introduction and geographic origin and distribution in Brazil, and these are important factors for the evolution, dynamics and control of dengue. © 2013 Drumond et al.