Computational fluid dynamics simulations of blood flow regularized by 3D phase contrast MRI

Abstract Background Phase contrast magnetic resonance imaging (PC-MRI) is used clinically for quantitative assessment of cardiovascular flow and function, as it is capable of providing directly-measured 3D velocity maps. Alternatively, vascular flow can be estimated from model-based computation fluid dynamics (CFD) calculations. CFD provides arbitrarily high resolution, but its accuracy hinges on model assumptions, while velocity fields measured with PC-MRI generally do not satisfy the equations of fluid dynamics, provide limited resolution, and suffer from partial volume effects. The purpose of this study is to develop a proof-of-concept numerical procedure for constructing a simulated flow field that is influenced by both direct PC-MRI measurements and a fluid physics model, thereby taking advantage of both the accuracy of PC-MRI and the high spatial resolution of CFD. The use of the proposed approach in regularizing 3D flow fields is evaluated. Methods The proposed algorithm incorporates both a Newtonian fluid physics model and a linear PC-MRI signal model. The model equations are solved numerically using a modified CFD algorithm. The numerical solution corresponds to the optimal solution of a generalized Tikhonov regularization, which provides a flow field that satisfies the flow physics equations, while being close enough to the measured PC-MRI velocity profile. The feasibility of the proposed approach is demonstrated on data from the carotid bifurcation of one healthy volunteer, and also from a pulsatile carotid flow phantom. Results The proposed solver produces flow fields that are in better agreement with direct PC-MRI measurements than CFD alone, and converges faster, while closely satisfying the fluid dynamics equations. For the implementation that provided the best results, the signal-to-error ratio (with respect to the PC-MRI measurements) in the phantom experiment was 6.56 dB higher than that of conventional CFD; in the in vivo experiment, it was 2.15 dB higher. Conclusions The proposed approach allows partial or complete measurements to be incorporated into a modified CFD solver, for improving the accuracy of the resulting flow fields estimates. This can be used for reducing scan time, increasing the spatial resolution, and/or denoising the PC-MRI measurements.http://deepblue.lib.umich.edu/bitstream/2027.42/116061/1/12938_2015_Article_104.pd

Anfíbios de Santa Isabel do Rio Negro, Amazônia Brasileira.

No presente estudo fornecemos uma lista de espécies de anfíbios de Santa Isabel do Rio Negro na Amazônia Brasileira. As amostragens foram realizadas de março a abril de 2012 em dois conjuntos de trilhas de 3 km de extensão, usando os seguintes métodos: (1) armadilhas de interceptação e queda com cerca direcionadora; (2) amostragens visuais e auditivas simultâneas; (3) encontros ocasionais. As trilhas foram instaladas ao norte (rio Daraá) e ao sul (rio Ayuanã) do rio Negro. Registramos 40 espécies de anuros e uma espécie de salamandra, pertencentes a 20 gêneros e nove famílias. A composição de espécies foi comparada com as de 16 outros estudos desenvolvidos nas áreas de endemismo Guiana, Imeri e Jaú, onde a riqueza de espécies variou de 21 a 63, e a similaridade, de 23 a 100%. A anurofauna das duas áreas estudadas foi mais similar à de Flota Faro, localizada na Amazônia Oriental, do que à de um sítio mais próximo, Departamento del Guainía, Colômbia. O índice de similaridade foi extremamente variável entre os sítios da mesma ou de distintas áreas de endemismo. Esse padrão também foi observado nas análises de agrupamento. Como esperado, áreas geograficamente mais próximas foram mais similares na composição da anurofauna. No entanto, a anurofauna do Parque Nacional do Jaú (área de endemismo Jaú) foi mais similar à de Manaus (área de endemismo Guiana) do que à do rio Ayuanã, que pretence à mesma área de endemismo que o Parque Nacional do Jaú. Os limites das áreas de endemismo podem ser melhor definidos para outros vertebrados terrestres, como aves e mamíferos, do que para anfíbios e répteis Squamata.A species list of amphibians from Santa Isabel do Rio Negro in Brazilian Amazonia is provided. Collections were made from March–April 2012 along each of two 3-km trails with the following sampling methods: (1) pitfall traps with drift fences; (2) visual and auditory surveys; and (3) chance encounters. The trail at Daraá is north of the Rio Negro, whereas the other in Ayuanã is south of the river. Forty species of anurans and one salamander species representing 20 genera and nine families were recorded. The species composition was compared with those of 16 other studies conducted in the Guiana, Imeri, and Jaú areas of endemism, where species richness varies from 21–63, and similarity indices range from 23–100%. The anuran fauna at our sites resembles that of Flota Faro in eastern Amazonia more than it does that of the nearest site in the Departamento del Guainía of Colombia. The index of similarity is extremely variable between sites of the same and distinct areas of endemism. This pattern also was observed in the cluster analysis. As expected, geographically close areas have similar faunal compositions. However, the anuran fauna of Parque Nacional do Jaú (Jaú area of endemism) resembles that of Manaus (Guiana area of endemism) more closely than it does that of the Ayuanã River, which belongs to the same area of endemism as Parque Nacional do Jaú. The limits of the areas of endemism are better defined by the presence / absence of other terrestrial vertebrates, such as birds and mammals, than by the assemblage of amphibians and squamate reptiles

Activation of PPARγ reduces N-acetyl-cysteine -induced hypercorticoidism by down-regulating MC2R expression into adrenal glands

We previously demonstrated that oral supplementation with antioxidants induced hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis, attested by hypercorticoidism, through an up-regulation of adrenocorticotrophic hormone (ACTH) receptors (MC2R) in adrenal. This study analyzed the role of peroxisome proliferator-activated receptor (PPAR)-γ on HPA axis hyperactivity induced by N-acetyl-cysteine (NAC). Male Swiss-Webster mice were orally treated with NAC for 1, 3, 5, 10, 15, or 18 consecutive days. The PPAR-γ agonist rosiglitazone and/or antagonist GW9662 were daily-injected i.p. for 5 consecutive days, starting concomitantly with NAC treatment. Rosiglitazone treatment inhibited NAC-induced adrenal hypertrophy and hypercorticoidism. Rosiglitazone also significantly reversed the NAC-induced increase in the MC2R expression in adrenal, but not steroidogenic acute regulatory protein (StAR). NAC treatment reduces the expression of PPARγ in the adrenals, but rosiglitazone did not restore the expression of this cytoprotective gene. In addition, GW9662 blocked the ability of rosiglitazone to decrease plasma corticosterone levels in NAC-treated mice. In conclusion, our findings showed that antioxidant supplementation induced a state of hypercorticoidism through down-regulation of PPARγ expression in the adrenals, in a mechanism probably related to a down-regulation of ACTH receptor expression.Fil: Ventura, Raíssa D.. Fundación Oswaldo Cruz; BrasilFil: Chaves, Amanda S.. Fundación Oswaldo Cruz; BrasilFil: Magalhães, Nathalia S.. Fundación Oswaldo Cruz; BrasilFil: González, Florencia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Pacini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Pérez Ransanz, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Silva, Patrícia M.R.. Fundación Oswaldo Cruz; BrasilFil: Martins, Marco A.. Fundación Oswaldo Cruz; BrasilFil: Carvalho, Vinicius F.. Fundación Oswaldo Cruz; Brasi

Síntese de aminoálcoois derivados do D-manitol

Aminoalcohols have found important applications in synthetic and medicinal chemistry, being used as chiral building blocks for the synthesis of many biologically active compounds. This class of compounds has been also used as chiral auxiliaries and ligands in asymmetric synthesis. Due to the importance of aminoalcohols in the treatment of several diseases, such as tuberculosis, the aim of this article is the synthesis and preliminary evaluation against tuberculosis of six aminoalcohols in 5 or 6 steps using D-mannitol as starting material, which is a useful carbohydrate employed in many syntheses

Meiotic chromosomes and nucleolar behavior in testicular cells of the grassland spittlebugs Deois flavopicta, Mahanarva fimbriolata and Notozulia entreriana (Hemiptera, Auchenorrhyncha)

Spittlebugs annually infest pastures and cause severe damage, representing a serious problem for the tropical American beef cattle industry. Spittlebugs are an important biotic constraint to forage production and there is a lack of cytogenetic data for this group of insects. For these reasons, we conducted this work, in which the spermatogenesis and nucleolar behavior of Deois flavopicta, Mahanarva fimbriolata and Notozulia entreriana were studied. The males possessed testes in the shape of a “bunch of grapes”; a variable number of testicular lobes per individual and polyploid nuclei composed of several heteropycnotic bodies. A heteropycnotic area was located in the periphery of the nucleus (prophase I); the chiasmata were terminal or interstitial; metaphases I were circular or linear and anaphase showed late migration of the sex chromosome. The chromosome complement had 2n = 19, except for N. entreriana (2n = 15); the spermatids were round with heteropycnotic material in the center and elongated with conspicuos chromatin. The analysis of testes after silver nitrate staining showed polyploid nuclei with three large and three smaller nucleolar bodies. Early prophase cells had an intensely stained nucleolar body located close to the chromatin and another less evident body located away from the chromatin. The nucleolar bodies disintegrated during diplotene. Silver staining occurred in two autosomes, in terminal and subterminal locations, the latter probably corresponding to the nucleolus organizer regions (NORs). The spermatids were round with a round nucleolar body and silver staining was observed in the medial and posterior region of the elongated part of the spermatid head

Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy

Genetic modification of mesenchymal stem cells (MSCs) is a promising strategy to improve their therapeutic effects. Granulocyte-colony stimulating factor (G-CSF) is a growth factor widely used in the clinical practice with known regenerative and immunomodulatory actions, including the mobilization of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Here we evaluated the therapeutic potential of MSCs overexpressing G-CSF (MSC_G-CSF) in a model of inflammatory cardiomyopathy due to chronic Chagas disease. C57BL/6 mice were treated with wild-type MSCs, MSC_G-CSF, or vehicle (saline) 6 months after infection with Trypanosoma cruzi. Transplantation of MSC_G-CSF caused an increase in the number of circulating leukocytes compared to wild-type MSCs. Moreover, G-CSF overexpression caused an increase in migration capacity of MSCs to the hearts of infected mice. Transplantation of either MSCs or MSC_G-CSF improved exercise capacity, when compared to saline-treated chagasic mice. MSC_G-CSF mice, however, were more potent than MSCs in reducing the number of infiltrating leukocytes and fibrosis in the heart. Similarly, MSC_G-CSF-treated mice presented significantly lower levels of inflammatory mediators, such as IFNγ, TNFα, and Tbet, with increased IL-10 production. A marked increase in the percentage of Tregs and MDSCs in the hearts of infected mice was seen after administration of MSC_G-CSF, but not MSCs. Moreover, Tregs were positive for IL-10 in the hearts of T. cruzi-infected mice. In vitro analysis showed that recombinant hG-CSF and conditioned medium of MSC_G-CSF, but not wild-type MSCs, induce chemoattraction of MDSCs in a transwell assay. Finally, MDSCs purified from hearts of MSC_G-CSF transplanted mice inhibited the proliferation of activated splenocytes in a co-culture assay. Our results demonstrate that G-CSF overexpression by MSCs potentiates their immunomodulatory effects in our model of Chagas disease and suggest that mobilization of suppressor cell populations such as Tregs and MDSCs as a promising strategy for the treatment of chronic Chagas disease. Finally, our results reinforce the therapeutic potential of genetic modification of MSCs, aiming at increasing their paracrine actions

The Genomic Ancestry of Individuals from Different Geographical Regions of Brazil Is More Uniform Than Expected

Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a “total ancestry” estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries - a phenomenon described and intended as the “whitening of Brazil” - is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be relevant to other countries with ancestrally admixed populations