19 research outputs found
Prevalence and predictors of coronary artery disease in patients with a calcium score of zero
The absence of coronary calcification is associated with an excellent prognosis. However, a calcium score of zero does not exclude the presence of coronary artery disease (CAD) or the possibility of future cardiovascular events. Our aim was to study the prevalence and predictors of coronary artery disease in patients with a calcium score of zero. Prospective registry consisted of 3,012 consecutive patients that underwent cardiac CT (dual source CT). Stable patients referred for evaluation of possible CAD that had a calcium score of zero (n = 864) were selected for this analysis. The variables that were statistically significant were included in a multivariable logistic regression model. From 864 patients with a calcium score of zero, 107 (12.4 %) had coronary plaques on the contrast CT (10.8 %, n = 93 with nonobstructive CAD and 1.6 %, n = 14 with obstructive CAD). By logistic regression analysis, the independent predictors of CAD in this population were age >55 years [odds ratio (OR) 1.63 (1.05-2.52)], hypertension [OR 1.64 (1.05-2.56)] and dyslipidemia [OR 1.54 (1.00-2.36)]. In the presence of these 3 variables, the probability of having coronary plaques was 21 %. The absence of coronary artery calcification does not exclude the presence of coron
A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B
Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans.Juliana Garcia, Vera Marisa Costa, Ricardo Dinis-Oliveira and Ricardo Silvestre thank FCT-Foundation for Science and Technology-for their PhD grant (SFRH/BD/74979/2010), Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/110001/2015) and Investigator grants (IF/01147/2013) and (IF/00021/2014), respectively. This work was supported by the Fundacao para a Ciencia e Tecnologia (FCT) - project PTDC/DTPFTO/4973/2014 - and the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundacao para a Ciencia e Tecnologia) through project Pest-C/EQB/LA0006/2013
Resolution of inflammation: a new therapeutic frontier
Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field
Probing selectivity of mixed-mode reversed-phase/weak-anion-exchange liquid chromatography to advance method development
The current study comprises a systematic investigation to assess retention properties and selectivity of a mixed-mode reversed-phase/weak-anion-exchange (RP/WAX) stationary phase to aid method development. Retention was investigated for different compound classes which vary in hydrophobicity, van der Waals surface area, and charge as function of organic content, pH, and ionic strength of the mobile phase. The linear-solvent-strength model was successfully applied for aromatic hydrocarbons to obtain retention-time predictions based on log P values and van der Waals surface area values. For phenols, predictions were based on log P values and data from a single scouting run performed in isocratic mode to estimate the S parameter; the deviations between experimental and predicted retention times were smaller than 6 To describe the mixed-mode (RP/WAX) retention behavior of singly and doubly negatively-charged aromatic acids, a novel model combining the linear-solvent-strength and the empirical stoichiometric-displacement-net-charge models is proposed and validated. Using combinations of three scouting runs that are not linearly dependent, the maximum prediction error was 11% and changes in selectivity were correctly forecasted when altering the mobile-phase composition, i.e., either organic modifier content or ionic strength. When using nine scouting runs in combination with a least-squares regression approach to determine the model parameters, the maximum prediction error was 6%
Recycling organic wastes to agricultural land as a way to improve its quality: A field study to evaluate benefits and risks
A field study was established to assess the effects of a sewage sludge (SS), a mixed municipal solid waste compost (MMSWC) and a compost produced from agricultural wastes (AWC), in a Vertisol, using Lolium multiflorum L The amendments were applied for two consecutive years: 6, 12 and 24 t dry matter ha(-1) for SS, and the amendment doses for MMSWC and AWC were calculated to deliver the same amount of organic matter (OM) per unit area. The amendments had significant beneficial effects on some soil properties (e.g. soil OM, N-Kjeldahl, extractable P and K), and on plant productivity parameters (e.g. biomass yield, chlorophyll, foliar area). For instance, soil OM increased from 0.78% to 1.71, 2.48 and 2.51%, after two consecutive years of application of 24 t dry matter ha(-1) of SS, MMSWC and AWC, respectively, while the plant biomass obtained increased from 7.75 t ha(-1) to 152.41, 78.14 and 29.26 t ha(-1), for the same amendments. On the plant, effects were more pronounced for SS than for both compost applications, a consequence of its higher capacity to provide N to the plant in a readily available form. However, after two years of application, the effects on foil properties were more noticeable for both composts, as their OM is more-resistant to mineralization, which endures their beneficial effects on soil. Cadmium, Cr, Ni and Pb pseudo-total concentrations, were not affected significantly by the application of the organic wastes to soil, in all tested doses, neither their extractability by 0.01 M CaCl2. On the contrary, Cu and Zn pseudo-total concentrations increased significantly in the second year of the experiment, following the application of the higher rate of MMSWC and AWC, although their extractability remained very low (<0.5% of their pseudo-total fraction). Trace elements concentrations in the aboveground plant material were lower than their maximum tolerable levels for cattle, used as an indicator of risk of their entry into the human food chain. Despite these results, it is interesting to note that the SS promoted a significant increase in the foliar concentrations of Cu, Ni and Zn that did not happen in composts application, which can be explained by the reduction of the soil pH, as a consequence of SS degradation in soil. Concluding, if this type of organic wastes were to be used in a single application, the rate could be as high as 12 or even 24 t ha(-1), however, if they are to be applied in an annual basis, the application rates should be lowered to assure their safe application (e.g. to 6 t ha(-1)). Moreover, it is advisable to use more stable and mature organic wastes, which have longer lasting positive effects on soil characteristics. (C) 2017 Elsevier Ltd. All rights reserved.FEDER, through Eixo I - Programa Operacional Fatores de Competitividade (POFC) from QREN [FCOMP-01-0124-FEDER-019330][UID/AGR/04129/2013
Estudo Prospectivo de Leguminosas da Amazônia Central. II. Composição Química dos Óleos das Sementes
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Previous issue date: 14Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Produtos Naturais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Produtos Naturais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Produtos Naturais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Produtos Naturais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Produtos Naturais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Produtos Naturais. Rio de Janeiro, RJ, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Pesquisas de Produtos Florestais.Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Pesquisas de Produtos Florestais.Manaus, AM, Brasil.As constituições lipídicas das sementes das onze espécies de Leguminosae da Amazônia Central, Acosmium nitens Yakovl, Bauhinia splendens Kunt, Caesalpinia ferrea Martius var. ferrea, Clathrotropis nitida (Benth.) Harms., Cynometria spruceana Benth., Macrolobium acaciifolium (Benth.) Benth., Ormosia excelsa Benth., Parkia discolor Benth., Peltogyne venosa (Vahl.) Benth., Stryphnodendron guianense Benth., Vatairea guianensis Aubl. foram determinadas. Os componentes individuais dos óleos foram analisados por cromatografia em fase gasosa acoplada à espectrometria de massas, usando-se duas colunas de diferentes polaridades. Os ácidos graxos foram analisados na forma de ésteres metílicos, preparados por hidrólise alcalina dos triglicerídeos seguida de tratamento com diazometano. As misturas de ésteres graxos foram mais bem resolvidas quando se utilizou a fase estacionária mais polar para a coluna (polietilenoglicol). O ácido palmítico foi representativo (18% a 35%) em cinco espécies, com presença relevante (52%) em C. ferrea. O conteúdo de ácido esteárico foi significante (18% a 31%) em quatro espécies, alcançando cerca de 80% em B. splendens. O ácido oléico constituiu 44% dos ácidos graxos totais de A. nitens, e foi representativo (20% a 29%) em outras quatro espécies. Outros constituintes, como os ácidos araquídico, behênico e lignocérico, apareceram em concentrações variáveis (até 20%) na maioria das amostras. A presença de ácido linolênico é também significante em S. guianense (15%) and C. spruceana (6.2%). O alto rendimento bruto do óleo de B. splendens (acima de 20%) sugere o seu potencial como fonte de ácido esteárico. Sementes de outras cinco espécies produziram óleos brutos entre 6% e 10%. The fatty acid constitution of oils from the seeds of eleven Amazonian
species of Leguminosae, namely Acosmium nitens Yakovl, Bauhinia splendens Kunt, Caesalpinia ferrea Martius var. ferrea, Clathrotropis nitida (Benth.) Harms., Cynometria spruceana Benth., Macrolobium acaciifolium (Benth.) Benth., Ormosia excelsa Benth., Parkia discolor Benth., Peltogyne venosa (Vahl.) Benth., Stryphnodendron guianense Benth., Vatairea guianensis Aubl., were determined. The individual components of the oils were analyzed by gas chromatography coupled to mass spectrometry, using two columns having stationary phases with different
polarities. The fatty acids were analyzed as methyl esters, prepared by alcaline hydrolysis of the triglycerides followed by treatment with diazomethane. The mixture of fatty esters was better separated in the more polar stationary phase (polyethylene glycol). Palmitic acid was representative (18% to 35%) in five species, being especially high (52%)
in C. ferrea. The stearic acid content is significant (18% to 31%) in four species, rising to about 80% in B. splendens. Oleic acid constitutes 44% of the fatty acids in A. nitens and is representative (20% to 29%) in four other species. Other constituents, such as arachidic, behenic and lignoceric acids, are present at variable concentrations (up to 20%) in most of the samples. The presence of linolenic acid is also notable in S. guianense (15%) and C. spruceana (6.2%). The high crude oil yield of B. splendens (higher than 20%) suggests it as a potential source of stearic acid for industrial purposes. Seeds of five other species had crude oil content between 6% and 10%