First-time Isolation of Flavonoids and Cytotoxic Potential of the Amazonian Shrub Ptychopetalum olacoides Benth

In the present study, three flavonoids, 3-O-methylquercetin (1), 3,4'-O-dimethylquercetin (2) and 3,7-O-dimethylquercetin (3) were isolated and characterized for the first time from a methanol extract obtained from the species Ptychopetalum olacoides. The structures of compounds were identified by spectroscopic methods (1D-, 2D-NMR, MS and UV) and confirmed by comparison with the respective literature data. The cytotoxic effect of crude extract was evaluated in vitro against three human cancer cell lines. The results showed a mild cytotoxic activity (IC50 = 45.16 mu g/mL) against breast cancer (MCF-7). However, crude extract did not exhibit any cytotoxic effect against normal cell human fibroblast (MRC-5).FAPERJCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Fluminense, Inst Quim, Dept Quim Organ, Campus Valonguinho, BR-24020141 Niteroi, RJ, BrazilUniv Fed Para, Inst Ciencias Biol, BR-66075110 Belem, Para, BrazilUniv Fed Sao Paulo, Dept Ciencias Mar, BR-11070100 Santos, SP, BrazilUniv Fed Rural Rio de Janeiro, Dept Quim, BR-23897000 Seropedica, RJ, BrazilUniv Fed Sao Paulo, Dept Ciencias Mar, BR-11070100 Santos, SP, BrazilWeb of Scienc

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

<p>Abstract</p> <p>Background</p> <p>Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.</p> <p>Methods</p> <p>This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.</p> <p>Discussion</p> <p>The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.</p> <p>Trial Registration</p> <p>Clinical Trials <a href="http://www.clinicaltrials.gov/ct2/show/NCT00970931">NCT00970931</a>.</p

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Comparação entre a composição química e capacidade antioxidante de diferentes extratos de própolis verde#

In this work were determined the total phenolic contents, antioxidant activity and chemical composition of twelve samples of green propolis acquired from beekeepers and other twelve commercial extracts samples from different regions of Southeast Brazil. The phenolic contents and the antioxidant activity were evaluated by the Folin-Ciocalteau and DPPH, ABTS and FRAP methods, respectively. Both types of propolis showed significant radical scavenging properties. HPLC-PDA was applied for quantification of chlorogenic acid, caffeic acid, ferulic acid, para-coumaric acid, rosmarinic acid, vanillin, hesperidin, naringenin, pinobanksin, kaempferol, Artepillin-C (4-hydroxy-3,5-diprenyl cinnamic acid), kampheride and pinostrobin. Despite the chemical composition of both in natura and commercial propolis extracts were similar the multivariate analysis allowed the discrimination between them

INFLUENCE OF AGE OF THE LEAVES OF E. uniflora

<p>GC-FID, GC-MS and NMR spectral data were used to analyze the composition of the essential oils extracted from young and mature leaves of <italic>E. uniflora</italic> L. grown in Seropédica - RJ. Thirty and twenty-five compounds were identified, corresponding to approximately 98.19% and 93.77% of the total amount of oils, respectively. The major components of the young leaves were (3<italic>Z</italic>,7<italic>E</italic>)-3,7-dimethyl-10-(propan-2-ylidene)cyclodeca-3,7-dienone (germacrone, 34.59%), 4,5,6,7-tetrahydro-3,6-dimethyl-5-(prop-1-en-2-yl)-6-vinylbenzofuran (curzerene, 26.56%) and (1<italic>Z</italic>,5<italic>E</italic>)-1,5-dimethyl-8-(propan-2-ylidene)cyclodeca-1,5-diene (germacrene B, 12.72%), and of the mature leaves were curzerene (35.75%), germacrene B (19.22%) and β-(<italic>E</italic>,1<italic>R</italic>,9<italic>S</italic>)-4,11,11-trimethyl-8-methylenebicyclo[7.2.0]undec-4-ene (caryophyllene, 12.55%). The multivariate analysis applied to data from GC-MS allowed discrimination of the differences in the chemical composition of oils based on the age of the leaves. The components germacrone, curzerene e furanodiene (not observed during conventional chromatographic analysis) were isolated from the essential oil of young leaves. These compounds were characterized by GC-MS, and ¹H and ¹³C NMR (1D and 2D).</p

PHENOLIC COMPOSITION AND ANTIOXIDANT PROPERTIES OF BRAZILIAN HONEYS

The antioxidant activities and polyphenolic levels of "assa peixe," "cambara," and "morrão de candeia" Brazilian honeys were investigated. Phenolic extracts of 11 honeys were evaluated spectrophotometrically to determine their total phenolic and flavonoid contents, and their antioxidant activities were measured using DPPH, ABTS, and FRAP assays. High-performance liquid chromatography coupled with diode array detection was applied to determine the phenolic composition of the honey extracts. The presence of fourteen phenolic compounds was established (eleven phenolic acids and three flavonoids), as well as HMF and abscisic acid. Principal component analysis was applied to classify the honey samples according to their floral origins