A validated NMR approach for MDMA quantification in Ecstasy tablets

In recent years, ecstasy trafficking has grown in complexity and tablets has been commonly sold containing different contents of 3,4-methylenedioxymethamphetamine (MDMA) or even other psychoactive substances. In contrast, identification and quantification of drugs of abuse is still a challenge, once the access to drug standards is very restricted in Brazil. In this work, ecstasy tablets seized by the Brazilian Federal Police have their chemical composition identified and quantified by gas chromatography and quantitative 1H nuclear magnetic resonance based on an internal standard approach (IS-1H-qNMR). Both methods were validated and showed suitable results for the figures of merit. IS-1H-qNMR shows excellent results of accuracy (relative error < 5%) and precision (relative standard deviation (RSD) < 2%). Comparatively, IS-1H-qNMR is more efficient and versatile than gas chromatography to accomplish in a single analysis the identification and quantification of target analytes. Since the method does not require a specific reference material, it is cost effective and provides agility to routine forensic analysis

Self-reported training variables are poor predictors of laboratory measures in cyclists.

Purpose: Cycling is an activity that depends on a range of physiological attributes, as well as genetic, dietary, lifestyle and training factors. The aim of this study was to determine what self-reported training-related factors (e.g. intensity, frequency, supervision, etc) might predict laboratory-measured physiological and performance characteristics of a heterogeneous group of male and female self-classified cyclists. Methods: Forty-eight male and fourteen female cyclists completed all aspects of the study including a training questionnaire, incremental cycling test to determine maximal oxygen uptake (VO2max), 30-s Wingate test and a 4-km cycling time-trial. Principle component analysis and LASSO regression modelling were used to analyse laboratory-measures and training variables and the predictive capacity of the latter. Results: Total distance covered across all intensities was the only training variable included in most bootstrap models (63.8%), although the actual contribution was very low with a median f2 effect size equal to 0.01. Self-reported classification of cycling level was weakly correlated to guideline classification of relative VO2max in men (r=0.396, p=0.004), but not women (r=0.024, p=0.925). Conclusions: Self-reported training variables were poor predictors of laboratory-based physiological and performance variables in this heterogeneous group of cyclists. Total distance covered was the only training variable included in most regression models, but the predictive capability of outcomes was low. This suggests that most of these self-report variables are not useful pre-screening tools for categorising non-elite cyclists or raises the potential that non-elite cyclists cannot accurately quantify their own training intensities. Researchers and coaches should be wary that self-reported classification may not directly reflect the level of the cyclist

Maternal consumption of ultra-processed foods-rich diet and perinatal outcomes : a systematic review and meta-analysis

The consumption of ultra-processed food (UPF)-rich diets represents a potential threat to human health. Considering maternal diet adequacy during pregnancy is a major determinant for perinatal health outcomes, this study aimed to systematically review and meta-analyze studies investigating the association between maternal consumption of a UPF-rich diet and perinatal outcomes. Conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, five electronic databases and gray literature using Google Scholar and ProQuest Dissertations and Theses Global were searched up to 31 May 2022. No restrictions were applied on language and publication date. Two reviewers independently conducted the study selection and data extraction process. Meta-analysis was conducted according to the random-effects model. In total, 61 studies were included in the systematic review and the overall population comprised 698,803 women from all gestational trimesters. Meta-analysis of cohort studies showed that maternal consumption of UPF-rich diets was associated with an increased risk of gestational diabetes mellitus (odds ratio (OR): 1.48; 95% confidence interval (CI): 1.17, 1.87) and preeclampsia (OR: 1.28; 95% CI: 1.15, 1.42). Neonatal outcomes showed no association. The overall GRADE quality of the evidence for the associations was very low. The findings highlight the need to monitor and reduce UPF consumption, specifically during the gestational period, as a strategy to prevent adverse perinatal outcomes

β-cyclodextrin/isopentyl caffeate inclusion complex: synthesis, characterization and antileishmanial activity

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings. In this work, we have proposed the development of an inclusion complex of ICaf in -cyclodextrin (-CD), with the aim to improve the drug solubility, and thus, its bioavailability. The inclusion complex (ICaf:-CD) was developed applying three distinct methods, i.e., physical mixture (PM), kneading (KN) or co-evaporation (CO) in different molar proportions (0.25:1, 1:1 and 2:1). Characterization of the complexes was carried out by thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and molecular docking. The ICaf:-CD complex in a molar ratio of 1:1 obtained by CO showed the best complexation and, therefore, was selected for further analysis. Solubility assay showed a marked improvement in the ICaf:-CD (CO, 1:1) solubility profile when compared to the pure ICaf compound. Cell proliferation assay using ICaf:-CD complex showed an IC50 of 3.8 and 2.7 µg/mL against L. amazonesis and L. chagasi promastigotes, respectively. These results demonstrate the great potential of the inclusion complex to improve the treatment options for visceral and cutaneous leishmaniases.This research was funded by Banco do Nordeste (grant FUNDECI/2016.0015), Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and Fundação de Ámparo à Pesquisa do Estado de Sergipe (FAPITEC) (PROCESSO: 88887.159533/2017-00 extração, encapsulação e caracterização de bioativos para o interesse biotecnologico). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 301964/2019-0 Chamada 06/2019, and Chamada CNPq nº 01/2019) and from the Portuguese Science and Technology Foundation (FCT) project UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio

Efferent Pathways in Sodium Overload-Induced Renal Vasodilation in Rats

Hypernatremia stimulates the secretion of oxytocin (OT), but the physiological role of OT remains unclear. the present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g) were anesthetized with sodium thiopental (40 mg. kg(-1), i.v.). A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP) and renal blood flow (RBF). Renal vascular conductance (RVC) was calculated as the ratio of RBF by MAP. in anesthetized rats (n = 6), OT infusion (0.03 mu g . kg(-1), i.v.) induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR) reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml . kg(-1) b.wt., i.v.) was infused over 60 s. in sham rats (n = 6), hypertonic saline induced renal vasodilation. the OXTR antagonist (AT; atosiban, 40 mu g . kg(-1) . h(-1), i.v.; n = 7) and renal denervation (RX) reduced the renal vasodilation induced by hypernatremia. the combination of atosiban and renal denervation (RX+AT; n = 7) completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively), whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Goias, Ctr Neurosci & Cardiovasc Physiol, Inst Biol Sci, Dept Physiol Sci, Goiania, Go, BrazilUniv Fed Uberlandia, Fac Phys Educ, Inst Biol Sci, BR-38400 Uberlandia, MG, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniv Fed Goias, Inst Biol Sci, Mol Biol Lab, Goiania, Go, BrazilUniv Fed Goias, Inst Biol Sci, Dept Biochem & Mol Biol, Goiania, Go, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilFundacao de Amparo a Pesquisa do Estado de Goias (FAPEG): 2012/0055431086Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG): 2009/10267000352CNPq: 477832/2010-5CNPq: 483411/2012-4Web of Scienc

Structurally Related Monoterpenes p-Cymene, Carvacrol and Thymol Isolated from Essential Oil from Leaves of Lippia sidoides Cham. (Verbenaceae) Protect Mice against Elastase-Induced Emphysema

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes (p-cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). Methods: Mices received porcine pancreatic elastase (PPE) and were treated with p-cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. Results: In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1 beta, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-kappa B-positive cells in lung parenchyma (p < 0.05). All treatments attenuated levels of 8-iso-PGF2 alpha but only thymol was able to reduced exhaled nitric oxide (p < 0.05). Conclusion: Monoterpenes p-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Laboratorio de Investigacao Medica, Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo (LIM)Univ Fed Sao Paulo, Dept Biol Sci, BR-09913030 Diadema, BrazilUniv Sao Paulo, Sch Med, Dept Med, BR-01246903 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Exact Sci & Earth, BR-09913030 Diadema, BrazilFed Univ ABC, Ctr Nat Sci & Humanities, BR-09606045 Santo Andre, SP, BrazilUniv Fed Sao Paulo, Dept Biosci, Campus Baixada Santista, BR-11015020 Santos, SP, BrazilDepartment of Biological Science, Universidade Federal de São Paulo, Diadema 09913-030, BrazilDepartment of Exact Science and Earth, Universidade Federal de São Paulo, Diadema 09913-030, BrazilDepartment of Bioscience, Federal University of São Paulo, Campus Baixada Santista, Santos 11015-020, SP, BrazilCNPq: 300546/2012-2CNPq: 304465/2012-7CNPq: 476877/2012-1CNPq: 306278/2015-4FAPESP: 2011/51739-0FAPESP: 2013/02881-4FAPESP: 2008/55359-5FAPESP: 2015/11936-2FAPESP: 2014/25689-4LIM: LIM20Web of Scienc