Peripheral antinociceptive action of mangiferin in mouse models of experimental pain: Role of endogenous opioids, KATP-channels and adenosine

AbstractThis study aimed to assess the possible systemic antinociceptive activity of mangiferin and to clarify the underlying mechanism, using the acute models of chemical (acetic acid, formalin, and capsaicin) and thermal (hot-plate and tail-flick) nociception in mice. Mangiferin at oral doses of 10 to 100mg/kg evidenced significant antinociception against chemogenic pain in the test models of acetic acid-induced visceral pain and in formalin- and capsaicin-induced neuro-inflammatory pain, in a naloxone-sensitive manner, suggesting the participation of endogenous opiates in its mechanism. In capsaicin test, the antinociceptive effect of mangiferin (30mg/kg) was not modified by respective competitive and non-competitive transient receptor potential vanilloid 1 (TRPV1) antagonists, capsazepine and ruthenium red, or by pretreatment with l-NAME, a non-selective nitric oxide synthase inhibitor, or by ODQ, an inhibitor of soluble guanylyl cyclase. However, mangiferin effect was significantly reversed by glibenclamide, a blocker of KATP channels and in animals pretreated with 8-phenyltheophylline, an adenosine receptor antagonist. Mangiferin failed to modify the thermal nociception in hot-plate and tail-flick test models, suggesting that its analgesic effect is only peripheral but not central. The orally administered mangiferin (10–100mg/kg) was well tolerated and did not impair the ambulation or the motor coordination of mice in respective open-field and rota-rod tests, indicating that the observed antinociception was unrelated to sedation or motor abnormality. The findings of this study suggest that mangiferin has a peripheral antinociceptive action through mechanisms that involve endogenous opioids, KATP-channels and adenosine receptors

Extratos etanólicos de manga como antioxidantes na alimentação de poedeiras

O objetivo deste trabalho foi avaliar o efeito de extratos etanólicos do caroço e da casca de manga, sobre o desempenho de poedeiras e sobre a qualidade e estabilidade lipídica dos ovos. Um total de 180 poedeiras comerciais Hisex White foi distribuído ao acaso em seis tratamentos, com cinco repetições de seis aves. Os tratamentos consistiram de: ração sem adição de antioxidante; ração com 200 ppm do antioxidante butilato de hidroxitolueno (BHT); ração com 200 ou 400 ppm de extrato da casca de manga (Ecas); ração com 200 ou 400 ppm de extrato de caroço de manga (Ecar). Foram avaliados: o consumo de ração, a produção de ovos, o peso do ovo, a massa de ovo produzida (grama por ave por dia), a conversão alimentar e características de qualidade dos ovos. A oxidação lipídica da gema durante o armazenamento foi determinada pela quantificação das substâncias reativas ao ácido tiobarbitúrico. As aves alimentadas com a ração sem adição de antioxidantes produziram ovos com os piores valores de unidade Haugh e maior oxidação lipídica da gema. Os teores de 400 ppm de Ecas e 200 ou 400 ppm de Ecar foram efetivos na prevenção de danos oxidativos aos ovos durante o armazenamento e podem ser utilizados na alimentação das poedeiras como substituto ao antioxidante sintético

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

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

EVALITA Evaluation of NLP and Speech Tools for Italian - December 17th, 2020

Welcome to EVALITA 2020! EVALITA is the evaluation campaign of Natural Language Processing and Speech Tools for Italian. EVALITA is an initiative of the Italian Association for Computational Linguistics (AILC, http://www.ai-lc.it) and it is endorsed by the Italian Association for Artificial Intelligence (AIxIA, http://www.aixia.it) and the Italian Association for Speech Sciences (AISV, http://www.aisv.it)

The functional equation for the twisted spinor L-series of genus 2

Based on its essential role in the life cycle of Trypanosoma cruzi, the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) has been considered a promising target for the development of novel chemotherapeutic agents for the treatment of Chagas` disease. In the course of our research program to discover novel inhibitors of this trypanosomatid enzyme, we have explored a combination of structure and ligand-based virtual screening techniques as a complementary approach to a biochemical screening of natural products using a standard biochemical assay. Seven natural products, including anacardic acids,. avonoid derivatives, and one glucosylxanthone were identified as novel inhibitors of T. cruzi GAPDH. Promiscuous inhibition induced by nonspecific aggregation has been discarded as specific inhibition was not reversed or affected in all cases in the presence of Triton X-100, demonstrating the ability of the assay to find authentic inhibitors of the enzyme. The structural diversity of this series of promising natural products is of special interest in drug design, and should therefore be useful in future medicinal chemistry efforts aimed at the development of new GAPDH inhibitors having increased potency. (C) 2009 Elsevier Ltd. All rights reserved.CNPq (Conselho Nacional de Desenvolvimento Cientico e Tecnologico)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Luminescent Ru(II) Phenanthroline Complexes as a Probe for Real-Time Imaging of A beta Self-Aggregation and Therapeutic Applications in Alzheimer's Disease

The complexes, cis-[Ru(phen)(2)(Apy)(2)](2+), Apy = 4-aminopyridine and 3,4-aminopyridine, are stable in aqueous solution with strong visible absorption. They present emission in the visible region with long lifetime that accumulates in the cytoplasm of Neuro2A cell line without appreciable cytotoxicity. The complexes also serve as mixed-type reversible inhibitors of human AChE and BuChE with high active Site contact. cis-[Ru(phen)(2)(3,4Apy)(2)](2+) competes efficiently with DMPO by the OH center dot radical. Luminescence using fluorescence lifetime imaging (FLIM) enables real-time imaging of the onformational Changes of the self-aggregation, of A beta with incubation of complexes (0-24 h) in phosphate buffer at micromolar concentrations. By this technique, we identified protofibrillsin the self-assembly of A beta(1-40) and globular structures in the short fragment A beta(15-21) in aqueous solution.FAPESP [2014/12538-8, 2014/07935-8, 2012/02065-0, 2014/24643-0, 2014/26895-7]CNPq [304981/2012-5]CAPESUniv Fed Sao Carlos, Dept Quim, BR-13565905 Sao Carlos, SP, BrazilUniv Sao Paulo, Dept Fis, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14040901 Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Dept Biofis, Escola Paulista Med, BR-04023062 Sao Paulo, SP, BrazilUniv Fed Ceara, Dept Quim Organ & Inorgan, BR-60451970 Fortaleza, Ceara, BrazilDepartamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, São Paulo 04023-062, BrazilFAPESP: 2014/12538-8FAPESP: 2014/07935-8FAPESP: 2012/02065-0FAPESP: 2014/24643-0FAPESP: 2014/26895-7CNPq: 304981/2012-5Web of Scienc