Análise estrutural e funcional do gene rpoN de Herbaspirillum seropedicae /

Orientador : Emanuel M. de SouzaCo-orientador : Fabio O. PedrosaTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Bioquímica. Defesa: Curitiba, 2006Inclui bibliografi

A epidemia do Diabetes mellitus encontra a pandemia da SARS-CoV-2 (COVID-19) / The Diabetes mellitus epidemic meets the SARS-CoV-2 (COVID-19) pandemic

A pandemia da doença coronavírus 2019 (COVID-19; SARS-Co-2) surgiu como um dos maiores desafios enfrentados pela humanidade. O diabetes mellitus, associado a hiperglicemia crônica, favorece comorbidades que podem ampliar o risco de severidade ou morte quando associado a viremia de COVID-19. A Idade avançada, múltiplas morbidades, hiperglicemia, doença cardíaca e resposta inflamatória severa são preditores de desfechos desfavoráveis na presença da viremia. Os diferentes aspectos da COVID-19 e suas associações com o diabetes mellitus, são abordados. A relação da enzima conversora de angiotensionogênio (ACE2), o controle glicêmico e diferentes aspectos da severidade e prognóstico são descritos em relação ao diabetes-COVID-19. Também são comentadas as medidas para prevenir a propagação da viremia com ênfase em orientações e no gerenciamento de procedimentos hospitalares e ambulatórias para o paciente com diabetes, em particular no sistema público de saúde. Esta revisão resume o conhecimento atual e os desafios percebidos para prevenção e gestão de COVID-19 em pessoas com diabetes

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Análise estrutural e funcional do gene rpoN de Herbaspirillum seropedicae /

Orientador : Emanuel M. de SouzaCo-orientador : Fabio O. PedrosaTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Bioquímica. Defesa: Curitiba, 2006Inclui bibliografi

Type 2 diabetes-associated genetic variants of FTO, LEPR, PPARg, and TCF7L2 in gestational diabetes in a Brazilian population

ABSTRACT Objective Gestational diabetes mellitus (GDM) is a metabolic disorder that shares pathophysiologic features with type 2 diabetes mellitus. The aim of this study was to investigate the association of the polymorphisms fat mass and obesity-associated (FTO) rs1421085, leptin receptor (LEPR) rs1137100, rs1137101, peroxisome proliferator-activated receptor gamma (PPARg) rs1801282, and transcription factor 7-like 2 (TCF7L2) rs7901695 with GDM. Subjects and methods 252 unrelated Euro-Brazilian pregnant women were classified into two groups according to the 2015 criteria of the American and Brazilian Diabetes Association: healthy pregnant women (n = 125) and pregnant women with GDM (n = 127), matched by age. The polymorphisms were genotyped using fluorescent probes (TaqMan®). Results All groups were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of the studied polymorphisms did not show significant differences between the groups (P > 0.05). In the healthy and GDM groups, the C allele frequencies (95% CI) of the FTO rs1421085 polymorphism were 36.8% [31–43%] and 35.0% [29–41%]; the G allele frequencies (95% CI) of the LEPR rs1137100 polymorphism were 24.8% [19–30%] and 22.8% [18–28%]; the G allele frequencies (95% CI) of the LEPR rs1137101 polymorphism were 43.6% [37–50%] and 42.9% [37–49%]; the G allele frequencies (95% CI) of the PPARg rs1801282 polymorphism were 7.6% [4–11%] and 8.3% [5–12%]; and the C allele frequencies (95% CI) of the TCF7L2 rs7901695 polymorphism were 33.6% [28–39%] and 39.0% [33–45%], respectively. Conclusion The studied polymorphisms were not associated with GDM in a Brazilian population

The rs10885122 polymorphism of the adrenoceptor alpha 2A (ADRA2A) gene in Euro-Brazilians with type 2 diabetes mellitus

Objective To investigate the association of the rs10885122G>T polymorphism in the ADRA2A gene in a Euro-Brazilian sample of healthy (controls) and type 2 diabetic (T2D) subjects. Subjects and methods We used fluorescent probes (TaqMan) to genotype 241 subjects, that is, 121 healthy and 120 T2D subjects, who were classified based on the Brazilian Diabetes Association (2013) and American Diabetes Association (2014) criteria. Results The genotype and allele frequencies showed no significant (P > 0.05) difference between the two studied groups. The minor allele (T) frequencies (95%CI) for rs10885122 were 19% (14-24%) and 20% (15-26%) for healthy and T2D groups, respectively. Carriers of the T allele (genotypes GT+TT) were significantly associated (P = 0.016) with approximately a 7-kg body weight reduction compared with the genotype GG, which was only found in the T2D group. Conclusion The rs10885122G>T polymorphism of the ADRA2A gene was not associated with T2D in Euro-Brazilians, and carriers of the T allele had lower body weight in the presence of T2D. Arch Endocrinol Metab. 2015;59(1):29-3

Evaluation of 1,5-Anhydroglucitol as a Biomarker for Type 2 Diabetes Mellitus in Patients without Overt Nephropathy

1,5-Anhydroglucitol (1,5-AG) is a non-fasting glycemic marker that responds to hyperglycemia excursions. The reduction in serum levels of 1,5-AG is associated with an increase in postprandial glycemia and glycosuria, phenomena that increase the risk and severity of diabetic complications. The objective is to assess the ability of 1,5-AG to discriminate type 2 diabetes (T2D) patients without overt kidney disease, for screening or diagnostic purposes. The Human Research Ethics Committee of Universidade Federal do Paraná (UFPR) approved the project. Serum samples from 567 individuals classified as healthy subjects (n = 291) and T2D (n = 276) with moderate glycemic control (HbA1c of 7-8%), matched by gender, were analyzed. Serum 1,5-AG levels were measured using an automated enzymatic method (GlycoMark, Inc.). Receiver Operating Characteristic (ROC) curve analysis for 1,5- AG showed sensibility of 65.3% and specificity of 91.1% to detect T2D at cut-off point of 92 µmol/L. The results were similar to the groups’ discrimination by glycemia (sensibility/specificity, 62.2%; 89.0%) at cut-off point of 6.3 mmol/L. HbA1c was the best discriminator (sensibility/specificity, 87.4%; 94.2%) at a cut-off point of 5.8% (40 mmol/mol). The serum 1,5-AG concentration was not able to discriminate T2D in the presence of moderate glycemic control with no overt nephropathy

RAGE receptor and its soluble isoforms in diabetes mellitus complications

Chronic hyperglycemia, which is present in all types of diabetes, increases the formation of advanced glycation end-products (AGEs). The interaction of AGEs with receptor of advanced glycation end-products (RAGE) initiates a cascade of pro-inflammatory and pro-coagulant processes that result in oxidative stress, stimulating the formation and accumulation of more AGE molecules. This cyclic process, denominated metabolic memory, may explain the persistency of diabetic vascular complications in patients with satisfactory glycemic control. The RAGE found in several cell membranes is also present in soluble isoforms (esRAGE and cRAGE), which are generated by alternative deoxyribonucleic acid splicing or by proteolytic cleavage. This review focuses on new research into these mediators as potential biomarkers for vascular complications in diabetes

Serum Fluorescent Advanced Glycation End (F-AGE) products in gestational diabetes patients

ABSTRACT Objectives Advanced glycation end products (AGEs) are involved in the pathogenesis and complications of diabetes mellitus (DM). Gestational DM (GDM) is characterized by increased glycemia and oxidative stress, which are factors associated with high serum AGE concentrations. The aim of this study was to evaluate the utility of a serum fluorescence AGE (F-AGE) method as a screening tool for gestational diabetes. Subjects and methods Serum samples from 225 GDM patients and 217 healthy pregnant women (healthy controls) were diluted 50-fold in phosphate-buffered saline, and the AGEs were estimated by fluorometric analysis (λEx 350 nm/ λEm 440 nm). Results No significant (P > 0.05) differences in AGE concentrations, expressed in Arbitrary Units (UA/mL × 104), were observed in the women with GDM or in the healthy controls. Furthermore, F-AGE concentrations did not change significantly during the pregnancy (12-32 weeks of gestation). Only the GDM group had a positive correlation (r = 0.421; P < 0.001) between F-AGEs and serum creatinine concentrations. Conclusion It was not possible to distinguish women with gestational diabetes from the healthy controls on the basis of serum F-AGE concentrations