PÉ DIABÉTICO: PERFIL METABÓLICO E SOCIOECONÔMICO DE PACIENTES ATENDIDOS PELO LABORATÓRIO DE ENSINO E PESQUISA DA UNIVERSIDADE ESTADUAL DE MARINGÁ

O pé diabético é uma das complicações crônicas mais devastadoras em pacientes diabéticos, gerando alto impacto social e econômico, além de diminuir a qualidade de vida. Neste estudo exploratório-descritivo foram avaliados 39 pacientes diabéticos tipo 2 (PDT2), atendidos pelo Laboratório de Ensino e Pesquisa da Universidade Estadual de Maringá (agosto/2009 e abril/2010). Os pacientes foram submetidos a uma entrevista para obtenção de informações sobre o perfil socioeconômico e a avaliação laboratorial da glicemia e lipidemia (perfil metabólico). Os resultados revelaram: prevalência do gênero feminino, média de idade de 60,1 ± 9,5 anos, 71,8% tinham Ensino Fundamental incompleto, 61,5% eram casados, 74,3% eram sedentários, o tempo de doença foi de 9,2 ± 7,3 anos, 53,8% desconheciam os cuidados e complicações do pé e 70,6% estavam com a hemoglobina glicada alterada. Conclui-se que a baixa escolaridade e pouco conhecimento em relação à doença comprometem o processo de autocuidado, aumentando as chances do aparecimento das complicações crônicas

Dexamethasone during pregnancy impairs maternal pancreatic β-cell renewal during lactation

Pancreatic islets from pregnant rats develop a transitory increase in the pancreatic β-cell proliferation rate and mass. Increased apoptosis during early lactation contributes to the rapid reversal of those morphological changes. Exposure to synthetic glucocorticoids during pregnancy has been previously reported to impair insulin secretion, but its impacts on pancreatic islet morphological changes during pregnancy and lactation have not been described. To address this issue, we assessed the morphological and molecular characteristics of pancreatic islets from rats that underwent undisturbed pregnancy (CTL) or were treated with dexamethasone between the 14th and 19th days of pregnancy (DEX). Pancreatic islets were analyzed on the 20th day of pregnancy (P20) and on the 3rd, 8th, 14th and 21st days of lactation (L3, L8, L14 and L21, respectively). Pancreatic islets from CTL rats exhibited transitory increases in cellular proliferation and pancreatic β-cell mass at P20, which were reversed at L3, when a transitory increase in apoptosis was observed. This was followed by the appearance of morphological features of pancreatic islet neogenesis at L8. Islets from DEX rats did not demonstrate an increase in apoptosis at L3, which coincided with an increase in the expression of M2 macrophage markers relative to M1 macrophage and T lymphocyte markers. Islets from DEX rats also did not exhibit the morphological characteristics of pancreatic islet neogenesis at L8. Our data demonstrate that maternal pancreatic islets undergo a renewal process during lactation that is impaired by exposure to DEX during pregnancy

Changes in PGC-1α-Dependent Mitochondrial Biogenesis Are Associated with Inflexible Hepatic Energy Metabolism in the Offspring Born to Dexamethasone-Treated Mothers

In the present study we investigated the participation of hepatic peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) in the metabolic programming of newborn rats exposed in utero to dexamethasone (DEX). On the 21st day of life, fasted offspring born to DEX-treated mothers displayed increased conversion of pyruvate into glucose with simultaneous upregulation of PEPCK (phosphoenolpyruvate carboxykinase) and G6Pase (glucose-6-phosphatase). Increased oxidative phosphorylation, higher ATP/ADP ratio and mitochondrial biogenesis and lower pyruvate levels were also found in the progeny of DEX-treated mothers. On the other hand, the 21-day-old progeny of DEX-treated mothers had increased hepatic triglycerides (TAG) and lower CPT-1 activity when subjected to short-term fasting. At the mechanistic level, rats exposed in utero to DEX exhibited increased hepatic PGC-1α protein content with lower miR-29a-c expression. Increased PGC-1α content was concurrent with increased association to HNF-4α and NRF1 and reduced PPARα expression. The data presented herein reveal that changes in the transcription machinery in neonatal liver of rats born to DEX-treated mothers leads to an inflexible metabolic response to fasting. Such programming is hallmarked by increased oxidative phosphorylation of pyruvate with impaired FFA oxidation and hepatic TAG accumulation.</jats:p

High anti-SARS-CoV-2 antibody seroconversion rates before the second wave in Manaus, Brazil, and the protective effect of social behaviour measures: results from the prospective DETECTCoV-19 cohort

Background: The city of Manaus, Brazil, has seen two collapses of the health system due to the COVID-19 pandemic. We report anti-SARS-CoV-2 nucleocapsid IgG antibody seroconversion rates and associated risk factors in Manaus residents before the second wave of the epidemic in Brazil. Methods: A convenience sample of adult (aged ≥18 years) residents of Manaus was recruited through online and university website advertising into the DETECTCoV-19 study cohort. The current analysis of seroconversion included a subgroup of DETECTCoV-19 participants who had at least two serum sample collections separated by at least 4 weeks between Aug 19 and Oct 2, 2020 (visit 1), and Oct 19 and Nov 27, 2020 (visit 2). Those who reported (or had no data on) having a COVID-19 diagnosis before visit 1, and who were positive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at visit 1 were excluded. Using an in-house ELISA, the reactivity index (RI; calculated as the optical density ratio of the sample to the negative control) for serum anti-SARS-CoV-2 nucleocapsid IgG antibodies was measured at both visits. We calculated the incidence of seroconversion (defined as RI values ≤1·5 at visit 1 and ≥1·5 at visit 2, and a ratio >2 between the visit 2 and visit 1 RI values) during the study period, as well as incidence rate ratios (IRRs) through cluster-corrected and adjusted Poisson regression models to analyse associations between seroconversion and variables related to sociodemographic characteristics, health access, comorbidities, COVID-19 exposure, protective behaviours, and symptoms. Findings: 2496 DETECTCoV-19 cohort participants returned for a follow-up visit between Oct 19 and Nov 27, 2020, of whom 204 reported having COVID-19 before the first visit and 24 had no data regarding previous disease status. 559 participants were seropositive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at baseline. Of the remaining 1709 participants who were seronegative at baseline, 71 did not meet the criteria for seroconversion and were excluded from the analyses. Among the remaining 1638 participants who were seronegative at baseline, 214 showed seroconversion at visit 2. The seroconversion incidence was 13·06% (95% CI 11·52–14·79) overall and 6·78% (5·61–8·10) for symptomatic seroconversion, over a median follow-up period of 57 days (IQR 54–61). 48·1% of seroconversion events were estimated to be asymptomatic. The sample had higher proportions of affluent and higher-educated people than those reported for the Manaus city population. In the fully adjusted and corrected model, risk factors for seroconversion before visit 2 were having a COVID-19 case in the household (IRR 1·49 [95% CI 1·21–1·83]), not wearing a mask during contact with a person with COVID-19 (1·25 [1·09–1·45]), relaxation of physical distancing (1·31 [1·05–1·64]), and having flu-like symptoms (1·79 [1·23–2·59]) or a COVID-19 diagnosis (3·57 [2·27–5·63]) between the first and second visits, whereas working remotely was associated with lower incidence (0·74 [0·56–0·97]). Interpretation: An intense infection transmission period preceded the second wave of COVID-19 in Manaus. Several modifiable behaviours increased the risk of seroconversion, including non-compliance with non-pharmaceutical interventions measures such as not wearing a mask during contact, relaxation of protective measures, and non-remote working. Increased testing in high-transmission areas is needed to provide timely information about ongoing transmission and aid appropriate implementation of transmission mitigation measures. Funding: Ministry of Education, Brazil; Fundação de Amparo à Pesquisa do Estado do Amazonas; Pan American Health Organization (PAHO)/WHO.World Health OrganizationRevisión por pare

Gonadectomy and DHEA: metabolic effects in adult female rats fed with high-fat diet.

A privação dos hormônios sexuais em fêmeas contribui para o aparecimento de distúrbios metabólicos e endócrinos devido à ausência de estrógenos. Nesse estudo foi avaliado o efeito da castração e da suplementação com DHEA sobre aspectos metabólicos em ratas. A ovariectomia aumentou a adiposidade e o consumo de ração, diminuiu o consumo hídrico, além de promover resistência à insulina e intolerância à glicose, e o uso do DHEA reduziu a sensibilidade à insulina. Ainda, a castração levou a redução nos níveis plasmáticos de DHEA, estradiol, VLDL-c e triacilglicerol, albumina, uréia e creatinina, e o tratamento com DHEA restaurou parcialmente a concentração de estradiol no grupo OVX+DHEA. E por fim, a ooforectomia reduziu a expressão proteica do IRb, IRS1, PI3K e AKT no fígado, músculo gastrocnêmio ou coração, além diminuir o grau de fosforilação em tirosina da pp185 (IRS1/2). Deste modo, concluímos que a castração promoveu resistência à insulina e intolerância à glicose associada à obesidade, e neste modelo, o uso do DHEA piorou a sensibilidade à insulina nos animais.Deprivation of sex hormones in females contributes to the onset of metabolic and endocrine disorders due loss of estrogen. In this study the effect of castration and supplementation with DHEA on metabolic aspects in rats was evaluated. Ovariectomy increased adiposity and food consumption, decreased water consumption, besides promoting insulin resistance and glucose intolerance, and the use of DHEA reduced insulin sensitivity. Furthermore, castration led to decreasing of DHEA plasma levels, estradiol, VLDL-c and triacylglycerol, albumin, urea and creatinine, and DHEA treatment partially restored the concentration of estradiol in OVX+DHEA group. Finally, ovariectomy reduced the protein expression IRb, IRS1, PI3K and AKT in the liver, gastrocnemius muscle or heart. Indeed, decrease tyrosine phosphorylation status of pp185 (IRS1/2) was observed. Thus, we conclude that castration promoted insulin resistance and glucose intolerance associated with obesity, and in this model, the use of DHEA impairs insulin sensitivity in animals

Oxidative stress parameters as biomarkers of risk factor for diabetic foot among the patients with type 2 diabetes

The aim of this study was to determine whether plasma levels of carbonylated proteins, total antioxidant capacity (TAC) and reduced protein thiols could be suitable biomarkers of risk factors for diabetic foot. Individuals with type 2 diabetes with normal protective sensation (normal foot group) vs. loss of protective sensation and/or signs of peripheral arterial disease and/or foot deformities and/or history of ulcers and/or neuropathic fractures and/or amputation (diabetic foot group) were compared. The diabetic foot group showed higher carbonylated protein levels (P = 0.0457) and lower levels of TAC (P = 0.0148) and reduced protein thiols (P = 0.0088), compared with the normal foot group. In general, several other parameters of risk of diabetes complication (blood levels of glycated hemoglobin, glucose and cholesterol, duration of diabetes, body mass index and waist circumference) showed a tendency of higher values in the diabetic foot group. The results suggest that the plasma levels of carbonylated proteins, TAC and reduced protein thiols could furnish information about the risk of diabetic foot, considering that the changes in these biomarkers were associated with the loss of sensitivity and foot ulcerations

Dexamethasone programs lower fatty acid absorption and reduced PPAR-γ and fat/CD36 expression in the jejunum of the adult rat offspring

The progeny of rats born and breastfed by mothers receiving dexamethasone (DEX) during pregnancy exhibits permanent reduction in body weight and adiposity but the precise mechanisms related to this programming are not fully understood. In order to clarify this issue, the present study investigated key aspects of lipoprotein production and lipid metabolism by the liver and the intestine that would explain the reduced adiposity seen in the adult offspring exposed to DEX in utero. Female Wistar rats were treated with DEX (0.1 mg/kg/day) between the 15th and the 21st days of pregnancy, while control mothers were treated with vehicle. Male offspring born to control mothers were nursed by either adoptive control mothers (CTL/CTL) or DEX-treated mothers (CTL/DEX). Male offspring born to DEX-treated mothers were nursed by either control mothers (DEX/CTL) or adoptive DEX-treated mothers (DEX/DEX). We found that only the male DEX/DEX offspring had reduced adiposity. Additionally, male DEX/DEX progeny had lower circulating triacylglycerol (TAG) levels only in fed-state. The four groups of offspring presented similar energy expenditure, respiratory quotient and very low-density lipoprotein (VLDL) production. On the other hand, DEX/DEX rats displayed reduced TAG levels after gavage with olive oil and reduced expression of fatty acid translocase Cd36 (Fat/Cd36) and peroxisome proliferator-activated receptor γ (Pparg) in the jejunum. Altogether, our study supports the notion that reduced fat absorption by the jejunum may contribute to the lower adiposity of the adult offspring born and breastfed by mothers treated with DEX during pregnancy265CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPnão temnão tem2013/07607-8; 2015/23285-6; 2016/13138-9; 2019/03196-0; 2019/19488-0; 2020/06397-