CNC. IBILI

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Crescent-like lesions as an early signature of nephropathy in a rat model of prediabetes induced by a hypercaloric diet

Publication . Nunes, Sara; Alves, André; Preguiça, Inês; Barbosa, Adelaide; Vieira, Pedro; Mendes, Fernando; Martins, Diana; Viana, Sofia; Reis, Flávio

Diabetic nephropathy (DN) is a major microvascular complication of diabetes. Obesity and hyperlipidemia, fueled by unhealthy food habits, are risk factors to glomerular filtration rate (GFR) decline and DN progression. Several studies recommend that diabetic patients should be screened early (in prediabetes) for kidney disease, in order to prevent advanced stages, for whom the current interventions are clearly inefficient. This ambition greatly depends on the existence of accurate early biomarkers and novel molecular targets, which only may arise with a more thorough knowledge of disease pathophysiology. We used a rat model of prediabetes induced by 23 weeks of high-sugar/high-fat (HSuHF) diet to characterize the phenotype of early renal dysfunction and injury. When compared with the control animals, HSuHF-treated rats displayed a metabolic phenotype compatible with obese prediabetes, displaying impaired glucose tolerance and insulin sensitivity, along with hypertriglyceridemia, and lipid peroxidation. Despite unchanged creatinine levels, the prediabetic animals presented glomerular crescent-like lesions, accompanied by increased kidney Oil-Red-O staining, triglycerides content and mRNA expression of IL-6 and iNOS. This model of HSuHF-induced prediabetes can be a useful tool to study early features of DN, namely crescent-like lesions, an early signature that deserves in-depth elucidation.

2020-03-25Journal article

Open access

FORSCells: 40-days fixed prepared reagent for detection of anti-Forssman in humans

Publication . Ferreira, Sofia; Mourato, Cristiana; Corpuz, Alyssa; Galvão, Sofia; Hesse, Camilla; Rocha, Clara; Jesus, Carlos; Mendes, Fernando, 1973-

In 2012, the FORS system was accepted by the International Society of Blood Transfusion as the 31st blood group system. Forssman (Fs) antigen (Ag) expression is most commonly found on sheep red blood cells (RBC) but rare in human RBC. Anti-Fs antibodies (Ab) are naturally occurring in human sera and are predominantly IgM but they can also be IgG. To this day, the global prevalence of the FORS system is unknown. Currently, there is a lack of natural FORS1-positive RBC available to use for anti-Fs screening in large populations. This study was designed to produce FORS1-positive cells viable for 40 days use in the anti-Fs screening. Three to 5% FORS1-positive cells were produced using sheep's blood and CellStab stabilizer solution. The quality of the FORS1-positive cells was investigated in more than three independent experiments of ABO titration, osmotic fragility test and supernatant haemolysis. For each batch of FORS1-positive cells produced, an extended antibody panel was performed. To demonstrate that the FORS1-positive cells can be used for up to 40 days, anti-Fs screening and classification were carried out in a patient and donor population. Antigenic expression and membrane integrity of FORS1-positive cells remained stable for 40 days. Good FORS1 Ag preservation was established, and minimal haemolysis was observed. In conclusion, a novel and easy-to-produce reagent has been developed and submitted to a patent with stable FORS1 Ag expression. With this FORS1-positive cell suspension, it is now possible to screen and classify anti-Fs Ab in large populations.

2019-12-06Journal article

Open access