Adsorption of plasma protein decreases urinary protein excretion in patients with recurrence of the nephrotic syndrome after renal transplantation. Studies of the adsorbed proteins should provide information about the mechanism of this disease.
Septic shock is a systemic inflammation associated with cell metabolism disorders and cardiovascular dysfunction. Increases in O-GlcNAcylation have shown beneficial cardiovascular effects in acute pathologies. We used two different rat models to evaluate the beneficial effects of O-GlcNAc stimulation at the early phase of septic shock. Rats received lipopolysaccharide (LPS) to induce endotoxemic shock or saline (control) and fluid resuscitation (R) with or without O-GlcNAc stimulation (NButGT–10 mg/kg) 1 hour after shock induction. For the second model, rats received cecal ligature and puncture (CLP) surgery and fluid therapy with or without NButGT. Cardiovascular function was evaluated and heart and blood samples were collected and analysed. NButGT treatment efficiently increased total O-GlcNAc without modification of HBP enzyme expression.Treatment improved circulating parameters and cardiovascular function in both models, and restored SERCA2a expression levels. NButGT treatment also reduced animal mortality. In this study, we demonstrate that in septic shock O-GlcNAc stimulation improves global animal and cardiovascular function outcomes associated with a restoration of SERCA2a levels. This pre-clinical study opens avenues for a potential therapy of early-stage septic shock.
Singlet oxygen (1O2) is produced by leucocytes during inflammatory reactions, various biochemical reactions and during photoreactions. It deactivates by reacting with a number of targets to produce reactive oxygen species (ROS) and peroxides (that in turn produce ROS). To verify whether serum had the same capability to deactivate secondary oxidants after exposure to 1O2, we provoked a photoreaction using rose bengal added to sera of 53 healthy donors and, after light delivery, reduced 2',7'-dichlorofluorescein (DCFH) was added at the end of irradiation and fluorescence of the oxidized derivative (DCF) was recorded. To avoid optical artifacts, we analyzed the influence of hemolysis. Deactivation capability of secondary oxidants after exposure to (1)O(2) was stable over a long period of time, slightly different between men and women, but standard biochemistry parameters had little influence. Hemolysis, age and platelet number reduced deactivation of 1O2-induced secondary oxidants. Addition of lysed cancer cells had no influence. Blood sampling in clot act tubes gave a better signal than in heparinized tubes. Red blood cells (RBCs) loaded with antioxidants strongly decreased deactivation of secondary oxidants. Assays are in progress to evaluate the clinical implications of these findings.
Objective:
Male sex is a determinant of severe coronavirus disease-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19.
Methods:
We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation [IMV], death, intensive care unit [ICU] admission and home discharge at day 7 [D7] or day 28 [D28]) in 2,380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736).
Results:
The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR 0.66 [0.49-0.88]), death (OR 0.49 [0.30-0.79]) and ICU admission (OR 0.57 [0.43-0.77]) at D7, but only with ICU admission (OR 0.58 [0.43-0.77]) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, CRP, AST and eGFR predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only.
Conclusions:
In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.
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