SummaryOedema factor (OF) and protective antigen (PA) are secreted by Bacillus anthracis , and their binary combination yields oedema toxin (OT). Following PAmediated delivery to the cytosol, OF functions as an adenylate cyclase generating high levels of cAMP. To assess OT as a possible cause of tissue damage and cell death, a novel approach was developed, which utilized a developing zebrafish embryo model to study toxin activity. Zebrafish embryos incubated with OT exhibited marked necrosis of the liver, cranium and gastrointestinal tract, as well as reduced swim bladder inflation. The OT-treated embryos survived after all stages of development but succumbed to the toxin within 7 days. Additional analysis of specific cell lines, including macrophage and non-macrophage, showed OT-induced cell death is cell type-specific. There was no discernible correlation between levels of OF-generated cAMP and cell death. Depending on the type of cell analysed, cell death could be detected in low levels of cAMP, and, conversely, cell survival was observed in one cell line in which high levels of cAMP were found following treatment with OT. Collectively, these data suggest OT is cytotoxic in a celldependent manner and may contribute to disease through direct cell killing leading to tissue necrosis.
Background:
Young adults with congenital heart disease (CHD) are increasing in number with an increased risk for acute kidney injury. Little is known concerning the impact of non-recovery of kidney function for these patients. Therefore, we sought to explore the rates of acute kidney disease, persistent renal dysfunction, and their associations with adverse outcomes in young adults with CHD.
Methods:
This is a single-centre retrospective study including all patients at the ages of 18–40 with CHD who were admitted to an intensive care unit between 2010 and 2014. Patients with a creatinine ≥ 1.5 times the baseline at the time of hospital discharge were deemed to have persistent renal dysfunction, while acute kidney disease was defined as a creatinine ≥ 1.5 times the baseline 7–28 days after a diagnosis of acute kidney injury. Outcomes of death at 5 years and length of hospital stay were examined using multivariable logistic regression and negative binomial regression, respectively.
Results:
Of the (89/195) 45.6% of patients with acute kidney injury, 33.7% had persistent renal dysfunction and 23.6% met the criteria for acute kidney disease. Persistent renal dysfunction [odds ratio (OR), 3.27; 95% confidence interval (CI): 1.15–9.29] and acute kidney disease (OR: 11.79; 95% CI: 3.75–39.09) were independently associated with mortality at 5 years. Persistent renal dysfunction was associated with a longer duration of hospital stay (Incidence Rate Ratio: 1.96; 95% CI: 1.53–2.51).
Conclusions:
In young adults with CHD, acute kidney injury was common and persistent renal dysfunction, as well as acute kidney disease, were associated with increased mortality and length of hospitalisation.
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