BACKGROUND AND PURPOSEStrategies designed to enhance cerebral cAMP have been proposed as symptomatic treatments to counteract cognitive deficits. However, pharmacological therapies aimed at reducing PDE4, the main class of cAMP catabolizing enzymes in the brain, produce severe emetic side effects. We have recently synthesized a 3-cyclopentyloxy-4-methoxybenzaldehyde derivative, structurally related to rolipram, and endowed with selective PDE4D inhibitory activity. The aim of the present study was to investigate the effect of the new drug, namely GEBR-7b, on memory performance, nausea, hippocampal cAMP and amyloid-b (Ab) levels. EXPERIMENTAL APPROACHTo measure memory performance, we performed object recognition tests on rats and mice treated with GEBR-7b or rolipram. The emetic potential of the drug, again compared with rolipram, was evaluated in rats using the taste reactivity test and in mice using the xylazine/ketamine anaesthesia test. Extracellular hippocampal cAMP was evaluated by intracerebral microdialysis in freely moving rats. Levels of soluble Ab peptides were measured in hippocampal tissues and cultured N2a cells by ELISA. KEY RESULTSGEBR-7b increased hippocampal cAMP, did not influence Ab levels and improved spatial, as well as object memory performance in the object recognition tests. The effect of GEBR-7b on memory was 3 to 10 times more potent than that of rolipram, and its effective doses had no effect on surrogate measures of emesis in rodents. CONCLUSION AND IMPLICATIONSOur results demonstrate that GEBR-7b enhances memory functions at doses that do not cause emesis-like behaviour in rodents, thus offering a promising pharmacological perspective for the treatment of memory impairment.

Background Peritoneal dialysis (PD) is still widely used for acute renal failure (ARF) in developing countries despite concerns about its inadequacy. Continuous PD has been evaluated in ARF by analyzing the resolution of metabolic abnormality and normalization of plasma pH, bicarbonate, and potassium. Methodology A prospective study was performed on 30 ARF patients who were assigned to high-dose continuous PD (Kt/V = 0.65 per session) via a flexible catheter (Tenckhoff) and automated PD with a cycler. Fluid removal, pH and metabolic control, protein loss, and patient outcome were evaluated. Results Patients received 236 continuous PD sessions; 76% were admitted to ICUs. APACHE II score was 32.2 ± 8.65. BUN concentrations stabilized after 3 sessions, creatinine after 4, and bicarbonate and pH after 2. Fluid removal was 2.1 ± 0.62 L/day. Creatinine and urea clearances were 15.8 ± 4.16 and 17.3 ± 5.01 mL/minute respectively. Normalized creatinine clearance and urea Kt/V values were 110.6 ± 22.5 L/week/1.73 m2 body surface area and 3.8 ± 0.6 respectively. Solute reduction index was 41% ± 6.5% per session. Serum albumin values remained stable in spite of considerable protein losses (median 21.7 g/day, interquartile range 9.1 – 29.8 g/day). Regarding ARF outcome, 23% of patients presented renal function recovery, 13% remained on dialysis after 30 days of follow-up, and 57% died. Conclusion High-dose continuous PD by flexible catheter and cycler was an effective treatment for ARF. It provided high solute removal, allowing appropriate metabolic and pH control, and adequate dialysis dose and fluid removal. Continuous PD can therefore be considered an alternative to other forms of renal replacement therapy in ARF.

Renal involvement is frequent in COVID-19 (4–37%). This study evaluated the incidence and risk factors of acute kidney injury (AKI) in hospitalized patients with COVID-19.Methodology: This study represents a prospective cohort in a public and tertiary university hospital in São Paulo, Brazil, during the first 90 days of the COVID-19 pandemic, with patients followed up until the clinical outcome (discharge or death).Results: There were 101 patients hospitalized with COVID-19, of which 51.9% were admitted to the intensive care unit (ICU). The overall AKI incidence was 50%; 36.8% had hematuria or proteinuria (66.6% of those with AKI), 10.2% had rhabdomyolysis, and mortality was 36.6%. Of the ICU patients, AKI occurred in 77.3% and the mortality was 65.4%. The mean time for the AKI diagnosis was 6 ± 2 days, and Kidney Disease Improving Global Outcomes (KDIGO) stage 3 AKI was the most frequent (58.9%). Acute renal replacement therapy was indicated in 61.5% of patients. The factors associated with AKI were obesity [odds ratio (OR) 1.98, 95% confidence interval (CI) 1.04–2.76, p < 0.05] and the APACHE II score (OR 1.97, 95% CI 1.08–2.64, p < 0.05). Mortality was higher in the elderly (OR 1.03, 95% CI 1.01–1.66, p < 0.05), in those with the highest APACHE II score (OR 1.08, 95% CI 1.02–1.98, p < 0.05), and in the presence of KDIGO stage 3 AKI (OR 1.11, 95% CI 1.05–2.57, p < 0.05).Conclusion: AKI associated with severe COVID-19 in this Brazilian cohort was more frequent than Chinese, European, and North American data, and the risk factors associated with its development were obesity and higher APACHE II scores. Mortality was high, mainly in elderly patients, in those with a more severe disease manifestation, and in those who developed KDIGO stage 3 AKI.

To our knowledge, this report was the first available study of the equipment and human resources utilized for RRT in AKI patients in Latin America.

Objective: To compare the clinical features and outcomes of patients with and without acute kidney injury in an intensive care unit of a tertiary university hospital and to identify acute kidney injury and mortality risk factors. Methods: This was a prospective observational study of a cohort including 564 patients followed during their stay in the intensive care unit of Hospital das Clinicas da Faculdade de Medicina de Botucatu (Botucatu, São Paulo, Brazil) between May 2008 and May 2010. Patients were allocated to two different groups: with (G1) and without (G2) acute kidney injury. Results: The incidence of acute kidney injury was 25.5%. The groups were different with respect to the reason for admission to the intensive care unit (