Age-related changes in voiding function might not be a result of impaired detrusor contractility or increased outflow obstruction, intrinsic causes must be suspected. Changes in the storage function of the bladder represent specific pathophysiological mechanisms influenced by aging.

Purpose: To describe our experience in the management of retained encrusted ureteral stents using a single session combined endourological approach. Materials and Methods: Patients with retained encrusted ureteral stents who had been submitted to a single session combined endourological approach from June 2010 to June 2018 were prospectively evaluated. Patients were divided according to the Forgotten-Encrusted-Calcified (FECal) classification. The stone burden, surgical intervention, number of interventions until stone free status, operation time, hospital stay, complications, stone analysis, and stone-free rate were compared between groups. ANOVA was used to compare numerical variables, and the Mann-Whitney or Chi-square test to compare categorical variables between groups. Results: We evaluated 50 patients with a mean follow-up of 2.9±1.4 years (mean±SD). The groups were comparable in terms of age, sex, laterality, BMI, comorbidities, ASA, reason for stent passage, and indwelling time. The stone burden was higher for grades IV and V (p=0.027). Percutaneous nephrolithotomy was the most common procedure (p=0.004) for grades IV and V. The number of procedures until the patients were stonefree was 1.92±1.40, and the hospital stay (4.2±2.5 days), complications (22%), and stone analysis (66% calcium oxalate) were similar between groups. The stone-free rate was lower in grades III to V (60%, 54.5%, and 50%). Conclusions: The endoscopic combined approach in the supine position is a safe and feasible technique that allows removal of retained and encrusted stents in a single procedure. The FECal classification seems to be useful for surgical planning.

Background Pulmonary arterial hypertension (PAH) is a disease characterized by pulmonary vascular remodeling with subsequent right ventricular (RV) failure. This work investigated the effects of a new p38-alpha mitogen-activated protein kinase (p38-α MAPK) inhibitor, named LASSBio-1824, on PAH model in rats. Methods All experiments were in accordance with the Animal Care and Use Committee at our university (039/19). Male Wistar rats was exposed to hypoxia (10% O2) during 3 weeks plus i.p. injection of an antagonist of vascular endothelial growth factor receptor (SU5416; 20 mg/kg/week) to induce PAH. Control rats were kept in normoxia (21% O2). After 21 days of protocol, echocardiography images confirmed PAH using the pulmonary artery (PA) outflow waveform. After disease onset, animals were randomly divided into three groups: control + vehicle (DMSO), HAP + vehicle and HAP + LASSBio-1824 (50 mg/kg/day). Vehicle and LASSBio-1824 were administered by oral gavage during two weeks. Results Pulmonary acceleration time (PAT; ms) was reduced from 33.2±2.7 (control) to 22.7±1.1 in PAH + vehicle group (p<0.05) and restored to 29.6±1.9 after treatment with LASSBio-1824 (p<0.05). RV afterload was detected in HAP group because of the increase of systolic pressure (mmHg) from 22.2±1.5 (control) to 47.2±3.6 (p<0.05) and reduced to 18.0±2.9 with LASSBio-1824. Medial wall thickness (%) of distal PA (<50 μm) was measured by using immunohistochemistry for alpha smooth muscle actin (α-SMA) which was increased from 62.5±5.6 (control) to 78.0±7.9 in PAH group (p<0.05), but it was significantly reduced to 54.4±2.3 in PAH + LASSBio-1824 group (p<0.05). Vascular reactivity was evaluated comparing the acetylcholine (ACh)-induced maximal relaxation (%) in PA from normal and PAH rats, which was reduced from 67.5±2.1 to 49.63±5.6 (PAH group; p<0.05). Therefore, the treatment with the p38 inhibitor normalized the ACh-induced response to 73.7±4.1%. The immunohistochemistry for c-fos protein, a product of the p38 pathway related to cell proliferation, showed an increased ratio of stained and total myocyte nuclei (%) in PAH animals of 38.0±0.5 compared to normal group of 20.2±4.2. LASSBio-1824 significantly reduced ratio to 24.0±2.3% (p<0.05). PAH increased inflammatory condition because the expression of inducible nitric oxide synthase increased from 0.31±0.01 (control) to 0.57±0.02 and it was recovered by the treatment with LASSBio-1824 to 0.31±0.10 (p<0.05). Conclusion LASSBio-1824, an inhibitor of p38-alpha MAPK represents an important approach for the future treatment of PAH which improves the underlying remodeling and inflammation processes in the cardiopulmonary system. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES; Conselho Nacional de Desenvolvimento Científico e Tecnolόgico - CNPq

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Introduction: Prevention of cardiac remodeling induced by myocardial infarction (MI) is of great importance because it is one of the factors for the development of heart failure (HF). Thus, LASSBio-1027 was tested in acute model of MI due to its vasodilatory and anti-proliferative profile through the activation of adenosine A 2A and A 3 receptors.Methods: Protocols were approved by Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. MI was induced in male Wistar rats (180-200 g) which were subjected to ligation of the anterior descending coronary artery under isoflorane anesthesia (3% v/v). Animals were randomly divided into groups treated orally (gavage) with either vehicle or LASSBio-1027 (30 and 70 umol/kg) for 7 days. All groups underwent echocardiographic analysis and anterior wall thickness (AWTd) during diastole; mitral flow using the ratio between early transmitral filling velocity (E) and tissue doppler (e , ) were determined. The border of infarcted area was used to evaluate interstitial cells and expression of alpha-SMA. Expression of TNF-alpha, SERCA2, p-ERK-1/2 and ERK-1/2 were also investigated. Results: MI reduced AWTd from 1.24 ± 0.17 to 0.42 ± 0.02 mm (P<0.01) which was recovered after treatment with LASSBio-1027. Mitral flow was increased from 22.9 ± 1.6 to 37.0 ± 3.6 (P<0.01) after experimental MI and reduced with LASSBio-1027. The ejection fraction in MI group was 36.6 ± 2.0% which was increased to 46.99 ± 7.40% after treatment (P<0.05). An increase of collagen deposition was observed in MI group of 33.35 ± 5.74% and treatment with LASSBio-1027 (70 µmol/kg) reduced to 14.50 ± 0.32% (P<0.05). LASSBio-1027 reduced interstitial cells from 275.5 ± 49.13 (MI group) to 110.1 ±17.09 (P<0.05). It was observed an increased alpha-SMA expression in the MI group with 36.83 ± 2.89% and a reduction after treatment with LASSBio-1027, 6.28 ± 4.12% and 14.01 ± 4.31%, for 30 and 70 µmol/kg. MI increased the expression of TNF-alpha, p-ERK1-2/ERK1-2 and SERCA2 in comparison to Sham. LASSBio-1027 at 30 μmol/kg recovered the expression of all proteins to control values. Conclusion: LASSBio-1027 prevented the development of HF by improving cardiac remodeling after acute MI.

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