Polyphenols present in some alcoholic beverages have been linked to beneficial effects in preventing cardiovascular diseases. Polyphenols found in beer with anti-proliferative and anti-cancer properties are appealing in the context of the quasi-malignant phenotype of pulmonary arterial hypertension (PAH). Our purpose was to evaluate if the chronic ingestion of a xanthohumol-fortified beer (FB) would be able to modulate the pathophysiology of experimental PAH. Male Wistar rats with monocrotaline (MCT)-induced PAH (60 mg/kg) were allowed to drink either xanthohumol-fortified beer (MCT + FB) or 5.2% ethanol (MCT + SHAM) for a period 4 weeks. At the end of the protocol, cardiopulmonary exercise testing and hemodynamic recordings were performed, followed by sample collection for further analysis. FB intake resulted in a significant attenuation of the pulmonary vascular remodeling in MCT + FB animals. This improvement was paralleled with the downregulation in expression of proteins responsible for proliferation (ERK1/2), cell viability (AKT), and apoptosis (BCL-XL). Moreover, MCT + FB animals presented improved right ventricle (RV) function and remodeling accompanied by VEGFR-2 pathway downregulation. The present study demonstrates that a regular consumption of xanthohumol through FB modulates major remodeling pathways activated in experimental PAH.
Purpose
To evaluate the effectiveness and safety of nonpapillary prone endoscopic combined intrarenal surgery (ECIRS) and provide practical tips and tricks for the successful accomplishment of the procedure respecting the anatomical particularities.
Material and methods
This study is an analysis of a prospectively collected database including all cases of ECIRS performed between January 2019 and December 2021 in a high-volume tertiary center. All patients underwent the procedure in prone-split leg position. A nonpapillary renal puncture was performed. The used access sheaths were 22Fr or 30Fr. Lithotripsy was performed anterogradely with a dual-energy lithotripter with incorporated suction and retrogradely with holmium Yttrium–Aluminum–Garnet laser.
Results
A total of 33 patients were included. The initial stone-free rate (SFR) was 84.8% and the final SFR was 90.9%. The median stone size was 35 mm and 60% of patients had staghorn calculi. The prevalence of renal abnormalities was 21.3%, including 3 cases of horseshoe kidney, 2 cases of malrotation and 2 cases with complete duplicated systems. The median operative time was 47 min. The median hospital stay was 3 days and median hemoglobin loss was 1.2 gr/dL. Overall, the complication rate was 9.1%, all being Grade II complications (n = 2 fever and n = 1 transient bleeding).
Conclusions
Nonpapillary prone ECIRS is an effective and safe procedure. Standardization of the procedure is critical to achieve good outcomes. Patients who benefit the most are probably the ones where additional punctures can be avoided using this technique, namely patients with renal abnormalities, incrusted ureteral stents and staghorn stones.
The angiotensin type 2 receptor, AT2R, has been described as having opposite effects to the angiotensin type 1 receptor, AT1R. Although the quantities of the AT2R found in the adult are low, its expression rises in pathological situations. The AT2R has three major signaling pathways: activation of serine/threonine phosphatases (promoting apoptosis and antioxidant effects), activation of the bradykinin/NO/cGMP pathway (promoting vasodilation), and activation of phospholipase A2 (associated with regulation of potassium currents). The AT2R appears to have effects in vascular remodeling, atherosclerosis prevention and blood pressure lowering (when associated with an AT1R inhibitor). After myocardial infarction, the AT2R appears to decrease infarct size, cardiac hypertrophy and fibrosis, and to improve cardiac function. However, its role in the heart is controversial. In the kidney, the AT2R promotes natriuresis. Until now, treatment directed at the renin-angiotensin-aldosterone system has been based on angiotensin-converting enzyme inhibitors or angiotensin type 1 receptor blockers. The study of the AT2R has been revolutionized by the discovery of a direct agonist, C21, which promises to become part of the treatment of cardiovascular disease.
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