Redox Regulation of Heart Regeneration: An Evolutionary Tradeoff

Heart failure is a costly and deadly disease, affecting over 23 million patients worldwide, half of which die within 5 years of diagnosis. The pathophysiological basis of heart failure is the inability of the adult heart to regenerate lost or damaged myocardium. Although limited myocyte turnover does occur in the adult heart, it is insufficient for restoration of contractile function1-6. In contrast to lower vertebrates which can regenerate their myocardium through cardiomyocyte proliferation,7-13, adult mammalian heart cardiomyogenesis very limited1-5. Studies in the late 90s elegantly demonstrated that mammalian cardiomyocytes continue to divide for a few days after birth 14-16, only to undergo permanent cell cycle arrest shortly thereafter. Recently, we demonstrated that resection of up to 15% of the apex of the left ventricle of postnatal day 1 (P1) mice results in complete regeneration within 21 days following injury, without significant fibrosis and cardiac dysfunction17. Moreover, we described a similar regenerative response following ischemic myocardial infarction 18. This response was well characterized by robust cardiomyocyte proliferation, with gradual restoration of normal cardiac morphology and function. In addition to the histological evidence of proliferating myocytes, genetic fate-mapping studies confirmed that the majority of newly formed cardiomyocytes are derived from proliferation of preexisting cardiomyocytes17. Intriguingly, this regenerative capacity is lost by P7, after which injury results in the cardiomyocyte hypertrophy and scar-formation, which coincides with binucleation and cell cycle exit of cardiomyocytes 14, 19. An important approach to understanding the loss of regenerative ability of the mammalian heart is to first consider why, and not only how, this happens. The regenerative ability of the early postnatal heart following resection or ischemic infarction involves regeneration of the lost myocardium and vasculature with restoration of normal myocardial thickness and architecture, and long-term functional recovery. Why would the heart permanently forego such a remarkable regenerative program shortly after birth? The answer may lie in within the fundamental principal of evolutionary tradeoff

The use of urodynamic to assess the mechanism of incontinence in patients with Yang-Monti based catheterizable cutaneous stomas

Objective: To analyze the static and dynamic urodynamic parameters of reservoirs and continent conduits in continent cutaneous urinary diversion with catheterizable stoma. Materials and methods: 76 patients had augmented ileocystoplasty or continent urinary diversion with catheterizable urinary stoma based on Mitrofanoff principle and Yang-Monti procedure using subserous tunnel as continence mechanism. They were followed up for at least 6 months post-operatively for continence through stoma and divided into two groups (continents vs non-continent) according to stomal continence. Both groups had urodynamic assessment performed via the stoma to assess reservoir capacity, pressure and contractions, efferent limb functional length, reservoir overactivity, static and dynamic maximal closure pressures and leak point pressure. Results: Continence rate was 87%. Continent group included 66 patients and incontinent group included 10 patients. In both groups at rest, the reservoir pressure after filling did not exceed 25 cm H2O. During peristaltic contraction, the pressure did not exceed 30 cm H2O and the duct remained continent. After Valsalva maneuver, the reservoir pressure increased up to 34 (+ 7.4) cm H2O and leakage occur in 10 patients (13%). Reservoir (wall) overactivity was recorded in 54 patients, with insignificant rise in intraluminal pressure during the contractions. In both groups, the efferent tract closing pressure was always higher than the reservoir pressure. The mean of maximal closing pressure at Valsalva was 82.5 (+ 4.18) cm H2O in the continent group and 61.66 (+ 8.16) cm H2O in the incontinent group. The mean functional length of the conduit was 4.95 + 1.62 in the continent group and 2.80 + 1.50 cm in the incontinent group. Conclusions: Urodynamic evaluation of continent catheterizable cutaneous stoma after Yang-Monti procedure has a practical significance. Functional length of the conduit seems to be the most influential factor for continence reflecting static & dynamic maximal closure pressure. Higher conduit closing pressure is associated with better continence. Contractions of the pouch and peristaltic contraction of the conduit has no effect on continence mechanism

Effect of preoperative ureteral stenting on the surgical outcomes of patients with 1-2 cm renal stones managed by retrograde intrarenal surgery using a ureteral access sheath

Objective: To assess the surgical results of patients who underwent retrograde intrarenal surgery (RIRS) using a ureteral access sheath (UAS) for management of renal stones sized 1-2 cm compared between patients who did and did not undergo preoperative ureteral stenting. Materials and methods: This prospective study included 83 patients (aged ≥ 20 years) who underwent RIRS from July 2021 to January 2023. All patients had renal calculi (stone size: 1-2 cm) located within the pelvicalyceal system. 43 and 40 patients were allocated to the non-prestent (group A) and prestent (group B), respectively. Patient baseline characteristics, renal stone details, operative data, stone-free rate (SFR) at 4 weeks and 6 months, and perioperative complications were compared between groups. Results: The baseline characteristics of all patients were comparable across the groups. Four weeks after surgery, the overall stone-free rate (SFR) stood at 62.65%. In the non-prestent and prestent groups, the SFRs were 58.12% and 67.5%, respectively (p = 0.89). By the sixth month post-surgery, the overall SFR rose to 80.72%. In the non-prestent and prestent groups, the SFRs were 76.74% and 85%, respectively (p = 0.081). No notable differences emerged in other variables, including perioperative complications, between the two groups. Conclusions: The SFR showed no significant difference between the prestenting and non-prestenting groups at the 4-week and 6-month postoperative marks. Additionally, there were no substantial differences in complications during surgery and recovery between the groups. Notably, the SFR increased from 4 weeks to 6 months without any additional procedures in either group

A calcineurin–Hoxb13 axis regulates growth mode of mammalian cardiomyocytes

10.1038/s41586-020-2228-6Nature5827811271-27

Urethral advancement and glanuloplasty versus tubularized incised plate urethroplasty for distal hypospadias repair: a prospective randomized study

Abstract Background About one in 200 to one in 300 male births has hypospadias. The prevalence of this congenital anomaly varies worldwide. The meatus is located distally in approximately 70% of cases. Several surgical techniques were described for distal hypospadias repair; despite this, there is no ideal approach. This study compares urethral advancement &glanuloplasty, and TIP techniques in terms of feasibility, duration of operation, and complications. Patients and. Methods This prospective randomized comparative study was conducted at Al-Azhar University Hospitals from April 2022 to October 2022. Fifty-seven cases with different types of hypospadias were assessed for eligibility. Among them, seven cases were excluded due to the presence of severe chordee (n = 3), proximal variant (n = 2), and recurrent cases of hypospadias (n = 2). Fifty cases were randomly divided into two groups using a 1:1 ratio (computer-generated randomization). Twenty-five cases were subjected to urethral advancement and glanuloplasty, and the rest were subjected to tubularized incised plate (TIP) urethroplasty. Results The mean age of all studied cases was 4.2 years. Approximately 52% had coronal or sub-coronal meatus, whereas 48% had glandular meatus. Both groups were matched according to age and meatus location (p > 0.05). No statistically significant difference was observed between the two groups regarding duration of operation, postoperative pain, and postoperative hospital stay. In addition, both groups did not differ significantly in late complications (meatal stenosis, meatal retraction, fistula, and glans dehiscence). Conclusions Both urethral advancement &glanuloplasty, and TIP urethroplasty have comparable short-term outcomes. Urethral advancement and glanuloplasty is preferred in certain conditions, especially in circumcised children or those with a narrow urethral plate. Trial registration The study protocol was approved by the Pan African Clinical Trials Registry (number for the registry is: PACTR202211757905870) on (29/11/2022). All procedures were performed per the Helsinki Declaration

Protective effects of hesperidin and diosmin against acrylamide-induced liver, kidney, and brain oxidative damage in rats

International audienceAcrylamide (AA) is a heat-induced toxin formed during thermal processing of many commonly consumed foods, including meat products, French fries, potato crisps, bread, cereals, cookies, and coffee. There is thus potentially high dietary exposure of humans to AA, which can induce significant oxidative stress. Hesperidin (HS) and diosmin (DS) are flavone glycosides that have antioxidant properties. The aim of this study was to investigate the protective effects of HS and DS against AA toxicity. Fifty-six adult male Wistar albino rats were divided into seven groups. The first group was orally administered 0.5% (w/v) dimethyl sulfoxide (DMSO) and considered as the control group. The second and third groups were orally administered 10 mg/kg/day of HS or DS, respectively. The fourth group received 20 mg/kg/day of AA orally for 14 days. The fifth and sixth groups were given 10 mg/kg/day of HS or DS, respectively, followed by AA. The seventh group was given both HS and DS after AA administration. AA intoxication significantly (p ≤ 0.05) increased serum levels of liver function enzymes (ALT, AST, and ALP), kidney function products (urea and creatinine), oxidative DNA damage marker (OHdG), proinflammatory markers (TNF-α, IL-1β, and IL-6), lipid peroxidation marker (malondialdehyde), and nitric oxide (NO). On the other hand, it significantly (p ≤ 0.05) decreased levels of reduced glutathione (GSH) in the liver, kidney, and brain. The activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) in the liver, kidney, and brain tissues were also reduced. HS and DS supplementation prevented lipid peroxidation, normalized the serum parameters altered by AA, and enhanced the tissue concentrations and activities of antioxidant biomarkers. It could be concluded that HS and DS have potent protective effects against oxidative stress, lipid peroxidation, and DNA damage induced by AA toxicity in rats

RETRACTION: Effect of preoperative ureteral stenting on the surgical outcomes of patients with 1-2 cm renal stones managed by retrograde intrarenal surgery using a ureteral access sheath

This retracts the article “Effect of preoperative ureteral stenting on the surgical outcomes of patients with 1-2 cm renal stones managed by retrograde intrarenal surgery using a ureteral access sheath”  (https://doi.org/10.4081/aiua.2023.12102) published on December 28, 2023