Are oxidative stress and ischemia significant causes of bladder damage leading to lower urinary tract dysfunction? Report from the ICI-RS 2019

Several studies indicate that pelvic ischemia and oxidative stress may play a significant role in lower urinary tract dysfunction (LUTD), including detrusor overactivity (DO)/overactive bladder (OAB) and detrusor underactivity (DU)/underactive bladder (UAB). The present article addresses proposal 1: “Are oxidative stress and ischemia significant causes of bladder damage leading to LUTD?” from the 2019 International Consultation on Incontinence—Research Society (ICI-RS) meeting. Bladder ischemia in animals and humans is briefly described, along with the proposed progression from ischemia to LUTD. Bladder ischemia is compared with ischemia of other organs, and the ongoing development of pelvic ischemia animal models is discussed. In addition, the distribution of blood within the bladder during filling and voiding and the challenges of quantification of blood flow in vivo are described. Furthermore, oxidative stress, including potential biomarkers and treatments, and challenges regarding antioxidant therapy for the treatment of LUTD are discussed. Finally, seven critical research questions and proposed studies to answer those questions were identified as priorities that would lead to major advances in the understanding and treatment of lower urinary tract symptoms (LUTS)/LUTD associated with pelvic ischemia and oxidative stress.     

Pregnancy in women with Fowler’s syndrome treated with sacral neuromodulation

Introduction and hypothesis

Our aim was to determine the impact of pregnancy on sacral neuromodulation (SNM) and vice versa in patients with Fowler’s syndrome (FS), which is typified by chronic urinary retention (CUR).

Methods

We performed a retrospective study of pregnancy in patients with FS who underwent a two-stage SNM implantation. Data were obtained using a standard questionnaire and clinical interview.

Results

There were a total of ten patients with 13 pregnancies. The SNM was switched off in ten of the 13 pregnancies, with CUR recurring in nine of the ten pregnancies and recurrent urinary tract infections (UTI) occurring in four of these pregnancies (more than three UTI in the pregnancy). Those in whom the device was left on continued to void normally. One woman had a first trimester miscarriage, eight pregnancies went to term, and four deliveries were premature. Caesarean section was performed in eight pregnancies for obstetric reasons. Four pregnancies resulted in a vaginal delivery. There were no congenital anomalies reported. Following delivery, four of nine women experienced dysfunction of their SNM device when it was switched back on.

Conclusion

Turing off the SNM during pregnancy results in recurrence of CUR, with an increased risk of recurrent UTI associated with preterm delivery. This did not impact foetal well-being. The option of keeping the SNM on during pregnancy should therefore be considered, and as caesarean section affects the SNM device, we advise that caesarean section should only be performed for obstetric reasons.     

Warfarin-induced leukocytoclastic vasculitis

Skin reactions associated with oral coumarin-derived anticoagulants are an uncommon occurrence. Leukocytoclastic vasculitis (LV) is primarily a cutaneous small vessel vasculitis, though systemic involvement may be encountered. We report 4 patients with late-onset LV probably due to warfarin. All 4 patients presented with skin eruptions that developed after receiving warfarin for several years. The results of skin lesion biopsies were available in 3 patients, confirming LV Cutaneous lesions resolved in all patients after warfarin was discontinued. In 2 of the 4 patients, rechallenge with warfarin led to recurrence of the lesions. LV may be a late-onset adverse reaction associated with warfarin therapy.     

Applications of Cu(0) encapsulated nanocatalysts as superior catalytic systems in Cu-catalyzed organic transformations

Recently, Cu nanoparticles (NPs) encapsulated into various materials as supports (e.g., zeolite, silica) have attracted much devotion due to their unique catalytic properties such as high catalytic activity, intensive reactivity and selectivity through highly protective properties. Nowadays, the superior catalytic activity of Cu-NPs, encapsulated onto zeolite, silica and different porous systems, is extensively investigated and now well-established. As a matter of fact, Cu-NPs are protected from deactivation by this kind of encapsulation. Thus, their exclusion proceeds smoothly, and their recyclability is significantly increased. Cu-NPs have been used as potential heterogeneous catalysts in different chemical transformations. In this review, we try to show the preparation and applications of Cu(0) encapsulated nanocatalysts in zeolite and silica as superior catalytic systems in Cu-catalyzed organic transformations. In addition, the catalytic activity of these encapsulated Cu-NPs in different important organic transformations (such as hydrogenation, oxidation and carbon–carbon bond formations) are compared with those of a variety of organic, inorganic and hybrid porous bearing a traded metal ion. Moreover, the results from the TGA/DTA analysis and optical properties of Cu-complexes are demonstrated. The inherited characteristic merits of the encapsulated Cu-NPs onto zeolite and silica, such as their low leaching, catalytic activity, reusability economic feasibility and originality are critically considered.

In this review, the catalytic activity of encapsulated Cu-NPs in different important organic transformations is compared with those of a variety of organic, inorganic and hybrid porous materials bearing a traded metal ion.     

Facile one-pot synthesis of NiCo2Se4-rGO on Ni foam for high performance hybrid supercapacitors

A facile, innovative synthesis for the fabrication of NiCo₂Se₄-rGO on a Ni foam nanocomposite via a simple hydrothermal reaction is proposed. The as-prepared NiCo₂Se₄-rGO@Ni foam electrode was tested through pxrd, TEM, SEM, and EDS to characterize the morphology and the purity of the material. The bimetallic electrode exhibited outstanding electrochemical performance with a high specific capacitance of 2038.55 F g⁻¹ at 1 A g⁻¹. NiCo₂Se₄-rGO@Ni foam exhibits an extensive cycling stability after 1000 cycles by retaining 90% of its initial capacity. A superior energy density of 67.01 W h kg⁻¹ along with a high power density of 903.61 W kg⁻¹ further proved the high performance of this electrode towards hybrid supercapacitors. The excellent electrochemical performance of NiCo₂Se₄-rGO@Ni foam can be explained through the high electrocatalytic activity of NiCo₂Se₄ in combination with reduced graphene oxide which increases conductivity and surface area of the electrode. This study proved that NiCo₂Se₄-rGO@Ni foam can be utilized as a high energy density-high power density electrode in energy storage applications.

A hybrid supercapacitor comprising a NiCo₂Se₄-rGO composite has been fabricated on Ni foam and shows high energy and power density and superior flexibility.     

Successful Treatment of Focal Segmental Glomerulosclerosis in Association with Mantle Cell Lymphoma

We have examined the role of reactive oxygen metabolites (ROM) in gentamicin nephrotoxicity and in glycerol-induced acute renal failure, a model for myoglobinuric acute renal failure. Several agents which affect mitochondrial respiration have been shown to enhance the generation of hydrogen peroxide. Based on gentamicin s ability to alter mitochondrial respiration both in vitro and in vivo we postulated that gentamicin may enhance the generation of ROM by renal com'cal mitochondria. Gentamicin, in a dose-dependent farhion, enhanced hydrogen peroxide production by rat renal cortical mitochondria as measured by the decrease in scopoletin jluorescence. At the highest concentration of gentamicin tested (4.0 mM), the rate of hydrogen peroxide generation w s markedly increased from 0. I7 f 0.02 to 6.21 f 0.67 nmol/mg/m*n. We next demonstrated that hydroxyl radical scavengers and an iron chelator provide a marked functional and histological protection in gentamicin-induced acute renal failure in rats. Hydroxyl radical scavengers and the iron chelator deferoxamine also protected renal function in glycerol-injected rats, a model for acute renal failure due to muscle injury. Although these data suggest that ROM may be important mediators of toxic renal injury, in vivo generation of ROM by kidney in normal and pathological states has not been previously examined. Aminotriazole (An irreversibly inactivates catalase only in the presence of hydrogen peroxide and previous studies have shown that AT-medated inhibition of catalase in a sensitive measure of in vivo changes in the hydrogen peroxide generation. Using this method, we have demonstrated the in vivo generation of hydrogen peroxide under normal conditions and enhanced generation of hydrogen peroxide in rats treated with gentamicin or glycerol. Finally, in in vitro studies we have shown that iron and intracellular calcium play a critical role in hydrogen peroxide-mediated cytotoxicity to LLC-PK, cells, a renal tubular epithelial cell line. Taken together our data provide evidence for a role of ROM in gentamicin and glycerol-induced acute renal failure and provide evidence for the role of iron and calcium in oxidant injury to renal tubular epithelial cells.     

Anti-CD52 blocks EAE independent of PD-1 signals and promotes repopulation dominated by double-negative T cells and newly generated T and B cells

Lymphocyte depletion using anti-CD52 antibody effectively reduces relapses of multiple sclerosis (MS). To begin to understand what mechanisms might control this outcome, we examined the effect of a murine-CD52-specific mAb on the depletion and repopulation of immune cells in mice with experimental autoimmune encephalomyelitis (EAE), a model of MS. We tested whether the tolerance-promoting receptor programmed cell death protein-1 (PD-1) is required for disease remission post anti-CD52, and found that PD-1-deficient mice with a more severe EAE were nevertheless effectively treated with anti-CD52. Anti-CD52 increased the proportions of newly generated T cells and double-negative (DN) T cells while reducing newly generated B cells; the latter effect being associated with a higher expression of CD52 by these cells. In the longer term, anti-CD52 caused substantial increases in the proportion of newly generated lymphocytes and DN T cells in mice with EAE. Thus, the rapid repopulation of lymphocytes from central lymphoid organs post anti-CD52 may limit further disease. Furthermore, these data identify DN T cells, a subset with immunoregulatory potential, as a significant hyperrepopulating subset following CD52-mediated depletion.