Targeting NADPH Oxidase as an Approach for Diabetic Bladder Dysfunction.

Diabetic bladder dysfunction (DBD) is the most prevalent complication of diabetes mellitus (DM), affecting >50% of all patients. Currently, no specific treatment is available for this condition. In the early stages of DBD, patients typically complain of frequent urination and often have difficulty sensing when their bladders are full.

Neurogenic-derived 6-nitrodopamine is the most potent endogenous modulator of the mouse urinary bladder relaxation.

6-Nitrodopamine (6-ND) modulates vas deferens, seminal vesicles, and corpus cavernosum contractility; however, its role on the lower urinary tract organs has not been evaluated. Investigations of isolated urinary bladders from wild-type (WT) mice revealed 6-ND release was comparable to that of dopamine and adrenaline, whereas noradrenaline was hardly detected, as assessed by liquid chromatography coupled to tandem mass spectrometry. In vitro, 6-ND induced concentration-dependent relaxations in carbachol pre-contracted bladders with high potency (pEC: 8.

Nebivolol prevents redox imbalance and attenuates bladder dysfunction induced by cyclophosphamide in mice.

Cyclophosphamide (CYP) is combined with cytoprotective agents to minimize its toxicity in the bladder, which is mediated by reactive oxygen species (ROS). Using multiple antioxidant mechanisms, nebivolol protects from oxidative stress in distinctive conditions. We hypothesized that nebivolol would attenuate both molecular and functional alterations induced by CYP in the bladder.

The multidrug resistance protein 4 is expressed and functionally active in isolated bladder from pig.

Multidrug resistance proteins type 4 (MRP4) and 5 (MRP5) play pivotal roles in the transport of cyclic nucleotides in various tissues. However, their specific functions within the lower urinary tract remain relatively unexplored. This study aimed to investigate the effect of pharmacological inhibition of MRPs on cyclic nucleotide signaling in isolated pig bladder.

A LC-MS/MS method for the simultaneous determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma and its clinical application in patients with chronic kidney disease.

The aim of this study was to develop a high-performance liquid chromatography-tandem mass spectrometry method for the determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma samples. Strata-X 33 μm solid-phase extraction cartridges were used for the extraction of the catecholamines from human plasma samples. The catecholamines were separated in a 150 × 3 mm Shim-pack GIST C-AQ column with 3 μm particle size, placed in an oven at 40°C and perfused with 82% mobile phase A (acetonitrile-HO; 90:10, v/v) + 0.

Methylglyoxal and Advanced Glycation End Products (AGEs): Targets for the Prevention and Treatment of Diabetes-Associated Bladder Dysfunction?

Methylglyoxal (MGO) is a highly reactive α-dicarbonyl compound formed endogenously from 3-carbon glycolytic intermediates. Methylglyoxal accumulated in plasma and urine of hyperglycemic and diabetic individuals acts as a potent peptide glycation molecule, giving rise to advanced glycation end products (AGEs) like arginine-derived hydroimidazolone (MG-H1) and carboxyethyl-lysine (CEL). Methylglyoxal-derived AGEs exert their effects mostly via activation of RAGE, a cell surface receptor that initiates multiple intracellular signaling pathways, favoring a pro-oxidant environment through NADPH oxidase activation and generation of high levels of reactive oxygen species (ROS).

GKT137831 and hydrogen peroxide increase the release of 6-nitrodopamine from the human umbilical artery, rat-isolated right atrium, and rat-isolated vas deferens.

The human umbilical artery (HUA), rat-isolated right atrium, and rat-isolated vas deferens present a basal release of 6-nitrodopamine (6-ND). The basal release of 6-ND from these tissues was significantly decreased (but not abolished) when the tissues were pre-incubated with N-nitro-L-arginine methyl ester (L-NAME). In this study, the effect of the pharmacological modulation of the redox environment on the basal release of 6-ND was investigated.

Factors Associated with Low Volumes of Mother's Own Milk at Neonatal Intensive Care Unit Discharge of Very Low Birth Weight Infants-a Cohort Study.

Mother's own milk (MOM) provides health benefits for infants with very low birth weight (VLBW). This study aimed to describe the incidence and factors associated with low volumes of MOM (<50% of total diet volume) at discharge for VLBW infants. A prospective cohort study of infants with VLBW and gestational age of <30 weeks, who survived to discharge and had no contraindication to MOM.

Enhanced degradation and removal of ciprofloxacin and ofloxacin through advanced oxidation and adsorption processes using environmentally friendly modified carbon nanotubes.

This study explores the utilization of adsorption and advanced oxidation processes for the degradation of ofloxacin (OFL) and ciprofloxacin (CIP) using a green functionalized carbon nanotube (MWCNT-OH/COOH-E) as adsorbent and catalyst material. The stability and catalytic activity of the solid material were proved by FT-IR and TG/DTG, which also helped to elucidate the reaction mechanisms. In adsorption kinetic studies, both antibiotics showed similar behavior, with an equilibrium at 30 min and 60% removal.

A 2-week treatment with 5-azacytidine improved the hypercontractility state in prostate from obese mice: Role of the nitric oxide-cyclic guanosine monophosphate signalling pathway.

Benign prostatic hyperplasia (BPH) is characterised by increases in prostate volume and contraction. Downregulation of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signalling pathway contributes to prostate dysfunctions. Previous studies in cancer cells or vessels have shown that the epigenetic mechanisms control the gene and protein expression of the enzymes involved in the production of NO and cGMP.

Adverse events in the postoperative period of cardiac surgery in a pediatric intensive care unit: the contribution of the VIS score and the RACHS-1.

Objective: To evaluate the occurrence of adverse events in the postoperative period of cardiac surgery in a pediatric intensive care unit and to find any patient characteristics that can predict such events.

Methods: This was a historical cohort study of patients recovering in the pediatric intensive care unit for the first 7 days after cardiac surgery between April and December 2019, by reviewing the medical records. The following were reviewed: demographic, clinical, and laboratory characteristics; patient severity scores; and selected adverse events, grouped into device-related, surgical, and nonsurgical.

Propranolol adsorption onto multiwalled carbon nanotubes modified by green synthesis: pH, kinetic, and equilibrium studies.

This research investigated the adsorption of propranolol (PROP) by functionalized green carbon nanotubes (MWCNT-B), assessing the influence of pH, in addition to kinetic, equilibrium, and thermodynamic studies and reuse of the material. For this purpose, speciation of PROP and the point of zero charge (pH) of MWCNT-B were performed, indicating a pKa of 9.67 and pH of 3.

Periprostatic adipose tissue (PPAT) supernatant from obese mice releases anticontractile substances and increases human prostate epithelial cell proliferation: the role of nitric oxide and adenosine.

The prostate gland is surrounded by periprostatic adipose tissue (PPAT) that can release mediators that interfere in prostate function. In this study, we examined the effect of periprostatic adipose tissue supernatant obtained from obese mice on prostate reactivity and on the viability of human prostatic epithelial cell lines. Male C57BL/6 mice were fed a standard or high-fat diet after which PPAT was isolated, incubated in Krebs-Henseleit solution for 30 min (without prostate) or 60 min (with prostate), and the supernatant was then collected and screened for biological activity.

A Spectrum of Age- and Gender-Dependent Lower Urinary Tract Phenotypes in Three Mouse Models of Type 2 Diabetes.

Lower urinary tract symptoms are extremely common in people with diabetes and obesity, but the causes are unclear. Furthermore, it has proven difficult to reliably demonstrate bladder dysfunction in diabetic mouse models, thus limiting the ability to gain mechanistic insights. Therefore, the main objective of this experimental study was to characterize diabetic bladder dysfunction in three promising polygenic mouse models of type 2 diabetes.

Adsorption kinetics of ciprofloxacin and ofloxacin by green-modified carbon nanotubes.

This paper investigated the uptake of CIP and OFL in single and multicomponent adsorptive systems using modified carbon nanotubes (CNTs) as adsorbent material. The characterization analyses of the pre- and post-process material by XPS, TG/DTG, FT-IR, SEM/EDS, and XRD helped in the elucidation of the mechanisms, indicating greater involvement of n-n and π -π interactions. In the kinetic studies, the simple systems with CIP and OFL were similar, both showed equilibrium time around 20/30 min and increased adsorptive capacity with increasing initial drug concentration.

Selective Pharmacological Inhibition of NOX2 by GSK2795039 Improves Bladder Dysfunction in Cyclophosphamide-Induced Cystitis in Mice.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory disease without consistently effective treatment. Among the many mediators implicated in cystitis, the overproduction of reactive oxygen species (ROS) seems to play a key role, although the main source of ROS remains unclear. This study aimed to investigate the contribution of NADPH oxidase (NOX) isoforms in ROS generation and the voiding dysfunction of cyclophosphamide (CYP, 300 mg/Kg, ip, 24 h)-induced cystitis in adult female mice, a well-recognized animal model to study IC/BPS, by using GKT137831 (5 mg/Kg, ip, three times in a 24 h period) or GSK2795039 (5 mg/Kg, ip, three times in a 24 h period) to inhibit NOX1/4 or NOX2, respectively.

Inhibition of multidrug resistance proteins by MK571 restored the erectile function in obese mice through cGMP accumulation.

Background: Intracellular levels of cyclic nucleotides can also be controlled by the action of multidrug resistance protein types 4 (MRP4) and 5 (MRP5). To date, no studies evaluated the role of their inhibition in an animal model of erectile dysfunction (ED).

Objectives: To evaluate the effect of a 2-week treatment with MK571, an inhibitor of the efflux of cyclic nucleotides in the ED of obese mice.

Viral Hepatitis A, B and C in a Group of Transgender Women in Central Brazil.

Transgender women (TGW) have limited access to affordable viral hepatitis testing, hepatitis B vaccination, and treatment. We aimed to estimate the prevalence of viral hepatitis A, B, and C, as well as to compare the adherence and immunogenicity of two hepatitis B vaccine schedules among TGW in Central Brazil. A total of 440 TGW were interviewed and tested for hepatitis A, B, and C serological markers from 2017 to 2018.

Endothelial and vascular smooth muscle dysfunction in hypertension.

The development of essential hypertension involves several factors. Vascular dysfunction, characterized by endothelial dysfunction, low-grade inflammation and structural remodeling, plays an important role in the initiation and maintenance of essential hypertension. Although the mechanistic pathways by which essential hypertension develops are poorly understood, several pharmacological classes available on the clinical settings improve blood pressure by interfering in the cardiac output and/or vascular function.

Exact Gestational Age, Term Versus Early Term, Is Associated with Different Breastfeeding Success Rates in Mothers Delivered by Elective Cesarean Section.

The study was intended to verify the association between the gestational age of newborns classified as term and the success of breastfeeding in babies born by elective cesarean section. Also, to analyze how the variability of gestational age within the term influences breastfeeding. Retrospective study of a cohort, which included full-term newborns and their mothers, whose deliveries occurred by elective cesarean section.

Deletion of Mechanosensory β1-integrin From Bladder Smooth Muscle Results in Voiding Dysfunction and Tissue Remodeling.

The bladder undergoes large shape changes as it fills and empties and experiences complex mechanical forces. These forces become abnormal in diseases of the lower urinary tract such as overactive bladder, neurogenic bladder, and urinary retention. As the primary mechanosensors linking the actin cytoskeleton to the extracellular matrix (ECM), integrins are likely to play vital roles in maintaining bladder smooth muscle (BSM) homeostasis.

6-NitroDopamine is an endogenous modulator of rat heart chronotropism.

6-Nitrodopamine (6-ND) is released by rat vas deferens and exerts a potent contractile response that is antagonized by tricyclic antidepressants and α-, β- and β/β-adrenoceptor antagonists. The release of 6-ND, noradrenaline, adrenaline and dopamine from rat isolated right atria was assessed by tandem mass spectrometry. The effects of the catecholamines were evaluated in both rat isolated right atria and in anaesthetized rats.

Enhanced RAGE Expression and Excess Reactive-Oxygen Species Production Mediates Rho Kinase-Dependent Detrusor Overactivity After Methylglyoxal Exposure.

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound implicated in diabetes-associated diseases. In vascular tissues, MGO induces the formation of advanced glycation end products (AGEs) that bounds its receptor RAGE, initiating the downstream tissue injury. Outside the cardiovascular system, MGO intake produces mouse voiding dysfunction and bladder overactivity.

Reduced blood pressure in sickle cell disease is associated with decreased angiotensin converting enzyme (ACE) activity and is not modulated by ACE inhibition.

Background: Sickle cell disease (SCD) incurs vaso-occlusive episodes and organ damage, including nephropathy. Despite displaying characteristics of vascular dysfunction, SCD patients tend to present relatively lower systemic blood pressure (BP), via an unknown mechanism. We investigated associations between BP and renin-angiotensin-system (RAS) components in SCD and determined whether an inhibitor of angiotensin converting enzyme (ACE; often used to slow SCD glomerulopathy) further modulates BP and RAS components in a murine model of SCD.