Neutrophil NADPH oxidase promotes bacterial eradication and regulates NF-κB-Mediated inflammation via NRF2 signaling during urinary tract infections.

The precise role of neutrophil-derived reactive oxygen species (ROS) in combating bacterial uropathogens during urinary tract infections (UTI) remains largely unexplored. In this study, we elucidate the antimicrobial significance of NADPH oxidase 2 (NOX2)-derived ROS, as opposed to mitochondrial ROS, in facilitating neutrophil-mediated eradication of uropathogenic Escherichia coli (UPEC), the primary causative agent of UTI. Furthermore, NOX2-derived ROS regulates NF-κB-mediated inflammatory responses in neutrophils against UPEC by inducing the release of nuclear factor erythroid 2-related factor 2 (Nrf2) from its inhibitor, Kelch-like ECH-associated protein 1 (Keap1).

Analysing the influence of dapagliflozin on urinary tract infection vulnerability and kidney injury in mice infected with uropathogenic Escherichia coli.

Aim: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have revolutionized clinical medicine, but their association with urinary tract infection (UTI) risk remains debated. This study investigates the influence of dapagliflozin on UTI outcomes, focusing on kidney injury.

Materials And Methods: Female non-diabetic C57BL/6J and C3H/HeOuJ mice, along with diabetic db/db mice, were orally administered dapagliflozin (1 mg/kg or 10 mg/kg) for 7 days before transurethral uropathogenic Escherichia coli (UPEC) infection.

Murine Ribonuclease 6 Limits Bacterial Dissemination during Experimental Urinary Tract Infection.

Introduction: The ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTIs). In this study, we generated Rnase6-deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI.

Current and emerging strategies to curb antibiotic-resistant urinary tract infections.

Rising rates of antibiotic resistance in uropathogenic bacteria compromise patient outcomes and prolong hospital stays. Consequently, new strategies are needed to prevent and control the spread of antibiotic resistance in uropathogenic bacteria. Over the past two decades, sizeable clinical efforts and research advances have changed urinary tract infection (UTI) treatment and prevention strategies to conserve antibiotic use.

Urinary Tract Infections in Children.

Despite the American Academy of Pediatrics guidelines for the evaluation, treatment, and management of urinary tract infections (UTIs), UTI diagnosis and management remains challenging for clinicians. Challenges with acute UTI management stem from vague presenting signs and symptoms, diagnostic uncertainty, limitations in laboratory testing, and selecting appropriate antibiotic therapy in an era with increasing rates of antibiotic-resistant uropathogens. Recurrent UTI management remains difficult due to an incomplete understanding of the factors contributing to UTI, when to assess a child with repeated infections for kidney and urinary tract anomalies, and limited prevention strategies.

Chondronecrosis of the cricoid treated with hyperbaric oxygen therapy: A case series.

We present two cases of cricoid chondronecrosis treated with hyperbaric oxygen (HBO) therapy. Both patients presented with biphasic stridor and dyspnea several weeks after an intubation event. Tracheostomy was ultimately performed for airway protection, followed by antibiotic treatment and outpatient HBO therapy.

Insulin receptor signaling engages bladder urothelial defenses that limit urinary tract infection.

Urinary tract infections (UTIs) commonly afflict people with diabetes. To better understand the mechanisms that predispose diabetics to UTIs, we employ diabetic mouse models and altered insulin signaling to show that insulin receptor (IR) shapes UTI defenses. Our findings are validated in human biosamples.

Biomarkers for urinary tract infection: present and future perspectives.

A prompt diagnosis of urinary tract infection (UTI) is necessary to minimize its symptoms and limit sequelae. The current UTI screening by urine test strip analysis and microscopic examination has suboptimal diagnostic accuracy. A definitive diagnosis of UTI by urine culture takes two to three days for the results.

Human Ribonuclease 6 Has a Protective Role during Experimental Urinary Tract Infection.

Mounting evidence suggests that antimicrobial peptides and proteins (AMPs) belonging to the RNase A superfamily have a critical role in defending the bladder and kidney from bacterial infection. RNase 6 has been identified as a potent, leukocyte-derived AMP, but its impact on urinary tract infection (UTI) in vivo has not been demonstrated. To test the functional role of human RNase 6, we generated RNASE6 transgenic mice and studied their susceptibility to experimental UTI.

Uropathogen and host responses in pyelonephritis.

Urinary tract infections (UTIs) are among the most common bacterial infections seen in clinical practice. The ascent of UTI-causing pathogens to the kidneys results in pyelonephritis, which can trigger kidney injury, scarring and ultimately impair kidney function. Despite sizable efforts to understand how infections develop or are cleared in the bladder, our appreciation of the mechanisms by which infections develop, progress or are eradicated in the kidney is limited.

Repurposing HDAC inhibitors to enhance ribonuclease 4 and 7 expression and reduce urinary tract infection.

With the emergence of antibiotic-resistant bacteria, innovative approaches are needed for the treatment of urinary tract infections. Boosting antimicrobial peptide expression may provide an alternative to antibiotics. Here, we developed reporter cell lines and performed a high-throughput screen of clinically used drugs to identify compounds that boost ribonuclease 4 and 7 expression (RNase 4 and 7), peptides that have antimicrobial activity against antibiotic-resistant uropathogens.

Expression and function of human ribonuclease 4 in the kidney and urinary tract.

Antimicrobial peptides are essential host defense mechanisms that prevent urinary tract infections. Recent studies have demonstrated that peptides in the ribonuclease A superfamily have antimicrobial activity against uropathogens and protect the urinary tract from uropathogenic (UPEC). Little is known about the antibacterial function or expression of ribonuclease 4 (RNase 4) in the human urinary tract.

Neutrophil-Macrophage Imbalance Drives the Development of Renal Scarring during Experimental Pyelonephritis.

Background: In children, the acute pyelonephritis that can result from urinary tract infections (UTIs), which commonly ascend from the bladder to the kidney, is a growing concern because it poses a risk of renal scarring and irreversible loss of kidney function. To date, the cellular mechanisms underlying acute pyelonephritis-driven renal scarring remain unknown.

Methods: We used a preclinical model of uropathogenic -induced acute pyelonephritis to determine the contribution of neutrophils and monocytes to resolution of the condition and the subsequent development of kidney fibrosis.

The Responses of the Ribonuclease A Superfamily to Urinary Tract Infection.

The lower urinary tract is routinely exposed to microbes residing in the gastrointestinal tract, yet the urothelium resists invasive infections by gut microorganisms. This infection resistance is attributed to innate defenses in the bladder urothelium, kidney epithelium, and resident or circulating immune cells. In recent years, surmounting evidence suggests that these cell types produce and secrete soluble host defense peptides, including members of the Ribonuclease (RNase) A Superfamily, to combat invasive bacterial challenge.

Ribonuclease 7 Shields the Kidney and Bladder from Invasive Uropathogenic Infection.

Background: Evidence suggests that antimicrobial peptides, components of the innate immune response, protect the kidneys and bladder from bacterial challenge. We previously identified ribonuclease 7 (RNase 7) as a human antimicrobial peptide that has bactericidal activity against uropathogenic (UPEC). Functional studies assessing RNase 7's contributions to urinary tract defense are limited.

Innate immunity and urinary tract infection.

Urinary tract infections are a severe public health problem. The emergence and spread of antimicrobial resistance among uropathogens threaten to further compromise the quality of life and health of people who develop acute and recurrent upper and lower urinary tract infections. The host defense mechanisms that prevent invasive bacterial infection are not entirely delineated.

Analysis of the Ribonuclease A Superfamily of Antimicrobial Peptides in Patients Undergoing Chronic Peritoneal Dialysis.

Infectious peritonitis is a common complication in patients undergoing chronic peritoneal dialysis (PD), limiting the duration of PD as a modality for renal replacement therapy and increasing patient morbidity and mortality. Antimicrobial peptides (AMPs) serve critical roles in mucosal defense, but their expression and activity during peritonitis are poorly understood. We hypothesized that AMPs belonging to the Ribonuclease (RNase) A Superfamily are present in peritoneal fluid and increase during peritonitis in patients undergoing chronic PD.

Adolescents with urinary stones have elevated urine levels of inflammatory mediators.

Urinary stones are increasing in children, primarily during adolescence. Although urinary stones are often viewed in the context of intermittent stone events, increasing evidence indicates that stones are a metabolic process associated with chronic kidney disease and cardiovascular disease. These aforementioned stone-associated conditions may have pediatric origins.

Congenital Anomalies of the Kidney and Urinary Tract: A Clinical Review.

Purpose Of Review: This review highlights the most common congenital anomalies of the kidney and urinary tract (CAKUT) that are encountered in pediatric practices. CAKUT are the most common cause of prenatally diagnosed developmental malformations and encompass a spectrum of disorders impacting lower urinary tract development as well as kidney development and function. In pediatric and adolescent populations, developmental abnormalities are the leading cause of end-stage kidney disease.

The Immunomodulatory and Antimicrobial Properties of the Vertebrate Ribonuclease A Superfamily.

The Ribonuclease A Superfamily is composed of cationic peptides that are secreted by immune cells and epithelial tissues. Although their physiological roles are unclear, several members of the vertebrate Ribonuclease A Superfamily demonstrate antimicrobial and immune modulation activities. The objective of this review is to provide an overview of the published literature on the Ribonuclease A Superfamily with an emphasis on each peptide's regulation, antimicrobial properties, and immunomodulatory functions.

Insulin receptor signaling regulates renal collecting duct and intercalated cell antibacterial defenses.

People with diabetes mellitus have increased infection risk. With diabetes, urinary tract infection (UTI) is more common and has worse outcomes. Here, we investigate how diabetes and insulin resistance impact the kidney's innate defenses and urine sterility.

The burden of common infections in children and adolescents with diabetes mellitus: A Pediatric Health Information System study.

Background: People with diabetes mellitus (DM) have increased infection risk. The healthcare utilization of pediatric and adolescent diabetic patients with infection is not well defined. This study evaluates the number of pediatric and adolescent patients with DM that seek medical treatment for infection management and assesses its socioeconomic impact.

The clinical diagnosis and management of urinary tract infections in children and adolescents.

Urinary tract infections (UTI) are one of the most common and serious bacterial infections encountered by paediatricians and primary care physicians. Although the diagnosis and management of UTI appear simplistic, they remain among the most contentious issues in paediatrics. In part, UTI controversies stem from the absence of classic clinical symptoms, inappropriate urine specimen collection, modified urinary tract imaging recommendations, and diverse treatment and prevention strategies.