-
Trends in Molecular Medicine Nov 2016The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise... (Review)
Review
The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities.
Topics: Acute Disease; Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Cystitis; Female; Humans; Male; Recurrence; Secondary Prevention; Urinary Tract; Urinary Tract Infections
PubMed: 27692880
DOI: 10.1016/j.molmed.2016.09.003 -
Jornal de Pediatria 2020This review aimed to provide a critical overview on the pathogenesis, clinical findings, diagnosis, imaging investigation, treatment, chemoprophylaxis, and complications... (Review)
Review
OBJECTIVE
This review aimed to provide a critical overview on the pathogenesis, clinical findings, diagnosis, imaging investigation, treatment, chemoprophylaxis, and complications of urinary tract infection in pediatric patients.
SOURCE OF DATA
Data were obtained independently by two authors, who carried out a comprehensive and non-systematic search in public databases.
SUMMARY OF FINDINGS
Urinary tract infection is the most common bacterial infection in children. Urinary tract infection in pediatric patients can be the early clinical manifestation of congenital anomalies of the kidney and urinary tract (CAKUT) or be related to bladder dysfunctions. E. coli is responsible for 80-90% of community-acquired acute pyelonephritis episodes, especially in children. Bacterial virulence factors and the innate host immune systems may contribute to the occurrence and severity of urinary tract infection. The clinical presentation of urinary tract infections in children is highly heterogeneous, with symptoms that can be quite obscure. Urine culture is still the gold standard for diagnosing urinary tract infection and methods of urine collection in individual centers should be determined based on the accuracy of voided specimens. The debate on the ideal imaging protocol is still ongoing and there is tendency of less use of prophylaxis. Alternative measures and management of risk factors for recurrent urinary tract infection should be emphasized. However, in selected patients, prophylaxis can protect from recurrent urinary tract infection and long-term consequences. According to population-based studies, hypertension and chronic kidney disease are rarely associated with urinary tract infection.
CONCLUSION
Many aspects regarding urinary tract infection in children are still matters of debate, especially imaging investigation and indication of antibiotic prophylaxis. Further longitudinal studies are needed to establish tailored approach of urinary tract infection in childhood.
Topics: Child; Escherichia coli; Humans; Kidney; Pediatrics; Urinary Tract; Urinary Tract Infections; Urine Specimen Collection
PubMed: 31783012
DOI: 10.1016/j.jped.2019.10.006 -
Biology of Sex Differences Oct 2018Females and males differ significantly in gross anatomy and physiology of the lower urinary tract, and these differences are commonly discussed in the medical and... (Review)
Review
Females and males differ significantly in gross anatomy and physiology of the lower urinary tract, and these differences are commonly discussed in the medical and scientific literature. However, less attention is dedicated to investigating the varied development, function, and biology between females and males on a cellular level. Recognizing that cell biology is not uniform, especially in the lower urinary tract of females and males, is crucial for providing context and relevance for diverse fields of biomedical investigation. This review serves to characterize the current understanding of biological sex differences between female and male lower urinary tracts, while identifying areas for future research. First, the differences in overall cell populations are discussed in the detrusor smooth muscle, urothelium, and trigone. Second, the urethra is discussed, including anatomic discussions of the female and male urethra followed by discussions of cellular differences in the urothelial and muscular layers. The pelvic floor is then reviewed, followed by an examination of the sex differences in hormonal regulation, the urinary tract microbiome, and the reticuloendothelial system. Understanding the complex and dynamic development, anatomy, and physiology of the lower urinary tract should be contextualized by the sex differences described in this review.
Topics: Animals; Female; Gonadal Steroid Hormones; Humans; Male; Sex Characteristics; Urinary Tract; Urinary Tract Physiological Phenomena
PubMed: 30343668
DOI: 10.1186/s13293-018-0204-8 -
Comprehensive Physiology Jan 2015This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural... (Review)
Review
This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.
Topics: Animals; Humans; Neuronal Plasticity; Neurons, Afferent; Neurotransmitter Agents; Peripheral Nervous System; Reflex; Spinal Cord; Urethra; Urinary Bladder; Urinary Tract; Urination
PubMed: 25589273
DOI: 10.1002/cphy.c130056 -
Frontiers in Cellular and Infection... 2021Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. Uropathogenic (UPEC) accounts for a... (Review)
Review
Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. Uropathogenic (UPEC) accounts for a significant proportion of UTI, but a large number of other species can infect the urinary tract, each of which will have unique host-pathogen interactions with the bladder environment. Given the substantial economic burden of UTI and its increasing antibiotic resistance, there is an urgent need to better understand UTI pathophysiology - especially its tendency to relapse and recur. Most models developed to date use murine infection; few human-relevant models exist. Of these, the majority of UTI models have utilized cells in static culture, but UTI needs to be studied in the context of the unique aspects of the bladder's biophysical environment (e.g., tissue architecture, urine, fluid flow, and stretch). In this review, we summarize the complexities of recurrent UTI, critically assess current infection models and discuss potential improvements. More advanced human cell-based models have the potential to enable a better understanding of the etiology of UTI disease and to provide a complementary platform alongside animals for drug screening and the search for better treatments.
Topics: Animals; Escherichia coli Infections; Humans; Mice; Urinary Bladder; Urinary Tract; Urinary Tract Infections; Uropathogenic Escherichia coli
PubMed: 34123879
DOI: 10.3389/fcimb.2021.691210 -
Nature Dec 2020Henry Miller stated that "to relieve a full bladder is one of the great human joys". Urination is critically important in health and ailments of the lower urinary tract...
Henry Miller stated that "to relieve a full bladder is one of the great human joys". Urination is critically important in health and ailments of the lower urinary tract cause high pathological burden. Although there have been advances in understanding the central circuitry in the brain that facilitates urination, there is a lack of in-depth mechanistic insight into the process. In addition to central control, micturition reflexes that govern urination are all initiated by peripheral mechanical stimuli such as bladder stretch and urethral flow. The mechanotransduction molecules and cell types that function as the primary stretch and pressure detectors in the urinary tract mostly remain unknown. Here we identify expression of the mechanosensitive ion channel PIEZO2 in lower urinary tract tissues, where it is required for low-threshold bladder-stretch sensing and urethral micturition reflexes. We show that PIEZO2 acts as a sensor in both the bladder urothelium and innervating sensory neurons. Humans and mice lacking functional PIEZO2 have impaired bladder control, and humans lacking functional PIEZO2 report deficient bladder-filling sensation. This study identifies PIEZO2 as a key mechanosensor in urinary function. These findings set the foundation for future work to identify the interactions between urothelial cells and sensory neurons that control urination.
Topics: Animals; Female; Humans; Ion Channels; Mechanotransduction, Cellular; Mice; Pressure; Reflex; Sensory Receptor Cells; Urinary Bladder; Urinary Tract; Urination; Urothelium
PubMed: 33057202
DOI: 10.1038/s41586-020-2830-7 -
BioMed Research International 2018Urinary tract infections (UTIs) caused by are the most common types of infections in women. The antibiotic resistance of is increasing rapidly, causing physicians to... (Review)
Review
Urinary tract infections (UTIs) caused by are the most common types of infections in women. The antibiotic resistance of is increasing rapidly, causing physicians to hesitate when selecting oral antibiotics. In this review, our objective is to ensure that clinicians understand the current seriousness of antibiotic-resistant , the mechanisms by which resistance is selected for, and methods that can be used to prevent antibiotic resistance.
Topics: Animals; Anti-Bacterial Agents; Community-Acquired Infections; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Urinary Tract; Urinary Tract Infections
PubMed: 30356438
DOI: 10.1155/2018/7656752 -
Advanced Science (Weinheim,... Feb 2022Upper tract urothelial carcinomas (UTUCs) are rare entities that are usually diagnosed at advanced stages. Research on UTUC pathobiology and clinical management has been...
Upper tract urothelial carcinomas (UTUCs) are rare entities that are usually diagnosed at advanced stages. Research on UTUC pathobiology and clinical management has been hampered by the lack of models accurately reflecting disease nature and diversity. In this study, a modified organoid culture system is used to generate a library of 25 patient-derived UTUC organoid lines retaining the histological architectures, marker gene expressions, genomic landscapes, and gene expression profiles of their parental tumors. The study demonstrates that the responses of UTUC organoids to anticancer drugs can be identified and the model supports the exploration of novel treatment strategies. This work proposes a modified protocol for generating patient-derived UTUC organoid lines that may help elucidate UTUC pathophysiology and assess the responses of these diseases to various drug therapies in personalized medicine.
Topics: Antineoplastic Agents; Humans; Organoids; Urinary Tract; Urologic Neoplasms; Urothelium
PubMed: 34914855
DOI: 10.1002/advs.202103999 -
Nature Communications Jun 2021Current kidney organoids model development and diseases of the nephron but not the contiguous epithelial network of the kidney's collecting duct (CD) system. Here, we...
Current kidney organoids model development and diseases of the nephron but not the contiguous epithelial network of the kidney's collecting duct (CD) system. Here, we report the generation of an expandable, 3D branching ureteric bud (UB) organoid culture model that can be derived from primary UB progenitors from mouse and human fetal kidneys, or generated de novo from human pluripotent stem cells. In chemically-defined culture conditions, UB organoids generate CD organoids, with differentiated principal and intercalated cells adopting spatial assemblies reflective of the adult kidney's collecting system. Aggregating 3D-cultured nephron progenitor cells with UB organoids in vitro results in a reiterative process of branching morphogenesis and nephron induction, similar to kidney development. Applying an efficient gene editing strategy to remove RET activity, we demonstrate genetically modified UB organoids can model congenital anomalies of kidney and urinary tract. Taken together, these platforms will facilitate an enhanced understanding of development, regeneration and diseases of the mammalian collecting duct system.
Topics: Adult; Animals; Cell Differentiation; Cells, Cultured; Humans; Kidney; Kidney Tubules, Collecting; Male; Mice; Morphogenesis; Nephrons; Organogenesis; Organoids; Pluripotent Stem Cells; Ureter; Urinary Tract
PubMed: 34131121
DOI: 10.1038/s41467-021-23911-5 -
Medicina (Kaunas, Lithuania) May 2022The role of imaging in healthcare has become more and more significant in the last decades [...].
The role of imaging in healthcare has become more and more significant in the last decades [...].
Topics: Forecasting; Humans; Kidney; Urinary Tract; Urinary Tract Infections
PubMed: 35630091
DOI: 10.3390/medicina58050673