Ureaplasma spp. lipid-associated membrane proteins induce human monocyte U937 cell cycle arrest through p53-independent p21 pathway.

Ureaplasma spp. are known to be associated with human genitourinary tract diseases and perinatal diseases and Ureaplasma spp. Lipid-associated membrane proteins (LAMPs) play important roles in their related diseases. However, the exact mechanism underlying pathogenesis of Ureaplasma spp. LAMPs is largely unknown. In this study, we explored the pathogenic mechanisms of Ureaplasma spp. LAMPs by elucidating their role in modulating the cell cycle and related signaling pathways in human monocytic cell U937, which is highly related to the inflammatory and protective effect in infectious diseases. We utilized the two ATCC reference strains (Ureaplasma parvum serovar 3 str. ATCC 27,815 (UPA3) and Ureaplasma urealyticum serovar 8 str. ATCC 27,618 (UUR8)) and nine clinical isolates which including both UPA and UUR to study the effects of Ureaplasma spp. LAMPs on U937 in vitro. We found that LAMPs derived from UUR8 and both UPA and UUR of clinical strains markedly inhibited the cell proliferation, while UPA3 LAMPs suppressed slightly. Besides, the result of flow cytometry analysis indicated all the Ureaplasma spp. LAMPs could arrest U937 cells in G1 phase. Next, we found that the cell cycle arrest was associated with increased levels of p53 and p21, and a concomitant decrease in the levels of CDK2, CDK4, CDK6 and cyclin E1 at both transcriptional and translational levels after treatment with LAMPs derived from UUR8 or clinical strains, while only cyclin E1 was down-regulated after treatment with UPA3 LAMPs. Further study showed that p53 down-regulation had almost no effect on the distribution of cell cycle and the expression of p21. In conclusion, this study demonstrated that LAMPs derived from UUR8 and clinical strains could inhibit the proliferation of U937 cells by inducing G1 cell cycle arrest through increasing the p21 expression in a p53-independent manner, while UPA3 LAMPs could induce the cell cycle arrest slightly. Our study could contribute to the understanding of Ureaplasma spp. pathogenesis, which has potential value for the treatment of Ureaplasma spp. infections.

The Role of the Genitourinary Microbiome in Pediatric Urology: a Review.

PURPOSE OF REVIEW: In this review, we highlight the effects of the microbiome on urologic diseases that affect the pediatric patient. RECENT FINDINGS: Perturbations in the urinary microbiome have been shown to be associated with a number of urologic diseases affecting children, namely urinary tract infection, overactive bladder/urge urinary incontinence, and urolithiasis. Recently, improved cultivation and sequencing technologies have allowed for the discovery of a significant and diverse microbiome in the bladder, previously assumed to be sterile. Early studies aimed to identify the resident bacterial species and demonstrate the efficacy of sequencing and enhanced quantitative urine culture. More recently, research has sought to elucidate the association between the microbiome and urologic disease, as well as to demonstrate effects of manipulation of the microbiome on various urologic pathologies. With an improved appreciation for the impact of the urinary microbiome on urologic disease, researchers have begun to explore the impact of these resident bacteria in pediatric urology.

Clinical implications of the microbiome in urinary tract diseases.

PURPOSE OF REVIEW: The purpose of this review is to outline and evaluate the most recent literature on the role of the microbiome in urinary tract diseases. RECENT FINDINGS: High throughput molecular DNA sequencing of bacterial 16S rRNA genes enabled the analysis of complex microbial communities inhabiting the human urinary tract. Several recent studies have identified bacterial taxa of the urinary microbiome to impact urinary tract diseases including interstitial cystitis, urgency urinary incontinence or calcium oxalate stone formation. Furthermore, treatment of urinary tract infections by antibiotics globally impacts community profiles of the intestinal microbiota and might indirectly influence human health. Alternative treatment options like application of probiotics for the treatment of urinary tract infections are currently under investigation. SUMMARY: The urinary microbiome and its relationship to urinary tract diseases is currently under comprehensive investigation. Further studies are needed to shed light on the role of commensal microbiota for urinary tract infections.

Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes.

AIMS: To assess the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes enrolled in the CANagliflozin cardioVascular Assessment Study (CANVAS) who were on an incretin mimetic [dipeptidyl peptidase-4 (DPP-4) inhibitor or glucagon-like peptide-1 (GLP-1) receptor agonist]. METHODS: CANVAS is a double-blind, placebo-controlled study that randomized participants to canagliflozin 100 or 300 mg or placebo added to routine therapy. The present post hoc analysis assessed the efficacy and safety of canagliflozin 100 and 300 mg compared with placebo in subsets of patients from CANVAS who were taking background DPP-4 inhibitors or GLP-1 receptor agonists with or without other antihyperglycaemic agents at week 18. RESULTS: Of the 4330 patients in CANVAS, 316 were taking DPP-4 inhibitors and 95 were taking GLP-1 receptor agonists. At 18 weeks, canagliflozin 100 and 300 mg provided larger placebo-subtracted reductions in glycated haemoglobin (HbA1c) in patients taking DPP-4 inhibitors [-0.56% (95% confidence interval [CI]: -0.77, -0.35), and -0.75% (95% CI: -0.95, -0.54), respectively] and GLP-1 receptor agonists [-1.00% (95% CI: -1.35, -0.65), and -1.06% (95% CI: -1.43, -0.69), respectively]. Body weight and blood pressure (BP) reductions were seen with canagliflozin versus placebo in both subsets. Higher incidences of genital mycotic infections and osmotic diuresis-related adverse events (AEs) were seen with canagliflozin compared with placebo. The incidence of hypoglycaemia was numerically higher with canagliflozin versus placebo; nearly all events occurred in patients on background insulin or insulin secretagogues. CONCLUSIONS: In patients on background incretin mimetics, canagliflozin improved HbA1c, body weight and BP, with an increased incidence of AEs related to SGLT2 inhibition.

[The application of the preformed physical factors for the combined treatment of the patients presenting with chronic vesiculitis]. / Preformirovannye fizicheskie faktory v kompleksnoi terapii patsientov s khronicheskim vezikulitom.

UNLABELLED: The problem of the development of the new efficient methods for the treatment of the patients presenting with chronic bacterial vesiculitis (CBV) is currently considered among the important priorities. AIM: The objective of the present study was to provide a scientifically sound substantiation for the application of sinusoidal modulated currents (SMC), magnetic fields, and laser radiation in the combined treatment of the patients with CBV. PATIENTS AND METHODS: A total of 121 patients presenting with chronic bacterial vesiculitis were examined and treated during the latent phase of the inflammatory process. They were randomly divided into three groups. Group 1 (main) was comprised of 40 patients treated, in addition to basal pharmacotherapy, by supravascular contact laser irradiation of the cubital vein area followed after 2-3 hours by the application of sinusoidal modulated currents to the pubosacral region. Group 2 included 41patents given, besides basal pharmacotherapy, laser therapy in the same regimen as in group 1 supplemented after 2-3 hours by abdominal magnetic therapy. Group 3 (control) received traditional pharmacotherapy in the combination with antibacterial and anti-inflammatory medicines. RESULTS: It was demonstrated that the patients of group 2 exhibited the most pronounced positive dynamics of the clinical signs and symptoms estimated from the total National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and of the characteristics of the quality of life evaluated based on the QLS scale. The patients of the two former groups experienced a more conspicuous decrease in the activity of the inflammatory process in seminal vesicles, restoration of their structural and anatomical features (as shown by the transrectal ultrasound study), improvement of testosterone metabolism, and normalization of the spermogram characteristics in comparison with controls. The analysis of the spermograms revealed the tendency toward the increase in the number of actively motile spermatozoa only in the patients of group 2. The combined treatment of the patients of the two former groups resulted in the decrease of the level of sex hormone-binding globulin and the increase of the free androgen index. CONCLUSION: The results of the study indicate that the application of the preformed physical factors for the treatment of the patients presenting with chronic bacterial vesiculitis enhances the effectiveness of pharmacotherapy and decreases both the frequency and the duration of relapses of the disease.

[Analysis of grant of special nephrological help to childrensi in Chernivtsi region].

Nephrological morbidity is important indicator of the state of the health of children's population. The aim of this study is analysis of the activity of nephrological service care for children's population of the Chernivtsi region. The material for this study is reporting documentation about the condition of the nephrological service care for children's population of the Chernivtsi region in 2008-2012 and the data of The Center of medical statistics of Ministry of Health of Ukraine. The incidence of prevalence of diseases of the urinary system between teenagers of Chernivtsi region during the 2008-2012 period had a wave-like nature and have lower rates comparing general Ukraine rates, with the exception of 2011, when the incidence of child population in the region amounted to 32.60 in 1000 to 29.65 against children 1000 children in Ukraine. The age structure of patients is determined by many factors, including the demographic situation in the region, "continuity" and these primary healthcare units. Value of microbial and inflammatory diseases to nephropathy--2.9:1 (2009), but over the last three years there is a tendency to change its value--3.5-4:1 (2012). Is marked resistance to antibiotic therapy--3/4 of surveyed high school age children and teenagers found mycoplasma pathogens (M. hominis, M. genitalium) and ureaplasma (U. urealyticum) origin, especially against the background of comorbidity of "modern child". Analyzes the main indicators of child nephrology service in Chernivtsi region. The research, carried out by authors, will allow to hold the reasoned medical and rehabilitation events in all stages of rendering of specialized medical care for teenagers with nephrological pathology and to develop the programs, directed on improvement of indicators of health and prevention of disability in children.

The impact of mixing surgical subspecialty patients on wound infection rates.

To investigate the impact of mixing surgical subspecialty patients on post-operative wound infections. A retrospective analysis of post-operative wound infections in head and neck surgery patients before and after mixing them with urology patients. We selected two periods that are identical in duration and seasonal spread. The first was from March 2005 to November 2005 and the second was from March 2006 to November 2006. 1,381 patients underwent head and neck surgery at our institution in the two periods; 705 in the first and 676 in the second. Excluding MRSA positive swabs, the rate of positive swabs or "episodes" was 4% in the first group (2005) and 10% in the second group (2006). The monthly breakdown showed a significant increase in the second group (2006) (p = 0.024). Uro-genital microorganisms were the main factor contributing to the increase in wound infection rates in the second period (p = 0.008). Other organisms like MRSA, remained statistically unchanged (p = 0.464). It is recommend that head and neck surgery patients are better managed on separate wards. Clinicians should have a low threshold of suspecting a broader range of microorganisms when other specialty patients are on the same ward.

[Combined action of levofloxacin and DNAase on biofilms of urogenital infection pathogens].

The effect of antibiotics and DNAase on biofilms of unrelated gram-positive and gram-negative bacteria was studied on strains isolated from patients with infectious and inflammatory urinary diseases. It was found that destruction of extracellular DNA biofilms by DNAase increases sensitivity of the bacteria to environmental factors including antibacterial drugs. DNAase addition to forming and formed biofilms created by unrelated bacteria leads to similar dose-dependent changes This evidences for universal action of the enzyme. A synergetic effect occurs in combined action of antibiotic biofilm and DNAase on bacteria.

Candida bezoars with urinary tract obstruction in two women without immunocompromising conditions.

More than half of the cases of fungal infections of the urinary tract are caused by Candida sp., but occurrence of obstructive uropathy caused by mycetomas or fungus balls (urobezoars) is extremely rare. The latter are conglomerates of fungal hyphae. Diabetes mellitus, immunosuppression, chronic disease, and malignancies are known predisposing factors. Preoperative imaging is not pathognomonic; blood clots, radiolucent urinary calculi, air bubbles, and inflammatory debris can mimic urobezoars. We report on two otherwise healthy women presenting with urinary tract obstruction caused by candidal mycetomas of the renal pelvis that mimicked matrix lithiasis.

The Diagnosis and Management of Life-threatening Urologic Infections.

Genitourinary infections are commonly encountered and managed in inpatient, outpatient, and emergency settings. Fournier's gangrene, emphysematous pyelonephritis, and obstructive pyelonephritis represent the most serious urologic infections and have a high risk of mortality if not managed promptly. Due to the rarity of these infections, the evidence for specific treatment strategies is scattered. This review aims to provide comprehensive, evidence-based recommendations for the diagnosis and management of these life-threatening urologic infections.

Urobiome: An outlook on the metagenome of urological diseases.

The urinary tract likely plays a role in the development of various urinary diseases due to the recently recognized notion that urine is not sterile. In this mini review, we summarize the current literature regarding the urinary microbiome and mycobiome and its relationship to various urinary diseases. It has been recently discovered that the healthy urinary tract contains a host of microorganisms, creating a urinary microbiome. The relative abundance and type of bacteria varies, but generally, deviations in the standard microbiome are observed in individuals with urologic diseases, such as bladder cancer, benign prostatic hyperplasia, urgency urinary incontinence, overactive bladder syndrome, interstitial cystitis, bladder pain syndrome, and urinary tract infections. However, whether this change is causative, or correlative has yet to be determined. In summary, the urinary tract hosts a complex microbiome. Changes in this microbiome may be indicative of urologic diseases and can be tracked to predict, prevent, and treat them in individuals. However, current analytical and sampling collection methods may present limitations to the development in the understanding of the urinary microbiome and its relationship with various urinary diseases. Further research on the differences between healthy and diseased microbiomes, the long-term effects of antibiotic treatments on the urobiome, and the effect of the urinary mycobiome on general health will be important in developing a comprehensive understanding of the urinary microbiome and its relationship to the human body.

[Efficacy of fluoroquinolones on urological infection pathogens within biofilms].

Our investigations demonstrated that fluoroquinalones affect both formation and established urological bacterial biofilms which present difficulties for antimicrobial therapy because incomplete eradication of uroinfection promotes persistence and development of chronic processes. Fluoroquinalones reduce biofilm mass and number of CFU. The affected biofilms become less resistant to external impacts. This provides a more potent action of antibiotic and, finally, a good therapeutic effect of the drug. Levofloxacin (floracid) showed the highest activity among fluoroquinalones studied. It actively suppresses uroinfection bacteria in biofilms and lowers the risk of the infection recurrence.

The microbiome in urological diseases.

Due to the rapid development of next-generation sequencing, it has become possible to obtain information on the sequences of all genes in a specific microbiome. The detection of bacteria in patients with no urinary tract infections indicated that the dogma that "urine is sterile" was false, leading to active research regarding the roles of the urinary microbiome in the human urinary tract. Here, we present a review of the current literature regarding the role of the microbiome in urology.

The impact of microbiome in urological diseases: a systematic review.

OBJECTIVE: The term microbiome is used to signify the ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body space, in which there were increasing evidences to suggest that they might have potential roles in various medical conditions. While the study of microbiome in the urinary system is not as robust as the systems included in the Human Microbiome Project, there are still evidences in the literature showing that microbiome may have a role in urological diseases. Therefore, we would like to perform a systematic review on the topic and summarize the available evidence on the impact of microbiome on urological diseases. METHODOLOGY: This review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. After screening 589 abstracts and including additional studies (such as references from review papers), 76 studies were included for review and discussion. RESULTS: Studies had suggested that there were correlations of microbiome of different body cavities (e.g., fecal, urinary and seminal fluid) with urological diseases. Also, different diseases would have different microbiome profile in different body cavities. Unfortunately, the studies on the association of microbiome and urological diseases were still either weak or inconsistent. CONCLUSION: Studies suggested that there might be some relationship between microbiome and various urological diseases. However, further large-scale studies with control of confounding factors should be performed under a standardized methodology in order to have better understanding of the relationship. Also, more standardized reporting protocol for microbiome studies should be considered for better communications in future studies.

Greetings from Africa: The Emergence of Tropical Urological Diseases in Europe. We Had Better Be Prepared!

The increasing incidence of tropical urological diseases due to migration represents a challenge for local practitioners. Face-to-face and webinar learning courses could be a simple first step in increasing awareness of this issue.

Longitudinal study of wild koalas (Phascolarctos cinereus) reveals chlamydial disease progression in two thirds of infected animals.

Chlamydial disease threatens many of Australia's koala populations, and yet our understanding of chlamydial epidemiology and disease dynamics in koalas is limited by a lack of comprehensive, longitudinal population studies. To address this, we utilised longitudinal samples from a large-scale population study of wild koalas in south-east Queensland, to follow chlamydial infections over time and to investigate some of the drivers of disease progression. Our findings show, firstly, that almost two thirds of chlamydial infections progressed to disease, challenging the notion that chlamydial infections in koalas commonly remain chronic and asymptomatic. Secondly, disease progression at the urogenital tract site was associated with infection load, and urogenital tract shedding was significantly higher when koalas acquired a new infection. Thirdly, chronic chlamydial exposure was not necessary for pathogenic sequelae to develop, such as infertility and mortality. Fourthly, ompA-characterised strain sub-types may reflect tissue tropisms and pathogenicity, and the chlamydial status of some chronically infected koalas may be explained by reinfections with novel genotypes. Finally, successful antimicrobial treatment provided only short-term protection against reinfection and disease progression in susceptible koalas. These findings highlight the importance of identifying and preventing chlamydial infections in koalas, informing new population management strategies and research priorities.

The Urinary Tract Microbiome in Health and Disease.

CONTEXT: The urinary tract, previously considered a sterile body niche, has emerged as the host of an array of bacteria in healthy individuals, revolutionizing the urology research field. OBJECTIVE: To review the literature on microbiome implications in the urinary tract and the usefulness of probiotics/prebiotics and diet as treatment for urologic disorders. EVIDENCE ACQUISITION: A systematic review was conducted using PubMed and Medline from inception until July 2016. The initial search identified 1419 studies and 89 were included in this systematic review. EVIDENCE SYNTHESIS: Specific bacterial communities have been found in the healthy urinary tract. Changes in this microbiome have been observed in certain urologic disorders such as urinary incontinence, urologic cancers, interstitial cystitis, neurogenic bladder dysfunction, sexually transmitted infections, and chronic prostatitis/chronic pelvic pain syndrome. The role of probiotics, prebiotics, and diet as treatment or preventive agents for urologic disorders requires further investigation. CONCLUSIONS: There is a microbiome associated with the healthy urinary tract that can change in urologic disorders. This represents a propitious context to identify new diagnostic, prognostic, and predictive microbiome-based biomarkers that could be used in clinical urology practice. In addition, probiotics, prebiotics, and diet modifications appear to represent an opportunity to regulate the urinary microbiome. PATIENT SUMMARY: We review the urinary microbiome of healthy individuals and its changes in relation to urinary disorders. The question to resolve is how we can modulate the microbiome to improve urinary tract health.

[Lavomax in outpatient treatment of urogenital chlamidiasis in males].

Sixty four males (age 21-45 years) with urogenital chlamidiasis were divided into two groups. 34 patients of the study group received interferon inductor and lavomax. 30 patients of the control group--interferon inductor and cycloferon. Treatment efficacy in the study group was higher.