Cystitis Group Research Articles

Fosaprepitant improves cyclophosphamide-induced bladder damage by alleviating inflammatory response in mice

Inhibition of inflammatory process is a key therapeutic target for the treatment of interstitial cystitis (IC). Recent reports indicate that neurokinin 1 receptor (NK1R) antagonists have beneficial roles in inflammatory-based diseases. Herein, we investigate the protective effects of fosaprepitant (FOS), a NK1R antagonist, in cyclophosphamide (CP)-induced cystitis. The cystitis model was established multiple CP (80 mg/kg; i.p.) injection one day apart, and mice were treated with FOS (20 and 60 mg/kg/day; i.p.) for seven consecutive days. Detrusor contractility, vesical vascular permeability, myeloperoxidase (MPO) activity and protein expression levels of the TLR4 pathway were evaluated in mice bladder. Carbachol and electric field stimulation-evoked contractions of detrusor strips were significantly increased in CP-treated mice, which was significantly attenuated by FOS (60 mg/kg/day) treatment (p<0.001, p<0.05). Notably, vesical vascular permeability was markedly impaired in CP-induced cystitis, that was restored by FOS (60 mg/kg/day) treatment (p<0.01). MPO activity was significantly increased in cystitis group whereas FOS (20 and 60 mg/kg/day) treatment remarkably suppressed MPO activity in bladder tissue (p<0.001). Although TLR4 expression increased with cystitis, MyD88 and p-NFκBSer536/total NFκB did not change, FOS (20 and 60 mg/kg/day) treatment caused a dramatic decrease in TLR4 expression (p<0.001), indicating the anti-inflammatory effect of FOS. In conclusion, FOS improved detrusor overactivity and inflammatory response by inhibiting MPO activity and TLR4 expression, resulting in functional and histological recovery in CP-induced cystitis.

Do Vitamin D Levels Play a Role in Urinary Tract Infection in Children?

Previous studies have shown the protective effects of vitamin D supplementation against urinary tract infection (UTI). However, there are a few contradictory studies on the negative effect of vitamin D supplementation on UTI. Our objective was to establish whether there existed a relationship between serum vitamin D levels and UTIs in children. This study compared the serum 25-hydroxy vitamin D [25(OH)D] levels of children diagnosed with UTIs with those of healthy children (control group). We found a high rate of 25(OH)D deficiency in both the control and case groups (90% and 66.7%, respectively). Therefore, we added the laboratory parameters calcium, phosphate, and parathormone (PTH) to our analysis. We assessed the medical records of 60 patients diagnosed with UTIs and 20 healthy controls. The mean serum 25(OH)D level and PTH level were significantly higher in the patient group than in the control group. The PTH level was significantly lower in the acute pyelonephritis (APN) group than in the control group (p=0.016). Phosphate levels in the APN group were significantly lower than those in the control and cystitis groups (p=0.04, p=0.006 respectively). Because there was no correlation between 25(OH)D level and UTI, we concluded that 25(OH)D had no effect on UTI.

Adult zymosan re-exposure exacerbates the molecular alterations in the brainstem rostral ventromedial medulla of rats with early life zymosan-induced cystitis

Recent evidence suggests that the descending modulatory pathways from the brainstem rostral ventromedial medulla (RVM) are important for bladder inflammatory pain. This study aimed to identify the long-term molecular changes in RVM neurons due to early life cystitis during neuronal development and the effect of reexposure later in adulthood. RVM tissues from two treatment protocols were used: (1) neonatal zymosan exposures with acute adult rechallenge (RC) and (2) only neonatal zymosan exposures (NRC). RNAseq analysis showed upregulation of several genes associated with synaptic plasticity (Grin1, Grip2, Notch1, Arc, and Scn2b) in the cystitis groups compared to controls in both protocols. The RC protocol exhibited a stronger treatment effect with significantly higher fold differences between the groups compared to the NRC protocol (p < 0.001, fold differences RC vs NRC). In microarrays, miR-34a-5p showed cystitis-induced downregulation in both protocols. Bioinformatics analysis identified multiple 3′UTRs complementary binding sites for miR-34a-5p on Grin2b, Notch1, Grip2, Scn2b, and Arc genes. The enhanced response in the RC protocol indicates a possible priming effect of early life cystitis on rechallenge in adulthood. These long-term molecular alterations may play a critical role in the development of chronic bladder pain conditions as seen in patients with Interstitial Cystitis/Bladder pain syndrome.

Urinary Tract Infections in Men in Primary Care in Catalonia, Spain.

Antimicrobial resistance is a major global problem that is primarily driven by the excessive and inappropriate utilization of antibiotics. Urinary tract infections (UTIs) are frequent in primary health care (PHC) and are typically treated with antibiotics. There is ample evidence on the management of this condition in women but not in men. The aim of this study was to describe the epidemiology of UTIs in men in Catalonia, Spain. We conducted a population-based observational cohort study that included male patients diagnosed with UTI within our SIDIAP and CMBD database during the period from 2012 to 2021. UTI diagnoses were grouped into five main groups (cystitis, prostatitis, orchitis and epididymitis, urethritis, and pyelonephritis). Of the 316,762 men with at least one recorded UTI episode, the majority were registered with a diagnosis of cystitis in PHC (212,958 patients). Quinolones were the most commonly recorded treatment for UTIs (between 18.3% and 38.6%, depending on the group), except for urethritis in which a combination of antibiotics (36.7%) was most frequently used. The treatment duration period was between 9 days and 18 days, except for the prostatitis group, in which treatment was extended to 21 days. Urine cultures were documented in up to 30% in the cystitis group. Pyelonephritis was the category linked to most septicemia cases (3.0%). Conclusions: This is the first study to assess UTIs in men using a large PHC database in Spain. The sociodemographic characteristics of our sample are similar to other studies in the literature. In our setting, the use of quinolones for the treatment of UTIs is the most registered, and its duration was between 9 days and 18 days, despite the fact that resistance to quinolones exceeds 20% of the strains in our area.

Utility of immature granulocyte count in differentiating between pyelonephritis and cystitis in pediatric patients

Aims: Immature granulocyte (IG) is an easily accessible and inexpensive test that can be measured in hemogram parameters without additional analysis. It can be used in differentiation because of its practical applicability. This study aimed to investigate the role of IG count and inflammation-related complete blood count (CBC) parameters in differentiating between cystitis (CYS) and pyelonephritis (PYL) in pediatric patients.&#x0D; Methods: This retrospective cross-sectional study analyzed data from 79 pediatric patients (40 with PYL and 39 with CYS) who presented at a hospital pediatric outpatient clinic between January 2020 - February 2021. In addition to clinical symptoms and signs, laboratory and urinalysis results were evaluated. Laboratory analyses focused on IG count, IG percentage, and all hemogram parameters. &#x0D; Results: No significant demographic differences were observed between the PYL and CYS groups (p&gt;0.05). IG counts, and C-reactive protein levels significantly differed between the two conditions (p

Serum anandamide and lipids associated with linoleic acid can distinguish interstitial cystitis/bladder pain syndrome from overactive bladder: An exploratory study.

Diagnosing interstitial cystitis/bladder pain syndrome presents a major challenge because it relies on subjective symptoms and empirical cystoscopic findings. A practical biomarker should discriminate diseases that cause increased urinary frequency, particularly overactive bladder. Therefore, we aimed to identify blood biomarkers that can discriminate between interstitial cystitis/bladder pain syndrome and overactive bladder. We enrolled patients with Hunner-type interstitial cystitis (n = 20), bladder pain syndrome (n = 20), and overactive bladder (n = 20) and without lower urinary tract symptoms (controls, n = 15) at Ueda Clinic and Nara Medical University Hospital from February 2020 to August 2021. The degree of interstitial cystitis/bladder pain syndrome symptoms was evaluated using the interstitial cystitis symptom and problem indices. Metabolomics analysis was performed on 323 serum metabolites using liquid chromatography time-of-flight mass spectrometry. In the Hunner-type interstitial cystitis or bladder pain syndrome group, we observed smaller relative areas, including anandamide, acylcarnitine (18:2), linoleoyl ethanolamide, and arachidonic acid, compared to those in the overactive bladder or control group. Notably, the differences in the relative areas of anandamide were statistically significant (median: 3.950e-005 and 4.150e-005 vs. 8.300e-005 and 9.800e-005), with an area under the curve of 0.9321, demonstrating its ability to discriminate interstitial cystitis/bladder pain syndrome. Serum anandamide may be a feasible diagnostic biomarker for interstitial cystitis/bladder pain syndrome. Reduced serum anandamide levels may be associated with pain and inflammation initiation, reflecting the pathology of interstitial cystitis/bladder pain syndrome. Furthermore, our findings suggest that abnormal linoleic acid metabolism may be involved in the pathogenesis of interstitial cystitis/bladder pain syndrome.

8-Hydroxy-2'-deoxyguanosine and malondialdehyde in plasma and their association with disease severity in 20 cats with chronic kidney disease.

Oxidative stress is associated with the development and progression of chronic kidney disease (CKD) in humans. The aim of this study was to evaluate the concentrations of oxidative stress markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), in the plasma and urine of cats with different stages of CKD. Plasma and urine samples were collected from cats with CKD that were referred to the Veterinary Medical Center of the University of Tokyo between April 2019 and October 2022. Plasma and urine samples were collected from healthy cats (n = 6 at most), cats with stage 2 CKD (n = 8) and stage 3-4 CKD (n = 12), and cats with idiopathic cystitis (disease control, n = 5). Plasma and urine concentrations of 8-OHdG and MDA were measured using ELISA and thiobarbituric acid reactive substances assay kits, respectively. The median plasma 8-OHdG concentrations were 0.156 ng/ml (<0.125-0.210 ng/ml) in the healthy group, <0.125 ng/ml (range <0.125 ng/ml) in the idiopathic cystitis group, 0.246 ng/ml (range 0.170-0.403 ng/ml) in cats with stage 2 CKD and 0.433 ng/ml (range 0.209-1.052 ng/ml) in cats with stage 3-4 CKD. Concentrations in stage 3-4 CKD were significantly higher than those in the healthy and disease control groups. Plasma MDA concentrations were low in the healthy and disease control groups and significantly higher in cats with stage 3-4 CKD. In every cat with CKD, plasma 8-OHdG and MDA concentrations were positively correlated with plasma creatinine concentrations (8-OHdG, rs = 0.68; MDA, rs = 0.67). Urinary 8-OHdG/urinary creatinine (u-CRE) and urinary MDA/u-CRE levels did not differ significantly between the groups; however, it was difficult to evaluate them because of the small sample size. This report shows that plasma 8-OHdG and MDA concentrations increase with the severity of feline CKD. These markers may be useful for assessing oxidative stress in cats with CKD.

Etiology of recurrent cystitis in postmenopausal women based on vaginal microbiota and the role of Lactobacillus vaginal suppository.

The vaginal microbiota can be altered by uropathogenic bacteria associated with recurrent cystitis (RC), and the vaginal administration of Lactobacillus have suggested certain effects to prevent RC. The relationship between vaginal microbiota and the development of RC has not been elucidated. We aimed to clarify the etiology of RC from vaginal microbiota and importance of vaginal Lactobacillus. Vaginal samples obtained from 39 postmenopausal women were classified into four groups: healthy controls; uncomplicated cystitis; RC; and prevention (prevented RC by Lactobacillus crispatus-containing vaginal suppositories). Principal coordinate analysis and beta-diversity analysis was used to assess 16S rRNA gene sequencing data from the vaginal microbiome. Cluster analysis divided the vaginal bacterial communities among 129 vaginal samples into three clusters (A, B, and C). Fourteen of 14 (100%) samples from the RC group and 51 of 53 (96%) samples from the prevention group were in clusters B and C, while 29 of 38 (76%) samples from the healthy group and 14 of 24 (58%) samples from the uncomplicated cystitis group were in cluster A. The principal coordinate analysis showed that plots in the uncomplicated cystitis group were similar to the healthy group, indicating a large separation between the RC group and the uncomplicated cystitis group. On beta-diversity analysis, there were significant differences between the healthy group and the uncomplicated cystitis group (p = 0.045), and between the RC group and the uncomplicated cystitis group or the healthy group (p = 0.001, p = 0.001, respectively). There were no significant differences between the RC group and the prevention group (p = 0.446). The top six taxa were as follows: Prevotella, Lactobacillus, Streptococcus, Enterobacteriaceae, Anaerococcus, and Bifidobacterium. Among patients with RC, Lactobacillus was undetectable before administration of suppositories, while the median relative abundance of Lactobacillus was 19% during administration of suppositories (p = 0.0211), reducing the average cystitis episodes per year (6.3 vs. 2.4, p = 0.0015). The vaginal microbiota of postmenopausal women with RC is differed from healthy controls and uncomplicated cystitis in terms of lack of Lactobacillus and relatively dominant of Enterobacteriaceae. Vaginal administration of Lactobacillus-containing suppositories can prevent RC by stabilizing vaginal dysbiosis and causing a loss of pathogenic bacteria virulence.

MP34-08 ETIOLOGY OF RECURRENT CYSTITIS BASED ON VAGINAL MICROBIOME: THINKING BEYOND THE BLADDER

You have accessJournal of UrologyCME1 Apr 2023MP34-08 ETIOLOGY OF RECURRENT CYSTITIS BASED ON VAGINAL MICROBIOME: THINKING BEYOND THE BLADDER Takuya Sadahira, Takanori Sekito, Takehiro Iwata, Yuki Maruyama, and Motoo Araki Takuya SadahiraTakuya Sadahira More articles by this author , Takanori SekitoTakanori Sekito More articles by this author , Takehiro IwataTakehiro Iwata More articles by this author , Yuki MaruyamaYuki Maruyama More articles by this author , and Motoo ArakiMotoo Araki More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003268.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We aimed to determine the etiology of recurrent cystitis from vaginal microbiome and to evaluate the importance of the presence of Lactobacillus in the vagina. METHODS: Vaginal samples were obtained from postmenopausal women classified into four groups: healthy controls (“Healthy”) group, patients with uncomplicated cystitis (“Uncomplicated Cystitis”) group, patients with recurrent cystitis (“RC”) group, and patients with recurrent cystitis prevented by administration of Lactobacillus crispatus-containing vaginal suppositories (“Prevention”) group. 16S rRNA gene sequencing data from vaginal microbiome was analyzed among four groups by principal coordinate analysis. RESULTS: A total of 129 vaginal samples from 39 women were studied. The vaginal bacterial communities could be divided into three clusters (A, B, C), based on differences in relative abundances of bacterial taxa among samples (Figure 1A). Among the four groups of postmenopausal women, 39/39 (100%) samples from "Healthy" group were in Cluster A and B, 24/24 (100%) samples from "Uncomplicated Cystitis" group were in Cluster A and B, 3/4 (75%%) samples from "RC" group were in Cluster C, and 61/63 (97%) samples from "Prevention" group were in Cluster B and C. In principal coordinate analysis, the plots in the “Uncomplicated cystitis” group was similar to those of "Healthy" group (Figure 1A). In addition, principal coordinate analysis indicated a large separation between the plots in the “RC” group and "Uncomplicated cystitis" group. Among four patients in "RC" group, the median (range) relative abundance of Lactobacillus was not detected before administration of Lactobacillus crispatus-containing vaginal suppositories, while Lactobacillus was 18% (12%-25%) during administration on average reducing the onset of cystitis per year (7.8 vs 2.5, p=0.0061) (Figure 1B). CONCLUSIONS: The vaginal microbiome of recurrent cystitis is essentially different from that of uncomplicated cystitis. Moreover, lack of Lactobacillus in postmenopausal vaginal microbiome is associated with the development of recurrent cystitis. Vaginal administration of Lactobacillus prevents recurrent cystitis by improving vaginal dysbiosis. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e462 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takuya Sadahira More articles by this author Takanori Sekito More articles by this author Takehiro Iwata More articles by this author Yuki Maruyama More articles by this author Motoo Araki More articles by this author Expand All Advertisement PDF downloadLoading ...

Can montelukast sodium be an alternative treatment in the treatment of interstitial cystitis?

The leukotriene D4 receptors have been detected in human bladder detrusor myocytes, and they can play the role of interstitial cystitis etiology. Our study aims to explain the role of mast cells histologically and immunohistochemically in the pathogenesis and the effectiveness of montelukast that leukotriene D4 receptor antagonist in the treatment of interstitial cystitis. Twenty-four Wistar albino adult female rats were used. Group 1 (n = 8): control (sham) group, Group 2 (n = 8): interstitial cystitis group, and Group 3 (n = 8): treatment group. Groups 2 and 3 rats were administered 75 mg/kg cyclophosphamide four times every three days intraperitoneally. The rats in the treatment group were started on montelukast sodium as 10 mg/kg, 1 × 1/day per orally after the last administration of cyclophosphamide and were given for 14 days. Mast cells in the bladder tissues were examined histologically, and the presence of IL-6, 8, VEGF, and TNF alpha was examined immunohistochemically. Thin transitional epithelium, loose connective tissue, weak smooth muscle bundles, and signs of chronic inflammation were observed in the interstitial cystitis group. Regenerated transitional epithelium, intact basement membrane, compact lamina propia, thick smooth muscle bundles, and rare inflammatory cells were observed after the treatment with the montelukast. Mast cells were decreased in bladder tissue after treatment. IL-6, IL-8, VEGF, and TNF alpha levels were significantly decreased after treatment. We found that inflammatory mediators were significantly reduced after treatment with montelukast in the interstitial cystitis group. Montelukast can be used as an effective drug in the treatment of interstitial cystitis.

Decreased Expression of Urethral Caveolin-1, -2, and -3 in the Rat Model of Overactive Bladder: Potential Mediator of Functional Interaction of Urethra and Urinary Bladder.

To investigate the effect of detrusor overactivity (DO) on the urethral expression of caveolin (CAV)-1, -2, and -3 of urethra in an animal model of cyclophosphamide (CYP)-induced cystitis rat. Female Sprague-Dawley rats were divided into the control group (n=20) and the cystitis group (n=20). Cystitis was induced by intraperitoneal injection of CYP (200 mg/kg). An urodynamic study was done 3 days after the CYP injection to measure functional change of the urinary bladder and urethra. Cellular localization and expression of CAV-1, -2, and -3 in the rat urethra were determined by immunohistochemistry (IHC) and Western blot. Urodynamic experiments demonstrated a decreased contraction interval in the cystitis group compared to the control (3.9±1.0 minutes vs. 6.6±1.2 minutes, P<0.05). Conversely, contraction pressure increased significantly in the cystitis group compared to the control (22.4±0.7 mmHg vs. 11.5±0.4 mmHg, P<0.05). The urethral pressure was decreased in the cystitis group compared to the control (4.05 ±2.5 mmHg vs. 5.8 ±2.8 mmHg, P <0.05). The IHC and Western blot data showed that CAV-1, -2, and -3 expression decreased significantly in the cystitis group compared control group (P<0.05). The decreased urethral CAV-1, -2, and -3 in the DO rats suggests that CAVs might be related with the functional change of urethra in association with DO of urinay bladder.

Development of a Sensitive Digital Droplet PCR Screening Assay for the Detection of GPR126 Non-Coding Mutations in Bladder Cancer Urine Liquid Biopsies.

Recent whole-genome sequencing studies identified two novel recurrent mutations in the enhancer region of GPR126 in urothelial bladder cancer (UBC) tumor samples. This mutational hotspot is the second most common after the TERT promoter in UBC. The aim of the study was to develop a digital droplet PCR screening assay for the simultaneous detection of GPR126 mutations in a single tube. Its performance combined with TERT promoter mutation analysis was evaluated in urine of healthy volunteers (n = 50) and patients with cystitis (n = 22) and UBC (n = 70). The developed assay was validated using DNA constructs carrying the studied variants. None of the mutations were detected in control and cystitis group samples. GPR126 mutations were observed in the urine of 25/70 UBC patients (area under the ROC curve (AUC) of 0.679; mutant allele fraction (MAF) of 21.61 [8.30-44.52] %); TERT mutations-in 40/70 (AUC of 0.786; MAF = 28.29 [19.03-38.08] %); ≥1 mutation-in 47/70 (AUC of 0.836)). The simultaneous presence of GPR126 and TERT mutations was observed in 18/70 cases, with no difference in MAFs for the paired samples (31.96 [14.78-47.49] % vs. 27.13 [17.00-37.62] %, p = 0.349, respectively). The combined analysis of these common non-coding mutations in urine allows the sensitive and non-invasive detection of UBC.

Cystitis Induces Altered CREB Expression Related with Micturition Reflex.

Background and objectives: Bladder stimulation upregulates neurotrophins associated with voiding reflex. Bacterial cystitis can be a stimulant that activates this system, resulting in a pathological state. Phosphorylated responsive element of binding protein (p-CREB) is a pivotal transcriptional factor in the neurotrophin signaling cascade. The goal of our study was to examine the change in expression of p-CREB in dorsal root ganglia (DRG) of rats after uropathogenic Escherichia coli infection of the bladder. Materials and methods: A total of 19 adult female Sprague–Dawley rats were induced with acute E. coli infection (n = 7), chronic E. coli infection (n = 6), or served as controls (n = 6). In each group, the profiles of p-CREB cell were counted in 6–10 sections of each of the DRG collected. DRG cells exhibiting intense nuclear staining were considered to be positive for p-CREB immunoreactivity (p-CREB-IR). Results: Overall, the immunoreactivity of p-CREB was examined in smaller cell profiles with nuclear staining or nuclear and cytoplasmic staining in the DRGs (L1–L6, S1). In the chronic cystitis group, p-CREB-IR in the L1–L6 and S1 DRG was significantly higher than the control group (p < 0.05). Further, p-CREB-IR in the L3–L6 and S1 DRG of the chronic cystitis group was significantly greater than that in the acute cystitis group (p < 0.05). In the control and acute cystitis groups, p-CREB-IR in the L4–L5 DRG was significantly lower than that found in the other DRG sections (p < 0.05). Conclusions: Altogether, acute or chronic E.coli cystitis changed the immunoreactivity of p-CREB in lumbosacral DRG cells. In particular, chronic E. coli infection triggered p-CREB overexpression in L1–L6 and S1 DRG, indicating subsequent pathologic changes.

Effectiveness of hydrodistention procedure under local anesthesia in the treatment of bladder pain syndrome/interstitial cystitis

Objective: We aimed to indicate the effectiveness of local anesthesia in the treatment of hydrodistention in women with Bladder Pain Syndrome/interstitial Cystitis (BPS/IC) in our study.&#x0D; Material and Method: The data of a total of 77 female patients who underwent hydrodistention treatment for BPS/IC in our clinic between January 2015 and July 2021 were analyzed retrospectively. The patients were divided into two groups as local anesthesia (LA, n=41) and spinal anesthesia (SA, n=36) groups according to the type of anesthesia applied. The groups were compared by determining the preoperative and postoperative O'Leary symptom index (SI) and problem index (PI), minimum voiding volume (MinVV), maximum voiding volume (MaxVV), average voiding volume (AvgVV) and daily frequency. &#x0D; Results: The mean age of the patients was 48.97±11.09 years in the LA group and 45.19±14.35 years in the SA group (p=0.197). There was no significant difference between the groups in terms of the preoperative European Society for the Study of Interstitial Cystitis (ESSIC) group (p=0.999). During the postoperative period, a median (IQR) improvement of 11.0 (2.0) points was observed in the SI of the LA group, while a median improvement of 11.0 (2.0) points were observed in the SA group (p=0.437). The median improvement in PI score was 8.4 (4.0) points in the SA group, while it was 7.0 (3.0) points in the LA group (p=0.415). There was no significant difference between the groups in terms of improvements in minVV, maxVV, avgVV and daily frequency (p=0.480, p=0.460, p=0.614 and p=0.910, respectively).&#x0D; Conclusion: Hydrodistention treatment in women with BPS/IC can be performed safely and with high success rate under local anesthesia and it is well tolerated by the patients. Local anesthesia offers a minimally invasive treatment option as well as the advantage of avoiding possible complications of spinal, epidural or general anesthesia.

Notch1 Signaling Contributes to Mechanical Allodynia Associated with Cyclophosphamide-Induced Cystitis by Promoting Microglia Activation and Neuroinflammation.

Aims Notch1 signaling regulates microglia activation, which promotes neuroinflammation. Neuroinflammation plays an essential role in various kinds of pain sensation, including bladder-related pain in bladder pain syndrome/interstitial cystitis (BPS/IC). However, the impact of Notch1 signaling on mechanical allodynia in cyclophosphamide- (CYP-) induced cystitis is unclear. This study is aimed at determining whether and how Notch1 signaling modulates mechanical allodynia of CYP-induced cystitis. Methods CYP was peritoneally injected to establish a bladder pain syndrome/interstitial cystitis (BPS/IC) rat model. A γ-secretase inhibitor, DAPT, was intrathecally injected to modulate Notch1 signaling indirectly. Mechanical withdrawal threshold in the lower abdomen was measured with von Frey filaments using the up-down method. The expression of Notch1 signaling, Iba-1, OX-42, TNF-α, and IL-1β in the L6-S1 spinal dorsal horn (SDH) was measured with Western blotting analysis and immunofluorescence staining. Results Notch1 and Notch intracellular domain (NICD) were both upregulated in the SDH of the cystitis group. Moreover, the expression of Notch1 and NICD was negatively correlated with the mechanical withdrawal threshold of the cystitis rats. Furthermore, treatment with DAPT attenuated mechanical allodynia in CYP-induced cystitis and inhibited microglia activation, leading to decreased production of TNF-α and IL-1β. Conclusion Notch1 signaling contributes to mechanical allodynia associated with CYP-induced cystitis by promoting microglia activation and neuroinflammation. Our study showed that inhibition of Notch1 signaling might have therapeutic value for treating pain symptoms in BPS/IC.

Risk of Renal Function Decline in Patients with Ketamine-Associated Uropathy.

Ketamine-associated diseases have been increasing with the rise in ketamine abuse. Ketamine-associated uropathy is one of the most common complications. We investigated the effects of ketamine-associated uropathy on renal health and determined predictors of renal function decline in chronic ketamine abusers. This retrospective cohort study analyzed 51 patients (22 with ketamine-associated hydronephrosis and 29 with ketamine cystitis) from Kaohsiung Veterans General Hospital in Taiwan. Primary renal outcome was end-stage renal disease or estimated glomerular filtration rate decline >30% from baseline. Compared with the ketamine cystitis group, the hydronephrosis group had lower initial and final estimated glomerular filtration rates and higher alkaline phosphatase and gamma-glutamyl transferase levels (p < 0.05). Elevated cholestatic liver enzyme levels correlated with renal dysfunction in ketamine-associated uropathy. The hydronephrosis group had a higher proportion of patients reaching endpoints than the ketamine cystitis group (50% and 7%, respectively, p < 0.001). After adjusting for age, sex, and initial serum creatinine level, hydronephrosis remained an independent risk factor for renal function deterioration. Ketamine-associated hydronephrosis was a poor renal outcome and strong predictor of renal function decline in chronic ketamine abusers. Elevated cholestatic liver enzyme levels correlated with the severity of ketamine-associated uropathy. Ultrasonography screening of these high-risk groups and regular renal function follow-ups are necessary.

The predictability of mean platelet volume as a biomarker of pyelonephritis among pediatrics with urinary tract infection

Introduction: Delayed diagnosis of acute pyelonephritis and its differentiation from cystitis can lead to irreversible complications in renal tissue, hypertension and even renal failure. Objectives: The present study aimed to evaluate the diagnostic value of platelet volume in acute pyelonephritis. Patients and Methods: This cross-sectional study was conducted on 110 children with febrile acute urinary tract infection (UTI) referred to our educational hospital in Qom, Iran. Individuals with inclusion criteria were examined for mean platelet volume (MPV), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) and platelet counts. Additionally, Tc 99m-dimercaptosuccinic acid scan (DMSA scan) was used as the gold standard for differentiation of cystitis from acute pyelonephritis. Urine culture was also used to confirm diagnosis of UTI. Results: The mean age of the participants was two years with a range of two months to 13 years. The MPV (P=0.001), CRP (P=0.001), ESR (P=0.001), platelet (P=0.013) and WBC count (P=0.001) were significantly higher in the pyelonephritis group compared to cystitis group. We showed that MPV has similar potency in differentiating pyelonephritis from cystitis compared to other inflammatory markers; however CRP was more accurate than other markers. The cut-off point for MPV was estimated 7.8 fl, with sensitivity of 91%, specificity of 92.7%, and positive predictive value of 92.6%. Conclusion: The high level of ESR is a risk factor to develop pyelonephritis. MPV as an inflammatory marker is similar to that of other inflammatory markers in segregating pyelonephritis in children, although further studies are needed to confirm the results of this study.

Relationship between low serum vitamin D status and urinary tract infection in children: a case–control study

ABSTRACT Background A link between vitamin D deficiency and susceptibility to bacterial and viral infections has recently been suggested. Aim To investigate a possible association between vitamin D deficiency and urinary tract infection (UTI). Methods A case–control study was undertaken comprising 75 children aged 2–7 years with UTI (cases) compared with 75 healthy controls in terms of serum 25 hydroxyvitamin D [25(OH)D] levels. Serum 25(OH)D levels were measured using a chemiluminescence assay. For cases, dimercaptosuccinic acid (DMSA) renal scan was used as the gold standard to distinguish between acute lower UTI (cystitis) and acute pyelonephritis. Results Median (IQR) 25(OH)D levels were lower in the UTI group [14.5 ng/mL (9.4–18.8)] than in the controls [27 ng/mL (22.4–39.0)] (p< 0.001). In addition, the prevalence of 25(OH)D levels <20 ng/mL was higher in the children with UTI than in the controls (68% vs 18%) (p< 0.001). There was a statistically significant difference between the cystitis and pyelonephritis groups in mean (SD) serum 25(OH)D levels—18.76 (9.35) ng/mL vs 13.94 (6.97) ng/mL, p< 0.05, respectively. Conclusion Low serum vitamin D is associated with UTI and supports the hypothesis that children with low vitamin D levels could be at greater risk of UTI.

PD24-06 MOLECULAR ALTERATION OF GABAERGIC PAIN MODULATORY PATHWAY IN THE ROSTRAL VENTROMEDIAL MEDULLA FOLLOWING ZYMOSAN-INDUCED CYSTITIS IN RATS

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology II (PD24)1 Apr 2020PD24-06 MOLECULAR ALTERATION OF GABAERGIC PAIN MODULATORY PATHWAY IN THE ROSTRAL VENTROMEDIAL MEDULLA FOLLOWING ZYMOSAN-INDUCED CYSTITIS IN RATS Bidyut K. Medda*, Sankar Addya, Bhavana Talluri, Faith Hoelzel, Maia Terashvili, Patrick Sanvanson, Reza Shaker, Jyoti N. Sengupta, and Banani Banerjee Bidyut K. Medda*Bidyut K. Medda* More articles by this author , Sankar AddyaSankar Addya More articles by this author , Bhavana TalluriBhavana Talluri More articles by this author , Faith HoelzelFaith Hoelzel More articles by this author , Maia TerashviliMaia Terashvili More articles by this author , Patrick SanvansonPatrick Sanvanson More articles by this author , Reza ShakerReza Shaker More articles by this author , Jyoti N. SenguptaJyoti N. Sengupta More articles by this author , and Banani BanerjeeBanani Banerjee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000881.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The rostral ventromedial medulla (RVM) comprises of several subsets of neurons, which send descending projections to the spinal cord to modulate pain. These neurons are the major targets of efferent projections from the periaqueductal gray (PAG), the site of action of opioid-mediated analgesia. The majority of RVM originating descending neurons are GABAergic. Recently, we have documented microRNA (miRNA)-mediated transcriptional deregulation of spinal GABAergic system and visceral hypersensitivity (colon and bladder) in rats with zymosan-induced cystitis. The objective was to study the effect of noxious bladder insult on molecular expression of GABAergic RVM neurons of rats with zymosan-induced cystitis. METHODS: Two groups of Sprague Dawley rats (n=8 /group) were used in this study. Experimental and control groups received transurethral zymosan (1% in saline, 300ul) and saline respectively for 3 days from postnatal (P) days P58 through P60. Rats in both groups were euthanized on P60 and RVM tissues were collected for analysis. Gene expression profiles of experimental and control groups were evaluated using Rat Clariton S transcriptome arrays. miRNA expression profiles were examine using Affymatrix Gene Chips miRNA arrays. Individual gene was further evaluated using immunohistochemistry (IHC) and in situ hybridization (ISH). RESULTS: Intravesical zymosan treatment resulted in 4-fold downregulation of GABAA receptor subunit alpha 6 (GABAAα6) and glycine transporter Gly 2 (p<0.05 vs controls). Fourteen miRNAs demonstrated differential expression in zymosan treated rats (p<0.05 vs controls). The target gene prediction identified two upregulated miRNAs; miR-129-5p and miR-300 with complementary binding sites for 3’UTRs of GABAAα6 gene indicating a possible post-transcriptional deregulation of the RVM GABAergic pathway in zymosan-treated cystitis rats. A significant downregulation of RVM vesicular GABA transporter VGAT expression was observed in cystitis group by ISH (p<0.05 vs controls). The expression profile of GABAAα6 in RVM was validated by IHC. CONCLUSIONS: Cystitis results in miRNA-mediated transcriptional deregulation of GABA receptor and transporter expression in RVM neurons. This finding strongly suggests that the suppression of the RVM inhibitory transmission may contribute towards the development of spinal neuron hyperexcitability and bladder pain. Source of Funding: NIH R01DK099201 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e534-e534 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bidyut K. Medda* More articles by this author Sankar Addya More articles by this author Bhavana Talluri More articles by this author Faith Hoelzel More articles by this author Maia Terashvili More articles by this author Patrick Sanvanson More articles by this author Reza Shaker More articles by this author Jyoti N. Sengupta More articles by this author Banani Banerjee More articles by this author Expand All Advertisement PDF downloadLoading ...

Urinary carbohydrate antigen 19-9 level as a biomarker in children with acute pyelonephritis.

Early and prompt diagnosis of pyelonephritis is of great importance in children. The aim of this study is to evaluate the diagnostic accuracy of urinary carbohydrate antigen 19-9 (CA19-9) levels for predicting acute pyelonephritis (APN) in children with urinary tract infection (UTI). Patients were allocated into two groups of APN and acute cystitis according to their diagnosis. Urine samples of all patients were collected. Also, complete history was taken, and physical examination, kidney and bladder ultrasonography, 99mTc-dimercaptosuccinic acid renal cortical scintigraphy, and urine analysis and culture were performed. Urinary CA19-9 was measured by an electrochemiluminescence enzyme immunometric kit. In addition, CA19-9 levels were measured in the APN group 2weeks and 3months later. A total of 100 children were included in this study (mean age 46 ± 31months, 16 males and 84 females). CA19-9 levels were significantly greater in the APN group than acute cystitis group (510 ± 328 vs. 18.7 ± 18.6 U/ml, P < 0.001). During follow-up periods of the APN group, CA19-9 levels decreased to 180 ± 124 U/ml after 2weeks (P < 0.001) and 30 ± 23 U/ml after 3months (P < 0.001). Urinary CA-19-9 had 95.3% sensitivity and 80% specificity for the diagnosis of APN. The area under the curve value of CA19-9 was 0.904 (95% CI 0.831-0.977).Conclusion: Urinary CA19-9 level can be used as a reliable biomarker for early detection of APN prior to urine culture confirmation in children with UTI. What is known: • Early and prompt diagnosis of pyelonephritis is necessary in children to prevent renal damage. • Acute pyelonephritis can present with vague and nonspecific symptoms in infants and children. What is new: • Urinary carbohydrate antigen 19-9 is a reliable biomarker for early detection of acute pyelonephritis prior to urine culture confirmation. • Urinary carbohydrate antigen 19-9 has 95.3% sensitivity and 80% specificity for diagnosis of acute pyelonephritis.