A Comparison of Outcomes from Antibiotic Treatment with and without Probiotics in 897 Patients with Lower Urogenital Tract Infections, Including Cystitis, Urethritis, Prostatitis, and Vulvovaginitis.

BACKGROUND Urogenital bacterial infections have a high incidence in humans. The most frequent cause of infections of the urogenital tract is gram-negative bacteria. Antibiotics are very effective in curing infectious diseases but they are accompanied by health complications. Probiotics are live microorganisms that are believed to confer a beneficial effect on human health when consumed in adequate amounts. This study aimed to compare outcomes from antibiotic treatment with and without the use of probiotics in 897 patients with lower urogenital tract infections, including cystitis, urethritis, prostatitis, and vulvovaginitis. MATERIAL AND METHODS A total of 897 patients aged 18 to 55 years were included in this research. Patients were divided into an intervention group including 460 patients (254 women, 206 men) and a comparison group including 437 patients (240 women, 197 men). The probiotics received by patients were capsules of ProBalans®. The diagnosis of cystitis, urethritis, prostatitis, vulvovaginitis, and sexually transmitted infection was done using several tests, and antibiotics were used for treatment. Qualitative data were analyzed using the chi-square or Fisher exact test. RESULTS We found a significant difference regarding patients' impressions of improvement after therapy between patients in the intervention group and the comparison group. CONCLUSIONS Use of probiotics together with antibiotics in the treatment of urogenital tract infection can help to reduce the adverse effects of antibiotics, increase the efficiency of antibiotic therapy, and reduce bacterial resistance to antibiotics. However, further research is needed to confirm these potential health benefits.

'Male cystitis does not exist': A qualitative study of general practitioners' experiences and management of male urinary tract infections in France.

BACKGROUND: Male urinary tract infections (mUTIs) are rare in primary care. The definition of mUTIs varies across countries. The therapeutic management of mUTIs in France is based on a 14-day course of fluoroquinolones despite a high risk of antimicrobial resistance. OBJECTIVES: The objective of this qualitative study was to explore general practitioners' (GPs) experiences and behaviours regarding the diagnostic and therapeutic management of mUTIs. METHODS: GPs were recruited by convenience sampling in Haute Normandie (France) and interviewed individually with semi-structured guides. GPs' experiences and behaviours were recorded and analysed using an interpretive phenomenological approach. RESULTS: From March 2021 to May 2022, 20 GPs were included in the study. Defining a mUTI was perceived as a diagnostic challenge. A diagnosis based on clinical evidence alone was insufficient and complementary tests were required. For GPs: 'male cystitis does not exist'. A mUTI was considered an unusual disease that could reveal an underlying condition. GPs considered fluoroquinolones to be 'potent' antibiotics and treated all patients with the same 14-day course. GPs implemented improvement strategies for antibiotic stewardship and followed the guidelines using a computerised decision support system. CONCLUSIONS: GPs' experiences of mUTIs are limited due to low exposure and variable clinical presentations in primary care, representing a diagnostic and therapeutic challenge. In order to modify GPs' antibiotic prescribing behaviours, a paradigm shift in the guidelines will need to be proposed.KEY MESSAGESDefining a male urinary tract infection represents a diagnostic challenge for GPs.A diagnosis based on clinical evidence alone is insufficient and complementary tests are required.A male urinary tract infection is an unusual disease in primary care and suggests a more serious underlying condition.

[The management and treatment of cystitis: same challenges, new strategies]. / Prise en charge et traitement des cystites : mêmes défis, nouvelles stratégies.

Cystitis is an inflammation of the bladder that is most often caused by bacterial infection and is the most common urinary tract infection. This lower urinary tract infection (UTI) is one of the most frequently encountered infections in women in outpatient practice. The concept of the urobiome, the microbiome of the urinary tract, has recently emerged and has improved our comprehension of the physiopathology of UTI. Recent studies have highlighted the potential limits of additional examinations used in our clinical practice. The emergence of delayed therapy is a novelty in the treatment of lower UTI; it likely allows for an overall reduction in antibiotic consumption while remaining an effective treatment. Alternatives to antibiotic treatment exist but most have yet to be tested in sufficiently powered randomized trials.

La cystite est une inflammation de la vessie, le plus souvent provoquée par une infection bactérienne, et est l'infection urinaire (IU) la plus fréquente. Par ailleurs, l'infection urinaire basse (IUB) est l'infection la plus souvent rencontrée chez la femme dans la pratique ambulatoire. L'étude de l'urobiome, le microbiome du tractus urinaire, a permis des avancées dans la compréhension de la physiopathologie des IU. Des études ont mis en avant les possibles limites des examens complémentaires utilisés dans notre pratique clinique. L'émergence du traitement différé (Delayed Therapy) est une nouveauté dans le traitement des IUB, dans le sens où il permettrait de diminuer la consommation d'antibiotiques tout en restant un traitement efficace. Les alternatives au traitement antibiotique existent, mais la majorité doit encore être validée dans des essais randomisés de meilleure qualité.

Prospective evaluation of single-dose aminoglycosides for treatment of complicated cystitis in the emergency department.

BACKGROUND: Antimicrobial resistance among Enterobacterales continues to be a growing problem, particularly in those with urinary infections. Previous studies have demonstrated safety and efficacy with the use of single-dose aminoglycosides in uncomplicated cystitis. However, data in complicated infections are limited. Single-dose aminoglycosides may provide a convenient alternative for those with or at risk for resistant pathogens causing complicated urinary infections, especially when oral options are unavailable due to resistance, allergy, intolerance, or interactions with other medications. This study evaluated the safety and effectiveness of single-dose aminoglycosides in treatment of complicated cystitis in the emergency department (ED). METHODS: This was a multicenter, prospective study performed between July 2022 and March 2023 of patients who met criteria for complicated cystitis and were otherwise stable for discharge at an academic ED. Primary outcomes were clinical or microbiologic failure within 14 days of treatment. Safety was assessed by review of adverse events. Descriptive statistics were used. RESULTS: Thirteen patients were included. Complicating factors were male sex (n = 4), kidney stone (n = 2), urinary catheter (n = 6), recent urologic procedure (n = 1), urinary hardware (n = 1), antibiotic allergy precluding use of alternate oral options (n = 4), immunocompromised status (n = 2), and <1-year history of multidrug-resistant organisms on urine culture (n = 8). Eleven patients (85%) had positive urine cultures in the preceding 12 months with no oral antimicrobial option. Eight patients (62%) received amikacin (median dose 15 mg/kg), four patients (31%) received gentamicin (median dose 5 mg/kg), and one patient (8%) received tobramycin (5 mg/kg) for treatment. Ten patients (77%) reported resolved urinary symptoms after treatment and 11 patients (85%) reported no new urinary symptoms since discharge. No patient required hospital admission for treatment failure, and no adverse events were noted. CONCLUSIONS: Single-dose aminoglycosides appear to be a reasonably effective and safe treatment for complicated cystitis, which avoided hospital admission in this cohort.

Multidrug resistance among uropathogenic clonal group A E. Coli isolates from Pakistani women with uncomplicated urinary tract infections.

OBJECTIVE: Multi-drug resistance (MDR) has notably increased in community acquired uropathogens causing urinary tract infections (UTIs), predominantly Escherichia coli. Uropathogenic E. coli causes 80% of uncomplicated community acquired UTIs, particularly in pre-menopausal women. Considering this high prevalence and the potential to spread antimicrobial resistant genes, the current study was conducted to investigate the presence of clinically important strains of E. coli in Pakistani women having uncomplicated cystitis and pyelonephritis. Women belonging to low-income groups were exclusively included in the study. Seventy-four isolates from urine samples were processed, phylotyped, and screened for the presence of two Single Nucleotide Polymorphisms (SNPs) particularly associated with a clinically important clonal group A of E. coli (CgA) followed by antibiotic susceptibility testing and genome sequence analysis. RESULTS: Phylogroup B2 was most prevalent in patients and 44% of isolates were positive for the presence of CgA specific SNPs in Fumarate hydratase and DNA gyrase subunit B genes. Antibiotic susceptibility testing showed widespread resistance to trimethoprim-sulfamethoxazole and extended-spectrum beta-lactamase production. The infection analysis revealed the phylogroup B2 to be more pathogenic as compared to the other groups. The genome sequence of E. coli strain U17 revealed genes encoding virulence, multidrug resistance, and host colonization mechanisms. CONCLUSIONS: Our research findings not only validate the significant occurrence of multidrug-resistant clonal group A E. coli (CgA) in premenopausal Pakistani women suffering from cystitis and pyelonephritis but also reveal the presence of genes associated withvirulence, and drug efflux pumps. The detection of highly pathogenic, antimicrobial-resistant phylogroup B2 and CgA E. coli strains is likely to help in understanding the epidemiology of the pathogen and may ultimately help to reduce the impact of these strains on human health. Furthermore, the findings of this study will particularly help to reduce the prevalence of uncomplicated UTIs and the cost associated with their treatment in women belonging to low-income groups.

Evaluating ChatGPT ability to answer urinary tract Infection-Related questions.

INTRODUCTION: For the first time, the accuracy and proficiency of ChatGPT answers on urogenital tract infection (UTIs) were evaluated. METHODS: The study aimed to create two lists of questions: frequently asked questions (FAQs, public-based inquiries) on relevant topics, and questions based on guideline information (guideline-based inquiries). ChatGPT responses to FAQs and scientific questions were scored by two urologists and an infectious disease specialist. Quality and reliability of all ChatGPT answers were checked using the Global Quality Score (GQS). The reproducibility of ChatGPT answers was analyzed by asking each question twice. RESULTS: All in all, 96.2 % of FAQs (75/78 inquiries) related to UTIs were correctly and adequately answered by ChatGPT, and scored GQS 5. None of the ChatGPT answers were classified as GQS 2 and GQS 1. Moreover, FAQs about cystitis, urethritis, and epididymo-orchitis were answered by ChatGPT with 100 % accuracy (GQS 5). ChatGPT answers for EAU urological infections guidelines showed that 61 (89.7 %), 5 (7.4 %), and 2 (2.9 %) ChatGPT responses were scored GQS 5, GQS 4, and GQS 3, respectively. None of the ChatGPT responses for EAU urological infections guidelines were categorized as GQS 2 and GQS 1. Comparison of mean GQS values of ChatGPT answers for FAQs and EAU urological guideline questions showed that ChatGPT was similarly able to respond to both question groups (p = 0.168). The ChatGPT response reproducibility rate was highest for the FAQ subgroups of cystitis, urethritis, and epididymo-orchitis (100 % for each subgroup). CONCLUSION: The present study showed that ChatGPT gave accurate and satisfactory answers for both public-based inquiries, and EAU urological infection guideline-based questions. Reproducibility of ChatGPT answers exceeded 90% for both FAQs and scientific questions.

The effects of a galectin-3 inhibitor on bladder pain syndrome in mice with cyclophosphamide-induced cystitis.

AIMS: To explore the effect of blocking galectin-3 in the bladder pain syndrome associated with interstitial cystitis. METHODS: A galectin-3 inhibitor was used to treat mice with cyclophosphamide-induced cystitis. The expression of galectin-3 in bladder tissues and urine was examined by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. Suprapubic-pelvic pain, bladder voiding, bladder pain-like nociceptive behavior, and referred hyperalgesia were assessed. The weights of the bladders were also measured, and inflammatory cell infiltration and inflammatory cytokine levels were examined by histopathological evaluation. The inflammatory cytokines interleukin 1ß (IL-1ß), nerve growth factor (NGF), IL-6, and tumor necrosis factor α (TNF-α) were measured by ELISA. RESULTS: Increases in galectin-3 levels, inflammation, bladder weight, and bladder pain-related symptoms were observed in bladders with cyclophosphamide-induced cystitis. Administration of the galectin-3 inhibitor significantly mitigated bladder pain-related symptoms and inflammatory response. In response to the 500 µM dose of the galectin-3 inhibitor, nociceptive behaviors, nociceptive score, and bladder-to-body weight ratios were reduced by 65.1%, 65.3%, and 40.3%, respectively, while 500 µM Gal-3 inhibitor increased pelvic pain threshold by 86.7%. Moreover, galectin-3 inhibitor treatment inhibited the inflammation. Compared to untreated CYP-induced mice, there were significant changes in the levels of IL-1ß (41.72 ± 2.05 vs. 18.91 ± 2.26 pg/mg tissues), NGF (9.64 ± 0.38 vs. 1.88 ± 0.05 pg/mg tissues), IL-6 (42.67 + 1.51 vs. 21.26 + 2.78 pg/mg tissues, and TNF-α (22.02 ± 1.08 vs. 10.70 ± 0.80 pg/mg tissues) in response to the highest dose of the Gal-3 inhibitor subgroup (500 µM), and 500 µM Gal-3 inhibitor reduced mast cell infiltration ratios by 71.8%. CONCLUSIONS: The galectin-3 inhibitor relieved pelvic pain, urinary symptoms, and bladder inflammation in mice with cyclophosphamide-induced cystitis. Thus, galectin-3 inhibitors may be novel agents in interstitial cystitis treatment.

[Risk Factors of Late-Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation].

To analyze the risk factors for late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the risk factors for the progression of LOHC to severe LOHC, and the effect of LOHC on survival. METHODS: The clinical data of 300 patients who underwent allo-HSCT at the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2021 were retrospectively analyzed. The relevant clinical parameters that may affect the occurance of LOHC after allo-HSCT were selected for univariate and multivariate analysis. Then, the differences in overall survival (OS) and progression-free survival (PFS) between different groups were analyzed. RESULTS: The results of multivariate analysis showed that the independent risk factors for LOHC after allo-HSCT were as follows: age≤45 years old (P =0.039), intensified conditioning regimen with fludarabine/cladribine and cytarabine (P =0.002), albumin≤30 g/L on d30 after transplantation (P =0.007), CMV-DNA positive (P =0.028), fungal infection before transplantation (P =0.026), and the occurrence of grade Ⅱ - Ⅳ aGVHD (P =0.006). In the transplant patients who have already developed LOHC, the occurance of LOHC within 32 days after transplantation (P =0.008) and albumin≤30 g/L on d30 after transplantation (P =0.032) were independent risk factors for the progression to severe LOHC. The OS rate of patients with severe LOHC was significantly lower than that of patients without LOHC (P =0.041). CONCLUSION: For the patients aged≤45 years old and with intensified conditioning regimen, it is necessary to be vigilant about the occurrence of LOHC; For the patients with earlier occurrence of LOHC, it is necessary to be vigilant that it develops into severe LOHC. Early prevention and treatment of LOHC are essential. Regular monitoring of CMV-DNA and albumin levels, highly effective antiviral and antifungal therapies, and prevention of aGVHD are effective measures to prevent the occurrence and development of LOHC.

Third nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by the Japanese surveillance committee during 2020 and 2021: Antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus.

The Japanese surveillance committee conducted a third nationwide surveillance of antimicrobial susceptibility of acute uncomplicated cystitis at 55 facilities throughout Japan between April 2020 and September 2021. In this surveillance, we investigated the susceptibility of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus saprophyticus (S. saprophyticus) for various antimicrobial agents by isolating and culturing bacteria from urine samples. In total, 823 strains were isolated from 848 patients and 569 strains of target bacteria, including E. coli (n = 529, 92.9 %), K. pneumoniae (n = 28, 4.9 %), and S. saprophyticus (n = 12, 2.2 %) were isolated. The minimum inhibitory concentrations of 18 antibacterial agents were determined according to the Clinical and Laboratory Standards Institute manual. In premenopausal patients, there were 31 (10.5 %) and 20 (6.8 %) fluoroquinolone (FQ)-resistant E. coli and extended-spectrum ß-lactamase (ESBL)-producing E. coli, respectively. On the other hand, in postmenopausal patients, there were 75 (32.1 %) and 36 (15.4 %) FQ-resistant E. coli and ESBL-producing E. coli, respectively. The rate of FQ-resistant E. coli and ESBL-producing E. coli in post-menopausal women was higher than that for our previous nationwide surveillance (20.7 % and 32.1 %: p = 0.0004, 10.0 % and 15.4 %; p = 0.0259). For pre-menopausal women, there was no significant difference in the rate of FQ-resistant E. coli and ESBL-producing E. coli between this and previous reports, but the frequency of FQ-resistant E. coli and ESBL-producing E. coli exhibited a gradual increase. For appropriate antimicrobial agent selection and usage, it is essential for clinicians to be aware of the high rate of these antimicrobial-resistant bacteria in acute uncomplicated cystitis in Japan.

Purine nucleoside phosphorylase inhibition is an effective approach for the treatment of chemical hemorrhagic cystitis.

Hemorrhagic cystitis may be induced by infection, radiation therapy, or medications or may be idiopathic. Along with hemorrhagic features, symptoms include urinary urgency and frequency, dysuria (painful urination), and visceral pain. Cystitis-induced visceral pain is one of the most challenging types of pain to treat, and an effective treatment would address a major unmet medical need. We assessed the efficacy of a purine nucleoside phosphorylase inhibitor, 8-aminoguanine (8-AG), for the treatment of hemorrhagic/ulcerative cystitis. Lower urinary tract (LUT) function and structure were assessed in adult Sprague-Dawley rats, treated chronically with cyclophosphamide (CYP; sacrificed day 8) and randomized to daily oral treatment with 8-AG (begun 14 days prior to CYP induction) or its vehicle. CYP-treated rats exhibited multiple abnormalities, including increased urinary frequency and neural mechanosensitivity, reduced bladder levels of inosine, urothelial inflammation/damage, and activation of spinal cord microglia, which is associated with pain hypersensitivity. 8-AG treatment of CYP-treated rats normalized all observed histological, structural, biochemical, and physiological abnormalities. In cystitis 8-AG improved function and reduced both pain and inflammation likely by increasing inosine, a tissue-protective purine metabolite. These findings demonstrate that 8-AG has translational potential for reducing pain and preventing bladder damage in cystitis-associated LUT dysfunctions.

Ketamine cystitis following ketamine therapy for treatment-resistant depression - case report.

BACKGROUND: Ketamine is a novel and exciting putative antidepressant medication for patients with treatment-resistant depression. A complication commonly seen in frequent and heavy recreational use of ketamine is ulcerative cystitis, which presents with lower urinary tract symptoms (LUTS) and upper renal tract damage and can be seen in over 25% of regular users. Although Ketamine-induced cystitis (KIC) is a recognised complication in recreational use of ketamine, its occurrence in therapeutic use of ketamine in depression has so far not been reported. The exact pathogenesis of KIC is currently unknown, making treatment and prevention advice much more difficult. Early diagnosis of KIC and immediate cessation of ketamine has been shown to improve adverse urinary tract symptoms and prevent further damage. CASE PRESENTATION: We present a case of a 28-year-old female who was started on ketamine treatment for depression, and who then developed symptoms of KIC, which was confirmed by urine microscopy, culture and analysis. CONCLUSIONS: To our knowledge, this is the first reported case of KIC in a patient receiving treatment-dose ketamine as part of their antidepressant therapy.

Intravesical liposomal tacrolimus for hemorrhagic cystitis: a phase 2a multicenter dose-escalation study.

BACKGROUND: Hemorrhagic cystitis (HC) is an inflammatory disease of the bladder with sustained hematuria for which there is currently no approved drug treatment. We evaluated a liposomal tacrolimus preparation (LP-10) in patients with refractory moderate to severe sterile HC. METHODS: This phase 2a dose-escalation study assessed the safety and efficacy of up to 2 intravesical instillations of LP-10 (2, 4, or 8 mg tacrolimus) in 13 patients with HC. Primary efficacy outcomes were changes from baseline in the number of bleeding sites on cystoscopy, microscopic urine analysis for red blood cells (RBCs), and hematuria on dipstick. Additional efficacy measures included urinary incontinence, frequency, and urgency on a 3-day diary and cystoscopy global response assessment (GRA). Blood samples for pharmacokinetic (PK) assessment were obtained in all patients. RESULTS: Intravesical LP-10 was well tolerated, with no treatment-related severe or serious adverse events (AEs) and only 3 drug-related AEs (artificial urinary sphincter malfunction, dysuria, and bladder spasms). LP-10 blood levels showed short durations of minimal systemic uptake. Treatment resulted in significant improvements in bleeding on cystoscopy, RBC counts in urine, hematuria on dipstick, and urinary incontinence. Bleeding on cystoscopy and urinary incontinence showed dose-dependent improvements that were more pronounced in the 4 mg and 8 mg dose groups. All dose groups showed a significant improvement in cystoscopy GRA. CONCLUSION: LP-10 was well tolerated, with clinically relevant efficacy seen in improvements in cystoscopic bleeding, hematuria, and urinary incontinence. The benefit-risk profile supports the further clinical development of LP-10 at a tacrolimus dose of 4 mg.

Propolis as an adjunctive therapy for treatment of uncomplicated cystitis in women: A randomized double-blind placebo-controlled trial.

The current research is designed to investigate the effect of propolis supplementation on the clinical manifestations in women suffering from uncomplicated cystitis. In this randomized double-blind, placebo-controlled trial, 120 women with uncomplicated cystitis were selected and randomly assigned into two groups to receive two 500 mg capsules of propolis or placebo daily for 7 days along with ciprofloxacin (250 mg). Clinical symptoms including hematuria, urinary frequency, dysuria, suprapubic pain, and urgency, as well as bacteriuria, were assessed before and after the intervention. After supplementation, participants in the intervention group had significantly fewer days of urinary frequency (p < 0.001), dysuria (p = 0.005), and urgency (p = 0.03). However, there was no significant difference between the two groups regarding hematuria and suprapubic pain (p > 0.05). Furthermore, the severity of bacteriuria decreased significantly in both groups. In conclusion, it seems that propolis supplementation in women with uncomplicated cystitis could improve urinary frequency, dysuria, and urgency. However, further clinical trials should be conducted to fully understand the effects of propolis in women suffering from uncomplicated cystitis.

Predicting Antibiotic Susceptibility Among Patients With Recurrent Urinary Tract Infection Using a Prior Culture.

PURPOSE: Recurrent cystitis guidelines recommend relying on a local antibiogram or prior urine culture to guide empirical prescribing, yet little data exist to quantify the predictive value of a prior culture. We constructed a urinary antibiogram and evaluated test metrics (sensitivity, specificity, and Bayes' positive and negative predictive values) of a prior gram-negative organism on predicting subsequent resistance or susceptibility among patients with uncomplicated, recurrent cystitis. MATERIALS AND METHODS: We performed a retrospective database study of adults with recurrent, uncomplicated cystitis (cystitis occurring 2 times in 6 months or 3 times in 12 months) from urology or primary care clinics between November 1, 2016, and December 31, 2018. We excluded pregnant females, patients with complicated cystitis, or pyelonephritis. Test metrics were calculated between sequential, paired cultures using standard formulas. RESULTS: We included 597 visits from 232 unique patients wherein 310 (51.2%) visits had a urine culture and 165 had gram-negative uropathogens isolated. Patients with gram-negative uropathogens were mostly females (97%), with a median age of 58.5 years. Our antibiogram found 38.0%, 27.9%, and 5.5% of Escherichia coli isolates had resistance to trimethoprim-sulfamethoxazole, ciprofloxacin, and nitrofurantoin, respectively. Prior cultures (within 2 years) had good predictive value for detecting future susceptibility to first-line agents nitrofurantoin (0.85) and trimethoprim-sulfamethoxazole (0.78) and excellent predictive values (≥0.90) for cefepime, ceftriaxone, cefuroxime, ciprofloxacin, levofloxacin, gentamicin, tobramycin, piperacillin-tazobactam, and imipenem. CONCLUSIONS: Considerable antibiotic resistance was detected among E coli isolates in patients with recurrent, uncomplicated cystitis. Using a prior culture as a guide can enhance the probability of selecting an effective empirical agent.

Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3.

PURPOSE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. METHODS: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. RESULTS: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. CONCLUSIONS: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Prospective Phycocompounds for Developing Therapeutics for Urinary Tract Infection.

Antibiotic resistance of bacteria is causing clinical and public health concerns that are challenging to treat. Infections are becoming more common in the present era, and patients admitted to hospitals often have drug-resistant bacteria that can spread nosocomial infections. Urinary tract infections (UTIs) are among the most common infectious diseases affecting all age groups. There has been an increase in the proportion of bacteria that are resistant to multiple drugs. Herein is a comprehensive update on UTI-associated diseases: cystitis, urethritis, acute urethral syndrome, pyelonephritis, and recurrent UTIs. Further emphasis on the global statistical incidence and recent advancement of the role of natural products in treating notorious infections are described. This updated compendium will inspire the development of novel phycocompounds as the prospective antibacterial candidate.

[Onto-phylogenetic prerequisites for development of chronic cystitis in women].

INTRODUCTION: Urinary tract infections (UTIs) are among the most common bacterial infections. At the request "cystitis", there are 12,067 publications in the RSCI system (e.library) as of 10/08/2023 and 16,332 articles were screened in the Pubmed. This is evidence that the problem of cystitis is far from being resolved. MATERIAL AND METHODS: A total of 425 patients with bacterial vaginosis and 77 women with chronic recurrent cystitis were included in the study. In all patients, the vaginal biocenosis was assessed through molecular genetic testing. The examination included filling out the Russian version of the Acute Cystitis Symptom Score (ACSS), urinalysis, and urine culture. In addition, local microcirculation was measured using laser Doppler flowmetry (LDF). After examination, patients were prescribed basic therapy and randomly assigned to one of three groups. In a control group (n=17), only basic therapy, consisting of fosfomycin 3.0 once at night + furagin 100 mg after meals 3 times a day for 5 days was prescribed. In the main group 1, 29 women received basic therapy plus Superlymph suppositories 10 units 2 times a day vaginally for 10 days. In the main group 2, 31 patients received basic therapy plus suppositories Superlymph 10 units (rectally in the morning) and Acylact Duo (vaginally in the evening) for 10 days. RESULTS: Among 425 patients with bacterial vaginosis, 78 (18.3%) complained of various urinary disorders, but only 21 women (4.9% of those with vaginal dysbiosis and 26.9% with dysuria) had a diagnosis of cystitis. In all cases, it was an exacerbation of a chronic disease. Among 77 patients with chronic cystitis, normal vaginal flora was initially present in 32 patients (41.6%), and bacterial vaginosis was found in 45 (58.4%) cases. After therapy, positive results were noted in patients of all groups. Complete eradication of the pathogen occurred in 15 women (88.2%) who received only basic therapy; in the main groups 1 and 2, uropathogens were not detected in 27 (93.1%) and 28 (90.3%) cases, respectively. In the control group, the proportion of patients with normal vaginal flora remained virtually unchanged (41.2% [n=7] vs. 47.1% [n=8]). In the main group 1, the proportion of patients with normal vaginal flora almost doubled: from 41.4% (n=12) to 79.3% (n=23). In main group 2, restoration of vaginal flora was noted in 87.1% of cases. CONCLUSION: According to our data, only 4.9% of patients with bacterial vaginosis were diagnosed with chronic cystitis, however, 58.4% of patients with chronic cystitis had vaginal dysbiosis. The use of a complex of antimicrobial peptides and cytokines has significantly increased the bidirectional effect of therapy. Suppositories Superlymph in a combination with vaginal use of Acylact Duo allow to obtain the best results.