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Abstract Apocynin (APO) is a naturally occurring acetophenone with eminent anti-inflammatory and anti-oxidant peculiarities. It suffers from poor bioavailability due to low aqueous solubility. Herein, APO was loaded in a Clove oil (CO) based Nanostructured lipid carrier (NSLC) system using a simple method (ultrasonic emulsification) guided by a quality-by-design approach (23 full factorial design) to optimize the formulated NSLCs. The prepared NSLCs were evaluated regarding particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). The optimal formula (F2) was extensively investigated through transmission electron microscope (TEM), Fourier transform infrared (FT-IR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), in vitro release, and stability studies. Cytotoxicity against human urinary bladder carcinoma (T24) cell line and in vivo activity studies in rats with induced cystitis were also assessed. The results disclosed that the optimal formula (F2) had PS of 214.8 ± 5.8 nm with EE% of 79.3 ± 0.9%. F2 also exhibited a strong cytotoxic effect toward the T24 cancer cells expressed by IC50 value of 5.8 ± 1.3 µg/mL. Pretreatment with the optimal formula (orally) hinted uroprotective effect against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rat models, emphasized by histopathological, immunohistochemical, and biochemical investigations. In consideration of the simple fabrication process, APO-loaded CO-based NSLCs can hold prospective potential in the prophylaxis of oncologic and urologic diseases.

Abstract One of the most prevalent disorders of the urinary system is urinary tract infection, which is mostly brought on by uropathogenic Escherichia coli (UPEC). The objective of this study was to evaluate the regenerative therapeutic and antibacterial efficacy of PRP for induced bacterial cystitis in dogs in comparison to conventional antibiotics. 25 healthy male mongrel dogs were divided into 5 groups (n = 5). Control negative group that received neither induced infection nor treatments. 20 dogs were randomized into 4 groups after two weeks of induction of UPEC cystitis into; Group 1 (control positive; G1) received weekly intravesicular instillation of sodium chloride 0.9%. Group 2 (syst/PRP; G2), treated with both systemic intramuscular antibiotic and weekly intravesicular instillation of PRP; Group 3 (PRP; G3), treated with weekly intravesicular instillation of PRP, and Group 4 (syst; G4) treated with an intramuscular systemic antibiotic. Animals were subjected to weekly clinical, ultrasonographic evaluation, urinary microbiological analysis, and redox status biomarkers estimation. Urinary matrix metalloproteinases (MMP-2, MMP-9) and urinary gene expression for platelet-derived growth factor -B (PDGF-B), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were measured. At the end of the study, dogs were euthanized, and the bladder tissues were examined macroscopically, histologically, and immunohistochemically for NF-κB P65 and Cox-2. The PRP-treated group showed significant improvement for all the clinical, Doppler parameters, and the urinary redox status (p

Introduction: The ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTIs). In this study, we generated Rnase6-deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI. Methods: We generated a Rnase6EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility. Results: We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6EGFP/+ mice. Rnase6 deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+ controls. UPEC displayed increased intracellular survival in Rnase6-deficient macrophages. Conclusion: Our findings establish that RNase6 prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.

Objective: Due to the need for better treatments for infectious disorders, the antibacterial and anti-inflammatory potential of silver nanoparticles (AgNPs) of Mitracarpus scaber (M.scaber) extracts were assessed in this study. Methods: AgNPs were synthesized from 0.1M AgNO3 solution using M.scaber aqueous and ethanolic extracts as capping and reducing agents. FTIR, UV-VIS, FESEM and XRD studies were used to analyze the generated AgNPs. The Agar well diffusion method was used to evaluate their antibacterial activity against E. coli, while egg albumin and carrageenan-induced paw oedema assays were used to measure the anti-inflammatory activity of silver nanoparticles of aqueous and ethanol extracts of M.scaber (A.AgNPs and E.AgNPs). Result: The formation of A.AgNPs and E.AgNPs at λ max = 425 nm and 410 nm, respectively, were demonstrated by UV–vis spectroscopy. The XRD pattern showed that the crystalline phase of silver and the generation of A.AgNPs and E.AgNPs were well aligned. Agglomerated A.AgNPs and E.AgNPs with particle sizes ranging from 5 to 20 nm were seen in the FESEM micrograph. The antibacterial activity result showed that, in a dose-dependent manner, A.AgNPs had a significantly (P

Mounting evidence suggests that antimicrobial peptides and proteins (AMPs) belonging to the RNase A superfamily have a critical role in defending the bladder and kidney from bacterial infection. RNase 6 has been identified as a potent, leukocyte-derived AMP, but its impact on urinary tract infection (UTI) in vivo has not been demonstrated. To test the functional role of human RNase 6, we generated RNASE6 transgenic mice and studied their susceptibility to experimental UTI. In addition, we generated bone marrow-derived macrophages to study the impact of RNase 6 on antimicrobial activity within a cellular context. When subjected to experimental UTI, RNASE6 transgenic mice developed reduced uropathogenic Escherichia coli (UPEC) burden, mucosal injury, and inflammation compared to non-transgenic controls. Monocytes and macrophages were the predominant cellular sources of RNase 6 during UTI, and RNASE6 transgenic macrophages were more proficient at intracellular UPEC killing than non-transgenic controls. Altogether, our findings indicate a protective role for human RNase 6 during experimental UTI.

Objective(s): To investigate the potential of Tropomyosin receptor kinase A (TrkA) for the treatment of interstitial cystitis/ bladder pain syndrome (IC/BPS).Materials and Methods: Sixty-four female rats were randomly assigned to the control and cyclophosphamide (CYP) groups. Quantitative reverse transcription polymerase chain reaction was utilized to detect the mRNA level of TrkA. Western blot analysis was used to measure the protein levels of TNF-α, IL-6, and TrkA. Immunostaining was used to detect the expression of TrkA in bladder sections. Contractility studies and urodynamic measurements were utilized to test the spontaneous contractions of detrusor muscle strips and the global bladder activity, respectively.Results: Rat models of chronic cystitis were successfully established. The mRNA and protein levels of TrkA were significantly increased in the bladders of CYP-treated rats. Also, results of immunohistochemical staining and immunofluorescence staining showed that increased TrkA expression in the CYP group was mainly observed in the urothelium layer and bladder interstitial Cajal-like cells (ICC-LCs) but not in the detrusor smooth muscle cells. The specific inhibitor of TrkA, GW441756 (10 μM), significantly suppressed the robust spontaneous contractions of detrusor muscle strips in the CYP group and alleviated the overall bladder overactivity of CYP-treated rats. However, the inhibitory effects of GW441756 (10 μM) on the spontaneous contractions of detrusor muscle strips and the overall bladder activity were eliminated after pretreatments with the specific blocker of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, ZD7288 (50 μM).Conclusion: Our results suggested that increased TrkA expression during chronic cystitis promotes the development of bladder overactivity by targeting the HCN channels.

Ketamine is illegally used as a recreational drug in many Asian countries. Long-term ketamine abusers often develop irritable bladder symptoms that gradually develop into more severe urinary frequency and urgency and eventually into a painful ulcerated bladder. These patients typically have reduced functional bladder capacity, increased bladder sensation, detrusor overactivity, severe urgency, urinary incontinence, and bladder contracture. Ketamine metabolites can cause severe inflammation of the urothelium, urothelial barrier deficits, vascular endothelial fibrinoid changes, increased oxidative stress, and bladder wall fibrosis. A decrease in bladder compliance, urinary tract infection, severe bladder pain with a full bladder, and painful micturition are also common symptoms. Finally, with continued abuse of ketamine, hydronephrosis, ureteral stricture, vesicoureteral reflux, and renal failure may develop. Cessation of ketamine is the mainstay of treatment. Lower urinary tract symptoms usually relapse if patients reuse ketamine after stopping. In cases of severe ketamine cystitis, only augmentation enterocystoplasty can relieve bladder pain and restore normal lower urinary tract function. This article reviews the underlying pathophysiology, clinical characteristics, and management of ketamine cystitis.

In non-muscle invasive bladder cancer, Bacillus Calmette–Guérin (BCG) responders benefit from strong Th1-type inflammatory and T cell responses mediating tumor rejection. However, the corresponding lack of anti-inflammatory Th2-type immunity impairs tissue repair in the bladder wall and facilitates the development of cystitis, causing urinary pain, urgency, incontinence, and frequency. Mechanistically, the leakage of the glycosaminoglycan (GAG) layer enables an influx of potassium ions, bacteria, and urine solutes towards the underlying bladder tissue, promoting chronic inflammation. Treatments directed towards re-establishing this mucopolysaccharide-based protective barrier are urgently needed. We discuss the pathomechanisms, as well as the therapeutic rationale of how chondroitin and hyaluronic acid instillations can reduce or prevent BCG-induced irritative bladder symptoms. Moreover, we present a case series of five patients with refractory BCG-induced cystitis successfully treated with combined chondroitin and hyaluronic acid instillations.

The urinary system, primarily responsible for the filtration of blood and waste, is affected by several infectious and inflammatory conditions. Focusing on the lower tract, this review outlines the physiological and immune landscape of the urethra and bladder, addressing key immunological and microbiological aspects of important infectious/inflammatory conditions. The conditions addressed include urethritis, interstitial cystitis/bladder pain syndrome, urinary tract infections, and urosepsis. Key aspects of each condition are addressed, including epidemiology, pathophysiology, and clinical considerations. Finally, therapeutic options are outlined, highlighting gaps in the knowledge and novel therapeutic approaches.

Worldwide, urinary tract infections (UTIs) are reported in 150-250 million people per year. Annual direct and indirect costs of UTIs for overall patients are estimated to be from $2.4 billion to $3.5 billion Uropathogenic Escherichia coli is the most common cause of UTIs. These bacteria have the ability to colonize urothelium, persist in epithelial cells, and form quiescent biofilms. This bacterial reservoir may provide a source for bacterial persistence and UTIs recurrence. Besides, recurrent UTIs may be caused by the translocation of other bacteria which originate from the gastrointestinal tract or reinfections due to external sources. Menopause and pregnancy are considered as complicating factors that predispose to UTIs. Oral vaccine OM-89 and D-mannose are specified in the European Urological Association guidelines among non-pharmacological methods for the prevention of recurrent UTIs in postmenopausal women. The rationale to the use of D-mannose in UTI prophylaxis is based on its competitive inhibition of bacterial adherence to urothelial cells due to binding of type 1 fimbriae expressed on the bacteria. Exogenous D-mannose is absorbed, but not metabolized by the human body and it is excreted intact in urine. In vivo and in vitro studies showed the ability of mannose-like molecules to provide a 2-fold reduction of bacterial load in the urinary tract after 4 intravesical instillations. Clinical studies also demonstrated a high efficacy of the six months course of oral mannose in the prevention of UTIs.

Background Uropathogenic Escherichia coli (UPEC) is the predominant agent causing various categories of complicated urinary tract infections (cUTI). Although existing data reveals that UPEC harboured numerous virulence determinants to aid its survival in the urinary tract, the reason behind the occurrence of differences in the clinical severity of uninary tract infections (UTI) demonstrated by the UPEC infection is poorly understood. Therefore, the present study aims to determine the distribution of virulence determinants and antimicrobial resistance among different phylogroups of UPEC isolated from various clinical categories of cUTI and asymptomatic bacteriuria (ASB) E. coli isolates. The study will also attempt a relational analysis of the genotypic characteristics of cUTI UPEC and ASB E. coli isolates. Methods A total of 141 UPEC isolates from cUTI and 160 ASB E. coli isolates were obtained from Universiti Malaya Medical Centre (UMMC). Phylogrouping and the occurrence of virulence genes were investigated using polymerase chain reaction (PCR). Antimicrobial susceptibility of the isolates to different classes of antibiotics was determined using the Kirby Bauer Disc Diffusion method. Results The cUTI isolates were distributed differentially among both Extraintestinal Pathogenic E. coli (ExPEC) and non-ExPEC phylogroups. Phylogroup B2 isolates were observed to possess the highest average aggregative virulence score (7.17), a probable representation of the capability to cause severe disease. Approximately 50% of the cUTI isolates tested in this study were multidrug resistant against common antibiotics used to treat UTI. Analysis of the occurrence of virulence genes among different cUTI categories demonstrated that UPEC isolates of pyelonephritis and urosepsis were highly virulent and had the highest average aggregative virulence scores of 7.80 and 6.89 respectively, compared to other clinical categories. Relational analysis of the occurrence of phylogroups and virulence determinants of UPEC and ASB E. coli isolates showed that 46.1% of UPEC and 34.3% of ASB E. coli from both categories were distributed in phylogroup B2 and had the highest average aggregative virulence score of 7.17 and 5.37, respectively. The data suggest that UPEC isolates which carry virulence genes from all four virulence genes groups studied (adhesions, iron uptake systems, toxins and capsule synthesis) and isolates from phylogroup B2 specifically could predispose to severe UTI involving the upper urinary tract. Therefore, specific analysis of the genotypic characteristics of UPEC could be further explored by incorporating the combination of virulence genes as a prognostic marker for predicting disease severity, in an attempt to propose a more evidence driven treatment decision-making for all UTI patients. This will go a long way in enhancing favourable therapeutic outcomes and reducing the antimicrobial resistance burden among UTI patients.

Introduction. Cyclophosphamide (CP) is used to treat malignant neoplasias and control autoimmune diseases. Still, one of its metabolites, acrolein, is toxic to the urothelium and can lead to hemorrhagic cystitis and severe discomfort. Objective. To evaluate the ability of red propolis to prevent and treat CP-induced hemorrhagic cystitis in rats. Materials and methods. Red propolis was extracted in 1% gum arabic and administered subcutaneously (sc). In the first experiment, groups IA, IIA, and IIIA and groups IB, IIB, and IIIB received water, gum arabic (GA), or propolis, respectively, for 30 days. Then water (controls) or CP (treatment) was administered i.p. In the second experiment, groups IVA, VA, and VIA received water i.p. while groups IVB, VB, and VIB received CP i.p. This was followed by 5 injections at 2-hour intervals with either water, GA, or propolis. Bladder tissue was examined according to Gray’s criteria. Results. The total inflammatory histology score was significantly smaller in group VIB (11.33 ± 2.07). Mild inflammation predominated in group VIB while most of the animals in group IVB had severe inflammation (p=0.0375). Ulcers were predominantly multiple in Groups IVA and VB but rare or absent in Group VIB (p=0.0118). Urothelial cells were mostly absent in groups IVB and VB and present/normal in group VIB (p=0.0052). Fibrin was abundant in groups IVB and VA but mostly absent in group VIB (p=0.0273). Conclusions. Red propolis can reduce inflammation in CP-induced hemorrhagic cystitis in rats.

Urinary tract infection (UTI) referred to microbial invasion of the urinary tract system, typically due to bacteria. UTI is more common in women than men, which is thought to be due to differences in lower urinary tract anatomy. Making a diagnosis of UTI begins with the presence of clinical symptoms consistent with either pyelonephritis and cystitis. When pyelonephritis symptoms are present, it is usually associated with bacterial infection, while the symptoms of clinical cystitis may or may not be caused by infection. As both urologic and non-urologic conditions can produce the clinical symptoms of cystitis, diagnosis of UTI requires both pyuria and bacteriuria on urine examination. Complicated UTI is when the infection is associated with either host or bacterial factors that increase the chance of reinfection and decrease treatment efficacy, such as altered organism virulence, immunocompromise, or urinary tract abnormalities. The urologist’s primary role in UTI management is to evaluate for such urinary tract abnormalities and, if needed, resolve those conditions to prevent recurrent infection. This review will describe the urologists’ evaluation and management of complicated and recurrent UTI and inform physician about the urinary tract abnormalities that can predispose to recurrent UTI.

Urinary tract infections during pregnancy are associated with severe complications. Earlier initiation of antibiotic treatment for acute uncomplicated cystitis, reduces the various complications.Objective. To assess the effectiveness of fosfomycin in the treatment of acute uncomplicated cystitis during II and III trimester of pregnancy.Material and methods. The study included 74 pregnant women who had acute uncomplicated cystitis in II or III trimesters. All patients received fosfomycin trometamol 3.754 g (equivalent to 3 g fosfomycin) as antimicrobial therapy for acute uncomplicated cystitis. The drug was prescribed to 24 pregnant women in the II, and 50 in the III trimester of pregnancy.Results. After treatment with fosfomycin signs of acute cystitis gone in all patients. At the same time, regression of clinical symptoms was noted during the next days after therapy in 95.9% (n = 71) of cases. Repeated microbiological test of the middle portion of urine was performed 7 days after the end of antibiotic therapy. In 94.6% (n = 70) cases, total elimination of the pathogen was achieved. In 5.4% (n = 4) cases, there was a significant decrease of colonization Follow-up for three months showed the absence of recurrence of acute cystitis in all pregnant women who were included in the study.Conclusion. Fosfomycin is a highly effective drug in the treatment of uncomplicated cystitis during pregnancy.

Background: Treatment for urinary tract infections (UTIs) is usually empiric and is based on local antimicrobial resistance data. These data, however, are scarce in low-resource settings. The aim of this study is to determine the impact of antibiotic treatment on clinical and bacteriological outcomes in patients presenting with UTI symptoms to primary care in Harare. Methods: This cohort study enrolled participants presenting with UTI symptoms to 10 primary healthcare clinics in Harare between July 2019 and July 2020. A questionnaire was administered and a urine sample was collected for culture. If the urine culture showed growth of ≥105 colony forming units/mL of a uropathogen, a follow up visit at 7-21 days was conducted. Results: The analysis included 168 participants with a median age of 33.6 years (IQR 25.1-51.4) and of whom 131/168 (78.0%) were female. Effective treatment was taken by 54/168 (32.1%) participants. The urine culture was negative at follow up in 41/54 (75.9%) of participants who took appropriate treatment and in 33/114 (28.9%, p

Objective: Radiation-induced hemorrhagic cystitis (RHC) is an accepted hyperbaric oxygen therapy (HBOT) indication. We aimed to analyze the knowledge and the opinions of urology physicians on HBOT in RHS patients with a survey. Material and Methods: The questionnaires were conducted face to face or online on urology physicians. Results: Seventy-seven urology physicians participated in our study. Physicians have been working for 11 ± 10.5 years in the field of Urology. The 84.4% of our physicians had an average of 0-10 RHC patient administration in a year. However, the majority of the participants stated that they have never referred RHC patients to HBOT. Similarly, 48.1% of the physicians stated that they have insufficient knowledge of HBOT for their specialty. On the other hand, the majority were not sure about the HBOT as an effective treatment option in RHC patients (54.5%), about the cost-effectiveness of HBOT for RHC (66.2%), and the ability of HBOT on shortening the recovery period of RHC patients (49.9%). We observed that physicians who did not have any knowledge on HBOT had statistically significantly lower RHC patient referral rates to HBOT and had more negative opinions on the effectiveness of HBOT in RHC patients (respectively p

Interstitial cystitis is associated with neurogenic inflammation and neuropathic bladder pain. Dual leucine zipper kinase (DLK) expressed in sensory neurons is implicated in neuropathic pain. We hypothesized that neuronal DLK is involved in the regulation of inflammation and nociceptive behavior in cystitis. Mice deficient in DLK in sensory neurons (cKO) were generated by crossing DLK floxed mice with mice expressing Cre recombinase under Advillin promoter. Cystitis was induced by cyclophosphamide (CYP) administration in mice. Nociceptive behavior, bladder inflammation, and pathology were assessed following cystitis induction in control and cKO mice. The role of DLK in CYP-induced cystitis was further determined by pharmacological inhibition of DLK with GNE-3511. Deletion of neuronal DLK attenuated CYP-induced pain-like nociceptive behavior and suppressed histamine release from mast cells, neuronal activation in the spinal cord, and bladder pathology. Mice deficient in neuronal DLK also showed reduced inflammation induced by CYP and reduced c-Jun activation in the dorsal root ganglia (DRG). Pharmacological inhibition of DLK with GNE-3511 recapitulated the effects of neuronal DLK depletion in CYP treatment mice. Our study suggests that DLK is a potential target for the treatment of neuropathic pain and bladder pathology associated with cystitis.

Recurrent urinary tract infections (RUTI) are one of the most common manifestations of the genitourinary menopausal syndrome and occur in more than 20% of peri- and post-menopausal women. The most common risk factor for RUTI in peri- and post-menopausal women is sex steroid deficiency. The urinary and genital tracts share a common embryonic origin due to the presence of α- and β-estrogen receptors, progesterone and androgen receptors in all structures of the urogenital tract: lower third of the ureters, urinary bladder, vascular plexus, urothelium, pelvic floor muscles, pelvic ligamentous apparatus. Patients with RUTI are treated in two stages: treatment of exacerbations and prevention of relapses. During exacerbations, short courses of antibiotic therapy are administered according to the sensitivity of the bacterial agent. If microbiological testing of urine samples is not possible, antibiotics are selected empirically, taking into account the most common pathogens of a UTI. Vaccine prophylaxis is the leading method of preventing a UTI recurrence. The efficacy and safety of E. coli bacterial extracts have been proven in numerous RCTs. The Uro-Vaxom vaccine reliably reduces the incidence of cystitis recurrence, reduces the need for antibacterial drugs, and therefore improves the quality of life of menopausal women with RUTIs. Vaccine prophylaxis in menopause can be administered as monotherapy or in combination with topical estrogen therapy, which also plays a positive role in the treatment of urinary tract infections.

Pentosan polysulfate (PPS), a small semi-synthetic highly sulfated heparan sulfate (HS)-like molecule, shares many of the interactive properties of HS. The aim of this review was to outline the potential of PPS as an interventional therapeutic protective agent in physiological processes affecting pathological tissues. PPS is a multifunctional molecule with diverse therapeutic actions against many disease processes. PPS has been used for decades in the treatment of interstitial cystitis and painful bowel disease, it has tissue-protective properties as a protease inhibitor in cartilage, tendon and IVD, and it has been used as a cell-directive component in bioscaffolds in tissue engineering applications. PPS regulates complement activation, coagulation, fibrinolysis and thrombocytopenia, and it promotes the synthesis of hyaluronan. Nerve growth factor production in osteocytes is inhibited by PPS, reducing bone pain in osteoarthritis and rheumatoid arthritis (OA/RA). PPS also removes fatty compounds from lipid-engorged subchondral blood vessels in OA/RA cartilage, reducing joint pain. PPS regulates cytokine and inflammatory mediator production and is also an anti-tumor agent that promotes the proliferation and differentiation of mesenchymal stem cells and the development of progenitor cell lineages that have proven to be useful in strategies designed to effect repair of the degenerate intervertebral disc (IVD) and OA cartilage. PPS stimulates proteoglycan synthesis by chondrocytes in the presence or absence of interleukin (IL)-1, and stimulates hyaluronan production by synoviocytes. PPS is thus a multifunctional tissue-protective molecule of potential therapeutic application for a diverse range of disease processes.

Urinary tract infections (UTIs) are one of childhood’s most common bacterial infections. The study aimed to determine the clinical symptoms, laboratory tests, risk factors, and etiology of different UTIs in children admitted to pediatric hospitals for three years. Methods: Patients with positive urine cultures diagnosed with acute pyelonephritis (APN) or cystitis (CYS) were analyzed for clinical symptoms, laboratory tests, risk factors, and etiology, depending on their age and sex. Results: We studied 948 children with UTIs (531 girls and 417 boys), with a median age of 12 (IQR 5–48 months). A total of 789 children had clinical symptoms; the main symptom was fever (63.4% of patients). Specific symptoms of UTIs were presented only in 16.3% of patients. Children with APN had shown significantly more frequent loss of appetite, vomiting, lethargy, seizures, and less frequent dysuria and haematuria than children with CYS. We found significantly higher median WBC, CRP, and leukocyturia in children with APN than with CYS. The risk factors of UTIs were presented in 46.6% of patients, of which 35.6% were children with APN and 61.7% with CYS. The main risk factor was CAKUT, more frequently diagnosed in children with CYS than APN, mainly in children E. coli in girls than in boys. Other bacteria found were Klebsiella species, Pseudomonas aeruginosa, Proteus mirabilis, and Enterococcus species. Conclusions: Patients with APN were younger and had higher inflammatory markers. Often, fever is the only symptom of UTI in children, and other clinical signs are usually non-specific. The most common UTI etiology is E. coli, regardless of the clinical presentation and risk factors.

Tuberculosis is a common infectious disease in developing countries, which can cause a variety of complications and atypical manifestations with high morbidity and mortality. The urogenital form is rarely suspected, resulting in delayed diagnosis or even no diagnosis, which can have serious consequences for the patients, such as chronic endstage renal disease. We report on a patient with chronic endstage renal failure caused by a delayed diagnosis of bilateral renal tuberculosis and a literature review on this topic.

Introduction: Urinary bladder diseases are quite frequent in clinical practices. Both non neoplastic and neoplastic lesions are quite common. Bladder malignancies are on an increasing incidence and are considered as an important cause of cancer related morbidity and mortality. To provide accurate diagnosis and treatment histopathology remains as the gold standard investigation. Aim: To study the histomorphology of lesions of bladder obtained through Trans Urethral Resection of Bladder Tumour (TURBT) and cystoscopic biopsies. Materials and Methods: The present study was a five years descriptive retrospective study conducted over a period of six months starting from July 2020 to December 2020 and data were collected from records for the period of January 2015 to December 2019 carried out in the Department of Pathology, Government Medical College, Trivandrum, Kerala, India. Record of all patients who visited to Urology Outpatient Department (OPD) with lower urinary tract symptoms and obstructive bladder symptoms and subjected to cystoscopy were included in study. The detailed clinico-histomorphological features of all biopsies were studied using World Health Organization (WHO)/ International Society of Urologic Pathologists (ISUP) 2016 histological grading and Tumour (T), Nodes (N), and Metastasis (M) (TNM) staging were used in classifying the bladder tumours. Results: The data for the present study was collected over a period of five years; during which a total of 742 lesions were histopathologically evaluated. A total of 688 cases (92.72%) were neoplastic, 46 cases (6.19%) were diagnosed as non neoplastic and 8 cases were (1.07%) were metastatic malignancy. A total of 646 cases (87.06%) were males. Most common affected age group was 61-80 years. Haematuria was the most common clinical presentation. A 332 cases (48.25%) were of non invasive papillary urothelial neoplasm low grade. Conclusion: Lesions of urinary bladder are heterogenous in nature. Detailed awareness regarding the various histological features of these lesions, their neoplastic potential, risk of recurrence and possible pitfalls can help pathologists for accurate diagnosis. The study also emphasised on inclusion of smooth muscle in the biopsy for accurate grading and staging in bladder tumours.

The urinary tract infection continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy reproductive women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial urinary tract infection. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental investigation.

This review of literature discusses modern data on the diagnosis and treatment of the acute cystitis. Epidemiology and etiology of acute cystitis are described. The basic and alternative treatment protocols for the acute cystitis are presented from the documented medicine viewpoint.

Background: Urinary Bladder lesions are one of the most common presenting lesions in the Outpatient department. On the other hand neoplastic conditions of the urinary bladder are the major cause of morbidity and mortality. Bladder carcinoma is the 7th most common carcinoma worldwide and is the major cause of morbidity and mortality. Material & Methods: All the cystoscopic biopsy received in the Department of Pathology at Nobel medical college and teaching hospital from August 1st 2016 to July 31st 2017 was included in the study. Received cystoscopic biopsies were processed and classified as per 2004 WHO/ISUP classification of urothelial tumors Patients were also categorized according to the age and sex to find out the prevalence of urothelial lesions on them. Results: Out of the 78 patients 54 were males and 24 were females. Very few (n=15, 19.23%) cases of non neoplastic lesions were biopsied. Low grade urothelial carcinoma was the most common diagnosis in the patients which accounts for 49.2 % (n=31) of the total neoplastic conditions. Conclusion: Low grade urothelial carcinoma was the most common lesion encountered with the peak age range of 61-70 years. Journal of Nobel Medical College Volume 7, Number 1, Issue 12, January-June 2018, Page: 6-10

Urinary tract infections (UTIs) are common in childhood and represent approximately 10% of hospital-acquired infections. It is clinically challenging to distinguish cystitis (lower UTI) from pyelonephritis (upper UTI) in those younger than two years. Most UTI patients can however be safely managed as outpatients if diligent follow-up procedures are in place. Recurrent UTIs in children may indicate malfunction or an anatomical defect of the urinary tract, and require specialised diagnostic studies. The proper approach for a child with UTI remains controversial, and treatment often differs according to regional or institutional empirical guidelines.

Urinary tract infection (UTI) is one of the most frequent problems in children, especially early age. A practicing pediatrician, pediatric urologist, nephrologist is frequently faced with the problem of diagnosis and treatment of UTI. Clinical manifestations of UTI in children are diverse and depend on the age and sex of child, severity of the inflammatory process, presence and nature of comorbidity. The experts dealing with the problem of UTI in children in different countries initiated the establishment of clinical guidelines that can assist clinicians in the diagnosis and treatment of UTI in children. The paper presents national European recommendations for the treatment and diagnosis of UTI in pediatrics.

Abstract Background The aim of this study was to investigate the effect of the herbal medicine Canephron®N, particularly regarding its ability to prevent recurrences of cystitis, associated with E.Coli in women of child-bearing age. Methods Ninety patients were randomised into two treatment groups. Both, the test group (n = 45) and the control group (n = 45), received an antibacterial therapy (fluoroquinolones) for 7 days determined by urine culture. Furthermore, in both groups general recommendations on preventing cystitis were made (sufficient liquid consumption, avoidance of hypothermia etc.). The test group received an additional Canephron®N therapy for 3 months (2 tablets, three times a day). Control examinations were conducted on day 7 and after 3, 6 and 12 months; or immediately in the case of a recurrent episode. The following cystitis symptoms were recorded at each time point: pain in the bladder, burning and stinging during urination, urinary urgency and frequent urination in small amounts. The criteria for defining a recurrent episode of cystitis were rebound lower urinary tract infection symptoms with pyuria and positive bacteriological urine culture. Results Canephron®N in addition to fluoroquinolones helps to reduce cystitis symptoms after 7 days better compared to treatment with fluoroquinolones only, as well as pyuria after 3, 6 and 12 months and urine levels of E. coli at 3 and 12 months. The frequency rate of recurrent episodes of cystitis was in the test group always lower than in the control group with a statistically significant difference at 6 months (8.9% vs. 17.8%) and at 12 months (15.5% vs. 35.5%). At 12 months, the mean score of the LUTI Symptom Severity Index was 6 (p ≤ 0.05) in the control patients and 3 (p ≤ 0.05) in the test patients. This may indicate that the relapses were less severe in the test group. Conclusion Treatment with the herbal medicine Canephron®N is a novel treatment method of alleviating the symptoms of cystitis and especially for reducing the rate of recurrent cystitis episodes.

Abstract Until recently the generally accepted paradigm implied that urine of healthy people is sterile. In the meantime several studies have established also a microbiome in the bladder with many different species. Whether bacteria cause damage in the bladder depends not only on their virulence, but also on the inflammatory response of the host. Under certain circumstances asymptomatic bacteriuria can even protect from recurrent urinary tract infections (UTI). Some bacteria in the gut microbiome, such as Oxalobacter formigenes, are protective for calcium oxalate stone formation. The rapid rise of bacterial antibiotic resistance also among uropathogens due to wrong and often unreflected use of antibiotics has become a great concern. Instead of combating the pathogens, it appears to be more useful in many cases to treat the inflammatory host reaction - and to preserve the protective bacterial flora. Due to its antiphlogistic, spasmolytic and antinociceptive properties in a pilot study the herbal triad combination - centaury, lovage, and rosmary leaves (CLR (Canephron® N (Bionorica SE, Neumarkt, Germany))) – showed very good results in the treatment of acute uncomplicated cystitis. In the meantime a phase 3 study with CLR in comparison with fosfomycin trometamol has started. Analysing microbiome profiles in mice showed that even a single dose of fosfomycin as well as daily application of nitrofurantoin resulted in massive microbiome shifts, whereas phytotherapy with CLR largely preserved the gut microbiota.

The study evaluated the quality of life and incidence of recurrent cystitis in perimenopausal women who had received the first course of herbal vitamin complex 5 years ago, followed by the annual two-month course (twice a year). The initial study included 29 patients of which 18 were followed-up. The patients completed a special questionnaire which focused on the degree of dysuria, dyspareunia (only in patients who had sexual intercourse) and quality of life with respect to the urogenital problems which occurred 5 years back when the study was undertaken. Additionally, outpatient medical records and history were analyzed to confirm the incidence of recurrent cystitis over the past 5 years.

Traditionally, the diagnostic mainstay of recurrent urinary tract infection has been urinary culture. However, the causative uropathogen of recurrent cystitis has not been well established. Urine DNA next-generation sequencing (NGS) can provide additional information on these infections. Herein, we compared urine NGS results and urine cultures in patients with acute uncomplicated cystitis (AUC) and recurrent cystitis (RC), and evaluated the difference in microbiome patterns in the NGS results. Patients who underwent urine culture and NGS due to AUC or RC were retrospectively reviewed. All urine samples were collected via a transurethral catheter and studied utilizing a type of NGS called 16S ribosomal RNA gene amplification and sequencing. The sensitivity of urine NGS was significantly higher than that of conventional urine culture (69.0% vs. 16.7%, p < 0.05). The detection rate of urine NGS was slightly lower in the RC group than in the AUC group (67.7% vs. 72.7%). Microbiome diversity was significantly higher in the RC group compared to the AUC group (p = 0.007), and the microbiome composition was significantly different between the AUC and RC groups. In the urine NGS results, Pseudomonas, Acinetobacter, and Enterobacteriaceae were found in the AUC group, and Sphingomonas, Staphylococcus, Streptococcus, and Rothia spp. were detected in the RC group. Urine NGS can significantly increase the diagnostic sensitivity compared to traditional urine culture methods, especially in RC patients. AUC and RC patients had significant differences in bacterial diversity and patterns. Therefore, recurrent cystitis might be approached from a different perspective.

Background: Pyelonephritis is the most common bacterial infection in children that can cause renal failure if not diagnosed or treated early. We used serum biomarker interleukins (IL-6 and IL-8) and then confirmed the results by the findings dimercaptosuccinic acid (DMSA) scan to distinguish upper-tract infection from lower-tract infection. Methods: Serum IL-6 and IL-8 were measured in 57 children with newly diagnosed untreated urinary tract infection (UTI) documented by a positive urine culture. All children had a DMSA to determine whether serum IL6, IL-8 can be used as a marker to predict upper-tract from lower-tract infection. IL-6 and IL8 were determined by the enzyme link immunosorbent assay (ELISA) technique. Results: Of the 57 patients, 24 (42%) had renal parenchymal lesions on the DMSA scan. Patients with abnormal DMSA had significantly higher serum IL-6 and IL-8 compared with those with normal DMSA scan (187.1 ± 113.1 ng/mL vs. 396.1 ± 246.0 ng/mL, P = 0.005; and 165 ± 76.1 ng/mLvs. 190.8 ± 60.8 ng/mL, P = 0.026, respectively). Pyelonephritis was more frequent in children younger than 20 months old (n = 36, 63%, P < 0.005) and more prevalent in girls (n = 36, 63%, P = 0.005). Serum IL-6 had a sensitivity of 67.3% and a specificity of 63.0% and serum IL8 had a sensitivity of 80.1% and a specificity of 73.5% in the differential diagnosis of pyelonephritis and cystitis (P = 0.03). Conclusions: Serum levels of IL-6 and IL-8 are both sensitive biomarkers of UTI and can discriminate the upper from lower tract urinary infections. Determination of these biomarkers may help to identify patients with acute pyelonephritis and need for DMSA study.

Urinary tract infection (UTI) is a common pathology among children, especially infants. [1] Clinical manifestations of UTI are varied and depend on the severity of the inflammatory process, age, sex and the nature of comorbidities. UTI is a collective term that unites all infectious and inflammatory diseases of the urinary system. Only a comprehensive nephrological examination and determination of the level of damage to the urinary system allow to make a more accurate diagnosis (pyelonephritis, cystitis, urethritis, abacterial leukocyturia).