[The effect of a medicinal plant preparation on the frequency of episodes of exacerbation of recurrent cystitis and metabolic parameters in patients with type 2 diabetes mellitus taking glyphlosins].

BACKGROUND: The problem of recurrent urinary tract infections (UTI) in patients with type 2 diabetes mellitus (DM 2) is relevant, especially when there is a combination of predisposing factors, such as female gender, history of UTI episodes, and therapy with sodium glucose cotransporter type 2 (SGLT-2) inhibitors, and the choice of effective and safe means could cause some difficulties, including ina terms of the burden of antibiotic resistance. AIM: To evaluate the effectiveness and safety of the phytoproduct Canephron® N for the prevention of exacerbations of recurrent cystitis and the effect on metabolic parameters in patients with type 2 diabetes taking SGLT-2 inhibitors. MATERIALS AND METHODS: Prospective, randomized, open, parallel group study in 60 women. The main group took the drug Canephron® N for 3 months. The main parameters for evaluating were the frequency of recurrence of cystitis, level of albuminuria and LDL-cholesterol peroxidation product - malondialdehyde. RESULTS: Within 3 months of taking Canephron® N, exacerbations of chronic cystitis were diagnosed 2 times less often, a decrease in albuminuria was found in the form of an increase in the proportion of patients with an optimal level of albuminuria by 20%, a 50% reduction in the frequency of the initial increase in albuminuria, and the absence of moderate albuminuria in all patients at the end of course of therapy. A decrease in the level of MDA by 1.4 times was noted (p=0.019). CONCLUSION: Thus, the herbal drug Canephron® N can be used for accompanying therapy and prophylactic treatment in patients with recurrent cystitis on the background of DM 2, taking SGLT-2 inhibitors. The course of therapy should last at least 3 months.

Algorithms to Enhance Empiric Antimicrobial Choice for Outpatients With Afebrile Complicated Cystitis Reflects Importance of Status of the Urinary Tract and Patient Place of Residence.

OBJECTIVE: To determine predictive factors for antimicrobial resistance patterns and to develop an antimicrobial treatment algorithm for afebrile outpatients presenting with complicated cystitis. MATERIALS AND METHODS: We performed a retrospective, single-center, cross-sectional study of 2,891 outpatients with a diagnosed afebrile complicated cystitis from 2012 to 2018. For patients with confirmed urinary tract infection and antimicrobial sensitivities, univariate analyses and multivariable regression models were used to determine odds ratios for predicting resistance to trimethoprim-sulfamethoxazole, ciprofloxacin, nitrofurantoin, first-generation cephalosporin, and third-generation cephalosporin for the 2012-2016 data. Antimicrobial choice algorithms were created using 2012-2016 results and tested on 2017-2018 data. RESULTS: For afebrile outpatients presenting with complicated cystitis, overall prevalence of resistance for trimethoprim-sulfamethoxazole, ciprofloxacin, nitrofurantoin, first-generation cephalosporin, and third-generation cephalosporin was 25.6%, 19.5%, 19.1%, 15.0%, and 6.9%, respectively. Consistent predictive factors influencing resistance to all 5 antimicrobials were patient place of residence (ZIP code), status of host urinary tract (complicated vs uncomplicated), and prior resistance to the antimicrobial. Resulting treatment algorithm for complicated cystitis (whether or not prior microbiologic data was available) outperformed real-life provider choice and our previously published algorithm for uncomplicated cystitis. CONCLUSION: Treatment algorithms for urinary tract infections are dependent on patient place of residence (ZIP code), status of the host urinary tract (complicated or uncomplicated), and prior urine culture resistance data. When using our complicated cystitis treatment algorithm regardless of uropathogen, our results outperformed real-life scenario provider choice and our prior published algorithm for uncomplicated cystitis, which can help guide empiric antimicrobial choice.

Normalization of magnesium deficiency attenuated mechanical allodynia, depressive-like behaviors, and memory deficits associated with cyclophosphamide-induced cystitis by inhibiting TNF-α/NF-κB signaling in female rats.

BACKGROUND: Bladder-related pain symptoms in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) are often accompanied by depression and memory deficits. Magnesium deficiency contributes to neuroinflammation and is associated with pain, depression, and memory deficits. Neuroinflammation is involved in the mechanical allodynia of cyclophosphamide (CYP)-induced cystitis. Magnesium-L-Threonate (L-TAMS) supplementation can attenuate neuroinflammation. This study aimed to determine whether and how L-TAMS influences mechanical allodynia and accompanying depressive symptoms and memory deficits in CYP-induced cystitis. METHODS: Injection of CYP (50 mg/kg, intraperitoneally, every 3 days for 3 doses) was used to establish a rat model of BPS/IC. L-TAMS was administered in drinking water (604 mg·kg-1·day-1). Mechanical allodynia in the lower abdomen was assessed with von Frey filaments using the up-down method. Forced swim test (FST) and sucrose preference test (SPT) were used to measure depressive-like behaviors. Novel object recognition test (NORT) was used to detect short-term memory function. Concentrations of Mg2+ in serum and cerebrospinal fluid (CSF) were measured by calmagite chronometry. Western blot and immunofluorescence staining measured the expression of tumor necrosis factor-α/nuclear factor-κB (TNF-α/NF-κB), interleukin-1ß (IL-1ß), and N-methyl-D-aspartate receptor type 2B subunit (NR2B) of the N-methyl-D-aspartate receptor in the L6-S1 spinal dorsal horn (SDH) and hippocampus. RESULTS: Free Mg2+ was reduced in the serum and CSF of the CYP-induced cystitis rats on days 8, 12, and 20 after the first CYP injection. Magnesium deficiency in the serum and CSF correlated with the mechanical withdrawal threshold, depressive-like behaviors, and short-term memory deficits (STMD). Oral application of L-TAMS prevented magnesium deficiency and attenuated mechanical allodynia (n = 14) and normalized depressive-like behaviors (n = 10) and STMD (n = 10). The upregulation of TNF-α/NF-κB signaling and IL-1ß in the L6-S1 SDH or hippocampus was reversed by L-TAMS. The change in NR2B expression in the SDH and hippocampus in the cystitis model was normalized by L-TAMS. CONCLUSIONS: Normalization of magnesium deficiency by L-TAMS attenuated mechanical allodynia, depressive-like behaviors, and STMD in the CYP-induced cystitis model via inhibition of TNF-α/NF-κВ signaling and normalization of NR2B expression. Our study provides evidence that L-TAMS may have therapeutic value for treating pain and comorbid depression or memory deficits in BPS/IC patients.

Impairment of cholinergic bladder contractility in rat model of type I diabetes complicated by cystitis: Contribution of neurotransmitter-degrading ectoenzymes.

Parasympathetic regulation of urinary bladder contractions primarily involves acetylcholine release and activation of detrusor smooth muscle (DSM) muscarinic acetylcholine (mACh) receptors. Co-release of ATP and activation of DSM purinergic P2X1-receptors may participate as well in some species. Both types of neuromuscular transmission (NMT) are impaired in diabetes, however, which factors may contribute to such impairment remains poorly understood. Here by using rats with streptozotocin(STZ)-induced type I diabetes (8th week after induction) we show that contribution of atropine-sensitive m-cholinergic component to the contractions of urothelium-denuded DSM strips evoked by electric field stimulation (EFS) greatly increased when diabetic bladders presented overt signs of accompanying cystitis. Modeling of hemorrhagic cystitis alone in control rats by cyclophosphamide injection only modestly increased m-cholinergic component of EFS-contractions. However, exposure of DSM strips from control animals to acetylcholinesterase (AChE) inhibitor, neostigmine (1-10 µM) largely reproduced alterations in EFS contractions observed in diabetic DSM complicated by cystitis. Ellman's assay revealed statistically significant 31% decrease of AChE activities in diabetic vs. control DSM. Changes in purinergic contractility of diabetic DSM were consistent with altered P2X1-receptor desensitization and re-sensitization. They could be mimicked by pharmacological inhibition of ATP-degrading ecto-ATPases with ARL 67156 (50 µM), pointing to compromised extracellular ATP clearance as underlying reason. We conclude that decreased AChE activities associated with diabetes and likely cystitis provide complementary factor to the described in literature altered expression of mACh receptor subtypes linked to diabetes as well as to cystitis to produce dramatic modification of cholinergic NMT.

The standardized herbal combination BNO 2103 contained in Canephron® N alleviates inflammatory pain in experimental cystitis and prostatitis.

BACKGROUND: Urinary tract infections are among the most common types of infections and give rise to inflammation with pain as one of the main symptoms. The herbal medicinal product Canephron® N contains BNO 2103, a defined mixture of pulverized rosemary leaves, centaury herb, and lovage root, and has been used in the treatment of urinary tract infections for more than 25 years. PURPOSE: To test the hypothesis that BNO 2103 reduces pain in cystitis and prostatitis by virtue of anti-inflammatory properties, and to reveal potential mechanisms underlying the anti-inflammatory features. STUDY DESIGN: BNO 2103 was studied for anti-inflammatory and analgesic properties in three animal models in vivo, and the mode of action underlying the anti-inflammatory features was investigated in human leukocytes and cell-free assays in vitro. METHODS: To assess the anti-inflammatory and analgesic efficacy of BNO 2103 we employed cyclophosphamide-induced cystitis and carrageenan-induced prostatitis in rats, and zymosan-induced peritonitis in mice. Human neutrophils and monocytes as well as isolated human 5-lipoxygenase and microsomal prostaglandin E2 synthase-1-containing microsomes were utilized to assess inhibition of leukotriene and/or prostaglandin E2 production by HPLC and/or ELISA. RESULTS: When given orally, BNO 2103 reduced inflammation and hyperalgesia in experimental cystitis in rats, while individual components of BNO 2103 also reduced hyperalgesia. Furthermore, BNO 2103 reduced hyperalgesia in rats with carrageenan-induced prostatitis. Cell-based and cell-free studies implicate inhibition of prostaglandin E2 and leukotriene B4 biosynthesis as potential mechanisms underlying the analgesic and anti-inflammatory effects. CONCLUSION: Our data support the hypothesis that BNO 2103 reduces pain by virtue of its anti-inflammatory properties, possibly related to suppression of prostaglandin E2 and leukotriene B4 formation, and suggest that this combination has the potential to treat clinical symptoms such as inflammatory pain. Thus BNO 2103 may represent an alternative to reduce the use of antibiotics in urinary tract infections.

Hyperbaric oxygen significantly improves frequent urination, hyperalgesia, and tissue damage in a mouse long-lasting cystitis model induced by an intravesical instillation of hydrogen peroxide.

AIM: To investigate whether hyperbaric oxygen (HBO) is effective for the pathophysiological findings in an IC/PBS-like mouse model induced by intravesical hydrogen peroxide (H2 O2 ). METHODS: Six-week-old ICR female mice (N = 16) were divided into four experimental groups: (1) sham control with intravesical vehicle instillation twice, and without subsequent treatment (N = 4); (2) H2 O2 instillation twice, followed by HBO (100% O2 , 2 ATA, 30 min per session) (N = 4); (3) H2 O2 instillation twice, followed by dummy hyperbaric treatment (air, 2ATA, 30 min per session) (N = 4); and (4) H2 O2 instillation twice, followed by no treatment (N = 4). Body weight, voiding frequency, tidal voiding volume, and individual bladder pain threshold using the von-Frey test were measured. Whole body uptake of an inflammation-specific fluorescent pan-cathepsin was assessed by an in vivo imaging. Immunohistochemical staining and the mRNA expression of several biomarkers associated with chronic inflammation in resected bladders were evaluated. RESULTS: The HBO-treated group showed significant improvement in voiding frequency, tidal voiding volume, and the individual bladder pain threshold. Moreover, HBO markedly suppressed H2 O2 -induced inflammation, edema, and fibrosis in bladder wall, concomitant with a significant decrease in mRNA expressions of inflammation biomarkers and a significant increase in endothelial nitric oxide synthase expression. HBO also inhibited the expression of transient receptor potential channels induced by H2 O2 instillation. CONCLUSION: These results suggest that HBO contributes to elimination of H2 O2 -induced long-lasting cystitis through the repair of chronically inflamed bladder tissue and inhibition of the bladder sensory system.

[NefroCAPS phytolysin in complex management of women with chronic recurrent cystitis].

RELEVANCE: Recurrent lower urinary tract infections (UTI) in women are one of the most challenging problems of modern urology, which is associated both with their high incidence and increasing resistance of uropathogens to antibacterial drugs. Due to this fact, the phytotherapy of infectious and inflammatory diseases of the urinary tract has received increased attention. AIM: To investigate the effectiveness of Phytolysin nefroCAPS in the complex management of women with chronic recurrent cystitis. MATERIALS AND METHODS: 50 women with chronic recurrent cystitis underwent a complex examination. They were divided into two groups depending on the treatment they received. Patients of the 1st group (n=27) received a combination therapy: fosfomycin (monural) 3 g (single dose) and Phytolysin nefroCAPS one capsule three times daily for three months. Patients of the 2nd group (n=23) were administered a single 3-g dose of fosfomycin (monural). RESULTS: Follow-up examinations were performed 1, 3 and six months after initiation of the treatment. In patients of the 1st group, clinical manifestations of the disease disappeared earlier, and they had fewer recurrences than the patients of the 2nd group. Also, bacteriological study of urine showed a more persistent antimicrobial effect among patients of the 1st group. CONCLUSION: In patients with chronic recurrent cystitis, plant-based preparation Phytolysin nefroCAPS administered concurrently with an antibacterial drug is more effective than antibiotic monotherapy.

[Experience of using phytolysin in combination therapy of chronic cystitis in patients with urate nephrolythisis].

AIM: To evaluate the effectiveness of the herbal preparation Phytolysin in the comprehensive management of urate nephrolithiasis against the background of chronic cystitis exacerbation. MATERIALS AND METHODS: The study comprised 21 patients aged 19 to 57; 11 of them (the study group) received ciprofloxacin 500 mg once daily for 7 days, Phytolysin (for 1 month) and Blemaren (for 3 months), while 10 patients of control group were treated with antibacterial therapy and Blemaren. The clinical evaluation of the patients included laboratory testing and ultrasound imaging. RESULTS: The combination therapy resulted in a decrease in leukocyturia and bacteriuria. There was no tendency to relapse. The occurrence of relapse was identified by dysuria, urgent and frequent urination, suprapubic pain and results of laboratory testing (leukocyturia, bacteriuria >103) on days 15, 29, 57, 85 and 112 of the study. CONCLUSIONS: The findings suggest that the use of Phytolysin can be an effective and safe way to prevent exacerbation of chronic cystitis in patients with urate nephrolithiasis.

[Troyakov. Experience in using hytolysin in the integrated management of urinary tract infections and methapylactics of nephrolithiasis].

RELEVANCE: Urinary tract infection (UTI) are a risk factor for diseases leading to impairment of renal function and kidney stone disease (KSD). Growing resistance of uropathogens to antibacterial agents is a challenging issue in most countries of the world. Urolithiasis is the second most prevalent urologic condition following urinary tract infections and has a pronounced tendency to recur. Rational stone metaphylaxis leads to a significant reduction in the incidence of recurrent stones. In recent decades, there has been a markedly increasing interest in plant-based therapies in managing urologic diseases. AIM: To evaluate the effectiveness of phytotherapeutic medication Phytolysin in the integrated management of UTI and metaphylaxis of urolithiasis. MATERIALS AND METHODS: Comprehensive evaluation of the effectiveness of Phytolysin was conducted at the Department of Urology, I.M. Sechenov First MSMU and Department of Urology, Andrology and Sexology, Voino-Yasenetsky Krasnoyarsk SMU in 40 women with episodes of exacerbation of chronic cystitis and 30 patients of both sexes during the postoperative metaphylaxis of the KSD. The age of the patients ranged from 20 to 68 years (mean age 40+/-2,8 years). RESULTS: Adding Phytolysin to the integrated management results in the improvement in general clinical signs and laboratory parameters of blood and urine, leads to a decrease in the level of leukocyturia, bacteriuria and an increase in diuresis and urinary alkalinization, reduces the number relapses of UTI and stone formation. CONCLUSION: Phytolysin is an effective and safe medication.

[Prognostic factors of hyperbaric oxygen therapy in hemorrhagic radiation cystitis]. / Facteurs pronostiques d'efficacite de l'oxygénothérapie hyperbare dans le cadre de la cystite radique hemorragique.

OBJECTIVE: To emphasize prognostic factors of hyperbaric oxygen therapy (HBOT) on hematuria at 3 and 12 months in the context of a radiation cystitis. MATERIAL AND METHODS: A cohort of 134 patients was treated from 2008 to 2013 in the hyperbaric medicine center of Toulouse University Hospital, France for radiation cystitis. Hematuria was ranked using the SOMA score. HBOT has been applied according to a standardized protocol of 20 renewable sessions, with pure oxygen to 2.5 ATA. The median number of sessions at 12 months was 50. RESULTS: HBOT had an efficacy of 83% at 3 months and 81% at 12 months. Twenty percent of patients had minor side effects. Compared to the pre-HBOT period, the number of hospitalizations decreased by 75% following treatment. The efficacy at 3 months was predictive of efficacy at 12 months (P<0.0001). There was an inverse correlation between the initial grade and efficacy at 3 months (P=0.026) and 12 months (P=0.001). A high WHO status diminished HBOT efficacy at 3 and 12 months (P=0.0014 and P<0.0001, respectively). An anticoagulant intake decreased the HBOT response at 12 months (P=0.002). Other parameters had no effects on efficacy. CONCLUSION: The efficacy at 3 months seems to be predictive of efficacy at 12 months. The initial hematuria grade is inversely correlated with efficacy at 3 and 12 months. It appears necessary to achieve at least 32 HBOT sessions. Moreover, a high WHO status and an anticoagulant intake seem to have a negative prognostic value. LEVEL OF EVIDENCE: 4.

Cidofovir / Cidofovir

INTRODUCCIÓN: La cistitis hemorrágica (HC) es una complicación grave del trasplante de células madre hematopoyéticas (HSCT) y presenta una incidencia variable del 7 al 70%(1). Generalmente, la HC es una complicación dolorosa que prolonga la internación, aumenta el requerimiento de transfusiones de sangre y en sus formas severas puede causar obstrucción del tracto urinario. La ocurrencia de HC ha sido asociada con mayor mortalidad. Los factores predisponentes, incluyen: HSCT alogénico, edad avanzada en el trasplante, enfermedad de injerto contra huésped (GVHD), trombocitopenia, coagulopatía e infección viral. Las HC se clasifican en dos tipos: (1) inicio temprano, que ocurre dentro de las primeras 48 a 72 horas después de HSCT y generalmente debido a los efectos tóxicos de la quimioterapia; (2) inicio tardío, ocurre luego de 72 horas, usualmente de causa infecciosa, particularmente el virus BK (BKV)(2). La HC asociada al virus BK (BKV-HC) es una complicación frecuente luego de un trasplante alogénico de células hematopoyéticas. De acuerdo a su presentación clínica, se clasifica en diferentes grados de severidad: Grado I: Hematuria microscópica; Grado II: Hematuria macroscópica; Grado III: Hematuria macroscópica con presencia de coágulos en orina; Grado IV: Hematuria macroscópica con presencia de coágulos en orina y alteración de la función renal secundaria a obstrucción de las vías urinarias. TECNOLOGÍA: El cidofovir es un nucleósido análogo de citosina activo contra varios virus ADN. Ejerce una inhibición selectiva en la síntesis de ADN, suprimiendo la replicación viral. La EMA (European Medicines Agency) y la FDA (Food and Drug Administration) lo aprobaron para el tratamiento de la retinitis por citomegalovirus en adultos con síndrome de inmunodeficiencia adquirida y sin alteración de la función renal. El cidofovir causa nefrotoxicidad con daño a células tubulares proximales y aumento de la creatinina sérica. La nefrotoxicidad es muy frecuente y es dosis dependiente. La mayoría de las veces se recomienda la asociación con Probenecid vía oral para mantener una concentración plasmática útil de cidofovir que permita su administración semanal, disminuyendo la penetración y acumulación del cidofovir en las células renales y así atenuar su nefrotoxicidad. La modalidad de tratamiento varía en dosis y vías de administración. La vía intravesical se usa en casos de viruria con baja viremia y daño renal previo, aunque su efectividad es cuestionada. Por vía endovenosa, se usa en una dosis variable de 0,5 a 5 mg/kg, una o dos veces por semana. La elección de dosis y frecuencia depende de la severidad del cuadro y fundamentalmente, de la nefrotoxicidad. OBJETIVO: Evaluar la eficacia y seguridad de cidofovir en la HC por BK virus post HSCT. DISCUSIÓN: El cidofovir constituye una tecnología sanitaria experimental para el tratamiento de la HC-BKV. Se han utilizado diferentes dosis y vías de administración. La evidencia disponible sugiere que su eficacia para el tratamiento oscila entre el 60 y 100%. En el diseño de los estudios se constata que sólo en uno fue comparado vs tratamiento convencional pero fue un estudio descriptivo de dos grupos independientes. En este estudio, el cidofovir no fue superior en respuesta clínica ni en duración de la HC. La respuesta clínica de la HC en cuanto a disminución de hematuria, eliminación de coágulos y disuria, no siempre correlaciona con una significativa disminución de la carga viral en sangre o en orina. La mitad de los pacientes pos-trasplante presenta viruria y no desarrollan HC. Este aspecto no permite definir con absoluta certeza el grado de responsabilidad del virus ni del cidofovir en el desarrollo de la HC y su tratamiento. Se describen varios eventos adversos pero el más importante y serio, es la nefrotoxicidad que se relaciona con las dosis utilizadas y la duración del tratamiento. La función renal basal y la viruria/viremia deben ser tenidas en cuenta en la prescripción y vía de administración del cidofovir. Los criterios de elección de la ruta de administración local o sistémica no fueron expresamente definidos pero se relacionan con la ubicación del virus, la nefrotoxicidad y la función renal previa. El contexto peri-trasplante agrega varios tratamientos potencialmente nefrotóxicos que se suman al cidofovir y a la nefropatía derivada de la obstrucción urinaria por HC, lo que impone la necesidad de un extremo cuidado para la función renal. RECOMENDACIONES: El cidofovir es una opción terapéutica en el tratamiento de la HC-BKV y requiere control estricto de la función renal dado el alto riesgo de nefrotoxicidad. Es por ahora un tratamiento experimental. Su uso adecuado y en ámbito adecuado, es de estricta responsabilidad del médico tratante.

Hemostatic Efficacy and Histopathological Effects of Ankaferd Blood Stopper in an Experimental Rat Model of Cyclophosphamide-induced Hemorrhagic Cystitis.

OBJECTIVE: To evaluate the hemostatic efficacy and histopathological effects of Ankaferd Blood Stopper (ABS) in an experimental rat model of cyclophosphamide-induced (CYP) hemorrhagic cystitis (HC). MATERIALS AND METHODS: Forty male Sprague-Dawley rats were included in the study. Firstly, 10 rats were divided equally into 2 groups where the first group was administered only an intraperitoneal (i.p.) injection of normal saline to constitute the negative control group (CON). The remaining 5 rats were administered only a single i.p. injection of CYP (without any further treatment) for induction of HC to constitute the positive control group (HC). Subsequently, the remaining 30 rats, which also received i.p. CYP for induction of HC, were divided into 3 groups to which intravesical saline (SAL group), epinephrine (EPN group), and ABS (ANK group) were administered for 3 consecutive days. Ten days after the third instillation, cystectomy was performed for histopathological examination. Specimens were evaluated for presence of congestion, edema, necrosis, ulceration, and regenerated epithelium, and scores were given for each parameter according to the severity. RESULTS: No statistically significant difference was observed for congestion, edema, necrosis, and ulceration between HC-SAL, and also between CON-ANK groups (all P values >.05). There was a significant difference for total scores between EPN and ANK groups (P = .009). There was statistically significant difference for regenerating epithelium between CON-EPN, CON-ANK, HC-ANK, and SAL-ANK groups. CONCLUSION: Intravesical administration of ABS is at least as efficacious as EPN in terms of congestion, edema, necrosis, and ulceration. Moreover, ABS can be considered as a better option in inducing regenerating epithelium than EPN.

Omega-3 fatty acids are able to modulate the painful symptoms associated to cyclophosphamide-induced-hemorrhagic cystitis in mice.

This study investigated the effects of the long-term dietary fish oil supplementation or the acute administration of the omega-3 fatty acid docosahexaenoic acid (DHA) in the mouse hemorrhagic cystitis (HC) induced by the anticancer drug cyclophosphamide (CYP). HC was induced in mice by a single CYP injection (300mg/kg ip). Animals received four different diets containing 10% and 20% of corn or fish oil, during 21days. Separated groups received DHA by ip (1µmol/kg) or intrathecal (i.t.; 10µg/site) routes, 1h or 15min before CYP. The behavioral tests (spontaneous nociception and mechanical allodynia) were carried out from 1h to 6h following CYP injection. Bladder inflammatory changes, blood cell counts and serum cytokines were evaluated after euthanasia (at 6h). Immunohistochemistry analysis was performed for assessing spinal astrocyte and microglia activation or GPR40/FFAR1 expression. Either fish oil supplementation or DHA treatment (ip and i.t.) markedly prevented visceral pain, without affecting CYP-evoked bladder inflammatory changes. Moreover, systemic DHA significantly prevented the neutrophilia/lymphopenia caused by CYP, whereas this fatty acid did not significantly affect serum cytokines. DHA also modulated the spinal astrocyte activation and the GPR40/FFAR1 expression. The supplementation with fish oil enriched in omega-3 fatty acids or parenteral DHA might be interesting nutritional approaches for cancer patients under chemotherapy schemes with CYP.

The Quinovic Acid Glycosides Purified Fraction from Uncaria tomentosa Protects against Hemorrhagic Cystitis Induced by Cyclophosphamide in Mice.

Uncaria tomentosa is widely used in folk medicine for the treatment of numerous diseases, such as urinary tract disease. Hemorrhagic cystitis (HE) is an inflammatory condition of the bladder associated with the use of anticancer drugs such as cyclophosphamide (CYP). Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions. It has been demonstrated that the purinergic system is involved in several pathophysiological events. Among purinergic receptors, P2X7 deserves attention because it is involved in HE induced by CYP and, therefore, can be considered a therapeutic target. The objective of this study was to investigate the potential therapeutic effect of the quinovic acid glycosides purified fraction (QAPF) from U. tomentosa in the mouse model of CYP-induced HE. Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1ß levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder. This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy. QAPF represents a promising therapeutic option for this pathological condition.

Improvement by phytotherapeutic agent of detrusor overactivity, down-regulation of pharmacological receptors and urinary cytokines in rats with cyclophosphamide induced cystitis.

PURPOSE: We characterized pharmacological effects of the phytotherapeutic agent Eviprostat® on urodynamic parameters, bladder muscarinic and purinergic receptors, and urinary cytokines in rats with cyclophosphamide induced cystitis. MATERIALS AND METHODS: Urodynamic parameters in cyclophosphamide (150 mg/kg intraperitoneally) treated rats were measured by a cystometric method. Muscarinic and purinergic receptors in the bladder and other tissues were measured by radioreceptor assays using [N-methyl-(3)H]scopolamine methyl chloride and [(3)H]αß-MeATP, respectively. The urinary cytokines interleukin-1ß, 6 and 17 were measured with enzyme-linked immunoassay kits. Eviprostat (36 mg/kg per day twice daily for 7 days) was orally administered. RESULTS: On cystometry the micturition interval and micturition volume were significantly decreased in cyclophosphamide vs sham treated rats, while micturition frequency, basal pressure and post-void residual urine volume were significantly increased. Repeat oral administration of Eviprostat in cyclophosphamide treated rats significantly increased the micturition interval and micturition volume, and decreased micturition frequency, basal pressure and post-void residual urine volume. The maximal number of binding sites for [N-methyl-(3)H]scopolamine methyl chloride and [(3)H]αß-MeATP was significantly decreased in the bladder of cyclophosphamide vs sham treated rats. Such decreases were significantly attenuated by repeat Eviprostat treatment. Increased urinary cytokine levels in cyclophosphamide treated rats were also effectively attenuated by Eviprostat. CONCLUSIONS: Repeat Eviprostat treatment significantly improved detrusor overactivity, down-regulated the expression of bladder pharmacological receptors and increased urinary cytokine levels in rats with cyclophosphamide induced cystitis. Therefore, Eviprostat may be a pharmacologically useful phytotherapeutic agent for cystitis.

Irritation induced bladder overactivity is suppressed by tibial nerve stimulation in cats.

PURPOSE: We investigated the effects of tibial nerve stimulation on bladder overactivity induced by acetic acid irritation. MATERIALS AND METHODS: Cystometry was performed in 10 α-chloralose anesthetized female cats by infusing saline or acetic acid through a urethral catheter that was secured by a ligature around the urethra. Intravesical infusion of 0.25% acetic acid was used to irritate the bladder and induce bladder overactivity. Multiple cystometrograms were done before, during and after tibial nerve stimulation to determine the inhibitory effect on the micturition reflex. RESULTS: Infusion of 0.25% acetic acid irritated the bladder, induced bladder overactivity and significantly decreased bladder capacity to about 20% of control capacity measured during saline infusion. Tibial nerve stimulation at low (5 Hz) or high (30 Hz) frequency significantly increased bladder capacity to about 40% of saline control capacity when it was applied during acetic acid infusion cystometrogram. Bladder contraction amplitude was smaller during acetic acid irritation than during saline distention due to significantly smaller bladder capacity. Tibial nerve stimulation at 5 Hz increased bladder capacity and bladder contraction amplitude. CONCLUSIONS: Activation of somatic afferents in the tibial nerve of cats can partially reverse the bladder overactivity induced by intravesical administration of a chemical irritant that activates C-fiber afferent nerves. These data are consistent with clinical studies showing that tibial nerve neuromodulation is effective treatment for overactive bladder symptoms.

[Intravesical electrostimulation and magnetotherapy in chronic pyelonephritis and cystitis in children with urodynamic disorders].

The results of the treatment of 38 children (6 boys and 32 girls, age 6-14 years) with chronic pyelonephritis and/or cystitis complicated with neurogenic dysfunction of the urinary bladder (NDUB) and/or vesicoureteral reflux (VUR) of the first-third degree demonstrate efficacy of intravesical electrostimulation (IVES) and adrenal magnetotherapy. IVES was conducted with high-frequency current impulses (2.2 kHz) by means of INTRASTIM attachment to the device AMUS-01-INTRAMAG in the region of the urethrovesical anastomosis via solution of the drugs for instillation. As the result of exposure to both physical factors in the presence of standard medication, NDUB symptoms alleviated (by E.L. Vishnevsky's criteria) by 59.5% against 38.1% in the control group. Dopplerographic examination of renal vessels stated a 24.3% increase in blood flow in the major renal artery in the study group against 10.5% in the control. The proposed complex pharmacological plus physiotherapeutic treatment of chronic pyelonephritis and cystitis in abnormal urodynamics resulted in a 2.2-fold decrease in the number of recurrences compared to the standard treatment.

[Efficacy of combined treatment of women with chronic cystitis associated with intracellular infections].

Forty female patients with urethrocystitis received sparfloxacin in a daily dose 400 mg for 20 days in combination with canefron H (50 drops three times a day for 8 weeks). Twenty patients received one more course of canefron H 4 months after etiopathogenetic therapy. The analysis of the treatment results allows the conclusion that sparfloxacin is highly effective in urethrocystitis associated with intracellular infections. Sparfloxacin provides complete urine sterility. 97.5% females after the combined treatment had no recurrences for a year while before the treatment remission lasted for 4.1 +/- 1.7 months. A preventive administration of canefron H improves microcirculation in the bladder wall and prevents recurrence in patients with urethrocystitis associated with intracellular infections given basic sparfloxacin therapy.

[Non-medication treatment of patients with chronic cystitis].

Combined application of ultrasound, modulated sinusoidal currents (MSC), and iodine-bromine baths is known to be a highly efficacious method for the rehabilitative treatment of patients with chronic cystitis in the phase of latent inflammation. The present study has demonstrated that combination of ultrasound with electrotherapeutic sleep and iodine-bromine baths exerts pronounced anti-inflammatory effect and bacteriostatic action whereas modulated sinusoidal currents combined with electrotherapeutic sleep and iodine-bromine baths significantly improve urodynamics in the lower urinary tract and produce marked anesthetic effect. Evaluation of the immediate and long-term results of the treatment of 16 patients presenting with chronic cystitis revealed the absence of exacerbation of infectious and inflammatory processes in the bladder within 6 months after physiotherapy

Cistitis y hematuria por Corynebacterium striatum. A propósito de un caso y revisión de la literatura científica / Cystitis and haematuria due to Corynebacterium striatum. A case report and review

Presentamos un caso de infección del tracto urinario inferior no complicada por Corynebacteriumstriatum en una paciente ambulatoria y sin factores de riesgo predisponentes. C. striatum es una bacteria saprofita de la piel y las mucosas, que se ha relacionado ocasionalmente con la infección en pacientes hospitalizados o inmunodeficientes con enfermedades subyacentes. Concluimos que este microorganismo debe considerarse un patógeno emergente, tanto en pacientes inmunodeficientes como en inmunocompetentes (AU)

We herewith report the first case of uncomplicated urinary tract infection due to Coryne bacterium striatum in an ambulatory patient without any other predisponent risk factors. C. striatum is a ubiquitous saprophyte of human skin and mucous membranes, which has been occasionally associated with infection in patients hospitalized or immunocompromised patients with underlying diseases. We conclude that C. striatum should be considered an emerging pathogen in both immunocompetent and immunocompromised hosts (AU)