Protective potential of pterostilbene against cyclophosphamide-induced nephrotoxicity and cystitis in rats.

PURPOSE: Cyclophosphamide (CYP) is an antitumor drug. However, in addition to its antitumor affect, CYP can also lead to nephrotoxicity and hemorrhagic cystitis. The purpose of this study was to investigate the potential protective effects of Pterostilbene (Pte), a natural antioxidant as a resveratrol analog against CYP-induced nephrotoxicity and cystitis in rats. METHODS: Twenty-one male Sprague Dawley rats were divided into 3 equal groups. The control group and the CYP group (CYPG) received 1 ml/kg sunflower oil per day, and the CYP + Pte group (CYP + PteG) 40 mg/kg per day Pte dissolved in sunflower oil once a day via the oral route for 14 days. In addition, on day 9 of the experiment, CYPG and CYP + PteG received a single dose of 200 mg/kg CYP dissolved in saline solution, while the control group received a single dose of 10 ml/kg saline solution, via the intraperitoneal route. Bladder and kidney tissues were collected for histological and biochemical evaluations. RESULTS: Pte was observed to reduce CYP-derived increases in malondialdehyde level, total oxidant status (TOS), the oxidative stress index (OSI), and apoptosis in kidney tissues and to cause an increase in superoxide dismutase levels. It also reduced CYP-derived increases in TOS, OSI, and apoptosis in bladder tissue. Moreover, Pte also ameliorated histopathological findings associated with CYP-induced tissue damage in both the kidney and bladder. CONCLUSION: Our study findings show that Pte may exhibit a protective effect against CYP-induced nephrotoxicity and cystitis.

[Treatment and prevention of chronic cystitis in women].

AIM: to evaluate the efficiency of the dietary supplement NefroBest in women with chronic cystitis. MATERIALS AND METHODS: On the basis of the Department of Urology and Nephrology of the Altai State Medical University and the urological department of the NUZ CH "RJD Medicine", Barnaul, from September 2019 to August 2020 a total of 40 women with chronic cystitis were treaeted. Depending on the type of treatment, all women were divided into the main and control groups, each of 20 people. In the main group, patients received standard therapy and dietary supplements NefroBest. In the control group, patients were prescribed only to standard therapy. RESULTS: The results were evaluated one and two months after the start of therapy. In the main group a more rapid resolution of symptoms and laboratory abnormalities were seen, as well as an improvement of the endoscopic picture and urodynamic parameters. CONCLUSION: The complex of biologically active substances in the dietary supplement NefroBest has an antimicrobial, anti-inflammatory and antispasmodic effect, and reduces the risk of recurrence of chronic cystitis. Thus, the dietary supplement NefroBest can be recommended as a component of the complex therapy of recurrences of chronic cystitis, as well as a prophylactic treatment during relapse-free period.

Downregulation of redox imbalance and iNOS/NF-ĸB/caspase-3 signalling with zinc supplementation prevents urotoxicity of cyclophosphamide-induced hemorrhagic cystitis in rats.

AIM: Cyclophosphamide (CYP) chemotherapy induces bladder toxicity and hemorrhagic cystitis in cancer patients constituting a current clinical concern. Oxidative inflammatory cascades have been implicated as the mechanism contributing to CYP bladder urotoxicity. We thus assayed to explore whether zinc (Zn) supplementation could mitigate CYP-induced urotoxicity and evaluate the possible underlying mechanism in rats. MAIN METHOD: Rats were orally administered Zn (100 mg/kg b.w./day) for 10 days against urotoxicity induced by single injection of CYP (150 mg/kg b.w., ip) on day 7. KEY FINDINGS: CYP significantly depressed bladder activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) levels, whereas malondialdehyde level was increased prominently. In addition, CYP induced marked increases in the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and nitric oxide (NO) confirmed by histological alterations. CYP prominently increased bladder inducible nitric oxide synthase (iNOS) activity, nuclear factor-kappa B (NF-ĸB) and expression of caspase-3 protein. Zinc supplementation considerably abrogated the bladder urotoxicity by restoring redox balance, proinflammatory and apoptotic cascades and alleviated histopathological changes. SIGNIFICANCE: This is the first to reveal zinc potential to prevent CYP-induced urotoxic hemorrhagic cystitis via restoring redox balance and enhancing anti-inflammatory and antiapoptotic mechanisms in rat bladder.

The effect of Seidlitzia rosmarinus (eshnan) on the prevention of recurrent cystitis in women of reproductive age: A randomized, controlled, clinical trial.

The World Health Organization has recommended herbal medicine for treatment and control of recurrent cystitis. This study was conducted to determine effect of eshnan on the prevention of recurrent cystitis. The present triple-blind clinical trial was conducted on 126 women (63 women per group) with recurrent cystitis. The participants were assigned to the intervention and control groups. Three 500-mg eshnan or placebo tablets were taken orally with a glass full of water by the participants half an hour after each meal for 2 months. The study subjects were clinically and paraclinically evaluated by the end of the second, fourth, and sixth months after the intervention and every time they showed clinical symptoms of cystitis. The present findings showed that the incidence rate of cystitis and symptoms of cystitis was significantly lower in the eshnan group compared with the placebo group 2, 4, and 6 months after the intervention (p < .05). The incidence of recurrent was also significantly lower in the intervention group compared with the control group (p < .001). No side effects were observed in the intervention and control groups. The consumption of eshnan can improve the symptoms of cystitis and prevent the incidence of recurrent cystitis in women of reproductive age.

A systematic review of preventive and therapeutic options for symptoms of cystitis in patients with bladder cancer receiving intravesical bacillus Calmette-Guérin immunotherapy.

Local adverse effects are the most common clinical issues in patients with bladder cancer receiving intravesical BCG immunotherapy. The aim of this systematic review was to present available options for prevention and treatment of cystitis symptoms related to bacillus Calmette-Guérin (BCG) intravesical instillations. A literature search within the Medline database was conducted in June 2018 with the following search terms: adverse events, Bacillus Calmette-Guerin, BCG, bladder cancer, cystitis, dose, dwell time, dysuria, frequency, intravesical instillations, haematuria, pain, side effects, toxicity and urgency. Eighteen relevant original articles were identified, including 15 randomized controlled trials. Potentially effective options to prevent symptoms of cystitis are BCG dose reduction, intravesical hyaluronic acid instillations and oral prulifloxacin or ofloxacin administration. For the treatment of BCG-related cystitis, available options include oral pentosan polysulphate or a combination of intravesical hyaluronic acid and chondroitin sulphate. The included studies were characterized by high heterogeneity in terms of BCG strains, schedules and endpoints. Studies on treatment of BCG-related cystitis included only small number of patients. Studies on directed medical interventions did not consider the influence on the BCG efficacy. Among few proposed preventive or therapeutic options for symptoms of cystitis related to BCG, none was proven to be both definitively effective and oncologically safe.

[Comparative effectivenesss of standard antibiotic therapy and Canephron N asymptomatic bacteriuria in pregnant women].

Current international and Russian clinical guidelines recommend treating asymptomatic bacteriuria in pregnancy to prevent acute gestational pyelonephritis. At the same time, the growing resistance of uropathogens and the risks associated with antibiotic therapy in pregnancy dictate the need to limit the use of antibiotics and seek alternative approaches to antibacterial therapy. MATERIALS AND METHODS: A retrospective analysis was performed on 60 pregnant women who received either a standard antibiotic regimen (n=32) or the herbal preparation Canephron N (n=28). The primary outcomes were the incidence of symptomatic infections (cystitis or pyelonephritis), premature birth and low birth weight delivery, and incidence of persistent/recurrent bacteriuria. RESULTS: In the group of antibiotic therapy, one patient developed cystitis and three had pyelonephritis; in the Canephron N group, cystitis occurred in one patient, no pyelonephritis cases were observed. Among the whole study cohort (n=60), the incidence of symptomatic infections and pyelonephritis was 8.3 and 5.0%, respectively. The incidence of symptomatic infections (cystitis, pyelonephritis) did not differ statistically significantly between the study groups (p=0.2157). There were three and one premature births in the group of antibiotic therapy and the Canephron N group, respectively (p=0,373), and two low birth weight deliveries in each group (p=0.891). Recurrent bacteriuria was registered in 17 patients from the group of antibiotic therapy and in three in the Canephron N group (p=0.0006). CONCLUSIONS: The management of asymptomatic bacteriuria in pregnancy using Canephron N is not inferior to standard antibiotic therapy regarding the incidence of symptomatic infection, premature birth, and low birth weight delivery. Persistent/recurrent bacteriuria was more common in women receiving the antibiotic therapy.

[Recurrent cystisis: No medicine preventive means]. / Cystites récidivantes : des moyens de prévention non médicamenteux.

OBJECTIVE: To estimate from the literature review, the interest of hygienic and behavioural measures and the use of food supplements (herbal) to prevent female urinary tract infection. METHODS: Pubmed research was focused on the efficiency of prophylactic measures in recurrent cystisis management. RESULTS: Due to many predisposing factors such as anatomical charasteristics, hydration and lifestyle, cystisis is more common in female subjects than in male. The infection is mostly caused by uropathgenic Escherichia coli which is mostly found in the intestine. Recomendations propose a better use of antibiotics that causes undesirable side effects (such as nausea, candidiasis) and favours the development of resistant bacterial strains. Hygienic measures, good hydration, and respecting a good urinary rythm help to protect from new infectious episodes. Food supplements such as cranberry or D-mannose can also interfere with the recurrence of cystisis, by preventing the bacteria sticking to urinary tract epithelia. Their efficency is relative and seems to be dose-dependent. Better tolerated than prophylactic antibiotic treatments, they can increase times of respite. CONCLUSION: Using prophylactic treatment still have an interest, even if they are questionable. Moreover, the combination of these methods (diet and lifestyle advice) can be an alternative to long-term prophylactic medical treatment.

[Are there alternatives to antimicrobial therapy and prophylaxis of uncomplicated urinary tract infections?]

The acute uncomplicated cystitis in women is one of the most frequently diagnosed bacterial infection. A clinically symptomatic urinary tract infection must be differentiated from the asymptomatic bacteriuria, which is not considered an infection but rather a colonization which should not be treated. For the antimicrobial therapy according to the European guidelines the old oral antibiotics (fosfomycin trometamol, nitrofurantoin, pivmecillinam) should be prescribed, against which E. coli is still susceptible in over 90%. With new therapeutic concepts not mainly the elimination of bacteria but rather the treatment of the inflammatory (over)reaction of the host is highlighted. To establish the significance of these therapeutic options as compared to the standard antibiotic therapy, the results of the ongoing and planned phase 3 studies need to be awaited. Thus reliable clinical measuring parameters for diagnostics and outcome are needed. The acute cystitis symptom score (ACSS) was developed and validated in Russian and Uzbec languages. Because of its high reliability, validity and predictive value it can be used not only in daily practice but also for clinical studies for the diagnosis of an acute uncomplicated cystitis in women.

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.

Acupuncture points used in the prophylaxis against recurrent uncomplicated cystitis, patterns identified and their possible relationship to physiological measurements.

OBJECTIVE: To explore the correlation between single acupoints used and the recurrence rate of cystitis among cystitis-prone women receiving acupuncture as a prophylactic treatment. METHODS: In all, 58 cystitis-prone women were included in the analysis. Customised acupuncture treatments were given twice a week, over 4 weeks. The main effect parameter was the number of cystitis episodes during the 6-month observation time. Residual urine was measured at baseline, 2, 4 and 6 months using portable ultrasound equipment. Sympathetic and vagotone nerve activities were measured by using skin conductance and respiratory sinus arrhythmia, respectively. RESULTS: The main acupoints used for patients with Kidney (Shen) qi/yang deficiency were Shenshu (BL23), Taixi (KI3), Zhongji (CV3), Sanyinjiao (SP6) and Pangguangshu (BL28), compared with Taichong (LR3), CV3, BL28, Yinlingquan (SP9) and SP6 for Liver (Gan) qi stagnation, and SP6, CV3, BL28, Zusanli (ST36) and SP9 for Spleen (Pi) qi/yang deficiency patients. The combination BL23 and KI3 were used in 16 women, 13 of which were Kidney pattern related patients. When used, the number of symptomatic episodes were reduced to a third compared with what occurred in the 42 women where this combination was not used (3/16 vs. 28/42, P<0.05). BL23 application correlated to a significant reduction in residual urine measured a few days after treatment. Patients with the pattern of Spleen qi/yang deficiency had an initial increase in residual urine after treatments. CONCLUSION: Treating Kidney pattern related patients with the combination of BL23 and KI3 resulted in far better outcome than other points/combination of points for other Chinese medicine diagnoses. The acupoint SP6 may be less indicated than previously assumed when treating cystitis-prone women prophylactically.

Is intravesical instillation of hyaluronic acid and chondroitin sulfate useful in preventing recurrent bacterial cystitis? A multicenter case control analysis.

OBJECTIVE: Urinary tract infections (UTIs) are common in the female population and, over a lifetime, about half of women have at least one episode of UTI requiring antibiotic therapy. The aim of the current study was to compare two different strategies for preventing recurrent bacterial cystitis: intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS), and antibiotic prophylaxis with sulfamethoxazole plus trimethoprim. MATERIALS AND METHODS: This was a retrospective review of two different cohorts of women affected by recurrent bacterial cystitis. Cases (experimental group) were women who received intravesical instillations of a sterile solution of high concentration of HA + CS in 50 mL water with calcium chloride every week during the 1(st) month and then once monthly for 4 months. The control group included women who received traditional therapy for recurrent cystitis based on daily antibiotic prophylaxis using sulfamethoxazole 200 mg plus trimethoprim 40 mg for 6 weeks. RESULTS: Ninety-eight and 76 patients were treated with experimental and control treatments, respectively. At 12 months after treatment, 69 and 109 UTIs were detected in the experimental and control groups, respectively. The proportion of patients free from UTIs was significantly higher in the experimental than in the control group (36.7% vs. 21.0%; p = 0.03). Experimental treatment was well tolerated and none of the patients stopped it. CONCLUSION: The intravesical instillation of HA + CS is more effective than long-term antibiotic prophylaxis for preventing recurrent bacterial cystitis.

Standardized cranberry capsules for radiation cystitis in prostate cancer patients in New Zealand: a randomized double blinded, placebo controlled pilot study.

PURPOSE: Acute radiation cystitis, inflammation of the bladder, is a common side effect in men receiving external beam radiation for prostate cancer. Although several treatments provide symptomatic relief, there is no effective treatment to prevent or treat radiation cystitis. Cranberry products have been associated with urinary tract health. This study aimed to determine the effect of highly standardized cranberry capsules (containing 72 mg proanthocyanidins [PACS]) compared with that of placebo capsules on the incidence and severity of radiation cystitis. METHODS: Forty-one men with prostate cancer participated in a double blinded randomized placebo controlled study. Men took one capsule a day at breakfast during treatment and for 2 weeks after treatment completion. Severity of urinary symptoms and the bother these caused were measured using the individual items of the urinary domain of the Modified Expanded Prostate Index Composite (EPIC). RESULTS: The incidence of cystitis was lower in men taking cranberry capsules (65%) compared with those that took placebo capsules (90%) (p = 0.058); severe cystitis was seen in 30% of men in the cranberry arm and 45% in the placebo arm (p = 0.30). Overall, the incidence of pain/burning was significantly lower in the cranberry cohort (p = 0.045). Men on the low hydration regimen who took cranberry had less pain/burning (p = 0.038), stronger urine steam (p = 0.030) and used significantly fewer pads/liners (p = 0.042), which was significantly different from those on the high hydration regimen (p = 0.028). CONCLUSION: Men receiving radiation therapy for prostate cancer may benefit from using cranberry capsules, particularly those on low hydration regimens or with baseline urinary symptoms.

Radiation-induced hemorrhagic cystitis.

PURPOSE OF REVIEW: To better understand the mechanism of radiation-induced hemorrhagic cystitis and the advantages and disadvantages of available treatment options for bladder hemorrhage as well as preventive measures. RECENT FINDINGS: There have been several attempts recently to manage hemorrhagic cystitis with hyperbaric oxygen therapy, transurethral coagulation using Greenlight potassium-titanyl-phosphate laser and other different treatment modalities, but we still need more investigation on larger cohort studies. SUMMARY: Hemorrhagic cystitis is an uncommon urological problem. It is most often caused by radiation therapy and cyclophosphamide, but can be associated with other contributing factors. Technological advances in radiation therapy have resulted in greater treatment efficacy, with significant reduction in side-effects such as hemorrhagic cystitis. Higher dose radiation treatment, however, is more often associated with problematic hemorrhagic cystitis. Treatment of hemorrhagic cystitis is multifactorial and can range from simple bladder irrigation to cystectomy with urinary diversion.

Cranberry and recurrent cystitis: more than marketing?

Epidemiologic studies indicate that millions of people suffer from recurrent cystitis, a pathology requiring antibiotic prophylaxis and entailing high social costs. Cranberry is a traditional folk remedy for cystitis and, which, in the form of a variety of products and formulations has over several decades undergone extensive evaluation for the management of urinary tract infections (UTI). The aim of this retrospective study is to summarize and review the most relevant and recent preclinical and clinical studies on cranberries for the treatment of UTIs. The scientific literature selected for this review was identified by searches of Medline via PubMed. A variety of recent experimental evidence has shed light on the mechanism underlying the anti-adhesive properties of proanthrocyanidins, their structure-activity relationships, and pharmacokinetics. Analysis of clinical studies and evaluation of the cranberry efficacy/safety ratio in the prevention of UTIs strongly support the use of cranberry in the prophylaxis of recurrent UTIs in young and middle-aged women. However, evidence of its clinical use among other patients remains controversial.

[Features of the incidence of cystitis depending on the type of contraception].

For the purpose of evaluation the effect of contraceptive methods on the incidence of recurrent bacterial cystitis in women, 215 clinical records of patients with cystitis were analyzed. In addition, incidence of recurrent cystitis in three groups of sexually active women of reproductive age was compared: 26 patients (Group 1) received conventional therapy and used condom as a method of contraception; 31 patients (Group 2) received combined oral contraceptives (COC), and 32 patients (Group 3) received COC and two courses of treatment with canephrone. A negative correlation between COC use and the risk of cystitis was detected. After conventional therapy, recurrences were observed in 43.3% of patients in Group 1, in 25.8% of patients in Group 2, and only in 15.6% of women in Group 3. Thus, the choice of COCs for contraception lead to 2-fold reduction of risk of recurrence of bacterial cystitis, and additional use of canephrone--to 3-fold reduction.

Introduction of sodium pentosan polysulfate and avoidance of urethral catheterisation: improved outcomes in children with haemorrhagic cystitis post stem cell transplant/chemotherapy.

PURPOSE: Haemorrhagic cystitis (HC) is an uncommon but potentially devastating complication of chemotherapy and bone marrow transplantation in children. We aimed to test the hypothesis that early recognition, sodium pentosan polysulfate (SPP), and avoidance of urethral catheterisation improve outcomes in children with HC. METHODS: A retrospective case note review was performed of all patients treated for HC in our hospital from 2002 to 2010. A protocol for the management of HC was introduced in 2007 advocating early detection, use of SPP, and avoidance of urethral catheterisation. Data collected on each patient included primary condition, medications at onset, blood transfusions, duration of symptoms, catheter usage, and outcome. Statistical analysis was performed using the Mann-Whitney U test, and Fisher's Exact test as appropriate, P < .05 being significant. RESULTS: Five patients were treated using protocol with 5 historical controls. There was no significant difference between the ages of the group, diagnosis, and treatment at onset of HC. In the historical group, 4 of 5 died with HC, but all recovered in the protocol group (P < .05). Blood transfusion requirements were also significantly reduced after protocol introduction (P < .05). CONCLUSION: Early identification, avoidance of urethral catheterisation, and use of SPP significantly reduces blood transfusion requirements and mortality from HC.