The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran R). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran R were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran TM Phytosome TM, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone was found effective thus confirming the ex-vivo results.

OBJECTIVES: The purpose of the study was to compare the efficacy of a product containing cranberry and propolis (DUAB) to placebo for reducing frequency of cystitis in women with recurrent acute cystitis.METHOD: A multicenter, placebo-controlled, randomized study of women aged >18 years with at least 4 episodes of cystitis in the previous 12 months was performed. The number of cystitis episodes over a 6-month follow-up was the primary end point.RESULTS: Forty-two women were included in the cranberry + propolis group, and 43 women were in the placebo group. The mean age was 53 +/- 18 years, with 6.2 +/- 3.6 cystitis episodes in the previous year, with no differences between the 2 groups. The mean number of infections was lower in the propolis + cranberry group (respectively, 2.3 +/- 1.8 vs. 3.1 +/- 1.8). The total number of cystitis episodes in the first 3 months was lower in the propolis + cranberry group (0.7 +/- 1.1 vs. 1.3 +/- 1.1, p = 0.0257) after adjusting for water consumption. The mean time to onset of the first urinary tract infection (UTI) was also significantly longer in the propolis + cranberry group (69.9 +/- 45.8 days vs. 43.3 +/- 45.9, p = 0.0258). Tolerance to the treatments was good and comparable in both groups.CONCLUSIONS: We demonstrate for the first time that cranberry and propolis supplementation significantly reduces the incidence of UTIs during the first 3 months and delays the onset of an episode of cystitis.

Background: Cranberries are the most widely used nonantibiotic prophylaxis for recurrent urinary tract infection (rUTI) in women; however, their efficacy still remains uncertain. Hence, this meta-analysis was aimed to assess the effectiveness, safety, and adherence of cranberry as a prophylactic drug for treating rUTI. Methods: Literature search was conducted using PubMed, EBSCO, Science Direct, Scopus, Cochrane, and Google Scholar. Studies were screened for duplication, inclusion and exclusion criteria, and then reviewed by two authors independently. This included all randomized controlled trials of cranberry derivatives versus placebo and antibiotic prophylaxis. Cochrane risk-of-bias assessment tools were used to evaluate the quality of the study. Quantitative analysis was performed using the Review Manager 5.0 software. Results: Nine studies were included. Among 1,542 participants, cranberry consumption reduced incidence of rUTI in women compared with placebo (p=0.02). The subgroup analysis revealed that only cranberry capsules were superior to placebo (relative risk [RR]=0.67, 95% confidence interval [CI]=0.45-0.98), but not for cranberry juice (RR=0.85, 95% CI: 0.7-1.04). Antibiotics had better outcome than cranberry for rUTI (RR=0.83, 95% CI=0.70-0.98). Most of the participants experienced minor adverse events such as rash and gastrointestinal symptoms. There was also a good adherence rate, ranging from 90.3-99% monthly dose. Conclusion: Cranberry, especially cranberry capsule consumption, had a significant effect in reducing the incidence of rUTI compared with placebo, with good adherence rates, and minor adverse events. In contrast, although antibiotic use had a greater efficacy, it was associated with a higher risk of severe adverse events.

Objective: We assessed the effect on lower urinary tract symptoms (LUTS) of a supplement containing cranberry, D-mannose and anti-inflammatory molecules in postmenopausal women undergoing surgery for cystocele.Study design: Forty postmenopausal women were randomized 1:1 to an active group receiving the nutritional supplement twice a day for 2 weeks starting from surgery, or to a control group receiving surgery only. Primary outcomes were the effectiveness in the postoperative LUTS and urinary tract infections (UTI). LUTS were investigated by a validated questionnaire (ICIQ-FLUTS) at baseline and at week 4. Secondary outcomes were the safety and tolerability of the supplement and other perioperative outcomes.Results: No significant differences were found in perioperative outcomes and in incidence of UTI. After surgery, women treated with the supplement experienced significantly better scores on the filling domain of the questionnaire. A non-significant decrease in voiding scores was also found. No adverse events were detected.Conclusion: The use of an oral supplement containing cranberry, D-mannose and anti-inflammatory molecules decreases the perception of LUTS in postmenopausal women after anterior colporraphy. Our data suggest that perioperative use of nutritional supplements may be useful in the management of postoperative LUTS.

Objectives: To assess efficacy and safety of Bio-Kult Pro-Cyan (BKPro-Cyan), a product containing two strains of Lactobacilli plus cranberry extract, for preventing recurrent UTIs in pre-menopausal adult women. Methods: This was a randomized, double-blind, placebo-controlled pilot study. Subjects received BKPro-Cyan or placebo twice-daily for 26 weeks. The primary endpoint was the proportion of subjects with recurrent UTI at the end of the study. Results: 115 subjects were screened; 90 were enrolled; 81 completed the study. After 26 weeks, a significantly lower number of women experienced recurrent UTIs with BKPro-Cyan compared to placebo (9.1 vs 33.3%; P=0.0053). BKPro-Cyan produced statistically significant improvements compared to placebo for multiple secondary endpoints, including: greater number of subjects who experienced no UTIs (90 vs 67%; P<0.05); longer time to first UTI (174 vs 90 days; P=0.001); shorter duration of active UTI (5 vs 12 days; P=0.009); Fewer subjects requiring antibiotics (3 vs 11; P<0.05); and shorter median duration of antibiotic treatment (4 vs 7 days; P=0.09). Conclusions: BKPro-Cyan was safe and effective for preventing recurrent UTI in pre-menopausal adult women. These findings support the need for further well-designed trials to clarify the benefits that may be achieved.

Urinary tract infections (UTIs) are one of the common bacterial infections treated with antibiotics.The North American cranberry is recommended for prophylaxis in women with recurrent UTIs as a nutritional alternative. The ability of cranberry components and their metabolites to inhibit adhesion of uropathogenic Escherichia coli (E. coli) is an important mechanism by which cranberry mitigates UTIs. The objective of this study was to evaluate urinary anti-adhesion activity against type 1 and P-type uropathogenic E. coli after consumption of cranberry +health™ cranberry supplement (cranberry chew). In this randomized, double-blind, placebo-controlled, crossover design pilot trial (n = 20), subjects consumed two cranberry or placebo chews, one in the morning and one in the evening. Clean-catch urine samples collected at the baseline and post-intervention (0–3, 3–6, 6–9, 9–12, 12–24, 24–30, 30–36 h) were tested for anti-adhesion effects with a mannose-resistant human red blood cell hemagglutination assay specific for P-type E. coli, or a T24 cell line model for type 1 E. coli. Urinary anti-adhesion activity against P-type E. coli after consumption of the cranberry chew was significantly greater (p < 0.05) than that observed with placebo chew at all time points except 24–36 h. Ex vivo anti-adhesion effects on type 1 E. coli were greater (p < 0.05) after cranberry chew consumption than placebo chew at 3–6 and 6–9 h urine collections. In conclusion, consumption of cranberry +health™ cranberry supplement exhibited greater ex vivo urinary anti-adhesion activity compared to placebo, suggesting that it may have the potential to help promote urinary tract health.

The results of a study of cats with signs of urocystitis are presented. The general principles of diagnostics based on clinical, laboratory and additional research methods are established. Clinically acute urocystitis was manifested by disorders of urination - pollakiuria, dysuria, stranguria. Some of the animals showed an increase in body temperature, pain in the bladder and tightness of the walls of the abdominal cavity. According to the results of urine study, it was observed that 43.7% of the cats with urocystitis showed an increase in relative density of the urine, a change in urine pH towards higher alkaline levels, urine residue - erythrocytes, leukocytes and microorganisms were indicated. Impurities of salt and sand were found in 58.4% of the cats. In 31.4% of the cats, urocystitis was a complication of urolithiasis. Early diagnosis, especially differential diagnosis of acute and chronic, secondary urocystitis presents difficulties. Therefore, in cases of suspected inflammatory diseases of the urinary tract, a complex examination using ultrasound of the kidneys, bladder, prostate gland (in males) and the uterus (in females) is recommended. With therapeutic purpose, sick cats (two groups of 8 animals/group) were administered: anti-microbial agent (5% solution of Enrofloxacin), spasmolytic medicinal agent - RiabalReg.. Animals of the second group were additionally administered the drug Cystocure (Candioli Farmaceutici). According to the instructions, the plant basis of the powder Cystocure is presented by extracts of cranberries and orange peels. These substances provide the main properties of the drug - help in resisting the bacterial colonization of the lower urinary tract and change in urine pH to the acid side. The applied therapy positively influenced the clinical condition of the cats. Their general health was improved, painful sensations during the act of urination disappeared, the quantity and frequency of diuresis normalized. On the seventh day of treatment, according to the results of the study, the urine became transparent, no microorganisms were detected. In cats of the second group, which additionally used the drug Cystocure, the amount of salts and sand decreased significantly, the pH of the urine did not exceed the recommended value of 6.4, in contrast to animals of the first group.

The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran R). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran R were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran TM Phytosome TM, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone was found effective thus confirming the ex-vivo results.

OBJECTIVE: This article provides a comprehensive literature review on nonantibiotic agents used for the prevention of urinary tract infections (UTIs) in women >=45 years of age.DESIGN: A structured review was performed by conducting a literature search to identify relevant studies pertaining to the use of nonantibiotic agents to prevent UTIs in women who were perimenopausal through postmenopausal. Recommendations were made for or against the use of each nonantibiotic agent, unless data were unavailable. Levels of evidence were assigned to each recommendation made.SETTING AND PARTICIPANTS: Studies on the prevention of UTIs with women subjects >=45 years of age in the community, inpatient, and long-term care settings were considered for inclusion.MEASURE: The efficacy and safety of using ascorbic acid, cranberry products, d-mannose, estrogens, lactobacilli, and methenamine hippurate for prevention of UTIs was assessed.RESULTS: There is evidence to support use of estrogens (A-I) in postmenopausal women, and cranberry capsules (C-I) in women >=45 years of age for the prevention of UTIs. There was a lack of evidence to make recommendations for or against the use of ascorbic acid, cranberry juice, cranberry capsules with high proanthocyanidin (PAC) content, d-mannose, lactobacillus, and methenamine hippurate in this population.CONCLUSIONS/IMPLICATIONS: Current studies support that estrogens and cranberry capsules may have a role in preventing UTIs in women >=45 years of age. Further research is needed to elucidate the role of these nonantibiotic agents and how they may be used to decrease antibiotic use.

Cranberry ( Vaccinium macrocarpon) juice is traditionally used for the prevention of urinary tract infections. Human urine produced after cranberry juice consumption can prevent Escherichia coli adhesion, but the antiadhesive urinary metabolites responsible have not been conclusively identified. Adult female sows were therefore fed spray-dried cranberry powder (5 g/kg/day), and urine was collected via catheter. Urine fractions were tested for antiadhesion activity using a human red blood cell (A+) anti-hemagglutination assay with uropathogenic P-fimbriated E. coli. Components were isolated from fractions of interest using Sephadex LH-20 gel filtration chromatography followed by HPLC on normal and reversed-phase sorbents with evaporative light scattering detection. Active urine fractions were found to contain a complex series of oligosaccharides but not proanthocyanidins, and a single representative arabinoxyloglucan octasaccharide was isolated in sufficient quantity and purity for full structural characterization by chemical derivatization and NMR spectroscopic methods. Analogous cranberry material contained a similar complex series of arabinoxyloglucan oligosaccharides that exhibited antiadhesion properties in preliminary testing. These results indicate that oligosaccharides structurally related to those found in cranberry may contribute to the antiadhesion properties of urine after cranberry consumption.