Randomized, placebo-controlled, double-blinded study of prophylactic cranberries use in women with recurrent uncomplicated cystitis.

BACKGROUND: Τhe adherence of p-fimbriated Escherichia coli (E. coli) to urothelial cells leading to recurrent urinary tract infections (rUTIs) may be prevented by proanthocyanidins (PACs) contained in American cranberries. PURPOSE: The purpose of this clinical trial was to assess the clinical utility of prophylactic use of high-dose PACs daily in women with a history of rUTIs. MATERIALS AND METHODS: 172 adult women with a history of rUTIs, defined as ≥ 2 within a 6-month period or ≥ 3 within a 12-month period were enrolled and randomized in two groups to receive either Cysticlean™ 240 mg or placebo for a 12-month period. Urine samples, vaginal and rectal swabs were collected at initial and quarterly study visits. The primary study endpoints were the number of urinary tract infections (UTIs) and changes in Quality of Life (QoL), assessed by the 36-Item Short Form Survey (SF-36) questionnaire. RESULTS: 160 adult women of median age 40 years old (range 19-82) were finally analyzed in this randomized, placebo-controlled, double-blinded clinical trial. In response to intervention, the number of UTIs was significantly lower (Incidence rate ratio IRR 0.49, p < 0.001) and QoL was slightly improved. The numbers of E. coli isolates detected in vaginal (IRR 0.71, p value < 0.001) and in rectal swabs (IRR 0.87, p value < 0.001) were also significantly decreased. No adverse events were reported. CONCLUSION: The daily use of Cysticlean™ 240 mg was associated with a reduction of UTIs and a prolongation of UTI-free survival compared to placebo treatment, supporting its use as prophylaxis in this patient population. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT03032003.

Segmental Acupuncture for Prevention of Recurrent Urinary Tract Infections. A Randomised Clinical Trial.

INTRODUCTION AND HYPOTHESIS: Urinary tract infections (UTIs) are a common medical problem and prophylaxis of recurrent UTIs is an ongoing clinical challenge. In the present study we examined whether acupuncture is able to prevent recurrent UTIs in women. METHODS: This multicentre randomised controlled trial, based at a University clinic and private acupuncture clinics, recruited women suffering from recurrent uncomplicated UTIs. Participants were randomised to the acupuncture group or control group. Acupuncture therapy consisted of 12 treatments over a period of 18 weeks, using a set of predefined body and ear acupuncture points. Cranberry products were recommended to all participants as standard of care. RESULTS: A total of 137 women were randomised (68 acupuncture, 69 control group) and occurrence of UTIs at 6 and 12 months could be assessed in 123 and 120 women respectively. Acupuncture combined with cranberry slightly increased the proportion of UTI-free women compared with cranberry alone at 6 months (59% vs 46%, p = 0.2). Between 6 and 12 months the proportion of UTI-free women was significantly higher in the acupuncture group (66 vs 45%, p = 0.03). The number of UTIs decreased from baseline to 12 months in both study groups. The number of UTIs at 12 months was significantly lower in the acupuncture group (median difference 1, p = 0.01). CONCLUSIONS: Segmental acupuncture may be an effective treatment option for women with recurrent UTIs over a longer follow-up period and may limit antibiotics use. Further studies are needed.

The effects of blueberry and cranberry supplementation on blood pressure in patients with cardiovascular diseases: A systematic review and meta-analysis of randomized clinical trials.

Blueberries and cranberries are berry fruits with the highest number of randomized clinical trials (RCTs) focusing on blood pressure (BP). This systematic review and meta-analysis of RCTs analyzed the effects of blueberry and cranberry supplementation alone and in concert with systolic BP (SBP) and diastolic BP (DBP) in patients with cardiometabolic diseases. The searches were performed until August 2023 in the following databases: PubMed, Scopus, Web of Science, Cochrane, and Embase. Studies that examined the effects of blueberry or cranberry intake/supplementation were included. The risk of bias was evaluated using the Rob 2 scale. A meta-analysis was performed to estimate the effects of blueberry and cranberry supplementation on BP levels in patients with cardiometabolic diseases. A total of 17 articles were included, from which two found significant results from blueberry and/or cranberry supplementation in reducing BP. Pooled results revealed statistically non-significant reductions of -0.81 mm Hg for SBP (95% confidence interval [CI]: -2.26, 0.63; I2 = 0%) and -0.15 mm Hg for DBP (95% CI: -1.36, 1.05; I2 = 27%). Blueberry and/or cranberry supplementation had neutral effects on SBP and DBP in patients with cardiometabolic diseases, regardless of duration or age. Further high-quality studies are needed to firmly establish clinical efficacy.

Effect of flavonoids from grape seed and cranberry extracts on the microbiological activity of Streptococcus mutans: a systematic review of in vitro studies.

OBJECTIVE: To provide an overview of the available scientific evidence from in vitro studies regarding the effect induced by the flavonoids contained in grape seed extracts (GSE) and cranberry on the microbiological activity of Streptococcus mutans (S. mutans). METHODS: This systematic review was performed following the parameters of the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Electronic and manual searches were conducted using PubMed, ScienceDirect, Web of Science, EBSCO, and Cochrane databases. Reference lists of selected articles were reviewed to identify relevant studies. The search was not limited by year and was conducted solely in English. Eligible studies comprised publications describing in vitro studies that evaluated the effect of flavonoids derived from GSE and cranberry extracts on the microbiological activity of S. mutans. Common variables were identified to consolidate the data. Authors of this review independently screened search results, extracted data, and assessed the risk of bias. RESULTS: Of the 420 studies identified from the different databases, 22 publications were finally selected for review. The risk of bias was low in 13 articles and moderate in 9. The studies analyzed in this review revealed that cranberry extract has an inhibitory effect on the bacterial growth of S. mutans in ranges from 0.5 mg/mL to 25 mg/mL, and GSE exerts a similar effect from 0.5 mg/mL to 250 mg/mL. Additionally, the extracts or their fractions showed reduced biofilm formation capacity, decreased polymicrobial biofilm biomass, deregulation of glycosyltransferases (Gtf) B and C expression, and buffering of pH drop. In addition to adequate antioxidant activity related to polyphenol content. CONCLUSIONS: The overall results showed that the extracts of cranberry and grape seed were effective in reducing the virulence factors of the oral pathogen. According to the data, proanthocyanidins are the active components in cranberry and grape seed that effectively resist S. mutans. They can inhibit the formation of insoluble polysaccharides in the extracellular matrix and prevent glycan-mediated adhesion, cohesion, and aggregation of the proteins in S. mutans. This suggests that these natural extracts could play an important role in the prevention of cariogenic bacterial colonization, as well as induce a decrease in their microbiological activity.

Evaluation of phenolic content in selected red fruit juices.

BACKGROUND: Red fruits are characterised by a particularly high content of bioactive compounds, e.g. anthocyanins, tannins, pectins, vitamins and minerals. Dietary supply of proper amounts of antioxidants is essential to reduce oxidative stress, and thus is an important element in the prevention of lifestyle diseases. OBJECTIVE: The aim of the study was to evaluate and compare the content of polyphenols in selected red fruit juices (chokeberry, elderberry, pomegranate, cranberry), as well as to assess the impact of storage time on the content of these compounds in the analysed samples. MATERIAL AND METHODS: The research material consisted of 17 juices (100%): 3 chokeberry juices, 4 elderberry juices, 5 pomegranate juices and 5 cranberry juices, which differed in terms of the manufacturer, type, price range, country of origin and production method. The total polyphenol content was measured by spectrophotometry using the Folin�Ciocalteu reagent. The procedure was based on a modified method described by Waterhouse. Active acidity (pH) was measured with the potentiometric method using a pH-meter and the sucrose content was measured using a refractometer. RESULTS: The highest mean content of polyphenolic compounds was found in chokeberry and elderberry juices. Juice storage time did not reduce the mean content of polyphenolic compounds. The highest sucrose content was found in chokeberry juices and the lowest in cranberry juice. CONCLUSIONS: Chokeberry and elderberry juices had the highest content of polyphenols among the tested products. Juices stored after opening in accordance with the manufacturer's instructions (at 4°C) do not lose their nutritional properties.

Candida krusei is the major contaminant of ultrafiltration and reverse osmosis membranes used for cranberry juice production.

Ultrafiltration (UF) and reverse osmosis (RO) are commonly used for the clarification and concentration of fruit juices. However, one of the main limitations of filtration membranes is biofouling, which reduces membrane efficiency and can contaminate the filtered product and lead to spoilage. In this study, the microbial fouling layers of UF and RO membranes from a Canadian cranberry juice processing plant were characterized. Unlike the microbiota found in cranberry juice, which is dominated by Bacillus sp. and other bacteria, both UF and RO membranes were mainly colonized by several strains of the yeast Candida krusei. A variation in bacterial and yeasts count was observed between tubular UF and spiral-wound RO membranes, and the analysis of the spatial distribution highlighted the homogeneity of the contamination across each membrane. Surprisingly, RO membranes had a higher level of contamination when compared to UF membranes. Furthermore, six strains of C. krusei were further characterized through multilocus sequence typing analysis, five of which exhibited unique allelic profiles and two of which were found to contain a new TRP1 allele.

Root canal disinfection and maintenance of the remnant tooth tissues by using grape seed and cranberry extracts.

The purpose of this study was to perform an integrative review on the effects of cranberry and grape seed extracts concerning the disinfection of root canals maintaining the strength of the remnant tooth tissues' structure. A bibliographical search was carried out on the PubMed electronic platform using the following key terms: cranberry, grape seed, vaccinium macrocarpon, proanthocyanidin, antibacterial, antimicrobial, decontamination, disinfection, bacteria removal, bacteria eradication, bacteria elimination, endodontic, root canal, faecalis, and strength. The inclusion criteria involved articles published in the English language, until March, 2022, reporting the antibacterial effect of grape seed and cranberry extracts. Of 185 studies identified, 13 studies were selected for the present review. The grape seed extract (GSE), composed of proanthocyanidins, showed an antioxidant activity against the main bacteria found in endodontic secondary infection. The percentage of bacteria removal was recorded at around 96.97% by using GSE. Studies on cranberry extracts, which are composed of proanthocyanidins, revealed antimicrobial effects against bacteria related to periodontitis and dental caries. Additionally, GSE or cranberry allowed the dentin collagen cross-linking that preserved the 3D collagen network leading to the maintenance of the strength of the remnant tooth structure. However, the contaminated smear layer could not be removed by using only GSE or cranberry. Cranberry extracts and GSE revealed a significant antimicrobial activity in endodontic disinfection without changing the mechanical properties of the remnant dentin tissues. Furthermore, those components can be associated with traditional compounds to enhance their antimicrobial effects and eliminate the smear layer.

Peculiarities of the Variation of Biologically Active Compounds in Fruit of Vaccinium oxycoccos L. Growing in the Cepkeliai State Strict Nature Reserve.

This study was carried out to analyze the accumulation patterns of anthocyanins, proanthocyanidins, flavonols, chlorogenic acid, and triterpene compounds in fruit samples of Vaccinium oxycoccos L. berries growing in the Cepkeliai State Strict Nature Reserve in Lithuania. Studies were carried out on the phytochemical composition of cranberry fruit samples during the period of 2020-2022. Anthocyanins, flavonols, chlorogenic acid and triterpene compounds were identified and quantified using UPLC-DAD methods, and proanthocyanins were determined using spectrophotometric methods. The content of identified compounds varied, as reflected in the total amounts of anthocyanins (710.3 ± 40 µg/g to 6993.8 ± 119 µg/g), proanthocyanidins (378.4 ± 10 µg EE/g to 3557. 3 ± 75 µg EE/g), flavonols (479.6 ± 9 µg/g to 7291.2 ± 226 µg/g), chlorogenic acid (68.0 ± 1 µg/g to 3858.2 ± 119 µg/g), and triterpenoids (3780.8 ± 98 µg/g to 7226.9 ± 224 µg/g). Cranberry fruit samples harvested from open oligotrophic wetland habitats contained higher levels of anthocyanins, anthocyanidins, flavonol glycosides, and proanthocyanidins. The highest levels of triterpene compounds were found in the cranberry fruits harvested in the spring of the following year after the snowmelt. The use of principal component analysis showed that cranberry plant material harvested in October and November had higher levels of bioactive compounds.

[Prevention of the development of catheter-associated urinary system infections in the early postoperative period].

BACKGROUND: Bladder catheterization is a common medical manipulation that is associated with the risk of complications, including catheter-associated urinary tract infection (CAUTI), which accounts for 80% of all nosocomial infections of the urological profile. AIM: To evaluate the combined use of the biologically active additive Uronext and ceftriaxone in the prevention of the development of CAUTI in the early postoperative period in 120 patients aged 20-80 years with a Foley indwelling catheter. MATERIALS AND METHODS: The patients were divided into 2 groups: in group I (n=60), D-mannose with cranberry extract and vitamin D3 as part of Uronext dietary supplement was administered orally in the form of sachets 48 hours before surgery and after surgery until urethral catheter was placed, as well as intravenous ceftriaxone 1000 mg 2 hours before surgery and in the postoperative period within 7 days. In group II (n=60), ceftriaxone monotherapy was prescribed in a similar way. RESULTS: According to the results of bacteriological examination of the removed urinary catheter on 3-7 days in Uronext group, bacterial growth was absent in 40 patients (66.67%, p<0.05), versus 23 cases (38.33%) in the control group. CONCLUSIONS: The data obtained confirm the efficiency of the use of the biologically active additive Uronext in combination with an antibacterial drug, which allows to recommend this scheme in patients with an indwelling urinary catheter for the prevention of the development of CAUTI.

Proanthocyanidins mitigate bile acid-induced changes in GSTT2 levels in a panel of racially diverse patient-derived primary esophageal cell cultures.

Persistent and symptomatic reflux of gastric and duodenal contents, known as gastroesophageal reflux disease (GERD), is the strongest risk factor for esophageal adenocarcinoma (EAC). Despite similar rates of GERD and other risk factors across racial groups, EAC progression disproportionately impacts Caucasians. We recently reported that elevated tissue levels of the detoxification enzyme GSTT2 in the esophagi of Blacks compared to Caucasians may contribute protection. Herein, we extend our research to investigate whether cranberry proanthocyanidins (C-PAC) mitigate bile acid-induced damage and GSTT2 levels utilizing a racially diverse panel of patient-derived primary esophageal cultures. We have shown that C-PACs mitigate reflux-induced DNA damage through GSTT2 upregulation in a rat esophageal reflux model, but whether effects are recapitulated in humans or differentially based on race remains unknown. We isolated normal primary esophageal cells from Black and Caucasian patients and assessed GSTT2 protein levels and cellular viability following exposure to a bile acid cocktail with and without C-PAC treatment. Constitutive GSTT2 levels were significantly elevated in Black (2.9-fold) compared to Caucasian patients, as were GSTT2 levels in Black patients with GERD. C-PAC treatment induced GSTT2 levels 1.6-fold in primary normal esophageal cells. GSTT2 induction by C-PAC was greatest in cells with constitutively low GSTT2 expression. Overall, C-PAC mitigated bile-induced reductions of GSTT2 and subsequent loss of cell viability regardless of basal GSTT2 expression or race. These data support that C-PAC may be a safe efficacious agent to promote epithelial fitness through GSTT2 induction and in turn protect against bile acid-induced esophageal injury.

The effect of cranberry supplementation on Helicobacter pylori eradication in H. pylori positive subjects: a systematic review and meta-analysis of randomised controlled trials.

Helicobacter pylori infection is one of the most common chronic bacterial infections. Cranberry has been suggested for H. pylori eradication. We aimed to conduct the first meta-analysis to summarise current evidence on effects of cranberry supplementation on H. pylori eradication in H. pylori positive subjects. We searched the online databases up to December 2020. Four randomised clinical trials (RCT) were included with human subjects, investigating the effect of cranberry on H. pylori eradication. The pooled results were expressed as the OR with 95 % CI. Based on five effect sizes with a total sample size of 1935 individuals, we found that according to the OR, there was a positive effect of cranberry supplementation on H. pylori eradication, increasing the chance of H. pylori eradication by 1·27 times, but this relationship was not statistically significant (overall OR: 1·27; 95 % CI 0·63, 2·58). The results also indicated the moderate between-study heterogeneity (I2 = 63·40 %; P = 0·03) of the studies. However, there were no significant differences in some subgroup analyses in the duration of treatment, the duration of follow-up and the Jadad score. Our findings revealed that although cranberry had a positive effect on H. pylori eradication in adults, this effect was not statistically significant. Due to the small number of included studies and moderate heterogeneities, the potential of cranberry supplementation on H. pylori eradication should be validated in large, multicentre and well-designed RCT in the future.

Effects of blueberry and cranberry on type 2 diabetes parameters in individuals with or without diabetes: A systematic review and meta-analysis of randomized clinical trials.

AIMS: Blueberry and cranberry are rich in polyphenols that are associated with diabetes reduction. This study aimed: 1) to systematically review the literature on the effects of blueberry and cranberry consumption and type 2 diabetes parameters in individuals with or without type 2 diabetes and 2) to quantify these effects by carrying out a meta-analysis. DATA SYNTHESIS: A systematic review and meta-analysis were performed using articles present in seven databases (PubMed, LILACS, Scielo, Scopus, Web of Science, Cochrane, and Embase), including publications until May 2021. We included randomized clinical trials that compared blueberry or cranberry effects on type 2 diabetes parameters, such as fasting blood glucose, insulin resistance, and glycated hemoglobin. Quality of the studies was performed using the Cochrane scale, while the Egger test assessed the publication bias and meta-regression the estimated effect sizes with potential moderator variables. From the 2034 studies identified, 39 were read in full and 22 were included in meta-analysis. In individuals with diabetes, the consumption of blueberry or cranberry significantly reduced fasting blood glucose [MD: -17.72 mg/dl; 95% CI: -29.62, -5.82; p = 0.03; I2 = 57%] and glycated hemoglobin [MD: -0.32%; 95% CI: -0.57, -0.07; p = 0.15; I2 = 39%], whereas for insulin resistance the effects were null. Results were not significant for the general population, except in the sensitivity analysis for fasting blood glucose. CONCLUSIONS: The consumption of blueberry and cranberry significantly reduced fasting blood glucose and glycated hemoglobin levels in individuals with diabetes, with high credibility of the evidence.

Non-antibiotic Approaches to Preventing Pediatric UTIs: a Role for D-Mannose, Cranberry, and Probiotics?

PURPOSE OF REVIEW: While antibiotics have been a staple in the management and even prevention of urinary tract infections (UTIs), it is not without significant consequences due to intolerance and development of antibiotic resistant bacteria. These concerns necessitate alternatives to antibiotic use in the management of pediatric UTIs. This review seeks to evaluate non-antibiotic means of preventing UTI in the pediatric population. RECENT FINDINGS: The search for preventative alternatives to antibiotics has included D-mannose, cranberry, and probiotics. These products similarly work through competitive inhibition of uropathogens in the urinary tract. Pediatric studies exist highlighting the use of cranberry extract/juice and probiotics in UTI prevention, although significant heterogeneity amongst studies have limited overarching recommendations for their use. Data of D-mannose use is extrapolated from adult literature. More studies are required in the utility of each treatment, with some emphasis on larger sample sizes and clarifications regarding dosing and formulation.

Quantitative Trait Locus Mapping of Marsh Spot Disease Resistance in Cranberry Common Bean (Phaseolus vulgaris L.).

Common bean (Phaseolus vulgaris L.) is a food crop that is an important source of dietary proteins and carbohydrates. Marsh spot is a physiological disorder that diminishes seed quality in beans. Prior research suggested that this disease is likely caused by manganese (Mn) deficiency during seed development and that marsh spot resistance is controlled by at least four genes. In this study, genetic mapping was performed to identify quantitative trait loci (QTL) and the potential candidate genes associated with marsh spot resistance. All 138 recombinant inbred lines (RILs) from a bi-parental population were evaluated for marsh spot resistance during five years from 2015 to 2019 in sandy and heavy clay soils in Morden, Manitoba, Canada. The RILs were sequenced using a genotyping by sequencing approach. A total of 52,676 single nucleotide polymorphisms (SNPs) were identified and filtered to generate a high-quality set of 2066 SNPs for QTL mapping. A genetic map based on 1273 SNP markers distributed on 11 chromosomes and covering 1599 cm was constructed. A total of 12 stable and 4 environment-specific QTL were identified using additive effect models, and an additional two epistatic QTL interacting with two of the 16 QTL were identified using an epistasis model. Genome-wide scans of the candidate genes identified 13 metal transport-related candidate genes co-locating within six QTL regions. In particular, two QTL (QTL.3.1 and QTL.3.2) with the highest R2 values (21.8% and 24.5%, respectively) harbored several metal transport genes Phvul.003G086300, Phvul.003G092500, Phvul.003G104900, Phvul.003G099700, and Phvul.003G108900 in a large genomic region of 16.8-27.5 Mb on chromosome 3. These results advance the current understanding of the genetic mechanisms of marsh spot resistance in cranberry common bean and provide new genomic resources for use in genomics-assisted breeding and for candidate gene isolation and functional characterization.

Development, Validation, and Application of the UPLC-DAD Methodology for the Evaluation of the Qualitative and Quantitative Composition of Phenolic Compounds in the Fruit of American Cranberry (Vaccinium macrocarpon Aiton).

Phenolic compounds in the fruit of American cranberry (Vaccinium macrocarpon Aiton) determine the antioxidant, anti-inflammatory, anticancer, and other biological effects. The berries are used in the production of medicinal preparations and food supplements, which highlights the importance of qualitative and quantitative analysis of phenolic compounds in cranberry fruit raw material. The aim of our study was to develop and validate an efficient, cost-effective, reproducible, and fast UPLC-DAD methodology for the evaluation of the qualitative and quantitative composition of phenolic compounds in raw material and preparations of American cranberry fruit. During the development of the methodology, chlorogenic acid and the following flavonols were identified in cranberry fruit samples: myricetin-3-galactoside, quercetin-3-galactoside, quercetin-3-glucoside, quercetin-3-α-L-arabinopyranoside, quercetin-3-α-L-arabinofuranoside, quercetin-3-rhamnoside, myricetin, and quercetin. The developed and optimized UPLC-DAD methodology was validated according to the guidelines of the International Council for Harmonization (ICH), evaluating the following parameters: range, specificity, linearity (R2 > 0.999), precision (%RSD < 2%), LOD (0.38-1.01 µg/mL), LOQ (0.54-3.06 µg/mL), and recovery (80-110%). The developed methodology was applied to evaluate the qualitative and quantitative composition of phenolic compounds in fruit samples of cranberry cultivars 'Baifay', 'Bergman', 'Prolific', and 'Searles', as well as 'Bain-MC' and 'BL-12' clones. In the tested samples, the majority (about 70%) of the identified flavonols were quercetin derivatives. The greatest amount of quercetin-3-galactoside (1035.35 ± 4.26 µg/g DW) was found in fruit samples of the 'Searles' cultivar, and the greatest amount of myricetin-3-galactoside (940.06 ± 24.91 µg/g DW) was detected in fruit samples of the 'Woolman' cultivar.

Cranberry: Chemical Composition, Antioxidant Activity and Impact on Human Health: Overview.

Cranberries are a rich source of bioactive compounds that comprise a healthy diet. Cranberry is abundant in nutritional components and many bioactive compounds that have antioxidant properties. Both American (Vaccinium macrocarpon) and European (Vaccinium oxycoccus) cranberry species are rich in polyphenols such as phenolic acids, anthocyanins and flavonoids, and is one of the few fruits that is high in proanthocyanidins, which is linked to many health benefits. The review systematizes information on the chemical composition of cranberry, its antioxidant effect, and the beneficial impact on human health and disease prevention after cranberry consumption, and in particular, its effect against urinary tract inflammation with both adults and children, cardiovascular, oncology diseases, type 2 diabetes, metabolic syndrome, obesity, tooth decay and periodontitis, Helicobacter pylori bacteria in the stomach and other diseases. Additional research needs to study cranberry proteomics profiling, polyphenols interaction and synergism with other biologically active compounds from natural ingredients and what is important in formulation of new functional foods and supplements.

Cranberry Ingestion Modulated Drug Transporters and Metabolizing Enzymes: Gefitinib Used as a Probe Substrate in Rats.

Cranberry, a polyphenol-rich functional food, is commonly used for the prophylaxis of urinary tract infections. Gefitinib, an anticancer agent clinically prescribed to treat non-small-cell lung cancer, is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), and metabolized mainly by cytochrome P450 (CYP) 3A4 and CYP2D6. This study used gefitinib as a probe substrate to investigate the modulation of cranberry on P-gp, BCRP, CYP3A4 and CYP2D6. Rats were administered gefitinib with and without 5.0 g/kg of cranberry as juice (CJ). The concentration of gefitinib in serum was determined by LC-MS/MS. The results showed that CJ significantly increased the Cmax and AUC0-t of gefitinib by 28% and 55%, respectively. Mechanism studies indicated that CJ activated P-gp, and cranberry metabolites (CM) inhibited CYP2D6. Moreover, the protein level of P-gp in rat enterocytes was decreased, whereas that in hepatocytes was increased. In addition, the protein levels of BCRP, CYP3A4 and CYP2D6 in enterocytes and hepatocytes were decreased. In conclusion, CJ ingestion affected the activities and protein levels of P-gp, BCRP, CYP3A4 and CYP2D6.

The Effects of Berry Extracts on Oxidative Stress in Cultured Cardiomyocytes and Microglial Cells: A Potential Cardioprotective and Neuroprotective Mechanism.

Oxidative stress is a key underlying factor in cognitive decline and atherosclerosis. Oxidative stress occurs at the cellular level with an imbalance between reactive oxygen species and reactive nitrogen species and a deficiency in antioxidants. Mounting evidence suggests that berry flavonoids may promote cellular health by exerting antioxidant properties. Black currant and various berry extracts were tested in microglia (BV-2) and cardiomyocyte (HL-1) cell lines to study their biological effects. The principal ingredients in black currant and cranberry extract-delphinidin 3-rutinoside (D3R) and cyanidin 3-glucoside (C3G), were also assessed. A menadione-induced oxidative stressor was used, and its output was quantified to detect oxidative stress (CellROXTM). Black currant extract had similar antioxidant effects as N-acetylcysteine (NAC) in HL-1 cells with regard to cellular protection, whereas cranberry extract was ineffective. In contrast, cranberry extract was comparable in effectiveness to black currant extract in BV-2 cells. D3R and C3G also reduced oxidative stress similarly to whole berry extracts, which indicates that these ingredients may confer the antioxidant effects of berries. Black currant and cranberry extracts inhibit oxidative stress in microglial and cardiomyocyte cell lines. Black currant extract was more effective in reducing oxidative stress in the HL-1 cells, whereas cranberry extract was comparable in reducing oxidative stress in the BV-2 cells. The results suggest that berry flavonoids exert neuro- and cardioprotective effects.

[Clinical and pathogenetic aspects of the treatment and prevention of pyelonephritis in children].

INTRODUCTION: Treatment of pyelonephritis in children should be combined, long-term and individual-based. The success of the therapy in children largely depends on the prompt appointment and the correct choice of antimicrobial therapy. AIM: To evaluate the efficiency of the dietary supplement "Cystenium II" in a group of children aged 7 to 14 years with a diagnosis of acute and chronic recurrent pyelonephritis in the acute phase. MATERIALS AND METHODS: A total of 60 children aged 7 to 14 years with a diagnosis of acute or chronic recurrent pyelonephritis in the acute stage were included in the study. The clinical group consisted of 30 patients (mean age 12.1+/-1.8 years), while the control group included 30 patients of mean age 11.2+/-1.7 years. In the control group patients received only standard antibiotic therapy, while in the clinical group it was combined with a dietary supplement "Cystenium II" 1 tablet 2 times a day with meals for 14 days. After the course of antibacterial treatment, the children in the clinical group continued to take the studied dietary supplement for another 14 days in order to prevent the recurrence of pyelonephritis. The results of treatment (patient's condition, presence of pain, dysuria, fever) were assessed on the 3rd, 7th, 14th day, 1 and 6 months after the start of treatment. A urinalysis was performed at the baseline, on the 7th and 14th days, as well as after 1 and 6 months. Urine culture was performed before and after antibiotic therapy at the baseline, on the 14th day, 1 and 6 months after the start of treatment. RESULTS: The main indicators of urinalysis (leukocytes, red blood cells, protein) returned to normal values in 26 (86.7%) patients of the clinical group and in 23 (76.7%) patients of the control group on the 7th day after the start of treatment. At the completion of the basic therapy (after 14 days) normal clinical parameters (absence of leukocyturia, microhematuria, proteinuria) were observed in all patients of the clinical group and in 28 (93.3%) patients of the control group. After a month of follow-up, the disturbances in urinalysis (leukocytes, red blood cells, protein) in the control group were again seen in 3 (10%) patients, as well as after 6 months. However, in the clinical group all patients had normal urinalysis (absence of leukocyturia, microhematuria, proteinuria) after 1 month and only in 1 (3.3%) case leukocyturia, as well as an increase in the number of red blood cells and protein was detected by 6 months. DISCUSSION: According to our results, the use of dietary supplements "Cystenium II" (manufactured by Akvion, Russia), due to the constituents of D-mannose (450 mg), cranberry fruit extract with a standardized activity of 500 mg (36 mg of proanthocyanidins) and vitamin C (60 mg), may cause anti-inflammatory and anti-adhesive effects (resolving of leukocyturia and bacteriuria). This allows to use the dietary supplement Cystenium II in children from 7 years of age in the combination therapy of acute pyelonephritis, as well as exacerbation of chronic pyelonephritis. The obtained results showed a high overall therapeutic efficacy of combination therapy using Cystenium II after 6 months from the start of treatment (relapse in 1 patient), in contrast to the control group (relapse in 6 patients). CONCLUSIONS: the use of dietary supplement "Cystenium II" allowed to reduce the number of repeated courses of antibiotic therapy in children during 6 months of follow-up and, most likely, reduced the frequency of development of chronic pyelonephritis after an acute inflammation. Therefore, the wide clinical use of dietary supplements "Cystenium II" for the combined treatment of acute and exacerbation of chronic pyelonephritis in children older than 7 years seems to be very reasonable.

Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections.

BACKGROUND: Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs. RESULTS: The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor's association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions. CONCLUSION: While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI. TRIAL REGISTRATION: Clinical trial registration number: ClinicalTrials.gov NCT01776021 .