The present study was designed to evaluate the effect of cranberry extract (CRAN) and/or losartan (LOS) against aluminium chloride (AlCl3) induced hepatorenal damage associated cardiomyopathy in rats. To induce hepatorenal and cardiotoxicity, animals were received (AlCl3; 70mg/kg i.p.) for 8weeks day after day and treated with CRAN (100mg/kg b.wt.) orally daily for 4weeks started after 4weeks from AlCl3 injection accompanied with an administration of LOS (5mg/kg i.p.) three times weekly for 4weeks. Our data revealed that, compared to AlCl3, administration of CRAN extract and LOS produced a significant improvement which was evidenced by a significant amelioration in myocardial and vascular indices, kidney and liver markers, lipid profile and oxidative stress indices. Furthermore, histopathological and immunohistochemical examination reinforced the previous results. It could be concluded that combination of CRAN extract and LOS hindered AlCl3 induced hepatorenal damage complicated cardiomyopathy in rats.

PURPOSE: Obese individuals have higher production of reactive oxygen species, which leads to oxidative damage. We hypothesize that cranberry extract (CE) can improve this dysfunction in HFD-induced obesity in rats since it has an important antioxidant activity. Here, we evaluated the effects of CE in food intake, adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors, hepatic morphology and oxidative balance in a HFD model. METHODS: At postnatal day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36) fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5% (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups were killed while the others were subdivided into four groups (n = 12/group): animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30 days or water (SD, HFD). At PN180, animals were killed. RESULTS: HFD group showed higher body mass and visceral fat, hypercorticosteronemia, higher liver glucocorticoid sensitivity, cholesterol and triglyceride contents and microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and tissues) and higher protein carbonylation (liver and adipose tissue) compared to SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia, hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation (liver and adipose tissue) and accumulation of liver fat compared to HFD group. CONCLUSION: Although adiposity was not completely reversed, cranberry extract improved the metabolic profile and reduced oxidative damage and steatosis in HFD-fed rats, which suggests that it can help manage obesity-related disorders.

The defense against influenza virus (IV) infections still poses a series of challenges. The current antiviral arsenal against influenza viruses is in fact limited; therefore, the development of new anti-influenza strategies effective against antigenically different viruses is an urgent priority. Bioactive compounds derived from medicinal plants and fruits may provide a natural source of candidates for such broad-spectrum antivirals. In this regard, cranberry (Vaccinium macrocarpon Aiton) extracts on the basis of their recognized anti-adhesive activities against bacteria, may provide potential compounds able to prevent viral attachment to target cells. Nevertheless, only few studies have so far investigated the possible use of cranberry extracts as an antiviral tool. This study focuses on the suitability of a cranberry extract as a direct-acting anti-influenza compound. We show that the novel cranberry extract Oximacro inhibits influenza A and B viruses (IAV, IBV) replication in vitro because of its high content of A-type proanthocyanidins (PAC-A) dimers and trimers. Mechanistic studies revealed that Oximacro prevents attachment and entry of IAV and IBV into target cells and exerts a virucidal activity. Oximacro was observed to interact with the ectodomain of viral hemagglutinin (HA) glycoprotein, thus suggesting the interference with HA functions and a consequent loss of infectivity of IV particles. Fluorescence spectroscopy revealed a reduction in the intrinsic fluorescence of HA protein after incubation with purified dimeric PAC-A (PAC-A2), thus confirming a direct interaction between HA and Oximacro PAC-A2. In silico docking simulations further supported the in vitro results and indicated that among the different components of the Oximacro chemical profile, PAC-A2 exhibited the best binding propensity with an affinity below 10 nM. The role of PAC-A2 in the anti-IV activity of Oximacro was eventually confirmed by the observation that it prevented IAV and IVB replication and caused the loss of infectivity of IV particles, thus indicating PAC-A2 as the major active component of Oximacro. As a whole, these results suggest Oximacro as a potential candidate to create novel antiviral agents of natural origin for the prevention of IV infections.

Objective: The objective of this study was to assess relationships between clinical predictors of urinary tract infection (UTI) and effects of cranberry juice consumption on recurrence in a post hoc analysis of a 24-week, randomized, double-blind, placebo-controlled, multicenter clinical trial in women with a recent history of UTI. Methods: Participants consumed a cranberry (n=185) or placebo (n=188) beverage (240 mL) daily. Odds ratios (OR) from 20 candidate predictor variables were evaluated in univariate analyses to assess clinical UTI incidence relationships in the placebo group. A multivariate logistic regression model was developed. The effects of cranberry juice consumption were evaluated in subsets categorized by the likelihood of a UTI event based on the prediction model. Results: In the placebo group, the final multivariate regression model identified four variables associated with the odds for having >=1 UTI: intercourse frequency >=1 time during the prior 4 weeks (OR: 2.36; 95% confidence interval [CI]: 0.98, 5.71; p=0.057), use of vasectomy or hormonal methods for contraception (OR: 2.58; 95% CI: 1.20, 5.58; p=0.016), most recent UTI 90 days prior to screening (OR: 2.28; 95% CI; 1.12, 4.67; p=0.024), and living in France compared with the United States (OR: 0.17; 95% CI: 0.04, 0.79; p=0.024). Three propensity categories were investigated (24-week probability 10%, 10%-21%, and >21%). Incidence rate ratios for the cranberry vs placebo groups were 0.76 (95% CI: 0.22, 2.60; p=0.663) for those with 10% probability, 0.73 (95% CI: 0.35, 1.53; p=0.064) for those with 10% to 21% probability, and 0.58 (95% CI: 0.35, 0.97; p=0.039) for those with >21% probability. Conclusions: Results suggest that clinical predictors identify women with low and high risk of clinical UTI recurrence, which may be useful for design of clinical studies evaluating preventive therapies.

The relationship among diet, human health, and disease is an area of growing interest in biomarker research. Previous studies suggest that the consumption of cranberries (Vaccinium macrocarpon) could beneficially influence urinary and digestive health. The present study sought to determine if daily consumption of sweetened dried cranberries (SDC) changes the urinary proteome and fecal microbiome, as determined in a prospective sample of 10 healthy individuals. Baseline urine and fecal samples were collected from the subjects in the fasted (8-12h) state. The subjects then consumed one serving (42g) of SDC daily with lunch for 2 weeks. Urine and fecal samples were collected again the day after 2 weeks of SDC consumption. Orbitrap Q-Exactive mass spectrometry of urinary proteins showed that consumption of SDC resulted in changes to 22 urinary proteins. Multiplex sequencing of 16S ribosomal RNA genes in fecal samples indicated changes in relative abundance of several bacterial taxonomic units after consumption of SDC. There was a shift in the Firmicutes:Bacteroidetes ratio, increases in commensal bacteria, and decreases or the absence of bacteria associated with negative health effects. A decrease in uromodulin in all subjects and an increase in Akkermansia bacteria in most subjects were observed and warrant further investigation. Future larger clinical studies with multiomics and multitissue sampling designs are required to determine the effects of SDC consumption on nutrition and health.

PURPOSE: The study was conducted to investigate the effects of training provided by researcher and the use of cranberry capsule in preventing late term UTIs after urostomy. METHODS: The study included 60 patients who underwent ileal conduit diversion between June 2013 and November 2014. The participants were randomly divided into three groups. First group used cranberry capsule, second group received training about UTIs and the other control group. The patients were assessed for a UTI by laboratory analysis at 2, 3, and 4 months after discharge. RESULTS: When the effect of cranberry capsule use and training on the prevention of urinary tract infections were compared, we found that there was a significant difference between the group that used and didn't use cranberry capsules, favoring the cranberry capsule (log-rank test; p < 0.05). CONCLUSION: We found that the use of cranberry capsules is effective in the prevention of urinary tract infections.

OBJECTIVE: The Affordable Care Act (ACA) established the Hospital-Acquired Condition (HAC) Reduction Program. The Centers for Medicare and Medicaid Services (CMS) established a total HAC scoring methodology to rank hospitals based upon their HAC performance. Hospitals that rank in the lowest quartile based on their HAC score are subject to a 1% reduction in their total Medicare reimbursements. In FY 2017, 769 hospitals incurred payment reductions totaling $430 million. This study analyzes how improvements in the rate of catheter-associated urinary tract infections (CAUTI), based on the implementation of a cranberry-treatment regimen, impact hospitals' HAC scores and likelihood of avoiding the Medicare-reimbursement penalty. METHODS: A simulation model is developed and implemented using public data from the CMS' Hospital Compare website to determine how hospitals' unilateral and simultaneous adoption of cranberry to improve CAUTI outcomes can affect HAC scores and the likelihood of a hospital incurring the Medicare payment reduction, given results on cranberry effectiveness in preventing CAUTI based on scientific trials. The simulation framework can be adapted to consider other initiatives to improve hospitals' HAC scores. RESULTS: Nearly all simulated hospitals improved their overall HAC score by adopting cranberry as a CAUTI preventative, assuming mean effectiveness from scientific trials. Many hospitals with HAC scores in the lowest quartile of the HAC-score distribution and subject to Medicare reimbursement reductions can improve their scores sufficiently through adopting a cranberry-treatment regimen to avoid payment reduction. LIMITATIONS: The study was unable to replicate exactly the data used by CMS to establish HAC scores for FY 2018. The study assumes that hospitals subject to the Medicare payment reduction were not using cranberry as a prophylactic treatment for their catheterized patients, but is unable to confirm that this is true in all cases. The study also assumes that hospitalized catheter patients would be able to consume cranberry in either juice or capsule form, but this may not be true in 100% of cases. CONCLUSION: Most hospitals can improve their HAC scores and many can avoid Medicare reimbursement reductions if they are able to attain a percentage reduction in CAUTI comparable to that documented for cranberry-treatment regimes in the existing literature.

PURPOSE: Cranberry supplements are commonly used as a natural deterrent to urinary tract infection. However, one small study (n=5) which showed an increase in urinary oxalate levels following cranberry supplementation has led to its use with caution among patients susceptible to nephrolithiasis. Furthermore, most commonly available cranberry tablet preparations contain vitamin C, which has been independently shown to increase urinary oxalate excretion. The aim of this study is to investigate the influence of cranberry supplementation on urinary oxalate excretion. METHODS: Fifteen participants were randomised to receive cranberry tablets alone or cranberry tablets containing vitamin C. Tablets were taken at the manufacturers recommended dosage for a period of 14 days. Participants provided a 24 h urine collection at trial entry and day 14. Urinary variables were compared to assess for changes in oxalate levels. RESULTS: The median age was 27 years (21-43). There was no difference in the 24 h urine volume pre or post commencement of cranberry tablets (1.7 vs 2 L, p=0.07). An increase in median urinary oxalate excretion was observed in participants taking both cranberry-only tablets (0.10 mmol/day) and tablets containing vitamin C (1.15 mmol/day). CONCLUSION: Dietary supplementation with cranberry increases urinary oxalate excretion and should be avoided in patients at risk of urolithiasis.

OBJECTIVE: Previous studies have reported that polyphenol-rich extracts from various sources can prevent obesity and associated gastro-hepatic and metabolic disorders in diet-induced obese (DIO) mice. However, whether such extracts can reverse obesity-linked metabolic alterations remains unknown. In the present study, we aimed to investigate the potential of a polyphenol-rich extract from cranberry (CE) to reverse obesity and associated metabolic disorders in DIO-mice. METHODS: Mice were pre-fed either a Chow or a High Fat-High Sucrose (HFHS) diet for 13 weeks to induce obesity and then treated either with CE (200mg/kg, Chow+CE, HFHS+CE) or vehicle (Chow, HFHS) for 8 additional weeks. RESULTS: CE did not reverse weight gain or fat mass accretion in Chow- or HFHS-fed mice. However, HFHS+CE fully reversed hepatic steatosis and this was linked to upregulation of genes involved in lipid catabolism (e.g., PPARalpha) and downregulation of several pro-inflammatory genes (eg, COX2, TNFalpha) in the liver. These findings were associated with improved glucose tolerance and normalization of insulin sensitivity in HFHS+CE mice. The gut microbiota of HFHS+CE mice was characterized by lower Firmicutes to Bacteroidetes ratio and a drastic expansion of Akkermansia muciniphila and, to a lesser extent, of Barnesiella spp, as compared to HFHS controls. CONCLUSIONS: Taken together, our findings demonstrate that CE, without impacting body weight or adiposity, can fully reverse HFHS diet-induced insulin resistance and hepatic steatosis while triggering A. muciniphila blooming in the gut microbiota, thus underscoring the gut-liver axis as a primary target of cranberry polyphenols.

PURPOSE: Cranberries are a rich source of polyphenolic antioxidants. Purified sugars or artificial sweeteners are being added to cranberry-based food products to mask tartness. Refined sugar and artificial sweeteners intake modulate gut microbiota and result in metabolic complications. We evaluated effects of isomalto-oligosaccharides (IMOs; sweet tasting non-digestible oligosaccharides) with cranberry extract (CRX) on high fat diet (HFD)-induced metabolic alterations in mice. METHODS: Male Swiss albino mice were fed normal chow or HFD (58% fat kcal), and were administered either CRX (200 mg/kg) alone or in combination with IMOs (1 g/kg). Cecal short-chain fatty acids, abundances of selected (1) butyrate producing, (2) metabolically beneficial, and (3) selective lipopolysaccharides producing gram negative gut bacteria were studied. Further, gut-related histological, biochemical, genomic changes along with circulating pro-/anti-inflammatory markers and systemic obesity-associated metabolic changes were studied. RESULTS: Co-supplementation of CRX and IMOs significantly improved cecal SCFAs, especially butyrate levels, selected butyrate-producing bacteria (clostridial cluster XIVa bacteria) and butyrate kinase expression in HFD-fed mice. The combination also significantly improved gut beneficial bacterial abundance, gut histology and related changes (colon mucin production, gut permeability) as compared to individual agents. It also prevented HFD-induced systemic and tissue inflammation, glucose intolerance and systemic obesity-associated metabolic changes in adipose tissue and liver. The combination of CRX and IMOs appeared more effective in the prevention of HFD-induced gut derangements. CONCLUSION: Combination of CRX and IMOs could be advantageous for normalization of metabolic alterations seen in diet-induced obesity via beneficial modulation of gastrointestinal health.