PURPOSE: To assess the effects of NDM from cranberries on Staphylococcus epidermidis biofilm formed on soft contact lenses.

METHODS: Soft contact lenses were incubated in Tryptic Soy Broth (TSB) together with S. epidermidis (ATCC35984/RP62A) and various concentrations of NDM, and inspected by scanning electron and confocal microscopy. The TSB was collected after sonification and monitored turbidometrically.

RESULTS: NDM at >=500 mug/mL concentration caused a significant (P 0.01) reduction of biofilm. Scanning electron microscopy of biofilm in the presence of 500 to 1000 mug/mL NDM confirmed these results. In control lenses, multilayered mushroom-shaped biofilm and complete coverage of the lens surface were seen, whereas after incubation with 500 mug NDM per mL TSB, the biofilm was thinner with smaller protuberances, and exposed lens surface was partially seen. In samples incubated with 1000 mug NDM per mL TSB, the lens surface was clearly seen between sporadic microcolonies.

CONCLUSIONS: NDM reduces formation of biofilm on soft contact lenses. This has important implications for the prevention of contact lens-related corneal infections caused by S. epidermidis.

Bacterial motility plays a key role in the colonization of surfaces by bacteria and the subsequent formation of resistant communities of bacteria called biofilms. Derivatives of cranberry fruit, predominantly condensed tannins called proanthocyanidins (PACs) have been reported to interfere with bacterial adhesion, but the effects of PACs and other tannins on bacterial motilities remain largely unknown. In this study, we investigated whether cranberry PAC (CPAC) and the hydrolyzable tannin in pomegranate (PG; punicalagin) affected the levels of motilities exhibited by the bacterium Pseudomonas aeruginosa. This bacterium utilizes flagellum-mediated swimming motility to approach a surface, attaches, and then further spreads via the surface-associated motilities designated swarming and twitching, mediated by multiple flagella and type IV pili, respectively. Under the conditions tested, both CPAC and PG completely blocked swarming motility but did not block swimming or twitching motilities. Other cranberry-containing materials and extracts of green tea (also rich in tannins) were also able to block or impair swarming motility. Moreover, swarming bacteria were repelled by filter paper discs impregnated with many tannin-containing materials. Growth experiments demonstrated that the majority of these compounds did not impair bacterial growth. When CPAC- or PG-containing medium was supplemented with surfactant (rhamnolipid), swarming motility was partially restored, suggesting that the effective tannins are in part acting by a rhamnolipid-related mechanism. Further support for this theory was provided by demonstrating that the agar surrounding tannin-induced nonswarming bacteria was considerably less hydrophilic than the agar area surrounding swarming bacteria. This is the first study to show that natural compounds containing tannins are able to block P. aeruginosa swarming motility and that swarming bacteria are repelled by such compounds.

Ursolic acid and its cis- and trans-3-O-p-hydroxycinnamoyl esters have been identified as constituents of American cranberries (Vaccinium macrocarpon), which inhibit tumor cell proliferation. Since the compounds may contribute to berry anticancer properties, their content in cranberries, selected cranberry products, and three other Vaccinium species (V. oxycoccus, V. vitis-idaea and V. angustifolium) was determined by liquid chromatography-mass spectroscopy. The ability of these compounds to inhibit growth in a panel of tumor cell lines and inhibit matrix metalloproteinase (MMP) activity associated with tumor invasion and metastasis was determined in DU145 prostate tumor cells. RESULTS: The highest content of ursolic acid and esters was found in V. macrocarpon berries (0.460-1.090 g ursolic acid and 0.040-0.160 g each ester kg-1 fresh weight). V. vitis-idaea and V. angustifolium contained ursolic acid (0.230-0.260 g kg-1), but the esters were not detected. V. oxycoccus was lowest (0.129 g ursolic acid and esters per kg). Ursolic acid content was highest in cranberry products prepared from whole fruit. Ursolic acid and its esters inhibited tumor cell growth at micromolar concentrations, and inhibited MMP-2 and MMP-9 activity at concentrations below those previously reported for cranberry polyphenolics. CONCLUSION: Cranberries (V. macrocarpon) were the best source of ursolic acid and its esters among the fruit and products tested. These compounds may limit prostate carcinogenesis through matrix metalloproteinase inhibition.

OBJECTIVE: To report a case of warfarin-cranberry juice interaction, which resulted in an international normalized ratio (INR) elevation on 2 separate occasions.
CASE SUMMARY: A 46-year-old female was receiving a total weekly dose of 56 mg of warfarin. During the 4 months prior to the incident INR, her average INR was 2.0, with a range of 1.6-2.2, while taking the same weekly dose of warfarin. Her INR increased to 4.6 after drinking approximately 1.5 quarts (1420 mL) of cranberry juice cocktail daily for 2 days. Her INR 14 days later without cranberry juice cocktail consumption was 2.3. For the next 3 months, while taking warfarin 56 mg per week, her average INR was 2.1, with a range of 1.4-2.5. At a subsequent visit, after drinking approximately 2 quarts (1893 mL) of cranberry juice cocktail daily for 3-4 days, her INR had increased to 6.5. Her INR after holding warfarin for 3 days was 1.86. Her INR 7 days after resuming the weekly dose of warfarin 56 mg was 3.2. During both of the elevated INR episodes, no other factors were identified that would have resulted in an elevated INR, such as drug, herbal, disease, or other food interactions. An objective causality assessment revealed the interaction was highly probable.
DISCUSSION: Warfarin is the most commonly used anticoagulant for chronic therapy. There have been several case reports of cranberry juice or cranberry sauce potentiating the effects of warfarin by elevating the INR; however, clinical trials evaluating this interaction have failed to demonstrate a significant effect on an INR.
CONCLUSIONS: Our case report describes INR elevations in a patient previously stable on warfarin after ingestion of cranberry juice cocktail daily for several days. This elevation occurred on 2 separate occasions, which distinguishes our case from other published literature.

Traditional first-line treatment of chronic bacterial prostatitis (CBP) is administration of empirical antibiotics. However, the efficacy rate is low and long-term antibiotic therapy can result in adverse events and bacterial resistance. For these reasons, a new treatment or preventive modality that can replace traditional antibiotic therapy is required. There are several reports that E. coli extract has a preventive effect on recurrent urinary tract infection (UTI). Cranberries are also known to have beneficial effects in preventing UTI. To evaluate the preventive effect of E. coli extract and cranberries on CBP, 48 rats were randomly divided into 4 groups; control, ciprofloxacin, E. coli extract, and cranberry groups. All drug treatments were conducted for 3 weeks, and then we developed a CBP rat model. After 4 weeks, the results of microbiological culture of prostate and urine samples as well as histological findings for the prostate were analyzed for each group. The infection rate in the ciprofloxacin group was significantly lower than that in the control group. The microbiological cultures of the prostate and urine samples demonstrated reduced bacterial growth in all experimental groups compared with the control group. Histopathologic examination showed significantly decreased prostatic inflammation in all groups compared with the control group. These results suggest that E. coli extract has a potential preventive effect on the development of CBP, and cranberry also exhibits promising activity in this context

The effects of the industrial juice process on the ability of neutralized cranberry samples and extracts (polar, apolar and anthocyanins) to inhibit the growth of Enterococcus faecium resistant to vancomycin (ERV), Escherichia coli O157:H7 EDL 933, E. coli ATCC 25922, Listeria monocytogenes HPB 2812, Pseudomonas aeruginosa ATCC 15442, Salmonella Typhimurium SL1344 and Staphylococcus aureus ATCC 29213 were investigated. The juice process appeared to have a general enhancing effect on the antibacterial properties of cranberry polar and anthocyanin extracts. The lowest minimum inhibitory concentrations (MICs) (1.80-7.0 micro g phenol/well) were obtained when S. aureus, S. Typhimurium, and ERV were exposed to the juice concentrate. The growth of P. aeruginosa, L. monocytogenes, E. coli ATCC, and E. coli O157:H7 was not inhibited by the juice concentrate, but did show sensitivity (maximal tolerated concentrations of 0.007-0.4 micro g phenol/well). The lowest MICs (22.6-90.5 micro g phenol/well) for P. aeruginosa, S. aureus, S. Typhimurium, and ERV were observed when they were exposed to the cranberry anthocyanin extract obtained from cranberry pomace. The results also showed a negative effect of the juice process on the antibacterial properties of the cranberry apolar extracts: the one obtained from frozen cranberries was most efficient against P. aeruginosa, S. aureus, L. monocytogenes and S. Typhimirium (MIC of 45.50 micro g phenol/well). The tested bacteria showed the greatest resistance toward the cranberry extracts obtained from the mash and the macerated and depectinized mash

Cancer chemopreventive properties were evaluated in cranberries and cranberry products (mash, depectinized mash, pomace, raw juice, clarified juice and juice concentrate). Three extracts isolated from frozen cranberries and cranberry solids (mash, depectinized mash and pomace) containing anthocyanins, water-soluble and apolar phenolic compounds were tested. Cranberry juices and extracts were screened for their ability to induce the phase II xenobiotic detoxification enzyme quinone reductase (QR). The results showed that there was no cytotoxicity against the cells used in the test. All samples stimulated quinone reductase activity except the highest concentrations of the anthocyanin-rich extract of pomace, which inhibited QR activity. Also, the results showed that the QR induction for all samples varied with concentration and that there was an optimal concentration for which the QR induction was maximal. Although the three cranberry extracts were good QR inducers, our results indicated that the phenols present in aqueous extract showed QR inductions which were more important than those obtained with phenols present in solvent extracts. Also, the ability of phenols to stimulate the QR activity has been reduced continuously and significantly (P<=0.05) during the technological process. Especially, it appears that conditions of the evaporation to obtain a juice concentrate exerted a significant effect (P<=0.05) on inducer potencies of bioactive molecules.

BACKGROUND: Cranberry juice contains polyphenolic compounds that could improve endothelial function and reduce cardiovascular disease risk.
OBJECTIVE: The objective was to examine the effects of cranberry juice on vascular function in subjects with coronary artery disease.
DESIGN: We completed an acute pilot study with no placebo (n = 15) and a chronic placebo-controlled crossover study (n = 44) that examined the effects of cranberry juice on vascular function in subjects with coronary artery disease.
RESULTS: In the chronic crossover study, subjects with coronary heart disease consumed a research preparation of double-strength cranberry juice (54% juice, 835 mg total polyphenols, and 94 mg anthocyanins) or a matched placebo beverage (480 mL/d) for 4 wk each with a 2-wk rest period between beverages. Beverage order was randomly assigned, and participants refrained from consuming other flavonoid-containing beverages during the study. Vascular function was measured before and after each beverage, with follow-up testing >=12 h after consumption of the last beverage. Mean (+/-SD) carotid-femoral pulse wave velocity, a measure of central aortic stiffness, decreased after cranberry juice (8.3 +/- 2.3 to 7.8 +/- 2.2 m/s) in contrast with an increase after placebo (8.0 +/- 2.0 to 8.4 +/- 2.8 m/s) (P = 0.003). Brachial artery flow-mediated dilation, digital pulse amplitude tonometry, blood pressure, and carotid-radial pulse wave velocity did not change. In the uncontrolled pilot study, we observed improved brachial artery flow-mediated dilation (7.7 +/- 2.9% to 8.7 +/- 3.1%, P = 0.01) and digital pulse amplitude tonometry ratio (0.10 +/- 0.12 to 0.23 +/- 0.16, P = 0.001) 4 h after consumption of a single 480-mL portion of cranberry juice.
CONCLUSIONS: Chronic cranberry juice consumption reduced carotid femoral pulse wave velocity-a clinically relevant measure of arterial stiffness. The uncontrolled pilot study suggested an acute benefit; however, no chronic effect on measures of endothelial vasodilator function was found. This trial was registered at clinicaltrials.gov as NCT00553904.

This study investigated the effects of freeze-dried cranberry powder on anti-inflammation and lipid profiles of lipopolysaccharide (LPS)-treated rats fed an atherogenic diet for 6 weeks. Forty Sprague-Dawley male rats (6-weeks-old) were equally divided into the following five groups: 1) normal diet group + saline (NC); 2) atherogenic diet + saline (HFC); 3) atherogenic diet + LPS (HL); 4) atherogenic diet with 5% cranberry power + LPS (C5); 5) atherogenic diet with 10% cranberry power + LPS (C10). LPS (0.5 mg/kg) was injected into the abdominal cavities of rats 18 hours prior to sacrifice. At the end of the experimental period, we measured serum lipid profiles as well as levels of serum C-reactive protein (CRP), nitric oxide (NO), and pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-10 as an anti-inflammatory cytokine. The mean serum high density lipoprotein (HDL)-cholesterol level in C5 rats was significantly higher than that in NC and HL rats (P 0.05). The mean serum levels of CRP and IL-1β were significantly lower (P 0.05) in the cranberry powder groups compared to those in HL rats. Additionally, mean serum IL-6 levels tended to be lower in the cranberry groups than that in the HL group, whereas serum IL-10 and NO showed 29% and 88% higher mean values in the C5 group and 49% and 24% higher in the C10 group than those in the HL group, respectively. These results suggest that freeze-dried cranberry powder may have beneficial effects on cardiovascular diseases by modifying serum lipids and the early inflammatory response.

The effects of long-term cranberry consumption on age-related changes in endocrine pancreas are not fully understood. Here we treated male Fischer 344 rats with either 2% whole cranberry powder supplemented or normal rodent chow from 6 to 22 month old. Both groups displayed an age-related decline in basal plasma insulin concentrations, but this age-related decline was delayed by cranberry. Cranberry supplementation led to increased β-cell glucose responsiveness during the oral glucose tolerance test. Portal insulin concentration was 7.6-fold higher in rats fed cranberry, coupled with improved β-cell function. However, insulin resistance values were similar in both groups. Total β-cell mass and expression of pancreatic and duodenal homeobox 1 and insulin within islets were significantly enhanced in rats fed cranberry relative to controls. Furthermore, cranberry increased insulin release of an insulin-producing β-cell line, revealing its insulinotropic effect. These findings suggest that cranberry is of particular benefit to β-cell function in normal aging rats.