Twenty-seven patients with indwelling urinary catheters and chronic bacteriuria were studied for methenamine efficacy. In a crossover fashion, each patient received methenamine mandelate granules 4 g/day alone, with ascorbic acid 4 g/day, and with ascorbic acid 4 g/day plus cranberry cocktail one 1/day. Proteus vulgaris, Pseudomonas aeruginosa, and E. coli were the common pathogens. Urinary acidifiers had no significant effect on mean urine pH, however, high urinary formaldehyde concentrations were associated with the use of ascorbic acid. Bacteriocidal formaldehyde levels were more frequently present in patients with acidic urine pH than those with alkaline pH. Although ascorbic acid increased formaldehyde levels, additional cranberry cocktail had no further effect. Despite higher formaldehyde levels, urine culture results were positive in most cases with or without urine acidification. Methenamine therapy may be of limited value in asymptomatic chronic bacteriuric patients with indwelling catheters.

This study involved 27 geriatric patients with asymptomatic chronic bacteriuria; all had indwelling Foley catheters. The treatment regimens (daily oral dosage) were: methenamine mandelate (MM) granules, 4 gm; MM, 4 gm, plus ascorbic acid, 4 gm; and MM, 4 gm, plus ascorbic acid, 4 gm, plus cranberry cocktail, 1 liter--administered according to a cross-over design. Proteus vulgaris, Pseudomonas aeruginosa and E. coli were the most common urinary organisms. Proteus organisms were more often found in alkaline than in acidic urines, but the type of pathogen had no influence on urinary pH. Urinary formaldehyde concentration [HCHO] was lower in patients with Proteus infection (17.7 micrograms/ml) than in those with Pseudomonas (21.9 micrograms/ml) or E. coli infection (21.8 micrograms/ml). However, for Proteus infection, [HCHO] was higher in patients receiving MM plus ascorbic acid than in those receiving MM alone. Addition of cranberry cocktail to ascorbic acid did not enhance urinary pH, [HCHO] or methenamine efficacy. Our data suggest that in Foley catheter patients with chronic asymptomatic bacteriuria secondary to Proteus, Pseudomonas or E. coli infection, the type of urinary pathogen or the urinary pH cannot be used to predict the efficacy of methenamine therapy either with or without urinary acidifying agents.

Bacterial adhesion to the cell surface is a crucial step before infection can take place. Inhibition of bacterial binding offers a novel preventive approach against infections. Cranberry (Vaccinium macrocarpon Ait.) juice has been found to have antiadhesive activity against different bacteria. Streptococcus pneumoniae is an important pathogen and the most common cause for pneumonia, meningitis, and otitis media. In this study the inhibitory activity of cranberry (Vaccinium oxycoccos L.), bilberry (Vaccinium myrtillus L.) and crowberry (Empetrum nigrum and Empetrum hermaphroditum L.) juice fractions against pneumococcal binding was tested using human bronchial cells (Calu-3) as an adhesion model. In addition, the antimicrobial activity of the berry juice fractions was tested. It was found that the studied berry juice fractions had antiadhesion activity and cranberry juice was the most active. The adhesion inhibition activity of cranberry juice was nearly 90% at a concentration of 8.7mg/g of soluble solids. The antimicrobial activity of the studied berry juice fractions was found to be remarkable; pneumococcal growth was inhibited totally at a concentration of ~86mg/g. Both antiadhesion and antimicrobial activities were reduced after solid-phase extraction of the berry juices, which may suggest molecular synergistic effects of the berry juice molecules against S. pneumoniae. The findings indicate that cranberry, bilberry and crowberry juices have potential against pneumococcal infections.

Sucrose increases postprandial blood glucose concentrations, and diets with a high glycaemic response may be associated with increased risk of obesity, type 2 diabetes and CVD. Previous studies have suggested that polyphenols may influence carbohydrate digestion and absorption and thereby postprandial glycaemia. Berries are rich sources of various polyphenols and berry products are typically consumed with sucrose. We investigated the glycaemic effect of a berry puree made of bilberries, blackcurrants, cranberries and strawberries, and sweetened with sucrose, in comparison to sucrose with adjustment of available carbohydrates. A total of twelve healthy subjects (eleven women and one man, aged 25–69 years) with normal fasting plasma glucose ingested 150 g of the berry pure´e with 35 g sucrose or a control sucrose load in a randomised, controlled cross-over design. After consumption of the berry meal, the plasma glucose concentrations were significantly lower at 15 and 30 min (P<0·05, P<0·01, respectively) and significantly higher at 150 min (P<0·05) compared with the control meal. The peak glucose concentration was reached at 45 min after the berry meal and at 30 min after the control meal. The peak increase from the baseline was 1·0 mmol/l smaller (P=0·002) after ingestion of the berry meal. There was no statistically significant difference in the 3 h area under the glucose response curve. These results show that berries rich in polyphenols decrease the postprandial glucose response of sucrose in healthy subjects. The delayed and attenuated glycaemic response indicates reduced digestion and/or absorption of sucrose from the berry meal.

A cellular antioxidant activity (CAA) assay for quantifying the antioxidant activity of phytochemicals, food extracts, and dietary supplements has been developed. Dichlorofluorescin is a probe that is trapped within cells and is easily oxidized to fluorescent dichlorofluorescein (DCF). The method measures the ability of compounds to prevent the formation of DCF by 2,2′-azobis(2-amidinopropane)
dihydrochloride (ABAP)-generated peroxyl radicals in human hepatocarcinoma HepG2 cells. The decrease in cellular fluorescence when compared to the control cells indicates the antioxidant capacity of the compounds. The antioxidant activities of selected phytochemicals and fruit extracts were evaluated using the CAA assay, and the results were expressed in micromoles of quercetin equivalents per 100 μmol of phytochemical or micromoles of quercetin equivalents per 100 g of fresh fruit. Quercetin had the highest CAA value, followed by kaempferol, epigallocatechin gallate (EGCG), myricetin, and luteolin among the pure compounds tested. Among the selected fruits tested, blueberry had the highest CAA value, followed by cranberry > apple ) red grape > green grape. The CAA
assay is a more biologically relevant method than the popular chemistry antioxidant activity assays because it accounts for some aspects of uptake, metabolism, and location of antioxidant compounds within cells.

Chitosan binds to negatively charged soy lecithin liposomes by an electrostatic interaction driven by its positively charged amino group. This interaction allows stable covered vesicles (chitosomes) to be developed as a suitable targeted carrier and controlled release system. This study investigated the effect of chitosomes on the activation of cranberry proanthocyanidins (PAC) in Raw 264.7 macrophages. Chitosomes were characterized according to size, zeta potential, PAC-loading, and release properties. Results showed an increase in the net positive charge and size of the liposomes as the concentration of chitosan was increased, suggesting an effective covering of the vesicles by means of electrostatic interactions, as shown by transmission electron microscopy and fluorescence microscopy. About 85% of the PAC that was loaded remained in the chitosomes after release studies for 4 hours in phosphate-buffered saline. Cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are associated with inflammation. Activated RAW 264.7 macrophages increase the expression of COX-2 and iNOS in response to bacterial infection and inflammation; we, therefore, tested the ability of the PAC-loaded chitosomes to attenuate COX-2 and iNOS expression in LPS (lipopolysaccharide)-stimulated macrophages. Increasing the amount of PAC loaded into the chitosomes caused a dose-dependent attenuation of iNOS and COX-2 expression in LPS-stimulated macrophages. A 2% v/v PAC-loaded chitosomes formulation almost completely attenuated the LPS-induced expression of iNOS and COX-2. PAC-loaded chitosomes were more active than PAC alone, suggesting that the macrophage response to LPS occurs after endocytosis of the PAC-loaded chitosomes.

The in vitro effectivity of cranberry derived proanthocyanidins (PACs) for the mitigation of kidney cell
infection by selected uro- and entero-pathogens is examined with an adhesion/invasion assay and confocal
microscopy. This study demonstrates that PACs effectively reduce invasion of canine kidney cells by
pathogenic bacteria: Escherichia coli CFT073 and O157:H7, Enterococcus faecalis 29212, and Pseudomonas
aeruginosa 10145. These effects demonstrate the potential for cranberry derived PACs as a useful tool in
the prevention of kidney infection

Based on anecdotal reports, the question of whether cranberry juice interacts with warfarin has been raised. This article discusses the potential mechanism, and systematically reviews case reports as well as clinical trials examining the possible interaction. We systematically searched MEDLINE via PubMed, and the Cochrane Library database. Fifteen case reports were summarized, including the initial unpublished brief reports to the Committee on Safety of Medicines and the subsequent 6 published case reports. Seven clinical trials were analyzed, including 3 studies using warfarin and 4 surrogate drugs. Only 2 cases had a validation scale suggesting a "probable" interaction, but even in these patients there were many reasons to question the validity of a relevant drug interaction. Randomized clinical trials and surrogate markers found no evidence to support the interaction between cranberry juice and warfarin. Because the moderate consumption of cranberry juice does not affect anticoagulation, we encourage the reexamination of initial warnings based on scientific evidence. We conclude that the initial precautionary warnings by administrating bodies are limited to anecdotal case reports and represent misleading conclusions.

Flavonoids can bind the divalent cations frequently used to evaluate LDL antioxidant capacity in vitro. Flavonoids in cranberry juice (CBJ) may serve as antioxidants and promote cardiovascular health. This in vitro study characterizes CBJ effects on metal and non-metal based oxidation of human LDL. For cupric ion-initiated oxidation of LDL, thiobarbituric acid reactive substances (TBARS) formation and relative electrophoretic mobility (REM) were significantly inhibited by CBJ at a dilution of 1:10,000. Diene formation during LDL oxidation was evaluated by continuous measurement of absorbance at 234 nm. The time required for cupric ion-initiated LDL oxidations to reach maximum reaction velocity was significantly delayed by 1:10,000 dilutions of CBJ. Non-metal initiated LDL oxidation by 2,2'-azobis-amidinopropane was significantly inhibited by CBJ at dilutions of 1:10,000 and 1:5,000 for REM and TBARS tests, respectively. Protection of LDL from both metal and non-metal based oxidative injury confirms that the effects of CBJ are not due to flavonoid chelation of oxidants but due to a true and potent antioxidant capacity.

Abstract: Antioxidant activity of six fractions of cranberry phenolic compounds was determined by
inhibition of Cu2+-induced low-density lipoprotein (LDL) oxidation. The phenolic composition of each fraction was determined by high-performance liquid chromatography. The phenolic fractions were mixed with aliquots of modified human serum prior to LDL isolation. The serum was modified to remove very-low-density lipoprotein and chylomicrons that may bind phenolic compounds. Only fractions 5 and 6 that contained proanthocyanidins (PAs) significantly increased the lag time of LDL oxidation, and the lag time for fraction 6 was significantly higher than for fraction 5. The mass distribution of PAs in these fractions was obtained by matrix-assisted laser desorption/ionisation time- of-flight mass spectrometry, a technique that allows rapid characterisation of the molecular weight distribution in mixtures of oligomeric compounds. Fraction 5 contained trimers through heptamers, whereas fraction 6 contained pentamers through nonamers. In addition, fraction 6 contained PA oligomers with more doubly linked, A-type interflavan bonds. Results indicate that PAs specifically associate with LDL in modified serum and increase the lag time of Cu2+-induced oxidation. Differences between fractions 5 and 6 in PA structure and effects on LDL oxidation suggest that the degree of polymerisation and the nature of the interflavan bond influence antioxidant properties