This study investigated the effect of A-type cranberry proanthocyanidins (AC-PACs) on osteoclast formation and bone resorption activity. The differentiation of human pre-osteoclastic cells was assessed by tartrate-resistant acid phosphatase (TRAP) staining, while the secretion of interleukin-8 (IL-8) and matrix metalloproteinases (MMPs) was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen helical peptides. AC-PACs up to 100 microg/mL were atoxic for osteoclastic cells. TRAP staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 microg/mL caused a 95% inhibition of RANKL-dependent osteoclast differentiation. This concentration of AC-PACs also significantly increased the secretion of IL-8 (6-fold) and inhibited the secretion of both MMP-2 and MMP-9. Lastly, AC-PACs (10, 25, 50 and 100 microg/ml) affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption. These compounds may be considered as therapeutic agents for the prevention and treatment of periodontitis.

Plant material screening was performed to study anti-Helicobacter pylori activity in vitro using an agar diffusion method on Columbia blood agar. 33 substances, juices and plant extracts and 35 of their combinations were tested. Quince (Cydonia oblonga) juice demonstrated the strongest anti-H. pylori activity followed by cranberry juice. Concentrated apple juice, plum, red currant, black chokeberry, raspberry and bilberry juice also showed significant activity. Green tea and apple pomace extract as well as sweet flag rhizome, ginger and wild bergamot extract, cherry syrup, red beet juice and whey did not exhibit anti-Helicobacter activity. Quince juice in combination with bilberry, black chokeberry, red currant juice, green tea, sweet flag rhizome or apple pomace extract as well as cranberry juice in combination with sweet flag rhizome extract demonstrated a synergistic effect on inhibition of H. pylori. The obtained results offer new perspectives for development of functional anti-Helicobacter food product(s) for dietary management of H. pylori infection. The essential components of these products could be the most active juices and extracts like quince and cranberry juice supplemented with a corresponding synergist. Further studies are required to investigate the mechanism of antibacterial action of plant products and their efficacy in vivo.

The antimicrobial effect of cranberry juice and of three cranberry extracts (water-soluble (E1) and apolar phenolic compounds (E2), and anthocyanins (E3)) was investigated against seven bacterial strains (Enterococcus faecium resistant to vancomycin (ERV), Escherichia coli O157:H7 EDL 933, Escherichia coli ATCC 25922, Listeria monocytogenes HPB 2812, Pseudomonas aeruginosa ATCC 15442, Salmonella Typhimurium SL1344, and Staphylococcus aureus ATCC 29213). Each cranberry sample was analyzed to determine the minimum inhibitory concentration (MIC) and the maximal tolerated concentration (MTC) at neutral pH. The results, reported in micro g phenol/mL, indicated that all the bacterial strains, both Gram-positive and Gram-negative, were selectively inhibited by the cranberry phenolic compounds. The extract rich in water-soluble phenolic compounds caused the most important growth inhibitions. The bacteria ERV, and to a lesser degree, P. aeruginosa, S. aureus and E. coli ATCC 25922, were the most sensitive to the antimicrobial activity of extract E1. The growth of P. aeruginosa and E. coli ATCC was also affected by the presence of the anthocyanin-rich cranberry extract E3, although the observed antibacterial effect was not as important as with extract E1. In general, L. monocytogenes, E. coli O157:H7 and S. Typhimurium were the most resistant to the antibacterial activity of the cranberry extracts. Within 30 min of exposure with pure neutralized cranberry juice, L. monocytogenes and ERV were completely inactivated.

Cranberry juice (CJ) and grape juice (GJ) from Vaccinium macrocarpon and Vitis labrusca, respectively, and purified proanthocyanidins (PACs) from these species are recognized to possess antiviral activity. The effects of CJ and GJ on tight junction (TJ) structure and function among rotavirus-infected monkey kidney epithelial cells (MA-104) in monolayer cultures were evaluated. Antiviral activity by cranberry PACs of rotavirus in cell-free suspension was investigated by a rotavirus antigen [i.e., viral capsid protein 6 (VP6)] capture enzyme-linked immunosorbent assay (ELISA) and by transmission electron microscopy (TEM). MA-104 monolayers were treated with CJ, GJ, or cranberry juice cocktail (CJC) drink before inoculation with rotavirus. TJ function and structural integrity were measured by changes in transepithelial electrical resistance (TEER) and by reduction of signal intensity of the TJ α-claudin 1 by immunofluorescence. The inhibitory activity of CJ and GJ on viral RNA synthesis, as a function of viral concentration, was determined by reverse transcription polymerase chain reaction (rtPCR). After 4 days, virus-infected monolayers pretreated with GJ (Concord and Niagara GJs) had TEER readings similar to uninfected controls. CJ and CJC also had a significant protective effect (P 0.05) on TJ function, but to a lesser extent than GJ. Disorganization of TJ integrity commenced at 24- to 36-h post-viral inoculation, but this effect was reduced by pretreatment with CJ or GP of monolayer cultures. TEM showed aggregation of rotavirus by cranberry PACs. The destruction of rotavirus capsid proteins VP6, in cell-free suspension was inversely related to the concentration of cranberry PACs (C-PAC). Loss of rotavirus RNA by CJ or GJ was inversely related to viral infectivity titers. CJ, GJ, or PAC-associated antiviral activity has been linked to modifications in cellular physiologic events and to physical factors (e.g., PAC-mediated viral aggregation) that probably compromise viral infectivity. Multiple cell physiological and physical events must be considered when determining the mechanisms associated with the antiviral (i.e., rotavirus) activity of CJ, GJ, and PACs.

The effects of cranberry juice cocktail (CJC) and proanthocyanidins (PACs) on biofilm formation were investigated. Escherichia coli strain HB101pDC1 and nonfimbriated strain HB101 were grown in 10 wt% CJC or 120 μg/mL PACs for 12 consecutive cultures. Biofilm formation was investigated by incubating bacteria in 96-well polyvinyl chloride (PVC) plates and studying the optical density of the solution using the crystal violet method. We suspect that biofilm formation occurred due to non-specific interactions between the bacteria and the polymer. Both P-fimbriated E. coli HB101pDC1 and the non-fimbriated strain HB101 formed biofilms. E. coli strain HB101pDC1 formed a thicker and more mature biofilm. Cranberry juice inhibited biofilm formation after the first culture; however, for bacteria grown in PACs, a decrease in biofilm formation was observed with increasing number of cultures. The inhibitory effect was reversible. These results demonstrate that CJC is more effective than isolated PACs at preventing biofilm formation, possibly suggesting that other cranberry compounds also play a role in anti-biofilm activity.

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.

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

We studied the relation between sexual and health behaviors of women and first-time urinary tract infection (UTI). The study population was women using a university health service who were unmarried, had no UTI history, and who had engaged in sexual activity at least once. We found 86 cases of UTI, defined as one or more urinary symptoms and ^1,000colony-forming units per ml urine of a known pathogen. We randomly sampled 288 controls from the student body. Vaginal intercourse increased the risk of UTI; this risk was further increased with condom use. After adjusting for vaginal intercourse with other birth control methods and recentness of current sexual partnership, a single sex act with a condom in the past 2 weeks increased UTI risk by 43%. Having a sex partner for less than 1 year vs 1 year or more, after adjustment for frequency of vaginal intercourse and birth control method, was associated with about twice the risk of UTI [odds ratio (OR) = 1.97; 95% confidence interval (CI) = 1.04-3.74].After adjusting for frequency of vaginal intercourse, regular drinking of cranberry juice was protective against UTI (OR =
0.48; 95% CI = 0.19-1.02), whereas drinking carbonated soft
drinks appeared to be associated with increased risk (OR =
2.37; 95% CI = 0.75-7.81). Using deodorant sanitary napkins
or tampons was associated with a slight increase in risk of UTI (OR = 1.51; 95% CI = 0.74-3.06). Blacks had five times
greater risk of UTI than whites after adjusting for frequency of vaginal intercourse (OR = 5.2; 95% CI = 1.89-24.63). We
observed only modest differences in health behavior between racial groups.