Highly Active Cranberry's Polyphenolic Fraction: New Advances in Processing and Clinical Applications.

Cranberry is a fruit originally from New England and currently growing throughout the east and northeast parts of the USA and Canada. The supplementation of cranberry extracts as nutraceuticals showed to contribute to the prevention of urinary tract infections, and most likely it may help to prevent cardiovascular and gastroenteric diseases, as highlighted by several clinical trials. However, aiming to validate the efficacy and safety of clinical applications as long-term randomized clinical trials (RCTs), further investigations of the mechanisms of action are required. In addition, a real challenge for next years is the standardization of cranberry's polyphenolic fractions. In this context, the optimization of the extraction process and downstream processing represent a key point for a reliable active principle for the formulation of a food supplement. For this reason, new non-conventional extraction methods have been developed to improve the quality of the extracts and reduce the overall costs. The aim of this survey is to describe both technologies and processes for highly active cranberry extracts as well as the effects observed in clinical studies and the respective tolerability notes.

Gene interaction network approach to elucidate the multidrug resistance mechanisms in the pathogenic bacterial strain Proteus mirabilis.

Proteus mirabilis is one among the most frequently identified pathogen in patients with the urinary tract infection. The multidrug resistance exhibited by P. mirabilis renders the treatment ineffective, and new progressive strategies are needed to overcome the antibiotic resistance (AR). We have analyzed the evolutionary relationship of 29 P. mirabilis strains available in the National Center for Biotechnology Information-Genome database. The antimicrobial resistance genes of P. mirabilis along with the enriched pathways and the Gene Ontology terms are analyzed using gene networks to understand the molecular basis of AR. The genes rpoB, tufB, rpsl, fusA, and rpoA could be exploited as potential drug targets as they are involved in regulating the vital functions within the bacterium. The drug targets reported in the present study will aid researchers in developing new strategies to combat multidrug-resistant P. mirabilis.

Dietary restriction of iron availability attenuates UPEC pathogenesis in a mouse model of urinary tract infection.

Iron is a critical nutrient required by hosts and pathogens. Uropathogenic Escherichia coli (UPEC), the principal causative agent of urinary tract infections (UTIs), chelate iron for their survival and persistence. Here, we demonstrate that dietary modulation of iron availability limits UPEC burden in a mouse model of UTI. Mice on a low-iron diet exhibit reduced systemic and bladder mucosal iron availability and harbor significantly lower bacterial burden, concomitant with dampened inflammation. Hepcidin is a master regulator of iron that controls iron-dependent UPEC intracellular growth. Hepcidin-deficient mice ( Hamp1-/-) exhibit accumulation of iron deposits, persistent bacterial burden in the bladder, and a heightened inflammatory response to UTI. However, a low-iron dietary regimen reversed the iron overload and increased bacterial burden phenotypes in Hamp1-/- mice. Thus modulation of iron levels via diet can reduce UPEC infection and persistence, which may have significant implications for clinical management of UTI.

Treatment considerations for potential uropathogens detected by precision microbiological testing.

PURPOSE: The clinical and microbiological data for urinary tract infections (UTIs) for 6 organisms detected by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) at community health systems were examined. SUMMARY: The use of precision microbiological diagnostic testing such as MALDI-TOF and real-time quantitative polymerase chain reaction has increased the ability to detect a wider spectrum of organisms. This has raised questions of the clinical relevance of infrequently encountered organisms, especially when cultured from urine. This article reviews clinical and microbiological data for UTIs for 6 organisms detected by MALDI-TOF at community health systems (Actinotignum schaalii, Chryseobacterium indologenes, Aerococcus urinae, Aerococcus sanguinicola, Corynebacterium riegelii, and Corynebacterium urealyticum). Since little information currently exists, most of the data associating the aforementioned organisms with UTIs were derived from case reports. Although these organisms are more readily identified using precision microbiological diagnostic testing methods, infection should not be assumed based on culture results alone since asymptomatic bacteriuria has been reported. Similar to more common urinary pathogens, clinical correlation is essential. To facilitate treatment, we provide a table of empirical options likely to achieve clinical success based on in vivo and in vitro data. If available, pathogen-specific susceptibility data should be used to direct therapy. CONCLUSION: Clinical and microbiological data and potential treatment options were presented for 6 traditionally underrecognized organisms that are increasingly being found from urinary specimens. The treatment recommendations should be interpreted cautiously as they were devised through the use of very limited data.

Nutritional advice for community patients: insights from a panel discussion.

This article describes the conclusions of an expert panel that discussed four case studies; these were examples of patients typically encountered by nurses working in the community. The panel considered the nutritional and lifestyle advice that could be given by nurses relating to conditions such as irritable bowel syndrome (IBS), depression, chronic fatigue syndrome, vulnerability to common infections, elderly care, recurrent urinary tract infection, antibiotic use, and risk of type 2 diabetes. A general conclusion was the importance of motivational interviewing techniques in achieving full understanding of patients' concerns and to determine the best health strategy. As well as specific guidance appropriate for each disorder, a range of information sources for both health professionals and patients are listed in the paper. The panel noted that, although general nutritional advice can be given by nurses working at GP surgeries and in the community, patients should always be referred to registered dietitians or nutritionists if significant dietary changes are considered.

Methods to determine effects of cranberry proanthocyanidins on extraintestinal infections: Relevance for urinary tract health.

Urinary tract infections (UTI) are one of the most frequent extraintestinal infections caused by Escherichia coli (ExPEC). Cranberry juice has been used for decades to alleviate symptoms and prevent recurrent UTI. The putative compounds in cranberries are proanthocyanidins (PAC), specifically PAC with "A-type" bonds. Since PAC are not absorbed, their health benefits in UTI may occur through interactions at the mucosal surface in the gastrointestinal tract. Recent research showed that higher agglutination of ExPEC and reduced bacterial invasion are correlated with higher number of "A-type" bonds and higher degree of polymerization of PAC. An understanding of PAC structure-activity relationship is becoming feasible due to advancements, not only in obtaining purified PAC fractions that allow accurate estimation, but also in high-resolution MS methodologies, specifically, MALDI-TOF MS. A recent MALDI-TOF MS deconvolution method allows quantification of the ratios of "A-type" to "B-type" bonds enabling characteristic fingerprints. Moreover, the generation of fluorescently labeled PAC allows visualization of the interaction between ExPEC and PAC with microscopy. These tools can be used to establish structure-activity relationships between PAC and UTI and give insight on the mechanism of action of these compounds in the gut without being absorbed.

The effectiveness of cranberry products to reduce urinary tract infections in females: a literature review.

Cranberry products, especially cranberry juice, have been posited to prevent or treat urinary tract infections (UTIs) in females. Antimicrobial resistance has been correlated to repeated antibiotic treatment. Thus, evaluating cranberry products as a possible alternative to conventional antibiotic therapy is appropriate. This review of the literature evaluated research in which cranberry-based products are used to prevent or treat UTIs.

Comparing procyanidins in selected Vaccinium species by UHPLC-MS(2) with regard to authenticity and health effects.

Cranberry procyanidins have been associated with an effect against urinary tract infections (UTI) for decades, and European health claims are requested. This study compares the procyanidin profiles and concentrations of American cranberry ( Vaccinium macrocarpon Ait.), European cranberry ( Vaccinium oxycoccus L.), and lingonberry ( Vaccinium vitis-idaea L.) analyzed using ultrahigh-performance liquid chromatoraphy coupled to a triple-quadrupole mass spectrometer with electrospray interface (UHPLC-MS(2)). Concentrations of A-type trimers, procyanidin A2, catechin, epicatechin, and B-type dimers and trimers have been evaluated and compared for the first time in the three berries. The data clearly show remarkable differences in the procyanidin profiles and concentrations, especially the lack of A-type trimers in V. oxycoccus; thus, the effectiveness against UTI may vary among the Vaccinium species. These differences can be used to prove authenticity.

Study on the influence of cranberry extract Zuravit S·O·S(®) on the properties of uropathogenic Escherichia coli strains, their ability to form biofilm and its antioxidant properties.

Consumption of cranberries is known to exert positive health effects, especially against urinary tract infections. For this reason, presumably, they are widely used in folk medicine. Different aspects of cranberry phenolics activity were studied in individual papers but complex study in this matter is missing. The aim of the present study is to provide complex data concerning various aspects of cranberry extract activity. We studied the effects of subinhibitory concentrations of commercially available extract (Zuravit S·O·S(®)) against two Escherichia coli strains isolated from urine of patients with pyelonephritis. Additionally the main extract anthocyanins were characterized. The activity of extract against lipid peroxidation and its radical scavenging ability were also assessed. Zuravit S·O·S(®) decreased the hydrophobicity of one of the studied E. coli strains, reduced swimming motility and adhesion to epithelial cells of both studied strains, it also limited the ability of bacteria to form biofilm. Expression of curli was not affected by cranberry extract, the assessment of P fimbriae expression was not reliable due to extract-induced agglutination of erythrocytes. Cranberry extract caused filamentation in both studied E. coli strains. It also showed pronounced antioxidant and radical scavenging properties. The properties of the studied cranberry extract show that it could be effectively used in prevention and/or elimination of urinary tract infections, specially the recurrent ones.

Cranberry components for the therapy of infectious disease.

Summary of the in vitro data support a beneficial effect of cranberry or its proanthocyanin constituents by blocking adhesion to and biofilm formation on target tissues of pathogens. In vivo data partially support these beneficial effects. Consumption of various cranberry products benefited young and elderly females in preventing urinary tract infections, and in conjunction with antibiotic treatment in eradicating Helicobacter pylori infections in women. Mouthwash supplemented with an isolated cranberry derivative reduced significantly the caryogenic mutans streptococci. None of the mice infected intranasal with lethal dose of influenza virus and treated with cranberry fraction died after two weeks. Further studies should focus on the active cranberry component as supplement for food and other products especially where whole juice or powder cannot be used.

Evaluating kidney damage from vesico-ureteral reflux in children.

To review the most relevant clinical studies that evaluate kidney damage in children with primary vesico-ureteral reflux (VUR), we reviewed and compared randomized controlled trials and clinical trials from scientific literature. In these studies, vesico-ureteral reflux was diagnosed by voiding cystourethrogram and kidney damage was assessed by either DMSA scan or urography. Relative risk with 95% confidence intervals was calculated using Review Manager Software (The Cochrane Collaboration, 2000). The overall relative risk of kidney damage shown by DMSA scan and urography was statistically higher in children with vesico-ureteral reflux of various degrees than in controls (3.7 times and 2.8 times, respectively). However, in high-grade VUR, the relative risk of congenital kidney damage was 5.6 times that of controls. We conclude that severe VUR is frequently associated with early kidney damage, perhaps with prenatal onset. Progression of kidney damage may depend on the severity of VUR and untreated urinary tract infections. Prevention of congenital kidney damage from severe VUR is possible when there is early intervention, even during fetal growth.

Consumption of sweetened dried cranberries versus unsweetened raisins for inhibition of uropathogenic Escherichia coli adhesion in human urine: a pilot study.

OBJECTIVES: The aim of this study was to determine whether consumption of sweetened dried cranberries elicits urinary anti-adherence properties against Escherichia coli as previously demonstrated with cranberry juice and/or sweetened cranberry juice cocktail, compared to unsweetened raisins. DESIGN: Uropathogenic E. coli isolates were obtained from five women with culture-confirmed urinary tract infections (UTIs). Four urine samples were collected from each subject. The first urine sample was collected before any study intervention. The second urine sample was collected 2-5 hours after consumption of one box (42.5 g) of raisins. The third urine sample was collected 5-7 days later. The final urine sample was collected 2-5 hours after consumption of approximately 42.5 g of dried cranberries. MATERIALS AND METHODS: E. coli isolates were incubated separately in each of the four urine samples collected from the five subjects. Bacteria were harvested from the urine and tested for the ability to prevent adhesion of P-fimbriated E. coli bacteria using a mannose-resistant hemagglutination assay with human red blood cells (A1, Rh+). RESULTS: Of the urine samples collected after dried cranberry consumption, one demonstrated 50% antiadherence activity, two demonstrated 25% activity, and two did not show any increased activity. None of the control urine samples and none of the postraisin consumption samples demonstrated any inhibitory activity. CONCLUSIONS: Data from this pilot study on only five subjects suggest that consumption of a single serving of sweetened dried cranberries may elicit bacterial antiadhesion activity in human urine, whereas consumption of a single serving of raisins does not. Further studies are needed to verify the antiadhesion effect of sweetened dried cranberries. In addition, dose-response and pharmacokinetics of the active compounds in the dried cranberries need to be determined. If clinical research is positive, dried cranberries could potentially be a viable alternative to cranberry juice consumption for prevention of UTIs.

Vaginal colonization by orally administered Lactobacillus rhamnosus GG.

BACKGROUND: The lack of lactobacilli in the vagina of postmenopausal women due to estrogen deficiency plays an important role in the development of bacteriuria. In the last few years the use of lactobacilli for the prevention of genitourinary infections has been explored using different probiotic strains. OBJECTIVES: To evaluate the vaginal colonization by Lactobacillus rhamnosus GG in postmenopausal healthy women following oral administration of the bacteria in a yogurt base for 1 month, as a first step in evaluating the potential probiotic role of LGG in the prevention of recurrent urinary tract infections. METHODS: One or two doses per day of yogurt containing 10(9) colony-forming units of LGG were administered orally to 42 postmenopausal healthy women for 1 month. Vaginal and rectal swabs were cultured at the beginning and end of the study. RESULTS: At the end of the study the vaginas of only four women (9.5%) were colonized with LGG, at a very low number of bacteria, despite the fact that the gastrointestinal tracts of 33 women (78.6%) were colonized. There were no significant differences between one or two doses daily. CONCLUSIONS: LGG should not be considered as a probiotic agent in urinary infections since it does not attach well to the vaginal epithelium.

Urinary tract infections cranberry juice, underwear, and probiotics in the 21st century.

There is a substantial gap between the viewpoint of urologists and the rest of society regarding UTIs. Urologists spend little time and effort thinking about UTIs. In contrast, UTIs are a major issue for many women. There is substantial concern about "natural compounds" and probiotics that allow women to take charge of their health care. It is easy to understand this concern because UTIs are common, costly, and cause considerable morbidity.

Probiotics and non-intestinal infectious conditions.

Orally ingested probiotic micro-organisms do not exert health effects exclusively in the intestine. Some strains can alleviate or prevent bacterial, fungal or viral infections in other organs by stimulation of the immune system. By preservation or improvement of the barrier function of the intestinal mucosa, they may inhibit translocation of potential pathogens and thus prevent infections of the blood stream and other tissues and organs. Modulation of the intestinal microflora can affect the local microflora of the urogenital tract and possibly of the oral cavity. Finally, some strains of orally ingested bacteria reach target organs like the urogenital tract in a viable state; alternatively they can be applied locally. Despite the infection-preventing properties of probiotic bacteria, lactic acid bacteria have rarely been identified in infections of the blood stream, heart valves and other organs, usually only in patients with severe disease. It is the general opinion that in most cases the source of infection was the commensal microflora of the intestine or the oral cavity. Until now only one case of infection associated with administration of a probiotic strain has been published. The most promising health-promoting effects have been seen in vaginosis, urinary tract infections, Helicobacter pylori gastritis and infections of the respiratory tract in children. More controlled clinical trials with sufficient numbers of participants are needed to determine the scientific basis for the use of probiotic bacteria in infections in locations of the body other than the intestine.