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Urinary Tract Health and Antibacterial Benefits: Animal

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Effect of Cranberry Extract on the Frequency of Bacteriuria in Dogs with Acute Thoracolumbar Disk Herniation: A Randomized Controlled Clinical Trial.

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Authors
Olby NJ; Vaden SL; Williams K; Griffith EH; Harris T; Mariani CL; Munana KR; Early PJ; Platt SR; Boozer L; Giovanella C; Longshore R.
Journal
Journal of Veterinary Internal Medicine. 31(1):60-68
Abstract

BACKGROUND: Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria. HYPOTHESIS: Cranberry extract reduces risk of bacteriuria in dogs after acute TL-IVDH. ANIMALS: Client-owned dogs with acute onset TL-IVDH causing nonambulatory status. METHODS: Randomized, placebo-controlled, blinded, prospective clinical trial. Dogs with acute TL-IVDH were recruited 48 hours postoperatively and randomized to receive cranberry extract or placebo in a masked fashion. Urine cultures and neurological examinations were performed 2, 4, and 6 weeks postoperatively. The number of dogs with bacteriuria (all bacterial species) and bacteriuria (E. coli) were primary and secondary outcome measures and were evaluated using chi-squared test. Urine antiadhesion activity (AAA) was measured in a subset (N = 47) and examined in a secondary analysis evaluating additional risk factors for bacteriuria. RESULTS: Bacteriuria was detected 17 times in 94 dogs (6 placebo, 11 cranberry, P = .12). There were 7 E. coli. positive cultures (1 placebo, 6 cranberry, P = .09). Dogs in both groups had positive urine AAA (14/21: placebo, 16/26: cranberry), and dogs with urine AAA had significantly fewer E. coli positive cultures (n = 1) than dogs without it (n = 4) (P = .047). CONCLUSIONS AND CLINICAL IMPORTANCE: This clinical trial did not show a benefit of oral cranberry extract but had low power. Cranberry extract supplementation did not impact urine AAA, but a possible association between urine AAA and lower risk of E. coli bacteriuria was identified. Other doses could be investigated.

Effects of cranberry extract on prevention of urinary tract infection in dogs and on adhesion of Escherichia coli to Madin-Darby canine kidney cells.

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Authors
Chou HI, Chen KS, Wang HC,Lee WM
Journal
American Journal of Veterinary Research; 2016. 77(4):421-427.
Abstract

OBJECTIVE: To determine effects of cranberry extract on development of urinary tract infection (UTI) in dogs and on adherence of Escherichia coli to Madin-Darby canine kidney (MDCK) cells. ANIMALS: 12 client-owned dogs (in vivo experiment) and 6 client-owned dogs (in vitro experiment). PROCEDURES: 12 dogs with a history of recurrent UTI received an antimicrobial (n=6) or cranberry extract (6) orally for 6 months. Dogs were monitored for a UTI. For the in vitro experiment, cranberry extract was orally administered to 6 dogs for 60 days. Voided urine samples were collected from each dog before and 30 and 60 days after onset of extract administration. Urine was evaluated by use of a bacteriostasis assay. An antiadhesion assay and microscopic examination were used to determine inhibition of bacterial adherence to MDCK cells. RESULTS: None of the 12 dogs developed a UTI. The bacteriostasis assay revealed no zone of inhibition for any urine samples. Bacterial adhesion was significantly reduced after culture with urine samples obtained at 30 and 60 days, compared with results for urine samples obtained before extract administration. Microscopic examination revealed that bacterial adherence to MDCK cells was significantly reduced after culture with urine samples obtained at 30 and 60 days, compared with results after culture with urine samples obtained before extract administration. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of cranberry extract prevented development of a UTI and prevented E. coli adherence to MDCK cells, which may indicate it has benefit for preventing UTIs in dogs.

In vivo and in vitro antibacterial activities of cranberry extract against E. coli O157:H7 in urinary tract infected rats.

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Authors
Ibrahim OMS, Sarhan SR, Hameed AA
Journal
Adv Anim Vet Sci 3(4):233-244
Abstract

The objective of this study was to determine the in-vitro and in-vivo activity of cranberry extracts against Escherichia coli O157:H7. This strain of E. coli was the most common etiologic agent of urinary tract infections isolated from patients. Filter sterilized aqueous and methanol extract of cranberry was prepared and used in the present study. The aqueous extract of cranberry produced inhibition zone ranging from (10.8-23.8) mm against the tested bacteria. While the methanol extract produces larger zones of inhibition (12.1-24.2) mm against the bacteria. The minimum inhibitory concentration (MIC) for the methanol and aqueous extract was 0.35 and 0.625 mg/ml, respectively. In vivo study involved inducing UTI in rats and then treated with (200 mg/kg B.W) aqueous and methanol extract and compared with Gentamicin treatment at a dose of (2 mg/kg B.W) subcutaneously for 14 days. Methanol extract succeeded in treated UTI caused by Escherichia coli in the infected rats and prevented infection comparing with aqueous extract and Gentamicin. Food, water intake, body weight, pH and creatinine level returned to normal values after treatment with methanol extract of Cranberry fruit (200 mg/Kg.B.W) comparing with aqueous extract of Cranberry fruit and 2 mg/Kg.B.W. of Gentamicin. These parameters used in this current study as indicator for curing from infection. These findings indicated that cranberry extract was effective at all levels in inhibiting E. coli O157:H7; thus it possesses antimicrobial activity and hold great promise as an antimicrobial agent.

Preventive effects of cranberry products on experimental colitis induced by dextran sulphate sodium in mice

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Authors
Xiao X, Kim J, Sun Q, Kim D, Park CS, Lu TS, Park Y
Journal
Food Chem 167:438-46
Abstract

With the prevalence of inflammatory bowel disease (IBD) and its associated risk for development of colorectal cancer, it is of great importance to prevent and treat IBD. However, due to the complexity of etiology and potentially serious adverse effects, treatment options for IBD are relatively limited. Thus, the purpose of this study was to identify a safe food-based approach for the prevention and treatment of IBD. In this study, we tested the effects of cranberry products on preventing dextran sulphate sodium-induced murine colitis. Our results suggest that both cranberry extract and dried cranberries-fed groups had a significantly reduced disease activity index, where dried cranberries were more effective in preventing colitis than cranberry extract. Shortening of colon length, colonic myeloperoxidase activity and production of pro-inflammatory cytokines were attenuated in animals fed dried cranberries compared to the controls. The current report suggests that cranberries can be applied to prevent and reduce the symptoms of IBD.

Attenuation of quorum sensing controlled virulence of Pseudomonas aeruginosa by cranberry.

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Authors
Harjai K, Gupta RK, Sehgal H
Journal
Indian J Med Res 139(3):446-53
Abstract

BACKGROUND & OBJECTIVES: Emergence of antimicrobial resistance in Pseudomonas aeruginosa has led to the search for alternative agents for infections control. Natural products have been a good alternative to present antibiotics. The present study was undertaken to evaluate the effectiveness of cranberry in attenuation of virulence of P. aeruginosa in experimental urinary tract infection (UTI) in mouse model. Efforts were also directed to explore the action of cranberry towards virulence of P. aeruginosa through quorum sensing (QS) inhibition.

METHODS: Efficacy of cranberry was evaluated in an experimental UTI mouse model and on production of QS signals, alginate, pyochelin, haemolysin, phospholipase-C, cell-surface hydrophobicity, uroepithelial cell-adhesion assay and biofilm formation by already standardized methods.

RESULTS: Presence of cranberry showed significant decline in the production of QS signals, biofilm formation and virulence factors of P. aeruginosa in vitro (P<0.001). Further, cranberry was found to be useful in prevention of experimental UTI in mouse model as indicated by reduced renal bacterial colonization and kidney tissues destruction.

INTERPRETATION & CONCLUSIONS: The findings of the present study indicated that cranberry inhibited QS and hence elaboration of virulence factors of P. aeruginosa. It also affected the adherence ability of this pathogen. This approach can lead to the discovery of new category of safe anti-bacterial drugs from dietary sources such as cranberry with reduced toxicity without the risk of antibiotic resistance.

Consumption of cranberry beverage improved endogenous antioxidant status and protected against bacteria adhesion in healthy humans: a randomized controlled trial.

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Authors
Mathison BD, Kimble LL, Kaspar KL, Khoo C, Chew BP
Journal
Nutr Res 34(5):420-7
Abstract

Consumption of polyphenol-rich foods is associated with lower risk from many chronic diseases. We hypothesized that a single dose of cranberry beverage would improve indices of oxidative stress, inflammation, and urinary antibacterial adhesion activity in healthy humans. Six males and 6 females (18-35 years; body mass index, 19-25 kg/m(2)) consumed placebo, cranberry leaf extract beverage, or low-calorie cranberry juice cocktail (LCJC) once in a randomized, double-blind, placebo-controlled cross-over experimental design trial. The washout period between beverages was 1 week. Blood was collected 0, 2, 4, 8, and 24 hours after beverage consumption for measuring oxidative and inflammatory biomarkers. Urine was collected at 0, 0 to 3, 3 to 6, 6 to 9, 9 to 12, and 24 hours postintervention to assess antibacterial adhesion activity. Consumption of cranberry leaf extract beverage elevated (P < .05) blood glutathione peroxidase activity, whereas LCJC consumption increased (P < .05) glutathione concentrations and superoxide dismutase activity compared with placebo. Cranberry leaf extract beverage and LCJC consumption had no effect on the inflammatory biomarkers measured as compared with placebo. At 0 to 3 hours postconsumption, urine from participants who consumed cranberry beverages had higher (P < .05) ex vivo antiadhesion activity against P-fimbriated Escherichia coli compared with placebo. An acute dose of cranberry beverages improved biomarkers of antioxidant status and inhibition of bacterial adhesion in urine. Copyright 2014 Elsevier Inc. All rights reserved.

Urine post equivalent daily cranberry juice consumption may opsonize uropathogenicity of Escherichia coli.

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Authors
Chen CS, Ho DR, Chang PJ, Lin WY, Huang YC
Journal
J Infect Chemother 19(5):812-7
Abstract

Basic studies have proven that cranberries may prevent urinary tract infections through changing the adhesiveness of Escherichia coli (E. coli) to urothelial cells. Various cranberry preparations, including extract powder, capsules, and juice, have been shown to be effective in clinical and epidemiological research. Because cranberries are most commonly consumed as juice in a diluted concentration, the aim of this study was to investigate whether the equivalent daily dose of cranberry juice is sufficient to modify host urine to change the uropathogenicity of E. coli. Urine from rats taking an equivalent daily dose of cranberry juice has been shown to decrease the capability of E. coli in hemagglutination, urothelium adhesion, nematode killing, and biofilm formation. All these changes occurred after E. coli was incubated in cranberry metabolite-containing urine, defined as urine opsonization. Urine opsonization of E. coli resulted in 40.9% (p = 0.0038) decrease in hemagglutination ability, 66.7% (p = 0.0181) decrease in urothelium adhesiveness, 16.7% (p = 0.0004) increase in the 50% lethal time in killing nematodes, and 53.9% (p = 5.9 x 10(-4)) decrease in biofilm formation. Thus, an equivalent daily dose of cranberry juice should be considered sufficiently potent to demonstrate urine opsonization in E. coli.

In vitro and in vivo antibacterial activities of cranberry press cake extracts alone or in combination with -lactams against Staphylococcus aureus

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Authors
Diarra MS, Block G, Rempel H, Oomah BD, Harrison J, McCallum J, Boulanger S, Brouillette E, Gattuso M, Malouin F
Journal
BMC Complem Altern M 13:90
Abstract

BACKGROUND: Cranberry fruits possess many biological activities partly due to their various phenolic compounds; however the underlying modes of action are poorly understood. We studied the effect of cranberry fruit extracts on the gene expression of Staphylococcus aureus to identify specific cellular processes involved in the antibacterial action.
METHODS: Transcriptional profiles of four S. aureus strains grown in broth supplemented or not with 2 mg/ml of a commercial cranberry preparation (Nutricran90) were compared using DNA arrays to reveal gene modulations serving as markers for biological activity. Ethanol extracted pressed cakes from fresh fruits also produced various fractions and their effects on marker genes were demonstrated by qPCR. Minimal inhibitory concentrations (MICs) of the most effective cranberry fraction (FC111) were determined against multiple S. aureus strains and drug interactions with -lactam antibiotics were also evaluated. Incorporation assays with [(3)H]-radiolabeled precursors were performed to evaluate the effect of FC111 on DNA, RNA, peptidoglycan (PG) and protein biosynthesis.
RESULTS: Treatment of S. aureus with Nutricran90 or FC111 revealed a transcriptional signature typical of PG-acting antibiotics (up-regulation of genes vraR/S, murZ, lytM, pbp2, sgtB, fmt). The effect of FC111 on PG was confirmed by the marked inhibition of incorporation of D-[(3)H]alanine. The combination of -lactams and FC111 in checkerboard assays revealed a synergistic activity against S. aureus including strain MRSA COL, which showed a 512-fold drop of amoxicillin MIC in the presence of FC111 at MIC/8. Finally, a therapeutic proof of concept was established in a mouse mastitis model of infection. S. aureus-infected mammary glands were treated with amoxicillin, FC111 or a combination of both; only the combination significantly reduced bacterial counts from infected glands (P0.05) compared to the untreated mice.
CONCLUSIONS: The cranberry fraction FC111 affects PG synthesis of S. aureus and acts in synergy with -lactam antibiotics. Such a fraction easily obtained from poorly exploited press-cake residues, may find interesting applications in the agri-food sector and help reduce antibiotic usage in animal food production.

Protective potential of non-dialyzable material fraction of cranberry juice on the virulence of P. gingivalis and F. nucleatum mixed infection.

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Authors
Polak D, Naddaf R, Shapira L, Weiss EI, Houri-Haddad Y
Journal
J Periodontol 84(7):1019-25
Abstract

BACKGROUND: Periodontitis is a polymicrobial infectious disease. A novel potential chemical treatment modality may lie in bacterial anti-adhesive materials, such as cranberry juice fractions. The aim of this study is to explore the effect of high molecular weight cranberry constituent (non-dialyzable material [NDM]) on the virulence of a mixed infection with Porphyromonas gingivalis and Fusobacterium nucleatum in mice.
METHODS: In vitro, the anti-adhesive property of NDM was validated on epithelial cell culture, and inhibition of coaggregation was tested using a coaggregation assay. The in vivo effect was tested on the outcome of experimental periodontitis induced by a P. gingivalis and F. nucleatum mixed infection, and also on the local host response using the subcutaneous chamber model of infection. Phagocytosis was also tested on RAW macrophages by the use of fluorescent-labeled bacteria.
RESULTS: NDM was found to inhibit the adhesion of both species of bacteria onto epithelial cells and to inhibit coaggregation in a dose-dependent manner. NDM consumption by mice attenuated the severity of experimental periodontitis compared with a mixed infection without NDM treatment. In infected subcutaneous chambers, NDM alone reduced tumor necrosis factor-alpha (TNF-alpha) levels induced by the mixed infection. In vitro, NDM eliminated TNF-alpha expression by macrophages that were exposed to P. gingivalis and F. nucleatum, without impairing their viability. Furthermore, NDM increased the phagocytosis of P. gingivalis.
CONCLUSIONS: The results indicate that the use of NDM may hold potential protective and/or preventive modalities in periodontal disease. Underlying mechanisms for this trait may perhaps be the anti-adhesive properties of NDM or its potential effect on inflammation.

Effects of cranberry extract in the treatment of urinary tract infections in sows

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Authors
Mazutti K, Alberton GC, Ferreira FM, Lunardon I, Zotti E, Weber S
Journal
"Arch Vet Sci
Abstract

The experiment consisted in assessing the effectiveness of a commercial product based on cranberry extracts (pHDReg.-Biomin LTDA) in the treatment of urinary tract infections (UTI) in sows. Were used 42 sows, with gestational ages ranging between 50 and 70 days, either suffering from UTI or not. Healthy animals were differentiated from affected animals by urinalysis and urine culture. The experiment was composed of sows with UTI that received the cranberry extract product in the diet for a period of 14 days; sows negative for UTI (negative controls) and sows positive for UTI (positive controls). The former two groups did not receive the cranberry extract product in the diet. Urine samples were collected on days zero, seven and 14 after initiation of treatment. Complete urinalysis of these samples, urine specific gravity, pH, bacterial count and bacterial isolation were performed. E. coli was the most frequent isolated agent (90.62%). The results showed that the commercial product made with cranberry extract was effective in promoting a reduction of urinary pH, but did not interfere in any other parameters observed.