D-Mannose

OBJECTIVE: Recent guidelines indicated that, in addition to antibiotics, nonantibiotic interventions serve as available preventive options for urinary tract infections (UTIs). This study aimed to compare the efficacy and safety of various nonantibiotic interventions in preventing UTIs. METHODS: The authors systematically searched databases for eligible studies. The inclusion criteria encompassed randomized controlled trials (RCTs) focusing on one or more nonantibiotic interventions for UTI prevention, with the incidence of UTIs being a key outcome measure. Subgroup analyses were performed according to age, sex, and follow-up. RESULTS: 50 RCTs comprising 10,495 subjects and investigating 14 interventions, were included. Nearly 80% of the RCTs utilized double-blind or triple-blind designs. In the whole group, D-mannose (risk ratio [RR] 0.34, 0.21 to 0.56), vaccine (RR 0.65, 0.52 to 0.82), probiotics (RR 0.69, 0.50 to 0.94), cranberry (RR 0.72, 0.60 to 0.87), and triple therapy (cranberry plus probiotics plus vitamin A) (RR 0.27, 0.09 to 0.87), exhibited a significant reduction in UTI incidence compared to the placebo. Probiotics (RR 0.50, 0.28 to 0.89) were the most effective in the nonadult group, while vitamin D (RR 0.46, 0.27 to 0.81) showed the highest efficacy in the long follow-up group (≥ 1 year). There was no significant difference in the incidence of adverse events between the interventions and the placebo group. CONCLUSIONS: D-mannose, triple therapy, vaccine, probiotics, and cranberry serve as potential nonantibiotic intervention options for clinical UTI prevention. © 2024. Springer-Verlag GmbH Germany, part of Springer Nature.

BACKGROUND: Wound healing is a current problem in surgery. Wounds most commonly occur from surgery, accidents, and burns. The purpose of this study was to reduce bleeding time and wound healing time as well as prevent or mitigate scarring by applying D-mannose with calcium propionate mixtures directly to the wound in powder form. METHODS: This study was a placebo, randomized, double-blind, crossover experiment involving a single group of twenty-five subjects. The number of incisions made was equal to the number of treatments required. Each subject had one incision per day. Only one treatment was applied to each wound. By the end, each subject was treated with all test mixtures and the placebo substance. RESULTS: The results show that the bleeding time can be reduced to about 50% compared to D-mannose when treating the wound with a mixture containing 20-60 moles of D-mannose per 1 mole of powdered calcium propionate. The wound healing time was reduced by about 40% compared to D-mannose. No visible scarring was observed after 40 days on skin treated with the mannose and calcium propionate mixture. CONCLUSIONS: Bleeding time can be reduced by approximately 50% when the wound is treated with a mixture containing 40 moles of D-mannose per 1 mole of calcium propionate and wound healing time by approximately 40% compared to D-mannose. Both substances contribute to the destruction of pathogens and to the processes of new tissue formation, which accelerates the healing process. Treatment with this powdered mixture prevents skin scarring. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . © 2025. The Author(s).

PURPOSE: Recurrent urinary tract infections (rUTIs) are a common and impactful clinical challenge in premenopausal women, significantly affecting quality of life and imposing high healthcare costs. Despite their prevalence, robust comparative studies evaluating preventive strategies are scarce, and growing antimicrobial resistance necessitates exploring non-antibiotic alternatives. The aim of this study is to compare the efficacy and safety of increased hydration, D-mannose, and antibiotic prophylaxis in preventing recurrent UTIs in premenopausal women. METHODS: This 12-month, prospective, randomized, controlled, multicenter, three-arm parallel study enrolled 75 premenopausal women (18-49 years) with ≥ 3 UTIs/year. Participants were randomized (1:1:1) to increased hydration, D-mannose, or low-dose antibiotic prophylaxis. Primary endpoints were number of UTI episodes/year. Secondary endpoints included time to first UTI and adverse events. Statistical analysis utilized ANOVA and Kaplan-Meier methods. RESULTS: All three groups demonstrated some degree of UTI prevention. The antibiotic prophylaxis group showed the lowest rUTI incidence (mean 0.2 episodes/year, median 0), significantly lower than the increased hydration group (mean 1.08 episodes/year, median 1; p < 0.05). D-mannose showed intermediate efficacy (mean 0.32 episodes/year, median 0), trending toward significance compared to increased hydration. Mean time to first UTI was longest in the antibiotic group (4.5 months) vs. D-mannose (2.5 months) and hydration (1 month). Minor adverse events (e.g., mild gastrointestinal issues) were more frequent with antibiotics; no severe adverse events occurred. CONCLUSION: Low-dose antibiotic prophylaxis remains the most effective strategy for rUTI prevention in premenopausal women. However, D-mannose emerges as a promising, safe non-antibiotic alternative, demonstrating notable efficacy in reducing episodes. Increased hydration, while less effective, remains a safe, economical, and easily implementable baseline measure. These findings advocate for a personalized approach to rUTI prevention, balancing efficacy, safety profile, and patient preference, particularly to mitig

BACKGROUND: To evaluate the efficacy of a new D-mannose dietary supplement containing D-mannose, Propolis-Quercetin, Bacillus Coagulans, Hyaluronic Acid and Chondroitin Sulfate with fosfomycin in reducing rUTI episodes and improving quality of life. RESEARCH DESIGN AND METHODS: Single-blind, randomized controlled trial conducted at tertiary-care hospital in Italy. Women aged 21-65 with a history of rUTIs were randomized into three groups: fosfomycin, the dietary supplement, and a combination of both treatments. Primary outcome was frequency of rUTI episodes per month. RESULTS: Combination therapy demonstrated greatest reduction in rUTI episodes per month at 12 months compared to fosfomycin or supplement monotherapy (0.23 ± 0.37 vs 0.58 ± 0.67 and 1.12 ± 0.96 for fosfomycin and supplement monotherapy respectively; p < 0.05) and to supplement monotherapy at 6 months (0.69 ± 1.03 vs 1.43 ± 1.33; p < 0.05), with significant improvement of ICIQ-FLUTS domains compared to other groups at 12 months (p < 0.05). Combination therapy had lower number of women matching rUTI criteria (55.32% vs 76.47% and 84%; p < 0.05) and symptoms remission at 12 months (89.36% vs 56.86% and 20%; p < 0.001). CONCLUSIONS: Combining fosfomycin and an integrated D-mannose supplement for managing rUTIs offers a potential reduction in antibiotic reliance. Further large-scale studies are recommended to confirm these findings. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT06659016).

AIM: To evaluate the efficacy and safety of UroBest complex in sachets for combined therapy of patients with acute cystitis in comparison with products of similar composition. MATERIALS AND METHODS: The randomized multi-center study included 90 patients with acute cystitis aged 18 to 49 years who were treated at the clinical bases of SRC FMBC, FMBA of Russia, Moscow, Russia, Altai State Medical University and Voronezh State Medical University named after N.N. Burdenko. Patients of all groups received Fosfomycin trometamol in a dosage of 3g once, at night. Depending on the additional drug received, they were divided into 3 groups of 30 patients each. In group 1, they took UroBest 1 sachet daily for 7 days from the first day of therapy, NefroBest-N one capsule 2 times a day for 1 month also from the first day of therapy, in combination with UroBest complex in the first week. In group 2, UroBest 1 sachet daily for 7 days was administered, while in group 3, biologically active supplement (BAA) "Uronext" 1 sachet daily for 7 days was given. The study included 4 control points, where the degree and dynamics of changes in laboratory parameters (urinalysis, complete cell count, urine culture with determination of sensitivity to antibiotics), quality of life according to the questionnaire, and pain intensity according to the visual analogue scale (VAS) were assessed, as well as the drug tolerability based on the analysis of adverse events. RESULTS: The efficacy and safety data were evaluated. Administration of complex preparations with extracts of medicinal plants as an additional to antibacterial therapy led to significant improvement of all parameters, except for the level of leucocytes in the complete cell count. The most pronounced improvement was observed in groups 1, and lesser improvement was noted in group 2. One patient in group 3 had an adverse event, which was resolved spontaneously. CONCLUSION: UroBest has a favorable efficacy and safety profile. According to our experience, combination of UroBest and NefroBest-N complexes leads to more pronounced positive changes in laboratory parameters and patient's condition according to the questionnaires compared to Uro

BACKGROUND: Intravesical instillation of hyaluronic acid (HA) has been associated with reduced sexual dysfunction in participants with recurrent urinary tract infections (rUTIs), but the efficacy of an oral treatment has never been investigated. AIM: To investigate the efficacy of an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C in improving sexual and urinary symptoms in a cohort of reproductive-age participants with rUTI. METHODS: In a monocentric randomized crossover pilot trial, participants with rUTI who were referred to our institute between March 2022 and April 2023 were randomized 1:1 in 2 groups: intervention vs control. All participants had an oral preparation of cranberry, D-mannose, propolis extract, turmeric, and Boswellia twice a day for 3 months. The intervention group also included an oral preparation of HA, chondroitin sulfate, N-acetylglucosamine, and vitamin C once a day for 3 months. Crossover of treatment occurred at 3 months for an additional 3 months. At baseline and 3 and 6 months, participants were evaluated clinically and with the International Prostate Symptom Score (IPSS) and Female Sexual Function Index (FSFI). Descriptive statistics and logistic regression models tested the impact of the intervention on urinary and sexual symptoms at each follow-up assessment. OUTCOMES: Improvement in sexual and urinary symptoms as measured by the FSFI and IPSS. RESULTS: Overall, 27 (54%) participants had an FSFI score <26.5 at enrollment. At 3 months, FSFI scores were higher in the intervention group vs control (P < .001), but IPSS scores were lower (P = .03). After crossover of treatment, FSFI and IPSS scores remained stable in the intervention group. However, after crossover, the control group showed a significant improvement in IPSS and FSFI scores (all P < .01) vs the 3-month assessment. At last follow-up, urinary and sexual symptoms were comparable between groups. In logistic regression analyses, the intervention group was associated with early improvement in sexual symptoms (odds ratio, 3.9; P = .04) and urinary symptoms (odds ratio, 5.1; P = .01) after accounting for clinical confounders. CLINICAL IMPLICATIO

BACKGROUND: Studies analyzing non-antibiotic alternatives in kidney transplant UTI's are lacking. d-Mannose, a simple sugar, inhibits bacterial attachment to the urothelium, as does Proanthocyanidins; both could act as a synergic strategy preventing UTI; nonetheless their efficacy and safety have not been evaluated in kidney transplant population yet. METHODS: This is a pilot prospective, double-blind randomized trial. Sixty de novo kidney transplant recipients were randomized (1:1) to receive a prophylactic strategy based on a 24-h prolonged release formulation of d-Mannose plus Proanthocyanidins vs. Proanthocyanidins (PAC) alone. The supplements were taken for the first 3 months after kidney transplant and then followed up for 3 months as well. The main objective of the study was to search if the addition of Mannose to PAC alone reduced the incidence of UTI and/or asymptomatic bacteriuria in the first 6 months post-transplantation. RESULTS: 27% of patients experienced one UTI episode (cystitis or pyelonephritis) while asymptomatic bacteriuria was very common (57%). Incidences according UTI type or AB were: 7% vs. 4% for cystitis episode (p 0.3), 4% vs. 5% for pyelonephritis (p 0.5) and 17% vs. 14% for asymptomatic bacteriuria (p 0.4) for patients in the Mannose+PAC group vs. PAC group respectively. The most frequent bacteria isolated in both groups was Escherichia coli (28% of all episodes), UTI or AB due to E. coli was not different according to study group (30% vs. 23% for Mannose+PAC vs. PAC alone p 0.37). CONCLUSIONS: Non-antibiotic therapy is an unmet need to prevent UTI after kidney transplantation; however, the use of d-Mannose plus PAC does not seem capable to prevent it.

Comment in JAMA Intern Med. 2024 Jun 1;184(6):629-630. doi: 10.1001/jamainternmed.2024.0261. IMPORTANCE: Recurrent urinary tract infection (UTI) is a common debilitating condition in women, with limited prophylactic options. d-Mannose has shown promise in trials based in secondary care, but effectiveness in placebo-controlled studies and community settings has not been established. OBJECTIVE: To determine whether d-mannose taken for 6 months reduces the proportion of women with recurrent UTI experiencing a medically attended UTI. DESIGN, SETTING, AND PARTICIPANTS: This 2-group, double-blind randomized placebo-controlled trial took place across 99 primary care centers in the UK. Participants were recruited between March 28, 2019, and January 31, 2020, with 6 months of follow-up. Participants were female, 18 years or older, living in the community, and had evidence in their primary care record of consultations for at least 2 UTIs in the preceding 6 months or 3 UTIs in 12 months. Invitation to participate was made by their primary care center. A total of 7591 participants were approached, 830 responded, and 232 were ineligible or did not proceed to randomization. Statistical analysis was reported in December 2022. INTERVENTION: Two grams daily of d-mannose powder or matched volume of placebo powder. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the proportion of women experiencing at least 1 further episode of clinically suspected UTI for which they contacted ambulatory care within 6 months of study entry. Secondary outcomes included symptom duration, antibiotic use, time to next medically attended UTI, number of suspected UTIs, and UTI-related hospital admissions. RESULTS: Of 598 women eligible (mean [range] age, 58 [18-93] years), 303 were randomized to d-mannose (50.7%) and 295 to placebo (49.3%). Primary outcome data were available for 583 participants (97.5%). The proportion contacting ambulatory care with a clinically suspected UTI was 150 of 294 (51.0%) in the d-mannose group and 161 of 289 (55.7%) in the placebo group (risk difference, -5%; 95% CI, -13% to 3%; P = .26). Estimates were similar in per protocol analyses, imputation analyses, and

Background and Objectives: Patients undergoing cystoscopy can experience discomfort or pain during the procedure. In some cases, a urinary tract infection (UTI) with storage lower urinary tract symptoms (LUTS) may occur in the days following the procedure. This study aimed to assess the efficacy of D-mannose plus Saccharomyces boulardii in the prevention of UTIs and discomfort in patients undergoing cystoscopy. Materials and Methods: A single-center prospective randomized pilot study was conducted between April 2019 and June 2020. Patients undergoing cystoscopy for suspected bladder cancer (BCa) or in the follow-up for BCa were enrolled. Patients were randomized into two groups: D-Mannose plus Saccharomyces boulardii (Group A) vs. no treatment (Group B). A urine culture was prescribed regardless of symptoms 7 days before and 7 days after cystoscopy. The International Prostatic Symptoms Score (IPSS), 0-10 numeric rating scale (NRS) for local pain/discomfort, and EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) were administered before cystoscopy and 7 days after. Results: A total of 32 patients (16 per group) were enrolled. No urine culture was positive in Group A 7 days after cystoscopy, while 3 patients (18.8%) in Group B had a positive control urine culture (p = 0.044). All patients with positive control urine culture reported the onset or worsening of urinary symptoms, excluding the diagnosis of asymptomatic bacteriuria. At 7 days after cystoscopy, the median IPSS of Group A was significantly lower than that of Group B (10.5 vs. 16.5 points; p = 0.021), and at 7 days, the median NRS for local discomfort/pain of Group A was significantly lower than that for Group B (1.5 vs. 4.0 points; p = 0.012). No statistically significant difference (p > 0.05) in the median IPSS-QoL and EORTC QLQ-C30 was found between groups. Conclusions: D-Mannose plus Saccharomyces boulardii administered after cystoscopy seem to significantly reduce the incidence of UTI, the severity of LUTS, and the intensity of local discomfort.

IMPORTANCE: Further research is needed to determine whether d-mannose plus vaginal estrogen therapy (VET) is beneficial over VET alone for recurrent urinary tract infection (rUTI) prevention. OBJECTIVE: The aim of this study was to evaluate d-mannose efficacy for rUTI prevention in postmenopausal women using VET. STUDY DESIGN: We conducted a randomized controlled trial comparing d-mannose (2 g/d) with control. Participants were required to have a history of uncomplicated rUTIs and to remain on VET throughout the trial. They were followed up 90 days for incident UTIs. Cumulative UTI incidences were calculated by the Kaplan-Meier method and compared by Cox proportional hazards regression. For the planned interim analysis, P < 0.001 was considered statistically significant. Futility analysis was performed by generating post hoc conditional power for multiple scenarios. RESULTS: We evaluated 545 patients for frequent/recurrent UTIs from March 1, 2018, to January 18, 2020. Of these women, 213 had culture-proven rUTIs, 71 were eligible, 57 enrolled, 44 began their planned 90-day study period, and 32 completed the study. At interim analysis, the overall cumulative UTI incidence was 46.6%; 41.1% in the treatment arm (median time to first UTI, 24 days) and 50.4% in the control arm (median, 21 days); hazard ratio, 0.76; 99.9% confidence interval, 0.15-3.97. d-Mannose was well tolerated with high participant adherence. Futility analysis suggested the study lacked power to detect the planned (25%) or observed (9%) difference as statistically significant; the study was halted before conclusion. CONCLUSIONS: d-Mannose is a well-tolerated nutraceutical, but further research is needed to determine whether d-mannose in combination with VET has a significant, beneficial effect beyond VET alone in postmenopausal women with rUTIs.

BACKGROUND: The rise in antimicrobial resistance means that alternative approaches for the treatment and prevention of urinary tract infection (UTIs) are required. OBJECTIVE: To evaluate the safety and efficacy of a D-mannose-based dietary supplement (D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion; DAPAD complex) for the treatment of uncomplicated acute E. coli UTIs. DESIGN, SETTING, AND PARTICIPANTS: This was a single-center, randomized, double-blind, placebo-controlled trial conducted from April 2021 to October 2021 in Rajalakshmi Hospital and Research Centre (Bangalore, India). The participants were nonmenopausal women with an acute uncomplicated E. coli UTI. UTI was diagnosed according to the presence of at least one urinary symptom and bacteriuria (>100 000 CFU/ml). INTERVENTION: The DAPAD complex was administered twice a day for 5 d, with phenazopyridine and alkalizing agents as the standard of care (SOC). The control group received placebo with SOC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Subjective (clinical resolution/response) and objective (midstream bacteriuria) outcomes were evaluated at the end of therapy (day 6) and at day 35 of follow-up. Adverse events were recorded. Categorical variables were analyzed using χ2 and Fisher's exact tests; a p value <0.05 was considered significant. RESULTS AND LIMITATIONS: Seventy women were enrolled and equally randomized to the two groups. Clinical resolution was higher in the DAPAD group at 6 d (34.3% vs 0%; p < 0.0001) and 35 d from baseline (88.6% vs 20%, p < 0.0001). At day 35, no patients in the DAPAD group had moderate or severe symptoms, whereas 25.7% (nine/35) and 11.4% (four/35) of patients in the placebo group had moderate and severe symptoms, respectively. Bacteriological resolution was also higher in the DAPAD group at day 6 (85.7% vs 14.3%; p < 0.0001) and day 35 (100% vs 40%; p < 0.0001). Three mild adverse events (4.26%) unrelated to the investigated product were recorded, all of which were medically treated. CONCLUSIONS: The DAPAD complex dietary supplement is effective and safe for treatment of acute uncomplicated E. coli UTIs. PATIENT SUMMARY: Our results show that f

AIMS: We determined the synergistic effects of tea tree essential oil nano-emulsion (nanoTTO) and antibiotics against multidrug-resistant (MDR) bacteria in vitro and in vivo. Then, the underlying mechanism of action of nanoTTO was investigated. METHODS AND RESULTS: Minimum inhibitory concentrations and fractional inhibitory concentration index (FICI) were determined. The transepithelial electrical resistance (TEER) and the expression of tight junction (TJ) protein of IPEC-J2 cells were measured to determine the in vitro efficacy of nanoTTO in combination with antibiotics. A mouse intestinal infection model evaluated the in vivo synergistic efficacy. Proteome, adhesion assays, quantitative real-time PCR, and scanning electron microscopy were used to explore the underlying mechanisms. Results showed that nanoTTO was synergistic (FICI ≤ 0.5) or partial synergistic (0.5 < FICI < 1) with antibiotics against MDR Gram-positive and Gram-negative bacteria strains. Moreover, combinations increased the TEER values and the TJ protein expression of IPEC-J2 cells infected with MDR Escherichia coli. The in vivo study showed that the combination of nanoTTO and amoxicillin improved the relative weight gain and maintained the structural integrity of intestinal barriers. Proteome showed that type 1 fimbriae d-mannose specific adhesin of E. coli was downregulated by nanoTTO. Then, nanoTTO reduced bacterial adhesion and invasion and inhibited the mRNA expression of fimC, fimG, and fliC, and disrupted bacterial membranes. © The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.

In AIDS, only a few types of tumors (mainly Kaposi's sarcoma and non-Hodgkin's lymphoma) increase in incidence despite global abnormalities in the immune system. In addition, the reason for the higher incidence of these tumors is not immunosuppression but other agents. This shows that the immune system has no absolute role in the prevention of tumors. Consequently, the fact that tumors do not develop in the majority of the population during their lifetime, indicates the existence of other defense system(s). We demonstrated previously that a mixture of 16 substances (selected experimentally out of 89 compounds of the circulatory system using the synergistic tumor cell-killing effect as criteria) had a cytotoxic effect (inducing apoptosis) in vitro and in vivo on tumor cell lines, but not on normal cells in vitro or animals. In our hypothesis these substances (L-tryptophan, L-tyrosine, L-methionine, L(-)malate, L-ascorbate, L-arginine, L-phenylalanine, L-histidine, 2-deoxy-D-ribose, d-biotin, pyridoxine, adenine, riboflavin, D(+)-mannose, orotate, and hippurate) are the active agents of a passive antitumor defense system (PADS). On the basis of the results, a tablet and a cream were developed, and an infusion is in preclinical phase. In this study we demonstrate that the above-mentioned substances can kill tumor cells when the experimental protocols, concentrations, and cell numbers are chosen to be comparable to the physiological conditions that exist in the living system when these substances fight against arising cancer cells. The results of our experiments demonstrate that the PADS really works in the human body.

Three oligosaccharide fractions from the root of Amorphophallus Konjac, which was reported with hypoglycemic effects on diabetes subjects, were isolated and studied using the STZ-treated diabetes model. Among them, one fraction named as KOS-A, was found with nitric oxide (NO(*)) free radical regulation effect, while the other two were not. At concentrations less than 1.5 mM, KOS-A positively decreased STZ-induced NO(*) level of islets, but normal NO(*) release for non-STZ-treated islets was not affected within the range. At 15 mM, KOS-A played a contrary role and increased NO(*) level for islets both with and without STZ-treatment. Islets insulin secretion changed corresponding to NO(*) level in the assay. Increased insulin secretion appeared parallel to the decrease of NO(*), and normal insulin release was not affected by KOS-A less than 1.5 mM. Structure determination of KOS-A shows that it is a tetrasaccharide with Mw of 666 Da and reductive end of alpha-D-mannose. These results indicate that low dosage of KOS-A, with its function on attenuating STZ-induced NO(*) level, doesn't alter normal NO(*) and insulin secretion pathways of isolated islets. The NO(*) attenuation function of KOS-A on the diabetes model is mainly resulted from environmental free radical scavenging by the oligosaccharide. Present results also imply the mechanism of clinical Amorphophallus Konjac hypoglycemic function maybe related with free radical attenuation and lower risks of islets damage from NO(*) radical.

Overexpression of the human epidermal growth factor receptor (HER) 2 has been linked to the development and maintenance of malignant phenotypes in breast tumors. In addition, the growth and dissemination of human cancers are regulated in part by the autocrine motility factor (AMF)/phosphoglucose isomerase shown to be up-regulated by heregulin (HRG) in breast cancer cells. This study was undertaken to explore the effect of anti-HER2 monoclonal antibody 4D5 [Herceptin (HCT)] on AMF expression and the potential of its augmentation by specific simple sugar AMF inhibitors. Here we show that HCT treatment of high HER2-expressing breast cancer SK-BR3, BT-474, and ZR-75R cells resulted in down-regulation of AMF mRNA and protein. HCT inhibited the ability of HRG to induce AMF expression in cells with a normal HER2 level, and HCT-mediated down-regulation could be reversed by HRG treatment in breast cancer cells with a high HER2 level. HCT also inhibited transcription from a chimeric pGL3-Luc vector-based reporter system containing the 1.8-kb promoter region of human AMF. Treatment of breast cancer cells with the combination of HCT and specific AMF inhibitors, erythrose 4-phosphate or D-mannose 6-phosphate, resulted in an additive inhibitory effect on both the growth rate and invasiveness of cells as compared with treatment with each agent alone. Results presented here suggest that HCT can effectively block both ligand-induced and constitutive expression of AMF associated with high HER2 overexpression, implying a role of the AMF pathway in the action of HCT. Accordingly, the combination of AMF inhibitor with HCT can potentiate the growth-inhibitory and anti-invasive action of HCT in breast cancer cells.

The mutagenicity of 2-chloro-4-methylthiobutanoic acid (CMBA), a nitrite-treated Sanma fish mutagen, in Salmonella typhimurium TA100 was enhanced by addition of D-glucose during the CMBA-treatment. Several other monosaccharides also enhanced the mutagenicity of CMBA, and the order of the enhancing potency was found to be D-mannose, D-glucose>D-fructose, D-ribose, D-galactose. A disaccharide, maltose, showed only little enhancement. No enhancement was found with L-glucose. We investigated whether saccharides affect uptake of [methyl-14C]CMBA into S. typhimurium TA100. Saccharides which enhanced CMBA-induced mutagenesis increased the uptake. L-Glucose did not enhance the uptake. There was good correlation between the enhanced mutagenesis and increased radioactivity in Salmonella, suggesting that the enhancing effect of monosaccharide on the CMBA-induced mutagenesis results from the enhanced uptake of the mutagen into bacteria.

Decreases in insulin-responsive glucose transport and associated levels of cell surface GLUT4 occur in rat adipocytes maintained in culture for 20 h under hyperinsulinaemic and hyperglycaemic conditions. We have investigated whether this defect is due to reduced signalling from the insulin receptor, GLUT4 expression or impaired GLUT4 trafficking. The effects of chronic insulin treatment on glucose transport and GLUT4 trafficking were ameliorated by inclusion of metformin in the culture medium. In comparison with the ic insulin treatment attenuated changes in signalling processes leading to glucose transport. These included insulin receptor tyrosine phosphorylation, phosphoinositide 3-kinase activity and Akt activity, which were all reduced by 60-70%. Inclusion of metformin in the culture medium prevented the effects of the chronic insulin treatment on these signalling processes. In comparison with cells maintained in culture without insulin, the total expression of GLUT4 protein was not significantly altered by chronic insulin treatment, although the level of GLUT1 expression was increased. Trafficking rate constants for wortmannin-induced cell-surface loss of GLUT4 and GLUT1 were assessed by 2-N-4-(1-azi-2, 2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannose-4-yloxy)-2-propyla min e (ATB-BMPA) photolabelling. In comparison with cells acutely treated with insulin, chronic insulin treatment resulted in a doubling of the rate constants for GLUT4 endocytosis. These results suggest that the GLUT4 endocytosis process is very sensitive to the perturbations in signalling that occur under hyperinsulinaemic and hyperglycaemic conditions, and that the resulting elevation of endocytosis accounts for the reduced levels of net GLUT4 translocation observed.

7. Clin Chem. 1991 Mar;37(3):477. Interference of D-mannose in glucose measurements by glucose oxidase and hexokinase methods. Ho CS, Fung SL, Chan AY. Comment on Clin Chem. 1987 May;33(5):708-10.

8. Ontogenez. 1987 Jul-Aug;18(4):394-8. [Immunochemical analysis of lectin receptors in the structure of trophoblastic beta 1-glycoprotein and pregnancy-associated alpha 2-glycoprotein]. [Article in Russian] Krivonosov SK, Zorin NA, Ionova NK, Pogorelova TIu, Tatarinov IuS. Trophoblastic beta-glycoprotein (TBG), pregnancy-associated alpha 2-glycoprotein (AGP) and alpha-fetoprotein (AFP) bind to concanavalin A, phytohemagglutinin P and pea lectin. Lentil lectin interacts with TBG only, whereas peanut lectin and castor bean lectin are characterized by affinity to AGP. Hence, TBG, AGP and AFP contain the following carbohydrate components: alpha-D-mannose, alpha-D-glucose, N-acetyl-D-glucosamine and N-acetyl-D-galactosamine. In addition, AGP contains beta-D-galactose.

9. J Biol Chem. 1987 Jan 5;262(1):189-97. Glucose and insulin co-regulate the glucose transport system in primary cultured adipocytes. A new mechanism of insulin resistance. Garvey WT, Olefsky JM, Matthaei S, Marshall S. We have previously shown in primary cultured rat adipocytes that insulin acts at receptor and multiple postreceptor sites to decrease insulin's subsequent ability to stimulate glucose transport. To examine whether D-glucose can regulate glucose transport activity and whether it has a role in insulin-induced insulin resistance, we cultured cells for 24 h in the absence and presence of various glucose and insulin concentrations. After washing cells and allowing the glucose transport system to deactivate, we measured basal and maximally insulin-stimulated 2-deoxyglucose uptake rates (37 degrees C) and cell surface insulin binding (16 degrees C). Alone, incubation with D-glucose had no effect on basal or maximal glucose transport activity, and incubation with insulin, in the absence of glucose, decreased maximal (but not basal) glucose transport rates only 18% at the highest preincubation concentration (50 ng/ml). However, in combination, D-glucose (1-20 mM) markedly enhanced the long-term ability of insulin (1-50 ng/ml) to decrease glucose transport rates in a dose-responsive manner. For example, at 50 ng/ml preincubation insulin concentration, the maximal glucose transport rate fell from 18 to 63%, and the basal uptake rate fell by 89%, as the preincubation D-glucose level was increased from 0 to 20 mM. Moreover, D-glucose more effectively promoted decreases in basal glucose uptake (Ki = 2.2 +/- 0.4 mM) compared with maximal transport rates (Ki = 4.1 +/- 0.4 mM) at all preincubation insulin concentrations (1-50 ng/ml). Similar results were obtained when initial rates of 3-O-methylglucose uptake were used to measure glucose transport. D-glucose, in contrast, did not influence insulin-induced receptor loss. In other studies, D-mannose and D-glucosamine could substitute for D-glucose to promote the insulin-induced changes in glucose transport, but other substrates such as L-glucose, L-arabinase, D-fructose, pyruvate, and maltose were without effec

10. J Exp Med. 1985 Nov 1;162(5):1512-30. doi: 10.1084/jem.162.5.1512. Natural killer (NK) cell-derived hematopoietic colony-inhibiting activity and NK cytotoxic factor. Relationship with tumor necrosis factor and synergism with immune interferon. Degliantoni G, Murphy M, Kobayashi M, Francis MK, Perussia B, Trinchieri G. We characterize the natural killer (NK) cell colony-inhibiting activity (CIA) produced in supernatants from cultures of human peripheral blood lymphocytes (PBL) with NK-sensitive target cell lines, and study its relationship with NK cell-derived cytotoxic factor (NKCF). Using monoclonal antibodies (mAb) specific for NK cells or other lymphocyte populations, we unambiguously identify NK cells as the only PBL subset able to produce both NKCF and NK-CIA. We present functional and biochemical data suggesting that NKCF and NK-CIA represent the same molecule: (a) a highly significant positive correlation exists between the quantity of NKCF and NK-CIA in supernatants independently produced by different PBL subsets; (b) both NK-CIA and NKCF are induced by culture of PBL with NK-sensitive, but not with NK-insensitive cell lines, and with HLA-DR+ bone marrow cells; (c) both NKCF and NK-CIA are absorbed on the same cell lines or bone marrow cell types; (d) the two activities coelute in the same gel filtration fractions; (e) D-mannose-6-phosphate blocks both NKCF and NK-CIA activity, and prevents their absorption by K562 cells; and (f) both NKCF and NK-CIA activity are lost after 2 d at 37 degrees C. The NK-CIA-containing preparations are devoid of antiviral activity, and antiinterferon (anti-IFN) antibodies do not block the inhibitor activity of NK-CIA. The effect of NK-CIA on day 14 (early) colony-forming units of granulocytes and macrophages (CFU-GM) is synergistic with that of IFN-gamma, and this synergy is also evident on day 7 (late) CFU-GM growth. A combination of NK-CIA and IFN-gamma suppresses late CFU-GM, at concentrations of the two lymphokines that are completely ineffective when used independently. No synergy between NK-CIA and IFN-alpha or -beta was observed, due to a direct inhibitory effect of these two IFN types on late CFU-GM. Antibodi

INTRODUCTION: Recurrent urinary tract infections (UTIs) significantly impact the quality of life due to symptoms, effects on sexual activity, persistent pain, and recurrent antibiotic use. This systematic review and meta-analysis aimed to evaluate the efficacy of D-mannose in preventing recurrent UTIs. METHODS: In May 2024, we systematically searched PubMed, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) comparing D-mannose treatment with no intervention or standard antibiotic therapy in patients at high risk for recurrent UTI. We applied a random-effects model to pool relative risks (RR) and 95% confidence intervals (CI). RESULTS: We included 6 RCTs comprising 1,167 participants, of whom 534 received D-mannose and 521 (97.6%) were women. D-mannose was not associated with a reduction in recurrent UTI compared with control (RR: 0.57, 95% CI 0.29 - 1.15; p < 0.01) or antibiotics (RR: 0.39, 95% CI 0.12 - 1.25; p < 0.01). Further analyses showed that D-mannose did not improve outcomes in a subgroup of postmenopausal women. CONCLUSION: In this meta-analysis of RCTs, D-mannose did not reduce the incidence of recurrent UTIs compared with control or antibiotics in high-risk patients. INTRODUÇÃO: As infecções do trato urinário (ITUs) recorrentes afetam significativamente a qualidade de vida devido aos sintomas, aos efeitos sobre a atividade sexual, à dor persistente e ao uso recorrente de antibióticos. Esta revisão sistemática e metanálise teve como objetivo avaliar a eficácia da D-manose na prevenção de ITUs recorrentes. MÉTODOS: Em maio de 2024, realizamos uma busca sistemática nas bases de dados PubMed, EMBASE e Cochrane Library por ensaios clínicos randomizados (ECRs) que comparassem o tratamento com D-manose à ausência de intervenção ou à terapia antibiótica padrão em pacientes com alto risco de ITU recorrente. Aplicamos um modelo de efeitos aleatórios para agrupar os riscos relativos (RR) e os intervalos de confiança (IC) de 95%. RESULTADOS: Incluímos 6 ECRs envolvendo 1.167 participantes, dos quais 534 receberam D-manose e 521 (97,6%) eram mulheres. A D-manose não se associou a uma redução na ITU recorrente em comparação ao grupo control

BACKGROUND: Urinary tract infections (UTIs) are very common, affecting more than 7 million people worldwide. Whilst many people may only experience a single episode in their lifetime and are generally responsive to standard antibiotics, a significant proportion of adults and children (approximately 15% to 25%) are chronic symptomatic UTI sufferers. Certain population groups are at greater risk than others, such as immunosuppressed and people with chronic kidney disease. D-mannose is a sugar part of normal human metabolism found within most diets. The mechanism of action is to prevent bacterial adherence to the uroepithelial cells. The D-mannose-based inhibitors can block uropathogenic Escherichia coli adhesion and invasion of the uroepithelial cells. The bacteria are then understood to essentially be eliminated by urination. Early pilot studies on animals and humans have trialled concentrated forms of D-mannose (tablets or sachets) in doses ranging from 200 mg up to 2 to 3 g and found possible efficacy in reducing UTI symptoms or recurrence. Although the anti-adhesive effects of D-mannose have been well-established, only recently have we seen a small number of pilot studies and small clinical trials conducted. OBJECTIVES: To assess the benefits and harms of D-mannose for preventing and treating UTIs in adults and children. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 22 February 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included RCTs measuring and reporting the effect of D-mannose, in any combination and any formulation, to prevent or treat UTIs in adults and children, females and males, in any setting (including perioperative). Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS: Data extraction was independently

The inexorable rise of antimicrobial resistance reinforces the need for alternative approaches to both treat and prevent urinary tract infections (UTIs). A potential approach is administration of D-mannose, an inert monosaccharide that is metabolised and excreted in urine and acts by inhibiting bacterial adhesion to the urothelium. We performed a systematic review to assess the effect of D-mannose in the prevention of recurrent UTIs. Of the eight studies reporting on D-mannose in this context, six were clinical and included 695 individuals. Three studies reported that time to UTI recurrence was longer with D-mannose. D-Mannose improved quality of life and significantly reduced recurrent UTIs in both catheter and non-catheter users. D-Mannose was effective in reducing the incidence of recurrent UTIs and prolonging UTI-free periods, which consequently increased quality of life. PATIENT SUMMARY: D-Mannose is a sugar that seems to reduce the incidence of recurrent urinary tract infections and associated bothersome symptoms. It also leads to a longer duration between episodes of recurrences and consequently improves patient quality of life. D-Mannose can be used as a supplementary or alternate treatment for recurrent urinary tract infections.

OBJECTIVE: We performed a systematic review and meta-analysis to determine whether D-mannose reduces urinary tract infection recurrence (ie, cumulative incidence) in adult women with recurrent urinary tract infection compared with other prevention agents. Secondary outcomes included side effects and compliance with D-mannose use. DATA SOURCES: Ovid Medline 1946-, Embase 1947-, Scopus 1823-, Cochrane Library, Web of Science 1900-, and ClinicalTrials.gov were searched through 4/15/2020. STUDY ELIGIBILITY CRITERIA: Systematic review inclusion: randomized controlled trials, prospective cohorts, and retrospective cohorts written in English of women ≥18 years old with recurrent urinary tract infection in which D-mannose was utilized as an outpatient prevention regimen. Systematic review exclusion: lab or animal-based research, study protocols only, and conference abstracts. Meta-analysis inclusion: stated D-mannose dose, follow-up time ≥6 months, a comparison arm to D-mannose, and data available from women ≥18 years of age. STUDY APPRAISAL AND SYNTHESIS METHODS: Two independent reviewers made abstract, full text, and data extraction decisions. Study methodologic quality was assessed using the Cochrane Risk of Bias tool. Relative risks, confidence intervals, and heterogeneity were computed. RESULTS: Searches identified 776 unique citations. Eight publications met eligibility: 2 using D-mannose only; 6 using D-mannose combined with another treatment. Seven studies were prospective: 2 randomized controlled trials, 1 randomized cross-over trial, and 4 prospective cohort studies. One retrospective cohort study was included. Three studies met meta-analysis eligibility (1 randomized controlled trial, 1 randomized cross-over trial, and 1 prospective cohort). Pooled relative risk of urinary tract infection recurrence comparing D-mannose to placebo was 0.23 (95% confidence interval, 0.14-0.37; heterogeneity=0%; D-mannose n=125, placebo n=123). Pooled relative risk of urinary tract infection recurrence comparing D-mannose to preventative antibiotics was 0.39 (95% confidence interval, 0.12-1.25; heterogeneity=88%; D-mannose n=163, antibiotics n=163). Adverse side effects were rep

PURPOSE: Urinary tract infections (UTIs) are one of the more common infections encountered in everyday clinical practice. They account for 10-20% of all infections treated in primary care units and 30-40% of those treated in hospitals. The risk of UTI in the female population is considered to be 14 times higher than in the male population. The prevalence of bacterial etiology results in a large consumption of broad-spectrum antibiotics, which in turn leads to increased rates of resistant uropathogens. Therefore, non-antibiotic prevention and treatment options are now of great importance. METHODS: A systematic literature search was performed for the last 20 years (1999-2019) and the efficiencies of these eight different non-antibiotic interventions were analysed and discussed. RESULTS: This article provides an overview on non-antibiotic options for management of UTI, including the application of cranberry products, the phytodrug Canephron N, probiotics, nonsteroidal anti-inflammatory drugs (NSAID), D-mannose, estrogens, vitamins, and immunotherapy. CONCLUSIONS: The last 20 years of research on non-antibiotic approaches in UTI have not brought conclusive evidence that antibiotic usage can be replaced completely by non-antibiotic options. Hence, antibiotics still remain a gold standard for UTI treatment and prevention. However, changing the therapeutic strategy by including non-antibiotic measures in the management of UTI could be successful in avoiding antimicrobial resistance at least to some extent.

OBJECTIVE: To address clinical uncertainties about the effectiveness and safety of long-term antibiotic therapy for preventing recurrent urinary tract infections (UTIs) in older adults. DESIGN: Systematic review andmeta-analysis of randomised trials. METHOD: We searched Medline, Embase, The Cumulative Index to Nursing and Allied Health Literature(CINAHL), and the Cochrane Register of Controlled Trials from inception to August 2016. Eligible studies compared long-term antibiotic therapy with non-antibiotic therapy or placebo in men or women aged over 65, or in postmenopausal women, with recurrent UTIs. RESULTS: We did not identify any studies that included older men. Three randomised controlled trials compared long-term antibiotics with vaginal oestrogens (n=150), oral lactobacilli (n=238) and D-mannose powder (n=94) in postmenopausal women. Long-term antibiotics reduced the risk of UTI recurrence by 24% (three trials, n=482; pooled risk ratio (RR) 0.76; 95% CI 0.61 to 0.95, number needed to treat=8.5). There was no statistically significant increase in risk of adverse events (mild adverse events: pooled RR 1.52; 95% CI 0.76 to 3.03; serious adverse events: pooled RR 0.90, 95% CI 0.31 to 2.66). One trial showed 90% of urinary and faecal Escherichia coli isolates were resistant to trimethoprim-sulfamethoxazole after 1 month of prophylaxis. CONCLUSIONS: Findings from three small trials with relatively short follow-up periods suggest long-term antibiotic therapy reduces the risk of recurrence in postmenopausal women with recurrent UTI. We did not identify any evidence to inform several clinically important scenarios including, benefits and harms in older men or frail care home residents, optimal duration of prophylaxis, recurrence rates once prophylaxis stops and effects on urinary antibiotic resistance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.