A Randomized Controlled Trial Comparing a New D-Mannose-based Dietary Supplement to Placebo for the Treatment of Uncomplicated Escherichia coli Urinary Tract Infections.

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 for nonmenopausal women with an uncomplicated Escherichia coli urinary tract infection, those treated with a dietary supplement (containing D-mannose, citric acid, prebiotic fibers, Astragalus, and dandelion) had a higher rate of clinical resolution or response than women who received a placebo.

Anti-inflammatory properties of a proprietary bromelain extract (Bromeyal™) after in vitro simulated gastrointestinal digestion.

INTRODUCTION: Bromelain is a complex mixture of thiol proteases and other non-proteolytic constituents, commercially extracted primarily from the pineapple stem. Evidence from several in vitro and in vivo studies highlights its excellent bioavailability, lack of side effects, and broad spectrum of medical efficacies, of which the antiphlogistic properties are among the most valuable ones. Bromelain has indeed been employed for the efficient treatment of many inflammatory disorders, ranging from osteoarthritis and inflammatory bowel diseases to cancer-related inflammation. METHODS: The aim of the current study was to assess the anti-inflammatory effects of bromelain after gastrointestinal digestion simulated in vitro using stomach, intestinal, and chondrocyte human cellular models (AGS, Caco-2, and SW1353, respectively). RESULTS: We successfully demonstrated the capability of bromelain to reduce an inflammatory stimulus by reproducing its exposure to the gastro-enteric environment in vitro and assaying its effect in human cell lines derived from stomach, intestinal, and chondrocytes. CONCLUSION: Consistently with the previously published data, our work underpins the relevance of bromelain in the development of safer and more effective anti-inflammatory therapies.

Efficacy and safety of a new vaginal gel for the treatment of symptoms associated with vulvovaginal atrophy in postmenopausal women: A double-blind randomized placebo-controlled study.

OBJECTIVE: The aim of the present randomized placebo-controlled single-center study was to assess the efficacy and safety of a new vaginal gel (Meclon Idra - Alfasigma) in the treatment of vulvovaginal atrophy (VVA). The gel is composed of sea buckthorn (Hippophaë rhamnoides) oil, aloe vera, 18ß-glycyrrhetic acid, hyaluronic acid and glycogen. The study assessed whether the gel can reduce VVA symptoms (vaginal dryness, itching, burning sensation) and improve sexual function in postmenopausal women over 12 weeks. STUDY DESIGN: Postmenopausal women (n° = 60) reporting VVA symptoms were recruited and randomized in a 1:1 ratio to the gel or placebo. Active vaginal gel or placebo was applied for 14 days and then twice a week for 90 consecutive days. MAIN OUTCOME MEASURE: The Vaginal Health Index (VHI), including vaginal pH, was used to assess changes in objective signs, whereas the self-reported Female Sexual Function Index (FSFI) was used to investigate sexual function. RESULTS: Meclon Idra was effective in reducing vaginal pain, dyspareunia and vaginal pH, with the VHI showing significant improvement at day 90 (P < .0001), and in reducing each VVA symptom (vaginal dryness, vaginal itching, burning sensation) at weeks 2 and 4, and the end of the study (P < .0001). The analysis of FSFI scores showed, after the end of treatment, an improvement of sexual function in the active-treatment group, with a statistically significant increase (P < 0.001) in all domains scores and total score (P < 0.001). CONCLUSIONS: The present single-center randomized clinical trial demonstrated the efficacy, tolerability and safety of 12-week treatment with a new vaginal gel in postmenopausal women with symptoms associated with VVA. Based on this trial, the gel seems to be a valid choice as a single, local agent for relieving VVA symptoms and improving sexual function, and to have good compliance. This trial is registered prospectively with the Clinical Trials Registry - India, number CTRI/2019/05/01911.

Protective and regenerative effects of a novel medical device against esophageal mucosal damage using in vitro and ex vivo models.

Gastroesophageal reflux disease (GERD) is a common digestive disorder that causes esophagitis and injuries to the esophageal mucosa. GERD symptoms are recurrent during pregnancy and their treatment is focused on lifestyle changes and nonprescription medicines. The aim of this study was to characterize the mechanism of action of a new patented medical device, an oral formulation containing hyaluronic acid, rice extract, and amino acids dispersed in a bioadhesive polymer matrix, by assessing its protective effects in in vitro and ex vivo models of esophageal mucosa damage. Acidic bile salts and pepsin cocktail (BSC) added to CP-A and COLO-680 N esophagus cells were used as an in vitro GERD model to evaluate the binding capacities, anti-inflammatory effects and reparative properties of the investigational product (IP) in comparison to a viscous control. Our results showed that the IP prevents cell permeability and tight junction dysfunction induced by BSC. Furthermore, the IP was also able to down-regulate IL-6 and IL-8 mRNA expression induced by BSC stimulation and to promote tissue repair and wound healing. The results were confirmed by ex vivo experiments in excised rat esophagi through the quantification of Evans Blue permeability assay. These experiments provided evidence that the IP is able to bind to the human esophagus cells, preventing the damage caused by gastroesophageal reflux, showing potential anti-irritative, soothing, and reparative properties.

Randomised clinical trial in women with Recurrent Vulvovaginal Candidiasis: Efficacy of probiotics and lactoferrin as maintenance treatment.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a recurrent vaginal condition in childbearing women. OBJECTIVES: The aim of this study was to assess the efficacy of an oral formulation containing Lactobacillus acidophilus GLA-14, Lactobacillus rhamnosus HN001 and bovine lactoferrin on symptoms and recurrence of VVC as adjuvant therapy to topical clotrimazole. PATIENTS/METHODS: Forty-eight women positive for C. albicans, symptoms of VVC and documented history of recurrences were randomised into 2 groups receiving verum or placebo (2 capsules/day for 5 days followed by 1 capsule/day for additional 10 days) as adjuvant treatment to clotrimazole (induction phase) followed by a maintenance cycle of 6 months (1 capsule/day verum or placebo for 10 consecutive days each month). Symptoms, overall cure rate and recurrence rate were assessed. RESULTS: After clotrimazole therapy, a significant improvement of symptoms was shown in both groups. However, only women treated with probiotics and lactoferrin showed a significant improvement of itching and discharge at 3 and 6 months. During the six-month follow-up, recurrences were significantly less in the intervention group vs placebo (33.3% vs 91.7% after 3 months and 29.2% vs 100% after 6 months). CONCLUSIONS: The results show that the investigated lactobacilli mixture in combination with lactoferrin represents a safe and effective adjuvant approach for reducing symptoms and recurrences of RVVC.

Boric Acid and Commercial Organoboron Products as Inhibitors of Drug-Resistant Candida albicans.

Clinical use of boric acid as a topical antifungal in women who have failed standard antifungal therapy with azole drugs has been used sporadically for decades. Our previous in vitro work showing inhibition of Candida albicans growth was conducted on clinical isolates without antifungal drug susceptibility profiling. Here, we report that boric acid restricts growth of drug-resistant Candida albicans and inhibits hyphal growth and diminishes cell volume. The availability of over-the-counter organoboron compounds intended for use as oral nutritional supplements led us to determine if these also were inhibitory toward resistant Candida and show here that they also possess antifungal activity. Candida glabrata was also found to be inhibited by boric acid and organoboron compounds. Further development of organoboron compounds as topical therapeutics is of potential value.

Dynamic quadripolar radiofrequency treatment of vaginal laxity/menopausal vulvo-vaginal atrophy: 12-month efficacy and safety.

BACKGROUND: Twelve-month extension of a previous spontaneous exploratory study investigating safety and efficacy of a new low-energy dynamic quadripolar radiofrequency (DQRF) device in: A) premenopausal women with symptoms of vaginal laxity, with special reference to dysuria, urinary incontinence and unsatisfactory sexual life (vaginal laxity arm of the study); B) postmenopausal women with vulvovaginal atrophy/genitourinary syndrome of menopause (VVA/GSM) and VVA/GSM-related symptoms (VVA/GSM arm of the study). DQRF treatment schedule in both study arms: 4 to 6 procedures of 15 to 20 min every 14 days (vaginal laxity, range 12-17 days; VVA/GSM, range 13-16). Operative temperatures in vaginal target tissues during procedure: vaginal laxity, 42 °C (range 40-43 °C); VVA/GSM, 40 °C (range 40-42 °C). METHODS: In the vaginal laxity arm of the study, 25 women with subjective sensation of vaginal introital laxity (very to slightly loose). Assessment of urinary incontinence, satisfaction with sexual relationship and contribution of pelvic organ prolapse: Vaginal Laxity Questionnaire (VLQ, Italian certified translation) and short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12, Italian certified translation). Further evaluation of sexual gratification: Sexual Satisfaction Questionnaire (SSQ). In the VVA/GSM arm of the study, 32 women with objective evidence of VVA and vaginal dryness and/or dyspareunia as most bothersome symptoms. Assessment of VVA/GSM symptoms and overall satisfaction with sexual life: specifically designed 10-cm visual analogue scales. RESULTS: All 4 to 6 planned DQRF sessions were well tolerated in both the vaginal laxity and VVA/GSM arms of the study, with no troubling pain, thermal injury or other immediate adverse effects during all the procedures. All screened women completed the planned DQRF treatment sessions in both arms of the extension study. There was no participant attrition with only a few occasionally missing visits over the 12-month follow-up period. Improvements were rapid in self-perception of introital looseness and related symptoms like dysuria/urinary incontinence and unrewarding sexual relationship (vaginal laxity patients) and atrophy-related symptoms including painful and unsatisfactory sexual activity (VVA/GSM patients). Participating women consistently reported wide-spectrum strong clinical improvements by the end of the planned DQRF sessions. Clinical improvements remained steady for the whole follow-up period in postmenopausal women; a statistically non-significant tendency to slight deterioration in VLQ, PISQ-12 and SSQ mean scores was detected after 6 to 9 months of follow-up in the vaginal laxity arm of the study. CONCLUSIONS: Safety was excellent during all DQRF procedures and over the 12 months following the end of the treatment sessions. VLQ, PISQ-12 and SSQ scores (women with vaginal laxity), VAS self-evaluation of VVA/GSM symptoms and overall satisfaction with sexual life (women with VVA/GSM symptoms) improved rapidly, reaching almost normal levels by the last DQRF session and suggesting rapid, but also persistent, vaginal rejuvenation in both indications. A late tendency to some slight deterioration in women treated for vaginal laxity suggests such women might benefit from new DQRF treatments 6 to 9 months after the previous cycle.

Antifungal mechanisms supporting boric acid therapy of Candida vaginitis.

BACKGROUND: Boric acid is a commonly cited treatment for recurrent and resistant yeast vaginitis, but data about the extent and mechanism of its antifungal activity are lacking. OBJECTIVES: The aim of this study was to use in vitro methods to understand the spectrum and mechanism of boric acid as a potential treatment for vaginal infection. METHODS: Yeast and bacterial isolates were tested by agar dilution to determine the intrinsic antimicrobial activity of boric acid. Established microbial physiology methods illuminated the mechanism of the action of boric acid against Candida albicans. RESULTS: C. albicans strains (including fluconazole-resistant strains) were inhibited at concentrations attainable intravaginally; as were bacteria. Broth dilution MICs were between 1563 and 6250 mg/L and boric acid proved fungistatic (also reflected by a decrease in CO(2) generation); prolonged culture at 50,000 mg/L was fungicidal. Several organic acids in yeast nitrogen broth yielded a lower pH than equimolar boric acid and sodium borate but were less inhibitory. Cold or anaerobic incubation protected yeast at high boric acid concentrations. Cells maintained integrity for 6 h in boric acid at 37 degrees C, but after 24 h modest intrusion of propidium iodide occurred; loss of plate count viability preceded uptake of vital stain. Growth at sub-MIC concentrations of boric acid decreased cellular ergosterol. The drug efflux pump CDR1 did not protect Candida as CDR1 expression was abrogated by boric acid. Boric acid interfered with the development of biofilm and hyphal transformation. CONCLUSIONS: Boric acid is fungistatic to fungicidal depending on concentration and temperature. Inhibition of oxidative metabolism appears to be a key antifungal mechanism, but inhibition of virulence probably contributes to therapeutic efficacy in vivo.