epiglucan and Candidiasis--Vulvovaginal

The role played by antibodies (Abs) in the anticandidal defense has long been a matter of controversy, mostly due to the past inability to clearly define antigen specificity, the relationship between the type of immune response within the different settings of experimental and human candidiasis and, last but not least, a misunderstanding about the role of T helper cell in cell-mediated versus the humoral immunity. Contributory was also the lack of precise identification of virulence traits of the fungus which are the best candidates for a protective Ab response. In recent years, an impressive amount of experimental evidence, and also some clinical proof, have been generated which assign to Abs of defined specificity an important role in the anticandidal defense both at systemic and mucosal sites. Paradigmatic among them, Abs against defined virulence factors such as adhesins or aspartyl-proteinase enzymes, or against critical viability molecules such as beta-glucan, have been detected or generated which hold great promise for immunotherapeutic interventions in humans.

Topics: Animals; Antibodies, Fungal; Antibodies, Monoclonal; beta-Glucans; Candida albicans; Candidiasis; Candidiasis, Vulvovaginal; Disease Models, Animal; Female; Humans; Immunization, Passive

The aim of the study was to examine the effects of beta-glucan treatment in women with recurrent vulvar candidiasis or previously treated with diathermocoagulation (DTC) for vulvar lesions caused by human papillomavirus (HPV) infection.. From January to March 2008, 23 women with a history of recurrent candidiasis and 209 women who underwent to DTC for HPV-correlated vulvar lesions were recruited at the Department of Obstetrics and Gynaeco-logy of San Camillo-Forlanini Hospital of Rome. The two groups were treated with two cycles of a daily topical application of beta-glucan for 15 consecutive days with a suspension of 20 days. The effects of beta-glucan were analyzed at the 1st and the 3rd month from the start of the therapy.. A total of 209 women, 21 with recurrent candidiasis and 188 who underwent to DTC for HPV-correlated lesions, completed the study. After the first month of treatment we not found any evidence of disease in both groups; otherwise we observed, a month after the term of the therapy, 5% and 3% of recurrence of candidiasis or lesions secondary to HPV infection, respectively, even if with low grade.. Our results demonstrate the efficacy of beta-glucan treatment for recurrent candidiasis, HPV-correlated lesions and in the reparative process of epidermis.

Topics: Adjuvants, Immunologic; Administration, Topical; Adult; Alphapapillomavirus; beta-Glucans; Candidiasis, Vulvovaginal; Condylomata Acuminata; Epidermis; Female; Humans; Recurrence; Regeneration; Signal Transduction; Vulvar Diseases; Young Adult

Vulvovaginal candidiasis (VVC) is one of the most common infections in women. The purpose of this study was to evaluate the ability of a water-soluble β-glucan salecan to protect against Candida albicans (C. albicans) vaginal infection. The model was reproduced with intravaginal inoculation of yeast blastoconidia in pseudoestrus mice. We found that mice that received salecan (0.5 mg per mouse) after infection had 85% fewer CFU than infected mice given saline. Compared with the C.albicans group, salecan reduced the migration of polymorphonuclear neutrophils (PMNs) in the vagina, decreased mRNA levels of cytokines IL23, IL22, IL17a, and IL17f, anti-candidal genes S100a8 and S100a9 and C.albicans pattern recognition receptor Dectin1. The analysis for vaginal microbial community composition at different taxa levels revealed that the bacterial flora composition in the vagina of the salecan-treated mice was similar to that of the uninfected mice, and distinguished from the infected mice. The vaginal lavages from the salecan treated group had more Enterococcus and its metabolite lactate. Our results suggest salecan might be a potential therapeutic agent for vaginal infection of C.albicans.

Topics: Animals; Antifungal Agents; beta-Glucans; Candida albicans; Candidiasis, Vulvovaginal; Colony Count, Microbial; Cytokines; Disease Models, Animal; Female; Gene Expression Regulation, Fungal; Lactic Acid; Mice; Neutrophils; Receptors, Pattern Recognition; RNA, Messenger; Vagina

The aim of this study is to develop efficient localized therapy of sertaconazole nitrate for the treatment of vaginal candidiasis.. Sertaconazole nitrate-loaded cationic liposomes were prepared by thin-film hydration method and coated with different concentrations of pectin (0.05%, 0.1% and 0.2%) to develop mucoadhesive liposomes. The formulated mucoadhesive vesicles were characterized in terms of morphology, entrapment efficiency, particle size, zeta value, mucoadhesive properties and drug release. The selected formula was incorporated into a gel base and further characterized by an ex vivo permeation study in comparison with conventional sertaconazole gel. Also, the in vivo study was performed to assess the efficacy of sertaconazole mucoadhesive liposomal gel in treating rats with vaginal candidiasis.. The mucoadhesive liposomes were spherical. Coating liposomes with pectin results in increased entrapment efficiency and particle size compared with uncoated vesicles. On the contrary, zeta values were reduced upon coating liposomes with pectin indicating efficient coating of liposomes with pectin. Mucoadhesive liposomes showed a more prolonged and sustained drug release compared with uncoated liposomes. Ex vivo study results showed that mucoadhesive liposomal gel increased sertaconazole tissue retention and reduced drug tissue penetration. In the invivo study, the mucoadhesive liposomal gel showed a significant reduction in the microbial count with a subsequent reduction in inflammatory responses with the lowest histopathological change compared with conventional gel.. The study confirmed the potentiality of employing mucoadhesive liposomes as a successful carrier for the vaginal delivery of antifungal drugs.

Topics: Adhesiveness; Animals; Anti-Infective Agents; Antifungal Agents; beta-Glucans; Biomarkers; Candidiasis, Vulvovaginal; Delayed-Action Preparations; Drug Liberation; Female; Gels; Humans; Imidazoles; Immunoglobulin G; Immunoglobulin M; Inflammation Mediators; Liposomes; Mucins; Mucus; Particle Size; Rats, Sprague-Dawley; Sheep; Static Electricity; Thiophenes; Vagina

Vulvovaginal candidiasis (VVC) is among the most prevalent vaginal diseases. Candida albicans is still the most prevalent species associated with this pathology, however, the prevalence of other Candida species, such as C. glabrata, is increasing. The pathogenesis of these infections has been intensely studied, nevertheless, no consensus has been reached on the pathogenicity of VVC. In addition, inappropriate treatment or the presence of resistant strains can lead to RVVC (vulvovaginal candidiasis recurrent). Immunomodulation therapy studies have become increasingly promising, including with the β-glucans. Thus, in the present study, we evaluated microbicidal activity, phagocytosis, intracellular oxidant species production, oxygen consumption, myeloperoxidase (MPO) activity, and the release of tumor necrosis factor α (TNF-α), interleukin-8 (IL-8), IL-1β, and IL-1Ra in neutrophils previously treated or not with β-glucan. In all of the assays, human neutrophils were challenged with C. albicans and C. glabrata isolated from vulvovaginal candidiasis. β-glucan significantly increased oxidant species production, suggesting that β-glucan may be an efficient immunomodulator that triggers an increase in the microbicidal response of neutrophils for both of the species isolated from vulvovaginal candidiasis. The effects of β-glucan appeared to be mainly related to the activation of reactive oxygen species and modulation of cytokine release.

Topics: beta-Glucans; Candida albicans; Candida glabrata; Candidiasis, Vulvovaginal; Female; Humans; Hypochlorous Acid; Interleukin-1beta; Interleukin-8; Intracellular Space; Neutrophils; Oxygen Consumption; Peroxidase; Phagocytosis; Reactive Oxygen Species; Recurrence; Sulfhydryl Compounds; Tumor Necrosis Factor-alpha

The protective capacity of a parenterally administered beta-glucan-conjugate vaccine formulated with the human-compatible MF59 adjuvant was assessed in a murine model of vaginal candidiasis. To monitor infection, an in vivo imaging technique exploiting genetically engineered, luminescent Candida albicans was adopted, and compared with measurements of colony forming units. The vaccine conferred significant protection, and this was associated with production of serum and vaginal anti-beta-glucan IgG antibodies. Vaginal IgG molecules were the likely mediators of protection as inferred by the efficacy of passive transfer of immune vaginal fluid and passive protection by an anti-beta-1,3-glucan mAb. Overall, the in vivo imaging technique was more reliable than vaginal CFU counts in assessing the extent and duration of the vaginal infection, and the consequent protection level.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Anti-Idiotypic; beta-Glucans; Candida albicans; Candidiasis, Vulvovaginal; Colony Count, Microbial; Diagnostic Imaging; Female; Fungal Vaccines; Immunization, Passive; Mice; Polysorbates; Squalene; Vaccines, Conjugate

To generate a vaccine to protect against a variety of human pathogenic fungi, we conjugated laminarin (Lam), a well-characterized but poorly immunogenic beta-glucan preparation from the brown alga Laminaria digitata, with the diphtheria toxoid CRM197, a carrier protein used in some glyco-conjugate bacterial vaccines. This Lam-CRM conjugate proved to be immunogenic and protective as immunoprophylactic vaccine against both systemic and mucosal (vaginal) infections by Candida albicans. Protection probably was mediated by anti-beta-glucan antibodies as demonstrated by passive transfer of protection to naive mice by the whole immune serum, the immune vaginal fluid, and the affinity-purified anti-beta-glucan IgG fractions, as well as by administration of a beta-glucan-directed IgG2b mAb. Passive protection was prevented by adsorption of antibodies on Candida cells or beta-glucan particles before transfer. Anti-beta-glucan antibodies bound to C. albicans hyphae and inhibited their growth in vitro in the absence of immune-effector cells. Remarkably, Lam-CRM-vaccinated mice also were protected from a lethal challenge with conidia of Aspergillus fumigatus, and their serum also bound to and markedly inhibited the growth of A. fumigatus hyphae. Thus, this novel conjugate vaccine can efficiently immunize and protect against two major fungal pathogens by mechanisms that may include direct antifungal properties of anti-beta-glucan antibodies.

Topics: Analysis of Variance; Animals; Antibodies, Monoclonal; Aspergillosis; Aspergillus fumigatus; Bacterial Proteins; beta-Glucans; Candida albicans; Candidiasis, Vulvovaginal; Female; Fungal Vaccines; Glucans; Magnetic Resonance Spectroscopy; Mice; Mice, Mutant Strains; Polysaccharides; Rats; Rats, Wistar; Serologic Tests; Vaccines, Conjugate