Biofilms and vulvovaginal candidiasis.

Candida species, including C. albicans, are part of the mucosal flora of most healthy women, and inhabit the gastrointestinal and genitourinary tracts. Under favourable conditions, they can colonize the vulvovaginal mucosa, giving rise to symptomatic vulvovaginal candidiasis (VVC). The mechanism by which Candida spp. produces inflammation is unknown. Both, the blastoconidia and the pseudohyphae are capable of destroying the vaginal epithelium by direct invasion. Although the symptoms are not always related to the fungal burden, in general, VVC is associated with a greater number of yeasts and pseudohyphae. Some years ago, C. albicans was the species most frequently involved in the different forms of VVC. However, infections by different species have emerged during the last two decades producing an increase in causative species of VVC such as C. glabrata, C. parapsilosis, C. krusei and C. tropicalis. Candida species are pathogenic organisms that have two forms of development: planktonic and biofilm. A biofilm is defined as a community of microorganisms attached to a surface and encompassed by an extracellular matrix. This form of presentation gives microorganisms greater resistance to antifungal agents. This review, about Candia spp. with a special emphasis on Candida albicans discusses specific areas such as biofilm structure and development, cell morphology and biofilm formation, biofilm-associated gene expression, the cell surface and adherence, the extracellular matrix, biofilm metabolism, and biofilm drug resistance in vulvovaginitis biofilms as an important virulence factor in fungi.

Interleukin-2 and other cytokines in candidiasis: expression, clinical significance, and future therapeutic targets.

Susceptibility to Candida spp. infection is largely determined by the status of host immunity, whether immunocompromised/immunodeficient or immunocompetent. Interleukin-2 (IL-2), a potent lymphoid cell growth factor, is a four-α-helix bundle cytokine induced by activated T cells with two important roles: the activation and maintenance of immune responses, and lymphocyte production and differentiation. We reviewed the roles of cytokines as immune stimulators and suppressors of Candida spp. infections as an update on this continuously evolving field. We performed a comprehensive search of the Cochrane Central Register of Controlled Trials, Medline (PubMed), and Embase databases for articles published from March 2010 to March 2016 using the following search terms: interleukins, interleukin-2, Candida spp., and immunosuppression. Data from our own studies were also reviewed. Here, we provide an overview focusing on the ability of IL-2 to induce a large panel of trafficking receptors in skin inflammation and control T helper (Th)2 cytokine production in response to contact with Candida spp. Immunocompromised patients have reduced capacity to secrete Th1-related cytokines such as IL-2. The ability to secrete the Th1-related cytokine IL-2 is low in immunocompromised patients. This prevents an efficient Th1 immune response to Candida spp. antigens, making immunocompromised patients more susceptible to candidal infections.

Advances in Immunotherapy for Melanoma: A Comprehensive Review.

Melanomas are tumors originating from melanocytes and tend to show early metastasis secondary to the loss of cellular adhesion in the primary tumor, resulting in high mortality rates. Cancer-specific active immunotherapy is an experimental form of treatment that stimulates the immune system to recognize antigens on the surface of cancer cells. Current experimental approaches in immunotherapy include vaccines, biochemotherapy, and the transfer of adoptive T cells and dendritic cells. Several types of vaccines, including peptide, viral, and dendritic cell vaccines, are currently under investigation for the treatment of melanoma. These treatments have the same goal as drugs that are already used to stimulate the proliferation of T lymphocytes in order to destroy tumor cells; however, immunotherapies aim to selectively attack the tumor cells of each patient. In this comprehensive review, we describe recent advancements in the development of immunotherapies for melanoma, with a specific focus on the identification of neoantigens for the prediction of their elicited immune responses. This review is expected to provide important insights into the future of immunotherapy for melanoma.

Protein biomarkers of mood disorders.

Psychiatric evaluation presents a significant challenge because it conceptually integrates the input from multiple psychopathological approaches. Recent technological advances in the study of protein structure, function, and interactions have provided a breakthrough in the diagnosis and treatment of mood disorders (MD), and have identified novel biomarkers to be used as indicators of normal and disease states or response to drug treatment. The investigation of biomarkers for psychiatric disorders, such as enzymes (catechol-O-methyl transferase and monoamine oxidases) or neurotransmitters (dopamine, serotonin, norepinephrine) and their receptors, particularly their involvement in neuroendocrine activity, brain structure, and function, and response to psychotropic drugs, should facilitate the diagnosis of MD. In clinical settings, prognostic biomarkers may be revealed by analyzing serum, saliva, and/or the cerebrospinal fluid, which should promote timely diagnosis and personalized treatment. The mechanisms underlying the activity of most currently used drugs are based on the functional regulation of proteins, including receptors, enzymes, and metabolic factors. In this study, we analyzed recent advances in the identification of biomarkers for MD, which could be used for the timely diagnosis, treatment stratification, and prediction of clinical outcomes.

Clinical application of development of nonantibiotic macrolides that correct inflammation-driven immune dysfunction in inflammatory skin diseases.

BACKGROUND: Inflammation-driven immune dysfunction supports the development of several chronic human disorders including skin diseases. Nonantibiotic macrolides have anti-inflammatory and/or immunomodulatory activity that suggests the exploitation of these in the treatment of skin diseases characterized by inflammatory disorders. MATERIALS AND METHODS: We performed an extensive review of the nonantibiotic macrolide literature published between 2005 and 2012, including cross-references of any retrieved articles. We also included some data from our own experience. RESULTS: Calcineurin antagonists such as tacrolimus and ascomycins (e.g., pimecrolimus) act by inhibiting the activation of the nuclear factor for activated T cells (NFAT). There are new applications for these macrolides that have been available for several years and have been applied to skin and hair disorders such as atopic dermatitis, oral lichen planus, vitiligo, chronic autoimmune urticaria, rosacea, alopecia areata, pyoderma gangrenosum, Behcet's disease, neutrophilic dermatosis, and lupus erythematosus. We also reviewed new macrolides, like rapamycin, everolimus, and temsirolimus. In addition to the literature review, we report a novel class of nonantibiotic 14-member macrocycle with anti-inflammatory and immunomodulatory effects. CONCLUSIONS: This paper summarizes the most important clinical studies and case reports dealing with the potential benefits of nonantibiotic macrolides which have opened new avenues in the development of anti-inflammatory strategies in the treatment of cutaneous disorders.

Unveiling New Molecular Factors Useful for Detection of Pelvic Inflammatory Disease due to Chlamydia trachomatis Infection.

Background. Untreated Chlamydia trachomatis infections in women can result in disease sequelae such as pelvic inflammatory disease (PID), ultimately culminating in tubal occlusion and infertility. While nucleic acid amplification tests can effectively diagnose uncomplicated lower genital tract infections, they are not suitable for diagnosing upper genital tract pathological sequelae. Objective. The purpose of this paper was to provide a comprehensive review of new molecular factors associated with the diagnosis and prognosis of PID. Material and Methods. The literature was searched using the key words "Chlamydia trachomatis infections," "pelvic inflammatory disease," and "molecular factors" in the PubMed database. Relevant articles published between 1996 and 2012 were evaluated. Conclusions. The use of new molecular factors could potentially facilitate earlier diagnosis and prognosis in women with PID due to C. trachomatis infection.

Treatment of burning mouth syndrome with amisulpride.

BACKGROUND: Burning mouth syndrome (BMS) is a frequently occurring disease characterized by a burning or painful sensation in the tongue and/or other oral sites without clinical mucosal abnormalities or lesions. Its etiopathology is unknown, although local, systemic, and psychological factors have been associated with BMS. The syndrome is multifactorial, and its management remains unsatisfactory. The purpose of this study was to obtain preliminary data regarding the efficacy and tolerability of amisulpride in BMS treatment. METHODS: The subjects were treated with amisulpride (50 mg/day) for 24 weeks. Efficacy assessment included a visual analogue scale (VAS) for pain intensity, the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HASM-A), and the Clinical Global Impression Scale-Efficacy Index (CGI-EI). RESULTS: The treatment regimens resulted in a significant improvement in burning mouth symptoms from baseline at week 24, as indicated by the quantitative mean illness duration VAS score, HAM-D, and HAM-A. Amisulpride appears to be effective and patients show a rapid response to treatment. No serious adverse effects were encountered in these patients. CONCLUSIONS: Amisulpride is effective and well tolerated as a short-term treatment. It is particularly efficacious at the start of treatment and has shorter response latency. Double-blind placebo-controlled trials are needed for further assessment of the efficacy of amisulpride in BMS treatment.

Glycolic acid 15% plus salicylic acid 2%: a new therapeutic pearl for facial flat warts.

BACKGROUND: Facial flat warts are a contagious viral disease that can cause disturbing cosmetic problems. Topical glycolic acid has been reported to be effective in dermatological treatment depending on the exfoliant capacity, but has not often been reported to be effective in the treatment of facial flat warts. OBJECTIVE: The aim of this paper was to evaluate the efficacy and safety of glycolic acid 15% topical gel plus salicylic acid 2% in the treatment of recalcitrant facial flat warts. METHODS: A total of 20 consecutive patients 7 to 16 years of age with recalcitrant facial flat warts were enrolled in this study. Patients having warts by the eye and lip regions were excluded from the study. A fine layer of face gel was applied to the treatment area once daily. Most of the participants had tried different treatments with no success. Assessments for the response and the occurrence of side effects were performed every two weeks at Weeks 2, 4, 6, and 8. RESULTS: All the patients were clinically cured within eight weeks. Seven patients cleared in four weeks, and 13 patients cleared in eight weeks. No noticeable adverse events were related to the skin. CONCLUSION: Topical gel of glycolic acid 15% plus salicylic acid 2% is safe and effective when applied to facial flat warts once daily until clearance and may be considered as first-line treatment.