Aspectos da abordagem terapêutica sobre candidíase vulvovaginal / Aspects of the therapeutic approach to vulvovaginal candidiasis / Aspectos del abordaje terapéutico de la candidiasis vulvovaginal

A candidíase vulvovaginal, é uma infecção da vulva e vagina causada por vários tipos de Candida spp. Essa patologia afeta 75% de todas as mulheres pelo menos uma vez durante a vida, ocorrendo com mais frequência durante a idade fértil. A transmissão dessa infeção fúngica ocorre por meio de contato com mucosas e secreções em pele de portadores ou doentes, contato sexual, água contaminada e transmissão vertical. Alguns outros sintomas característicos mais vistos em casos de CVV, são lesões brancas, cremosas e planas, sendo mais intensos no período pré-menstrual, quando a acidez vaginal aumenta. numerosos antifúngicos estão disponíveis no mercado, os quais são encontrados para administração oral na forma de comprimidos ou, para uso tópico, na forma de cremes, loções, comprimidos vaginais, supositórios e tampões revestidos. O objetivo geral do trabalho foi analisar através da revisão de literatura, tratamentos convencionais e alternativos para abordagem terapêutica da Candidíase Vulvovaginal contextuando a mesma, utilizando definições, dados epidemiológicos e sua sintomatologia frente à sociedade. O presente trabalho é uma revisão integrativa, que teve a coleta de dados realizada de março de 2021 a outubro de 2021 nas bases de dados Lilacs, Scielo, Google acadêmico, A busca resultou em 902 artigos, dos quais 14 atenderam ao critério de inclusão. A busca por tratamentos frente a candidíase vulvovaginal tem se mostrado ampla de acordo com os artigos selecionadas. Concluímos que a patologia candidíase vulvovaginal, vem apresentando resistência em algumas abordagens terapêuticas, assim como algumas mulheres não aderem há algum tipo de tratamento, devido à falta de conhecimento sobre a patologia.

Vulvovaginal candidiasis is an infection of the vulva and vagina caused by various types of Candida spp. This condition affects 75% of all women at least once in their lifetime, occurring more frequently during their childbearing years. The transmission of this fungal infection occurs through contact with mucous membranes and secretions on the skin of patients or patients, sexual contact, contaminated water and vertical transmission. Some other characteristic symptoms more seen in cases of VVC are white, creamy and flat lesions, being more intense in the premenstrual period, when the vaginal acidity increases. numerous antifungals are available on the market which are available for oral administration in tablet form or, for topical use, in the form of creams, lotions, vaginal tablets, suppositories and coated tampons. The general objective of the work was to analyze, through a literature review, conventional and alternative treatments for the therapeutic approach of Vulvovaginal Candidiasis in its context, using definitions, epidemiological data and its symptoms in society. The present work is an integrative review, which had data collection carried out from March 2021 to October 2021 in the Lilacs, Scielo, Google academic databases. The search resulted in 902 articles, of which 14 met the inclusion criteria. The search for treatments against vulvovaginal candidiasis has been shown to be wide according to the selected articles. We conclude that the vulvovaginal candidiasis pathology has been showing resistance in some therapeutic approaches, as well as some women do not adhere to any type of treatment, due to lack of knowledge about the pathology.

La candidiasis vulvovaginal es una infección de la vulva y la vagina cau- sada por diversos tipos de Candida spp. Esta afección afecta al 75% de las mujeres al menos una vez en la vida, siendo más frecuente durante la edad fértil. La transmisión de esta infección fúngica se produce por contacto con mucosas y secreciones de la piel de pacientes o enfermos, contacto sexual, agua contaminada y transmisión vertical. Otros síntomas característicos más observados en los casos de CVV son las lesiones blancas, cremosas y planas, siendo más intensas en el período premenstrual, cuando aumenta la acidez vaginal. Existen en el mercado numerosos antifúngicos disponibles para adminis- tración oral en forma de comprimidos o, para uso tópico, en forma de cremas, lociones, comprimidos vaginales, supositorios y tampones recubiertos. El objetivo general del tra- bajo fue analizar, a través de una revisión bibliográfica, los tratamientos convencionales y alternativos para el abordaje terapéutico de la Candidiasis Vulvovaginal en su contexto, utilizando definiciones, datos epidemiológicos y su sintomatología en la sociedad. El pre- sente trabajo es una revisión integradora, que tuvo recolección de datos realizada de marzo de 2021 a octubre de 2021 en las bases de datos académicas Lilacs, Scielo, Google. La búsqueda resultó en 902 artículos, de los cuales 14 cumplieron los criterios de inclu- sión. La búsqueda de tratamientos contra la candidiasis vulvovaginal se ha mostrado am- plia según los artículos seleccionados. Concluimos que la patología de la candidiasis vul- vovaginal viene mostrando resistencia en algunos abordajes terapéuticos, así como algu- nas mujeres no se adhieren a ningún tipo de tratamiento, debido al desconocimiento de la patología.

Pomegranate Extract Potentiates the Anti-Demineralizing, Anti-Biofilm, and Anti-Inflammatory Actions of Non-Alcoholic Mouthwash When Associated with Sodium-Fluoride Trimetaphosphate.

This study investigated the anti-caries and anti-inflammatory effects of mouthwash formulations containing Punica granatum (pomegranate) peel extract (PPE), sodium-trimetaphosphate, and low concentrations of fluoride. PPE was characterized using high-performance liquid chromatography (ellagic acid and punicalagin). Total phenolics were quantified among formulations, and their stability was analyzed for 28 days. The formulation effects were evaluated as follows: (1) inorganic component concentration and reduced demineralization on bovine enamel blocks subjected to pH cycling; (2) anti-biofilm effect on dual-biofilms of Streptococcus mutans ATCC 25175 and Candida albicans ATCC 10231 treated for 1 and 10 min, respectively; and (3) cytotoxicity and production of inflammatory mediators (interleukin-6 and tumor necrosis factor-alpha). The formulation containing 3% PPE, 0.3% sodium-trimetaphosphate, and 225 ppm of fluoride resulted in a 34.5% surface hardness loss; a 13% (treated for 1 min) and 36% (treated for 10 min) biofilm reduction in S. mutans; a 26% (1 min) and 36% (10 min) biofilm reduction in C. albicans; absence of cytotoxicity; and anti-inflammatory activity confirmed by decreased interleukin-6 production in mouse macrophages. Thus, our results provide a promising prospect for the development of an alcohol-free commercial dental product with the health benefits of P. granatum that have been recognized for a millennium.

Artepillin C Reduces Allergic Airway Inflammation by Induction of Monocytic Myeloid-Derived Suppressor Cells.

Propolis is a natural product produced by bees that is primarily used in complementary and alternative medicine and has anti-inflammatory, antibacterial, antiviral, and antitumoral biological properties. Some studies have reported the beneficial effects of propolis in models of allergic asthma. In a previous study, our group showed that green propolis treatment reduced airway inflammation and mucus secretion in an ovalbumin (OVA)-induced asthma model and resulted in increased regulatory T cells (Treg) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) frequencies in the lungs, two leukocyte populations that have immunosuppressive functions. In this study, we evaluated the anti-inflammatory effects of artepillin C (ArtC), the major compound of green propolis, in the context of allergic airway inflammation. Our results show that ArtC induces in vitro differentiation of Treg cells and monocytic MDSC (M-MDSC). Furthermore, in an OVA-induced asthma model, ArtC treatment reduced pulmonary inflammation, eosinophil influx to the airways, mucus and IL-5 secretion along with increased frequency of M-MDSC, but not Treg cells, in the lungs. Using an adoptive transfer model, we confirmed that the effect of ArtC in the reduction in airway inflammation was dependent on M-MDSC. Altogether, our data show that ArtC exhibits an anti-inflammatory effect and might be an adjuvant therapy for allergic asthma.

Incorporation of indomethacin into a mesoporous silica nanoparticle enhances the anti-inflammatory effect Indomethacin into a mesoporous silica.

PURPOSE: We evaluated the analgesic, anti-inflammatory and toxicological effects of indomethacin incorporated into mesoporous silica nanoparticles (IND+NP). METHODS: Nociception was evaluated by the formalin assay. The anti-inflammatory potential was assessed by cell migration and paw edema assays, modulation of nitric oxide and cytokines (IL-6, IL-10 and TNF-α) by macrophages production. Toxicity was evaluated in peritoneal macrophages and by the locomotion assay and assessment of gastric injuries, presence of occult blood and hepatic and renal markers. RESULTS: IND+NP reduced nociception during phases 1 by 53% and 2 by 79% of the formalin assay and the influx of peritoneal cells by 94%, indicating an analgesic and anti-inflammatory effect more efficiently than indomethacin alone. Indomethacin, but not IND+NP, caused macroscopic gastric injuries, the presence of fecal occult blood, and an increase of ALT levels. In the paw edema assay, IND+NP reduced edema by 21%. IND+NP has no effect on the LPS-induced production of nitric oxide, IL-6, IL-10 and TNF-α on no cytotoxic concentrations. CONCLUSIONS: The incorporation of indomethacin into mesoporous silica nanoparticles effectively increased the activity of the drug observed in the formalin and cell migration assays and prevented the gastric and hepatic damage associated with its use.

Aspergillus fumigatus MADS-Box Transcription Factor rlmA Is Required for Regulation of the Cell Wall Integrity and Virulence.

The Cell Wall Integrity (CWI) pathway is the primary signaling cascade that controls the de novo synthesis of the fungal cell wall, and in Saccharomyces cerevisiae this event is highly dependent on the RLM1 transcription factor. Here, we investigated the function of RlmA in the fungal pathogen Aspergillus fumigatus We show that the ΔrlmA strain exhibits an altered cell wall organization in addition to defects related to vegetative growth and tolerance to cell wall-perturbing agents. A genetic analysis indicated that rlmA is positioned downstream of the pkcA and mpkA genes in the CWI pathway. As a consequence, rlmA loss-of-function leads to the altered expression of genes encoding cell wall-related proteins. RlmA positively regulates the phosphorylation of MpkA and is induced at both protein and transcriptional levels during cell wall stress. The rlmA was also involved in tolerance to oxidative damage and transcriptional regulation of genes related to oxidative stress adaptation. Moreover, the ΔrlmA strain had attenuated virulence in a neutropenic murine model of invasive pulmonary aspergillosis. Our results suggest that RlmA functions as a transcription factor in the A. fumigatus CWI pathway, acting downstream of PkcA-MpkA signaling and contributing to the virulence of this fungus.

Validation of a RP-HPLC-DAD Method for Chamomile (Matricaria recutita) Preparations and Assessment of the Marker, Apigenin-7-glucoside, Safety and Anti-Inflammatory Effect.

Chamomile is a medicinal plant, which presents several biological effects, especially the anti-inflammatory effect. One of the compounds related to this effect is apigenin, a flavonoid that is mostly found in its glycosylated form, apigenin-7-glucoside (APG), in natural sources. However, the affectivity and safety of this glycoside have not been well explored for topical application. In this context, the aim of this work was to develop and validate a reversed-phase high-performance liquid chromatography (RP-HPLC-DAD) method to quantify APG in chamomile preparations. Additionally, the safety and the anti-inflammatory potential of this flavonoid were verified. The RP-HPLC-DAD method was developed and validated with linearity at 24.0-36.0 µg/mL range (r = 0.9994). Intra- and interday precision (RSD) were 0.27-2.66% and accuracy was 98.27-101.21%. The validated method was applied in the analysis of chamomile flower heads, glycolic extract, and Kamillen cream, supporting the method application in the quality control of chamomile preparations. Furthermore, the APG safety was assessed by MTT cytotoxicity assay and mutagenic protocols and the anti-inflammatory activity was confirmed by a diminished TNF-α production showed by mice macrophages treated with APG following LPS treatment.

The Aspergillus fumigatus pkcA G579R Mutant Is Defective in the Activation of the Cell Wall Integrity Pathway but Is Dispensable for Virulence in a Neutropenic Mouse Infection Model.

Aspergillus fumigatus is an opportunistic human pathogen, which causes the life-threatening disease, invasive pulmonary aspergillosis. In fungi, cell wall homeostasis is controlled by the conserved Cell Wall Integrity (CWI) pathway. In A. fumigatus this signaling cascade is partially characterized, but the mechanisms by which it is activated are not fully elucidated. In this study we investigated the role of protein kinase C (PkcA) in this signaling cascade. Our results suggest that pkcA is an essential gene and is activated in response to cell wall stress. Subsequently, we constructed and analyzed a non-essential A. fumigatus pkcAG579R mutant, carrying a Gly579Arg substitution in the PkcA C1B regulatory domain. The pkcAG579R mutation has a reduced activation of the downstream Mitogen-Activated Protein Kinase, MpkA, resulting in the altered expression of genes encoding cell wall-related proteins, markers of endoplasmic reticulum stress and the unfolded protein response. Furthermore, PkcAG579R is involved in the formation of proper conidial architecture and protection to oxidative damage. The pkcAG579R mutant elicits increased production of TNF-α and phagocytosis but it has no impact on virulence in a murine model of invasive pulmonary aspergillosis. These results highlight the importance of PkcA to the CWI pathway but also indicated that additional regulatory circuits may be involved in the biosynthesis and/or reinforcement of the A. fumigatus cell wall during infection.

Inflammasome activation is critical to the protective immune response during chemically induced squamous cell carcinoma.

Chronic inflammation affects most stages of tumorigenesis, including initiation, promotion, malignant differentiation, invasion and metastasis. Inflammasomes have been described as involved with persistent inflammation and are known to exert both pro and antitumour effects. We evaluated the influence of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase (CASP)-1 in the antitumor immune response using a multistage model of squamous cell carcinoma (SCC) development. Absence of ASC and CASP-1 resulted in an earlier incidence and increased number of papilloma. Loss of inflammassome function in mice resulted in decreased presence of natural killer (NK), dendritic (DC), CD4(+), CD8(+) and CD45RB(+) T cells in the tumor lesions as well as in lymph nodes (LN) compared with WT mice. Increased percentage of CD4(+)CD25(+)Foxp3(+) T cells was associated with association with inflammasome loss of function. Moreover, significant differences were also found with neutrophils and macrophage infiltrating the lesions. Myeloperoxidase (MPO), but not elastase (ELA), activity oscillated among the groups during the SCC development. Levels of proinflammatory cytokines IL-1ß, IL-18, Tumor Necrosis Factor (TNF)-α and Interferon (IFN)-γ were decreased in the tumor microenvironment in the absence of inflammasome proteins. These observations suggest a link between inflammasome function and SCC tumorigenesis, indicating an important role for inflammasome activation in the control of SCC development.