In Vivo Antifungal Activity of Monolaurin against Candida albicans Biofilms.

Monolaurin is a natural compound that has been known for its broad antimicrobial activities. We evaluate the antifungal activity of monolaurin against Candida albicans biofilms in vivo using a novel bioluminescent model to longitudinally monitor oral fungal infection. Oral fungal infection in vivo was performed using bioluminescent engineered C. albicans (SKCa23-ActgLUC) biofilms on Balb/c mice. The antifungal activity of monolaurin was determined by comparing three groups of mice (n=5/group): monolaurin, vehicle control, and positive control (nystatin). All mice were immunosuppressed with cortisone acetate and oral topical treatments were applied for 5 d. In vivo imaging system (IVIS) imaging was used to monitor the progression of infection over a 5-d period. Total photon flux and ex vivo microbiological analysis of the excised tongues were used to determine the overall fungal burden. Oral topical treatments of monolaurin have resulted in a significant decrease (p<0.05) in the total photon flux over 4 and 5 d post-infection in comparison to the vehicle control group. Furthermore, monolaurin treated group had a significant decrease in colony formation unit of tongue tissue compared to the vehicle control. Our findings support monolaurin as a promising antifungal compound in vivo, which may translate to its future use in the treatment of oral candidiasis.

Antifungal Activity of Alkaloids Against Candida albicans.

Candida albicans is a pathogen in the mouth responsible for opportunistic infections that are usually harmless. Natural products have been used to develop several drugs, mostly anticancer and anti-infective agents. Among these, alkaloids have been studied for their medicinal properties. In this study, we examined their antifungal activity against C. albicans in vitro. Among the alkaloids studied in this work, berberine hydrochloride showed the best activity against C. albicans.

Dental Considerations and Precautions Associated with Oral Excisional Biopsy on a Patient with Cushing's Syndrome (Hypercortisolism).

Chronic exposure to endogenous and exogenous glucocorticoids will cause CS. Endogenous CS is uncommon, with an annual incidence of 0.2-5 individuals per million. Endogenous causes could be 1. adrenocorticotropic hormone (ACTH) dependent or 2. ACTH independent. The use of exogenous glucocorticoids to manage chronic autoimmune or inflammatory diseases is the most common cause of CS and results in iatrogenic CS. Cushing disease is caused by excess ACTH production by a pituitary tumor. CS's clinical manifestations in the head and neck region include a moon-shaped face, acne flares, and hirsutism.

A Patient with Addison Disease (Primary Adrenal Insufficiency) Presenting for Surgical Extraction of Third Molars.

The local prevalence of primary adrenal insufficiency (PAI) depends on various factors such as genetics, environment, and timely disease diagnosis. PAI is uncommon, and the prevalence is reported to be 2 per 10,000 population. PAI is commonly caused by an autoimmune process that destroys the adrenal gland, resulting in the loss of glucocorticoid and mineralocorticoid secretion from the adrenal cortex. The lack of cortisol results in impaired glucose/fat/protein metabolism, hypotension, increased adrenocorticotropic hormone secretion, impaired fluid excretion, and hyperpigmentation. PAI has a female predominance and is commonly seen in ages 20 to 50 years but can occur at any age.

Mandibular Jaw Lesion Excisional Biopsy on a Patient with Hyperparathyroidism (Primary).

Most of the primary hyperparathyroidism is due to adenomas in the parathyroid glands. Hypercalcemia is more common in primary hyperparathyroidism. Hyperparathyroidism may be asymptomatic and detected incidentally as part of a routine serological evaluation. Oral health care providers should recognize distinct changes in the jawbone associated with primary and secondary hyperparathyroidism.

The in vivo anti-Candida albicans activity of flavonoids.

BACKGROUND: Emerging drug-resistant strains of Candida albicans have led to the recurrence of fungal disease, rendering conventional drug therapies ineffective. Although in vitro studies on flavonoids as novel antifungal products have shown promising results, there is currently limited information regarding their in vivo effects. The aim of this review is to evaluate in vivo studies on the antifungal activity of flavonoids against C. albicans, as novel therapeutic agents. In this regard, we conducted broad searches of PubMed, Web of Science, and Embase covering the years 2009-2020. HIGHLIGHT: Flavonoids represent new natural therapeutic compounds to treat oral candidiasis. Among subclasses of flavonoids, flavonols and chalcones appear to have the most significant antifungal activities. Oral administration of Canthin-6-one, a flavonol, has the potential to damage fungal cell membrane while having minimal toxic effects on mice. Similarly, topical oral application of lichochalcone-A, a chalcone, reduces oral candidiasis in mice. There appears to be structural similarities in the hydroxyl residues among compounds within the same subclass of flavonoids, which may contribute to antibiofilm activity. Oral topical application of flavonoids shows low toxicity and has clinical relevance as potential novel antifungal treatments. CONCLUSION: Flavonoids are a group of natural products exhibiting antifungal activity. The subclasses flavonols and chalcones appear to have the most significant in vivo antifungal activity against C. albicans infections in mouse models. Specifically, quercetin (flavonol) has been applied via vaginal gavage in a murine vulvovaginal candidiasis model, whereas lichochalcone-A (chalcone) has shown topical oral application in C. albicans-inoculated mice. Both compounds show efficacy in fungal elimination via biofilm inhibition for their respective subclasses. The translational significance of these in vivo studies should be examined in clinical trials of selected potent compounds for the treatment of oral candidiasis. Further studies are necessary to elucidate the specific mechanisms of flavonoids as antifungal agents.

Effect of 10% Carbamide Peroxide on Tooth Shade, Plaque Index and Gingival Index during Invisalign Treatment.

Invisalign has improved periodontal health in comparison to traditional metal wire braces. Due to a growing interest in attaining better teeth esthetics, there are more adults seeking Invisalign treatment. Ten percent carbamide peroxide (CP) breaks down to 6.5% urea and 3.5% hydrogen peroxide, which elevates oral pH, removes stains, and diminishes caries by inhibiting plaque formation. The aim of this study is to investigate whether 10% CP use during Invisalign treatment can enhance tooth shade esthetics while decreasing plaque levels and improving gingival health indices. Twenty-eight patients at Western University dental center undergoing Invisalign were assigned to two groups where the experimental group applied daily bleaching material (10% CP, Ultradent Inc., South Jordan, UT, USA), while the control group did not for 4 weeks. Tooth shade, plaque index (PI), and gingival index (GI) were assessed at baseline and in 2-week intervals for 6 weeks. Results showed that 10% CP had significant change in tooth shade over the 2- and 4-weeks periods (p < 0.05) and significantly reduced plaque and gingival indices (p < 0.05), with minimal to no relapse after 2 weeks post-op. Thus, applying CP at 10% may be a useful application during Invisalign treatment in improving teeth shade and overall gingival health.

Periodontitis and diabetes mellitus co-morbidity: A molecular dialogue.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and periodontitis are two biologically linked diseases that often coexist in complex interaction. While periodontitis may lead to insulin receptor desensitization, diabetes may increase the expression of inflammatory cytokines, such as Tumor Necrosis Factor-α (TNF-α) and Interleukin 6 (IL-6), in the gingival crevicular fluid and activate osteoclasts via Receptor activator of nuclear factor kappa-Β ligand (RANK-L) production, leading to bone resorption. However, the association between the two diseases processes, where one may exacerbate the progression of the other, is unclear. In addition, both diseases have similar mechanistic themes, such as chronic inflammation and oxidative stress. This review aimed to investigate the pathophysiological and molecular mechanisms underlying T2DM and periodontitis. HIGHLIGHT: Uncontrolled diabetes is often associated with severe periodontitis, measured by clinical attachment loss. Alteration in the oral microbiome composition, which may activate the host inflammatory response and lead to irreversible oxidative stress, is a common finding in both diseases. An understanding of the molecular crosstalk between the two disease processes is crucial for developing therapeutic targets that inhibit bone resorption and halt the progression of periodontitis in patients with diabetes. CONCLUSION: The Oral microbiome composition in T2DM and periodontitis shifts toward dysbiosis, favoring bacterial pathogens, such as Fusobacteria and Porphyromonas species. Both conditions are marked by pro-inflammatory immune activity via the activation of Interleukin 17 (IL-17), Interleukin 1 (IL-1), TNF-α, and Nuclear Factor Kappa Beta (NF-κB). Common molecular crosstalk signaling appears to involve advanced glycation end products (AGEs) and oxidative stress. Thus, future drug targets are multifactorial, ranging from modulatory of host inflammatory response to preventing the accumulation of AGEs and oxidative free radicals.

Rosmarinic Acid/ Blue Light Combination Treatment Inhibits Head and Neck Squamous Cell Carcinoma In Vitro.

BACKGROUND/AIM: This study investigated a novel combined therapy of rosmarinic acid (RA)/blue light on head and neck squamous cell carcinoma (HNSCC) cell proliferation in vitro. MATERIALS AND METHODS: HNSCC cells were exposed to BL (500 mW/cm2) for 90 s, and incubated with 80 µg/ml RA for 1 hour. Cell viability was determined after 24 h using WST-1 assay. Western blot was used to detect treatment-induced changes in epidermal growth factor receptor (EGFR) activation. Hydrogen peroxide (H2O2) and nitric oxide levels were quantified using CM-H2DCFH-DA assays. Apoptosis was assessed using Annexin V/PI staining and flow cytometry. RESULTS: RA/blue light treatment resulted in a significant reduction in cell viability, EGFR activation and H2O2 levels in all HNSCC cell lines. However, no significant changes in NO production or apoptosis induction were found. CONCLUSION: RA/blue light effectively decreased HNSCC cell proliferation through reduction in EGFR activation and H2O2 production, and not via induction of apoptosis.

Fungal-Host Interaction: Curcumin Modulates Proteolytic Enzyme Activity of Candida albicans and Inflammatory Host Response In Vitro.

Current treatments for Candida albicans infection are limited due to the limited number of antifungal drugs available and the increase in antifungal resistance. Curcumin is used as a spice, food preservative, flavoring, and coloring agent that has been shown to have many pharmacological activities. Thus, this study evaluated the modulatory effects of curcumin on major virulence factors associated with the pathogenicity of C. albicans. The minimum inhibitory concentration (MIC) of curcumin against C. albicans (SC5314) was determined. Biofilm formation was quantified and the proteinase and phospholipase secretion was measured. The cytotoxicity was tested in oral fibroblast cells. A cocultured model was used to analyze the gene expression of proinflammatory cytokines (IL-1ß, IL-1α, and IL-6) from host cells, as well SAP-1 and PLB-1 by RT-PCR. The MIC was between 6.25 and 12.5 µM, and the activity of proteinase enzyme was significantly decreased in biofilms treated with curcumin. However, proteinase gene expression was not downregulated after curcumin treatment. Furthermore, gene expressions of host inflammatory response, IL-1ß and IL-1α, were significantly downregulated after exposure to curcumin. In conclusion, curcumin exhibited antifungal activity against C. albicans and modulated the proteolytic enzyme activities without downregulating the gene expression. In host inflammatory response, curcumin downregulated IL-1ß and IL-1α gene expression.

Review of flavonoids: A diverse group of natural compounds with anti-Candida albicans activity in vitro.

Flavonoids are a subdivision of polyphenols, a versatile class of natural compounds that represent secondary metabolites from higher plants and are abundant in human diet. Various protective effects of flavonoids have been reported, including antimicrobial and antifungal activities. Due to the nature of oral candidiasis and the increased use of antifungal agents, several drug-resistant strains have emerged making it impractical to rely on one standard therapeutic regime. The aim of this review is to summarize the antifungal activity of some examples of the major subclasses of flavonoids in pure extract forms against C. albicans in vitro, as reported in literature over the past 10 years (2004-2015). In addition, this review outlines the potential mechanism of actions of flavonoids studied in vitro, which may contribute to a better understanding of flavonoids as multi-targets agents in the treatment and/or prevention of oral candidiasis in clinical settings.

In Vitro and In Vivo Antifungal Activity of Lichochalcone-A against Candida albicans Biofilms.

Oral candidiasis (OC) is an opportunistic fungal infection with high prevalence among immunocompromised patients. Candida albicans is the most common fungal pathogen responsible for OC, often manifested in denture stomatitis and oral thrush. Virulence factors, such as biofilms formation and secretion of proteolytic enzymes, are key components in the pathogenicity of C. albicans. Given the limited number of available antifungal therapies and the increase in antifungal resistance, demand the search for new safe and effective antifungal treatments. Lichochalcone-A is a polyphenol natural compound, known for its broad protective activities, as an antimicrobial agent. In this study, we investigated the antifungal activity of lichochalcone-A against C. albicans biofilms both in vitro and in vivo. Lichochalcone-A (625 µM; equivalent to 10x MIC) significantly reduced C. albicans (MYA 2876) biofilm growth compared to the vehicle control group (1% ethanol), as indicated by the reduction in the colony formation unit (CFU)/ml/g of biofilm dry weight. Furthermore, proteolytic enzymatic activities of proteinases and phospholipases, secreted by C. albicans were significantly decreased in the lichochalcone-A treated biofilms. In vivo model utilized longitudinal imaging of OC fungal load using a bioluminescent-engineered C. albicans (SKCa23-ActgLUC) and coelenterazine substrate. Mice treated with lichochalcone-A topical treatments exhibited a significant reduction in total photon flux over 4 and 5 days post-infection. Similarly, ex vivo analysis of tongue samples, showed a significant decrease in CFU/ml/mg in tongue tissue sample of lichochalcone-A treated group, which suggest the potential of lichochalcone-A as a novel antifungal agent for future clinical use.

In vitro evaluation of antifungal activity of monolaurin against Candida albicans biofilms.

Monolaurin (also known as glycerol monolaurate) is a natural compound found in coconut oil and is known for its protective biological activities as an antimicrobial agent. The nature of oral candidiasis and the increased antifungal resistance demand the search for novel antifungal therapeutic agents. In this study, we examine the antifungal activity of monolaurin against Candida albicans biofilms (strain ATCC:SC5314/MYA2876) in vitro and investigate whether monolaurin can alter gene expression of host inflammatory cytokines, IL-1α and IL-1ß. In a co-culture model, oral fibroblast cells were cultured simultaneously with C. albicans for 24 hrs followed by the exposure to treatments of monolaurin (3.9-2,500 µM), positive control fluconazole (32.2 µM), and vehicle control group (1% ethanol), which was a model used to evaluate the cytotoxicity of monolaurin on fibroblasts as well as to analyze morphological characteristics of biofilms through fluorescence microscopy. In addition, the co-culture model was used for RNA extraction of oral fibroblasts to assess gene expression of host inflammatory cytokines, using quantitative real-time PCR. Our results showed the MIC and MFC of monolaurin were in the range 62.5-125 µM and 125-250 µM, respectively. Biofilm antifungal assay showed significant reduction in Log (CFU/ml) of biofilms treated with 1,250 and 2,500 µM of 1-monolaurin when compared to the control groups . There was also a significant down-regulation of IL-1α and IL-1ß in the co-culture treated with monolaurin. It can be concluded that monolaurin has a potential antifungal activity against C. albicans and can modulate the pro-inflammatory response of the host.