Synergistic effect of the verapamil and amphotericin B against Cryptococcus neoformans.

Cryptococcus neoformans is an encapsulated yeast that can cause cryptococcosis and cryptococcal meningitis, which conventional treatment involves antifungal drugs such as polyenes, flucytosine, azoles, and their combinations. However, the high cost, toxicity, and increase in fungi resistance to antifungal agents stimulate the search for therapeutic strategies such as drug repurposing and combination therapy. This study evaluated the activity of the antihypertensive verapamil (VEH) alone and combined with amphotericin B (AmB) against C. neoformans. VEH exhibited antifungal activity against C. neoformans with minimum inhibitory concentration and minimum fungicidal concentration of 118 µg per mL. The combination of VEH and AmB exhibited synergism, reducing at least eightfold both drugs' concentrations. Moreover, the combination decreased the size and glucuronoxylomannnan content of C. neoformans capsule. However, no difference was observed in ergosterol levels of C. neoformans after treatment with VEH and AmB in combination. Altogether, VEH in combination with AmB exhibits potential as a candidate as for the development of anti-cryptococcal drug.

IL10 promoter rs6667202 polymorphism is functional in health but not in grade c periodontitis patients: A pilot study.

BACKGROUND AND OBJECTIVE: Previous studies have demonstrated an association between the IL10 promoter rs6667202 (C > A) single-nucleotide polymorphism (SNP) and grade C, stage 3 or 4 periodontitis (Perio4C) in the Brazilian population, where the altered A allele was detected more frequently in these patients. However, no functional analysis of this variation has yet been performed. Thus, the objective of this preliminary study was to evaluate the functionality of rs6667202 in gingival fibroblasts (GFs) of individuals with Perio4C and with periodontal health (PH) stimulated with Aggregatibacter actinomycetencomitans protein extract (AaPE). METHODS: Patients with PH and Perio4C were segregated according to their genotype (AA, AC, or CC), and a biopsy was performed to establish the culture of the GFs. After GFs exposure to AaPE at 5 µg/ml for 1.5 h, RNA was extracted to analyze IL10 expression by qPCR. Aliquots of the cell's supernatant were subjected to immunoenzymatic analysis (MAGpix) to detect interleukin-10 (IL-10). RESULTS: In PH, the genotypes AA and AC are related to less expression of IL10 (p = 0.027 and p < 0.0001) and less production of IL-10 (p = 0.002 and p = 0.001), when compared to CC. In Perio4C, there was no statistical difference between the genotypes (p > 0.05), although a lower IL-10 expression and release compared with PH CC was seen (p = 0.033 and p < 0.001). CONCLUSION: The rs6667202 SNP is functional in PH, as it decreases the expression and production of IL-10. In Perio4C, other factors may be masking its action by altering the IL-10's response.

Curcuma longa L. helps macrophages to control opportunistic micro-organisms during host-microbe interactions.

Aim: Plant products have been evaluated to control opportunistic micro-organisms, as well as fortify immune system cells. Thus, Curcuma longa L. (turmeric) extract was evaluated in interactions of murine macrophages (RAW 264.7) with Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans, in order to establish cooperation with defense cells. Materials & methods: Effects of minimal inhibitory concentrations (MIC) of the plant extract were analyzed on phagocytosis, cell viability of RAW 264.7 and production of inflammation-related molecules (IL-1ß, TNF-α, IL-10 and NO). Results: The plant extract was cytocompatible and promoted significant reductions of micro-organisms, and synthesis of inflammation-related molecules, during interactions. Conclusion:C. longa L. extract showed significant antimicrobial response and cooperation with macrophages, by fighting bacteria and yeasts during host-microbe interactions.

Two different antibiotic protocols as adjuncts to one-stage full-mouth ultrasonic debridement to treat generalized aggressive periodontitis: A pilot randomized controlled clinical trial.

BACKGROUND: To assess the clinical and microbiological responses of amoxicillin + metronidazole (AMX + MET) versus clarithromycin (CLM) as adjuncts to one-stage full-mouth ultrasonic debridement (FMUD) in the treatment of generalized aggressive periodontitis (GAgP). METHODS: For this parallel, double-masked, pilot randomized clinical trial, 46 patients with GAgP were selected and randomly assigned into two groups: AMX+MET group (n = 23): FMUD associated with AMX (500 mg three times a day) and MET (400 mg three times a day) for 7 days; and CLM group (n = 23): FMUD associated with CLM (500 mg twice a day) for 7 days. Clinical parameters were evaluated at baseline, 3, and 6 months post-treatment. The levels of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and Fusobacterium nucleatum from subgingival biofilm were determined by quantitative polymerase chain reaction. RESULTS: Both treatments significantly improved all clinical parameters compared with baseline and promoted a significant reduction of A. actinomycetemcomitans and P. gingivalis counts (P > 0.05). CLM succeeded in decreasing T. forsythia at 6 months (P < 0.05), but no antibiotic was able to reduce F. nucleatum. There was no difference between the two protocols regarding the reported adverse effects (P > 0.05). CONCLUSIONS: The results suggest that CLM is not superior than AMX + MET in the treatment of GAgP. However, this antibiotic led to good clinical outcomes and may be a possible alternative to AMX+MET in the treatment of severe periodontitis in young patients. Future studies with larger sample sizes are needed to confirm this statement (NCT02969928).