Antimicrobial effect of oral care gel containing hinokitiol and 4-isopropyl-3-methylphenol against intraoral pathogenic microorganisms.

OBJECTIVE: Deterioration of oral hygiene is closely related to an increase in severity and mortality of corona virus disease-19 (COVID-19), and also contributes to the development of various diseases such as aspiration pneumonia or Alzheimer's. Oral care is attracting high interest in Japan, which has entered a super-aging society. In this study, we aimed to investigate whether commercially available Hinora® (HO), an oral care gel containing hinokitiol and 4-isopropyl-3-methylphenol (IPMP), has biofilm formation inhibitory and antimicrobial activities against various intraoral pathogen microorganisms. METHOD: Candida species, Aggregatibacter actinomycetemcomitans, Staphylococcus aureus, and Pseudomonas aeruginosa were selected during the study period, all of which were analyzed using antimicrobial disc, microorganism turbidity, and crystal violet assays. In addition, the germ tube test using Candida albicans (C. albicans) was performed with a modification of Mackenzie's method. Images for morphological observation of the germ tubes were acquired using an inverted microscope. For comparison between products, we used Refrecare® (RC), which only contains hinokitiol (not containing IPMP). RESULTS: All the intraoral pathogenic microorganisms showed drug susceptibility against undiluted forms of HO and/or RC. In particular, HO was more effective at lower concentrations than RC. In the HO-added group, inhibition circles were observed in all bacteria except P. aeruginosa when added at a concentration of 0.5 g/mL or more. The optical density values at 590 nm (crystal violet) and/or 600 nm (microorganism turbidity) of all the fungi and bacteria were significantly lower when cultured in medium with HO. Inhibition of growth or biofilm formation was observed when HO was added at a concentration of 0.05 g/mL or higher. To investigate the action mechanism of HO, germ tube tests were performed in C. albicans. The results showed that culturing C. albicans in soybean-casein digest broth with HO (0.05 g/mL) significantly suppressed germ tube formation. CONCLUSIONS: These data suggest that oral care gel-containing hinokitiol and IPMP has strong biofilm formation inhibitory activity, as well as antifungal and antimicrobial effects against Candida fungi and multiple intraoral pathogenic microorganisms. Therefore, it may be a promising treatment option for oral infections.

[Construction of Pre-clinical Practice and Survey of Consciousness for Pharmacy Students with Hearing Disability].

Various types of pre-learning-including pre-learning for practical training-provide pharmacy students with practical training and sufficient knowledge, skills, and attitudes for practical work. Opportunities in the medical field, including for pharmacists, have been greatly expanded for students with a hearing disability, and we have responded with appropriate training for such students. In this study, we report on the results of an evaluation of a survey on the preparatory training conducted by the students and the changes in their consciousness, such as in their level of understanding, knowledge, and self-confidence. Before the training, the participants' anxiety concerning items related to dispensing and communication were quite high; after the training, however, these anxiety levels were reduced. In addition, we were able to encourage the participant's concern for people and to face the difficulty of expressing words in letters, as well as to drive enthusiasm for the Objective Structured Clinical Examination (OSCE) and practical training. These results suggest that having a teacher as an assistant is useful for helping students with hearing disability in practical training.

Biotin Regulates Colonization and Growth of Candida albicans in the Catheter Lumen During Nutrient Infusions.

Bacterial and fungal catheter-related bloodstream infections (CRBSI) cause high fever and blindness due to fungal endophthalmitis. Candidal CRBSI have a particularly high mortality rate and needs attention. In this study, we examined the effect of biotin on the colonization and growth of Candida albicans in the lumen of the catheter used for nutrient infusions. In the current study, nutrient infusion-1: commercially available peripheral parenteral nutrition (PPN) infusion solution with vitamin B1 (control), nutrient infusion-2: biotin added to the PPN infusion, nutrient infusion-3: water-soluble vitamins (B2, B6, B12, C, folic acid, nicotinamide, panthenol) except biotin added to the PPN infusion, and nutrient infusion-4: commercially available PPN infusion with all water soluble vitamins (B1, B2, B6, B12, C, folic acid, nicotinamide, biotin, panthenol) were used. Candida albicans suspension was injected into a Planecta infusion set, which was connected to one of the test solutions, and the infusions flow pass was blocked for approximately 30 minutes. Subsequently, the infusions were resumed, and the test solution was collected at 24 hours, 48 hours, and 72 hours to estimate the Candida albicans colony-forming units in each infusion. We demonstrated that nutrient infusion with biotin promoted colonization and proliferation in the catheter lumen, whereas those without biotin had no effect. These results suggest that biotin may accelerate the colonization and growth of Candida albicans in catheter lumen and using biotin-containing nutrient infusions may increase the risk of CRBSI.

Bactericidal and Antiproliferative Effects of Peripheral Parenteral Nutrition Solutions with Sodium Bisulfite on Pathogenic Microorganisms in Catheter Lumens.

Catheter-related bloodstream infections (CRBSIs) due to pathogenic microorganisms pose a major threat to patients requiring parenteral nutrition (PN). Additives contained in medicines and foods have antiproliferative and bacteriostatic effects on pathogenic microorganisms. Therefore, PN solutions containing additives may also have an antibacterial effect. However, so far, there have been no reports on or observations of a PN solution with bactericidal activity. In this study, we assessed several nutrition solutions with antimicrobial activities and investigated their effects on pathogenic microorganisms colonizing catheter lumens. We selected the highly acidic Plas-Amino® (PA), which contains a large amount of sodium bisulfite as a preservative and potentially has an antimicrobial effect. In this study, we used the following pathogenic bacteria as the main causatives of CRBSIs: Staphylococcus aureus, Staphylococcus epidermidis, Bacillus cereus, Serratia marcescens, Pseudomonas aeruginosa, and Candida albicans. We then created a catheter lumen microorganism contamination model and evaluated the antibacterial effect of PA; we found that all bacteria in the control group grew significantly in the catheter lumen in a time-dependent manner at 48 and 72 h. On the other hand, we demonstrated that PA has bactericidal effects on S. aureus, S. epidermidis, B. cereus, S. marcescens, and P. aeruginosa in the catheter lumen and confirmed that it has a remarkable antiproliferative effect on C. albicans. Hence, we concluded that highly acidic PN solutions that contain a preservative like sodium bisulfite have bactericidal and growth inhibition effects on microorganisms in the catheter lumens of patients with CRBSIs and patients with totally implantable central venous access devices, in whom it is difficult to remove the catheter.

Enantioselective uptake of fexofenadine by Caco-2 cells as model intestinal epithelial cells.

OBJECTIVES: Fexofenadine contains a chiral carbon in its chemical structure and is orally administered as a racemic mixture. This study evaluated the selective uptake of fexofenadine enantiomers by Caco-2 cells as a model of intestinal epithelial cells. METHODS: R(+)-fexofenadine or S(-)-fexofenadine was applied to Caco-2 cells, followed by incubation. After incubation, the amounts of fexofenadine enantiomers in cells were determined. The kinetic parameters for the uptake of fexofenadine enantiomers by Caco-2 cells were estimated using the Michaelis-Menten equation. KEY FINDINGS: The transporter-mediated uptake rate of R(+)-fexofenadine was 1.7-fold higher than that of S(-)-fexofenadine. The difference in transporter-mediated R(+)-fexofenadine and S(-)-fexofenadine uptake was completely diminished under ATP-depleted conditions and in the presence of organic anion transporter peptide (OATP) inhibitors. Also, a Dixon plot showed that each fexofenadine enantiomer was competitively inhibited by the other enantiomer. The ratio of R(+)-fexofenadine uptake to S(-)-fexofenadine uptake in the case of a racemic mixture was higher than that in the case of a single enantiomer. CONCLUSION: This study suggested that the selective absorption of fexofenadine enantiomers by intestinal epithelial cells might have been due to the selective uptake mediated by OATPs and that the difference in intestinal absorption was enhanced with a racemic mixture.