Examination of pain relief effect of Goreisan for glossodynia.

BACKGROUND: Pain in glossodynia may be severe; it may prevent patients from working, interfere with daily life activities, and necessitate a patient's visit to a medical institution for consultation and treatment. The pain may be described as persistent and burning (tingling, tingling) or stinging. Patients may complain of dry mouth (dryness), which is thought to cause inflammation of the tongue and gingival mucous membranes and increased pain. Medications are prescribed based on the symptoms of glossodynia, and the therapeutic effect is confirmed. However, each drug has side effects, for example, pain may reduce, but drowsiness and dizziness may occur; further, there is always a tendency of drowsiness.On the other hand, Goreisan, a Chinese herbal medicine, has already been used by physicians to treat pain in the oral and maxillofacial regions resulting from rapid changes in air pressure. However, the lack of high-quality clinical research has been of concern, and a randomized clinical trial to investigate the efficacy and safety of Goreisan for treatment of pain in glossodynia is warranted. METHODS/DESIGN: This multicenter, randomized, controlled study will involve patients treated for glossodynia-related pain. In the experimental group, Goreisan will be taken for 12 weeks in combination with conventional treatment. Participants in the control group will not take any Kampo medicine; only the standard treatment will be taken. Subsequently, the degree of pain will be assessed, and saliva tests of all the patients on their first visit will be performed. Goreisan will be taken at a dose of 7.5 g/d (minute 3) for 12 consecutive weeks. Twelve weeks later, the degree of pain of each patient will be assessed. DISCUSSION: The purpose of this study is to investigate the efficacy of Goreisan for pain reduction in patients undergoing treatment for glossodynia-related pain. If pain in glossodynia patients can be reduced by the administration of Goreisan, its candidacy as an alternative treatment for pain in glossodynia can be further supported by more reliable research. TRIAL REGISTRATION: The study was registered in the jRCTs071200017. URL https://jrct.niph.go.jp/latest-detail/jRCTs071200017.

The heme-binding protein Dap1 links iron homeostasis to azole resistance via the P450 protein Erg11 in Candida glabrata.

The pathogenic fungus Candida glabrata is relatively resistant to azole antifungals, which target lanosterol 14α-demethylase (Erg11p) in the ergosterol biosynthesis pathway. Our study revealed that C. glabrata exhibits increased azole susceptibility under low-iron conditions. To investigate the molecular basis of this phenomenon, we generated a strain lacking the heme (iron protoporphyrin IX)-binding protein Dap1 in C. glabrata. The Δdap1 mutant displayed growth defects under iron-limited conditions, decreased azole tolerance, decreased production of ergosterol, and increased accumulation of 14α-methylated sterols lanosterol and squalene. All the Δdap1 phenotypes were complemented by wild-type DAP1, but not by DAP1(D91G) , in which a heme-binding site is mutated. Furthermore, azole tolerance of the Δdap1 mutant was rescued by exogenous ergosterol but not by iron supplementation alone. These results suggest that heme binding by Dap1 is crucial for Erg11 activity and ergosterol biosynthesis, thereby being required for azole tolerance. A Dap1-GFP fusion protein predominantly localized to vacuolar membranes and endosomes, and the Δdap1 cells exhibited aberrant vacuole morphologies, suggesting that Dap1 is also involved in the regulation of vacuole structures that could be important for iron storage. Our study demonstrates that Dap1 mediates a functional link between iron homeostasis and azole resistance in C. glabrata.

Correlation between triazole treatment history and susceptibility in clinically isolated Aspergillus fumigatus.

This is the first report of a detailed relationship between triazole treatment history and triazole MICs for 154 Aspergillus fumigatus clinical isolates. The duration of itraconazole dosage increased as the itraconazole MIC increased, and a positive correlation was observed (r = 0.5700, P < 0.0001). The number of itraconazole-naïve isolates dramatically decreased as the itraconazole MIC increased, particularly for MICs exceeding 2 µg/ml (0.5 µg/ml versus 2 µg/ml, P = 0.03). We also examined the relationship between cumulative itraconazole usage and the MICs of other azoles. A positive correlation existed between itraconazole dosage period and posaconazole MIC (r = 0.5237, P < 0.0001). The number of itraconazole-naïve isolates also decreased as the posaconazole MIC increased, particularly for MICs exceeding 0.5 µg/ml (0.25 µg/ml versus 0.5 µg/ml, P = 0.004). Conversely, the correlation coefficient obtained from the scattergram of itraconazole usage and voriconazole MICs was small (r = -0.2627, P = 0.001). Susceptibility to three triazole agents did not change as the duration of voriconazole exposure changed. In addition, we carried out detailed analysis, including microsatellite genotyping, for isolates obtained from patients infected with azole-resistant A. fumigatus. We confirmed the presence of acquired resistance to itraconazole and posaconazole due to a G54 substitution in the cyp51A gene for a patient with chronic pulmonary aspergillosis after oral itraconazole therapy. We should consider the possible appearance of azole-resistant A. fumigatus if itraconazole is used for extended periods.