• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.135-140
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• 2003

Fluconazole is an orally active bis-triazole antifungal agent, which is used in the treatment of superficial and systemic candidiasis and in the treatment of cryptococcal infections in patients with the acquired immuno deficiency syndrome (AIDS). The purpose of the present study was to evaluate the bioequivalence of two fluconazole capsules, Diflucan (Pfizer Pharmaceuticals Korea Inc.) and Flucona (Korean Drug Pharmaceuticals Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The fluconazole release from the two fluconazole capsules in vitro was tested using KP VII Apparatus II method at 0.1 M hydrochloride dissolution media. Twenty normal male volunteers, $23.60{\pm}1.88$ years in age and $63.57{\pm}6.17\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three capsules containing 50 mg as fluconazole was orally administered, blood was taken at predetermined time intervals and the concentrations of fluconazole in serum were determined using HPLC method with UV detector. The dissolution profiles of two fluconazole capsules were very similar at 0.1 M hydrochloride dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$ and $C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two capsules based on the Diflucan were 4.96%, 5.65% and -13.76%, respectively. There were no sequence effects between two capsules in these parameter. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(1.01){\sim}log(1.08)\;and\;log(1.00){\sim}log(1.12)\;for\;AUC_t\;and\;C_{max},\;respectively)$, indicating that Flucona capsule is bioequivalent to Diflucan capsule.

• Journal of Oral Medicine and Pain
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• v.20 no.1
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• pp.39-52
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• 1995

Burning mouth syndrome is characterized by a burning sensation in oral cavity without clinical signs. There has b een no established theories about the diagnosis and treatment. The purpose of this article is to examine the clinical feature of BMS patients of Korean and to present a treatment protocol that can be helpful in clinical applications. The subjects chosen for the study were 52 patients who had visited Department of Oral Diagnosis at Yonsei University Dental Hospital and were diagnosed as BMS. We did questionnaires and precise oral exam, laboratory exam, grouping of our patients, individual treatment for the groups and classification of responses to the treatment. The following results were obtained: 1. Chief complaints were throbbing (71.2%), pricking, stinging, tingling (30.8%), burning(25a%). The tongue is the most frequently affected site (82.7%), followed by full mouth, gingiva, palate, buccal mucosa, lips, throat, labial mucosa and floor of mouth. 2. The average age of onset was 48.1 year and the male to female ratio was 1 to 3. The average duration of symptom was 11.69 months for male and 23.07 months for female. 3. 32.7% of patients had appealed continuous pain, which was the most cases. Aggravating factors were peppery food, salty food, hot food, fatigue, tension conversation, sour food, cold food and toothpaste. Reducing factors were cold food, diet, going to sleep and smoking. 4. Associated symptoms were dry mouth, other life problem, altered taste perception, bad taste, throat pain, tingle and difficulty in swallowing. 5. Most of patients had appealed that there was not associated event on onset of symptom, and the order of prevalence is as fallow; dental treatment, stress, denture wearing, an attack of a systemic disease. 92.3% of patient appealed that there was no psychological withering and 7.7% of patients appealed positively. 6. There were eight males and four females that had jobs. 7. There was no family history in 100% of patients in questions about presence of family history. 8. 96.2% of patients appealed that there was no oral habits. 13.5% of patients had dryness of oral mucosa in oral exam. A significant relation to dental prosthesis was not observable, but incidence of diseases due to stress appeared high in BMS which had the clinical characteristics as above. A group having low serum iron was 63.5% and in this group period of potential iron deficiency appeared high in incidence just before move to anemia. A group represented positive response was 38.5% in fungus study for Candida albicans. Since we can expect high treatment response by prescription of iron-contained drug and antifungal drug in these patients, diagnosing patients' condition of BMS can be achieved in more various aspects through study for serum iron and Candida albicans. Furthermore, it is expected that treatment protocol can be made.

• Biomolecules & Therapeutics
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• v.11 no.1
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• pp.65-71
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• 2003

Terbinafine is a synthetic allylamine that is available in an oral formulation and is used at a dosage of 250mg/day. It is used as an active antifungal agent and inhibits the fungal enzyme squalene epoxidase, which leads to the accumulation of the sterol squalene, which is toxic to the organism. The purpose of the present study was to evaluate the bioequivalence of two terbinafine tablets, Lamisil (Novartis Korea Ltd.) and Terbinex (C-TRI Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, 26.00$\pm$2.57 year in age and 70.51$\pm$9.36 kg in body weight, were divided into two groups and a randomized 2${\times}$2 cross-over study was employed. After one tablet containing 125 mg of terbinafine was orally administered, blood was taken at predetermined time intervals and the concentrations of terbinafine in plasma were determined using HPLC with UV detector. Pharmacokinetic parameters such as AUC, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUC, $C_{max}$ and $T_{max}$ between two tablets were －4.191％, 5.223％ and －25.720％, respectively when calculated against the Lamisil, tablet. The powers (1-$\beta$) for AUC, $C_{max}$ and $T_{max}$ were 81％, 87％ and below 60％, respectively. Minimum detectable differences(.il) at alpha=O.1 and 1-/3=0.8 were less than 20％ (e.g., 19.72％ and 17.77％ for AUC and $C_{max}$, respectively). But minimum detectable differences($\Delta$) at alpha=0.1 and 1-$\beta$=0.8 for $T_{max}$ were more than 20％ (e.g., 26.25％). The 90％ confidence intervals were within $\pm$20％ (e.g., －17.440∼9.06 and －6.713∼17.160 for AUC and $C_{max}$ respectively). But 90％ confidence intervals for $T_{max}$ were not within $\pm$20％ (e.g., －43.346∼8.083). Another ANOVA test was conducted for logarithmically transformed AUC and $C_{max}$. These results showed that there are no significant differences in AUC and $C_{max}$ between the two formulations: The differences between the formulations in these log transformed parameters were all for less than 20％ (e.g., －4.19％ and 5.22％ for AUC and $C_{max}$, respectively). The 90％ confidence intervals for the log transformed data were not the acceptance range of log 0.8 to log 1.25 in AUC but the acceptance range of log 0.8 to log 1.25 in $C_{max}$ (e.g., log 1.13∼log 1.50 and log 0.94-log 1.22 for AUC and $C_{max}$ respectively). The major parameters, AUC and $C_{max}$ met the criteria of KFDA for bioequivalence although $T_{max}$ did not meet the criteria of KFDA (1998 year) for bioequivalence, indicating that Onfran tablet is bioequivalent to Zofran tablet. But in another ANOVA test AUC did not meet the criteria of KFDA (2002) for bioequivalence but $C_{max}$ met the criteria of KFDA (2002 year) for bioequivalence.or bioequivalence.equivalence.equivalence.equivalence.

• Journal of Microbiology and Biotechnology
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• v.30 no.2
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• pp.279-286
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• 2020

A novel compound named 'kanakugiol' was recently isolated from Lindera erythrocarpa and showed free radical-scavenging and antifungal activities. However, the details of the anti-cancer effect of kanakugiol on breast cancer cells remain unclear. We investigated the effect of kanakugiol on the growth of MCF-7 human breast cancer cells. Kanakugiol affected cell cycle progression, and decreased cell viability in MCF-7 cells in a dose-dependent manner. It also enhanced PARP cleavage (50 kDa), whereas DNA laddering was not induced. FACS analysis with annexin V-FITC/PI staining showed necrosis induction in kanakugiol-treated cells. Caspase-9 cleavage was also induced. Expression of death receptors was not altered. However, Bcl-2 expression was suppressed, and mitochondrial membrane potential collapsed, indicating limited apoptosis induction by kanakugiol. Immunofluorescence analysis using α-tubulin staining revealed mitotic exit without cytokinesis (4N cells with two nuclei) due to kanakugiol treatment, suggesting that mitotic catastrophe may have been induced via microtubule destabilization. Furthermore, cell cycle analysis results also indicated mitotic catastrophe after cell cycle arrest in MCF-7 cells due to kanakugiol treatment. These findings suggest that kanakugiol inhibits cell proliferation and promotes cell death by inducing mitotic catastrophe after cell cycle arrest. Thus, kanakugiol shows potential for use as a drug in the treatment of human breast cancer.

• Korean Journal of Clinical Pharmacy
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• v.22 no.4
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• pp.340-346
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• 2012

Background: Amphotericin B is a mainstay in the treatment of many systemic fungal infections due to its wide antifungal spectrum and low incidence of resistance. However, the use of amphotericin B is limited by its nephrotoxicity. Objectives: The objective of this study was to evaluate the incidence and risk factors of renal adverse drug reactions (ADRs) of conventional amphotericin B (Fungizone$^{(R)}$). In addition, we compared the changes of serum creatinine (SCr) between patients who remained conventional amphotericin B and patients who were switched to liposomal amphotericin B after occurrence of renal adverse reactions. Methods: Adult hospitalized patients who reported renal adverse reactions caused by conventional amphotericin B from January 2011 to July 2012 at pharmacovigilance center in Yonsei University Healthcare System included in this study. ADRs scored as 'doubtful' in Naranjo probability ADR scale were excluded. We retrospectively analyzed patients' basic clinical characteristics, concurrent diseases or nephrotoxic drugs in order to find variables that can correlate with occurrence of renal ADRs. Changes in SCr were compared between conventional amphotericin B group and liposomal amphotericin B group. Results: A total of 231 ADRs after administration of conventional amphotericin B in 75 patients were reported to pharmacovigilance center and assessed their severities as 'possible', 'probable', or 'definite'. Renal adverse reaction was the most common ADR with incidence rate of 42% (96 of 231 ADRs). Mean change in SCr from baseline was 0.26 mg/dL (change % 37.8) and statistically significant (p=0.000). Simple correlations analysis revealed that the number of concurrent diseases and number of nephrotoxic drugs were positively correlated with changes in SCr, but these results were not statistically significant. Among 43 patients who remained amphotericin B after occurrence of renal ADRs, 27 patients was administered conventional amphotericin B and 16 patients changed to liposomal amphotericin B. Mean change in SCr in amphotericin B group was 0.23 mg/dL (32.75%), whereas mean change in SCr in liposomal amphotericin B group were -0.28 mg/dL (19.38%) and difference between two groups was statistically significant (p=0.003). The numbers of patient with SCr elevation more than 30% were 9 (33.3%) in amphotericin B group and 2 (12.5%) in liposomal amphotericin B group (Odd Ratio=3.50, 95% Confidence Interval 0.65-18.85; p=0.130). Conclusion: An analysis of ADRs due to amphotericin B administration revealed significant mean changes in SCr from baseline. Switching to liposomal amphotericin B showed significant decrease in SCr compared with conventional amphotericin B.

• Journal of Life Science
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• v.29 no.2
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• pp.223-230
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• 2019

Ozone is a gaseous molecule able to kill microorganisms, such as yeast, fungi, bacteria, and protozoa. However, ozone gas is unstable and cannot be used easily. In order to utilize ozone properly and efficiently, plant oil can be employed. Ozone reacts with C-C double bonds of fatty acids, converting to ozonized oil. In this reaction, ozonide is produced within fatty acids and the resulting ozonized oil has various biological functions. In this study, we showed that ozonized oil has antimicrobial activity against fungi and bacteria. To test the antimicrobial activity of ozonized oil, we produced ozonized olive oil. Ozonized olive oil was applied to Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. Antimicrobial activity was assayed using the disk diffusion method following the National Committee for Clinical Laboratory Standards. Minimal inhibitory concentrations (MIC) were 0.25 mg for S. aureus, 0.5 mg for S. epidermidis, 3.0 mg for P. aeruginosa, and 1.0 mg for E. coli. Gram positive bacteria were more susceptible than Gram negative bacteria. We compared growth inhibition zones against S. aureus and MRSA, showing that the ozonized olive oil was more effective on MRSA than S. aureus. Furthermore, the ozonized olive oil killed C. albicans within an hour. These data suggested that ozonized olive oil could be an alternative drug for MRSA infection and could be utilized as a potent antimicrobial and antifungal substance.

• 한국균학회소식:학술대회논문집
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• 2015.05a
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• pp.59-59
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• 2015

Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but the treatment of cryptococcosis remains challenging. To develop novel therapeutic targets and approaches, signaling cascades controlling pathogenicity of C. neoformans have been extensively studied but the underlying biological regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs) in this basidiomycetous fungus. In this study, we constructed a high-quality of 322 signature-tagged gene deletion strains for 155 putative TF genes, which were previously predicted using the DNA-binding domain TF database (http://www.transcriptionfactor.org/). We tested in vivo and in vitro phenotypic traits under 32 distinct growth conditions using 322 TF gene deletion strains. At least one phenotypic trait was exhibited by 145 out of 155 TF mutants (93%) and approximately 85% of the TFs (132/155) have been functionally characterized for the first time in this study. Through high-coverage phenome analysis, we discovered myriad novel TFs that play critical roles in growth, differentiation, virulence-factor (melanin, capsule, and urease) formation, stress responses, antifungal drug resistance, and virulence. Large-scale virulence and infectivity assays in insect (Galleria mellonella) and mouse host models identified 34 novel TFs that are critical for pathogenicity. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and ubiquitous human fungal pathogens.

• Journal of the Korean Chemical Society
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• v.55 no.3
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• pp.418-429
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• 2011

Novel chromium(III), manganese(II), iron(III), cobalt(II), nickel(II), copper(II), ruthenium(III), and zirconyl(II) complexes of $N^1,N^2$-bis(3-((3-hydroxynaphthalen-2-yl)methylene-amino)propyl)phthalamide ($H_4L$, 1) have been synthesized and characterized by elemental, physical, and spectral analyses. The spectral data showed that the ligand behaves as either neutral tridentate ligand as in complexes 2-5 with the general formula $[H_4LMX_2(H_2O)]{\cdot}nH_2O$ (M=Cu(II), Ni(II), Co(II), X = Cl or $NO_3$), neutral hexadentate ligand as in complexes 10-12 with the general formula $[H_4LM_2Cl_6]{\cdot}nH_2O$ (M=Fe(III), Cr(III) or Ru(III)), or dibasic hexadentate ligand as in complexes 6-9 with the general formula $[H_2LM_2Cl_2(H_2O)_4]{\cdot}nH_2O$ (M = Cu(II), Ni(II), Co(II) or Mn(II), and 13 with general formula $[H_4L(ZrO)_2Cl_2]{\cdot}8H_2O$. Molar conductance in DMF solution indicated the non-ionic nature of the complexes. The ESR spectra of solid copper(II) complexes 2, 5, and 6 showed $g_{\parallel}$ >g> $g_e$, indicating distorted octahedral structure and the presence of the unpaired electron in the $N^1,N^2$ orbital with significant covalent bond character. For the dimeric copper(II) complex $[H_2LCu_2Cl_2(H_2O)_4]{\cdot}3H_2O$ (6), the distance between the two copper centers was calculated using field zero splitting parameter for the parallel component that was estimated from the ESR spectrum. The antibacterial and antifungal activities of the compounds showed that, some of metal complexes exhibited a greater inhibitory effect than standard drug as tetracycline (bacteria) and Amphotricene B (fungi).

• Pediatric Infection and Vaccine
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• v.13 no.2
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• pp.155-162
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• 2006

Purpose : Appropriate use of antimicrobials is an essential factor to treat infectious diseases and prevent acquisition of antimicrobial resistant pathogens. This study was undertaken to search that application of computerized management program for restriction of antimicrobials use in a hospital is helpful to decrease antimicrobial use density. Methods : Antibiotics utilization committee decided to restrict the use of 16 antimicrobials(14 expensive drugs having fear of drug resistance by pathogens and additional two drugs with inappropriate using tendency). Retrospective evaluation of antimicrobial user numbers between May and July of 2004 and 2005(study group) was conducted to compare with previous use density during same period of 2002 and 2003(control group). Results : Inpatients number of control group($823.5{\pm}37.1$ persons) was more than study group($809.2{\pm}39.3$ persons, P<0.001), but, outpatients number and hospitalized duration were equal in two groups. Antimicrobial user number/100 inpatients per day of glycopeptides and antifungal agents was equal in two groups, and study group was significantly higher density than control group in the use of carbapenems, piperacillin-tazobactam and quinolones(P<0.001). But study group was significantly lower density than control group in the use of drugs with inappropriately using tendency and expensive cephalosporins having broad antimicrobial spectrum(P<0.001). Conclusion : Application of computerized management program for restriction of antimicrobials use in a hospital is effective to decrease the use density of antimicrobials with inappropriately using tendency, but it is an insufficient measures for the restricted use of other antimicrobials on the whole.