• Mycobiology
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• v.48 no.2
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• pp.148-152
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• 2020

We investigated the antifungal susceptibilities and the cyp51 mutant strains among Aspergillus fumigatus clinical isolates obtained from 10 university hospitals in Korea. Of the 84 isolates examined, two itraconazole-resistant isolates were found with no amino acid substitution in the cyp51A/cyp51B genes. However, 19 (23.2%) azole-susceptible isolates harbored amino acid substitutions: Nine isolates harbored one to five mutations in cyp51A with high polymorphism, and 11 isolates exhibited the same Q42L mutation in cyp51B. Overall, a low azole resistance rate and high frequency of cyp51A/cyp51B amino acid substitutions were observed in the azole-susceptible A. fumigatus isolates in Korea.

• Journal of Veterinary Clinics
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• v.39 no.2
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• pp.70-74
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• 2022

A 14-year-old intact male captive leopard (Panthera pardus) first presented with a focal alopecic lesion on the dorsal aspect of the distal one-third of its tail. Although itraconazole was administered, the lesion progressed deeper and became ulcerated due to self-trauma. Due to the wild nature of the leopard, daily dressing of the wound and replacing the bandages without anesthesia became too dangerous, and amputation became necessary. A postoperative tissue sample was submitted for histopathological examination, and tramadol, amoxicillin/clavulanate, and gabapentin were administered. In the days following the amputation, the leopard's appetite significantly decreased, and the patient passed away 18 days later. Histopathological examination of the specimen revealed well-differentiated squamous cell carcinoma (SCC). In hindsight, had more cells been collected by a fine-needle aspirate (FNA) biopsy or had additional FNA biopsies been performed, SCC might have been diagnosed based on its cytological features rather than delayed histopathological findings. The current study highlights the critical reasons why clinicians may often misdiagnose SCC and the importance of being more aware of potential tumors in ulcerative lesions, which are often incorrectly treated as infectious skin diseases. This is also the first report of cutaneous SCC in a leopard.

• Korean Journal of Clinical Pharmacy
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• v.34 no.1
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• pp.71-78
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• 2024

Background: Oral cancer drugs, particularly tyrosine kinase inhibitors (TKIs), are increasingly popular due to their convenience. However, they pose challenges like drug interactions, especially with medications like azole antifungals. While the FDA provides some guidance, more detailed information is needed to manage these interactions effectively. A meta-analysis was conducted to understand the impact of interactions between TKIs and azole antifungals on adverse events during clinical studies. Methods: A meta-analysis followed PRISMA guidelines. Data from PubMed, EMBASE, and references were searched until November 30, 2021. Inclusion criteria encompassed studies on TKI-antifungal interactions in English. Study selection and quality assessment were conducted by two independent investigators. Results: Out of 158 articles, 11 were selected for analysis. Combination therapy showed a slight increase in adverse events but was not statistically significant (OR 1.02, 95% CI 0.49-2.13, p=0.95). AUC and Cmax fold changes did not significantly impact adverse event development. Both itraconazole and ketoconazole showed no significant difference in adverse event development compared to TKI alone. Conclusions: Study finds TKI-DDI not significantly linked to AE increase; azole antifungal types not related to AE. Future DDI research crucial for drug development.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.364-367
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• 2004

Aspergillus species cause a wide spectrum of diseases in humans and most frequent site of infection is lung. Pleural aspergillosis is a rare disease with only 3 cases having been in Korea. It may occur as a complication of tuberculosis, especially after pneumonectomy for this condition, or rupture of cavitary pulmonary aspergillosis into the pleura. We report a patient with pleural aspergillosis who showed a clinical improvement with antifungal therapy.

• Tuberculosis and Respiratory Diseases
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• v.71 no.4
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• pp.278-281
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• 2011

Allergic bronchopulmonary aspergillosis (ABPA) is a complex clinical entity resulting from an allergic immune response to Aspergillus species, and most often occurs in patients with asthma. ABPA is rarely observed in the absence of asthma, which is, in fact, the principal criterion for its diagnosis. Our patient was a 53-year-old woman with no history of bronchial asthma. She presented with a 1-month history of cough, mucopurulent nasal discharge, and localized pulmonary consolidation. Peripheral blood eosinophilia and elevated serum IgE were observed. Sinus radiography showed right maxillary sinusitis. Pathologic examination of bronchoscopic biopsy specimens revealed conglomerates of fungal hyphae. Pulmonary function and bronchial provocation tests were within normal ranges. The patient was successfully treated for 3 months with itraconazole and oral prednisolone. There has been no evidence of recurrence over a 7-month follow-up. ABPA coupled with sinusitis in a nonasthmatic patient is a very rare occurrence and warrants reporting.

• Tuberculosis and Respiratory Diseases
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• v.49 no.1
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• pp.105-110
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• 2000

Pulmonary aspergillosis is classified as a saprophytic, allergic, and invasive disease. Chronic necrotizing pulmonary aspergillosis is categorized as an invasive pulmonary aspergillosis. Most invasive pulmonary aspergillosis have acute and toxic clinical features but chronic necrotizing pulmonary aspergillosis is characterized by a subacute infection, most commonly seen in patients with altered local defense system from preexisting pulmonary disease or in mild immunocompromised patients. Pulmonary artery aneurysm due to this infection is termed as a mycotic aneurysm, etiology of which are tuberculosis, syphilis, bacteria and fungus. We report a case of chronic necrotizing pulmonary aspergillosis complicating pulmonary aneurysm in a 62 year-old man who was presented with cough, sputum, and fever. Chest radiographs showed a rapid, progressive cavitary lesion and pulmonary artery aneurysm. Angioinvasion of asper gillus was revealed by pathology after operative removal of left upper lobe containing the pulmonary artery aneurysm. He was treated with itraconazole.

• Advances in Traditional Medicine
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• v.3 no.4
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• pp.191-195
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• 2003

Euphorbia hirta, locally called 'ara tanah' or 'susun nabi' in Malaysia is a small annual herb common to the tropical countries and belongs to the same family as the tic and tapioca. E. hirta has had a long history of usage in the treatment of various ailments. In this current study, in vitro sensitivity test of crude aqueous and ethanol extracts of leaves and barks of E. hirta was carried out against bacteria (Escherichia coli, Salmonella enteritidis, Staphylocccus aureus and Bacillus subtilis) and fungi (Microsporum canis, Aspergillus fumigatus, Candida albicans and Candida tropicalis) using the discs diffusion method. The extract-impregnated discs (20, 40 and $80\;{\mu}g/{\mu}l$), the E. hirta extracts inhibited the growth of all the bacteria tested. The growth of C. albicans was inhibited in a concentration dependent manner by the aqueous leaves and barks extracts. C. tropicalis was found to be sensitive to the aqueous leaves extracts. The results were compared to antibacterial drugs of chloramphenicol, ampicilin, penicillin G, and enrofloxacine; and to antifungal drug of ketoconazole, itraconazole and miconazole. In this current study, it can be concluded that this plant has antimicrobial activity that is as potent as the standard antimicrobial drugs against certain microorganisms.

• Animal cells and systems
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• v.10 no.4
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• pp.203-209
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• 2006

Azoles are widely used antifungal agents, which inhibit the biosynthesis of fungal cell-membrane ergosterol. In this study, using an amphibian follicle culture system, the effects of azoles on follicular steroidogenesis in frogs were examined. Itraconazole (ICZ), clotrimazole (CTZ) and ketoconazole (KCZ) suppressed pregnenolone ($P_5$) production by the follicles ($ED_{50};\;0.04_{\mu}M,\;0.33_{\mu} M,\;and\;0.91_{\mu}M$, respectively) in response to frog pituitary homogenates (FPH). However, fluconazole (FCZ), miconazole (MCZ) and econazole (ECZ) were not effective in the suppression of $P_5$ production. Not all the azoles examined suppressed the conversion of exogenous $P_5$ to progesterone ($P_4$) (by $3{\beta}$- HSD) or $P_4$ to $17{\alpha}$-hydroxyprogesterone ($17{\alpha}$-OHP) (by $17{\alpha}$-hydroxylase), or androstenedione (AD) to testosterone (T) (by $17{\beta}$-HSD). In contrast, CTZ, MCZ and ECZ in medium partially suppressed the conversion of $17{\alpha}$-OHP to AD (by C17-20 lyase) ($ED_{50};\;0.25{\mu} M,\;4.5{\mu}M,\;and\;0.7{mu}M$, respectively) and CTZ, KCZ, ECZ and MCZ strongly suppressed the conversion of exogenous T to estradiol ($E_2$) (by aromatase) ($ED_{50};\;0.02{\mu}M,\;8{\mu}M,\;0.07{\mu}M,\;0.8{\mu}M$, respectively). These results demonstrated that some azole agents strongly suppress amphibian follicular steroidogenesis and particularly, P450scc and aromatase are more sensitive to azoles than other steroidogenic enzymes.

• YAKHAK HOEJI
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• v.43 no.6
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• pp.716-728
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• 1999

Whole oil and ketonic fraction (KF) of Leptospermum scoparium have been tested for their antimicrobial activity and combination effect with several antibiotics against various bacterial strains and fungi by using microbiological assay methods. Antibacterial activities of KF against a number of test strains were 2-3 fold stronger than those of whole oil. MICs of the KF were $65~125{\;}{\mu\textrm{g}}/ml$ against seven gram positive bacterial strains, $65~250{\;}{\mu\textrm{g}}/ml$ against 19 methicillin resistance Staphylococcus aureus strains, and $65~50{\;}{\mu\textrm{g}}/ml$ against 14 quinolone resistance strains. However, KF showed little or no activity against gram negative bacteria. MICs of the KF were $16~250{\;}{\mu\textrm{g}}/ml$ against more than 50% of the anaerobic bacterial strains tested. KF showed the higher antibacterial activity than bacitracin against 10 strains of Bacteroids thetaiotaomicron, or three strains of Bacteroides ovatus, and the more active than ciprofloxacin against one strain of Bacteroides thetaiotaomicron and three strains of Bacteroids ovatus. The MICs of KF was 63 and $250{\;}{\mu\textrm{g}}/ml$ against Aspergillus niger and Candida albicans, respectively. Antibacterial activities of KF in combination with 19 antibiotics against 14 strains and with four antifungal agents against one fungal strain were determined by paper strip diffusion method. While most of combination showed additivity, KF showed synergism with bacitracin, exfadroxil, cephradin, and meropenem for 29~57% of the strains tested. However, ofloxacin, enoxacin, sparfloxacin showed antagonism with KF for 43~71% of the strains. KF alone and in combination with bacitracin, gentamycin, neomycin, itraconazole, fluconazole, terfinafine and ketoconazole against five bacterial strains or one fungus strain synergistic effect was demonstrated against 33% of strains examined with FIC index value below 0.5 by checkerboard study. Synergistic effect of KF with gentamicin against Staphylococcus epidermidis 329 (QRS) was found by time-kill study.

• Animal cells and systems
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• v.11 no.1
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• pp.1-8
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• 2007

Recently, we have shown that some endocrine disruptors, heavy metals, organotins and azoles suppressed steroidogenic enzymes such as P450 side-chain cleavage enzyme (P450scc) and aromatase in bullfrog ovarian follicles. In the present study, by using an amphibian ovarian follicle culture system, we examined the effects of these endocrine disruptors on maturation and ovulation of oocytes from Rana dybowskii in vitro. Ovarian fragments or isolated follicles were cultured for 24 h in a medium containing frog pituitary homogenate (FPH) or progesterone ($P_{4}$) with or without endocrine disruptors, and oocyte maturation (germinal vesicle breakdown, GVBD) and ovulation were examined. Among the organotins, tributyltin (TBT) strongly inhibited both FPH-and $P_{4}-induced$ oocyte maturation ($ED_{50}$:0.6 and 0.7 ${\mu}M$, respectively); however, tetrabutyltin (TTBT) and dibutyltin (DBT) showed only partial suppression, while monobutyltin (MBT) showed no inhibitory effect. All of the organotins suppressed $P_{4}-induced$ oocyte ovulation very effectively at a low concentration, and TBT and DBT exerted an inhibitory effect on FPH-induced ovulation. Among the heavy metals, mercury (Hg), cadmium (Cd) and cobalt (Co) were very effective in inhibiting FPH-induced oocyte maturation and ovulation, while lead (Pb), arsenite (As) and zinc (Zn) were less effective. However, all of the heavy metals suppressed FPH-induced oocyte ovulation at a high dose ($100{\mu}M$). Among the azoles, itraconazole (ICZ), ketoconazole (KCZ) and clotrimazole (CTZ) effectively inhibited FPH-induced oocyte maturation and ovulation, while econazole (ECZ), miconazole (MCZ) and fluconazole (FCZ) were considerably less effective. These results demonstrated that the abovementioned endocrine disruptors exhibited differential effects on oocyte maturation and ovulation in amphibian follicles and that the frog ovarian culture system could be used as an effective experimental tool to screen and evaluate the toxicity of various endocrine disruptors in vitro.