Efficacy of antifungal-impregnated cement spacer against chronic fungal periprosthetic joint infections after total knee arthroplasty

Kim, Jong-Keun,Lee, Do-Yoon,Kang, Dong-Wan,Ro, Du-Hyun,Lee, Myung Chul,Han, Hyuk-Soo Elsevier 2018 The knee Vol.25 No.4

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Although two-stage exchange arthroplasty is considered a treatment of choice for chronic features of fungal PJI (periprosthetic joint infection), there is no consensus for local use of antifungal agent. The purpose of this study was to evaluate the efficacy of antifungal-impregnated cement spacer (AICS).</P> <P><B>Methods</B></P> <P>Nine patients who were diagnosed and treated for chronic fungal PJI after TKA in a single center from January 2001 to December 2016 were enrolled. Two-stage exchange arthroplasty was performed. During the 1st stage resection arthroplasty, AICS was inserted for all patients. Systemic antifungal medication was used during the interval between the two stage operations.</P> <P><B>Results</B></P> <P>The average duration from the initial symptom to fungal PJI diagnosis was 20 months (range, five to 72 months). Average erythrocyte sedimentation rate and C-reactive protein level at diagnosis were 56 mm/h (range, 30 to 89 mm/h) and 2.25 mg/dl (range, 0.11 to 3.97 mg/dl), respectively. Fungal PJI was confirmed by open debridement tissue culture in three cases (33%). The average number of operations before final exchange arthroplasty was 2.7 times (range, one to five times). Average duration of antifungal agent use confirmed by sensitivity test was seven months (range, four to 15 months). Mean interval between the two stage operations was six months (range, 1.5 to 15 months). After two-stage exchange arthroplasty, no patient had recurrent fungal infection during a mean follow-up of 66 months (range, 24 to 144 months).</P> <P><B>Conclusion</B></P> <P>Two-stage exchange arthroplasty with AICS is a very effective strategy with excellent outcomes.</P> <P><B>Level of evidence</B></P> <P>Case series, IV.</P>

Quality and storage characteristics of yogurt containing Lacobacillus sakei ALI033 and cinnamon ethanol extract

( Yu Jin Choi ),( Hee Yeon Jin ),( Hee Sun Yang ),( Sang Cheon Lee ),( Chang Ki Huh ) 한국동물자원과학회(구 한국축산학회) 2016 한국축산학회지 Vol.58 No.4

Background: This study was conducted to examine the quality and storage characteristics of yogurt containing antifungal-active lactic acid bacteria (ALH, Lacobacillus sakei ALI033) isolated from kimchi and cinnamon ethanol extract. The starter was used for culture inoculation (1.0 % commercial starter culture YF-L812 and ALH). Results: The antifungal activity of cinnamon extracts was observed in treatments with either cinnamon ethanol extracts or cinnamon methanol extracts. Changes in fermented milk made with ALH and cinnamon extract during fermentation at 40 °C were as follows. The pH was 4.6 after only 6 h of fermentation. Titratable acidity values were maintained at 0.8 % in all treatment groups. Viable cell counts were maintained at 4 × 109 CFU/mL in all groups except for 1.00 % cinnamon treatment. Sensory evaluations of fermented milk sample made with ALH and 0.05 % cinnamon ethanol extract were the highest. Changes in fermented milk made with ALH and cinnamon ethanol extract during storage at 4 °C for 28 days were as follows. In fermented milk containing ALH and cinnamon ethanol extracts, the changes in pH and titratable acidity were moderate and smaller compared with those of the control. Viable cell counts were maintained within a proper range of 108 CFU/mL. Conclusions: The results of this study suggest that the overgrowth of fermentation strains or post acidification during storage can be effectively delayed, thereby maintaining the storage quality of yogurt products in a stable way, using cinnamon ethanol extract, which exhibits excellent antifungal and antibacterial activity, in combination with lactic acid bacteria isolated from kimchi.

Paeonia lactiflora Inhibits Cell Wall Synthesis and Triggers Membrane Depolarization in Candida albicans

( Heung-shick Lee ),( Younhee Kim ) 한국미생물 · 생명공학회 2017 Journal of microbiology and biotechnology Vol.27 No.2

Fungal cell walls and cell membranes are the main targets of antifungals. In this study, we report on the antifungal activity of an ethanol extract from Paeonia lactiflora against Candida albicans, showing that the antifungal activity is associated with the synergistic actions of preventing cell wall synthesis, enabling membrane depolarization, and compromising permeability. First, it was shown that the ethanol extract from P. lactiflora was involved in damaging the integrity of cell walls in C. albicans. In isotonic media, cell bursts of C. albicans by the P. lactiflora ethanol extract could be restored, and the minimum inhibitory concentration (MIC) of the P. lactiflora ethanol extract against C. albicans cells increased 4-fold. In addition, synthesis of (1,3)-β-D-glucan polymer was inhibited by 87% and 83% following treatment of C. albicans microsomes with the P. lactiflora ethanol extract at their 1× MIC and 2× MIC, respectively. Second, the ethanol extract from P. lactiflora influenced the function of C. albicans cell membranes. C. albicans cells treated with the P. lactiflora ethanol extract formed red aggregates by staining with a membrane-impermeable dye, propidium iodide. Membrane depolarization manifested as increased fluorescence intensity by staining P. lactiflora-treated C. albicans cells with a membrane-potential marker, DiBAC4(3) ((bis-1,3-dibutylbarbituric acid) trimethine oxonol). Membrane permeability was assessed by crystal violet assay, and C. albicans cells treated with the P. lactiflora ethanol extract exhibited significant uptake of crystal violet in a concentration-dependent manner. The findings suggest that P. lactiflora ethanol extract is a viable and effective candidate for the development of new antifungal agents to treat Candida-associated diseases.

Systematic Target Screening Revealed That Tif302 Could Be an Off - Target of the Antifungal Terbinafi ne in Fission Yeast

( Sol Lee ),( Miyoung Nam ),( Ah-reum Lee ),( Jaewoong Lee ),( Jihye Woo ),( Nam Sook Kang ),( Anand Balupuri ),( Minho Lee ),( Seon-young Kim ),( Hyunju Ro ),( Youn-woong Choi ),( Dong-uk Kim ),( Kwa 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.2

We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the Erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.

Tyrosine Kinase 억제제와의 약물 상호작용이 약물 혈중농도 변화에 따라 부작 용 발생에 미치는 영향 : 메타분석 연구

황진아,이희영 한국임상약학회 2024 한국임상약학회지 Vol.34 No.1

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.

Antifungal-demelanizing properties and RAW264.7 macrophages stimulation of glucan sulfate from the mycelium of the mushroom Ganoderma lucidum

Wan Abd Al Qadr Imad Wan-Mohtar,Christina Viegelmann,Anita Klaus,Sarina Abdul Halim Lim 한국식품과학회 2017 Food Science and Biotechnology Vol.26 No.1

Underutilized mycelium of Ganoderma lucidum BCCM 31549 has been a significant source of a glucan sulfate (GS) possessing therapeutic activities. GS have been evaluated for their antifungaldemelanizing properties and nitrite oxide production from stimulated RAW264.7 macrophages. GS exhibited antifungal activity against Aspergillus niger A60 with a minimum inhibitory concentration of 60 mg/mL and a minimum fungicidal concentration of 100 mg/mL. At 60mg/mL (sublethal) and 30mg/mL (subinhibitory) doses of GS, the mycelium of A. niger A60 was successfully demelanized with a conidiophore head and black pigment reduction. Additionally, GS successfully stimulated RAW264.7 macrophage cells at a concentration of 500 μg/mL to produce 0.45 μM of nitric oxide. The GSstimulated RAW264.7 macrophages were morphologically similar to those treated with lipopolysaccharide. The results highlight a novel bifunctional property of mycelial GS from G. lucidum.

Myricetin Disturbs the Cell Wall Integrity and Increases the Membrane Permeability of Candida albicans

( Heung-shick Lee ),( Younhee Kim ) 한국미생물 · 생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.1

The fungal cell wall and membrane are the principal targets of antifungals. Herein, we report that myricetin exerts antifungal activity against Candida albicans by damaging the cell wall integrity and notably enhancing the membrane permeability. In the presence of sorbitol, an osmotic protectant, the minimum inhibitory concentration (MIC) of myricetin against C. albicans increased from 20 to 40 and 80 μg/ml in 24 and 72 h, respectively, demonstrating that myricetin disturbs the cell wall integrity of C. albicans. Fluorescence microscopic images showed the presence of propidium iodide-stained C. albicans cells, indicating the myricetin-induced initial damage of the cell membrane. The effects of myricetin on the membrane permeability of C. albicans cells were assessed using crystal violet-uptake and intracellular material-leakage assays. The percentage uptakes of crystal violet for myricetin-treated C. albicans cells at 1×, 2×, and 4× the MIC of myricetin were 36.5, 60.6, and 79.4%, respectively, while those for DMSO-treated C. albicans cells were 28.2, 28.9, and 29.7%, respectively. Additionally, myricetin-treated C. albicans cells showed notable DNA and protein leakage, compared with the DMSO-treated controls. Furthermore, treatment of C. albicans cells with 1× the MIC of myricetin showed a 17.2 and 28.0% reduction in the binding of the lipophilic probes diphenylhexatriene and Nile red, respectively, indicating that myricetin alters the lipid components or order in the C. albicans cell membrane, leading to increased membrane permeability. Therefore, these data will provide insights into the pharmacological worth of myricetin as a prospective antifungal for treating C. albicans infections.

Antifungal Activities of Isothiazoline/Cabamate based Organic Antifungal Agent Activated-Cement Mortars (AACM)

Do Jeong-Yun,So Hyoung-Seok,Soh Yang-Seob Korea Concrete Institute 2002 KCI concrete journal Vol.14 No.4

Antifungal agents are used to impart antibacterial or bactericidal properties to commodities and various articles used in industries and can be classified into two broad groups i.e organic and inorganic. Inorganic antifungal agents comprise of Ag, Zn, or Cu, etc. These elements tend to exhibit high level of antifungal activities, non-uniform dispersion in substrates, and have poor properties in expensive and cheap adhesiveness. In this study, the organic antifungal agent was used for the purpose of investigating the antifungal activity of antifungal agent activated-cement mortar (AACM) on the aspergilus niger of various fungus which can be easily discovered in the interiors and exteriors of buildings. In addition, an experiment on the basic physical properties of AACM such as compressive and flexural strength was carried out. The conclusion of this investigation revealed that a dosage increase of antifungal agent exhibits a high inhibitory effect on the aspergilus niger, and although there is a slight decrease in the strength of AACM, the strength of AACM was almost equal to that of inactivated cement mortar.

항균성 물질을 생산하는 Penicillium sp. KAC 균주의 배양적 특성에 따른 항균 활성

도은수,심성철,백수봉 建國大學校附設 農業資源開發硏究所 1998 農資源開發論集 Vol.20 No.-

Abstract The streai of Penicillium sp. KAC previously shown strong antifungal activity against Rhizoctonia solani AG 1-1 and AG 2-2 was cultured in liquid media on the different growth conditions. After the liquid culrures of Penicillium sp. KAC strain were filtrated, their antifungal activities against Rhizoctonia solani AG 1-1 and AG 2-2 were compared through growing Rhizoctonia solani AG 1-1 and AG 2-2 on potato dextrose agar amended with different culture filtrates. Depending on the media for the growth of Penicillium sp. KAC, the culture filtrate from potato dextrose broth showed the highest antifungal activity with inhibition efficiencies of 94.3% and 71.1% against Rhizoctonia solani AG 1-1 and AG 2-2, respectively. Depending on the growth periods of Penicillium sp. KAC, the culture filtrate from 7 day showed the highest antifungal activity with inghibition efficiencies of 100.0% and 100.0% against Rhizoctonia solani AG 1-1 and AG 2-2, respectively. Depending on the temperatures for the growth of Penicillium sp. KAC. the culture filtrate form 20℃ showed the highest antifungal activity with inhibition efficiencies of 92.9% and 94.2% against Rhizoctonia solani AG 1-1 and AG 2-2, respectively. Depending on the pH of the media for growth of Penicillium sp. KAC. the culture filtrate form pH 7.0 showed the highest antifungal activity with inhibition efficiencies of 85.7% and 94.2% against Rhizoctonia solani AG 1-1 and AG 2-2, respectively. Depending on the glucose contents of media for the growth of Penicillium sp. KAC, the culture filtrate form 30g of glucose content showed the highest antifungal activity with inhibition efficiencies of 69.6% and 43.5% against Rhizoctonia solani AG 1-1 and AG 2-2, respectively. However, there was no effect of nitrate contents amended in media used for the growth of Penicillium sp. KAC. on the inhibition of Rhizoctonia solani AG 1-1 and AG 2-2. The strain of Penicillium sp. KAC previously shown strong antifungal activity against Rhizoctonia solani AG 1-1 and AG 2-2 was cultured in liquid media on the different growth conditions. After the liquid cultures of Penicillium sp. KAC strain were filtrated, their antifungal activities against Rhizoctonia solani AG 1-1 and AG 2-2 were compared through growing Rhizoctonia solani AG 1-1 and AG 2-2 on potato dextrose agar amended with different culture filtrates. Depending on the media for the growth of Penicillium sp. KAC, the culture filtrate from potato dextrose broth showed the highest antifungal activity with inhibition efficiencies of 94.3% and 71.1% against Rhizoctonia solani AG 1-1 and AG 2-2, respectively. Depending on the growth periods of Penicillium sp. KAC, the culture filtrate from 7 day showed the highest antifungal activity with inhibition efficiencies of 100.0% and 100.0% against Rhizoctonia solani AG 1-1 and AG 2-2, respectively. Depending on the temperatures for the growth of Penicillium sp. KAC. the culture filtrate from 20℃ showed the highest antifungal activity with inhibition efficiencies of 92.9% and 94.2% aganist Rhizoctonia solani AG 1-1 and AG 2-2 , respectively. Depending on the pH of media for the growth of Penicillium sp. KAC, the culuture filtrate from pH 7.0 showed the highest. antifungal activity with inhibition efficiencies of 85.7% and 94.2% against Rhizoctonia solani AG 1-1 and AG 2-2, respectively. Depending on the glucose contents of media for the growth of Penicillium sp. KAC, the culture fi1trate from 3Og of glucose content showed the highest antifui1gal activity with inhibition efficiencies of 69.6% and 43.5% against Rhizoctonia solani AG 1-1 and AG 2-2, respectively. However, there was no effect of nitrate contents amended in media used for the growth of Penicillium sp. KAC on the inhibition of Rhizoctonia solani AG 1-1 and AG 2-2.

Antifungal performance of BFS mortar with various natural antifungal substances and their physical properties

So, H.s.,Jang, H.s.,Lee, B.r.,So, S.y. Butterworth Scientific ; Elsevier Science Ltd 2016 Construction and Building Materials Vol.108 No.-

This study discusses the basic physical properties, as well as the durability and antifungal performance of blast furnace slag (BFS) mortar with various natural antifungal substances. As a series of basic experiments, the antifungal performances of various natural antifungal substances extracted from Marjoram, Phytoncide, Thyme, Ginkgo leaves, and Chitosan were investigated on five types of mold: Chaetomium globosum, Aspergillus niger, Aureobasidium pullulans, Gliocladium virens, and Penicillium pinophilum. Marjoram and phytoncide extracts, which showed excellent antifungal performance in the basic experiment, were selected and applied to the antifungal mortars. The physical properties in addition to the durability and antifungal performance of the antifungal mortars were investigated. The results clearly showed that the antifungal mortars with the marjoram extract had excellent antifungal performance compared with other antifungal mortars with natural antifungal substances. Their antifungal performance was at an equivalent level to that of the mortars with organic chemical antifungal agents. It was also shown that the optimum addition rate of marjoram extract in the mortar was 3% by mass of binder, considering antifungal performance and durability. The adverse effect of marjoram and phytoncide extract on the consistency and strength of antifungal mortars was insignificant.