• Biomolecules & Therapeutics
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• 제32권4호
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• pp.481-491
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• 2024

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (M^pro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in M^pro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the M^pro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC₅₀ values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

• 대한소아치과학회지
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• 제42권4호
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• pp.302-311
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• 2015

본 연구는 Planktonic growth inhibition test와 CDC Biofilm Reactor를 사용한 Biofilm assay를 통해 S-PRG filler를 함유하는 치면열구전색제의 S. mutans에 대한 항미생물 효과를 기존의 치면열구전색제와 비교하고자 하였다. S-PRG 필러를 함유하는 치면열구전색제인 BeautiSealant, 불소를 방출하는 치면열구전색제인 Clinpro$^{TM}$ sealant, 불소 미방출 치면열구전색제인 Concise$^{TM}$ sealant를 실험군으로 선정하였다. 성장억제평가를 위해 치면열구전색제를 사용하지 않은 군을 음성 대조군으로 설정하였으며, 3개의 실험군 모두 대조군보다 유의할 정도로 낮은 집락 형성 단위를 보였고, Clinpro$^{TM}$ sealant가 BeautiSealant와 Concise$^{TM}$ sealant보다 유의할 정도로 낮은 집락 형성 단위를 보였다. BeautiSealant와 Concise$^{TM}$ sealant 군간에는 유의한 차이가 관찰되지 않았다. 바이오 필름 평가에서도 Clinpro$^{TM}$ sealant군이 BeautiSealant와 Concise$^{TM}$ sealant군들에 비해 유의할 정도로 낮은 집락 형성을 보였으며, BeautiSealant와 Concise$^{TM}$ sealant 군간에 유의한 차이는 관찰되지 않았다. 본 연구 결과 S-PRG filler를 포함하는 치면열구전색제인 BeautiSealant는 기존의 불소방출 치면열구전색제에 비하여 낮은 항미생물 효과와 높은 바이오 필름 형성능을 보였다.

• 미생물학회지
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• 제48권1호
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• pp.52-56
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• 2012

본 연구는 치아우식증 및 치주질환 원인균들에 대한 carvacrol의 항균능을 알아보고, 사람의 구강조직 세포에서 세포의 생존율을 분석하여 세포독성 정도를 알아보기 위해 실시하였다. Carvacrol의 항균능은 뮤탄스 연쇄상구균과 5종류의 치주질환 원인균을 이용하여 MIC 및 MBC 값을 측정하여 분석하였고, 세포생존율은 정상 사람 치은섬유모세포를 이용하여 MTT 분석법으로 평가하였다. 구강질환 원인균에 대한 carvacrol의 MIC 및 MBC 값은 각각 $16-128{\mu}g/ml$과 $32-128{\mu}g/ml$이었다. 세포독성 실험 결과 carvacrol은 $128{\mu}g/ml$ 농도에서 세포생존율이 현저히 감소하였다. 따라서 carvacrol은 치아우식증과 치주질환 원인균에 대한 항균작용이 뛰어나지만, 구강조직 세포에 대해 세포독성을 가지고 있어 가글린제 및 치약 등의 구강위생용품에 활용하기 위해서는 $64{\mu}g/ml$ 이하의 농도로 사용하고 정상 사람 치은섬유모세포에 대한 독성이 없는 다른 항균물질과 혼합하여 사용하는 것이 효과적일 것으로 생각된다.

• Journal of Periodontal and Implant Science
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• 제43권2호
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• pp.72-78
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• 2013

Purpose: The purpose of this study was to compare the phototoxic effects of blue light exposure on periodontal pathogens in both planktonic and biofilm cultures. Methods: Strains of Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Porphyromonas gingivalis, in planktonic or biofilm states, were exposed to visible light at wavelengths of 400.520 nm. A quartz-tungsten-halogen lamp at a power density of $500mW/cm^2$ was used for the light source. Each sample was exposed to 15, 30, 60, 90, or 120 seconds of each bacterial strain in the planktonic or biofilm state. Confocal scanning laser microscopy (CSLM) was used to observe the distribution of live/dead bacterial cells in biofilms. After light exposure, the bacterial killing rates were calculated from colony forming unit (CFU) counts. Results: CLSM images that were obtained from biofilms showed a mixture of dead and live bacterial cells extending to a depth of $30-45{\mu}m$. Obvious differences in the live-to-dead bacterial cell ratio were found in P. gingivalis biofilm according to light exposure time. In the planktonic state, almost all bacteria were killed with 60 seconds of light exposure to F. nucleatum (99.1%) and with 15 seconds to P. gingivalis (100%). In the biofilm state, however, only the CFU of P. gingivalis demonstrated a decreasing tendency with increasing light exposure time, and there was a lower efficacy of phototoxicity to P. gingivalis as biofilm than in the planktonic state. Conclusions: Blue light exposure using a dental halogen curing unit is effective in reducing periodontal pathogens in the planktonic state. It is recommended that an adjunctive exogenous photosensitizer be used and that pathogens be exposed to visible light for clinical antimicrobial periodontal therapy.

• Journal of Oral Medicine and Pain
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• 제30권1호
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• pp.35-44
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• 2005

본 예비연구는 강의중심학습 (LBL) 방식 과 문제중심학습 (PBL) 방식이 기초의학 지식의 이해력의 향상에 미치는 영향을 사후-사전 검사의 변화량의 차이의 비교를 통해서 그리고 과학적 추론을 동반한 반 구조화된 문제해결의 질에 미치는 영향을 사후 검사의 차이의 비교를 통해서 평가하는 것이 목적이다. 이 반 구조화된 문제는 다섯 개- 샘플 크기, 원인과 결과의 연구설계, 위험요인 구성, 데이터의 통계 분석, 결과 해석- 의 요소를 포함하고 있다. 본 실험은 2004년 이 주에 걸쳐 서울대학교 치과대학 100명의 학부 학생들을 대상으로 실시되었다. 상이한 두 학습들이 실시되기 전 과 후에 감염방지와 예방에 관한 48개의 사지 혹은 오지 선다형의 문제가 학생들에게 주어졌다. 또 두 학습이 종결된 후에 역학관련 반 구조화된 문제를 해결하도록 하는 과제를 통하여 문제해결의 능력에 미치는 두 학습 방식의 영향을 분석하였다. 사전-사후 테스트의 결과 기초의학 지식의 이해 향상 정도는 두 그룹 간의 유 의미한 차이를 보이지 않았다. 반면, 반 구조화된 문제해결의 질은 문제중심학습 방식이 유 의미하게 높았으며 (p=.029), 특히 문제 해결 과정에서 나타난 인과성 연구설계 (p=.000)와 결과 해석(p=.001)에 관한 과학적 추론의 점수가 유 의미하게 우수하였다. 결론적으로 동일한 시간 동안 문제중심학습 방식은 강의중심학습 방식에 비해 하위 기초지식의 이해를 위한 학습 환경에서 불리하지 않았을 뿐만 아니라 상위 인지 활동인 문제해결 과정에서 과학적 추론을 개발하는데 공헌 하였다.

• 동의생리병리학회지
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• 제29권1호
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• pp.27-32
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• 2015

Streptococcus mutans triggers dental caries establishment by two major factors. One is synthesis of organic acids which demineralize dental enamel and the other is synthesis of glucans which mediate the attachment of bacteria to the tooth surface. In the present study, we evaluated the effect of the ethanol extracts of Aconitum koreanum (A. koreanum ) on the growth and acid production of S. mutans. Ethanol extracts of the A. koreanum showed concentration dependent inhibitory activity against the growth and acid production of S. mutans, and produced significant inhibition at the concentration of 0.016 mg/ml compared to the control groups (p<0.05). The extracts inhibited S. mutans adherence to hydroxyapatite treated with saliva, and cell adherence was repressed by 50%, 54% at the concentration of 0.063, 0.125 mg/ml. On the study of activation of glucosyltransferase which synthesizes water insoluble glucan form sucrose, the ethanol extract of A. koreanum showed remarkable inhibition over the concentration of 0.016, 0.031, 0.063 and 0.125 mg/ml (p<0.05). Especially on the concentration of 0.063, 0.125 mg/ml, the extracts suppressed the glucan synthesis by 100%. We analyzed the component of the extracts of A. koreanum. The results showed that the extract of A. koreanum had strong phenolic compound, glycosides and organic acids. These results suggest that A. koreanum may inhibit the caries-inducing properties of S. mutans, and which may be related with strong phenolic compound, glycosides and organic acids.

• Journal of Periodontal and Implant Science
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• 제51권1호
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• pp.53-62
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• 2021

Purpose: This study aimed to evaluate the clinical and microbiological efficacy of adjunctive local delivery of minocycline (Periocline^®) in patients receiving supportive periodontal therapy (SPT) after initial treatment. Methods: The participants were 16 men and 8 women (age, 20-65 years) who had at least 15 natural teeth, underwent SPT for more than 1 year due to chronic periodontitis, had 4 or more periodontal pocket sites deeper than 5 mm, and showed >25% gingival bleeding on probing (BoP). They were randomly assigned to the test and control groups. In the test group, mechanical debridement and local antibiotic delivery were performed for all periodontal sulci/pockets; in the control group, mechanical debridement and saline irrigation were performed. In patients who underwent SPT for more than 1 year, clinical and microbiological examinations were performed at baseline and 1 and 3 months after SPT. The clinical examination included an assessment of the periodontal pocket depth, clinical attachment level, plaque index, and BoP. Microbial tests were performed using real-time polymerase chain reaction; the relative ratios of Porphyromonas gingivalis and Fusobacterium nucleatum were determined. Results: Both groups showed significant improvements in clinical parameters at 1 and 3 months from baseline; there were no significant changes between months 1 and 3. Intergroup differences were insignificant. The microbiological analysis revealed no significant differences in P. gingivalis and F. nucleatum ratios across time points. While intergroup differences were insignificant, there was a tendency for the P. gingivalis and F. nucleatum ratios to decrease in the test group. Conclusions: Mechanical debridement in patients receiving maintenance therapy resulted in clinically significant improvement; the effectiveness of additional local delivery of antibiotics was not significant. The ratios of P. gingivalis and F. nucleatum showed a tendency to decrease in the test group, although it was not significant.

• 미생물학회지
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• 제46권4호
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• pp.334-340
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• 2010

흡연은 음주와 더불어 치과질환을 유발하는 원인인자로 알려져 있으나, 흡연자와 비흡연자간의 구강 내 분포하는 미생물을 조사한 연구는 현재 매우 미비한 상태이다. 본 연구에서는 흡연자 30명, 비흡연자 30명으로 나누어 구강 내 분포하는 세균을 분리하고 혈액한천배지에서 배양하였다. 분리된 병원성 세균은 Kirby-Bauer 항생제 감수성 검사 방법으로 항생제에 대한 감수성 및 내성을 검사하였다. 각각의 콜로니는 그람 염색을 하였고 자동 동정기인 VITEK을 이용하여 동정하였다. 그람 염색법을 이용한 결과 흡연자의 구강에서는 총 41개 균주가 분리되었고, 그 중 그람 양성 구균 63%, 그람 음성 구균 29%, 그람 양성 간균 3%, 그람 음성 간균 5%가 나타났고, 비흡연자의 구강에서는 총 38개 균주가 분리되었고 그 중 그람 양성 구균 55%, 그람 음성 구균 26%, 그람 양성 간균 3%, 그람 음성 간균 16%가 나타났다. VITEK system을 이용하여 세균의 특이적 분포를 조사한 결과 흡연자의 구강에서는 Streptococcus mutans (6/41), Gemella morillorum (6/41), Streptococcus oralis (2/41), Streptococcus pneumoniae (1/41), Staphylococcus aureus (3/41), Streptococcus anginosus (1/41), Streptococcus intermedius (1/41), Streptococcus uberis (1/41), and Streptococcus sanguinis (1/41) 반면 비흡연자의 구강에서는 Streptococcus sanguinis (8/38), Staphylococcus aureus (1/38), Staphylococcus auricularis (1/38), Streptococcus uberis (1/38), Streptococcus intermedius (1/38), Streptococcus mutans (1/38), and Streptococcus oralis (1/38)로 나타났다. 3명의 흡연자에서 분리된 S. aureus는 Beta-lactamase를 분비하는 MRSA로 동정된 반면 비흡연자 한 명에서 분리된 S. aureus는 Beta-lactamase를 분비하지 않고 methicilin에 감수성을 보였다. 흡연자와 비흡연자의 상재균은 다른 분포를 보였고 특히 G. morillorum와 MRSA가 흡연자의 구강에서 흔히 발견됨을 알 수 있었다. 이러한 결과들은 흡연자의 구강질환을 예방 및 치료에 유용할 것으로 사료된다.

• 대한미생물학회지
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• 제21권1호
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• pp.133-144
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• 1986

This study was undertaken to assess the effect of ginseng administration on T lymphocyte induced local xenogenic graft-versus-host(GVM) reactions which were induced with thymocyte, spleen cell and lymph node cell of ICR mice. Mice received daily 10mg of 70% alcohol ginseng extract oral1y for 100days and control mice remained untreated for the same period of time. The cells from donor mice were injected intradermally into the closely shaven abdominal skin of Sprague-Dawley rats for GVH tests. The thymocyte from control(ginseng-untreated) mice showed a negative local GVH reaction, whereas thymocyte from experimental(ginseng-treated) mice showed a positive reaction with the rate of 17.4%. When spleen cells were injected, the incidence of positive local GVH reaction was 66.7% among ginseng-treated mice, as opposed to incidence of 45.5% of positive local GVH reaction among control mice. The incidence of positive local GVH reaction of the lymph node cells when injected into a recipient was 71.4% among ginseng-treated mice as compared with that of 18.9% among control mice. The relationship between spleen cell inoculum and intensity of the local GVH reaction was assessed in ginseng-untreated mice. The intensity of GVH reaction clearly appears to be dose related. In ginseng-treated mice, a minimum of $1{\times}10^7$ spleen cell was required for production of positive local GVH reaction with almost linear relationship up to an inoculum of $5{\times}10^8$ cells. In control mice, however, a minimum of $1{\times}10^8$ spleen cells was required for positive GVH reaction. These results strongly suggest that the ginseng administration augments significantly the local xenogenic GVH reaction which was used to assess T lymphocyte function and immunocompetence of mice and in addition to this, these results appear to support previous suggestions that the local GVH reaction consitutes a qualitative test of the functional activity of T lymphocytes. These results may be the first to induce local GVH reaction, employing rats as recipient and mice as donor. This study was also desingned to investigate some of the effects of ginseng extract on lymphocyte-macrophage interactions. This was accomplished by in vitro quantification of 1) migratory inhibitory factor(MIF) synthetic capacity of splenic lymphocytes in mice previously primed with ginseng 2) MIF responsiveness of mouse peritoneal macrophages or chicken peripheral leucocytes under the presence of ginseng extract 3) migration ability of chicken peripheral leucocytes by direct stimulation of ginseng extract or ginseng saponin and 4) immunosuppressive effects of immunosuppressants such as cyclophosphamide, cyclosporin A or dexamethasone. Mice divided equally into the ginseng and the saline groups, which received intraperitoneally daily 0.2ml of ginseng absolute alcohol-extract(5mg/ml) and same amount of saline for 15 days, respectively. The cellular immune responsiveness of these mice was assayed 15 days after ginseng pretreatment. Splenic lymphocytes of mice treated with ginseng, when stimulated with sensitized specific-antigen such as sheep red blood cells or toxoplasmin, or with polyclonal activator concanavalin A, produced significantly more MIF than those of control saline group. MIF responsiveness of normal mouse macrophages was significantly augmented when assayed under the presence of ginseng extract (1mg/ml). The migratory ability of normal chicken leucocytes in the absence of MIF was significantly decreased by the stimulation of ginseng extract alone. MIF response was significantly decreased by immunosuppressants and this impaired response was not restored by ginseng pretreatment. This study was additionally performed to evaluate the effect of ginseng on the expulsion of adult Trichinella spiralis in mice. ICR mice were infected experimentally by esophageal incubation of 300 T. spiralis infective muscle larvae prepared by acid-pepsin digestion of infected mice. and received oral administration of 70% alcohol ginseng extract(10mg/mouse/day) for the indicated days plus 4 days before infection. At various times after infection, the number of adult T. spiralis worms in small intestines was determined. Interestingly, ginseng-treatment was accompanied by accelerated expulson of T. spiralis. These results led to the conclusion that Panax ginseng caused some enhancing effect on GVH reaction, macrophage migration inhibition reaction and expulsion of T. spiralis. In addition these results suggested that the mechanisms responsible for this enhancement of ginseng may be chiefly or partially due to nonspecific stimulation of cell-mediated immune response.

• Mycobiology
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• 제33권3호
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• pp.158-162
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• 2005

The immunomodulatory effect of aqueous extract of Inonotus obliquus, called as Chaga, was tested on bone marrow cells from chemically immunosuppressed mice. The Chaga water extract was daily administered for 24 days to mice that had been treated with cyclophosphamide (400 mg/kg body weight), immunosuppressive alkylating agent. The number of colony-forming unit (CFU)-granulocytes/macrophages (GM) and erythroid burst-forming unit (BFU-E), increased almost to the levels seen in non-treated control as early as 8 days after treatment. Oral administration of the extract highly increased serum levels of IL-6. Also, the level of $TNF-{\alpha}$ was elevated by the chemical treatment in control mice, whereas was maintained at the background level in the extract-treated mice, indicating that the extract might effectively suppress $TNF-{\alpha}$ related pathologic conditions. These results strongly suggest the great potential of the aqueous extract from Inonotus obliquus as immune enhancer during chemotherapy.