• Bulletin of the Korean Chemical Society
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• 제33권4호
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• pp.1123-1127
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• 2012

P-gp (P-glycoprotein) is a member of the ATP binding cassette (ABC) family of transporters. It transports many kinds of anticancer drugs out of the cell. It plays a major role as a cause of multidrug resistance (MDR). MDR function may be a cause of the failure of chemotherapy in cancer and influence pharmacokinetic properties of many drugs. Hence classification of candidate drugs as substrates or nonsubstrate of the P-gp is important in drug development. Therefore to identify whether a compound is a P-gp substrate or not, in silico method is promising. Recursive Partitioning (RP) method was explored for prediction of P-gp substrate. A set of 261 compounds, including 146 substrates and 115 nonsubstrates of P-gp, was used to training and validation. Using molecular descriptors that we can interpret their own meaning, we have established two models for prediction of P-gp substrates. In the first model, we chose only 6 descriptors which have simple physical meaning. In the training set, the overall predictability of our model is 78.95%. In case of test set, overall predictability is 69.23%. Second model with 2D and 3D descriptors shows a little better predictability (overall predictability of training set is 79.29%, test set is 79.37%), the second model with 2D and 3D descriptors shows better discriminating power than first model with only 2D descriptors. This approach will be used to reduce the number of compounds required to be run in the P-gp efflux assay.

• Tuberculosis and Respiratory Diseases
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• 제76권2호
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• pp.66-74
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• 2014

Background: The increasing number of outpatients with multidrug-resistant (MDR) pathogens has led to a new category of pneumonia, termed healthcare-associated pneumonia (HCAP). We determined the differences in etiology and outcomes between patients with HCAP and those with community-acquired pneumonia (CAP) to clarify the risk factors for HCAP mortality. Methods: A retrospective study comparing patients with HCAP and CAP at Jeju National University Hospital. The primary outcome was 30-day mortality. Results: A total of 483 patients (208 patients HCAP, 275 patients with CAP) were evaluated. Patients with HCAP were older than those with CAP (median, 74 years; interquartile range [IQR], 65-81 vs. median, 69 years; IQR, 52-78; p<0.0001). Streptococcus pneumoniae was the major pathogen in both groups, and MDR pathogens were isolated more frequently from patients with HCAP than with CAP (18.8% vs. 4.9%, p<0.0001). Initial pneumonia severity was greater in patients with HCAP than with CAP. The total 30-day mortality rate was 9.9% and was higher in patients with HCAP based on univariate analysis (16.3% vs. 5.1%; odds ratio (OR), 3.64; 95% confidence interval (CI), 1.90-6.99; p<0.0001). After adjusting for age, sex, comorbidities, and initial severity, the association between HCAP and 30-day mortality became non-significant (OR, 1.98; 95% CI, 0.94-4.18; p=0.167). Conclusion: HCAP was a common cause of hospital admissions and was associated with a high mortality rate. This increased mortality was related primarily to age and initial clinical vital signs, rather than combination antibiotic therapy or type of pneumonia.

• Journal of Oral Medicine and Pain
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• 제46권3호
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• pp.75-83
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• 2021

Odontogenic infection in the oral and maxillofacial regions caused by bacteria (mostly of oral origin) is one of the most common diseases encountered by dentists. Localized infection can easily be treated with incision and drainage followed by antibiotics. Emergence of multidrug resistant (MDR) bacteria called "Superbacteria" has become one of the serious problems in modern society, due to its small window of opportunity for treatment and high casualty. The acronym "ESKAPE", encompassing the common and serious MDR pathogens stand for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. Literature search was performed in Medline, PubMed and Google Scholar ranging from 2012 to 2020. ESKAPE patient's infection period was longer than that of non-ESKAPE group, and the treatment method due to antibiotic resistance was also complicated. The purpose of this study is to investigate infection caused by ESKAPE pathogens in the oral and maxillofacial regions through literature review and to inform dental surgeons of the danger of ESKAPE pathogens and to suggest viable treatment options. Many studies worldwide reported infections associated with ESKAPE pathogens, but only limited number of studies targeted infection in oral and maxillofacial regions. Further research is required with more data on ESKAPE bacteria and their infection, especially in oral and maxillofacial regions.

• Journal of Chest Surgery
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• 제32권3호
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• pp.287-293
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• 1999

Isoniazid와 rifampin을 포함한 여러 항결핵약제에 내성을 보이는 다제내성 폐결핵의 경우 기존의 화학요법으로는 치료성공률이 낮고 장기생존율도 낮은 것으로 보고되고 있다. 최근 들어 다제내성 페결핵환자에 대한 약물치료의 보조적인 요법으로 적극적인 수술적 치료에 대한 보고가 이루어지고 있으며 좋은 치료성적을 보고하고 있다. 서울대학교병원 과에서는 1994년 1월부터 1998년 3월까지 다제내성 폐결핵으로 폐절제술을 시행 받은 27례의 임상기록에 대한 분석을 시행하였다. 환자들의 평균나이는 40세였고 술전 병력기간은 평균 3.1년이었다. 모든 환자들은 술전 2차 약제를 투여 받고 있었으며 약물 감수성 검사상 평균 4.4개의 약물에 내성을 보였다. 방사선 검사상 대부분의 환자(96%)에서 주된 병변으로 공동을 발견할 수 있었고 양측성 병변은 19례 (70%)에서 발견되었다. 술전 객담검사상 11례 (41%)에서 객담균 음전화가 이루어졌다. 수술은 전폐적출술이 9례, 폐엽절제술을 16례, 구역절제술을 2례에서 시행하였다. 술후 사망은 없었으며 술후 합병증으로는 1주이상의 지속적인 공기누출이 3례, 출혈로 인한 재수술이 2례, 술후 4개월 후에 발생한 기관지늑막루로 인한 재수술이 1례, 일시적인 신경학적 이상소견이 1례에서 관찰되었다. 수술 직후 22례 (82%)의 환자에서 객담균음전이 이루어졌고, 술후 지속적인 약물치료로 나머지 4례 (14%)에서 균음전이 이루어졌다. 양측성 공동병변을 갖고 있던 1례(4%)에서 객담균음전이 이루어지지 않았다. 다제내성 폐결핵 환자에서 그 병변이 국한되어 있고 수술적 치료를 견딜 수 있는 경우 적극적인 수술적 치료와 내과적 치료를 병합한 경우 높은 치료성공률을 보임을 확인할 수 있었다.

• Tuberculosis and Respiratory Diseases
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• 제57권3호
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• pp.226-233
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• 2004

연구 배경 : IFN-${\gamma}$는 결핵에 대한 방어기전에서 가장 중요한 역할을 하는 사이토카인이다. 최근 일부 다제내성결핵 환자에서 치료제로써 사용되어 왔으나 아직 그 효과는 확실히 알려져 있지 않다. 본 연구는 난치성 다제내성폐결핵 환자에서 피하주사 IFN-${\gamma}$의 효과를 알아보기 위하여 시행되었다. 방 법 : 6명의 다제내성폐결핵 환자에서 기존의 항결핵치료를 유지하면서 200만 IU의 IFN-${\gamma}$를 1주 3회, 피하주사하였다. 16주간 치료후 반응이 없으면 치료를 중단하였고, 반응이 있거나 판정이 모호한 경우에는 12주간 더 연장하여 사용하였다. 치료중 4주간격으로 객담 항산균 도말 및 배양검사, 임상상, 및 단순흉부촬영을 시행하였다. 결 과 : 대상환자는 남녀비가 4:2이었고 평균 연령은 37세(15-61)이었다. 5명에서 과거 폐결핵의 기왕력이 있었다. 약제감수성검사상 isoniazid와 rifampicin을 포함하여 평균 6.8(${\pm}1.2$)개의 항결핵약제에 내성을 보였고, IFN-${\gamma}$ 치료 전 10.8개(${\pm}1.3$) 약제를 투여하였다. IFN-${\gamma}$ 치료 28주 후 총 2명에서 균음전되었다. 그러나 IFN-${\gamma}$ 종료후 다시 균배양 양성으로 재발되었다. 모든 환자에서 IFN-${\gamma}$ 피하주사를 종료할 만한 중증 부작용은 관찰되지 않았다. 결 론 : 일부 난치성 다제내성폐결핵 환자에서 피하주사 IFN-${\gamma}$ 병합치료는 균음전 및 치료성공을 유도하였다. 추후 최적 용량, 치료기간, 투여경로, 및 반응의 예측인자를 찾기 위한 연구가 진행되어야 할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제80권2호
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• pp.159-168
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• 2017

Background: Streptomycin (SM) is recommended by the World Health Organization (WHO) as a part of standard regimens for retreating multidrug-resistant tuberculosis (MDR-TB) cases. The incidence of MDR-TB in retreatment cases was 19% in Thailand. To date, information on SM resistance (SMR) gene mutations correlated to the SMR of Mycobacterium tuberculosis Thai isolates is limited. In this study, the mutations in rpsL, rrs, gidB, and whiB7 were investigated and their association to SMR and the lineage of M. tuberculosis were explored. Methods: The lineages of 287 M. tuberculosis collected from 2007 to 2011 were identified by spoligotyping. Drug susceptibility profiles were evaluated by the absolute concentration method. Mutations in SMR genes of 46 SM-resistant and 55 SM-susceptible isolates were examined by DNA sequencing. Results: Three rpsL (Lys43Arg, Lys88Arg, and Lys88Thr) and two gidB (Trp45Ter and Gly69Asp) mutations were present exclusively in the SM resistant M. tuberculosis. Lys43Arg rpsL was the most predominant SMR mutations (69.6%) and prevailed among Beijing isolates (p<0.001). No SMR-related mutation in was found rrs. The combination of rpsL and gidB mutations provided 76.1% sensitivity for detecting SMR in M. tuberculosis Thai isolates. whiB7 was not responsible for SMR in SM resistant isolates lacking rpsL and rrs mutations. The significance of the three gidB mutations, 276A>C, 615A>G, and 330G>T, as lineage signatures for Beijing and EAI were underscored. This study identified 423G>A gidB as a novel sub-lineage marker for EAI6-BGD1. Conclusion: Our study suggested that the majority of SMR in M. tuberculosis Thai isolates were responsible by rpsL and gidB polymorphisms constantly providing the novel lineage specific makers.

• Natural Product Sciences
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• 제20권1호
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• pp.1-6
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• 2014

P-glycoprotein (P-gp) is a permeability glycoprotein also known as multidrug resistance protein 1 (MDR1). P-gp is an ATP-binding cassette (ABC) transporter that pumps various types of drugs out of cells. These transporters reduce the intracellular concentrations of drugs and disturb drug absorption. The Caco-2 cell permeability assay system is an effective in vitro system that predicts the intestinal absorption of drugs and the functions of enzymes and transporters. Rhodamine-123 (R-123) and digoxin are well-known P-gp substrates that have been used to determine the function of P-gp. Efflux of P-gp substrates by P-gp has been routinely evaluated. To date, a number of herbal medicines have been tested with Caco-2 cell permeability assay system to assess bioavailability. There are growing efforts to find phytochemicals that potentially regulate P-gp function. The Caco-2 cell permeability assay system is a primary strategy to search for candidates of P-gp inhibitors. In this mini review, we have summarized the P-gp modulation by herbal extracts, decoctions or single components from natural products using Caco-2 cell permeability assays. Many natural products are known to regulate P-gp and herbal medicines could be used in combination with conventional drugs to enhance bioavailability.

• 한국미생물·생명공학회지
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• 제47권4호
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• pp.651-661
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• 2019

Targeting the pathogen viability using drugs is associated with development of drug resistance due to selective pressure. Hence, there is an increased interest in developing agents that target bacterial virulence. In this study, the inhibitory effect of ciclopirox, an antifungal agent with iron chelation potential, on the microbial virulence factors was evaluated in 26 clinical MDR Pseudomonas aeruginosa isolates collected from Alexandria Main University Hospital, a tertiary hospital in Egypt. Treatment with 9 ㎍/ml ciclopirox inhibited the hemolytic activity in 70% isolates, reduced pyocyanin production, decreased protease secretion in 46% isolates, lowered twitching and swarming motility, and decreased biofilm formation by 1.5- to 4.5-fold. The quantitative real-time PCR analysis revealed that treatment with ciclopirox downregulated the expression levels of alkaline protease (aprA) and pyocyanin (phzA1). Ciclopirox is used to treat hematological malignancies and the systemic administration of ciclopirox is reported to have adequate oral absorption with a satisfactory drug safety profile. It is important to calculate the appropriate clinical dose and therapeutic index to reposition ciclopirox from a topical antifungal agent to a promising virulence-modifying agent agent against P. aeruginosa, a problematic Gram-negative pathogen.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6935-6938
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• 2014

Gastric cancer (GC) is one of the most common malignancies worldwide. The ABCB1 protein, a member of the ATP-binding cassette (ABC) transporter family, encoded by the ABCB1 gene, considerably influences the distribution of drugs across cell membranes as well as multidrug resistance (MDR) of antineoplastic drugs. In contrast to the extensive knowledge on the pharmacological action of ABCB1 protein, the correlation between the clinical-pathological data and ABCB1 protein expression in patients with GC remains unclear. The aim was to investigate association between ABCB1 expression and overall survival in GC patients. Human tumor fragments from 57 GC patients were examined by immunohistochemistry assay. We observed lower survival rate of patients with GC who were positive for ABCB1 expression (p=0.030). Based on these observations, we conclude that GC patients with positive ABCB1 protein immunohistochemical expression in their tumors suffer shorter overall survival.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2003년도 춘계 학술발표대회
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• pp.102-102
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• 2003

The present study has been undertaken to characterize availability of camellia(Camellia japonica L.) as a medicinal plant with antineoplastic and chemosensitizing activities. The crude extracts from fresn camellia flower, young leaves and nutraceutical tea of camellia leaf and flower buds were evaluated on their potential activities against various human cancer cells and multidrug resistance to cancer cells in vitro. The range of cytotoxicity displayed from 120$\mu\textrm{g}$/mL to 200$\mu\textrm{g}$/mL. Catemix 1(CT-1) mixed with camellia and green tea showed high toxicity(respectively IC$\sub$50/=l16$\mu\textrm{g}$/mL, 129$\mu\textrm{g}$/mL) against AML-2/WT, acute myelogenous leukemia cell and MCF-7, brest adenocarcinoma pleual effusion cell. Generally camellia tea mixed with green tea showed higher cytotoxicity than the other camellia teas mixed with some herbs(CH). Methanol extract of steamed camellia tea and roasted camellia tea had a chemosensitizing effect to reverse Pgp-mediated MDR. In addition, camellia flower tea of insignificant cytotoxicity, chemosensitizing effect were increased remarkably chemosensitizing effect in mixed flower tea with some herbs.