• 한국미생물·생명공학회지
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• 제51권4호
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• pp.432-440
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• 2023

Irrational and injudicious use of antibiotics, easy availability of them as over-the-counter drugs in economically developing countries, and unavailability of regulatory policies governing antimicrobial use in agriculture, animals, and humans, has led to the development of multi-drug resistance (MDR) bacteria. The use of medicinal plants can be considered as an alternative, with a consequent impact on microbial resistance. We tested extracts of Piper longum fruits as new natural products as agents for reversing the resistance to antibiotics. Six crude extracts of P. longum fruits were utilized against a clinical isolate of multidrug-resistant Staphylococcus aureus.The antibiotic susceptibility testing disc method was used in the antibiotic resistance reversal analysis. Apart from cefoxitin and erythromycin, all other antibiotics used (lincosamides [clindamycin], quinolones [levofloxacin and ciprofloxacin], and aminoglycosides [amikacin and gentamicin]) were enhanced by P. longum extracts. The extracts that showed the greatest synergy with the antibiotics were EAPL (ethyl acetate [extract of] P. longum), n-BPL (n-butanol [extract of] P. longum), and MPL (methanolic [extract of] P. longum The results of this study suggest that P. longum extracts have the ability to increase the effectiveness of different classes of antibiotics and reverse their resistance. However, future studies are needed to elucidate the molecular mechanisms behind the synergy between antibiotic and phytocompound(s) and identify the active biomolecules of P. longum responsible for the synergy in S. aureus.

• Clinical and Experimental Pediatrics
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• 제52권1호
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• pp.61-67
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• 2009

목 적 : 소아에서의 항결핵제 내성률은 지역 사회에서의 결핵 관리의 효율성을 파악하는 척도가 되나 국내외의 보고가 많지 않다. 이에 저자들은 소아청소년 결핵에서의 약제 내성률과 변화 경향을 조사하여 결핵 치료 및 예방적 화학요법 처방 선정에 도움을 얻고자 하였다. 방 법 : 1999년 1월부터 2007년 7월까지 대한결핵협회 결핵 연구원 미생물부(세계보건기구 지정 국제자문검사소)에 배양 및 감수성 검사가 의뢰되어 M. tuberculosis가 분리되어 항결핵제에 대한 감수성 검사가 실시된 예 중 19세 이하를 대상으로 항결핵제에 대한 감수성 검사를 실시하였다. 결 과 : 소아청소년에서 한 가지 이상의 약제에 대해 내성을 보인 균주는 607균주(16.6%)였고, IHN에 대해 내성을 보인 균주는 503균주(13.8%), RFP에 대해서는 326균주(8.9%), PZA에 대해서는 155균주(4.2%), SM에 대해서는 134균주(3.7%), EMB에 대해서는 215균주(5.9%), PAS에 대해서는 70균주(1.9%)였다. 다제내성결핵균은 276균주(7.6%)였고 광범위약제내성결핵균은 5균주(0.2%)였다. 15세 이하에서보다(20.5%) 15세 이상에서의 한 가지 이상의 약제에 대한 내성률(16.1%)이 유의하게 낮았고(P=0.016), 다제내성결핵이 차지하는 비율도 낮았으나(각각 8.7 %, 7.4%) 통계적으로 유의하지는 않았다. 본 조사 기간 동안 한 가지 이상의 결핵 약제에 대한 내성률과 다제내성결핵이 차지하는 비율은 유의하게 감소하였다(P<0.001). 이전 1987년부터 1995년까지의 조사와 비교해 보면, 한 가지 이상의 결핵 약제에 대한 내성률은 37.5%에서 20.5%로 유의하게 감소하였고(P=0.007), INH, EMB, PAS에 대한 내성률의 감소는 통계적으로 유의하였으며(P<0.05), 다제내성결핵이 차지하는 비율도 감소하였으나 통계적으로 유의하지는 않았다. 결 론 : 소아청소년 결핵에서의 약제 내성률은 과거에 비해 점차로 감소하는 양상을 보이고 있으나, 아직은 다른 나라보다 높고 다제내성결핵과 광범위약제내성결핵이 새로운 문제로 대두되고 있어 약제 감수성 검사와 내성균 감염 위험 요인 파악을 통한 효율적인 치료 약제 선정으로 치료 성공률을 높이면서 항결핵제 내성균의 증가를 막아야 할 것으로 사료된다.

• 한국식품영양과학회지
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• 제34권5호
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• pp.613-618
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• 2005

율무종자에 0, 1, 4, 8, 16, 32 및 64 Gy 선량의 감마선을 조사한 후 메탄을 추출하였으며 조사 종자 추출물이 인체의 유방암세포주(MCF-7), 폐암세포주(Calu-6), 위암세포주(SNU-601), 그리고 인체 급성골수성백혈암세포주(AML-2/WT)에 대한 세포독성 및 다제내성세포주(AML-2/D100)에 대한 다제내성 극복활성에 미치는 영향을 알아보고자 MTT 방법을 이용하여 분석하였다. 감마선 조사한 율무종자의 추출물은 대조구보다 비교적 낮은 농도에서 암세포 증식 저해 활성을 나타내는 경향을 보였으며 그 활성은 암세포 주와 조사선량별 추출물에 따라 다르게 나타났다. Calu-6의 경우 4, 8 및 16 Gy 추출물에서 암세포 증식 억제 효과를 나타냄을 알 수 있었으며 MCF-7에서 는 유일하게 8 Gy 추출물에서 $IC_{50}$값을 측정할 수 있었다. 그리고 SNU-601의 경우는 Calu-6에서와 같이 4, 8 및 16 Gy 추출물에서 증식저해 활성을 관찰할 수 있었으나 그 활성은 대조구인 0 Gy 추출물 보다 약간 높은 농도에서 관찰되었다. 한편, 선량이 높을수록 즉, 32 Gy 이상 감마선 조사는 암세포 증식억제 활성을 거의 나타내지 않았다. 유의할 만한 결과로는 8 Gy추출물이 3가지 암세포$(Calu-6:\;633\;{\mu}g/mL,\;MCF-7:\;653\;{\mu}g/mL,\;SNU-601:\;683\;{\mu}g/mL)$ 모두에서 증식 억제 활성을 나타냈다. 다제내성 세포에 대한 감수성 세포의 세포독성도를 측정하여 선택독성을 관찰한 결과 4,8 및 16 Gy추출물들은 오히려 감수성 세포에 대한 세포독성이 높게 나타나 교차내성을 나타내지 않았다. 그러나 다제내성 세포에 대하여 항암제인 vincristine과 함께 추출물을 처리한 결과 내성극복도(RF)가 4, 8 및 16 Gy 추출물에서 각각 1.7, 1.8 및 1.6으로서 다제내성 조절 활성을 관찰할 수 있었다. 따라서 감마선 조사기술은 약용식물 종자의 생리활성 증진에 활용 가능성이 매우 높을 것으로 기대된다.

• Tuberculosis and Respiratory Diseases
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• 제79권4호
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• pp.282-288
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• 2016

Background: Tuberculosis (TB) is a major health problem, and accurate and rapid diagnosis of multidrug-resistant (MDR) and extended drug-resistant (XDR) TB is important for appropriate treatment. In this study, performances of solid and liquid culture methods were compared with respect to MDR- and XDR-TB isolate recovery and drug susceptibility testing. Methods: Sputum specimens from 304 patients were stained with Ziehl-Neelsen method. Mycobacterium tuberculosis (Mtb) isolates were tested for recovery on $L{\ddot{o}wenstein$-Jensen (LJ) medium and the BacT Alert 3D system. For drug susceptibility testing of Mtb, isolates were evaluated on M-KIT plates and the BacT Alert 3D system. Results: The recovery rates were 94.9% (206/217) and 98.2% (213/217) for LJ medium and the BacT Alert 3D system, respectively (kappa coefficient, 0.884). The rate of drug resistance was 13.4% for at least one or more drugs, 6.0% for MDR-TB and 2.3% for XDR-TB. M-KIT plate and BacT 3D Alert 3D system were comparable in drug susceptibility testing for isoniazid (97.7%; kappa coefficient, 0.905) and rifampin (98.6%; kappa coefficient, 0.907). Antibiotic resistance was observed using M-KIT plates for 24 of the total 29 Mtb isolates (82.8%). Conclusion: The liquid culture system showed greater reduction in the culture period, as compared with LJ medium; however, drug susceptibility testing using M-KIT plates was advantageous for simultaneous testing against multiple drug targets.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4353-4358
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• 2014

Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.

• BMB Reports
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• 제34권2호
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• pp.176-181
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• 2001

Using a retrovirus, foreign genes can be introduced into mammalian cells. The purpose of this study is to produce a retrovirus that can make the infected cells express two genes; the human multidrug resistance gene (MDR1) and the HLA-B7 gene, which is one of the major human histocompatibility complex (MHC) class I genes. For the expression of these genes, the internal ribosome entry site (IRES) was used, which was derived from the encephalomyocarditis (EMC) virus. In order to produce retroviruses, a retroviral vector was transfected into a packaging cell line and the transfected cells were treated with vincristine, which is an anti-cancer drug and a substrate for the MDRI gene product. This study revealed that two genes were incorporated into chromosomes of selected cells and expressed in the same cells. The production of the retrovirus was confirmed by the reverse transcription (RT)-PCR of the viral RNA. The retrovirus that was produced infected mouse fibroblast cells as well as the human U937. This study showed that packaging cells produced the retroviruses, which can infect the target cells. Once the conditions for the high infectivity of retrovirus into human cells are optimized, thus virus will be used to infect hematopoietic stem cells to co-express MDRl and HLA-B7 genes, and develop the lymphocytes that can be used for the immnogene therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2979-2984
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• 2012

Recent studies have indicated a link between levels of cyclooxygenase-2 (COX-2) and development of the multidrug resistance (MDR) phenotype. The ATP-binding cassette sub-family G member 2 (ABCG2) is a major MDR-related transporter protein that is frequently overexpressed in cancer patients. In this study, we aimed to evaluate any positive correlation between COX-2 and ABCG2 gene expression using the COX-2 inducer 12-O-tetradecanoylphorbol-13-acetate (TPA) in human breast cancer cell lines. ABCG2 mRNA and protein expression was studied using real-time RT-PCR and flow cytometry, respectively. A significant increase of COX-2 mRNA expression (up to 11-fold by 4 h) was induced by TPA in MDA-MB-231 cells, this induction effect being lower in MCF-7 cells. TPA caused a considerable increase up to 9-fold in ABCG2 mRNA expression in parental MCF-7 cells, while it caused a small enhancement in ABCG2 expression up to 67 % by 4 h followed by a time-dependent decrease in ABCG2 mRNA expression in MDA-MB-231 cells. TPA treatment resulted in a slight increase of ABCG2 protein expression in MCF-7 cells, while a time-dependent decrease in ABCG2 protein expression was occurred in MDA-MB-231 cells. In conclusion, based on the observed effects of TPA in MDA-Mb-231 cells, it is proposed that TPA up-regulates ABCG2 expression in the drug sensitive MCF-7 breast cancer cell line through COX-2 unrelated pathways.

• 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.