• Journal of Life Science
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• v.18 no.9
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• pp.1244-1248
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• 2008

P-glycoprotein (P-gp) is a very important drug transporter, which plays an important role in drug disposition and represents an additional mechanism for the development of multidrug resistance. Flavonoids, a major class of natural compounds widely present in foods and herbal products, have been shown to be P-gp inhibitors. The objective of the present study was to identify new chemosensitizer candidates through the screening of various herbal extracts. The inhibitory effects of herbal extracts on P-gp activity were assessed by measuring accumulation of calcein AM using P-gp overexpressed L-MDR1 cells. Curcuma longa showed the most potent inhibition on P-gp function. The inhibitory potential of P-gp was in the order: Curcuma longa > Curcuma aromatica > Ageratum conizoids > Zanthoxylum planispinum > Zedoariae rhizome > Rakta chandan > Dalbergia odorifera > Caesalpinia Sappan > Aloe ferox. To identify individual constituents with inhibitory activity, the herbal extracts were analyzed by LC/MS/MS. Several flavonoids such as curcumin, a well-known P-gp inhibitor, were identified through mass spectral library search. These in vitro data indicate that herbal extracts contain constituents that can potently inhibit the activities of P-gp and suggest that these herbal extracts should be examined for potential chemosensitizer in vivo.

• Development and Reproduction
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• v.18 no.4
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• pp.197-212
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• 2014

Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF-${\kappa}B$ appears to play a causative role, but the mechanisms are poorly understood. OS is one of the pleomorphic, highly metastasized and invasive neoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix. Its high incidence has been reported in adolescent and children. Cell signal cascade is the pivotal functional mechanism acquired during the differentiation, proliferation, growth and survival of the cells in neoplasm including OS. The major limitation to the success of chemotherapy in OS is the development of multidrug resistance (MDR). Answers to all such queries might come from the knock-in experiments in which the combined approach of miRNAs with NF-${\kappa}B$ pathway is put into use. Abnormal miRNAs can modulate several epigenetical switching as a hallmark of number of diseases via different cell signaling. Studies on miRNAs have opened up the new avenues for both the diagnosis and treatment of cancers including OS. Collectively, through the present study an attempt has been made to establish a new systematic approach for the investigation of microRNAs, bio-physiological factors and their target pairs with NF-${\kappa}B$ to ameliorate oncogenesis with the "bridge between miRNAs and NF-${\kappa}B$". The application of NF-${\kappa}B$ inhibitors in combination with miRNAs is expected to result in a more efficient killing of the cancer stem cells and a slower or less likely recurrence of cancer.

• Biomedical Science Letters
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• v.5 no.2
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• pp.191-200
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• 1999

In recent years continuously increasing number of tuberculosis (TB) cases due to the emergence of strains with multidrug resistance and AIDS is a significant global health problem. Therefore, more rapid and reliable diagnosis of TB may be one of the most urgent needs in efforts to eradicate the disease. The present study was designed to compare and assess the diagnostic values and efficiencies between the conventional methods (X-ray, AFB stain and culture) and PCR for pulmonary TB on 171 cases. Chest X-ray finding and clinical features revealed that 39 (22.8%) of 171 sputum specimens were pulmonary TB cases. The statistical data were taken on the basis of the definitive diagnosis: In X-ray, overall sensitivity, specificity, efficiency and false positive and false negative incidence was respectively 69.2%, 87.1％, 83.0%, 12.9%, and 30.8％； 79.5%, 95.5%, 91.8%,4.6％ and 20.5％ in AFB-stain; 56.4%, 99.2%,89.5%, 0.8% and 43.6% in culture; 82.1%, 96.2%, 93.0%, 3.8% and 17.9% in PCR. PCR got a highest sensitivity and efficiency as well as a lowest false negative incidence. Culture had a highest specificity with a lowest false positive incidence. These results imply that PCR assay is fast, sensitive and efficient method for diagnosis of pulmonary TB. However, combined use of the conventional methods with thorough quality control may offer more opportunities for detecting Mycobacterium tuberculosis and diagnosting TB although they have some limits.

• Biomedical Science Letters
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• v.16 no.2
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• pp.75-82
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• 2010

The molecular epidemiological characteristics of methicillin-resistant Staphylococcus aureus (MRSA) isolates have demonstrated their genetic diversity and evolution. A total of 137 strains of MRSA clinical isolates was collected from Korean healthcare facility in 2007. The MRSA clinical isolates were analyzed by molecular typings (SCCmec element and agr locus typing), virule nce factor gene detections {(Panton-Valentine leukocidin (PVL), enterotoxin, exfoliative toxin and toxic shock syndrome toxin-1), and amplified fragment length polymorphism (AFLP)}. The MRSA clinical isolates were classified as SCCmec type II-agr type 1 (2 strains), type II-agr type 2 (79 strains), type III-agr type 1 (24 strains), type III-agr type 2 (2 strains), type IV-agr type 1 (27 strains), type IV-agr type 2 (2 strains), and non-typable (1 strain, agr type 3). Based on SCCmec types, SCCmec type II (95.1%) and III (88.5%) indicated higher multidrug resistance rate than SCCmec type IV (10.3%) (P<0.001). The most common enterotoxin genes were seg (83.8%), sei (83.1%), and sec (80.2%). The tst gene was present in 86 out of 137 (62.8%) MRSA isolates. All MRSA isolates were negative for PVL and exfoliative toxin genes. The combinations of toxin genes were observed in particular SCCmec types; 97.6% of SCCmec type II strains carried sec, seg, sei and tst genes, 73.0% of SCCmec type III strains carried sea gene, and 89.7% of SCCmec type IV strains carried sec, seg and sei genes. Each of the SCCmec types of MRSA isolates had distinct AFLP profile. In conclusion, SCCmec type II, agr type 1 and 2 have demonstrated to be the most common types in Korea, and the results indicated that the virulence factors are closely associated with their molecular types (SCCmec and agr types).

• Tuberculosis and Respiratory Diseases
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• v.73 no.1
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• pp.48-55
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• 2012

Background: The epidemiology of tuberculosis (TB) has been assessed based on the data of the analysis of TB patients notified to the surveillance system in Korea. However, the national status of TB is not validated through this surveillance system. The objective is to determine the epidemiology of TB and to understand the accurate status of TB patients treated in private institutions. Methods: Medical records of 53,579 patients who had been diagnosed with TB in 2008 were analyzed. Results: Among 53,579 patients, the number of sputum smear positive cases was 15,639(29.2%) and the number of new cases was 39,191 (73.1%). The drug resistance rate of new cases was 5.3%, while the rate stood at 13.3% for TB patients with treatment history. The number of multi-drug resistant TB (MDR-TB) patients was 2,472 (4.6%), which consists of 2.9% of new cases and 9.3% of TB patients with prior treatment history. The number of extensively drug-resistant TB patients was 749 (1.4%), consisting of 1.1% of new cases and 2.2% of TB patients with prior treatment history. In terms of treatment outcomes, 66.4% of all TB patients, 70.5% of new cases, 64.4% of relapse cases, and 46.8% of MDR-TB cases were cured or completed. It was inferred that in 2008, the total number of TB patients reached 70,767, 145.6 per 100,000 people (95% confidence interval, 145.5~145.7). Conclusion: We conclude that the medical records review of the Health Insurance Review and Assessment Service (HIRA) data can be very effective in promoting the understanding of the current status of TB in private institutions.

• Tuberculosis and Respiratory Diseases
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• v.83 no.4
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• pp.289-294
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• 2020

Background: Line probe assay (LPA) is standard diagnostic tool to detect multidrug resistant tuberculosis. Non-interpretable (NI) results in LPA (complete missing or light wild-type 3 and 8 bands with no mutation band in rpoB gene region) poses a diagnostic challenge. Methods: Sputum samples obtained between October 2016 and July 2017 at the Intermediate Reference Laboratory, All India Institute of Medical Sciences Hospital, New Delhi, India were screened. Smear-positive and smear-negative culture-positive specimens were subjected to LPA Genotype MTBDRplus Ver 2.0. Smear-negative with culture-negative and culture contamination were excluded. LPA NI samples were subjected to phenotypic drug susceptibility testing (pDST) using MGIT-960 and sequencing. Results: A total of 1,614 sputum specimens were screened and 1,340 were included for the study (smear-positive [n=1,188] and smear-negative culture-positive [n=152]). LPA demonstrated 1,306 (97.5%) valid results with TUB (Mycobacterium tuberculosis) band, 24 (1.8%) NI, three (0.2%) valid results without TUB band, and seven (0.5%) invalid results. Among the NI results, 22 isolates (91.7%) were found to be rifampicin (RIF) resistant and two (8.3%) were RIF sensitive in the pDST. Sequencing revealed that rpoB mutations were noted in all 22 cases with RIF resistance, whereas the remaining two cases had wild-type strains. Of the 22 cases with rpoB mutations, the most frequent mutation was S531W (n=10, 45.5%), followed by S531F (n=6, 27.2%), L530P (n=2, 9.1%), A532V (n=2, 9.1%), and L533P (n=2, 9.1%). Conclusion: The present study showed that the results of the Genotype MTBDRplus assay were NI in a small proportion of isolates. pDST and rpoB sequencing were useful in elucidating the cause and clinical meaning of the NI results.

• Journal of Chest Surgery
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• v.32 no.3
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• pp.287-293
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• 1999

Background: Medical treatment of multiple drug resistant(MDR) pulmonary tuberculosis has been quite unsuccessful. We analyzed our experience to identify the benefits and complications of the pulmonary resection in MDR pulmonary tuberculosis. Material and Method: A retrospective review was performed in 27 patients who unerwent pulmonary resection for MDR pulmonary tuberculosis between January 1994 and March 1998. Mean age was 40 years and the average history of diagnosis prior to surgery was 3.1 years. All had resistance to an average of 4.4 drugs, and received second line drugs selected according to the drug sensitivity test. Most patients (93%) had cavitary lesions as the main focus. Bilateral lesions were identified in 19 patients (70%), however, the main focus was recognized in one side of the lung. Eleven patients (41%) were converted to negative sputum smear and/or culture before surgery. Result: Pneumonectomy was performed in 9 patients, lobectomy in 16 and segmentectomy in 2. There was no operative mortality. Morbidity had occurred in 7 patients (26%), prolonged air leak in 3 patients, reoperation due to bleeding in 2, bronchopleural fistula in 1, and reversible neurologic defect in 1. Median follow up period was 15 months (3-45 months). Sputum negative conversion was initially achieved in 22 patients (82%), and with continuous postopertive chemotherapy negative conversion was achieved in other 4 patients (14%). Only one pneumonectized patient (4%) failed due to considerable contralateral cavity. Conclusion: For patients with localized MDR pulmonary tuberculosis and with adequate pulmonary reserve function, surgical pulmonary resection combined with appropriate pre and postoperative anti-tuberculosis chemotherapy can achieve high success rate with acceptable morbidity.

• Journal of Ginseng Research
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• v.43 no.3
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• pp.460-474
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• 2019

Background: Ginsenoside compound K (CK) is a promising drug candidate for rheumatoid arthritis. This study examined the impact of polymorphisms in NR1I2, adenosine triphosphate-binding cassette (ABC) transporter genes on the pharmacokinetics of CK in healthy Chinese individuals. Methods: Forty-two targeted variants in seven genes were genotyped in 54 participants using Sequenom MassARRAY system to investigate their association with major pharmacokinetic parameters of CK and its metabolite 20(S)-protopanaxadiol (PPD). Subsequently, molecular docking was simulated using the AutoDock Vina program. Results: ABCC4 rs1751034 TT and rs1189437 TT were associated with increased exposure of CK and decreased exposure of 20(S)-PPD, whereas CFTR rs4148688 heterozygous carriers had the lowest maximum concentration ($C_{max}$) of CK. The area under the curve from zero to the time of the last quantifiable concentration ($AUC_{last}$) of CK was decreased in NR1I2 rs1464602 and rs2472682 homozygous carriers, while $C_{max}$ was significantly reduced only in rs2472682. ABCC4 rs1151471 and CFTR rs2283054 influenced the pharmacokinetics of 20(S)-PPD. In addition, several variations in ABCC2, ABCC4, CFTR, and NR1I2 had minor effects on the pharmacokinetics of CK. Quality of the best homology model of multidrug resistance protein 4 (MRP4) was assessed, and the ligand interaction plot showed the mode of interaction of CK with different MRP4 residues. Conlusion: ABCC4 rs1751034 and rs1189437 affected the pharmacokinetics of both CK and 20(S)-PPD. NR1I2 rs1464602 and rs2472682 were only associated with the pharmacokinetics of CK. Thus, these hereditary variances could partly explain the interindividual differences in the pharmacokinetics of CK.

• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.168-184
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• 2001

Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

• Korean Journal of Environmental Agriculture
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• v.27 no.2
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• pp.156-162
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• 2008

Salmonellosis is a major bacterial zoonosis that causes a variety of disease syndromes, self-limited enteritis to fatal infection in animals and food-borne infection and typhoid fever in humans. Recently, the emergence of multidrug resistant strains of Salmonella spp. causes more serious problems in environment and public health. The present study was investigated the antibacterial effect of Houttuynia cordata ethanol extract(HCEE) for murine salmonellosis. In the cytotoxic effect of HCEE on RAW 264.7 cells, there was no detectable effect with any concentrations between 25 and 100 ${\mu}g/ml$ after 8 h incubation. The bacteriocidal effect of HCEE was not showed on a Salmonella enterica serovar Typhimurium(S. typhimurium). HCEE makes morphological change of the RAW 264.7 cells, and there was significant decreased bacterial uptake and intracellular replication within Salmonella infected cells. And further nitric oxide(NO) production of Salmonella infected RAW 264.7 cells with HCEE was decreased comparing to RAW 264.7 cells without HCEE until 8 h post infection. Oral administration of HCEE showed a therapeutic effect for S. typhimurium infected BALB/c mice. The mortality of HCEE treated mouse was 80% until 12 days, while that of HCEE untreated mouse was 100 % until 8 days after lethal dose of S. typhimurium infection. These data suggested that HCEE has a potency treatment for intracellular replicative pathogen including salmonellosis, brucellosis, tuberculosis, listeriosis etc., and the application of HCEE makes new strategies for safety medicine development without antibiotic resistance bacterial appearance and residue problem in food and solves the public health problem from antibiotic mis- and over use.