• Title/Summary/Keyword: MDR3

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Reversal of Multidrug Resistance with KR-30035: Evaluated with Biodistribution of Tc-99m MIBI in Nude Mice Bearing Human Tumor Xenografts (이종이식된 인체종양에서 KR-30035가 Tc-99m MIBI체내 분포에 미치는 영향으로 평가한 다약제내성 역전가능성)

  • Kim, Jung-Kyun;Lee, Byung-Ho;Choi, Sang-Woon;Yoo, Sung-Eun;Lee, Sang-Woo;Chun, Kyung-Ah;Ahn, Byeong-Cheol;Park, Jae-Young;Suh, Jang-Soo;Lee, Kyu-Bo;Lee, Jae-Tae
    • 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.

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Study on the Anti-oxydative, Anti-tumor effect of Whakijogyungtang (화기조경탕(化氣調經湯)이 항산화 및 항암효과)

  • Yu, Mi-Kyung;Kim, Jong-Han;Park, Su-Yeon;Choi, Jeong-Hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.20 no.1 s.32
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    • pp.80-98
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    • 2007
  • Objectives : This study was carried out to evaluate anti-oxydative, anti-tumor effect for clinical application of Whakijogyungtang (WJT) Results : 1. DPPH radical scavenging activities of WJT water extracts(Exts) were in proportion as concentration of WJT.(3 ${\mu}g/ml:12.6{\pm}2.3$ %) 2. ABTS+ scavenging activities of WJT water Exts were more effective in high density.(3 ${\mu}g/ml:4.3{\pm}1.6$ %, 10 ${\mu}g/ml$: $11.8{\pm}2.5$ %, 30 ${\mu}g/ml:45.3{\pm}3.2%$ 100 ${\mu}g/ml$: $62.7{\pm}4.8%$) 3. Hydrogen peroxide$(H_2O_2)$ scavenging activities of WJT water Exts were effective.(3 ${\mu}g/ml:4.7{\pm}0.8$ %, 10 ${\mu}g/ml: $8.2{\pm}1.6$ %, 30 ${\mu}g/ml:19.5{\pm}3.2$ % 100 ${\mu}g/ml$: $24.6{\pm}3.8$ %) 4. Anti oxidative effects against linoleic acid were not effective. 5. The generation of $O_2\;^-$ in S-180 cells were according to the concentration of WJT water Exts, specially effective over 100 ${\mu}g/ml$ concentration. 6. The SOD activities in S-180 cells were in proportion as cytotoxicity against S-180 cells of WJT water Exts. 7. The GPx activities in S-180 cells were in proportion as cytotoxicity against S-180 cells of WJT water Exts(more effective on 300 ${\mu}g/ml$ and 1000 ${\mu}g/ml$ concentration), but the catalase activities in S-180 cells were not effective. 8. The results of activites against multi-drug-resistance(MDR) of WJT were as follows. 1) In water Exts from WJT, cytotoxicity against AML-2/D100 with vincristine($IC_{50:}39.78$ ${\mu}g/ml$) was more effective than without vincristine($IC_{50:}$ 183.58 ${\mu}g/ml$), Cross resistance(CR:3.85) was not effective, and anti-MDR activites(RF) was effective.(RF:3.85) 2) In hexane fraction, cytotoxicity against AML-2/D100 with vincristine ($IC_{50:}130.88$ ${\mu}g/ml$) was more effective than without vincristine ($IC_{50:}293.10$ ${\mu}g/ml$) and anti-MDR activites(RF) was effective.(RF:4.61) 3) In chloroform fraction, the cytotoxicity against AML-2/WT and AML-2/D100 was not effective. 4) In ethyl acetate fraction, cytotoxicity against AML-2/D100 with vincristine($IC_{50:}36.43$ ${\mu}g/ml$) was more effective than without vincristine ($IC_{50:}73.07$ ${\mu}g/ml$), Cross resistance(CR:0.53) was not effective, and anti-MDR activites(RF) was effective.(RF:2) 5) In butanol fraction, the cytotoxicity against AML-2/WT and AML-2/D100 was not effective. 6) In $H_2O$ fraction, the cytotoxicity against AML-2/WT and AML-2/D100 was not effective. Conclusion : These result suggest that WJT has antioxidative effects, anti-tumor effects by apoptosis of free radical$(O_2\;^-)$ activity, and anti-MDR activites(especially hexane and ethyl acetate fraction).

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Clinical Features and Management of Multidrug-Resistant Tuberculosis (다제 내성 폐결핵 환자의 임상상 및 치료에 대한 고찰)

  • Lee, Jae-Cheol;Lee, Seung-Jun;Kim, Gye-Soo;Yoo, Chul-Gyu;Cheong, Hee-Soon;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.1
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    • pp.14-21
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    • 1996
  • Objectives: Although outbreak of MDR Tb has been a recent problem in western countries, it has been a longstanding problem in Korea. The poor outcome of MDR Tb is mainly due to poor compliance, high rate of side reaction of secondary drugs, and limitation in number of available drugs. Thus, to improve the outcome of MDR Tb, it is crucial to make individualized adequate prescription based on the knowledge of the patterns of resistance to each drugs in the community as well as the natural history. The purpose of present study is to evaluate the clinical features of Korean MDR Tb patients including patterns of drug resistance and success rate of treatment which was prescribed according to the sensitivity tests. Methods: Retroscpective analysis of 71 Korean patients with MDR Tb was made. All strains isolated from patients showed resistence to at least two first line drugs. Patients profile, previous treatment history, patterns of drug resistance, outcome of treatment was analysed. Initial treatment regimen was selected according to the previous treatment history and was modified according to the sensitivity reports. The regimen was composed to include at least 4 sensitive drugs when possible. Results: The patients showed resistance to 4.1 drugs on average. 90% of them were resistant to INH and RFP. Among 71 patients, 35 patients(49%) had cavitary lesions in CXR. Treatment outcome was analysed in 55 patients. 35 patients(67%) were improved after treatment and 18 patients(33%) showed treatment failure. 5 patients showed primary resistance. Treatment outcome could be evaluated in 4 of them and all showed improvement after treatment. 14 patients(20%) had to change their regimens due to drug side effects. The most frequent side effect was elevation of liver enzymes(6 patients). Others included dizziness, hyperuricemia, tinnitus, skin rash, GI troubles. More than 50% of side effects developed within 3 months. In repeated drug sensitivity test, the concordance rate of resistance to INH was 100% and RFP 98%. EMB, PZA showed 80% concordance rate. But in the other drugs, the concordances were less than 50%. Operation was done in 5 patient - 1 patients as a adjunctive means of chemotherapy -. In that case, negative conversion of sputum AFB was done. Conclusion: 2/3 patients of multidrug-resistant tuberculosis were improved by appropriate prescription and regular medication suggesting that more aggressive management and monitoring is indicated in multidrug-resistant tuberculosis.

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A MDR Location Polling Algorithm for Location Based Alert Service (위치기반 경보서비스를 위한 MDR위치조회 알고리듬)

  • Ahn, Byung-Ik;Yang, Sung-Bong
    • Journal of Korea Spatial Information System Society
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    • v.8 no.3
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    • pp.89-103
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    • 2006
  • Location-Based Services(LBS) has been varied and expanded rapidly in local and overseas markets due to technology developments and expanded applications of wireless internet. Location Based Alert Service(LBA) capable of automatically furnishing data when entering or outing a specific location is expected to become one of the most important services in LBS. For LBA operation, it is essential to periodically get location information about moving object. However, this can cause a serious system load because system should continuously and largely receive location information of many moving objects. Existing and current methods for location polling of moving object are not suitable for an efficient location acquisition and a search structure required for LBA. In this study, to acquire large-scaled location information for LBA, a MDR moving object location polling algorithm will be suggested to reduce unnecessary location information and decrease system load by using mobility patterns of moving object.

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Polymorphisms of XRCC1 and XRCC2 DNA Repair Genes and Interaction with Environmental Factors Influence the Risk of Nasopharyngeal Carcinoma in Northeast India

  • Singh, Seram Anil;Ghosh, Sankar Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2811-2819
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    • 2016
  • Multiple genetic and environmental factors have been reported to play key role in the development of nasopharyngeal carcinoma (NPC). Here, we investigated interactions of XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms and environmental factors in modulating susceptibility to NPC in Northeast India. One-hundred NPC patients, 90 first-degree relatives of patients and 120 controls were enrolled in the study. XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms were determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. The XRCC1 Gln/Gln genotype showed increased risk (OR=2.76; P<0.024) of NPC. However, individuals with both XRCC1 and XRCC2 polymorphic variants had 3.2 fold elevated risk (P<0.041). An enhanced risk of NPC was also observed in smoked meat (OR=4.07; P=0.004) and fermented fish consumers (OR=4.34, P=0.001), and tobacco-betel quid chewers (OR=7.00; P=0.0001) carrying XRCC1 polymorphic variants. However, smokers carrying defective XRCC1 gene showed the highest risk (OR = 7.47; P<0.0001). On MDR analysis, the best model for NPC risk was the five-factor model combination of XRCC1 variant genotype, fermented fish, smoked meat, smoking and chewing (CVC=10/10; TBA=0.636; P<0.0001); whereas in interaction entropy graphs, smoked meat and tobacco chewing showed synergistic interactions with XRCC1. These findings suggest that interaction of genetic and environmental factors might increase susceptibility to NPC in Northeast Indian populations.

Efficacy of Disinfectants against Health-Associated Multi-drug Resistant Clinical Isolates

  • An, Jeong-Lib;Kim, Sang-Ha;Yu, Young-Bin;Kim, Sunghyun;Lee, Moo-Sik;Kim, Young-Kwon
    • Biomedical Science Letters
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    • v.27 no.4
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    • pp.264-269
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    • 2021
  • The purpose of this study was to evaluate the disinfecting efficacy of peracetic acid (PAA), sodium hypochlorite (NaOCl) and phenol, which are representative disinfectants in medical environments using four types of multi-drug resistance (MDR) clinical isolates with healthcare-associated infections (HAI). 26 antibiotic susceptibility tests were conducted for the four types of MDR clinical isolates in the same way as for clinical specimens. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the disinfectants were determined by using in vitro liquid medium dilution method and inoculation of the plate medium. Both the MIC and MBC of phenol against MRSA and VRE were 3.1%, while those against KPC and MRPA were 6.2%. The MIC and MBC of peracetic acid (PAA) against MRSA, VRE, KPC, and MRPA were 0.18%. The MIC and MBC of sodium hypochlorite (NaOCl) against MRSA were 0.39% and 0.78%, respectively. Both values of MIC and MBC were 0.78% for VRE. In addition, KPC and MRPA showed 0.39% for MIC and 0.78% for MBC. For all MDR strains used in this study, sodium hypochlorite and peracetic acid showed significant sterilizing efficiency, while no clear correlation was identified between antibiotic resistance clinical isolated and ability of disinfection.

ISO14971:2019 Detailed Analysis and Periodic Safety Update Report Establishment Method for the Single Use Medical Device - Focusing on Medical Device Regulation 2017/745 requirements (일회용 의료기기에 적용을 위한 ISO 14971:2019 분석과 Periodic Safety Update Report 작성 방법 - Medical Device Regulation 2017/745 요구사항 중심으로)

  • Sang Min, Park;Gyu Ha, Ryu
    • Journal of Biomedical Engineering Research
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    • v.44 no.1
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    • pp.1-10
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    • 2023
  • With the announcement of MEDICAL DEVICE REGULATION 2017/745 (MDR) on April 5 2017, medical device manufacturers shall apply ISO 14971:2019 (3rd) revised in December 2019. However, there is not much related information and guidance available to medical device manufacturers, especially single use medical device. Risk management process basically follow 5 steps which are Risk Analysis, Risk Evaluation, Risk Control, Evaluation of overall residual risk and post-production activities. The purpose of this study is to provide a guidance of from risk analysis with Failure Mode and Effects Analysis (FMEA) table to overall residual risk evaluation for the single use medical device and to reflect it in a Periodic Safety Update Reports (PSUR) to satisfy with MDR requirements with single use medical device which are widely used and manufactured FDA class 2 or CE class IIb as examples. For this study, single use medical device manufacturer can adopt ISO 14971:2019 in accordance with MDR requirements and it can be extended to the PSUR. But there are still limitations to adopt to the all-single use medical device especially high class, private device and implantable device. So, Competent Authority (CA) shall publish more guidance for the single use medical device.

Prevalence and Molecular Characterization of Methicillin-Resistant Staphylococcus aureus from Nasal Specimens: Overcoming MRSA with Silver Nanoparticles and Their Applications

  • Aly E. Abo-Amer;Sanaa M. F. Gad El-Rab;Eman M. Halawani;Ameen M. Niaz;Mohammed S. Bamaga
    • Journal of Microbiology and Biotechnology
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    • v.32 no.12
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    • pp.1537-1546
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    • 2022
  • Staphylococcus aureus is a cause of high mortality in humans and therefore it is necessary to prevent its transmission and reduce infections. Our goals in this research were to investigate the frequency of methicillin-resistant S. aureus (MRSA) in Taif, Saudi Arabia, and assess the relationship between the phenotypic antimicrobial sensitivity patterns and the genes responsible for resistance. In addition, we examined the antimicrobial efficiency and application of silver nanoparticles (AgNPs) against MRSA isolates. Seventy-two nasal swabs were taken from patients; MRSA was cultivated on Mannitol Salt Agar supplemented with methicillin, and 16S rRNA sequencing was conducted in addition to morphological and biochemical identification. Specific resistance genes such as ermAC, aacA-aphD, tetKM, vatABC and mecA were PCR-amplified and resistance plasmids were also investigated. The MRSA incidence was ~49 % among the 72 S. aureus isolates and all MRSA strains were resistant to oxacillin, penicillin, and cefoxitin. However, vancomycin, linezolid, teicoplanin, mupirocin, and rifampicin were effective against 100% of MRSA strains. About 61% of MRSA strains exhibited multidrug resistance and were resistant to 3-12 antimicrobial medications (MDR). Methicillin resistance gene mecA was presented in all MDR-MRSA strains. Most MDR-MRSA contained a plasmid of > 10 kb. To overcome bacterial resistance, AgNPs were applied and displayed high antimicrobial activity and synergistic effect with penicillin. Our findings may help establish programs to control bacterial spread in communities as AgNPs appeared to exert a synergistic effect with penicillin to control bacterial resistance.

Major gene interaction identification in Hanwoo by adjusted environmental effects (환경적인 요인을 보정한 한우의 우수 유전자 조합 선별)

  • Lee, Jea-Young;Jin, Mi-Hyun
    • Journal of the Korean Data and Information Science Society
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    • v.23 no.3
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    • pp.467-474
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    • 2012
  • Human diseases and livestock economic traits are not typically the result of variation of a single genetic locus, but are rather the result of interplay between interactions among multiple genes and a variety of environmental exposures. We have used linear regression model for adjusted environmental effects and multifactor dimensionality reduction (MDR) method to identify gene-gene interaction effect of statistical model in general. Of course, we use 5 SNPs (single uncleotide polymorphism) which were studied recently by Oh et al. (2011). We apply the MDR (multifactor demensionality reduction) method on the identify major interaction effects of single nucleotide polymorphisms responsible for economic traits in a Korean cattle population.

Clinical Evaluation of Surgical Resection on Pulmonary Tuberculosis -Multiple Drug Resistent Pulmonary Tuberculosis (폐결핵 환자에 적용된 폐절제술의 임상적 연구 -다제약제내성 결핵환자를 중심으로-)

  • 전희재;한동기
    • Journal of Chest Surgery
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    • v.30 no.8
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    • pp.786-792
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    • 1997
  • A clinical study of 71 cases of pulmonary tuberculosis that had had surgical resection during the period of 7 years and 6months from January 1989 to June 1996 in National Masan Tuberculosis Hospital. The results were as follows. 1. The ratio of male to female was 3.7:1 and in the age incidence the fourth decade was 22%, the third decade 15%. Although medical treatment was performed for more than 3 to 6 months, preoHeratively the conversion failure rate of positive sputum to negative state was 66.2%(47 cases). Of the failure cases, multiple-drug-resistant(MDR) patients were 41 cases(87.2%), 3. In MDR group, preoperatively conversion failure rate was 71.9%. 4. From the view of indica ion for lung resection on the radiographic finding, cavitary lesions were 43 cases(60.6%), destroyed lung lesions were 24 cases(33.8%). 5. The incidence of postoperative complication was 28.2%(20 cases). All cases were MDR 6. group and the most common of complication was tuberculosis spreading. In bilateral lesion, incidence of postoperative tuberculosis spreading was 25%(7 cases). Of the 7 cases, there was the cavitary lesion in 6 cases(86.7%). Total conversion rate of AFB positive sputum to negative state related to resectional sugery was 76.6% and in MDR group conversion rate of AFB positive sputum to negative state was 73.2% Conversion rate of MDR group with bilateral lesion was the lowest(60%). Conversion rate of drug-sensitivity group was 100% regardeless of lesions Slt to. In conclusion, despite of long-standing medical treatment, it is difficult to converse sputum-positive to negative state in multiple-drug resistance patients and that increases postoperative complications su h as tuberculosis relapse as a lack of appropriate drugs postoperatively. Postoperative conversion rate of sputum-positive to negative state was decreased in multiple-drug resistance patients. Because multiple-drug resistance patients have inireased due to several factors in Korea, it is important to prevent spreading of multiple-drug resistnce patients through the aggressive operative treatment. When the first medical therapy is fail or drug-resistance is found, operative treatment should be considered with the secondary medical therapy. The operation should be aggressively attempted even though at first medical treatment if indicated.

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