• Title/Summary/Keyword: MDR3

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Phagocytosis of Drug-Resistant Mycobacterium Tuberculosis by Peripheral Blood Monocytes (결핵균의 약제내성과 말초혈액단핵구의 결핵균 탐식능에 관한 연구)

  • Park, Jae-Seuk;Kim, Jae-Yeal;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.3
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    • pp.470-478
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    • 1997
  • Background : Phagocytosis is probably the first step for mycobacteria to be virulent in host because virulent strains are more readily phagocytosed by macrophage than attenuated strains. According to the traditional concept, multi-drug resistant strains have been regarded as less virulent. However, this concept has been challenged, since recent studies(reported) showed that the degree of virulence and drug-resistance is not related. The purpose of this study is to evaluate whether the phagocytic activity of M.tuberculosis by peripheral blood mononuclear cells(PBMC) is different according to drug-resistance or host factor. To evaluate this, we estimated the difference of phagocytic activity of drug-resistant and drug-sensitive M.tuberculosis and also estimated the phagocytic activity of PBMC from intractable tuberculosis patients and healthy controls. Methods : PBMC from ten intractable tuberculosis patients and twelve healthy control, and three different strains of heat-killed M.tuberculosis, ie, ADS(all drug sensitive), MDR(multi-drug resistant), and ADR(all drug resistant) were used. After incubation of various strains of M.tuberculosis with PBMC, the phagocytic activity was evaluated by estimating proportion of PBMC which have phagocytosed M.tuberculosis. Results : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains(Percentage of PBMC phagocytosed M.tuberculosis in healthy control : ADS : $32.3{\pm}2.9%$, ADR : $49.6{\pm}3.4%$, p = 0.0022, Percentage of PBMC phagocytosed M.tuberculosis in intractable tuberculosis patients : ADS : $34.9{\pm}3.6%$, ADR : $50.7{\pm}4.5%$, p = 0.0069). However, there was no difference in phagocytic activity of PBMC from healthy control and intractable tuberculosis patients. Conclusion : Drug-resistant strains of M.tuberculosis were phagocytosed easily than drug sensitive strains and host factors does not seems to influence the phagocytosis of M.tuberculosis.

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Cytotoxicity and Chemosensitizing Effect of Camellia(Camellia japonica) Tea Extracts (동백엽차와 화차의 세포독성 및 다제내성 극복효과)

  • 황은주;차영주;박민희;이장원;이숙영
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.3
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    • pp.487-493
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    • 2004
  • This study has been undertaken to increase availability of native camellia in Jeonnam as a medicinal resource and to isolate the effective components from them. Fresh leaf and flower of camellia, single camellia tea and camellia tea mixed with green tea, herbs were screened for cytotoxicity on MCF -7 (human breast adenocarcinoma pleual effusion), Calu-6 (human pulmonary carcinoma), SNU-601 (human gastric carcinoma) cells. Also their multidrug-resistance reversing activity were evaluated using drug sensitive AML-2/WT and multidrug-resistant AML-2/D100 cells. Among the camellia extracts, young leaf and camellia tea mixed with green tea had strong growth inhibitory effects in below 100 $\mu\textrm{g}$/mL against human cancer cells. In result, young leaf showed the strongest inhibitory effects on MCF -7 ($IC_{50}$/ = 100 $\mu\textrm{g}$/mL ↑), Calu-6 ($IC_{50}$/ = 79 $\mu\textrm{g}$/mL), and SNU -601 ($IC_{50}$/ = 39 $\mu\textrm{g}$/mL), and AML-2/WT ($IC_{50}$/ = 64 $\mu\textrm{g}$/mL). Chemosensitizing effect was the extracts of mature leaf ($IC_{50}$/ = 97 $\mu\textrm{g}$/mL, RF=3.0), roasted tea ($IC_{50}$/ = 76 $\mu\textrm{g}$/mL, RF = 2.6 ↑) and steam tea ($IC_{50}$/ = 70 $\mu\textrm{g}$/mL, RF=2.8 ↑) strongly potentiate vincristine cytotoxicity in AML-2/D100 cells. But their cytotoxicities to both sensitive AML-2/WT and resistant AML-2/D100 cells were in the same order of magnitude. This results indicate that crude extracts of camellia mature leaves would contain some principles which have chemosensitizing activity.

The Clinical Characteristics, Diagnosis, Treatment, and Outcomes of Patients with Tuberculosis at a Private University Hospital in Korea (국내 한 민간종합병원에서 결핵 환자의 진료 실태)

  • Jung, Young Ju;Park, I-Nae;Hong, Sang Bum;Oh, Yeon-Mok;Lim, Chae-Man;Lee, Sang Do;Koh, Younsuck;Kim, Woo Sung;Kim, Dong Soon;Kim, Won Dong;Shim, Tae Sun
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.2
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    • pp.194-204
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    • 2006
  • Background : Even though tuberculosis (TB) is still a major public concern in Korea, there is little data on the management of TB patients and its outcomes in the private sector. This study evaluated the status of TB treatment in the private sector. Methods : Sixteen-hundred-sixty-six TB patients who were notified in a private university hospital from 2001 to 2002 were enrolled in this study. The patients were divided into pulmonary ($TB_P$), extrapulmonary ($TB_E$), and combined ($TB_{P+E}$) groups, and were also divided into initial and retreatment groups. The clinical characteristics, diagnostic methods, treatment regimens, and outcomes were analyzed and compared. Results : The mean age of the 1,666 patients was 48.9 years and the male-to-female ratio was 1.3:1. The number of patients in the initial and retreatment groups of $TB_P$, and those of ($TB_E+TB_{P+E}$) were 809, 276, 480, 101, respectively. A bacteriological study was performed in 92.0% of cases, and a positive culture was confirmed in 58.1% and 31.7% of patients with TBP and ($TB_E+TB_{P+E}$), respectively (p<0.05). The AFB smear was positive in 45.4 % of the $TB_P$ patients. PCR was carried out in 60.4% of the ($TB_E+TB_{P+E}$) group. The MDR was detected in 14.0% of isolates. Overall, the treatment completion, default, and death rates were 70.2%, 13.5% and 1.9%, respectively. Conclusion : Even though the management of TB patients in a private hospital was satisfactory in terms of the national guidelines, the high default rate was is still a problem. Efforts to decrease the default rate either independently or in cooperation with the public sector will be needed.

Transfer of Genes for Antimicrobial Resistance and Toxin of Hemolytic Escherichia coli Isolated from Feces of Pig Suffering Diarrhea to Human Isolates (설사 증상의 돼지 분변에서 분리된 용혈성 대장균의 항생제 내성과 독소의 인체로부터 분리된 균주로의 전이)

  • Lee Kyenam;Jung Byeong Yeal;Lee Yeonhee
    • Korean Journal of Microbiology
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    • v.40 no.4
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    • pp.286-294
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    • 2004
  • Between 1997 and 1998 in Korea, 56 isolates of Escherichia coli were obtained from pig suffering diarrhea. Among those, 38 isolates that showed the hemolytic activity, antimicrobial resistance, and toxin production were studied. Among 38 isolates, thirty-six isolates $(94.7\%)$ were resistant to tetracycline, 27 isolates $(71.0\%)$ were resistant to ampicillin, 26 isolates $(68.4\%)$ were resistant to chloramphenicol, and 21 isolates $(55.2\%)$ were resistant to trimethoprim, while none was resistant to aztreonam, amikacin, and norfloxacin. Among these iso­lates, 21 isolates $(55.3\%)$ were multiple drug resistant to at least four different class antimicrobial agents. Extended spectrum $\beta-lactamase$ producing isolates were not detected in the double disk synergy test. In these hemolytic Escherichia coli, heat-stable enterotoxin $(89.5\%)$ was the most prevalent toxin, followed by vero­toxins $(47.4\%),$ and then heat-labile enterotoxin $(31.6\%).$ Except 8 isolates $(21.0\%)$ which produced ST only, 12 isolates $(31.6\%)$ produced ST and LT, 13 isolates $(34.2\%)$ produced ST, VT, and VTe, and 5 isolates $(13.2\%)$ produced VT and VTe. However, none produced all 4 types of toxin, simultaneously. The predominant serotype could not be determined by the agglutination method. Sixteen isolates $(42.1\%)$ were strongly adhered to T-24 bladder cell and 17 isolates $(44.7\%)$ were to Caco-2 intestinal cell. Especially, 11 strains $(28.9\%)$ were evaluated as strongly adhesive to both T-24 cells and Caco-2 cells. Genes for toxin and the antimicrobial resistance were transferred to clinical isolates of Escherichia coli from human urine by the filter mating method. Results suggest the possibility that antimicrobial resistance and toxin can be transferred from animals to humans by direct con­tact of resistant bacteria as well as gene transfer, although there was no correlation between toxin production, adherent activity, and antimicrobial resistance among hemolytic E. coli isolated from pig suffering diarrhea.

Clinical Meaning of INNO-LiPA Test in the Diagnosis of Rifampin Resistant Tuberculosis (Rifampin 내성 결핵의 진단에서 INNO-LiPA 검사법의 임상적 의미)

  • Chang, Yoon Soo;Kim, Young;Lee, Chang Youl;Choi, Jong Rak;Kim, Hyung Jung;Ahn, Chul Min;Kim, Sung Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.4
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    • pp.344-352
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    • 2003
  • Background : The prevalence of multidrug resistant tuberculosis (MDR-TB), resistant to isoniazid (INH) and rifampin (RFP), was 5.3% worldwide in 1995 and its increment has raised important public health problems. Resistance to RFP, one of the key drugs in the treatment of tuberculosis, results in grim clinical outcome. Recently rapid detection of RFP-resistant mutations in rpoB gene based on PCR method has become available. This study evaluated the prevalence of RFP resistance in first diagnosed, treatment failure, and recurred patients using INNO-LiPA test, and compared the results of INNO-LiPA with those of conventional mycobacterial drug susceptibility test. Methods : Forty-six patients, who were diagnosed of pulmonary tuberculosis and had revealed positive sputum AFB smear, were enrolled in this study from 1998 to 2002. The cases were classified as one three groups; first diagnosed, treatment failure, or recurred. RFP resistance was studied using an INNO-LiPA Rif. TB kit and compared with that obtained from drug susceptibility based on M. tuberculosis culture study. Results : Twenty-one out of 46 patients were enrolled under first diagnosis of pulmonary tuberculosis, 17 under treatment failure with first line drugs, and 8 under recurrence. The positive and negative predictive values of INNO-LiPA test in diagnosis in RFP resistant tuberculosis compared with conventional mycobacterial drug susceptibility test were 85.7% and 76.0%, respectively. INNO-LiPA result revealed rpoB gene mutation in 20 (80.0%) out of 25 patients who were diagnosed as treatment failure or recurrence, but in only 4 (19.0%) out of 21 patients who were first diagnosed as pulmonary tuberculosis. Conclusion : This study showed that RFP resistance could be diagnosed rapidly and accurately using INNO-LiPA test and that this test might be helpful for choosing second line anti-mycobacterial drugs. It might be of great help in clinical diagnosis and decision when used in complimentarily with drug susceptibility test based on M. tuberculosis culture.

Cytotoxicity and Multidrug -Resistance Reversing Activity of Extracts from Gamma-Irradiated Coix Zachryma-jobi L. var. ma-yuen Stapf Seed (감마선 조사된 율무종자의 세포독성 및 다제내성 극복활성)

  • Cha, Young-Ju;Lee, Sook-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.5
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    • pp.613-618
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    • 2005
  • This study was carried out to examine the effects of gamma irradiation on the cytotoxicity and multidrug-resistance reversing activity of methanol extracts from Coix lachryma-jobi L. var. me-yuen Stapf seed. The seed was irradiated with doses of 1, 4, 8, 16, 32 and 64 Gy of the gamma radiation, and then extracted by methanol. The extracts were examined for cytotoxicity on the human cancer cell lines, MCF-7 (human breast adenocarcinoma pleural effusion), Calu-6 (human pulmonary carcinoma) and SNU-601 (human gastric carcinoma) cells, and investigated for multidrug-resistance reversing activity using drug sensitive AML-2/WT and multidrug-resistant AML-2/D100 cells. The growth inhibitory activity of irradiated seed extracts on human cancer cell lines was higher than that of the control. In the case of Calu-6 cell line, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. $IC_{50}$ value in the MCF-7 cell line was measured in the only 8 Gy extract. And in the SNU-601 cell line as Calu-6, the effect of cytotoxicity was observed in the extracts of 4, 8 and 16 Gy. But the extracts of gamma-irradiated seed over 32 Gy showed little growth inhibitory effect against human cancer cell lines. In this result, 8 Gy extract had significant growth inhibitory in all human cancer cell lines $(Calu-6:\;633\;{\mu}g/mL,\;MCF-7:\;653\;{\mu}g/mL\;and\;SNU-601:\;683\;{\mu}g/mL)$. The extracts of 4, 8 and 16 Gy strongly potentiated vincristine cytotoxicity in AML-2/D100 cells. The reversal fold (RF) of 4, 8 and 16 Gy extracts was 1.7, 1.8 and 1.6, respectively. But their cytotoxicities to both sensitive AML-2/WT and resistant AML-2/D100 cells were in the same order of magnitude. These results indicate that the above samples would contain some principles which have cytotoxicity and multidrug-resistance reversing activity. Irradiation technology can be applied to promote physiological activities of medicinal plant seeds.

Trial for Drug Susceptibility Testing of Mycobacterium tuberculosis with Live and Dead Cell Differentiation (세포 염색 방법을 이용한 결핵균 감수성 검사법)

  • Ryu, Sung-Weon;Kim, Hyun-Ho;Bang, Mun-Nam;Park, Young-Kil;Park, Sue-Nie;Shim, Young-Soo;Kang, Seongman;Bai, Gill-Han
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.3
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    • pp.261-268
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    • 2004
  • Background : The resurgence of tuberculosis and outbreaks of multidrug resistant (MDR) tuberculosis have increased the emphasis for the development of new susceptibility testing of the Mycobacterium tuberculosis for the effective treatment and control of the disease. Conventional drug susceptibility testings, such as those using egg-based or agar-based media have some limits, such as the time required and difficulties in determining critical inhibitory concentrations, but these are still being used in many diagnostic laboratories because of no better lternatives, considering cost and accuracy. To overcome these limits, a rapid and simple method for new susceptibility testing, using live and dead assays, was applied for a bacterial cell viability assay to distinguish dead from live bacterial cells based on two-color fluorescence. Materials and Methods Strains : Forty strains were used in this study, 20 susceptible to all antituberculosis drugs and the other 20 resistant to the four first line antituberculosis drugs isoniazid, rifampicin, streptomycin and ethambutol. Antibiotics : The four antibiotics were dissolved in 7H9 broth to make the following solutions: $0.1{\mu}g\;isoniazid(INH)/m{\ell}$, $0.4{\mu}g\;rifampicin(RMP)/m{\ell}$, $4.0{\mu}g\;streptomycin(SM)/m{\ell}$ and $4.0{\mu}g\;ethambutol(EMB)/m{\ell}$. Results : Live and dead Mycobacterium tuberculosis cells fluoresced green and red with the acridin (Syto 9) and propidium treatments, respectively. These results are very well accorded with conventional drug susceptibility testing by proportional method on Lowensen-Jensen media (L-J) containing 4 drugs (INH, RMP, EMB and SM), showing a 93.7 % accordance rate in susceptible strains and 95% in resistant strains. Conclusion : The results of the drug susceptibility testing using the live and dead bacterial cell assay showed high accordance rates compared with the conventional proportion method on L-J. This finding suggests that the live and dead bacterial cell assay can be used as an alternative to conventional drug susceptibility testing for M. tuberculosis strains.

Gene Expression of Enzymes Related to Glutathione Metabolism in Anticancer Drug-resistant L1210 Sublines (항암제 내성 L1210세포의 Glutathione 대사 관련효소 유전자의 발현 양상)

  • Kim, Seong-Yong;Kim, Jae-Ryong;Kim, Jung-Hye
    • Journal of Yeungnam Medical Science
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    • v.12 no.1
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    • pp.32-47
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    • 1995
  • Glutathione(GSH) has a very important role in detoxification of cells and is closely related to antitumor drug-resistance of cancer cells. In order to evaluate the importance of glutathione metabolism in the drug-resistant cancer cells, the concentration of celluar GSH and activities of ${\gamma}$-glutamylcysteine synthetase(GCS), ${\gamma}$-glutamyl transpeptidase (GGT) and glutathione S-transferases(GST) in the adriamycin, vincristine, or cisplatin resistant L1210 (L1210AdR, L1210VcR, or L1210Cis) sublines were measured. Expression and amplification of GCS, GGT, and GST-${\pi}$ genes were also observed in the parent Ll210 and the drug-resistant Ll210 sublines. The concentration of GSH was increased 5.34 fold in L1210Cis, 2.83 fold in L1210VcR, and 1.78 fold in L1210AdR, compared to L1210. The activities of GCS and GGT were increased in drug-resistant L1210 sublines. The GST activity was increased in L1210VcR and L1210Cis but decreased in L1210AdR compared to Ll210. Expression of GCS, GGT, and GST-${\pi}$ genes were increased in the resistant L1210 sublines compare to the parent L1210 in northern blot analyses. Overexpression of GCS, GGT, and GST-${\pi}$ were observed in the resistant sublines, and the increases of the concentration of glutathione and the activities of GCS and GGT in the resistant sublines may be involved in a part of the drug-resistance in the resistant sublines.

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A Comparative Study of Domestic and International regulation on Mixed-fleet Flying of Flight crew (운항승무원의 항공기 2개 형식 운항관련 국내외 기준 비교 연구)

  • Lee, Koo-Hee
    • The Korean Journal of Air & Space Law and Policy
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    • v.30 no.2
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    • pp.403-425
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    • 2015
  • The Chicago Convention and Annexes have become the basis of aviation safety regulations for every contracting state. Generally, the State's aviation safety regulations refer to the Standards and Recommended Practices(SARPs) provided in the Annexes of the Chicago Convention. In order to properly reflect international aviation safety regulations, constant studies of the aviation fields are of paramount importance. This Paper is intended to identify the main differences between korean and foreign regulation and suggest a few amendment proposals on Mixed-fleet Flying(at or more two aircraft type operation) of flight crew. Comparing with these regulations, the korean regulations and implementations have some insufficiency points. I suggest some amendment proposals of korean regulations concerning Mixed-fleet Flying that flight crew operate aircraft of different types. Basically an operator shall not assign a pilot-in-command or a co-pilot to operate at the flight controls of a type of airplane during take-off and landing unless that pilot has operated the flight controls during at least three take-offs and landings within the preceding 90 days on the same type of airplane or in a flight simulator. Also, flight crew members are familiarized with the significant differences in equipment and/or procedures between concurrently operated types. An operator shall ensure that piloting technique and the ability to execute emergency procedures is checked in such a way as to demonstrate the pilot's competence on each type or variant of a type of airplane. Proficiency check shall be performed periodically. When an operator schedules flight crew on different types of airplanes with similar characteristics in terms of operating procedures, systems and handling, the State shall decide the requirements for each type of airplane can be combined. In conclusion, it is necessary for flight crew members to remain concurrently qualified to operate multiple types. The operator shall have a program to include, as a minimum, required differences training between types and qualification to maintain currency on each type. If the Operator utilizes flight crew members to concurrently operate aircraft of different types, the operator shall have qualification processes approved or accepted by the State. If applicable, the qualification curriculum as defined in the operator's Advanced Qualification Program could be applied. Flight crew members are familiarized with the significant differences in equipment and/or procedures between concurrently operated types. The difference among different types of airpcrafts decrease and standards for these airpcrafts can be applied increasingly because function and performance have been improved by aircraft manufacture company in accordance to basic aircraft system in terms of developing new aircrafts for flight standard procedure and safety of flight. Also, it becomes more necessary for flight crews to control multi aircraft types due to various aviation business and activation of leisure business. Nevertheless, in terms of flight crew training and qualification program, there are no regulations in Korea to be applied to new aircraft types differently in accordance with different levels. In addition, it has no choice different programs based on different levels because there are not provisions to restrict or limit and specific standards to operate at or more than two aircraft types for flight safety. Therefore the aviation authority introduce Flight Standardization and/or Operational Evaluation Board in order to analysis differences among aircraft types. In addition to that, the aviation authority should also improve standard flight evaluation and qualification system among different aircraft types for flight crews to apply reasonable training and qualification efficiently. For all the issue mentioned above, I have studied the ICAO SARPs and some state's regulation concerning operating aircraft of different types(Mixed-fleet flying), and suggested some proposals on the different aircraft type operation as an example of comprehensive problem solving. I hope that this paper is 1) to help understanding about the international issue, 2) to help the improvement of korean aviation regulations, 3) to help compliance with international standards and to contribute to the promotion of aviation safety, in addition.