• Title/Summary/Keyword: MDR3

Search Result 199, Processing Time 0.054 seconds

Pharmacokinetics of ofloxacin in Patients with Multidrug-Resistant Tuberculosis (다제내성결핵 환자에서 ofloxacin의 약동학적 분석)

  • Park, Seung-Kyu;Yoon, Young-Ran;Lee, Woo-Chul;Jun, Hyung-Min;Shon, Ji-Hong;Kim, Kyoung-Ah;Park, Ji-Young;Shin, Jae-Gook
    • Tuberculosis and Respiratory Diseases
    • /
    • v.52 no.2
    • /
    • pp.128-136
    • /
    • 2002
  • Background: There are few studies that have reported on the pharmacokinetic(PK) disposition of fluoroquinolones in patients with multi-drug resistant tuberculosis(MDR-Tb), even though fluoroquinolones are frequently co-prescribed to those patients. In this study, the PK disposition of ofloxacin, a fluoroquinolone, was evaluated in patients with MD R -Tb. Methods: Twenty patients with MDR-Tb were given 2nd line Tb drugs including ofloxacin (300mg twice a day), prothionamide, cycloserine, para-aminosalicylic acid, kanamycin, and streptomycin. The patients were grouped according to their body mass index(BMI) as an index of emaciation (group A : 18.5$\leq$BMI <23, group B : BMI < 18.5). Blood samples were serially drawn and urine samples were collected upto 24 hours after the last dose of those drugs at steady state (over 1 month). The ofloxacin concentrations were determined using HPLC (High Performance Liquid Chromatography). Results: The AUC of ofloxacin in group B was greater than that in group A ($31.4{\pm}8.9{\mu}g/ml{\cdot}h$ vs. $24.1{\pm}6.2{\mu}g/ml{\cdot}h$)(Check the symbols), (p<0.05). The total clearance(Cl/F) of ofloxacin was $0.16{\pm}0.03$ L/h/kg in group A, and $0.14{\pm}0.03$ L/h/kg in group B. The half-lives of ofloxacin in two groups were similar (group A : $5.3{\pm}0.8$ hours, group B : $5.7{\pm}0.9$ hours). In addition, the other PK parameters in two groups were also similar. Conclusions: The pharmacokinetics of ofloxacin in patients with MDR-Tb appears to be comparable with those of normal subjects, and the extent of emaciation appears to have an influence on the pharmacokinetics of ofloxaicn in chronic debilitated MDR-Tb patients.

High Expression of Lung Resistance Protein mRNA at Diagnosis Predicts Poor Early Response to Induction Chemotherapy in Childhood Acute Lymphoblastic Leukemia

  • Bhatia, Prateek;Masih, Shet;Varma, Neelam;Bansal, Deepak;Trehan, Amita
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.15
    • /
    • pp.6663-6668
    • /
    • 2015
  • Background: Treatment failure in leukemia is due to either pharmacokinetic resistance or cell resistance to drugs. Materials and Methods: Gene expression of multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and low resistance protein (LRP) was assessed in 45 pediatric ALL cases and 7 healthy controls by real time PCR. The expression was scored as negative, weak, moderate and strong. Results: The male female ratio of cases was 2.75:1 and the mean age was 5.2 years. Some 26/45 (58%) were in standard risk, 17/45(38%) intermediate and 2/45 (4%) in high risk categorie, 42/45 (93%) being B-ALL and recurrent translocations being noted in 5/45 (11.0%). Rapid early response (RER) at day 14 was seen in 37/45 (82.3%) and slow early response (SER) in 8/45 (17.7%) cases. Positive expression of MDR-1, LRP and MRP was noted in 14/45 (31%), 15/45 (33%) and 27/45 (60%) cases and strong expression in 3/14 (21%), 11/27 (40.7%) and 8/15 (53.3%) cases respectively. Dual or more gene positivity was noted in 17/45 (38%) cases. 46.5 % (7/15) of LRP positive cases at day 14 were in RER as compared to 100% (30/30) of LRP negative cases (p<0.05). All 8 (100%) LRP positive cases in SER had strong LRP expression (p=<0.05). Moreover, only 53.3% of LRP positive cases were in haematological remission at day 30 as compared to 100% of LRP negative cases (p=<0.05). Conclusions: Our study indicated that increased LRP expression at diagnosis in pediatric ALL predicts poor response to early treatment and hence can be used as a prognostic marker. However, larger prospective studies with longer follow up are needed, to understand the clinical relevance of drug resistance proteins.

The Criticality Analysis of Spent Fuel Pool with Consolidated Fuel in KNU 9 & 10 (조밀화 집합체로 중간저장하는 경우 원자력 발전소 9, 10호기의 사용 후 핵연료 저장조의 임계분석)

  • Jae, Moo-Sung;Park, Goon-Cherl;Chung, Chang-Hyun;Jang, Jong-Hwa
    • Nuclear Engineering and Technology
    • /
    • v.20 no.1
    • /
    • pp.27-34
    • /
    • 1988
  • Since the lack of the spent fuel storage capcity has been expected for all Korean nuclear power plants in the mid-1990s, the maximum density rack (MDR) with consolidated fuels can be proposed to overcome the shortage of the storage capacity in KNU 9 & 10 which have most limited capacities. To ensure the safety when the alternatives are applied in the KNU 9 & 10, the multiplication factor are calculated with varying the rack pitch and the thickness of consolidated storage box by the AMPX-KENO IV codes. The computing system is verified by the benchmark calculation with criticality experiments for arrays of consolidated fuel modules, which was reported by B & W in 1981. Also an abnormal condition, i.e. malposition accident, is simulated. The results indicate that the KNU 9 & 10 storage pools with consolidated fuel are safe in the view of the criticality. Thus the storage capacity can be expanded from 9/3 cores into 27/3 cores even with considering equipments and cooling spaces.

  • PDF

Prediction Models of P-Glycoprotein Substrates Using Simple 2D and 3D Descriptors by a Recursive Partitioning Approach

  • Joung, Jong-Young;Kim, Hyoung-Joon;Kim, Hwan-Mook;Ahn, Soon-Kil;Nam, Ky-Youb;No, Kyoung-Tai
    • Bulletin of the Korean Chemical Society
    • /
    • v.33 no.4
    • /
    • pp.1123-1127
    • /
    • 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.

Formal Modeling and Verification of an Information Retrieval System (정보검색시스템의 모델링 및 정형 검증)

  • 김종환;박혜숙;방기석;장성호;백두권
    • Proceedings of the Korean Information Science Society Conference
    • /
    • 2001.10a
    • /
    • pp.457-459
    • /
    • 2001
  • 정보검색시스템은 지역적으로 분산된 이기종의 컴퓨터들 간의 데이터 교환과 다양한 종류의 DB에 대한접근을 가능하게 함으로써, 기업에게 공급망 관리에 대한 통합된 정보를 제공한다. 정보검색시스템은 X3.285에 기반한 데이터 레지스트리 모델을 이용하여 모델링되었고, 모델링이 주어진 가정 하에서 요구사항을 만족하는지를 검증하기 위해 핵심 부분인 메타데이터 레지스트리 관리기(MDR Manager) 부분 만을 SMV를 이용하여 검증하였다.

  • PDF

Occurrence and Characteristics of Methicillin-Resistant and -Susceptible Staphylococcus aureus Isolated from the Beef Production Chain in Korea

  • Lee, Haeng Ho;Lee, Gi Yong;Eom, Hong Sik;Yang, Soo-Jin
    • Food Science of Animal Resources
    • /
    • v.40 no.3
    • /
    • pp.401-414
    • /
    • 2020
  • The emergence and persistence of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in livestock animals have been reported as a potential risk factor for transmission to humans. In this study, we investigated the nationwide prevalence and characteristics of MRSA and MSSA in the Korean beef production system, including retail markets, slaughterhouses, and cattle farms. From a total of 1,285 samples, only 5 MRSA strains were isolated: from a farmer (1 ST72 MRSA), a carcass sample from a slaughterhouse (1 ST72 MRSA), and beef cattle (3 ST5 MRSA). In addition, 11 MSSA strains were isolated from beef cattle (n=3), humans (1 farmer, 1 slaughterhouse worker, and 4 retail market workers), and carcass samples (n=1) and slaughterhouse environment (n=1). Although the prevalence of MRSA and MSSA in beef cattle was much lower than that reported in pigs, 5/5 MRSA and 2/11 MSSA strains displayed multiple drug resistance (MDR) phenotypes. Unlike the swine-associated MRSA, no correlation was found between tetracycline/zinc resistance and MDR phenotype. However, MRSA strains had an identical set of staphylococcal enterotoxins and exhibited enhanced levels of resistance to antimicrobial peptides (PMAP-36 and LL-37) compared to the MSSA strains. In conclusion, continued and systemic surveillance of livestock, meat products, and humans in close contact with livestock/meat products is necessary to prevent the transmission of MRSA and MSSA to humans.

Role of Microbiologic Culture Results of Specimens Prior to Onset of Ventilator-Associated Pneumonia in the Patients Admitted to Intensive Care Unit (인공호흡기연관 폐렴의 경험적 항생제 선택 시 이전 호흡기검체의 유용성)

  • Kim, Ji-Hye;Yoon, Sung-Chul;Lee, Yu-Mi;Son, Ji-Woong;Choi, Eu-Gene;Na, Moon-Jun;Kwon, Sun-Jung
    • Tuberculosis and Respiratory Diseases
    • /
    • v.72 no.1
    • /
    • pp.30-36
    • /
    • 2012
  • Background: Patients with ventilator-associated pneumonia (VAP) in intensive care unit (ICU) have a high mortality rate. The routine surveillance cultures obtained previously or an ATS guideline for hospital-acquired pneumonia was used in selecting initial antimicrobials. The object of this study was to compare the respiratory samples before VAP and bronchoalveolar lavage (BAL) culture. Methods: 54 patients underwent fiberoptic bronchoscopy to obtain BAL samples. We reviewed microbiologic specimen results of prior respiratory specimens (pre-VAP) and BAL. Results: Among 51 patients with 54 VAP episodes, 52 microorganisms of pre-VAP and 56 BAL samples were isolated. Pre-VAP included 21.2% of MRSA, and 32.6% of multidrug resistant-Acinetobacter baumannii (MDR-AB). BAL samples comprised 25.0% of MRSA, 26.7% of MDR-AB, 14.3% of Stenotrophomonas maltophilia and 3.6% of Klebsiella pneumonia in order. In pre-VAP samples compared to BAL samples, only 35.2% were identical. In BAL samples compared to pre-VAP samples obtained in 5 days before the onset of VAP, only 43.6% were identical. However, among BAL samples compared to pre-VAP samples obtained after more than 5 days, 13.3% were identical (p=0.037). Conclusion: Based on these data, pre-VAP samples obtained prior to 5 day onset of VAP may help to predict the causative microorganisms and to select appropriate initial antimicrobials.

Effect of Korean Red Ginseng extracts on drug-drug interactions

  • Kim, Se-Jin;Choi, Seungmok;Kim, Minsoo;Park, Changmin;Kim, Gyu-Lee;Lee, Si-On;Kang, Wonku;Rhee, Dong-Kwon
    • Journal of Ginseng Research
    • /
    • v.42 no.3
    • /
    • pp.370-378
    • /
    • 2018
  • Background: Ginseng has been the subject of many experimental and clinical studies to uncover the diverse biological activities of its constituent compounds. It is a traditional medicine that has been used for its immunostimulatory, antithrombotic, antioxidative, anti-inflammatory, and anticancer effects. Ginseng may interact with concomitant medications and alter metabolism and/or drug transport, which may alter the known efficacy and safety of a drug; thus, the role of ginseng may be controversial when taken with other medications. Methods: We extensively assessed the effects of Korean Red Ginseng (KRG) in rats on the expression of enzymes responsible for drug metabolism [cytochrome p450 (CYP)] and transporters [multiple drug resistance (MDR) and organic anion transporter (OAT)] in vitro and on the pharmacokinetics of two probe drugs, midazolam and fexofenadine, after a 2-wk repeated administration of KRG at different doses. Results: The results showed that 30 mg/kg KRG significantly increased the expression level of CYP3A11 protein in the liver and 100 mg/kg KRG increased both the mRNA and protein expression of OAT1 in the kidney. Additionally, KRG significantly increased the mRNA and protein expression of OAT1, OAT3, and MDR1 in the liver. Although there were no significant changes in the metabolism of midazolam to its major metabolite, 1'-hydroxymidazolam, KRG significantly decreased the systemic exposure of fexofenadine in a dose-dependent manner. Conclusion: Because KRG is used as a health supplement, there is a risk of KRG overdose; thus, a clinical trial of high doses would be useful. The use of KRG in combination with P-glycoprotein substrate drugs should also be carefully monitored.