• Title/Summary/Keyword: Drug response

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Gene Expression Profiling of 6-MP (6-mercaptopurine) in Liver

  • Kim Hyung-Lae;Kim Han-Na;Lee Eun-Ju
    • Genomics & Informatics
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    • v.4 no.1
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    • pp.16-22
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    • 2006
  • The KFDA (Korea Food & Drug Administration) has performed a collaborative toxicogenomics project since 2003. Its aim is to construct a toxicology database of 12 compounds administered to mice at initial phase. We chose 6-MP (6-mercaptopurine) which has been used in the treatment of childhood leukemia. It was administered at low (0.224 mg/kg) and at high (2.24 mg/kg) dose (5 mice per group) intraperitonealy to the postnatal 6 weeks mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after scarification. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to 6-MP induced toxicity, including lipid metabolism abnormality, inflammatory response, oxidative stress, ATP depletion and cell death. The potential toxic effects appearing as gene expression changes are dependent of the time of 6-MP but independent of the dosage of it. This study would contribute to establishment of international database as well as national one about hepatotoxicity.

CONSCIOUS SEDATIVE DRUGS: A CLINICAL STUDY (의식하 진정에 사용된 약물에 관한 임상적 연구)

  • Kim, Sang-Ryul;Kim, Su-Gwan;Yeo, Hwan-Ho
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.22 no.4
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    • pp.436-441
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    • 2000
  • The purpose of this retrospective study is to investigate the effects of conscious sedation in an outpatient setting. Data from 292 patients (154 males, 138 females), sedated for minor oral surgery, were studied using various parameters including age and sex distribution, as well as according to procedures and each drug group. Results show that this intravenous conscious sedation technique is a safe and effective method of controlling behaviour, but one has to be prepared to deal with any emergencies or complications. The specific results are as follows: 1. Most procedures (265/292) were used to Valium mixed with Demerol and Midazolam mixed with Demerol. 2. Valium revealed a high incidence of pain upon injection and symptoms limited to daily activity and thrombophlebitis. 3. Nausea and vomiting manifested in the procedure using Demerol. 4. The patient manifested comfort similar in response to the same drugs used in another treatment.

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STABILITY OF DELAY-DISTRIBUTED HIV INFECTION MODELS WITH MULTIPLE VIRAL PRODUCER CELLS

  • ELAIW, A.M.;ELNAHARY, E.KH.;SHEHATA, A.M.;ABUL-EZ, M.
    • Journal of the Korean Society for Industrial and Applied Mathematics
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    • v.22 no.1
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    • pp.29-62
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    • 2018
  • We investigate a class of HIV infection models with two kinds of target cells: $CD4^+$ T cells and macrophages. We incorporate three distributed time delays into the models. Moreover, we consider the effect of humoral immunity on the dynamical behavior of the HIV. The viruses are produced from four types of infected cells: short-lived infected $CD4^+$T cells, long-lived chronically infected $CD4^+$T cells, short-lived infected macrophages and long-lived chronically infected macrophages. The drug efficacy is assumed to be different for the two types of target cells. The HIV-target incidence rate is given by bilinear and saturation functional response while, for the third model, both HIV-target incidence rate and neutralization rate of viruses are given by nonlinear general functions. We show that the solutions of the proposed models are nonnegative and ultimately bounded. We derive two threshold parameters which fully determine the positivity and stability of the three steady states of the models. Using Lyapunov functionals, we established the global stability of the steady states of the models. The theoretical results are confirmed by numerical simulations.

Preventive Effects of a Probiotic Mixture in an Ovalbumin-Induced Food Allergy Model

  • Shin, Hee-Soon;Eom, Ji-Eun;Shin, Dong-Uk;Yeon, Sung-Hum;Lim, Seong-Il;Lee, So-Young
    • Journal of Microbiology and Biotechnology
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    • v.28 no.1
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    • pp.65-76
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    • 2018
  • Although there has been a steady increase in the prevalence of food allergies worldwide in recent decades, no effective therapeutic strategies have been developed. Modulation of the gut microbiota composition and/or function through probiotics has been highlighted as a promising target for protection against food allergies. In this study, we aimed to investigate the allergy-reducing effects of a probiotic mixture (P5: Lactococcus lactis KF140, Pediococcus pentosaceus KF159, Lactobacillus pentosus KF340, Lactobacillus paracasei 698, and Bacillus amyloliquefaciens 26N) in mice with ovalbumin (OVA)-induced food allergy. Administration of P5 significantly suppressed the oral OVA challenge-induced anaphylactic response and rectal temperature decline, and reduced diarrhea symptoms. Moreover, P5 also significantly inhibited the secretion of IgE, Th2 cytokines (interleukin (IL)-4, IL-5, IL-10, and IL-13), and Th17 cytokines (IL-17), which were increased in mice with OVA-induced food allergy, and induced generation of CD4+Foxp3+ regulatory T cells. These results revealed that P5 may have applications as a preventive agent against food allergy.

Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samples

  • Barwe, Sonali P.;Gopalakrisnapillai, Anilkumar;Mahajan, Nitin;Druley, Todd E.;Kolb, E. Anders;Crowgey, Erin L.
    • Genomics & Informatics
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    • v.18 no.1
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    • pp.6.1-6.9
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    • 2020
  • Acute leukemia represents the most common pediatric malignancy comprising diverse subtypes with varying prognosis and treatment outcomes. New and targeted treatment options are warranted for this disease. Patient-derived xenograft (PDX) models are increasingly being used for preclinical testing of novel treatment modalities. A novel approach involving targeted error-corrected RNA sequencing using ArcherDX HemeV2 kit was employed to compare 25 primary pediatric acute leukemia samples and their corresponding PDX samples. A comparison of the primary samples and PDX samples revealed a high concordance between single nucleotide variants and gene fusions whereas other complex structural variants were not as consistent. The presence of gene fusions representing the major driver mutations at similar allelic frequencies in PDX samples compared to primary samples and over multiple passages confirms the utility of PDX models for preclinical drug testing. Characterization and tracking of these novel cryptic fusions and exonal variants in PDX models is critical in assessing response to potential new therapies.

REGULATION OF RAT ADRENAL MEDULLARY PHENYLETHANOL AMINE N-METHYLTRANSFERASE

  • Yoo, Young-Sook;Wong, Dona L.
    • Toxicological Research
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    • v.6 no.1
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    • pp.89-97
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    • 1990
  • Neural regulation of phenylethanolamine N-meth-yltransferase (PNMT) was studied with reserpine as a neuronal agent in rat adrenal medulla. The enzyme activity assay and northern blot analysis were performed to determine whether the induction of PNMT activity after reserpine treatment was associated with elevation of mRNA coding for PNMT. The i.p. administration of reserpine (2.5 mg/kg) on alternate days fot 4 injections to rats brought about 30% increase of adrenal medullary PNMT activity and approximately 60% stimulation of the PNMT mRNA level in rat adrenal gland. A dose of 10 mg/kg of reserpine was chosen to perform optimum induction of PNMT activity in the rat adrenal gland based on the results of dose response curve of reserpine. Time course reserpine (10 mg/kg) effects on the rat adrenal medullary PNMT were as follows: 1. Peripheral PNMT activity reached maximum level after 7 days of drug treatment on alternate days. 2. Trans-synaptic stimulation by reserpine increased pretranslational activity of rat adrenal PNMT, but not translational activity. 3. Immunotitration of PNMT molecule after reserpine treatment indicated that reserpine produced an enzyme with greater antibody affinity than endogenous molecule in the rat adrenal gland.

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Genetic characteristics of Phytophthora capsici mutants induced by dimethomorph

  • Nam Moon;Lee, Kyoung-Mi;Jang, Kuang-Il;Jeong young Song;Kim, Hong-Gi
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.117.1-117
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    • 2003
  • Phytophthora blight, caused by P. capsici, is very important disease of pepper. Many fungicides to control of Phytophthora blight have been developed, but most of fungicides disappeared in short periods. Nowadays dimethomorph was known as one of the most effective to control of this disease. P. capsici isolates from pepper fields were collected and surveyed their growth in dimethomorph amended V8 medium in order to evaluate their fungicides resistance. The fungicide resistant isolates were not founded among them. Most of the sensitive isolates were inhibited perfectly in V8 medium amended with 10ppm dimethomorph. Mutants of P. capsici by dimethomorph, was grown very well in 250ppm. The difference of pathogenicity, colony morphology, drug response, RT-PCR results was identified between sensitive and resistance isolates. This study should be provided a basic information about the occurrence of dimethomorph resistant isolates and genetic changes in P. capsici population.

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Downregulated microRNAs in the colorectal cancer: diagnostic and therapeutic perspectives

  • Hernandez, Rosa;Sanchez-Jimenez, Ester;Melguizo, Consolacion;Prados, Jose;Rama, Ana Rosa
    • BMB Reports
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    • v.51 no.11
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    • pp.563-571
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    • 2018
  • Colorectal cancer (CRC), the third most common cancer in the world, has no specific biomarkers that facilitate its diagnosis and subsequent treatment. The miRNAs, small single-stranded RNAs that repress the mRNA translation and trigger the mRNA degradation, show aberrant levels in the CRC, by which these molecules have been related with the initiation, progression, and drug-resistance of this cancer type. Numerous studies show the microRNAs influence the cellular mechanisms related to the cell cycle, differentiation, apoptosis, and migration of the cancer cells through the post-transcriptionally regulated gene expression. Specific patterns of the upregulated and down-regulated miRNA have been associated with the CRC diagnosis, prognosis, and therapeutic response. Concretely, the downregulated miRNAs represent attractive candidates, not only for the CRC diagnosis, but for the targeted therapies via the tumor-suppressing microRNA replacement. This review shows a general overview of the potential uses of the miRNAs in the CRC diagnosis, prognosis, and treatment with a special focus on the downregulated ones.

Switch to Olanzapine from Clozapine or Risperidone and 12-months Follow Up (Clozapine과 Risperidone에서 Olanzapine으로 교체 연구 : 12개월 추적연구)

  • Cho, Bang Hyun;Jung, In Kwa;Paik, Jong Woo
    • Korean Journal of Biological Psychiatry
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    • v.8 no.1
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    • pp.140-146
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    • 2001
  • In clinical setting, treatment-refractoriness, medication induced tardive dyskinesia and amenorrhea in chronic schizophrenia are frequently problematic. However, there are few guideline solving these problem available to clinicians. The goal of this study was collecting clinical data on clinical effectiveness and predictors of response of switching to olanzapine. We attempted to switch to olanzapine from risperidone and clozapine in chronic 31(risperidone 17, clozapine 14) schizophrenia and schizoaffective disorder patients suffering from sustained symptoms, weekly blood monitoring, medication induced tardive dyskinesia and amenorrhea. Previous antipsychotics dosage was gradually decreased for 2 or 3weeks, at the same time olanzapine dosage was gradually increased. At baseline, after 1 week, after 2 weeks and after 4 weeks we checked Brief Psychiatric Rating Scale, Clinical Global Impression Scale, Sympson-Angus Rating Scale, Barnes Akathisia Rating Scale and followed up after 12 months. Successful switch after 4 weeks was achieved in 25 patients(clozapine 9(64.2%), risperidone 16(94.1%)). Overall, mean BPRS and CGI scores increased significantly. Successful maintenance after 12 months was achieved in 17 patients(clozapine 5(35.7%), risperidone 12(70.5%)). Overall, mean BPRS and CGI scores increased significantly too. Switching to olanzapine from other atypical antipsychotics is recommendable in chronic schizophrenia with treatment refractoriness and drug induced side effect.

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Comparative Analysis of the Seriousness of the Adverse Events and Risk of Targeted Therapy for Metastatic Renal Cell Carcinoma Among Medical Professionals (전이성신세포암 표적치료제의 부작용 심각도 및 위해에 대한 전문가그룹별 비교분석)

  • Park, Mi-Hae;Rhee, Jin-Nie;Lee, Eui-Kyung
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.100-105
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    • 2011
  • The perception of the 20 adverse events of targeted therapy for metastatic renal cell carcinoma was compared among medical professionals. Thirty-seven oncologists, 167 nurses and 79 pharmacists participated in the survey, and the response rate was 61.9%, 98.2%, 84.9%, respectively. Results showed that the most serious adverse event was GI perforation (8.83 points, 10 being the most serious), whereas the least serious was anemia (5.32 points). There were significant differences among oncologists, nurses and pharmacists especially for the moderately-serious adverse event such as wound-healing complication and lymphopenia. Adverse Events Composite Score (AECS) for each targeted therapy was calculated by multiplying adverse event incidence rate and seriousness score. Sunitinib had the highest score at 6.86 point and bevacizumab had the lowest at 2.1. Among professional groups oncologists showed the lowest AECS, whereas nurses had the highest. The gap on the perception of the adverse events among medical professionals needs to be reduced to get better outcomes of medical therapies for cancer patients.