• Journal of The Korean Society of Clinical Toxicology
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• v.1 no.1
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• pp.27-33
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• 2003

Purpose: According as the accessibility about drugs becomes various, the occurrence of drug intoxication is increasing. Since report that doxylamine causes rhabdomyolysis often, drug-induced rhabdomyolysis is one of the most important complications in patients with drug intoxication. Acute renal failure (ARF)'s availability is important to the management in rhabdomyolysis, but report about rhabdomyolysis or ARF occurrence for whole intoxicated drugs is lacking up to now. Methods: This research did to 61 patient who had rhabdomyolysis of drug intoxication. First, object patients were divided into two gruops: doxylamine-ingested (Group I) vs non-doxylamine ingested (Group II). And then we analyzed on the early patient's clinical events and laboratory data. We used ROC curve to recognize'the early clinical factors that could forecast ARF appearance among these patients in addition. Results: Almost rhabdomyolysis was happened by doxylamine in drug intoxication ($55.7\%$). However, as compared to group II, group I showed better clinical course, lesser ARF occurrence and hemodialysis requirement. In group II, time was longer in hospital reaching from intoxication, the ARF occurrence rate was higher ($52.6\%$). Analyzing the ROC curve to useful initial factors, they were creatinine, uric acid and interval time from ingestion to hospital. These cut-off values were 1.44 mg/dL, 6.8 mg/dL and 5 hrs. Sensitivity for ARF estimate was $100\%$, specificity $69-98\%$. Conclusion: Compared to group II, Doxylamine-ingested group showed good clinical course. Creatinine, uric acid, interval time from ingestion to hospital aided in ARF estimate in drug-induced rhabdomyolysis.

• YAKHAK HOEJI
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• v.55 no.2
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• pp.106-115
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• 2011

Systematic toxicological analysis (STA) means the process for general unknown screening of drugs and toxic compounds in biological fluids. In order to establish STA, in previous study we investigated pattern of drugs & poisons in autopsy cases during 2007~2009 in Korea, and finally selected 62 drugs as target drugs for STA. In this study, rapid and simple drug identification and quantitative analytical program by gas chromatography-mass spectrometry(GC-MS) was developed. The in-house program, "DrugMan", consisted of modified chemstation data analysis menu and newly developed macro modules. Total 55 drugs among 62 target drugs were applied to this program, they were 14 antidepressants, 8 anti-histamines, 5 sedatives/hypnotics, 5 narcotic analgesics, 3 antipsychotic drugs, and etc. For calibration curves, fifty five drugs were divided into four groups of range considering their therapeutic or toxic concentrations in blood specimen, i.e. 0.05~1 mg/l, 0.1~1 mg/l, 0.1~5 mg/l or 0.5~10 mg/l. Standards spiked bloods were extracted by solid-phase extraction (SPE) with trimipramine-D3 as internal standard. Parameters such as retention times, 3 mass fragment ions, and calibration curves for each drug were registered to DrugMan. A series of identification, semi quantitation of target drugs and reporting the results were performed automatically. Calibration curves for most drugs were linear with correlation coefficients exceeding 0.98. Sensitivity rate of DrugMan was 0.90 (90%) for 55 drugs at the level of 0.5 mg/l. For standard spiked bloods at the level of 0.5 mg/l for 29 drugs, semi quantitative concentrations were ranged 0.36~0.64 mg/l by DrugMan. If more drugs are registered to database in DrugMan in further study, it will be useful tools for STA in forensic toxicology.

• Mycobiology
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• v.42 no.1
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• pp.52-58
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• 2014

A nucleoside diphosphate-linked moiety X (Nudix) hydrolase-like gene, YSA1, has been identified as one of the gromwell plant extract-responsive genes in Cryptococcus neoformans. Ysa1 is known to control intracellular concentrations of ADP-ribose or O-acetyl-ADP-ribose, and has diverse biological functions, including the response to oxidative stress in the ascomycete yeast, Saccharomyces cerevisiae. In this study, we characterized the role of YSA1 in the stress response and adaptation of the basidiomycete yeast, C. neoformans. We constructed three independent deletion mutants for YSA1, and analyzed their mutant phenotypes. We found that ysa1 mutants did not show increased sensitivity to reactive oxygen species-producing oxidative damage agents, such as hydrogen peroxide and menadione, but exhibited increased sensitivity to diamide, which is a thiol-specific oxidant. Ysa1 was dispensable for the response to most environmental stresses, such as genotoxic, osmotic, and endoplasmic reticulum stress. In conclusion, modulation of YSA1 may regulate the cellular response and adaptation of C. neoformans to certain oxidative stresses and contribute to the evolution of antifungal drug resistance.

• Journal of Yeungnam Medical Science
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• v.37 no.4
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• pp.277-285
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• 2020

Tuberculosis (TB) is still a major health problem worldwide. Especially, multidrug-resistant TB (MDR-TB), which is defined as TB that shows resistance to both isoniazid and rifampicin, is a barrier in the treatment of TB. Globally, approximately 3.4% of new TB patients and 20% of the patients with a history of previous treatment for TB were diagnosed with MDR-TB. The treatment of MDR-TB requires medications for a long duration (up to 20-24 months) with less effective and toxic second-line drugs and has unfavorable outcomes. However, treatment outcomes are expected to improve due to the introduction of a new agent (bedaquiline), repurposed drugs (linezolid, clofazimine, and cycloserine), and technological advancement in rapid drug sensitivity testing. The World Health Organization (WHO) released a rapid communication in 2018, followed by consolidated guidelines for the treatment of MDR-TB in 2019 based on clinical trials and an individual patient data meta-analysis. In these guidelines, the WHO suggested reclassification of second-line anti-TB drugs and recommended oral treatment regimens that included the new and repurposed agents. The aims of this article are to review the treatment strategies of MDR-TB based on the 2019 WHO guidelines regarding the management of MDR-TB and the diagnostic techniques for detecting resistance, including phenotypic and molecular drug sensitivity tests.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.2
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• pp.89-97
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• 2004

Many strains of Staphylococcus aureus were isolated from pus samples from primary, secondary, and tertiary medical institutions and were subjected to an antibiotic sensitivity test. Ciprofloxacin, clindamycin, erythromycin, gentamicin, oxacillin penicillin, tetracycline, trimethoprim/sulfamethoxazole, vancomycin and teicoplanin were used for the antibiotic sensitivity test. The strains showed hightest resistance to penicillin(91%), but all of strains tested were susceptible to vancomycin and teicoplanin. The isolated multi-drug(penicillin-tetracycline-ciprofloxacin-clindamycin-erythromycin- oxacillin-gentamicin) resistant S. aureus were analyzed genotypically using an AP-PCR(Arbitrarily Primed polymerase chain reaction) with an arbitrary 3 primers. Based on the result for genotype analysis, the genotypes identified by S1 primer did not coincide with those of S2 or E2 primers. Genotypes identified by S2 primer did not coincide with those of S1 or E2 primers. Also genotypes identified by the E2 primer did not coincide with those of S1 or S2 primers. Therefore, an analysis of AP-PCR test with multiple primers will provide more sensitive identification. A strain from a secondary medical institution and a strain from a tertiary medical institution which showed the same genotype for S1, S2, and E2 primers are required for further epidemiological study.

• Korean Journal of Food Science and Technology
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• v.39 no.4
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• pp.372-379
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• 2007

A high-performance liquid chromatography-electrospray ionization (HPLC-ESI) tandem MS was developed for the rapid and simultaneous determination of forbidden medicines in dietary supplements. Thirteen medicinal components such as PDE-5 inhibitors and their analogues, and the newly identified dimethylsildenafil and xanthoanthrafil, were included in this study. After tentative standardization of molecular ions in both polarities using thirteen references on the mass spectrometer, with ESI-continuous infusion via the syringe pump method, the relative intensity of the ions present in the resulting spectra was quantitatively compared. From the results, the ion mode was selected depending on each reference's characteristics. A HPLC method coupled with the ESI mode was developed considering the matrix effect and interference depending on the type of sample. The validation test of the developed method was followed by carrying out precision, accuracy, recovery, sensitivity and linearity, etc. The method showed sufficiently high sensitivity, reproducibility, and specificity, and produced 4 times faster results when compared with the existing HPLC/UV method for the determination of forbidden compounds in dietary supplements.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6569-6572
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• 2013

In cervical cancer, one of the most common malignant tumors in women worldwide, miR-126 has been reported to exhibit decreased expression. However, its role in cervical cancer cell proliferation and drug sensitivity has remained relatively unexplored. Here, we compared the expression of miR-126 in cervical cancer tissues (n = 20) with that in normal cervical tissue (n = 20) using quantitative RT-PCR. The viability of Siha cervical cancer cells was further measured by MTT assay after transfection with miR-126 mimic (Siha-miR-126 mimic) or microRNA mimic negative control (Siha-miR mimic NC) and after treatment with various concentrations of bleomycin (BLM). IC50s were calculated, and the survival rates (SRs) of Siha cells were calculated. miR-126 expression in cervical cancer tissue was significantly decreased compared with that in normal cervical tissue (P < 0.01). The relative SRs of Siha-miR-126 mimic cells were also significantly decreased compared with those of Siha-miR mimic NC cells at 24-96 h after transfection. The IC50 of BLM in Siha-miR-126 mimic cells ($50.3{\pm}2.02{\mu}g/mL$) was decreased compared with that in Siha-miR mimic NC cells ($70.5{\pm}4.33{\mu}g/mL$) at 48 h after transfection (P < 0.05). Finally, the SRs of Siha-miR-126 mimic cells were significantly lower than those of SihamiR mimic NC cells after cultured in medium containing 40 ${\mu}g/mL$ BLM for 24-96 h (P < 0.05). These results suggest that miR-126 is expressed at low levels in cervical cancer. Upregulation of miR-126 inhibited cervical cancer cell proliferation and enhanced the sensitivity to BLM. Thus, miR-126 may represent a novel approach to cervical cancer treatment.

• The Journal of the Korean Society for Microbiology
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• v.22 no.2
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• pp.175-184
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• 1987

The use of alkylating agent cyclophosphamide(CY), a widely used antitumor drug is well known as a potent immunosuppressant and has been used as a probe for investigating the functional capabilities of lymphocyte subsets of both T and B cells that play an important role in the regulation of the immune response. The present study was undertaken in an effort to assess the effects of CY on immunological memory in murine model. CY, given as a single dose of CY(250mg/kg) before sensitization with sheep red blood cells(SRBC) enhanced the primary response of Arthus and delayed-type hypersensitivity(DTH), as measured by footpad swelling reaction, but suppressed their tertiary DTH response. The similar CY pretreatment enhanced both the primary and tertiary hemagglutinin(HA) responses to SRBC, and the tertiary antibody response against polyvinylpyrroridone(PVP), a thymus-independent antigen but not the primary response against PVP. CY, given as a single dose of 250mg/kg 2 days before the primary immunization and two doses of 100mg/kg 2 days before the secondary and tertiary immunization, markedly suppressed the tertiary DTH and HA responses to SRBC. However, CY, given as small multiple daily doses(10mg/kg) over 4 days before sensitization but not after sensitization, enhanced the secondary HA response to SRBC. Contact sensitivity to dinitrofluorobenzene(DNFB) was suppressed by the drug, given either as a single large dose(300mg/kg) or as multiple dose(10mg/kg) administered 2 days before, together with or after DNFB sensitization. This suppression was more pronounced and more significant when CY was given as multiple dose. However, the enhancement of the secondary contact sensitivity to DNFB by CY was not clear-cut. The splenectomy appears to increase the enhancing effect of CY on contact sensitivity. These results suggest that CY selectively influences the immune response depending on the time of the drug administration relative to immunization and that the secondary or tertiary immune response involve memory cells with different susceptibilities to CY. Moreover, these results suggest that multiple low doses may sesectivley inhibit suppressor T cell proliferation involving DTH, HA or contact sensitivity without effecting helper T cells, but high doses presumably inhibit helper T cells and suppressor T cells with effecting B cells.

• Korean Journal of Microbiology
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• v.45 no.3
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• pp.281-285
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• 2009

In this study, we compared the BacT/Alert liquid culture system with Ogawa and $L\ddot{o}wenstein$-Jensen (L-J) media for sputum culture and drug susceptibility test (DST) of Mycobacterium tuberculosis. Rapid liquid culture systems have been widely employed both for primary cultures of M. tuberculosis from clinical specimens and for drug susceptibility test because of its greater sensitivity and faster turn-around time than the conventional egg-based culture methods (Ogawa, $L\ddot{o}wenstein$-Jensen media). Sputum specimens were decontaminated with N-acetyl-L-cysteine (NALC)-4% NaOH and inoculated into the BacT/Alert culture bottles and Ogawa media. 95 from among 135 sputa were smear-positive, 97 (71.9%) were culture-positive by the BacT/Alert culture system, while 89 (65.9%) were positive by Ogawa media. The mean time to culture-positive by the BacT/Alert process system was about 11.3 days, which was significantly shorter than that by Ogawa media (22.4 days). Of 32 M. tuberculosis cultures examined for drug sensitivity, the concordant rate between the two methods (BacT/ Alert liquid culture system, $L\ddot{o}wenstein$-Jensen media) ranged from 87.5% for isoniazid and 90.6% for rifampicin.

• Journal of Food Hygiene and Safety
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• v.31 no.6
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• pp.432-438
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• 2016

Ethoxyquin (EQ, 1,2-dihydro-6-ethoxy-2,2,4-trimethyl-quinoline) is quinoline-based antioxidant used in the animal feed and food industry to protect the raw materials and final products against oxidation. In recent years the use of synthetic antioxidants in fishmeal ingredients carry-over to farmed fish fillets has received increasing attention in food safety. This study was conducted to develop an analytical method to determine EQ in aquatic products. The analytes were confirmed and quantified via liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the positive ion mode using multiple reaction monitoring (MRM). The sample was extracted with 1 N HCl (in case of flatfish extracted with 1 N HCl containing 10% acetonitrile). Then, solid phase extraction (SPE) was used for the cleanup. Standard calibration curves presented linearity with the correlation coefficient ($r^2$) > 0.99, analyzed at 0.005-0.2 mg/kg concentration. The developed method was validated according to the Codex Alimentarius Commission (CAC) guideline. The limits of quantitation for EQ were 0.01 mg/kg. Average recoveries ranged from 81.3% to 107%. The repeatability of measurements, expressed as the coefficient of variation (CV, %), was below 10%. The analytical method was characterized with high accuracy and acceptable sensitivity to meet CODEX guideline requirements and would be applicable to analyze the EQ residue in aquatic products.