• Title/Summary/Keyword: Drug Toxicity

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Anti-Tuberculosis Activity of Pediococcus acidilactici Isolated from Young Radish Kimchi against Mycobacterium tuberculosis

  • Yoon, Youjin;Seo, Hoonhee;Kim, Sukyung;Lee, Youngkyoung;Rahim, MD Abdur;Lee, Saebim;Song, Ho-Yeon
    • Journal of Microbiology and Biotechnology
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    • v.31 no.12
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    • pp.1632-1642
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    • 2021
  • Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis. It affects about 10 million people each year and is still one of the leading causes of death worldwide. About 2 to 3 billion people (equivalent to 1 in 3 people in the world) are infected with latent tuberculosis. Moreover, as the number of multidrug-resistant, extensively drug-resistant, and totally drug-resistant strains of M. tuberculosis continues to increase, there is an urgent need to develop new anti-tuberculosis drugs that are different from existing drugs to combat antibiotic-resistant M. tuberculosis. Against this background, we aimed to develop new anti-tuberculosis drugs using probiotics. Here, we report the anti-tuberculosis effect of Pediococcus acidilactici PMC202 isolated from young radish kimchi, a traditional Korean fermented food. Under coculture conditions, PMC202 inhibited the growth of M. tuberculosis. In addition, PMC202 inhibited the growth of drug-sensitive and -resistant M. tuberculosis- infected macrophages at a concentration that did not show cytotoxicity and showed a synergistic effect with isoniazid. In a 2-week, repeated oral administration toxicity study using mice, PMC202 did not cause weight change or specific clinical symptoms. Furthermore, the results of 16S rRNA-based metagenomics analysis confirmed that dysbiosis was not induced in bronchoalveolar lavage fluid after oral administration of PMC202. The anti-tuberculosis effect of PMC202 was found to be related to the reduction of nitric oxide. Our findings indicate that PMC202 could be used as an anti-tuberculosis drug candidate with the potential to replace current chemical-based drugs. However, more extensive toxicity, mechanism of action, and animal efficacy studies with clinical trials are needed.

Establishment of Acceptable Daily Intakes (ADIs) and Risk Assessment for Ephedrine, Menichlopholan, Anacolin, and Etisazole Hydrochloride

  • Min Ji Kim;Ji Young Kim;Jang Duck Choi;Guiim Moon
    • Korean Journal of Environmental Agriculture
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    • v.41 no.4
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    • pp.261-275
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    • 2022
  • BACKGROUND: Prior to implementing a positive list system (PLS), there is a need to establish acceptable daily intake (ADI) and maximum residue limit (MRL) for veterinary drugs that have been approved a few decades ago in South Korea. On top of that, chronic dietary exposure assessment of veterinary drug residues should be performed to determine whether the use of these veterinary drugs would cause health concerns or not. METHODS AND RESULTS: To establish the ADI, the relevant toxicological data were collected from evaluation reports issued by international organizations. A slightly modified global estimate of chronic dietary exposure (GECDE) model was employed in the exposure assessment owing to the limited residual data. Therefore, only the ADI of ephedrine was established due to insufficient data for the other veterinary drugs. Thus, instead of ADI, the threshold of toxicological concern (TTC) value was used for the other drugs. Lastly, the hazard index (HI) was calculated, except for etizazole hydrochloride, due to the potential of mutagenicity. CONCLUSION(S): The HI values of ephedrine, menichlopholan, and anacolin were found to be as high as 6.4%, suggesting that chronic dietary exposure to the residues from these uses was unlikely to be a public health concern. Further research for exposure assessment of veterinary drug residues should be performed using up-todate Korean national health and nutrition examination survey (KNHANES) food consumption data. In addition, all relevant available data sources should be utilized for identifying the potentials of toxicity.

Pharmacological Studies on Forsythiae Fructus (연교(連翹)추출물의 일반(一般) 약리작용(藥理作用))

  • Lee, Eun-Bang;Keum, Hye-Jeong
    • Korean Journal of Pharmacognosy
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    • v.19 no.4
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    • pp.262-269
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    • 1988
  • The Forsythiae fructus is described to be used as an antiinflammatory drug, diuretics, antidotes and antibacterials in oriental literatures. In order to investigate the efficacy of Forsythiae viridissima (Oleaceae), the methanol extract and its fraction have been evaluated for the acute toxicity, antiinflammatory, analgesic and spasmolytic action in animals. The methanol extract of Forsythiae fructus was found to have significant antiinflammatory activity in the acute and subacute antiinflammatory model in rats, but have no analgesic action. Furthermore, through fractionation procedure, it was found that the active compounds were easily soluble in chloroform and butanol. It is also noted that the extracts had spasmolytic activities in the rat fundus and uterus and had low acute toxicity in mice.

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Estimation of Maximal Tolerated Dose in Sequential Phase I Clinical Trials

  • Park, In-Hye;Song, Hae-Hiang
    • Communications for Statistical Applications and Methods
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    • v.6 no.2
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    • pp.543-564
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    • 1999
  • The principal aim of a sequential phase I clinical trial in which the toxicity reponses of a group of patient(s) determine the dose level of the next patient(s) group is to estimate the maximal tolerated dose(MTD) of a new drug, In this paper we compared with a simulation study the performance of the MTD estimates that are determined by a stopping rule in a design and also those that are determined by analyzing the data after a clinical trial is terminated. To the latter belong the mean median mode and maximum likelihood estimates. For the Standard Methods the stopping rule MTD is quite inefficient but the median MTD has a best efficiency and is robust with respect to the three different toxicity curves. The problem of non-convergence of MLE MTD is severe. A more improved MTD estimate is produced by combining the advantages of the various MTD estimates and its efficiency is better than the single median MTD estimate especially for the toxicity curve of an unlucky choice of dose levels. The simulation results suggest that simple types of phase I designs can be combined with relatively standard analytic techniques to provide a more efficient MTD estimate.

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Maximum Tolerated Dose Estimate by Curve Fitting in Phase I Clinical Trial (제1상 임상시험에서 곡선적합을 이용한 MTD 추정법)

  • Heo, Eun-Ha;Kim, Dong-Jae
    • Communications for Statistical Applications and Methods
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    • v.18 no.2
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    • pp.179-187
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    • 2011
  • The purpose of a Phase I clinical trial is to estimate the maximum tolerated dose, MTD, of a new drug. In this paper, the MTD estimation method is suggested by curve fitting the dose-toxicity data to an S-shaped curve. The suggested MTD estimation method is compared with established MTD estimation procedures using a Monte Carlo simulation study.

Toxicity of nanoparticles_ challenges and opportunities

  • Ramanathan, Amall
    • Applied Microscopy
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    • v.49
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    • pp.2.1-2.11
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    • 2019
  • Nanomaterials (NMs) find widespread use in different industries that range from agriculture, food, medicine, pharmaceuticals, and electronics to cosmetics. It is the exceptional properties of these materials at the nanoscale, which make them successful as growth promoters, drug carriers, catalysts, filters and fillers, but a price must be paid via the potential toxity of these materials. The harmful effects of nanoparticles (NPs) to environment, human and animal health needs to be investigated and critically examined, to find appropriate solutions and lower the risks involved in the manufacture and use of these exotic materials. The vast number and complex interaction of NM/NPs with different biological systems implies that there is no universal toxicity mechanism or assessment method. The various challenges need to be overcome and a number of research studies have been conducted during the past decade on different NMs to explore the possible mechanisms of uptake, concentrations/dosage and toxicity levels. This review article examines critically the recent reports in this field to summarize and present opportunities for safer design using case studies from published literature.

The Optimization of Method for Prediction of Drug-Induced Liver Injury Using HepG2 Cells Cultured with Human Liver Microsomes (Human Liver Microsomes과 HepG2 세포를 이용한 약물유래 간독성 평가 방법의 최적화)

  • Choi, Jong Min;Jeon, Jang Su;Kim, Sang Kyum
    • YAKHAK HOEJI
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    • v.59 no.5
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    • pp.201-206
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    • 2015
  • The aim of the present study was to optimize in vitro method for the prediction of drug-induced liver injury using human liver microsomes (HLM). Cytotoxicity test of cyclophosphamide and acetaminophen in HepG2 cells cultured with HLM showed that the newly established condition using 0.375 mg/ml HLM for 24 hr incubation was comparable or more sensitive than the previously established condition using 0.75 mg/ml HLM for 12 hr incubation. Although the cytotoxic effect of troglitazone was completely attenuated by 0.75 mg/ml HLM, it was augmented by 0.375 mg/ml HLM in the presence of the NADPH-generating system. The cytotoxic effect of chlormezanone, a withdrawn drug due to hepatotoxicity in human, was increased by HLM in the presence of the NADPH-generating system. In contrast, the cytotoxic effect of methapyrilene, a withdrawn drug due to hepatotoxicity in rats, was decreased by HLM in the presence of the NADPH-generating system. The present study suggests that the optimized in vitro method using HLM can be useful for the prediction of drug-induced hepatotoxicity.

Adverse Drug Reaction Surveillance System in Korea (우리나라 약물유해반응 감시체계)

  • Choi, Nam-Kyong;Park, Byung-Joo
    • Journal of Preventive Medicine and Public Health
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    • v.40 no.4
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    • pp.278-284
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    • 2007
  • Despite extensive researches and pre-market clinical trials, only limited information on the adverse drug reactions (ADRs) of a drug can be collected at the time of market approval from regulatory agency. ADRs constitute a major public health problem. Post-marketing surveillance of drugs is important to detect signals for ADR. In Korea, one of the main methods for monitoring the safety of marketed drugs is spontaneous reporting system of suspected ADRs. Re-examination and re-evaluation system are in force for monitoring safety of new market approval drugs and currently under marketing drugs, respectively. Recently, regional pharmacovigilance centers were designated from Korean Food and Drug Administration for facilitating ADR surveillance. Over recent years, with the development of information technology, there has been an increased interest in establishing data mining system for detecting signals from Health Insurance Review Agency database. The purpose of this paper is to review the current status of Korean ADR surveillance system and suggest the possible solutions for developing active pharmacovigilance system in Korea.

The antidiabetic drug rosiglitazone blocks Kv1.5 potassium channels in an open state

  • Lee, Hyang Mi;Hahn, Sang June;Choi, Bok Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.2
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    • pp.135-144
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    • 2022
  • An antidiabetic drug, rosiglitazone is a member of the drug class of thiazolidinedione. Although restrictions on use due to the possibility of heart toxicity have been removed, it is still a drug that is concerned about side effects on the heart. We here examined, using Chinese hamster ovary cells, the action of rosiglitazone on Kv1.5 channels, which is a major determinant of the duration of cardiac action potential. Rosiglitazone rapidly and reversibly inhibited Kv1.5 currents in a concentrationdependent manner (IC50 = 18.9 μM) and accelerated the decay of Kv1.5 currents without modifying the activation kinetics. In addition, the deactivation of Kv1.5 current, assayed with tail current, was slowed by the drug. All of the results as well as the usedependence of the rosiglitazone-mediated blockade indicate that rosiglitazone acts on Kv1.5 channels as an open channel blocker. This study suggests that the cardiac side effects of rosiglitazone might be mediated in part by suppression of Kv1.5 channels, and therefore, raises a concern of using the drug for diabetic therapeutics.

The Needs on the Drug Free Education in Adolescents (청소년의 약물남용 예방교육 요구도 조사)

  • Jung Hyang-Mi;Lee Hwa-Za;Kim Young-Hae
    • Child Health Nursing Research
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    • v.9 no.1
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    • pp.57-65
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    • 2003
  • Purpose: This study was intended to present basic data of a more effective drug free education program by examining and analyzing the needs of drug and health education in the adolescent. Method: The study subjects were 480 students from six high schools in Pusan. The data were collected by a self-administered questionnaire between June 1 and June 10, 1999. Descriptive statistics, t-test, one-way ANOVA, Scheffe test in SPSS program were used for data analysis. Result: The scoring rate of knowledge for drug abuse of the subjects was 26.8%. For the scores of knowledge according to the type of drug, cigarettes were the highest at 38.4%, and for the scores of knowledge according to items, the abuse part was 59%, also the highest. The needs of drugs and drug education for the subjects had an average of 19.59. For the score of needs according to the items, plans to maintain and improve health was 1.72, the highest, methods to control anger and stress was 1.66, toxicity of drugs was 1.51, and medicinal use of drugs was 1.44. For the characteristics of the subject and characteristics relating to drugs, and the comparison of needs of drug education, consisted of students who said they liked or disliked their school life, those who have had drug education at school, who having received drug education by various kinds of materials, all had high needs for the education. Conclusion: It is necessary that drug free education plans including plans to maintain and improve health on the basis of the needs of drug education for the adolescent and other contents such as the methods to control anger and stress are established. Development of various kinds of audio-visual materials, publicity booklets and educational programs for parents etc. are needed in order to make the adolescent have an interest in drug free education, and recognize its importance.

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