• Journal of Pharmacopuncture
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• v.19 no.1
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• pp.21-27
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• 2016

Objectives: The present study was undertaken to evaluate the immunomodulatory (IM) activity of IM-133N, a herbal combination in various immunotherapeutic experimental models. Methods: The IM activity of IM-133N was evaluated against three experimental models namely, effect of IM-133N against Escherichia coli (E. coli)-induced abdominal sepsis in mice, and carbon clearance test was performed in Wistar albino rats to evaluated the phagocytic potential of IM-133N, in addition IM-133N was evaluated for its immunoglobulin enhancing potential in rats, where the immunoglobulin levels were measured by zinc sulphate turbity (ZST) test. Further, IM-133N was subjected for detailed liquid chromatography-mass spectrometry (LC-MS)/MS analysis to identify the probable active constituents present in it. Results: The findings of the present study has demonstrated very promising IM property of IM-133N in all the experimental models. Briefly, pretreatment with IM-133N at 125, 250, 500 and 1,000 mg/kg, p.o. doses had protected the mice against E. coli-induced abdominal sepsis and mortality, further the effect of IM-133N was found to be significant and dose-dependent. In support of this, in another study administration of IM-133N showed a significant and dose-dependent increase in serum immunoglobulin levels, estimated by ZST test. In line with the above findings, in the carbon clearance test the low doses (125 and 250 mg/kg, p.o.) of IM-133N increased the rate of carbon clearance, whereas the higher doses (500 and 1,000 mg/kg, p.o.) did not sustain the response, and saturation effect was considered as one of the possible reason for futility of higher doses for IM-133N. In addition, A detailed LC-MS/MS analysis of IM-133N showed 17 bioactive phytochemical constituents: namely, apigenin, chaulmoogric acid, mesquitol, quercetin, symphoxanthone, salireposide, ${\beta}$-sitosterol, nonaeicosanol, ${\beta}$-amyrin, betulic acid, oleanolic acid, symplososide, symponoside, symploveroside, symplocomoside, symconoside A and locoracemoside B. Conclusion: These findings suggest that IM-133N possesses significant IM activity and, hence, could be useful for eradicating opportunistic disease-triggering pathogens via immunotherapeutic mechanisms. The findings also suggest IM-133N may also useful in other immunity disorders.

• Journal of Food Hygiene and Safety
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• v.26 no.2
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• pp.91-99
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• 2011

Risk ranking must be determined for various hazards/food combinations to conduct microbial risk management effectively. Risk Ranger is a simple, easy-to-use calculation tool developed in Microsoft Excel and designed to rank the risk (low, medium, and high) for semi-quantitative microbial risk assessment. The user is required to answer 11 questions in Risk Ranger related to 1) severity of the hazard, 2) likelihood of a disease-causing dose of the hazard being present in the meal, and 3) the probability of exposure to the hazard in a defined time. This study determined the risk ranking for twenty three combinations of foodborne pathogens/potentially hazardous foods (PHFs) using a Risk Ranger. In this study, pathogenic E. coli in fresh cut produce salad was scored as 79, which was the highest rank among the 23 combinations of the foodborne pathogens and PHFs. On the other hand, zero risk was obtained with V parahaemolyticus in sushi, Salmonella in meat products and E. coli O157:H7 in hamburger patties. Although Risk Ranger is very simple method to rate the risk of foodborne pathogens and PHFs combination, the accuracy of result was mainly affected by the availability and accuracy of data in the literature. According to the result of literature review, the data are needed for contamination rate of raw materials, consumption amount/frequency of PHFs, and the effect of processing on pathogen. Risk ranking must be continuously revalidated with new data.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.4
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• pp.207-218
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• 2019

It is necessary to investigate the efficacy of commercial Korean herbal medicine for cognitive disorder. The purpose of this study is to select candidates among licensed herbal medicines that are expected to be effective in the treatment of cognitive disorders and can be used in future clinical trial. From laboratory experiments, we first found individual single herbal drugs that could be effective for cognitive disorder, and then through experts recommendation, selected five priorities of single herbal drug and obtained the information of the best herb as a combination of each herbal drug. To derive the final herbal prescriptions, we searched the KFDA drug information system for licensed herbal medicines containing each drug and its combination. As a result of laboratory experiments and experts recommendation, we found that the five effective single herbal drugs for cognitive disorders. They are Ginseng Radix, Acori Graminei Rhizoma, Cyperi Rhizoma, Coptidis Rhizoma, Pinelliae Rhizoma, Hoelen cum Pini Radix, and Rehmanniae Radix Preparata(Pinelliae Rhizoma, Hoelen cum Pini Radix, and Rehmanniae Radix Preparata were tied for $5^{th}$). And licensed herbal prescriptions derived from the planned search are Palbohoichoon-tang, Taehwa-hwan, Bosim-hwan, and so on. Among these, in consideration of the feasibility of research and possibility of success in development, Yukgunja-tang, Samhwangjichul-hwan can be selected as future study subjects. Through experimental studies and expert recommendations, we have derived herbal prescriptions that can be effective in treating cognitive disorders from licensed herbal medicines.

• Korean Journal of Pharmacognosy
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• v.42 no.4
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• pp.336-340
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• 2011

The aim of this study was to investigate the possible utilization of Zanthoxylum schinifolium as a source of antimicrobial agents. The antimicrobial effects of Zanthoxylum schinifolium extracts were investigated against Acinetobacter baumannii, which is a multi-drug resistant pathogen, and 5 other pathogenic microorganisms. The hexane extract of Zanthoxylum schinifolium was more effective than the ethyl acetate, n-butanol and methanol extracts which were active against Acinetobacter baumannii 25, with minimum inhibitory concentrations(MIC) ranging from 0.8 mg/ml to 1.6 mg/ml. Tetracycline had no effect on Acinetobacter baumanniii. The hexane extract was highly active against Candida albicans IFO 6258, with an MIC of 1.5 mg/ml. In contrast, the ethyl acetate, n-butanol and methanol extracts showed no activity against the 5 pathogenic microorganisms. Furthermore, a combination of hexane extract and ethyl acetate extract was significantly more active against the 5 Acinetobacter baumannii strains than n-butanol and methanol. These results suggest that Zanthoxylum schinifolium extracts have great potential as antimicrobial compounds against multi-drug resistant pathogens, and further studies are warranted.

• Archives of Pharmacal Research
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• v.24 no.1
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• pp.1-15
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• 2001

Gene therapy has emerged as a new concept of therapeutic strategies to treat diseases which do not respond to the conventional therapies. The principle of gene therapy is to Introduce genetic materials into patient cells to produce therapeutic proteins in these cells. Gene therapy is now at the stage where a number of clinical trials have been carried out to patients with gene-deficiency disease or cancer. Genetic materials for gene therapy are generally composed of gene expression system and gene delivery system. For the clinical application of gene therapy in a way which conventional drugs are used, researches have been focused on the design of gene delivery system which can offer high transfection efficiency with minimal toxicity. Currently, viral delivery systems generally provide higher transfection efficiency compared with non-viral delivery systems while non-viral delivery systems are less toxic, less immunogenic and manufacturable in large scale compared with viral systems. Recently, novel strategies towards the design of new non-viral delivery system, combination of viral and non-viral delivery systems and targeted delivery system have been extensively studied. The continued effort in this area will lead us to develop gene medicine as "gene as a drug" in the near future.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.371-389
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• 2011

A new strategy for cancer therapy has emerged during the past decade based on molecular targets that are less likely to be essential in all cells in the body, therefore confer a wider therapeutic window than traditional cytotoxic drugs which mechanism of action is to inhibit essential cellular functions. Exceptional heterogeneity and adaptability of cancer impose significant challenges in oncology drug discovery, and the concept of complex tumor biology has led the framework of developing many anticancer therapeutics. Protein kinases are the most pursued targets in oncology drug discovery. To date, 12 small molecule kinase inhibitors have been approved by US Food and Drug Administration, and many more are in clinical development. With demonstrated clinical efficacy of bortezomib, ubiquitin proteasome and ubiquitin-like protein conjugation systems are also emerging as new therapeutic targets in cancer therapy. In this review, strategies of targeted cancer therapies with inhibitors of kinases and proteasome systems are discussed. Combinational cancer therapy to overcome drug resistance and to achieve greater treatment benefit through the additive or synergistic effects of each individual agent is also discussed. Finally, the opportunities in the future cancer therapy with molecularly targeted anticancer therapeutics are addressed.

• Journal of The Korean Society of Clinical Toxicology
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• v.1 no.1
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• pp.34-39
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• 2003

Carisoprodol (CSP) is commonly prescribed as a skeletal muscle relaxant. Recently, we encountered 7 suicidal cases in which carisoprodol was detected. We developed a rugged, sensitive, and specific method for the determination of CSP and meprobamate (MPB) by GC and GC/MS. Postmortem blood concentrations of CSP and MPB ranged 22.9-124.4 ,$\mu$g/ml and its metabolite, 26.8-144.5 ,$\mu$g/ml respectively. Among 7 cases studied, Only CSP was ingested in 4 cases and combination of CSP and dextromethorphan was ingested in 2 cases according to the case history and one case was with ethanol. The order of the tissue concentration of CSP and MPB was liver> kidney > brain, and the concentration of MPB was higher than that of CSP in all tissues. The MPB /CSP concentration ratios of urine, bile juice, liver, kidney, brain and blood were 15.7, 4.0, 1.2, 1.4, 1.4 and 1.0 respectively. There was a big difference in concentration of CSP and MPB in 7 cases due to differences in the amount of dose administered and time to death after dosing.

• Tuberculosis and Respiratory Diseases
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• v.81 no.3
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• pp.222-227
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• 2018

Background: Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis, and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFP-resistant M. tuberculosis strains with mutations in rpoB. To investigate rpoC mutation patterns, we analyzed 93 clinical M. tuberculosis isolates from patients in South Korea. Methods: Drug-resistant mycobacterial isolates were cultured to determine their susceptibility to anti-tubercular agents. Mutations in rpoC were identified by sequencing and compared with the relevant wild-type DNA sequence. Results: In total, 93 M. tuberculosis clinical isolates were successfully cultured and tested for drug susceptibilities. They included 75 drug-resistant tuberculosis species, of which 66 were RFP-resistant strains. rpoC mutations were found in 24 of the 66 RFP-resistant isolates (36.4%). Fifteen different types of mutations, including single mutations (22/24, 91.7%) and multiple mutations (2/24, 8.3%), were identified, and 12 of these mutations are reported for the first time in this study. The most frequent mutation involved a substitution at codon 452 (nt 1356) resulting in amino acid change F452L. Conclusion: Fifteen different types of mutations were identified and were predominantly single-nucleotide substitutions (91.7%). Mutations were found only in dual isoniazid- and RFP-resistant isolates of M. tuberculosis. No mutations were identified in any of the drug-susceptible strains.

• Korean Journal of Clinical Pharmacy
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• v.24 no.1
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• pp.45-52
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• 2014

Objective: To evaluate the clinical manifestations and causative drugs of the outpatient adverse drug reactions (ADRs) reported by community pharmacy. Methods: From April 2013 to September 2013, all outpatient ADRs reported by community pharmacy to Regional Pharmacovigilance Center of Korean Pharmaceutical Association were included. The causality of ADRs was assessed by the criteria of WHO-Uppsala Monitoring Centre. The clinical features and the offending drugs were analyzed using the WHO-Adverse Reaction Terminology and the classification of American Hospital Formulary Service Drug Information, respectively. Results: 2,826 (97.0%) of the total 2,912 ADRs had causal relationship. The 1,923 patients with mean age of 55.1 years and female fraction of 66.5% were included in the ADRs. Gastrointestinal (33.6%), nervous system (14.9%), and skin (13.5%) symptoms were common in ADRs. Analgesic drugs (19.7%), gastrointestinal drugs (17.7%), and central nervous system drugs (11.0%) were prevalent offending drugs. The leading causative generic drug was the complex of acetaminophen and tramadol. Among 203 ADRs by the nonprescription drugs, the most common clinical features were skin (37.4%) and gastrointestinal (23.6%) symptoms and the most prevalent offending drugs were analgesic drugs (40.0%) and mucocutaneous system drugs (16.3%). The combination of acetaminophen and chlorzoxazone was the leading causative generic in nonprescription drugs. Conclusion: In this study, gastrointestinal symptom was the most common manifestation and analgesic drug was the most common causative drug in outpatient ADRs reported by community pharmacy.

• Parasites, Hosts and Diseases
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• v.47 no.2
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• pp.139-144
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• 2009

The aim of the present study was to investigate antimalarial drug pressure resulting from the clinical use of different antimalarials in Thailand. The phenotypic diversity of the susceptibility profiles of antimalarials, i.e., chloroquine (CQ), quinine (QN), mefloquine (MQ), and artesunate (ARS) in Plasmodium falciparum isolates collected during the period from 1988 to 2003 were studied. P. falciparum isolates from infected patients were collected from the Thai-Cambodian border area at different time periods (1988-1989, 1991-1992, and 2003), during which 3 different patterns of drug use had been implemented: MQ+sulphadoxine (S)+pyrimethamine (P), MQ alone and MQ+ARS, respectively. The in vitro drug susceptibilities were investigated using a method based on the incorporation of $[^3H]$ hypoxanthine. A total of 50 isolates were tested for susceptibilities to CQ, QN, MQ, and ARS. Of these isolates, 19, 16, and 15 were adapted during the periods 1988-1989, 1991-1993, and 2003, respectively. P. falciparum isolates collected during the 3 periods were resistant to CQ. Sensitivities to MQ declined from 1988 to 2003. In contrast, the parasite was sensitive to QN, and similar sensitivity profile patterns were observed during the 3 time periods. There was a significantly positive but weak correlation between the $IC_{50}$ values of CQ and QN, as well as between the $IC_{50}$, values of QN and MQ. Drug pressure has impact on sensitivity of P. falciparum to MQ. A combination therapy of MQ and ARS is being applied to reduce the parasite resistance, and also increasing the efficacy of the drug.