• Archives of Pharmacal Research
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• v.28 no.9
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• pp.1002-1012
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• 2005

5-Substituted 4-oxo-2-thioxo-1,,2,3,4-tetrahydropyrimidine were synthesized by interaction of 4­oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-sulfonylhydrazide with some aldehydes to give the corresponding Schiff-bases, which after cyclization gave corresponding thiazolidinones. For some of the thiazolidinones, Mannich bases reaction was carried out. All the derivatives were tested for their possible inhibitory effect on Schistosoma mansoni cercarial elastase (CE). Only, N'-(4-methylbenzyledine)-4-oxo-2-thioxo-1,2 ,3,4-tetrahydropyrimidine-5-sulfonylhydrazide was found to have potent inhibitory effect on the CE activity with $IC_{50} = 264{\mu}M.$ Upon its use as a paint for mice tails before infection with S. mansoni cercariae, the compound formulated in jojoba oil caused a significant reduction ($93\%$; P-value = 0.0002) in the worm burden. IgG & IgM in mice sera were measured by using several S. mansoni antigens by ELISA. Sera from treated infected mice (TIM) 2, 4, and 6 weeks (W) post infection (PI) showed 1.2 folds lower, 1.2 folds higher, 1.7 folds lower IgM reactivity against soluble cercarial antigenic preparation (CAP), respectively, when compared with sera collected from infected untreated mice (IUM). Sera from TIM 2, 4, and 6WPI showed 1.3, 1.6, and 1.7 folds higher IgG reactivity, respectively against CAP than the IgG reactivity from IUM. Sera from TIM 2, 4 and 6WPI showed 1.5, 1.2 folds lower and 1.4 folds higher IgM reactivity, respectively against soluble worm antigenic preparation (SWAP) when compared with sera collected from IUM. Sera from TIM 2, 4, and 6WPI showed 1.4, 1 folds lower and 1 fold higher IgG reactivity, respectivley to SWAP when compared with sera from IUM. Sera from TIM 2, 4, and 6WPI had generaly lower IgM and IgG reactivities against soluble egg antigen (SEA) when compared with sera from IUM.

• Journal of Society of Preventive Korean Medicine
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• v.21 no.2
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• pp.1-13
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• 2017

Objectives : This paper serves to explore current trends of systems biology in Traditional Chinese Medicine (TCM) and examine how it may influence the Traditional Korean medicine. Methods : Literature review method was collectively used to classify Introduction to systems biology, diagnosis and syndrome classification of systems biology in TCM perspective, physiotherapy including acupuncture, herbs and formula functions, TCM systems biology, and directions of academic development. Results : The term 'Systems biology' is coined as a combination of systems science and biology. It is a field of study that tries to understand living organism by establishing a theory based on an ideal model that analyzes and predicts the desired output with understanding of interrelationships and dynamics between variables. Systems biology has an integrated and multi-dimensional nature that observes the interaction among the elements constructing the network. The current state of systems biology in TCM is categorized into 4 parts: diagnosis and syndrome, physical therapy, herbs and formulas and academic development of TCM systems biology and its technology. Diagnosis and syndrome field is focusing on developing TCM into personalized medicine by clarifying Kidney yin deficiency patterns and metabolic differences among five patterns of diabetes and analyzing plasma metabolism and biomarkers of coronary heart disease patients. In the field of physical therapy such as acupuncture and moxibustion, researchers discovered the effect of stimulating acupoint ST40 on gene expression and the effects of acupuncture on treating functional dyspepsia and acute ischemic stroke. Herbs and formulas were analyzed with TCM network pharmacology. The therapeutic mechanisms of Si Wu Tang and its series formulas are explained by identifying potential active substances, targets and mechanism of action, including metabolic pathways of amino acid and fatty acid. For the academic development of TCM systems biology and its technology, it is necessary to integrate massive database, integrate pharmacokinetics and pharmacodynamics, as well as systems biology. It is also essential to establish a platform to maximize herbal treatment through accumulation of research data and diseases-specific, or drug-specific network combined with clinical experiences, and identify functions and roles of molecules in herbs and conduct animal-based studies within TCM frame. So far, few literature reviews exist for systems biology in traditional Korean medicine and they merely re-examine known efficacies of simple substances, herbs and formulas. For the future, it is necessary to identify specific mechanisms of working agents and targets to maximize the effects of traditional medicine modalities. Conclusions : Systems biology is widely accepted and studied in TCM and already advanced into a field known as 'TCM systems biology', which calls for the study of incorporating TCM and systems biology. It is time for traditional Korean medicine to acknowledge the importance of systems biology and present scientific basis of traditional medicine and establish the principles of diagnosis, prevention and treatment of diseases. By doing so, traditional Korean medicine would be innovated and further developed into a personalized medicine.

• Journal of Life Science
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• v.21 no.11
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• pp.1558-1564
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• 2011

Cytochrome P450 2J2 (CYP2J2) plays important roles in the metabolism of endogenous metabolites such as arachidonic acid as well as therapeutic drugs. CYP2J2 is overexpressed in human cancer tissues and cancer cell lines, as well as in epoxyeicosatrienoic acids (EETs) and CYP2J2-mediated metabolites, and prevent apoptosis of cancer cells. This study aimed to screen marketed drugs for inhibitory potential on CYP2J2 isoforms using human liver microsomes. The initial screen isolated 4 compounds, from 120 marketed drugs, that inhibited the CYP2J2-mediated astemizole O-demethylation more than 50% in the following the order: haloperidol (75%) > terfenadine (56%) > aripiprazole (55%) > miconazole (52%). Miconazole strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=11.2 ${\mu}M$) and terfenadine hydroxylation ($IC_{50}$=2.2 ${\mu}M$), and terfenadine also inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}$=13.6 ${\mu}M$) in a dose dependent manner. The present data suggest that these drugs are potential candidates for further evaluation for their anti-cancer activities.

• The Korea Journal of Herbology
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• v.31 no.5
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• pp.93-98
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• 2016

Objectives : Hwangheuk-san is a complex prescription composed of oriental traditional medicine and has been reported for antioxidant, antimicrobial and anticancer effects in the recent study. Methicillin-resistant Staphylococcus aureus (MRSA) is one of important causes of fatal infectious diseases such as septicemia, endocarditis, toxic shock syndrome, pneumonia, skin and soft tissue infections (SSTIs). S. aureus is reported as being for a variety of human diseases and its epidemiological relevance is mainly due to their ability of becoming highly resistant to common antimicrobials such as tetracycline, penicillin, cphalosporin and aminoglycoside. The objective of this study is to determine the antimicrobial effect of Hwangheuk-san ethanol extracts (HHS) and synergistic effects with antibiotics oxacillin against MRSA.Methods : The antimicrobial activity of HHS was measured by the disc diffusion method, broth microdilution method and the checkerboard dilution test, time-kill curve assay was performed to investigate synergistic effects with antibiotics oxacillin against MRSA.Results : HHS showed antimicrobial activity against MRSA with a MIC value of 125 ㎍/㎖. In the checkerboard test, the interaction of HHS with antibiotics oxacillin produced almost synergy or partial synergy against MRSA. This study showed that HHS reduced the MICs of oxacillin tested, and a remarkable antibacterial effect of HHS, with membrane permeability enhancers.Conclusions : These results suggest that HHS has the antimicrobial effect and synergistic effects with antibiotics oxacillin against MRSA. This study thus can be a valuable source for the development of a new drug with low MRSA resistance.

• Journal of Life Science
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• v.17 no.3 s.83
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• pp.334-339
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• 2007

We evaluated the potential of 20 herbal medications (HMs), commonly used in Korea, to inhibit the catalytic activities of several cytochrome P450 (CYP) isoforms. The abilities of 500 ${\mu}g/ml$ of aqueous extracts of 20 HMs to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), rosiglitazone hydroxylation (CYP2C8), tolbutamide 4-methylhydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The HMs Woohwangcheongsimwon suspension and Hwanglyeonhaedok-Tang strongly inhibited CYP2B6 and CYP2D6 isoform activity, respectively. These results suggest that some of the HMs used in Korea have potential to inhibit CYP isoforms in vitro. Although the plasma concentrations of the active constituents of the HMs were not determined, some herbs could cause clinically significant interactions because the usual doses of those individual herbs are several grams of freeze-dried extracts.

• Korean Journal of Food Science and Technology
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• v.42 no.2
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• pp.217-222
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• 2010

Resveratrol is a natural polyphenolic compound frequently found in grapes. The biological actions of resveratrol have been extensively investigated both in vitro and in vivo. The interactions of resveratrol with commonly-consumed drugs, however, have rarely been studied. In this study, the cytotoxic properties of resveratrol on the hepatic and intestinal cells in the presence of over-the-counter (OTC) drugs, including acetaminophen (AAP), aspirin (Asp), and ibuprofen (Ibu), were evaluated. The cytotoxic effects of resveratrol on hepatic HepG2 and colonic HCT 116 cells were not markdely changed in the presence of AAP, Asp, or Ibu. Conversely, the cytotoxicity of OTC drugs was not affected by resveratrol either. Concentrations of resveratrol below 10 mM significantly increased HepG2 cell growth after 48 or 72 hr incubation; however, the growth-stimulating effect was not observed in the presence of AAP. When HCT 116 cells were treated with OTC drugs before or after resveratrol, the cytotoxic effects were not significantly altered. The present study provides basic information for the potential health effects of the interactions between resveratrol and commonly-consumed OTC drugs.

• Translational and Clinical Pharmacology
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• v.26 no.4
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• pp.160-165
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• 2018

Indobufen ($Ibustrin^{(R)}$), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using $NONMEM^{(R)}$ and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid $I_{max}$ model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2003.09a
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• pp.44-44
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• 2003

As a basic measurement tool in the areas of animal models of human disease, gene expression and therapy, and drug discovery and development, small animal PET imaging is being used increasingly. An ideal small animal PET should have high sensitivity and high and uniform resolution across the field of view to achieve high image quality. However, the combination of long narrow pixellated crystal array and small ring diameter of small animal PET leads to the degradation of spatial resolution for the source located at off center. This degradation of resolution can be improved by determining the depth of interaction (DOI) in the crystal and by taking into account the information in sorting the coincident events. Among a number of 001 identification schemes, dual layer phsowich detector has been widely investigated by many research groups due to its practicability and effectiveness on extracting DOI information. However, the effects of each crystal length composing dual layer phoswich detector on DOI measurements and image qualities were not fully characterized. In order to minimize the DOI effect, the length of each layer of phoswich detector should be optimized. The aim of this study was to perform simulations using a simulation tool, GATE to design the optimum lengths of crystals composing a dual layer phoswich detector. The simulated small PET system employed LSO front layer LuYAP back layer phoswich detector modules and the module consisted of 8${\times}$8 arrays of dual layer crystals with 2 mm ${\times}$ 2 mm sensitive area coupled to a Hamamatsu R7600 00 M64 PSPMT. Sensitivities and variation of radial resolutions were simulated by varying the length of LSO front layer from 0 to 10 mm while the total length (LSO + LuYAP) was fixed to 20 mm for 10 cm diameter ring scanner. The radial resolution uniformity was markedly improved by using DOI information. There existed the optimal lengths of crystal layers to minimize the variation of radial resolutions. In 10 cm ring scanner configuration, the radial resolution was kept below 3.4 mm over 8 cm FOV while the sensitivity was higher than 7.4% for LSO 5 mm : LuYAP 15 mm phoswich detector. In this study, the optimal length of dual layer phoswich detector was derived to achieve high and uniform radial resolution.

• Korean Journal of Health Education and Promotion
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• v.2 no.1
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• pp.31-61
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• 2000

Introduction. Despite the fact that half of premature deaths are caused by unhealthy lifestyles such as smoking tobacco, sedentary lifestyle, alcohol and drug abuse and poor nutrition, there are no theoretical models which accurately explain these health promotion related behaviors. This study tests a new model of health behavior called the Model of Health Promotion Behavior. This model draws on elements and frameworks suggested by the Health Belief Model, Social Cognitive Theory, the Theory of Planned Action and the Health Promotion Model. This model is intended as a general model of behavior but this first test of the model uses amount of exercise as the outcome behavior. Design. This study utilized a cross sectional mail-out, mail-back survey design to determine the elements within the model that best explained intentions to exercise and those that best explained amount of exercise. A follow-up questionnaire was mailed to all respondents to the first questionnaire about 10 months after the initial survey. A pretest was conducted to refine the questionnaire and a pilot study to test the protocols and assumptions used to calculate the required sample size. Sample. The sample was drawn from 2000 eligible participants at two blue collar (utility company and part of a hospital) and two white collar (bank and pharmaceutical) companies located in Southeastern Michigan. Both white collar site had employee fitness centers and all four sites offered health promotion programs. In the first survey, 982 responses were received (49.1％) after two mailings to non-respondents and one additional mailing to secure answers to missing data, with 845 usable cases for the analyzing current intentions and 918 usable cases for the explaining of amount of current exercise analysis. In the follow-up survey, questionnaires were mailed to the 982 employees who responded to the initial survey. After one follow-up mailing to non-respondents, and one mailing to secure answers to missing data, 697 (71.0％) responses were received, with 627 (63.8％) usable cases to predict intentions and 673 (68.5％) usable cases to predict amount of exercise. Measures. The questionnaire in the initial survey had 15 scales and 134 items; these scales measured each of the variables in the model. Thirteen of the scales were drawn from the literature, all had Cronbach's alpha scores above .74 and all but three had scores above .80. The questionnaire in the second mailing had only 10 items, and measured only outcome variables. Analysis. The analysis included calculation of scale scores, Cronbach's alpha, zero order correlations, and factor analysis, ordinary least square analysis, hierarchical tests of interaction terms and path analysis, and comparisons of results based on a random split of the data and splits based on gender and employer site. The power of the regression analysis was .99 at the .01 significance level for the model as a whole. Results. Self efficacy and Non-Health Benefits emerged as the most powerful predictors of Intentions to exercise, together explaining approximately 19％ of the variance in future Intentions. Intentions, and the interaction of Intentions with Barriers, with Support of Friends, and with Self Efficacy were the most consistent predictors of amount of future exercise, together explaining 38％ of the variance. With the inclusion of Prior Exercise History the model explained 52％ of the variance in amount of exercise 10 months later. There were very few differences in the variables that emerged as important predictors of intentions or exercise in the different employer sites or between males and females. Discussion. This new model is viable in predicting intentions to exercise and amount of exercise, both in absolute terms and when compared to existing models.

• Herbal Formula Science
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• v.15 no.1
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• pp.185-197
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• 2007

Objective : This study was conducted to investigate the effects of Hwangryunhaedok-Tang and Geongangbuja-Tang on the change of interleukin-6 (IL-6) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) level induced by LPS I.C.V. injection in mice. Method : We devided group into 6 mice and 6 mice were assingned to each group. In the normal group only saline was administered intragastrically, and in the control group LPS was injected intracerebroventricularly 1 hr after intragastric administration of saline. In the experiment groups Hwangryunhaedok-Tang(0.5g/kg, 1.0g/kg, 3.0g/kg) was administered intragastrically to mice 1 hr prior to LPS(100mg/mouse) I.C.V. injection.. Also Geongangbuja-Tang (0.5g/kg, 1.0g/kg, 3.0g/kg) was administered intragastrically to mice 1 hr prior to LPS(100mg/mouse) I.C.V. injection. To measure the plasma IL-6 and $TNF-{\alpha}$ level of mice, their blood samples were collected from retro-orbital plexus, immediately centrifuged at $4^{\circ}C$, and plasma was removed and stored frozen at $-83^{\circ}C$ for later determination of IL-6 and $TNF-{\alpha}$. The level of IL-6 and $TNF-{\alpha}$ production was measured by enzyme-linked immunosorbent assay in the plasma. Result : Regarding IL-6 level, The 0.5g/kg and the 1g/kg groups of Geongangbuja-Tang decreased IL-6 level. Especially the 3g/kg control group decreased IL-6 level significantly than the normal group(p<0.01). Regarding $TNF-{\alpha}$ level, the 3g/kg group of Geongangbuja-Tang decreased it significantly(p<0.05). Conclusion : These data revealed that Hwangryunhaedok-Tang might not have the anti imflammatory effect and Geongangbuja-Tang(3g/kg)might have the anti imflammatory effect by reducing the plasma IL-6 and $TNF-{\alpha}$ level in mice LPS Injection.EIM (Eighteen Incompatible Medicaments) is an important component in Oriental pharmacology and is directly related to clinical prescriptions. Medical practitioners argued that the definite cause and meaning of EIM was ambiguous and therefore debated the issue of clinical application of the EIM. This study conducted an in-depth literary research on the origin, meaning and contents of EIM with the purpose to contribute in its efforts to be used clinically. Even after thousands of years have past since establishment of Oriental medicine, EIM is still tabooed and was an obstacle that hindered ideologies. Modern herbal medicine texts claim that the use of EIM can reduce treatment effects and promote poisoning and side effects. However, since long ago, there has been medical practitioners who reject this as false. Recently, poisoning caused by EIM has been claimed to be from the toxicity of the drug itself, rather than the result of interaction between the drugs, and therefore they suggest that EIM is not a forbidden domain. In addition, EIM showed a difference in number depending on the era. However, this can be understood not as a definite number, but instead as a warning to be careful during combination of drugs for use as clinical medicine. Historically, there were very few cases in which EIM was used for clinical tests and thus, the clinical value is not, while others applied EIM directly to their bodies, which showed signs for the usefulness and potential of EIM for us. A more concrete and in-depth study must be made on EIM.