• The Journal of Korean Medicine
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• v.31 no.3
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• pp.1-7
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• 2010

Objectives: To introduce to TKM scientific dose conversion methods of human to animal or animal to human for new drug investigations. Methods: We searched guidelines of the FDA and KFDA, and compared them with references for drug-dose conversion from various databases such as PubMed and Google. Then, we analyzed the potential issues and problems related to dose conversion in safety documentation of new herbal drugs based on our experiences during Investigational New Drug (IND) applications of TKM. Results: Dose conversion from human to animal or animal to human must be appropriately translated during new drug development. From time to time, investigators have some difficulty in determining the appropriate dose, because of misunderstandings of dose conversion, especially when they estimate starting dose in clinical or animal studies to investigate efficacy, toxicology and mechanisms. Therefore, education of appropriate dose calculation is crucial for investigators. The animal dose should not be extrapolated to humans by a simple conversion method based only on body weight, because many studies suggest the normalization method is based mainly on body surface area (BSA). In general, the body surface area seems to have good correlation among species with several parameters including oxygen utilization, caloric expenditure, basal metabolism, blood volume and circulating plasma protein. Likewise, a safety factor should be taken into consideration when deciding high dose in animal toxicology study. Conclusion: Herein, we explain the significance of dose conversion based on body surface area and starting dose estimation for clinical trials with safety factor.

• Microbiology and Biotechnology Letters
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• v.16 no.6
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• pp.522-525
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• 1988

A method to produce tissue type Plasminogen Activator (tPA) from normal human fibroblast is developed by cultivating cells in serum free media containing heparin as an inducer. Optimal dose of this inducer was 30$\mu$g/m$\ell$. The composition of serum free medium was also defined to fit to the industrial scale cultivation. 1.42 ug of tPA per 10$^5$ viable cells per ml was produced. 1.1 gram of tPA can be produced every day from this cell line under normal perfusion chemostat operations assuming that same productivity is maintained when the process is sealed up. This method could reduce pro-duction costs and simplify purification processes by using serum free medium. Tissue type PA produced from this cell line has high ability of dissolving clots, based upon fibrin lysis test showing 50mm$^2$ of clearing zones in agarose gel plate. These results were reproducible and in good agreement with results of ELISA assay. tPA from normal human cells will be safer than that from melanoma and recombinant cells in human clinical trials.

• Molecules and Cells
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• v.46 no.9
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• pp.558-572
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• 2023

Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2030. One of its components, emphysema, has been defined as a lung disease that irreversibly damages the lungs' alveoli. Treatment is currently unavailable for emphysema symptoms and complete cure of the disease. Hyaluronan (HA) and proteoglycan link protein 1 (HAPLN1), an HA-binding protein linking HA in the extracellular matrix to stabilize the proteoglycan structure, forms a bulky hydrogel-like aggregate. Studies on the biological role of the full-length HAPLN1, a simple structure-stabilizing protein, are limited. Here, we demonstrated for the first time that treating human alveolar epithelial type 2 cells with recombinant human HAPLN1 (rhHAPLN1) increased TGF-β receptor 1 (TGF-β RI) protein levels, but not TGF-β RII, in a CD44-dependent manner with concurrent enhancement of the phosphorylated Smad3 (p-Smad3), but not p-Smad2, upon TGF-β1 stimulation. Furthermore, rhHAPLN1 significantly increased sirtuins levels (i.e., SIRT1/2/6) without TGF-β1 and inhibited acetylated p300 levels that were increased by TGF-β1. rhHAPLN1 is crucial in regulating cellular senescence, including p53, p21, and p16, and inflammation markers such as p-NF-κB and Nrf2. Both senile emphysema mouse model induced via intraperitoneal rhHAPLN1 injections and porcine pancreatic elastase (PPE)-induced COPD mouse model generated via rhHAPLN1-containing aerosols inhalations showed a significantly potent efficacy in reducing alveolar spaces enlargement. Preclinical trials are underway to investigate the effects of inhaled rhHAPLN1-containing aerosols on several COPD animal models.

• Journal of Korean Medicine for Obesity Research
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• v.13 no.2
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• pp.58-65
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• 2013

Objectives: The objective of this study was to analyse the methods being used to control food intake and physical activity in RCTs of human obesity. Methods: A total of 21 randomized controlled trials (RCTs) were investigated. Nine of which were domestic studies from "http://oasis.kiom.re.kr" and the other of which were foreign studies from systematic reviews of RCTs on herbal medicine for treatment of human obesity. Results: According to domestic studies, "low calorie diet" were recommended in five cases of the domestic studies, "maintain current dietary habit" were recommended in two and no information on diet was two. Considering the seven cases where the information on diet was available, patients' food intake were checked at every visit in six cases. Only two cases among the six had been dropped owing to the violation of dietary habit by patients. Exercises were prohibited in two cases, "maintain current level of phisical activity" were recommended in three cases and, from the rest, no information was available. The level of physical activity were not strictly controlled by any means hence no drop out. According to foreign studies, "low calorie diet" were recommended in two cases, "very low calorie diet (less than 700 kcal/day)" in one case, "maintain current dietary habit" in two cases, "do not eat fat" in two cases and no information was available in the rest five cases. Exercises which concerns spending about 300 kcal/day was recommended in one case, "moderate exercise" were recommended in three cases, "maintain current level of physical activity" were recommended in three cases and no information available in the rest five cases. Conclusions: In order to improve the accuracy of RCT, for the dietary side, researchers should record patient food intake at every visit by means of 24-hour dietary recall methods. This can be supplemented by multiple choice survey that are designed to help patients to diagnose themselves more accurately leading to less bias. For the exercise side, it is highly recommended to confine the exercises to walking only so as to quantify the amount of physical activity more easily by using pedometer.

• Journal of Pharmaceutical Investigation
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• v.17 no.2
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• pp.55-60
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• 1987

WR 2721 (S-2-(3-aminopropylaminoethylphosphorothioate) is a radioprotective drug that is now undergoing clinical trials in the United States and Japan. a liquid chromatographic electrochemical method for the determination of WR 2721 an WR 3689 [S-2-(3-methylaminopropylamino)ethylphorothioate] in human plasma was developed in this study. This method includes the use of a Hg/Au electrochemical detector and a cyano column for the direct measurement of WR 2721 and WR 3689 in plasma. An analog of WR 2721, WR 149846 was used as an internal standard. WR 2721 and WR 3689 could be well separated from the solvent front, with a mobile phase of acetonitrile-water (20:80), 0.1M acetic acid and 1.2 mM sodium octane sulfonate. This method was shown to be precise. Both intra-day and inter-day results were within 10% CV. Also, sample preparation was fairly simple. Since WR 2721 and WR 3689 were unstable at room temperature, it was essential to use an automatic sample processor with a refrigerator, especially for carrying out routine analyses.

• Journal of the Korean Institute of Intelligent Systems
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• v.11 no.7
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• pp.603-610
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• 2001

Industrial processes are normally operated by skilled humans who have the cumulative and logical information about the system. Fuzzy control has been investigated for many application. Intelligent control approaches based on fuzzy logic have a chance to include human thinking. This paper represents modeling approach based upon operators knowledge without mathematical model of the system and optimize the controller. The experimented system is constructed for sending a ball to the goal position using wind of two DC motors in the predefined path. A vision camera to mimic human eyes detects the ball position. The system used in this experiment could be hardly modeled by mathematical methods and ould not be easily controlled by conventional manners. The controller is designed based on the input-output data and experimental knowledge obtained by trials, and optimized under the predefined performance criterion. And this paper shows the data adaptation for changeable operating condition. When the system is driven in the abnormal condition with unconsidered noise, the new optimal operating parameters could be defined by adjusting membership functions. Thus, this technique could be applied in industrial fields.

• Journal of the Korean Institute of Intelligent Systems
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• v.14 no.5
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• pp.610-616
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• 2004

In the research of biomechanical engineering, robotics and neurophysiology, to clarify the mechanism of human bipedal walking is of major interest. It serves as a basis of developing several applications such as rehabilitation tools and humanoid robots. Nevertheless, because of complexity of the neuronal system that interacts with the body dynamics system to make walking movements, much is left unknown about the details of locomotion mechanism. Researchers were looking for the optimal model of the neuronal system by trials and errors. In this paper, we applied Genetic Programming to induce the model of the nervous system automatically and showed its effectiveness by simulating a human bipedal walking with the obtained model.

• International Journal of Human Ecology
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• v.14 no.2
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• pp.93-103
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• 2013

This study investigated the relationship of clothing microclimate and physiological responses in order to examine the layering effects on the clothing microclimate as an index to predict clothing thermal insulation ($I_{cl}$). Experiments were conducted in a $15^{\circ}C$ environment on six physically active males. Increased clothing layers resulted in higher mean temperature inside the clothing ($\bar{T}_{cl}$) and $I_{cl}$. The $I_{cl}$ had a high correlation with: $\bar{T}_{cl}$ (r = 0.556), the difference between the innermost surface temperature and the outermost surface temperature at the chest (DST) (r = 0.549) and the temperature inside clothing at the abdomen (r = 0.478). $\bar{T}_{cl}$ had the highest correlation with the temperature inside clothing at the abdomen (r = 0.889). $\bar{T}_{cl}$ also had the highest correlation with $\bar{T}_{sk}$ (r = 0.860). The results showed that the relationship between $I_{cl}$ and $\bar{T}_{cl}$ was linear (p < .01). Thermal comfort had a negative correlation with $\bar{T}_{cl-thigh}$ (r=-0.411) and $\bar{T}_{cl}$ (r = -0.323) (p < .01.)

• Development and Reproduction
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• v.21 no.1
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• pp.1-10
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• 2017

The use of human mesenchymal stem cells (hMSCs) in cell-based therapy has attracted extensive interest in the field of regenerative medicine, and it shows applications to numerous incurable diseases. hMSCs show several superior properties for therapeutic use compared to other types of stem cells. Different cell types are discussed in terms of their advantages and disadvantages, with focus on the characteristics of hMSCs. hMSCs can proliferate readily and produce differentiated cells that can substitute for the targeted affected tissue. To maximize the therapeutic effects of hMSCs, a substantial number of these cells are essential, requiring extensive ex vivo cell expansion. However, hMSCs have a limited lifespan in an in vitro culture condition. The senescence of hMSCs is a double-edged sword from the viewpoint of clinical applications. Although their limited cell proliferation potency protects them from malignant transformation after transplantation, senescence can alter various cell functions including proliferation, differentiation, and migration, that are essential for their therapeutic efficacy. Numerous trials to overcome the limited lifespan of mesenchymal stem cells are discussed.

• Clinical and Experimental Pediatrics
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• v.59 no.10
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• pp.395-401
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• 2016

Since the outbreak of the enterovirus 71 (EV71) infection in Malaysia in 1997, large epidemics of EV71 have occurred in the Asia-Pacific region. Many children and infants have died from serious neurological complications during these epidemics, and EV71 infection has become a serious public health problem in these areas. EV71 infection causes hand, foot and mouth disease (HFMD) in children, and usually resolves spontaneously. However, EV71 occasionally involves the central nervous system (CNS), and induces diverse neurological complications such as brainstem encephalitis, aseptic meningitis, and acute flaccid paralysis. Among those complications, brainstem encephalitis is the most critical neurological manifestation because it can cause neurogenic pulmonary hemorrhage/edema leading to death. The characteristic clinical symptoms such as myoclonus and ataxia, cerebrospinal fluid (CSF) pleocytosis, and brainstem lesions on magnetic resonance imaging, in conjunction with the skin rash of HFMD and the isolation of EV71 from a stool, throat-swab, or CSF sample are typical findings indicating CNS involvement of EV71 infection. Treatment with intravenous immunoglobulin and milrinone are recommended in cases with severe neurological complications from EV71 infection, such as brainstem encephalitis. Despite the recent discovery of receptors for EV71 in human cells, such as the scavenger receptor B2 and P-selection glycoprotein ligand 1, it is not known why EV71 infection predominantly involves the brainstem. Recently, 3 companies in China have completed phase III clinical trials of EV71 vaccines. However, the promotion and approval of these vaccines in various countries are problems yet to be resolved.