• Title/Summary/Keyword: Drug response

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Development of Predictive Growth Model of Listeria monocytogenes Using Mathematical Quantitative Assessment Model (수학적 정량평가모델을 이용한 Listeria monocytogenes의 성장 예측모델의 개발)

  • Moon, Sung-Yang;Woo, Gun-Jo;Shin, Il-Shik
    • Korean Journal of Food Science and Technology
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    • v.37 no.2
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    • pp.194-198
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    • 2005
  • Growth curves of Listeria monocytogenes in modified surimi-based imitation crab (MIC) broth were obtained by measuring cell concentration in MIC broth at different culture conditions [initial cell numbers, $1.0{\times}10^{2},\;1.0{\times}10^{3}\;and\;1.0{\times}10^{4}$, colony forming unit (CFU)/mL; temperature, 15, 20, 25, 37, and $40^{\circ}C$] and applied to Gompertz model to determine microbial growth indicators, maximum specific growth rate constant (k), lag time (LT), and generation time (GT). Maximum specific growth rate of L. monocytogenes increased rapidly with increasing temperature and reached maximum at $37^{\circ}C$, whereas LT and GT decreased with increasing temperature and reached minimum at $37^{\circ}C$. Initial cell number had no effect on k, LT, and GT (p > 0.05). Polynomial and square root models were developed to express combined effects of temperature and initial cell number using Gauss-Newton Algorism. Relative coefficients of experimental k and predicted k of polynomial and square root models were 0.92 and 0.95, respectively, based on response surface model. Results indicate L. monocytogenes growth was mainly affected by temperature and square root model was more effective than polynomial model for growth prediction.

Induction of Apoptosis by Samgibopae-tang in Human Non-small-cell Lung Cancer Cells (인체폐암세포 NCI-H460 및 A549의 증식에 미치는 삼기보폐탕의 영향 비교)

  • Heo, Man-Kyu;Park, Cheol;Choi, Young-Hyun;Kam, Cheol-Woo;Park, Dong-Il
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.4
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    • pp.973-981
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    • 2007
  • In the present study, we investigated the antiproliferative activity of the water extract of Samgibopae-tang (SGBPT) in NCI-H460 and A549 non-small-cell lung cancer cell lines. We found that exposure of A549 cells to SGBPT resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay, however SGBPT did not affect the growth of NCI-H460 cells. The antiproliferative effect by SGBPT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. SGBPT treatment did not induce the cell cycle arrest in both cell lines, however the frequency of sub-G1 population was concentration-dependently increased by SGBPT treatment in A549 cells. SGBPT treatment partially induced the expression of tumor suppressor p53 in A549 cells and the expression of cyclin-dependent kinase inhibitor p21(WAF1/CIP1) was markedly increased in both transcriptional and translational levels in A549 cells. The up-regulation of p21 by SGBPT occurred in a similar a concentration dependent manner to that observed with the inhibition of cell viability and induction of sub-G1 population of the cell cycle. However SGBPT treatment did not affect other growth regulation-related genes such as early growth response-1 (Egr-1), nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), inducible nitric oxide synthease (iNOS), cyclooxygenases (COXs), telomere-regulatory factors in A549 as well as NCI-H460 cells. Taken together, these findings suggested that SGBPT-induced inhibition of human lung carcinoma A549 cell growth was aoosciated with the induction of p21 and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of SGBPT.

Development of an aequorin-based assay for the screening of corticotropin-releasing factor receptor antagonists (CRF1 길항제 스크리닝을 위한 에쿼린 기반 세포실험 개발연구)

  • Noh, Hyojin;Lee, Sunghou
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.16 no.11
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    • pp.7575-7581
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    • 2015
  • Corticotropin-releasing factor(CRF), one of the stress driven neuropeptides, was widely proposed to influence hair loss and re-growth. For the development of receptor antagonists, the screening system based on intracellular calcium signal process was developed and optimized. The aequorin parental cells were transfected with CRF1 receptor and alpha 16 promiscuous G protein cDNA to establish HEK293a16/hCRF1, a stable cell line for the human CRF1 receptor. In HEK293a16/hCRF1 cells, the range of sauvagine dose response was 12-fold higher($EC_{50}:15.21{\pm}1.83nM$) than in the transiently expressed cells, hence essential conditions for the antagonist screening experiments such as the robust signals and high solvent tolerance were secured. The standard antagonists for the CRF1 receptor, antalarmin and CP154526, resulted $IC_{50}$ values of $414.1{\pm}5.5$ and $290.7{\pm}1.9nM$, respectively. Similar results were presented with frozen HEK293a16/hCRF1 cells. Finally, our HEK293a16/hCRF1 cells with the aequorin based cellular functional assay can be a model system for the development of functional cosmetics and modulators that can have a clinical efficacy on hair re-growth.

The study on the measurement of volatile organic compounds in the air of A and B industrial area (모 공단 대기 중 휘발성 유기화합물 측정에 관한 연구)

  • Shin, Ho-Sang;Ahn, Hye-Sil
    • Analytical Science and Technology
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    • v.17 no.2
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    • pp.130-144
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    • 2004
  • Recently, the air pollution in A and B industrial area has become one of the most important issues, then 60 VOCs in the area were measured using a highly sensitive method. The VOCs were adsorbed onto Carbotrap using air sampler and subsequently desorbed by a thermal desorber system into gas chromatograph-mass spectrometry (TDS-GC-MS). The peaks of all compounds had good chromatographic properties and offered very sensitive response for the EI-MS (SIM). Method detection limits (MDL) ranged from 0.01 to 0.1 ppt(v/v), and linearities of calibration curves were over 0.995. We analyzed total 90 atmosphere air samples of A and B industrial complex using the method. Benzene, toluene, ethylbenzene, xylene, n-hexane, fluorotrichloromethane, carbon tetrachloride, 1,2-dichloroethane, 1,1,1-trichloroethane, trichloroethylene, tetrachloroethylene, styrene, 1,3,5-trimethylbenzene, 1,2,4-trimethylbenzene, sec-butylbenzene and naphthalen were identified as the major compounds in the air, and their average concentrations were 0.81, 5.02 1.30, 3.0, 0.81, 37.9, 0.07, 0.15, 0.15, 0.79, 0.06, 0.33, 0.03, 0.12, 0.23, and 0.35 ppb(v/v), respectively. The concentrations of VOCs were low in summer and high in fall or winter. When the concentrations detected in air compare with WHO's norm, no case exceed it.

An expert survey for developing pattern diagnosis instrument of persistent allergic rhinitis (통년성 알레르기 비염의 변증 도구 개발을 위한 전문가 집단 설문조사 연구)

  • Kim, Nam-Kwen;Lee, Dong-Hyo;Choi, In-Hwa;Ko, Seong-Gyu
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.26 no.2
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    • pp.1-9
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    • 2013
  • Background : According to the rising cases of clinical researches with Traditional Korean Medicine for persistent allergic rhinitis patients, the need for developing and applying Pattern diagnosis instrument has been increasing. Objective : This study was done to investigate and pragmatize the Pattern diagnosis instrument for persistent allergic rhinitis patients launched by KFDA in 2008. Methods : Data was collected by structured survey papers from Korean Medicine doctors participate in the Conference of The Korean Oriental Medical Ophthalmology & Otolaryngology & Dermatology Society in October 2012. We investigated their representative Patterns(변증) of every questions and used the mean results for assuming agreement rates. The importance order of 8 symptom domains for considering Pattern diagnostic steps were also asked and analyzed for inducing importance rates. Finally based on above two results, we developed weight points of each questions by multiplying agrement percents with importance rates. Results : 50 Korean medicine doctors described the informed consent and survey papers. Response agreement rates of each questions of Pattern diagnosis instruments were analyzed and described in Table 2. Comparing the survey results with diagnostic references, matched percent of 肺胃熱 was the 87.9%, 肺氣虛寒 was 62.5%, 肺脾氣虛 was 62.5% and 腎元虧虛 was 50%. Mean importance rates of rhinorrhea was 7.28, otoscope diagnosis 5.12, obstruction 5.04, sneeze 4.82, symptom duration 4.63, other body condition 3.54, tongue diagnosis 3.02, nasal pruritus 2.86, accordingly. Final importance rates of each questions were assumed, and the range of them was from 1.60 to 4.72, which were listed in Table 5. Conclusion : These results might provide the rational backgrounds and practical methods for developing and utilizing methods of Pattern diagnosis questionnaire for perennial allergic rhinitis.

Development of Differential Diagnosis and Treatment Method of Reproductive Disorders Using Ultrasonography in Cows 1. Response of Ovarian Structures to CIDR Treatment at Day 16 of Estrous Cycle in Dairy Heifers (초음파검사에 의한 소의 번식장애 감별진단 및 치료법 개발 1. 처녀젖소에서 발정주기의 16일째에 CIDR의 치료에 대한 난소구조물의 반응)

  • 강현구;강병규;칠한선;중미역언;서국현;손창호
    • Journal of Veterinary Clinics
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    • v.15 no.1
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    • pp.131-139
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    • 1998
  • Progesterone을 함유하고 있는 CIDR(Controlled Internal Drug Release)의 질내삽 입은 황체기를 인위적으로 연장시킬 수 있다. CIDR의 삽입이,삽입시 존재했던 우세난포 (dominant follicle)의 반응과 난포의 발육반응 그리고 2회 또는 3회의 난포주기를 가지고 있는 처려우에서 CIDR의 삽입기간동안 난포의 성장 및 발육에 어떠한 영향을 미치는가를 비교검 토하기 위하여 배란후 16일째의 처녀우 4마리에 7일동안 CIDR를 삽입하였다. CIDR의 삽입 은 발정의 발현을 억제시켰으며 그리고 발정주기의 길이를 정상 발정주기보다 유의성있게 연 장시켰다($26.3{\pm} 0.5 vs 20.8{\pm}$ 1.5일, p<0.05). CIDR의 삽입시 혈장 progesterone 농도는 $3.6{\pm}$ 2.7 ng/ml 이었으며, 17일과 23일 사이에는 2.1-4.4 ng/ml($3.6{\pm}1.2 ng/ml$) 사이를 유지했다. 혈 장 estradiol-179의 농도는 난포의 발육 및 배란전 배란난포의 성숙을 나타내는 특징적인 변화 양상을 나타래었다. 4마리의 처녀우중 2마리는 CIDR 삽입전 발정주기당 2회의 난포주기를 가진 반면, 나머지 2마리는 주기당 3회의 난포주기를 가졌다. 그렇지만 CIDR의 삽입기간동안 모든 처녀우는 주기당 3회의 발정주기를 가졌다. CIDR의 삽입전 발정주기당 3회의 난포주기 를 갖는 처녀우에서 CRR의 삽입은 세 번째 난포주기에서 배란성 우세난포의 우세기 (dominant phase)를 연장시켰다. 3회의 난포주기를 갖는 2마리에서 CIDR의 삽입후 배란난포 는 존속시간과 우세기가 유의성있게 연장되었다. CIDR의 삽입전 발정주기당 2회의 난포주기 를 갖는 다른 2마리의 처녀우에서 CIDR의 삽입후 우세난포는 곧바로 퇴행되었고 새로운 난 포주기를 형성하였으며, 우세난포의 우세기와 배란난포의 존속기간을 연장시키지 않았다. CRR의 삽입은 CIDR의 삽입후 이어지는 발정주기동안 난포의 발육 및 성장에 영향을 미치 지 않았으며 발정주기의 길이, 난포주기, 혈장 progesterone 및 estradiol-179 농도에 영향을 미치지 않았다. 결과적으로 황체기 후반부에 CIDR의 삽입은 CIDR삽입전 발정주기동안 3회 의 난포주기를 갖는 처녀우에서 배란성 우세난포의 발육과 배란까지의 기간을 연장시켰고 2회 난포주기를 갖는 처녀우에서는 우세난포를 곧바로 퇴행시킨후, 새로운 난포주기를 형성 하였다.

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Adverse Effects of Ephedra According to Sasang Typology in Healthy Adults : A Double-Blind Randomized Controlled Trial (마황복용 후 사상체질별 이상반응에 관한 임상연구 : 무작위배정 이중맹검시험)

  • Lee, Tae-Ho;Hsing, Li-Chang;Yang, Chang-Sop;Kim, Lak-Hyung;Seo, Eui-Seok;Jang, In-Soo
    • The Journal of Internal Korean Medicine
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    • v.30 no.1
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    • pp.144-152
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    • 2009
  • Background : Ephedra (Ephedra sinica) has been widely used to treat respiratory disease in traditional medicine of East Asia for over a hundred years. Despite safety concerns raised by some, the use of ephedra in traditional medicine is documented over more than 1,800 years. It is well established that ephedra is one of the central medicines in Korean 'Seseng constitution' medicine. In Sasang constitution medicine, all humans can be divided into one of four types: Soeumin, Soyangin, Taeumin or Taeyangin, and each constitution type has their own typical characteristics. Accordingly, it is hypothesized that the adverse effects of ephedra differ depending on the Sasang constitution classification. Objectives : The aim of this study was to determine adverse effects of ephedra which is classified as a Taeumin herb, and to observe whether the response differs or not. according to Sasang constitution classification. Methods : The study design was a double-blind randomized controlled trial. The subjects were healthy adults 20 - 50 years old who agreed to participate in this study. They were allocated through randomization to either ephedra group (N=55) or placebo group (N=24). where ephedra extract (6 g of dried ephedra) and placebo with similar opaque capsules were given twice for one day. To compare the adverse events of ephedra according to Sasang constitution classification, we analyzed blood pressure (systolic and diastolic), pulse rate, the morning questionnaire, and patient's global assessment scale score for well known adverse events: palpitation, headache, sweating, tiredness, dyspepsia, and dry mouth. Results : After ingestion of ephedra, the pulse rate had a significant increase in all constitution types. The changes of diastolic pressure in Soeumin and the changes of pulse rate in Soeumin, Soyangin and Taeumin had a significant increase in the ephedra over the control group. In the ephedra group, the palpitation and dyspepsia score of the patients' global assessment scale had a significant increase in Soeumin, with palpitation and sweating score increasing in Soyangin. Others observations were insignificant results. Conclusion : The results of this study may confirm that the physical responses or adverse effects of herbs differ for each type of Sasang constitution. Future studies using other herbs will be required to ascertain the herbal drug reaction of Sasang constitutions.

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Study on Development of Assessment Guideline and Endpoints for Clinical Trial with Antitumor Natural Products (천연물 항암제제 임상시험 평가지표 개발연구)

  • Namgung, Mi-Ae;Chang, Yoo-Sung;Jeong, Seung-Gi;Kim, Jin-Seung;Yoon, Sung-Woo;Jang, Ki-Young;Yoo, Hwa-Seung;Jung, Myeon-Woo;Lee, Sung-Ho;Kim, Sung-Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1678-1727
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    • 2006
  • This study was perfromed to develop the assessment guideline and endpoints for clinical trial with anticancer herbal medicine. The botanical products used to humans for long time may be applied to phase 3 clinical trial after submitting the evidences for safety and efficacy of them or completion of basic requirement of phase 1 and phase 2 for safety confirmation and dose determination. Syndrome improvement was chiefly evaluated by Zubrod and karnofsky(%) methods. We suggest the general clinical trial assessment with botanical products, by following assessment points, that is, tumor size for 50 points, survival fate for 10 points, major syndromes for 40 points. It is recommendable that the each symptom of Qi deficiency syndrome, blood deficiency syndrome and Qi stagnation syndrome was allocated by assessment points, Similarly, the each symptom was given the assessment points according to the severity of symptom, for example, slight for 3 points, moderate for 2 points and severe for 1 point in hepatocelluar carcinoma and lung cancer. Then, the efficacy of botanical products was evaluated by the difference between pre-treatment and post-treatment. Asking the neoplastic patients of questionnaire on physical, emotional, cognitive, social and role subjects availability, three more syndromes (Fatigue, Pain and Nausea/Vomit), quality of life(QOL) will be evaluated by GLM statistics. In addition, in case of lung cancer, 13 questions will be asked by the EORTC QLQ-C13 forms. As the assessment of endpoints for efficacy to reduce side effects induced by chemotherapy and radiotherapy, the data of image scanning and hemato-urinalysis can be usefully applied on immune response, weight loss, indigestion, hemopoietic damage and injury of liver and kidney, while the changes of syndromes of side effect can be evaluated by differentiation methods of Qi and blood and five viscera. However, it is still necessary to determine the ratio between scientific analytical method and Oriental differentiation method as well as confirm the Oriental assessment endpoints by clinical trial. In addition, we suggest the continuous development of assessment endpoints on other carcinomas except of hepatocelluar carcinoma and lung cancer in future.

Composition Comprising the Extract of Anethi Fructus for the Treatment and Protection of Immune Activity (시라자 추출물을 함유하는 면역질환의 치료 및 예방을 위한 면역증강용 조성물)

  • Park, Gil-Soon;Chang, In-Ae;Kim, Youn-Chul;Lee, Moo-Hyung;Shin, Hye-Young;Choi, Du-Young;Yun, Yong-Gab;Park, Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.3
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    • pp.700-704
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    • 2007
  • In the recent, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Here we investigated the role of the extract of Anethi Fructus in the expression of inflammatory mediators, surface molecule, and related receptors in vitro. In murine macrophage RAW 264.7 cells and peritoneal macrophages of C57BL/6N mice, water extract of Anethi Fructus increased the production of secretary tumor necrosis factor (TNF)-a and Nitric oxide (NO), and the expression level of CD14, LPS co-receptor and CD86, co-stimulatory molecule compared to negative natural extract ex vivo. The water extract of Anethi Fructus increased the production of interferon (IFN)-g from splenocytes. Also, water extract of Anethi Fructus increased ConA-induced cell proliferation. These results suggest that water extract of Anethi Fructus may enhance the immune response through immune modulation of macrophage and lymphocytes.

The Abuse Potential of α-Piperidinopropiophenone (PIPP) and α-Piperidinopentiothiophenone (PIVT), Two New Synthetic Cathinones with Piperidine Ring Substituent

  • Botanas, Chrislean Jun;Yoon, Seong Shoon;de la Pena, June Bryan;dela Pena, Irene Joy;Kim, Mikyung;Woo, Taeseon;Seo, Joung-Wook;Jang, Choon-Gon;Park, Kyung-Tae;Lee, Young Hun;Lee, Yong Sup;Kim, Hee Jin;Cheong, Jae Hoon
    • Biomolecules & Therapeutics
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    • v.25 no.2
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    • pp.122-129
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    • 2017
  • A diversity of synthetic cathinones has flooded the recreational drug marketplace worldwide. This variety is often a response to legal control actions for one specific compound (e.g. methcathinone) which has resulted in the emergence of closely related replacement. Based on recent trends, the nitrogen atom is one of the sites in the cathinone molecule being explored by designer type modifications. In this study, we designed and synthesized two new synthetic cathinones, (1) ${\alpha}-piperidinopropiophenone$ (PIPP) and (2) ${\alpha}-piperidinopentiothiophenone$ (PIVT), which have piperidine ring substituent on their nitrogen atom. Thereafter, we evaluated whether these two compounds have an abuse potential through the conditioned place preference (CPP) in mice and self-administration (SA) in rats. We also investigated whether the substances can induce locomotor sensitization in mice following 7 days daily injection and challenge. qRT-PCR analyses were conducted to determine their effects on dopamine-related genes in the striatum. PIPP (10 and 30 mg/kg) induced CPP in mice, but not PIVT. However, both synthetic cathinones were not self-administered by the rats and did not induce locomotor sensitization in mice. qRT-PCR analyses showed that PIPP, but not PIVT, reduced dopamine transporter gene expression in the striatum. These data indicate that PIPP, but not PIVT, has rewarding effects, which may be attributed to its ability to affect dopamine transporter gene expression. Altogether, this study suggests that PIPP may have abuse potential. Careful monitoring of this type of cathinone and related drugs are advocated.