• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.125-125
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• 1995

Quinolone계 항균제인 rufloxacin의 전임상시험의 일환으로 항원성 유발여부를 평가하기 여부를 평가하기 위하여 아나필락시스 쇼크 반응시험, 수동 피부 아나필락시스 반응시험 및 간접 적혈구 응집 반응시험을 실시하여 다음과 같은 결과를 얻었다. 1. 기니픽을 이용한 아나필락시스 쇼크 반응시험에서 rufloxacin의 저용량투여군(1mg/body, 추정임상용량), 고용량투여군(5mg/body), 고용량혼합투여군(5mg/body mixed with Freunds' complete or incomplete adjuvant) 및 단백결합혼합투여군(rufloxacin-BSA, 1mg/body)에 있어서 아나필락시스 쇼크 반응이 관찰되지 않았다. 2. 마우스-랫드를 이용한 수동 피부 아나필락시스 반응시험에서 저용량투여군, 고용량투여군, 오용량혼합투여군 및 bovine serum albumin(BSA)과 결합시킨 단백결합혼합투여군 모두에서 음성의 반응을 나타내었다. 3. 간접 적혈구 응집 반응시험 결과 저용량투여군, 고용량투여군, 고용량혼합투여군 및 단백결합혼합투여군에서는 각군당 1-4마리에서 16-32배에서 양성반응을 나타내었다. 그러나 음성대조군에서도 10마리 중 4마리에서 16-32배에서 양성반응을 나타낸 것으로 미루어 약물투여군에서의 미약란 양성반응이 약물특이적 반응은 아닌 것으로 사료된다. 이상의 실험결과로 미루어 rufloxacin은 항체 생성능은 가지지 않는 것으로 사료된다. 이상의 실험결과를 종합하여 볼 때 ndloxacin은 전반적인 항원성 potential은 없는 것으로 사료되며 또한 생체내에서 체내 단백과 결합하여 hapten으로 작용할 가능성은 없는 것으로 사료된다.

• Translational and Clinical Pharmacology
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• 제26권3호
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• pp.118-127
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• 2018

The safety and efficacy of fimasartan have been evaluated through post-marketing surveillance in real world clinical practice. The multi-center, prospective, open-label and non-interventional study. A total of 3,945 patients (3,729 patients for safety assessment and 3,473 patients for efficacy assessment) were screened in patients with essential hypertension in 89 study centers from 9 September 2010 through 8 September 2016. Among the total patients, 2,893 patients (77.6%) were administered fimasartan for 24 weeks or longer and were classified as 'patients with long-term follow-up', and the additional safety and efficacy analysis were performed. The improvement was defined as systolic blood pressure (SBP) controlled to ${\leq}140mmHg$ or decreased SBP differences ${\geq}20mmHg$ after treatment or diastolic blood pressure (DBP) controlled to ${\leq}90mmHg$ or decreased DBP differences ${\geq}10mmHg$ after treatment. Adverse drug reactions (ADRs) were reported in 3.8% patients; dizziness, and hypotension were the most frequently reported ADRs in total patients. The results of patients with long-term follow-up were comparable with total patients. The overall improvement rate in all efficacy assessment at the last visit was 87.1% (3,025/3,473 patients). The overall improvement rate of the patients with long-term follow-up was 88.9%. Fimasartan was well tolerated, with no new safety concerns identified and an effective treatment in the real world clinical practice for Korean patients with hypertension.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.597-603
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• 2015

Synthetic cannabinoids JWH-018 and JWH-250 in 'herbal incense' also called 'spice' were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.

• Biomolecules & Therapeutics
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• 제19권3호
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• pp.302-307
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• 2011

Peptidoglycan (PGN) is detected in inflammatory cell-rich regions of human atheromatous plaques. The present study investigated the effects of PGN on CC chemokine ligand 3 (CCL3) expression, which is elevated in the atherosclerotic arteries, and determined cellular factors involved in PGN-mediated CCL3 up-regulation in mononuclear cells, with the goal of understanding the molecular mechanisms of inflammatory responses to bacterial pathogen-associated molecular patterns in diseased arteries. Exposure of human monocytic leukemia THP-1 cells to PGN resulted in enhanced secretion of CCL3 and profound induction of the CCL3 gene transcript. Both events were abrogated by oxidized 1-palmitoyl-2-arachidonosyl-sn-phosphatidylcholine, an inhibitor of Toll-like receptors 2/4. Pharmacological inhibitors such as U0126, SP6001250, Akt inhibitor IV, rapamycin, RO318220, diphenyleneiodonium chloride, and N-acetylcysteine also significantly attenuated PGN-mediated CCL3 up-regulation. However, polymyxin B, LY294002, and SB202190 did not influence CCL3 expression. We propose that PGN contributes to enhanced CCL3 expression in atherosclerotic plaques and that Toll-like receptors (TLR2), Akt, mTOR, mitogen-activated protein kinase, and reactive oxygen species are involved in that process.

• Advances in Traditional Medicine
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• 제7권2호
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• pp.205-210
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• 2007

The objectives of the study were (1) To evaluate the safety and tolerability of Damtab. (2) To characterize hypoglycemic effect of Damtab, if any. (3) To evaluate insulin sensitivity effect of Damtab, if any. Hypoglycemic effect of Damtab (700 mg and 1,400 mg) were examined. Gliclazide (80 mg) was used as an active control. Placebo was used as control. Breakfast was given, half an hour before dosing whereas lunch, snacks and dinner were given at 6, 10 and 14 h post dose. An oral glucose tolerance test was conducted to calculate the insulin sensitivity index from the values of glucose and insulin during oral glucose tolerance test. Both giclazide 80 mg and Damtab 1,400 mg significantly lowered plasma glucose level up to 6 h. Insulin sensitivity index of Damtab (1,400 mg) was found to be similar to that of placebo. A significant increase in insulin level at 1 h post dose of Damtab (1,400 mg) was observed. Damtab 700 mg shows placebo like effect whereas Damtab 1,400 mg possesses hypoglycemic effect.

• 동의생리병리학회지
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• 제30권6호
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• pp.385-396
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• 2016

It is a fact that the existing pharmacological research method is difficult to explain the effect and mechanism of action of herbal formula of Korean medicine. We are now very pleased with the development of modern science and the development of a methodology for studying herbal formula characterized by network targets and multi-component therapeutics over the human body. In this review, systems pharmacology or network pharmacology is demonstrated how these are applied to explain the effectiveness of herbal medicine. The post-genomic era provides a unique opportunity for the two fields to understand and benefit from each other. In particular, recent research trends, research methodology, useful databases and results of research on herbal formula are introduced. China already has a policy of scientific development of traditional chinese medicine (TCM) and the development of Chinese medicine industry with a focus on herbal formula research at national level, and in Korea, it is urgent to support and nurture the methodology appropriate to the characteristics of the herbal formula in order to study the safety and efficacy of Korean medicine.

• The Korean Journal of Physiology and Pharmacology
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• 제18권6호
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• pp.475-480
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• 2014

We investigated the question of whether cholesterol catabolite can influence expression of inflammatory cytokines via Toll-like receptors (TLR) in monocytic cells. Treatment of THP-1 monocytic cells with 27-hydroxycholesterol (27OHChol) resulted in induction of gene transcription of TLR6 and elevated level of cell surface TLR6. Addition of FSL-1, a TLR6 agonist, to 27OHChol-treated cells resulted in transcription of the $IL-1{\alpha}$ gene and enhanced secretion of the corresponding gene product. However, cholesterol did not affect TLR6 expression, and addition of FSL-1 to cholesterol-treated cells did not induce expression of $IL-1{\alpha}$. Using pharmacological inhibitors, we investigated molecular mechanisms underlying the expression of TLR6 and $IL-1{\alpha}$. Treatment with Akt inhibitor IV or U0126 resulted in significantly attenuated expression of TLR6 and $IL-1{\alpha}$ induced by 27OHChol and 27OHChol plus FSL-1, respectively. In addition, treatment with LY294002, SB202190, or SP600125 resulted in significantly attenuated secretion of $IL-1{\alpha}$. These results indicate that 27OHChol can induce inflammation by augmentation of TLR6-mediated production of $IL-1{\alpha}$ in monocytic cells via multiple signaling pathways.

• Biomolecules & Therapeutics
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• 제21권1호
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• pp.42-48
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• 2013

Nystatin, a polyene antifungal antibiotic, is a cholesterol sequestering agent. The antifungal agent alters composition of the plasma membrane of eukaryotic cells, whereas its effects on cells are poorly investigated. In the current study, we investigated the question of whether nystatin was able to induce expression of macrophage inflammatory protein-1 (MIP-1). THP-1 cells rarely express MIP-$1{\alpha}$ and MIP-$1{\beta}$, however, upon exposure to nystatin, significantly elevated expression of MIP-$1{\alpha}$ and MIP-$1{\beta}$ was observed in a dose-dependent fashion at the messenger and protein levels. Cellular factors activated by nystatin as well as involved in nystatin-induced expression of MIP-1 proteins were identified in order to understand the molecular mechanisms of action of the anti-fungal agent. Treatment with nystatin resulted in enhanced phosphorylation of Akt, ERK, p38 MAPK, and JNK. Abrogation or significant attenuation of nystatin-induced expression of MIP-$1{\alpha}$ and MIP-$1{\beta}$ was observed by treatment with Akt inhibitor IV, LY294002, and SP6001250. Inhibition of ERK or p38MAPK using U0126 and SB202190 did not lead to attenuation of MIP-1 expression. In addition, inhibitors of protein kinase C, such as GF109203X and Ro-318220, also attenuated expression of MIP-1. These results indicate that nystatin is able to activate multiple cellular kinases and, among them, Akt and JNK play primary roles in nystatin-induced expression of MIP-1 proteins.

• Genomics & Informatics
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• 제6권3호
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• pp.117-125
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• 2008

Recently, obesity has become a worldwide public health concern and the use of anorectic drugs has drastically increased. In this study, sibutramine and phendimetrazine, representative marketed anorectics, were repeatedly administered per os on a daily basis into C57BL/6 mice and the effects of these drugs on food intakes, body weight changes and gene expression profiles were monitored for up to following 7 days. Methamphetamine, which has a potent anorectic effect, was used as a positive control. Anorectic effects were sustained only for two days by phendimetrazine or methamphetamine, but for six days by sibutramine. The modulations of gene expressions in the hypothalamus and the striatum were investigated using microarrays on day 2 and day 7 post-administration, which corresponded to the anorectic period and a return of appetite respectively, for all three drugs tested. Differences in overall gene expression profiles in the stratum on day 2 for sibutramine and phendimetrazine seems to reflect difference between the two in terms of the onsets of drug tolerance. According to microarray findings, the Ankrd26 gene appears to have an important anorectic role, whereas the up-regulation of the olfaction system appeared to be involved in the drug tolerance of anorectics. The microarray data presented in this study demonstrates the usefulness of gene expression analysis for gathering information on the efficacy and safety of anorectic drugs.

• Biomolecules & Therapeutics
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• 제7권3호
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• pp.271-277
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• 1999

Safety evaluation of LB71350, a new HIV-1 protease inhibitor, was performed in mice, rats and dogs. For the general behavior of mice, LB71350 at an oral dose of 200 mg/kg did not show any significant effects on muscle tone and locomotor activity. In terms of central nervous system, at oral doses of 200 mg/kg and 1000 mg/kg, LB71350 inhibited acetic acid-induced pain response approximately 41% and 83% of control. respectively. At oral doses of 200 mg/kg and 500 mg/kg, it reduced the rectal body temperature in rats. Pentylenetetrazole-induced seizure in mice was slightly potentiated by oral administration of LB71350 at doses ranging from 200 mg/kg to 1000 mg/Ag. Single or five day treatment of LB71350 doubled the hexobarbital- induced sleeping time in mice at oral doses ranging from 50 mg/kg to 500 mg/kg. It did not cause any effects on gastric secretion and acidity in rat at oral doses of 200 mg/kg and 1000 mg/kg and also it did not change intestinal motility in mice up to 1000 mg/kg. Blood coagulation indices such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) in rats were not affected by the treatment of LB71350 up to 500 mg/kg. LB71350 caused no significant effects on the cardiac output, stroke volume, heart rate, and mean blood pressure when infused intravenously to the anesthetized rats and dogs. Taken together, LB71350 at high oral doses caused significant pharmacological effects on the central nervous system and the hexobarbital-induced sleeping time.