• Natural Product Sciences
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• v.18 no.3
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• pp.177-182
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• 2012

Oxidative stress potentially induces neurotoxicity which is believed to underlie several major age-related diseases of the central nervous system. This study sought to identify the cytoprotective effects of sixty-nine Cambodian plants against glutamate-induced cell death. Cultured HT22 cells were applied as an in vitro model, and neurotoxicity was induced in these neuronal cells by exposure to a determined concentration of glutamate. Sixty-nine plant sources, as Cambodia's indigenous species, were purchased from O'reusey Market, Phnom Penh, and extracted with ethanol. These extracts were screened for cytoprotective effects against glutamate-triggered neurotoxicity in HT22 cells at concentrations of 100 and 300 ${\mu}g/ml$. Of these, eight ethanol extracts, bark of Anacardium occidentale, bark and sapwood of Bauhinia pulla, flowers of Borassus flabellifer, stems and leaves of Coix lacryma-jobi, bark and sapwood of Diospyros nitida, sapwood of Dipterocarpus obtusifolius, stems of Oryza rufipogon, and fruits of Phyllanthus emblica, showed significant cytoprotective effects against glutamate-induced cell damage and degeneration in HT22 cells.

• Journal of Korean Neurosurgical Society
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• v.38 no.1
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• pp.47-53
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• 2005

Objective : Anti-malaria drugs may modulate tumor resistance to chemotherapeutic agents, but it has not been proven effective in the treatment of malignant gliomas. The aim of this study was to determine whether adequate pre-clinical data on co-administration of chemotherapeutic agents with anti-malaria drugs on malignant cell lines could be obtained that would warrant its further potential consideration for use in a clinical trial for malignant gliomas. Methods : Two malignant glioma cell lines [U87MG, T98G] were treated with chemotherapeutic agents alone or with anti-malaria drugs. Cells were incubated with drugs for 4 days. Following the 4-day incubation, drug sensitivity assays were performed using 3-[4,5-dimethyl-2-thiazol-2-yl] 2,5-diphenyltetrazolium bromide [MTT] assay following optimization of experimental conditions for each cell lines and cell viability was calculated. Results : In all of four chemotherapeutic agents[doxorubicin. vincrisitne, nimustine, and cisplatin], the cell viability was found to be markedly decreased when hydroxychloroquine was co-administered on both U87MG and T98G cell lines. The two way analysis of variance[ANOVA] yielded a statistically significant two-sided p-value of 0.0033[doxorubicin], 0.0005[vincrisitne], 0.0007[nimustine], and 0.0003[cisplatin] on U87MG cell lines and 0.0006[doxorubicin], 0.0421[vincrisitne], 0.0317[nimustine], and 0.0001[cisplatin] on T98G cell lines, respectively. However, treatment with chloroquine and primaquine did not induce a decrease in cell viability on both U87MG and T98G cell lines. Conclusion : Our data support further consideration of the use of hydroxychloroquine prior to systemic chemotherapy to maximize its tumoricidal effect for patients with malignant gliomas.

• Journal of The Korean Society of Clinical Toxicology
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• v.14 no.2
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• pp.100-106
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• 2016

Purpose: Beta blocker (BB) has been prescribed for anxiety and panic disorder. Patients intoxicated by psychiatric drugs have often been exposed to BB. Moreover, BB overdose has adverse effects including cardiovascular effects, which can be life-threatening. This study was conducted to identify the characteristics of BB intoxication with psychiatric drugs and the adverse effects on the cardiovascular system. Methods: A single center, retrospective study was performed from January 2010 to December 2015. A total of 4,192 patients visited the emergency department (ED) with intoxication, and 69 with BB intoxication were enrolled. Results: Overall, 64 patients (92.8%) of enrolled patients were intoxicated with drugs prescribed for the purpose of psychiatric disorders. Propranolol was the most common BB (62 cases, 96.2%), and the median dose was 140.0 mg (25%-75% 80.0-260.0). Twenty-four patients (37.5%) had experienced cardiovascular events, and these patients tended to have decreased mentality, hypotension and coingestion with quetiapine. An initial mean arterial pressure (MAP) below 65 mmHg (odds ratio 10.069, 95% confidence interval 1.572-64.481, p=0.015) was identified as a factor of cardiovascular event upon multiple logistic regression analysis. Conclusion: Initial MAP below 65 mmHg was a factor of cardiovascular adverse effect in patients of BB intoxication with psychiatric drugs.

• The Korean Journal of Pharmacology
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• v.9 no.1
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• pp.23-37
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• 1973

This paper presents the effect of chronic administration of psychotropic drugs on rats. The experimental animals were litter mates (average initial body weight $47{\pm}1.1g$) whose mother were bred at our laboratory. Each litter mate was treated as one group. Control animals were treated with tap water and each experimental group was treated with caffeine citrate 0.1%, nialamide 0.1%, ethyl alcohol 2.5%, phenobarbital sod. 0.1%, diphenylhydantoin 0.1%, chlorpromazine 0.1%, reserpine 0.005%, diazepam 0.01%, chlorpheniramine 0.01% solutions respectively in drinking water over a period of ten weeks. All rats were allowed food and drinking water ad libitum. The mortality rate and the per cent increase of body weight were recorded weekly throughout the course of the experiment. The effects of above agents on the pentobarbital sleeping time, gastric secretion, and brain and liver weights were studied at the end of ten weeks treatment. The obtained results are summarized as follows: 1. Mortality rate was highest in the groups treated with phenobarbital and chlorpromazine respectively. Through the experimental period (ten weeks), the mortality rate was higher in earlier stage than in the later period. 2. During the period of prolonged administration of psychotropic drugs, only diazepam treated group showed remarkable difference in per cent increase of body weight from the control group of rats. 3. Acute treatment with psychotropic drugs delayed the onset of pentobarbital sleeping time. In contrast, the sleeping time was significantly shortened (p<0.001) when the rats were treated chronically with those agents. 4. The effects of chronic treatment with phenobarbital or diphenylhydantoin on the gastric secretion are as follows: the total acidity was remarkably decreased while the pH was increased. 5. The brain weight was significantly decreased in the ethyl alchol and in the chlorpheniramine treated groups, in the mean time, there was no change in liver weight treated with any psychotropic drugs.

• Molecules and Cells
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• v.40 no.1
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• pp.54-65
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• 2017

Although cancer/testis antigen DDX53 confers anti-cancer drug-resistance, the effect of DDX53 on cancer stem cell-like properties and autophagy remains unknown. MDA-MB-231 ($CD133^+$) cells showed higher expression of DDX53, SOX-2, NANOG and MDR1 than MDA-MB-231 ($CD133^-$). DDX53 increased in vitro self-renewal activity of MCF-7 while decreasing expression of DDX53 by siRNA lowered in vitro self-renewal activity of MDA-MB-231. DDX53 showed an interaction with EGFR and binding to the promoter sequences of EGFR. DDX53 induced resistance to anti-cancer drugs in MCF-7 cells while decreased expression of DDX53 by siRNA increased the sensitivity of MDA-MB-231 to anti-cancer drugs. Negative regulators of DDX53, such as miR-200b and miR-217, increased the sensitivity of MDA-MB-231 to anti-cancer drugs. MDA-MB-231 showed higher expression of autophagy marker proteins such as ATG-5, $pBeclin1^{Ser15}$ and LC-3I/II compared with MCF-7. DDX53 regulated the expression of marker proteins of autophagy in MCF-7 and MDA-MB-231 cells. miR-200b and miR-217 negatively regulated the expression of autophagy marker proteins. Chromatin immunoprecipitation assays showed the direct regulation of ATG-5. The decreased expression of ATG-5 by siRNA increased the sensitivity to anti-cancer drugs in MDA-MB-231 cells. In conclusion, DDX53 promotes stem cell-like properties, autophagy, and confers resistance to anti-cancer drugs in breast cancer cells.

• Herbal Formula Science
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• v.10 no.1
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• pp.157-167
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• 2002

This study was performed to investigate what effect the taste and quality of drugs would have on the cold and heat mechanisms of human body. We administered Hwangryeunhaedok-tang composed of bitter-tasted, cold-qualified drugs and Gungangbuza-tang composed of spice-tasted. hot-qualified drugs, respectively to the mice 1 hr before exposure to heat stress or cold stress. Plasma corticosterone level of mice was measured. The results were as follows: 1. The elevated corticosterone level in the mice exposed to heat stress was significantly decreased after administration of Gungangbuza-tang but there was no decrease after administration of Hwangryeunhaedok-tang. 2. The elevated corticosterone level in the mice exposed to cold stress was significantly decreased after administration of Hwangryeunhaedok-tang but there was mild decrease after administration of Gungangbuza-tang. 3. When the doses, 3g/kg and 1g/kg were administerd to mice exposed to heat stress. both dose showed significant decrease of corticosterone level and the dose. 3g/kg was more effective. However, in the mice exposed to cold stress, the dose, 3g/kg showed mild decrease and 1g/kg showed significant decrease. These data suggested that HW decreased the plasma corticosterone level in the mice exposed to cold stress and GB also decreased the plasma corticosterone level in the mice exposed to heat stress. In conclusion, our study revealed that the taste and quality of drugs controled the cold and heat mechanism of human body.

• Proceedings of the Ginseng society Conference
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• 2005.11a
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• pp.41-63
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• 2005

Ginseng has been useful for the treatment of diverse disease in oriental countries for thousands of years. In addition, a folk medicine prescribed by seven herbal drugs including Panax ginseng has been antinarcotics in the treatment of morphine-dependent patients. Many articles have been reported on these works. Therefore, we review the protective effects of Panax ginseng on the neurotoxicity induced by abuse drugs. Ginseng total saponins (GTS) extracted and isolated by Panax ginseng antagonized morphine-induced analgesia, and inhibited the development of analgesic tolerance to and physical dependence on morphine. CTS inhibited morphine-6 dehydrogenase, which catalyzes production of mophinone from morphine, and increased hepatic glutathione level responsible to toxicity. Therefore, wehypothesized that these dual actions of ginseng can be associated with the detoxication of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contraction in guinea pig ileum (${\mu}$-receptors) and mouse vas deferens(${\delta}$-receptors) were not mediated through opioid receptors, suggesting non-opioid mechanisms. On the hand, antagonism of U-50,488H (${\kappa}$-agonist)-induced antinociception is mediated by serotonergic mechanisms. GTS also inhibited hyperactivity, reverse tolerance (sensitization) and conditioned place preference-induced by psychostimulants such as methamphetamine, cocaine and morphine. On the other hand, GTS reduced the dopamine levels induced by methamphetamine. Moreover, GTS blocked the development of dopamine receptor activation, showing antidopaminergic effect. We suggest that GTS prevent the methamphetamine-induced striatal dopaminergic neurotoxicity. In addition, Ginsenoside also attenuates morphine-induced CAMP signaling pathway. These results suggested that GTS might be useful for the therapy of the adverse actions of drugs with abuse liability.

• Preventive Nutrition and Food Science
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• v.12 no.4
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• pp.202-208
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• 2007

Persimmon is well-known as a Korean traditional medicine for alleviating coughs and enhancing blood circulation; it is also used for treatment of hypertension, cancer, diabetes and atherosclerosis. To evaluate the protective properties of persimmon leaf methanol extract (PLME) and persimmon fruit methanol extract (PFME) administration on acute ethanol-induced hepatotoxicity, C57BL/6 male mice were gavaged with or without persimmon extracts for 1 week. Hepatotoxicity was then induced by gavage of 5 g/kg BW ethanol. After 12 hr of ethanol administration, blood and liver were collected and analyzed for biochemical markers of hepatotoxicity. The results showed PLME and PFME treatments decreased the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with ethanol control. Both PLME and PFME reduced serum lactate dehydrogenase (LDH) activity, but elevated alcohol dehydrogenase (ADH) activity. Serum triglyceride (TG) and hepatic cholesterol levels were significantly decreased when treated with PLME and PFME. Liver malondialdehyde (MDA) levels were significantly decreased in PLME and PFME groups compared with ethanol control. Furthermore, the administration of PLME and PFME significantly increased the activities of catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-red). In summary, PLME and PFME appeared to prevent hepatic injury by accelerating alcohol metabolism by increasing alcohol-metabolizing enzyme activities, by activating the antioxidative enzyme system against oxidative stress, and by decreasing fat accumulation, which is evidenced by decreased hepatotoxic indices in serum.

• Health Policy and Management
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• v.20 no.1
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• pp.64-86
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• 2010

Korea has had problems with the price and supply of essential drugs such as Gleevec for leukemia, Fuzeon for HIV/AIDS, and Tamiflu for both avian flu and swine flu. The shortage or refusal of patented drugs supply is imposing a heavy burden in not only developing countries but also developed countries. Thinking over the serious results, we need to concern about the limited access to patented drugs by multinational drug companies' patent monopoly especially for pandemic and life threatening diseases. The effective response regarding to pandemic and life threatening diseases. The effective response regarding to pandemic situation requests collaborative and unbiased provisions of all countries in the world, however, sometimes patent monopoly may hinder the efforts. Compulsory licensing has been considered to be a useful alternative to the abuse of patent rights. However, the Korean experiences of compulsory licensing have left some controversial issues in connection with the availability of it in Korea. 'Flexibility' allowed in TRIPS and Doha Declaration has not come into effect in Korea for several reasons. Although the situation shows the limitations of compulsory licensing as a pharmaceutical supply policy, it is clear that compulsory licensing still has the possibilities of enhancing the access to medicines of all countries in need. Through searching the institutionalization process and experiments of compulsory licensing in Korea, this article explores the possibilities and the limits.

• The Korean Journal of Pain
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• v.30 no.3
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• pp.183-191
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• 2017

Background: Current therapy for the treatment of neuropathic pain is often unsatisfactory. Considerable variation in treatment pattern still exists in spite of availability of sufficient literature from various guidelines. Recent Indian market data suggested that the utilization (sale) of drugs such as amitriptyline, pregabalin, and gabapentin was more for low-dose unit packs than that of the high-dose unit packs, raising the belief that these drugs are prescribed at a lower dose than is actually recommended in the guidelines. To test this hypothesis, a survey was conducted across speciality throughout the country to observe the prescription pattern of these drugs amongst the health care providers in India. Methods: Three hundred fifty survey forms were distributed of which 281 forms were included for analysis. Results: It was observed that the commonly used initiation and maintenance dose for amitriptyline, pregabalin, and gabapentin was 5-10 mg/day, 50-75 mg/day, and 100-300 mg/day, respectively. The reason to select the lower dosages was to have a balancing effect to achieve good efficacy with minimum side effects. Care-givers reported no side effects/not many side effects as a reason in 22.2%, 16.88%, and 23.86% patients with amitriptyline, pregabalin, and gabapentin, respectively. Sedation and giddiness were commonly reported with all three drugs. Conclusions: Commonly prescribed drugs for management of neuropathic pain, such as amitriptyline, pregabalin, and gabapentin are preferred at lower doses in Indian clinical settings. Acceptable efficacy and low tolerance to the standard dosage is believed to be the reason behind the prescribed dose.