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Antinociceptive Effect of Intrathecal Nefopam and Interaction with Morphine in Formalin-Induced Pain of Rats

  • Cho, Soo Young;Park, A Reum;Yoon, Myung Ha;Lee, Hyung Gon;Kim, Woong Mo;Choi, Jeong Il
    • The Korean Journal of Pain
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    • v.26 no.1
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    • pp.14-20
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    • 2013
  • Background: Nefopam, a non-opiate analgesic, has been regarded as a substance that reduces the requirement for morphine, but conflicting results have also been reported. The inhibition of monoamine reuptake is a mechanism of action for the analgesia of nefopam. The spinal cord is an important site for the action of monoamines however, the antinociceptive effect of intrathecal nefopam was not clear. This study was performed to examine the antinociceptive effect of intrathecal (i.t.) nefopam and the pattern of pharmacologic interaction with i.t. morphine in the formalin test. Methods: Male Sprague-Dawley rats were implanted with an i.t. catheter, and were randomly treated with a vehicle, nefopam, or morphine. Formalin was injected into the hind-paw 10 min. after an i.t. injection of the above experiment drugs. After obtaining antinociceptive $ED_{50}$ of nefopam and morphine, the mixture of nefopam and morphine was tested for the antinociceptive effect in the formalin test at a dose of 1/8, 1/4, 1/2 of $ED_{50}$, or $ED_{50}$ of each drug followed by an isobolographic analysis. Results: Intrathecal nefopam significantly reduced the flinching responses in both phases of the formalin test in a dose-dependent manner. Its effect, however, peaked at a dose of $30{\mu}g$ in phase 1 (39.8% of control) and $10{\mu}g$ during phase 2 (37.6% of control). The isobolograhic analysis indicated an additive interaction of nefopam and morphine during phase 2, and a synergy effect in antinociception during phase 1. Conclusions: This study demonstrated that i.t. nefopam produces an antinociceptive effect in formalin induced pain behavior during both phases of the formalin test, while interacting differently with i.t. morphine, synergistically during phase 1, and additively during phase 2.

Method for Screening and Confirming Meldonium in Human Urine by High-Resolution Mass Spectrometry and Identification of Endogenous Interferences for Anti-Doping Testing

  • Kim, Yongseok;Jeong, Dawon;Min, Hophil;Sung, Changmin;Park, Ju-hyung;Son, Junghyun;Lee, Kang Mi;Kim, Ho Jun;Lee, Jaeick;Kwon, Oh-Seung;Kim, Ki Hun
    • Mass Spectrometry Letters
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    • v.8 no.2
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    • pp.39-43
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    • 2017
  • Meldonium is a drug for treating ischemia by expanding the arteries but it can also enhance the performance of sports players. The World Anti-Doping Agency (WADA) has included it in the list of prohibited substances since 2016. Meldonium is one of the challenging substances for anti-doping testing because it is difficult to recover by general liquid-liquid or solid phase extraction due to its permanent charge and high polarity. Therefore, high-performance liquid chromatography (HPLC) is currently used by injecting a diluted urine sample (known as the "dilute-and-shoot" strategy). There is no loss of target compounds in the extraction/cleanup procedure but its high matrix effect could interfere in their separation or detection from the endogenous urinary compounds. We report a single method using high-resolution mass spectrometry that can be used for both screening and confirmation, which follows the "dilute-and-shoot" strategy. In this method, the endogenous compounds' interfering peaks in the mass spectrum are separated at a high resolution of FWHM 140,000, and the results are suitable for substance detection following the WADA guidelines. The interferences in the obtained mass spectrum of the urine matrix are identified as acetylcholine, lysine, and glutamine by further analysis and database searching. Validation of the method is performed in routine anti-doping testing, and the limit of detection is 50 ng/mL. This method uses simple sample preparation and a general reverse phase HPLC column, and it can be easily applied to other substances.

Causative Substance and Time of Mortality Presented to Emergency Department Following Acute Poisoning: 2014-2018 National Emergency Department Information System (NEDIS) (급성 중독으로 응급실에 내원하여 사망한 환자의 원인물질 및 시간 분포)

  • Lee, Hyeonjae;Choa, Minhong;Han, Eunah;Ko, Dong Ryul;Ko, Jaiwoog;Kong, Taeyoung;Cho, Junho;Chung, Sung Phil
    • Journal of The Korean Society of Clinical Toxicology
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    • v.19 no.2
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    • pp.65-71
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    • 2021
  • Purpose: The purpose of this study was to investigate the cause of acute fatal poisoning and the time of death by analyzing the National Emergency Department Information System (NEDIS) of South Korea. Methods: The NEDIS data from 2014 to 2018 excluding non-medical visits were used for this study. The patients with acute poisoning were extracted using diagnostic codes. The toxic substances were classified into pharmaceuticals, pesticides, gases, artificial poisonous substances, and natural toxic substances. Patients were classified according to the time of death, place of death, and region. In each case, the most causative substances of poisoning were identified. Results: There were 380,531 patients including poisoning-related diagnoses, of which 4,148 (1.1%) died, and the WHO age-standardized mortality rate was 4.8 per 100,000. Analysis of 2,702 death patients whose primary diagnosis was acute poisoning, the most common cause of poisoning death was pesticides (62%), followed by therapeutic drugs, gas, and artificial toxic substances. Herbicides were the most common pesticides at 64.5%. The proportion of mortality by time, hyperacute (<6 h) 27.9%, acute (6-24 h) 32.6%, subacute (1-7 d) 29.7%, and delayed period (>7 d) were 9.8%. Conclusion: This study suggests that the most common cause of poisoning death was pesticides, and 60% of deaths occurred within 24 hours. The 71% of mortality from pesticides occurred within 6-24 hours, but mortality from gas was mostly within 6 hours. According to the geographic region, the primary cause of poisoning death was varied to pesticides or pharmaceuticals.

The history of ginseng cultivation in Orient (동양에 있어서의 인삼재배 역사)

  • Koh, Seungtae
    • Journal of Ginseng Culture
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    • v.1
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    • pp.57-66
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    • 2019
  • Ginseng has been recognized as a lifespan extending medicine which has been regarded as one of the medicines classified as top medicines, as the Boncho (medical herbs) study which is influenced by the idea of guidance's costume and food concept mainly in China is gaining its bona fide form. As the demand for ginseng has been expanded to other levels, the demand for ginseng has been increasing. Ginseng from the nature reached its supply chain limit due to its extinction and difficulty of picking, so it translated into ginseng cultivation of economy rather than harvesting in nature. After the start of ginseng cultivation, the ginseng cultivation was further enhanced by the rapid development of processing methods such as white-ginseng and red-ginseng, and the surge of consumption due to the traditional belief in ginseng drug efficacy and support of scientific research. In the Joseon Dynasty, the name Gasam (cultivated ginseng) had been created as ginseng was cultivated on farmland after the stage of SanYang (wild cultivated ginseng), the purpose of the new name Gasam is to differentiate from natural ginseng, and natural ginseng lost its firm position as the genuine ginseng as the Gasam replaced the genuine ginseng, and the natural ginseng got a new name of SanSam (wild ginseng). Because the real ginseng substance concept dissipated, and as Gasam is being called ginseng, the name Gasam was also disappeared. As a result, it was possible to grow large quantities according to the arrival of the Gasam era, and it was possible to supply the demand for ginseng, and it could become one agricultural industry. In this ginseng cultivation, in Japan where ginseng did not grow naturally, it was difficult to obtain ginseng from Joseon and faced with a shortage of ginseng at all times. Therefore, the shogun cultivated the Gasam systematically at the national level by the inside of the shogunate. However, since the natural ginseng is native to China and Korea, there is a concern about the deterioration of the quality of natural ginseng due to the incorporation of cultivated ginseng (Gasam). To protect the interests, the cultivation of ginseng was subject to control. For this reason, the lack of historical information on Gasam cultivation, which had to be started secretly, would be a natural result. In this paper, althouh not sufficient enough, the historical informations were used to summarize the history of ginseng cultivation in China, Japan and Korea.

Anti-microbial Activity Effects of Ozonized Olive Oil Against Bacteria and Candida albicans (오존화 올리브 오일의 세균과 Candida alicans에 대한 항미생물 활성 효과)

  • Chung, Kyung Tae;Kim, Byoung Woo
    • Journal of Life Science
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    • v.29 no.2
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    • pp.223-230
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    • 2019
  • Ozone is a gaseous molecule able to kill microorganisms, such as yeast, fungi, bacteria, and protozoa. However, ozone gas is unstable and cannot be used easily. In order to utilize ozone properly and efficiently, plant oil can be employed. Ozone reacts with C-C double bonds of fatty acids, converting to ozonized oil. In this reaction, ozonide is produced within fatty acids and the resulting ozonized oil has various biological functions. In this study, we showed that ozonized oil has antimicrobial activity against fungi and bacteria. To test the antimicrobial activity of ozonized oil, we produced ozonized olive oil. Ozonized olive oil was applied to Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. Antimicrobial activity was assayed using the disk diffusion method following the National Committee for Clinical Laboratory Standards. Minimal inhibitory concentrations (MIC) were 0.25 mg for S. aureus, 0.5 mg for S. epidermidis, 3.0 mg for P. aeruginosa, and 1.0 mg for E. coli. Gram positive bacteria were more susceptible than Gram negative bacteria. We compared growth inhibition zones against S. aureus and MRSA, showing that the ozonized olive oil was more effective on MRSA than S. aureus. Furthermore, the ozonized olive oil killed C. albicans within an hour. These data suggested that ozonized olive oil could be an alternative drug for MRSA infection and could be utilized as a potent antimicrobial and antifungal substance.

Analysis of Poisoning Patients Using 2017-18 ED Based Injury in-depth Surveillance Data (응급실 손상환자 심층조사 자료를 이용한 2017-2018년 중독 환자의 분석)

  • Koh, Jiyoon;Jeon, Woochan;Kang, Hyunggoo;Kim, Yang Weon;Kim, Hyun;Oh, Bum Jin;Lee, Mi Jin;Chun, Byeong Jo;Chung, Sung Phil;Kim, Kyung Hwan
    • Journal of The Korean Society of Clinical Toxicology
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    • v.18 no.2
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    • pp.85-93
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    • 2020
  • Purpose: The annual statistics for poisoning are reported based on the data from poison control centers in many advanced countries. In 2016 a study was conducted to analyze the 2016 Korea Poisoning status. This study was conducted to make a better annual report for poisoning statistics in Korea from a 2017-2018 national representative database. Methods: This study was a retrospective analysis of poisoning patients based on the data from an emergency department (ED) based injury in-depth surveillance project by the Korea Centers for Disease Control and Prevention in 2017-2018. Bite or sting injuries were not included. Results: A total of 17714 patients presented to 23 EDs because of poisoning. Adults above 20 years old age accounted for 84.6% of the population, while the proportion of intentional poisoning was 60.8%. The poisoning substance presented in the ED were therapeutic drugs (51.2%), gas (20.3%), pesticides (16.4%), and artificial substances (11.4%). Overall, 35% of patients were admitted for further treatment. The mortality was 2.4% (422 cases), and the most common fatal substances in order were carbon monoxide, other herbicides, and paraquat. Conclusion: This study showed the 2017-2018 status of poisoning in Korea. The prognosis is different from the cause of poisoning and the initial mental state of the patient. Therefore, appropriate methods for preventing poisoning and therapeutic plans in specific situations are needed.

A case study of verifying a suicide by carbon monoxide intoxication committed by burning an ignition charcoal briquette (착화탄 연소에 의한 일산화탄소 중독사에서 자살입증에 관한 사례연구)

  • Sung, Tae-myung;Jo, Ju-ik;Ahn, Phil-sang
    • Analytical Science and Technology
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    • v.28 no.6
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    • pp.398-408
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    • 2015
  • Carbon monoxide (CO) intoxication, arising from CO from an ignited charcoal briquette (ICB), is a popular means of committing suicide in Korea. Most CO intoxications are related to suicide attempts; however, the possibility of a homicide disguised as a suicide cannot be ruled out. Therefore, forensic investigation of the deceased and the crime scene is crucial to confirm that the deceased committed suicide. Detection of the components of an ICB on the objects suspected of being contacted by the deceased, such as the hands, nostrils, and doorknobs, is essential for linking the crime scene to the victim in the case of suicides by ignited ICBs. The traces from an ICB were analyzed by investigating the morphological characteristics and obtaining elemental compositions. The ICBs were completely different from blackened wood, as detected by discriminant analysis with the elements of carbon and oxygen. We analyzed one case of CO intoxication to demonstrate an excellent procedure for verifying whether a suicide occurred with an ICB. We employed SEM-EDX for the analysis of an ICB, microscope-FT/IR and pyrolysis-GC/MS for a partly burnt resin-type substance, GC/MS for diphenhydramine (a sleeping drug), and GC/TCD for the CO-Hb level. We detected traces of an ICB on the hands, nostrils, and doorknobs, which were all discriminated into an ICB group. Detection of ICB traces from the nostrils could indicate that the deceased started the fire themselves to commit suicide. The partially burnt black material was analyzed as an acrylronitrilestyrene polymer, which is normally used to make bags for carrying or wrapping and could be assumed to have been used to transport the ICB. Diphenhydramine, a sleeping drug, was detected at a level of 2.3 mg/L in the blood, which was lower than that in fatal cases (8-31 mg/L; mean 16 mg/L). A CO-Hb level of 79% was found in the blood, which means that the cause of death was CO intoxication. The steps shown here could represent an ideal method for reaching a verdict of suicide by CO intoxication produced by burning an ICB in a sealed room or a car.

AN EXPERIMENTAL STUDY ON THE EFFECT OF Ca(OH)2 UPON THE HEALING PROCESS OF THE PULP AND PERIAPICAL TISSUE IN THE DOGS' TEETH (수산화칼슘이 손상치수조직 및 치근조직의 치유에 미치는 영향에 관한 연구)

  • Lim, S.S.;Yoon, S.H.;Lee, C.S.;Lee, M.J.;Kim, Y.H.;Kwon, H.C.;Um, C.M.
    • Restorative Dentistry and Endodontics
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    • v.8 no.1
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    • pp.123-131
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    • 1982
  • The purpose of this study was to observe the responses of the remaining pulp tissue after pulpotomy upon the several kinds of $Ca(OH)_2$ products and the responses of periapical tissue upon some root canal filling materials after extirpation. For pulpotomy, the class V cavities were prepared on the premolars, molars and upper canines, and the pulp was amputated. Each drug was placed over the amputated tissue and cavity was sealed with zinc oxide eugenol cement. The drugs which were used for the study were Dycal (Caulk Co. U.S.A.), Cavitec (Kerr Co. U.S.A.), Calvital, Nobudyne and Neodyne (Neo Dental Chemical Products). For extirpation, the endodontic cavities were prepared on the lingual surfaces of anterior teeth, and the pulp tissues were extirpated as routine method. After enlarging, irrigation, and measuring of root length by taking X-ray, each root canal filling material was filled in the canal with gutta percha cone, and endodontic cavity was sealed with zinc oxide eugenol cement. Zinc oxide eugenol, $Ca(OH)_2$ (Eli Lilly Co. U.S.A.) and Vitapex (Neo Dental Chemical Products) were used as root canal filling materials. Animals were sacrificed after 1, 3 and 6 weeks following the operation. The teeth were decalcified in formic acid, sectioned and stained with hematoxylin eosin. Microscopic examination revealed as follows. 1. Dycal: The dentin bridge formation was observed at the 3rd week after pulpotomy. Inflammatory conditions which were infiltration of inflammatory cells and dilatation of blood vessels were kept in remaining pulp tissue at the 6th week. 2. Calvital: The dentin bridge was observed at the 1st week after pulpotomy. As the time clasped, the pulp tended to be the fibrous degeneration. 3. Cavitec, Nobudyne and Neodyne: In the case of Cavitec and Nobudyne, the incompleted and irregular dentin bridge was observed at the 6th week, and in Neodyne, was observed at the 3rd week. The severe inflammatory changes were seen in the remaining pulp tissue. As the time clasped, the fibrous degeneration tended to spread in the remaining pulp tissue. 4. $Ca(OH)_2$: Osteocementum was formed at the 3rd week, the matrix of cementum and dentin were resorted, and infiltration of lymphocytes was seen in periapical tissue when $Ca(OH)_2$ was used as canal-filling materials. S. ZOE and Vitapex The cementum like substance was seen in periapical portion at the 1st week, when ZOE and Vitapex were used as root canal filling materials. As the time elapsed, the matrix of cementum and dentin tended to be resorted. At the 6th week, the inflammatory condition of periapical tissue was continued in the case of ZOE, but was reduced in the case of Vitapex.

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The Effect of Quinolyl Piperazine Phosphate on the Silicotic Rats (Quinolyl Piperazine Phosphate가 흰쥐 규폐증에 미치는 영향)

  • Yim, Hyeon-Woo;Jung, Chang-Young;Oh, Sang-Yong;Kim, Kyung-Ah;Lim, Young;Yun, Im-Goung;Roh, Young-Man
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.2
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    • pp.112-122
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    • 1993
  • Backgrounds : The goal of drug therapy in pneumoconiosis is to inhibit the progression of pulmonary fibrosis related to a toxic effect of the inhaled substance. Although there have been many studies on the therapy of pneumoconiosis, it is still elusive. Quinolyl piperazine phosphate (QP), a derivative of chloroquine, is less toxic, more effective, and longer action than chloroquine. This investigation was performed to examine the effect of the quinolyl piperazine phosphate in silicotic rats. Methods : The silica group was administered intratracheally by 40 mg free silica dust with 0.5 ml normal saline, and the QP group was orally administered QP 10 mg per week after free silica instillation. The animals in the silica group and the QP group were killed at the 1st, 3rd, 8th and 20th week after free silica instillation. We observed the total cell count in bronchoalveolar lavage fluid, luminol-dependent chemiluminescence by viable alveolar inflammatory cells, the dry weights and the amount of hydroxyproline in the left lung and the histopathologic examination in the right lung. Results : 1) The total number of cells of bronchoalveolar lavage fluid in the QP group tended to be decreased in comparison with the silical group. But, It was not significant. 2) Luminol-induced chemiluminescence by viable alveolar inflammatory cells in the QP group was similiar to that in the silical group. 3) The dry weights in the left lung at the 3th and 8th week in the QP group were significantly decreased compared to the silical group. 4) The total amount of hydroxyproline at the 3rd week of the QP group were significantly decreased compared to the silical group. In the silica group, the total amount of hydroxyproline was significantly increased at the 3rd week compared with the 1st group. But, in the QP group, it was significantly increased at the 8th week. 5) In tissue pathology, the infiltration of inflammatory cells around bronchiole, and the number and the size of silicotic nodule in the QP group were similar to the silica group. But, the extent of fibrosis is less than the silica group. Especially we observed progressive massive fibrosis which located in the periphery in 3 cases among the silica group, but couldn't observe in the QP group. Conclusions : QP doesn't significantly suppress the pulmonary fibrosis consequent to the intratracheal instillation of free silica dust, but delay the progression of fibrosis.

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Investigation of Unintentionally Hazardous Substance in Commercial Herbs for Food and Medicine (유통 식약공용농산물 중 비의도적 유해물질 오염도 조사)

  • Seo, Mi-Young;Kim, Myung-Gil;Kim, Jae-Kwan;Jang, Mi-Kyung;Lee, Yu-Na;Ku, Eun-Jung;Park, Kwang-Hee;Yoon, Mi-Hye
    • Journal of Food Hygiene and Safety
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    • v.33 no.6
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    • pp.453-459
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    • 2018
  • This study was performed to investigate the contamination levels of heavy metals (such as lead, cadmium, arsenic and mercury) and aflatoxin (such as $B_1$, $B_2$, $G_1$ and $G_2$) in commercial herbs for food and medicine. The concentrations of the heavy metals were measured by the ICP-MS and a mercury analyzer. The aflatoxins were analyzed by a HPLC-florescence coupled with photochemical derivatization. The detection ranges of the lead, cadmium, arsenic and mercury were found to be 0.006~4.088 mg/kg, 0.002~2.150 mg/kg, ND~0.610 mg/kg and ND~0.0139 mg/kg respectively. Among the total samples, the 3 samples (2.6%) were not suitable for the specification of cadmium by the MFDS (Ministry of Food and Drug Safety). The 13 samples of the total 117 samples were aflatoxin positive (11.1%). The amount of aflatoxin $G_1$ was $0.7834{\mu}g/kg$ in the Puerariae Radix and aflatoxin $G_2$ were $0.3517{\mu}g/kg$, $0.4881{\mu}g/kg$ in two samples of the Glycyrrhizae Radix et Rhizoma, respectively. The aflatoxins $B_2$ and $G_1$ were simultaneously detected in the 10 Angelicae Gigantis Radix. The detection ranges of aflatoxins $B_2$ and $G_1$ were $0.2324{\sim}1.0358{\mu}g/kg$ and $0.7552{\sim}1.6545{\mu}g/kg$ respectively in Angelicae Gigantis Radix. The results of the current study suggest that continuous monitoring is needed for the proactive management of commercial herbs for food and medicine safety.