• Title/Summary/Keyword: 반복투여

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Spinal α2 Adrenoceptor and Antiallodynic Effect by Clonidine after Chronic Administration of 4-Methylcatechol in Neuropathic Rat Pain Model (신경병증성 통증모델에서 신경영양인자 유도물질의 반복 투여가 척수 아드레날린계에 미치는 영향)

  • Chung, Kyu Yeon;Shin, Sang Wook;Choi, Bong Soo;Kim, Chul Hong;Kim, Kyung Hoon;Kim, Hae Kyu
    • The Korean Journal of Pain
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    • v.21 no.3
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    • pp.179-186
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    • 2008
  • Background: The adrenergic nervous system in the spinal cord contributes to the development of neuropathic pain after nerve injury. Brain derived neurotrophic factor may facilitate the sympathetic change in the spinal cord and influence the state of neuropathic pain. We probed the effect of chronic repetitive administration of systemic 4-methylcatechol, which is known to be a neurotrophic factor inducer, in a spinal nerve ligation model. Methods: We made the rat neuropathic pain model by the ligation of the L5 spinal nerve. Intraperitoneal 4-methylcatechol ($10{\mu}g/kg$) or the same volume of saline wasadministrated twice daily just after the operation for 7 days. The tactile allodynia was measured by using von Frey filaments and its change was followed up from 3 days after SNL. The lumbosacral enlargement of the spinal cord was taken out and the mRNA contents of the ${\alpha}_2-adrenoceptor$ subtypes were measured by real time polymerase chain reaction and this was then compared with the control groups. The antiallodynic effect of intrathecal clonidine (3, 10, $30{\mu}g$) was evaluated and compared in the 4-methylcatechol treated rats and the control rats. Results: The expression of the ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptor subtypes did not change after 4-methylcatechol treatment. Intrathecal clonidine showed an earlier and better effect at the highest dose ($30{\mu}g$ intrathecal), but not with any other doses. Conclusions: Chronic intraperitoneal administration of 4-methylcatechol may improve the effect of intrathecal clonidine, but we could not prove the increase of ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptors in the spinal cord of 4-methylcatechol treated rats.

A case of idiopathic pulmonary hemosiderosis with seasonal recurrence (계절성으로 재발한 특발성 폐 혈철 침착증 1예)

  • Kwak, Ga Young;Lee, Na Young;Lee, Moon Hee;Lee, Soo Young;Chung, Seung Yun;Kang, Jin Han;Jeong, Dae Chul
    • Clinical and Experimental Pediatrics
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    • v.52 no.2
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    • pp.256-260
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    • 2009
  • Idiopathic pulmonary hemosiderosis (IPH) is a rare disease affecting mostly children. This disorder is characterized by recurrent episodes of hemoptysis, bilateral diffuse pulmonary infiltrates, and iron-deficiency anemia. An acute fulminant alveolar hemorrhage can be fatal due to respiratory failure, while chronic hemorrhage leads to hemosiderin-laden macrophages and pulmonary fibrosis. Genetic, autoimmune, allergic, environmental, and metabolic mechanisms of pathogenesis have been suggested, but the etiology of IPH remains unknown. We report on a 9-year-old girl with idiopathic pulmonary hemosiderosis who showed seasonal recurrences without cause.

Multiple-dose Intramuscular Toxicity Study of Shinbaro Pharmacopuncture in Sprague-Dawley Rats over a 4-week period (SD(Sprague-Dawley) 랫드를 이용한 신바로 약침의 4주 반복 근육투여 독성시험)

  • Lee, Jin Ho;Ha, In Hyuk;Kim, Me Riong;Kim, Min Jeong;Lee, Jae Woong;Lee, In Hee;Chung, Hwa Jin;Kim, Eun Jee
    • Journal of Acupuncture Research
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    • v.32 no.4
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    • pp.77-89
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    • 2015
  • Objectives : To evaluate the safety of multiple-dose intramuscular Shinbaro Pharmacopuncture in male and female Sprague-Dawley(SD) rats over a period of 4 weeks(12 sessions). Methods : In order to test the safety of multiple-dose intramuscular Shinbaro Pharmacopuncture we used 40 healthy male and female 6-week old SD rats(male weight 171.79~196.37 g, female weight 127.93~146.43 g). Shinbaro Pharmacopuncture was administered intramuscularly to male and female SD rats at doses of 4.6 (low dose group, n=10), 9.2 (moderate dose group, n=10), and 18.5 mg/kg(high dose group, n=10), respectively. General symptoms, body weight changes, blood tests, biochemical testing, necropsy, organ weight and histopathogical findings were examined over a 4-week period. Results : 1. No mortalities or adverse effects were caused by the investigational substance were observed during the study period. 2. There was no significant difference in body weight caused by the the investigational substance across all groups. 3. No significant between-group difference was found to be caused by the investigational substance in blood tests and biochemical testing. 4. No abnormalities were detected by a necropsy examination with the unaided eye at the macro level after treatment with the investigational substance. 5. Difference in organ weight between groups caused by the investigational substance was not found. 6. All groups did not exhibit pathological findings caused by the investigational substance in histopathogical examination. Conclusions : According to these results, Shinbaro Pharmacopuncture has no systemic or organ toxicity with multiple-dose intramuscular administrations in male and female SD rats over a 4-week period (12 sessions). These results imply that no adverse effects are observed at a level (NOAEL) of Shinbaro Pharmacopuncture of 18.5 mg/kg.

Effects of white ginseng and red ginseng extract on learning performance and acetylcholinesterase activity inhibition (백삼과 홍삼추출물의 학습수행과 Acetylcholinesterase 억제에 미치는 효과)

  • Lee, Mi-Ra;Sun, Bai-Shen;Gu, Li-Juan;Wang, Chun-Yan;Mo, Eun-Kyoung;Yang, Sun-Ah;Ly, Sun-Young;Sung, Chang-Keun
    • Journal of Ginseng Research
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    • v.32 no.4
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    • pp.341-346
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    • 2008
  • In the present study, we assessed the effects of white ginseng and red ginseng extract on the learning and memory impairments induced by scopolamine. The cognition-enhancing effect of ginseng extracts was investigated using the Morris water maze and Y-maze test. Drug-induced amnesia was induced by treating animals with scopolamine (2 mg/kg, i.p.), an antagonist of muscarinic acetylcholine (ACh) receptor. Tacrine was used a positive control. Ginseng extract (200 mg/kg, p.o.), tacrine (10 mg/kg, p.o.) administration significantly reduced the escape latency during training in the Morris water maze (p<0.05). At the probe trial session, scopolamine significantly increased the escape latency on day 5 in comparison with control (p<0.01). The effect of ginseng extracts on spontaneous alternation in Y-maze was similar to that of scopolamine treated group. In addition, numbers of arm entries were similar in all experimental groups. Moreover, red ginseng extract significantly inhibited acetylcholinesterase activity in the cortex and serum (p<0.05). Brain ACh contents of ginseng extract treated groups increased more than that of scopolamine group, which did not show statistically significant. These results suggest that ginseng extract may be useful for the treatment of cognitive impairment.

Effect of Functional Yogurt (R&B Rhythm®) on the Improvement of Constipation in Animal Models (실험동물에서 기능성 요구르트(R&B Rhythm®)의 변비개선효과)

  • Im, Joong-Hyun;Choi, Jae-Kyoung;Lee, Myoung-Hee;Ahn, Young-Tae;Lee, Jung-Hee;Huh, Chul-Sung;Kim, Geun-Bae
    • Food Science of Animal Resources
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    • v.31 no.3
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    • pp.442-450
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    • 2011
  • We investigated the improvement in intestinal function and the constipation preventive and remedial effects of the fermented milk product R&B $Rhythm^{(R)}$ in mice and rats. The results showed that the effects varied significantly among different doses. The digestive tract transfer rate increased dramatically in a dose-dependent manner in both animals. Compared with treating constipation with loperamide alone, treatment with loperamide and the fermented milk R&B Rhythm improved the number of fecal pellets from the animals, suggesting that it is effective for preventing and relieving constipation. Both the quantity of feces and water content of the feces increased significantly at high levels of yogurt feeding. These results suggest that repetitively ingesting fermented milk products could be effective for preventing and treating constipation symptoms.

Hydrate Production Performance Analysis with Multi-Well, Plate-Type Apparatus Using Depressurization and Thermal Methods (다중공 평판형 장비를 이용한 감압법과 열자극법에 의한 하이드레이트 가스 생산성 분석)

  • Lee, Youngsoo;Wang, Jihoon;Park, Jungkyoon;Sung, Wonmo
    • Korean Chemical Engineering Research
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    • v.47 no.1
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    • pp.133-140
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    • 2009
  • This paper presents the experimental study to analyze the pressure and production behavior using depressurization and thermal methods in order to evaluate the hydrate productivity in the 2-D multi-well, plate-type apparatus which has 80 md permeability and 30% hydrate saturation. Injecting methane gas through multi-well allowed to set up the highly saturated hydrate system and combining two different sorts of sands made possible to build up the low permeability system. In this system, both depressurization and electric stimulation methods were applied. When operating pressure was low, according to the depressurization experiments results, the gas recovery was high, however strong pulses which appeared at initial stage of production would damage the operation system. Moreover, cases that hydrate reformed have occurred by endothermic reaction. We have conducted experiments four and six times for the depressurization magnitudes of 140 psi and 320 psi, respectively, to analyze production behavior for the method more in detail. For the cases that the depressurization magnitude was set as 140 psi, the unstable period appears in the results, but stabilized soon. In the experiment results for 320 psi the discontinuous and intermittent behavior has been observed. Thermal stimulation experiments was conducted with depressurizing 80 psi which is the case that shows stable behavior and low recovery. In the results, the gas recovery was high and the energy efficiency was low for long stimulating time. The energy efficiency and gas recovery increased for the soaking time of 1 minute after 2 minute-preheating. In the cases of which the soaking time exceeds 1 minute, energy loss by long soaking time caused low gas recovery and poor energy efficiency.

Synergistic Effect of Oxygen Pressure and Sonophoresis for Skin Permeability (산소 압력과 초음파를 이용한 피부투과도 증대에 관한 연구)

  • 차민석;이철규;윤영로;이원수
    • Journal of Biomedical Engineering Research
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    • v.23 no.3
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    • pp.189-196
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    • 2002
  • Transdermal drug delivery offers an alternative method to the conventional oral and injection delivery method. Its advantages include its ability to deliver drugs directly into systemic circulation. However, there have been restrictions in its application to deliver drugs because of the skin's barrier function. In this study, we try to combine a Sonophoresis and oxygen Pressure method in order to increase the Permeability of the skin. we used water as the compound and by utilizing the skin impedance method. we measured the hydration Permeability of skin Ultrasound was applied using a sonicator(Solcare-U1000. Solco, Korea) operating at a frequency of 1MHz. oxygen Pressure was applied using a compressor(Oxyjet-Pointer, Nora Bode. Germany) operating at a pressure of 2Bar/cm2. Experiment was performed in vivo for 42 People. We divided the subjects into four smaller groups. A different transdermal drug delivery method was applied for each group on the back of their hand. We measured the skin impedance variations on the hand. during a 20-minute time Period. The control group did not show any significant increase or variation of skin impedance to water. In comparison to the control group(Passive diffusion) the hydration Permeability of the ultrasound group and the oxygen Pressure group was approximately 25 and 30 times higher consecutively. Futhermore, the hydration permeability of the combination of ultrasound and oxygen Pressure group was about 70-fold higher in comparison to the control group(passive diffusion) . The results reveal that a combination of ultrasound and oxygen Pressure will significantly enhance transdermal water transport compared when only one of them is used.

Role of Adenosine and Protein Kinase C in the Anti-ischemic Process of Ischemic Preconditioning in Rat Heart (허혈전처치의 허혈심장 보호과정에서 Adenosine 및 Protein Kinase C의 역할)

  • You, Ho-Jin;Park, Jong-Wan;Kim, Myung-Suk
    • The Korean Journal of Pharmacology
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    • v.32 no.1
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    • pp.31-37
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    • 1996
  • The protective effect of 'ischemic preconditioning (IP)'on ischemia-reperfusion injury of heart has been reported in various animal species, but the mechanism is unclear. In an attempt to elucidate the mechanism of IP, we examined the effects of blockers against adenosine and protein kinase C in preconditioned heart of rat. The hearts perfused with oxygen-saturated Krebs-Henseleit solution by Langendorff method were exposed to 30 min global ischemia followed by 20 min reperfusion. IP was performed with three episodes of 5 min ischcmia and 5 min reperfusion just before ischemia-reperfusion. IP prevented the depression of contractile function and the myocardial contracture in the ischemic-reperfused heart and reduced the release of lactate dehydrogenase during the reperfusion period. Polymyxin B, chelerythrine and colchicine, PKC inhibitors, attenuated almost completely the anti-ischemic effect of IP, while adenosine receptor antagonists did not. These results indicate that PKC may be a crucial intracellular mediator in anti-ischemic action of IP in ischemic-reperfused rat heart, while adenosine may not be involved in the mechanism of IP.

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Toxicity Assessment of Polygalae Radix Aqueous Extract Orally Administered to Rats for 2 Consecutive Weeks (원지 추출물의 랫드에서 2주 반복 경구투여 독성평가)

  • Han, Hyoung-Yun;Kim, Soo Nam;Yang, Young-Su;Han, Su-Cheol;Seok, Ji-Hyeon;Roh, Hang Sik;Lee, Jong-Kwon;Jeong, Jayoung;Jeong, Yeon Woo;Kim, Jeong Ah;Min, Byung Sun
    • Korean Journal of Pharmacognosy
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    • v.46 no.1
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    • pp.44-51
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    • 2015
  • The objective of this study is to characterize a toxicity of Polygalae Radix (PR) in F344 rats and to find a dose levels for the 13 weeks toxicity study. PR is well known as medicinal herb in many Asian countries for treatment of expectorant, tonic, tranquillizer, antipsychotic agent and functional diet for improving memory. However, there is insufficient background information on toxicological evaluation of PR extract to support its safe use. Therefore, we conducted toxicological evaluation of this drug in compliance with OECD and KFDA guideline in this study. The extract of PR was administered orally to F344 rats at dose levels of 0, 500, 1000, 2000, 3500 and 5000 mg/kg/day for 2 weeks. Each group was composed to five male and five female rats. In the result, there were no treatment PR-related adverse changes in food consumption, hematology, clinical chemistry, urinalysis, gross finding at necropsy, organ weight examination. Four males at 5000 mg/kg/day were found dead during the treatment period. These animals showed salivation. The cause of death is still under investigation. The animals treated at 500, 1000, 2000, 3500 and 5000 mg/kg/day showed salivation and all animals at 5000 mg/kg/day exhibited lower body weight and cumulative weight gain in compared to those of control animals. Therefore, we recommend that a dose group of 3500 mg/kg/day is a highest treatment group in 13-week exposure study.

An Experimental Study on Single-dose and 4 Weeks Repeated-dose Toxicity of Aconitum ciliare Decaisne Pharmacopuncture (초오약침의 단회 및 4주 반복 투여 독성에 관한 실험적 연구)

  • Lee, Hyun Su;Lee, Yun Kyu;Lee, Bong Hyo;Kim, Jae Soo;Lim, Sung Chul;Lee, Hyun-Jong
    • Korean Journal of Acupuncture
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    • v.34 no.4
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    • pp.241-250
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    • 2017
  • Objectives : This study was performed to examine the toxicity of Aconitum ciliare Decaisne pharmacopuncture(ADP). Methods : The toxicity was evaluated for lethal dose for 50 percent kill(LD50), single dose and repeated dose for 4 weeks. Toxic symptoms, weight measurement, hematological test, blood biochemical test, visual examination and weight measurement of major organs and histopathological test were observed for 4 weeks. Dose of 300, 600, 1,200, 2,400, 3,600, 4,800, 6,000, 7,200 mg/kg in the LD50 experiment, 300, 600, 1,200 mg/kg/day in the single experiment, 150, 300, 600 mg/kg/day in 4 weeks experiments were injected into BALB/c mice. The ADP was injected into ST36 of the right leg. Normal saline solution of same volume was used for control group. In 24 hours after the last treatment, blood samples were taken after anesthesia by inhalation of ethyl ether. After that, the BALB/c mice were euthanized. Their heart, lungs, kidneys, liver and reproductive organs were removed and weighed. Histopathological evaluation was also performed. Results : ADP's LD50 was measured at 6,000 mg/kg. In both single and repeated dose toxicity test, no BALB/c mouse died during the experiments. ADP treatment for 4 weeks did not show any significant changes in toxic symptoms, weight measurement, hematological test, blood biochemical test, visual examination and weight measurement of major organs and histopathological test. Conclusions : As a result, ADP's LD50 was 6,000 mg/kg and repeated dose at a concentration of 600 mg/kg or less is considered to be not harmful for clinical treatment.