• Title/Summary/Keyword: Dose-related effect

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Melittin Inhibits Human Prostate Cancer Cell Growth through Induction of Apoptotic Cell Death

  • Park Hye-Ji;Lee Yong-Kyung;Song Ho-Seub;Kim Goon-Joung;Son Dong-Ju;Lee Jae-Woong;Hong Jin-Tae
    • Toxicological Research
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    • v.22 no.1
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    • pp.31-37
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    • 2006
  • It was previously found that melittin inhibited $NF-{\kappa}B$ activity by reacting with signal molecules of $NF-{\kappa}B$ which is critical contributor in cancer cell growth by induction of apoptotic cell death. We here investigated whether melittin inhibits cell growth of human prostate cancer cells through induction of apoptotic cell death, and the possible signal pathways. Melittin ($0{\sim}1\;{\mu}g/ml$) inhibited prostate cancer cell growth in a dose dependent manner. Conversely related to the growth inhibitory effect, melittin increased the induction of apoptotic cell death in a dose dependent manner. Melittin also inhibited DNA binding activity of $NF-{\kappa}B$, an anti-apoptotic transcriptional factor. Consistent with the induction of apoptotic cell death and inhibition of $NF-{\kappa}B$, melittin increased the expression of pro-apoptotic proteins caspase-3, and Bax but down-regulated anti-apoptotic protein Bcl-2. These findings suggest that melittin could inhibit prostate cancer cell growth, and this effect may be related with the induction of apoptotic cell death via inactivation of $NF-{\kappa}B$.

Effect of Econazole on ATP- and Compound 48/80-Induced Histamine Release in Rat Peritoneal Mast Cells (흰쥐의 복강비만세포에서 ATP와 Compound 48/80에 의한 Histamine 유리에 미치는 Econazole의 영향)

  • 장용운;이윤혜;이승준;서무현;윤정이
    • YAKHAK HOEJI
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    • v.45 no.3
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    • pp.282-286
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    • 2001
  • To investigate the different mechanism between ATP and compound 48/80 (C$_{48}$80/)-induced histamine release, we observed effects of calcium antagonists in histamine release of rat peritoneal mast cells. Verapamil and diltiazem (voltage-dependent calcium channel blocker) and TMB-8 (a blocker of intracellular calcium release) significantly inhibited ATP-induced histamine release, but did not inhibit $C_{48}$80/-induced histamine release. Econazole (a blocker of receptor-operated calcium channel) dose-dependently inhibited both ATP and $C_{48}$80/-induced histamine release, but inhibitory effect of econazole in ATP-induced histamine release was more potent than that in $C_{48}$80/-induced histamine. EGTA dose-dependently inhibited ATP and $C_{48}$80/-induced histamine release, but $C_{48}$80/-induced histamine release was slightly inhibited by high concentrations (>2 mM) of EGTA. These results suggest that ATP-induced histamine release is related to broth intracellular calcium release and extracellular calcium influx via voltage-dependent calcium channel and receptor-operated calcium channel. $C_{48}$80/-induced histamine release is related to extracellular calcium influx, especially by receptor-operated calcium channel rather than voltage-dependent calcium channel.

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Cardiovascular effect of epinephrine in endodontic microsurgery: a review

  • Jang, Youngjune;Kim, Euiseong
    • Restorative Dentistry and Endodontics
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    • v.38 no.4
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    • pp.187-193
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    • 2013
  • Epinephrine is one of the most widely-used vasoconstrictors in dental treatment including endodontic microsurgery. However, the systemic safety of epinephrine has been in debate for many years because of its potential risk to cause cardiovascular complications. The purpose of this review was to assess the cardiovascular effect of epinephrine use in endodontic microsurgery. Endodontic microsurgery directly applies epinephrine into the bone cavity, and the amount is reported to be much larger than other dental surgeries. Moreover, when considering that systemic potency of intraosseous application is reported to be comparable to intravenous application, the systemic influence of epinephrine could be increased in endodontic microsurgery. Besides, pre-existing cardiovascular complications or drug interactions can enhance its systemic influence, resulting in increased susceptibility to cardiovascular complications. Although clinical studies have not reported significant complications for patients without severe systemic complications, many epinephrine-induced emergency cases are warning the cardiovascular risk related with pre-existing systemic disease or drug interactions. Epinephrine is a dose-sensitive drug, and its hypersensitivity reaction can be fatal to patients when it is related to cardiovascular complications. Therefore, clinicians should recognize the risk, and the usage of pre-operative patient evaluation, dose control and patient monitoring are required to ensure patient's safety during endodontic microsurgery.

Molecular Biological Study of Anti-cancer Effects of Bee Venom Aqua-acupuncture (봉독약침(蜂毒藥鍼)의 항암효과(抗癌效果)에 대한 분자생물학적(分子生物學的) 연구(硏究))

  • Park, Chan-Yol;Seo, Jung-Chul;Choi, Do-Young;Ahn, Byoung-Choul
    • Journal of Pharmacopuncture
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    • v.3 no.1
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    • pp.1-19
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    • 2000
  • To study anti-cancer effect and molecular biological mechanism of bee venom for aqua-acupuncture, the effects of bee venom on cell viability and apoptosis were analyzed using MTT assay, tryphan blue assay, $[^3H]$thymidine release assay, flow cytometric analysis, and activity of caspase-3 protease activity assay. To explore whether anti-cancer effects of bee venom are associated with the transcriptional control of gene expression, quantitative RT-PCR analysis of apoptosis-related genes was performed. The obtained results are summarized as follows: 1. The MTT assay demonstrated that cell viability was decreased by bee venom in a dose-dependant manner. 2. Significant induction of apoptosis was identified using tryphan blue assay, $[^3H]$thymidine release assay, and flow cytomet1 ric analysis of sub $G_1$ fraction. 3. In analysis of caspase-3 protease activity, the activity had increased significantly, in a dose-dependant manner. 4. Quantitative RT-PCR analysis of the apoptosis-related genes showed that Bcl-2 and Bcl-$X_L$ were down-regulated whereas Bax was up-regulated by bee venom treatment.

Skin Radioprotector (Diethone) Modifying Dermal Response of Radiation on Rats (방사선 보호제(Diethone)의 랫드 피부반응에 대한 수식작용)

  • Hong, Seong-Eon;Urahashi, Shingo;Kamata, Rikisaburo
    • Radiation Oncology Journal
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    • v.7 no.1
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    • pp.15-22
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    • 1989
  • Investigations were carried out into the time-and dose-related changes in acute skin reaction following graded single dose (20,30 and 40 Gy) of x-ray irradiation in Wistar rats, in order to evaluate the radioprotective effect of Diethon on skin. For the duration of skin response over 1. 5 score in dose of 40 Gy, the Diethone group of 24.7 days was significantly different (p<0.02) from that of control (29.8 days) and vaseline (29.2 days) groups, it was $17.1\%$ diminution of skin response period compared with that of control group. By the averaging daily scores for 10 days during peak skin reaction the mean scores were obtained. Mean score of Diethone group $(2.43\pm0.22)$ was significantly different (p<0.01) from that of control $(2.91\pm0.23)$ and vaseline $(2.81\pm0.18)$ groups of 40Gy dose. By iso-effect dose obtained at level of 2.5 score the dose reduction factor (DRF) was 1.41 which reduced radiation dose of $41\%$ by radioprotective effect of Diethone. From this experimental data, it may be possible to give higer radiation dose to large and/or radioresistant tumor mass rather than conventional treatment doses for improving therapeutic ratio by using topical application of skin radioprotector.

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A Study of Side Effects from Korean Herb Medicine on Children (한약을 복용한 소아에게 발생한 부작용에 대한 연구)

  • Jung, Sun-Kyung;Gok, Su-Yeong;Yu, Sun-Ae;Lee, Seung-Yeon
    • The Journal of Pediatrics of Korean Medicine
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    • v.24 no.3
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    • pp.33-42
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    • 2010
  • Objectives: The purpose of this study is to investigate the frequency of side effects, and the range of the side effects from Korean herb medicine on children. Methods: The study has been carried out from 212 children who took Korean herb medicine in Department of Pediatrics, $\bigcirc\;\bigcirc$ Oriental Medical Hospital from September 2009 to February 2010. The study was completed through patients chart review and telephone survey. Results: 1. There were 6 side effect cases on male, and 3 side effect cases on female out of 212 children. The incidence of side effect was 4.2%. 2. The most common side effect was abdominal pain. The most common related organ was digestive organ. 3. The side effect occurred within one to three days after taking Korean herb medicine, and the symptoms were mostly disappeared after taking the Korean herb medicine into divided dose or less dose. Conclusions: The symptom of side effects on children was not as severe as other adverse drug reactions often seen in Western medication. The most common symptom was abdominal pain. Further studies are needed.

Picrotoxin-induced Hyperglycemia and the Influences of Several Drugs on the Hyperglycemia (Picrotoxin의 과혈당작용(過血糖作用)과 그에 대(對)한 몇 약물(藥物)의 영향(影響))

  • Chun, Boe-Gwun
    • The Korean Journal of Pharmacology
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    • v.14 no.1_2
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    • pp.55-62
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    • 1978
  • Ban formulated the concept of 'sympathetic center' and 'parasympathetic center' in the central nervous system, and Folkow et al. reported that the electric stimulation of the posterior part of hypothalamus induced the marked liberation of catecholamines from the adrenal medulla. Tatum reported that the hyperglycemic action of picrotoxin is contributed to the cathecholamines liberation from adrenal medulla by the excitation of hypothalamus via splanchnic nervous plexus. In this paper, the relationship between the convulsive action and the hyperglycemic effect of picrotoxin was investigated, with references to the influences of several drugs related with adrenergic function and two intravenous anesthetics on the picrotoxin hyperglycemia. The results obtained were summarized as follows; 1) There was no difference between the convulsive dose(1. 5mg/kg) and the subconvulsive dose (0.75mg/kg) of picrotoxin in its hyperglycemic effect that was not affected with the phenobarbital pretreatment, but the efficacy of its hyperglycemic action was more prominent than that of strychnine. 2) The hyperglycemic effect of picrotoxin was markedly suppressed by the pretreatment of thiopental or ketamine. 3) The hyperglycemic effect was not affected by the reserpine pretreatment, but the effect was markedly suppressed by the pretreatment of iproniazid or chlorpromazine. 4) The hyperglycemic effect of picrotoxin was significantly suppressed by the pretreatment of hexamethonium, propranolol or guanethidine, and the order of those suppressing efficacy was propranolol> hexamethonium> guanethidine.

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Ion Beam Assisted Crystallization Behavior of Sol-Gel Derived $PbTiO_3$ Thin Films

  • Oh, Young-Jei;Oh, Tae-Sung;Jung, Hyung-Jin
    • The Korean Journal of Ceramics
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    • v.2 no.1
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    • pp.48-53
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    • 1996
  • Ion beam assisted crystallization behavior of sol-gel derived $PbTiO_3$ thin films, deposited on bare silicon(100) substrates by spin-casting method, has been investigated. Ar ion bombardment was directly conducted on the spincoated film surface with or without heating the film from room temperature to $300^{\circ}C$. Ion dose was changed from $5{\times}10^{15}$ to $7.5{\times}10^{16}$ $Ar^-/cm^2$. Formation of (110) oriented perovskite phase was obseerved with ion dose above $5{\times}10^{16}\; Ar^+/cm^2$. Crystallization of $PbTiO_3$ thin film could be enhanced with increasing the Air ion dose, or heating the substrate during ion bombardment. Crystallization of the $PbTiO_3$ films by ion bombardment was related to the local heating effect during ion bombardment.

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Combined Repeated Dose and Reproductive/Developmental Toxicities of Benzoyl Peroxide (Benzoyl Peroxide의 반복투여 독성과 생식 및 발생독성)

  • 송상환;김수현;배희경;김미경;구현주;박광식;이상균;박중훈;최은실
    • Toxicological Research
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    • v.19 no.2
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    • pp.123-131
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    • 2003
  • This study was carried out to assess the combined repeated dose, reproduction and developmental toxicities of benzoyl peroxide for OECD SIDS (Screening Information Data Set) program. Male and female Sprague-Dawley rats were exposed to benzoyl peroxide at dose levels of 0, 250, 500 and 1,000 mg/kg/day for 29 days for males and for 41-51 days for females. No deaths were found in all animals including control group during exposure period. No hematological effects attributable to benzoyl peroxide were observed in all treated groups. Significant decrease in the weight of testes and epididymis were observed in males at 1,000 mg/kg/day. In females at 1,000 mg/kg/day, slight histopathological effects in uterus such as epithelial vacuolation or hyperplasia were observed. No treatment-related changes in precoital time and rate of copulation, fertility and gestation period were noted in all treated groups. There was no evidence of teratogenic effect of benzoyl peroxide, but body weight of pups at 1,000 mg/kg/day was significantly decreased. NOAEL for combined repeated dose and reproduction/developmental toxicity was 500 mg/kg/day.

Four-Week Repeated-Dose Toxicity Studies of CONP01 in Rats (랫드에서 CONP01에 대한 4주 반복투여 독성연구)

  • Hong Dong Ho;Zhang Hu-Song;Kim Kwang-Ho;Gil Gi Hyun;Kim Jae Min;Han Myong Kyu;Bae Jin-Sook;Kim Nam Du;Lee Hyun Kul;Lee Jung Suk;Lee Sun Kyung;Park Chan Koo;Song Si Whan
    • Toxicological Research
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    • v.20 no.4
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    • pp.349-357
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    • 2004
  • This study was performed to evaluate repeated-dose toxicities of CONP01 in Sprague-Dawley rats. CONP01, a new antiarthritic agent was administered orally to rats at dose levels of 0, 125, 500 and 2,000 mg/kg/day for 4 weeks. In present study, there were no dose response changes in mortality, clinical signs, body weight changes, food and water consumption, ophthalmoscopy, organ weights, urine analysis, hematological findings, and biochemical examination of all animals treated with CONP01. Gross and histopathological findings revealed no evidence of specific toxicity related to CONP01. These result suggest that no observed adverse effect level (NOAEL) of CONP01 may be over 2,000 mg/kg in rats.