• Title/Summary/Keyword: single and repeated administration

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Effect of Acupuncture(PC6) on Behavior, Dopamine Release in the Nucleus Accumbens in Rats Sensitized to Morphine (몰핀에 민감화된 흰쥐의 내관부위 자침이 행동과 측핵의 도파민 유리에 미치는 효과)

  • Kim, Sang-Ho;Lyu, Seung-Jun;Kim, Tae-Heon;Kang, Hyung-Won;Lyu, Yeoung-Su
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.4
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    • pp.982-992
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    • 2005
  • Acupuncture as a therapeutic intervention is widely used for the treatment of many functional disorders such as substance abuse and mental dysfunction. Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug addiction. Yet, there are still many unanswered questions about the basic mechanism of acupuncture. Studies have shown that both the psychomotor stimulant effects and rewarding properties of addictive drugs, including morphine, are sensitized by repeated drug administration and raised the possibility that both of these effects may De linked to the same or closely overlapping the mesolimbic dopamine systems. Neiguan (PC6) point on the pericardium channel which is associated with the brain and its mental function, has been used to treat mental, psychosomatic disorders and gastroenterological disorders. The present study was designed to investigate the effect of acupuncture on repeated morphine-induced changes in extracellular dopamine levels using in vivo microdialysis and to measure the effect of acupuncture on repeated morphine-induced behavioral changes. Male Sprague-Dawley rats were treated twice a day for three days with increasing doses of morphine (10, 20 and 40 mg/kg, s.c.) or with saline. After 15 days of withdrawal, rats were challenged with morphine hydrochloride (5 mg/kg, s.c.). Acupuncture was applied at bilateral Neiguan (PC6) points for 1min after the morphine challenge. Results showed that acupuncture at the specific acupoint PC6, but not at control points (tail and HE8) significantly decreased both dopamine release, behavior induced by a systemic morphine challenge or a single s.c. morphine injection in the morphine-repeated animals. These results suggest that reduction in sensitization may be one mechanism whereby acupuncture alleviates morphine craving in addicts. Moreover, in a more general sense these results suggest that acupuncture can be used as a therapeutic intervention for correcting reversible malfunction of the body by direction of brain pathway and thus acupuncture can contribute to the biochemical balance in the central nervous system by regulating neurotransmitters.

Blockade of ERK Phosphorylation in the Nucleus Accumbens Inhibits the Expression of Cocaine-induced Behavioral Sensitization in Rats

  • Kim, Seung-Woo;Shin, Joong-Keun;Yoon, Hyung-Shin;Kim, Jeong-Hoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.6
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    • pp.389-395
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    • 2011
  • Repeated administration of psychostimulants such as cocaine leads to the development of behavioral sensitization. Extracellular signal-Regulated Kinase (ERK), an enzyme important for long-term neuronal plasticity, has been implicated in such effects of these drugs. Although the nucleus accumbens (NAcc) is the site mediating the expression of behavioral sensitization by drugs of abuse, the precise role of ERK activation in this site has not been determined. In this study we demonstrate that blockade of ERK phosphorylation in the NAcc by a single bilateral microinjections of PD98059 (0.5 or $2.0{\mu}g/side$), or U0126 (0.1 or $1.0{\mu}g/side$), into this site dose-dependently inhibited the expression of cocaine-induced behavioral sensitization when measured at day 7 following 6 consecutive daily cocaine injections (15 mg/kg, i.p.). Acute microinjection of either vehicle or PD98059 alone produced no different locomotor activity compared to saline control. Further, microinjection of PD98059 ($2.0{\mu}g/side$) in the NAcc specifically lowered cocaine-induced increase of ERK phosphorylation levels in this site, while unaffecting p-38 protein levels. These results indicate that ERK activation in the NAcc is necessary for the expression of cocaine-induced behavioral sensitization, and further suggest that repeated cocaine evokes neuronal plasticity involving ERK pathway in this site leading to long-lasting behavioral changes.

Effects of Multiple Exposures to Pesticides on Plasma Cholinesterase Activity and p-nitrophenol Excretion in Rats (농약의 복합투여가 백서의 혈장 콜린에스테라제 활성도 및 요중 파라-니트로페놀 배설에 미치는 영향)

  • Cha, Bong-Suk;Park, Jung-Gyun;Park, Jong-Ku;Chang, Sei-Jin
    • Journal of Preventive Medicine and Public Health
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    • v.25 no.2 s.38
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    • pp.180-188
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    • 1992
  • The effects of multiple exposures to pesticides on plasma cholinesterase(ChE) activities and urinary p-nitrophenol excretion were evaluated in rats. Rats were received single dose i.p. with $LD_{50}/100(mg/kg)$ of organophosphorous(OP), organophosphorous-organochroline(OP-OC), organophosphorous-carbamate(OP-CAB), organophosphorous-organoarsenate(OP-OA) pesticides for 4 consecutive days. In repeated administration of pesticides, plasma ChE activities were decreased, but urinary p-nitrophenol were increased after the first injection and then decreased gradually The recovery rates of ChE activities and p-nitrophenol excretion at 48 hours after the fourth Injection were delayed in comparision with the baseline value of 24 hours before the first injection. Statistical significances were found between OP and other groups except OP-OA group after the second injection in plasma ChE activities, but in urinary p-nitrophenol excretion there was statistical significance only between OP and OP-CAB.

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Ginseng Saponins Prevent the Adverse Effect of Dependence-liable Drugs

  • Kim, Hack-Seang;Lim, Hwa-Kyung
    • Proceedings of the Ginseng society Conference
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    • 1998.06a
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    • pp.168-173
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    • 1998
  • A single administration of cocaine (CO), morphine (MOR) and methamphetamine (MA) showed hyperactivity in mice. Ginseng total saponin (GTS), ginsenosides Rbl and Rgl inhibited the hyperactivity induced by the drugs. The repeated administration of CO, MOR and MA showed the development of psychological dependence showing a.: the development of conditioned place preference (CPP) in mice and the development of dopamine (DA) receptor supersensitivity showing as sensitization of the drugs. GTS and Rgl inhibited the development of not only psychological dependence but also of DA receptor supersensitivity induced by CO and MA Rbl prevented also the development of psychological dependence and DA receptor supersensitivity induced by CO and MA but not by MOR. These results suggest that the development psychological dependence induced by the drugs is closely related with the development of DA receptor supersensitivity since both phenomena were inhibited by them. Apomorphine induced climbing behavior was also inhibited by G75 but not by both of Rbl and Rgl, indicating that GTS modulate dopaminergic action at both of pre and postsynaptic sites, but both of Rbl and Rgl , only at the presynaptic site. These results suggest that active components acting at the postsynaptic site exist in GTS. In this study, it was found that GTS, ginsenosides Rbl and Rgl inhibited tyrosine hydroxylase (TH) and these components exerted inhibitory effects on both Cal' currents and $\Delta$ Cm in rat adrenal chromaffin cells. These results suggest that G75 and ginsenosides regulate catecholamine synthesis and secretion. Meanwhile, it has been demonstrated that Rbl, at high doses has more powerful inhibition of cartecholamine secretion at the presynaptic site than Rbl. Therefore, it was presumed that inhibition of morphine induced psychological dependence by Rgl, but not by Rbl results from differences in the extent of this inhibitory action on dopaminergic synthesis and secretion.

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Trends of Intentional Poisoning: A Retrospective Single Center Study During 15 Years (의도성 중독의 변화 양상: 15년간의 후향적 단일병원 연구)

  • Kong, Sung Kyu;Oh, Sang Hoon;Park, Kyu Nam;Kim, Han Joon
    • Journal of The Korean Society of Clinical Toxicology
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    • v.14 no.1
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    • pp.47-53
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    • 2016
  • Purpose: Intentional poisoning is a major public health issue in many parts of the world. This study was conducted to provide details regarding the epidemiology of intentional poisoning in a metropolitan emergency department and to identify the changing patterns and epidemiology of poisoning. Methods: A retrospective study was conducted to evaluate intentional poisoning of patients who visited the emergency department in a tertiary teaching hospital between 2001 and 2015. All intentional poisoning-related emergency department visits over three five year periods (2001-2005 (P1), 2006-2010 (P2) and 2011-2015 (P3)) were reviewed to investigate trends in intentional poisoning patients. Information regarding patient sex, age, time from episode to admission, psychiatric history, type of intoxicants, alcohol co-ingestion, gastric lavage, charcoal administration, any previous suicide attempts, need for hospitalization and death before discharge was reviewed. Results: A total of 1269 patients were enrolled in this study. The number of patients admitted during each period was P1=515, P2=439 and P3=315. Comparison of the three groups revealed significant differences according to age (p<0.001), psychiatric history (p<0.001), alcohol co-ingestion (p=0.013), gastric lavage (p<0.001), charcoal administration (p<0.001), need for hospitalization (p=0.044), repeated attempt (p<0.001) and type of intoxicants (p<0.001). Conclusion: The average age of intentional poisoning patients has increased. While the use of sedatives and multiple drugs increased, the use of pesticides and the antihistamine decreased.

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Pharmacomkinetics of Roxithromycin after Intravenous Administration in Broilers (록시스로마이신의 정맥주사 후 육계에서의 약물동태학적 분석)

  • Lim Jong-Hwan;Park Byung-Kwon;Kim Myoung-Seok;Hwang Youn-Hwan;Yun Hyo-In
    • Journal of Veterinary Clinics
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    • v.23 no.2
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    • pp.87-90
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    • 2006
  • The aim of the present study was to investigate the disposition pharmacokinetics of roxithromycin in broilers. Roxithromycin was administered at a single dose of 20 mg/kg body weight by intravenous (i.v.) routes. Plasma concentrations of roxithromycin were determined by liquid chromatography/mass spectrometry. After a single i.v. dose plasma concentrations were best fitted to a two-compartment open model. The values of the pharmacokinetic parameters after i.v. administration were: elimination half-life = $5.83{\pm}1.79h$, mean residence time = $6.33{\pm}0.32h$, total body clearance = $0.55{\pm}0.15L/h/kg$, and volume of distribution at steady state = $3.47{\pm}0.84L/kg$. The pharmacokinetic interpretation of roxithromycin after i.v. administration revealed that the drug was well distributed throughout the body in broilers and slowly eliminated. More studies for the application of roxithromycin against poultry disease are needed to establish a suitable pharmaceutical formulation, propose optimum dosage regimens, investigate clinical efficacy and study the tolerability of repeated doses.

Failure of Repeated MDA with Albendazole for Trichuriasis Control in Schoolchildren of the Yangon Region, Myanmar

  • Hong, Sooji;Jung, Bong-Kwang;Song, Hyemi;Cho, Jaeeun;Sohn, Woon-Mok;Hong, Sung-Jong;Ryu, Jin-Youp;Kim, Hyun-Seung;Jeong, Mun-Hyoo;Htoon, Thi Thi;Tin, Htay Htay;Chai, Jong-Yil
    • Parasites, Hosts and Diseases
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    • v.59 no.6
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    • pp.607-613
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    • 2021
  • Soil-transmitted helminth (STH) infections are still a considerable challenge in Myanmar. We undertook a control program for STH infections (especially Trichuris trichiura) among schoolchildren in Myanmar using mass drug administration (MDA) and health education. Around 1,700 schoolchildren from 15 primary schools in 3 suburban districts (Shwe Pyi Thar, Twantay, and Kyauktan) of the Yangon Region were subjected in this study during 2017-2019. All of the schoolchildren in each school were orally administered albendazole (400 mg in a single dose) 2, 3, and 4 times a year in 2017, 2018, and 2019, respectively. The results revealed that the egg positive rate of any intestinal helminths (including STH) was reduced from 37.6% (649/1,724) in 2017 to 22.8% (352/1,542) in 2019. The egg positive rate of Ascaris lumbricoides was decreased remarkably from 23.3% (402/1,724) in 2017 to 3.6% (56/1,542) in 2019. However, that of T. trichiura was only slightly reduced from 26.9% (464/1,724) in 2017 to 20.2% (312/1,542) in 2019. The intensity of infection with A. lumbricoides and T. trichiura was both more or less reduced, and the proportion of light infection cases with A. lumbricoides and T. trichiura increased from 35.6% in 2017 to 64.3% in 2019 and from 70.3% in 2017 to 81.7% in 2019, respectively. The results indicated that repeated MDAs (2-4 times a year for 3 years) using albendazole on schoolchildren in Myanmar failed to control T. trichiura infection. For a successful control of trichuriasis in Myanmar, new MDA strategies, using a modified albendazole regimen (multiple daily doses for 2 or 3 days) or an alternative anthelmintic drug, such as oxantel pamoate, is strongly recommended.

Cytogenetic Mapping of Carthamus tinctorius L. with Tandemly Repeated DNA Sequences by Fluorescence in situ Hybridization

  • Mancia, Franklin Hinosa;Ju, Yoon Ha;Lim, Ki-Byung;Kim, Jung Sun;Nam, Sang Yong;Hwang, Yoon-Jung
    • Korean Journal of Plant Resources
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    • v.30 no.6
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    • pp.654-661
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    • 2017
  • Dual-color fluorescence in situ hybridization karyotype analysis was created using repetitive sequences including two types of rDNA repeats (45S and 5S rDNAs) and Arabidopsis-type telomere sequence repeats. The somatic metaphase cells of Carthamus tinctorius were observed as diploids (2n=2x=24). A symmetrical or slightly asymmetrical karyotype with seven pairs of metacentric and five pairs of submetacentric chromosomes was observed. The lengths of the somatic metaphase chromosomes ranged from 4.18 to $6.53{\mu}m$, with a total length of $60.71{\mu}m$. One locus of 45S rDNA was located on the pericentromeric regions of three pairs of chromosomes and the other pair was situated on the terminal regions of the short arms of a single pair of chromosomes. One locus of 5S rDNA was detected on the interstitial regions of the short arms of two pairs of chromosomes. Arabidopsis-type telomeric repeats were detected on the terminal regions of all pairs of chromosomes. Co-localization of loci between telomeric repeats and 45S rDNA was observed in a single pair of chromosomes. The results provide additional information for the existing physical mapping project of C. tinctorius and will also serve as a benchmark to a more intricate cytogenetic investigation of C. tinctorius and its related species.

Alterations of c-Fos mRNA Expression in Hypothalamic-Pituitary-Adrenal Axis and Various Brain Regions Induced by Intrathecal Single and Repeated Substance P Administrations in Mice

  • Choi, Seong-Soo;Lee, Han-Kyu;Shim, Eon-Jeong;Kwon, Min-Soo;Seo, Young-Jun;Lee, Jin-Young;Suh, Hong-Won
    • Archives of Pharmacal Research
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    • v.27 no.8
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    • pp.863-866
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    • 2004
  • The effect of substance P (Sub P) injected intrathecally (I.t.) on c-fos mRNA expression in vari-ous tissues was examined in the present study. We found that a single administration of Sub P(0.5 nM) caused an increase of the c-fos mRNA level in the hypothalamic-pituitary-adrenal(HPA) axis, hippocampus, and spinal cord. The time-course study showed that c-fos mRNA level was maximal at 10 min and began to decrease 30 min after the Sub P injection in all tis-sues, and the Sub P-induced increase of the c-fos mRNA level was returned to the control level 1 h after the injection. The kinetics of the c-fos mRNA expression in mice that were repeatedly injected with Sub P (every 30 min interval up to 4 times) were different in the HPA axis, hippocampus, and spinal cord. The increased c-fos mRNA level in the hypothalamus and the spinal cord induced by I.t. injected Sub P remained at a high level. In the pituitary gland, adrenal gland, and hippocampus, the increased level of c-fos mRNA expression gradually returned to the control level during the repeated substance P injections up to 4 times. Our results suggest that spinally injected Sub P-induced pain stress increases c-fos mRNA expres-sion in the spinal cord, hippocampus, and HPA axis. In mice repeatedly injected with Sub P, the kinetics of c-fos mRNA appear to be different varied from tissue to tissue.

Safety Evaluation of Recombinant Human Factor VIII(GC-γ AHF) (유전자 재조합 Human Factor VIII(GC-γ AHF)의 안전성에 관한 연구)

  • 김민영;손장원;신민기;배미옥;김현우;최진혁;김준성;문서현;김정현
    • Toxicological Research
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    • v.18 no.1
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    • pp.87-98
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    • 2002
  • This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-$\gamma$ AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-$\gamma$ AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-$\gamma$ AHF treated group. Therefore, the 50% lethal dose ($LD_{50}$) of GC-$\gamma$ AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-$\gamma$ AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-$\gamma$ AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-$\gamma$ AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-$\gamma$ AHF were 0. Therefore, the GC-$\gamma$ AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-$\gamma$ AHF and GC-$\gamma$ AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-$\gamma$ AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-$\gamma$ AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-$\gamma$ AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.