• Title/Summary/Keyword: 신경작용제

Search Result 190, Processing Time 0.023 seconds

Participation of Central $P2X_7$ Receptors in CFA-induced Inflammatory Pain in the Orofacial Area of Rats

  • Yang, Kui-Ye;Kim, Myung-Dong;Ju, Jin-Sook;Kim, Min-Ji;Ahn, Dong-Kuk
    • International Journal of Oral Biology
    • /
    • v.39 no.1
    • /
    • pp.49-56
    • /
    • 2014
  • We investigated the role of central P2X receptors in inflammatory pain transmission in the orofacial area in rats. Experiments were carried out using male Sprague-Dawley rats weighing 230-280g. Complete Freund's adjuvant (CFA, $40{\mu}L$) was applied subcutaneously to the vibrissa pad to produce inflammatory pain. The intracisternal administration of iso-PPADS tetrasodium salt, a non-selective P2X receptor antagonist, A317491 sodium salt hydrate, a $P2X_{2/3}$ receptor antagonist, 5-BDBD, a $P2X_4$ receptor antagonist, or A438079 hydrochloride, a $P2X_7$ receptor antagonist, was performed 5 days after CFA injection. Subcutaneous injections of CFA produced increases in thermal hypersensitivity. Intracisternal injections of iso-PPADS ($25{\mu}g$) or A438079 (25 or $50{\mu}g$) produced significant anti-hyperalgesic effects against thermal stimuli compared to the vehicle group. A317491 or 5-BDBD did not affect the head withdrawal latency times in rats showing an inflammatory response. Subcutaneous injections of CFA resulted in the up-regulation of OX-42, a microglia marker, and GFAP, an astrocyte marker, in the medullary dorsal horn. The intracisternal administration of A438079 reduced the numbers of activated microglia and astrocytes in the medullary dorsal horn. These results suggest that a blockade of the central $P2X_7$ receptor produces antinociceptive effects, mediated by inhibition of glial cell function in the medullary dorsal horn. These data also indicate that central $P2X_7$ receptors are potential targets for future therapeutic approaches to inflammatory pain in the orofacial area.

Effects of Bisphenol A and BPA Alternatives on the Nervous System (Bisphenol A와 대체물질들이 신경계에 미치는 영향)

  • Ha Jung Moon;Seung Hyun Lee;Hyun Seung Shin;Eui-Man Jung
    • Journal of Life Science
    • /
    • v.33 no.4
    • /
    • pp.371-381
    • /
    • 2023
  • Endocrine disrupting chemicals (EDCs), used in a variety of products in modern society, are hormone-like substances that cause various diseases. Humans are exposed to EDCs through their inclusion in pesticides, plastics, cosmetics, detergents, and drugs. Bisphenol A (BPA), one of the representative endocrine disruptors, is an estrogen-like substance that has been widely used commercially in plastic and epoxy resins. BPA is a chemical that can disrupt the endocrine system, leading to reduced reproductive function, obesity, cancer, and neurodevelopmental disorders. Since the adverse health effects of BPA began to be reported the use of BPA has been regulated worldwide. Various alternatives to BPA have been widely used worldwide; representatively, bisphenol S (BPS) and bisphenol F (BPF) are the most commonly used in commercial contexts. BPS and BPF may cause endocrine-disrupting effects like those of BPA due to their similar chemical structures. Recent studies have reported that BPS and BPF disrupt the neurodevelopmental process and cause neurodevelopmental disorders. Therefore, future studies will be required for safety verification of BPA alternatives and the development of new alternatives to BPA for brain health. In this review, we reviewed the effects of BPA and the alternatives, BPS and BPF, on the nervous system.

Screening Test(I) of Several Antipsychotic Agents on NO Formation (수종 정신병치료제들의 NO형성에 대한 검색(I))

  • Lee, Jong-Hwa;EI-fakahany, Esam E.
    • The Korean Journal of Pharmacology
    • /
    • v.30 no.3
    • /
    • pp.343-349
    • /
    • 1994
  • A number of neurological syndromes(e.g. tardive dyskinesia) are developed as a consequence of chronic treatment with neuroleptics or antipsychotic agents. Despite the long and succesful use of phenothiazine derivatives and related agents in the treatment of certain states of mental disease, the mechanisms of these drugs are still poorly understood. One current hypothesis from extensive reviews is that these compounds might significantly interfere with the cyclic nucleotide system in brain (Levin and Weiss, 1977; Nowicki et al., 1991; Haley et al., 1992). Nitric oxide (NO), one of an interesting messenger molecule and aberrant transmitter, is believed to play a important role in biological functions of cyclic nucleotides in nervous system. It has been reported that calcium-dependent NO synthesis in endothelial cytosol is mediated by calmodulin which is supposed to be tightly related to pharmacological actions of antipsychotic agents. In the present study, the effect of several antipsychotic agents on the activity of NO synthesis and formation of cyclic GMP were investigated. These agents inhibited both the formation of $[^3H]L-citrulline$ and that of $[^3H]cyclic$ GMP by concentration-dependent manner, and their inhibiting patterns are so similar to that of calmodulin antagonist.

  • PDF

Circadian Rhythm of Urinary Free Cortisol in Brain Injuryed Patients (뇌손상 환자의 요중 Free Cortisol의 Circadian Rhythm)

  • Min, Soon
    • Journal of Korean Biological Nursing Science
    • /
    • v.3 no.1
    • /
    • pp.1-10
    • /
    • 2001
  • 뇌손상이라고 하는 과도한 stress를 받았을 때 free cortisol의 분비되는 양과 urinary free cortisol의 circadian 리듬에 어떻게 영향을 주는지 확인하기 위하여 시도하였다. 연구대상은 대조군은 건강한 젊은 여성 6명과 실험군응 CT상 뇌에 손상을 받은 4명의 여성으로 30대 환자이었다. 담당의사와 중환자실 관리책임자의 동의하에서 시도되었으며, 실험기간은 2000년 7월 1일에서 7월 10일까지였다. 대조군과 실험군의 뇨를 채취하여 뇨중 free cortisol 농도의 circadian rhythm을 알아보기 위해 채뇨 후 분석하였다. 채뇨는 뇌손상을 받고 응급실을 통해 신경외과 중환자실에 입원한 지 5시간 이내에 해당된 환자로 24시간 유지되는 foley catherization 상태하에서 12:00부터 3일동안 72시간을 2시간 간격으로 채뇨하였고, 대조군은 오전 12시부터 24시간 동안 2시간 간격으로 채뇨하였다. 측정방법으로는 cortisol의 정량은 solid-phase radioimmuoassay 방법을 이용하였으며, 분석재료는 Coat-A-Count(R) Cortisol kit(DPC, U.S.A.)을 사용하여 DPC사의 측정방법을 따랐다. 연구대상자의 free cortisol의 총량은 대조군에서는 $42.8{\mu}g$이었고, 실험군은 1일에 $991.2{\mu}g$, 2일에 $809{\mu}g$, 3일에 $544.2{\mu}g$으로 대조군과 통계적으로 유의한 차이를 나타내(p<.05), 실험군에서 현저하게 증가된 양상을 보였고, 시간이 지나면서 점점 감소하는 경향을 나타냈다. 시간별로 t-검정으로 분석한 결과로는 모든 시간대에서 대조군과 실험군의 평균치는 통계적으로 유의한 차이를 나타냈다. Free cortisol의 circadian에서는 대조군에서는 정상인의 cortisol의 circadian의 경우와 같은 리듬을 보였으나, 손상을 받은 실험군의 경우 분비량은 현저하게 증가했음을 보여주었다. 최고치가 제1일에 18:00과 다음날 10:00에 나타나 최고치가 2회 나타났으며, 제2일에도 제1일과 마찬가지로 18:00에 나타났고, 제3일에는 24:00에 나타나 제1일보다 제2일에는 최고치가 한 번 나타난 리듬을 보여주었고, 분비량은 2일에 감소하였다. 제3일에는 최고치가 8시간 지연된 나타난 리듬의 변화를 보여주었다. 최저치는 제1일, 제2일, 제3일 모두 24:00에 나타난 리듬을 보여주었다. 이상의 결과에서 실험군인 뇌손상 환자군에서는 뇌손상이 과도한 stress로 작용하여 환자의 free cortisol 분비량과 circadian 리듬에도 영향을 주는 것으로 나타났다. 그러므로 뇌손상환자를 간호하는 간호사는 스트레스상태인 것을 인지하여 환자 개개인에 필요한 간호를 해야 할 것으로 사료된다.

  • PDF

Autometallography for Zinc Detection in the Central Nervous System (중추신경계통내 분포하는 Zinc의 조직화학적 동정)

  • Jo, Seung-Mook;Gorm, Danscher;Kim, Sung-Jun;Park, Seung-Kook;Kang, Tae-Cheon;Won, Moo-Ho
    • Applied Microscopy
    • /
    • v.30 no.4
    • /
    • pp.347-355
    • /
    • 2000
  • Zinc is one of the most abundant oligoelements in the living cell. It appears tightly bound to some metalloproteins and nucleic acids, loosely bound to some metallothioneins or even as free ion. Small amounts of zinc ions (in the nanomolar range) regulate a plentitude of enzymatic proteins, receptors and transcription factors, thus rolls need accurate homeostasis of zinc ions. Zinc is an essential catalytic or structural element of many proteins, and a signaling messenger that is released by neural activity at many central excitatory synapses. Growing evidences suggest that zinc may also be a key mediator and modulator of the neuronal death associated with transient global ischemia and sustained seizures, as well as perhaps other neurological disease stoles. Some neurons have developed mechanisms to accumulate zinc in specific membrane compartment ('vesicular zinc') which can be evidenced using histochemical techniques. Substances giving a bright colour or emitting fluorescence when in contact with divalent metal ions are currently used to detect them inside cells; their use leads to the so called 'direct' methods. The fixation and precipitation of metal ions as insoluble salt precipitates, their maintenance along the histological process and, finally, their demonstration after autometallographic development are essential steps for other methods, the so called 'indirect methods'. This study is a short report on the autometallograhical approaches for zinc detection in the central nervous system (CNS) by means of a modified selenium method.

  • PDF

Identifying Bridging Nodes and Their Essentiality in the Protein-Protein Interaction Networks (단백질 상호작용 네트워크에서 연결노드 추출과 그 중요도 측정)

  • Ahn, Myoung-Sang;Ko, Jeong-Hwan;Yoo, Jae-Soo;Cho, Wan-Sup
    • Journal of Korea Society of Industrial Information Systems
    • /
    • v.12 no.5
    • /
    • pp.1-13
    • /
    • 2007
  • In this research, we found out that bridging nodes have great effect on the robustness of protein-protein interaction networks. Until now, many researchers have focused on node's degree as node's essentiality. Hub nodes in the scale-free network are very essential in the network robustness. Some researchers have tried to relate node's essentiality with node's betweenness centrality. These approaches with betweenness centrality are reasonable but there is a positive relation between node's degree and betweenness centrality value. So, there are no differences between two approaches. We first define a bridging node as the node with low connectivity and high betweenness value, we then verify that such a bridging node is a primary factor in the network robustness. For a biological network database from Internet, we demonstrate that the removal of bridging nodes defragment an entire network severally and the importance of the bridging nodes in the network robustness.

  • PDF

Involvement of Multiple Signaling Molecules in Peptidoglycan-induced Expression of Interleukin-1α in THP-1 Monocytes/Macrophages (THP-1 단핵구의 펩티도글리칸 유래 인터루킨-1 알파 발현에서 TLR2, PI3K/Akt/mTOR, MAPKs의 역할)

  • Heo, Weon;Son, Yonghae;Cho, Hyok-rae;Kim, Koanhoi
    • Journal of Life Science
    • /
    • v.32 no.6
    • /
    • pp.421-429
    • /
    • 2022
  • The expression of interleukin-1α (IL-1α) is elevated in monocytic cells, such as monocytes and macro-phages, within atherosclerotic arteries, yet the cellular molecules involved in cytokine upregulation remain unclear. Because peptidoglycan (PG), a major component of gram-positive bacterial cell walls, is detected within the inflammatory cell-rich regions of atheromatous plaques, it was investigated if PG contributes to IL-1α expression in monocytes/macrophages. Exposure of THP-1 monocytic cells to PG resulted in elevated levels of IL-1α gene transcripts and increased secretion of IL-1α protein. The transcription and secretion of IL-1α were abrogated by OxPAPC, an inhibitor of TLR2/4, but not by polymyxin B that inhibits lipopolysaccharide-induced TLR4 activation. To understand the molecular mechanisms of the inflammatory responses due to bacterial pathogen-associated molecular patterns (PAMPs) in diseased arteries, we attempted to determine the cellular factors involved in the PG-induced upregulation of IL-1α expression. Pharmacological inhibition of cell signaling pathways with LY294002 (a PI3K inhibitor), Akti IV (an inhibitor of Akt activation), rapamycin (an mTOR inhibitor), U0126 (a MEK inhibitor), SB202190 (a p38 MAPK inhibitor), SP6001250 (a JNK inhibitor), and DPI (a NOX inhibitor) also significantly attenuated the PG-mediated expression of IL-1α. These results suggest that PG induces the monocytic or macrophagic expression of IL-1α, thereby contributing to vascular inflammation, via multiple signaling molecules, including TLR2, PI3K/Akt/mTOR, and MAPKs.

Development of Prototype Biosensor for The Detection of Organophosporus Compounds (유기인화합물 측정용 광바이오센서 개발)

  • 최정우;김종민;이원홍;김영기
    • KSBB Journal
    • /
    • v.17 no.2
    • /
    • pp.158-161
    • /
    • 2002
  • In this study, a prototype fiber-optic biosensor was fabricated using the inhibition of enzyme reaction by organophosphorus compounds to detect organophosphorus compounds, which is nervous toxic material an? is used as chemical weapon and pesticide. Enzyme, substrate, and inhibitor for enzyme reaction were acetylcholinesterase (key enzyme in nervous cell), acetylthiocholine iodide, and paraoxon (a kind of organophosphorus compounds), respectively. The detection principle of sensor is the detection of enzyme reaction inhibited by organophosphorus compounds by the quantitative measurement of acetic acid, which was achieved by absorbance measurement using litmus solution that maximum absorbance band is changed by pH. To fabricate prototype fiber-optic biosensor, high bright LED and photodiode was used as light source and light intensity detector, respectively. From the experimental results using a prototype biosensor, the linear change of sensor signal was obtained in a range of 0-2 ppm inhibitor concentrations. From these results, it was verified that the quantitative measurement of organophosphorus compounds could be achieved fast (within 2 minutes) and accurately by a prototype fiber-optic biosensor.

Roles of Monoamine Neurotransmitters in Regulation of Hypothalamic PITUITITARY-ADRENAL AXIS(HPA) (III) - Role of 5-hydroxytryptamine in Controlling the Stress-Induced Elevation of Corticosterone in Rat - (시상하부-뇌하수체-부신계 조절에 대한 Monoamine 신경전달물질의 역할에 관한 연구(III)-뇌 5-hydroxytyptamine(Serotonin)이 Stress 시 Corticosteroid 변동에 미치는 영향)

  • Suh, Yoo-Hun;Lim, Jung-Kyoo;Park, Chan-Woong
    • The Korean Journal of Pharmacology
    • /
    • v.19 no.2
    • /
    • pp.45-55
    • /
    • 1983
  • A role for brain serotonin(5-HT) in regulation of the HPA axis has been suggested but remains contoversial and poorly defined. The present experiments were designed to check kinetic parameters of 5-HT turnover in rat hypothalamus and remainder brain areas before and after stress and to test whether using various different pharmacologic approaches to stimulate or eliminate the control serotonergic system have any consistent effect on the stress-induced activation of HPA system. Steady state brain serotonin and 5-HIAA concentrations during 1 min ether stress were significantly elevated without significant rise in the levels of plasma corticosterone, which highly increased 2 minutes after stress. This suggests that the increase in serotonergic neuron activity precede that in HPA activity. Furthermore, during 1 ruin-ether stress or 30 min immobilization stress there is a marked increase in hypothalamic and remainder brain serotonin (5-HT) turnover or synthesis rates assessed by both the pargline/5-HT method and pargyline/5-HIAA method. The stress-induced corticosterone levels were increased by serotonin precursors and serotonin agonist in a dose-related fashion. The stress- induced corticosterone levels were highly elevated by L-tryptophan (100 mg/kg) and Potentiated by monoamine oxidase inhibitor, pargyline or serotonin agonist, 5-MeoDMT. The stress-induced elevation of corticosterone and 5-HT levels in rat brain were not significantly decreased by the administration of 5-HT synthesis inhibitor, PCPA and 5-HT neurotoxin, 5,7-DHT. However, the stress-induced elevation of corticosterone and 5-HT levels were decreased by the destruction of midline raphe nuclei. There was a strong positive correlation between plasma corticosterone and 5-HT concentrations changed by drugs which mainly manipulating 5-HT system in the hyhothalamus and in the remainder of the brain. In conclusion, our present data stongly suggest that 5-HT is an important key neurotransmitter involved in the stress-induced activation of the HPA system.

  • PDF

Developmental Abnormality in Agricultural Region and Toxicity of the Fungicide Benomyl on Korea salamander, Hynobius leechii (한국산 도롱뇽(Hynobius leechii)의 농경지에서의 배 발생 이상과 살균제 Benomyl의 독성효과)

  • Choi, Yeoung-Ju;Yoon, Chun-Sik;Park, Joo-Hung;Jin, Jung-Hyo;Cheong, Seon-Woo
    • Korean Journal of Ecology and Environment
    • /
    • v.35 no.3 s.99
    • /
    • pp.198-212
    • /
    • 2002
  • A numerical variation and abnormalities were studied on egg bags and embryos of Korean salamander, Hynobius leechii from agricultural habitat. The teratogenic and toxic effects of fungicide benomyl were also investigated with early embryos from non-agricultural habitat. We collected 144 egg bags from agricultural region, and 3418 of early embryos were contained. The lengths of egg bags were varied from 10 to 23 cm and the most frequent length was 19 cm. The number of embryos was varied from 7 to 43, and the most frequent range was 22 to 26. Spontaneous abnormalities were occurred in 406 embryos among 116 egg bags, and 24 kinds of external abnormalities were found. Individuals showing severe external defect were histologically studied and they showed optic dyspalsia, thyroid carcinoma, somatic muscular dysplasia, partial biaxial structure, decrease of red blood cells in the heart, cephalic degeneration and intestinal dysplasia. 385 embryos from non-agricultural region were exposed to 200 nM${\sim}$ 1 ${\mu}$M of benomyl at blastula or gastrula for 12 days. All embryo were dead in the concentration of 1 ${\mu}$M (LD$_{100}$) and 75% of embryos were dead in 800nM of benomyl. Speciflc effect due to benomyl was acrania or cephalic dysplasia and this restult suggests that the benomyl inhibit stongly to the development of neural tissue. These abnormal developments may be caused by antimitotic action, inhibition of tubulin complex, destruction of microtubule, inhibitions of neurulation and closing of neural fold, and by the inhibition of the movement of neural crest cells.