• 제목/요약/키워드: Antagonists

검색결과 548건 처리시간 0.023초

Neuronal injury in AIDS dementia: Potential treatment with NMDA open-channel blockers and nitric oxide-related species

  • Lipton, Stuart A.
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1996년도 춘계학술대회
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    • pp.19-29
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    • 1996
  • The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

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빨간지렁이(Lumbricus rubellus)를 이용(利用)한 산업폐유기물의 분해물질(分解物質)이 시설원예(施設園藝) 상토특성(床土特性)에 미치는 영향(影響) -I. 빨간지렁이가 우분분해(牛糞分解)에 미치는 영향(影響) (Study on Properties of Pot Media Under Controlled Horticulture for Compost from Agro-industrial Wastes by Earthworm (Lumbricus rubellus) -I. The Effect of Degradation on Cow Manure by Earthworm Rearing)

  • 김성필;주영희
    • 한국토양비료학회지
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    • 제23권2호
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    • pp.140-145
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    • 1990
  • 지렁이에 의(依)한 우분(牛糞)의 속성퇴비화방법 규명을 위하여 우분(牛糞)단일구, 우분(牛糞)+지렁이, 우분(牛糞)(50)+메탄발효(醱酵)스럿지(50)+지렁이로 처리(處理)하여 pH, C/N비(比), 환원당률(還元糖率), 미생물상(微生物相), Bacillus sp.의 수(數), 항균력(抗菌力) 검정(檢定)을 7일 간격으로 4회 실시(實施)한 결과는 다음과 같다. 1. 지렁이 사양(飼養)으로 우분(牛糞)의 pH를 상승(上昇)시키나 메탄발효(醱酵) 스럿지를 첨가했을때는 저하시켰다. 2. C/N비(比) 및 환원당률(還元糖率)이 우분(牛糞)단일구(區)에서는 9.67%, 12.01%, 지렁이 사양구(飼養區)는 40.89~41.90% 및 37.05~37.50%로 감소되었다. 3. 세균수(細菌數)는 우분(牛糞)단일구(區)는 14일(日)까지 증가(增加)하다 그 후 감소(減少)하나 지렁이사양구(飼養區)는 28일(日)까지 계속 증가되는 경향이 있다. 4. Bacillus sp. 수(數)는 일반토양(一般土壤)에 비(比)해 지렁이분(糞)에서 월등히 많았다. 5. 항생물질(抗生物質)인 Chloram phenicol의 Fusarium oxysporum에 대한 Inhibition zones diameter가 36.3mm인데 비(比)하여 지렁이분(糞)에서 분리한 Bacillus sp. 7의 Inhibition zones diameter는 22mm였다.

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Atropine, Phentolamine과 Propranolol이 활성화된 다형핵 백혈구에서의 칼슘 흡수, $O_2-$ 생성 및 식작용에 미치는 효과 (Effects of Atropine, Phentolamine and Propranolol on Calcium uptake, Superoxide generation and Phagocytic activity in activated PMN Leukocytes)

  • 이정수;한은숙;이광수
    • 대한약리학회지
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    • 제24권1호
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    • pp.83-92
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    • 1988
  • 세포질 내 칼슘 농도의 증가는 다형핵 백혈구의 산화성 대사를 자극하는 주요 인자로 여겨지고 있다. 활성화된 다형핵 백혈구로부터 lysosomal enzyme의 유리는 세포내 cyclic nucleotide농도에 따라 조절될 수 있지만 신경전달물질과 ${\beta}$-아드레날린 또는 무스카린성 수용체의 결합에 따른 그밖의 반응은 아직도 분명하지 않다. 덧붙여, ${\alpha}$-아드레날린성 수용체의 중개에 의한 다형핵 백혈구의 기능은 알려져 있지 않다. Atropine, phentolamine과 propranolol은 활성화된 다형핵 백혈구의 칼슘흡수, superoxide 생성, NADPH oxidase 활성도 그리고 식작용을 억제하였으며, 이에 반하여 carbachol과 isoproterenol은 활성화된 세포의 반응을 약간 더 자극하였다. Carbachol또는 isoproterenol 의하여 항진된 superoxide 생성은 각각 그들의 길항제인 atropine과 propranolol 의하여 억제되었다. 활성화된 다형핵 백혈구의 반응은 chlorpromazine, verapamil과 dantrolene에 의하여 억제되었으나 lithium에 의 하여 약긴 항진되었다. 한편 chlorpromazine과 dibucaine은 NADPH oxidase 활성도에 영향을 주지 않았다. Atropine, phentolamine과 propranolol은 칼슘에 의존적인 식작용을 억제 하였다. 이상의 결과로부터 atropine, phentolamine과 propranolol은 칼슘 유입을 억제하고 자율 신경계의 수용체와 연관이 있는 NADPH oxidase계에 직접 작용함으로써 활성화된 다형핵 백혈구로부터 superoxide 생성을 억제할 것으로 시사되었다.

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The Modulatory Role of Spinally Located Histamine Receptors in the Regulation of the Blood Glucose Level in D-Glucose-Fed Mice

  • Sim, Yun-Beom;Park, Soo-Hyun;Kim, Sung-Su;Kim, Chea-Ha;Kim, Su-Jin;Lim, Su-Min;Jung, Jun-Sub;Ryu, Ohk-Hyun;Choi, Moon-Gi;Suh, Hong-Won
    • The Korean Journal of Physiology and Pharmacology
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    • 제18권1호
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    • pp.41-46
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    • 2014
  • The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (${\alpha}$-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with ${\alpha}$-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, ${\alpha}$-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

해명(海冥) 회종편(回腫片)에서 Morphine과 Naloxone 작용(作用)에 미치는 전해질(電解質)의 영향(影響) (Influences of Electrolytes on the Action of Morphine and Naloxone in Guinea-pig Ileum)

  • 권용춘;은홍배;조규박
    • 대한약리학회지
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    • 제19권2호
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    • pp.57-67
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    • 1983
  • Guinea-Pig의 myenteric plexus-longitudinal muscle preparation에서 morphine과 naloxone 효과(效果)에 미치는 전해질(電解質)의 영향(影響)을 관찰(觀察)하였다. 표본(標本)은 Krebs-Henseleit bicarbonate tufter solution 으로 채운 organ bath에 현수(懸垂)하고 0.2Hz로 전기자극(電氣刺戟)하였다. Morphine은 전기자극(電氣刺戟)에 의(依)한 근편수축(筋片收縮)을 억제(抑制)하였으며, 이때 $ID_{30}$은 약(約) 190nM이었다. 이와같은 morphine의 억제작용(抑制作用)은 bath내(內) $Na^+$ 또는 $K+$ 농도(濃度)를 감소(減少)시키거나 $Mg^{2+}$을 가(加)하면 강화(强化)되었으며, $Ca^{2+}$ 농도(濃度)를 증가(增加)시키거나 $Mg^{2+}$를 농도(濃度)를 감소(減少)시키면 약화(弱化)되었다. Naloxone은 morphine의 작용(作用)을 억제(抑制)하였으며, 이때 naloxone에 대(對)한 affinity index인 $pA_2$ value는 약(約) 8.8이었고 that내(內) 전해질(電解質) 농도(濃度)를 변동(變動)시켜도 영향(影響)받지 않았다. 이 성적(成積)은 전해질(電解質) 변동(變動)으로 인(因)한 morphine의 작용변동(作用變動)은 전해질(電解質)이 opiate receptor의 affinity를 변동(變動)시킨다는 opiate-receptor binding실험(實驗)에서와는 달리 전해질(電解質) 변동(變動)에 의(依)한 functional opiate receptor의 affinity 변동(變動)에 의(依)한 것이 아님을 시사(示唆)한다.

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들잔디 갈색퍼짐병의 생물학적 방제를 위한 길항 세균의 분리와 동정 (Isolation and Identification of Antagonistic Bacteria for Biological Control of Large Patch Disease of Zoysiagrass Caused by Rhizoctonia solani AG2-2 (IV))

  • 송치헌;;장태현;이용세
    • 아시안잔디학회지
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    • 제26권1호
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    • pp.8-16
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    • 2012
  • 한국 들잔디에 발생하는 Rhizoctonia solani에 의한 라지패치를 생물학적으로 방제하기위해 일반토양에서 길항미생물을 분리하여 in vitro와 in vivo에서 길항효과 및 병 발생억제효과를 검정하였다. 토양에서 분리한 216개 균주 중 15개 균주가 R. solani AG2-2 (IV)의 균사생장을 70%이상 억제하였으며, 온실실험 결과 11개 균주는 잔디의 생장을 촉진시켰으며, 병 발생 억제효과가 있었다. 분리한 길항미생물 중 H33 균주는 in vitro 및 in vivo에서 R. solani AG2-2 (IV)에 대한 길항효과가 다른 균주에 비해 높았으며, 공시한 17개 식물병원성 진균에 대해 길항효과가 높아 생물방제균으로 선발하였다. H33 균주를 ISP 배지에 배양한 후 배양적 특성 및 형태를 관찰한 결과 Streptomyces sp.로 동정되었으며, 16S rDNA를 분석한 결과 Streptomyces arenae와 99% 상동성을 보였다.

매복된 하악 제2유구치의 교정적 견인 (ORTHODONTIC TRACTION OF IMPACTED MANDIBULAR SECOND PRIMARY MOLAR)

  • 김민정;이상호;이난영;장향길
    • 대한소아치과학회지
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    • 제38권3호
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    • pp.303-308
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    • 2011
  • 치아 매복이란 치아 맹출 경로에 존재하는 물리적 장벽으로 인하여 치아 맹출에 장애가 발생하는 것으로, 정상 맹출 시기까지 치아가 맹출하지 못하는 상태를 말한다. 치아 매복의 병인론은 여전히 논쟁의 대상이지만, 치아의 유착이 가장 유력한 원인 요소로 제시되고 있다. 치아 매복은 임상적으로 악궁 내 공간의 소실, 인접치의 경사, 대합치의 정출, 하방에 위치한 치배의 변위, 낭성 변이나 감염 등 다양한 문제점을 야기할 수 있다. 매복된 유구치에 대한 치료로 조기 발거 혹은 공간 소실이 발생한 경우 교정적으로 공간확장술을 시행한 후 외과적 발치를 하는 것이 전통적인 방법으로 여겨져왔다. 그러나 매복된 치아가 정상적인 형태이고 유착되지 않은 경우라면 외과적 노출 후 교정적 견인을 시행하는 방법을 고려할 수 있다. 본 증례는 하악 우측 제2유구치의 미맹출을 주소로 본원에 내원한 3세 9개월 된 남아를 대상으로 매복된 유구치 상방에 존재하는 치은 조직을 절제한 후 교정적 견인을 시행함으로써, 유치열기에 양호한 교합관계를 얻었을 뿐 만 아니라, 이후 정기 검진을 통해 혼합치열기의 올바른 치아배열 및 맹출을 유도하였음을 관찰하였기에 이를 보고하는 바이다.

Inhibitory Effects of Cordycepin on Platelet Activation via Regulation of Cyclic Adenosine Monophosphate-downstream Pathway

  • Lee, Dong-Ha
    • 대한의생명과학회지
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    • 제23권3호
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    • pp.251-260
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    • 2017
  • Platelet activation is essential at the sites of vascular injury, which leads to hemostasis through adhesion, aggregation, and secretion process. However, potent and continuous platelet activation may be an important reason of circulatory disorders. Therefore, proper regulation of platelet activation may be an effective treatment for vascular diseases. In this research, inhibitory effects of cordycepin (3'-deoxyadenosine) on platelet activation were determined. As the results, cordycepin increased cAMP and cGMP, which are intracellular $Ca^{2+}$-antagonists. In addition, cordycepin reduced collagen-elevated $[Ca^{2+}]_i$ mobilization, which was increased by a cAMP-dependent protein kinase (PKA) inhibitor (Rp-8-Br-cAMPS), but not a cGMP-protein kinase (PKG) inhibitor (Rp-8-Br-cGMPS). Furthermore, cordycepin increased $IP_3RI$ ($Ser^{1756}$) phosphorylation, indicating inhibition of $IP_3$-mediated $Ca^{2+}$ release from internal store via the $IP_3RI$, which was strongly inhibited by Rp-8-Br-cAMPS, but was not so much inhibited by Rp-8-Br-cGMPS. These results suggest that the reduction of $[Ca^{2+}]_i$ mobilization is caused by the cAMP/A-kinase-dependent $IP_3RI$ ($Ser^{1756}$) phosphorylation. In addition, cordycepin increased the phosphorylation of VASP ($Ser^{157}$) known as PKA substrate, but not VASP ($Ser^{239}$) known as PKG substrate. Cordycepin-induced VASP ($Ser^{157}$) phosphorylation was inhibited by Rp-8-Br-cAMPS, but was not inhibited by Rp-8-Br-cGMPS, and cordycepin inhibited collagen-induced fibrinogen binding to ${\alpha}IIb/{\beta}_3$, which was increased by Rp-8-Br-cAMPS, but was not inhibited by Rp-8-Br-cGMPS. These results suggest that the inhibition of ${\alpha}IIb/{\beta}_3$ activation is caused by the cAMP/A-kinase-dependent VASP ($Ser^{157}$) phosphorylation. In conclusion, these results demonstrate that inhibitory effects of cordycepin on platelet activation were due to inhibition of $[Ca^{2+}]_i$ mobilization through cAMP-dependent $IP_3RI$ ($Ser^{1756}$) phosphorylation and suppression of ${\alpha}IIb/{\beta}_3$ activation through cAMP-dependent VASP ($Ser^{157}$) phosphorylation. These results strongly indicated that cordycepin might have therapeutic or preventive potential for platelet activation-mediated disorders including thrombosis, atherosclerosis, myocardial infarction, or cardiovascular disease.

오이 덩굴쪼김병균에 대한 오이 근권길항미생물의 분리, 동정 및 길항작용 (Isolation, Identification and Antagonisms of Rhizospheric Antagonists to Cucumber Wilt Pathogen, Fusarium oxysporum f. sp. cucumerinum Owen)

  • 지형진;김희규
    • 한국식물병리학회지
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    • 제3권3호
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    • pp.187-197
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    • 1987
  • 진주근교와 금산, 남지 등의 17개 오이연작재배지역에서 건전식물의 근권토양으로부터 Triple Layer Agar(TLA)법을 변형개량하여, 오이덩굴쪼김병균에 대한 길항균을 효과적으로 분리하였고, 예비실험(in vitro, in vivo)결과에서 길항력이 우수한 세균(15 isolates)과 곰팡이(9 isolates)를 선별하여 동정하였다. 이들 중 Serratia sp., Pseudomaonas fluorescens, P. putida등 세균 3균주와 Gliocladium sp., Trichoderma harzianum, T. viride 등 곰팡이 3균주를 공시하여 얻은 실내실험의 결과는 다음과 같다. Water Agar(WA) 상에서 길하세균에 의한 오이덩굴쪼김병원균의 소형분생포자의 발아율은 $26\~45\%$ 억제 되었으며, 발아관의 길이도 $41\~56\%$ 억제되었는데, P. fluorescens가 그 중 가장 우수한 길항력을 나타내었다. WA상의 대치배양에서 길항곰팡이의 균사가 본병원균의 균사를 Coiling, Penetration, Overgrowing, Lysis 하는 등의 길항현상을 관찰할 수 있었으며, 그 중 T. harzianum이 가장 강력한 길항력을 나타내었다. 배양기의 pH별 길항곰팡이에 의한 오이덩굴쪼김병균의 Lysis정도는 pH4.6에서 가장 높았으며 다음은 3.6, 5.6, 6.6의 순이었는데 pH 6.6에서는 길항현상이 잘 나타나지 않았으나, 길항곰팡이의 후막포자가 다량 형성되었다.

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지역소재 종합병원에서 소화성궤양 환자의 약물요법 사용실태 분석 (The Study of Different Regimens Prescribed for the Treatment of Peptic Ulcer Disease in a Community Hospital)

  • 박영미;오정미
    • 한국임상약학회지
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    • 제10권3호
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    • pp.111-119
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    • 2000
  • The objective of this study was to evaluate the efficacy and the pattern of regimens prescribed for the treatment of peptic ulcer disease in a regional community hospital. 226 patients were treated as an outpatient and followed for one year. 88 patients $(38.9\%)$ had gastric ulcer (GU) alone, 6 patients $(2.7\%)$ had duodenal ulcer (DV) alone, 5 patients $(2.2\%)$ had gastroesophageal reflux disease (GERD) alone, 25 patients $(11.1\%)$ had both GU and DU, 88 patients $(38.9\%)$ had both GU and GERD, and 14 patients $(6.2\%)$ had both DU and GERD. During this study period no one was treated for Zollinger-Ellison Syndrome. The disease showed higher occurrence in male population (139 patients, $61.5\%$) and among the ages of 30 and 40 $(62.4\%)$. The average age of these patients was 41.3 years and there was no difference between the genders. $81.4\%$ of these patients underwent CLO test to check for the existence of Helicobacter and $66.3\%$ of these Patients showed the positive response. $65.6\%$ of patients with GU and $80\%$ of patients with DU showed the positive response and there was no difference between the genders $(65.4\%\;vs.\;67.6\%)$. 184 patients $(81.4\%)$ were deemed to be cured based on the disappearance of their symptoms after completing the regimens. Compliance rate did not differ for gender or different diseases, while showing a difference in age. Patients between the ages of 20 to 30 years old showed the worst compliance rate. In addition, the compliance was lower among the patients who had previous occurrence of the disease, and this was more evident among female patients. Although 184 patients out of the total 226 patients were deemed to be cured, 36 patients $(20.65\%)$ of these returned to the hospital for relapsed diseases within one year. The factors that affected for patients to relapse were the diseases accompanied by ulcer and social environments, such as smoking, alcohol consumption, and previous history of the diseases (smoking P<0.001, alcohol consumption P<0.02, previous history of disease P<0.05). The regimen using $H_2$ receptor antagonists+tripotassium dicitrato bismuthate+clarithromycin showed the lower rate of relapse, and the regimens of omeprazole (OMP)+amoxicillin+tripotassium dicitrato bismuthate and OMP+amoxicillin+metronidazole showed better compliance rate. Patient education by pharmacists on the importance of compliance to regimens and the risk factors fer relapse can provide a better patient care. This would ultimately result in more cost-effective treatments by preventing additional cost for treating relapsed symptoms in approximately $20\%$ of patients.

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