• Title/Summary/Keyword: Nerve Agent

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Investigation of the Pharmacological Mechanisms and the R&D of Medical Countermeasures Against Nerve Agent Poisoning (신경작용제 해독제의 약리기전 및 연구개발)

  • Cho, Young
    • Journal of the Korea Institute of Military Science and Technology
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    • v.14 no.5
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    • pp.920-931
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    • 2011
  • Nerve agents are irreversible inhibitors of the cholinesterase enzyme. Exposure causes a progression of toxic signs, including hypersecretions, fasciculations, tremor, convulsions, respiratory distress, epileptiform seizures, brain injuries and death. A combined regimen of prophylaxis and therapy is the most effective medical countermeasure for dealing with the threat of nerve agent poisoning to military personnel. In this paper, the author investigated the updated technologies regarding various pre- and post-treatment drugs for nerve agents detoxification which are under development in several countries including Korea. Some characteristics of active ingredients in the formulations of drugs, their action mechanisms, and effectiveness were analyzed. Additionally, part of experimental data on the transdermal patch studied in ADD using beagle dogs was introduced.

A Case Study on the FDA Approval of Medical Treatments against Nerve Agent Poisoning (신경작용제 해독제 의약품 품목허가 사례 연구)

  • Lee, Keunwoo;An, Seoyeon;Hur, Byungil
    • Journal of the Korea Institute of Military Science and Technology
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    • v.19 no.1
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    • pp.119-126
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    • 2016
  • The US Army used MARK-1 composed of atropine autoinjector and 2-PAM autoinjector as a medical countermeasure against nerve agent poisoning. Recently, it has been being replaced by the ATNAA(Antidote Treatment Nerve Agent AutoInjector) for improvement the convenience in use and rapid detoxification effect. ATNAA(FDA approval, NDA 21-175, 2002. 1. 17) is a multi-chambered autoinjector that sequentially delivers atropine and 2-PAM through a single needle to allow Warfighters to survive against lethal exposure to nerve agents. In this paper, our group investigated the case of FDA approval of ATNAA in a point of the various data required by FDA guideline, thereby making it easy to meet the KFDA guideline for the approval of the prototype our group has been developed. The purpose of this study is to provide a reference for efficient research activities to minimize time and cost. Additionally, the purpose of this study is to provide a reference for the planning for the development of similar drug.

Kinetics of In-situ Degradation of Nerve Agent Simulants and Sarin on Carbon with and without Impregnants

  • Saxena, Amit;Sharma, Abha;Singh, Beer;Suryanarayana, Malladi Venkata Satya;Mahato, Timir Haran;Sharma, Mamta;Semwal, Rajendra Prasad;Gupta, Arvind Kumar;Sekhar, Krishnamurthy
    • Carbon letters
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    • v.6 no.3
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    • pp.158-165
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    • 2005
  • Room temperature kinetics of degradation of nerve agent simulants and sarin, an actual nerve agent at the surface of different carbon based adsorbent materials such as active carbon grade 80 CTC, modified whetlerite containing 2.0 and 4.0 % NaOH, active carbon with 4.0 % NaOH, active carbon with 10.0 % Cu (II) ethylenediamine and active carbon with 10.0 % Cu (II) 1,1,1,5,5,5-hexafluoroacetylacetonate were studied. The used adsorbent materials were characterized for surface area and micropore volume by $N_2$ BET. For degradation studies solution of simulants of nerve agent such as dimethyl methylphosphonate (DMMP), diethyl chlorophosphate (DEClP), diethyl cyanophosphate (DECnP) and nerve agent, i.e., sarin in chloroform were prepared and used for the uniform adsorption on the adsorbent systems using their incipient volume at room temperature. Degradation kinetics was monitored by GC/FID and was found to be following pseudo first order reaction. Kinetics parameters such as rate constant and half life were calculated. Half life of degradation with modified whetlerite (MWh/NaOH) system having 4.0 % NaOH was found to be 1.5, 7.9, 1206 and 20 minutes for DECnP, DEClP, DMMP and sarin respectively. MWh/NaOH system showed maximum degradation of simulants of nerve agents and sarin to their hydrolysis products. The reaction products were characterized using NMR technique. MWh/NaOH adsorbent was also found to be active against sulphur mustard.

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IN VIVO EFFECTS OF DENTIN BONDING AGENTS ON DENTINAL FLUID MOVEMENT AND INTRADENTAL NERVE ACTIVITY (In vivo에서 상아질 접착제 도포가 상아세관액 이동과 치수신경활동에 미치는 영향)

  • Son, Ho-Hyun;Lee, Kwang-Won;Park, Soo-Jung
    • Restorative Dentistry and Endodontics
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    • v.21 no.1
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    • pp.425-435
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    • 1996
  • The effect of application of dentin bonding agent to the exposed dentin on the intradental nerve activity (INA), dentinal fluid movement and sealing of the dentinal tubules, was investigated in this study. The INA was recorded from the single pulp nerve unit dissected from the inferior alveolar nerve. And specimen of dentin was observed by SEM. Dentinal fluid 'movement through exposed dentin surface was measured before and after the application of dentin bonding agent. 1. Eight Ao-fiber units (conduction velocity: $8.0{\pm}4.0m$/sec) were identified. 4M NaCl evoked an irregular burst of action potentials which ceased immediately after washing. 2. In 4 $A{\delta}$-fiber units, appliction of All Bond 2 completely abolished the INA induced by 4M NaCl. Also, application of Scotchbond Multipurpose(SBMP) totally abolished the INA induced by 4M NaCl in 4 $A{\delta}$-fiber units. 3. Before the application of dentin bonding agent, outward dentinal fluid movement of $10.2{\pm}5.7\;pl{\cdot}s^{-1}{\cdot}mm^{-2}$ was obsered. But after the application of dentin bonding agent the movement of dentinal fluid was stopped. 4. The gap width of 2-$3{\mu}m$ was formed between exposed dentin and adhesive resin in the specimens applied with dentin bonding agents of All Bone 2 and SBMP. But the formation of hybrid layer and the penetration of resin into were dentinal tubules were not clearly observed in interface between dentin and adhesive resin.

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3D-QSAR Study of Competitive Inhibitor for Acethylcholine Esterase (AChE) Nerve Agent Toxicity

  • San Juan, Amor A.;Cho, Seung-Joo
    • Molecular & Cellular Toxicology
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    • v.2 no.3
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    • pp.216-221
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    • 2006
  • The cholinesterase-inhibiting organophosphorous (OP) compounds known as nerve agents are highly toxic. The principal toxic mechanism of OP compounds is the inhibition of acethylcholine esterase (AChE) by phosphorylation of its catalytic site. The reversible competitive inhibition of AChE may prevent the subsequent OP intoxication. In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) was performed to investigate the relationship between the 29 compounds with structural diversity and their bioactivities against AChE. In particular, predictive models were constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The results indicate reasonable model for CoMFA ($q^{2}=0.453,\;r^{2}=0.697$) and CoMSIA ($q^{2}=0.518,\;r^{2}=0.696$). The presence of steric and hydophobic group at naphtyl moiety of the model may lead to the design of improved competitive inhibitors for organophosphorous intoxication.

Updates on the Inferior Alveolar Nerve Block Anesthesia (하치조신경전달마취의 최신지견)

  • Paeng, Jun-Young
    • Journal of The Korean Dental Society of Anesthesiology
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    • v.14 no.1
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    • pp.3-10
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    • 2014
  • The inferior alveolar nerve (IAN) block is the most frequently used mandibular injection technique for achieving local anesthesia for restorative and surgical procedures. However, The IAN block does not always result in successful anesthesia, especially pulpal anesthesia. Lidocaine is used as a "standard" local anesthetic for the inferior alveolar nerve. Articaine recently joined Korean market as a form of dental cartridge. It has an advantage of superior diffusion through bony tissue. A variety of trial was performed to improve the success rate of inferior alveolar nerve block. In this review, the recent update related with inferior alveolar nerve block anesthesia will be discussed on the anatomical consideration, anesthetic agent, technique, and complications.

A Study on the Neurotoxic Effects of Tellurium on Murine Nervous System (랫드의 신경조직에 미치는 Tellurium의 독성에 관한 연구)

  • 김기석;정문호
    • Journal of Environmental Health Sciences
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    • v.24 no.3
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    • pp.35-40
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    • 1998
  • This study was conducted to examine the pathological changes of rat peripheral nervous system during exposure to tellurium known to be a demyelinating agent by using teasing nerve fiber method and quantitative light microscopic analysis by image analyzer. The pellet containing 1.2% of tellurium were fed for 3, 5, 7, 9, 13 days to male wistar rats (21 days old) and then neurologic symptom and the feature of nerve fiber myelination were studied. From this study, following results were obtained. In 3 days treated group, it showed various neurologic symptom and teased nerve fiber showed slight irregularity of the myeline sheath. In 5 days and 7 days treated groups, it showed the segmental demyetination in larger size fiber and widening of nodes of ranvier. In 9 days and 13 days treated groups, the remyelinated fibers were observed and it was generally small in size. We consequently suggest that teasing nerve fiber method and quantitative analysis of nerve fiber were useful pathologic screening method of neurotoxicity of the peripheral nervous system.

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Removal of a broken needle using three-dimensional computed tomography: a case report

  • Kim, Jin-Ha;Moon, Seong-Yong
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.39 no.5
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    • pp.251-253
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    • 2013
  • Inferior alveolar nerve block obtained maximum anesthetic effect using a small dose of local anesthetic agent, which also has low a complication incidence. Complications of an inferior alveolar nerve block include direct nerve damage, bleeding, trismus, temporary facial nerve palsy, and etc. Among them, the major iatrogenic complication is dental needle fracture. A fragment that disappears into the soft tissue would be hard to remove, giving rise to a legal problem. A 31-year-old woman was referred for the removal of a broken needle, following an inferior alveolar nerve block. Management involved the removal of the needle under local anesthesia with pre- and peri-operative computed tomography scans.

Protective Effect of Combinational Antidotes Composed of Physostigmine and Procyclidine Against Nerve-agent Poisoning

  • Kim, Yun-Bae;Cheon, Ki-Cheol;Hur, Gyeung-Haeng;Phi, Taek-San;Kim, Jee-Cheon;Deasik Hang
    • Toxicological Research
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    • v.16 no.3
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    • pp.195-200
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    • 2000
  • Antidotal efficacy of physostigmine plus procyclidine, the combinational prophylactics for organophosphate poisoning, was evaluated in rats and guinea pigs. To assess the dose-response relation-ship in rats, various doses (0.3-6.0mg/kg) of procyclidine in combination with a fixed dose (0.1mg/kg) of physostigmine were pretreated subcutaneously 30 min prior to subcutaneous exposure to nerve-agents. Physostigmine alone exerted protection ratios of 2.44, 1.20, 1.50, 1.50 and 2.20 folds for tabun, sarin, soman, cyclosarin and V-agent, respectively. Interestingly, coadmnistration of procyclidine with physostigmine exhibited remarkable synergistic effects in a dose-dependent manner, leading to 4.00~8.00 folds for tabun, 2.15-8.50 folds for sarin, 1.92~507 folds for so man, 2.15~2.90 folds for cyclosarin, and 2.71~10.50 folds for V-agent. On the contrary, a low effect (l.65 fold) was achieved with the traditional antidotes atropine (17.4 mg/kg) plus 2-pralidoxime (30 mg/kg) treated immediately after soman poisoning. Noteworthy, the combinational prophylactics markedly potentiated the effect of atropine plus 2-pralidoxime to 6.13 and 12.27 folds with 1.0 and 3.0 mg/kg of procyclidine, respectively, against soman poisoning. In guinea pigs, the physostigmine plus procyclidine prophylactics exerted protective effects of 3.00~4.70 folds against soman intoxcation, which were much higher at low doses (0.3~1.0 mg/kg) of procyclidine than those in rats. Taken together, it is proposed that the combinational prophylactics composed oj physostigmine and procyclidine could be a promising antidote regimen for the poisoning with organophosphates possessing diverse properties.

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Ameliorative Potential of Rengyolone Against CCI-induced Neuropathic Pain in Rats

  • Lee, Gil-Hyun;Hyun, Kyung-Yae
    • Biomedical Science Letters
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    • v.26 no.4
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    • pp.310-318
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    • 2020
  • The sciatic nerve is the largest nerve among the peripheral nerves, and the damage to the sciatic nerve is caused by mechanical and physical pressure. This is an important disease that consumes a lot of time and money in the treatment process. Among them, research on relieving nerve pain caused by damage to the peripheral sciatic nerve has been made efforts to prevent and treat this disease through various methods such as drugs, natural products, electrical stimulation, exercise therapy, and massage. Existing treatments are not very effective in neurological pain, and countermeasures are needed. Forsythia Fructus, used in this study, has been used as a therapeutic agent for infectious diseases and a pain reliever for cancer from the past, and in past studies, it has been known to properly control the inflammatory response. In this study, rengyolone, a physiologically active substance of Forsythiae Fructus, was administered to rats that caused chronic left nerve pain to verify the pain relief effect. As a result of the experiment, it was found that mechanical pain and cold stimulation pain were significantly reduced in the rengyolone-treated group compared to the non-administered group. In addition, it was found that nerve growth factor (NGF) mRNA expression was significantly reduced and Cyclin-dependent kinase 2 (Cdc2) expression was increased in the rengyolone administration group. This increase in NGF expression is thought to be related to rengyolone's anti-inflammatory regulatory mechanism. It is expected that the reduced NGF was directly involved in pain relief.