• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1996.04a
• /
• pp.19-29
• /
• 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.

• Journal of the Korean Society of Safety
• /
• v.32 no.2
• /
• pp.59-65
• /
• 2017

Calculation of the damage impact of chemical accidents is an important element in site, and the initial isolation distance and the protective action distances are significant factors in coping the chemical accident. In this study, three major cities that represent each Province were selected, and the safety distances were calculated considering regional climate conditions. The results were compared with the prescribed values in Emergency Response Guidebook. It is concluded that the regional meteorological conditions such as temperature, vapour pressure, relative humidity, wind speed, and cloud cover should be reflected in estimating the initial isolation distance and the protective action distance.

• The Korean Journal of Physiology
• /
• v.17 no.2
• /
• pp.169-176
• /
• 1983

It is well known that the acupuncture has been used effectively for the relief of certain types of pain. Although the precise mechanism of action of acupuncture analgesia is unknown, it is generally accepted that their analgesic properties are related to the activation of endogenous opiate system in central nervous system. And it is suggested that pain-relieving properties of acupunture may be related to a stimulation of peripheral nerve underlying the acupuncture point on the skin. However, the efficacy of acupuncture has no relationship between the site of pain and the acupuncture point. Consequently, the present study was undertaken to investigate electroacupuncture analgesia in relation to the site of peripheral nerve stimulation. Cats were decerebrated ischemically and the flexion reflex as an index of pain was elicited by stimulating the sural nerve (20V, 0.5 msec duration) and recored as a compound action potential from the nerve innervated to the posterior biceps femoris muscle in the ipsilateral hindlimb. Bilateral common peroneal nerve and contralateral superficial radial nerve were selected as the site of peripheral nerve stimulation. For the stimulation of peripheral nerve, a stimulus of 20 V intensity, 2 msec-duration and 2 Hz-frequency was applied for 60 min respectively. The results obtained are summarized as follows: 1) Both stimulation of contralateral common peronal nerve and contralateral superficial radial nerve did not change the flexion reflex and there were no significant differences between them. 2) Stimulation of ipsilateral common peroneal nerve markedly depress the flexion reflex, the effect being reversed by naloxone application. These results suggest that stimulation of ipsilateral common peroneal nerve has the analgesic effect but both stimulation of contralteral common peroneal nerve and contralateral superficial radial nerve to the pain site where flexion reflex was elicited have no analgesic effect.

• Earthquakes and Structures
• /
• v.17 no.6
• /
• pp.557-566
• /
• 2019

The evaluation of the seismic hazard for a given site is to estimate the seismic ground motion at the surface. This is the result of the combination of the action of the seismic source, which generates seismic waves, the propagation of these waves between the source and the site, and site local conditions. The aim of this work is to evaluate the sensitivity of dynamic response of extended structures to spatial variable ground motions (SVGM). All factors of spatial variability of ground motion are considered, especially local site effect. In this paper, a method is presented to simulate spatially varying earthquake ground motions. The scheme for generating spatially varying ground motions is established for spatial locations on the ground surface with varying site conditions. In this proposed method, two steps are necessary. Firstly, the base rock motions are assumed to have the same intensity and are modelled with a filtered Tajimi-Kanai power spectral density function. An empirical coherency loss model is used to define spatial variable seismic ground motions at the base rock. In the second step, power spectral density function of ground motion on surface is derived by considering site amplification effect based on the one dimensional seismic wave propagation theory. Several dynamics analysis of a curved viaduct to various cases of spatially varying seismic ground motions are performed. For comparison, responses to uniform ground motion, to spatial ground motions without considering local site effect, to spatial ground motions with considering coherency loss, phase delay and local site effects are also calculated. The results showed that the generated seismic signals are strongly conditioned by the local site effect. In the same sense, the dynamic response of the viaduct is very sensitive of the variation of local geological conditions of the site. The effect of neglecting local site effect in dynamic analysis gives rise to a significant underestimation of the seismic demand of the structure.

• Journal of the Society of Disaster Information
• /
• v.13 no.2
• /
• pp.155-162
• /
• 2017

This study has some issues about the elderly, the disabled, and the vulnerable groups whose economic ability is low even if the disaster or disaster situation is not a big problem for the people. we should emphasize the necessity of disaster preparedness action manual considering the characteristics of disaster vulnerable classes and taking serious risks to them even in the same situation. We also want to conduct research only for people with disabilities who are choosing the same definition of the world among the vulnerable groups. I would like to provide a basis for developing a site action manual for people with disabilities by comparing the cases of Korea and Japan. Therefore, through the cases of Japan and Korea, it is possible to maintain the independence of everyday life during disasters, the communication function in disasters, the method of moving information and mobile information, the function of recognizing emergency response, Action Emphasize the urgency of developing action manuals. From this domestic situation, we will conclude the discussion on the disaster safety and action manual for the disabled.

• Journal of Applied Biological Chemistry
• /
• v.44 no.3
• /
• pp.105-112
• /
• 2001

Insect pests can be controlled through direct application of insecticides. Insect control by residual protectants is relatively inexpensive and has an advantage of destroying all stages of infestations. The efficacy of control is largely determined by the concentration of insecticides to which the pest species is exposed. A reduction in the period of control in the field afforded by a specific level of a protectant indicates that resistance has developed. An increase in the level of protectant is required to maintain control, and the efficacy of currently used insecticides has been severely reduced by insecticide resistance in pest species. Development of resistance to particular insecticide varies with species because insecticide resistance is often correlated with increased levels of certain enzymes, which are cytochrome P450-dependent monooxygenases, glutathione S-transferases and esterases. Some sections of insecticide molecules can be modified by one or more of these primary enzymes. A reduction in the sensitivity of the action site of a xenobiotic also constitutes a mechanism of resistance. Acetylcholinesterase is a major target site for insecticide action, as are axonal sodium ion channels and ${\gamma}$-aminobutyric acid receptors. Development of reduced sensitivity of these target sites to insecticides usually occurs. This review not only may contribute to a better understanding of insecticide resistance, but also illustrates the gaps still present for a full biochemical understanding of the resistance.

• The Korean Journal of Physiology and Pharmacology
• /
• v.3 no.2
• /
• pp.215-222
• /
• 1999

Nonylphenol (NP) is a widespread environmental pollutant that has been shown to exert both toxic and estrogenic effects on mammalian cells. As the effects of NP on the reproductive system of adult male vertebrates are virtually unknown, we investigated not only the changes of reproductive hormone secretion in serum after chronic exposure to NP but also, in order to identify the site of its action, the reproductive hormone secretion in serum 48 hours after microinfusion of NP within hypothalamic preoptic area (POA). In the chronic exposure, the luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone in serum were decreased but prolactin (PRL) concentrations were increased. The LH, FSH, and testosterone in serum were decreased through the direct infusion of NP into POA, while there was no difference in mean serum prolactin between NP and control groups. These observations suggest that NP as endocrine disruptor has modulatory effects on hypothalamo-pituitary-gonadal axis and that the site of action of NP could be hypothalamic POA.

• Journal of Pharmaceutical Investigation
• /
• v.36 no.5
• /
• pp.315-320
• /
• 2006

Silymarin showed P-glycoprptein(P-gp) inhibitory activity as much as verapamil, a well-known P-gp inhibitor, by decreasing $IC_{50}$ value of daunomycin(DNM)($16.0{\pm}0.7{\mu}M$), increasing the DNM accumulation($224.9{\pm}3.2%$), and decreasing DNM efflux($58.5{\pm}6.7%$), concurrently. In this study, we clarified the mechanism of action of silymarin for P-gp inhibitory function. First, silymarin may bind to the ATP-binding site and thus, prevent ATP hydrolysis. Second, the P-gp inhibitory activity of silymarin is not related to changing the cellular P-gp level. Third, the cytotoxicity of silymarin was increased in the presence of verapamil, reflecting that silymarin is a competent P-gp substrate against verapamil in the P-gp-overexpressed adriamycin-resistant MCF-7 breast cancer(MCF-7/ADR) cells. Conclusively, silymarin had the P-gp inhibitory activity through the action of competent binding to the P-gp substrate-binding site. Therefore, silymarin can be a good candidate for safe and effective MDR reversing agent in clinical chemotherapy by administering concomitantly with anticancer drugs.

• KSBB Journal
• /
• v.6 no.2
• /
• pp.157-166
• /
• 1991

The structural properties of cellulose are significantly changed with the progress of hydrolysis reaction. The effects of changes on such properties of cellulosic substrate as crystallinity, amicessibility of enzyme to the active site of cellulose surface, and particle size on the kinetics of enzymatic hydrolysis have been studied. Among those physical studies, the apparent surface active site of cellulose particle was found to have the most significant effect on the hydrolysis kinetics. Based on the experimental results, the adsorption affinity of enzyme and hydrolysis rate were mainly influenced by the surface roughness of cellulose particle. The extent of accesssible active site may be expressed as the change of particle diameter. The Langmuir isotherm was proposed in terms of enzyme activity to explain the actual action of enzyme protein.

• Korean Journal of Biological Psychiatry
• /
• v.7 no.1
• /
• pp.21-33
• /
• 2000

As the clinical practice of using more than one drug at a time increase, the clinician is faced with ever-increasing number of potential drug interactions. Although many interactions have little clinical significances, some may interfere with treatment or even be life-threatening. This review provides a better understanding of drug-drug interactions often encountered in pharmacotherapy of depression. Drug interactions can be grouped into two principal subdivisions : pharmacokinetic and pharmacodynamic. These subgroups serve to focus attention on possible sites of interaction as a drug moves from the site of administration and absorption to its site of action. Pharmacokinetic processes are those that include transport to and from the receptor site and consist of absorption, distribution on body tissue, plasma protein binding, metabolism, and excretion. Pharmacodynamic interactions occur at biologically active sites. In this review, emphasis is placed on antidepressant medications, how they are metabolized by the P450 system, and how they alter the metabolism of other drugs. When prescribing antidepressant medications, the clinician must consider the drug-drug interactions that are potentially problematic.