• Journal of Applied Biological Chemistry
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• v.66
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• pp.250-257
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• 2023

Glutamate is an excitatory neurotransmitter distributed in the central nervous system of mammals. However, high concentrations of glutamate are known to cause neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and stroke by causing nerve cell death. In this study, the antioxidant activity and neuroprotective effect of subtropical natural products were analyzed. Among 11 subtropical plant extracts mainly tested, Sallacca wallichiana extract (SE) showed the greatest free radical scavenging activity. Then, we confirmed through WST-1 assay that SE protected HT22 cells against glutamate-induced cell death in a concentration-dependent manner. The protective effects of SE against glutamate-induced apoptosis in HT22 cells were also confirmed by flow cytometry analysis using Annexin V/PI double staining. We also confirmed using H₂DCF-DA single staining that SE inhibits glutamate-induced intracellular reactive oxygen species. And we were confirmed through that SE inhibited glutamate-induced phosphorylation of Mitogen-activated Protein kinases. Consequently, our results propose that SE may contribute to the development of therapeutics to prevent neurodegenerative diseases.

• Journal of fish pathology
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• v.14 no.1
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• pp.46-53
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• 2001

The present study was undertaken to investigate and compare the effect and mode of action of tachykinins on isolated strip preparations of the intestinal smooth muscle from the nile tilapia, Oreochromis niloticus and the Israel carp, Cyprinus carpio. Both of neurokinin 1(NK-1) receptor agonist, substance P(SP) and neurokinin 2(NK-2) receptor agonist, neurokinin A(NKA) caused concentration-dependent contractions of intestinal smooth muscle in the nile tilapia and the israel carp. The efficiency and potency of these agonists varied between two fish species. In the nile tilapia intestine, the efficiency and potency of SP were greater than those of NKA. However, the efficiency and potency of SP were similar to those of NKA. In the nile tilapia intestine and the israel carp intestine, the contractile responses of SP and NKA were noncompetitively antagonized by NK-1 receptor antagonist, L-732, 138 but unaffected by NK-2 receptor antagonist, MDL 29913. In addition, SP-induced contractions in the both of preparation were significantly inhibited by muscarinic antagonist, atropine($5{\times}10^{-7}$M) and ganglionic inhibitor, tetrodotoxin($2{\times}10^{-7}$M) but NKA-induced contractions were unaffected by those. These results indicate that two tachykinin agonists, SP and NKA predominately modulate the mechanical activity of isolated preparation from the nile tilapia and the israle carp directly through the activation of NK-1 receptor on the intestinal smooth muscle cells, but in the case of SP action, the indirect action through activation of cholinergic nerve terminals seems to be also implicated.

• Journal of Life Science
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• v.21 no.8
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• pp.1134-1141
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• 2011

Transmembrane protein 21 (TMP21) is a member of the p24 cargo protein family and has been shown to modulate ${\alpha}$-secretase-mediated A${\beta}$ production which was specifically observed in the brains of subjects with Alzheimer's disease (AD). In order to investigate whether TMP21 could affect nerve growth factor (NGF) receptor signaling pathway, the alteration of NGF receptors and their downstream proteins were detected in TMP21 over-expressed cells. CMV/hTMP21 vector used in this study was successfully expressed into TMP21 proteins in B35 cells after lipofectamin transfection. Expressed TMP21 proteins induced the down-regulation of ${\gamma}$-secretase complex components including Presenlin-1 (PS-1), PS-2, Nicastrin (NST), Pen-2 and APH-1. Also, the expression level of NGF receptor $p75^{NTR}$ and RhoA were significantly higher in CMV/hTMP21 transfectants than vehicle transfectants, while their levels returned to vehicle levels after NGF treatment. However, the phosphorylation of NGF receptor TrkA was dramtically decreased in NGF No-treated CMV/hTMP21 transfectants compared with vehicle transfectants, and increased in NGF treated CMV/hTMP21 transfectants. In TrkA downstream signaling pathway, the phosphorylation level of ERK was also decreased in CMV/hTMP21 transfectants, while the phosphorylation of Akt was increased in the same transfectants. Furthermore, NGF treatment induced the increase of phosphorylation level of Akt and ERK in CMV/hTMP21 transfectants. Therefore, these results suggested that over-expression of TMP21may simultaneously induce the up-regulation of $p75^{NTR}$/RhoA expression and the down-regulation of TrkA/ERK phosphorylation through the inhibition of ${\gamma}$-secretase activity.

• The Korean Society of Law and Medicine
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• v.24 no.2
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• pp.147-196
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• 2023

Advances in brain science have made it possible to stimulate the brain to treat brain disorder or to connect directly between the neuron activity and an external devices. Non-invasive neurotechnologies already exist, but invasive neurotechnologies can provide more precise stimulation or measure brainwaves more precisely. Nowadays deep brain stimulation (DBS) is recognized as an accepted treatment for Parkinson's disease and essential tremor. In addition DBS has shown a certain positive effect in patients with Alzheimer's disease and depression. Brain-computer interfaces (BCI) are in the clinical stage but help patients in vegetative state can communicate or support rehabilitation for nerve-damaged people. The issue is that the people who need these invasive neurotechnologies are those whose capacity to consent is impaired or who are unable to communicate due to disease or nerve damage, while DBS and BCI operations are highly invasive and require informed consent of patients. Especially in areas where neurotechnology is still in clinical trials, the risks are greater and the benefits are uncertain, so more explanation should be provided to let patients make an informed decision. If the patient is under guardianship, the guardian is able to substitute for the patient's consent, if necessary with the authorization of court. If the patient is not under guardianship and the patient's capacity to consent is impaired or he is unable to express the consent, korean healthcare institution tend to rely on the patient's near relative guardian(de facto guardian) to give consent. But the concept of a de facto guardian is not provided by our civil law system. In the long run, it would be more appropriate to provide that a patient's spouse or next of kin may be authorized to give consent for the patient, if he or she is neither under guardianship nor appointed enduring power of attorney. If the patient was not properly informed of the risks involved in the neurosurgery, he or she may be entitled to compensation of intangible damages. If there is a causal relation between the malpractice and the side effects, the patient may also be able to recover damages for those side effects. In addition, both BCI and DBS involve the implantation of electrodes or microchips in the brain, which are controlled by an external devices. Since implantable medical devices are subject to product liability laws, the patient may be able to sue the manufacturer for damages if the defect caused the adverse effects. Recently, Korea's medical device regulation mandated liability insurance system for implantable medical devices to strengthen consumer protection.

• Microbiology and Biotechnology Letters
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• v.28 no.2
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• pp.97-104
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• 2000

Screening of Biologically Active Essential Oils from Ligusticum tenuissimum. Kim, Min-Hae, Young-Gil Kim, Jin-Ha Lee, Keo-Pyo Hong, Jung-Ki Hong, Young-Joon Kong, and Hyeon-Yong Lee*. Division of Food and Biotechnology, Kangwon National University, Chunchon 200-701, Korea, 1 Regional Crop Development Station, Kangwon Agricultural Research & Extension Services, Chunchon 200-150, Korea-The biological activities of the crude essential oils from Ligusticum tenuissimum and the control(phthalic anhydride) were compared. About 60% of the growth of MCF7, A549, and Rep3B cells were inhibited by adding 1.0 mg/ml of the crude essential oils and below 40% was observed by the control. Cytotoxicity on human normal lung cell(IMR90) was scored as 34.4% for the crude oil and 26.4% for control, respectively. It was found that the crude essential oils were more effective than the control in anti mutagenecity tested by both Rec-assay and CRG V79 cells. The growth of human T-cell(Jurkat) was enhanced up to 1.21 times by adding the crude essential oil compared with the control. 50% of a-glucosidase activity was inhibited by both the crude essential oil and the control. ACE activities were inhibited 80.1 % and 65.3% by adding 1.0 mg/ml of the crude oil and the control, respectively. The higher enhancement of glutathione-S-transferase activity was observed in the crude oil than those in the control: 301 % v.s 234% at 1.0 mg/ml of the treatment. Thrombolytic activity was measured as 42.9% and 28.6% for the crude oil and the standard, respectively. The effect of the oil on the nerve cells PCI2, was observed as follows: the neurite of PCl2 cells was lengthened up to 255 /-lm longer than 205 /-lm of control. The number of neurite-bearing cells were about two times higher than control. The survival ratio of the crude essential oil was also increased up to 56.4% which was about two fold higher than in control.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.1-14
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• 1982

The effects of xanthine-xanthine oxidase reaction on brain microsomal $Na^+-K^+-ATPase$ activity were studied to see possible involvement of oxygen free radicals in pathologic change occurring in ischemic state of CNS accompanied by cerebral vascular occlusion or impact injury. When microsomal fraction was incubated with xanthine ana xanthine oxidase, $Na^+-K^+-ATPase$ activity of the fraction was markedly inactivated (80% inactivation) whereas btssl $Mg^{++}-ATPase$ was much less sensitive (less than 10% inactivation) compared to that of $Na^+-K^+-ATPase$. The inactivation was observed only in the presence of both xanthine and xanthine oxidase, not either of them alone, and the extent of inactivation was dependent on the concentration of xanthine. In an attempt to determine which of the oxygen species was responsible for the inactivation, the ability of various scavengers to overcome the inactivation was tested. Superoxide dismutase, catalase and 1,4-diazabicyclo(2,2,2)octane were shown to reverse the inactivation of the ATPase in dose-dependent manner. In contrast, mannitol as well as other $OH{\cdot}$quenchers were ineffective in limiting oxygen radical-induced inactivation. Thus $O_{\bar{2}}{\cdot},\;H_2O_2$ and $^1O_2$ were implicated to be mediators involved in the inactivation. Since oxygen radicals are suspected as being a cause of the peroxidative damaging process in train ischemia, the ATPase inactivation by oxygen radicals may be a possible contributing factor which gives rise to functional derangement of nerve cells observed in the pathologic process.

• The Journal of Korean Academy of Sensory Integration
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• v.9 no.1
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• pp.45-52
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• 2011

Objective : The aim of this study was to provide the method to measure physiologic response using equipments and auditory stimulation, and the physiologic response features of adult psychiatric disorders through a systemic review. Methods : The systemic review was executed using PubMed. The key words for search were "auditory stimulation, auditory startle, electromyograph, skin conductance, heart rate, psychiatric disorder, anxiety disorder, schizophrenia, depression". 8 studies were used for data analysis, and all of levels of evidence were level II. The substances of the review were subject(population), auditory stimulation, measure equipments and physiologic response features of psychiatric disorder. Results : 1. The subjects for the studies were anxiety disorder(4) and schizophrenia(4). 2. Auditory stimulation was used in 8 studies and visual stimulation with auditory stimulation was used in 2 studies to induce physiologic response. 3. Every study used electromyograph, and skin conductance was used in 2 studies and heart rate was used in 2 studies with electromyograph to measure physiologic response. 4. The subjects for the studies, schizophrenia and anxiety disorder(PTSD, OCD) have different physiologic response features with the normal control group. Conclusion : All studies used simple tones as an auditory stimulation and electromyograph to measure physiologic response. Psychiatric disorders indicated larger response, shorter and delayed habituation. The objective and systematic study using physiologic measure to investigate the sensory feature of psychologic disorders.

• Journal of Life Science
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• v.22 no.4
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• pp.532-537
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• 2012

We investigated the effect of smoking on cardiovascular responses during acute dynamic exercise. Eleven college students who had been smoking (duration of smoking: $7.45{\pm}0.90$ years; number of cigarettes per day: $17.72{\pm}1.22$) participated in this study. All subjects completed a graded exercise testing to determine the relative exercise intensity. The cardiovascular responses were measured at rest, and during mild and moderate exercise immediately, 24, and 48 hours after smoking. The same procedures were repeated during 24-h smoking withdrawal. All subjects were continuously instrumented to measure systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), stroke volume (SV), cardiac output (CO), and total vascular conductance (TVC) at rest and during exercise. The results showed that compared to the nicotine abstention, SBP, DBP, MAP, and HR were significantly higher at 24 and 48 hours after smoking ($p$<0.05), and CO was significantly higher at rest and during moderate exercise ($p$<0.05). There were no differences in SV and TVC before and after smoking. Thus, the results suggest that smoking is associated with an exaggerated sympathetic nerve activity during dynamic exercise. Consequently, smoking cessation may help reduce cardiac events, such as stroke and heart attack, during exercise.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.5
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• pp.509-519
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• 2013

Through the study on judgment of Body form and settle Energy flow(立形定氣) before diagnose the patients, the results are as follows. The observation of the body form is to determine prosperity and deficiency of each internal organ. It is necessary to distinguish Body form loss(形脫) and Body form fullness(形充). Fat man(肥人), Thin man(瘦人), Creamy man(膏人), Muscular man(肉人), Small Fat man(脂人) are discriminated by fat distribution, fat content, and muscle mass. The observation of the body form means the observation of structure disorder, color change, develop part at body, head and face. The observation of the body form that is to determine prosperity and deficiency of each internal organ is from the limited knowledge of the anatomy. The observation of face color is considered by blood perfusion, blood oxygenation and accumulation of carotinoid, bilirubin and change of melanin in the facial skin. The prosperity and the deficiency of energy flow is considered by symptom combined with growth (<40 years) and aging (>40 years). The prosperity of energy flow includes the anger, anxious emotion and the deficiency of energy flow includes the fear, depressive emotion. The breathing type is expiratory exhalation like asthma patients in the prosperity of energy flow. The deficiency of energy flow is weakness to overcome the disease. The prosperity and the deficiency of energy flow are considered by body metabolic ratios (Basal metabolic Rate: BMR, Resting metabolic rate: RMR, Physical activity ratios: PASs). Development of subcutaneous fat is good in the person of prosperous energy flow. The person of prosperous energy flow is hard to overcome to heat weather than cold weather. The person of deficiency of energy flow has tendencies of low blood pressure, insufficiency of blood flow in the peripheral and being shocked. The person of deficiency of energy flow has tendencies of chronic fatigue syndrome or automatic nerve disorder. If the patient who has deficiency of energy flow has severe weight loss should be checked for the presence of disease. The observation of small and large of bone is to check the development and disorder of bone growth and aging. The observation of thickness and weakness of muscle is to check the development of muscle, particularly biceps, gastrocnemius, and rectus abdominal muscle. The observation of thickness and weakness of skin is to check the ability of regulating body temperature by sweating.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.94-99
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• 1997

Capsaicin is known to be an analgesic agent, affecting the synthesis, storage, , transport and release of substance p, the principal neurotransmitter of pain from periphery to the central nervous system(CNS). DA-5018, a newly synthesized capsaicin derivative has shown potent analgesic effect comparable to that of morphine in various rat models of experimentally inducted acute pairs. In this study the mechanism of analgesic actlvity of DA-5018 was examined. First, the electrically-evoked contraction of guinea pig trachea was inhibited by DA-5018 and these inhibition was recovered by incubation with capsafepine(3$\muM$), capsaicin receptor antagonist and this result suggested that DA-5018 has affinity on capsaicin receptor. The correlation between the norciceptive threshold and the release of substance P was evaluated. In vivo perfusion of slices of the rat spinal cord with DA-5018(10, 100$\muM$) produced a significant increase of the release of substance P and this increase was less than that of capsaicin(10$\muM$). The norciceptive threshold of rat treated with DA-5018(1 mg/kg, p.o) in tall pinch test increased from 2.9$\pm$0.3 to 23.5 $\pm$6.61. Tail pinch latency increased to a maximun at 15 min after DA-5018 treatment and then declined to control values by 120 min. The capsaicin-evoked release ot substance P from the spinal cord slices of rat treated with DA-5018 reduced from 2.38$\pm$ 0.79 to 0.69$\pm$ 0.26 pg/mg wet weight. This reduction reached to a minium at 15 min after DA-5018 treatment and then recovered to control value by 120 min. These results mean that analgesic activity of DA-5018 is due to release of substance P The effect of DA-5018 cream on electrically-evoked neurogenic inflammation of rat saphenous nerve was compared with capsaicin (zostrix-HP). DA-5018 showed 34% inhibition of the neurogenic extravasation while capsaicin showed significant 67% inhibition. This result indicates that the potency of DA-5018 in the release of substance P is less than that of capsaicin. These results suggest that the release of substance P is partially involved in the mechanism of analgesic action of DA-50l8.