• Journal of the Korean Applied Science and Technology
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• v.36 no.1
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• pp.142-152
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• 2019

This study aimed to explore the association between obesity index and heart rate variability (HRV) in college-aged male smokers. A total of 85 male college students (> 10 cigarettes per day for at least 3 years) were participated in this study. According to a standardized protocol, body mass index (BMI), percent body fat (%BF), waist circumference (WC), and waist-to-hip ratio (WHR) were taken as obesity indices. Resting r-r interval was monitored for HRV analysis as an indicator of cardiac autonomic regulation. Compared with low WHR subjects, high WHR subjects had significantly lower values of rMSSD, pNN50, HF, and SD1, suggesting decreased parasympathetic activity. No such differences in LF/HF ratio were found between the WHR-based subgroups. Bivariate correlation analysis showed that obesity indices of WC, WHR, and %BF were significantly associated with rMSSD, pNN50, HF, and SD1, with a tendency for correlation coefficient to be higher with WHR than with WC or %BF. No significant association was found between BMI and HRV parameters indicative of parasympathetic activity. This study suggest that central obesity is significantly associated with decrease in parasympathetic activation, independent of BMI as an indicator of obesity, in male college smokers.

• Journal of Pharmacopuncture
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• v.7 no.1 s.12
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• pp.53-61
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• 2004

Substantial evidence suggests that behavioral and reinforcing effects of cocaine can be mediated by the mesolimbic dopaminergic system. It has been shown that repeated injections of cocaine produce increase in locomotor activity, expression of the immediate-early gene, c-fos in the nucleus accumbens (NAc), which was one of the main dopaminergic terminal areas. Herbal-acupuncture as a therapeutic intervention has been widely used for the treatment of many functional disorders such as drug abuse. Coptidis Rhizoma (CR) and its main component, berberine (BER) were selected as herbal medicine of herbal-acupuncture. Both medicines have been known to have the therapeutic effect on the central nervous system. In order to investigate the effects of CR and BER herbalacupuncture at shenmen (HT7) point (CR/H and BER/H) on the cocaine-induced behavioral sensitization, the influence of CR/H and BER/H on repeated cocaine-induced locomotor activity, the change of c-Fos expression in the brain by immunohistochemistry were examined. Male SD rats were given CR/H (0.4mg/kg) and BER/H (0.1mg/kg) 30 min before daily injections of cocaine hydrochloride (15mg/kg. i.p.) 10 days. After 3 days withdrawal, rats received a challenge injection of cocaine (15mg/kg, i.p.). Systemic challenge with cocaine produced much larger increased locomotor activity, accumbal Fos-like immunoreactivity in the NAc. Pretreatment with CR/H and BER/H significantly inhibited cocaine-induced locomotor activity, the change of c-Fos expression in the rats. Our data demonstrated that the inhibitory effects of cocaine-induced behavioral sensitization by CR/H and BER/H were closely associated with the reduction of presynaptic dopamine release in the NAc. These results suggest that CR/H and BER/H can be effectively applied to cocaine addiction.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.153-164
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• 1988

The potential role of endogenous opioid peptides (EOPS) in cardiovascular regulation has only recently been entertained. EOPS have been localized in brain, spinal cord, autonomic ganglia, particularly the adrenal gland, and many other peripheral tissues. There are at least five major types of opioid receptors; namely ${\mu},\;{\delta},\;k,\;{\sigma},\;and\;{\varepsilon}$ and Experimental evidence indicates that cardiovascular actions of the peptide are mediated primarily by ${\mu},\;{\delta}$ and k receptors, and that these receptor types may be allosterically coupled. In anesthetized rabbits met-enkephalin decreased blood pressure and heart rate, which closely paralleled a reduction in sympathetic discharge. Naloxone, but not naloxone methobromide, antagonized these effects, which suggests a central site of action of met-enkephalin. A number of autonomic agents, particularly adrenergic ${\alpha}$-and, ${\beta}-agonists$ and antagonists modify the cardiovascular actions of met-enkephalin. Experiments in reserpine-treated and adrenalectomized rats provide no evidence of sympathetic nervous system involvement in the pressor responses to intravenous injection of opioid peptides, but rather suggest a direct peripheral action. Finally, activation of a beta-endorphinergic pathway projecting from the arcuate nucleus to the nucleus tractos solitarii in rats can cause naloxone reversible hypotension and bradycardia. There is evidence to implicate this pathway in antihypertensive drug action and in the modulation of baroreflex activity.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.161-170
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• 2004

Molecular Nuclear Neuro-Imaging in "CNS" drug discovery and development tan be divided into four categories that are clearly inter-related.(1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and "CNS fingerprinting" the neuroanatomy of drug effects;(4) Functional mapping to examing disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering, might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy.

• Korean Journal of Pharmacognosy
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• v.42 no.2
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• pp.175-181
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• 2011

Oxidative stress or accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate is one of the major excitatory neurotransmitter in the central nervous system (CNS). Glutamate contributes to fast synaptic transmission, neuronal plasticity, outgrowth and survival, behavior, learning and memory. In spite of these physiological functions, high concentration of glutamate causes neuronal cell damage, acute insults and chronic neuronal neurodegenerative diseases. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. NNMBS020, the water-insoluble fraction of the 70% EtOH extract of root barks of Dictamnus dasycarpus, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS020 makes the nuclear accumulation of Nrf2 and stimulates extracellular signal-regulated kinase (ERK) pathway. The ERK MAPK pathway inhibitor significantly reduced NNMBS020-induced HO-1 expression, whereas the JNK and p38 inhibitors did not. In conclusion, the water-insoluble fraction of the 70% EtOH extract of root barks of D. dasycarpus (NNMBS020) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 and ERK pathway in mouse hippocampal HT22 cells.

• Korean Journal of Pharmacognosy
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• v.42 no.3
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• pp.276-281
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• 2011

Oxidative stress or the accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. The expression of HO-1 has cytoprotective effects in glutamate-induced oxidative cytotoxicity in HT22 cells. The induction of HO-1 is primarily regulated at the transcriptional level, and its induction by various inducers is related to the nuclear transcription factor-E2-related factor 2 (Nrf2). Nrf2 is a master regulator of the antioxidant response. NNMBS008, the water-insoluble fraction of the 70% EtOH extract of roots of Sophora flavescens, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS008 makes the nuclear accumulation of Nrf2 pathway. In conclusion, the waterinsoluble fraction of the 70% EtOH extract of roots of S. flavescens (NNMBS008) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 pathway in mouse hippocampal HT22 cells. These results suggest that these extracts could be the effective candidates for the treatment of ROS-related neurological diseases.

• Korean Journal of Biological Psychiatry
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• v.4 no.1
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• pp.102-107
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• 1997

Ginseng root, as a folk medicine, has been used in far eastern countries for thousands of years. Ginseng extract has been shown to have a variety of effects on the activity of the central nervous system, promoting stimulation as well as inhibition of the cortical activity. A survey of the relevant literatures has indicated that the putative anxiolytic activity of red ginseng has not been scientifically investigated. Therefore, the present study was designed to assess anxiolytic effect of gingseng total saponins(GTS). The putative anxiolytic effects of several fractions of GTS were investigated in mice using an elevated plus maze paradigm. Single dose administration of TS Fr.-I showed anxiolytic action in mice. Anxiolytic effect induced by TS Fr.-I was similar to that induced by diazepam. TS Fr.-II, TS Fr.-III and TS Fr.-IV did not show the anxiolytic action compared with that of TS Fr.-I. It was suggested that regulation of GABAergic neurotransmission may be important in the action of GTS. The Interaction of GTS fractions with benzodiazepine receptor was performed using rat cortical membranes. GTS inhibited the binding of [3H] Ro 15-1788 on the benzodiazepine receptor. Among from TS fractions, the binding activity of GTS in the TS Fr.-IV was highest, which did not show the anxiolytic activity. From these results, we conclude that GTS has anxiolytic action, and this is not related to benzodiazepine receptor binding activity.

• Biomolecules & Therapeutics
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• v.15 no.1
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• pp.16-26
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• 2007

Tissue plasminogen activator (tPA) is a serine protease catalyzing the proteolytic conversion of plasminogen into plasmin, which is involved in thrombolysis. During last two decades, the role of tPA in brain physiology and pathology has been extensively investigated. tPA is expressed in brain regions such as cortex, hippocampus, amygdala and cerebellum, and major neural cell types such as neuron, astrocyte, microglia and endothelial cells express tPA in basal status. After strong neural stimulation such as seizure, tPA behaves as an immediate early gene increasing the expression level within an hour. Neural activity and/or postsynaptic stimulation increased the release of tPA from axonal terminal and presumably from dendritic compartment. Neuronal tPA regulates plastic changes in neuronal function and structure mediating key neurologic processes such as visual cortex plasticity, seizure spreading, cerebellar motor learning, long term potentiation and addictive or withdrawal behavior after morphine discontinuance. In addition to these physiological roles, tPA mediates excitotoxicity leading to the neurodegeneration in several pathological conditions including ischemic stroke. Increasing amount of evidence also suggest the role of tPA in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis even though beneficial effects was also reported in case of Alzheimer's disease based on the observation of tPA-induced degradation of $A{\beta}$ aggregates. Target proteins of tPA action include extracellular matrix protein laminin, proteoglycans and NMDA receptor. In addition, several receptors (or binding partners) for tPA has been reported such as low-density lipoprotein receptor-related protein (LRP) and annexin II, even though intracellular signaling mechanism underlying tPA action is not clear yet. Interestingly, the action of tPA comprises both proteolytic and non-proteolytic mechanism. In case of microglial activation, tPA showed non-proteolytic cytokine-like function. The search for exact target proteins and receptor molecules for tPA along with the identification of the mechanism regulating tPA expression and release in the nervous system will enable us to better understand several key neurological processes like teaming and memory as well as to obtain therapeutic tools against neurodegenerative diseases.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.164-174
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• 2000

Background: After an injury to tissue such as the skin, hyperalgesia develops. Hyperalgesia is characterized by an increase in the magnitude of pain evoked by noxious stimuli. It has been postulated that in the mechanism of hyperalgesia (especially secondary hyperalgesia) and allodynia, a sensitization of central nervous system such as spinal dorsal horn may contribute to development of hyperalgesia. However, the precise mechanism is still unclear. In the present study, we investigated the roles of N-methyl-D-aspartate (NMDA) receptor and nitric oxide (NO) system in the mechanism of hyperalgesia, and their relations with c-fos expression Methods: Inflammation was induced by injection of complete Freund adjuvant (CFA) into unilateral hindpaw of Sprague-Dawley rat. Behavioral studies measuring paw withdrawal responses by von Frey filaments and paw withdrawal latencies by radiant heat stimuli and stainings of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and c-fos immunoreactivity were performed. The effects of MK-801, an NMDA receptor blocker and $N^\omega$-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor were evaluated. Results: 1) Injection of CFA induced mechanical allodynia, mechanical hyperalgesia and thermal hyperalgesia. And it increased the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 2) MK-801 inhibited mechanical hyperalgesia and thermal hyperalgesia induced by CFA and reduced the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 3) L-NNA inhibited the thermal hyperalgesia and reduced the number of NADPH-diaphorase positive neurons, but did not affect the number of c-fos expression neurons. Conclusions: These results suggest that in the mechanism of mechanical hyperalgesia, NMDA receptor but not NO-system is involved and in the case of thermal hyperalgesia both NMDA receptor and NO system are involved. NO system did not affect the expression of c-fos, but c-fos expression and NOS activity were dependent on the activity of NMDA receptor.

• Journal of Veterinary Clinics
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• v.31 no.3
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• pp.226-232
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• 2014

An 8-month-old domestic shorthair cat presented with decreased activity and anorexia. Diagnostic imaging revealed cranial mediastinal mass and enlarged mesenteric lymph nodes. Fine needle aspirates showed a marked increase in malignant lymphocytes. Multicentric lymphoma (stage V-b) was diagnosed. The cat treated with COP protocol chemotherapy, and complete remission was induced. CNS relapse developed 314 days after the initiation of chemotherapy. Treatment with rescue protocol greatly reduced the clinical signs for a short period. The cat was in partial remission for 33 days and overall survival time was 383 days. Multicentric T-cell lymphoma with brain involvement was confirmed after necropsy by histopathology and immunohistochemistry.