• Toxicological Research
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• v.16 no.3
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• pp.211-219
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• 2000

The therapeutic effect of AS2-006A, a derivative of asiaticoside, has been studied and is being developed as a new wound-healing agent. In the present study, the general pharmacological effects on 1) central nervous system, 2) autonomic nervous system, 3) respiratory system, 4) gastrointestinal system. 5) cardiovascular system. and 6) urinary system were assessed in experimental animals and in in vitro models. 1. In vivo animal study: External applications of the 1 % gel ointment of AS2-006A to rats at the doses of 200. 600 or 2000 mg/kg body weight showed no observable pharmacological effects. The effects on the central nervous system were assessed by observation of behavior, hexobarbital-induced sleeping time, pentetrazole-induced convulsion assay, body temperature measurements, and observations on spontaneous activity and catalepsy. The gel ointment exhibited no effects on the cardiovascular system (i.e. blood pressure and heart rate), renal physiology (i.e. urine volume and electrolytes excretion) and gas-trointestinal physiology (i.e. intestinal charcoal propulsion and gastric mucosal irritation). 2. In vitro experiments: The effects of AS2-006A on the physiology of smooth and cardiac muscles were assessed. Muscle contractions were isotonically and isometrically measured in organ chambers using a physiograph. Cumulative additions of AS2-006A (10$^{-9}$ -10$^{-5}$ M) induced no changes in the tension of isolated guinea pig ileum and tracheal muscles. AS2-006A only slightly increased contractility of rat atrial and papillary muscles at 10$^{-2}$ M, which was not statistically different from control. These data showed that the gel ointment of AS2-006A could be externally applied as a wound-healing agent with no potential side effects.

• Proceedings of the Korea Society for Simulation Conference
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• 2004.05a
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• pp.109-117
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• 2004

In this paper, we consider the aortic sinus baroreceptor, which is the most representative baroreceptor sensing the variance of pressure in the cardiovascular system, and propose heart activity control model to observe the effect of delay time in heart period and stroke volume under the regulation of baroreflex in the aortic sinus. The proposed heart activity baroreflex regulation model contains electric circuit sub-model. We constituted the time delay sub-model to observe sensitivity of heart activity baroreflex regulation model by using the variable value to represent the control signal transmission time from the output of baroreflex regulation model to efferent nerve through central nervous system. The simulation object of this model is to observe variability of the cardiovascular system by variable value in time delay sub-model. As simulation results, we observe three patterns of the cardiovascular system variability by the time delay, First, if the time delay over 2.5 second, aortic pressure and stroke volume and heart rate is observed nonperiodically and observed. Finally, if time delay under 0.1 second, then heart rate and aortic pressure-heart rate trajectory is maintained in stable state.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.3
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• pp.149-154
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• 2002

The blood pressure (BP) is regulated by the nervous system and humoral factors, such as renin- angiotensin system, vasopressin and others. In the present study, we examined the central effects of glutamate and GABA on the cardiovascular regulation by injection of these substances into the lateral ventricle and also investigated the relationship between these central effects and the action of angiotensin II (Ang). Male Sprague Dawley rats, $350{\sim}400$ g, were anesthetized with urethane and instrumented with an arterial catheter for direct measurement of BP and heart rate (HR), and an guide cannula in the lateral ventricle for drug injection. A glass microelectode was inserted into the rostral ventrolateral medulla (RVLM) for recording single unit spikes. Barosensitive neurons were identified by changes of single unit spikes in RVLM following intravenous injection of nitroprusside and phenylephrine. The effects of GABA and glutamate injected into the lateral ventricle were studied in single neuronal activity of the RVLM in addition to changes in BP and heart rate, and compared the results before and after treatment with intravenous losartan, nonpeptide Ang II-type 1 receptor antagonist (1 mg/100 g BW). Intracerebroventricular administration of GABA decreased systolic blood pressure (SBP) and HR, but increased the firing rates in the RVLM. However, intracerebroventricular glutamate injection produced effects opposite to GABA. After pretreatment of intravenous losartan, the central effects of GABA on BP and firing rate in the RVLM were significantly attenuated and that of glutamate showed a tendency of attenuation. These results suggested that central GABA and glutamate regulated BP and firing rates in RVLM were inversely related to BP change. The central effects of GABA or glutamate on the autonomic nervous function were modulated by humoral factor, Ang II, by maintaining BP.

• Journal of Oriental Neuropsychiatry
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• v.10 no.2
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• pp.59-70
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• 1999

We investigated whether an aqueous extract of Rehmannia glutinosa steamed root (RGAE) inhibits secretion of inflammatory cytolanes from primary cultures of mouse astrocytes. RGAE dose-dependently inhibited the $TNF-{\alpha}$ secretion by astrocytes stimulated with substance P (SP) and lipopolysaccharide (LPS). Interleukin-1 (IL-1) has been shown to elevate $TNF-{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore also investigated whether IL-1 mediated inhibition of $TNF-{\alpha}$ secretion from primary astrocytes by RGAE. Treatment of RGAE to astrocytes stimulated with both LPS and SP decreased IL-1 secretion to the level observed with LPS alone. Moreover, incubation of astrocytes with IL-1 antibody abolished the synergistic cooperative effect of LPS and SP. These results suggest that RGAE has an antiinflammatory activity on the central nervous system curing some pathological disease states.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.84-84
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• 2003

Lead has long been considered as a toxic environmental pollutant, which severely damages central nervous system. Lead can cause hypo- and de-myelination, and glial cells are closely related with myelination or demyelination. Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in the remodelling of the extracellular matrix in a variety of physiological and pathological processes. MMPs also seem to be important in the pathogenesis of inflammatory demyelinating diseases of the central and peripheral nervous system. In this study, we investigated whether lead affects MMP-9 expression in rat primary glial cells. Treatment of 0.1-5 ${\mu}$M lead dose- and time-dependently increased MMP-9 expression in rat primary glial cells. The activity of MMPs was determined using zymography. Lead activated Erk(1/2) but neither of the other endogenous MAP kinases, p38 or JNK. Inhibition of Erk(1/2) activation by PD98059, a MEK inihibitor, prevented lead-induced expression of MMP-9. The results of the present study suggest that lead intoxication may adversely affect brain function at least in part by inducing MMP-9 expression through Erk(1/2) activation in primary glial cells.

• Journal of Biomedical Engineering Research
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• v.15 no.4
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• pp.429-438
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• 1994

An electrical stimulator was designed to induce locomotion for paraplegic patients caused by central nervous system injury. Optimal stimulus parameters, which can minimize muscle fatigue and can achieve effective muscle contraction were determined in slow and fast muscles in Sprague-Dawley rats. Stimulus patterns of our stimulator were designed to simulate eleclromyographic activity monitored during locomotion of normal subjects. Muscle types of the lower extremity were classified according to their mechanical property of contraction, which are slow muscle (msoleus m.) and fast muscle (medial gastrocnemius m., rectus femoris m., vastus lateralis m.). Optimal parameters of electrical stimulation for slow muscles were 20 Hz, 0.2 ms square pulse. For fast muscle, 40 Hz, 0.3 ms square pulse was optimal to produce repeated contraction. Higher'stimulus intensity was required when synergistic muscles were stimulated simultaneously than when they were stimulated individually. Electrical stimulation for each muscle was designed to generate bipedal locomotion, so that individual muscles alternate contraction and relaxation to simulate stance and swing phases. Portable electrical stimulator with 16 channels built in microprocessor was constructed and applied to paraplegic patients due to lumbar cord injury. The electrical slimulator restored partially gait function in paraplegic patients.

• Biomolecules & Therapeutics
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• v.2 no.4
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• pp.347-360
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• 1994

The general and some pharmacological actions of DWP 301 were investigated in animals and the following results were obtained. In central nervous system, DWP 301 had no effects on the pentobarbital induced anaesthesia, rotarod test, traction test, analgesic action, anticonvulsant action in mice and body temperature in rat. But DWP 301 showed a little decrease of locomotor activity at a dose of 3,000 mg/kg. From these results, DWP 301 was considered to have little pharmacological effect on the central nervous system. Furthermore, DWP 301 had no influences on the normal blood pressure and heart rate. DWP 301 showed no effect on the isolated guinea pig ileum, trachea, right atrium, and nonpregnant rat uterus. But, in the isolated guinea pig vas deference, DWP 301 had showed inhibitory effect on the contractions produced by norepinephrine. DWP 301 showed rise of gastric juice pH and decrease of urine volume. Also, DWP 301 had no effect on the gastrointestinal motility and blood aggregation. From these results, it is concluded that the general pharmacological effect of DWP 301 are similar to or weaker than M and AGA.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.173-184
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• 1994

The general and some pharmacological actions of DWP 305 were investigated in animals and the following results were obtained. In central nervous system, DWP 305 had no effects on the pentobarbital induced anaesthesia, locomotor activity, rotarod test, traction test, analgesic action in mice and body temperature in rat. DWP 305 showed no depressive action on convulsion induced by strychnine, electronic shock and pentylenetetrazole. From these results, DWP 305 was considered to have no pharmacological effect on the central nervous system. Furthermore, DWP 305 had no influences on the normal blood pressure and heart rate. In the isolated ileum of guinea pig, DWP 305 inhibited contractive effects against the acetylcholine (10$^{-6}$ g/mι), histamine (10$^{-6}$ g/mι), 5-hydroxytryptamine (10$^{-6}$ g/mι) and BaCl$_2$(10$^{-4}$ g/mι) at a concentration of 2.15$\times$10$^{-4}$ g/ml in bath. In the isolated trachea and vats deference, DWP 305 showed no effect on the contractions produced by histamine and norepinephrine, respectively. DWP 305 showed inhibitory effect on the contractions produced by acetylcholine and oxytocin at a concentration of 2.15$\times$10$^{-4}$ g/ml on the isolated nonpregnant rat uterus. DWP 305 had no effect on the isolated right atrium of guinea pig, bile excretion, urine volume, pH, gastrointestinal motility, gastric secretion and blood aggregation.

• The Korean Journal of Emergency Medical Services
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• v.9 no.1
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• pp.111-119
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• 2005

Glucose is the most importantenergy source in the central nervous system. Because the central nervous system cannot synthesize or store glucose. low blood glucose even for a short period results in no functionally normal activity of the brain. In addition, continuous low blood glucosecan cause irreversible brain damage and brain death. Therefore, the current status of emergency care by first aid staffs during transfer of patients with hypoglycemia has been investigated in this study, 114 patients who have visited the hospital using 119 Emergency Medical Service from January 1, 2004 till December, 2004 and shown blood glucose of 2.8 mmol/L and less on arrival have been involved. In case of nurses, assistant nurses, first aid staffs receiving first aid training and second-class emergency medical technicians(EMTs), they provided basic life support (BLS). In case of first-class EMTs, they measured blood sugar and then they orally administered glucose to conscious patients or provided simple first aids and prompt transfer for unconscious patients. As a result of analysis, it is suggested that first aid retraining is required.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.555-563
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• 1998

The renal function is under regulatory influence of central nervous system (CNS), in which various neurotransmitter and neuromodulator systems take part. However, a possible role of central GABA-benzodiazepine system on the central regulation of renal function has not been explored. This study was undertaken to delineate the renal effects of diazepam. Diazepam, a benzodiazepine agonist, administered into a lateral ventricle (icv) of the rabbit brain in doses ranging from 10 to 100 ${\mu}g/kg,$ elicited dose-related diuresis and natriuresis along with improved renal hemodynamics. However, when given intravenously, 100 ${\mu}g/kg$ diazepam did not produce any significant changes in all parameters of renal function and systemic blood pressure. Diazepam, 100 ${\mu}g/kg$ icv, transiently decreased the renal nerve activity (RNA), which recovered after 3 min. The plasma level of atrial natriuretic peptide (ANP) increased 7-fold, the peak coinciding with the natriuresis and diuresis. Muscimol, a GABAergic agonist, 1.0 ${\mu}g/kg$ given icv, elicited marked antidiuresis and antinatriuresis, accompanied by decreases in systemic blood pressure and renal hemodynamics. When icv 0.3 ${\mu}g/kg$ muscimol was given 3 min prior to 30 ${\mu}g/kg$ of diazepam icv, urinary flow and Na excretion rates did not change significantly, while systemic hypotension was produced. These results indicate that icv diazepam may bring about natriuresis and diuresis by influencing the central regulation of renal function, and that the renal effects are related to the increased plasma ANP levels, not to the decreased renal nerve activity, and suggest that the effects may not be mediated by the activation of central GABAergic system.