• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.71-71
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• 1993

Carboxylesterase is widely distributed in the tissues of vertebrates, insects, plants and mycobacteria. Among various tissues of animals and humans, the highest esterase activity with various substrates is found in the liver. Kidney has moderate carboxylesterase activity in the proximal tubules. Considerable esterase activity is also found in the small intestine epithet elial cells and serum of mammals. Besides these tissues, carboxylesterase has been found in the lung, testis, adipose tissue, nasal mucosa and even in the central nervous system. Hepatic microsomal carboxylesterase catalyzes the hydrolysis of a wide variety of endogenous and exogenous compounds such as carboxylester, thioester and aromatic amide. Since carboxylesterases are important for metabolic activation of prodrugs and detoxification of xenobiotics, differences in substrate specificity and immunological properties of this enzyme are important in connection with choosing a suitable laboratory animal for the evaluation of biotransformation and toxicity of drugs. On the other hand, liver, kidney, intestine and serum were found to contain multiple forms of carboxylesterases in animal species and humans. In fact, we have purified more than fifteen isoforms of carboxylesterases from microsomes of liver, kidney and intestinal mucosa of nine animal species and humans. and characteristics of these isoforms were compared each other in terms of their physical and immunochemical properties. On the other hand, we have reported that hepatic microsomal carboxylesterases are induced by many exogenous compounds such as phenobarbital, polycyclic aromatic hydrocarbons, Aroclor 1254, aminopyrine and clofibrate. Later, we showed that some isoforms of hepatic carboxylesterase were induced by glucocorticoids such as dexamethasone and 16 ${\alpha}$-carbonitrile, but other isoforms were rather inhibited by these compounds. These findings indicate that involvement of carboxylesterases in the metabolism and toxicity of drugs should be explained by the isoforms involved. Since 1991, we have carried out detailed research investigating the types of carboxylesterases involved in the metabolic activation of CPT-11, a derivative of camptothecin, to the active metabolite, SN-38. The results obtained strongly suggest that some isoforms of carboxylesterase of liver microsomes and intestinal mucosal membrane are exclusively involved in CPT-11 metabolism. In this symposium, the properties of carboxylesterase isoforms purified from liver, kidney and intestine of animal species and humans are outlined. In addition, metabolism of CPT-11, a novel antitumor agent, by carboxylesterases in relation to the effectiveness will also be discussed.

• The Korean Journal of Physiology
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• v.20 no.1
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• pp.1-7
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• 1986

It has been well documented that the peripheral autonomic nervous system plays an important role in exocrine pancreatic secretion. However, the role of the central nervous system in pancreatic function is still obscure even though the central nervous system has been known to control gastrointestinal functions through the autonomic nervous system. Since the reticular formation in the mesencephalone seems to integrate the autonomic function, the present study was undertaken to investigate a possible influence of the reticular formation upon the exocrine pancreatic secretion. Twenty·two albino rats fasted for 24 hours were anesthetized by intraperitoneal injection of urethane in a dose of 1 g/kg, The pancreatic duct was cannulated to collect pancreatic juice and bile juice was diverted to the jejunum. The gastroduodenal junction was ligated to Prevent passage of gastic juice into the duodenum. A pair of electrodes were bilaterally inserted in the reticualr formation of the mesencephalone with aid of a stereotaxic apparatus. When the volume of pancreatic juice secreted for 10 min became constant, the reticular formation was electrically stimulated for 10 min. Parameters of the electical stimulation was 1.3V, 40 Hz and 2 msec. When the pancreatic secretion returned to the level before the electrical stimulation, cervical vagotomy (11 rats) or administration of propranolol (11 rats) in a dose of 0.1 mg/kg through the jugular vein was carried out. Ten minutes after the treatment, the electrical stimulation of the reticular formation was repeated. The brain was fixed by perfusion of 10% formaline solution through the heart, and then placement of the electrode tip was examined histologically. Protein concentration and amylase activity in samples of Pancreatic secretion were measured. The electrical stimulation of the reticular formation significantly increased in volume $({\mu}l/10\;min)$, Protein output $({\mu}g/10\;min)$ and amylase output (U/10 min) in the pancreatic secretion. The stimulatroy effects were not affected by the cervical vagotomy but completely abolished by propranolol. Meantime, it was also observed that both vagotomy and propranolol significantly reduced the pancreatic secretory function. These results indicate that the reticular formation in the mesencephalone may exert a stimulatory effect upon the Pancreatic secretory function not through the vagus nerve but through the sympathetic pathway in anesthetized rats.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.205-217
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• 1993

In order to evalute the effects of radiation on mammalian neuronal system, we have examined the effect of gamma-ray radiation on the monoamine oxidase (MAO) activity in monoaminergic neurons. Following the whole body irradiation, MAO activity in the rat brain was measured as well as in the liver for the comparative studies between the neuronal and nonneuronal system. The effects of some radiation protectors and sensitizers were also examined in addition to the $O_2$ effect. The results can be summarized as follows. 1) The MAO activity of rat brain was minimally affected by the radiation dose up to 1,700 cGy Radiation dose above 2,500 cGy inhibited the brain MAO activity by no less than $l0\%.$ MAO-A form was found to be particularly sensitive to radiation. The liver MAO was somewhat inhibited (by about $5\%$) but hardly dependent on the dose of radiation. 2) The inhibitory effect on the brain was initiated immediately by the radiation dose of 2,500 cGy. On the contrary, for the liver, the inhibitory effect became apparent only 2 days after irradiation. 3) Two days after a dose of 2,500 cGy, Vmax and Km of the brain mitochondrial MAO decreased. For liver, Vmax decreased while Km increased, which indicates the kinetic patterns for the neuronal and nonneruronal systems are not affected similarly by radiation. 4) The effect of several known radiation protectors and sensitizers on MAO activity was tested ut no definite results were obtained. The level of -SH group increased in some degree upon radiation but not by the compounds. 5) MAO activity was not affected by $O_2$ concentration, while an elevated level of lipid peroxidase was found under the same condition. The results described here indicate that characteristics of MAO, one of the most important central nervous system enzymes, are liable to radiation, which is partially differentiated from the liver MAO. Also indicated are that the -SH groups are hardly related to the effect of radiation but the production of the lipid peroxide seems to be somewhat correlated to the effect of radiation.

• Journal of Biomedical Engineering Research
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• v.25 no.6
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• pp.565-573
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• 2004

In this paper, we proposed a heart activity control model for simulation of the aortic sinus baroreceptor, which was the most representative baroreceptor sensing the variance of pressure in the cardiovascular system. And then, the heart activity control model composed electric circuit model of the cardiovascular system with baroreflex control and time delay sub-model to observe the effect of time delay in heart period and stroke volume under the regulation of baroreflex in the aortic sinus. The mechanism of time delay in the heart activity baroreflex control model is as follows. A control function is conduct sensing pressure information in the aortic sinus baroreceptor to transmit the efferent nerve through central nervous system. As simulation results of the proposed model, we observed three patterns of the cardiovascular system variability by the time delay. First of all, if the time delay over 2.5 second, aortic pressure and stroke volume and heart rate was observed non-periodically and irregularly. However, if the time delay from 0.1 second to 0.25 second, the regular oscillation was observed. And then, if time delay under 0.1 second, then heart rate and aortic pressure-heart rate trajectory were maintained in stable state.

• Korean Journal of Psychosomatic Medicine
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• v.5 no.1
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• pp.89-96
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• 1997

This study was designed to determine whether cognitive impairment was evident in patients with SLE. Also, it aimed to examine the association of cognitive impairment with other clinical variables. The subjects consisted of 20 patients with mildly active SLE and 20 healthy controls. Methods : A total of 20 SLE patients and 20 normal controls completed a computerized neuropsychological test battery using Vienna Test System. These included Cognitrone test, Continuous attention test, Corsi block tapping test, Standard progressive matrices. Also, neuro-behavioral cognitive status examination was done. The symptom severity of depression was measured with Beck Depression Inventory, Hamilton Depression Rating Scale, and current medications were documented. Disease activity was rated using the SLE diasease activity index (SLEDAI). Results : SLE patients had poorer performance than normal controls on the tests of Cognitrone, attention, nonverbal IQ and memory, independent of age, education, disease activity, steroid use and depression status. Conclusion : Cognitive dysfunction was not uncommon in ambulatory SLE patients as measured by standardized neuropsychological tests. It seemed to occur independently of various clinical variables. These findings would suggest that cognitive dysfunction in SLE may be explained by reflecting subclinical central nervous system(CNS) involvement, rather than coexisting psychological distress due to chronic illness or side effect of medication.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.767-773
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• 2004

Substantial evidence suggests that repeated injections of nicotine produce increase in locomotor activity and expression of the immediate-early gene, c-fos in the dopaminergic target areas. Herbal medicine as a therapeutic intervention has been widely used for the treatment of mental dysfunction. Many studies have shown that Cortex Phellodendris (CP) can affect the biochemical balance in the central nervous system. In order to investigate whether CP have an influence on their nicotine-induced behavioral sensitization, we examined the effect of CP on nicotine-induced locomotor activity and c-Fos expression in the striatum and nucleus accumbens utilizing the Fos-like immunohistochemistry (FLI). Male SD rats received CP (200㎎/㎏, i.p.) 30 min before repeated daily injections of nicotine (0.4㎎/㎏, s.c.) for 7 days. Rats were followed withdrawal for 3 days and one challenge for 1 day. System challenge with nicotine produced a much larger increase in locomotor activity and accumbal FLI. Pretreatment with CP significanly inhibited nicotine-induced locomotor activity and FLI in the striuatum and nucleus accumbens. These results demonstrated that reduction in locomotor activity by CP may be reflected by reduction of dopamine release and postsynaptic neuronal activity in the striatum and nucleus accumbens. Our results suggest that CP may have therapeutic effect on nicotine addiction. Supported by a fund (99-PJ9-PG1-002-0004).

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.3
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• pp.95-99
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• 2008

Calcium ($Ca^{2+}$) is an intracellular second messenger associated with neuronal plasticity of the central nervous system. The calcium-binding proteins regulate the $Ca^{2+}$-mediated signals in the cytoplasm and buffer the calcium concentration. This study examined temporal changes of three calcium-binding proteins (calretinin, calbindin and parvalbumin) in the medial vestibular nucleus (MVN) during vestibular compensation after unilateral labyrinthectomy (UL) in rats. Rats underwent UL, and the changes in the expression of these proteins at 2, 6, 12, 24, 48, and 72 h were examined by immuno-fluorescence staining. The expression levels of all three proteins increased immediately after UL and returned to the control level by 48 h. However, the level of calretinin showed changes different from the other two proteins, being expressed at significantly higher level in the contralateral MVN than in the ipsilateral MVN 2 h after UL, whereas the other two proteins showed similar expression levels in both the ipsilateral and contralateral MVN. These results suggest that the calcium binding proteins have some protective activity against the increased $Ca^{2+}$ levels in the MVN. In particular, calretinin might be more responsive to neuronal activity than calbindin or parvalbumin.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.1
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• pp.17-20
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• 2004

PTEN (phosphatase and tensin homolog) is a dual specific phosphatase antagonizing phosphoinositide 3-kinase activity, and has first been cloned as a tumor suppressor for glioma. Although the role of PTEN as a tumor suppressor has been well studied, little is known about signaling mechanisms regulating expression and/or activity of PTEN in the central nervous system. In this study, we investigated whether PTEN expression is regulated by sensory deprivation. P5 rat pups were unilaterally naris-closed, and olfactory bulbs were immunohistochemically analyzed with PTEN antibody at the $7^{th}$ day after naris closure. PTEN immunoreactivity was found to be down-regulated in both glomerular, external plexiform and subependymal cell layers, suggesting that odor deprivation signals down-regulate expression of PTEN in the olfactory bulb. To the best of our knowledge, this is the first report to suggest that PTEN expression is regulated by sensory deprivation signals in neonatal rats.

• Archives of Pharmacal Research
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• v.22 no.2
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• pp.219-224
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• 1999

In our search for the anticonvulsant consitutent of Gastrodia elata repeated column chromatographies guided by activity assay led to isolation of an active compound, which was identified as gastrodin on the basis of spectral data. Brain succinic semialdehyde dehydrogenase (SSADH) was inactivated by preincubation with gastrodin in a time-dependent manner and the reaction was monitored by absorption and fluorescene spectroscopic methods. The inactivation followed pseudo-first-order kinetics with the second-rate order constant of $1.2{\times}10^{3} M^{-1} min^{-1}$. The time course of the reaction was significantly affected by the coenzyme NAD^{+}$, which affected complete protection against the loss of the catalytic activity, whereas substrate succinic semialdehyde failed to prevent the inactivation of the enzyme. It is postulated that the gastrodin is able to elevate the neurotransmitter GABA levels in central nervous system by inhibitory action on one of the GABA degradative enzymes, SSADH.

• Applied Microscopy
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• v.40 no.4
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• pp.211-218
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• 2010

The mammalian ovary is innervated by sympathetic and sensory neurons which contribute to regulating several aspects of ovarian function, including blood flow, steroidogenesis and follicular development. The existence of a neural connection between central neurons and the ovary has been rarely reported, but the mechanism underlying integration of ovarian activity to broader neuroendocrine responses has not been reported. We have now used a viral transneuronal tracing technique combined with a conventional retrograde labeling procedure of CT-HRP to demonstrate that oxytocin-producing neurons of the hypothalamus are synaptically connected to the ovary. Since ovarian activity is suppressed but the activity of oxytocin neurons is increased during breast feeding. Our finding that the oxytocinergic neural connection is likely to provide a direct transsynaptic mechanism by which the central nervous system maintains the state of infertility that accompanies lactation in mammals.