• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.33-44
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• 1982

The binding in vitro of an opiate agonist, $(^3H)-morphine$, was studied using rat brain slices which were incubated in the modified Krebs-Henseleit bicarbonate buffer solution containing various concentrations of electrolytes with or without morphine, naloxone or morphine+naloxone at $4^{\circ}C$ for 24 hours. The binding of $(^3H)-morphine$ may be seperated into two component; one a saturable binding and the other nonsaturable. The saturable binding may be calculated from the differences in binding observed in the absence and presence of high concentration of morphine. The maximal saturable binding and $K_D$ value in the naive preparations were $0.32{\pm}0.02\;pmole/mg$ protein and $0.75{\pm}0.07\;nM$ respectively. The saturable binding of $(^3H)-morphine$ was significantly increased by low temperature-treatment, while $K_D$ value was not changed. Morphine in the incubation media significantly increased the saturable binding of $(^3H)-morphine$ and $K_D$ value. Naloxone also increased the maximal saturable binding of $(^3H)-morphine$ and $K_D$ value of the drug. Decrease of $K^+\;and\;Mg^{++}$, and addition of $Mn^{++}$ in the incubation media significantly increased the saturable binding of $(^3H)-morphine$, but decrease of $Na^+$and increase of $Ca^{++}$ in the incubation media did not influence the binding. The increment of the saturable binding of $(^3H)-morphine$ by nonlabeled morphine in the incubation media was notaffected by decrease of $Na^+,\;K^+\;or\;Mg^{++}$, or addition of $Mn^{++}$ into the incubation media, but was inhibited by increase of $Ca^{++}$ in the incubation media, while the increment of the saturable binding of $(^3H)-morphine$ was net observed by decrease of $Na^+,\;K^+\;or\;Mg^{++}$, or increase of $Ca^{++}$ in the incubation media. The above results indicate that change of opiate binding sites in quality, i.e. affinity, and quantity, i.e. number of binding sites, may occur by low temperature-treatment in the absence and presence of morphine or naloxone and that electrolytes play role of the changes of opiate binding sites.

• Journal of Korean Neurosurgical Society
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• v.29 no.9
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• pp.1171-1178
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• 2000

Objective : The purpose of the present study was to determine the appropriate time of clinical intervention by observing and analyzing the changes in the size of infarct, penumbra and cerebral edema and the extend of neurological deficit due to reperfusion damage according to time in a reversible cerebral ischemic model of reperfusing blood flow after inducing ischemia by maintaining middle cerebral artery occlusion for 2 hours(h) in rats. Methods : The rats were divided according to reperfusion time into control group(0 h reperfusion time) and experimental groups(0.5, 1, 2, 3, 4, 5, 6, 12, and 24 h of reperfusion time). Results : Changes in the size of infarction due to reperfusion damage were 0.93, 1.48 and 1.16% at 0.5, 1 and 2 h after reperfusion, respectively, and although a statistical significance was not present compared to 1.35% of the control group, damages increased drastically up to 6 h(6.64%), and the size increased were 6.65 and 6.78% at 12 and 24 h, respectively. Also there was no significant difference after 6 h up to 24 h in the size of infarction. In the areas where infarction occurred, reperfusion damage increased significantly with time in cortex than in subcortex. Accordingly, the size of penumbra area also showed a statistically significant decrease from 2 h up to 6 h after reperfusion, and 6 h after reperfusion, the area almost disappeared, becoming permanent infarction. Thus, reperfusion damage showed a significant increase from 2 h up to 6 h after reperfusion, and became steady thereafter. As for the mean ratio of the extend of cerebral edema, the control group and reperfusion 0.5 h group were 1.073 and 1.081, respectively ; up to 2 h thereafter, the ratio decreased to 1.01 but increased again with time ; and in reperfusion 12 h and reperfusion 24 h, the ratios were 1.070 and 1.075, respectively, showing similar size with that of control group. As for neurological deficit scores, the score of the control group was 2.67, that of reperfusion 2 h was 2, those of reperfusion 3 h and 6 h groups were 3.2 and 3.8, respectively, and those of reperfusion 12 h and 24 h groups were 4.2 and 4.6, respectively. Thus, as for the test results, the neurological deficit increased with time 2 h after reperfusion, and in reperfusion 12 and 24 h groups, almost all the symptoms appeared. Conclusion : As shown in these results, although the changes in the size of infarction due to reperfusion damage did not increase up to 2 h after reperfusion in the experimental groups compared to the control group, damage increased significantly thereafter up to 6 h, and the size remained about the same from 6 h to 24 h after reperfusion, becoming permanent infarction ; thus, the appropriate time of intervention according to the present study is at least 6 h before after maintaining reperfusion, including the time of cerebral artery occlusion.

• The Korean Journal of Pharmacology
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• v.19 no.2
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• pp.45-55
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• 1983

A role for brain serotonin(5-HT) in regulation of the HPA axis has been suggested but remains contoversial and poorly defined. The present experiments were designed to check kinetic parameters of 5-HT turnover in rat hypothalamus and remainder brain areas before and after stress and to test whether using various different pharmacologic approaches to stimulate or eliminate the control serotonergic system have any consistent effect on the stress-induced activation of HPA system. Steady state brain serotonin and 5-HIAA concentrations during 1 min ether stress were significantly elevated without significant rise in the levels of plasma corticosterone, which highly increased 2 minutes after stress. This suggests that the increase in serotonergic neuron activity precede that in HPA activity. Furthermore, during 1 ruin-ether stress or 30 min immobilization stress there is a marked increase in hypothalamic and remainder brain serotonin (5-HT) turnover or synthesis rates assessed by both the pargline/5-HT method and pargyline/5-HIAA method. The stress-induced corticosterone levels were increased by serotonin precursors and serotonin agonist in a dose-related fashion. The stress- induced corticosterone levels were highly elevated by L-tryptophan (100 mg/kg) and Potentiated by monoamine oxidase inhibitor, pargyline or serotonin agonist, 5-MeoDMT. The stress-induced elevation of corticosterone and 5-HT levels in rat brain were not significantly decreased by the administration of 5-HT synthesis inhibitor, PCPA and 5-HT neurotoxin, 5,7-DHT. However, the stress-induced elevation of corticosterone and 5-HT levels were decreased by the destruction of midline raphe nuclei. There was a strong positive correlation between plasma corticosterone and 5-HT concentrations changed by drugs which mainly manipulating 5-HT system in the hyhothalamus and in the remainder of the brain. In conclusion, our present data stongly suggest that 5-HT is an important key neurotransmitter involved in the stress-induced activation of the HPA system.

• Journal of Acupuncture Research
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• v.19 no.5
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• pp.92-111
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• 2002

Objective : Carthami Flos has been used as a herb to promote blood circulation to remove blood stasis in oriental medicine for many centuries, and Amun(GV15) has been used as a meridian point to treat apoplexy etc. To investigate treatment of cerevral vascular disease(CVA) by promoting blood circulation and removing blood stasis(活血化瘀法), we observed the experimental effects and mechanism of auqa-acupunture of Carthami Flos(ACF) injected into GV15 on cerevral hemodynamics and cardiovascular system of rats. Method : Aqua-acupuncture of Carthami Flos(ACF) was injected into GV15, and then we investigated experimental effects and mechanism of ACF on the cerebral hemodynamics[regional cerebral blood flow(rCBF), pial arterial diameter(PAD), meal arterial blood pressure(MABP)] and cardiovascular system[cardiac muscle contractile force(CMF), heart rate(HR)I by pretreatment with methylene blue(MTB) and indomethacin(IDN). The changes in rCBF, MABP, CMF and HR were tested by Laser Doppler Flowmetry(LDF), and the changes in PAD was determinated by video microscopy methods and video analyzer. Results :The results were as follows in normal rats ; The changes of rCBF and PAD were significantly increased by ACF($120{\mu}{\ell}/kg$) in a injected time-dependent manner, but MABP was not changed by ACF. The changes of cardiovascular system were increased by ACF in a injected time-dependent manner. And pretreatment with MTB was significantly inhibited ACE induced increase of rCBF and PAD, and was decreased ACF induced increase of HR. And pretreatment with IDN was increased ACF induced MABP and CMF. And the results were as follows in cerebral ischemic rats ; The changes of rCBF was increased stabilizly by treatment with ACF($120{\mu}{\ell}/kg$) in during the period of cerebral reperfusion, but pretreatment with MTB was increased ACF induced increase of rCBF during the period of cerebral reperfusion. The results were as follows in normal rats ; The changes of rCBF and PAD were significantly increased by ACF($120{\mu}{\ell}/kg$) in a injected time-dependent manner, but MABP was not changed by ACF. The changes of cardiovascular system were increased by ACF in a injected time-dependent manner. And pretreatment with MTB was significantly inhibited ACF induced increase of rCBF and PAD, and was decreased ACF induced increase of HR. And pretreatment with IDN was increased ACF induced MABP and CMF. And the results were as follows in cerebral ischemic rats ; The changes of rCBF was increased stabilizly by treatment with ACF($120{\mu}{\ell}/kg$) in during the period of cerebral reperfusion, but pretreatment with MTB was increased ACF induced increase of rCBF during the period of cerebral reperfusion Conclusions : In conclusion, ACF causes a diverse response of rCBF, PAD an HR, and action of ACF is mediated by cyclic GMP. I suggested that ACF has an anti-ischemic effect through the improvement of crebral hemodynamics in a transient cerebral ischemia.

• The korean journal of orthodontics
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• v.31 no.4 s.87
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• pp.447-458
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• 2001

The purpose of this study was to evaluate 1) in vivo, the expression of chondroitin 4-sulfate (CH-4S), a structural element of glycosaminoglycans(GAGs), in periodontal tissue during the experimental movement of rat incisors, by labelled streptavidine biotin immunohistochemical staining for CH-4S, 2) In vitro, the expression of CH-4S in cultured human periodontal ligament(PDL) cells supplemented with 10ng/ml of $TGF-{\beta}_1$, 20ng/ml of PDGF-BB, 1ng/ml $TNF-\alpha$, or $1{\mu}g/ml$ LPS by western blot analysis. The results of this study were as follows ; 1. The expression of CH-4S was stronger in pulp, PDL, osteoblasts, osteoclasts and osteocytes in experimental group than in control group, but was rare in dentin, and cementum of experimental groups, regardless of the duration of force application, which was not different from that of control group. 2. In experimental group, the expression of CH-4S in pulp began to increase at 1 day after force application and got to the highest degree at 7 days. After 14 days, the expression in CH-4S immunoreactivity was decreased, and became similar to that of control group at 28 days. 3. The expression of CH-4S in PDL was noted in adjacent to alveolar bone. PDL showed higher intensity of immunolabelling after 1 day of orthodontic tooth movement. And the expression was more stronger in the tension side than that of pressure side of PDL at 1 day, but more stronger in the pressure side than that of tension side of PDL at 4 days. After 7 days, a decrease in CH-4S expression was observed. 4. The expression of CH-4S in alveolar bone got to the highest degree at 4 days, and At 7 days, a decrease in CH-4S expression was observed. 5. PDGF-BB notably raised the expression of CH-4S in the PDL cells at 3 days of cultivation 6. The expression of CH-4S of PDL cells was decreased with the application of $TNF-\alpha$ at 1 day. 7. Admixture of $TGF-{\beta}_1$ and PDGF-BB got more expression of CH-4S in PDL as compared to only $TGF-{\beta}1$ or PDGF-BB. A similar decrease of the expression of CH-4S was observed in the case of application of LPS or $TNF-\alpha$.

• Journal of Oral Medicine and Pain
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• v.36 no.4
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• pp.261-271
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• 2011

Osteoarthritis in patients with temporomandibular disorders(TMDs) induces pain, limitation of mouth opening, occlusal problems, and most commonly affects their life quality. Control method and progressive process of osteoarthritis are being extensively researched. The researchers focus on histologic changes, synovial changes, muscular and ligamental changes and observed reaction to pain. Therefore most of them developed the animal model for osteoarthritis in TMD patients. In this study, we applied several methods which induces osteoarthritis of temporomandibular joint(TMJ) in rats or mice. For locally induce osteoarthritis in TMJ, Monosodium iodoacetate(MIA) or interleukin-$1{\alpha}$(IL-$1{\alpha}$) were injected into TMJ joint space for 5 or 3 weeks. Other groups are chosen for osteoarthritis under systemic control including hormonal changes and aging. To observe cellular change, increased collagen, degenerative bony destruction and distribution of proteoglycans (PGs), safranin-O staining and Masson's trichrome staining were used.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.219-229
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• 2002

Background : Sepsis-induced acute lung injury (ALI) is caused by many cellular and humoral mediators induced by an endotoxin. Histamine, which is widely distributed in the lungs and has been considered as an important mediator of sepsis. It increases P-selectin expression on the endothelial cell surfaces and induces IL-8 secretion. Therefore, an endotoxin-induced histamine may be related to neutrophil-mediated ALI by inducing the migration and activation of neutrophils in the lung tissue. However, the role of endogenous histamine in endotoxin ALI has not been clarified. The purpose of this study was to investigate how endotoxin-induced ALI is influenced by endogenous histamine and to identify the possible mechanism of action. Materials and Methods : The study consisted of 4 groups using Sprague-Dawley rats : 1) control group, where the rats were infused intratracheally by normal saline, 2) an endotoxin group, where lipopolysaccharide (LPS) was administered intratracheally 3) the $H_2$ receptor antagonist-treated group ($H_2$ group) and 4) the $H_1$ receptor antagonist-treated group ($H_1$ group), where $H_2$-receptor blocker (ranitidine) and $H_1$-receptor blocker(pyrilamine) were co-treated intravenously with the intratracheal administration of an endotoxin. The lung leak index using $I^{125}$-BSA, the total protein and LDH concentration in the lung lavage fluid, myeloperoxidase(MPO) activity in the lung tissue, the pathologic score and the total number of neutrophils, TNF-$\alpha$, IL-$1{\beta}$ and IL-10 in lung lavage (BAL) fluid were measured in each group as the indices of lung injury. Results : Compared to the control group, the endotoxin group exhibited significant increases in all lung injury indices. Significant reductions in the endotoxin-mediated increases in lung leak index (p<0.05) were observed in both the $H_1$ and $H_2$ groups. In addition the total protein (p<0.05) and LDH concentration (p<0.05) in the BAL fluid were also lower in the $H_2$ group compared to the endotoxin group. However, there was no change in the MPO activity in the lung tissue, the pathologic score and the total number of neutrophils in the BAL fluid in both the $H_2$ and $H_1$ groups compared to the endotoxin group. The increases in TNF-$\alpha$ IL-$1{\beta}$ and IL-10 concentrations in the BAL fluid observed in the endotoxin group were not reduced in the $H_2$ and $H_1$ groups. Conclusion : Antihistamine attenuated the enhanced alveolar-capillary permeability induced by the endotoxin via the $H_2$ receptor. However the attenuating mechanism may not be related to the pathogenesis of neutrophil dependent lung injury.

• The korean journal of orthodontics
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• v.31 no.3 s.86
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• pp.357-367
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• 2001

The purpose of this study was to investigate the alveolar bone turnover in diabetic rat, and to compare the alveolar bone turnover during tooth movement in diabetes with that in normal control Eighty Male Sprague-Dawley strain rats(8th week) were divided into normal control(N), normal-tooth movement (N-tm), diabetes(D), and diabetes-tooth movement(D-tm) groups. Eighteen days before the start of the experiment, diabetes was induced with a single injection of streptozotocin 50 mg/kg of body weight in citrate buffer as vehicle via the tail vein. Maxillary first molars of rats were moved mesially by 40 grams of the closed coil spring. Experimental animals were sacrificed after 1d, 3d, 7d, and 14d experimental period, and the alveolar bone around the maxillary first molars were assayed biochemically for acid phsophatase(ACP) and tartrate-resistant acid phosphatase (TRAP) as bone resorption markers, and alkaline phosphatase(ALP) and osteocalcin(OC) as bone formation markers. TRAP and OC concentration in serum and alveolar bone of D group were lower than those in N group, and especially OC concentration decreased mote following diabetes prolonged, which showed the decreased skeletal and alveolar bone resorption and formation potential in diabetic rats. In N-tm group compared with N group, alveolar bone ACP and TRAP concentrations were highest at 1d and 3d(p<0.01), decreased after then, and showed lowest at 14d, and alveolar bone OC concentration was higher at 3d, 7d, and 14d(p<0.001) and showed a tendency of peak level at 7d. which showed the peak of concentration of bone resorption markets at 1d-3d and those of bone formation markers at 7d. In D-tm group compared with N group, alveolar bone ACP and TRAP concentrations were higher at 3d, 7d and 14d(p<0.001), and tended to reach peak value at 7d and persisted through 14d, and alveolar bone ALP and OC concentration increased but not different from that of N group. The amount of tooth movement in D group were greater than that of N group at all experimental period. Those results were suggested that during diabetes, the alveolar and skeletal bone undergo low bone turnover and the mote amount of tooth movement, hut because the peak time of alveolar bone resorption activity was delayed and sustained in longer period of tooth movement and alveolar bone formation activity is lower than that of normal tooth movement, the periodontal space is supposed to be larger doting tooth movement.

• Journal of Oral Medicine and Pain
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• v.33 no.3
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• pp.247-256
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• 2008

The belief that stress leads to illness has a long history. A number of the orofacial disease are also closely associated with stress. Despite research in the relationship of stress and the orofacial diseases leading to statistically significant correlations, the pathology remains vague. In the present study, the expression of clusterin, a stress protein responsible for antiapoptosis and cytoprotection, under restraint stress condition was observed in the submandibular gland, one of the major salivary glands. Sprague-Dawley rats were divided into 2 groups: normal group and restraint stress group. The rats of restraint stress group were placed in the stress cages and then sacrificed at day 0, 3 and 5 day of the experiment. After that, the submandibular glands of all the rats were excised immediately. The levels of clusterin proteins and mRNA in the tissues were measured by immunohistochemistry and Northern blot analyses, respectively. The results were as follows: 1. In the immunohistochemistry, clusterin protein was detected only immediately after the application of restraint stress. 2. In the restraint stress group, at day 3 and 5, histologically apoptosis was induced with karyorrhectic and pyknotic changes. 3. By the restraint stress, acinic cells were destructed earlier than ductal cells. 4. In the Northern blot, mRNA of clusterin was expressed only immediately after the application of restraint stress. The overall results suggest that as an early response to stress, clusterin is expressed in the glands to protect the glandular cells from the stress. But if stress is so strong and prolonged that it can exceed the stress adaptability of the cells, then the cells may undergo apoptosis instead of producing clusterin. An Epidemiologic Study of Symptoms of Temporomandibular Disorders in Korean College Students.

• The Journal of Korean Academy of Prosthodontics
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• v.51 no.3
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• pp.175-182
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• 2013

Purpose: The purpose of this study was to investigate the effect of different administration duration of alendronate on initial wound healing and new bone formation of extraction socket in rats. Materials and methods: Fifteen male Sprague-Dawley rats (body weight 130-140 g, 4 weeks old, male) were divided into control group (no alendronate administration) and experimental group (alendronate administration). Experimental group was subdivided into 1 week administrated group, 2 week administrated group, 4 week administrated group and 6 week administrated group according to duration of administration. For the experimental groups, during the designated time period (at the time of extraction, 1 week before extraction, 3 week before extraction and 5 week before extraction) till 1 week after extraction, rats were subcutaneously injected with Alendronate at the dose of 1.0 mg/Kg three times a week. Each specimen from 6 week experimental group and control group were used for microarray analysis, and other specimens were used for histological analysis. The rate of new bone formation within the extraction site and bone loss activity was analyzed using TRAP staining. Statistical analysis was performed using Kruskal Wallis test. (${\alpha}=.05$) Results: After one week from the time of extraction, the rate of new bone formation within extraction site for the control group ($16.77%{\pm}1.36%$) compared to the 4 week experimental group ($14.99%{\pm}6.26%$) was lower. However, no statistically significant difference was found. Increase in the number of inactive lacuna (empty lacuna) and decrease in the number of TRAP positive cell were identified with increased duration of administration. There was no significant difference. Conclusion: The results of this study showed as the duration of Alendronate administration increased the rate of new bone formation decreased with loss of bone activity and reduced number of osteoclast.