• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.25 no.4
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• pp.281-294
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• 1999

Vasospasm causes microvascular surgery to fail as a main factor in the loss of transferred flap dye to the diminution of blood flow in reconstruction surgery. Although there has been extensive research to resolve the vasospasm problem, no one has reached an ideal solution to date. However, cryotherapy, which is often used for destruction of tumor lesions, is being presented as a new way of releasing vasospasm. After making a histomorphometric measurement on vasodialation during the course of 1, 3 and 7 days, 2 and 4 weeks, and 5 months periods and observing the change of blood vessel in a histologic, immunohistochemical, and scanning electronic microscopic approach, the results were as follows : 1. Vascular inner diameters of the experimental 1 and 3 days groups were measured $476.3{\pm}28.20{\mu}m$, $497.15{\pm}48.79{\mu}m$ respectively showing statistically meaningful vasodilation(P<0.05), which continued by the experiment 4 weeks group. However, in the experimental 5 months group, the vascular inner diameter appeared similar to the control groups. Even though the thickness of smooth muscular layers come out to be thinner in all the experimental groups compared to the control group, it was difficult to find any statistical meaningfulness. In addition, the vascular external diameters of every experimental groups were shown to be longer than the control group. 2. In light microscopic view, severe injury was evident on the smooth muscular layer cell from the experimental 1 day group, started recovering partially from the experimental 7 days group, and was mostly restored in the experimental 4 weeks group and layer of adventitial stripping were nearly recoverd 2 weeks group. 3. The PCNA positive cells of smooth muscular layer were observed from the experimental 7 days group and had a tendency to increase by the experimental 2 weeks group. In the experimental 4 weeks and 5 months group, the number of PCNA possitive cells observed was comparable to the control group. 4. ${\alpha}$-SMA level of smooth muscular layer cells, having been significantly lower than the control group in the severly damaged experimental 1 day group. It was seen to be increased in the experimental 7 days group and turned out to show similar ${\alpha}$-SMA level in 4 weeks to the control group. 5. In the view of SEM, the endothelial cells were destructed and falling off, and also present the appearance of flattening in the experiment 1 day group. The endothelial layer cells started partially recovering from the 7 days group after the freezing injury. On 4 weeks and 5 months, the endothelial cells were fully coverd the damaged area, also it's appearance is similar to control group. In conclusion, the vascular freezing after the removal of adventitia caused damages to smooth muscular layer cells, and brought about vasodilation, which continued by the 4th week. The smooth muscular layer cells started partially reviving from the 7rd day after the damage by vascular freezing, and recovered their similar figure to the control group's 4 weeks later. This was considered the result of cells which surround the damaged blood vessel being influxed into the smooth muscular layers. Therefore, this local freezing injury on the blood vessel was thought to be applied clinically to relieve severe vasospasm which cannot be treated by vasodilation drug, a microvascular surgery.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.5
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• pp.366-374
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• 2010

Introduction: This study evaluated the capability of silk fibroin (SF) and recombinant human bone morphogenetic protein-2 loaded SF (SF-BMP) as a bone defect replacement matrix when grafted in a calvarial bone defect of rats in vivo. Materials and Methods: A total 70 calvarial critical size defects (5.0 mm in diameter) made on 35 adult female Sprague-Dawley rats were used in this study. The defects were transplanted with (1) rhBMP-2 loaded silk fibroin graft (SF-BMP: 0.8+$10\;{\mu}g$), (2) Silk fibroin (SF: $10\;{\mu}g$), and (3) no graft material (Raw). The samples were evaluated with soft x-rays, alkaline phosphatase activity, calcium/phosphate quantification, histological and histomorphometric analysis at postoperative 4 and 8 weeks. Results: The SF-BMP group ($48.86{\pm}14.92%$) had a significantly higher mean percentage bone area than the SF group ($24.96{\pm}11.01%$) at postoperative 4 weeks.(P<0.05) In addition, the SF-BMP group ($40.01{\pm}12.43%$) had a higher % bone area at postoperative 8 weeks than the SF group ($33.26{\pm}5.15%$). The mean ratio of gray scale levels to the host bone showed that the SF-BMP group ($0.67{\pm}0.08$) had a higher mean ratio level than the SF group ($0.61{\pm}0.09$) at postoperative 8 weeks. These differences were not statistically significant.(P=0.168 and P=0.243, respectively) The ratio of the calcium and phosphate contents of the SF-BMP ($0.93{\pm}0.22$) group was lower than that of the SF ($1.90{\pm}1.42$) group at postoperative 4 weeks. However, the SF-BMP group ($0.75{\pm}0.31$) had a higher Ca/$PO_4$ ratio than the SF ($0.68{\pm}0.04$) at postoperative 8 weeks. These differences were not statistically significant.(P=0.126 and P=0.627, respectively) For the bone-specific alkaline phosphatase (ALP) activity, which is recognized as a reliable indicator of the osteoblast function, the SF-BMP ($23.71{\pm}8.60\;U/L$) groups had a significantly higher value than the SF group ($12.65{\pm}6.47\;U/L$) at postoperative 4 weeks.(P<0.05) At postoperative 8 weeks, the SF-BMP ($21.65{\pm}10.02\;U/L$) group had a lower bone-specific ALP activity than the SF group ($16.72{\pm}7.35\;U/L$). This difference was not statistically significant.(P=0.263) For the histological evaluation, the SF-BMP group revealed less inflammation, lower foreign body reactions and higher bone healing than the SF group at postoperative 4 and 8 weeks. The SF group revealed more foreign body reactions at postoperative 4 weeks. However, this immunogenic reaction decreased and the remnant of grafted material was observed at postoperative 8 weeks. For histomorphometric analysis, the SF-BMP group had a significantly longer bone length to total length ratio than those of the SF group at postoperative 4 and 8 weeks.(P<0.05) Conclusion: The rhBMP-2 loaded silk fibroin graft revealed fewer immunoreactions and inflammation as well as more new bone formation than the pure silk fibroin graft. Therefore, silk fibroin may be a candidate scaffold for tissue engineered bone regeneration.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.5
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• pp.346-352
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• 2010

Introduction: Heat shock protein70 (HSP70) is a highly conserved family of proteins produced after a variety of stresses. Many studies reported that the overexpression of HSP70 can improve the prognosis of the patients with sepsis through a reduction of the nitric oxide concentration. However, these results only revealed the effect of HSP70 and nitric oxide. No studies have examined the relationship between HSP70 and nitric oxide. The aim of this study was to evaluate the effect of the overexpression of HSP70 on the expression of inducible nitric oxide synthase and the nitric oxide concentration. In addition, the mechanism of the relationship of HSP70 and inducible nitric oxide synthase (iNOS) in sepsis was examined. Materials and Methods: The experiments were performed on male sprague-dawley rats. Sepsis was induced by a cecal ligation and puncture (CLP). Glutamine (GLN) or saline was administered 1 hour after the initiation of sepsis. Serum and lung tissues were acquired from the rats 12 hours or 24 hours after the initiation of sepsis. The nitric oxide concentration, the expression of HSP70 in lung, and the gene expression of iNOS in lung were analyzed. The three groups, sham operation, CLP and CLP+GLN, were compared. Results: Compared to the other groups, in CLP+GLN, GLN administered after the initiation of sepsis enhanced the expression of HSP70 in the lung at 12 hours ($47.19{\pm}10.04$ vs. $33.22{\pm}8.28$, P=0.025) and 24 hours ($47.06{\pm}10.60$ vs. $31.90{\pm}4.83$, P=0.004). In CLP+GLN, GLN attenuated the expression of iNOS messenger RNA (mRNA) in the lung at 12 hours ($5,513.73{\pm}1,051.60$ vs. $4,167.17{\pm}951.59$, P=0.025) and 24 hours ($18,740.27{\pm}8,241.20$ vs. $9,437.65{\pm}2,521.07$, P=0.016), and reduced the concentration of nitric oxide in the serum at 12 hours ($0.86{\pm}0.48$ vs. $3.82{\pm}2.53$, P=0.016) and 24 hours ($0.39{\pm}0.25$ vs. $1.85{\pm}1.70$, P=0.025). Conclusion: The overexpression of HSP70 induced by the administration of GLN in sepsis attenuates the expression of the iNOS gene but reduces the nitric oxide concentration.

• The korean journal of orthodontics
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• v.28 no.5 s.70
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• pp.699-716
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• 1998

This study was designed to evaluate the expression of non-collagenous protein in periodontal tissue during the experimental movement of rat incisors, by LSAB(labelled streptavidine biotin) immunohistochemical staining for osteonectin and osteocalcin. Twenty seven Sprague-Dawley rats were divided into a control group(3 rats) and 6 experimental groups(24 rats) where 75g of force was applied from helical springs across the maxillary incisors. Rats of experimental groups were sacrificed at 12 hours, 1, 4, 7, 14 and 28 days after force application, respectively. And the tissues of a control group and experimental groups were studied immunohistochemically and histologically. The results were as follows : 1. Until 28 days after force application, periodontal fibers had been strectched on tension side and compressed in pressure side of all the experimental groups, and the arrangement of periodontal fibers had not been recovered yet. 2. The expression of osteonectin in control group was rare in dentin, cementum and osteocyte, and was mild in odontoblasts and matrix of alveolar bone. 3. The expression of osteocalcin in control group was negative in gingiva, osteoblasts, osteocyte and cementum, and was rare in predentin, capillaries in pulp and periodontal ligament and the matrix of alveolar bone. 4. There was no difference in the expression of osteocalcin or osteonectin in dentin, cementum, pulp, odontoblasts, between of control and of experimental groups. 5. The expression of osteonectin in intermaxillary suture got the peak in 7-day and was declined after 14-day. The expression of osteocalcin remained in a same degree since it became mild in 14-day. 6. The expression of osteonectin in pressure side of periodontal ligament of experimental group was rare, which was similar to control group. But in tension side, it was increased until 14-day aftrer which it was declined. 7. The expression of osteocalcin in periodntal ligament was rare in 12-hour to 14-day, but became severe in 28-day, which was greater in tension side than in pressure side, and in the periodontal fiber next to alveolar bone than to tooth surface. 8. The expression of osteocalcin in alveolar bone was rare until 14-day in pressure side, but became moderate in 28-day. The expression of osteonectin was increased from 7-day by time dependency, which was greater in tension side than in pressure side.

• The Korean Journal of Nuclear Medicine
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• v.35 no.5
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• pp.334-341
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• 2001

Purpose: Ascorbic acid us known to act as an antioxidant. Therefore, it can be used in increasing the efficiency of radiochemical labeling of Technetium-99m setamibi by inhibition of oxidation of $Sn^{2+}$ at low concentration. We intended to estimate the efficiency of radiochemical labeling and the stability of the newly formed formulation when ascorbic acid was added to a commercial kit. Materials and Methods: Synthesis of sestamibi was performed according to Dong-A's patent procedure (No.10-2001-0012877). First, we undertook a study to evaluate the efficiency of radiochemical labeling of sestamibi containing ascorbic acid. The stability of the vials was assessed using either $7.5{\mu}g\;or\;75{\mu}g$ of ascorbic acid, added to commercial vials under the accelerated condition(Temp : $40^{\circ}C{\pm}2^{\circ}C$, Relative humidity : $75{\pm}5%$). Results: Sestamibi was synthesized in overall 35-40% yield over 5 steps from a commercially available methallyl chloride as a starling material. When ascorbic acid was added, the efficiency of radiochemical labeling was maintained compared to the vial with no ascorbic acid. The accelerated test showed that the addition of ascorbic acid inhibited the oxidation of $Sn^{2+}$ ion by antioxidation mechanism. Also, the efficiency of radiochemical labeling of this vial after 9 months was nearly the same as the starting point. Therefore, the storage period of the kit is likely to be extended. Taken together, it suggests that the addition of ascorbic acid as a stabilizer is desirable. Conclusion: To increase the stability of a sestamibi cold kit, it is desirable to add ascorbic acid as a stabilizer to the commercial formulation.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.1
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• pp.28-39
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• 2017

Persistent organic pollutants (POPs) can affect epigenetic mechanisms and obesity development. Polybrominated diphenyl ethers (PBDEs)-widely used to make flames-are one of the important POPs. Prenatal exposure to endocrine disrupting chemicals (EDCs), such as POPs, may affect global DNA methylation in long interspersed nuclear elements (LINE-1), increasing the risk of obesity later in life. Therefore, pregnant Sprague-Dawley (SD) rats were used to elucidate whether BDE-47 and BDE-209 transferred through placenta and breast milk cause epigenetic changes in LINE-1 and increase genetic susceptibility to obesity as obesogen during the developmental periods. Global DNA methylation in LINE-1 and gene expression related to obesity were measured in dams and offspring, using a methylation-sensitive high resolution melting analysis (MS-HRM) and direct bisulfite sequencing and quantitative real time polymerase chain reaction (qPCR), respectively. The results of MS-HRM showed global DNA hypomethylation patterns in LINE-1 of exposed offspring (2 of total 4) at PND 4, but bisulfite sequencing showed no difference in both the exposed and non-exposed groups. Gene expression in dams related to ${\beta}$-oxidation pathway and those related to adipokines showed different patterns between the two groups. On the contrary, gene expressions of offspring showed a similar pattern. Gene expressions related to ${\beta}$-oxidation pathway and obesity were significantly increased when compared with 'at birth', but not $PPAR-{\alpha}$. In conclusion, this study demonstrated the possibility that co-exposure to BDE-47 and BDE-209-via the placenta and breast milk-may affect epigenetic changes and modulate gene expression levels related to obesity.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.240-245
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• 1999

Object : This study was designed to evaluate the effects of olanzapine on the schedule-induced polydipsia(SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered olanzapine as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol for the dopamine antagonist to rats which showed schedule-induced polydipsic behavior. Methods : Spraque-Dawley rats weighing 200-250gm were individually housed and maintained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds(FT-60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior(greater than 3 times of water per session on average). 5 groups of rats were administered olanzapine(3mg/kg, i.p), olanzapine(10mg/kg, i.p), fluoxetine(5mg/kg, i.p.), haloperidol(0.1mg/kg, i.p.), and vehicle(1cc/kg, i.p.) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighed before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a posthoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats(N=8) were individually housed and given a single bolus(14.5gm) of food per day which maintained them at their average body weight. Results and Conclusion : The results were as follows ; 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake over the 3 weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 3mg group showed significant decrease in the amount of water intake at 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 10mg group showed significant decrease in the amount of water intake at 2nd and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their average amount of polydipsic water intakes. 3) The fluoxetine group showed significantly lower amounts of water intake than the haloperidol group at 2nd weeks of drug treatment. And also the fluoxetine group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. The olanzapine 3mg group and the olanzapine 10mg group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. Above findings suggest that the fixed time feeding procedure for schedule-induced polydipsia as an animal model of obsessive compulsive disorder was effective to the evaluation of pharmacological challenge study. The authors assume that the serotonin hypothesis and the serotonin-dopamine interaction hypothesis are preferred to the dopamine hypothesis in the biological etiology of obsessive-compulsive disorder.

• Korean Journal of Biological Psychiatry
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• v.6 no.1
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• pp.74-80
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• 1999

This study was performed to investigate the mechanism of the clozapine-induced seizures in partially restrained rats by concomitant treatment with drugs affecting monoaminergic systems. Partially restrained rats treated with acute single doses of 10mg/kg clozapine exhibited myoclonic jerks (MJs). Drugs affecting the monoaminergic systems, including 2mg/kg haloperidol, 5mg/kg propranolol, 2mg/kg ritanserin, 20mg/kg fluoxetine, and 20mg/kg imipramine, were concomitantly treated with clozapine to observe the effects of these drugs on the MJs. The drugs were given intraperitoneally either as acute single doses(haloperidol, propranolol, ritanserin, and fluoxetine) or as chronic doses for 21days(haloperidol, imipramine, ritanserin, and fluoxetine). The effects of the concomitant treatment of other drugs on the clozapine-induced MJs were evaluated by comparison of the total numbers of the MJs between the clozapine-treated and concomitantly treated groups. The results were as follows. 1) Concomitant treatment with acute single doses of haloperidol, propranolol, and fluoxetine reduced the total numbers of the clozapine-induced MJs, while concomitant treatment with ritanserin did not. 2) Concomitant treatment with chronic doses of imipramine and ritanserin increased the total numbers of the MJs, while concomitant treatment with fluoxetine reduced them. Concomitant chronic treatment with haloperidol did not affect the numbers of the MJs. These results suggest that dopamine and serotonin, not noradrenalin may be involved in the clozapine-induced MJs in partially restrained rats. Future research needs to study the function of each subtype of monoaminergic receptors on the mechanism of the clozapine-induced seizure.

• Korean Journal of Biological Psychiatry
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• v.2 no.1
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• pp.63-69
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• 1995

The effects of chronic treatment with haloperidol and sulpiride on the binding capacities of dopamine(DA) receptor were examined in rat striatum and olfactory tubercle. Additionally, the stereotypy scores were assessed after apomorphine administration. Rats were treated with haloperidol(0.5mg/kg/day) or sulpiride(40mg/kg/day) for four weeks. Apomorphine(0.5mg/kg) was injected after three-day washout from neuroleptics, and stereotypy scores were assessed. Haloperidol group showed high scores of stereotyped behavior in comparison with control and sulpiride groups. With control group, sulpiride group displayed similar stereotyped behaviors. Saturation analysis of the binding of [$^3H$]spiperone to striatal membranes showed that the Bmax of haloperidol and sulpiride groups increased significantly in comparison with that of control group. The $K_D$ decreased significantly after sulpiride treatment in striatum. Although sulpiride produces the same proliferation of DA receptor, the low stereotypy scores of sulpiride group indirectly suggest that sulpiride acts differently from haloperidol in brain DA system. The Bmax increased remarkably following both treatment with haloperidol and sulpiride in olfactory tubercle. Also, the increase in $K_D$ was significant after treatment with haloperidol and sulpiride in olfactory tubercle. Moreover, the $K_D$ of control group in olfactory tubercle was more than twice the $K_D$ of control group in striatum. The $K_D$ was 86.2 in striatum and 37.5 pM in olfactory tubercle. The present finding indicates that sulpiride also induces the proliferation of DA receptor in olfactory tubercle and may interact with some DA receptor subtype with high affinity profile. The different affinities of the control groups of striatum and olfactory tubercle suggest that striatal DA receptor subtypes labeled by [$^3H$]spiperone could differ from those of olfactory tubercle.

• Journal of Oriental Neuropsychiatry
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• v.10 no.1
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• pp.17-38
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• 1999

The effects of Sahyangsohapwon on the affective reactivity of rats were studied with open-field behavior. Sample group was treated with the medicine for 8 weeks, whereas control group was treated with the vehicle. The effects of Sahyangsohapwon on the enhancement of learning and memory of AD model rats were studied with two-way avoidance task. Sample group electrically lesioned on nbM(nucleus basalis of Meynert) was treated with the medicine for 8 weeks, whereas control group with nbM lesion and sham group with the sham operation were treated with the vehicle. 1. In the open-field behavior task, the start latency from start box was measured $27.08{\pm}7.51sec$ in control group, $23.15{\pm}5.98sec$ in sample group. Rats in sample group showed a tendency of shortened latency going out to a strange place compared with those in control group, but with no statistical significance(p>0.05). 2. In the open-field behavior task, the number of locomotion crossing the grid lines was measured $84.54{\pm}3.55$ in control group, $116.93{\pm}6.41$ in sample group. There was an increased locomotion in sample group compared with control group with statistical significance(p<0.01). This can be interpreted as rats in sample group showed lowerd anxiety under a strange environment. 3. In the open-field behavior task, the rearing number was measured $7.46{\pm}0.57$ in control group, $10.13{\pm}0.95$ in sample group. There was an increased rearing in sample group compared with control group with statistical significance(p<0.05). This can also be interpreted as rats in sample group showed lowerd anxiety under a strange environment. 4. In the open-field behavior task, the number of crossing behavior was measured $5.54{\pm}1.50$ in control group, $9.20{\pm}1.67$ in sample group. There was a increasing tendency of crossing behavior in sample group compared with control group, but with no statistical significance(p<0.05). 5. In the open-field behavior task, the total activity was measured $97.54{\pm}4.70$ in control group, $136.27{\pm}792$ in sample group. There was an increased total activity in sample group compared with control group with statistical significance(p<0.01). This can also be interpreted as rats in sample group showed lowerd anxiety under a strange environment. 6. In the analysis of effects on the learning and memory in AD model rats with two-way avoidance task, the response latency was measured $6717{\pm}134msec$ in the 1st session, $5416{\pm}160msec$ in the 2nd session, $5252{\pm}148msec$ in the 3rd session in control group. It was measured $6724{\pm}155msec$ in the 1st session, $4642{\pm}139msec$ in the 2nd session, $4914{\pm}148msec$ in the 3rd session in sample group and $4357{\pm}144msec$ in the 1st session, $3125{\pm}115msec$ in the 2nd session, $3091{\pm}98msec$ in the 3rd session in sham group. There were differences between sham group and nbM lesioned groups with statistical significance in post hoc analysis(p<0.000). And in the 2nd session, there was a reduction of latency in sample group compared with control group with statistical significance (p<0.000). This showed that sample group had better learning capacity than control group. 7. In the analysis of effects on the learning and memory in AD model rats with two-way avoidance task, the number of avoidance response was measured $5.85{\pm}1.41$ in the 1st session, $14.23{\pm}2.89$ in the 2nd session, $15.69{\pm}2.56$ in the 3rd session in control group. It was measured $7.92{\pm}1.94$ in the 1st session, $16.83{\pm}2.29$ in the 2nd session, $15.42{\pm}2.81$ in the 3rd session in sample group and $14.38{\pm}1.62$ in the 1st session, $22.88{\pm}0.89$ in the 2nd session, $23.88{\pm}1.64$ in the 3rd session in sham group. There were differences between sham group and nbM lesioned groups with statistical significance in post hoc analysis(p<0.001). But between control and sample group, there was no significant difference. With the experimental results above, Sahyangsohapwon can be supposed to have the enhancing effects on the affect reactivity and learning with memory of AD model rats induced by electrolyte injury of nbM.