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Differential Role of Central GABA Receptors in Nociception of Orofacial Area in Rats

  • Lee, Ah-Ram;Lim, Nak-hyung;Kim, Hye-Jin;Kim, Min-Ji;Ju, Jin-Sook;Park, Min-Kyoung;Lee, Min-Kyung;Yang, Kui-Ye;Ahn, Dong-Kuk
    • International Journal of Oral Biology
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    • v.40 no.3
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    • pp.117-125
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    • 2015
  • The present study investigated the role of central $GABA_A$ and $GABA_B$ receptors in orofacial pain in rats. Experiments were conducted on Sprague-Dawley rats weighing between 230 and 280 g. Intracisternal catheterization was performed for intracisternal injection, under ketamine anesthesia. Complete Freund's Adjuvant (CFA)-induced thermal hyperalgesia and inferior alveolar nerve injury-induced mechanical allodynia were employed as orofacial pain models. Intracisternal administration of bicuculline, a $GABA_A$ receptor antagonist, produced mechanical allodynia in naive rats, but not thermal hyperalgesia. However, CGP35348, a $GABA_B$ receptor antagonist, did not show any pain behavior in naive rats. Intracisternal administration of muscimol, a $GABA_A$ receptor agonist, attenuated the thermal hyperalgesia and mechanical allodynia in rats with CFA treatment and inferior alveolar nerve injury, respectively. On the contrary, intracisternal administration of bicuculline also attenuated the mechanical allodynia in rats with inferior alveolar nerve injury. Intracisternal administration of baclofen, a $GABA_B$ receptor agonist, attenuated the thermal hyperalgesia and mechanical allodynia in rats with CFA treatment and inferior alveolar nerve injury, respectively. In contrast to $GABA_A$ receptor antagonist, intracisternal administration of CGP35348 did not affect either the thermal hyperalgesia or mechanical allodynia. Our current findings suggest that the $GABA_A$ receptor, but not the $GABA_B$ receptor, participates in pain processing under normal conditions. Intracisternal administration of $GABA_A$ receptor antagonist, but not $GABA_B$ receptor antagonist, produces paradoxical antinociception under pain conditions. These results suggest that central GABA has differential roles in the processing of orofacial pain, and the blockade of $GABA_A$ receptor provides new therapeutic targets for the treatment of chronic pain.

Bone formation effect of $HA/{\beta}-TCP$ composite powders in rabbit calvarial bone defects;Histologic study (토끼의 두개골내에 형성된 골결손부에서 $HA/{\beta}-TCP$ composite powders의 골형성에 관한 조직학적 연구)

  • Lee, Kwang-Ho;Jang, Hyun-seon;Park, Joo-Cheol;Kim, Heung-Joong;Kim, Chong-Kwan;Kim, Byung-Ock
    • Journal of Periodontal and Implant Science
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    • v.36 no.1
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    • pp.1-14
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    • 2006
  • The purpose of the present study was to evaluate the histologic results of bone cavities that were surgically created in the calvaria of rabbit and filled with $HA/{\beta}-TCP$ composite powders, which had been developed in Korea (Dentium, Korea). Ten young adult rabbits were used. Four defects were surgically produced in calvaria of each rabbit. Each rabbit was anesthetized with Ketamine-HCI (5 mg/kg, Yuhan Cor. Korea) and Xylazine-HCI (1.5 ml/kg, Yuhan Cor. Korea)). An incision was made to the bony cranium and the periosteum was reflected. Using a trephine bur (external diameter: 8 mm, 3i, USA), 4 'through-and-through' bone defects were created with copious irrigation, and classified into 4 groups: control group: no graft materials, experimental group I: normal saline + graft materials: experimental group II: venous blood + graft materials: experimental group III: graft materials only. The defects were randomly filled with graft materials. The defects were closed with resorbable suture material. At the end of the surgical procedure, all animals received a single intramuscular injection of antibiotics Gentamicin (0.1 mg/kg, Dae Sung Microb. Korea). Rabbits were sacrificed with phentobarbital (100 mg/kg) intravenously at 1-, 2-, 4-, 6- and 8-week after. Specimens were treated with hydrochloric acid decalcifying solution (Fisher Scientific, Tustin, CA) and sectioned by bisecting the 8 mm diameter defects. The histologic specimens were prepared in the general method with H & E staining at 6 ${\mu}m$ in thickness. The results were as follows; 1. New bone formation showed from after 2-week of surgery in defect area. As time lapsed, lots of new bone formation and mature bones showed. 2. Histologically, degree of new bone formation could not be discerned among the experimental groups. But, for experimental group II, lots of cells gathered around graft materials after 1-week of surgery, new bone formed slightly faster and than the others at 1-week after. For experimental group I, a few inflammatory finding showed around graft material at after 1-week and after 2-week of surgery. 3. No bone formation did show for control group. Based on histologic results, the new $HA/{\beta}-TCP$ composite powders appeared to act as a scaffolding material for regeneration of osseous defects.

Role of the periosteum on bone regeneration in rabbit calvarial defects (가토의 두개골 결손부에서 골재생에 끼치는 골막의 역할)

  • Jang, Hyun-Seon;Kim, Sang-Mok;Park, Joo-Cheol;Kim, Byung-Ock
    • Journal of Periodontal and Implant Science
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    • v.35 no.4
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    • pp.939-948
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    • 2005
  • The role of the periosteum on osteointegration of $Bio-Oss^{(R)}$(Geistlich, Wolhusen/Switzerland) was studied in rabbit calvarial defect. 12 New Zealand white male rabbits between 2.8 and 4 kg were included in this randomized, blinded, prospective study. Each rabbit was anesthetized with Ketamine HCl(5 mg/kg) and Xylazine HCl(1.5 ml/kg). An incision was made to the bony cranium and the periosteum was reflected. Using a 6-mm trephine bur(3i. USA), four 8-mm defects were created with copious irrigation. The defects were classified into barrier membrane($Tefgen^{(R)}$, Lifecore Biomedical. Inc, U.S.A.) only group as a control, $Bio-Oss^{(R)}$ with barrier membrane group, $Bio-Oss^{(R)}$ with periosteum covering group, and $Bio-Oss^{(R)}$ without periosteum covering group. There were 2 rabbits in each group. The wound was closed with resorbable suture materials. Rabbits were sacrificed using phentobarbital(100 mg/kg) intravenously at 1, 2, and 4 weeks after surgery. The samples were fixed in 4% paraformaldehyde, and decalcified in hydrochloric acid decalcifying solution(Fisher Scientific, Tustin, CA) at $4^{\circ}C$ for 2-4 weeks. It was embedded in paraffin and cut into 6 ${\mu}m$ thickness. The sections were stained with H & E and observed by optical microscope. The results were as follows; 1. The periosteum played an important role in osteointegration of $Bio-Oss^{(R)}$ in bone defects. 2. When the periosteum remained intact and $Bio-Oss^{(R)}$ was placed on the defect, $Bio-Oss^{(R)}$ with periosteum covering has been incorporated into the newly formed bone from 2-week postoperatively. 3. When the periosteum was removed at the surgical procedure, invasion of connective tissue took place among the granules, and new bone formation was delayed compared to periosteum covering group. Therefore, when the bone grafting was performed with periosteal incision procedure to achieve tension-free suture, the integrity of the overlying periosteum should be maintained to avoid fibrous tissue ingrowth.

Dental Treatment of a Patient with Cerebral Palsy under General Anesthesia (뇌성마비 환자의 전신마취 하 치과치료)

  • Chung, Jun-Min;Seo, Kwang-Suk;Yi, Young-Eun;Han, Hee-Jung;Han, Jin-Hee;Kim, Hye-Jung;Shin, Teo-Jeon;Kim, Hyun-Jeong;Yum, Kwang-Won;Chang, Ju-He
    • Journal of The Korean Dental Society of Anesthesiology
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    • v.8 no.1
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    • pp.22-28
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    • 2008
  • Background: Cerebral palsy (CP) is non-progressive disorder of motion and posture. In CP patient, there are difficulties in dental treatment because of uncontrolled movement of limb and head, and conjoined disabilities such as cognitive impairment, sensory loss, seizures, communication and behavioral disturbances. It is reported that CP patients have high incidence in caries and a higher prevalence of periodontal disease. But, despite the need for oro-dental care, these patients often are unlikely to receive adequate treatment without sedation or general anesthesia because of uncontrolled movements of the trunk or head. Methods: We reviewed the 58 cases of 56 patients with CP who underwent outpatient general anesthesia for dental treatment at the clinic for the disabled in Seoul National University Dental Hospital. Results: The mean age was 19 (2-54) years. The number of male patient was 40 and that of female was 18. They all had severe spastic cerebral palsy and 22 had sever mental retardation, 15 epilepsy, 8 organic brain disorder, 1 blindness, 2 deafness and cleft palate. For anesthesia induction, 14 cases was needed physical restriction who had sever mental retardation and cooperation difficulty, but 44 cases showed good or moderate cooperation. Drugs used for anesthesia induction were thiopental (37 cases), sevoflurane (14 cases), ketamine (3 cases ) and propofol (4 cases). All patients except one were done nasotracheal intubation for airway management and 4 cases were needed difficult airway management and 1 patient already had tracheostomy tube. Mean total anesthetic time was $174{\pm}56$ min and staying time at PACU was $88{\pm}39$ min. There was no death or long term hospitalization because of severe complications. Conclusion: If general anesthesia is needed, pertinent diagnostic tests and workup about anomaly, and appropriate anesthetic planning are essential for safety.

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PULPAL AND PERIAPICAL REACT10N TO FORMOCRESOL AND DEPULPIN® IN THE RAT TEETH (백서에서 Depulpin®과 Formocresol에 대한 치수와 치근단 조직의 반응)

  • Moon, Hyung-In;Kim, Sun-Ho;Hwang, Yun-Chan;Oh, Byung-Ju;Hwang, In-Nam;Kim, Sun-Hun;Jeong, Sun-Wa;Youn, Chang;Oh, Won-Mann
    • Restorative Dentistry and Endodontics
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    • v.27 no.4
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    • pp.355-362
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    • 2002
  • One fifth dilution of formocresol is usually used for pulpotomy of the primary teeth and emergency pulpotomy of the permanent teeth. However the use of formaldehyde has been subjected to criticism because it may be absorbed into the blood stream and become distributed systemically, it nay also alter the pulp tissue rendering it immunologically active, and have carcinogenic potential. Recently Depulpin$^{\circledR}$(VoCo., Germany) gains popularity as a devitalizing agent during root canal therapy in spite of high concentration of 49 % paraformaldehyde because it facilitate devitalization of pulp and make root canal therapy easier But there have been not enough publications about the reaction of pulp and periapical tissue caused by Depulpin. This study was performed to evaluate the histological changes in pulp and periapical tissue of rats after pulpotomy using formocresol and Depulpin and to elucidate the toxic effects of these agents. Thirty six Sprague-Dawley rats were anesthetized by intraperitoneal injection of ketamine Maxillary first molar teeth were used for pulpotomy with formocresol and Depulpin. Rats were sacrificed after 2 days, 4 days, 1 week, 2 weeks, 3 weeks and 4 weeks respectively. Specimens were histologically observed by light microscope changes in pulp and periapical tissue. The obtained results were as follows. 1. Formocresol group A zone of fixed tissue. in which odontoblasts could clearly be defined, was present directly underneath the pulpotomy dressing in almost all teeth of this group. This was followed by an area of necrotic tissue which resembled dried out fibrous tissue with no cellular detail except some pyknotic nuclei. In the specimens of after 2 days, 4 days, 1 week, 2 weeks in which vital tissue was present, it was separated from the fibrous area by a zone of inflammation. In the specimens of after 3 weeks and after 4 weeks, inflammatory infiltrate was in the periodontal ligament adjacent to the apical foramina of the teeth. 2. Depulpin$^{\circledR}$ group The area of necrotic tissue which had no cells and fibers, was present adjacent to the dressing. This was followed by dried out fibrous tissue with no cellular details except some pyknotic nuclei, A short stump of vital pulp with odontoblasts was present at the end of the canal after 2 days. Inflammatory infiltrate was in the periodontal ligament after 4 days and after 1week. Severe root resolution and necrosis of periapical tissue opposite the root resorption site were defined after 2 weeks and after 3 weeks. Periapical lesion which consist of necrotic tissue surrounded by a fibrous connective wall, was found after 4 weeks. The results indicated that Depulpin can cause more adverse reaction to the dental pulp and periapical tissue than formocresol, and further studies are needed for its clinical use with safety.

Experimental Fetal Cardiopulmonary Bypass in the Fetal Lamb Model (태아양 모델을 이용한 실험적 태아 심폐우회술)

  • 이정렬;임홍국;김원곤;김종성;최정연;김용진
    • Journal of Chest Surgery
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    • v.32 no.6
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    • pp.495-503
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    • 1999
  • Background: We tested the technical feasibility of fetal cardiac bypass and collected baseline data on the fetal hemodynamics and placental functions related to the cardiopulmonary bypass in the fetal lamb model. Material and Method: Eleven fetuses at 120 to 150 days of gestation were subjected to bypass via trans-sternal approach with a 12 G pulmonary arterial cannula and 14 to 18 F venous cannula for 30 minutes. All ewes received general anesthesia with ketamine. In all the fetuses, no anesthetic agents were used except muscle relaxant. Eight served as a group in which placenta was excluded from the extracorporeal circulation by clamping the umbilical cord during the bypass(the oxygenator group) and in the remaining three, the placenta worked as the only source of oxygen supply(the placenta group). Observations were made every 10 minute during a 30-minute bypass and 30-minute post bypass period. No prostaglandin inhibitors were used both in ewes and in fetuses. Result: Weights of the fetuses ranged from 1.9 to 5.2 kg. In the oxygenator group, means of arterial pressure, PaO2, atrial pressure, heart rate, and bypass flow rate ranged 69.8 to 82.6 mmHg, 201.7 to 220.9 mmHg, 4.1 to 4.3 mmHg, 169 to 182/min, and 140.3 to 164.0 ml/kg/min, respectively during bypass, but rapid deterioration of the fetal cardiac functions and the placental gas exchange was observed after the cessation of bypass. In the placenta group, means of arterial pressure decreased from 44.7 to 14.4 mmHg and means of PaCO2 increased from 61.9 to 129.6 mmHg during bypass. Flow rate was suboptimal(74.3 to 97.0 ml/kg/min) during bypass. All hearts fibrillated immediately after the discontinuation of bypass. Conclusion: In this study, the technical feasibility of fetal cardiopulmonary bypass was confirmed in the fetal lamb model. However, further studies with modifications of the bypass including an addition of prostaglandin inhibitor, an application of the total spinal anesthesia on the fetus, a creation of more concise bypass circuit, and a use of active pump are mandatory to improve the outcome.

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Changes in the Lung after Pulmonary Hypertension Induced by Obstruction of the Pulmonary Vein in Rats (흰쥐에서 폐정맥 폐쇄에 의해 유도된 폐동맥고혈압 발생 후의 폐장의 변화)

  • Jang Won-Chae;Jeong In-Suk;Cho Kyu-Sung;Oh Bong-Suk
    • Journal of Chest Surgery
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    • v.39 no.9 s.266
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    • pp.659-667
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    • 2006
  • Background: Experimental studies of vascular remodeling in the pulmonary arteries have been performed actively. These models required a persistent vascular insult for intimal injury induced by chronic hypoxia, monocrotaline intoxication or chronic air embolism and characterized medial hypertrophy and neointimal formation by active synthesis of the extracellular matrix protein. The purpose of this study was to determine the pattern of pulmonary vascular remodeling after obstruction of the pulmonary vein. Material and Method: Obstruction of the right pulmonary vein with a metal clip was performed in Sprague-Dawley rats $(352{\pm}18g,\;n=10)$ to cause pulmonary vascular disease. Fifteen days later, experimental studies were done and finally the both lungs and hearts were extirpated for experimental measurement. Pulmonary arterial pressure, weight ratio of right ventricle (RV) to left ventricle (LV) and ventricular septum (S) (RV/LV +S weight ratio), and pulmonary artery morphology (percent wall thickness, %WT) were evaluated and compared with normal control groups. Result: Pulmonary hypertension $(38{\pm}12mmHg\;vs\;13{\pm}4mmHg;\;p<0.05)$ and right ventricular hypertrophy (right ventricular/left ventricular and septal weight ratio, $0.52{\pm}0.07\;vs\;0.35{\pm}0.04;\;p<0.05$) with hypertrophy of the muscular layer of the pulmonary arterial wall (percent wall thickness, $22.4{\pm}6.7%\;vs\;6.7{\pm}3.4%;\;p<0.05$) were developed by 15 days after obstruction of the pulmonary vein. Conclusion: Obstruction of the pulmonary vein developed elevation of pulmonary blood pressure and medial hypertrophy of the pulmonary artery. These results are a part of the characteristic vascular remodeling. Theses results demonstrate that obstruction of the pulmonary vein can develope not only high pulmoanry blood flow of contralateral lung but also intima injury inducing vascular remodeling.

Establishment of Featal Heart Surgery with an Improvement of the Placental Blood Flow in Cardiopulmonary Bypass Using Fetal Lamb Model (양태아를 이용한 심폐우회술에서의 태반혈류개선을 통한 태아심장수술의 기반기술 확립)

  • 이정렬;박천수;임홍국;배은정;안규리
    • Journal of Chest Surgery
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    • v.37 no.1
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    • pp.11-18
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    • 2004
  • Background: We tested the effect of indomethacine and total spinal anesthesia on the improvement of placental flow during cardiopulmonary bypass on fetal lamb. Material and Method: Twenty fetuses at 120 to 150 days of gestation were subjected to bypass via trans-sternal approach with a 12 G pulmonary arterial cannula and 14 to 18 F venous cannula for 30 minutes. All ewes received general anesthesia with ketamine. In all the fetuses, no anesthetic agents were used except muscle relaxant. Ten served as a control group in which placenta was worked as an oxygenator during bypass (Control group). The remainder worked as an experimental group in which pretreatment with indomethacine and total spinal anesthesia was performed before bypass with the same extracorporeal circulation technique as control group (Experimental group). Observations were made every 10 minutes during a 30-minute bypass and 30-minute post bypass period. Result: Weights of the fetuses ranged from 2.2 to 5.2 kg. In Control group, means of arterial pressure decreased from 44.7 to 14.4 mmHg and means of Pa$CO_2$ increased from 61.9 to 129.6 mmHg at each time points during bypass. Flow rate was suboptimal (74.3 to 97.0 $m\ell$/kg/min) during bypass. All hearts fibrillated immediately after the discontinuation of bypass. On the contrary, in Experimental group, means of arterial pressure reamined higher (45.8 to 30 mmHg) during bypass (p<0.05). Means of Pa$CO_2$ were less ranging from 59.8 to 79.4 mmHg during bypass (P<0.05). Flow rates were higher (78.8 to 120.2 $m\ell$/kg/min) during bypass (p<0.05). There were slower deterioration of cardiac function after cessation of bypass. Conclusion: In this study, we demonstrated that the placental flow was increased during fetal cardiopulmonary bypass in the group pretreated with indomethacine and total spinal anesthesia. However, further studies with modifications of the bypass including a creation of more concise bypass circuit, and a use of axial pump are mandatory for the clinical application.

The Role of Endoscopy for Tumorous Conditions of the Upper Gastrointestinal Tract in Children (내시경으로 진단된 소아 상부 위장관의 종양성 질환에 대한 고찰)

  • Kim, Hye Young;Park, Jae Hong
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.8 no.1
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    • pp.31-40
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    • 2005
  • Purpose: This study aimed to provide, as a basic material, the experiences of endoscopy in diagnosis and treatment of tumorous conditions in the upper gastrointestinal tract in children. Methods: The objects were 26 patients diagnosed as having tumorous conditions in the upper gastrointestinal tract among 1,283 patients who underwent upper gastrointestinal endoscopic examination at the Department of Pediatrics, Pusan National University Hospital, from January 1994 to July 2004 retrospectively. The characteristics of patients, the chief complaints for endoscopic examination, the sorts of tumors diagnosed, the endoscopic findings of tumors, and the treatment of tumors were analysed. Results: 1) Eleven male and fifteen female were included, whose mean age was $6.93{\pm}4.02years$. 2) The chief complaints for endoscopic examination were abdominal pain (80.7%), vomiting or nausea (30.8%), and gastrointestinal beeding (30.7%) in order. 3) Six cases of ectopic pancreas, five cases of sentinel polyp, three cases of papilloma and vallecular cyst, two cases of Brunner's gland hyperplasia and gastric submucosal tumor, one case of gastrointestinal stromal tumor, duodenal intramural hematoma, T cell lymphoma, lipoma, and Peutz-Jeghers syndrome were diagnosed by endoscopy with or without biopsy. 4) The location of tumors was in the pharynx (19.2%), esophagus (7.7%), gastro-esophageal junction (23.0%), stomach (30.7%) and duodeneum (26.9%). 5) The size of tumors was less than 10 mm in 53.8%, 10~20 mm in 26.9%, more than 20 mm 19.2%. 6) Treatments for tumors included resection by laser, surgical resection, endoscopic polypectomy with a forcep or snare, and observation 7) There was no significant complication. Conclusion: Various and not a few tumors were found in the upper gastrointestinal tract. The endoscopy was accurate, effective, and safe means for diagnosis and treatment of those lesions in children.

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EVALUATION OF PERIODONTAL LIGAMENT CELL VIABILITY IN RAT TEETH ACCORDING TO VARIOUS EXTRA-ORAL DRY STORAGE TIMES USING MTT ASSAY (구강 외 노출시간에 따른 흰쥐 치아 치주인대세포 활성도의 MTT 검색법을 이용한 평가)

  • Jeon, In-Soo;Kim, Eui-Seong;Kim, Jin;Lee, Seung-Jong
    • Restorative Dentistry and Endodontics
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    • v.31 no.5
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    • pp.398-408
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    • 2006
  • The purpose of this study was to verify the usefulness of MTT analysis as a tool of measurement of the periodontal ligament cell viability from the extracted rat molar. A total of 80 Sprague-Dawley white female rat of 4 week-old with a body weight of 100 grams were used. The maxillary left and right, first and second molars were extracted under Ketamine anesthesia. Twenty-four teeth of each group (divided as five groups depending upon the time-lapse after extraction such as Immediate, 10, 20, 40 and 60 minutes) were immersed in $200{\mu}l$ of MTT solution (0.5 mg/ml) and processed for optical density measurements. Another 10 teeth of each group were treated as same as above and sectioned at $10{\mu}m$ for microscopic examination. All measurements values were divided by the value of hematoxylin-eosin staining which represented the volume of each corresponding samples. Immediate and 10 minute groups showed highest MTT values followed by 20, 40, and 60 minutes consecutively. Statistical significance (p<0.05) existed between all groups except in immediate versus 10 minute groups and 40 versus 60 minutes. Histological findings also showed similar findings with MTT results in crystal shape and crystal numbers between the experimental groups. These data indicate that in vivo MTT analysis nay be of value for evaluation of the periodontal ligament cell viability without time- consuming cell culturing processes.