Ipriflavone is non-hormonal antiosteoporotic drug which inhibits bone resorption by reducing recruitment and/or differentiation of osteoclasts, and stimulates proliferation and differentiation of osteoblast, and also enhances calcitonin secretion in the presence of estrogen. Although some kinds of immediately-released preparation of ipriflavone are available in commercial market, in present study, we tried to formulate sustained-release tablet using coating method with hydrophobic and hydrophilic coating materials. In vitro dissolution test was applied to evaluate sustained-release patterns of several test preparations (Test tablet A, B and C) designed using different preparation method or different compositions. From the results of dissolution test, test tablet A which showed suitable dissolution profile was selected as the candidate of new product. Pharmacokinetic evaluation of test drug, ipriflavone sustained-release tablets, was conducted in 6 beagle dogs weighing $11.5{\pm}0.5\;Kg$ compared with $Theobon^{\circledR}$ tablet, immediately-released tablet (Kukjae Pharm. Co.) as reference drug. Two products were randomly administered to 6 beagle dogs, and after 1 week, cross-over study was conducted. From the present study, AUC and $T_{max}$ of test product were significantly different from those of reference product (p<0.05), respectively$(AUC\;:\;3646.28{\pm}472.56\;vs\;3646.28{\pm}472.56\;ng{\cdot}hr/ml,\;T_{max}\;:\;4.33{\pm}1.03\;vs\;1.42{\pm}0.38\;hr)$. But $C_{max}$ was not significantly different between two products (p>0.05) $(\;512.52{\pm}48.18\;vs\;443.97{\pm}140.53\;ng/ml)$. From the results of pharmacokinetic evaluations, it was noted that absorption amount of test product was increased, but absorption rate was delayed and $C_{max}$ of two products were not changed. And it was concluded that redesign of the sustained-release preparation which has a lower content of iprifavone rather than test tablet A must be considered.
The aim of this study was to establish an injection protocol of a test bolus and a main bolus of contrast material for computed tomographic pulmonary angiography (CTPA) for visualizing optimal pulmonary arteries in normal beagle dogs. CTPA using a test bolus method from either protocol A or B were performed in each of four normal beagle dogs. In protocol A, CTPA was conducted with a scan duration for around 8 s, setting the contrast enhancement peak of the pulmonary trunk in the middle of the scan duration. The arrival time to the contrast enhancement peak was predicted from a previous dynamic scan using a test bolus (150 mg iodine/kg) injected with the same injection duration using for a main bolus (450 mg iodine/kg). In protocol B, CTPA was started at the predicted appearance time of contrast material in the pulmonary trunk based on a previous dynamic scan using a test bolus injected with the same injection rate as a main bolus. CTPA using protocol A showed the optimal opacification of the pulmonary artery with pulmonary venous contamination. Proper CTPA images in the absence of venous contamination were obtained in protocol B. CTPA with a scan duration for 8 s should be started at the appearance time of contrast enhancement in the pulmonary trunk, which can be identified exactly when a test bolus is injected at the same injection rate used for the main bolus.
The present study was performed to evaluate histomorphological difference in various surface-treated implants in beagle. Implants($Implantium^{(R)}$, Dentium Co. Korea) with pure titanium machined surface, acid treated surface, and $Al_2O_3(50{\sim}100\;{\mu}m)$blasted with acid treated surface were used in this study. All mandibular premolars of $1.5{\sim}2$ year old male beagle dogs were extracted. At 3 months after extraction, the implants(${\Phi}$ 4mm, l 6mm) were installed. The beagle were sacrificed at 1, 3 months after installation and then tissues including implants were prepared for non-decalcified specimens. These specimens were analyzed comparatively under light microscope. The results of this study were as follow 1. Higher rate of osseointegration were showed in the $Al_2O_3(50{\sim}100\;{\mu}m)$blasted with acid-treated surface. 2. Increased osseointegration were showed in the $Al_2O_3(50{\sim}100\;{\mu}m)$blasted with acidtreated surface with time. 3. Higher maturation of integration were showed in the $Al_2O_3(50{\sim}100\;{\mu}m)$blasted with acid-treated surface. In conclusion, surface treatment of $Al_2O_3blasted$ with acid might be considered to shorten healing time and improve success rate as increasing contact of implant and bone.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
/
v.33
no.4
/
pp.312-321
/
2007
Purpose: Distraction osteogenesis has been applied to the maxillofacial implantology and good experimental and clinical results have been reported. However, histologic studies of implants placement on distraction osteogenesis of atrophic alveolar ridges are scarce. In this study, we compare the bone formation between in the transport part and in the distraction part by histomorphometric analysis. Materials & methods: Three adult beagle dogs were served as experimental subjects. The 2 premolars and 1st molar were extracted on the Lt. side of mandible in each beagle dog. After one month later, osteotomy was performed and distraction device was adapted. Distraction was performed with gradual incremental separation of two bone pieces at a rate of 1.0mm per day for 5 days. During consolidation phase, new bone was formed in the distraction zone between the separated bone pieces. 5 weeks after distraction phase, 3 implants were placed in each beagle dog. The implants were inserted through transport part and distraction part and inferior basal bone. The animals were sacrificed at 2 weeks, 4 weeks, and 12 weeks after implant placement. BIC and BA of implants on distraction part and transport part were measured histomorphometrically. Results: BIC, BA increased after implant placement as time goes by passes and new bone formation was slightly higher in transport part than in distraction part at 2 weeks, 4 weeks after implant placement. At 12 weeks after implant placement, BIC, BA of were 74%, 61% in transport part and 77%, 59% in distraction part, therefore there were no difference in BIC and BA between transport part and distraction part at 12 weeks after implant placement.
The current study was performed to determine the acute oral toxicity of P55A, a crude extract of 1 : 1 mixture of Phellodendron amurense cortex and Aralia elata cortex, in SD rats and beagle dogs. 5 rats of each sex were treated with a single dose of P55A orally at doses of 0 and 5,000 mg/kg respectively. Also 2 dogs of each sex were treated with a single dose of P55A orally at doses of 0 and 2,000 mgAg, respectively. After the treatment, clinical signs, and body weight change were observed for 14 days. All rats survived during the study and did not show any clinical sign. Body weight gain showed no significant difference between the control and treated rats. Grossly, no lesion was observed in the rats. All dogs survived during the study. In clinical signs, dark stool was observed in the 2,000 mg/kg treated dogs at day 1 after administration. The animals recovered from general signs at day 2 after administration. Body weight gain showed no significant difference between the control and treated dogs. Grossly, no lesion was observed in the dogs. It is suggested that the LD$_{50}$ of P55A by oral administration was estimated to be over 5,000 mg/kg in both sexes of rats and 2,000 mg/kg in both sexes of beagle dogs.s.
Recently, recombinant human erythropoietin (rHu-EPO) has been used to treat various types of anemia. YHB216 is a new rHu-EPO developed by Yuhan Research Institute. In this study, we investigated the single dose and 4-week repeated dose toxicity of YHB216 in Beagle dogs. In the single dose toxicity study, YHB216 was administered intravenously at single dose levels of 0 and 25,000 IU/kg to dogs (2 dogs/sex/group). There were no treament-related changes in survivals, clinical signs, body weight gain, hematological values, blood chemical values, and necropsy finding during experimental period. In the repeated dose toxicity study, YHB216 was administered intravenously to dogs for 4 weeks at the dose levels of 0, 100, 500, and 2,500IU/kg (3 dogs/sex/group). There were no toxicologically significant changes in clinical signs, body weights, food and water consumptions, ophthalmoscopy, urinalysis and blood chemistry. There were increased values of red blood cell, hemoglobin, and hematocrit at all treated groups. Spleen revealed increased weight and extramedullary hematopoiesis at 500 IU/kg or more. These changes are all considered to be Pharmacology-related effects and were recovered after 4-week recovery period. From these results, it is concluded that LD50 value was above 25,000 IU/kg in the single dose toxicity study of YHB216 in dogs and the no observed adverse effect level (NOAEL) was 100 IU/kg day in the repeated dose toxicity study of YHB216 in dogs.
This study was performed to validate the procedure of transarterial embolization of the renal artery (TAE-RA) and sclerotherapy of renal pelvis using iohexol-ethanol solution in dogs with unilateral experimental hydronephrosis. Experimental hydronephrosis was induced by unilateral ureter ligation for 20 days in five Beagle dogs. Renal artery embolization with iohexol-ethanol solution was performed using selective catheterization technique in the hydronephrotic kidney and sclerotherapy was done by injection of the iohexol-ethanol solution through percutaneously placed pig-tail catheter. EKG, $SpO_2$ body temperature, pulse, and respiratory rate were within normal ranges during procedures. Average pure ethanol dose for renal artery embolization was $1.1\pm0.3ml/kg$. Renal artery embolization was confirmed by the detection of no blood flow signal at the interlobar and arcuate artery using color Doppler ultrasonography. There were no dogs expired after TAE-RA and sclerotherapy and no side effects associated with regurgitation of iohexol-ethanol solution. The value of BUN, creatinine, ALT, AST, Ca, P in five dogs were within normal range during the experiment period. Ultrasonographically, the mean longitudinal and transverse length and the depth of the embolized kidney significantly decreased at 28 days after TAE-RA. We may conclude that TAE-RA and sclerotherapy with iohexol-ethanol solution is an effective methods for the treatment of unilateral hydronephrosis in dogs.
To compare the sedative effects using intermittent intravenous bolus injection with tiletamine-zolazepam (n = 5, TZ group), xylazine-ketamine (n = 5, XK group) and propofol (n = 5, PI group), we investigated the changes of hemodynamic (heart rate, arterial pressure), $SpO_2$, rectal temperature, respiratory rate and pain score during 60 minute sedation and 40 minute recovery period in beagle dogs. The value of rectal temperature was significantly higher in PI groups (p<0.05) during recovery period. The value of heart rate was significantly lower in XK group (p<0.05) during sedation. The changes of respiratory rate were similar tendency in all groups. The change of $SpO_2$ was stable during sedation and value was significantly higher in PI group (p<0.05) during recovery period. The value of systolic arterial pressure (SAP) was significantly lower in XK group (p<0.05) than PI group during sedation and recovery period. Low analgesic effect occurred in PI group. We concluded that intravenous anesthesia by intermittent bolus injection with propofol is useful in stabilizing rectal temperature, $SpO_2$ and hemodynamic during sedation and provide fast recovery, but have low analgesic effect.
Kim, Jae-Kwang;Lim, Sung-Bin;Chung, Chin-Hyung;Lee, Chong-Heon
Journal of Periodontal and Implant Science
/
v.32
no.1
/
pp.161-172
/
2002
The present study evaluated the effects of guided tissue regeneration using xenograft material(deproteinated bovine bone powder), with and without biodegradable membrane in beagle dogs. Contralateral fenestration defects (6 ${\times}$ 4mm) were created 4 mm apical to the buccal alveolar crest of maxillary premolar teeth in 5 beagle dogs. Deproteinated bovine bone powders were implanted into fenestration defect and one randomly covered biodegradable membrane (experimental group). Biodegradable membrane was used to provide GTR. Tissue blocks including defects with soft tissues which were harvested following four & eight weeks healing interval, prepared for histo-phathologic analysis. The results of this study were as follows. 1. In control group, at 4 weeks after surgery, new bony trabecular contacted with interstitial tissue and osteocytes like cell were arranged in new bony trabecule. Bony lamellation was not observed. 2. In control gruop, at 8 weeks after surgery, scar-like interstitial tissue was filled defect and bony trabecule form lamellation. New bony trabecular was contacted with interstitial tissue but defect was not filled yet. 3. In experimental group, at 4 weeks after surgery, new bony trabecular partially recovered around damaged bone. But new bony trabecular was observed as irregularity and lower density. 4. In experimental group, at 8 weeks after surgery, lamella bone trabecular developed around bone cavity and damaged tissue was replaced with dense interstitial tissue. In conclusion, new bone formation regenerated more in experimental than control groups and there was seen observe more regular bony trabecular in experimental than control groups at 4 weeks after surgery. In control group, at 8 weeks after surgery, the defects was filled with scar-like interstitial tissue but, in experimental group, the defects was connected with new bone. Therefore xenograft material had osteoconduction but could not fill the defects. We thought that the effective regeneration of periodontal tissue, could be achieved using GTR with biodegradable membrane.
Purpose: Recently, dental implant systems have been widely used for the treatment of the extraction site, but we have been confronted with many limitations in esthetics, phonetics and function. Transitional implants(TI) were developed as a method of providing fixed provisional restorations during conventional implant healing. Until now, little data have been provided on korean transitional implants. The purpose of this study is to evaluate the implant placement site histologically after 4 weeks and 8 weeks. Materials and Methods : Test group( IntermetzzoTM MEGAGEN, KOREA) and control group(Mini Drive Lock, Intra Rock, U.S.A.) were immediately placed in interseptal or interproximal bone of beagle dog after mandibular premolars extraction, and had a healing period with non-submerged state but without loading, Both TI surfaces were composed of rough surfaces. Results: In the test group, the average percentage of BIC were respectively 39.40%(SD7.35) after 4 weeks and 44.05%(16.76) after 8 weeks, and In the control group were 50.75%(1.48) and 59.40%(0.00). Discussion: We evaluated the initial ability of the osseointegration of TI through this study. Because TI is placed with a conventional implant simultaneously and loaded immediately, the ability of osseointegration is a very important factor for the success of TI during the initial healing phase. Conclusion: The results of the histological evaluation of these two groups were similar to those mentioned in other studies for osseointegration of implant.
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