• Mass Spectrometry Letters
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• v.11 no.1
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• pp.10-14
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• 2020

Riboflavin is a water-soluble vitamin, which serves as a precursor to flavin mononucleotide and flavin adenine dinucleotide. This study aimed to develop a simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for the quantification of riboflavin in the Beagle dog plasma. This method utilized simple protein precipitation with acetonitrile and ¹³C₄, ¹⁵N₂-riboflavin was used as an internal standard (IS). For chromatographic separation, a hydrophilic interaction liquid chromatography (HILIC) column was used with gradient elution. The mobile phase consisted of 0.1% (v/v) aqueous formic acid with 10 mM ammonium formate and acetonitrile with 0.1% (v/v) formic acid. Since riboflavin is an endogenous compound, 4% bovine serum albumin in phosphate buffered saline was used as a surrogate matrix to prepare the calibration curve. The quantification limit for riboflavin in the Beagle dog plasma was 5 ng/mL. The method was fully validated for its specificity, sensitivity, accuracy and precision, recovery, and stability according to the US FDA guidance. The developed LC-MS/MS method may be useful for the in vivo pharmacokinetic studies of riboflavin.

• YAKHAK HOEJI
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• v.52 no.2
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• pp.93-100
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• 2008

A liquid chromatographic method with tandom spectrometric detection (LC/MS/MS) for the simultaneous determination of doxifluridine and its active metabolite, 5-fluorouracil (5-FU) was developed over the concentration range of $5{\sim}2000$ ng/ml, respectively. Doxifluridine, 5-FU and internal standard, 5-chlorouracil (5-CU), were extracted from liver and intestine tissue via protein precipitation. Acetonitrile was used as the extraction solvent and the supernatant was evaporated and reconstructed in mobile phase. Optimum chromatographic separation was achieved on a Agilent Zorbax $C_{18}$ ($100\;mm{\times}2.1\;mm$, $3.5\;{\mu}m$) column with mobile phase run in isocratic with methanol : water (20 : 80, v/v). The flow rate was 0.2 ml/min with total cycle time of 5 min. The lower limit of quantification was validated at 5.0 ng/ml of liver and intestine tissue, for both doxifluridine and 5-FU, respectively. The intra-day and inter-day precision and accuracy of quality control (QC) samples were <11% coefficient of variation and <7% relative error from theoretical concentration for both analytes. In addition, the special designed stability study was performed, because the metabolism of doxifluridine occurs spontaneously even in ice bath for monkey liver. The stability of doxifluridine in liver and intestine of monkey and beagle dog was compared. It was found that bioanalytical validation could not be performed for the monkey liver; however, beagle dog's liver has relatively low speed of metabolism compared to monkey liver and instead of monkey liver, beagle dog's liver could be used for the validation. Bioanalytical validation could be performed in monkey intestine. Eventually, this developed method for liver and intestine will be useful in support of the toxicokinetic and pharmacokinetic studies of doxifluridine and 5-FU.

• Toxicological Research
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• v.17 no.4
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• pp.297-301
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• 2001

The acute toxicity of CJ-50005, an inactivated whole virus vaccine derived from hepatitis A virus (HM175) grown in human MRC-5 diploid fibroblast culture, was tested in Sprague Dawley (SD) rats and beagle dogs. CJ-50005 was orally and intramuscularly administered up to the maximum dose of 81$\mu\textrm{g}$/kg. as much as 3,000 times of the expected clinical dose, in SD rats and was intramuscularly administered up to 27 $\mu\textrm{g}$/kg, as much as 1,000 times of the expected clinical dose, in beagle dogs. In these experiments, there were no death and clinical changes which were related to CJ-50005 administration. In addition, there were no significant changes between control and treated groups in body weights and autopsy findings. In conclusion, the administration of CJ-50005 over 81$\mu\textrm{g}$/kg in SD rats and over 27$\mu\textrm{g}$/kg in beagle dogs was proved to be safe, and it is thought that CJ-50005 may not show any toxicity in its clinical use.

• Journal of Pharmacopuncture
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• v.13 no.3
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• pp.15-46
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• 2010

Objectives: This study was performed to analyse the effects of Sweet Bee Venom(Sweet BV) on cardiovascular system in the conscious telemetered Beagle Dogs. Methods: All experiments were conducted at Biotoxtech Company, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP). Male Beagle dogs of 13-19 months old were chosen for the pilot study and surgical implantation was performed for conscious telemetered Beagle dogs. And after confirming condition of Beagle dogs was stable, Sweet BV was administered 4 times(first: 0.0 mg/kg, 2nd: 0.01 mg/kg, 3rd: 0.1 mg/kg, and forth: 0.5 mg/kg, one time/week) in thigh muscle of Beagle dogs. And blood pressure, heart rate, electrocardiography and clinical responses were measured. Equal amount of normal saline to the Sweet BV experiment groups was administered to the control group. Results: 1. In the analysis of body weight and taking amount, Beagle dogs did not show significant changes. 2. In the clinical observation, responses of pain and edema were showed depend on dosage of Sweet BV. 3. In the analysis of blood pressure, treatment with Sweet BV did not show significant changes in the dosage of 0.01 mg/kg, but in the dosage of 0.1 mg/kg and 0.5 mg/kg, treatment with Sweet BV increased blood pressure significantly. 4. In the analysis of heart rate, treatment of Sweet BV did not show significant changes in all dosage and period. 5. In the analysis of electrocardiography, treatment of Sweet BV was not showed significant changes in all dosage and period. Conclusion: Above findings suggest that Sweet BV is relatively safe treatment in the cardiovascular system. But in the using of over dosage, Sweet BV may the cause of increasing blood pressure. Further studies on the subject should be conducted to yield more concrete evidences.

• Journal of Life Science
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• v.18 no.1
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• pp.91-95
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• 2008

In human, sympathetic nerve blocks with local anesthetics are widely used to treat a variety of diseases in the innervating regions. However, its procedure in dogs is difficult to approach and process repeatedly because of anatomically location. Therefore, this study was designed to develop a new technique of sympathetic nerve block in beagle dogs. Fifteen healthy beagle dogs, which did not show any neurologic abnormalities and disease, were used for the study. Radiograghs were taken after injected radiopaque material mixed with 2% lidocaine at the cranial cervical ganglion and injected methylene blue using the same percutaneous technique to verify the reliability of this newly developed technique. The successful block rate of the cranial cervical ganglion block was present in 80% of all dogs and the stained cranial cervical ganglions were shown in all dogs. The results show that this new technique of the cranial cervical ganglion block is a reliable and simple method that can be used for clinical studies in dogs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.4
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• pp.312-321
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• 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.

• Journal of Periodontal and Implant Science
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• v.36 no.1
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• pp.253-263
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• 2006

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.

• Journal of Periodontal and Implant Science
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• v.31 no.2
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• pp.299-315
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• 2001

Application of membranes for guided tissue regeneration(GTR) have been confined to the subgingival barrier functions; however, many studies have provided evidence that some drugs, including tetracycline, initially can promote the growth of periodontal ligament or alveolar bone in peridontal therapy. Osseous regeneration in periodontal defects is increased by local administration of tetracycline due to its anti-collagenolytic effect, which enhances bone-forming ability via osteoblast cell chemotaxis and reduced bone resorption. The aim of this study was to evaluate effects of tetracycline loaded poly-L-lactide(PLLA) barrier membranes for guided bone regenerative potential. Tetracycline was incorporated into the PLLA membrane with the ratio 10% to PLLA by weight. Ability to guided bone regeneration of the membranes were tested by measuring new bone in the tibial defects($7{\times}10{\times}5\;mm^3$) of the beagle dog for 4,5, and 6 weeks. In control, drug-unloaded PLLA membranes were used in same size of defect. In histologic finding of the defect area, a few inflammatory cells were observed in both groups. These membrane were not perforated by connective tissue and maintained their mechanical integrity for the barrier function for 4-6 weeks. New bone formation was greater in defects covered by tetracycline-loaded membrane than in defects covered by drug- unloaded membranes. In bone regeneration guiding potential test, tetracycline-loaded membrane was more effective than drug- unloaded membranes(p<0.05). These results suggest that tetracycline-loaded PLLA membranes potentially enhance guided bone regenerative efficacy and might be a useful barrier for GTR in periodontal treatment.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.2
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• pp.73-80
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• 2015

Objectives To assess the safety of Shinbaro3 Pharmacopuncture by analyzing the potential single-dose intramuscular toxicity of Shinbaro3 Pharmacopuncture at various dose levels in SD (Spraque-Dawley) rats and Beagle dogs. Methods For evaluation of single-dose intramuscular toxicity of Shinbaro3 Pharmacopuncture, 40 SD rats (20 male and 20 famale) and 4 Beagle dogs (2 male and 2 female) were used. The rats were divided in four groups of 10 each, and treated intramuscularly with Shinbaro3 Pharmacopuncture at doses of 0.3, 0.6 and 1.2 mg/kg in distilled water, and distilled water as a vehicle control group, respectively. The Beagle dogs were divided into two groups of 2 each, and treated intramuscularly with Shinbaro3 Pharmacopuncture at doses of 0.15, and 0.3 mg/kg in distilled water, respectively, and signs of toxicity were observed. After a wash-out period of 3 days, the procedure was repeated with Shinbaro3 Pharmacopuncture at doses of 0.6, and 1.2 mg/kg in distilled water, respectively. Mortality, body weight changes, and necropsy findings were examined during the study period. Results There were no mortalities in either the SD rats or Beagle dogs. There were also no significant differences in adverse effects, body weight, or necropsy findings between the Shinbaro3 Pharmacopuncture and control groups. Conclusions There results suggest that the lethal dose 50 ($LD_{50}$) and approximate lethal dose (ALD) value of the test substance Shinbaro3 Pharmacopuncture are higher than 1.2 mg/kg in SD rats and Beagle dogs.

• Toxicological Research
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• v.22 no.2
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• pp.153-156
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• 2006

The acute toxicity of STB-HO-BM was evaluated in Sprague Dawley (SS) rats and beagle dogs. STB-HO-BM was administered orally to rats at dose levels of 0 and 2,000mg/kg/day and to dogs at dose levels of 0, 500, 1,000 and 2,000 mg/kg/day. In these experiments, there were no death and clinical changes which were related to STB-HO-BM administration. In addition, there were no significant changes between control and treated groups in body weights and autopsy findings. In conclusion, the administration of STB-HO-BM 2,000 mg/kg in SD rats and up to 2,000mg/kg in beagle dogs was proved to be safe, and it is thought that STB-HO-BM may not show any toxicity in its clinical use.