• YAKHAK HOEJI
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• v.58 no.4
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• pp.255-261
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• 2014

Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

• Journal of Chest Surgery
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• v.51 no.2
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• pp.92-99
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• 2018

Background: We evaluated the early clinical outcomes of tricuspid valve annuloplasty (TAP) with the Tri-Ad annuloplasty ring for functional tricuspid regurgitation (TR). Methods: From January 2015 to March 2017, 36 patients underwent TAP with a Tri-Ad ring for functional TR. To evaluate the early clinical outcomes of TAP with the Tri-Ad ring, we conducted a propensity score-matched analysis comparing the Tri-Ad and $MC^3$ tricuspid annuloplasty rings (n=34 in each group). The follow-up duration was $11.0{\pm}7.07$ months. Results: There was 1 case of operative mortality (2.8%) and no cases of late mortality. Postoperative complications occurred in 15 patients (41%), including acute kidney injury in 6 patients (16%), bleeding requiring reoperation in 4 patients (11%), and low cardiac output syndrome in 4 patients (11%). There were no ring-related complications, such as atrioventricular block or ring dehiscence. The TR grade decreased significantly (from $2.03{\pm}1.06$ to $1.18{\pm}0.92$, p<0.01), as did the systolic pulmonary artery pressure (from $43.53{\pm}13.84$ to $38.00{\pm}9.72mm\;Hg$, p=0.03). There were no cases of severe residual TR, but moderate TR was observed in 3 patients, all of whom had severe TR preoperatively. Severe preoperative TR was also associated with moderate in the univariate analysis (p<0.01). In the propensity score-matched analysis comparing the Tri-Ad and $MC^3$ rings, there was no significant difference in early clinical outcomes. Conclusion: TAP with the Tri-Ad ring corrected functional TR effectively and provided good early clinical and echocardiographic results without ring-related complications. However, severe preoperative TR was associated with moderate or severe residual TR in the immediate postoperative period. A follow-up study is necessary to confirm the stability of this procedure.

• Journal of Veterinary Clinics
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• v.23 no.3
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• pp.320-324
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• 2006

The purpose of the present study was to compare pulsatile type(Twin Pulse Life Support; TPLS) with rotary type hemodialyzer(AK95) in order to reduce the dialysis time and to improve dialysis effect. Three healthy dogs(about 30 kg BW) were used. Experimental renal failure was induced by the ligation of bilateral renal artery. A pair of catheters were implanted in jugular vein for dialysis. Daily investigated parameters included clinical signs such as vomiting, fecal appearance and activity, and also laboratory data such as PCV, TP, BUN and creatinine. Hemodialysis was started above 90 mg/100 ml BUN level and, laboratory data were measured every an hour for 4 hours. Heparin was administered 300 IU/Kg before dialysis and 150 IU/Kg via IV route every 90 minutes during dialysis. Clinical signs after induction renal failure were shown severe vomiting, anorexia, diarrhea, mucous feces, ataxia, dilated pupil and episcleral hyperemia. The average of BUN value decreased hourly $99{\pm}12.1,\;84{\pm}12.2,\;72{\pm}8.0,\;58{\pm}7.1,\;48{\pm}5.2,\;and\;39{\pm}3.2mg/100ml$ by hemodialysis. The average of creatinine value decreased $7.8{\pm}0.61,\;6.4{\pm}0.40,\;5.3{\pm}0.42,\;4.5{\pm}0.23,\;4.0{\pm}0.41,\;and\;3.4{\pm}0.42mg/100ml$ according to hemodialysis an hour. There are not significantly differences BUN, creatinine, PCV and TP values between pulsatile and rotary type hemodialysis. These results suggested that effects of hemodialysis with Pulsatile type(TPLS) are not significantly difference as compared with hemodialysis of rotary type(AK95). Further research is needed in order to estimate the influence of cardiovascular and pulmonary system in hemodialysis of pulsatile type.

• Journal of Veterinary Clinics
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• v.29 no.6
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• pp.483-487
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• 2012

Primary and metastatic tumors involving the heart are relatively uncommon in dogs. In this study, we provide the echocardiographic diagnosis of intracardiac masses in 2 Yorksire terrier dogs. In the first case, the mass was attached between ascending aorta and pulmonary artery and caused moderate aortic regurgitation and moderate left ventricular dilation. The case was graded into ISACHC II heart failure. The dog was treated with common cardiac medications (i.e. furosemide, enalapril, pimobendan) and oral chemotherapeutic agent (i.e. lomustine). In the second case, the mass was occupied 2/3 of the left atrium and caused marked dilation of left atrium and severe mitral regurgitation (~5 m/s), but not severe congestive heart failure (ISACHC Ib). Although the nature of progression of the mass was likely to cardiac myxoma, the biopsy was not performed due to the owner's refusal. The dog was currently treated with cardiac medications (i.e. ramipril, clopidogrel) and bronchodilator (i.e. aminophylline). Those two dogs are still survived and are currently regularly checked.

• Journal of Chest Surgery
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• v.36 no.9
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• pp.687-690
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• 2003

Although surgical options for double outlet right ventricle (DORV) with non-committed ventricular septal defect (VSD) are vary in accordance to the morphological characteristics, it is very difficult to use biventricular repair technique when there is tricuspid chordae originating from conal septum or when the distance between the tricuspid valve and the pulmonic valve is too short. We report our clinical experience of biventricular repair of DORV with non-committed VSD by VSD rerouting to the pulmonary artery and arterial switch in case of a presence of conal tricuspid chordae and short distance between the tricuspid valve and the pulmonic valve.

• Journal of Chest Surgery
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• v.29 no.1
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• pp.7-13
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• 1996

The conventional glutaraldehyde (GA) fixation method of tissue valves is considered to be responsible for accelerated valve degeneration. The release of toxic GA from the valve tissue is believed to limit endothelial cell (EC) ingrowth. Removal of toxic GA by reaction with L-glutamic acid and storage in a Paraben solution may offer good EC growth. To investigate the conditions for endothelialization of tissue valves, the growth properties of ECs on the conventionally and alternatively treated pericardial tissue were compared. Conventional preparation included zero-pressure fixation for 72 hours in phosphated-buffered saline (PBS) solution containing 0.5% GA at 4$^{\circ}C$ and storage into PBS containing 0.2% GA(group I). Alternatively treated pericardial tissues were divided into three postfixation treatment groups : (1) storage in PBS solution containing Paraben(group II), (2) treatment with PBS containing 8$^{\circ}C$ L-glutamic acid(PH 7.35) and storage in PBS solution containing Paraben (g oup III), (3) treatment with L-glutamic acid dissolved in distilled water (PH 3.5) (group IV). Pericardial tissue were transferred into the 24-well plate after storage for 4 weeks. ECs were harvested enzymatically from the bovine pulmonary artery and grown to confluence on culture flask surfaces. Detached ECs by trypsin were incubated into the each well of the 24-well plate including test pericardial tissues. Cells were detached by trypsin, 1, 2, 3, 5, 7 days after incubation and counted on the hemacytometer. Cell viability test was performed by frypan-blue exclusion method. Acute cell death in the group I were found even after prolonged washing. The group II showed prolonged cell survival compared with the group I. Both group III and group IV showed better cell growth than group II. There was no statistically significant difference between group III and group IV method in terms of EC growth. This results suggest that treatment by L-glutamic ac id and storage in a Paraben solution be a promising approach for improvement of durability of GA-treated tissue valves.

• Applied Biological Chemistry
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• v.51 no.2
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• pp.102-107
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• 2008

Nitric oxide (NO) is a potent antihypertensive and vasodilator which plays an important role in regulating vascular tones. In this study, we investigated the effects of adventitious root extracts of wild ginseng on NO production and NO linked physiological activities. When human endothelial cell line (ECV304) was incubated with either water extracts of wild ginseng adventitious root (WE) or aqueous fraction of butanol extracts of wild ginseng adventitious root (ABE), considerable amounts of NO were released by the cells. The level of endothelial nitric oxide synthase (eNOS) expression was unchanged and about 6% of the angiotensin converting enzyme (ACE) was inhibited with treatment of ABE. The vasodilating activities of pulmonary artery rings in response to different doses of extracts were shown as 44.8% and 91.3% in 2.5 mg/ml WE and 0.1 mg/ml ABE, respectively. The blood pressure lowering effect was observed from the oral administered spontaneously hypertensive rat (SHR) with the lowest blood pressure (154.5${\pm}$8.6 mmHg) after 8 h. The blood pressure was recovered to the initial level after 24 h.

• Clinical and Experimental Pediatrics
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• v.61 no.6
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• pp.187-193
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• 2018

Purpose: The efficacy of percutaneous stent implantation for congenital heart disease (CHD) in Korea, where stent availability is limited, has not been determined. This study evaluated the acute and midterm results of stent implantation in different CHD subgroups. Methods: Stents were implanted in 75 patients with 81 lesions: (1) pulmonary artery stenosis (PAS) group, 56 lesions in 51 patients; (2) coarctation of the aorta (CoA) group, 5 lesions in 5 patients; (3) Fontan group, 13 lesions in 12 patients; (4) ductal stent group, 3 lesions in 3 patients; and (5) other CHD group, 4 lesions in 4 patients. Mean follow-up duration was 2.1 years (0.1-4 years). Medical records were reviewed retrospectively. Results: The minimum lumen diameter (MLD) in PAS and CoA increased from $5.0{\pm}1.9mm$ and $8.4{\pm}1.6mm$ to $10.1{\pm}3.6mm$ and $12.3{\pm}2.5mm$, respectively (P<0.01). In the PAS group, pressure gradient decreased from $25.7{\pm}15.6mmHg$ to $10.4{\pm}10.1mmHg$, and right ventricular to aortic pressure ratio from $0.56{\pm}0.21$ to $0.46{\pm}0.19$. In the CoA group, the pressure gradient decreased from $50{\pm}33mmHg$ to $17{\pm}8mmHg$. In the ductal stent group, the MLD of the ductus increased from 2.3 mm to 4.3 mm and arterial oxygen saturation from 40%-70% to 90%. No deaths were associated with stent implantation. Stent migration occurred in 3 patients, but repositioning was successful in all. Stent redilation was performed successfully in 26 cases after $29{\pm}12months$. Conclusion: Percutaneous stent implantation was safe and effective, with acceptable short and mid-term outcomes in Korean CHD patients.

• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.123-129
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• 2009

Patent ductus arteriosus(PDA) is an abnormal shunt between the descending aorta and pulmonary artery through the incompletely closed ductus arteriosus and is the most common congenital heart defect in dogs. Recent human genetic studies found that a the gene mutation in transcription factor AP-2 beta(TFAP2B) was responsible for syndromic cases of PDA. Mutations in the TFAP2B gene are associated with certain congenital cardiac defects in humans that include PDA. In this study, we isolated the entire coding exons of canine TFAP2B gene for genetic screening in dogs with PDA. Analysis of the deduced amino acid sequence suggested that the canine TFAP2B are phylogenetically closer to the human TFAP2B(100% identity in amino acid sequence) than mouse and rat. In cTFAP2B gene screening, one single c.936+203G>A base change was found in affected Maltese dogs with PDA. However, further screening found the same base change in one unaffected control dog, suggesting this base change might be polymorphism. No other base changes were found in other dog breeds enrolled in this study. Because the base change was located in the intronic region and found in an unaffected control dog, TFAP2B might not be responsible for familial PDA in Malteses and sporadic cases of other dog breeds, although the gene promoter region should be investigated before reaching to this conclusion. A future study that may take this study further would be to collect more samples and to screen TFAP2B in various breeds of dogs with PDA and other various congenital heart defects.

• Journal of Chest Surgery
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• v.12 no.3
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• pp.281-288
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• 1979

For years, physicians and anatomists have been interested in the heart that has one functioning ventricle. Various terms have been suggested for this entity including single ventricle, common ventricle, double-inlet left ventricle, cor biatriatum triloculare, and primitive ventricle. In this report, the term "single ventricle" is utilized as suggested by Van Praagh, and is defined as that congenital cardiac anomaly in which a common or separate atrioventricular valves open into a ventricular chamber from which both great arterial trunks emerge. An outlet chamber, or infundibulum, may or may not be present and give rise to the origin of either of the great arteries. This definition excludes the entity of mitral and tricuspid atresia. An 11 year old cyanotic boy was admitted chief complaints of exertional dyspnea and frequent upper respiratory infection since 2 weeks after birth. He was diagnosed as inoperable cyanotic congenital heart disease, and remained without any corrective treatment up to his age of 11 year when he suffered from aggravation of symptoms and signs of congestive heart failure for 2 months before this admission. On 22nd of May 1979, he was admitted for total corrective operation under the impression of tricuspid atresia suggested by a pediatrician. Physical check revealed deep cyanosis with finger and toe clubbing, and grade V systolic ejection murmur with single second heart sound was audible at the left 3rd intercostal space. Development was moderate in height [135 cm] and weight[28Kg]. Routine lab findings were normal except increased hemoglobin [21.1gm%], hematocrit [64 %], and left axis deviation with left ventricular hypertrophy on EKG. Cardiac catheterization and angiography revealed 1-transposition of aorta, pulmonic valvular stenosis, double inlet of a single ventricle with d-loop, and normal atriovisceral relationship [Type III C solitus according to the classification of Van Praagh]. At operation, longitudinal incision at the outflow tract of right ventricle in between the right coronary artery and its branch [LAD from RCA] revealed high far anterior aortic valve which had fibrous continuity with mitral annulus, and pulmonic valve was stenotic up to 4 mm in diameter positioned posterolaterally to the aorta. Ventricular septum was totally defective, and one markedly hypertrophied moderator band originated from crista supraventricularis was connected down to the imaginary septum of the ventricular cavity as a pseudoseptum of the ventricle. Size of the defect was 3X3 cm2 in total. Patch closure of the defect with a Teflon felt of 3.5 x 4 cm2 was done with interrupted multiple sutures after cut off of the moderator band, which was resutured to the artificial septum after reconstruction of the ventricular septum. Pulmonic valvotomy was done from 4 mm to 11 mm in diameter thru another pulmonary arteriotomy incision, and right ventriculotomy wound was closed reconstructing the right ventricular outflow tract with pericardial autograft of 3 x 4 cm2. Atrial septal defect of 2 cm in diameter was closed with 3-0 Erdeck suture, and atrial wall was sutured also when rectal temperature reached from 24`C to 35.5`C. Complete A-V block was managed with temporary external pacemaker with a pacing rate of 110/min. thru myocardial wire, and arterial blood pressure of 80/50 mmHg was maintained with Isuprel or Dopamine dripping under the CVP of 25-cm saline. Consciousness was recovered one hour after the operation when his blood pressure reached 100 /70 mmHg, but vital signs were not stable, and bleeding from the pericardial drainage and complete anuria were persisted until his heart could not capture the pacemaker impulse, and patient died of low output syndrome 320 min after the operation.