• Journal of Veterinary Clinics
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• v.34 no.4
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• pp.283-286
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• 2017

A 4-month-old, female Maltese dog was referred with continuous heart murmur. Patent ductus arteriosus was diagnosed via radiography and echocardiography. The patient was untreated because of client's refusal. After 13 months, the dog was referred again with seizure and salivation. Laboratory examination revealed increased liver enzymes, hyperammonemia and decreased total cholesterol and total protein. Microhepatica was identified on abdominal radiography. CT angiography showed a shunt vessel that originated from the portal trunk to the prehepatic caudal vena cava and patent ductus arteriosus connecting proximal descending aorta with the main pulmonary artery. No portal vasculature toward liver is observed after shunt vessel. The patient was diagnosed as concurrent patent ductus arteriosus and congenital extrahepatic portosystemic shunt with suspected portal vein aplasia. In human, cardiac malformations are frequently observed in patients with congenital extrahepatic portosystemic shunt with portal vein aplasia. This report described concurrent patent ductus arteriosus and congenital extrahepatic portosystemic shunt with suspected portal vein aplasia in a dog.

• Journal of Chest Surgery
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• v.31 no.10
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• pp.919-923
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• 1998

Background: Calcific degeneration is unavoidable in either homo- or heterografts implanted in the human body. We have developed a calcification-resistant cardiovascular tissue patch using a novel technique of anticalcification. Materials and methods: Fresh bovine pericardium was harvested at the slaughter house and transfered to the laboratory in Hank's solution. After trimming and fixing the pericardium, it was embedded in 4$^{\circ}C$ 0.65% glutaraldehyde for a week and then washed by phosphate-buffered saline(PBS) of pH 7.4. This prepared pericardium was then stored in 2.5% sulphonated polyethyleneoxide(PEO-SO3) solution for 2 days at room temperature and reversed by 4$^{\circ}C$ NaBH4 solution for 16 hours. To evaluate the calcification-resistance of surface modified bovine pericardium with PEO-SO3, either glutaraldehyde- treated(GA group, n=4) or PEO-SO3-treated pericardial patch(PEO-SO3 group, n=4) was implanted into adult mongrel dog to reconstruct the main pulmonary artery and the descending aorta using a partial clamp technique. After 1 month follow-up, the implanted patches were retrieved to evaluate the pathologic findings and the content of calcium and phosphorous. Results: The PEO-SO3 group showed substantially less retraction and significantly less calcium deposition than the GA group in both aortic(7.10$\pm$1.05 vs. 13.81$\pm$2.33 mg/g of dried tissue) and pulmonary positions(1.55$\pm$0.29 vs. 6.72$\pm$0.70 mg/g)(p<0.01). Phosphorous contents were also less in the PEO-SO3 group than the GA group significantly, 8.11$\pm$1.07 mg/g vs. 19.33$\pm$4.31 mg/g in the aortic and 2.58$\pm$0.40 vs. 12.60$\pm$3.40 mg/g in thepulmonary position(p<0.01). Conclusions: These findings suggest that PEO-SO3 modified bovine pericardium is highly calcification-resistant but further study is needed to evaluate the long-term biological safety and compatibility of the prosthesis.

• Journal of Chest Surgery
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• v.35 no.7
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• pp.501-510
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• 2002

Background: The various pathogeneses of acute respiratory distress syndrome have been suggested but not established yet. In the present study, the role of group II phospholipase $A_2$($PLA_2$) in the pathogenesis of gut ischemia-reperfusion(I/R) induced acute lung injury (ALI), especially in the pulmonary oxidative stress with infiltration of neutrophils was investigated. Material and Method: To induce ALI, reperfusion of mesentery was done for 120 min after clamping of superior mesenteric artery for 60 min in Sprague-Dawley rats that weighed about 300g. To exmaine the role of group II $PLA_2$ in ALI, especially endothelial injury associated with the action of neutrophils, lung myeloperoxidase activity, lung leak index, bronchoalveolar lavage fluid protein were measured, and pulmonary $PLA_2$ activity changes in gut I/R were also measured. The role of group II $PLA_2$in the neutrophilic generation of free radicals was assessed by inhibiting group II $PLA_2$ with rutin, manoalide and scalaradial. Furthermore, to verify the oxidative stress in the lung, histologic and free radical detecting cytochemical electron microscopy were done. Result: After reperfusion, ALI was developed with accumulation of neutrophils in the lung, which was confirmed by the increase of myeloperoxidase activity, lung leak index and bronchoalveolar lavage protein (p<0.001). The pulmonary and intestinal group II $PLA_2$ activities significantly increased after gut I/R which were reversed by rutin(p<0.001). In vitro, cytochrome-c reduction assay denoted the inhibitory effects of rutin, scalaradial and manoalide on the production of free radicals from isolated human neutrophils. Histologically, neutrophilic accumulation and pericapillary edema in the lung after gut I/R was detected by light microscopy which was suppressed by rutin. In $CeCl_3$ cytochemical electron microscopy, the increased production of hydrogen peroxide in the lung after gut I/R was confirmed and also the production of hydrogen peroxide was decreased by rutin. Conclusion: On the basis of these experimental results, the inhibition of group II $PLA_2$ seemed to mitigate gut I/R-induced ALI by suppressing the production of free radicals from the infiltrated neutrophils. Collectively, group II $PLA_2$ seems to play a crucial role in gut I/R-induced ALI by neutrophilic oxidative stress.

• 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.

• 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.

• 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.

• Journal of Veterinary Clinics
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• v.33 no.1
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• pp.6-9
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• 2016

Bronchoarterial (BA) ratio is a commonly used criterion to define airway dilatation despite the lack of normative human and animals. The objective of our study was to compare the range of normal bronchial to accompanying arterial diameter ratio with previous reports on CT scan of the thorax in dogs and assess influence anesthetics on BA ratio in dogs. Dogs undergoing multidetector CT scan of the chest for nonpulmonary conditions at a single center were prospectively identified. High-resolution reconstruction was performed on those included and both airway lumen and vessel diameters were measured in the lobar bronchi of the left cranial (cranial and caudal parts), right cranial, right middle, left caudal, and right caudal lung lobes. Eight dog were included; Mean of the mean BA ratios was $1.43{\pm}0.24$ (95% CI = 1.36 - 1.50) in inhalation anesthetic group. In propofol group, the mean of the mean BA ratios was $1.13{\pm}0.29$ (95% CI = 1.04 - 1.22). In medetomidine group, the mean of the mean BA ratios was $0.89{\pm}0.19$ (95% CI = 0.83 - 0.95). Comparing individual lobes within anesthetic category, there was no signicant difference in mean BA ratio between lung lobes or between dog according to inhalation, propofol, and medetomidine group (P = 0.630, P = 0.878, and P = 0.508, respectively). The BA ratio in these clinically normal dogs was consistent and may be a useful tool in evaluating for bronchiectasis on CT images. However, some different criteria for bronchiectasis were applied by the anesthetic methods.