Expression of MIP-1alpha, MCP-1, and RANTES in ex vivio cardiac xenograft model

Thesis(master`s)--서울대학교 대학원 :의학과 흉부외과학전공,2006.Maste

Anti-calcification treatment of porcine pericardial heterograft using L-lysine

학위논문(박사) --서울대학교 대학원 :의학과(흉부외과학 전공),2009.2.Docto

Spontaneous pneumothorax as the first manifestation of lung cancer: two case report

Spontaneous pneumothorax (SP), as the first manifestation of lung cancer, is relatively rare, with reported occurrence rate of between 0.03% and 0.05%. The mechanism of concurrent pneumothorax with lung cancer is not clear, however several theories were proposed, including tumor necrosis mechanism and rupture of the bulla which contains tumor. We herein report two cases of lung cancer, in which the initial manifestations was only limited to SP. Without any radiologic abnormalities preoperatively, wedge resection of bullatous lung and subsequent histologic study followed. Pathologic study revealed the presence of bullatous change of the lung and combined lung cancer

Localized malignant pleural sarcomatoid mesothelioma misdiagnosed as benign localized fibrous tumor

Localized malignant pleural mesothelioma (LMPM) is a rare tumor with good prognosis by surgical resection. We report an atypical case of malignant pleural sarcomatoid mesothelioma (SM) in an asymptomatic 65-year-old woman, who had no history of exposure to asbestos. She presented with a small pleural mass without pleural effusion and was misdiagnosed as a benign localized fibrous tumor (BLFT) on pathologic examination through a surgical tumor specimen. However, seven months later, the patient returned with serious cancerous symptoms. A large recurrent tumor mass was found within the chest wall invading at the old surgical resection site. SM, a subtype of LMPM, was confirmed with histopathogy and immunohistochemisty. In conclusion, malignant pleural mesothelioma (MPM) can present with typical radiologic finding similar to a BLFT, and has a wide histopathologic presentation in biopsy specimen. A thorough pathologic investigation should be attempted even when a pleural mass resembles benign, localized, and small on radiologic studies

Detoxification of glutaraldehyde treated porcine pericardium using L-arginine & NABH 4

Background: Calcification is the most frequent cause of clinical failure of bioprosthetic tissues fabricated from GA-fixed porcine valves or bovine pericardium. A multi-factorial approach using different mechanisms was recently developed to reduce the calcification of bioprosthetic tissues. The purpose of the present study was to evaluate the synchronized synergism of using L-arginine and NaBH 4, compared with ethanol and L-lysine, in glutaraldehyde treated porcine pericardium from the standpoint of calcification and tissue elasticity. Materials and Methods: Porcine pericardium was fixed at 0.625% GA (7 days at room temperature after 2 days at 4°C). An interim step of ethanol (80%; 1 day at room temperature) or L-lysine (0.1 M; 2 days at 37°C) or L-arginine (0.1 M; 2 days at 37°C) was followed by completion of the GA fixation. A final step of NABH 4 (0.1 M; 2 days at room temperature) was followed. Their tensile strength, thickness, and thermal stability were measured. Treated pericardia were implanted subcutaneously into three-week-old Sprague-Dawley rats for 8 weeks. Calcium content was assessed by atomic absorption spectroscopy and histology. Results: L-arginine and NABH 4 pretreatment (1.81±0.39 kgf/5 mm p=0.001, 0.30±0.08 mm p<0.001) significantly increased tensile strength and thickness compared with the control (0.53±0.34 kgf/5 mm, 0.10±0.02 mm). In a thermal stability test, L-arginine and NABH 4 pretreatment (84.25±1.12°C, p=0.023) caused a significant difference from the control (86.25±0.00°C). L-lysine and NABH 4 pretreatment (183.8±42.6 ug/mg, p=0.804), and L-arginine and NABH 4 pretreatment (163.3±27.5 ug/mg, p=0.621) did not significantly inhibit calcification compared to the control (175.5±45.3 ug/mg), but ethanol and NABH 4 pretreatment did (38.5±37.3 ug/mg, p=0.003). Conclusion: The combined pretreatment using L-arginine and NABH 4 after GA fixation seemed to increase the tensile strength and thickness of porcine pericardium, fixed with GA. Additionally, it seemed to keep thermal stability. However it could not decrease the calcification of porcine pericardium fixed with GA. NABH 4 pretreatment seemed to decrease the calcification of porcine pericardium fixed with GA, but only with ethanol. © The Korean Society for Thoracic and Cardiovascular Surgery. 2011

Changes of bax, bcl-2, CCR-2, MCP-1, and TGF-β1 genes in the left ventricle of spontaneously hypertensive rat after losartan treatment

Purpose: Increased apoptosis was recently found in the hypertrophied left ventricle of spontaneously hypertensive rats (SHRs). Although the available evidence suggests that apoptosis can be induced in cardiac cells by various insults including pressure overload, cardiac apoptosis appears to result from an exaggerated local production of angiotensin in adult SHRs. Altered expressions of Bcl associated X (Bax), Bcl-2, chemokine receptor (CCR)-2, monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-β1, phosphorylated extracellular signal-regulated kinases (PERK), and connexin 43 proteins, and kallikrein mRNA were investigated to explore the effects of losartan on the SHR model. Methods: Twelve-week-old male rats were grouped as follows: control (C), SHR (hypertension: H), and losartan (L; SHRs were treated with losartan [10 mg/kg/day] for 5 weeks). Western blot and reverse transcription polymerase chain reaction assays were performed. Results: Expression of Bax, CCR-2, MCP-1, TGF-β1, PERK, and connexin 43 proteins, and kallikrein mRNA was significantly increased in the H group compared to that in the C group at weeks 3 and 5. Expression of Bax, CCR-2, MCP-1, TGF-β1, and connexin 43 proteins and kallikrein mRNA was significantly decreased after losartan treatment at week 5. PERK protein expression was significantly decreased after losartan treatment at weeks 3 and 5. Bcl-2 protein expression was significantly decreased in the H group compared to that in the C group at weeks 3 and 5. Conclusion: Losartan treatment reduced expression of Bax, CCR-2, MCP-1, TGF-β1, PERK, and connexin 43 proteins, and kallikrein mRNA in SHRs, along with decreased inflammation and apoptosis. © 2019 by The Korean Pediatric Society

Optimal Dose and Timing of Umbilical Stem Cells Treatment in Pulmonary Arterial Hypertensive Rats

Purpose: Pulmonary arterial hypertension (PAH) is a fatal disease which is characterized by an increase in pulmonary arterial pressure leading to increases in right ventricular afterload. Human umbilical cord blood derived-mesenchymal stem cells (hUCB-MSCs) administered via the jugular vein have been previously shown to improve PAH by reversal treatment. However, the effect of low dosage and transfusion timing of hUCB-MSCs on PAH has not yet been clearly established. Obviously, low dosage treatment can lead to a reduction in costs. This is the first study on early transfusion effect. Materials and Methods: This study was divided into two parts. The first part is an investigation of dose-dependent effect. hUCBMSCs were administered into 3 groups of rats (UA: 3x10(6) cells, UB: 1.5x10(6) cells, UC: 3x10(5) cells) via the external jugular vein at week 1 after monocrotaline (MCT) injection. The second part is a search for optimal treatment timing in 3x10(5) cells dose of hUCBMSCs administered at day 1 for UD group (low dose of hUCB-MSCs at day 1), at day 1 and week 1 for the UE group (dual transfusion of low dose of hUCB-MSCs at day 1 and week 1) and at 1 week for the UF group (reversal treatment of low dose hUCB-MSC at week 1) after MCT injection. Results: The administration of 3x10(5) hUCB-MSCs was as effective as the 3x10(6) dose in decreasing mean right ventricle (RV) pressure and pulmonary pathological changes. Early treatment with hUCB-MSCs improved mean RV pressure, pulmonary pathological changes and heart collagen 3 protein expression levels in PAH. Conclusion: Low-dose early treatment of hUCB-MSCs is as effective as a high dose treatment of hUCB-MSCs in improving PAH although dual or reversal treatment is still more effective

Effect of Ambrisentan Therapy on the Expression of Endothelin Receptor, Endothelial Nitric Oxide Synthase and NADPH Oxidase 4 in Monocrotaline-induced Pulmonary Arterial Hypertension Rat Model

Background and Objectives: Elevated endothelin (ET)-1 level is strongly correlated with the pathogenesis of pulmonary arterial hypertension (PAH). Expression level of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4 is increased in the PAH patients. Ambrisentan, a selective endothelin receptor A (ERA) antagonist, is widely used in PAH therapy. The current study was undertaken to evaluate the effects of ambrisentan treatment in the monocrotaline (MCT)-induced PAH rat model. Methods: Rats were categorized into control group (C), monocrotaline group (M) and ambrisentan group (Am). The M and Am were subcutaneously injected 60 mg/kg MCT at day 0, and in Am, ambrisentan was orally administered the day after MCI injection for 4 weeks. The right ventricle (RV) pressure was measured and pathological changes of the lung tissues were observed by Victoria blue staining. Protein expressions of ET-1, ERA, endothelial nitric oxide synthase (eNOS) and NOX4 were confirmed by western blot analysis. Results: Ambrisentan treatment resulted in a recovery of the body weight and RV/left ventricle+septum at week 4. The RV pressure was lowered at weeks 2 and 4 after ambrisentan administration. Medial wall thickening of pulmonary arterioles and the number of intra-acinar arteries were also attenuated by ambrisentan at week 4. Protein expression levels of ET-1 and eNOS were recovered at weeks 2 and 4, and ERA levels recovered at week 4. Conclusions: Ambrisentan administration resulted in the recovery of ET-1, ERA and eNOS protein expression levels in the PAH model. However, the expression level of NOX4 remained unaffected after ambrisentan treatment

The effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline-induced right ventricular failure

Purpose: Pulmonary arterial hypertension (PAH) leads to right ventricular failure (RVF) as well as an increase in pulmonary vascular resistance. Our purpose was to study the effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline (MCT)-induced RVF. Methods: The rats were distributed randomly into 3 groups. The control (C) group, the monocrotaline (M) group (MCT 60 mg/kg) and the sildenafil (S) group (MCT 60 mg/kg+ sildenafil 30 mg/kg/ day for 28 days). Masson Trichrome staining was used for heart tissues. Western blot analysis and immunohistochemical staining were performed. Results: The mean right ventricular pressure (RVP) was significantly lower in the S group at weeks 1, 2, and 4. The number of intra-acinar arteries and the medial wall thickness of the pulmonary arterioles significantly lessened in the S group at week 4. The collagen content also decreased in heart tissues in the S group at week 4. Protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X, caspase-3, Bcl-2, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, endothelial nitric oxide synthase (eNOS), endothelin (ET)-1 and ET receptor A (ERA) in lung tissues greatly decreased in the S group at week 4 according to immunohistochemical staining. According to Western blotting, protein expression levels of troponin I, brain natriuretic peptide, caspase-3, Bcl-2, tumor necrosis factor-α, IL-6, MMP-2, eNOS, ET-1, and ERA in heart tissues greatly diminished in the S group at week 4. Conclusion: Sildenafil alleviated right ventricular hypertrophy and mean RVP. These data suggest that sildenafil improves right ventricular function. © 2016 by The Korean Pediatric Society

Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatmen

Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. © 2016. Anatomy & Cell Biology