• Title/Summary/Keyword: Pulmonary Hypertension

Search Result 386, Processing Time 0.038 seconds

Measurement of CYP450 Enzymes Activity of Bosentan in HepaRG Cell (HepaRG 세포를 이용한 Bosentan 약물의 CYP450 효소활성 측정)

  • Han, Kyoung-Moon;Jung, Jung-A;Sin, Ji-Soon;Cha, Hye-Jin;Bae, Young-Ji;Kim, Hyun-Uk;Kim, Young-Hoon;Seong, Won-Keun;Kang, Hoil
    • YAKHAK HOEJI
    • /
    • v.58 no.4
    • /
    • pp.255-261
    • /
    • 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.

Interaction Effects of Lipoprotein Lipase Polymorphisms with Lifestyle on Lipid Levels in a Korean Population: A Cross-sectional Study

  • Pyun, Jung-A;Kim, Sun-Shin;Park, Kyung-Chae;Baik, In-Kyung;Cho, Nam-H.;Koh, In-Song;Lee, Jong-Young;Cho, Yoon-Shin;Kim, Young-Jin;Go, Min-Jin;Shim, Eu-Gene;Kwack, Kyu-Bum;Shin, Chol
    • Genomics & Informatics
    • /
    • v.10 no.2
    • /
    • pp.88-98
    • /
    • 2012
  • Lipoprotein lipase (LPL) plays an essential role in the regulation of high-density lipoprotein cholesterol (HDLC) and triglyceride levels, which have been closely associated with cardiovascular diseases. Genetic studies in European have shown that LPL single-nucleotide polymorphisms (SNPs) are strongly associated with lipid levels. However, studies about the influence of interactions between LPL SNPs and lifestyle factors have not been sufficiently performed. Here, we examine if LPL polymorphisms, as well as their interaction with lifestyle factors, influence lipid concentrations in a Korean population. A two-stage association study was performed using genotype data for SNPs on the LPL gene, including the 3' flanking region from 7,536 (stage 1) and 3,703 (stage 2) individuals. The association study showed that 15 SNPs and 4 haplotypes were strongly associated with HDLC (lowest $p=2.86{\times}10^{-22}$) and triglyceride levels (lowest $p=3.0{\times}10^{-15}$). Interactions between LPL polymorphisms and lifestyle factors (lowest $p=9.6{\times}10^{-4}$) were also observed on lipid concentrations. These findings suggest that there are interaction effects of LPL polymorphisms with lifestyle variables, including energy intake, fat intake, smoking, and alcohol consumption, as well as effects of LPL polymorphisms themselves, on lipid concentrations in a Korean population.

The Antihypertensive and Vasodilating Effects of Adventitious Root Extracts of Wild Ginseng (산삼 배양근 추출물의 혈압강화 및 혈관이완 효과)

  • Hong, Min-Hee;Lim, Hee-Kyoung;Park, Ji-Eun;Jun, Neung-Jae;Lee, Young-Jae;Cho, Moon-Jae;Kim, So-Mi
    • Applied Biological Chemistry
    • /
    • v.51 no.2
    • /
    • pp.102-107
    • /
    • 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.

Early Results in Surgical Treatment of Thoracic Aortic Aneurysm (흉부 대동맥류의 외과적 치료)

  • An, Byeong-Hui;Sin, Seong-Hyeon;Na, Guk-Ju
    • Journal of Chest Surgery
    • /
    • v.30 no.7
    • /
    • pp.686-692
    • /
    • 1997
  • This study represents an attempt to present an analysis of early surgical results in 15 cases of aortic surgery conducted at Chonnam University Hospital between February 1994 to August 1995. The subject, 9 males and 6 females, ranged in age from 32 to 73 years with a mean age of 55.07$\pm$ 1176 years. The patients were treated for dissecting aortic aneurysm in nine, atherosclerotic aneurysm in 4, and traumatic aortic aneurysm in two. There were 9 cases of median stemotomy, 4 cases of posterolateral thoracotomy, and 2 cases of thoracoabdominal incision. Graft replacement of ascending aorta andfor partial or total aortic arch were performed in 9 patients, descending aorta andfor t oracoabdominal aorta in 3 and total aorta in 1, Two traumatic aortic aneurysms were closed directly. Associate procedures were resuspension of aortic valve in three patients and elephant trunk procedure, coronary reimplantation and aortic valve replacement in one patient. Nine patients underwent operation for ascending aorta andfor aortic arch with retrograde cerebral perfusion during deep hypothermia and circulatory arrest. Perfusion pressure was maintained below 25 mmHg and the mean duration of circulatory arrest was 56.67 $\pm$ 29.25 minutes. Three patients underwent graft replacement of desending thoracic and thoracoabdominal aorta during deep hypothermia and circulatory arrest. Three patients died of traumatic bile peritonitis, multioragn failure, and rupture of residual dissecting aortic aneurysm by malignant hypertension. Postoperative complications included reoperation for bleeding in 4 patients, temporary confusion in 3, pulmonary complication in 3, and pericardial effusion in .

  • PDF

Analysis of Risk Factors for Postoperative Morbidity in Perforated Peptic Ulcer

  • Kim, Jae-Myung;Jeong, Sang-Ho;Lee, Young-Joon;Park, Soon-Tae;Choi, Sang-Kyung;Hong, Soon-Chan;Jung, Eun-Jung;Ju, Young-Tae;Jeong, Chi-Young;Ha, Woo-Song
    • Journal of Gastric Cancer
    • /
    • v.12 no.1
    • /
    • pp.26-35
    • /
    • 2012
  • Purpose: Emergency operations for perforated peptic ulcer are associated with a high incidence of postoperative complications. While several studies have investigated the impact of perioperative risk factors and underlying diseases on the postoperative morbidity after abdominal surgery, only a few have analyzed their role in perforated peptic ulcer disease. The purpose of this study was to determine any possible associations between postoperative morbidity and comorbid disease or perioperative risk factors in perforated peptic ulcer. Materials and Methods: In total, 142 consecutive patients, who underwent surgery for perforated peptic ulcer, at a single institution, between January 2005 and October 2010 were included in this study. The clinical data concerning the patient characteristics, operative methods, and complications were collected retrospectively. Results: The postoperative morbidity rate associated with perforated peptic ulcer operations was 36.6% (52/142). Univariate analysis revealed that a long operating time, the open surgical method, age (${\geq}60$), sex (female), high American Society of Anesthesiologists (ASA) score and presence of preoperative shock were significant perioperative risk factors for postoperative morbidity. Significant comorbid risk factors included hypertension, diabetes mellitus and pulmonary disease. Multivariate analysis revealed a long operating time, the open surgical method, high ASA score and the presence of preoperative shock were all independent risk factors for the postoperative morbidity in perforated peptic ulcer. Conclusions: A high ASA score, preoperative shock, open surgery and long operating time of more than 150 minutes are high risk factors for morbidity. However, there is no association between postoperative morbidity and comorbid disease in patients with a perforated peptic ulcer.

Left Atrial Myxoma Associated with Mitral Regurgitation and Coronary Artery Disease (승모판막폐쇄부전 및 관상동맥질환과 동반된 좌심방 점액종)

  • Baek, Man-Jong;Na, Chan-Young;Oh, Sam-Sae;Kim, Woong-Han;Whang, Sung-Wook;Lee, Cheol;Chang, Yun-Hee;Jo, Won-Min;Kim, Jae-Hyun;Seo, Hong-Ju;Park, Yoon-Ock;Moon, Hyun-Soo;Paik, Young-Kwan;Kim, Chong-Whan
    • Journal of Chest Surgery
    • /
    • v.36 no.11
    • /
    • pp.862-865
    • /
    • 2003
  • Obstructive intracardiac lesions, like mitral stenosis or insufficiency (MR), by myxomas of the left atrium have been commonly reported, but the attenuation of MR by myxoma combined with coronary artery disease is very rare. We report a 70-year-old female patient whose left atrial myxoma had attenuated moderate MR to mild MR and required mitral valve surgery after removal of the myxoma. She also had coronary artery disease, severe pulmonary hypertension and moderate tricuspid regurgitation due to the mitral valve lesions obstructed by myxoma. The patient underwent removal of myxoma, mitral and tricuspid valve reconstructions, and coronary artery bypass grafting. She was discharged at the postoperative 14 day without any problems.

Echocardiographic Evaluation of Cardiovascular Function in Cloned Dogs (심장 초음파를 이용한 복제견의 심혈관계 기능 평가)

  • Yeo, Ju-Hwan;Kim, Jae-Hwan;Kim, So-Young;Lee, Seung-Jun;Park, Noh-Won;Oh, Hyun-Ju;Kim, Min-Jung;Kim, Geon-A;Jo, Young-Kwang;Lee, Byeong-Chun;Eom, Kidong
    • Journal of Veterinary Clinics
    • /
    • v.32 no.4
    • /
    • pp.301-307
    • /
    • 2015
  • The purpose of this study was to compare echocardiographic parameters of cloned beagle dogs with the previously reported reference range. Seven cloned dogs were assessed for anatomical features and cardiac function through left- and right-sided heart and right ventricle outflow tract from M-mode, 2D-mode, pulsed wave Doppler and tissue Doppler imaging. In all the cloned dogs, there were no abnormalities in anatomical structure and measurements were within the normal reference range. In addition, left- and right-sided myocardial function was within the normal reference range. Especially, pulmonary hypertension and right-sided heart failure frequently encountered in cloned animals were not recognized in cloned dogs. In conclusion, no evidence of cardiovascular dysfunction in mature cloned dogs could be identified either at birth or the growing stage in this study. Therefore, serious adverse effects of somatic cell nuclear transfer technology including transgenesis on cardiac morphology and function were not found in cloned dogs.

Korean Red Ginseng affects ovalbumin-induced asthma by modulating IL-12, IL-4, and IL-6 levels and the NF-κB/COX-2 and PGE2 pathways

  • Lee, Soon-Young;Kim, Min-Hee;Kim, Seung-Hyun;Ahn, Taeho;Kim, Sung-Won;Kwak, Yi-Seong;Cho, Ik-Hyun;Nah, Seung-Yeol;Cho, Seung-Sik;Park, Kyung Mok;Park, Dae-Hun;Bae, Chun-Sik
    • Journal of Ginseng Research
    • /
    • v.45 no.4
    • /
    • pp.482-489
    • /
    • 2021
  • Background: Asthma is an incurable hyper-responsive disease of the pulmonary system that is caused by various allergens, including indoor and outdoor stimulators. According to the Global Asthma Network, 339 million people suffered from asthma in 2018, with particularly severe forms in children. Numerous treatments for asthma are available; however, they are frequently associated with adverse effects such as growth retardation, neurological disorders (e.g., catatonia, poor concentration, and insomnia), and physiological disorders (e.g., immunosuppression, hypertension, hyperglycemia, and osteoporosis). Methods: Korean Red Ginseng has long been used to treat numerous diseases in many countries, and we investigated the anti-asthmatic effects and mechanisms of action of Korean Red Ginseng. Eighty-four BALB/c mice were assigned to 6 treatment groups: control, ovalbumin-induced asthma group, dexamethasone treatment group, and 3 groups treated with Korean Red Ginseng water extract (KRGWE) at 5, 25, or 50 mg/kg/day for 5 days. Anti-asthmatic effects of KRGWE were assessed based on biological changes, such as white blood cell counts and differential counts in the bronchoalveolar lavage fluid, serum IgE levels, and histopathological changes in the lungs, and by examining anti-asthmatic mechanisms, such as the cytokines associated with Th1, Th2, and Treg cells and inflammation pathways. Results: KRGWE affected ovalbumin-induced changes, such as increased white blood cell counts, increased IgE levels, and morphological changes (mucous hypersecretion, epithelial cell hyperplasia, inflammatory cell infiltration) by downregulating cytokines such as IL-12, IL-4, and IL-6 via GATA-3 inactivation and suppression of inflammation via NF-κB/COX-2 and PGE2 pathways. Conclusion: KRGWE is a promising drug for asthma treatment.

Effect of Simple VSD Repair on Doppler-Derived Right Ventricular Systolic Time Interval (심실중격결손 봉합이 우심실 수축기 시간 간격에 미치는 영향)

  • 정태은;이영환
    • Journal of Chest Surgery
    • /
    • v.32 no.2
    • /
    • pp.124-129
    • /
    • 1999
  • Background: Ventricular septal defect(VSD) that causes pulmonary hypertension increase right ventricular workload. Echocardiographic assessment of right ventricular systolic time interval (RVSTI) has been used to predict pulmonary artery pressure in various cardiopulmonary diseases. This study was undertaken in infants with simple VSD to observe the alteration of the right ventricular workload through the changes of RVSTI after repair of VSD. Material and Method: We evaluated heart rate, the ratio of the left atrium/aortic root diameter (LA/Ao), right ventricular pre-ejection period(RVPEP), right ventricular ejection time(RVET), and its ratio(RVPEP/RVET) as a predictor of right ventricular workload in 12 children with simple VSD. These were measured three times at the preoperative period, at the 3 month and between 6 month and 1 year(average 9.5${\pm}$1.8month) after repair of VSD by M-mode & Doppler echocardiograph from the pulmonic valve echogram. Result: Heart rate was decreased significantly after repair(137.1${\pm}$13.7 vs 114.4${\pm}$21.1 and 104.1${\pm}$10.2, p<0.01). LA/Ao ratio was decreased significantly after repair(1.71${\pm}$0.32 vs 1.47${\pm}$0.33 and 1.39${\pm}$0.23, p<0.05). RVPEP/RVET were decreased after repair (0.38${\pm}$0.09 vs 0.32${\pm}$0.08 and 0.29${\pm}$0.09, p<0.01). Heart rate corrected RVPEP/RVET were significantly decreased only after 6 months(0.32${\pm}$0.03 vs 0.30${\pm}$0.05 and 0.28${\pm}$0.06, p<0.05). Conclusion: We found elevated right ventricular workload was progressively decreased until more than 6 months after repair and the RVSTI may serve a useful guide in postoperative care for children with VSD.

  • PDF

Clinical Validation of Nebulized Budesonide and Effect of Nebulized Budesonide on the Hypothalamic-Pituitary-Adrenal Axis in Adult Patients Admitted with Acute Asthmatic Attack (급성 발작으로 내원한 성인 천식 환자에서 Nebulized Budesonide의 임상적인 효과와 시상하부-뇌하수체-부신 축에 대한 작용)

  • Seo, Ki-Hyun;Moon, Seung-Hyug;Kim, Yong-Hoon
    • Tuberculosis and Respiratory Diseases
    • /
    • v.52 no.5
    • /
    • pp.529-538
    • /
    • 2002
  • Background : Many clinicians are reluctant to prescribe systemic corticosteroids to manage an asthmatic attack because of many complications such as osteoporosis, cushing's syndrome, diabetes, hypertension and bleeding tendency. The use of nebulized budesonide may be of value in some infants, old men, and in particular adult asthmatic patients who complain of severe dyspnea. A clinical validation and steroid-sparing effect of nebulized budesonide in asthmatic adults and COPD were evaluated, and the short-term effects of budesonide use on the HPA axis were assessed. Materials and Methods : Study A was prospectively done with 41 patients diagnosed with pure asthma and 30 patients diagnosed with COPD (including asthmatic component) in Soonchunhyang Hospital, Chunan from June. 2000 to Sep. 2001. They were treated with nebulized budesonide including systemic steroids (Group 1), a budesonide tubuhaler including a systemic steroid (Group 2), or only the systemic steroid(Group 3). The peak flow rate, arterial blood gas in room air, pulmonary function test, symptom scoring, steroid amount and hospital stay were analyzed. Study B was conducted with 19 patients to evaluate the short-term effects on the HPA axis of treatment with nebulized budesonide 1mg twice daily and a budesonide turbuhaler 5 puffs twice daily. The adrenal function was assessed prior to budesonide inhalation and after 7 days of budesonide inhalation. Results : In the pure asthmatic patients, the mean value of the symptoms (dyspnea, wheezing, cough, night asthma) or the arterial BGAs, total amounts of steroid or hospital stay and the difference in the results of the pulmonary function tests or peak expiratory flow rate were similar in the three groups. In COPD with an asthmatic component, there were no significant differences among the three groups. Although nebulized budesonide suppressed HPA function,(p=0.006) the HPA responses from the nebulized budesonide and turbuhaler budesonide were similar (p=0.288) Conclusion : This result suggests that systemic steroid should only be made available for acute asthmatic patients irrespective of the inhaled budesonides. Nebulized budesonide at the therapeutic dose has similar effects on the HPA axis compared to that of turbuhaler budesonide.