• Herbal Formula Science
• /
• v.30 no.3
• /
• pp.123-135
• /
• 2022

Oryeongsan (ORS), a formula composed of five herbal medicines, has long been used to treat impairments of the regulation of body fluid homeostasis. The purpose of this study was to determine the antihypertensive and renal protective effects of ORS in rats with hypertension. Spontaneously hypertensive rats (SHR) were divided into two groups with similar mean baseline systolic blood pressure (SBP). Then, 1 mL/kg of vehicle (distilled water) or 1.5, 3 g/kg of ORS extract were administered orally once a day for 4 weeks. SBP and diastolic blood pressure (DBP) were measured at weeks 1, 2, 3 and 4. At the end of the experiment, blood was collected, and heart were removed for histology. By the 2 weeks after initiation of treatment, the ORS treated group had significantly lower SBP than SHR rats. The ORS treatment significantly improved blood pressure and echocardiogram parameters compared to hypertensive rats. Additionally, the left ventricular (LV) remodeling and LV dysfunction were significantly improved in ORS treated group hypertensive rats. Furthermore, an increase in fibrotic area has been observed in SHR rats compared with Wistar-Kyoto rats (WKY). Furthermore, administration of ORS significantly attenuated cardiac fibrosis in hypertensive rats. Therefore, these findings suggest that ORS has a protective effect on heart failure by alleviating hypertensive heart disease and cardiovascular dysfunction in SHR.

• Journal of Life Science
• /
• v.29 no.9
• /
• pp.1034-1046
• /
• 2019

The mitochondria is the major cellular organelle of energy metabolism for the supply of cellular energy; it also plays an important role in controlling calcium regulation, reactive oxygen species (ROS) production, and apoptosis. Mitochondrial dysfunction causes various diseases, such as neurodegenerative diseases, Lou Gehrig's disease, cardiovascular disease, mental disorders, diabetes, and cancer. Most of the diseases are age-related diseases. In this review, we focus on the roles of mitochondrial dysfunction in cancer. Mitochondrial dysfunction induces carcinogenesis and is found in many cancers. The factors that cause mitochondrial dysfunction differ depending on the types of carcinoma, and those factors could cause cancer malignancy, such as resistance to therapy and metastasis. Mitochondrial dysfunction is caused by a lack of mitochondria, an inability to provide key substances, or a dysfunction in the ATP synthesis machinery. The main factor associated with cancer malignancy is mtDNA depletion. Mitochondrial dysfunction would leads to malignancy through changes in molecular activity or expression, but it is not known in detail which changes lead to cancer malignancy. In order to explore the relationship between mitochondrial dysfunction and cancer malignancy in detail, mitochondria dysfunctional cell lines are constructed using chemical methods such as EtBr treatment or gene editing methods, including shRNA and CRISPR/Cas9. Those mitochondria dysfunctional cell lines are used in the study of various diseases caused by mitochondrial dysfunction, including cancer.

• Journal of Chest Surgery
• /
• v.31 no.5
• /
• pp.494-501
• /
• 1998

From May 1, 1993 to May 31 1995, the authers studied retrospectively 211 patients who underwent cardiovascular operation with cardiopulmonary bypass(CPB). Because we were interested in new development of ARF(prevalence, mortality rate, and main risk factors), we performed a multivariate statistical analysis about data of patients with preoperative serum creatinine values of less than 1.5 mg/dL. Normal renal function before operation(serum creatinine level less than 1.5 mg/dL) was registered in 198(74%) patients. Of these, 27(14%) patients showed postoperative renal complication, including 20(10%) patients classified as renal dysfunction(serum creatinine level between 1.5 and 2.5 mg/dL) and 7(4%) patients as acute renal failure(serum creatinine level higher than 2.5 mg/dL). The mortality rate was 5.8% in normal patients, 5% in patients with renal dysfunction, and 43% when acute renal failure developed(p=0.036). Indeed, the renal impairment proved to be an independent predictor of mortality(odd ratio 2.52∼11.25), along with cardiovascular(odd ratio 4.20) and respiratory(odd ratio 2.18) complications. Multivariate analysis identified the following variables as independent risk factors for postoperative renal impairment : advanced age(odd ratio 1), need for emergency operation(odd ratio 3.78), low-output syndrome(odd ratio 3.66), respiratory complication(odd ratio 1.30), need for deep hypothermic circulatory arrest(odd ratio 1.4). The 13 patients(7%) with preoperative renal failure showed a significantly higher morbidity and mortality rate than those without renal complications before operation. We concluded that the likelihood of severe renal complications is resonably low in the patients undergoing cardiac operation without preexisting renal dysfunction, but associated mortality remains high. A prominant role of hemodynamic factor in the development of postoperative acute renal failure must be recognized during preoperative, intraoperative, and postoperative periods.

• Journal of Chest Surgery
• /
• v.49 no.4
• /
• pp.250-257
• /
• 2016

Background: Generalization of standardized surgical techniques to treat aortic valve (AV) and aortic root diseases has benefited large numbers of patients. As a consequence of the proliferation of patients receiving aortic root surgeries, surgeons are more frequently challenged by reoperative aortic root procedures. The aim of this study was to evaluate the outcomes of redo-aortic root replacement (ARR). Methods: We retrospectively reviewed 66 patients (36 male; mean age, $44.5{\pm}9.5years$) who underwent redo-ARR following AV or aortic root procedures between April 1995 and June 2015. Results: Emergency surgeries comprised 43.9% (n=29). Indications for the redo-ARR were aneurysm (n=12), pseudoaneurysm (n=1), or dissection (n=6) of the residual native aortic sinus in 19 patients (28.8%), native AV dysfunction in 8 patients (12.1%), structural dysfunction of an implanted bioprosthetic AV in 19 patients (28.8%), and infection of previously replaced AV or proximal aortic grafts in 30 patients (45.5%). There were 3 early deaths (4.5%). During follow-up (median, 54.65 months; quartile 1-3, 17.93 to 95.71 months), there were 14 late deaths (21.2%), and 9 valve-related complications including reoperation of the aortic root in 1 patient, infective endocarditis in 3 patients, and hemorrhagic events in 5 patients. Overall survival and event-free survival rates at 5 years were $81.5%{\pm}5.1%$ and $76.4%{\pm}5.4%$, respectively. Conclusion: Despite technical challenges and a high rate of emergency conditions in patients requiring redo-ARR, early and late outcomes were acceptable in these patients.

• Journal of Chest Surgery
• /
• v.45 no.2
• /
• pp.85-90
• /
• 2012

Background: At present, many surgeons prefer axillary artery cannulation because it facilitates antegrade cerebral perfusion and may diminish the risk of cerebral embolization. However, axillary artery cannulation has not been established as a routine procedure because there is controversy about its clinical advantage. Materials and Methods: We examined 111 patients diagnosed with acute type A aortic dissection between January 2000 and December 2009. The right axillary artery was cannulated in 58 patients (group A) and the femoral artery was cannulated in 53 (group F). The postoperative outcomes were retrospectively reviewed and compared between the two groups. Results: There were 46 male and 65 female patients with a mean age of $58.9{\pm}13.1$ years (range, 26 to 84 years). The extent of aortic replacement in both groups did not differ. There were 8 early deaths (7.2%) and 2 late deaths (1.8%). The mean follow-up duration was $46.0{\pm}32.6$ months (range, 1 month to 10 years). Transient neurologic dysfunction was observed in 11 patients (19.0%) in group A and 14 patients (26.4%) in group F. A total of 11 patients (9.9%) suffered from a permanent neurologic dysfunction. Early and delayed stroke were observed in 6 patients (10.3%) and 2 patients (3.4%), respectively, in group A as well as 2 patients (3.8%) and 1 patient (1.9%), respectively, in group F. There were no statistical differences in the cannulation-related complications between both groups (3 in group A vs. 0 in group F). Conclusion: There were no differences in postoperative neurologic outcomes and cannulation-related complications according to the cannulation sites. The cannulation site in an aortic dissection should be carefully chosen on a case-by-case basis. It is important to also pay attention to the possibility of intraoperative malperfusion syndrome occurring and the subsequent need to change the cannulation site.

• Journal of Chest Surgery
• /
• v.47 no.4
• /
• pp.434-436
• /
• 2014

Left ventricular thrombus is a common complication related to acute myocardial infarction. Removing this with an incision of the free wall of the left ventricle may cause fatal cardiac dysfunction or arrhythmias. Furthermore, performing incision and suture on the fragile myocardium of an acute myocardial infarction patient may cause serious bleeding complications. If there is a patient with left ventricular thrombus who needs thoracotomy for another reason, the case is attempted with the thought that if effective intraventricular visualization and manipulation can be done, fatalities caused by incision and suture may be reduced. For patients undergoing cardiopulmonary bypass, if intracardiac manipulation is required, an endoscope can be used, and given the potential complications after the incision and suturing of the infarcted tissue, the benefits are deemed sufficient.

• Biomolecules & Therapeutics
• /
• v.24 no.4
• /
• pp.371-379
• /
• 2016

Store-operated calcium entry (SOCE), a major mode of extracellular calcium entry, plays roles in a variety of cell activities. Accumulating evidence indicates that the intracellular calcium ion concentration and calcium signaling are critical for the responses induced by oxidative stress. The present study was designed to investigate the potential effect of SOCE inhibition on $H_2O_2$-induced apoptosis in endothelial progenitor cells (EPCs), which are the predominant cells involved in endothelial repair. The results showed that $H_2O_2$-induced EPC apoptosis was reversed by SOCE inhibition induced either using the SOCE antagonist ML-9 or via silencing of stromal interaction molecule 1 (STIM1), a component of SOCE. Furthermore, SOCE inhibition repressed the increases in intracellular reactive oxygen species (ROS) levels and endoplasmic reticulum (ER) stress and ameliorated the mitochondrial dysfunction caused by $H_2O_2$. Our findings provide evidence that SOCE inhibition exerts a protective effect on EPCs in response to oxidative stress induced by $H_2O_2$ and may serve as a potential therapeutic strategy against vascular endothelial injury.

• BMB Reports
• /
• v.47 no.10
• /
• pp.552-557
• /
• 2014

The main purpose of this study was to investigate whether type 3 muscarinic acetylcholine receptor (M3R) dysfunction induced vascular hyperpermeability. Transwell system analysis showed that M3R inhibition by selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and small interfering RNA both increased endothelial permeability. Using coimmunoprecipitation and Western blot assay, we found that M3R inhibition increased VE-cadherin and ${\beta}$-catenin tyrosine phosphorylation without affecting their expression. Using PTP1B siRNA, we found that PTP1B was required for maintaining VE-cadherin and ${\beta}$-catenin protein dephosphorylation. In addition, 4-DAMP suppressed PTP1B activity by reducing cyclic adenosine monophosphate (cAMP), but not protein kinase $C{\alpha}$ ($PKC{\alpha}$). These data indicate that M3R preserves the endothelial barrier function through a mechanism potentially maintaining PTP1B activity, keeping the adherens junction proteins (AJPs) dephosphorylation.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.6
• /
• pp.437-442
• /
• 2009

A non-steroidal anti-inflammatory drug (NSAID) has many adverse effects including cardiovascular (CV) risk. Diclofenac among the nonselective NSAIDs has the highest CV risk such as congestive heart failure, which resulted commonly from the impaired cardiac pumping due to a disrupted excitationcontraction (E-C) coupling. We investigated the effects of diclofenac on the L-type calcium channels which are essential to the E-C coupling at the level of single ventricular myocytes isolated from neonatal rat heart, using the whole-cell voltage-clamp technique. Only diclofenac of three NSAIDs, including naproxen and ibuprofen, significantly reduced inward whole cell currents. At concentrations higher than $3\;{\mu}M$, diclofenac inhibited reversibly the $Na^+$ current and did irreversibly the L-type $Ca^{2+}$ channels-mediated inward current $(IC_{50}=12.89\pm0.43\;{\mu}M)$ in a dose-dependent manner. However, nifedipine, a well-known L-type channel blocker, effectively inhibited the L-type $Ca^{2+}$ currents but not the $Na^+$ current. Our finding may explain that diclofenac causes the CV risk by the inhibition of L-type $Ca^{2+}$ channel, leading to the impairment of E-C coupling in cardiac myocytes.

• Analytical Science and Technology
• /
• v.29 no.4
• /
• pp.155-161
• /
• 2016

Distribution of various illegal or counterfeit drugs of seven approved erectile dysfunction drugs and their analogues has been increased, causing health problems such as cardiovascular disorder, tachycardia, headache, or vision disturbance. We used liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) to determine the erectile dysfunction drugs and their analogues in various counterfeit drugs. Eleven erectile dysfunction drugs and their analogues were detected, with sildenafil and its analogues being the most counterfeited compounds (73.8 %), followed by tadalafil and its analogues (25.4 %). The limits of detection (LOD) and the limits of quantitation (LOQ) of liquid-type and solid-type negative samples ranged from 0.1 to 3.3 ng/mL or ng/g and from 0.3 to 10.0 ng/mL or ng/g, respectively. The recoveries ranged from 84.3 to 112.3 % and 83.2 to 110.2 %, respectively. The contents of sildenafil and tadalafil in the various counterfeit drugs ranged from 21.0 to 947.5 mg/g and from 0.2 to 170.2 mg/g, respectively.