• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.281-296
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• 2021

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O₂ for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

• 한국식품과학회지
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• 제26권3호
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• pp.213-220
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• 1994

본 연구는 고혈압을 비롯한 순환기 질환의 예방이나 치료의 목적을 위해 민간요법으로 전수되어 사용되고 있는 천마의 효능에 대한 사실성을 확인하고, 나아가서는 이러한 효능에 대한 천마의 작용기전을 유추하려고 하였다. 현재까지 천마 extracts에 대한 유효성분의 분석이 이루어져 있지 않기 때문에, 본 연구는 SD 실험쥐와 선천성 고혈압의 소질을 지닌 SHR 실험쥐를 이용하여 천마의 water-extracts나 ethanol-extracts의 심장 및 관상 순환기능에 대한 약리적인 효능을 과학적으로 구체적인 실험방법을 통해서 조사하였다. 천마 extracts는 추출과정에 사용된 용매, 추출기간 및 실험쥐 model에 따라 관상 순환기능에 대한 작용효과가 상반된 현상으로 나타났다. 물이나 50% ethanol에 16시간 추출된 extracts는 사용된 농도에서 SD 실험쥐의 관상 혈관저항을 저하시켜 혈관확장의 효과를 가져왔지만, SHR 실험쥐에서는 ethanol에 추출된 extracts는 사용된 농도에서 심장기능 그 자체에 유의적인 독성효과를 주지 않는다는 것을 말해준다. 본 연구결과는 천마의 water-extracts에 의해서 나타난 혈관확장작용이 일반적으로 국소적인 혈관확장에 관여한다는 lactate 생성의 증가에 기인하는 것보다는 오히려 extracts에 의한 대사적 acidosis 현상에 기인한다는 사실을 제시하고 있다. 본 연구에서 천마의 수용성 extracts가 혈관확장작용 또는 혈압강하작용을 나타낸다는 사실이 제시된 것은 심장이나 순환기 질환을 예방하고 치료하기 위한 천마의 임상적인 활용측면에서 매우 중요한 성과이다. 그러나, 천마의 순환기능에 대한 약리적 효능을 나타내는 성분추출은 조사되어야 할 과제로 아직 남아 있다. 또한, 천마를 한방에서 약재로써 이용되는 반면에 천마를 식이로 이용하기 위해서 식이성 천마에 대한 효능을 연구해야 할 필요가 있다. 이러한 연구결과로써, 천마는 혈관순환기질환의 예방이나 치료에 이용되는 생약으로써 활용될 뿐만 아니라 안전성을 가진 건강식품으로 개발되어 국민보건 향상에 이바지하리라 기대된다.

• 인문언어
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• 제2권2호
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• pp.85-107
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• 2002

The word play on h(e)art-hunting has become a virtual commonplace in criticism of Chaucer′s Book of the Duchess. Less widely discussed is the third meaning of ME herte, "hurt." The "hart"/ "heart" pun is, however, only implicit in the poem, while the rhyme of "heart" and "hurt" in lines 883-84 makes clear the close association of the terms for Chaucer. Earlier commentators insisted that this was in fact an instance of rime riche or "identical rhyme," but if it is so it is striking that it is the unique instance of the rhyme in Chaucer, whose works are full of occasions for hurt hearts. The essay argues that this is, instead, an instance of near-rhyme and that the confusion in scribal spellings of ME hurten(with ′u,′ ′0,′ ′i,′ ′y,′ and ′e′ ) suggests uncertainties about its root vowel that modem linguistic study has not clarified completely. If the rhyme of herte ("hurt") with herte ("heart") is, however, established by these lines in BD, then it is probably reasonable to ask about all the occasions where characters in the poem are hurt by emotional or physical distress. In the cases of A1cyone and the Man in Blak, the hurt is revealed plainly as the death of a loved one, and Alcyone′s death and the Man in Blak′s return "homwarde" offer contrasting responses to the realization and acknowledgement of their loss. In the case of the Narrator, however, the exact nature of his "hurt" is nowhere made clear and the questions this Jack of clarity raises for the reader remain unanswered when the poem declares its "hert-huntyng" done. Further examination of the Narrator′s character and his role in the poem may reveal him to be a physician himself in need of healing, and this reading of his character may identify him as an ancestor as much of Chaucer′s Pardoner as of the Pilgrim Narrator of Canterbury Tales.

• Journal of Ginseng Research
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• 제39권3호
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• pp.206-212
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• 2015

Background: Ginseng total saponin (GTS) contains various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The aim of this study was to study the effects of GTS on cardiac injury after global ischemia and reperfusion (I/R) in isolated guinea pig hearts. Methods: Animals were subjected to normothermic ischemia for 60 minutes, followed by 120 minutes of reperfusion. GTS significantly increased aortic flow, coronary flow, and cardiac output. Moreover, GTS significantly increased left ventricular systolic pressure and the maximal rate of contraction ($+dP/dt_{max}$) and relaxation ($-dP/dt_{max}$). In addition, GTS has been shown to ameliorate electrocardiographic changes such as the QRS complex, QT interval, and RR interval. Results: GTS significantly suppressed the biochemical parameters (i.e., lactate dehydrogenase, creatine kinase-MB fraction, and cardiac troponin I levels) and normalized the oxidative stress markers (i.e., malondialdehyde, glutathione, and nitrite). In addition, GTS also markedly inhibits the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, and nuclear factor-${\kappa}B$, and improves the expression of IL-10 in cardiac tissue. Conclusion: These data indicate that GTS mitigates myocardial damage by modulating the biochemical and oxidative stress related to cardiac I/R injury.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.301-301
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• 1994

〔$^3$H〕Ouabain binding parameters(K$\_$D/ and B$\_$max/,) in homogenates prepared fpom control rat ventricular strip and Langendorff preparations which were not previously exposed to ouabain were compared to those in homogenates from ventricular strip and Langendorff preparations that had been first exposed to a complete ouabain dose-response curve(10$\^$-7/M to 10$\^$-4/ M). In rat ventricular strips and Langendorff perfused rat heart preparations, cumulative dose-response cruves of ouabain revealed biphasic positive inotropic effects, a "low-dose" and a "high-dose" effect with ED$\_$50/ values of 0.5${\mu}$M and 35${\mu}$M ouabain, respectively- The "low-dose" effect in rat ventricular strips disappeared or was diminished significantly when the ouabain dose-response curve wag repeated after the washout of the effects of the first curve, whereas the maximal "high-dose" effect was identical in both exposures to oubain. However, there was no change in the "low-dose" effects in both sets of the Langendorff perfused hearts. The contractile activity of the pre-exposed strips did not indicate the presence of residual ouabain since their basal contractile force was decreased 10% compared to initial control. 〔$^3$H〕Ouabain binding parameters, K$\_$D/ and B$\_$max/, were not changed comparing homogenate of control ventricular strips with that of strips pre-exposed to ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site(${\alpha}$$_2$ isoform).

• Clinical and Experimental Pediatrics
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• 제56권4호
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• pp.176-181
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• 2013

Purpose: Apical muscular ventricular septal defects (MVSDs), especially in small infants, can be difficult to manage using surgical and percutaneous closure. An intraoperative perventricular procedure is a good option for closing apical MVSDs in small children with or without associated cardiac anomalies. We evaluated the results of hybrid perventricular closure of apical MVSDs performed using an Amplatzer duct occluder (ADO). Methods: We retrospectively reviewed the medical records of 5 patients who underwent hybrid perventricular closure of MVSDs with ADOs, from March 2006 to May 2011. The median patient age at the time of the procedure was 12 months (range, 25 days to 25 months), and the median body weight was 9.1 kg (range, 4.3 to 15 kg). Two patients had multiple ventricular septal defects (VSDs; additional perimembranous VSD in 1 patient and multiple MVSDs in the other) and 3 patients had associated cardiac anomalies; complete transposition of the great arteries in 1 patient and an atrial septal defect in 2 patients. All the procedures were performed on beating hearts, exception in 1 case. The ADO selected for the aortic side was at least 1 to 2 mm larger than the largest VSD in the left ventricle side. Results: The procedure was successful in all patients and each device was well positioned. During the median follow-up of 2.4 years, a small residual VSD was noted in 2 patients who had multiple VSDs and no leakage was seen in the other 3 patients. Conclusion: Perventricular closure of MVSD with an ADO is a good option for patients with apical MVSD. However, careful manipulation is important, especially in the case of small infants.

• The Korean Journal of Physiology and Pharmacology
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• 제7권6호
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• pp.333-339
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• 2003

It has been demonstrated that an unidentified cytosolic factor(s) reduces $K_{ACh}$ channel function. Therefore, this study attempted to elucidate the cytosolic factor. Fresh cytosol isolated from normal heart (FC) depressed the $K_{ACh}$ channel activity, but cytosol isolated from the ischemic hearts (IC) did not modulate the channel function. Electrophorectic analysis revealed that a protein of ${\sim}80 kDa was markedly reduced or even lost in IC. By using peptide sequencing analysis and Western blot, this 80 kDa protein was identified as transferrin (receptor-mediated $Fe^{3+}$ transporter, 76 kDa). Direct application of transferrin (100 nM) to the cytoplasmic side of inside-out patches decreased the open probability ($P_o$, 12.7${\pm}6.4%, n=4) without change in mean open time (${\tau}_o$, $98.5{\pm}1.3$%, n=4). However, the equimolar apotransferrin, which is free of $Fe^{3+}$, had no effect on the channel activity (N*$P_o$, $129.1{\pm}13.5$%, n=3). Directly applied $Fe^{3+}$ (100 nM) showed results similar to those of transferrin (N*$P_o$: $21.1{\pm}3.9$%, n=5). However $Fe^{2+}$ failed to reduce the channel function (N*$P_o$, $106.3{\pm}26.8$%, n=5). Interestingly, trivalent cation La3+ inhibited N*$P_o$ of the channel ($6.1{\pm}3.0$%, n=3). Taken together, these results suggest that $Fe^{3+}$ bound to transferrin can modulate the $K_{ACh}$ channel function by its electrical property as a polyvalent cation.

• Advances in Traditional Medicine
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• 제4권3호
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• pp.157-161
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• 2004

We showed the effects of the traditional herbal medicine, Jukyeoondam-tang (JO-T, Zhu-ru-Wen-Dan-Tang in Chinese), on ventricular arrhythmia induced by aconitine. Electrophysiological experiments with conventional microelectrode techniques revealed that JO-T potently suppressed the aconitine-induced arrhythmias in ventricular strips of the rat. In the aconitine-induced arrhythmia model of the rat, pretreatment with JO-T $(100\;{\mu}g/ml)$ completely occluded the appearance of ventricular tachyarrhythmia (VT) or ventricular fibrillation (VF) induced by aconitine. Furthermore, the aconitine-induced ventricular arrhythmia was occluded by $Na^+$ channel blocker quinidine but was not occluded by $K^+$ channel blocker glibenclamide $(3\;{\mu}mol/L)\;and\;Ca^{2+}$ channel blocker nifedipine $(10\;{\mu}mol/L)$. We also confirmed the effect of JO-T in the ischemia-reperfusion (I/R)-induced arrhythmia model of the rat. JO-T did not affect the I/R-induced arrhythmias in rats. JO-T may alleviate the risk of ventricular arrhythmias following aconitine. These results suggest that JO-T is a potent antiarrhythmic drug having a$Na^+$ channel-blocking action.

• 디지털콘텐츠학회 논문지
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• 제13권4호
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• pp.547-557
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• 2012

청소년들은 자신의 부정적인 경험과 감정에 대하여 자신은 마음에 상처를 받았다고 표현하고 있다. 이러한 마음의 상처의 근본원인을 다른 사람이나 외부적인 환경에서 찾고자 한다. 청소년들은 과거의 사건을 재조명하여 기억의 치유를 하고자 한다. 본 연구는 청소년의 상담을 위해 마음의 병과 관련된 원인과 증상 정보를 제공하기 위한 마음의 병 온톨로지를 설계하였다. 온톨로지를 사용하는 경우 대용량, 복잡한 지식의 체계적 구축이 용이하고, 의미 있는 정보로 저장이 가능하다. 또한 복잡한 기존 상담용어 체계들 간 통합을 위한 도구로 매우 유용하다. 그리고 궁극적으로 자료의 재사용과 공유를 활성화함으로써 내담자 중심의 상담서비스 제공이 가능하게 된다. 따라서 본 연구는 내담자 개개인의 맞춤형 상담 서비스를 제공하기 위한 방법으로 내담자의 마음의 병의 원인 및 증상을 분석하여 청소년 상담을 위한 마음의 병 온톨로지를 구축하였다.

• Journal of Chest Surgery
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• 제28권6호
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• pp.533-541
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• 1995

We recently developed a new model of moving actuator type totally implantable artificial heart[TIAH , based on the reverse position of the aortic and pulmonary conduits. This concept was proposed by one of surgeons in our team[Joon-Ryang Rho, M.D. to facilitate anatomical fitting of TIAHs. The moving actuator type electromechanical TIAH consisted of the left and right blood sacs, and the moving actuator including a motor. The inverted umbrella type polyurethane valves were used in the blood pumps. The aortic conduit was positioned anterior to the pulmonary conduit, which was the opposite relation to the conventional configuration of other total artificial hearts. We also adapted slip-in connectors for the aortic and pulmonary conduits. Two sheep , weighing 60-69 kg, were used for implantation. After small cervical incision and trans-sternal bilateral thoracotomy, cardiopulmonary bypass [CPB was administered using an American Optical 5-head pump and a membrane oxygenator[Univox-IC, Bentley . The anterior and posterior vena cavae were drained separately for venous return. An arterial return cannula was inserted into the right common carotid artery. During CPB, almost all of the ventricular myocardium was excised down to the atrioventricular groove and the artificial heart was implanted. We achieved 3-day survival in the first sheep and 2-day survival in the second. The day after operation the first sheep was successfully extubated and the second sheep was weaned from a respirator with good condition. After extubation, the first sheep walked around in the cage and fed herself. Serial laboratory and hemodynamic examinations were done during the experiments. In both sheep, pulmonary dysfunction was gradually developed, which was accompanied by acute renal failure. The animals were sacrificed and autopsy was done. Unexpected pregnnacy was incidentally found in both sheep. To our knowledge this is the first report of significant survival cases in the orthotopic implantation of electric TIAH using sheep.