• The Korean Journal of Physiology and Pharmacology
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• 제20권6호
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• pp.657-667
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• 2016

Critical limb ischemia (CLI) is one of the most severe forms of peripheral artery diseases, but current treatment strategies do not guarantee complete recovery of vascular blood flow or reduce the risk of mortality. Recently, human bone marrow derived mesenchymal stem cells (MSCs) have been reported to have a paracrine influence on angiogenesis in several ischemic diseases. However, little evidence is available regarding optimal cell doses and injection frequencies. Thus, the authors undertook this study to investigate the effects of cell dose and injection frequency on cell survival and paracrine effects. MSCs were injected at $10^6$ or $10^5$ per injection (high and low doses) either once (single injection) or once in two consecutive weeks (double injection) into ischemic legs. Mice were sacrificed 4 weeks after first injection. Angiogenic effects were confirmed in vitro and in vivo, and M2 macrophage infiltration into ischemic tissues and rates of limb salvage were documented. MSCs were found to induce angiogenesis through a paracrine effect in vitro, and were found to survive in ischemic muscle for up to 4 weeks dependent on cell dose and injection frequency. In addition, double high dose and low dose of MSC injections increased vessel formation, and decreased fibrosis volumes and apoptotic cell numbers, whereas a single high dose did not. Our results showed MSCs protect against ischemic injury in a paracrine manner, and suggest that increasing injection frequency is more important than MSC dosage for the treatment CLI.

• 대한한방내과학회지
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• 제30권4호
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• pp.719-731
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• 2009

Objectives : Stroke is the most common disabling neurological disease of adult life. The treatment and rehabilitation of stroke patients is an important and challenging area in the field of medicine. In Korea, a lot of stroke patients are treated using oriental medicine and there have been reports on their functional recovery. The aim of this study was to prove the therapeutic effect of oriental medicine on ischemic stroke. We also tried to identify characteristics of patients whose functional recovery was prominent and studied whether or not the use of fluids, anticoagulants, antiplatelets and neuroprotective agents increased the functional recovery of patients. Methods : We studied 794 patients within 2 weeks after first attack of ischemic stroke who were admitted to Kyung-Hee Oriental Medical Center from 1999 to 2000. Their maximum admission period was 60 days. Results : Motor power grade, NIHSS and MBI scores of patients improved during hospitalization significantly. Factors affecting functional recovery were admission period, motor power grade, NIHSS and MBI at admission. Age, waist-hip ratio and HDL cholesterol also affected functional recovery of patients. Whether or not fluids, anticoagulants, antiplatelets and neuroprotective agents were administered had nothing to do with functional recovery. Conclusion : Oriental medicine is effective for treatment and rehabilitation of ischemic stroke patients. When we manage stroke, we have to consider some important factors.

• Journal of Chest Surgery
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• 제26권2호
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• pp.115-121
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• 1993

Between March, 1988 and July, 1992, 114 patients underwent Open Heart Surgery under hypothermic cardiopulmonary bypass. There were 29 cases of congenital heart anomalies (25％), and 85 cases of acquired heart diseases (75％) consisting of 53 cases of valvular heart disease, 31 cases of ischemic heart disease, and a case of left atrial myxoma. The age distribution of 114 cases was 4 to 73 years, and mean age was 43 years old consisting of mean age of congenital heart disease 23, valvular heart disease 47, and ischemic heart disease 57 years old. Overall operative mortality was about 7.9％.

• Childhood Kidney Diseases
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• 제8권1호
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• pp.86-90
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• 2004

저자들은 복통과 구토, 혈변을 주소로 내원한 환아의 바륨 대장 조영술에서 무지문양(thumb-printing)을 확인하여 허혈성 대장염 진단하에 치료 중 미세혈관성 용혈성 빈혈과 혈소판 감소, 전해질 불균형과 급격한 소변량 감소의 급성 신부전 소견을 확인하고 허혈성 대장염에 동반된 용혈성 요독 증후군을 경험하였기에 문헌고찰과 함께 보고하는 바이다.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.55-63
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• 2022

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to exert protective effects against several neurological diseases through its anti-oxidative and anti-inflammatory activities. The goal of the present study was to evaluate the therapeutic potential of OA against acute and chronic brain injuries after ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO, MCAO/reperfusion). OA administration immediately after reperfusion significantly attenuated acute brain injuries including brain infarction, functional neurological deficits, and neuronal apoptosis. Moreover, delayed administration of OA (at 3 h after reperfusion) attenuated brain infarction and improved functional neurological deficits during the acute phase. Such neuroprotective effects were associated with attenuation of microglial activation and lipid peroxidation in the injured brain after the tMCAO challenge. OA also attenuated NLRP3 inflammasome activation in activated microglia during the acute phase. In addition, daily administration of OA for 7 days starting from either immediately after reperfusion or 1 day after reperfusion significantly improved functional neurological deficits and attenuated brain tissue loss up to 21 days after the tMCAO challenge; these findings supported therapeutic effects of OA against ischemic stroke-induced chronic brain injury. Together, these findings showed that OA exerted neuroprotective effects against both acute and chronic brain injuries after tMCAO challenge, suggesting that OA is a potential therapeutic agent to treat ischemic stroke.

• 대한중풍순환신경학회지
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• 제13권1호
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• pp.1-12
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• 2012

Object : This is a study of ischemic stroke patients designed for comparison Combination therapy of western medical treatment and oriental medical treatment. and western medical treatments alone. Methods : 45 patients were diagnosed by Br-MRI scan as having suffered ischemic stroke. They had entered Kyung-Hee Medical hospital within ten days of attack, between March 2011 and October 2012. Patients were divided into two groups; a group treated with Combination therapy of western medical treatment and oriental medical treatment and other group treated with Western medical treatments. Scandinavian stroke scale and Motricity Index score was checked at admission, 2 weeks or 3 weeks later to assess neurologic improvement and motor function recovery. Results : Comparing the Scandinavian stroke scale and Motricity Index score between baseline and 2 or 3 weeks later, the combination therapy group and western medical treatment group had improved but there was no significance. Conclusions : Combination therapy have more beneficial effect on acute stage of stroke.

• 대한핵의학회:학술대회논문집
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• 대한핵의학회 2000년도 2nd Korea-China Congress of Nuclear Medicine and 39th Annual Spring Meeting if the Korea SOciety Nuclear Medicine
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• pp.61-61
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• 2000

• Journal of Chest Surgery
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• 제27권6호
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• pp.460-471
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• 1994

Between Feb. 1990 and Aug. 1993, 180 cases of the open heart surgery were performed under cardiopulmonary bypass in the Department of Thoracic & Cardiovascular surgery, Gil General Hospital. There were 83 cases with congenital heart diseases [CHD] and 97 cases with acquired heart diseases [AHD]. The CHD consisted of 78 acyanotic[mortality: 3.8 %] and 5 cyanotic cases with heart anomaly[mortality:l case]. The AHD were 97 cases, which contained 53 valvular, 27 ischemic heart diseases, 10 aortic diseases, 5 cases with myxoma, 1 case with post-infarct VSD, and 1 case with removal of infected pacing wire in right ventricle. In the 53 valvular heart diseases, there were 45 cases with valve replacement[MVR 27, AVR 9,MVR + AVR 9] and 8 cases with valvuloplasty. The number of the implanted prosthetic valves were 53. In MVR, 25 St. Jude, 6 Sorin, 3 Carpentier-Edward and 2 Intact medical valves were used. In aortic position, 13 St. Jude, 3 Sorin and 1 Intact medical valves were applied. The operative mortality was 5.6 % [3/53]. The annuloplasty applying artificial ring was performed in 17 patients[4 cases associated with MVR] and the number of the implanted ring was 19, which included 14 Duran ring[10 mitral, 4 tricuspid] and 5 Carpentier ring [3 mitral, 22 tricuspid]. In the 27 ischemic heart diseases, there were 9 cases with left main coronary artery lesions, 7 one vessel, 5 two vessels, and 6 three vessels. Average number of anastomosis was 2.8 per patient. The operative mortality was 14.3 % [4/27]. Among the 10 patients with aortic diseases, 7 cases were aortic dissection[type A: 5, type B: 2] and 3 cases were descending thoracic aortic aneurysm. The operative morality occurred in 3 cases. The overall mortality and the operative mortality of congenital and acquired heart disease was 7.8 %, 4.8% and 10.4%, respectively.

• Journal of Korean Neurosurgical Society
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• 제50권6호
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• pp.492-496
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• 2011

Objective : Direct revascularization surgery is regarded as the most effective method of treatment of adults with moyamoya disease. These patients, however, have a higher risk of perioperative ischemic complications than do patients with atherosclerotic stroke, and are at risk for ischemic complications in the hemisphere contralateral to the one operated on. We investigated the incidence and risk factors for ischemic stroke in the contralateral hemisphere after surgical treatment of adults with moyamoya disease. Methods : We retrospectively reviewed the medical records and results of neuroimaging studies on 79 hemispheres of 73 consecutive patients with adult moyamoya disease ($mean{\pm}SD$ age, $37.96{\pm}11.27$ years; range, 18-62 years) who underwent direct bypass surgery over 6 years. Results : Ischemic complications occurred in 4 of 79 (5.1%) contralateral hemispheres, one with Suzuki stage 3 and three with Suzuki stage 4. Three patients showed posterior cerebral artery (PCA) involvement by moyamoya vessels. Advanced stage of moyamoya disease (Suzuki stages 4/5/6; $p$=0.001), PCA involvement ($p$=0.001) and postoperative hypotension (mean arterial blood pressure <80% of preoperative mean arterial blood pressure) on the first ($p$<0.0001) and second ($p$=0.003) days after surgery were significantly correlated with postoperative contralateral ischemic complications. Conclusion : In patients with advanced moyamoya disease and involvement of the PCA, intentional hypotension can result in ischemic stroke in the hemisphere contralateral to the one operated on. Careful control of perioperative blood pressure is crucial for good surgical results.

• Toxicological Research
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• 제24권2호
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• pp.101-107
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• 2008

Studies on hypoxia-signaling pathways have revealed novel Fe(II) and $\alpha$-ketoglutarate-dependent dioxygenases that hydroxylate prolyl or asparaginyl residues of a transactivator, Hypoxia-Inducible $Factor-\alpha(HIF-\alpha)$ protein. The recognition of these unprecedented dioxygenases has led to open a new paradigm that the hydroxylation mediates an instant post-translational modification of a protein in response to the changes in cellular concentrations of oxygen, reducing agents, or $\alpha$-ketoglutarate. Activity of $HIF-\alpha$ is repressed by two hydroxylases. One is $HIF-\alpha$ specific prolyl-hydroxylases, referred as prolyl-hydroxylase domain(PHD). The other is $HIF-\alpha$ specific asparaginyl-hydroxylase, referred as factor-inhibiting HIF-1(FIH-1). The facts (i) that many dioxygenases commonly use molecular oxygen and reducing agents during detoxification of xenobiotics, (ii) that detoxification reaction produces radicals and reactive oxygen species, and (iii) that activities of both PHD and FIH-1 are regulated by the changes in the balance between oxygen species and reducing agents, imply the possibility that the activity of $HIF-\alpha$ can be increased during detoxification process. The importance of $HIF-\alpha$ in cancer and ischemic diseases has been emphasized since its target genes mediate various hypoxic responses including angiogenesis, erythropoiesis, glycolysis, pH balance, metastasis, invasion and cell survival. Therefore, activators of PHDs and FIH-1 can be potential anticancer drugs which could reduce the activity of HIF, whereas inhibitors, for preventing ischemic diseases. This review highlights these novel dioxygenases, PHDs and FIH-1 as specific target against not only cancers but also ischemic diseases.