• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.641-647
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• 2016

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats. Using hematoxylin and eosin staining, we confirmed vascular remodeling (i.e., medial thickening of PA) and right ventricle hypertrophy in PAH-MCT rats. The basal pulmonary arterial pressure (PAP) and PAP increase by a raised flow rate (40 mL/min) were higher in the PAH-MCT than in the control rats. In addition, both high $K^+$ (40 mM KCl)- and angiotensin II-induced PAP increases were higher in the PAH-MCT than in the control rats. Surprisingly, application of a nitric oxide synthase inhibitor, L-$N^G$-Nitroarginine methyl ester (L-NAME), induced a marked PAP increase in the PAH-MCT rats, suggesting that endothelial functions were recovered in the three-week PAH-MCT rats. In addition, the medial thickening of the PA was similar to that in chronic hypoxia-induced PAH (PAH-CH) rats. However, the HPV response (i.e., PAP increased by acute hypoxia) was not affected in the MCT rats, whereas HPV disappeared in the PAH-CH rats. These results showed that vascular contractility and HPV remain robust in the MCT-induced PAH rat model with vascular remodeling.

• Journal of Nutrition and Health
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• v.30 no.10
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• pp.1123-1131
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• 1997

This study examined the effect of dietary lipids and guar gum on lipid metabolism in ovariectomized rats. The experimental animals received ovarietomy (OVX). Lipids sources were divided into 3 groups (soybean oil(SB), beef tallow(BT)) and fish oil(FO)) and guar gum was supplemented to each lipid diet (SBG, BTG, FOG). Experimental diets were fed to therats for 16 weeks. Serum triglyceride (TG) levels were higher in the BT group and lower in the FO group as compared to the SB group .Serum total cholesterol (Tc) and HDL-C levels were lower in the FO group as compared to the SB group. Serum LDL-C and phospholipid levels were lower in the FO group as compared to the SB group. Serum lipids levels were lowered by guar gum supplement. Serum SFA(saturated fatty acids) contents were not significantly influenced by dietary lipids and guar gum. Serum MUFA(monounsaturated fatty acids) contents were the lowest in the SB group. Fecal weight was highest in the beef tallow group and lowest in the fish oil group. Fecal weight was increased by guar gum supplement in all lipid groups. Total bile acid content in feces was increased by guar gum supplement in the soybean oil and beef tallow groups. The endothelial cells of the beef tallow group changed from a flat shape to distorted round and enlarged shapes. The subendothelial layer was the thickness the thickest in the beef tallow group ; the interspace between elastic lamina was widened and elastic lamina was straightened and partly disrupted . The fish oil group showed more porminient endothelial cells and subendothelial layer. Internal elastic membrane and elastic lamina exhibited regularly wavy shapes. Guar gum supplement showed positive effects in all lipids groups. Based on the above results , it is suggested that beef tallow increased serum TG levels and injured the wall of the aorta. On the other hand, fish oil , which decreased serum lipid levels, has a positive effect on the walls of the aorta. Guar gum protects the aorta from injury by reducing the serum lipid levels. Therefore, it is suggested that soybean oil and beef tallow consumed with guar gum is beneficial.

• Journal of Gastric Cancer
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• v.11 no.1
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• pp.16-22
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• 2011

Purpose: Eupatilin is an antioxidative flavone and a phytopharmaceutical derived from Artemisia asiatica. It has been reported to possess anti-tumor activity in some types of cancer including gastric cancer. Eupatilin may modulate the angiogenesis pathway which is part of anti-inflammatory effect demonstrated in gastric mucosal injury models. Here we investigated the anti-tumor effects of eupatilin on gastric cancer cells and elucidated the potential underlying mechanism whereby eupatilin suppresses angiogenesis and tumor growth. Materials and Methods: The impact of eupatilin on the expression of angiogenesis pathway proteins was assessed using western blots in MKN45 cells. Using a chromatin immunoprecipitation assay, we tested whether eupatilin affects the recruitment of signal transducer and activator of transcription 3 (STAT3), aryl hydrocarbon receptor nuclear translocator (ARNT) and hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) to the human VEGF promoter. To investigate the effect of eupatilin on vasculogenesis, tube formation assays were conducted using human umbilical vein endothelial cells (HUVECs). The effect of eupatilin on tumor suppression in mouse xenografts was assessed. Results: Eupatilin significantly reduced VEGF, ARNT and STAT3 expression prominently under hypoxic conditions. The recruitment of STAT3, ARNT and HIF-$1{\alpha}$ to the VEGF promoter was inhibited by eupatilin treatment. HUVECs produced much foreshortened and severely broken tubes with eupatilin treatment. In addition, eupatilin effectively reduced tumor growth in a mouse xenograft model. Conclusions: Our results indicate that eupatilin inhibits angiogenesis in gastric cancer cells by blocking STAT3 and VEGF expression, suggesting its therapeutic potential in the treatment of gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8793-8796
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• 2014

Objective: To explore the influence of serum vascular endothelial growth factor (VEGF) level on therapeutic outcome and diagnosis/prognostic value in patients with cervical cancer. Materials and Methods: A total of 37 patients diagnosed with cervical cancer by biopsy were selected and treated with concurrent chemoradiotherapy. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was adopted before treatment to assess VEGF levels, and its relationships with clinicopathological features and short-term therapeutic effects were analyzed. Results: The median VEGF level in 37 patients before treatment was 647.15 (393.35~1125.16) pg/mL. Serum VEGF levels in patients aged <50 years, in International Federation of Gynecology and Obstetrics (FIGO) stage IIIa~IVa, with lymph node metastasis and tumor size >4 cm were significantly increased (P<0.05). The complete remission (CR) rate was 48.7% (18/37), partial remission (PR) rate was 35.1% (13/37), stable disease (SD) rate was 13.5% (5/37) and progressive disease (PD) rate was 2.70% (1/37), so the objective remission rate (ORR) after treatment was 83.8% (31/37). Logistic regression analysis showed that tumor size and serum VEGF level before treatment were independent risk factors affecting the therapeutic outcome, and the higher the level of serum VEGF, the worse the prognosis when tumor size>4 cm. Some 56.8% of patients manifested with myelosuppression, 37.8% with leucopenia, 24.3% with thrombocytopenia, 5.41% with diarrhea, 46.0% with nausea and vomiting, 21.6% with hair loss and 8.11% with hepatic and renal injury during the treatment. Conclusions: Serum VEGF level may reflect the degree of malignancy of cervical cancer and predict therapeutic effect, which is of great importance to cancer diagnosis and prognosis.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.1
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• pp.1-15
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• 2015

Objectives The aim of this study was to investigate the effects of Cannabis Fructus on exercise capacity and cognitive function in chronic hypoperfusion induced vascular dementia rat model. Methods Vascular dementia rat models were induced by chronic cerebral hypoperfusion through bilateral common carotid arteries occlusion (BCCAO). All rats were randomly divided into 4 groups: normal group; control group; CF I group (feeding Cannabis Fructus 100 mg/kg); CF II group (feeding Cannabis Fructus 300 mg/kg). In order to study the effects of oral administration of Cannabis Fructus on vascular dementia rat models, corner turn test, hole board test, radial arm maze test, passive avoidance test were taken and Acetylcholine (ACh) activity, Acetylcholinesterase (AChE) activity, serum of Vascular endothelial growth factor (VEGF) protein level were measured. Also histological findings of the liver, kidney, brain and the change of Tau immunoreactive neurons in hippocampus were observed. Results CF I and CF II showed significant improvement in corner turn test, hole board test, radial arm maze test, passive avoidance test, Acetylcholine (ACh) activity, Acetylcholinesterase (AChE) activity, the serum of Vascular endothelial growth factor (VEGF) protein level and the change of Tau immunoreactive neurons in hippocampus. CF I showed more significant effect than CF II in these tests. However in histological observations of the liver and kidney both CF I and CF II showed glomerular injury and hepatotoxicity. Conclusions These results suggest that Cannabis Fructus was helpful in improving exercise capacity and cognitive function on Chronic hypoperfusion induced Vascular Dementia rats. However Cannabis Fructus affects the liver and kidney, therefore suggest that this is an area for further study.

• Journal of Veterinary Clinics
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• v.28 no.1
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• pp.52-56
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• 2011

Acute renal injury induced by ischemia is a major cause of high morbidity and mortality in hospitalized patients and a common complication in hospitalized patients. Thus, the work with acute renal failure and renal ischemia has been studied for many years. Although serum creatinine concentration that is widely used as an index of renal function performs fairly well for estimating kidney function in patients with stable chronic kidney disease, it performs poorly in the setting of acute disease. Thus, an ideal biomarker for acute kidney injury would help clinicians and scientists diagnose the most common form of acute kidney injury in hospitalized patients, acute tubular necrosis, early and accurately, and may aid to risk-stratify patients with acute kidney injury by predicting the need for renal replacement therapy, the duration of acute kidney injury, the length of stay and mortality. In this study, renal ischemia and reperfusion were performed by clapming and un-clamping right renal artery in miniature pigs. Plasma blood urea nitrogen (BUN) and creatinine were examined at pre- clamping, after-clamping at 0, 1 and 3 hours. And we searched initial indicators in these samples. Also, renal tissue was collected and searched the initial indicator by PCR and western blotting. As a result, hypoxia inducible factor $1{\alpha}$ ($HIF1{\alpha}$), nuclear factor kappa-B ($NF{\kappa}B$), $I{\kappa}B$, erythropoietin (EPO), erythropoietin receptor (EPOR), angiopoietin-1 and vascular endothelial growth factor (VEGF) were showed significant changes among the renal protein. $HIF1{\alpha}$, EPO, and EPOR were showed significant changes among the renal gene. Thus, these markers will be used as initial diagnosis of acute renal failure.

• Journal of Radiation Protection and Research
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• v.42 no.4
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• pp.189-196
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• 2017

Background: The effects of radiation on tissues vary depending on the radiation type. In this study, a minipig model was used to compare the effects of ${\beta}$-rays from $^{166}Ho$ and ${\gamma}$-rays from $^{60}Co$ on the skin. Materials and Methods: In this study, the detrimental effects of ${\beta}$- and ${\gamma}$-irradiation on the skin were assessed in minipigs. The histopathological changes in the skin from 1 to 12 weeks after exposure to 50 Gy of either ${\beta}$- (using $^{166}Ho$ patches) or ${\gamma}$- (using $^{60}Co$) irradiation were assessed. Results and Discussion: The skin irradiated by ${\beta}$-rays was shown to exhibit more severe skin injury than that irradiated by ${\gamma}$-rays at 1-3 weeks post-exposure; however, while the skin lesions caused by ${\beta}$-rays recovered after 8 weeks, the ${\gamma}$-irradiated skin lesions were not repaired after this time. The observed histopathological changes corresponded with gross appearance scores. Seven days post-irradiation, apoptotic cells in the basal layer were detected more frequently in ${\beta}$-irradiated skin than in ${\gamma}$-irradiated skin. The basal cell density and skin thickness gradually decreased until 4 weeks after ${\gamma}$- and ${\beta}$- irradiation. In ${\beta}$-irradiated skin lesions, and the density and thickness increased sharply back to control levels by 6-9 weeks. However, this was not the case in ${\gamma}$-irradiated skin lesions. In ${\gamma}$-irradiated skin, cyclooxygenase-2 (COX-2) was shown to be expressed in the epidermis, endothelial cells of vessels, and fibroblasts, while ${\beta}$-irradiated lesions exhibited COX-2 expression that was mostly limited to the epidermis. Conclusion: In this study, ${\beta}$-rays were shown to induce more severe skin injury than ${\gamma}$-rays; however, the ${\beta}$-rays-induced injury was largely repaired over time, while the ${\gamma}$-rays-induced injury was not repaired and instead progressed to necrosis. These findings reveal the differential effects of ${\gamma}$- and ${\beta}$-irradiation on skin and demonstrate the use of minipigs as a beneficial experimental model for studying irradiation-induced skin damage.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.25 no.4
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• pp.281-294
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• 1999

Vasospasm causes microvascular surgery to fail as a main factor in the loss of transferred flap dye to the diminution of blood flow in reconstruction surgery. Although there has been extensive research to resolve the vasospasm problem, no one has reached an ideal solution to date. However, cryotherapy, which is often used for destruction of tumor lesions, is being presented as a new way of releasing vasospasm. After making a histomorphometric measurement on vasodialation during the course of 1, 3 and 7 days, 2 and 4 weeks, and 5 months periods and observing the change of blood vessel in a histologic, immunohistochemical, and scanning electronic microscopic approach, the results were as follows : 1. Vascular inner diameters of the experimental 1 and 3 days groups were measured $476.3{\pm}28.20{\mu}m$, $497.15{\pm}48.79{\mu}m$ respectively showing statistically meaningful vasodilation(P<0.05), which continued by the experiment 4 weeks group. However, in the experimental 5 months group, the vascular inner diameter appeared similar to the control groups. Even though the thickness of smooth muscular layers come out to be thinner in all the experimental groups compared to the control group, it was difficult to find any statistical meaningfulness. In addition, the vascular external diameters of every experimental groups were shown to be longer than the control group. 2. In light microscopic view, severe injury was evident on the smooth muscular layer cell from the experimental 1 day group, started recovering partially from the experimental 7 days group, and was mostly restored in the experimental 4 weeks group and layer of adventitial stripping were nearly recoverd 2 weeks group. 3. The PCNA positive cells of smooth muscular layer were observed from the experimental 7 days group and had a tendency to increase by the experimental 2 weeks group. In the experimental 4 weeks and 5 months group, the number of PCNA possitive cells observed was comparable to the control group. 4. ${\alpha}$-SMA level of smooth muscular layer cells, having been significantly lower than the control group in the severly damaged experimental 1 day group. It was seen to be increased in the experimental 7 days group and turned out to show similar ${\alpha}$-SMA level in 4 weeks to the control group. 5. In the view of SEM, the endothelial cells were destructed and falling off, and also present the appearance of flattening in the experiment 1 day group. The endothelial layer cells started partially recovering from the 7 days group after the freezing injury. On 4 weeks and 5 months, the endothelial cells were fully coverd the damaged area, also it's appearance is similar to control group. In conclusion, the vascular freezing after the removal of adventitia caused damages to smooth muscular layer cells, and brought about vasodilation, which continued by the 4th week. The smooth muscular layer cells started partially reviving from the 7rd day after the damage by vascular freezing, and recovered their similar figure to the control group's 4 weeks later. This was considered the result of cells which surround the damaged blood vessel being influxed into the smooth muscular layers. Therefore, this local freezing injury on the blood vessel was thought to be applied clinically to relieve severe vasospasm which cannot be treated by vasodilation drug, a microvascular surgery.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.512-522
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• 1999

Background: Due to the paucity of suitable donor organs for lung allotransplantation, a number of techniques have been developed to improve the lung preservation. Ultrastructural studies of the morphologic changes of the flushing, preservation and reperfusion injury in donor lungs have rarely been reported. Methods: Adult dogs (n=46) were matched as donors and recipients for the single lung transplantation. The donor lungs were preserved after flushing with preservation solution and transplanted after 20-hours of preservation at $10^{\circ}C$. Ultrastructural features of the lung were examined after flushing, preservation and 2 hours after lung transplantation (reperfusion) respectively. Results: Electron microscopy after flushing showed focal alveolar collapse and mild swelling of type I epithelial cells. After preservation both type I epithelial cells and endothelial cells were swollen and destroyed focally. The endothelial cells showed protrusion of tactile-like structures into the lumina, blebs or vacuoles of the cytoplasm After reperfusion the lung tissue showed fibrin material in the alveoli, prominent type I epithelial cell swelling with fragmented cytoplasmic debris and marked endothelial cell swelling with vacuoles or tactile-like projections. The alveolar macrophages showed active phagocytosis. Scanning electron microscopic examination of the pulmonary parenchyma showed focally alveolar collapse and focal consolidation after the preservation and more prominent changes after the reperfusion procedure. The lungs preserved with low potassium dextran glucose solution, with additional prostaglandin $E_1(PGE_1)$ and verapamil(VP) showed relatively well preserved ultrastructures compared with those which were preserved with modified Euro-Collins or University of Wisconsin, and with additional $PGE_1$ and/or VP. Conclusion: The ultrastructural changes associated with flushing were mild in severity, the donor lungs were injured during the preservation, and further damage was occurred during the reperfusion. The reperfusion injury resulted in prominent pulmonary parenchymal alterations with a pattern of acute lung injury.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.281-290
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• 1996

Purpose : Chest irradiation leads to a significant cardiac injury in a number of patients. To prevent, or to reduce the risk of radiation-induced cardiac injury, pentoxifylline(PTX), a haemorrheologic agent that improves the blood flow through small blood capillaries has been employed. Materials and Methods : One hundred and eighty ICR mice were divided into three study groups: control, radiation alone, and radiation-pentoxifylline. Each group was subdivided into 12 subgroups: 1 3, 6 and 10 days and 2, 3, 4, 6, 8, 12, 16 and 20 weeks by observation Period after irradiation. The total 15Gy of radiation was delivered in a single fraction through anterior mediastinal port. Pentoxifylline was injected subcutaneously daily 50mg/kg to the back of the mice from the first day of irradiation throughout the observation period. The mice of each group after a certain observation period were sacrificed and sectioned for histopathologic examination of the heart. Result : The findings of acute radiation-induced carditis i.e., heterophilic infiltration and vacuolization and ballooning of endothelial cells were observed upto 6 weeks and reduced sharply afterwards. The late radiation effects including pericarditis with mononuclear cell infiltration, pericardial fibrosis, endothelial cell changes, myocardial degeneration and fibrosis present from 4 weeks onwards after irradiation but with various degree of severity. The overall process of pathologic changes of radiation-pentoxifylline group was similar to those of radiation alone group but the duration of acute stage was relatively short and the severity of late cardiac toxicity was much lesser compared with those of radiation alone group. Conclusion : Pentoxifylline can effectively reduce the late radiation-induced cardiac injury and reslve the acute effects relatively rapidly.