• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.4
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• pp.506-510
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• 2010

As an attempt to develop new functional health beverage by using medicinal herb, we investigated the effect of medicinal plant extract (MPE) on mean arterial blood pressure (MABP) and regional cerebral blood flow (rCBF) of rats. The changes of MABP and rCBF were determined by LDF methods. LDF allows for real time, noninvasive, continuous recordings of local CBF. MABP in MPE treated rats showed significant change of MPE 1.0 and 10.0 mg/kg. MPE i.v. administration showed significant increase of rCBF in a dose-dependent manner. Propranolol pretreated MABP showed significant change in the increase of MPE. rCBF of propranolol pretreated rats showed significant change from the i.v. injection concentration of 1.0 and 10.0 mg/kg. The ischemia/reperfusion induced oxidative stress may have contributed to cerebral damage in rats, and the present study provides clear evidence for the beneficial effect of MPE on ischemia induced brain injury. Also, the action mechanism in elevation effect of MPE on rCBF might be concerned with the role of $\beta$-adrenoceptor. The exact component and mechanism remains for the future study.

• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.167-175
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• 2001

Recent studies have shown that cytokines are capable of modulating cardiovascular function and that some drugs used in the treatment of heart failure variably modulate the production of cytokines. Hige- namine, a positive inotropic isoquinoline alkaloid, has been used traditionally as cardiac stimulant, and reported to reduce nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression in LPS- and/or cytokine-activated cells in vitro and in vivo. Therefore, we investigated whether higenamine modulates the production of proinflammatory cytokines in myocardial infarction. In addition, effects of higenamine on antioxidant action and antioxidant enzyme expression (MnSOD) were studied. Myocardial infarction (MI) was confirmed by measuring left ventricular (LV) pressure after occlusion of the left anterior descending coronary artery (LAD) for 5 weeks in rats. Treatment of higenamine (10 mg/kg/day) reduced infarct size about 35 %, which accompanied by reduction of production TNF-$\alpha$, IL-6, but not IFN-${\gamma}$ and IL-1$\beta$ in the myocardium. The expression of TNF-$\alpha$ mRNA in infracted myocardium was significantly reduced by higenamine. Although iNOS mRNA was not detected, nitrotyrosine staining was significantly increased in myocardium of Ml compared to higenamine-treated one, Indicating that peroxynitrite-induced damage is evident in MI. Cytochrome c oxidation by peroxynitrite was concentration-dependently reduced by higenamine, an effect which was almost compatible to glutathion. Higenamine treatment did not affect the expression of MnSOD mRNA in myocardial tissues in MI. Taken together, higenamine may be beneficial in oxidative stress conditions such as ischemic-reperfusion injury and MI due to antioxidant action as well as modulation of cytokines.

• Applied Microscopy
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• v.34 no.4
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• pp.241-254
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• 2004

Kidney had recovery functions against toxicants, ischemia, reperfusion-induced damage, acute-renal failure (ARF). Urinary epidermal growth factor (EGF) is produced by the juxtaglomerular apparatus. Kidney accumulates or excretes the EGF. In case of renal diseases, excreted EGF was decreased. The aim of this study is to evaluate the effects squalene (SQ) on the prevention of experimental acute renal failure induced by glycerol. In case of in vitro study, we investigated the expression of EGF by RT-PCR. After the proximal tubular cells was isolated, glycerol (1, 2, 4 mM) or glycerol plus squalene (0.1, 0.05 or 0.1%) was added. In case of in vivo study, we investigated the changes of BUN, creatine, and ultrastructure. Experimental groups were divided into four groups. Group 1 was normal mouse. Group 2 was injected with SQ only (180 mg/kg). Group 3 was not treated with squalene after intraperitoneal contamination of glycerol (50%, 8 ml/kg). And, Group 4 was treated with squalene (180 mg/kg) after intraperitoneal contamination of glycerol (50%, 8 ml/kg). All groups were used to 7 mice. In the results, we investigated the glycerol induced renal failure. The expression of EGF mRNA was decreased in renal proximal tubules when treated with only glycerol. SQ increased the mRNA expression of EGF in renal proximal tubules. SQ also quickly recovered the levels of BUN and creatine compared with those of mice treated with only glycerol (P<0.01). In case of ultrastructure, group 3 had heavily damaged mitochondria, but, mitochondria in group 4 had evidences of the recovery. It was concluded that SQ had the recovery effects for the glycerol-induced acute renal failure.

• Journal of Korean Biological Nursing Science
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• v.1 no.1
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• pp.25-41
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• 1999

Physiological activity of osteoblast including bone formation is known to be closely related to the increase of intracellular $Ca^{2+}$ activity($[Ca^{2+}]_i$) in osteoblast. $Ca^{2+}$ is an important intracellular messenger in diverse cellular functions, and regulation of its level is mediated by the transmembrane $Ca^{2+}$ movement via $Ca^{2+}$ channels, $Na^+-Ca^{2+}$ exchange, and by intracellular $Ca^{2+}$ movement through the intracellular stores. The purpose of this study is to investigate how the intracellular $Ca^{2+}$ is regulated in osteoblast-like cells(OLCs) by measuring $Ca^{2+}$ activity with cell imaging technique. OLCs were isolated from femur and tibia of neonatal rats, and cultured for 7 days. Cultured OLCs were loaded with a $Ca^{2+}$-sensitive fluorescent dye, Fura-2, and fluorescence images were monitored with a cooled CCD camera. The images were processed and analyzed with an image analyzing software. The results were as follows. (1) $[Ca^{2+}]_i$ of OLC decreased as the $Ca^{2+}$ concentration in the superfusing Tyrode solution was lowered. When $Na^+$ concentration in the superfusing solution was decreased, $[Ca^{2+}]_i$ increased.. These suggest that $Ca^{2+}$ flux occurs via the $Na^+-Ca^{2+}$ exchange mechanism. (2) When $Na^+$ in the superfusing solution was removed. a transient $Ca^{2+}$, increase($Ca^{2+}$ spike) was occasionally observed. However, $Ca^{2+}$ spike was not observed after adding 1 ${\mu}M$ thapsigargin. This implies that the generation of $Ca^{2+}$ spike is mediated by the release of $Ca^{2+}$ from endoplasmic reticulum(ER). (3) As the $Ca^{2+}$ concentration in the superfusing solution was raised, the frequency of 0mM $Na^+$-induced $Ca^{2+}$ spike increased, suggesting that $Ca^{2+}$-induced $Ca^{2+}$ release(CICR) mechanism exists. (4) After $[Ca^{2+}]_i$ was decreased with the superfusion of $Ca^{2+}$-free solution containing thapsigargin, the recovery of $[Ca^{2+}]_i$ with reperfusion of 2.5mM $Ca^{2+}$ solution transiently exceeded the control level, suggesting that the depletion of $Ca^{2+}$ in ER induces $Ca^{2+}$ influx from extracellular medium via store-operated $Ca^{2+}$ influx(SOCI) mechanism. (5) $[Ca^{2+}]_i$ was not affected by the superfusion of 25mM $K^+$ Tyrode solution. These results suggest that intracellular $Ca^{2+}$ activity in osteoblast is regulated by transmembrane $Ca^{2+}$ flux via $Na^+-Ca^{2+}$ exchange, $Ca^{2+}$ release from the internal store (ER) via $Ca^{2+}$-induced $Ca^{2+}$ release, and store-operated $Ca^{2+}$ influx across the cell membrane.

• The Journal of Korean Medicine
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• v.23 no.4
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• pp.161-168
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• 2002

Objectives: Hwangryunhaedok-tang (Huang-lian-jie-du-tang, HRHDT, 黃連解毒湯) is a traditional Korean herbal medicine that is formulated with Coptidis Rhizoma, Phellodendri Cortex, Scutellariae Radix and Gardeniae Fructus. HRHDT is cold (寒) and bitter (苦) in nature and has general properties of clearing heat and detoxifying (淸熱解毒), strengthening the stomach and settling the liver (健胃平肝), and reducing inflammation, fever and swelling. This formula can prevent and treat artherosclerosis, hyperplasia of the endothelium, cerebral fluid circulation, cerebral vascular deterioration through aging, impairment of neurotransmitters, or disruption of the functioning of the cerebral cortex following infection or trauma. The purpose of the study reported here was to determine the neuroprotective effect of HRHDT on global ischemia induced by 4-vessel occlusion in Wistar rats. Methods: HRHDT extract was lyophilized after extraction with 85% methanol and 100% water. Rats were induced to 10 minutes of forebrain ischemia by 4-vessel occlusion (4-VO) and reperfused again. HRHDT was administered with a dose of 100 mg/kg, and 500 mg/kg of 85% methanol extracts and 100 mg/kg of 100% water extracts, respectively, at 0 min and 90 min after 4-VO. Rats were killed at 7 days after ischemia and the number of CA1 pyramidal neurons was counted in hippocampal sections stained with cresyl violet. Results: Body temperature of animals showed no significant difference between saline-treated groups and HRHDT extracts-treated groups until 5 hours of reperfusion. This result indicated that neuroprotective effects of HRHDT extracts were not due to hypothermic effects. The administration of HRHDT showed a significant neuroprotective effect on hippocampal CA1 neurons at 7 days after ischemia compared to the saline-treated group (P<0.001). HRHDT methanol extracts of 100 mg/kg, 500 mg/kg and HRHDT water extracts of 100 mg/kg showed 88.5%, 98.3% and 95.1 % neuroprotection, respectively. Conclusions: The results of this study demonstrate that administration of HRHDT is highly effective in reducing neuronal damage in response to transient global cerebral ischemia. HRHDT may involve many mechanisms that might account for its high degree of efficacy. A number of factors including free radicals, glutamate, calcium overload, NO, and various cytokines have been proposed to have an important role in causing neuronal death after short periods of global ischemia. Further studies are needed to know the neuroprotective mechanisms of HRHDT.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.4
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• pp.672-678
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• 2002

Oxidative stress contributes to cellular injury following clinical and experimental ischemia/reperfusion scenarios. Oxidative injury can induce cellular and nuclear damages that result in apoptotic cell death. We tested the hypothesis that the catechin flavonoid of (-)epigallocatechin gallate, a green tea polyphenol, inhibits hydrogen peroxide ($H_2O$$_2$)-induced apoptosis in human umbilical vein endothelial cells. The effect of apigenin, a flavone found in citrus fruits, on apoptosis parameters was also examined. A 30 min pulse treatment with 0.25 mM $H_2O$$_2$ decreased endothelial cell viability within 24 hrs by > 30% ; this was associated with nuclear condensation and biochemical DNA damage consistent with programmed cell death. In the 0.25 mM $H_2O$$_2$apoptosis model, 50${\mu}{\textrm}{m}$ (-)epigallocatechin gallate markedly increased cell viability with a reduction in the nuclear condensation and DNA fragmentation. In contrast, equimicromolar apigenin increased cell loss with intense DNA laddering, positive nick-end labeling and Hoechst 33258 staining. Thus, polyphenolic (-)epigallocatechin gallate, but not apigenin flavone, qualify as an antioxidant in apoptosis models caused by oxidative stress. Further work is necessary for elucidating the anti-apoptotic mechanisms of polyphenolic catechins.

• Journal of Chest Surgery
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• v.26 no.7
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• pp.513-520
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• 1993

Surgical treatment of aneurysm or dissection involving the ascending aorta and aortic arch still poses one of the most complicated technical and tactical challenges in surgery. The use of total circulatory arrest[TCA] with profound hypothermia in the surgical treatment of aneurysmal dissection involving the ascending aorta and aortic arch has been reported as popular surgical methods. However, the safe period of prolonged circulatory arrest with hypothermia remains controversial and ischemic damage to the central nervous system and uncontrollable perioperative bleeding have been the major problem. We have found profound hypothermic circulatory arrest with retrograde cerebral perfusion via the superior vena cava to achieve cerebral protection. We experiment the aortic anastomosis in 7 adult mongrel dogs, using profound hypothermic circulatory arrest with continuous retrograde cerebral perfusion[RGCP] via superior vena cava. We also studied the extent of cerebral protection using above surgical methods, by gas analysis of retrograde cerebral perfusion blood and returned blood of aortic arch, preoperative, intraoperative and postoperative electroencephalography and microscopic findings of brain tissue. The results were as follows: 1. The cooling time ranged from 15 minutes to 24 minutes[19.71$\pm$ 3.20 minutes] ; Aorta cross clamp time ranged from 70 minutes to 89 minutes[79.86 $\pm$ 7.54 minutes] ; Rewarming time ranged from 35 minutes to 47 minutes[42.86$\pm$ 4.30 minutes] ; The extracorporeal circulation time ranged from 118 minutes to 140 minutes[128.43$\pm$ 8.98 minutes] [Table 2]. 2. The oxygen content in the oxygenated blood after RGCP was 12.66$\pm$ 1.25 ml/dl. At 5 minutes after the initiation of RGCP, the oxygen content of returnedlood was 7.58$\pm$ 0.21 ml/dl, and at 15 minutes 7.35$\pm$ 0.17 ml/dl, at 30 minutes 7.20$\pm$ 0.19 ml/dl, at 60 minutes 6.63$\pm$ 0.14 ml/dl [Table 3]. 3. Intraoperative electroencephalographic finding revealed low amplitude potential during hypothermia, and no electrical impulse throughout the period of circulatory arrest and RGCP. Electrical activity appeared after reperfusion, and the electroencephalographic reading also recovered rapidly as body temperature returned to normal [Fig. 2]. 4. The microscopic finding of brain tissue showed widening of the interfibrillar spaces. But there was no evidence of tissue necrosis or hemorrhage [Fig. 3]. We concluded the retrograde cerebral perfusion during hypothermic circulatory arrest is a simplified technique that may have a excellent brain protection.

• Journal of Chest Surgery
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• v.22 no.2
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• pp.225-233
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• 1989

Cardioplegia and myocardial protection were performed under cardiopulmonary bypass during open heart surgery with the use of St. Thomas Hospital cardioplegic solution [4 [C] for the coronary artery perfusion and normal saline solution [4[ c] for the topical cardiac cooling. To maintain the state of myocardial protection, coronary artery reperfusion was carried out using St. Thomas Hospital cardioplegic solution at the interval of 30 minutes. A total number of patients studied were 57 cases, including 37 cases of correction for congenital anomalies and 20 cases for acquired heart diseases. Cardiopulmonary bypass time during the surgery was observed to be average of 87.89*47.55 hours, aortic cross-clamping time [ACCT] to be average of 76.68*44.27 hours raging from 30 to 191 minutes. In order to evaluate the effects of myocardial protection in the surgery, serum enzyme levels were determined. To observe the relationship between ACCT and myocardial protection effects, patients studied were divided into the following 3 groups. I group: ACCT 60 minutes, II group: ACCT 90 minutes, III group: ACCT over 91 minutes [1] SGOT; The positive value [increased over 200 units] for ischemic myocardial injury during operation was observed in 11 cases [19.3% of the total] of the total patients studied, of which 4 cases [13.3%] in I group, 1 case [10.0%] in II group, and 6 cases [35.3%] in III group. [2] LDH; The positive value [increased over 900 units] for ischemic myocardial injury during operation was observed in 9 cases [15.7% of the total] of the total patients studied, of which 2 cases [6.6%] in I group, 1 case [10.0%] in II group and 6 cases [35.3%] in III group. [3] CPK; The positive value [increased over 800 units] for ischemic myocardial injury during operation was observed in 10 cases [17.5% of the total] of the total patients studied, including 4 cases [13.3%] in I group, 1 case [10.0%] in II group, and 5 cases [29.4%] in III group [4] The myocardial protection method used in the present study was demonstrated to be effective for the myocardial protection in the surgery with ACCT of up to 90 minutes. A few ischemic myocardial injury were observed in the surgery with ACCT over 91 minutes, but no significant cardiac dysfunction was noted. The surgery with ACCT of up to 191 minutes did not appear to give rise any significant interference with postoperative recovery.

• Journal of Chest Surgery
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• v.48 no.3
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• pp.164-173
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• 2015

Background: Hypertrophied myocardium is especially vulnerable to ischemic injury. This study aimed to compare the early and late clinical outcomes of three different methods of myocardial protection in patients with aortic stenosis. Methods: This retrospective study included 225 consecutive patients (mean age, 65{\pm}10 years; 123 males) with severe aortic stenosis who underwent aortic valve replacement. Patients were excluded if they had coronary artery disease, an ejection fraction <50%, more than mild aortic regurgitation, or endocarditis. The patients were divided into three groups: group A, which was treated with antegrade and retrograde cold blood cardioplegia; group B, which was treated with antegrade crystalloid cardioplegia using histidine-tryptophan-ketoglutarate (HTK) solution; and group C, treated with retrograde cold blood cardioplegia. Results: Group A contained 70 patients (31.1%), group B contained 74 patients (32.9%), and group C contained 81 patients (36%). The three groups showed significant differences with regard to the proportion of patients with a New York Heart Association functional classification ${\geq}III$ (p=0.035), N-terminal pro-brain natriuretic peptide levels (p=0.042), ejection fraction (p=0.035), left ventricular dimensions (p<0.001), left ventricular mass index (p<0.001), and right ventricular systolic pressure (p <0.001). Differences in cardiopulmonary bypass time (p=0.532) and aortic cross-clamp time (p=0.48) among the three groups were not statistically significant. During postoperative recovery, no significant differences were found regarding the use of inotropes (p=0.328), mechanical support (n=0), arrhythmias (atrial fibrillation, p=0.347; non-sustained ventricular tachycardia, p=0.1), and ventilator support time (p=0.162). No operative mortality occurred. Similarly, no significant differences were found in long-term outcomes. Conclusion: Although the three groups showed some significant differences with regard to patient characteristics, both antegrade crystalloid cardioplegia with HTK solution and retrograde cold blood cardioplegia led to early and late clinical results similar to those achieved with combined antegrade and retrograde cold blood cardioplegia.

• Journal of Oriental Neuropsychiatry
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• v.24 no.4
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• pp.419-434
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• 2013

Objectives: The object of this study is to observe the cognition and motor function recovery effects of Joojakwhan (JJW), a traditional Korean poly-herbal formula for treating various neuropsychiatric diseases such as dementia, for the mildly stroke rats, with 60 minutes of reperfusion transient middle cerebral artery occlusion (tMCAO). Methods: In the present study, 125, 250 and 500 mg/kg of JJW were orally administered, once per day for 10 continuous days 2 hours after the tMCAO. The body weight changes, infarct sizes under 2% 2, 3, 5-triphenyl tetrazolium chloride (TTC) stain, sensorimotor functions and cognitive motor behavior tests were serially monitored with cerebral caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP)-immunoreactivities and histopathological changes. The effects of tMCAO on sensorimotor functions were evaluated by using of limb placing and body-swing tests, and the cognitive motor behaviors were also observed with water maze tests. Results: From the results of tMCAO, with marked decreases of body weights, disorders of sensorimotor functions increases the limb placing test scores, and decrease the numbers and percentages of body swings to the ipsilateral sides. The cognitive motor behaviors increases the distances and time to reach the escape platform which included the inhibitions of the decreases with repeated trials that were observed with focal cerebral cortex infarct volumes. In addition, the marked increases of the atrophy, numbers of degeneration, caspase-3- and PARP-immunoreactive cells around peri-infarct ipsilateral cerebral cortex were also observed in tMCAO controls when compared with the sham control rats, respectively. Conclusions: The results obtained from this study suggest that oral administrations of JJW indicate obvious cognitions and motor function recoveries of the rats with tMCAO, mild strokes, which are mediated by neuro-protective effects through known antioxidant effects of components.