Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by progressive accumulation of lipids, cells, and extracellular matrix. Matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases(TIMPS) contribute to vascular matrix remodeling in atherosclerosis, and some cytokines may play role in the synthesis or activation of MMPs or TIMPs. Material and Method: We produced experimental atherosclerotic plaques in 9 rabbits by atherogenic hypercholesterol diet for 12 weeks, and 10 other rabbits were used as control group with standard laboratory chow, At that time, 19 rabbits were sacrificed and aorta, coronary arteries and blood specimens were prepared. The expressions of MMP-9, TIMP-2 and interleukin(IL)-18, and the bioactivity of IL-6 were investigated with H&E stain, immunohistochemical stain, immunoblotting(Western blot analysis), and bioassay. Result: Serum cholesterol in the experimental group increased up to 1258$\pm$262 mg/dL(control group: 41$\pm$7 mg/dL). All experimental group showed well-developed atherosclerotic plaques in aorta and coronary artery. The expression of MMP-9 in aorta and coronary artery of the experimental group showed significant increase than that of the control group by immunohistochemistry. Among the experimental group, complicated lesions with intimal rupture or complete luminal occlusion, demonstrated stronger expression of MMP-9. Interestingly, there was no difference in expression of TIMP-2 between the experimental and the control group. These findings were confirmed by Western blot analysis. The bioassay revealed significant up-regulation of serum bioactivity of IL-6 in the experimental group(4819.60$\pm$2021.25 IU/$m\ell$) compared to that of IL-6 in the control group(27.20 $\pm$ 12.19 IU/$m\ell$). IL-18 was expressed in all atherosclerotic plaques, whereas little or no expression was detected in the control group. Conclusion: The increased MMP-9 expression along with the unchanged TIMP-2 expression seem to be contributory factors in extracellular matrix degradation in atherosclerosis. Focal overexpression of MMP-9 may promote plaque destabilization and cause complications of atherosclerotic plaques such as thrombosis with/without acute coronary syndrome. Elevation of IL-6 and IL-18 may be more than just markers of atherosclerosis but actual participants in lesion development. Identification of critical regulatory pathway is important to improve the understanding of the cellular and molecular basis of atherosclerosis and may open the way for novel therapeutic strategies.
Purpose: Thallium behaves similarly to potassium in vivo. Potassium channel opener (K-opener) opens ATP-sensitive $K^+$-channel located at cell membrane, resulting in potassium efflux from cytosol. We have previously reported that K-opener can alter biokinetics of Tl-201 in cultured cells and in vivo. Malignant tumor cells have high Na-K ATPase activity due to increased metabolic activities and dedifferentiation, and differential delineation of malignant tumor can be possible with Tl-201 imaging. K-opener may affect tumoral uptake of Tl-201 in vivo. To investigate the effects of pinacidil (one of the potent K-openers) on the localization of the tumor with Tl-201 chloride, we evaluated the changes in biodistribution of Tl-201 with pinacidil treatment in tumor-bearing mice. Materials and Methods: Baltic mice received subcutaneous implantation of murine breast cancer cells in the thigh and were used for biodistribution study 3 weeks later. $100{\mu}g$ of pinacidil dissolved in $200{\mu}l$ DMSO/PBS solution was injected intravenously via tail vein at 10 min after 185 KBq ($5{\mu}Ci$) Tl-201 injection. Percentage organ uptake and whole body retention ratio of Tl-201 were measured at various periods after injection, and values were compared between control and pinacidil-treated mice. Results: Pinacidil treatment resulted in mild decrease in blood levels of Tl-201, but renal uptakes were markedly decreased at 30-min, 1- and 2-hour, compared to control group. Hepatic, intestinal and muscular uptake were not different. Absolute percentage uptake and tumor to blood ratios of Tl-201 were lower in pinacidil treated mice than in the control group at all time points measured. Whole body retention ratio of Tl-201 was lower in pinacidil treated mice ($58{\pm}4%$ ), than in the control group ($67{\pm}3%$) at 24 hours after with injection of $100{\mu}g$ pinacidil. Conclusion: K-opener did not enhance, but rather decreased absolute tumoral uptake and tumor-to-blood ratios of Tl-201. Decreased whole body retention ratio and renal uptake were observed with pinacidil treatment in tumor-bearing mice.
The long-term effects of vegetable and animal high fat diet on the lipid metabolism were investigated in male weaning rats. The rats were fed one of four semipurified diet ad libitum : control diet supplied 12% of calories as fat(control group), low fat diet supplied 3% of calories as fat(3% F group), 45% corn oil diet supplied 45% calories from corn oil(45% C group) and 45% butter fat diet supplied 45% calories from butte. fat(45% B group). The weights of liver, content of triacylglycerol(TG), total cholesterol and phospholipid(PL) in liver were investigated. The weight of liver of rats, fed 45% corn oil at 12 weeks and fed 45% butter fat for all period of diet were higher than that of control group. The contents of TG in liver of rats, fed 45% corn oil from 8 weeks and fed 45% butter fat for all period of diet were higher than that of control group. The levels of TG in liver of rats fed 45% butter fat were higher than those of rats fed 45% corn oil. The contents of total lipid and cholesterol in liver of rats were increased with similar trend of TG level, but contents of PL in liver had no relation with the levels and types of dietary fat and feeding periods. The liver of rats were observed histochemically by light microscope. Mild to severe level of fatty changes in liver of 45% C and 45% B group were observed at 8 and 12 weeks of diet. The liver of rats in control group appeared to be healthy and normal electron-microscopically, but in fatty degenerated hepatocytes of 45% C and 45% B group, nuclear membranes were irregular and a great number of intracytoplasmic fat vacuoles in cells were variable in size and low in electon density. The numbers of lysosome were increased and secondary lysosomes among them were observed on electron microscope.
Although iron is an essential mineral, excess iron intake during pregnancy may increase oxidative stress in tissues. This study was conducted to investigate the effects of iron overload during pregnancy on iron status and oxidative stress in maternal rats. Ten week-old female Sprague-Dawley rats were mated with male rats. Non-pregnant (control) and pregnant rats were fed diets containing normal Fe (35 mg/kg diet), high Fe (350 mg/kg diet), or excess Fe (1,050 mg/kg diet) during pregnancy. Rats were sacrificed on pregnancy day 19. No significant difference in weight gain, diet intake, or litter size was observed according to iron intake levels. Furthermore, serum iron, hemoglobin, and hematocrit were not different among the rats administered the three levels of Fe both in the control and pregnant groups. However, the iron levels were lower in pregnant rats than those in the control. The liver and spleen iron contents increased significantly in the excess Fe group. An increase in liver ferritin levels with increasing iron intake was observed. Protein carbonyl content, as a marker of oxidative stress, increased significantly in liver with increasing iron intake but not malondialdehyde. Glutathione peroxidase activity in the liver of pregnant rats fed excess iron decreased significantly. Bcl-2 protein expression in the liver declined remarkably with increasing maternal iron intake in pregnant rats. Taken together, iron overload during pregnancy had little effect on hematology. However, the deposits of iron in the liver and the decline in antioxidant enzyme activity implied increased oxidative stress in tissues of the excess Fe group. These results suggest that excess iron intake during pregnancy increases oxidative stress in maternal tissues and may also affect fetal tissues.
Park, Surk-Hoon;Jang, Mi-Jin;Hong, Jung-Hee;Rhee, Soon-Jae;Choi, Kyung-Ho;Park, Mo-Ra
Journal of the Korean Society of Food Science and Nutrition
/
v.36
no.1
/
pp.43-50
/
2007
This study was to investigate the effect of mulberry leaf water extract on lipid metabolism of rats fed high cholesterol diets. Sprague-Dawley male rats were randomly assigned to two normal groups; mulberry extract-free (N), 0.16% mulberry leaf extract (NM) groups and high cholesterol groups with four different levels of mulberry leaf extract; 0% (HC), 0.08% (HCL), 0.16% (HCM), and 0.32% mulberry leaf extract (HCH) groups. Serum levels of triglyceride, cholesterol, LDL-cholesterol and AI index in mulberry leaf extract supplemented groups were significantly lower than the HC group (p<0.05). The level of HDL-cholesterol in the HC group was significantly (p<0.05) reduced, compared with N group, but it was increased by mulberry leaf extract supplementation. Mulberry leaf extract had no effect on the UDP-glucuronyl transferase activity. Also, there was no significant difference in the level of liver cholesterol between the HC and mulberry leaf extract supplemented groups, while there was significant difference in the levels of liver total lipid and triglyceride. The HCM and HCH groups had more significant reduction in the activity of lipoprotein lipase in epididymal fat tissue than the HC group. The levels of total lipid, triglyceride and total cholesterol in epididymal fat tissue of HCL, HCM and HCH groups were decreased compared to HC group. The levels of total lipid, triglyceride and total cholesterol in feces from HCL, HCM and HCH groups were higher than those of HC group.
The aim of this study is to know how the rat submandibular gland changes under various emotional stress condition, using molecular biological methods. Restraint and chronic unpredictable mild stress (CUMS) experiment is conducted on fifty one 7-week old Sprague-Dawley rats (restraint stress experiment: 21, CUMS: 30). The rats were sacrificed, the submandibular glands were excised immediately at certain time, and examined by the use of immunohistochemistry and western blotting. In CUMS experiment, sucrose preference test, water intake change, weight change were implemented at 1 week interval for the experimental period The results are as follows: 1. The number of clusterin-secreting cells of restraint stress group compared to control group showed significantly decreasing tendency in all experimental groups except for the 1st hour group (p<0.001 in the 9th, 24th, 72nd, 120th, and 168th hour group). 2. The number of clusterin-secreting cells of CUMS group compared to control group showed significantly increasing tendency in the 2nd week group (p<0.01), and significantly decreasing tendency in the 4th and 5th week group (p<0.001). 3. Sucrose preference test in CUMS experiment showed significant difference between the 5th week experimental group and control group (p<0.01). 4. Weight change in CUMS experiment showed significant difference between the 5th week experimental group and control group (p<0.01), but water intake change didn't show significant difference compared to control group. 5. In western blot analysis, clusterin expression was decreased on a gradual basis in due time compared to the control group in the restraint stress group. As for CUMS group (chronic unpredictable mild stress group), it was increased till the 2nd week and decreased till the 5th week after that, which is similar to immunohistochemical analysis result and the decreasing tendency of sucrose preference and weigh changes. Through the test, it was proved that expression of clusterin in saliva glands decreases after receiving either acute or chronic stress, indicating relation with depression caused by chronic stress. Unlike other data, however, apoptotic tendency was hardly found in tissues. Diverse possibilities could be suggested on that: first, the stress was not enough to expedite apoptosis; second, apoptosis-related protein was already being secreted though not detected with microscope; third, clusterin, a major secretion molecule of saliva, decreased with saliva's malfunction due to stress. In the respect, it will be necessary to examine proteins expressed in case of cell death or other heat-shock proteins at the same time, in order to see whether any cellular change or death is caused by decreasing clusterin under high stress, and whether the original state is restored as time goes by under mild stress, through longer-term tests using even higher acute stress.
Background: Luteolin, a flavone found in various Chinese herbal medicines is known to possess anti-inflammatory properties through its ability to inhibit various proinflammatory signaling pathways including NF-${\kappa}B$ and p38 MAPK. In this study, we investigated the potential therapeutic effect of luteolin on dextran sodium sulfate (DSS)-induced colitis. Materials and Methods: We used a transgenic mouse model expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-${\kappa}B$$cis$-elements. C57BL/6 NF-${\kappa}B^{EGFP}$ mice received 2.5% DSS in their drinking water for six days in combination with daily luteolin administration (1mg/kg body weight, 0.1ml vol, intragastric) or vehicle. NF-${\kappa}B$ activity was assessed macroscopically with a Charge-Coupled Device (CCD) camera and microscopically by confocal analysis. Results: A significant increase in the Disease Activity Index (DAI), histological score (p<0.05), IL-12 p40 secretion in colonic stripe culture (p<0.05) and EGFP expression was observed in luteolin and/or DSS-treated mice compared to water-treated mice. Interestingly, a trend toward a worse colitis (DAI, IL-12p40) was observed in luteolin-treated mice compared to non-treated DSS-exposed mice. In addition, EGFP expression (NF-${\kappa}B$ activity) strongly increased in the luteolin-treated mice compared to control mice. Confocal microscopy showed that EGFP positive cells were primarily lamina propria immune cells. Conclusions: These results suggest that luteolin is not a therapeutic alternative for intestinal inflammatory disorders derived for primary defects in barrier function. Thus, therapeutic intervention targeting these signaling pathways should be viewed with caution.
This paper considers the structure and meaning of the folktale accompaniment of the sound of UlsanSoeburisoree. The review process examined the meaning of each structure of the UlsanSoeburisoree in the preparation process while preparing the main elements of the structural features along with the historical background of the structure. UlsanSoeburisoree is Poongcheol ritual ceremony which means prayer ceremony for the production of iron. The sound of UlsanSoeburisoree is 1-Gilnori 2-Gosa 3-The sound of blowing smelting process 4-The sound of process of iron smelting 5-The sound of tabooline 6-The sound of blowing smelting process 7-The sound of blowing matches 8-The After-party. This structure is in line with the structure of folk play called Gilnory-Gosa-Performance-After-party. This is similar to the basic structure of folk beliefs Cheongsin(請神)-Osin(娛神)-Songsin(送神). Thus, the sound of UlsanSoeburisoree was formulated in a sequential parallel structure. The sound of UlsanSoeburisoree resemble the sacrifice of heaven ceremony since the time of the SamHan dynasty. The sound of the birth of life by physical sacrifice also plays the role of the song of creation of new life. The sound of UlsanSoeburisoree can be seen not only in Korea 's folk culture but also in folk culture of GyeongnamDo area. There are many festivals to pray for the abundance of life for UlsanSoeburisoree. Soil plays an absolute role in the process of producing iron. For those who soak it, the earth is a religious object. Among the folk tales handed down in the Yeongnam area, there are a lot of performances that are passed down through the blending of the people 's affection to overcome the harshness of life. In the case of the sound of UlsanSoeburisoree, it can be said that it was made and mixed with the wind that wanted to go beyond the harshness of life and the spirit of art.
The Parmenidean tradition of logos which previous researches fail to fully appreciate has three dimensions of reality-knowledge-discourse. Parmenides is not just an ontologist, as the traditional view emphasizes, but also an epistemologist, as the revisionist view begins to emphasize, and, at the same time, a meta-discourser, as those two established views fail to embrace. In order to reach the third view which fully grasps such a dynamic and integrated feature of Parmenides, we should closely pay attention to the organic interconnectedness of three discourse parts of truth-doxa-proem, especially the significance of proem and meta-discourse. In the Eleatic tradition of discourse, the figure who clearly appreciated and further developed such an authentic feature of Parmenides' discourse is not, as one might easily expect, one of the second-generation Eleatics, but Gorgias who has commonly been positioned at the opposite side of Eleatism. This paper investigates how he actually both innovated and succeeded the Parmenidean tradition of logos; especially, it characterizes his discourse as an antilogy(antilogia) from within the tradition: as a 'devil' advocate' who complemented and completed Parmenidean persuasion by positing the Parmenidean tradition of logos as an arena of a huge intellectual discipline and cultivation, offering himself as a sparring partner to it, and bringing up an antilogy. In the process of this antilogy he performed in his rhetorical speeches such as the Encomium of Helen and the Defense of Palamedes he experimented and examined a possibility of persuasion operating independently from truth, which, however, is not merely sacrificing truth in favor of persuasiveness and probability (to eikos) as Plato criticized mainly focussing on his 'philosophical' writing On not-being. Rather, it was an 'opposition for opposition's sake' and serious play which purported to provide balance and flexibility to contemporary intellectual society which had too much inclined towards truth and knowledge and become stiff and to put weight on the opposite side of mainstream. It is wholly our eranos (i.e. our share of contribution) to summon and examine such sophistic tradition for the sake of the task of our times, not for the sake of Plato's task, that we should build up a healthy culture of discourse where we can share serious play.
This study attempted to investigate the issue how stepmother's narrative was transferred to . For this agenda, the approach of this paper is described below to determine how Bbaengdeok's stepmother narrative was transferred episodically to . First, this paper started from the relation between stepmother narrative and affiliated with each root folk tale in Buddhist text. Among known as root folk tale until now, this paper investigated whether was the root folk tale affiliated to Buddhist literature. At that point, stepmother narrative showed relation with opening eyes motive. It has been reported that the text of opening eyes in Buddhist literature is originated from the south. This paper confirmed that 's stepmother narrative was related to Buddhist literature originated from south. Next, this paper investigated the background of opening eyes motive of stepmother types. After entering Gyeongpan , it formed Bbaengdeok narrative of Wanpan related to Literary geography of Jeollado enjoying space of Wanpan . There are two evidences for this. The first one is which was passed down around Jeollado. In the course of sudden Buddhist folklore's flow into the country, it is that combined stepmother narrative of sudden Buddhist literature with the characteristics of northern Buddhist literature which was reconstructed into son's filial behavior of northern Buddhist literature to make father's blinded eyes open. The other is the Buddhist trend of the late 18th Chosun when northern Buddhist literature and sudden Buddhist literature were combined. It appeared that stepmother narrative was formed in the Buddhist background of the late 18th Chosun when northern Buddhist literature and sudden Buddhist literature were combined.
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