• Journal of Nutrition and Health
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• v.35 no.1
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• pp.5-14
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• 2002

Alteration in the syntesis or enhanced inactivation of nitric oxide(NO) can induce impairment of endothelial cell function. Insulin dependent diabetes mellitus(IDDM) is characterized by impaired endothelial function and vascular disease. NO is produced through L-arginine pathway To elucidate the hypothesis that the decreased production on NO in IDDM reflects vascular damage and the NO production can be manipulated by either dietary fat(7% of kg diet) or the oral supplementation with L-arginine(2g/kg bw), plasma markers for vascular endothelial damage and plasma lipid profiles were measured in streptozotocin(STZ)-induced diabetic rats. Diabetic or normal Sprague-Dawley rats were fed 6 different experimental diets for 4 weeks(SO : soybean oil, SOA: soybean oil + L-arginine supplementation, BT : beef tallow, BTA_ beef tallow + L-arginine supplementation, OV olive oil, OVA : olive oil + L-arginine supplementation). Plasma glucose, total cholesterel, HDL-cholesterol, LDL-cholesterol and triglyceride were measured. Endothelial markers, plasma von Willebrand factor(vWf), thromboxane B$_2$, and 6-keto PGF1$\alpha$ of aorta were measured by ELISA. Plasma NO production was evaluated through the measurement of nitrite by EIA. Feeding saturated fatty acid(SFA, BT) increased relative liver size(RLS) in diabetic rats compared to either polyunsatunted fatty acid(PUFA, SO) or monounsaturated fatty acid(MUFA, OV) The supplementation of L-arginine inhibited the liver and kidney enlargement in olive oil find diabetic rats. Plasma glucose was lower in diabetic animal find the olive oil compared to fed beef tallow and the supplementation L-arginine decreased it in diabetic rats find beef tallow significantly(p < 0.05). Plasma TXB$_2$ levels were increased due to diabetes and the value of beef tallow group showed highest value. Plasma vWf concentration of beef tallow group was higher value in normal rats and was elevated more in diabetes. In diabetic groups, the vWf concentration of olive oil group was lower than beef tallow or soybean oil group. The supplementation of L-arginine in diabetic rats decreased plasma TXB$_2$ and vWf levels significantly(p < 0.05). NO production was higher in normal olive oil fed rats and was tend to be decreased in diabetic rats and the supplementation of L-arginine recovered to normal value(p < 0.05), Olive oil supplemented with L-arginine tended to lower plasma total cholesterol and LDL-cholesterol after 4 week treatment. These results suggest that generalized vascular endothelial changes based on plasma TXB$_2$and vWf occurs in diabetic rats. and olive oil with L-arginine supplementation contributes to a better control of the hyperglycemia, endothelial changes and hypercholesterolemia accompanying diabetes as compared with beef tallow or soy bean oil in this rat model.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.223-231
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• 2014

In this study, we prepared cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha, and investigated the effect of CE-WIB801C on collagen-induced human platelet aggregation. CE-WIB801C dose-dependently inhibited collagen-induced platelet aggregation, and its $IC_{50}$ value was $175{\mu}g/ml$. CE-WIB801C increased cAMP level more than cGMP level, but inhibited collagen-elevated $[CA^{2+}]_i$ mobilization and thromboxane $A_2$ ($TXA_2$) production. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased the CE-WIB801C-downregulated $[CA^{2+}]_i$ level in a dose dependent manner, and strongly inhibited CE-WIB801C-induced inositol 1, 4, 5-trisphosphate receptor ($IP_3R$) phosphorylation. These results suggest that the inhibition of $[CA^{2+}]_i$ mobilization by CE-WIB801C is resulted from the cAMP/A-kinase-dependent phosphorylation of $IP_3R$. CE-WIB801C suppressed $TXA_2$ production, but did not inhibit the activities of cyclooxygenase-1 (COX-1) and $TXA_2$ synthase (TXAS). These results suggest that the inhibition of $TXA_2$ production by WIB801C is not resulted from the direct inhibition of COX-1 and TXAS. In this study, we demonstrate that CE-WIB801C with cAMP-dependent $CA^{2+}$-antagonistic antiplatelet effects may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.375-383
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• 2006

The anti platelet effects of a novel guanidine derivative, KR-32570 ([5-(2-methoxy-5-chlorophenyl) furan-2-ylcarbonyl]guanidine), were investigated with an emphasis on the mechanisms underlying its inhibition of collagen-induced platelet aggregation. KR-32570 significantly inhibited the aggregation of washed rabbit platelets induced by collagen $(10{\mu}g/mL)$, thrombin (0.05 U/mL), arachidonic acid $(100{\mu}M)$, a thromboxane (TX) $A_2$ mimetic agent U46619 (9,11-dideoxy-9,11-methanoepoxy-prostaglandin $F_2,\;1{\mu}M$) and a $Ca^{2+}$ ATPase inhibitor thapsigargin $(0.5{\mu}M)$ ($IC_{50}$ values: $13.8{\pm}1.8,\;26.3{\pm}1.2,\;8.5{\pm}0.9,\;4.3{\pm}1.7\;and\;49.8{\pm}1.4{\mu}M$, respectively). KR-32570 inhibited the collagen-induced liberation of $[^3H]$arachidonic acid from the platelets in a concentration dependent manner with complete inhibition being observed at $50{\mu}M$. The $TXA_2$ synthase assay showed that KR-32570 also inhibited the conversion of the substrate $PGH_2$ to $TXB_2$ at all concentrations. Furthermore, KR-32570 significantly inhibited the $[Ca^{2+}]_i$ mobilization induced by collagen at $50{\mu}M$, which is the concentration that completely inhibits platelet aggregation. KR-32570 also decreased the level of collagen $(10{\mu}g/mL)$induced secretion of serotonin from the dense-granule contents of platelets, and inhibited the NHE-1-mediated rabbit platelet swelling induced by intracellular acidification. These results suggest that the antiplatelet activity of KR-32570 against collagen-induced platelet aggregation is mediated mainly by inhibiting the release of arachidonic acid, $TXA_2$ synthase, the mobilization of cytosolic $Ca^{2+}$ and NHE-1.

• Korean journal of applied entomology
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• v.61 no.1
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• pp.173-195
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• 2022

Like vertebrates, insects synthesize various eicosanoids after the committed catalytic step of phospholipase A₂ (PLA₂). However, the subsequent biosynthetic steps exhibit some deviation from those of vertebrates. Due to little composition of arachidonic acid in insect phospholipids, PLA₂ releases linoleic acid, which is another polyunsaturated fatty acid and relatively rich in insect phospholipids, to synthesize arachidonic acid via chain extension and desaturation. Resulting arachidonic acid is then oxygenated into a prostaglandin (PG), PGH₂, by a specific peroxidase called peroxynectin, but not by cyclooxygenase. PGH₂ is then isomerized to various PGs such as PGA₂, PGD₂, PGE₂, PGI₂, and a thromboxane (TXB₂). All four epoxyeicosatrienoic acids such as 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET are also synthesized from arachidonic acid by oxygenation of vertebrate types of monooxygenases. However, the other type of eicosanoids called leukotrienes are found in insect tissues but their synthetic pathway is unclear. Eicosanoids mediate various insect physiological processes such as metabolism, excretion, immunity, and reproduction. Thus, identification of novel compounds interrupting eicosanoid biosynthesis would be a novel approach to develop insecticides. This review focuses on PGs and their immune mediation.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.43-51
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• 1989

Responsiveness of muscarinic and alpha adrenoceptor activation on endothelial cells was studied in isolated canine renal artery rings. Ach (10-100 nM), dose dependently, relaxes endothelial intact rings precontracted with phenylephrine ($IC_{50}$ of Ach was 34.5 nM). Selective mechanical destruction of the endothelium transformed the activity of this substance from vasodilatation to vasoconstriction. Acetylcholine induced relaxations could be selectively inhibited competitively by atropine, but could not be inhibited by cyclooxygenase inhibitor. Methylene blue, however, an inhibitor of soluble guanylate cyclase activity, inhibited Ach as well as sodium nitroprusside (SNP) induced relaxation. Relaxation produced by prostacyclin was not modified by methylene blue. On the other hand, alpha adrenoceptor agonist did not relax but contract canine renal artery rings possessing an intact intima precontracted with U-46619. Clonidine, however, selective alpha-2 adrenergic agonist, is more susceptible than phenylepherine, selective alpha-1 adrenergic agonist, to the inhibitory effect of contraction. These results suggest that in canine renal artery rings, 1) muscarinic receptor is responsible for releasing endothelium dependent relaxation factor (EDRF). 2) alpha-1 and alpha-2 adrenergic receptors are present in canine renal artery. 3) relaxation via EDRF is antagonized by methylene blue, providing further evidence that EDRF acts through a cGMP mechanism.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.7
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• pp.936-942
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• 2012

In the present study, the effects of green tea catechin on microsomal phospholipase $A_2$ ($PLA_2$) activity and the arachidonic acid (AA) cascade in the lungs of microwave exposed rats were investigated. One Sprague-Dawley male rats weighting $100{\pm}10$ g was randomly assigned to the normal group and three were assigned to the microwave exposed groups. The microwave exposed groups were subdivided into three groups according to the levels of dietary catechin supplementation: catechin free diet (MW) group, 0.25% catechin (MW-0.25C) group and 0.5% catechin (MW-0.5C) group. Rats were sacrificed on the 6th day after microwave irradiation (2.45 GHz, 15 min). The lung microsomal $PLA_2$ activity in the MW and MW-0.25C groups was 30% and 15% greater than that of the normal group, respectively, whereas no significant difference between the normal group and MW-0.5C group was observed. The percentage of phosphatidylethanolamine (PE) hydrolyzed in the lung microsome in the MW, MW-0.25C and MW-0.5C group increased by 47%, 18% and 20%, respectively, due to microwave irradiation. The formation of thromboxane $A_2$ ($TXA_2$) in the lung microsome was 50% greater in the MW group than in the normal group. However, the levels of $TXA_2$ in the MW-0.25C and MW-0.5C group were normal. The formation of prostacyclin ($PGI_2$) in the lung microsome was 31% lower in the MW group than in the normal group, while the levels of $PGI_2$ in the MW-0.25C and MW-0.5C group were similar to the normal group. The lung microsomal thiobarbituric acid reactive substances (TBARS) concentration, which can be used as an index of lipid peroxide was 34% greater in the MW group, when compared with the normal group. However, there was no difference between the MW-0.25C, MW-0.5C and normal groups. In conclusion, lung function appeared to be improved by green tea catechin supplementation due to its antithrombus action, which in turn controls the AA cascade system.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.2
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• pp.199-204
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• 2006

This study was conducted to investigate the quality characteristics of noodles prepared with the addition of nanofiltered (NF) powder of sunmul. Noodles were prepared with different levels $(0\%,\;1.5\%,\;3\%\;and\;5\%,\;w/w)$ of NF powder and physico-chemical properties were examined. Results of rapid visco analyzer showed that peak, trough, final viscosity and set back decreased as the NF powder level increased. The weight and volume of cooked noodles increased with the addition of NF powder. Turbidity of soup also increased as the amount of NF powder increased, indicating higher cooking loss. The color of wet and cooked noodles became greenish yellow as the NF powder level increased. Hardness, springiness, gumminess and brittleness of cooked noodles decreased with the increasing amount of NF powder. Results of sensory evaluation showed that noodles prepared with up to $3\%$ addition of NF powder was considered to be as acceptable as noodles prepared without NF powder.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.39-49
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• 1996

In the present study, we observed change in intracellular $Ca^{2+}$$([Ca^{2+}]_i)$ as measured with the fluorescent $Ca^{2+}-indicator$ fura-2 in association with force development of the rat basilar arteries during activation by$K^+$ depolarizing solution and U46619, a thromboxane analogue, in the absence and the presence of calcitonin-gent related peptide (CGRP). CGRP (30 and 100 nM) caused a concentration-dependent inhibition of U46619-induced contraction with decrease in $[Ca^{2+}]_i$, whereas it did not exert any effect on the $K^+$ (90 mM)-induced contraction and increase in $[Ca^{2+}]_i$, Further, $[Ca^{2+}]_i-force$ relationships were determined by plotting the ratio of $F_{340}/F_{380}$ $([Ca^{2+}]_i)$ as a function of the force induced by U46619, and the results were compared with those obtained in the presence of CGRP. The curves obtained in the presence of CGRP (30 and 100 nM) were significantly moved to downward without right shift of the curves suggesting that CGRP inhibited the U46619-induced contraction only by mediation of reduction in $[Ca^{2+}]_i$ with out any change in the sensitivity of contractile apparatus to $Ca^{2+}$. The CGRP-induced attenuation of $[Ca^{2+}]_i$ and force development was significantly inhibited under pretreatment with CGRP $(8{\sim}37)$ fragment (100 nM), a CGRP1 receptor antagonist. Both the reduced contraction and reduction in $[Ca^{2+}]_i$ caused by CGRP were fully reversed by pretreatment with charybdotoxin (100 nM) and iberiotoxin (100 nM), large conductance $Ca^{2+}-activated$ $K^+$ channel blockers, but not by apamin (300 nM), a small conductance $Ca^{2+}-activated$ $K^+$ channel blocker, and glibenclamide ( 1 ${\mu}M$), an ATP-sensitive $K^+$ channel blocker. In conclusion, it is suggested that the CGRP1 receptor, upon activation by CGRP, are coupled to opening of $Ca^{2+}-activated$ $K^+$ channel and cause to decrease in $[Ca^{2+}]_i$, thereby leading to vasodilation of the rat basilar artery. However, it is not defined that the mechanism underlying vasodilation whether the $K^+$ channel blockers, charybdotoxin and iberiotoxin directly block the CGRP receptors and that CGRP-evoked relaxation is dependent on the cyclic AMP or $K^+$ channel opening or both actions.

• Journal of Chest Surgery
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• v.32 no.10
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• pp.863-873
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• 1999

배경: 혈전 생성은 심혈관계 삽입물이나 순환 보조장치의 발전에 있어서 중요한 문제이므로 이러한 장치들의 혈전성에 대한 평가는 필수적이다. 따라서 이러한 장치들의 혈전성 연구를 시행하기 위한 효과적인 생체 외 실험 방식이 개발되어 원심성 순환 펌프의 발전에 큰 도움이 되고 있으며, 최근 엄밀하게 혈액과 공기의 접촉을 차단하는 방식이 믿을 수 있는 생체 외 실험 방식으로 강조되고 있다. 본 논문에서는 모의 순환 회로를 이용하여 기존에 행해진 연구 방법 상의 공기 접촉에 따른 핼액 응고 기전의 활성화 여부를 알아보기 위하여 공기 접촉 여부에 따른 혈액 인자의 변화를 관찰하여 확인하고, 또한 회로 내에서 생성된 혈전을 생체 내에서 형성된 혈전과 비교 분석하여 이 모의 순환 회로를 이용한 생체 외 검사가 새로 고안된 심혈관계 장치들의 혈전성을 평가하는데 있어서 동물실험을 대신할 수 있다는 기존의 주장을 검증하고자 하였다. 연구재료 및 방법: 바이오펌프를 이용한 같은 모의 순환 회로 한 쌍을 준비하고 동일 개체에서 얻은 헤파린을 첨가한(1u/$m\ell$) 신선한 혈액을 공기와 접촉시키지 않도록 한 A-회로와 공기와 접촉시킨 B-회로에 충전시켜 실험을 동시에 진행하여 결과를 얻었으며 총 12번 시행하였다. 회로에 충전한 혈액의 activated clotting time(ACT)은 정상의 3~5배였으며 ACT가 정상 범위의 1.5배가되면 실험을 끝냈고, Hematocrit(HCT), 혈소판, 동맥혈가스분석(ABGA), factor Ⅷ, factor \ulcorner, 섬유소원, thromboxane B2(TXB2), free hemoglobin(fHb) 등을 측정하였다. 실험이 끝난 후 A-회로와 B-회로에서 얻은 각 검사를 평가하고 분석하였으며 생성된 혈전을 생체 내에서 생성된 혈전과 조직 검사로 비교하였다. 본 연구의 자료분석은 SPSS 통계 프로그램을 이용하였고 유의수준 0.05를 기준으로 유의도를 판단하였다. 결과: 정상 ACT는 186.9$\pm$20.5초(평균$\pm$표준편차)이었고, 헤파린을 넣은 초기 ACT는 982.2$\pm$165.5초이었으며, 실험시간은 보통 60분에서 180분 사이였다. HCT, fHb, 혈소판, TXB2, factor Ⅷ, factor \ulcorner, 섬유원소의 초기값은 35.5$\pm$3.2%, 12.4$\pm$6.5 mg/dL, 354$\pm$56($\times$103)/$\mu$L, 72.6$\pm$15.1 mg/dL, 29.3$\pm$1.2%, 137.9$\pm$42.1 mg/dL, 그리고 17.7$\pm$9.7%이었다. 공기 접촉에 따른 차이를 보았을 때 ACT(p=0.398), HCT(p=0.988), fHb(p=0.898), 혈소판 (p=0.904), TXB2(p=0.985), factor Ⅷ(p=0.872), factor \ulcorner(p=0.489), 섬유원소(p=0.973)으로 전 예에서 통계적 유의성이 없었다. 실험 후 양 군에서 생성된 혈전의 현미경 소견은 B-회로의 혈전에 여러 군데 공기 방울이 관찰되는 것 이외에 A-회로에서 생성된 혈전과 차이가 없었고, 생체에서 생성된 혈전과 비교했을 때 그 양상이 같았다. A-회로와 B-회로에서 생성된 혈전의 총 량은 8.4$\pm$3.7 mL와 9.4$\pm$3.1 mL로 통계상 유의성은 없었다. (p=0.624). 결론: 모의 순환 회로를 이용한 혈전성 평가를 위한 생체 외 실험에 있어서 공기와의 접촉 여부는 혈액 응고 기전의 활성화나 혈전 생성에 별다른 영향을 미치지 않는다. 모의 순환 회로에서 형성된 혈전과 문헌에 있는 인체 내에서 형성된 혈전을 비교한 결과 그 형태가 일치하므로 이 모의 순환회로를 이용한 실험이 동물실험을 대신할 수 있다고 판단된다.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.369-379
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• 1998

Background: Platelet-activating factor(PAF) might play an important role in the development of acute respiratory distress syndrome. Since PAF induced lung injury is similar to changes of acute respiratory distress gyndrome, and abnormalities in surfactant function have been described in acute respiratory distress syndrome, the authors investigated the effects of PAF on the regulation of surfactant protein A, B and C mRNA accumulation Method: The effects of PAF on gene expression of surfactant protein A, B and C in 24 hours after intratracheal injection of PAF in rats. Surfactant protein A, B and C mRNAs were measured by filter hybridization. Results: The accumulation of SP-A mRNA in PAF treated group was significantly decreased by 37.1 % and 41.6%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.025, p<0.01). The accumulation of SP-B mRNA in PAF treated group was decreased by 18.7% and 32.2 %, respectively compared to the control group and the group treated with Lyso-PAF but statistically not significant. The accumulation of SP-C mRNA in PAF treated group was significantly decreased by 30.7% and 38.5%, respectively compared to the control group and the group treated with Lyso-PAF(p<0.l, p<0.01). Conclusion: These findings represent a marked inhibitory effects of platelet-activating factor on surfactant proteins expression in vivo. This supports, in turn, 'platelet-activating factor might be related to pathogenesis of acute respiratory distress syndrome.