• Title/Summary/Keyword: $TXA_2$

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PKC inhibitors RO 31-8220 and Gö 6983 enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation

  • Kim, Sun-Young;Kim, Se-Woon;Kim, Jeong-Mi;Jho, Eek-Hoon;Park, Seon-Yang;Oh, Do-Yeun;Yun-Choi, Hye-Sook
    • BMB Reports
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    • v.44 no.2
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    • pp.140-145
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    • 2011
  • Impaired responsiveness of platelets to epinephrine (epi) and other catecholamines (CA) has been reported in approximately 20% of the healthy Korean and Japanese populations. In the present study, platelet aggregation induced by epi was potentiated by RO 31-8220 (RO) or G$\ddot{o}$ 6983 (G$\ddot{o}$). Phosphorylated Akt (p-Akt) was very low in epi-stimulated PRP from CA-hypo- responders (CA-HY), whereas it was detected in those from CA-good responders (CA-GR). RO and G$\ddot{o}$ increased p-Akt, one of the major downstream effectors of phosphoinositol-3 kinase (PI3K), in epi-stimulated PRP from both groups. Wortmannin, a PI3K inhibitor, attenuated the RO or G$\ddot{o}$-induced potentiation of p-Akt in epi-stimulated PRP, suggesting positive effects for RO and G$\ddot{o}$ on PI3K. $TXA_2$ formation was increased by the addition of either RO or G$\ddot{o}$ in epi-stimulated platelets. The present data also suggest that impaired Akt phosphorylation may be responsible for epinephrine hypo-responsiveness of platelets.

Inhibitory Effects of Moutan Cortex Radicis Extracts and Paeonol on Rabbit Platelet Aggregation

  • Lee, Kyung-Sup;Oh, Ki-Wan;Bae, Ki-Hwan;Kim, Young-Ho;Lee, Mi-Yea;Cho, Mi-Ra;Jin, Yong-Ri;Yun, Yeo-Pyo
    • Journal of Food Hygiene and Safety
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    • v.19 no.3
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    • pp.167-170
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    • 2004
  • The present study was undertaken to investigate the effects of Moutan Cortex Radicis extracts and paeonol, a major component, on rabbit platelet aggregation and thromboxane (TX) $A_2$ formation. Moutan Cortex Radicis methanol and butanol layers (100 ${\mu}g/mL$) showed the weak inhibitions, and water layer (100 ${\mu}g/mL$) had no effect on the collagen-induced platelet aggregation. Whereas, hexane and EtOAc layers potently inhibited the collagen (3 ${\mu}g/mL$)-induced platelet aggregation with the $IC_{50}$ values of 10.9${\pm}$1.0 and 31.5${\pm}$0.8 ${\mu}g/mL$, respectively. Paeonol isolated from the hexane-acetone layer specifically inhibited the collagen-induced platelet aggregation with the $IC_{50}$ value of 113.1 ${\pm}$ 0.9 ${\mu}M$, whereas it had little effects on the other agonists such as AA-, thrombin-, A23187- and thapsigargin-induced platelet aggregations. Paeonol also potently inhibited the collagen-induced TXB formation in rabbit platelet in a concentration-dependent manner. These results suggest that paeonol may inhibit rabbit platelet aggregation by interfering with an essential step in collagen-induced platelet activation and $TXA_2$ formation. Paeonol may be a promising candidate for an antiplatelet agent.

Pharmacological Mechanism of Action of GS283 and GS386 on Human Platelet and Pig Coronary Artery (관상동맥이완과 혈소판응집에 대한 GS283과 GS386의 약리작용기전에 관한 연구)

  • CHANG, Ki Churl;LEE, Hoi Young;LEE, Goun Woo;KOO, Eui Bon;KANG, Young Jin;LEE, Young Soo
    • Biomolecules & Therapeutics
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    • v.5 no.3
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    • pp.239-245
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    • 1997
  • Trimetoquinol (TMQ) and its analogs are known to have thromboxane $A_2$ antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS 386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited $Ca^{2+}$ -induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound\`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to $\alpha$-adrenergic receptor. Taken together. we concluded that the mechamism of action of GS283 and GS86 is not related with in TXA$_2$ receptor but concerned with calcium antagonistic action and a-blocking action.n.

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Effects of Green Tea Catechin on Microsomal Phospholipase $A_2$ Activity and Arachidonic Acid Cascade in Rat's Heart When Exposed to Microwave (녹차 Catechin의 마이크로웨이브 조사 흰쥐 심장 조직의 Phospholipae $A_2$ 활성과 Arachidonic Acid Cascade계 개선 효과)

  • Kim, Mi-Ji
    • Journal of the East Asian Society of Dietary Life
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    • v.23 no.3
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    • pp.311-319
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    • 2013
  • The purpose of the present study is to investigate the effects of green tea catechin on microsomal phospholipase $A_2(PLA_2)$ activity and the arachidonic acid (AA) cascade in hearts of microwave exposed rats. Sprague-Dawley male rats weighing $100{\pm}10$ g were randomly assigned to one normal group and three microwave exposed groups. The microwave exposed groups were subdivided into three groups: catechin free diet (MW) group, 0.25% catechin (MW-0.25C group and 0.5% catechin (MW-0.5C) group according to the levels of dietary catechin supplementation. Rats were sacrificed $6^{th}$ day after microwave irradiations (2.45 GHz, 15 min). The heart microsome $PLA_2$ activity in the MW group was 130% greater than that of normal groups, whereas there was no significant difference between normal group and MW-0.25C, MW-0.5C group. The per- centage phosphatidyl ethanolamine (PE) hydrolyzed in the heart microsome in the MW was increased 54% by microwave irra- diation, whereas there was no significant difference between normal group and MW-0.5C group. The percentage phosphatidyl choline (PC) hydrolyzed in the heart microsome in the MW group was increased by 104% and by microwave irradiation, whereas there was no significant difference between normal group and MW-0.5C group. The formation of thromboxane $A_2(TXA_2)$ in the heart microsome was 70% greater in the MW group than in the normal group. However, the MW-0.25C and MW-0.5C group maintained the normal level. The formation of prostacyclin ($PGI_2$) in the heart microsome was 21% lower in the MW group than in the normal group, while that of MW-0.25C and MW-0.5C group were maintained in the normal group. The heart microsomal thiobarbituric acid reactive substances (TBARS) concentrations, as an index of lipid peroxide, were 71% greater in the MW group, as compared with normal group. However, the MW-0.25C and MW-0.5C group were 4.6% and 9.2% lower, respectively, than that of MW group. In conclusion, heart function appeared to be improved by green tea catechin supplementation due to its antithrombus action, which in return controls the AA cascade system.

Cudrania Tricuspidata root extract (CTE) has an anti-platelet effect via cGMP-dependent VASP phosphorylation in human platelets (꾸지뽕나무 뿌리 추출물의 cGMP에 의한 VASP 인산화 기전을 통한 항혈소판 효과)

  • Ro, Ju-Ye;Cho, Hyun-Jeong
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.20 no.12
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    • pp.298-305
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    • 2019
  • Cudrania tricuspidata has been reported to have many biological activities, including anti-inflammatory, anti-cancer, and antioxidant properties. However, the effects of C. tricuspidata root extract (CTE) on human platelet aggregation induced by collagen as well as the signaling pathways involved remain unknown. In the present study, we investigated the effect of CTE on human platelets. CTE inhibited platelet aggregation via down-regulation of thromboxane A2 (TXA2) by blocking cyclooxygenase-1 (COX-1) activity and intracellular Ca2+ mobilization in collagen-induced platelets. CTE also reduced the phosphorylation of phospholipase C (PLC) γ2 and syk. CTE regulated platelet aggregation via cyclic guanosine monophosphate (cGMP)-dependent phosphorylation of vasodilator-stimulated phosphoprotein (VASP) Ser239. In addition, administration of CTE (50 and 100 mg/kg) significantly reduced hyper-aggregated platelet aggregation by collagen (5 ㎍/mL) without hepatotoxicity in HFD (high fat diet)-fed rats. Taken together, these results suggest that CTE has anti-platelet effects both in vitro and in vivo. Therefore, CTE may be an effective therapeutic and preventive agent for cardiovascular disease, and is a safe and natural product.

A Statistical Analysis of the Fereign Bodies in the Food and air Passages (식도 및 기도이물의 임상통계학적 고찰)

  • 정해영;권평중;박성준;민양기;김중환
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1978.06a
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    • pp.4.1-4
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    • 1978
  • The foreign bodies in the food and air passages are frequently observed in the field of otolaryngology, and the foreign bodies in the air passages have much significance in clinical practice because they may cause sudden death. A statistical study was done on 95 cases of foreign bodies in the food and air passages who had visited department of otolaryngology, Chung-Ang university from June, 1968 to April, 1978. The results were as follows; 1. The total cases of foreign bodies in the food and air passages was 95; 89 cases (93.7%) were in the food passage and the remaining (6.3%) were in the air passage. The ratio between the food passage and air passage was about 14. 8 to 1.0. 2. In distribution by sex, 64 cases (67.4%) were in male patients and the remaining 31 cases (32.6%) were in female patients. The ratio between male and female was 2.1 to 1.0. 3. The kinds of foreign bodies in the food in the order of their frequency, were coin, gogame stone and pebble. In the air passages, the peanut and bean were most frequently found. 4. In distribution by age, 64 cases (67.4%) of all foreign bodies were found in children under 5 year old, and coin was the most common kind of foreign body. Except for meat, almost all of foreign bodies were found in children under 10 year old. 5. There was chronologically no significant tendency in incidence; the incidence, however, had decreased during recent 2 years. 6. In the location of foreign bodies in the food passage, 70 cases (78.7%) were found at the first esophageal narrowing. Meat was more frequently found at second esophageal narrowing associated with cicatrical stenosis. Almost all of foreign bodies in the air passage was found in bronchi; 3 cases were in the right side of bronchi, and 2 cases were in the left side of bronchi and 1 case was in glottic region. 7. In duration of lodgement, 50 cases (52.6%) visited our hospital within 24 hours, and 3 cases after 30 days. 8. Under topical anesthesia, 83 cases (93.3%) of the foreign bodies in the food passage were removed by esophagoscopy, by 6 cases (6.7%) failed to be removed. All of the foreign bodies of the air passages (6 cases) were removed by bronchoscopy. Among them, 5 cases under 5 years old were removed by inferior bronchoscopy through tracheostomy site.

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Voluntary Motor Control Change after Gait Training in Patients with Spinal Cord Injury (척수신경손상 환자의 보행훈련 전.후의 능동적 근육제어의 변화)

  • 임현균;이동철;이영신;셔우드아더
    • Journal of Biomedical Engineering Research
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    • v.24 no.2
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    • pp.133-140
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    • 2003
  • In this study, muscle activity was measured using surface EMG (sEMG) during a voluntary maneuver (ankle dorsiflexion) in the supine position was compared pre and post gait training. Nine patients with incomplete spinal cord injury participated in a supported treadmill ambulation training (STAT), twenty minutes a day, five days a week for three months. Two tests, a gait speed test and a voluntary maneuver test, were made the same day, or at least the same week, pre and post gait training. Ten healthy subjects' data recorded using the same voluntary maneuvers were used for the reference. sEMG measured from ten lower limb muscles was used to observe the two features of amplitude and motor control distribution pattern, named response vector. The result showed that the average gait speed of patients increased significantly (p〈0.1) from 0.47$\pm$0.35 m/s to 0.68$\pm$0.52 m/s. In sEMG analysis, six out of nine patients showed a tendency to increase the right tibialis anterior activity during right ankle dorsiflexion from 109.7$\pm$148.5 $mutextrm{V}$ to 145.9$\pm$180.7 $mutextrm{V}$ but it was not significant (p〈0.055). In addition, only two patients showed increase of correlation coefficient and total muscle activity in the left fide during left dorsiflexion. Patients' muscle activity changes after gait training varied individually and generally depended on their muscle control abilities of the pre-STAT status. Response vector being introduced for quantitative analysis showed good Possibility to anticipate. evaluate, and/or guide patients with SCI, before and after gait training.

Blockade of Thromboxane Influences Does Not Affect Renal Blood Flow Deficit in Anesthetized Diabetic Rats (마취된 당뇨 흰쥐의 신혈류량 감소에 관여하는 기전 : 내인성 쓰롬복산계의 무관성)

  • Ha, Hun-Joo;Dunham, Earl W.
    • The Korean Journal of Pharmacology
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    • v.24 no.2
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    • pp.221-232
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    • 1988
  • Studies were conducted to determine whether reduced renal blood flow (RBF) exhibited by rats with uncontrolled, streptozotocin (STZ)-induced diabetes is attributable to diabetes-associated, enhanced renal vasoconstrictor influence of endogenous thromboxane $(TX)A_2$. Rats which were injected with STZ after pretreatment with 3-O-methyl glucose (3OMG), an agent which prevents STZ-induced hyperglycemia, were also studied. Basal values of total RBF (RBF; ml $min^{-1}$ $gKw^{-1}$; electromagnetic flow probe), systemic arterial pressure (BP; mm Hg) and renal vascular resistance (RVR;BP $RBF^{-1})$in pentobarbital-anesthetized rats during a control period were $5.9{\pm}0.3$(P<0.1_{VS}. CR), $115{\pm}3$ and $20.3{\pm}1.0$(P<0.1_{VS}. CR) for STZR (n=15), and $8.4{\pm}0.4$, $123{\pm}3$ and $15.1{\pm}0.8$ for age-matched control rats (CR; n= 15), respectively. Basal values of RBF, BP and RVR in 3OMG pretreated STZR were identical to CR. In preparations shown capable of renal vasodilatation, OKY 1581 (1 mg/kg, i.v. followed by 0.4 mg/kg min infusion) abolished arachidonate-induced $(TX)A_2$ synthesis, but did not alter basal BP, RBF or RVR in either STZR or CR (n=4/group). Similarly, i.r.a. infusion of SQ29548 (100 ng/ml RBF) abolished renal vasoconstriction induced by a TX/prostaglandin endoperoxide mimic, U46619, but had no discern able affect on RVR in either STZR (n=8) or CR (n=8). The data indicates that $TXA_2$ does not participate in the elevated basal RVR of STZR which are associated with the diabetic state.

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Research and Development Trends on Omega-3 Fatty Acid Fortified Foodstuffs (오메가 3계 지방산 강화 식품류의 연구개발 동향)

  • 이희애;유익종;이복희
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.1
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    • pp.161-174
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    • 1997
  • Omega-3 fatty acids have been major research interests in medical and nutritional science relating to life sciences since after the epidemiologic data on Green3and Eskimos reported by several researchers clearly showed fewer per capita deaths from heart diseases and a lower incidence of adult diseases. Linolenic acid(LNA) is an essential fatty acid for human beings as well as linoleic acid(LA) due to the fact that vertebrates lack an enzyme required to incorporate a double bond beyond carbon 9 in the chain. In addition the ratio of omega-6 and 3 fatty acids seems to be important in terms of alleviation of heart diseases since LA and LNA competes for the metabolic pathways of eicosanoids synthesis. High consumption of omega-3 fatty acids in seafoods may control heart diseases by reducing blood cholesterol, triglyceride, VLDL, LDL and increasing HDL and by inhibiting plaque development through the formation of antiaggregatory substances like PGI$_2$, PGI$_3$ and TXA$_3$ metabolized from LNA. Omega 3 fatty acids also play an important role in neuronal developments and visual functioning, in turn influence learning behaviors. Current dietary sources of omega-3 fatty acids are limited mostly to seafoods, leafy vegetables, marine and some seed oils and the most appropriate way to provide omega-3 fatty acids is as a part of the normal dietary regimen. The efforts to enhance the intake of omega-3 fatty acids due to several beneficial effects have been made nowadays by way of food processing technology. Two different ways can be applied: one is add Purified and concentrated omega-3 fatty acids into foods and the other is to produce foods with high amounts of omega-3 fatty acids by raising animals with specially formulated feed best for the transfer of omega-3 fatty acids. Recently, items of manufactured and marketed omega-3 fatty acids fortified foodstuffs are pork, milk, cheese, egg, formula milk and ham. In domestic food market, many of them are distributed already, but problem is that nutritional informations on the amounts of omega-3 fatty acids are not presented on the labeling, which might cause distrust of consumers on those products, result in lower sales volumes. It would be very much wise if we consume natural products, result in lower sales volumes. It would be very much wise if we consume natural products high in omega-3 fatty acids to Promote health related to many types of adult diseases rather than processed foods fortified with omega-3 fatty acids.

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