• 제목/요약/키워드: and Platelet

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U46619-유도의 혈소판에서 PI3K/Akt 및 MAPK 조절을 통한 Artemether의 응집억제효과 (Anti-aggregation Effect of Artemether Through Regulation of PI3K/Akt and MAPK in U46619-induced Platelets)

  • 박창은;이동하
    • 생약학회지
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    • 제53권2호
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    • pp.64-69
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    • 2022
  • When blood vessels are damaged, a rapid hemostatic response should occur in order to lower blood loss and keep normal circulation, and platelet activation and aggregation are essential. Nevertheless, abnormal or excessive platelet aggregation can be a reason of cardiovascular diseases including thrombosis, atherosclerosis, and stroke. Therefore, the screening for a substance which can regulate platelet activation and suppress aggregation reaction is very important for treatment and prevention of cardiovascular diseases. Artemether is a methyl ether derivative of artemisinin, which is isolated from the antimalarial plant Artemisia annua, but research on platelet aggregation or its mechanisms is still insufficient. This study identified the effects of artemether on U46619-induced human platelet aggregation and their granule secretion (ATP and serotonin release). In addition, the effects of artemether on the phosphorylation of PI3K/Akt or MAPK, which are related to signal transduction in platelet aggregation, were studied. As the results, artemether significantly lowered PI3K/Akt and MAPK phosphorylation, which inhibited platelet aggregation through granule secretion (ATP and serotonin release) dose-dependently. Therefore, we suggest that artemether is an antiplatelet substance that regulates PI3K/Akt and MAPK pathway and is of value as a therapeutic and preventive agent for platelet-derived cardiovascular diseases.

Esculetin이 PI3K/MAPK 경로 하향 조절을 통해 collagen 유도의 혈소판 응집 억제에 미치는 효과 (Inhibitory Effects of Esculetin Through the Down-Regulation of PI3K/MAPK Pathway on Collagen-Induced Platelets Aggregation)

  • 박창은;이동하
    • 생약학회지
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    • 제52권3호
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    • pp.127-133
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    • 2021
  • Platelet activation plays a major role in cardiovascular disorders (CVDs). Thus, disrupting platelet activation represents an attractive therapeutic target on CVDs. Esculetin, a bioactive 6,7-dihydroxy derivative of coumarin, possesses pharmacological activities against obesity, diabetes, renal failure, and CVDs. In other report, the effect of esculetin has been examined in human platelet activation and experimental mouse models, and esculetin inhibited collagen- and arachidonic acid-induced platelet aggregation in washed human platelets. However, it had no effects on other agonists such as thrombin and U46619, and its mechanism is not also clearly known. This study investigated the effect of esculetin on collagen-induced human platelet aggregation, and we clarified the mechanism. Esuletin has effects on the down regulation of PI3K/Akt and MAPK, phosphoproteins that act in the signaling process in platelet aggregation. The effects of esculetin reduced of TXA2 production and phospholipase A2 activation, and intracellular granule secretion including ATP and serotonin, leading to inhibit platelet aggregation. These results clearly clarified the effect of esculetin in inhibiting platelet activity and thrombus formation in humans.

Platelet Indices May be Useful in Discrimination of Benign and Malign Endometrial Lesions, and Early and Advanced Stage Endometrial Cancer

  • Kurtoglu, Emel;Kokcu, Arif;Celik, Handan;Sari, Seher;Tosun, Migraci
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권13호
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    • pp.5397-5400
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    • 2015
  • Background: The aim of this study was to investigate the predictive value of white blood cells (WBC), the neutrophil to lymphocyte ratio (NLR), platelet indices including mean platelet volume (MPV), platelet distribution width (PDW), platelet crit (PCT) and platelet to lymphocyte ratio (PLR) in discrimination between benign and malign endometrial lesions, and early and advanced stage endometrial adenocarcinomas. Materials and Methods: Data for 105 patients undergoing total abdominal or vaginal hysterectomy for benign uterine diseases and 114 patients surgically staged for endometrium adenocarcinoma at Ondokuz Mayis University, Department of Gynecology and Obstetrics, between 2008 and 2014, were collected. Parameters were preoperative and postoperative complete blood counts in the week prior to surgery with differentials including WBC, platelet count, platelet indices (MPV, PCT, PDW), NLR and PLR. Pathologic evaluations for both benign and malign endometrium lesions, grade of endometrium adenocarcinoma, tumor stage, presence of lymphovascular space invasion (LVI) were retrospectively analyzed. Results: Regarding definitive factors in discriminating patients with endometrium cancer from those with benign diseases, MPV was significantly increased in the malign group whereas there was a significant decrease in the PDW value compared to the benign group. The best cut-off value in differentiation of the benign and malign groups, malign cases were found to increase over the value of 7.54 for MPV, and under 37.8 for PDW. When definitive factors in discrimination of early stage endometrium cancer from advanced stage disease and LVI in the malign group were evaluated according to the ROC analysis, no significant relation was detected between blood parameters and the stage and the LVI of the disease. Conclusions: MPV and PDW may have predictive value in the discrimination of benign and malign endometrium diseases. Nevertheless, since there have been few reports on this topic, further large-scale prospective studies are necessary.

내인성 및 외인성 Estogen이 관상동맥질환 위험인자에 미치는 영향 -제2보: 내인성 및 외인성 Estrogen이 혈소판 응집에 미치는 영향- (The Effect of Endogenous and Exogenous Estrogen on Risk Factors of Coronary Heart Disease -Part II : On Platelet Aggregation-)

  • 박유신
    • Journal of Nutrition and Health
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    • 제32권5호
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    • pp.561-569
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    • 1999
  • In the atherosclerotic subjects, arterial endothelial cell injury and plaque formation are suspected to be strong causable factors in developing acute coronary syndrome, and it was revealed that platelets have a very important role in this case. Women are exposed to atherosclerosis at a different degree after menopause or oral contraception. The purpose of this study was to determine the effects of endogenous and exogenous estrogen on the degree of platelet aggregation in platelet rich plasma(PRP) in twenty nonsmoking healthy Korean women for 12 weeks. The subjects were assigned to three groups: (1) eight women aged 49 to 60(yr) for the postmenopausel(Pst) group, (2) eight, aged 22 to 30(yr) for the premenopausa(Pre) group, (3) four, aged 23 to 30(yr) for the oral contraceptive (OC) group which used triphasic OC formulation. Fasting blood sample were obtained from the subjects, (1) once per 6 weeks in the Pst group, (2) every phase of the menstrual cycle in the Pre group, (3) each once during and after OC administration in the OC group. ADP, collagen and epinephrine were used as aggregating reagents, and platelet aggregation and time(Δt: time reaching to the maximum point of aggregation) in PRP were measured at the maximum point of aggregation in five minutes. All the data were adjusted for dietary effects, personality type and body mass index(BMI) by using analysis of covariation(ANCOVA). Platelet aggregation to ADP and collagen(MADP and MCOLL) were not significantly different among the three groups, and Δt to ADP and collagen(TADP and TCOLL) were not either. But maximum platelet aggregability and Δt to epinephrine(MEPIN and TEPIN) were significantly different among the three groups, and the OC group showed the lowest value (p<0.01). Maxtimum platelet aggregability and Δt during the menstrual cycle were not significantly different in the Pre group. Any other significant differences in the maximum platelet aggregability and Δt were found between oral contraception phase and washing out phase(menstruation) in the OC group. In results, maximum platelet aggregability and aggregation time to ADP and collagen seemed not to be affected by endogenous and exogenous estrogen, even though MEPIN and TEPIN showed significantly low in the OC group among the three groups.

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혈소판 공여자의 불안과 불편감 - 첫 공여자를 중심으로 - (The Anxiety and Discomfort of Platelet Donors)

  • 홍숙임;최소은;박호란
    • 한국보건간호학회지
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    • 제14권1호
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    • pp.172-181
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    • 2000
  • This study was designed to evaluate the degree of the anxiety and discomfort experienced by first-time donors in platelet donation. The subject of this study was 309 first-time platelet donors visiting apheresis unit of St. Mary hospital in Seoul. The data was collected from Questionnaire during period of 28 April to 10 September 1999. The statistical methods used were t-test. ANOVA and stepwise multiple regression. The results were as follows. 1. The most common group were 21-30 years of age and soldier of job. 2. The mean scores of the platelet donor's anxiety was $1.60\pm0.32$. 3. The mean scores of platelet donor's discomfort was $1.72\pm0.44$. 4. The variables influencing anxiety were the physical condition. the level of education and donation experience. 5. The variables influencing discomfort were the job. diet before donation and physical condition. As the result above. the student group of the first time platelet donor experienced highest anxiety. It is important to assess the physical condition and diet before donation for more comfortable platelet donation. Furthermore. the developments of nursing interventions are required to reduce anxiety and discomfort of platelet donors.

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Cyclopiazonic acid 및 aflatoxin B1이 토끼의 혈소판 응집 및 ATP 방출에 미치는 영향 (Effects of cyclopiazonic acid and aflatoxin B1 on rabbit platelet aggregation and ATP release)

  • 홍충만;조명행
    • 대한수의학회지
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    • 제36권4호
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    • pp.887-894
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    • 1996
  • Cyclopiazonic acid(CPA) known as stimulating the release of intracellular calcium, aflatoxin $B_1(AFB_1)$ causing gastrointestinal hemorrhage frequently were used as model toxic mycotoxins in these studies. First of all, the effects of various mycotoxins on the platelet aggregation response were determined. The effects of mycotoxins on the ATP release from platelet by aggregating factors were investigated. The results and conclusions obtained from these studies are : 1) CPA promoted ADP, collagen, thrombin, A.A. and PAF-induced rabbit platelet aggregation. $AFB_1$ inhibited collagen, A.A. and PAF-induced rabbit platelet aggregation only. 2) CPA increased both aggregation and disaggregation time, whereas $AFB_1$ decreased in a dose dependent manner. 3) CPA increased ADP, thrombin, A.A. and PAF-induced ATP release. $AFB_1$ increased A.A.-induced ATP release and decreased PAF-induced release in a dose dependent manner. In conclusion, CPA promoted platelet aggregation by the increase of ATP. Antiaggregating effects of AFB1 may be due to decreases of ATP. These data provide the basis for the future study of roles of ATP release in platelet aggregation.

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The Fibrinogen to Mean Platelet Volume Ratio Can Predict Overall Survival of Patients with Non-Metastatic Gastric Cancer

  • Song, Shubin;Cong, Xiliang;Li, Fengke;Xue, Yingwei
    • Journal of Gastric Cancer
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    • 제18권4호
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    • pp.368-378
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    • 2018
  • Purpose: Fibrinogen and platelets have been reported to play important roles in tumorigenesis and cancer progression. The aim of this research was to investigate the combination of functions of fibrinogen, platelets, and mean platelet volume (MPV) in predicting the survival of patients with gastric cancer (GC). Materials and Methods: A retrospective study was conducted with 1,946 patients with GC and 299 patients with benign gastric tumor to analyze their fibrinogen, platelet, and MPV levels, and other clinicopathological characteristics along with their prognoses. Several indicators were evaluated along with fibrinogen, platelets, and MPV and their prognostic abilities were assessed. Univariate and multivariate survival analyses were conducted to determine the independent risk factors for overall survival. Results: Increased levels of fibrinogen, platelets, and MPV were observed with the progress of the GC stages. Elevated fibrinogen, platelets, and the combined indicators, including fibrinogen*MPV (FM), platelet*fibrinogen*MPV (PFM), fibrinogen/MPV (FMR), platelet*fibrinogen (PF), platelet*fibrinogen/MPV (PFMR), platelet*MPV (PM), and platelet/MPV (PMR), foreboded poor prognosis. Meanwhile fibrinogen and FMR can be considered as independent risk factors for overall survival in patients with non-metastatic GC. But these indicators can hardly predict survival of patients in stage IV. Conclusions: Elevated fibrinogen, platelets, and MPV levels were in accordance with advanced stages, and fibrinogen, platelet, and MPV, in combination, can be used to predict survival of patients with non-metastatic GC. FMR was an independent prognostic factor for overall survival of patients with GC.

Inhibitory Effect of Scopoletin on U46619-induced Platelet Aggregation through Regulation of Ca2+ Mobilization

  • Lee, Dong-Ha
    • 대한의생명과학회지
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    • 제25권2호
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    • pp.123-130
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    • 2019
  • Platelet aggregation is essential for hemostatic process in case of blood vessels damages. However, excessive platelet aggregation can cause cardiovascular disorders including atherosclerosis, thrombosis and myocardial infarction. Scopoletin is usually found in the roots of genus Scopolia or Artemisia, and is known to have anticoagulant and anti-malarial effects. This study investigated the effect of scopoletin on human platelet aggregation induced by U46619, an analogue of thromboxane $A_2(TXA_2)$. Scopoletin had anti-platelet effects by down-regulating $TXA_2$ and intracellular $Ca^{2+}$ mobilization ($[Ca^{2+}]_i$), the aggregation-inducing molecules generated in activated platelets. On the other hand, scopoletin increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are known to be intracellular $Ca^{2+}$ antagonists. This resulted in inhibition of fibrinogen binding to ${\alpha}IIb/{\beta}_3$ in U46619-induced human platelet aggregation. In addition, scopoletin inhibited the release of adenosine trisphosphate (ATP) in dose-dependent manner. This result means that the aggregation amplification activity through the granule secretion in platelets was suppressed by scopoletin. Therefore, we demonstrated that scopoletin has a potent antiplatelet effect and is highly likely to prevent platelet-derived vascular disease.

혈소판농축혈장이 조골세포주의 세포부착에 미치는 영향에 대한 연구 (The Effect of Platelet-Rich Plasma on the Cellular Attachment of Osteoblast Cell Line)

  • 정태욱;장경수;김창회;김영수
    • 구강회복응용과학지
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    • 제19권4호
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    • pp.281-290
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    • 2003
  • Platelet-rich plasma which is made with the newly developed technique concentrating platelets 3-folds or more is also proven to be very effective method to stimulate and accelerate the healing of bone and soft tissue. This study is aimed to investigate the effect of platelet-rich plasma on the attachment of osteoblast. To evaluate the effect on human, human osteoblast cell line was cultured. Platelet-rich plasma was extracted from the blood of a healthy volunteer. The effect on the attachment was evaluated by MTT assay. To evaluate autocrine and paracrine effect on osteoblast, conditioned medium was made and compared with platelet-rich plasma. By western blot analysis, the expression of fibronectin and vitronectin in experimental groups was examined. The results were as following: The cellular attachment of osteoblast cell line increased depending on the concentration of platelet-rich plasma and conditioned medium. The amount of increasing was similar between two groups. The expression of fibronectin and vitronectin in platelet-rich plasma and conditioned medium is more than control group in western blot analysis. These findings imply that platelet-rich plasma enhance the cellular attachment by inducing fibronectin, vitronectin from osteoblast and maximize the cellular attachment by using the autocrine and paracrine effect of platelet-rich plasma.

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
    • 한국식품위생안전성학회지
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    • 제19권3호
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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.