• Childhood Kidney Diseases
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• v.10 no.2
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• pp.109-118
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• 2006

Purpose : HUS usually occurs in children after infection with shiga toxin-producing microorganism(D＋HUS). In contrast, non-postdiarrheal(D-) HUS occurs at any age and has a high rate of relapse and a poor prognosis. The clinical presentation of D-HUS is similar to that of thrombotic thrombocytopenic purpura(TTP). Recently severe deficiencies of ADAMTS13 were reported not only in TTP and D- HUS but also in D+ HUS during their acute phase. The purpose of the study is to evaluate the plasma ADAMTS13 activity in D＋ and D-HUS. Methods : Nineteen children with HUS(D＋ HUS 12 and D- HUS 7) were enrolled. The assays of plasma ADAMTS13 activity were performed during the acute stage in the D＋ HUS and at various stages of relapsing courses in the D- HUS patients by multimer assay, based on electrophoresis. Results : The median plasma activity of ADAMTS13 in D＋ HUS and D- HUS were 80.9%(37.8-132.4%) and 53.9%(1.0-94.1%), respectively, which were not statistically significantly different from control(86.4%, 34.2-112.3%)(P>0.05). One boy with D- HUS had severe deficiency of ADAMTS13(1.0%). His platelet count was normalized temporarily by fresh frozen plasma infusion. Conclusion : We have demonstrated that there is no significant difference of the plasma ADAMTS13 activity between D＋ HUS, D- HUS and control. We detected severe deficiency of ADAMTS13 in one boy who presented with relapsing episodes of D- HUS. ADAMTS13 deficiency should be considered in the subgroup of D- HUS especially with early onset and recurrent courses. Plasma therapy can be beneficial in this subgroup.

• Journal of Ginseng Research
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• v.31 no.2
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• pp.109-116
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• 2007

Korean red ginseng has broad efficacious effects against hypertension, diabetes, nociception, and cancer, and it counteracts weakness. It has been reported that Korean red ginseng is able to normalize blood pressure, improve cholesterol and lower blood glucose levels. We have recently reported that Korean red ginseng extract (KRGE) significantly prevented rat carotid arterial thrombosis in vivo, and inhibited platelet aggregation ex vivo and in vitro in a dose-dependent manner. The purpose of this study was to examine the effects of KRGE on blood circulation in human by measuring ex vivo platelet aggregation, plasma coagulation and serum lipid profiles in healthy volunteers. Subjects were randomly divided into three groups (placebo-group, KRGE-low dose group, KRGE-high dose group). Administration of KRGE to subjects significantly inhibited ADP-induced platelet aggregations both in KRGE-low dose group from $72.79{\pm}20.53$ to $62.00{\pm}23.06%$ (p=0.0009), and in KRGE-high dose group from $75.14{\pm}21.86$ to $64.52{\pm}24.72%$ (p=0.0039), respectively. Administration of KRGE to subjects also significantly inhibited collagen-induced platelet aggregations both in KRGE-low dose group from $85.52{\pm}12.57$ to $79.62{\pm}20.47%$ (p=0.0916), and in KRGE-high dose group from $80.24{\pm}18.11$ to $70.31{\pm}25.93%$ (p=0.0565), respectively. Whereas, KRGE has no significant effects on coagulation system, such as prothrombin time (PT) and activated partial thromboplastin time (APTT), and serum lipid profiles, such as total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride. KRGE also has no significant effects on hematological and serum biochemical profiles. These results suggest that KRGE has a potential to improve blood circulation through antiplatelet activity in human, and KRGE intake may be beneficial for the individuals with high risks of thrombotic and cardiovascular diseases.

• Journal of Ginseng Research
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• v.37 no.2
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• pp.176-186
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• 2013

In this study, we have investigated the effects of total saponin from Korean red ginseng (TSKRG) on thrombin-induced platelet aggregation. TSKRG dose-dependently inhibited thrombin-induced platelet aggregation with $IC_{50}$ value of about 81.1 ${\mu}g/mL$. In addition, TSKRG dose-dependently decreased thrombin-elevated the level of cytosolic-free $Ca^{2+}$ ($[Ca^{2+}]_i$), one of aggregation-inducing molecules. Of two $Ca^{2+}$-antagonistic cyclic nucleotides as aggregation-inhibiting molecules, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), TSKRG significantly dose-dependently elevated intracellular level of cAMP, but not cGMP. In addition, TSKRG dose-dependently inhibited thrombin-elevated adenosine triphosphate (ATP) release from platelets. These results suggest that the suppression of $[Ca^{2+}]_i$ elevation, and of ATP release by TSKRG are associated with upregulation of cAMP. TSKRG elevated the phosphorylation of vasodilator-stimulated phosphoprotein (VASP)-$Ser^{157}$, a cAMP-dependent protein kinase (A-kinase) substrate, but not the phosphorylation of VASP-$Ser^{239}$, a cGMP-dependent protein kinase substrate, in thrombin-activated platelets. We demonstrate that TSKRG involves in increase of cAMP level and subsequent elevation of VASP-$Ser^{157}$ phosphorylation through A-kinase activation to inhibit $[Ca^{2+}]_i$ mobilization and ATP release in thrombin-induced platelet aggregation. These results strongly indicate that TSKRG is a beneficial herbal substance elevating cAMP level in thrombin-platelet interaction, which may result in preventing of platelet aggregation-mediated thrombotic diseases.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.898-903
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• 2006

The antiplatelet and antithrombotic activities of Korean Red Ginseng (KRG) were examined on rat carotid artery thrombosis in vivo, and platelet aggregation in vitro and ex vivo. Administration of KRG to rats not only prevented carotid artery thrombosis in vivo in a dose-dependent manner, but also significantly inhibited ADP- and collagen-induced platelet aggregation ex vivo, while failed to prolong coagulation times such as activated partial thromboplastin time (APTT) and prothrombin time (PT), indicating the antithrombotic effect of KRG might be due to its anti platelet aggregation rather than anticoagulation effect. In line with the above observations, KRG inhibited U46619-, arachidonic acid-, collagen- and thrombin-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with $IC_{50}$ values of $620{\pm}12$, $823{\pm}22$, $722{\pm}21$ and $650{\pm}14\;{\mu}g/mL$, respectively. Accordingly, KRG also inhibited various agonists-induced platelet serotonin secretions as it suppressed platelet aggregation. These results suggest that KRG has a potent antithrombotic effect in vivo, which may be due to antiplatelet rather than anticoagulation activity, and KRG intake may be beneficial to the individuals with high risks of thrombotic and cardiovascular diseases.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.402-407
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• 2023

The regulation of platelet aggregation is crucial for maintaining normal hemostasis, but abnormal or excessive platelet aggregation can contribute to cardiovascular disorders such as stroke, atherosclerosis, and thrombosis. Therefore, identifying substances that can control or suppress platelet aggregation is a promising approach for the prevention and treatment of these conditions. Artemisinin, a compound derived from Artemisia or Scopolia plants, has shown potential in various areas such as anticancer and Alzheimer's disease research. However, the specific role and mechanisms by which artemisinin influences platelet activation and thrombus formation are not yet fully understood. This study investigated the effects of artemisinin on platelet activation and thrombus formation. As a result, cAMP production were increased significantly by artemisinin, as well as phosphorylated VASP and IP₃R which are substrates to cAMP-dependent kinase by artemisinin in a significant manner. The Ca²⁺ normally mobilized from the dense tubular system was inhibited due to IP₃R phosphorylation from artemisinin, and phosphorylated VASP by artemisinin aided in inhibiting platelet activity via αIIb/β3 platelet membrane inactivation and inhibiting fibrinogen binding. Finally, artemisinin inhibited thrombin-induced thrombus formation. Therefore, we suggest that artemisinin has importance with cardiovascular diseases stemming from the abnormal platelets activation and thrombus formation by acting as an effective prophylactic and therapeutic agent.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.69-74
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• 1996

Background: The diagnosis of pulmonary embolism (PE) based on clinical findings is often elusive and therefore requires confirmative diagnostic method. Pulmonary angiography, though the gold standard for the diagnosis of pulmonary embolism, is an invasive method and requires trained personnel and special equipment. Lung V/Q scan, on the other hand, is a noninvasive method but the diagnostic specificity and sensitivity arc not satisfactory in case that the results are either intermediate or low probability scan. Plasma D-dimer is generated when a thrombus is fibrinolysed by plasmin and is known to be increased in various thrombotic disorders. The aim of this study was to investigate the value of the determination of plasma D-dimer level in the diagnosis of pulmonary embolism. Methods: Pulmonary angiography was performed in 17 patients who were clinically suspected to have pulmonary embolism. 9 patients(PE, $56{\pm}13.4$ yrs, M:F=8:1) were diagnosed to have pulmonary embolism by pulmonary angiography. The control group were the 8 patients with negative pulmonary angiography and 13 orthopedic patients with no evidence of pulmonary embolism on scintigraphic and impedance plethysmographic studies(n=21) (non-PE, $54.5{\pm}11.1$ yrs, M:F=11:10). Plasma D-dimer was measured by latex agglutination method in study subjects and the results were analyzed according to the presence or absence of pulmonary embolism. Results: 1) The increased level of plasma D-dimer was more frequently observed in the patients with pulmonary embolism than in the controls(>0.5 mg/L, 8 in PE, 10 in non-PE; <0.5 mg/L, 1 in PE, 11 in non-PE, p=0.049). 2) The diagnostic value of plasma D-dimer level higher than 0.5 mg/L were as follows: sensitivity 88.9%(8/9), specificity 52.4%(11/21), positive predictive value 44.4%(8/18), and negative predictive value 91.7%(11/12). Conclusion: Plasma D-dimer determination showed high sensitivity and negative predictive value in the diagnosis of pulmonary embolism and is therefore thought to be useful in excluding the possibility of pulmonary embolism.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.564-573
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• 1999

Background: With variable symptoms and nonspecific radiographic appearances, pulmonary embolism (PE) is a frequent and often undiagnosed cause of mortality and morbidity. The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study suggested that the majority of patients undergoing ventilation-perfusion (V-Q) scan would require additional studies to establish or to exclude the diagnosis of PE. Pulmonary angiography has been regarded as gold standard for diagnosis of PE. However, it is an invasive procedure that may be associated with significant notable morbidity and mortality. Thus, availability of an accurate, noninvasive screening examination is highly desirable. Method: From October 1994 to February 1997, twenty patients (male 13, female 7, range 23-91 years, median 58 years) who were suspected as pulmonary embolism on the basis of clinical evidence and underwent the spiral volumetric computed tomography (spiral CT), were studied retrospectively to evaluate the effectiveness of spiral CT as a diagnostic tool in PE. Results: PE could be excluded with spiral CT in 4 patients ; diagnoses of these patients were lung cancer, pneumonia with lung abscess, bilateral pleural effusion due to congestive heart failure, nonspecific pulmonary abnormality retrospectively. One patient who disclosed high probability in V/Q scan, could be diagnosed as pneumonia with lung abscess and underlying emphysema with spiral CT. Among 4 patients who showed intermediate and low probability in V/Q scan, 3 patients could be confirmed as PE with spiral CT. Spiral CT was helpful in 3 patients, in whom V/Q scan could not be performed due to other reasons (e.g. night time, mechanical ventilation) to confirm the diagnosis of PE. Spiral CT could demonstrate embolus above lobar artery level in 11 patients, and up to segmental artery level in 5 patients. Conclusion: This study demonstrated that spiral CT could allow accurate demonstration of thrombotic clots in centrally localized embolism. Spiral CT could be effective, specific, noninvasive and useful diagnostic screening modality for the diagnosis of pulmonary embolism.