• Childhood Kidney Diseases
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• 제26권1호
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• pp.58-62
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• 2022

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury without any association with preceding diarrhea. Dysregulation of the complement system is the most common cause of aHUS, and monoclonal humanized anti-C5 antibodies are now recommended as the first-line treatment for aHUS. However, if the complement pathway is not the cause of aHUS, C5 inhibitors are ineffective. In this study, we report the second reported case of aHUS caused by DGKE mutations in Republic of Korea. The patient was an 11-month-old infant who presented with prodromal diarrhea similar to typical HUS, self-remitted with conservative management unlike complement-mediated aHUS but recurred with fever. While infantile aHUS often implies genetic dysregulation of the complement system, other rare genetic causes, such as DGKE mutation, need to be considered before deciding long-term treatment with C5 inhibitors.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1311-1315
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• 2012

Objectives: Thrombotic risk is increased in patients with cancer and there are important implications for those who suffer a venous thromboembolism (VTE). We undertook this study to determine the frequency, clinical patterns, and outcome of VTE in Saudi patients with cancer. Methods: Cancer (solid tumors and lymphoma) patients who developed VTE from January 2004 to January 2009 were studied retrospectively. Demographics and clinical characteristics related to thrombosis and cancer were evaluated. Results: A total of 701 patients with cancer were seen during the study period. VTE was diagnosed in 47 (6.7%) patients (median age 52, range 18-80 years). Lower limb DVT was the most common type, seen in 47% patients, followed by PE in 19%, and 19% patients had both DVT & PE. Thrombosis was symptomatic in 72% patients while it was an incidental finding on routine workup in 28%. Cancer and VTE were diagnosed at the same time in 38% of patients, and 47% patients developed VTE during the course of disease after the cancer diagnosis. The majority of VTE post cancer diagnoses occurred during the first year (median 4 months, range 1-14). Additional risk factors for VTE were present in 22 (47%) patients and 14 (30%) of these patients were receiving chemotherapy at the time of thrombosis. Only 5 (10.6%) patients were receiving thrombo-prophylaxis at the time of VTE diagnosis. Most common types of tumors associated with thrombosis were breast cancer, non-Hodgkin's lymphoma and lung cancer. The majority of the affected patients (79%) had advanced stage of cancer. After a median follow-up of 13 (range 0.5-60) months, 38 (81%) patients had died. There was no difference in the mortality of patients with symptomatic or asymptomatic thrombosis (82% vs 78.6%). Conclusions: Thrombotic complications can develop in a significant number of patients with cancer, and almost half of the patients have additional risk factors for VTE. Thrombosis is usually associated with advanced disease and can be asymptomatic in more than a quarter of cases. Thromboprophylaxis in cancer patients is under-utilized. Community based studies are needed to accurately define the extent of this problem and to develop effective prophylactic strategies.

• 한국식품영양학회지
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• 제28권5호
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• pp.880-893
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• 2015

Taurine is an abundant amino acid in many animals, including humans. Relatively large amounts of taurine are found in leukocytes, heart, muscles, retinas, kidneys, bones, and liver. Taurine has antioxidant effects; it reacts with hydrogen peroxide to prevent oxidation of the cell membrane. Taurine enhances the effects of anticancer drugs, while also reducing side effects, and taurolidine, a taurine derivative, has been shown to exhibit anti-cancer effects without notable side effects in several types of cancer. Taurine aids in cholesterol metabolism by increasing the rate of synthesis of bile acids, and, thus, reduces triglyceride levels. In addition, taurine is involved in the growth and differentiation of nerve cells and is associated with some neurological disorders. Taurine aids in bone formation and prevents bone dissolution. Moreover, taurine prevents liver damage from a variety of drugs and, thus, protects the liver. Taurine is involved in the development and function of the retina and lens. It also has anti-atherosclerotic and anti-thrombotic effects that protect against cardiovascular disease. Taurine may have additional physiological functions, and warrants further investigation.

• Journal of Applied Biological Chemistry
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• 제63권3호
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• pp.235-241
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• 2020

An essential component of the hemostatic process during vascular damage is platelet activation. However, many cardiovascular diseases, such as atherosclerosis, thrombosis, and myocardial infarction, can develop due to excessive platelet activation. Isoscopoletin, found primarily in plant roots of the genus Artemisia or Scopolia, has been studied to demonstrate potential pharmacological effects on Alzheimer's disease and anticancer, but its mechanisms and role in relation to thrombus formation and platelet aggregation have not yet been discovered. This research investigated the effect of isoscopoletin on collagen-induced human platelet activation. As a result, isoscopoletin strongly increased cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in a concentration-dependent manner. In addition, isoscopoletin greatly phosphorylated inositol 1,4,5-triphosphate receptor (IP₃R) and vasodilator-stimulated phosphoprotein (VASP), known substrates of cAMP-dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by isoscopoletin induced Ca²⁺ inhibition from the dense tubular system Ca²⁺ channels, and VASP phosphorylation was involved in fibrinogen binding inhibition by inactivating αIIb/β₃ in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clot production and finally reduced thrombus formation. Therefore, this research suggests that isoscopoletin has strong antiplatelet effects and is likely to be helpful for thrombotic diseases involving platelets by acting as a prophylactic and therapeutic agent.

• Journal of Ginseng Research
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• 제32권2호
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• pp.89-98
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• 2008

There are increasing evidences in the literatures on the potential role of ginsenosides in treating cardiovascular diseases. In this article, current information about ginsenosides-mediated vascular relaxation are reviewed. From the published studies using isolated organs, cell culture systems and animal models, ginsenosides are shown to relax blood vessels and improve blood flow through diverse mechanisms, including nitric oxide release by activating eNOS phosphorylation via PI3K/Akt and/or ERK1/2 pathways in endothelial cells, induction of inducible nitric oxide synthase through activation of NF-${\kappa}$B, reducing the intracelluar Ca$^{2+}$ levels by activating Ca$^{2+}$-activated K$^{+}$ channels in vascular smooth muscle cells and reducing platelet aggregation by decreasing thromboxane A$_2$ formation and intracelluar Ca$^{2+}$in platelets. In addition, the relevant clinical trials regarding the effects of ginsenosides on the cardiovascular disease are summarized, particulary focusing on managing hypertension and improving thrombotic disorders. Finally, antagonistic effects of ginsenosides on the prostaglandin H$_2$ receptor and scavenging effects on the generation of oxygen-derived free radicals in spontaneously hypertensive rats (SHR) are discussed.

• 생약학회지
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• 제52권1호
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• pp.26-33
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• 2021

During blood vessel damage, an essential step in the hemostatic process is platelet activation. However, it is important to properly control platelet activation, as various cardiovascular diseases, such as stroke, atherosclerosis, and myocardial infarction, are also caused by excessive platelet activation. Found primarily in the roots of plants of the genus Artemisia or Scopolia, isoscopoletin has been studied to demonstrate its potential pharmacological effects against Alzheimer's disease and anticancer, but the mechanisms and roles involved in thrombus formation and platelet aggregation are insufficient. This study investigated the effect of isoscopoletin on U46619-induced human platelet activation. As a result, isoscopoletin significantly increased the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) dose-dependently. In addition, isoscopoletin significantly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphprotein (VASP), which are known substrates for cAMP-dependent kinases and cGMP-dependent kinases. Phosphorylated IP3R by isoscopoletin inhibited Ca2+ mobilization from the dense tubular system Ca2+ channels to cytosol, and phosphorylated VASP was involved in the inhibition of fibrinogen binding through αIIb/β3 inactivation in the platelet membrane. Isoscopoletin finally reduced thrombin-induced fibrin clotting production. Therefore, this study suggests that isoscopoletin has a potent antiplatelet effect and may be helpful for platelet-related thrombotic diseases.

• 대한의생명과학회지
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• 제23권4호
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• pp.310-320
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• 2017

Ginseng has been widely used for traditional medicine in eastern Asia and is known to have inhibitory effects on cardiovascular disease (CVD) such as thrombosis, atherosclerosis, and myocardial infarction. Because, platelet is a crucial mediator of CVD, many studies are focusing on inhibitory mechanism of platelet functions. Among platelet activating molecules, thromboxane $A_2$ ($TXA_2$) and P-selectin play a central role in CVD. $TXA_2$ leads to intracellular signaling cascades and P-selectin plays an important role in platelet-neutrophil and platelet-monocyte interactions leading to the inflammatory response. In this study, we investigated the inhibitory mechanisms of total saponin fraction from Korean red ginseng (KRG-TS) on $TXA_2$ production and P-selectin expression. Thrombin-elevated $TXA_2$ production and arachidonic acid release were decreased by KRG-TS dose (25 to $150{\mu}g/mL$)-dependently via down regulation of microsomal cyclooxygenase-1 (COX-1), $TXA_2$ synthase (TXAS) activity and dephosphorylation of cytosolic phospholipase $A_2$ ($cPLA_2$). In addition, KRG-TS suppressed thrombin-activated P-selectin expression, an indicator of granule release via dephosphorylation of mitogen-activated protein kinases (MAPK). Taken together, we revealed that KRG-TS is a beneficial novel compound inhibiting $TXA_2$ production and P-selectin expression, which may prevent platelet aggregation-mediated thrombotic disease.

• Journal of Ginseng Research
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• 제46권2호
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• pp.175-182
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• 2022

Coronavirus disease 2019 (COVID-19) not only targets the respiratory system but also triggers a cytokine storm and a series of complications, such as gastrointestinal problems, acute kidney injury, and myocardial ischemia. The use of natural products has been utilized to ease the symptoms of COVID-19, and in some cases, to strengthen the immune system against COVID-19. Natural products are readily available and have been regularly consumed for various health benefits. COVID-19 has been reported to be associated with the risk of thromboembolism and deep vein thrombosis. These thrombotic complications often affects mortality and morbidity. Panax ginseng, which has been widely consumed for its various health benefits has also been reported for its therapeutic effects against cardiovascular disease, thrombosis and platelet aggregation. In this review, we propose that P. ginseng can be consumed as a supplementation against the various associated complications of COVID-19, especially against thrombosis. We utilized the network pharmacology approach to validate the potential therapeutic properties of P. ginseng against COVID-19 mediated thrombosis, the coagulation pathway and platelet aggregation. Additionally, we aimed to investigate the roles of P. ginseng against COVID-19 with the involvement of platelet-leukocyte aggregates in relation to immunity-related responses in COVID-19.

• Preventive Nutrition and Food Science
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• 제12권3호
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• pp.141-147
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• 2007

Cordycepin (3'-deoxyadenosine), which comes from Cordyceps militaris, the Chinese medicinal fungal genus Cordyceps, is used in the treatment of various diseases such as cancer and chronic inflammation. We recently reported that cordycepin has a novel antiplatelet effect through the down regulation of $[Ca^{2+}]_{i}$ and the elevation of cGMP/cAMP production. In this study, we further investigated the effect of cordycepin on collagen-induced platelet aggregation in the presence of cGMP-dependent protein kinase (PKG)- or cAMP-dependent protein kinase (PKA)-inhibitor. PKG inhibitor Rp-8-pCPT-cGMPS potentiated the collagen-induced platelet aggregation, but PKA inhibitor Rp-8-Br-cAMPS did not. However, both Rp-8-pCPT-cGMPS and Rp-8-Br-cAMPS reduced inhibition by cordycepin of collagen-induced platelet aggregation. Moreover, cordycepin inhibited $Ca^{2+}-dependent$ phosphorylation of both 47 kDa- and 20 kDa-protein in the presence of both PKG inhibitor and PKA inhibitor. Taken altogether, these results suggest that the inhibitory effect of cordycepin on collagen-induced platelet aggregation is associated with cGMP/PKG- and cAMP/PKA-pathways, and thus cordycepin may be an efficacious intervention against platelet aggregation-mediated thrombotic disease.

• Archives of Plastic Surgery
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• 제37권3호
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• pp.239-244
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• 2010

Purpose: Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson's pseudoangiosarcoma, is a rare disease which is now considered as a reactive process of the endothelium rather than a benign neoplasm. It can occur in any blood vessels in the body but more common in the head and neck region as a solitary, often tender, bluish or reddish nodule. IPEH is characterized by the development of endothelial-lined papillary projections in a vascular lumen, usually associated with thrombotic material, the endothelial cells in the papillary structures showing only slight atypia and occasional mitotic Figures, the absence of tissue necrosis. Methods: 8 patients with IPEH were enrolled in the study from 2002 to 2007. All 8 lesions were surgically excised for histopathologic diagnosis. Results: 4 patients were female. The duration of the lesions ranged from 3 months to 15 years. The tumors were first noted between the ages of 20 and 72 years. 4 patients had lesions on the head; 2 on the toe; 1 on the back; and 1 on the finger, respectively. All lesions were solitary, ranged in size from 2 mm to 27 mm. There were no recurrences. Conclusion: The clinical appearance of IPEH is not specific, presented as a primary neoplasm, and the diagnosis can be established by microscopic examination. Complete surgical excision is the best choice of therapy for patients with IPEH, and is both diagnostic and curative. Awareness of this lesion will prevent incorrect diagnosis and overly aggressive treatment.