• Journal of Microbiology and Biotechnology
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• v.26 no.2
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• pp.295-308
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• 2016

This study investigated the effects of a flavonoid-rich ethanol extract of persimmon leaf (PL), an ethanol extract of Citrus junos Sieb (CJS), and a PL-CJS mixture (MPC) on mice fed a high-fat diet (HFD). We sought to elucidate the mechanisms of biological activity of these substances using measurements of blood coagulation indices and lipid metabolism parameters. C57BL/6J mice were fed a HFD with PL (0.5% (w/w)), CJS (0.1% (w/w)), or MPC (PL 0.5%, CJS 0.1% (w/w)) for 10 weeks. In comparison with data obtained for mice in the untreated HFD group, consumption of MPC remarkably prolonged the activated partial thromboplastin time (aPTT) and prothrombin time (PT), whereas exposure to PL prolonged aPTT only. Lower levels of plasma total cholesterol, hepatic cholesterol, and erythrocyte thiobarbituric acid-reactive substances, hepatic HMG-CoA reductase, and decreased SREBP-1c gene expression were observed in mice that received PL and MPC supplements compared with the respective values detected in the untreated HFD animals. Our results indicate that PL and MPC may have beneficial effects on blood circulation and lipid metabolism in obese mice.

• Journal of Ginseng Research
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• v.44 no.5
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• pp.717-724
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• 2020

Background: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II. Conclusion: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.

• YAKHAK HOEJI
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• v.43 no.6
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• pp.809-817
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• 1999

The effect of 2-(4-cyanophenyl)amino-1,4-naphthalenedione-3-pyridinium perchlorate (PQ5) on pla-telet aggregation and its action mechanisms were investigated with rat platelet. PQ5 inhibited the platelet aggregation induced by collagen ($6{\;}{\mu\textrm{g}}/ml$), thrombin (0.4 U/ml) and A23187 ($3{\mu}M$) in concentration-dependent manner with $IC_{50}$ values of 5.50, 25.89 and $37.12{\;}{\mu}M$, respectively. PQ5 also significantly reduced the thromboxane $A_2$ (TXA2) formation in a concentration dependent manner. The collagen-induced arachidonic acid (AA) release in [-3H]-AA incorporated platelet, an indication of the phospholipase $A_2$ activity, was decreased by PQ5 pretreatment PQ5 significantly inhibited the activity of thormboxane synthase only at high concentration ($100{\mu}M$), but did not affect the cyclooxygenase activity at all. Collagen-induced ATP release was significantly reduced by PQ5. Calcium-induced platelet aggregation experiment suggests that the elevation of intracellular free $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) by collagen stimulation is decreased by the pretreatment of PQ5, which is due to the inhibition of calcium release from intracellular store and influx from outside of the cell. PQ5 did not showed the effect of anticoagulation as prothrombin time (PT) or activated partial thromboplastin time (APTT). Form these results, it is suggested that PQ5 exerts its antiplatelet activity through the inhibition of the intracellular $Ca^{2+}$ mobilization and the decrease of the $TXA_2$ synthesis.

• Preventive Nutrition and Food Science
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• v.18 no.3
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• pp.181-187
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• 2013

Artemisia princeps Pampanini (AP) has been used as a traditional medicine in Korea, China and Japan and reported to exhibit various beneficial biological effects including anti-inflammatory, antioxidant, anti-atherogenic and lipid lowering activities; however, its antiplatelet and anticoagulant properties have not been studied. In the present study, we evaluated the effects of an ethanol extract of Artemisia princeps Pampanini (EAP) and its major flavonoids, eupatilin and jaceosidin, on platelet aggregation and coagulation. To determine the antiplatelet activity, arachidonic acid (AA)-, collagen- and ADP (adenosine diphosphate)-induced platelet aggregation were examined along with serotonin and thromboxane A2 ($TXA_2$) generation in vitro. The anticoagulant activity was determined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time (PT) in vitro. The data showed that EAP and its major flavonoids, eupatilin and jaceosidin, significantly reduced AA-induced platelet aggregation and the generation of serotonin and $TXA_2$, although no significant change in platelet aggregation induced by collagen and ADP was observed. Moreover, EAP significantly prolonged the PT and aPTT. The PT and/or aPTT were significantly increased in the presence of eupatilin and jaceosidin. Thus, these results suggest that EAP may have the potential to prevent or improve thrombosis by inhibiting platelet activation and blood coagulation.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.18 no.1
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• pp.39-47
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• 2015

Purpose: To determine clinically useful biochemical markers reflecting disease activity and/or gastrointestinal (GI) tract involvement in Henoch-$Sch{\ddot{o}}nlein$ purpura (HSP). Methods: A total of 185 children with HSP and 130 controls were included. Laboratory data indicating inflammation, standard coagulation, and activated coagulation were analyzed for the HSP patients, including measurements of the hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, prothrombin time, activated partial thromboplastin time, and fibrinogen, D-dimer, and fibrin degradation product (FDP) levels. The clinical scores of the skin, joints, abdomen, and kidneys were assessed during the acute and convalescence phases of HSP. Results: The WBC count, ANC, ESR, and CRP, fibrinogen, D-dimer, and FDP levels were significantly higher in the acute phase compared with the convalescent phase of HSP (p<0.05). The total clinical scores were more strongly correlated with the D-dimer (r=0.371, p<0.001) and FDP (r=0.369, p<0.001) levels than with inflammatory markers, such as the WBC count (r=0.241, p=0.001), ANC (r=0.261, p<0.001), and CRP (r=0.260, p<0.001) levels. The patients with GI symptoms had significantly higher ANC (median [interquartile range], 7,138.0 [4,446.4-9,470.0] vs. 5,534.1 [3,263.0-8,153.5], p<0.05) and CRP (0.49 [0.15-1.38] vs. 0.23 [0.01-0.67], p<0.05), D-dimer (2.63 [1.20-4.09] vs. 1.75 [0.62-3.39]), and FDP (7.10 [0.01-13.65] vs. 0.10 [0.01-7.90], p<0.05) levels than those without GI symptoms. Conclusion: D-dimer and FDPs are more strongly associated with disease activity and more consistently reflect GI involvement than inflammatory markers during the acute phase of HSP.

• The Journal of the Korean dental association
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• v.57 no.10
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• pp.613-622
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• 2019

The vitamin K antagonist (VKA), cumadin, or warfarin, is the only antithrombotic drug that can be orally administered and has excellent effective for decades. However, it is cumbersome to periodically inspect the prothrombin time (PT) order to maintain adequate concentrations that do not cause bleeding, takes a few days to indicate therapeutic effects, gets affected by several factors such as food and drugs etc, and narrow in the therapeutic range. Although recently in development, the non-vitamin K antagonist anticoagulants(NOACs) exhibit a rapid onset of action and have relatively short half- lives compared to Coumadin. Because of these pharmacokinetic properties, it is possible to modify an individual's anticoagulation status quite rapidly, minimizing the period where the anticoagulation activity is therapeutically suboptimal. And the short half -lives of these drug allow for the relatively rapid reduction of their anticoagulation effects. There are currently no published clinical trials specifically assessing the bleeding risks associated with dental procedures for patients taking the NOACs. It is not necessary to interrupt NOAC medication for dental procedures that are likely to cause bleeding, but which have a low risk of bleeding complications. Because the bleeding risk for these procedures is considered to be low, the balance of effects is in favour of continuing the NOAC treatment without modification, to avoid increasing the risk of a thromboembolic event. The patients should be advised to miss(apixaban or dabigatran) or delay(rivaroxaban) a dose of their NOAC prior to dental procedures that are likely to cause bleeding and which have a higher risk of bleeding complications. Because the risk of bleeding complications for these procedures is considered to be higher, the balance effects is in favour of missing or delaying the pretreatment NOAC dose. The interruption is only for a short time to minimize the effect on thromboembolic risk.

• Journal of Gastric Cancer
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• v.22 no.1
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• pp.47-55
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• 2022

Purpose: The use of direct oral Xa inhibitors (DXaIs) to prevent venothrombotic events is increasing. However, gastrointestinal bleeding, including that related to endoscopic resection, is a concern. In this study, we evaluated bleeding and coagulation times during the perioperative period of gastric endoscopic submucosal dissection (ESD). Materials and Methods: Patients who consecutively underwent gastric ESD from August 2016 to December 2018 were analyzed. Bleeding rates were compared among the 3 groups (antiplatelet, DXaIs, and control). DXaI administration was discontinued on the day of the procedure. Prothrombin time (PT), activated partial thromboplastin time, and the ratio of inhibited thrombin generation (RITG), which was based on dilute PT, were determined before and after ESD. Results: During the study period, 265 gastric ESDs were performed in 239 patients, where 23 and 50 patients received DXaIs and antiplatelets, respectively. Delayed bleeding occurred in 17 patients (7.4%) and 21 lesions (7.1%). The bleeding rate in the DXaI group was significantly higher than that in the other groups (30.4%, P<0.01), and the adjusted odds ratio of bleeding was 5.7 (95% confidence interval, 1.4-23.7; P=0.016). In patients using DXaIs, there was a significant (P=0.046) difference in the median RITG between bleeding cases (18.6%) and non-bleeding cases (3.8%). Conclusions: A one-day cessation of DXaIs was related to a high incidence of bleeding after gastric ESD, and monitoring of residual coagulation activity at trough levels might enable the predicted risk of delayed bleeding in patients using DXaIs.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.2
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• pp.147-162
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• 2022

Purpose: To design a prospective study on endovascular closure of congenital portosystemic shunts. The primary endpoint was to assess the safety of endovascular closure. The secondary endpoint was to evaluate the clinical, analytical and imaging outcomes of treatment. Methods: Fifteen patients (age range: 2 days to 21 years; 10 male) were referred to our center due to congenital portosystemic shunts. The following data were collected prior to treatment: age, sex, medical history, clinical and analytical data, urine trimethylaminuria, abdominal-US, and body-CT. The following data were collected at the time of intervention: anatomical and hemodynamic characteristics of the shunts, device used, and closure success. The following data were collected at various post-intervention time points: during hospital stay (to confirm shunt closure and detect complications) and at one year after (for clinical, analytical, and imaging purposes). Results: The treatment was successful in 12 participants, migration of the device was observed in two, while acute splanchnic thrombosis was observed in one. Off-label devices were used in attempting to close the side-to-side shunts, and success was achieved using Amplatzer™ Ductus-Occluder and Amplatzer™ Muscular-Vascular-Septal-Defect-Occluder. The main changes were: increased prothrombin activity (p=0.043); decreased AST, ALT, GGT, and bilirubin (p=0.007, p=0.056, p=0.036, p=0.013); thrombocytopenia resolution (p=0.131); expansion of portal veins (p=0.005); normalization of Doppler portal flow (100%); regression of liver nodules (p=0.001); ammonia normalization (p=0.003); and disappearance of trimethylaminuria (p=0.285). Conclusion: Endovascular closure is effective. Our results support the indication of endovascular closure for side-to-side shunts and for cases of congenital absence of portal vein.

• Natural Product Sciences
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• v.29 no.1
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• pp.42-49
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• 2023

This study investigated the effect of ethanol extracts of horsetail, alfalfa, ortie, chêne and aleppo oak on blood coagulation in vitro. Extraction was performed by the maceration method. Extracts were mixed with platelet and plasma, then prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet aggregation tests were conducted. Alfalfa extract had a dose-dependent effect on the PT. Ortie, and horsetail, reduced the PT significantly compared to control group. Alfalfa, horsetail, and ortie reduced the APTT, but their effect was insignificant compared to the control group. The pooled extract showed the highest effect compared to the single extracts in a dose-dependent manner. Horsetail and alfalfa induced platelet aggregation in response to arachidonic acid but not in response to collagen. In the case of ortie, no aggregation occurred regarding the arachidonic acid, and incomplete was observed in response to collagen. Interestingly, blood clotting occurred immediately after adding the chêne, aleppo oak and the pooled extract, and therefore platelet poor plasma (PPP) and platelet rich plasma (PRP) became jelly. Generally, chêne and aleppo oak, as well as pooled extract, were more effective in inducing both primary and secondary coagulation pathways via shortening the PT and APTT, and induction of platelet aggregation.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1972.03a
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• pp.17.1-17
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• 1972

Hemophilia B is hereditary disorder of blood coagulation known as a deficiency of P.T.C. or Christmas factor. Anyway it's indistinguishable clinically with hemophia A and C. Here's one of most interesting problems gave us because we could only find it out as a hemophilia B. when we stood a situation to be met continuous bleeding from the operative wound of tonsillectomy and Adenoidectomy. Wintrobe proposed that easy bruising, difficulty in stopping the bleeding from razor cuts, and prolonged bleeding after tonsillectomy or tooth extraction usually are the major manifestations. For a long time little attention was paid to reports of a milder form of the diseases. In such cases coagulation time, and even prothrombin consumption were normal and the symptoms were correspondinly mild, small wounds as a rule giving little trouble and hemoarthrosis being uncommon. In our cases, there's no specific contributory history except nasal bleeding intermittently and also no specific contributory laboratory data before the operation. After the T. & A., there's continuous bleeding from nasopharynx and the coagulas on the both tonsilar fossas being grown day by day. Therefore we suspected some abnormality of coagulation mechanism and then we could get conclusion of hemophilia B. after various laboratory tests including T.G.T., As I know, this case, hemophilia B. is 3rd one as a report in Korea. We have no data of hemophilia family at present time, so that I propose that we have to make system of hemophilia family in Korea. In a next, we have to make routinely complete laboratory test, ego routine C.B.C., bleeding time, coagulation time, prothrombine time, partial thromboplastine time, before operation of T.& A. If we can solve these problems we can get the T. & A. without any problems of bleeding according to get the operation of T. & A.