• Korean Journal of Clinical Pharmacy
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• v.24 no.1
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• pp.15-25
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• 2014

Background: Elderly patients with gastrointestinal (GI) and cardiovascular (CV) risk factors may be more easily exposed to NSAID-related side effects (SEs). Based on the ACG guideline of year 2009, the aim of the study is to evaluate proper use of NSAIDs and gastroprotective drugs according to the degree of GI and CV risk strengths in the patients. Methods: Retrospectively surveyed 410 elderly patients with NSAIDs for more than 30 days at a general hospital in Korea. GI risk factor includes age, ulcer history, high-dose NSIADs, concurrent aspirin use, steroids or anticoagulants. CV risk factor includes angina, myocardial infarction, cerebral infarction, atrial fibrillation or coronary intervention requiring low-dose aspirin. These factors were classified as high/low cardiovascular groups and high/moderate/low GI groups. Results: There were 14 patients in high CV risk group and high GI risk group. The group was recommended not to use NSAIDs as it is not adequate. There were 101 patients in high CV risk group and moderate GI risk group. This group was recommended to use naproxen and PPI/misoprostol. But all patients except one were not adequate. There were 9 patients in low CV risk group and high GI risk group. This group was recommended to use selective COX-2 inhibitor and PPI/misoprostol. 5 cases were proper while 4 cases did not. There were 285 patients in low CV risk and moderate GI risk group who were recommended to use non selective NSAIDs and PPI/misoprostol or selective COX-2 inhibitor only. 103 patients were proper while 182 patients not adequate. Overall, the SEs were higher in those cases for inadequate use of drugs comparing to the adequate. CV SEs were statistically significant. However, SEs for each risk groups were different. For the case of low CV risk group and high/moderate GI risk group, the inadequate use of drugs makes the SE high and the other groups are not. Also, it was not statistically significant. Conclusions: In elderly patients, the inappropriate use of NSAIDs can increase the risk of the disease. Therefore, GI and CV risk must be considered simultaneously, and the proper use of NSAIDs and gastroprotective drugs for each risk groups should be reconsidered.

• Journal of Life Science
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• v.20 no.6
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• pp.922-928
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• 2010

This study was carried out to develop safe and novel anticoagulation agents from oriental medicinal herbs. From 33 medicinal herbs, 40 different ethanol extracts were prepared according to place of origin or extraction parts, and anticoagulation activities were evaluated by determination of thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (aPTT). The average water content and average extraction ratio for the medicinal herbs were $6.85{\pm}2.26%$ and $5.27{\pm}4.25%$, respectively. Evaluation of TT at various concentrations of the extract led to the selection of Mucuna birdwoodiana, Prunus armeniaca, Cacalia ainsliaeiflora, Cinnamonum aromaticum, and Rhus javanica Linneas potent antithrombosis medicinal herbs. Evaluation of PT and aPTT showed that the extracts of R.javanica Linne, M. birdwoodiana, and P. armeniaca have strong anticoagulation activities. Determination of hemolytic activities of 40 different ethanol extracts against human red blood cells, however, showed that only M. birdwoodiana, C. ainsliaeiflora, C. aromaticum, and R. javanica Linnehas strong anticoagulation activity without hemolytic activity at a concentration of 500 mg/ml. Our results suggest that oriental medicinal herbs, which are under a mass-production system, have potentialas a safe and novel source of anticoagulants, as well being a thrombin-specific and coagulation factor-specific inhibitor.

• Journal of Life Science
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• v.20 no.11
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• pp.1640-1647
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• 2010

Seaweeds have been recognized as a health food, having anti-obesity, anti-constipation and anticoagulation activities, and the use of seaweeds in the food, medicine, and cosmetic industries have recently significantly increased. In this study, methanol extracts were prepared from 35 different seaweeds (17 phaeophyta, 11 rhodophyta and 7 chlorophyta), and thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (aPTT) were determined in order to develop safe and novel anticoagulation agents from natural products. In TT experiments, Ecklonia cava, Ecklonia stolonifera, Eisenia bicyclis (Kjellman) Setchell, Ishige foliacea, I. okamurai, Sargassum confusum and S. yamade showed strong thrombin inhibition activity among the 35 different seaweeds. In PT experiments, the inhibitions of prothrombin were identified in the selected seaweeds from TT experiment, with the exception of S. yamade. In aPTT experiments, the seaweeds with blood coagulation inhibition factors were E. cava, E. stolonifera, E. bicyclis (Kjellman) Setchell, I. foliacea, I. okamurai, S. confusum and Hixikia fusiforme Okamura. Further anticoagulation assay with the selected 8 seaweeds suggested that S. confusum is most effective in antithrombosis, and E. stolonifera, E. bicyclis (Kjellman) Setchell, and I. foliacea have high potential as antithrombosis agents. Based on components-activity correlation analysis, flavonoids are considered as active anticoagulation components of seaweeds These results suggest that edible seaweeds, especially S. confusum, have potential as safe and novel anticoagulants, and S. yamade and H. fusiforme Okamura could be used as a thrombin-specific and coagulation factor-specific inhibitors.

• Journal of Microbiology and Biotechnology
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• v.26 no.11
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• pp.1881-1890
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• 2016

Manganese superoxide dismutase (MnSOD) is a vital enzyme that protects cells from free radicals through eliminating superoxide radicals ($O^{2-}$). Hirudin, a kind of small active peptide molecule, is one of the strongest anticoagulants that can effectively cure thrombus diseases. In this study, we fused Hirudin to the C terminus of human MnSOD with the GGGGS linker to generate a novel dual-feature fusion protein, denoted as hMnSOD-Hirudin. The hMnSOD-Hirudin gene fragment was cloned into the pET15b (SmaI, CIAP) vector, forming a recombinant pET15b-hMnSOD-Hirudin plasmid, and then was transferred into Escherichia coli strain Rosetta-gami for expression. SDS-PAGE was used to detect the fusion protein, which was expected to be about 30 kDa upon IPTG induction. Furthermore, the hMnSOD-Hirudin protein was heavily detected as a soluble form in the supernatant. The purification rate observed after Ni NTA affinity chromatography was above 95%. The hMnSOD-Hirudin protein yield reached 67.25 mg per liter of bacterial culture. The identity of the purified protein was confirmed by western blotting. The hMnSOD-Hirudin protein activity assay evinced that the antioxidation activity of the hMnSOD-Hirudin protein obtained was $2,444.0{\pm}96.0U/mg$, and the anticoagulant activity of the hMnSOD-Hirudin protein was $599.0{\pm}35.0ATU/mg$. In addition, in vitro bioactivity assay showed that the hMnSOD-Hirudin protein had no or little cytotoxicity in H9c2, HK-2, and H9 (human $CD_4{^+}$, T cell) cell lines. Transwell migration assay and invasion assay showed that the hMnSOD-Hirudin protein could suppress human lung cancer 95-D cell metastasis and invasion in vitro.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.4
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• pp.300-305
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• 2005

Purpose: For the reconstruction of maxillofacial defect created by trauma, infection, or tumor etc, the role of microvascular anastomosis or vessel graft has been increased. Many methods has been tried to increase the success rate of microvascular anastomosis. Various anticoagulants and thrombolytic agents have been used to reduce the failure rate of microvascular anastomosis and avoid re-operation. Many drugs, however, have been used in the limited cases because most of these drugs may cause complications, such as allergy, fever or systemic bleeding. This study was performed to evaluate the influence of the Argatroban on patency and thrombosis in microvascular anastomosis when it is used for local irrigation or general administration. Materials & methods: Eight mature rabbits, weighing 2kg, were used. After exposing both femoral veins, the artificial thrombotic model was made by crushing injury using a smooth needle holder, and the transverse incision were made on femoral vein. The animals were divided into 4 groups according to Argatroban administration methods; control group (n=4), topical irrigation of lumen with saline solution; experimental group 1 (n=4), topical irrigation of lumen with Argatroban saline solution; experimental group 2 (n=4), topical irrigation of lumen with heparin followed by intravenous injection of Argatroban; experimental group 3 (n=4), topical irrigation of lumen with Argatroban followed by IV of Argatroban. Microvascular anastomosis was done with 10-0 Ethilon. The patency was evaluated by empty-and-refill test 30 minutes and 3 days after microanastomosis. The thrombus formation was examined 3 days after microanastomosis by surgical microscope. The histologic findings were also examined. Results: 1. Thirty minutes after microvascular anastomosis, the patency of all experimental groups was better than that of control group, but there was no significant difference among groups. 2. Three days after microvascular anastomosis, the patency of all experimental groups was more improved than that of control group (p<0.05). There was no significant difference among experimental groups. 3. Three days after microvascular anastomosis, the amount of thrombus in all experimental groups was less than that of control group (p<0.05). There was no significant difference among experimental groups. 4. Histologically, a lot of luminal thrombus was observed around sutured area in control group. Few luminal thrombus was observed in all experimental groups. The necrotic changes were observed on the sutured vein wall in all specimens. Conclusion: These results indicate that topical irrigation and/or intravenous administration of Argatroban is effective in improving patency and preventing thrombus formation after microvascular anastomosis.

• Journal of Chest Surgery
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• v.49 no.5
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• pp.329-336
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• 2016

Background: Guidelines for esophagogastroduodenoscopy (EGD) in the West allow the continued use of warfarin under therapeutic international normalized ratio (INR) level. In Korea, no guidelines have been issued regarding warfarin treatment before EGD. The authors surveyed Korean cardiac surgeons about how Korean cardiac surgeons handle warfarin therapy before EGD using a questionnaire. Participants were requested to make decisions regarding the continuation of warfarin therapy in two hypothetical cases. Methods: The questionnaire was administered to cardiac surgeons and consisted of eight questions, including two case scenarios. Results: Thirty- six cardiac surgeons at 28 hospitals participated in the survey, and 52.7% of the participants chose to stop warfarin before EGD in aortic valve replacement patients without risk factors for thromboembolism. When the patient's INR level was 2, 31% of the participants indicated that they would choose to continue warfarin therapy. For EGD with biopsy, 72.2% of the participants chose warfarin withdrawal, and 25% of the participants chose heparin replacement. In mitral valve replacement patients, 47.2% of the participants chose to discontinue warfarin, and 22.2% of the participants chose heparin replacement. For EGD with biopsy in patients with a mitral valve replacement, 58.3% of the participants chose to stop warfarin, and 41.7% of the participants chose heparin replacement. Conclusion: This study demonstrated that attitudes regarding warfarin treatment for EGD are very different among Korean surgeons. Guidelines specific to the Korean population are required.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.204-210
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• 2003

Membranoproliferative glomerulonephritis type II(MPGN II), also called dense deposit disease, was first described by Berger and Galle in 1963. The diagnosis of MPGN II is based on electron-microscopic finding of an intensely electron-dense substance which replaces the lamina densa of the glomerular basement membrane. Although the etiology and pathogenesis of MPGN II are unknown, it frequently progresses to end-stage renal failure. Typically in MPGN II, hypocomplementemia due to activation of the alternative complement pathway is present. In addition, the association of MPGN II with partial lipodystrophy and complement abnormalities is well documented. The relationship between these associated features and the patient's renal functional outcome is not clear. With respect to the therapy for MPGN II, an alternate-day prednisolone regimen was shown to be effective. Various treatment modalities, including immunosuppression with corticosteroids, cytotoxic drugs and cyclosporin A, anticoagulants and antiplatelet therapies are used, either alone or in combination, with varying degrees of success. The purpose of this paper is to present a case of MPGN II from a 7 years old girl with paroxysmal supraventricular tachycardia(PSVT).

• Journal of Korean Neurosurgical Society
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• v.66 no.6
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• pp.726-734
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• 2023

Objective : Chronic subdural hematoma (CSDH) patients using antithrombotic agents (AT) at high risk for cardiovascular disease are increasing. The authors aimed to analyze the factors influencing outcome by targeting patients using AT and to establish a desirable treatment strategy. Methods : A retrospective analysis was performed on data from 462 patients who underwent burr hole trephination (BHT) surgery for CSDH at five hospitals from March 2010 to June 2021. Outcomes included incidence of postoperative acute bleeding, recurrence rate, and morbidity or mortality rate. Patients were divided into the following four groups based on their history of AT use : no AT. Only antiplatelet agents (AP), only anticoagulants (AC), both of AP and AC. In addition, a concurrent literature review was conducted alongside our cohort study. Results : Of 462 patients, 119 (119/462, 25.76%) were using AT. AP prescription did not significantly delay surgery (p=0.318), but AC prescription led to a significant increase in the time interval from admission to operation (p=0.048). After BHT, AP or AC intake significantly increased the period required for an in-dwelling drain (p=0.026 and p=0.037). The use of AC was significantly related to acute bleeding (p=0.044), while the use of AP was not (p=0.808). Use of AP or AC had no significant effect on CSDH recurrence (p=0.517 and p=1.000) or reoperation (p=0.924 and p=1.000). Morbidity was not statistically correlated with use of either AP or AC (p=0.795 and p=0.557, respectively), and there was no significant correlation with mortality for use of these medications (p=0.470 and p=1.000). Conclusion : Elderly CSDH patients may benefit from maintenance of AT therapy during BHT due to reduced thromboembolic risk. However, the use of AC necessitates individualized due to potential postoperative bleeding. Careful post-operative monitoring could mitigate prognosis and recurrence impacts.

• Korean Circulation Journal
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• v.53 no.7
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• pp.425-451
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• 2023

Most patients with heart failure (HF) have multiple comorbidities, which impact their quality of life, aggravate HF, and increase mortality. Cardiovascular comorbidities include systemic and pulmonary hypertension, ischemic and valvular heart diseases, and atrial fibrillation. Non-cardiovascular comorbidities include diabetes mellitus (DM), chronic kidney and pulmonary diseases, iron deficiency and anemia, and sleep apnea. In patients with HF with hypertension and left ventricular hypertrophy, renin-angiotensin system inhibitors combined with calcium channel blockers and/or diuretics is an effective treatment regimen. Measurement of pulmonary vascular resistance via right heart catheterization is recommended for patients with HF considered suitable for implantation of mechanical circulatory support devices or as heart transplantation candidates. Coronary angiography remains the gold standard for the diagnosis and reperfusion in patients with HF and angina pectoris refractory to antianginal medications. In patients with HF and atrial fibrillation, longterm anticoagulants are recommended according to the CHA₂DS₂-VASc scores. Valvular heart diseases should be treated medically and/or surgically. In patients with HF and DM, metformin is relatively safer; thiazolidinediones cause fluid retention and should be avoided in patients with HF and dyspnea. In renal insufficiency, both volume status and cardiac performance are important for therapy guidance. In patients with HF and pulmonary disease, beta-blockers are underused, which may be related to increased mortality. In patients with HF and anemia, iron supplementation can help improve symptoms. In obstructive sleep apnea, continuous positive airway pressure therapy helps avoid severe nocturnal hypoxia. Appropriate management of comorbidities is important for improving clinical outcomes in patients with HF.

• Journal of Chest Surgery
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• v.41 no.3
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• pp.354-359
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• 2008

Background: Warfarin is used as an anticoagulant and it is mainly excreted by the liver metabolism (the R-form is mainly metabolized by cytochrome p450 3A4, and the S form by cytochrome p450 2C9). Rifampin is usually used for tuberculosis or endocarditis, and it is a representative drug that induces the CYP families, including 3A4 and 2C9. The anticoagulation effect of warfarin decreases through the increased metabolism that's due to the induction of enzymes, and this iscaused by rifampin when patients take these two medicines together. No one has suggested appropriate guidelines regarding this drug interaction even though an appropriate adjustment of warfarin's dosage is needed. We examined the drug interaction in patients who received warfarin-rifampin combination therapy according to the time interval, and the factors affecting drug interaction were analyzed. Based on the data, we tried to determine the clinically available warfarin dosage guidelines before and after taking this drug combination. Material and Method: We reviewed the OO University Hospital anticoagulation service team's follow up sheets that were filled out from Jan '1998 to Sep 2006 for the patient who took warfarin - rifampin combination therapy (n=15). Result: The average INR of all the patient before rifampin administration was $2.25{\pm}0.52$ $(mean{\pm}SD)$, and that value for the first 100 days after rifampin administration was $1.98{\pm}0.28$. The p value for these two sets of data showed no correlation (paired t-test, p>0.05). The average INR of all the patient before rifampin cessation was $2.19{\pm}0.34$, and the value after rifampin cessation was $2.49{\pm}0.43$. The p value of these two showed correlation (paired t-test, p<0.05) but the average INR falls between the therapeutic INR range. Conclusion: The warfarin dose adjustment equation of before and after warfarin-rifampin combination therapy was derived based on this study's results because the warfarin dosage adjustment of the anticoagulation service team was considered appropriate.