• 한국자원식물학회지
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• 제20권2호
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• pp.104-112
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• 2007

미강에서 추출한 tocotrienol의 생리활성 효과를 알아보기 위하여 동물식이 실험을 통한 혈액 분석과 간 및 심장의 조직을 조사한 바 그 결과는 다음과 같다. 1. Tocotrienol의 섭취는 혈중 triacylglycerol을 강하시키며 그 효과가 tocopherol보다 훨씬 큰 것으로 판단되었다. 또한 tocopherol과 tocotrienol은 모두 혈중 HDL의 농도를 증가시키는 반면 혈중 LDL 농도의 저하를 유도하는 것으로 판단되며, Duncan grouping을 통하여 tocotrienol이 tocopherol보다 더 큰 효과를 보임을 알 수 있었다. 2. Tocopherol과 tocotrienol 모두 혈능 AST의 활성을 저하시키는 것으로 나타났으며, 혈중 Alanine Transaminase(ALT) 활성의 변화도 같은 경향이었다. 따라서 tocopherol과 tocotrienol이 간 손상 억제나 복구, 간 기능의 회복 등에 효과가 있는 것으로 판단되었으며, tocotrienol이 tocopherol보다 간 기능의 보호에 더 큰 효과를 가지는 것으로 나타났다. 또한 심장이나 뇌 등의 다양한 조직에서 손상을 회복시키거나 기능을 보호하는 효과도 가지는 것으로 판단되었다. 3. 간과 심장 조직에 대한 현미경학적 조사를 한 결과 cholesterol을 투여한 군에서는 약간의 세포손상 현상을 보였으나, tocotrienol을 투여한 군들은 tocotrienol의 농도를 증가함에 따라 지방침착정도가 점점 감소하여 농도별로 간과 심장에 미치는 영향이 뚜렷이 차이가 남을 알 수 있었으며, 이러한 결과는 tocotrienol의 섭취가 각 조직의 지방침착을 뚜렷하게 억제하는 효과가 있음을 증명하는 것으로 판단되었다.

• 한국자원식물학회지
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• 제31권1호
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• pp.1-9
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• 2018

제주모시풀에서 각종 column chromatography법을 이용하여 2종의 flavonoid를 분리하여, $^1H$-, $^{13}C-NMR$, LC ESI-IT-TOF MS를 통해 구조동정 할 수 있었다. 분리된 물질이 심장세포에서 높은 항산화 활성을 가지고 있으며, 활성 산소종의 작용기전 연구 및 심근경색 질환의 예방과 치료에 효과적으로 사용할 수 있는 기초자료가 될 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.3035-3042
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• 2015

Background: Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells. Objectives: To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms. Materials and Methods: A549 cells were treated with $10{\sim}320{\mu}g/ml$ Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL). Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured. Results: Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at $20{\mu}g/ml$, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro. Conclusions: Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.

• 한국임상약학회지
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• 제19권2호
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• pp.167-179
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• 2009

Hypertension is one of the most common chronic diseases and it causes cardiovascular and cerebrovascular disease. While antihypertensive drug use increased, it took 15% of national health insurance drug expenditure. This study aimed to examine the pattern of antihypertensive drug prescription using National Health Insurance claims database and compare it with recommendations of Korea Hypertension Treatment Guidelines. Among the antihypertensive drugs, calcium channel blocker(64.4%) was most commonly prescribed class, and diuretics(44.6%), angiotensin II receptor blocker(33.3%), angiotensin converting enzyme inhibitor(11.7%) was followed. Approximately 81% of antihypertensives prescription were without cardiovascular or cerebrovascular disease, and among the comorbid conditions, diabetes(10.7%) was most common. calcium channel blocker(62.3%) was mostly prescribed class for hypertension with angina pectoris, angiotensin receptor blocker(45.3%) with myocardial infarction, diuretics(70.2%) and calcium channel blocker(49.5%) with congestive heart failure. For Hypertension with cerebrovascular disease, calcium channel blocker(68.0%) and angiotensin receptor blocker(43.3%) were prescribed mainly. When it comes to diabetes, calcium channel blocker(57.2%) was still mostly prescribed and angiotensin receptor blocker(45.9%) followed. But in hospitals and tertiary hospitals, angiotensin receptor blocker(65.7, 66.1%) was mostly prescribed for the patients with diabetes. For Hypertension with chronic renal disease, angiotensin receptor blocker(59.5%), calcium channel blocker(56.5%), diuretics(54.6%) were mainly used. Average number of classes per prescribing was $1.89{\pm}0.89$ class, average days per prescribing was $33{\pm}19$ day. Among the hypertension without comorbidity, 40.5% of prescription was monotherapy and 58.8% of polytherapy included diuretics. Among the outpatient prescriptions, calcium channel blocker was the most commonly used class, and the prescription pattern in clinic did not closely followed recommendations of Hypertension Treatment Guidelines.

• KSBB Journal
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• 제21권6호
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• pp.433-438
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• 2006

Bacillus subtilis BB-1 (KFCC l1344P)으로부터 분리된 혈전용해효소 유전자 (BCF-1)를 대량발현 벡터인 pEB 벡터에 크로닝하여 순수분리 된 혈전용해효소를 rat 경구 투여하여 출혈시간, 혈액의 응고, serum의 혈전용해능 등에 대한 in vivo 실험을 실시하였으며, 혈전용해효소의 단회경구투여에 따른 독성을 검사하였다. 효소의 경구투여에 따른 rat의 출혈시간에서는 대조군에 비하여 모든 경구 투여군에서 출혈시간이 유의적으로 약 1.75배 이상 길게 나타남을 확인하였고(P<0.05), 혈액의 출혈시간 또한 활발히 진행됨을 관찰하였다. 혈액으로부터 분리된 serum의 혈전용해작용 있어서는 경구투여 후 1시간부터 채혈한 혈액 내에서 혈전용해효소의 활성이 검출되기 시작하여 3시간째까지 높은 활성을 보였으며 4시간째부터 서서히 활성이 감소하는 것을 확인하였고 혈액의 응고 역시 대조군에 비하여 경구 투여군에서 상당히 지연되는 것을 알 수 있었다. Western blot에 의한 효소 검출에서는 경구 투여군에서 30,000 Da 크기의 단일밴드를 확인하였으며, 혈전용해효소의 rat에 대한 단회경구투여 독성실험에서 중량의 변화, 장기의 이상여부, 사망률 등에서 어떠한 이상이나 병변이 발견되지 않았다. 이상의 결과로 동물실험을 통한 혈전용해 효소의 경구투여에 의한 작용을 혈액 내에서 확인 할 수 있었으며, 본 효소의 단회 경구투여 시의 독성은 전혀 없음을 확인할 수 있었다.

• 한국임상약학회지
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• 제26권3호
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• pp.213-219
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• 2016

Objective: Although guideline recommends beta blockers (BBs) as first line antianginal agent and calcium channel blockers (CCBs) as alternatives after percutaneous coronary intervention (PCI), the prescription patterns in real practice are not in accordance with the guideline. We aimed to investigate the prescribing patterns of primary antianginal drug and relating factors in patients who underwent PCI. Methods: Patients who have undergone PCI without myocardial infarction (MI) from November 2012 to June 2014 and followed up at least one year in a tertiary teaching hospital were included. Prescribing patterns of primary antianginal drug before, at the time of, and one year after PCI were described. Factors affecting drug selection, and their relationship with incidence of clinical outcomes defined as MI and repeated PCI, unscheduled admission or visit related with heart problem were analyzed with multivariate logistic regression. Results: A total of 506 patients were included and as primary antianginal drugs, BB, CCB, and both were prescribed in 32.2%, 24.5%, and 17.8% of patients, respectively. Also, neither BB nor CCB was prescribed at the time of PCI in 25.5% of patients. Compared with BB, CCBs were more likely prescribed in patients who had hypertension (Odds Ratio, OR 2.18, 95% confidence interval, CI 1.16-4.07), use of same class before PCI (OR 7.18, 3.37-15.2) and concomitant angiotensin receptor blocker (ARB) use (OR, 1.92, 95% CI 1.10-3.33). Incidence of clinical outcomes were not significantly greater in patients who prescribed CCB compared with BB at the time of PCI (aOR 1.32, CI 0.65-2.68). Conclusion: This study demonstrated that half of the patients who underwent PCI were prescribed BB. CCB were favored in patients with hypertension, use of same class before PCI, and concomitant ARB use. Significant difference in clinical outcome was not observed between BB and CCB selection as primary antianginal drug.

• 한국임상약학회지
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• 제26권3호
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• pp.201-206
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• 2016

Objective: Direct current cardioversion for atrial fibrillation could be associated with the risk of thromboembolic events. Anticoagulation therapy with warfarin (INR 2.0-3.0) is recommended 3 weeks before and 4 weeks after cardioversion to reduce the risk of thromboembolism. This study evaluated warfarin therapy in pharmacist-managed anticoagulant services (ACS). Methods: This retrospective study was performed in 106 patients with atrial fibrillation from 2012 to 2013. The primary efficacy endpoint was the composite of stroke, transient ischemic attack, myocardial infarction, and cardiovascular death. The primary safety measure was major bleeding. To evaluate the peri-procedural effects of warfarin treatment, we studied whether target INR was maintained, as well as the maintenance period of the therapeutic range. Quality of treatment was measured by time in therapeutic range (TTR) by using the Rosendaal method. Results: There were no thromboembolic events, but TEE examination at time of cardioversion showed a left atrial thrombus in three patients (2.8%). Bleeding complications after cardioversion occurred in 2 patients (1.9%). The average INR value at the time of cardioversion was $2.59{\pm}0.8$, and was within the therapeutic range in 83 patients (78%). Analysis of the patients in whom the value was within the therapeutic range twice consecutively showed that the ratio of TTR was 80% and the therapeutic range was maintained in 67 patients (63%) for an average of 4.90 weeks prior to cardioversion. Similarly, 76 patients (72%) had a stable INR within the therapeutic range for an average of 5.70 weeks and a mean TTR of 83%. Conclusion: Pharmacists significantly contributed to appropriate warfarin treatment with close monitoring during cardioversion. Likewise, active pharmacist monitoring and systemic management should be considered to reduce thromboembolism and bleeding complications in the peri-cardioversion period.

• 대한의생명과학회지
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• 제23권3호
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• pp.251-260
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• 2017

Platelet activation is essential at the sites of vascular injury, which leads to hemostasis through adhesion, aggregation, and secretion process. However, potent and continuous platelet activation may be an important reason of circulatory disorders. Therefore, proper regulation of platelet activation may be an effective treatment for vascular diseases. In this research, inhibitory effects of cordycepin (3'-deoxyadenosine) on platelet activation were determined. As the results, cordycepin increased cAMP and cGMP, which are intracellular $Ca^{2+}$-antagonists. In addition, cordycepin reduced collagen-elevated $[Ca^{2+}]_i$ mobilization, which was increased by a cAMP-dependent protein kinase (PKA) inhibitor (Rp-8-Br-cAMPS), but not a cGMP-protein kinase (PKG) inhibitor (Rp-8-Br-cGMPS). Furthermore, cordycepin increased $IP_3RI$ ($Ser^{1756}$) phosphorylation, indicating inhibition of $IP_3$-mediated $Ca^{2+}$ release from internal store via the $IP_3RI$, which was strongly inhibited by Rp-8-Br-cAMPS, but was not so much inhibited by Rp-8-Br-cGMPS. These results suggest that the reduction of $[Ca^{2+}]_i$ mobilization is caused by the cAMP/A-kinase-dependent $IP_3RI$ ($Ser^{1756}$) phosphorylation. In addition, cordycepin increased the phosphorylation of VASP ($Ser^{157}$) known as PKA substrate, but not VASP ($Ser^{239}$) known as PKG substrate. Cordycepin-induced VASP ($Ser^{157}$) phosphorylation was inhibited by Rp-8-Br-cAMPS, but was not inhibited by Rp-8-Br-cGMPS, and cordycepin inhibited collagen-induced fibrinogen binding to ${\alpha}IIb/{\beta}_3$, which was increased by Rp-8-Br-cAMPS, but was not inhibited by Rp-8-Br-cGMPS. These results suggest that the inhibition of ${\alpha}IIb/{\beta}_3$ activation is caused by the cAMP/A-kinase-dependent VASP ($Ser^{157}$) phosphorylation. In conclusion, these results demonstrate that inhibitory effects of cordycepin on platelet activation were due to inhibition of $[Ca^{2+}]_i$ mobilization through cAMP-dependent $IP_3RI$ ($Ser^{1756}$) phosphorylation and suppression of ${\alpha}IIb/{\beta}_3$ activation through cAMP-dependent VASP ($Ser^{157}$) phosphorylation. These results strongly indicated that cordycepin might have therapeutic or preventive potential for platelet activation-mediated disorders including thrombosis, atherosclerosis, myocardial infarction, or cardiovascular disease.

• Journal of Yeungnam Medical Science
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• 제10권2호
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• pp.423-431
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• 1993

허혈성 뇌졸중의 재발에 관여된다고 생각되는 주요 위험인자들을 파악하기 위하여 영남대학교 의과대학 부속병원 신경과에 내원한 환자들중 재발된군과 비재발된군을 선정하여 통상적으로 알려진 뇌졸중 위험인자들을 조사하여 그 중 뇌졸중 재발에 영향을 끼치는 요인을 분석 검토하였다. 재발군의 성별은 77명중 남자가 55명, 여자가 22명이었으며, 비재발군은 124명중 남자가 84명, 여자가 40명으로 성별차이를 분석해보면 의미있는 위험인자로 작용하지 못했다. 재발군의 연령은 29세에서 85세까지 평균 62.1세였고 비재발군은 27세에서 90세로 평균연령은 60.7세로 두군 모두 다 60대에서 가장 높은 발병율을 보였고 이 역시 통계적 유의성이 없었다. 당뇨병, 심근경색, 심방세통, 일과성 뇌 허혈증등과 같은 위험 요인이 있더라도 재발에는 영향을 미치지 못한것으로 나타났고 또한 뇌졸중의 병형이나 병변부위도 재발에 미치는 영향은 별로 없는 것으로 조사되었다. 그러나, 고혈압의 병력이나 입원기간중 높은 혈압을 보인 경우는 두군간에 유의성이 있는 차이를 보였다(P<0.05). 이상의 결과로 처음 뇌졸중이 발병하여 입원중 측정한 혈압이 160mmHg/95mmHg 이상으로 높았거나 고혈압의 병력이 있는 경우에는, 그렇지 않은 환자에 비해 향후 2년 내에 허혈성 뇌졸중이 재발할 가능성이 높으므로 적절한 치료로서 예방에 도움을 얻는 것이 필요할 것으로 생각되며, 이외의 위험인자들에 대해서도 지속적 연구가 있어야 할 것으로 사료된다.

• 대한임상독성학회지
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• 제4권1호
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• pp.44-47
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• 2006

Symptoms of aspirin overdose may vary from acid-base disturbance, electrolyte abnormality, non-cardiogenic pulmonary edema, chemical hepatitis, seizure to cardiac toxicity. Cardiac adverse effects from aspirin are uncommon but there are reports of arrhythmia, cardiopulmonary arrest, and myocardial infarction. We report 2 cases of young women with aspirin overdose who exhibited ischemic changes on their ECGs a few hours after the ingestion with spontaneous recovery in a few days. First case, a 29 year old woman, presented to the emergency department 6 hours after ingesting 250 tablets of aspirin (325 mg/T). On examination, the temperature was $36.3^{\circ}C$: blood pressure, 105/72mmHg; Pulse, 111/min and respiratory rate, 24/min. Second case, a 27 year old woman, an hour after ingesting 60 tablets (325mg/T). On examination, the temperature was $36.0^{\circ}C$: blood pressure, 102/72 mmHg; pulse, 89/min and respiratory rate, 25/min. In both cases, ECG after 6 hours of ingestion had sinus tachycardia and developed T wave inversion on the anterior leads in the following ECGs. Their initial serum salicylate levels after 6 hours of ingestion were 71.2 mg/dL and 28.4 mg/dL respectively. These salicylate levels were resolving when these ECGs were observed. The ECG changes resolved in the following days and they were discharged without any further symptoms. Further studies are needed, but for the time being, when dealing with salicylate overdose, transient cardiac depression should be kept in mind to avoid adverse ischemic cardiac events.