• Bulletin of the Korean Chemical Society
• /
• 제33권9호
• /
• pp.3048-3054
• /
• 2012

The use of aspirin is widely recommended for the prevention of heart attacks owing to its ability to inhibit platelet activation by irreversibly blocking cyclooxygenase 1. However, aspirin also affects the fibrinolytic and hemostatic pathways by mechanisms that are not well understood, causing severe hemorrhagic complications. Here, we investigated the ability of aspirin and aspirin metabolites to inhibit thrombin-activatable fibrinolysis inhibitor (TAFI), the major inhibitor of plasma fibrinolysis. TAFI is activated via proteolytic cleavage by the thrombin-thrombomodulin complex to TAFIa, a carboxypeptidase B-like enzyme. TAFIa modulates fibrinolysis by removing the C-terminal arginine and lysine residues from partially degraded fibrin, which in turn inhibits the binding of plasminogen to fibrin clots. Aspirin and its major metabolites, salicylic acid, gentisic acid, and salicyluric acid, inhibit TAFIa carboxypeptidase activity. Salicyluric acid effectively blocks activation of TAFI by thrombin-thrombomodulin; however, salicylates do not inhibit carboxypeptidase N or pancreatic carboxypeptidase B. Aspirin and other salicylates accelerated the dissolution of fibrin clots and reduced thrombus formation in an in vitro model of fibrinolysis. Inhibition of TAFI represents a novel hemostatic mechanism that contributes to aspirin's therapy-associated antithrombotic activity and hemorrhagic complications.

• Journal of Pharmaceutical Investigation
• /
• 제39권1호
• /
• pp.43-49
• /
• 2009

Aspirin or acetylsalicylic acid, a member of the salicylate family, is frequently used as an analgesic, antipyretic, anti-inflammatory and antiplatelet drug. Because aspirin is chemically unstable in water and heat for tablet formulation, additives including lubricants are used in preparing aspirin tablets, using a dry-granulation process. Aspirin tablets are produced by a number of manufacturers which usually use their own unique combination of additives during the manufacturing process. In this study, we employed an NMR based metabolomics technique to identify the manufacturers of various aspirin tablets. Aspirin tablets from six different companies were analyzed by 1H 400 MHz NMR. The acquired data was then integrated and processed by principal component analysis (PCA). Based on the NMR data, we were able to identify peaks corresponding to acetylsalicylic acid in all of the six samples, whereas different NMR patterns were found in the aromatic and aliphatic regions depending on the unique additive used. These observations led to the conclusion that the differences in the NMR patterns among the different aspirin tablets were due to the presence of additives.

• 한국임상약학회지
• /
• 제27권3호
• /
• pp.127-135
• /
• 2017

Background: Kawasaki disease (KD) is an acute febrile, systemic vasculitis as a leading cause of acquired heart disease in children. Intravenous immunoglobulin G (IVIG) and aspirin are the standard initial therapy in the treatment of acute KD. The purpose of this study was to investigate drug utilization in children with KD, and to compare "IVIG + high-dose aspirin" and "IVIG + moderate-dose aspirin" in preventing cardiac complications. Methods: We analyzed pediatric patient sample data compiled by the Health Insurance Review & Assessment Service from 2010 to 2015. We identified patients with KD using the KCD-6 code of M30.3. We excluded patients in chronic phase or ${\geq}1$0 years. We also excluded patients who were diagnosed KD in November or December. Drug utilization pattern were assessed in acute KD patients and 30-day and 60-day cardiac complications were investigated between "IVIG + high-dose aspirin" group and "IVIG + moderate-dose aspirin" group. Results: In acute phase, IVIG was administered to 95.8% patients, and 57.1% patients were prescribed moderate-dose aspirin and 25% patients were with high-dose aspirin. Steroid use was rapidly increased from 4.0% in 2010 to 11.3% in 2015. Both 30-day and 60-day cardiac complications occurred less in "IVIG + high-dose aspirin" group compared to "IVIG + moderate-dose aspirin" group, but not statistically significant (0.9% vs 1.8%, p=0.252 for 30-day complication rate; 1.5% vs 2.7%. p=0.073 for 60-day complication rate). Conclusion: We were not able to demonstrate which aspirin therapy is superior for preventing cardiac complications in acute KD patients and further research is warranted.

• The Korean Journal of Physiology and Pharmacology
• /
• 제17권1호
• /
• pp.15-21
• /
• 2013

Aspirin (acetylsalicylic acid) is one of the most widely used therapeutic agents based on its pharmacological actions, including anti-inflammatory, analgesic, anti-pyretic, and anti-thrombotic effects. In this study, we investigated the effects of aspirin on seizure susceptibility and hippocampal neuropathology following pilocarpine-induced status epilepticus (SE). SE was induced by pilocarpine hydrochloride (280 mg/kg, i.p.) administration in C57BL/6 mice (aged 8 weeks). Aspirin was administered daily (15 mg/kg or 150 mg/kg, i.p.) for 10 days starting 3 days before SE, continuing until 6 days after SE. After pilocarpine injection, SE onset time and mortality were recorded. Neuronal cell death was examined using cresyl violet and Fluoro-Jade staining, and glial responses were observed 7 days post SE using immunohistochemistry. In the aspirin-treated group, the onset time of SE was significantly shortened and mortality was markedly increased compared to the control group. However, in this study, aspirin treatment did not affect SE-induced neuronal cell death or astroglial and microglial responses in the hippocampus. In conclusion, these results suggest that the safety of aspirin should be reevaluated in some patients, especially with neurological disorders such as temporal lobe epilepsy.

• Journal of Korean Neurosurgical Society
• /
• 제51권5호
• /
• pp.308-311
• /
• 2012

Hemorrhagic complications associated with aspirin use occur primarily at skin or gastrointestinal sites but can occasionally occur in the central nervous system. In particular, spontaneous spinal epidural hemorrhage (SSEH) associated with aspirin is very rare. We report a case of low-dose (100 mg daily) aspirin-related SSEH that was successfully treated with medical management. Our case indicates that low-dose aspirin could induce SSEH and that conservative treatment with close observation and repeated imaging studies should be considered in cases with neurological improvement or mild deficits.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.116.2-116.2
• /
• 2003

Aspirin and aspirin-like nonsteroidal antiinflammatory drug have been the mainstay of therapy for rheumatoid arthritis. In this study, we investigated the hepatoprotective effect of aspirin on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of aspirin (7.5, 15mg/kg daily for 4 weeks) into the DMN-treated rats remarkably prevented the elevation of serum alanine transaminase, aspartate transaminase and alkaline phosphatase, and bilirubin levels. Aspirin also increased serum protein level and reduced the hepatic level of malondialdehyde in DMN-treated rats. (omitted)

• 약학회지
• /
• 제57권5호
• /
• pp.337-347
• /
• 2013

Aspirin is widely used for treatment or prophylaxis of many diseases. Although aspirin is used chronically for preventing cardiovascular diseases especially, liver function is rarely monitored because of unpredictable and uncommon hepatotoxicity induced by aspirin. We evaluated changes in liver function indicators and compared to acetaminophen and NSAIDs. We retrospectively analyzed EMR data (n=28788) of patients who took study drugs and had liver function tests (LFT) during study period from 2009.7.1 to 2010.6.30 at a tertiary hospital and evaluated the above information. Patients not having LFT results at these three standard points of time (baseline, during medication, and after finishing medication) were excluded. During medication, mean changes of Alanine transaminase (ALT), Aspartate transaminase (AST), Total Bilirubin (TB) were increased and that of serum albumin (Alb) was decreased, with the largest effect from aspirin (n=461; 16.8, 14.9, 0.28, -0.24) and the smallest from celecoxib (n=127; 3.4, 5.2, 0.11, -0.16). In addition, aspirin caused more changes of blood liver function indicators in patient group with liver disease (n=128, 27.4, 26.9, 0.53, -0.3) than those in patient group without liver disease (n=357, 12.5, 13.1, 0.23, -0.24). Taking low dose aspirin for prophylaxis purpose with long-term medication may be associated with liver injury. Our study is just a signal regarding the possibility of hepatotoxicity among patients taking low dose aspirin in a hospital setting, and thus it needs to be further investigated.

• Clinical and Experimental Pediatrics
• /
• 제60권1호
• /
• pp.24-29
• /
• 2017

Purpose: Previously, Kawasaki disease (KD) treatment with low-dose aspirin was administered for 6-8 weeks after the acute phase. However, inflammatory marker levels normalize before 6-8 weeks. In this study, we aimed to investigate the clinical outcome of short-term low-dose aspirin treatment based on inflammatory and thrombotic marker levels. Methods: We performed a retrospective review of the medical records of patients with KD who were hospitalized at Chungnam National University Hospital between September 2012 and May 2014. When fever subsided, low-dose aspirin treatment was started. Inflammatory (white blood cell count, erythrocyte sedimentation rate, and C-reactive protein) and thrombotic markers (D-dimer) were monitored at follow-ups conducted in 1- to 2-week intervals. The low-dose aspirin administration was terminated when both markers were normalized and no cardiovascular complications were observed. Results: Eighty-four patients with KD (complete KD, n=49; incomplete KD, n=35) were enrolled. The inflammatory and thrombotic marker levels were normalized within 3-4 weeks on average. At the beginning the low-dose aspirin treatment, 9 patients had coronary artery lesions but 75 did not. When the low-dose aspirin administration was terminated at the time the inflammatory marker levels were normalized, no new CALs developed during the follow-up at 6-8 weeks. Conclusion: Most of the inflammatory marker levels were normalized within 3-4 weeks after the acute phase of KD. New cardiovascular complications did not develop during the course of the short-term aspirin treatment based on the inflammatory marker levels, clinical findings, and echocardiography.

• 생약학회지
• /
• 제16권1호
• /
• pp.7-11
• /
• 1985

The extract of Galgun-tang at oral doses of 200 and 400 mg/kg showed remarkable inhibition of 42.5% and 45.0%, respectively, on the carrageenin edema in rat paw. In case of combined oral administration of the extract at each dose of 100, 200 and 400mg/kg with 100mg/kg of aspirin, the inhibitions were 70.5%, 83.6% and 80.7% respectively. These results showed the remarkable effects as compared with those of aspirin which showed 50.3% and 69.4% of inhibition at doses of 100 and 200mg/kg, respectively. On the other hand, on the writhing syndrome in mice induced by 0.7% acetic acid solution, the oral administration of the extract showed remarkable inhibition of 18.5 and 47.7% at doses of 200 and 400mg/kg, respectively. In case of combined oral administration of the extract at each dose of 100, 200 and 400mg/kg with 100mg/kg of aspirin, the inhibition percentages of writhing syndromes were 66.6, 72.3 and 80.8, respectively, whereas the inhibition at doses of 100 and 200mg/kg of aspirin showed 59.9 and 69.5%, respectively.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권5호
• /
• pp.3041-3044
• /
• 2013

Background: The non-steroidal anti-inflammatory drug (NSAID) aspirin (acetylsalicylic acid) is an inhibitor of cyclooxygenase enzymes. Recent studies have shown that aspirin could be used as an anti-tumor drug. Triptolide, the major compound extracted from the Chinese herb Tripteryglum wilfordii Hook.f, has now been shown that it can inhibit tumor growth. The aim of this study was to analyze the anti-tumor efficiency of aspirin and triptolide in cervical cancer cells. Methods: Viability of cervical cancer cell lines was assessed by the MTT method at various concentrations of aspirin and triptolide. Siha and HeLa cell apoptotic analysis was performed by flow cytometry. Real time-PCR and Western Blotting were used to analyze the expression of Bcl-2/Bax, Cyclin D1 and p16. Results: Viability in the combination group was significantly decreased as compared with either drug used alone. Expression change of Bcl-2/Bax, CyclinD1 and p16 appeared to play an important role in the synergistic killing effect on cervical cancer cell apoptosis. Conclusion: Aspirin and triptolide combination treatment may have synergistic anti-tumor effects on cervical cancer cells.