• YAKHAK HOEJI
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• v.57 no.5
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• pp.337-347
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• 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.

• Korean Journal of Clinical Pharmacy
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• v.25 no.4
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• pp.246-253
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• 2015

Background & Object: Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes ankylosis and deformation of axial joints. Since current medicine cannot cure the disease yet, alleviating pain and preventing deformation with medications are the main therapy for patients with AS. The key medications for these purposes include nonsteroidal anti-inflammatory drugs (NSAIDs), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) inhibitors. This study aims to analyze prescribing patterns of AS patients in South Korea. Method: National Patients Sample data compiled by the Health Insurance Review and Assessment Service from 2013 was analyzed. Patients with AS were identified with Korean Standard Classification of Diseases code-6, which was M45. The rates of prescription, discontinuation, and switching ingredients were calculated for each medication during 2013. Results: Total number of patients was 655, and most of them were male (n = 514, 78.5%). Of all age groups, the proportion of 30-40 year old patients was the greatest (35.1%). The most utilized drug class was NSAIDs (82.4%). Less than half of patients were prescribed $TNF-{\alpha}$ inhibitors (n = 212, 32.4%). Meloxicam, aceclofenac, and celecoxib were the most frequently prescribed NSAIDs. In case of $TNF-{\alpha}$ inhibitors, adalimumab, etanercept and infliximab were the top three most prescribed drugs. Although not recommended by the current practice guideline, significant proportions of patients were identified using disease modifying anti-rheumatic drugs (DMARDs). Conclusion: Considering the current practice guideline and previous studies about the efficacy, the use of DMARDs should be reduced and medical insurance term in South Korea should be re-examined.

• The Journal of Internal Korean Medicine
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• v.39 no.2
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• pp.97-106
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• 2018

Objectives: The combined use of herbal and Western medicine is increasing. However, herbal medicine is highly likely to interact with Western medicine making it important to understand the effects of co-administration. This study investigates the ratio of patients who take Western medicine with herbal medicine, the types of medicines commonly prescribed together, and the results of hospital examinations. Methods: We investigated patients who were hospitalized at Kyung Hee University Korean Medical Hospital for at least one day from January 1, 2010 to December 31, 2017. There were some inclusion criteria. First, we chose patients aged 19 and over. Second, we chose patients who were diagnosed with osteoarthritis (OA) with diagnosis codes M13, M15, M17 according to KCD-7. Third, patients had liver function tests, renal function tests, and general hematology tests performed at least two times during hospitalization. Results: Among a total of 131 OA patients, 32 (24.4%) patients were treated with herbal-Western medicine combination therapy. The most commonly prescribed herbal medicine was Daegalwhal-tang, and the most commonly prescribed Western medicine was celecoxib. In the laboratory findings, all liver function tests, renal function tests, and general hematology tests showed no difference compared to admission day. There were also no differences between herbal medicine single treatment and herbal-Western medicine combination treatment. Conclusions: From these results, we suggest that herbal medicine single treatment and herbal-Western medicine combination treatment for OA patients does not cause adverse effects.

• KSBB Journal
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• v.27 no.5
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• pp.289-294
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• 2012

Resveratrol, natural polyphenol in grapes and red wine, is known to have the anti-proliferatory and anti-angiogenic effects in various cancer cells. In this study, we have investigated the effects of resveratrol in HT-29 colon cancer cells. Treatment of resveratrol in different concentrations and time inhibited proliferation of HT-29 colon cancer cells. We explored the effects of resveratrol on HT-29 colon cancer cell motility using a wound healing assay. In the absence of the resveratrol, the HT-29 cells are migrated along the edges of the wound and showed a large-scale migration, whereas dose- and time-dependent inhibition of cell flattening and spreading was observed in the presence of resveratrol. Resveratrol inhibited MMP-9 in a dose- and time-dependent on HT-29 colon cancer cells by Western blotting. In addition, resveratrol increased AMPK activity and decreased COX-2, VASP and VEGF expression. Treatment of compound C inhibited AMPK activity, however, the expression of VASP and COX-2 increased thus, COX-2 and VASP are modulated by AMPK. However treatment of celecoxib could not control AMPK activity but decreased VEGF expression. We suggest that resveratrol inhibits cell proliferation and migration through activation of AMPK and decreased COX-2, VASP and VEGF expression in HT-29 colon cancer cells.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.50-56
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• 2012

WIN-34B showed analgesic and anti-inflammatory effects in various animal models of pain and osteoarthritis. However, the molecular mechanism by which WIN-34B inhibits pain and inflammation in vivo remains to be elucidated. We investigated the molecular mechanisms of the actions of WIN-34B using various in vitro models using fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA FLSs), RAW264.7 cells and peritoneal macrophages. WIN-34B inhibited the level of IL-6, $PGE_2$, and MMP-13 in IL-$1{\beta}$-stimulated RA FLSs in a dose-dependent manner. The mRNA levels were also inhibited by WIN-34B. The level of $PGE_2$, NO, IL-$1{\beta}$, and TNF-${\alpha}$ were inhibited by WIN-34B at different concentrations in LPS-stimulated RAW264.7 cells. The production of NO and $PGE_2$ was inhibited by WIN-34B in a dose-dependent manner in LPS-stimulated peritoneal macrophages. All of these effects were comparable to the positive control, celecoxib or indomethacin. I${\kappa}B$B signaling pathways were inhibited by WIN-34B, and the migration of NF-${\kappa}B$ into the nucleus was inhibited, which is consistent with the degradation of $I{\kappa}B-{\alpha}$. Taken together, the results suggest that WIN-34B has potential as a therapeutic drug to reduce pain and inflammation by inhibiting the production of pro-inflammatory mediators.

• Archives of Plastic Surgery
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• v.38 no.4
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• pp.351-358
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• 2011

Purpose: The inflammatory phase is considered an integral part of adult wound healing, but fetal wound healing studies have shown scarless healing results in the absence of the inflammation process. The COX-2 pathway is an essential component of inflammation. The purpose of this study is to identify the effect of a topical selective COX-2 inhibitor on inflammation in rabbit skin wound healing and scarring. Methods: Full-thickness wounds were made on 6 New Zealand rabbits' ears. Topical 5% celecoxib + vehicle (experimental tissue) and vehicle only (controlled tissue) were applied daily for 14d on each side of the ears. Scar samples were harvested at 2 wks, 4 wks, and 8 wks after the wounding. Each sample was stained with hematoxylin and eosin and the Masson's trichrome stain to evaluate inflammation and scar formation. Results: Histological analysis demonstrated a significant reduction of inflammation, neovascularization, and scar elevation in the experimental tissue as compared to the control. Additionally, experimental tissue exhibited faster improvement of collagen organization similar to that of normal tissue. Conclusion: This study suggests that the topical application of a selective COX-2 inhibitor on a rabbit ear wound resulted in decreased inflammation and had a positive effect on the reduction of scar formation.

• KIPS Transactions on Software and Data Engineering
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• v.10 no.11
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• pp.465-472
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• 2021

In this paper, we present an approach for detection of adverse drug reactions from drug reviews to compensate limitations of the spontaneous adverse drug reactions reporting system. Considering negative reviews usually contain adverse drug reactions, sentiment analysis on drug reviews was performed and extracted negative reviews. After then, MedDRA dictionary and named entity recognition were applied to the negative reviews to detect adverse drug reactions. For the experiment, drug reviews of Celecoxib, Naproxen, and Ibuprofen from 5 drug review sites, and analyzed. Our results showed that detection of adverse drug reactions is able to compensate to limitation of under-reporting in the spontaneous adverse drugs reactions reporting system.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.342-351
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• 2021

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.

• Archives of Plastic Surgery
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• v.51 no.2
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• pp.156-162
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• 2024

Background Perioperative management in autologous breast reconstruction has gained focus in recent years. This study compares two pain management protocols in patients undergoing abdominal-based free flap breast reconstruction: a past protocol (PP) and a current protocol (CP)-both intended to reduce opioid consumption postoperatively. The PP entails use of a pain catheter in the abdominal wound and the CP consists of an intraoperative nerve block in addition to refinements in the oral pain management. We hypothesize that the CP reduces opioid consumption compared to PP. Methods From December 2017 to January 2020, 102 patients underwent breast reconstruction with an abdominal-based free flap. Two postoperative pain management strategies were used during the period; from December 2017 to September 2018, the PP was used which entailed the use of a pain catheter with ropivacaine applied in the abdominal wound with continuous distribution postoperatively in addition to paracetamol orally and oxycodone orally pro re nata (PRN). From October 2018 to January 2020, the CP was used. This protocol included a combination of intraoperative subfascial nerve block and a postoperative oral pain management regime that consisted of paracetamol, celecoxib, and gabapentin as well as oxycodone PRN. Results The CP group (n = 63) had lower opioid consumption compared to the PP group (n = 39) when examining all aspects of opioid consumption, including daily opioid usage in morphine milligram equivalents and total opioid usage during the stay (p < 0.001). The CP group had shorter length of hospital stay (LOS). Conclusion Introduction of the CP reduced opioid use and LOS was shorter.

• The Korean Journal of Pain
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• v.37 no.2
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• pp.151-163
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• 2024

Background: Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Methods: Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalin-induced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX-2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Results: Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenan-triggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF-κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Conclusions: Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.