• Bulletin of the Korean Chemical Society
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• v.25 no.11
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• pp.1699-1702
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• 2004

• Clinical and Experimental Pediatrics
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• v.59 no.10
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• pp.421-424
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• 2016

Recurrent macrophage activation syndrome (MAS) is very rare. We present the case of an adolescent boy with human leukocyte antigen (HLA) B27-positive ankylosing spondylitis (AS), who experienced episodes of recurrent MAS since he was a toddler. A 16-year-old boy was admitted because of remittent fever with pancytopenia and splenomegaly after surgical intervention for an intractable perianal abscess. He had been diagnosed with hemophagocytic lymphohistiocytosis (HLH) 4 different times, which was well controlled with intravenous immunoglobulin and steroids since the age of 3. We were unable to identify the cause for the HLH. He remained symptom-free until the development of back pain and right ankle joint pain with swelling at 15 years of age. He was diagnosed with HLA B27-positive AS with bilateral active sacroiliitis. He showed symptom aggravation despite taking naproxen and methotrexate, and the symptoms improved with etanercept. On admission, his laboratory data showed leukopenia with high ferritin and triglyceride levels. Bone marrow biopsy examination showed histiocytic hyperplasia with hemophagocytosis. There was no evidence of infection. He received naproxen alone, and his symptoms and laboratory data improved without any other immunomodulatory medications. Genetic study revealed no primary HLH or inflammasome abnormalities. In this case, underlying autoimmune disease should have been considered as the cause of recurrent MAS in the young patient once primary HLH was excluded.

• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.117-126
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• 1999

Differential scanning calorimetry(DSC) was used as a screening technique for assessing the compatibility of some drugs with excipients. On the basis of DSC results, interaction of ibuprofen with PVP K40 was found and eutectic formations with PEG 6000 or magnesium stearate were demonstrated. Fenoprofen Ca was found to interact with PEG 6000. Naproxen showed interactions with PEG 6000, PVP K40, PVPP and Mg stearate. Interactions of tiaprofenic acid with PVP K40 or PVPP were found and eutectic formations with PEG 6000 or Mg stearate were observed. Bisoprolol hemifumarate, metoprolol tartrate and penbutolol sulfate were found to interact with lactose.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.425-431
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• 1996

Human neutrophil elastases (HNElastase, EC 3.4.21.37), a causative factor of inflammatory diseases, are regulated by plasma proteinase inhibitors, alpha-proteinase inhibitor and ${\alpha}_2-macroglobulin$. Under certain pathological conditions, however, released enzymes or abnormal function of inhibitors may cause various inflammatory disease. NSAIDs have been clinically applied for treatment of inflammatory diseases. Inhibition of cyclooxygenase is a known mechanism of action of NSAIDs in the treatment of inflammatory disease. In in vitro experiments, HNElastase was inhibited by naproxen, phenylbutazone, and oxyphenbutazone, but ibuprofen, ketoprofen, aspirin, salicylic acid, and tolmetin did not inhibit elastase. HNElastase was also inhibited by chelating agents, EDTA & EGTA, and tetracyclines. Removal of divalent metal ions by EDTA caused inhibition of elastase, and reconstitution of the metal ions recovered the enzyme activity to a certain level. Frequencies and contours in the Raman spectra of various conditions of human neutrophil elastase undergo drastic changes upon partial removal and/or reconstitution of calcium and zinc ions. The metal ion content dependent activities and change of the contour of the Raman spectrogram suggest us that the mechanism of action of a chelator or chelator-like agents on neutrophil elastase may be related to the conformational change at/or near the active site, especially -C=O radical or -COOH radical.

• Bulletin of the Korean Chemical Society
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• v.27 no.11
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• pp.1769-1774
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• 2006

A new liquid chromatographic chiral stationary phase based on (2S,3S)-O,O'-bis-(10-undecenoyl)-N,N'-bis-(3,5-dinitrobenzoyl)-2,3-diamino-1,4-butandiol was prepared starting from (2R,3R)-1,4-bis(benzyloxy)-2,3-butanediol. The new chiral stationary phase was applied to the resolution of racemic anilide derivatives of N-acetyl-a-amino acids, 1,1'-bi-2-naphthol and 3,3'-diaryl-1,1'-bi-2-naphthols. The CSP was also applied to the resolution of some chiral drugs including a diuretic, bendroflumethiazide, and non-steroidal anti-inflammatory agents such naproxen and alminoprofen. In every case, the chiral recognition efficiency of the new CSP was quite excellent.

• Journal of Microbiology and Biotechnology
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• v.10 no.6
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• pp.764-769
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• 2000

The lipase gene(lip) from Bacillus stearothermophilus was recombined in vitro by utilizing the DNA shuffling technique. After four rounds of shuffling, transformation, and screening based on the initial rate of clear zone formation on a tricaprylin plate, a clone (M10) was isolated, the cell extract of which showed about 2.8-fold increased lipase activity. The DNA sequence of the mutant lipase gene (m10) showed 3 base changes, resulting in two cryptic mutations and one amino acid substitution: S113($AGC{\rightarrow}AGT$), L252 ($TTG{\rightarrow}TTA$), and G275E ($GGA{\rightarrow}GAA$). SDS-PAGE analysis revealed that the increased enzyme activity observed in M10 was partly caused by high expression of the m10 lipase gene. The amount of the expressed G275E lipase was estimated to comprise as much as 41% of the total soluble proteins of the cell. The maximum velocity ($V_{max}$) of the purified mutant enzyme for the hydrolysis of olive oil was measured to be 3,200 U/mg, which was 10% higher than that of the parental (WT) lipase (2,900 U/mg). Its optimum temperature for the hydrolysis of olive oil was $68^{\circ}C$ and it showed a typical $Ca^{2+}$-dependent thermostability, properties fo which were the same as those of the WT lipase. However, the mutant enzyme exhibited a high enantiospecificity towards (S)-naproxen compared with the WT lipase. In addition, it showed increased hydrolytic activity towards triolein, tricaprin, tricaprylin, and tricaproin.

• Molecules and Cells
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• v.26 no.2
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• pp.181-185
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• 2008

The effects of calcitonin gene-related peptide (CGRP) on pacemaker currents in cultured interstitial cells of Cajal (ICC) from the mouse small intestine were investigated using the whole-cell patch clamp technique at $30^{\circ}C$. Under voltage clamping at a holding potential of -70 mV, CGRP decreased the amplitude and frequency of pacemaker currents and activated outward resting currents. These effects were blocked by intracellular $GDP{\beta}S$, a G-protein inhibitor and glibenclamide, a specific ATP-sensitive $K^+$ channels blocker. During current clamping, CGRP hyperpolarized the membrane and this effect was antagonized by glibenclamide. Pretreatment with SQ-22536 (an adenylate cyclase inhibitor) or naproxen (a cyclooxygenase inhibitor) did not block the CGRP-induced effects, whereas pretreatment with ODQ (a guanylate cyclase inhibitor) or L-NAME (an inhibitor of nitric oxide synthase) did. In conclusion, CGRP inhibits pacemaker currents in ICC by generating nitric oxide via G-protein activation and so activating ATP-sensitive $K^+$ channels. Nitric oxide- and guanylate cyclase-dependent pathways are involved in these effects.

• Journal of Pharmaceutical Investigation
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• v.35 no.1
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• pp.51-55
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• 2005

A high-performance liquid chromatographic method was employed for the determination of bumetanide in human plasma. After addition of internal standard (IS, naproxen) and acidification of the plasma with 1 M hydrochloric acid, the drug and IS were extracted into dichloromethane. The organic phase was back-extracted into 1 M sodium bicarbonate solution and 50 ${\mu}l$ of the aqueous phase was injected onto a reversed-phase C18 column with a mobile phase consisting of methanol: water: glacial acetic acid = 65 : 35 : 1. The samples were detected utilizing a fluorescence detector (excitation wavelength 235 nm, emission wavelength 405 nm). The method was specific and validated with a lower limit of 5 ng/mL. Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification. The applicability of the method was demonstrated by analysis of plasma after oral administration of a single 2 mg dose to 24 healthy subjects. From the plasma bumetanide concentration vs. time curves, the mean AUC was $246.5{\pm}73.8\;ng{\cdot}hr/mL$ and $C_{max}$ of $132.1{\pm}40.9$ ng/mL reached 1.2 hr after administration. The mean biological half-life of burnet ani de was $1.1{\pm}0.2$hr. Based on the results, this simple and validated assay method could readily be used in any pharmacokinetic or bioequivalence studies using humans.

• 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.