• 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.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.51-54
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• 1990

Human leukocyte cathepsin-Gs are active participant in the active phase of inflammations like rheumatoid arthritis, emphysema and glomerular injury. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for treatment of these inflammatory diseases. Mechanism of action of NSAIDs for treatment of inflammatory diseases, especially like rheumatoid arthritis, are known as the inhibitors of prostaglandin synthesis. Inhibitions of the activities of human leukocyte cathepsin-Gs by non-steroidal anti-inflammatory drugs, however, were not same as the known pharmacological effects (inhibition of cyclooxygenase) of these drugs. Among them, especially, sulindac, salicylate, phenylbutazone, oxyphenbutazone, and salicyluric acid inhibited human leukocyte cathepsin-Gs effectively. $IC_{50}s$ of each drug were 4.3mM, 14.3mM, 6.5mM, 11mM and 15mM respectively. The drugs which have same chemical structure and same degree of inhibition effect on cyclooxygenase showed different degree or no effect on inhibition of cathepsin G. These inhibition effect might be, beside of inhibition of cyclooxygenase in the prostaglandin synthesis pathway, another benefitial antiinflammatory effect of NSAIDs by direct protection against tissue destruction in inflammatory diseases.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.145-153
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• 1991

Human neutrophil cathepsin-G, which has been known as one of the active enzymes causing inflammatory diseases, was purified by two steps procedure involving one size exclusion (Ultorogel AcA54) and one ion exchange (CM-Sephadex) chromatography. Purified HNCGs were cross-reacted with Anti-HNCathepsin-G antibodies which were radised in rabbits and purified by cathepsin-G labeled Sepharose 4B affinity chromatography. HNCGs were effectively inhibited by NSAIDs including phenylbutazone, sulindac, oxyphenbutazone, salicylic acid and salicyluric acid. $IC_{50}_s$ of these drugs for inhibition of Cathepsin G were 0.3-0.8 mM. Other NSAIDs including aspirin showed little or no inhibition effect on the activity of Cathepsin G. These results strongly indicated that NSAIDs which showed inhibition effect on the activity of HNCGs possibly be at least a part of mechanism of action which might be related to direct inhibition of cathepsin G at the tissue destruction sites beside of their known mechanism of action as an anticyclo-oxygenase in treatment of inflammatory diseases. Lipid soluble component of Korean Red Ginseng which was known as an anti-inflammatory agent inhibited HNCGs strongly, but no other fractions did inhibited HNCGs. Antibiotics including novobiosin and rifamycin showed some inhibition effect on HNCGs, i. e.., $IC_{50}$ of these drugs were 2.6 mM and 1.5 mM respectively, and other antibiotics including penicillin G showed no or negligible inhibition effect on the activity of HNCGs. However. tetracyclines inhibited HNCGs very effectively at the concentration of therapeutic range. The inhibition effect of the activity of HNCGs by tetracycline are not related to the N-dimethyl radical on the 4 position of the tetracycline molecule. Furthermore, N-dedimethylated tetracyclines may have beneficial effect for long term treatment of chronic inflammatory diseases without developing any drug resistance to microorganisms.

• Journal of the korean academy of Pediatric Dentistry
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• v.23 no.3
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• pp.593-600
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• 1996

This case report is a treatment of patient with hemophilia A and autism. The patient's chief complaint was treatment of dental caries on entire dentition and he has an impacted mesiodens located on the apex of the upper right primary central incisor. The patient was consulted with pediatrician and anesthetist about the detailed discussion of the complexities of hemorrhagic disorder. Because he had some problems of behavior management and bleeding, the treatment was done under the gerneral anesthesia. The following results were obtained. 1. Consult with the patient's physician and hematologist about the replacement therapy and bleeding tendency. 2. For the severe hemophiliac child who requires extensive or surgical treatment, general anesthesia may be indicated for the comprehensive care. 3. For the hemophiliac child who has a behavior management problem due to autism and other defects, general anesthesia may be considerable. 4. Care must be taken during dental procedures not to causing a bleeding. 5. Local hemostatic methods must be acquired for the emergency state. 6. Neve prescribe aspirin or non-steroidal anti-inflammatory drugs such as ibuprofen, indomethacin, and phenylbutazone. These drugs affect platelet aggregation and exaggerate the bleeding defect. 7. Do not be afraid of hemophiliac patient, and never compromise quality of dental care.

• Journal of Pharmaceutical Investigation
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• v.12 no.2
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• pp.37-44
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• 1982

In order to enhance water solubility, ketoprofen was made as lysine salt, such as acetylsalicylic acid lysine salt, ibuprofen lysine salt and amino acid salt of phenylbutazone. The purpose of this study was to make a comparison between ketoprofen lysine salt in aspects of analgesic, anti-inflammatory, and antipyretic effect. The experimental results were summerized as followings. 1. Ketoprofen lysinate was composed of one molecule of ketoprofen and one molecule of lysine. The product was water soluble and melting point was $92^{\circ}C{\sim}94^{\circ}C$. 2. Ketoprofen lysinate showed about 2 times stronger analgesic effect than that of ketoprofen while no difference in antipyretic effect was observed. 3. $LD_{50}$ of ketoprofen lysinate was higher than that of ketoprofen, suggesting ketoprofen lysinate as safer drug. 4. Blood concentration of ketoprofen lysinate was $156{\mu}g/ml$ while the concentration of ketoprofen was $116{\mu}g/ml$ in 30 min., suggesting long acting as well as high blood concentration.

• Journal of Veterinary Clinics
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• v.22 no.2
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• pp.144-147
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• 2005

This study was performed to investigate that electro-acupuncture might relieve chronic back pain in horses. Twenty horses with chronic back pain were chosen from referring to College of Veterinary Medicine, University of Florida. They were assigned the patients referred to 2 treatment groups and 1 control group. The treatment group I was electrostimulated to 4 acupoints. The acupuncture points of Lumbosacral point, GV-6, BL26, and BL54 were used.; The treatment group II was taken the phenylbutazone orally. Control group was administered the normal saline per oral. Back pain score system was used to evaluate the degree of back pain. The treatment group r had significant lower back pain score from two times of electroacupuncture treatment. However, the treatment group II and control group did not change back, pain scores during experimental periods. Thus, Electroacupuncture treatment might be effective therapy for chronic back pain in horses.