Aceclofenac is a non-steroidal anti-inflammatory drug (NSAIDs) for inflammatory diseases. In this report, we report a serious adverse event (AE) occurred during the phase I clinical trial for a new sustained-release (SR) formulation of aceclofenac. There was a serious adverse event (AE), agranulocytosis, induced by aceclofenac SR form. An open-labeled, repeated-doses, randomized, crossover study was conducted at Kyung Hee University Hospital and 26 Korean healthy male volunteers were enrolled. All subjects received both aceclofenac SR 200 mg once daily and aceclofenac IR 100 mg twice daily for 4 days with 11 days washout period. After 11 days washout period, one subject showed a serious decrease in the segment neutrophil (267/mm3) on a laboratory test prior to the reference drug administration in period 2. We first report a case of agranulocytosis, during a phase I clinical trial.
Agranulocytosis* ; Cross-Over Studies ; Humans ; Male ; Neutrophils ; Volunteers

BACKGROUND: In animal models of cerebral ischemic-reperfusion has been shown to have a beneficial effect. The object of this study is to compare the effect of pathologic findings between normotheimic and moderate hypothermic group. METHODS: We investigated the effect of moderate hypothermia induced 1 hour after transient(10 min) both carotid artery occlusion on the extent of ischemic-reperfusion cell damage in Mongolian Gerbil model. The terminal deoxyribonucleotidyl transferase (TdT) -mediated biotin-16-dUTP nick-end labelling(TUNEL staning) are used to detect apoptosis. RESULTS: 1. We suggest that Core body temperature is down to moderate hypothermia(30-32degrees C) beyond 10 minite by selective bain cooling method in Mongolian Gerbil model. 2. By light microscopy, ischemic-reperfusion damage were detected in the hippocampal CA1 pyramidal layer on the 3 day after transient ischemic insult, which showed chrosomal condensation and cytoplasmic eosinophilia. Ischemic-reperfusion cells were increased in the CA1 region on the 5 day. Apoptotic cells of the CA1 neurons seen by TUNEL staining than ischemic neurons seen by Hematoxylin-eosin staining were investigate 3 and 5 days after ischemic-reperfusion insult. CONCLUSION: We suggest that is not neuroprotective effects of Intraischemic(1 hour) moderate hypothermia in Gerbil brain global ischemic-reperfusion model.
Apoptosis ; Body Temperature ; Brain* ; Carotid Arteries ; Cytoplasm ; DNA Nucleotidylexotransferase ; Eosinophilia ; Gerbillinae* ; Hypothermia* ; In Situ Nick-End Labeling ; Microscopy ; Models, Animal ; Neurons ; Neuroprotective Agents*

In the published version of this article, an error in the sponsor's identity was discovered in the acknowledgment section.

BACKGROUND: Benzoic acid contained in some food can hinder the biological monitoring of hippuric acid in urine, which is frequently used as an exposure index of toluene and xylene. METHOD: 20 male examinees who are not exposed to organic solvents in their jobs were given a bottle of drink containing benzoic acid(70 mg/dl) and took it. Urine samples were taken from every person just before, in 1.5 hrs after, and in 3 hrs after taking the drink. Hippuric acid in urine was analyzed with improved Ogata and Taguchi method and creatinine with Jaffe method. RESULT: Mean hippuric acid concentrations in urine just before, in 1.5 hrs after, and in 3 hrs after taking the drink were 0.59+/-0.21 g/g creatinine, 2.75+/-0.98 g/g creatinine, 1.04+/-0.58 g/g creatinine, respectively. And, each group had statistically significant differences (p<0.01). There were no statistically significant differences between two groups categorized by age, smoking, and drinking. CONCLUSION: From the results, we suggest that when hippuric acid concentration in urine is used as a exposure index of toluene, it should be surveyed whether the food containing benzoic acid was taken or not.
Benzoic Acid* ; Creatinine ; Drinking ; Environmental Monitoring ; Humans ; Male ; Smoke ; Smoking ; Solvents ; Toluene ; Xylenes

One of the most remarkable medical achievements of the Korean War was the development of psychiatry. During the Korean War, soldiers and prisoners of war (POWs) experienced “gross stress reaction” and manifested poor concentration and memory as well as clinical depression and social alienation. Rest and relaxation rotations served as the primary treatment for their conditions. Civilians also bore the brunt of the war’s effects. Delusions of grandeur and megalomania appear to have been common among Koreans, but there were few mental health facilities to provide treatment and care. Out of the furnace of war, psychiatry emerged as a newly specialized field, and in the 1950s, Korea became the very place where military psychiatry training under the U.S. military laid the groundwork for civilian psychiatry. This essay aims to enrich the study of mental illness during and after the Korean War by providing a more detailed picture of the mental problems experienced not only by veterans and POWs, but also by civilians in Korea. Examining mental health issues from this period is challenging due to the scarcity of resources for delving into the minds of the civilians involved. Taking military psychiatry as a starting point, this essay goes beyond existing scholarship to discuss psychiatry-related responses to the Korean War, including the influence of military psychiatry on civilian psychiatry, the endeavors of medical professionals and government policies, and contemporary expressions of mental distress during and after the war.

BACKGROUND: Fighter pilots are frequently exposed to high gravitational acceleration force acting along the body axis from the head to the feet (+GZ) and this gravitational force causes considerable strain on several organ systems, including cardiovascular system and kidneys. Proteinuria had been observed after +GZ stress but the characteristics of urinary protein and the mechanism of proteinuria are not closely investigated up to now. METHODS: A total of 44 student pilots were exposed to +6GZ for 30 seconds using Human Centrifuge and urine samples were collected before and after +GZ load. The amount of urinary protein was measured quantitatively and semiquantitatively with chemistry and dipstick, and the protein components were analysed with electrophoresis. RESULTS: After a total of 44 student pilots were exposed to +6GZ for 30 seconds without anti-G suit, 19 urine samples were positive in dipstick protein test and electrophoresis revealed that their major protein component was albumin. The amount of urinary protein excretion and urinary protein and creatinine ratios (UProt/UCr) were significantly increased to levels of 33.4+/-29.3 mg/dL and 0.239+/-0.203 in comparison with pre-G training levels of 8.8+/-4.3 mg/dL and 0.046+/-0.018, respectively. All 44 urine samples collected the next day of G training were negative in dipstick protein test and had protein levels of 6.8+/-3.0 mg/dL. Of 19 subjects showed proteinuria, 15 performed the same +GZ training again with anti-G suit and so only three urine samples were positive in dip stick protein test. CONCLUSIONS: These results indicates that transient proteinuria can be developed after high +GZ stress most possibly due to increased glomerular permeability of albumin and be effectively protected by the anti-G suit.
Acceleration* ; Axis, Cervical Vertebra ; Cardiovascular System ; Chemistry ; Creatinine ; Electrophoresis ; Foot ; Head ; Humans ; Kidney ; Permeability ; Proteinuria*

Alcoholism is caused by a complex interaction between genetic and environmental factors. Findings obtained from several studies indicate that some tissue damage occurring in alcohol abusers is due to the generation of reactive oxygen species during the ethanol metabolism The objective of this study was to examine the associations between the polymorphisms of glutathione S-transferase (GST) M1 and T1 genes and Korean male patients with alcoholism. We investigated the distribution of deletion of GSTM1 and GSTT1 in Korean male patients diagnosed with alcoholism (n=133) and Korean male control subject without alcoholism (n=91) with polymerase chain reaction (PCR) method. GSTM1 showed significant associations with alcoholism susceptibility (p=0.0002). But GSTT1 showed no significant associations (p=0.0948). In combined analysis, both gene deletion and GSTM1 deletion were associated with alcoholism (p<0.0001 and p<0.0150). These results suggest that GSTM1 gene deletion might play an important role in risk for alcoholism.
Alcoholism ; Ethanol ; Gene Deletion ; Glutathione Transferase ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Reactive Oxygen Species

Simvastatin reduces plasma cholesterol by inhibiting HMG-CoA reductase (HMGR) and is widely used in the treatment of hypercholesterolemia. To screening the possible genetic factors affecting the pharmacokinetics (PK) of simvastatin, 35 male Korean volunteers were enrolled from two separate bioequivalence studies. Each subject was administered 20 mg simvastatin and reference drug PK parameters were used. We used Illumina Human610Quad v1.0 DNA Analysis BeadChip for whole genome SNPs analysis and whole genome genotyping data was processed by linear regression analysis for PK parameters of drug metabolizing enzymes and transporters. We found 145 significant SNPs (P < 0.01) in C(max), 135 significant SNPs (P < 0.01) in T(max) and 85 significant SNPs (P < 0.01) in AUC(inf) from whole genome analysis. In particular, we found that the ABCC2 gene had a significant effect on C(max) and AUC(inf). These results could provide information of possible candidate genes for personalized simvastatin therapy.
Cholesterol ; DNA ; Genome ; Humans ; Hypercholesterolemia ; Linear Models ; Male ; Mass Screening* ; Oxidoreductases ; Pharmacogenetics ; Pharmacokinetics* ; Plasma ; Polymorphism, Genetic* ; Polymorphism, Single Nucleotide ; Simvastatin* ; Therapeutic Equivalency ; Volunteers

BACKGROUND: Apoptosis has been implicated in pathogenesis of various disease. Apo-1/Fas (CD95) is one of the main pathway of apoptosis. To examine the possible relationship between Apo-1/Fas (CD95) and primary knee osteoarthritis, MvaI restriction length polymorphism (RFLP) in human Apo-1/Fas (CD95) gene was assessed. METHODS: Genotype and allele frequencies in promoter region in the Apo-1/Fas (CD95) gene were studied by PCR-RFLP in 226 Korean controls and 148 Korean patients with primary knee osteoarthritis. RESULTS: No statistically significant difference in the genotypic distribution and allelic frequencies was found between the control and the knee oateoarthritis patients. But in the severe grade (grade 3, 4) Kellgren-Lawrence score patients, the frequency of MvaI*1 (G) allele was significantly decreased (P=0.0392) and the of MvaI*2 (A) allele frequency was significantly increased (P=0.0473) compared to the normal controls. CONCLUSION: Apo-1/Fas (CD95) gene polymorphism is a part a determinant factor of severity in knee osteoarthritis, the patients with MvaI*2 (A) allele is more severe radiologic progression. Further substantiation studies are needed in larger patient samples and various other apoptosis related genes to elucidate the mechanism of osteoarthritis, including the Fas ligand gene analysis.
Alleles ; Apoptosis ; Fas Ligand Protein ; Gene Frequency ; Genotype ; Humans ; Knee* ; Osteoarthritis ; Osteoarthritis, Knee* ; Promoter Regions, Genetic

The potential therapeutic action of shikonin in an experimental model of rheumatoid arthritis (RA) was investigated. As a RA animal model, DBA/1J mice were immunized two times with type II collagen. After the second collagen immunization, mice were orally administered shikonin (2 mg/kg) once a day for 35 days, and the incidence, clinical score, bone mineral density (BMD), bone mineral content (BMC) and joint histopathology were evaluated. BMD in the proximal regions of the tibia largely increased in the shikonin treatment group compared with the control group. We also examined the effect of shikonin on inflammatory cytokines and cartilage protection. Shikonin treatment significantly reduced the incidence and severity of collagen-induced arthritis (CIA), markedly abrogating joint swelling and cartilage destruction. Shikonin also significantly inhibited the production of matrix metalloproteinase (MMP)-1 and up-regulated tissue inhibitors of metalloproteinase (TIMP)-1 in mice with CIA. In conclusion, shikonin exerted therapeutic effects through regulation of MMP/TIMP; these results suggest that shikonin is an outstanding candidate as a cartilage protective medicine for RA.
Animals ; Arthritis, Experimental ; Arthritis, Rheumatoid ; Bone Density ; Cartilage ; Collagen ; Collagen Type II ; Cytokines ; Immunization ; Incidence ; Joints ; Mice ; Models, Animal ; Models, Theoretical ; Naphthoquinones ; Tibia ; Tissue Inhibitor of Metalloproteinase-1