Our earlier studies found a significant correlation between the activities of ranitidine N-oxidation catalyzed by hepatic flavin-containing monooxygenase (FMO) and the presence of mutations in exon 4 (E158K) and exon 7 (E308G) of the FMO3 gene in Korean volunteers. However, caffeine N-1 demethylation (which is also partially catalyzed by FMO) was not significantly correlated with these FMO3 mutations. In this study, we examined another common mutation (V257M) in exon 6 of FMO3 gene. The V257M variant, which is caused by a point mutation (G769A), was commonly observed (13.21% allele frequency) in our subjects (n=159). This point mutation causes a substitution of Val257 to Met257, with transformation of the secondary structure. The presence of this mutant allele correlated significantly with a reduction in caffeine N-1-demethylating activity, but was not correlated with the activity of N-oxidation of ranitidine. In a family study, the low FMO activity observed in a person heterozygous for a nonsense mutation in exon 4 (G148X) and heterozygous for missense mutation in exon 6 (V257M) of FMO3 was attributed to the mutations. Our results suggest that various point mutations in the coding regions of FMO3 may influence FMO3 activity according to the probe substrates of varying chemical structure that correlate with each mutation on the FMO3 gene.
Alleles ; Caffeine ; Clinical Coding ; Codon, Nonsense ; Exons ; Genotype ; Humans* ; Mutation, Missense ; Phenotype ; Point Mutation ; Ranitidine ; Substrate Specificity* ; Volunteers

An ex vivo assay determining the flavin-containing monooxygenase (FMO) activity in perfused rat liver has been developed by assessing the rate of thiobenzamide S-oxide (TBSO) formation from the infused thiobenzamide (TB). The hepatotoxicity by TB or TBSO was not a critical factor for maintaining the FMO activity for up to 50 min. The FMO activity expressed in nmoles TBSO produced/g liver/min was the same for the recycling and non-recycling perfusion. This implies that reduction of the oxidized TBSO back to the parent compound (TB) is negligible. Hydrolysis of the collected perfusates with either beta-glucuronidase or arylsulfatase did not increase the TBSO level and thus, TBSO does not appear to undergo conjugation either to glucuronide or sulfate esters. Thus, measuring the rate of TB S-oxidation in the isolated perfused liver with 1 mM TB for 50 min provides a useful tool for evaluation of the hepatic FMO activity in the absence of hepatic necrosis and without the interferences caused by further conjugation or back reduction of the TBSO to the parent TB.
Animals ; Esters ; Glucuronidase ; Humans ; Hydrolysis ; Liver* ; Necrosis ; Parents ; Perfusion ; Rats* ; Recycling

PURPOSE: To evaluate the efficacy of Flexible intramedullary pin fixation in pediatric forearm diaphyseal fractures. MATERIALS AND METHODS: In this retrospective study, we reviewed 15 cases of forearm diaphyseal fractures operated using flexible intra-medullary nail fixation technique between January 2000 and December 2004. Of these 15 children, there were 11 boys and 4 girls with an average age of 11.6 years (range, 7~15 years). The implants were introduced in the distal radius and proximal ulna in all patients. An average duration of fixation was 5.3 months in the radius, 4.7 months in the ulna. After operation, all patient were applied with a long arm cast and the duration of immobilization was 5.2 weeks (range, 4~6 weeks) on average. RESULTS: All fractures in this series healed with normal range of supination (average 80.0) and pronation (average, 71.6 degrees). Average operation time including anesthesia was 123 minutes and hospital stay was 5.4 days. Time to union was 8.4 weeks on average. Range of motion and functional results were satisfactory in all cases. There were one case of incomplete ulnar nerve injury and two cases of refracture which were treated conservatively without any permanent complication. CONCLUSION: Flexible intramedullary pin fixation technique is a good method in case of unstable displaced fracture and difficult or failed closed treatment.
Anesthesia ; Arm ; Child* ; Female ; Forearm* ; Fractures, Bone* ; Humans ; Immobilization ; Length of Stay ; Pronation ; Radius ; Range of Motion, Articular ; Reference Values ; Retrospective Studies ; Supination ; Ulna ; Ulnar Nerve

PURPOSE: This study analyzed the treatment results of highly unstable trochanteric fractures and made treatment guidelines. MATERIALS AND METHODS: Among three hundred six cases of trochanteric fractures from October 2001 to February 2006, the patients were divided into group 1(highly unstable trochanteric fracture, 69 cases) and group 2(age and gender-matched control group, 70 cases). The two groups were compared clinically and radiologically. A highly unstable trochanteric was defined as a fracture with a neck-shaft angle<100degrees and anterior angulation. The mean follow-up duration in groups 1 and 2 was 13.2 and 15.5 months, respectively. The mean neck-shaft angle in groups 1 and 2 was 92.1degrees and 118.9degrees , respectively. The mean anterior angulation in groups 1 and 2 was 23.0degrees and 4.6degrees. RESULTS: In group 1, 39 cases were treated with a dynamic hip screw (DHS), 22 cases were treated with a proximal femoral nail (PFN), and 8 cases(11.6%) were treated with primary bipolar hemiarthroplasty. The average amount of sliding of the lag screw in groups 1 and 2 was 10.5 mm and 3.7 mm, respectively (p<0.05). The average change in the neck-shaft angle in groups 1 and 2 was 7.0degrees 1 and 2.1degrees , respectively (p<0.05). There were 7 complications in group 1, including 5 cutting-out, 1 back-out and 1 Z-effect, and 2 cases of cutting-out in group 2. CONCLUSION: A highly unstable trochanteric fracture has a high risk of the need for additional surgery. Therefore, considerable care should be taken to treat it with a consideration of the possible need for arthroplasty.
Arthroplasty ; Femur* ; Follow-Up Studies ; Hemiarthroplasty ; Hip ; Hip Fractures* ; Humans

To examine individual variation in drug metabolism catalyzed by flavin-containing monooxygenase (FMO), 179 Korean volunteers' urinary molar concentration ratio of theobromine (TB) and caffeine (CA) was determined. Their urine was collected for 1 hr (between 4 and 5 hrs) after they drank a cup of coffee containing 115 mg CA and analyzed by an HPLC system. The lowest TB/CA ratio obtained was 0.40, the highest ratio was 15.17 (38-fold difference), and the median ratio for all subjects was 1.87. The mean was 2.66 with 2.36 S.D.. In 134 nonsmokers, the mean ratio was 2.35 +/- 1.93, that of 51 males was 2.30 +/- 2.26 and 83 females was 2.37 +/- 1.85, respectively. There was no significant gender difference in the obtained TB/CA ratio (Mann-Whitney test; p=0.518). There were no smokers among the 83 female volunteers. In the remaining 96 male subjects, the ratio obtained in 51 nonsmokers was 2.30 +/- 2.06 and that of 45 smokers was 3.62 +/- 3.19. This indicated that the TB/CA ratio was increased significantly in smokers (p=0.007). However, when the TB/CA ratios (FMO activity) obtained in all 179 Korean volunteers are compared with the urinary concentration ratios of paraxanthine (PX) plus 1,7-dimethylurate (17U) to CA (CYP1A2 activity), there was a weak but significant correlation (Pearson's correlation coefficient test; r2=0.28, p<0.0001). This indicates that, although the urinary TB/CA ratio mostly represents FMO activity, minor contribution by CYP1A2 activity cannot be ignored. In conclusion, the FMO activity measured by taking the urinary TB/CA ratio from normal healthy Korean volunteers shows marked individual variations without significant gender differences and the increased TB/CA ratio observed in cigarette smokers may have been caused by the increased CYP1A2 activity.
Caffeine* ; Chromatography, High Pressure Liquid ; Coffee* ; Cytochrome P-450 CYP1A2 ; Drinking* ; Ethanol ; Female ; Humans ; Male ; Metabolism ; Molar ; Theobromine* ; Tobacco Products ; Volunteers

BACKGROUND/AIMS: Oxidative stress may contribute to gastric epithelial damage and mutagenesis caused by Helicobacter pylori (H. pylori). H. pylori induces recruitment and activation of inflammatory cells, which produces reactive oxygen species. H. pylori extract directly induces the synthesis of reactive oxygen species in gastric epithelial cells and causes DNA damage. The aim of this study was to investigate the association between the levels of glutathione (GSH) and H. pylori density, histological findings, endoscopic findings, clinical variables, and virulence factors. METHODS: Gastric biopsy specimens were obtained from 73 consecutive patients. The 5,5'-dithiobis-(2-nitrobenzoic acid) reaction was used to determine GSH levels. RESULTS: The infection rate of H. pylori was 68.5%. The GSH level was not related to age, sex, alcohol intake, and endoscopic findings. The GSH level was lower in patients infected with H. pylori. GSH levels were not correlated significantly with the grades of neutrophil, intestinal metaplasia, and atrophy. However, the GSH levels were significantly correlated with H. pylori density (r=-0.296, p=0.01) and monocyte grade (r=-0.257, p=0.02). The GSH levels were not related to CagA, VacA, and UreA. CONCLUSIONS: This study suggests that H. pylori causes oxidative stresses which deplete GSH in gastric mucosa of patients infected with H. pylori.
Adolescent ; Adult ; Aged ; Female ; Gastric Mucosa/*metabolism/pathology ; Glutathione/*metabolism ; Helicobacter Infections/*metabolism/pathology ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Oxidative Stress ; Stomach Diseases/*metabolism/microbiology/pathology

BACKGROUND/AIMS: Oxidative stress may contribute to gastric epithelial damage and mutagenesis caused by Helicobacter pylori (H. pylori). H. pylori induces recruitment and activation of inflammatory cells, which produces reactive oxygen species. H. pylori extract directly induces the synthesis of reactive oxygen species in gastric epithelial cells and causes DNA damage. The aim of this study was to investigate the association between the levels of glutathione (GSH) and H. pylori density, histological findings, endoscopic findings, clinical variables, and virulence factors. METHODS: Gastric biopsy specimens were obtained from 73 consecutive patients. The 5,5'-dithiobis-(2-nitrobenzoic acid) reaction was used to determine GSH levels. RESULTS: The infection rate of H. pylori was 68.5%. The GSH level was not related to age, sex, alcohol intake, and endoscopic findings. The GSH level was lower in patients infected with H. pylori. GSH levels were not correlated significantly with the grades of neutrophil, intestinal metaplasia, and atrophy. However, the GSH levels were significantly correlated with H. pylori density (r=-0.296, p=0.01) and monocyte grade (r=-0.257, p=0.02). The GSH levels were not related to CagA, VacA, and UreA. CONCLUSIONS: This study suggests that H. pylori causes oxidative stresses which deplete GSH in gastric mucosa of patients infected with H. pylori.
Adolescent ; Adult ; Aged ; Female ; Gastric Mucosa/*metabolism/pathology ; Glutathione/*metabolism ; Helicobacter Infections/*metabolism/pathology ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Oxidative Stress ; Stomach Diseases/*metabolism/microbiology/pathology