• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.104-110
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• 2009

Phenylketonuria (PKU) is an inherited metabolic disorder caused by mutations in the phenylalanine catabolic enzyme, phenylalanine hydroxylase (PAH). The use of phenylalanine ammonia-lase (PAL) by oral and parenteral routes as a therapeutic drug for PKU has been severely limited due to inactivation by intestinal proteolysis and immune reactions. PEGylation was applied to PAL to reduce the degrees of antigenicity and proteolytic inactivation. Kinetic experiments with native PAL and pegylated PALs were performed, and pH stability, temperature stability, and protease susceptibility were evaluated. Enzyme linked immunosorbent assay (ELISA) was carried out to measure the immune complex between pegylated PALs and antiserum that had been extracted from a PAL-immunized mouse. Pegylated PAL, especially branched pegylated PAL (10 kDa, 1:32), was more active for phenylalanine and more stable in pancreatic proteases than native PAL. Native PAL was optimal at pH 8.5, corresponding to the average pH range of the small intestine; the same finding was noted for pegylated PALs. All linear and branched pegylated PALs had low reactivity with mouse antiserum, especially the 1:16 formulation with linear 5-kDa PEG and the 1:32 formulation with branched 10-kDa PEG. Therefore, we suggest the 1:32 formulation with branched 10-kDa PEG as the most promising formulation for enzyme replacement therapy.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.19-19
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• 2003

We have developed a cardiac cell model (Kyoto Model) for the sinoatrial node and ventricle, which is composed of a common set of kinetic equations of membrane ionic currents, Ca$\^$2+/dynamics of sarcoplasmic reticulum and contractile protein. To expand this model by including metabolic pathways, the intracellular ATP metabolism, which is pivotal in cardiac excitation - contraction coupling, was incorporated. ATP consumption by the sarcolemmal Na$\^$+/ pump and the Ca pump in the sarcoplasmic reticulum were calculated with stoichiometry of 3Na:2K:1ATP and 2Ca:1ATP, respectively. ATP consumption by contraction was estimated according to experimental data. Dependence of contraction on ATP and inorganic phosphate was modeled, based on data of skinned cardiac fiber. in production by mitochondrial oxidative phosphorylation was modified from Korzeniewski '||'&'||' Zoladz (2001), and creatine kinase and adenylate kinase reactions were incorporated. ATP dependence of ATP-sensitive K channel and L type Ca channel were also included.

• Journal of Applied Biological Chemistry
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• v.43 no.1
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• pp.49-53
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• 2000

The in vitro metabolism of a new herbicide pyribenzoxim, {benzophenone O-[2,6-bis[(4,6-dimethoxy-2-pyrimidinyl)oxy]benzoyl]oxime} was studied using rice, barnyardgrass and rat liver microsomes. No metabolism of pyribenzoxim was observed with rice and barnyardgrass microsomes though the cvtochrome P450 was active, which was evidenced by the metabolism of cinnamic acid. With rat liver microsomes, four metabolites (M1, M2, M3, and M4) were produced while parent compound decreased. M1 and M2 were from the hydrolysis reactions and NADPH-dependent metabolites were M3 and M4 (major metabolite) which were hydroxylated by cytochrome P450. They were identified as bispyribac-sodium (M1), benzophenone oxime (M2), {benzophenone O-[2,6-bis[(5-hydroxy-4,6-dimethoxy-2-pyrimidinyl)oxy]-benzoyl]oxime}(M3), and {benzophenone O-[2[(5-hydroxy-4,6-dimethoxy-2l-pyrimidinyl)6-(4,.6dimethoxy-2-pyrimidinyl)oxy]benzoyl]oxime} (M4) through LC/MS/MS analyses. Based on the results obtained metabolic map of pyribenzoxim is proposed.

• The Korean Journal of Emergency Medical Services
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• v.25 no.1
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• pp.243-249
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• 2021

A decrease in coronary blood flow leads to an imbalance between the supply of oxygen to the myocardium and its demand, and reversible or irreversible damage to the myocardium could occur depending on the severity of the resultant ischemia and the duration of the imbalance. This imbalance results in a cascade of ischemic reactions in the following order: metabolic abnormalities, diastolic dysfunction, systolic dysfunction, and electrocardiogram changes. Variant angina is caused by the closure of the coronary artery due to reversible coronary artery spasm, resulting in myocardial ischemia and subsequent chest pain as a clinical symptom. Variant angina may be observed as ST segment elevation in electrocardiogram measured when present in chest pain. However, 12-lead electrocardiogram performed after the patient's chest pain resolves does not help in the diagnosis. Since the duration of chest pain appears to be <15 minutes, it is important to perform the 12-lead electrocardiogram when clinical symptoms are present. If nitroglycerin is administered without performing 12-lead electrocardiogram by 119 pre-hospital paramedics, the chest pain would be resolved, making it impossible to identify changes in the ST segment. Before administration of nitroglycerin, changes in the ST segment must be recorded by performing 12-lead electrocardiogram.

• Journal of Korean Society of Environmental Engineers
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• v.22 no.10
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• pp.1869-1879
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• 2000

A series of experiments were conducted for modeling the fate and effect of the coupled oxidation reduction reaction of ethanol and propionate recognized as important intermediates in anaerobic degradation metabolism. Anaerobic kinetics for conversion of propionate and the interaction with ethanol were investigated using the model of specific substrate priority utilization effect. Seed cultures for the experiment were obtained from an anaerobically enriched steady-state propionate master culture reactor (HPr-MCR), ethanol-propionate master culture reactor (EtPr-MCR) and glucose master culture reactor (Glu-MCR). Experiments were consisted of four phases. Phase I, II and III were conducted by fixing the propionate organic loading as 1.0 g COD/L with increasing ethanol loading of 0, 100, 200, 400 and 1,000 mg/L, to find metabolic interaction of ethanol and propionate degradation by each enriched anaerobic culture. In phase IV, different mixing ratios of Glu-MCR and HPr-MCR cultures with fixed propionate organic loading, 1.0 g COD/L, were applied to observe the propionate degradation metabolic behavior. In the results of this study, different pathways of propionate and ethanol conversion were found using a modified competitive inhibition kinetic model. Increase of $K_{s2}$ value reflected the formation of acetate followed by ethanol degradation. In addition. $K_3$ value was increased slightly as the reactions of acetate formation and degradation were occurred in acetoclastic methanogenesis.

• Korean Journal of Clinical Pharmacy
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• v.17 no.1
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• pp.13-18
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• 2007

The purpose of the present study was to investigate the effect of cimetidine on theophylline pharmacokinetics in Korean healthy normal subjects. Eight subjects were enrolled and open label, two period cross-over study was conducted without significant drug related adverse reactions. Cimetidine seemed that significantly inhibited the metabolism of theophylline, oral clearance decreased significantly when cimetidine was coadministered. Coadministered cimetidine increased $AUC_t$ and $C_{max}$ of theophylline. All subjects were genotyped using PCR-RFLP methods to evaluate the differences in metabolic capacity in accordance with CYP1A2 genotypes, but no mutant genotype was found. This suggests that metabolic capacities were not significantly affected by CYP1A2 genotypes among subjects. In conclusion, disposition of theophylline was significantly affected by coadministered cimetidine. Further evaluation with well-designed drug interaction study in accordance with various genotype of CYP1A2 is needed.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.77-79
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• 2002

The urea cycle, consisting of a series of six enzymatic reactions, plays key roles to prevent the accumulation of toxic nitrogenous compound and synthesize arginine de novo. Five well characterized diseases have been described, resulting from an enzymatic defect in the biosynthesis of one of the normally expressed enzyme. This presentation will focus on two representative diseases; ornithine transcarbamylase(OTC) deficiency and citrullinemia(argininosuccinate synthetase deficiency). OTC deficiency is one of the most common inborn error of urea cycle, which is inherited in X-linked manner. We identified 17 different mutations in 20 unrelated Korean patients with OTC deficiency; L9X, R26P, R26X, T44I, R92X, G100R, R141Q, G195R, M205T, H214Y, D249G, R277W, F281S, 853 del C, R320X, V323M and 10 bp del at nt. 796-805. These mutations occur at well conserved nucleotide sequences across species or CpG hot spot. The L9X and R26X lead to the disruption of leader sequences, required for directing mitochondrial localization of the OTC precursor. Their phenotypes are severe, and neonatal onset. The G100R, R277W and V323M mutations were uniquely identified in patients with late onset OTC deficiency. The other genotypes are associated with neonatal onset. Out of 20 patients with OTC deficiency, only 6 patients are alive; two were liver transplanted, and normal in growth and development at 2, 4 years after transplantation respectively. Citrullinemia is an autosomal recessive disease, caused by the mutations in the argininosuccinate synthetase(ASS) gene. We identified in 3 major mutations in 11 unrelated Korean patients with citrullinemia; G324S, $IVS6^{-2}$ A to G, and 67 bp ins at nt 1125-1126. Among these, the 67 base pair insertion mutation is novel. The allele frequency of each mutation is; G324S(45%), IVS6-2 A to G(32%), and 67 base pair insertion(14%). All patients are diagnosed at neonatal or infantile age. Interestingly, two patients presented with stroke like episode. Out of 11 patients, 5 patients died. Among 6 patients alive, one patient was successfully liver transplanted.

• Korean Journal of Applied Biomechanics
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• v.25 no.4
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• pp.453-463
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• 2015

Objective : The purpose of this study was to investigate the effects of the Probody Massage Program on the physical characteristics, gross motor function and ROM (Range Of Motion) of children with cerebral palsy. Method : The subjects of this study were two children who have been diagnosed with first grade cerebral palsy that utilized T development support center located in B Metropolitan city for 8 weeks, twice a week, to carry out the Probody Massage Program for 30 minutes. Physiological reactions (height, weight, BMI, blood pressure (an index of inflammation), pulse rate) and large operating functions (sitting, crawling and the joints' range of motion as an angle of the shoulders' upper limb articulation) were measured pretest, after 4 weeks, and after 8 weeks. Results : The Probody Massage Program showed positive changes in physical characteristics (blood pressure, sitting, and crawling), gross motor function (upper limb shoulder movement), joint range of motion, height, body weight, metabolic activation and blood circulation of children with cerebral palsy. Conclusion : We believe making a practical impact on the growth and development, functional recovery of daily life, and improvement of quality of life of children with cerebral palsy by utilizing Probody Massage Program improves blood pressure (an index of inflammation), pulse, sitting, crawling, and the joints' range of motion as an angle of the shoulder joints' upper limb movement of children with cerebral palsy.

• Journal of Applied Biological Chemistry
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• v.52 no.3
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• pp.93-102
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• 2009

Polyunsaturated fatty acids (PUFA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have significantly beneficial effects on health in relation to cardiovascular, immune, and inflammatory conditions and they are involved in determining the biophysical properties of membranes as well as being precursors for signaling molecules. PUFA biosynthesis is catalyzed by sequential desaturation and fatty acyl elongation reactions. This aerobic biosynthetic pathway was thought to be taxonomically conserved, but an alternative anaerobic pathway for the biosynthesis of PUFA is now known to contain analogous polyketide synthases (PKS). Certain fish oil can be a rich source of PUFA although processed marine oil is generally undesirable as food ingredients because of the associated objectionable flavors that are difficult and cost-prohibitive to remove. Oil-seed plants contain only the 18-carbon polyunsaturated fatty acid alpha-linolenic acid, which is not converted in the human body to EPA and DHA. It is now possible to engineer common oilseeds which can produce EPA and DHA and this has been the focus of a number of academic and industrial research groups. Recent advances and future prospects in the production of EPA and DHA in oilseed crops are discussed here.

• Nutrition Research and Practice
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• v.7 no.5
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• pp.347-351
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• 2013

Food-dependent exercise-induced anaphylaxis (FDEIAn) is induced by different types and various intensities of physical activity, and is distinct from food allergies. It has been shown that consumption of allergenic food followed by exercise causes FDEIAn symptoms. Intake of allergenic food or medication before exercise is a major predisposing factor for FDEIAn. Urticaria and severe allergic reactions are general symptoms of FDEIAn. Dermatological tests and serum IgE assays are the typical prescreening methods, and have been used for several decades. However, these screening tests are not sufficient for detecting or preventing FDEIAn. It has been found that exercise may stimulate the release of mediators from IgE-dependent mast cells that can result in FDEIAn when a certain threshold level has been exceeded. Mast cell degradation might be a major factor to induce FDEIAn but this has not been determined. A number of foods have been reported to be involved in the onset of FDEIAn including wheat, eggs, chicken, shrimp, shellfish, nuts, fruits, and vegetables. It is also known that aspirin increases the occurrence of type I allergy symptoms when combined with specific foods. Moreover, high intensity and frequent exercise are more likely to provoke an attack than low intensity and less frequent exercise. In this paper, we present the current views of the pathophysiological mechanisms underlying FDEIAn within the context of exercise immunology. We also present a detailed FDEIAn definition along with etiologic factors and medical treatment for cholinergic urticaria (UC) and exercise-induced anaphylaxis (EIA).