• The Korean Journal of Pharmacology
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• v.23 no.1
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• pp.1-7
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• 1987

The renal handling and tissue distribution of pyrazinamide were studied after administration of single dose intravenous injection for 15 min or constant infusion in New Zealand White rabbits. Peak pyrazinamide serum concentration ranged from 57.3 to $105.0{\mu}g/ml$ ($mean{\pm}SD;83.0{\pm}17.8$). The mean half-life of the a phase was $0.143{\pm}0.047$ hr while the ${\beta}$ phase ranged from 1.66 to 3.25 hr($mean{\pm}SD;2.38{\pm}0.57$). The mean steady-state volume of distribution in non-compartmental model was $0.935{\pm}0.362\;L/kg$ Excretion ratio of pyrazinamide was dramatically reduced from 1.02 to 0.30 when unbound serum pyrazinamide concentration was increased from 6.04 to $60.9\;{\mu}g/ml$. The urine flow dependency of renal clearance of pyrazinamide was demonstrated in steady-state serum concentration. The tissue/serum concentration ratio of pyrazinamide was highest in kidney and lowest in skeletal muscle among the tissues examined. The results suggested that a large fraction of pyrazinamide filtered by glomerulus and secreted by renal tubule was reabsorbed and this tubular reabsorption of pyrazinamide might be greatly influenced by urine flow.

• Journal of Nutrition and Health
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• v.42 no.1
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• pp.5-13
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• 2009

Mushrooms have become a largely untapped source of powerful new pharmaceutical products that poses anti-inflammatory, and antimutagenic, and antioxidant activities. The antioxidant effects of the mushroom may be partly explained by protecting cellular components against free radical. The aim of this study was to investigate the protective effect of chaga mushroom against diabetes, via the mitigation of oxidative stress and reduction of blood glucose, in streptozotocin-induced diabetic rats. Rats were rendered diabetic by intravenous administration of STZ through tail at a dose of 50 mg/kg. Animals were allocated into four groups with 8 rats each. The control and diabetic control group were fed with standard rat feed. The other diabeic groups, the low chaga extract group and the high chaga extract group were fed ad libitum using 0.5 g/kg and 5 g/kg of chaga mushroom extract, respectively, for 4 weeks. The blood glucose levels in the two chaga extract groups showed a tendency to decrease but did not reach statistical significance after the supplementation. Leukocyte DNA damage, expressed as tail length, was found to be significantly lower in the high chaga extract group than in the diabetic control group (p > 0.05). Plasma level of total radical-trapping antioxidant potential (TRAP) was tend to be higher in the high chaga extract group compared with the diabetic control group. Erythrocyte antioxidant enzyme activities of two groups did not differ. Although we did not obtain beneficial effect on lowering blood glucose levels in the STZ-induced diabetic rats, this results suggest that the chaga mushroom extracts may initially act on protecting endogenous DNA damage in the short-term experiment.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.12
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• pp.1727-1733
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• 2012

This study was conducted to investigate the effects of Vaccinium uliginosum L. (bilberry) on chemically induced diabetes and hypercholesterolemia. Sprague Dawley (SD) rats were divided into six groups, control (CON), bilberry added group (CBB), streptozotocin (STZ)-induced diabetic group (STZ), STZ and bilberry added group (SBB), high fat fed group (HFF) and high fat and bilberry added group (HFB). Diabetes was chemically induced by intravenous injection of 45 mg/kg body weight STZ in citrate buffer (pH 4.5). Serum triglycerides decreased significantly (p<0.05) in the STZ group that was fed bilberry. Additionally, the athrogenic index (AI) decreased significantly (p<0.05) when compared to the STZ group, while the liver triglycerides tended to decrease in the STZ group. HDL-cholesterol also increased significantly in response to bilberry. When compared to the STZ group, steady attenuation of the blood glucose level was observed upon fasting, 15 min, 30 min, 60 min and 120 min after oral glucose administration. The blood glucose level in the bilberry fed group decreased by 24% when compared to STZ group, while the superoxide dismutase (SOD) became significantly higher (p<0.05) in the STZ group when compared to the CON group. Overall, the results of this study suggest that bilberry stimulates lipid metabolism in both the serum and liver and has a positive effect on glucose metabolism in chemically induced diabetic rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.25 no.6
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• pp.969-975
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• 1996

The purpose of this study was to investigate the effect of dietary vitamin E on microsomal mixed function oxidase system of liver and lung in streptozotocin(STZ) induced diabetic rats. Sprague-Dawley male rats weighing 140 $\pm$ 10mg were randomly assigned to one control and three STZ-diabetic groups. Diabetic groups were divided into DM-0E(vitamin E free diet), DM-40E(40mg vitamin E kg/diet) and DM-400E(400mg vitamin E kg/diet) according to the level of vitamin E supplementation. Diabetes was experimentally induced by intravenous administration of 55mg/kg b.w of STZ in citrate buffer(pH 4.3) after 4 week feeding of three experimental diets. Animals were sacrificed at the 6th day of diabetic state. The contents of cytochrome P$_{450}$ in DM-0E, DM-40E and DM-400E groups of liver were increased by 162%, 150% and 56%, respectively, compared with that of control. Also the contents of cytochrome P$_{450}$ in lung were similar to liver. The activities of cytochrome bs in DM-0E and DM-40E groups of the liver were increased by 70% and 53%, respectively, compared with that of control, but not in DM-400E group. The activities of bs in DM-0E, DM-40E and DM-400E groups of lung were signficantly increased. Activity of cytochrome P$_{450}$ reductase in DM-0E, DM-40E of liver and lung were higher than that of control group, but the activity of DM-400E group was not different from that of control. The lipid peroxide values of DM-0E, DM-40E and DM-400E groups were 143%, 95% and 31% higher than those of control. It was concluded that dietary vitamin E had protective effects on lipid peroxidation accompanied with increased mixed function of oxidase activity in diabetic rats.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.187-200
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• 2006

Objectives: Acupuncture has been applied in Asia for thousands of years, especially to rehabilitation after stroke. It has been reported that acupuncture increased cerebral blood supply and stimulated the functional activity of brain nerve cells shown by using brain imaging techniques. This study was to evaluate the effect of GB 34-GB 39 electro-acupuncture (EA) on regional cerebral blood flow (rCBF) in stroke patients and normal volunteers using single photon emission computed tomography (SPECT). Methods: The study procedure was divided into two parts: patients and volunteers studies. For the patients study, ten ischemic stroke patients (3 males, 7 females, mean age $68.5{\pm}8.9$ years old) were selected. Baseline brain SPECT was done with triple head gamma camera (MultiSPECT3, Siemens, USA) after intravenous administration of 1,110 MBq of $^{99m}Tc-ECD$. Fifteen-minute EA at GB 34 and GB 39 were applied on the affected limb. The same dose of $^{99m}Tc-ECD$ was injected during the EA, and the second set of SPECT images wasobtained. Using the computer software (ICON 7.1, Siemens, USA), 3 SPECT slices (upper, middle, lower) surrounding the brain lesion were selected and each slice was divided into 10-16 brain regions. Asymmetry indexes (AI) were analyzed in each brain region. We regarded over 10% changes of AI between before and after EA as significance. For the volunteers study, 10 healthy human volunteers (5 males, 5 females, mean age $28.1{\pm}6$ years old) were selected. In the resting state, $^{99m}Tc-ECD$ brain SPECT scans were performed. On the 7th day after the resting examination, 15 minute EA was applied at GB 34 and GB 39 on the right side of the subjects. Immediately after EA, the second SPECT images were obtained inthe same manner as the resting state. Significant increases and decreases of rCBF after EA were estimated by comparing their SPECT images with those of the resting state using paired t statistics at every voxel, which were analyzed by statistical parametric mapping with a threshold of p = 0.01, uncorrected (extent threshold: k=100 voxels). Results: In stroke patients, six of the eight (75%) had significantly increased perfusion in post-acupuncture scans compared to their baseline state. In normal volunteers, GB 34-GB GB EA increased rCBF in both hemispheres including right ventral posterior cingulate (Brodmann area (BA) 23), left superior temporal, anterior transverse temporal (BA 22, 41), left parastriate, peristriate (BA 18, 19), right occipitotemporal, angular (BA 37, 39), left rostral postcentral, caudal postcentral and preparietal (BA 2, 3, 5). However GB 34-GB 39 EA decreased rCBF in the right hemisphere including triangular and middle frontal lobes. Conclusions: The results demonstrated that OB 34-GB 39 EA increased cerebral perfusion in ischemic stroke patients and increased rCBF grossly in temporal lobes of normal volunteers. It is also suggested that there may be a correlation between the GB meridian and the territory of the middle cerebral artery.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.34-41
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• 2016

Adult-onset type II citrullinemia (CTLN2) is characterized by episodes of neurologic symptoms associated with hyperammonemia leading to disorientation, irritability, seizures, and coma. CTLN2 is distinct from classical citrullinemia, which is caused by a mutation of the argininosuccinic acid synthetase (ASS) gene. The serum citrulline level is elevated, while the activity of ASS in liver tissue is decreased. CTLN2 is known to have a poor prognosis if the proper treatment is not taken. We reported a female aged 37 years who developed recurrent attacks of altered consciousness, aberrant behavior, and vomiting. We initially suspected the patient had CTLN2 because of the signs of hyperammonemic encephalopathy, such as altered mentality, memory disturbance, and aberrant behaviors provoked by exercise-induced stress and excessive intravenous amino acid administration. Through her peculiar diet preferences and laboratory findings that included hyperammonemia and citrullinemia, we diagnosed the patient as CTLN2, and SLC25A13 sequencing revealed known compound heterozygous mutations (IVS11+1G>A, c.674C> A). Her parents were heterozygous carriers, and we identified that her older sister had the same mutations. The older sister had not experienced any episodes of hyperammonemia, but she had peculiar diet preferences. The patient and her sister have been well with conservative management. When considering the clinical course of CTLN2, it was meaningful that the older sister could be diagnosed early in an asymptomatic period and that preemptive treatment was employed. Through this case, CTLN2 should be considered in adults who present symptoms of hyperammonemic encephalopathy without a definite etiology. Because of its rare incidence and similar clinical features, CTLN2 is frequently misdiagnosed as hepatic encephalopathy, and it shows a poor prognosis due to the lack of early diagnosis and proper treatment. A high-carbohydrate diet, which is usually used to treat other urea cycle defects, can also exaggerate the clinical course of CTLN2, so proper metabolic screening tests and genetic studies should be performed.

• Journal of Chest Surgery
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• v.33 no.3
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• pp.221-229
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• 2000

Background: Thromboxane A2 and endothelin-1 are the potent vasoconstrictors affecting pulmonary pathophysiology in response to whole body inflammatin following CPB. Aprotinin, as an antiiflammatory agent, may decrease the release of such vasoactive substance from pulmonary tissues, preventing pulmonary hypertension after cardiopulmonary bypass. Material and Method: Ten mongrel dogs(Bwt. ac. 20kg) were subjected to cardioupulmonary bypass for 2 hours and postbypass pulmonary vascular resistance(0, 1, 2, 3 hours) were compared with prebypass level. The dogs were divided into 2 groups; control group(n-5) and aprotinin group(n=5). In the aprotinin group, aprotinin was administered as follows; 50,000 KIU/kg mixed in pump priming solution, 50,000 KIU/kg prebypass intravenous infusion over 30 minutes, 10,000 KIU/kg/hour postbypass continuous infusion. Prebypass and postbypass 0, 1, 2, 3 hour pulmonary vascular resistance were measured. At prebypass and postbypass 0, 90, 180 minutes, blood samples were obtained from pulmonary arterial and left atrial catherers for the assay of plasma thromboxane B2 a stable metabolite of thromboxane A2, and endothelin-1 concentrations. Result: The ratios of pustbypass over prebypass pulmonary vascular at postbypass 0, 1, 2, 3 hours were 1.28$\pm$0.20, 1.82$\pm$0.23, 1.90$\pm$0.19, 2.14$\pm$0.18 in control group, 1.58$\pm$0.18, 1.73$\pm$0.01, 1.66$\pm$0.10, 1.50$\pm$0.08 in aprotinin group ; the ratios gradually increased in control group while decreased or fluctuated after postbypass 1 hour in aprotinin group. There was statistically significant difference between control group and aprotinin group at postbypass 3 hours(P=0.014). Pulmonary arterial plasma concentration of thromboxane B2(pg/ml) at prebypass, postbypass 0, 90, 180 minutes were 346.4$\pm$61.9, 529.3$\pm$197.6, 578.3$\pm$255.8, 493.3$\pm$171.3 in control group, 323.8$\pm$118.0, 422.6$\pm$75.6, 412.3$\pm$59.9, 394.5$\pm$154.0 in aprotinin group. Left atrial concentrations were 339.3$\pm$89.2, 667.0$\pm$65.7, 731.2$\pm$192.7, 607.5$\pm$165.9 in control group, 330.0$\pm$111.2, 468.4$\pm$190.3, 425.4$\pm$193.6, 4.7.3$\pm$142.8 in aprotinin group. These results showed decrement of pulmonary thromboxane A2 generation in aprotinin group. Pulmonary arterial concentrations of endothelin-1(fmol/ml) at the same time sequence were 7.84$\pm$0.31, 13.2$\pm$0.51, 15.0$\pm$1.22, 16.3$\pm$1.73 in control group, 7.76$\pm$0.12, 15.3$\pm$0.71, 22.6$\pm$6.62, 14.9$\pm$1.11 in aprotinin group. Left atrial concentrations were 7.61$\pm$17.2, 57.1$\pm$28.4, 18.9$\pm$18.2, 31.5$\pm$20.5 in control group, 5.61$\pm$7.61, 37.0$\pm$26.2, 28.6$\pm$21.7, 37.8$\pm$30.6 in aprotinin group. These results showed that aprotinin had no effect on plasma endothelin-1 concentration after cardiopulmonary bypass. Conclusion: Administration of aprotinin during cardiopulmonary bypass could attenuate the increase in pulmonary vascular resistance after bypass. Inhibition of pulmonary thromboxane A2 generation was thought to be one of the mechanism of this effect. Aprotinin had no effect on postbypass endothelin-1 concentration.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.5
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• pp.747-754
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• 2005

Nutritional regulation of gene expression associated with growth and feeding behavior in avian species can become an important technique to improve poultry production according to the supply of nutrients in the diet. Insulin-like growth factor-I (IGF-I) found in chickens has been characterized to be a 70 amino acid polypeptide and plays an important role in growth and metabolism. Although it is been well known that IGF-I is highly associated with embryonic development and post-hatching growth, changes in the distribution of IGF-I gene expression throughout early- to late-embryogenesis have not been studied so far. We revealed that the developmental pattern of IGF-I gene expression during embryogenesis differed among various tissues. No bands of IGF-I mRNA were detected in embryonic liver at 7 days of incubation, and thereafter the amount of hepatic IGF-I mRNA was increased from 14 to 20 days of incubation. In eyes, a peak in IGF-I mRNA levels occurred at mid-embryogenesis, but by contrast, IGF-I mRNA was barely detectable in the heart throughout all incubation periods. In the muscle, no significant difference in IGF-I gene expression was observed during different stages of embryogenesis. After hatching, hepatic IGF-I gene expression as well as plasma IGF-I concentration increases rapidly with age, reaches a peak before sexual maturity, and then declines. The IGF-I gene expression is very sensitive to changes in nutritional conditions. Food-restriction and fasting decreased hepatic IGF-I gene expression and refeeding restored IGF-I gene expression to the level of fed chickens. Dietary protein is also a very strong factor in changing hepatic IGF-I gene expression. Refeeding with dietary protein alone successfully restored hepatic IGF-I gene expression of fasted chickens to the level of fed controls. In most circumstances, IGF-I makes a complex with specific high-affinity IGF-binding proteins (IGFBPs). So far, four different IGFBPs have been identified in avian species and the major IGFBP in chicken plasma has been reported to be IGFBP-2. We studied the relationship between nutritional status and IGFBP-2 gene expression in various tissues of young chickens. In the liver of fed chickens, almost no IGFBP-2 mRNA was detected. However, fasting markedly increased hepatic IGFBP-2 gene expression, and the level was reduced after refeeding. In the gizzard of well-fed young chickens, IGFBP-2 gene expression was detected and fasting significantly elevated gizzard IGFBP-2 mRNA levels to about double that of fed controls. After refeeding, gizzard IGFBP-2 gene expression decreased similar to hepatic IGFBP-2 gene expression. In the brain, IGFBP-2 mRNA was observed in fed chickens and had significantly decreased by fasting. In the kidney, IGFBP-2 gene expression was observed but not influenced by fasting and refeeding. Recently, we have demonstrated in vivo that gizzard and hepatic IGFBP-2 gene expression in fasted chickens was rapidly reduced by intravenous administration of insulin, as indicated that in young chickens the reduction in gizzard and hepatic IGFBP-2 gene expression in vivo stimulated by malnutrition may be, in part, regulated by means of the increase in plasma insulin concentration via an insulin-response element. The influence of dietary protein source (isolated soybean protein vs. casein) and the supplementation of essential amino acids on gizzard IGFBP-2 gene expression was examined. In both soybean protein and casein diet groups, the deficiency of essential amino acids stimulated chickens to increase gizzard IGFBP-2 gene expression. Although amino acid supplementation of a soybean protein diet significantly decreased gizzard IGFBP-2 mRNA levels, a similar reduction was not observed in chickens fed a casein diet supplemented with amino acids. This overview of nutritional regulation of IGF-I and IGFBP-2 gene expression in young chickens would serve for the establishment of the supply of nutrients to diets to improve poultry production.

• Journal of the Korean Arthroscopy Society
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• v.16 no.2
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• pp.167-174
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• 2012

Purpose: The purpose of this study is investigation of clinical and functional outcomes in homogeneous group with positive culture after arthroscopic management for pyogenic knee arthritis and analysis of factors affecting those outcomes. Materials and Methods: Thirty-two patients with positive culture after arthroscopic management were included. Mean follow-up period was 41.6 months. Clinical evaluation included death related to infection, recurrence, time to normalize erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), duration of administration of intravenous antibiotics and readmission. Radiographic evaluation was performed according to Kellgren and Lawrence. The prevalence of total knee arthroplasty was investigated and functional evaluation included modified Lysholm, Tegner activity and Korean version of the Western Ontario and McMaster Universities (K-WOMAC) score. Results: Staphylococcus aureus was identified in 21 patients. Time to normalize ESR and CRP was 78.0 and 67.6 days, respectively. Two patients died while there were six recurrences and five readmissions. Rate of recurrence was significantly high in patients with chronic renal failure (P=0.034) and incidence of readmission was associated with higher radiographic grade of osteoarthritis and rate of reoperation (P=0.032 and P=0.006, respectively). At the final follow-up, radiographic grade worsened in 21 patients and was associated with those at first visit. Five arthroplasties were performed. Average modified Lysholm score, Tegner activity score and K-WOMAC score were 53.5, 2.7, 44.2 points, respectively. Conclusion: The severity of osteoarthritis on final radiographs was associated with those at first visit. Patients with higher grade of osteoarthritis at first visit showed higher incidence of readmission and those with chronic renal failure demonstrated higher chances of recurrence.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.41-51
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• 2004

PURPOSE: Tourette's disorder (TD), which is characterized by multiple waxing and waning motor tics and one or more vocal tics, is known to be associated with abnormalities in the dopaminergic system. To testify our hypothesis that risperidone would improve tic symptoms of TD patients through the change of the dopaminergic system, we measured the dopamine transporter (DAT) densities between drug-naive children with TD and normal children, and investigated the DAT density before and after treatment with risperidone in drug-naive children with TD, using iodine-123 labelled $N-(3-iodopropen-2-yl)-2{\beta}-carbomethoxy-3beta-(4-chlorophenyl)tropane$ ($[^{123}I]IPT$) single photon omission computed tomography (SPECT). MATERIALS and METHODS: $[^{123}I]IPT$ SPECT Imaging and Yale Global Tic Severity Scale-Korean version (YGTSS-K) for assessing the tic symptom severity were carried out before and after treatment with risperidone for 8 weeks in nine drug-naive children with TD. Eleven normal children also underwent SPECT imaging 2 hours after an intravenous administration of $[^{123}I]IPT$. RESULTS: Drug-naive children with TD had a significantly greater increase in the specific/nonspecific DAT binding ratio of both basal ganglia compared with the normal children. However, no significant difference in the specific/nonspecific DAT binding ratio of the basal ganglia before and after treatment with risperidone in children with TD was found, although tic symptoms were significantly improved with risperidone. CONCLUSION: These findings suggest that DAT densities are directly associated with the pathophysiology of TD, however, that the effect of risperidone on tic symptoms in children with TD is not attributed to the change of dopaminergic system.