• The Korean Journal of Applied Statistics
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• v.15 no.2
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• pp.281-296
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• 2002

On the new medical system separating the prescription and dispensing of the drug, the qualification of pharmacist in substitution of prescribed medicine was restricted, except bioequivalence-certified drugs. Also, Korean Food and Drug Association(KFDA) revised the bioequivalence regulation on August, 2001 Among many changes from old guideline, impressive one is the statistical consideration. Specially, to estimate and analyze bioequivalence measures, AUC and $C_{max}$, the log-transformed model is recommended and the equivalence interval is modified from $\pm$20 rule to [In(0.8),In(1.25)] one. This meaningful act is very hope-for because it is statistically reasonable and is agreed with worldwide bioequivalence guideline, including USA, EU, Japan and Canada. In this paper, we introduce the new regulation of assessing bioequivalence, announced at August, 2001, mainly on statistical view points. Key points for the new regulation are discussed and the minimum sample size based on simulation studies are proposed.

• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.399-408
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• 2018

In this study, we examined the molecular and functional characterization of choline uptake in the human esophageal cancer cells. In addition, we examined the influence of various drugs on the transport of [$^3H$]choline, and explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. We found that both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were highly expressed in esophageal cancer cell lines (KYSE series). CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is both $Na^+$-independent and pH-dependent. Choline uptake and cell viability were inhibited by various cationic drugs. Furthermore, a correlation analysis of the potencies of 47 drugs for the inhibition of choline uptake and cell viability showed a strong correlation. Choline uptake inhibitors and choline deficiency each inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be involved in choline uptake in mitochondria, which is the rate-limiting step in S-adenosylmethionine (SAM) synthesis and DNA methylation. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for esophageal cancer therapy.

• Korean Journal of Pharmacognosy
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• v.32 no.4 s.127
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• pp.327-329
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• 2001

Cordyceps militaris (CM) has been used as a tonics in the traditional medicine. To investigate the anti-diabetic principle of CM, activity guided fractionation was conducted. Hot water extract of CM was fractionated into 3 parts: above 100,000(A), $100,000{\sim}20,000(B)$, below 20,000(C) in molecular weight using in membrane filter system. All fractions showed mild hypoglycemic activity in streptozotocin (STZ)-induced diabetic rats by oral administration (300 mg/kg). The fraction C which was most active among them was fractionated again into two parts, C-1 and C-2 by Sephadex LH 20 column chromatography. The fraction C-1 showed hypoglycemic activity but C-2 did not show activity compared with control in STZ mice. In glucose-fed hyperglycemic mice, fraction C, C-1 and C-2 also showed significant glucose lowering activity. Their decreasing rates of plasma glucose level after 1 hours administrations of fraction C, C-1 and C-2 were 24.5%, 29.3% and 22.0%, respectively (Tolbutamide: 48.4%). These results suggested that CM has both insulin like and insulin release promoting activity and could be developed as an antidiabetic agent.

• Korean Journal of Pharmacognosy
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• v.12 no.1
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• pp.31-43
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• 1981

In order to determine the effect of Oryeongsan reputed to have diuretic action since Han Dynasty and possible synergetic action of Dianthi Semen, Polygonum avicularis Herba, Kochiae Fructus and Akebiae Lignum, herbs with similar reputation, when added to the above prescription, their decoction powders were solved into distilled water and injected into rabbits through the ear vein. Upon the treatment, the excretion of sodium, potassium and chloride ion together with urine volume was kinetically determined. At the same time the clearance of plasma creatinine and sodium ion was determined and the following results were obtained. Every experimental group demonstrated diuretic action, though feable, of relatively long duration. The diuretic mechanism in the case of Oryeongsan made up by mixing the seperate extracts of individual components and Oryeongsan(A) plus Dianthi Semen was found to be inhibitory effect of renal tubular reabsorption in contrast to the case of Oryeongsan(A) plus Polygonum avicularis Herba, Kochiae Fructus or Akebiae Lignum in which case the diuretic mechanism was found to be glomerular vascular dilatation. The urinary excretion of potassium ion was increased in the case of Oryeongsan(A) plus Dianthi Semen, Kochiae Fructus of Akebiae Lignum whereas in the other cases no similar change was registered. The diuretic action was most remarkable in the case of Oryeongsan(A) plus Polygonum avicularis Herba followed by Oryeongsan(A) plus Kochiae Fructus, Oryeongsan(A) plus Dianthi Semen, extract mixture of individual component of Oryeongsan, Oryeongsan(A) and Oryeongsan(A) plus Akebiae Lignum decreasing order. The duration of diuretic action was found to be 90 minutes in the case of Oryeongsan and mixture of individual component of Oryeongsan, and 60 minutes in the case of Oryeongsan(A) plus Dianthi Semen, Kochiae Fructus or Akebiae Lignum in contrast to the case of Oryeongsan(A) plus Polygonum avicularis Herba which lasted up to 120 minutes.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.25-30
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• 2012

Under some pathological conditions as bile flow obstruction or liver diseases with the enterohepatic circulation being disrupted, regurgitation of bile acids into the systemic circulation occurs and the plasma level of bile acids increases. Bile acids in circulation may affect the nervous system. We examined this possibility by studying the effects of bile acids on gating of neuronal (N)-type $Ca^{2+}$ channel that is essential for neurotransmitter release at synapses of the peripheral and central nervous system. N-type $Ca^{2+}$ channel currents were recorded from bullfrog sympathetic neuron under a cell-attached mode using 100 mM $Ba^{2+}$ as a charge carrier. Cholic acid (CA, $10^{-6}M$) that is relatively hydrophilic thus less cytotoxic was included in the pipette solution. CA suppressed the open probability of N-type $Ca^{2+}$ channel, which appeared to be due to an increase in (no activity) sweeps. For example, the proportion of sweep in the presence of CA was ~40% at +40 mV as compared with ~8% in the control recorded without CA. Other single channel properties including slope conductance, single channel current amplitude, open and shut times were not significantly affected by CA being present. The results suggest that CA could modulate N-type $Ca^{2+}$ channel gating at a concentration as low as $10^{-6}M$. Bile acids have been shown to activate nonselective cation conductance and depolarize the cell membrane. Under pathological conditions with increased circulating bile acids, CA suppression of N-type $Ca^{2+}$ channel function may be beneficial against overexcitation of the synapses.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.1-9
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• 2017

Intestinal disorders often co-occur with inflammation and dysmotility. However, drugs which simultaneously improve intestinal inflammation and co-occurring dysmotility are rarely reported. Atractylodin, a widely used herbal medicine, is used to treat digestive disorders. The present study was designed to characterize the effects of atractylodin on amelioration of both jejunal inflammation and the co-occurring dysmotility in both constipation-prominent (CP) and diarrhea-prominent (DP) rats. The results indicated that atractylodin reduced proinflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 in the plasma and inhibited the expression of inflammatory mediators iNOS and NF-kappa B in jejunal segments in both CP and DP rats. The results indicated that atractylodin exerted stimulatory effects and inhibitory effects on the contractility of jejunal segments isolated from CP and DP rats respectively, showing a contractile-state-dependent regulation. Atractylodin-induced contractile-state-dependent regulation was also observed by using rat jejunal segments in low and high contractile states respectively (5 pairs of low/high contractile states). Atractylodin up-regulated the decreased phosphorylation of 20 kDa myosin light chain, protein contents of myosin light chain kinase (MLCK), and MLCK mRNA expression in jejunal segments of CP rats and down-regulated those increased parameters in DP rats. Taken together, atractylodin alleviated rat jejunal inflammation and exerted contractile-state-dependent regulation on the contractility of jejunal segments isolated from CP and DP rats respectively, suggesting the potential clinical implication for ameliorating intestinal inflammation and co-occurring dysmotility.

• Nutrition Research and Practice
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• v.8 no.3
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• pp.319-326
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• 2014

BACKGROUND/OBJECTIVES: The immigrant population has grown considerably in South Korea since the early 1990s due to international marriages. Dietary changes in immigrants are an important issue, because they are related to health and disease patterns. This study was conducted to compare changes in dietary intake between baseline and follow-up periods. SUBJECTS/METHODS: Two hundreds thirty three Vietnamese female married immigrants. Baseline data were collected during 2006-2009, and the follow-up data were collected during 2008 and 2010. Food consumption was assessed using a 1-day 24-hour recall. RESULTS: The amount of the total food consumed (P < 0.001) including that of cereals (P = 0.004), vegetables (P = 0.003), and fruits (P = 0.002) decreased at follow-up compared to that at baseline, whereas consumption of milk and dairy products increased (P = 0.004). Accordingly, the overall energy and nutrient intake decreased at follow-up, including carbohydrates (P = 0.012), protein (P = 0.021), fiber (P = 0.008), iron (P = 0.009), zinc (P = 0.006), and folate (P = 0.002). Among various anthropometric and biochemical variables, mean skeletal muscle mass decreased (P = 0.012), plasma high density lipoprotein-cholesterol increased, (P = 0.020) and high sensitivity C-reactive protein decreased at follow-up (P < 0.001). CONCLUSIONS: A long-term follow-up study is needed to investigate the association between changes in food and nutrient intake and anthropometric and biochemical variables in these Vietnamese female marriage immigrants.

• Nutritional Sciences
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• v.7 no.2
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• pp.76-82
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• 2004

Pine needles are known as a traditional medicine and their ingestion has been shown to be beneficial to human beings. Following induction of the neoplastic process in rats by azoxymethane (AOM), we determined the effects of pine needle supplementation on colon carcinogenesis and on antioxidant systems in the blood and liver. Five week old male Fisher 344 rats were injected with AOM (15 mg/kg) once a week for two weeks. After the second injection, 18 rats were randomly assigned into two groups and were fed a casein-based high-fat diet (120 g fat and 1 g cholesterol/kg diet) with or without pine needle powder (10%w/w). After 6 weeks, rats receiving pine needle powder showed a 40% lower incidence of the number of colonic preneoplastic lesions (aberrant crypts) and a 52% lower incidence of aberrant crypt foci (p<0.01). A significantly elevated level of erythrocyte catalase activity was observed in the pine needle supplemented group (17.4$\pm$1.1 vs. 24.5$\pm$1.5, p<0.01). Pine needle supplementation also increased liver glutathione peroxidase activity (7.5$\pm$0.6 vs. 14.6$\pm$0.6, p<0.01). Other antioxidant parameters such as erythrocyte glutathione peroxidase, liver catalase activity, and plasma total antioxidant potential (TRAP), showed no statistical differences between the two groups. Our data demonstrate that pine needle supplementation improves the antioxidant system and suppresses the formation of colonic preneoplastic lesions in AOM-treated rats. This result provides additional insights into the chemo-preventative properties of pine needles.

• Journal of Korean Neurosurgical Society
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• v.61 no.5
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• pp.548-558
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• 2018

Objective : Diagnosing acute cerebral infarction is crucial in determining prognosis of stroke patients. Although many serologic tests for prompt diagnosis are available, the clinical application of serologic tests is currently limited. We investigated whether $S100{\beta}$, matrix metalloproteinase-9 (MMP-9), D-dimer, and heat shock protein 70 (HSP70) can be used as biomarkers for acute cerebral infarction. Methods : Focal cerebral ischemia was induced using the modified intraluminal filament technique. Mice were randomly assigned to 30-minute occlusion (n=10), 60-minute occlusion (n=10), or sham (n=5) groups. Four hours later, neurological deficits were evaluated and blood samples were obtained. Infarction volumes were calculated and plasma $S100{\beta}$, MMP-9, D-dimer, and HSP70 levels were measured using enzyme-linked immunosorbent assay. Results : The average infarction volume was $12.32{\pm}2.31mm^3$ and $46.9{\pm}7.43mm^3$ in the 30- and 60-minute groups, respectively. The mean neurological score in the two ischemic groups was $1.6{\pm}0.55$ and $3.2{\pm}0.70$, respectively. $S100{\beta}$, MMP-9, and HSP70 expressions significantly increased after 4 hours of ischemia (p=0.001). Furthermore, $S100{\beta}$ and MMP-9 expressions correlated with infarction volumes (p<0.001) and neurological deficits (p<0.001). There was no significant difference in D-dimer expression between groups (p=0.843). The area under the receiver operating characteristic curve (AUC) showed high sensitivity and specificity for MMP-9, HSP70 (AUC=1), and $S100{\beta}$ (AUC=0.98). Conclusion : $S100{\beta}$, MMP-9, and HSP70 can complement current diagnostic tools to assess cerebral infarction, suggesting their use as potential biomarkers for acute cerebral infarction.

• Korean Journal of Veterinary Research
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• v.11 no.2
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• pp.105-116
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• 1971

The effects of aconite root in rats and rabbits were studied following oral administration of the powder which was prepared by lyophilization of the decoction of the salted aconite roots. The $LD_{50}$ of the powder, the blood picture, total blood volume, uptake rate of ${42}^K$ and ${24}^Na$ in various organs, oxygen consumption, thyroid activity, and histopathological changes in various organs, were observed. The results obtained were as follows: 1. The $LD_{50}$ of the powder of decoction of the aconite root was 4.07g/kg of body weight in mice which is equivalent to approximately 40g/kg of the salted aconite roots. 2. The number of erythrocytes and leukocytes, hematocrit value, and the amount of hemoglobin in blood were increased in the rats administered daily dosages of 0.1, 0.5, and 1.0g/kg respectively. No significant differences were observed in the differential count of leukocytes. A slight tendency of hemoconcentration was recognized. 3. No changes in the erythrocyte volume, plasma volume and total blood volume were observed in the rats after administration of the powder for one, three, and six days. However, those were decreased in rats treated for ten days. 4. Generally, in various organs of rats the uptake rate of ${24}^Na$ showed a tendency of increasing but that of ${42}^K$ slowed a decreasing tendency. 5. The oxygen consumption was markedly decreased in rats administered the powder. 6. Iodine-131 uptake of thyroid gland was markedly decreased in the rabbits following administration of the powder. 7. In rabbits administered 0.5g/kg for 20 days, fatty changes of hepatic cells, cloudy swelling of the epithelial cells of proximal convoluted tubules of the kidney and the dilation of splenic sinuses were observed, however, milder changes were found in rabbits treated with 0.1g/kg for the same period.