• Journal of Nutrition and Health
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• v.51 no.5
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• pp.369-378
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• 2018

Purpose: Obesity is associated with a dysregulation of metabolic balance and is regarded as a low grade chronic inflammation. Western-style diet and physical inactivity are leading causes of obesity. This study examined the profiles of forty plasma cytokines and chemokines at the same time in the early stages of high-fat diet-induced obesity using a mouse model. Methods: A total of 30 male CD1 mice, 12 ~ 14 weeks of age, were enrolled. The mice were fed a high-fat diet for 6 weeks to induce obesity. The plasma glucose and triglyceride concentrations were measured using a hexokinase colorimetric assay kit and a serum triglyceride determination kit, respectively. The relative levels of multiple cytokines and chemokines in the plasma were determined using a mouse cytokine array kit. Results: The mice exhibited significant weight gain after 6 weeks of a high-fat diet. The genital fat depot was enlarged along with an increase in the number and the mean size of white adipocytes as early as 4 weeks after a high-fat diet. In addition, the plasma glucose and triglyceride levels increased significantly after 4 weeks of a high-fat diet. Cytokine array analysis revealed a remarkable increase in the expression of both CXCL12 and CXCL13, whereas the proinflammatory cytokines remained low after 4 weeks of a high-fat diet. Conclusion: A significant increase in plasma levels of CXCL12 and CXCL13 was observed after 4 weeks of a high-fat diet, which might induce the migration of B lymphocytes, T lymphocytes, and monocytes from the blood to expanding adipose tissue or fat associated lymphoid clusters, playing a key role in adipose tissue remodeling and local immunity during the early stages of high-fat diet-induced obesity.

• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.289-295
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• 1998

The bioequivalence of two nilvadipine products was evaluated in 16 normal male volunteers (age 22-32 yr, body weight 57-80 kg) following sidle oral dose. Test product was Overca $l_{R}$ tablet (Choong-Wae Pharm. Corp., Korea) and reference product was Nivadi $l_{R}$ tablet (Hyundai Pharm. Corp., Korea). Both products contain 4 mg of nilvadipine. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of nilvadipine was accomplished using a validated capillary column GC with electron-capture detection. As a result of the assay validation, the quantiflcation of nilvadipine in human plasma by this technique was possible down to 0.5 ng/ml using 1 ml of plasma. Absolute overall recovery from five replicate analyses of nilvadipine-spiked sample were 88.4$\pm$ 10.24% (mean$\pm$ 5.D.) for human plasma of 10 ng/ml. The coefficients of variation (C.V.) were less than 20% and the actual concentration of nilvadipine measured by GC ranged from 80 to 99% in all plasma. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05); the area under the curve from time zero to 8 hr (AUCo-$_{8 hr}$) (22.8$\pm$5.90 vs 22.2$\pm$6.10 ng . hr/ml), maximum plasma concentration ( $C_{max}$) (10.0$\pm$2.85 vs 9.3$\pm$3.28 ng/ml) and time to reach maximum plasma concentration ( $T_{max}$) (1.2$\pm$0.31 vs 1.3 $\pm$0.47 hr). The differences of mean AU $Co_{8hr}$ $C_{max}$, and $T_{max}$ between the two products (2.25, 7.65, and 10.30%, respectively) were less than 20%. The power (1-$\beta$) and treaeent difference (7) for AU $Co_{8hr}$, and $C_{max}$ were more than 0.8 and less than 0.2, respectively. Although the power for Tmax was under 0.8, Tm\ulcorner of the two products was not significantly different from each other (p>0. 05). These results suggest that the bioavailability of Overeat tablet is not significantly different from that of Nivadil tablet. Therefore, two products are bioequivalent based on the current results.sults.lts.lts.lts.

• Nutrition Research and Practice
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• v.7 no.5
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• pp.393-399
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• 2013

Asian populations are thought to receive significant health benefits from traditional diets rich in soybeans due to high isoflavone contents. However, available epidemiologic data only weakly support this hypothesis. The present study was carried out to assess the pharmacokinetics of isoflavones in South Korean women after ingestion of soy-based foods. Twenty-six healthy female volunteers (20-30 y old) consumed three different soy products (i.e., isogen, soymilk, and fermented soybeans) with different aglycone/glucoside ratios. Plasma and urine isoflavone concentrations were measured by high-performance liquid chromatography (HPLC) after ingestion of one of the soy products. Pharmacokinetic parameters were determined using the WinNonlin program. The area under the curve (AUC) for plasma daidzein levels of the soymilk group ($2,101{\pm}352ng{\cdot}h/mL$) was significantly smaller than those of the isogen ($2,628{\pm}573ng{\cdot}h/mL$) and fermented soybean ($2,593{\pm}465ng{\cdot}h/mL$) groups. The maximum plasma concentration ($C_{max}$) of daidzein for the soymilk group ($231{\pm}44$ ng/mL) was significantly higher than those of the isogen ($160{\pm}32$ ng/mL) and fermented soybean ($195{\pm}35$ ng/mL) groups. The half-lives of daidzein and genistein in the soymilk group (5.9 and 5.6 h, respectively) were significantly shorter than those in the individuals given isogen (9.6 and 8.5 h, respectively) or fermented soybean (9.5 and 8.2 h, respectively). The urinary recovery rates of daidzein and genistein were 42% and 17% for the isogen group, 46% and 23% for the fermented soybean group, and 33% and 22% for the soymilk group. In conclusion, our data indicated that soy products containing high levels of isoflavone aglycone are more effective for maintaining plasma isoflavone concentrations. Additional dose-response, durational, and interventional studies are required to evaluate the ability of soy-based foods to increase the bioavailability of isoflavones that positively affect human health.

• The Korean Journal of Physiology
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• v.18 no.1
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• pp.1-8
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• 1984

In order to determine the extent of the placental transfer of Lithium ion, pregnant rabbits at $27{\sim}29$ days of gestation, which has hemochorial placenta similar to the human placenta, received 2 mM/Kg of $Li^+$ in the form of LiCl intravenously. Maternal arterial blood, placental sinus blood, fetal blood, amniotic fluid and maternal urine were drawn two hours after the single dose of LiCl. Concentrations of $Li^+$, $Na^+$, $K^+$ and osmolarity were measured in plasma of collected bloods, amniotic fluid and urine. Followings are the results obtained. 1) Evident level of $Li^+$ was detected in fetal blood, although fetal plasma concentration of $Li^+$ found to be almost one third of maternal plasma. 2) Plasma concentration of $Li^+$ in placental sinus blood was higher than that in fetal plasma but lower than that in maternal plasma. It means that downward concentration gradient of $Li^+$ from mother to fetus was still remarkable two hours after the injection. 3) Significant level of $Li^+$ was also detected in amniotic fluid. It seemed likely that $Li^+$, at least in part, excreted by the fetal urinary tract. 4) There were no differences in $Na^+$ and osmolar concentration between fetal and maternal blood. 5) From above results, it was concluded that $Li^+$ may transfer across the placenta but limited passage capacity through placental barrier for $Li^+$ is significant, beacause net transfer assumed to be going on even at two hours, at which time maternal equlibrium has been reached.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.39 no.6
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• pp.466-471
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• 2006

We investigated the changes in body weight (BW), plasma sex steroid hormone profiles, and testicular development of cultured male eel Anguilla japonica during an artificial maturation process. Eels that received weekly intraperitoneal injections of eel's ringer solution containing human chronic gonadotropin (HCG) were examined. In the ringer-treated control, BW changes decreased slowly during the experimental period. Plasma testosterone (T), 11-ketotestosterone (11-KT) and $17{\alpha},\;20{\beta}$-dihydroxy-4-pregnen-3-one (DHP) levels In the control remained low and did not show significant changes. Moreover, all germ cells in the testes of the control were spermatogonia. In the HCG-treated male eels, however, BW changes increased gradually from the fifth week and then decreased slowly. The plasma T level increased rapidly (p<0.05) in the second week and then decreased slowly. The plasma 11-KT level increased dramatically (p<0.05) in the second week and was maintained until the end of the experiment. The plasma DHP level increased progressively from the second week and peaked in the eighth week (p<0.05). The testes of HCG-treated male eels were more developed than those of the control; most were at the spermatozoa and spermatid stages and showed active spermiation. Thus, spermatogenesis and spermiation in the cultured eel can be induced by repeated injections of HCG.

• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.476-480
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• 2013

Obesity is one of the most serious health problems in developed countries. It negatively affects diverse aspects of human wellbeing. Of these, a relationship between obesity and depression is widely recognized but biomarkers for assessment of obesity-associated mood changes in animal obesity models are rarely known. Here we explored the link between obesity and the plasma levels of monoamine neurotransmitters involved in mood control using a sensitive UPLC/MSMS technique in high fat diet (HFD)-induced obesity model in male C57BL/6 mice to explore the potential utility of plasma tests for obesity-associated mood change. HFD (60% of total calories, 8 weeks) induced significantly higher weight gains in body (+37.8%) and fat tissue (+306%) in male C57BL/6 mice. Bioanalysis of serotonin, dopamine and norepinephrine in plasma at 8 weeks of HFD revealed that serotonin decreased significantly in the obese mice when compared to normal diet-fed mice ($2.7{\pm}0.6$ vs $4.3{\pm}2.0ng/ml$, N=8). Notably, a negative correlation was found between the levels of serotonin and body weight gains. Furthermore, principal component analysis (PCA) with the individual levels of neurotransmitters revealed that plasma levels of dopamine and serotonin could apparently differentiate the obese mice from lean ones. Our study demonstrated that blood plasma levels of neurotransmitters can be employed to evaluate the mood changes associated with obesity and more importantly, provided an important clue for understanding of the relationship between obesity and mood disorders.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.194-194
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• 2002

Interferon has therapeutic potential for a wide range of infectious and proliferous disorders such as chronic hepatitis C. However, it has drawbacks such as relatively short serum half-life and rapid clearance like other therapeutic proteins. The attachment of a polyethylene glycol (PEG) moiety to interferon is considered as one of the most promising solutions for its ability to extend the plasma residence time.(omitted)

• Analytical Science and Technology
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• v.9 no.2
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• pp.145-160
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• 1996

Inorganic analytical laboratory of Korea Research Institute of Standards and Science participated in an interlaboratory comparison program operated by Quebec Toxicology Centre of Canada in 1994 and again in 1995. The objective of this program is to enable participating laboratories to assess reproducibility and accuracy of their analytical results for trace toxic elements in human biological fluids. This laboratory determined Cd and Pb concentrations in 3 levels of human blood samples by isotope dilution inductively coupled plasma mass spectrometry. 0.5mL of blood sample is added to the digestion bomb together with 2mL of nitric acid and enriched spike isotopes and then decomposed in the microwave digestion system. The decomposed sample is diluted to 10mL and nebulized into ICP-MS. The Cd and Pb values reported by all participating laboratories are presented and compared. The values reported by this laboratory are within the acceptable range of target values.

• Nutrition Research and Practice
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• v.6 no.5
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• pp.396-404
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• 2012

The aim of the study was to investigate the inhibitory effects of calcium against intestinal cancer in vitro and in vivo. We first investigated the effects of calcium treatment in HCT116 and HT29 human colon cancer cells. At the concentration range of 0.8-2.4 mM, calcium significantly inhibited cell growth (by 9-29%), attachment (by 12-26%), invasion (by 15-31%), and migration (by 19-61%). An immunofluorescence microscope analysis showed that the treatment with calcium (1.6 mM) for 24 h increased plasma membrane ${\beta}$-catenin but decreased nuclear ${\beta}$-catenin levels in HT29 cells. We then investigated the effect of dietary calcium on intestinal tumorigenesis in $Apc^{Min/+}$ mice. Mice received dietary treatment starting at 6 weeks of age for the consecutive 8 weeks. The basal control diet contained high-fat (20% mixed lipids by weight) and low-calcium (1.4 mg/g diet) to mimic the average Western diet, while the treatment diet contained an enriched level of calcium (5.2 mg calcium/g diet). The dietary calcium treatment decreased the total number of small intestinal tumors (by 31.4%; P < 0.05). The largest decrease was in tumors which were ${\geq}$ 2 mm in diameter, showing a 75.6% inhibition in the small intestinal tumor multiplicity (P < 0.001). Immunohistochemical analysis showed significantly reduced nuclear staining of ${\beta}$-catenin (expressed as nuclear positivity), but increased plasma membrane staining of ${\beta}$-catenin, in the adenomas from the calcium-treated groups in comparison to those from the control group (P < 0.001). These results demonstrate intestinal cancer inhibitory effects of calcium both in human colon cancer cells and $Apc^{Min/+}$ mice. The decreased ${\beta}$-catenin nuclear localization caused by the calcium treatment may contribute to the inhibitory action.

• The Korean Journal of Pharmacology
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• v.11 no.2
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• pp.55-59
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• 1975

Safety study of the continuous releasing dichlorvos-resin insecticide $(Mopari^{\circledR})$ was conducted in human volunteers and domestic fowls. For the purpose, the potential hazards in using the insecticide were observed in terms of the inhibition of plasma cholinesterase activity and the changes in the liver function (GOT, GPT, Alkaline phosphatase, Bilirubin, Thymol turbidity), the blood picture (RBC, WBC with differential count, Hemoglobin, Hematocrit and ESR) and the urine picture (sugar, albumin, pH and microscopic findings) in 40 healthy adult volunteers and 60 leghorn domestic fowls. In case of the human study the observation was continued for 2 months during the application of the insectiside ($1{\sim}3$ solid formulations/$30m^3$) in the living rooms of ordinary Korean dwelling houses or in the office. In the animal test, however, 1 to 5 solid formulations of the insecticide were applied in the fowl cage of $9.2m^3$ for 5 weeks. Any significant inhibition of the plasma cholinesterase activity was not observed in both the human volunteer and the fowl throughout the experimental period. And the liver function as well as the blood and urine pictures were also not changed after exposure to the vaporizing insecticide. It is considered from the result that the amount of dichlorvos released into the air by the continuous vaporizing dichlorvos-resin insecticide presents no significant hazardous effect on humans or animals in the present experimental condition.