• Toxicological Research
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• v.21 no.2
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• pp.179-186
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• 2005

Dimethylamine (DMA) is a widely used commodity chemical with few toxicity data. Groups of 10 male and female F-344 rats were exposed by inhalation to 0, 5, 10, 20, 40 and 80 ppm of DMA for 6 hrs/day, 5 days/week for 90 days. The changes of body weight, organ weight, hematology, clinical chemistry, and histopathological changes were evaluated after the exposure. As the results, the body weight was significantly decreased at 80 ppm in male and female rats (p<0.05). The absolute lung weight showed no statistically significant changes in any group. In contrast, the relative lung weight significantly increased at 80 ppm in male and female rats (p<0.05). Erythrocytes, mean cell hemoglobin, leukocytes, neutrophil, and platelet numbers were significantly increased in male and female at 40 or 80 ppm of DMA (p<0.05, p<0.01). In addition, the serum values of total protein, urea nitrogen were increased in male and creatine kinase, total protein were increased in female rats at 40 or 80 ppm (p<0.05, p<0.01). Histopathological examinations of the male and female lung samples showed slight hyperplasia and congestion at 80 ppm. Taken together, our study revealed that maximum tolerated dose of DMA would be over 40 ppm.

• The Journal of Korean Medicine
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• v.34 no.3
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• pp.54-68
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• 2013

Objectives: This study aimed to evaluate the effects of microparticles of Socheongryong-tang (SCRT) on chronic obstructive pulmonary disease (COPD) in a mouse model. Methods: The inhalable microparticles containing SCRT were produced by spray-drying with leucine as an excipient, and evaluated with respect to the aerodynamic properties of the powder by Andersen cascade impactor (ACI). Its equivalence to SCRT extract was evaluated using lipopolysaccharide (LPS) and a cigarette-smoking (CS)-induced murine COPD model. Results: SCRT microparticles provided desirable aerodynamic properties (fine particle fraction of $49.6{\pm}5.5%$ and mass median aerodynamic diameter of $4.8{\pm}0.3{\mu}m$). SCRT microparticles did not show mortality or clinical signs over 14 days. Also there were no significant differences in body weight, organ weights or serum chemical parameters between SCRT microparticle-treated and non-treated groups. After 14 days the platelet count significantly increased compared with the non-treated group, but the values were within the normal range. Inhalation of SCRT microparticles decreased the rate of neutrophils in blood, granulocytes in peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage fluid (BALF) and level of TNF-${\alpha}$ and IL-6 in BALF on COPD mouse model induced by LPS plus CS. This effect was verified by histological findings including immunofluorescence staining of elastin, collagen, and caspase 3 protein in lung tissue. Conclusions: These data demonstrate that SCRT microparticles are equivalent to SCRT extract in pharmaceutical properties for COPD. This study suggests that SCRT microparticles would be a potential agent of inhalation therapy for the treatment of COPD.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.8
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• pp.1190-1197
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• 2017

Objective: Adipose tissue is no longer considered as an inert storage organ for lipid, but instead is thought to play an active role in regulating insulin effects via secretion adipokines. However, conflicting reports have emerged regarding the effects of adipokines. In this study, we investigated the role of adipokines in glucose metabolism and insulin sensitivity in obese Bama mini-pigs. Methods: An obesity model was established in Bama mini-pigs, by feeding with high-fat and high-sucrose diet for 30 weeks. Plasma glucose and blood biochemistry levels were measured, and intravenous glucose tolerance test was performed. Adipokines, including adiponectin, interleukin-6 (IL-6), resistin and tumor necrosis factor alpha ($TNF-{\alpha}$), and glucose-induced insulin secretion were also examined by radioimmunoassay. AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscle, which is a useful insulin resistance marker, was examined by immunoblotting. Additionally, associations of AMPK phosphorylation with plasma adipokines and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed by Pearce's correlation analysis. Results: Obese pigs showed hyperglycemia, high triglycerides, and insulin resistance. Adiponectin levels were significantly decreased (p<0.05) and IL-6 amounts dramatically increased (p<0.05) in obese pigs both in serum and adipose tissue, corroborating data from obese mice and humans. However, circulating resistin and $TNF-{\alpha}$ showed no difference, while the values of $TNF-{\alpha}$ in adipose tissue were significantly higher in obese pigs, also in agreement with data from obese humans but not rodent models. Moreover, strong associations of skeletal muscle AMPK phosphorylation with plasma adiponectin and HOMA-IR index were obtained. Conclusion: AMPK impairment induced by adiponectin decrease mediates insulin resistance in high-fat and high-sucrose diet induction. In addition, Bama mini-pig has the possibility of a conformable model for human metabolic diseases.

• YAKHAK HOEJI
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• v.39 no.4
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• pp.360-366
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• 1995

1-$\beta$-Methyl carbapenem-2-substituted pyrroudine derivatives. CRB 529 and CRB 550, were synthesized as investigational carbapenem derivatives. It has been reported that the in vitro antibacterial activities of the compounds against G(+) and G(-) bacteria were almost the same or more effective than those of imipenem (IPM) and meropenem (MEPM), and also showed better in vivo efficacy than MEPM and inlipeneni/cilastatin (IPM/CS) against representative G(-) organisms, P. aeruginosa and MRSA organisms, S. aureus. The antibacterial activities, pharmacokinetics and protective efficacy of IPM/CS and CRB 529 and CRB 550 wereconducted after subcutaneous or intravenous administration to mice and rats. The pharmacokinetic parameters of CRB 529 and CRB 550 in mice were as follows: the observed maximal serum concentrations (C$_{max}$) following I.V. administration were 87.5 and 101 $\mu\textrm{g}$/ml for CRB 529 and CRB 550, respectively, and 63.6 $\mu\textrm{g}$/ml for IPM/CS. The half-lives (t$_{1/2}$) were 14.0 and 12.0 n-dn for CRB 529 and CRB 550, respectively, and 14.8 min for IPM/CS. In rats, $C_{max}$ after I.V. administration were 74.0 and 91.8 $\mu\textrm{g}$/ml for CRB 529 and CRB 550, respectively, and 41.2 $\mu\textrm{g}$/ml for IPM/CS. The tissue levels of CRB 529 and CRB 550 and IPM/CS after I.V. administration at a dose of 20 mg/kg decreased by the following order: lung, heart, kindney, liver and spleen for CRB 529, lddney, liver. lung, heart and spleen for CRB 550 and kidney, lung, liver, heart, spleen and brain for IPM/CS. In systemic infection, CRB 529 and CRB 550 showed excellent efficacies against P. aeruginosa and S. aureus (MRSA) at a dose of 5 mg/kg. The PD$_{50s}$ were 0.80, 0.36 mg/kg for CRB 529 and CRB 550, respectively, and 3.22 mg/kg for IPM/CS against P. aeruginosa. The corresponding values against S. aureus (MRSA) were 76.0, 55.3 mg/kg for CRB 529 and CRB 550, respectively, and 146 mg/kg for IPM/CS. In local infection, the antibacterial activities of CRB 529 and CRB 550 were more effective than those of IPM/CS against intrarenal infection with E. coli and P. aeruginosa and also showed as effective as IPM/CS against respiratory tract infection with E. coli and P. aeruginosa at a dose of 5 mg/kg.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.11
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• pp.1642-1647
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• 2014

In this study, we investigated the hepatoprotective effects of garlic extracts fermented with Lactobacillus plantarum on alcohol-induced fatty liver damage in C57BL/6J mice. The weight of liver tissue of the lactic acid-fermented garlic extract (LAFGE) diet groups decreased in a dose-dependent manner compared to that of the normal diet group. The activities of typical serum enzymes such as ALT, AST, and ALP were low in the LAFGE 200 mg/kg administered group. The LAFGE 200 mg/kg administered group significantly decreased values of TBIL and DBIL, which are an important index of liver damage. LAFGE also ameliorated alcohol-induced hepatic lipid accumulation in histological analysis dose-dependently. In addition, total GSH and reduced GSH levels in LAFGE-treated groups were gradually recovered up to normal levels. The present study revealed that LAFGE improved unique tastes and odors of raw garlic through lactic acid fermentation technology and thus could be a commercially potential material for hepatoprotective functional foods against alcoholic fatty liver.

• The Korean Journal of Nuclear Medicine
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• v.1 no.1
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• pp.67-78
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• 1967

Over the past 6 years, from May 1960 to June 1966, 1,716 patients with various diseases of thyroid were examined and thyroid function tests with $^{131}I$ were done. Among them, 545 patients with hyperthyroidism were treated with $^{131}I$. A summary of the clinical data of the $^{131}I$-thyroid function tests and the therapeutic results of $^{131}I$ were presented and discussed. 1. The patients examined consisted of; 596 cases(34.7%) with toxic diffuse goiter, 412 cases(24.0%) with non-toxic nodular goiter, 278 cases(16.2%) with euthyroidism, 236 cases(13.8%) with non-toxic diffuse goiter, 89 cases(5.2%) with hypothyroidism, 53 cases(3.1%) with toxic nodular goiter, 32 cases(1.9%) with thyroiditis and 20 cases(1.2%) with dyshormonogenesis. 2. There were 218(12.7%) male patients and 1,498(87.3%) female patients, showing a ratio of 1:6.9. female predominantly. 3. The majority of patients(79.6%) were in the 3rd through 5th decades of their lives showing the peak in the 4th decades(35.9%). 4. The diagnostic values and normal ranges of $^{131}I$ uptake test, 48 hour serum activity, $T_3$ red blood cell uptake and $PB^{131}I$ conversion ratio were discussed. 5. An attention was given to dyshormonogenesis, a qualitative hypothyroidism, due to its characteristic findings of clinical and $^{131}I$ thyroid function tests, and its pathogenesis was briefly reviewed. 6. Among 545 patients with hyperthyroidism treated with $^{131}I$, 68.3% was cured after single. therapeutic dose and another 24.0% was cured after second dose. 7. The complications of $^{131}I$ therapy were discussed in some details and myxedema had developed. in 3.9% of our cases. No thyroid cancer was found after $^{131}I$ therapy.

• Journal of Embryo Transfer
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• v.25 no.3
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• pp.189-193
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• 2010

We investigated the cleavage rate and blastocyst yield for each culture condition to enhance tolerance of cryo-preservation of bovine IVF embryo with relatively lower cryo-tolerance compared to in vivo embryo. The cleavage rate and blastocysts yield for CR1aa, IVMD, IVD, CR1aa+10% FBS were 73.2, 69.3, 72.8, 68.5% and 44.1, 30.8, 33.3, 48.0%, respectively. The values did not differ among each treatments without serum. For embryo vitrification, In vivo and In vitro blastocysts were exposed to VS1(10% glycerin, 0.1 M glucose, 0.1 M sucrose, PEG 1%) for 5 min, and VS2 (10% glycerin, 10% EG, 0.2 M glucose, 0.2 M sucrose, PEG 2%) for 5 min and then VS3 (10% glycerin, 30% EG, 0.3 M glucose, 0.3 M sucrose, PEG 3%) for 1 min. The exposed embryos were then loaded into the 0.25 ml plastic straws and then plunged into liquid nitrogen. The straws were held for period of 1 to 2 weeks before thawing. In embryo viability, no differences in blastocyst re-expansion rates were found between in vivo and in vitro embryos. whereas expansion-BL rates was significantly higher for in vivo-derived embryos (72.7%) when compared to in vitro-derived embryos (51.4%), respectively (P<0.05). In conclusion, our results indicate that combined use of CRIaa culture medium with vitrification might enhance tolerance of cryopreservation for bovine IVF embryo production.

• Toxicological Research
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• v.23 no.1
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• pp.79-86
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• 2007

The isolated plantamajoside from Plantago asiatica that is often used as a marker compound in chemotaxonomic studies has various bioactivites such as the inhibitions of cyclic AMP phosphodi-esterase and 5-lipoxygenase, microbial growth and inflammation, and currently demands the generation of toxicity data. The purpose of this study was to examine the toxicities of the single and 14 days repeated dose toxicity in Sprague-Dawley rats orally administrated with plantamajoside at dose levels of 0, 500, 1000, and 2000 mg of dried material/kg body weight/day. The results showed that there was no difference in body weight change, food intake, water consumption, or relative organ weight among different dose groups. Also we observed no death and abnormal clinical signs were observed during the experimental period. Between the groups orally administered Plantago asiatica and the control group, there was no statistical significance in hematological test or serum biochemical values. There were no gross findings at final sacrifice. There was no evidence of histopathological alteration mediated by 14 days treatment with Plantago asiatica. These results suggest that no observed adverse effect level (NOAEL) of the oral application was considered to be more than 2000 mg/kg in rats under the conditions employed in this study. Another observation was performed to investigate the safety of Plantago asiatica in respect of genotoxicity. This substance was examined that Salmonella typhimurium reversion assay (Ames test) in strain TA98, TA100, TA1535. In the reverse mutation test, Plantago asiatica did not induce mutagenicity in Samonella typhimurium with and without metabolic activation. These results indicated that Plantago asiatica had no genotoxicity.

• Toxicological Research
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• v.23 no.1
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• pp.87-96
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• 2007

Single and repeated-dose toxicity of anti-diabetic herb extract microcapsule (ADHEM) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity test, kneading ADHEM with sterilized water were administered orally once at dose levels of 0 and 2,000 mg/kg and examined for 14 days. No dead animals, clinical signs and abnormal necropsy findings were observed and also no significant difference in body weights was found. Therefore, the $LD_{50}$ of ADHEM was considered to be higher than 2,000 mg/kg in both male and female rats. For repeated-dose toxicity test, ADHEM were mixed with powder fodder and administerd orally for 28 days at dose levels of 0, 500, 1000 and 2000 mg/kg/day. No dead animals, clinical signs and significant difference in body weights were found. In hematology and serum biochemistry, all values were included within the normal ranges. In relative organ weights, kidney or liver were significantly increased in the 500, 1000 or 2000 mg/kg/day male groups, uterus was significantly increased in the 500 mg/kg/day female group and left adrenal glands were significantly decreased in the 2000 mg/kg/day female group. In histopathological examinations, vacuolation and microgranuloma in the liver, chronic progressive nephropathy and inflammation in the kidney were observed in the 500, 1000 or 2000 mg/kg/day both male and female groups. Therefore, the no observed adverse effect level (NOAEL) of ADHEM was considered to be lower than 500 mg/kg/day in both male and female rats.

• Korean Journal of Pharmacognosy
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• v.25 no.3
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• pp.238-248
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• 1994

The hypoglycemic and metabolic effects of Commelina communis L. extract were investigated in alloxan induced diabetic rats. The increased blood glucose level in the diabetic rats was significantly reduced and the loss of body weight was recovered with the treatment of the plant protein fractions($30{\sim}70%$ ammonium sulfate precipitates). Administration of the plant protein fractions elicited the significant increase of glucose-6-phosphate dehydrogenase (G-6-P DH) activity and liver weight which were decreased in the diabetic rat liver. G-6-P DH was partially purified from extract- or insulin-treated diabetics, diabetic control, and normal rat liver and studied for the biochemical properties. The $K_m$ value(9.002 mM) of diabetic rat liver enzyme was greatly higher than that (0.033 mM) of normal enzyme indicating the affinity of enzyme for the substrate was significantly reduced in the diabetic rat liver. This reduced affinity of enzyme for the substrate in the diabetic rat was recovered in the extract- or insulin-treated rat liver enzyme having 0.164 or 0.208 mM of their $K_m$ values, respectively. Although there was no significant difference in the optimum pH(6.0) and optimum temperature($37^{\circ}C$) of enzyme among the experimental groups, the dependence of their activities on pH appeared to be slightly resistant in the extract- or insulin-treated group compared to the diabetic group. In order to investigate the antigenicity of rat liver enzyme among experimental groups, enzyme-linked immunosorbent assay was carried out by using anti-G-6-P DH anti-serum. Absorbance(0.102) shown in the normal rat liver was reduced even below zero in the alloxan-diabetic rat liver, but increased again in the extract- or insulin-treated rat liver(0.096 or 0.118, respectively). The result of this study suggested that G-6-P DH may be used as a marker enzyme to diagnose and to indicate the progress of the diabetics, and the hypoglycemic effect of the extracts of Commelina communis L. was certainly associated with action or mode of G-6-P DH on the rat liver.