• Toxicological Research
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• v.19 no.1
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• pp.13-19
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• 2003

GX-12 is a naked DNA vaccine developed by the DongA Pharmaceutical Co. Ltd. and Genexine for the treatment of HIV infection. This study was peformed to evaluate the biodistribution and expression of GX-12 mRNA in gonadal tissues, and to investigate the histopathological changes after the repeated intramuscular injection. GX-12 (400 $\mu\textrm{g}$/head) was injected into the left anterior tibialis once a week for four weeks. On day 1, 5, 15, 30 and 45 after the final administration, gonadal tissues (testes, epididymis, seminal vesicles, penis, prostate glands, ovaries, vagina, uterus) and the injection site (muscle) were harvested and examined for the expression of mRNA by RT-PCR. In addition, histopathological examination was peformed at each time point. At the injection site, mRNA expression of GX-12 was detected only at early time points (1 ~ 15 days after injection) but not thereafter. However, in gonadal tissues, mRNA expression was not identified at all time points both in male and female rats. There were no histopathological changes in all reproductive organs and muscle. Based on these results, it is unlikely that the plasmid DNAs of GX-12 was distributed to- and expressed in gonadal tissues, suggesting that the chance of germline integration and transmission is negligible.

• Toxicological Research
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• v.30 no.2
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• pp.131-138
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• 2014

Radix Astragali, the root of Astragalus (A.) membranaceus, has been applied in a variety of diseases for a long time in Asian countries such as Korea and China. In addition, the aerial parts such as leaves and stems of A. membranaceus have received a great deal of attention. Recently, the polysaccharide fraction showing a potent immunomoduating activity was isolated from the aerial parts of A. membranaceus. Thus, the aerial parts of A. membranaceus would be worthy enough for a food material and a dietary supplement. However, they should be safe even though valuable. In our previous study, it was estimated that NOAEL for female rats are 5000 mg/kg/day of the crude polysaccharide fraction from A. membranaceus-aboveground parts. As a series of safety evaluation, genotoxicity test for the crude polysaccharide fraction was carried out in this study. In conclusion, the three genotoxicity assays provided strong overall support that the crude polysaccharide fraction lacks mutagenic and/or clastogenic potential under the GLP-based test conditions. This indicates the aerial parts of A. membranaceus would be safe enough for a food material and a dietary supplement.

• Korean Journal of Environmental Biology
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• v.21 no.2
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• pp.208-215
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• 2003

Bisphenol A (4,4'-isopropylidenediphenol, $C^{15}H_{16}O_{2}$) is the monomer used in the manufacture of polycarbonate. Polycarbonate, in turn, is used in a wide array of plastic products, with new applications continuously being developed. Also it has been used to produce epoxy resins and polycarbonate plastics for food container. This study was carried out to investigate the effects of bisphenol A on lactation period to dams and F1. Sprague-Dawley females were mated with on 2 : 1 ratio basis. Various doses of bisphenol A (0, 2, 20, 200, and 2,000 ${\mu}g kg^{-1}$) were daily administered to females for 21 days after parturition. Dams and offsprings were sacrificed at the time of weaning. The results were as fellows, 2000 ${\mu}g \; kg^{-1}$ / of bisphenol A decreased the dams' body weight at post-partum 18 days and also 200 and 2,000 ${\mu}g \;kg^{-1}$ of bisphenol A decreased the body weight of neonates at the days of post-partum 21 days. Bisphenol A increased the relative weights of liver and spleen in male offsprings, depending on the doses. But female offsprings showed high relative organ weights of ovaries, and low relative organ weights of uterine in a some dose-response manners. High dose of bisphenol A induced low viability of neonates exposed during lactation period. The dams treated with bisphenol A showed prematured estrous stage. Bisphenol A was recovered about 21.2% average in serum of dams, and also in offsprings'. The results indicate that the bisphenol A induces estrous cycle during lactation period in dams, also reaches to the offspring through breast milk. Thus bisphenol A exopsed to dams and neonates via lactation induces some estrogenic and tonic effects.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.117-123
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• 2016

Taxol (paclitaxel) is a powerful anti-cancer drug widely used against several types of malignant tumors. Because Taxol may exert several side effects, a variety of formulations have been developed. One of these features liposomes, regarded as one of the most promising drug carriers, biocompatible and best able to reduce drug toxicity without changing efficacy against tumor cells. Eruca sativa seed extract (SE) is considered a promising natural product from cruciferous vegetables against breast cancer, increasing chemotherapeutic and eliminating harmful side effects. The effects of Taxol-encapsulated liposomes (T) alone and in combination between Eruca sativa seed extract on nuclear factor kappa B (NF-${\kappa}B$), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels were investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(${\alpha}$) anthracene (DMBA) using qRT-PCR. The results showed that DMBA increased NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while decreasing glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. T and T-SE treatment reduced NF-${\kappa}B$, COX-2 and Bcl-2 gene expression levels and LP. Hence, T and T-SE treatment appeared to reduce inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC.

• The Journal of Korean Medicine
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• v.17 no.2 s.32
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• pp.296-302
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• 1996

Pericarpium Citri Nobilis Viride, a traditional herb medicine, has been used in Korea and China for many centuries as a treatment for respiratory disease. The purpose of the present study was to determine the effect of Pericarpium Citri Nobilis Viride on histamine-induced tracheal smooth muscle contraction in rats. Guinea pigs(500g , female) were killed by $CO_2$ exposure and a segment (8-10mm) of the thoracic trachea from each guinea pig was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of histamine which evoked 50% of maximal response $(ED_{50})$ was obtained from cumulative dose response curves for histamine $(10^{-7}-10^{-4}M)$. Contractions evoked by histamine ($ED_{50}$) were inhibited significantly by Pericarpium Citri Nobilis Viride. The mean percent inhibition was 53.7% (P<0.05) after 1.5mg／ml Pericarpium Citri Nobilis Viride, and 87.7% (P<0.01) after 5.0mg／ml Pericarpium Citri Nobilis Viride. Propranolol $(10^{-7}M)$ slightly but significantly attenuated the inhibitory effects of Pericarpium Citri Nobilis Viride. Following treatment with propranolol the mean present inhibition caused by 1.5 and 5.0mg／ml Pericarpium Citri Nobilis Viride. Indomethacin and methylene blue $(10^{-7}M)$ did not significantly alter the inhibitory effect of Pericarpium Citri Nobilis Viride These results indicate that Pericarpium Citri Nobilis Viride can relax histamine-induced contraction of guinea pig tracheal smooth muscle, and that this inhibition involves in part symphathetic nerve system.

• Journal of Korean Neurosurgical Society
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• v.60 no.3
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• pp.348-354
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• 2017

Objective : To identify and investigate differences in spinal fusion between the normal and osteopenic spine in a rat model. Methods : Female Sprague Dawley rats underwent either an ovariectomy (OVX) or sham operation and were randomized into two groups: non-OVX group and OVX group. Eight weeks after OVX, unilateral lumbar spinal fusion was performed using autologous iliac bone. Bone density (BD) was measured 2 days and 8 weeks after fusion surgery. Microcomputed tomography was used to evaluate the process of bone fusion every two weeks for 8 weeks after fusion surgery. The fusion rate, fusion process, and bone volume parameters of fusion bed were compared between the two groups. Results : BD was significantly higher in the non-OVX group than in the OVX group 2 days and 8 weeks after fusion surgery. The fusion rate in the non-OVX group was higher than that in the OVX group 8 weeks after surgery (p=0.044). The bony connection of bone fragments with transverse processes and bone formation between transverse processes in non-OVX group were significantly superior to those of OVX group from 6 weeks after fusion surgery. The compactness and bone maturation of fusion bed in non-OVX were prominent compared with the non-OVX group. Conclusion : The fusion rate in OVX group was inferior to non-OVX group at late stage after fusion surgery. Bone maturation of fusion bed in the OVX group was inferior compared with the non-OVX group. Fusion enhancement strategies at early stage may be needed to patients with osteoporosis who need spine fusion surgery.

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.1
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• pp.81-96
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• 2006

Purpose : this study is to examine what are the effects of the Sintongchukeatang(SCT) on the ovariectomized rat model of postmenopausal osteoporosis. Methods : 12weeks Female Sprague-Dawley 30 rats of weighting 250-300g, were divided into three groups including the sham operation groups(10heads) and overiectomy groups(10heads). then we observed changes in the body weight serum metabolic products and femoral trabecular bone. Results : 1. The level of serum ALP activity in control group showed significant increase in comparison with sham, but that in SCT-treated was significantly decreased in comparison with control. 2. The level of serum GOT in control group showed no change in comparison with sham, but that in SCT-treated was significantly decreased in comparison with control. The level of serum GPT did not significant change among the three groups. 3. The level of serum estrogen in control group showed slightly decreased in comparison with sham, but that in SCT-treated showed no change in comparison with control. 4. Trabecular bone area as well as trabecular thickness in control group showed significant decrease in comparison with sham. Those in SCT-treated showed significant increase in comparison with control. 5. Trabecular separation only in SCT-treated showed significant decrease in comparison with control. 6. Osteoclast number and oseoblast surface in control group showed significant increase in comparison with sham. Those in SCT-treated showed significant decrease in comparison with control. Conclusion : SCT has shown to be capable of preventing and curing osteoporosis caused by old-aged and postmenopause.

• Korean Journal of Veterinary Research
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• v.44 no.3
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• pp.373-378
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• 2004

To help the interpretation of causes of death, it is critical that the background incidence of factors contributing to death be recorded and archived. Information was gathered from the control groups of 19 rat carcinogenicity studies. All cases of death occurring within the 2-year period were reviewed. Out of 1124 males and 1084 females, 720 male (64.1%) and 689 female (63.6%) decedents were recorded. There was no difference in the probability of survival between two sexes. Analysis of factors contributing to death revealed that 400 males (48.7%) had neoplastic changes, 189 males (23.0%) had non-neoplastic lesions, and 232 males (28.3%) died from unknown causes. In females, these figures were 627 (76.4%), 62 (7.6%) and 132 (16.0%), for neoplastic, non-neoplastic and unknown findings, respectively. It could be suggested that the risk of death by non-neoplastic reasons was higher in the males than in the females, whereas females were more likely to be affected by tumours. In the neoplastic causes of death, pituitary tumours were the most common in both sexes, followed by mammary tumours in females, and haemopoietic tumours in males. In non-neoplastic cause of death, renal diseases were the most common in both sexes, followed by skin diseases and cardiovascular diseases in males, and skin diseases and poditis in males. A relatively large number of animals (28.3% in males and 16.0% in females) were found dead, without any significant clinical or histologically identifiable cause. Most of the animals with pituitary tumours were killed in extremis and the proportion of females (70.1%) being greater than males (46.8%). There were no case which died by accident, and also only minimal incidence which died by bleeding procedures.

• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.4
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• pp.36-53
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• 2005

Purpose : The Purpose of this research was to investigate the effects of Haingkyunghonghwatang (HKHHT) on anti-inflammatory effects. Methods : As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators were determined in mouse lung fibroblast cells(mLFC) and RAW264.7 cells. Also, changes in pathological features by drug treatment were investigated in the in vivo edema-induced rats by carrageenin/arachidonic acid or in the colitis-induced mice by DSS treatment. Results : The cytotoxicity of HKHHT on mLFC and RAW264.7 cells wasn't observed at 100, 50, 10, and $1{\mu}g/ml$ of The treatments. $IL-1{\beta}$, IL-6 and NOS-II mRNA expression of RAW264.7 cells was inhibited by The treatments in a dose-dependent manner. HKHHT treatment of RAW264.7cells(HtRc) inhibited $TNF-{\alpha}$ and COX-2 mRNA expression. HtRc significantly inhibited IL-6 and NO production. HtRc inhibited ROS production. HKHHT inhibited rat's paw edema induced by carrageenin or arachidonate treatment in all concentrations examined. The body weight and colon length of colitis-induced mice were recovered to a normal level by DSS treatment. Clinical disease levels were significantly improved compared to the control animals. HKHHT treatment of colitis-induced mice(HtCm) significantly increased hematological values such as WBC and RBC counts, Hgb and HCT levels, but decreased PLT values. HtCm decreased IL-6 and $TNF-{\alpha}$ production significantly HtCm significantly increased CD3+(T) cell counts. In contrast, HKHHT treatment decreased CD19+ B cell counts and CD3+/CD69+ significantly, and also decreased B/T ratio (%) though not significant. Conclusion : These results indicated that HKHHT could be used for treating diverse female diseases caused by the inflammation.

• YAKHAK HOEJI
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• v.36 no.5
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• pp.496-505
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• 1992

The correlation between GABA receptors($GABA_A$ and $GABA_B$ receptor) and benzodiazepine receptor on the saline infusion-induced micturition reflex contraction was studied in the female rat. To investigate the effect of ${\gamma}-aminobutyric$ acid(GABA) on the micturition reflex, exogenous GABA(10 mg/kg) and GABA transaminase inhibitor(aminooxyacetic acid; AOAA $1\;{\mu}g$) were administered intravenously(i.v.) and intracerebroventriculary(i.c.v.), respectively. In result, both GABA and AOAA inhibited the saline induced micturition reflex contraction. This AOAA induced inhibition of micturition reflex was blocked by both bicuculine. $GABA_A$ receptor antagonist, and Ro 15-1788, benzodiazepine receptor antagonist. Muscimol, $GABA_A$ receptor antagonist($0.1\;{\mu}g$ i.c.v., $3\;{\mu}g$ intrathecal; i.t., 1 mg/kg i.v.) and baclofen, $GABA_A$ receptor agonist($1\;{\mu}g$ i.c.v., $3\;{\mu}g$ i.t., 1 mg/kg i.v.) also inhibited the bladder contraction. Pretreatment of bicuculline($1\;{\mu}g$ i.c.v.), but not of 5-aminovaleric acid(AVA, $1\;{\mu}g$ i.c.v.), $GABA_B$ receptor antagonist blocked the central inhibition of muscimol. These inhibitory effects were reversed by Ro15-1788 but were potentiated by flurazepam, benzodiazepine receptor antagonist. On the other hand, the inhibitory effects of baclofen were not affected by Ro 15-1788. Diazepam and flurazepam also inhibited the micturition reflex contraction when they were administered $3\;{\mu}g$ i.c.v., $10\;{\mu}g$ i.t., $10\;{\mu}M$, $30\;{\mu}M$ transurethrally, respectively. In conclusion, these results suggest that the micturition reflex is mediated by $GABA_A$, $GABA_B$ receptor and benzodiazepine receptor. The bezodiazepines increase the receptor binding of GABA to the $GABA_A$ receptor, so that the benzodiiazepines show the synergistic effect on the inhibition of the micturition reflex contraction, but not to the $GABA_B$ receptor.