• Applied Microscopy
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• v.30 no.3
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• pp.285-293
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• 2000

The present study has been carried out to investigate the effect of fluoride toxicity on the morphology as well as inorganic chemical constituents of rat teeth. Rats were administered sodium fluoride at dose of 0 ppm, 100 ppm, 200 ppm and 300 ppm at the beginning of pregnancy. Animals were perfused intravascularly with glutaraldehyde and the incisors were removed. Changes in the protein composition of the secretory and maturation enamel were investigated using polyacrylamide gel electrophoresis (SDS PAGE). And the enamel surface of incisors was examined under scanning electron microscope (SEM). Changes of protein quantities were found significantly in high levels fluoride administration for experimental groups compared with control. The SDS PAGE analysis demonstrated as follows In control group, secretory phase enamel protein, amelogenins, was detected more quantities than experimental group. The enamelin, presence in maturation phase enamel , showed more quantifies than control enamel with an increasing fluoride concentration in the drinking water. Also, the scanning electron micrographic data showed hypoplastic, tough, uneven, pitted and cracked enamel surfaces covered with granular deposits as a result of excessive intake of fluoride. From these results we conclude that high dose of fluoride administration leads to severe structural alterations on the enamel surface and these structural changes could be through defective mineralization.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.197-205
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• 1991

Local extravasation during intravenous administration of adriamycin (doxorubicin HCl) can cause severe skin ulceration and necrosis. To investigate the mechanism of adriamycin-induced skin toxicity, effects of adriamycin on reactive oxygen radical metabolism using cultured skin cells of fetal rat. Adriamycin produced significant release of lactic dehydrogenase from cultured skin cell preparations dose- and time-dependently. The production of superoxide anion in sonicated suspensions of cultured skin cells was significantly increased by adriamycin under the presence of NADPH and NADH. The drug also stimulated malondialdehyde (MDA) production, an index of lipid peroxidation, in NADPH- and NADH-supported cell preparations. The increased production of MDA was significantly inhibited by oxygen radical scavengers (superoxide dismutase, catalase, thiourea) and antioxidants (butylated hydroxytoluene, ${\alpha}-tocopherol$). Treatment of cultured skin cells with 1, 3,-bis (2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase, enhanced the lipid peroxidation induced by adriamycin. The present study suggests that lipid peroxidation which is resulted from the stimulated production of reactive oxygen radical causes cellular damage in adriamycin-treated skin cells of rat.

• Applied Microscopy
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• v.29 no.2
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• pp.189-193
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• 1999

The response of ameloblast to long term (3 weeks) exposure to fluoride was examined in continuously erupting mandibular incisors of pregnancy rats as compared to control rats receiving a similar diet (Teklad L-356) but no sodium fluoride in there drinking water. Rats were started on water containing 0 ppm, 100 ppm, 200 ppm, and 300 ppm NaF at the beginning of pregnancy. To examine on the ultrastructural changes of the ameloblast, electron microscopy was used. The results indicated that rat incisors expressed two major changes in normal amelogenesis that could be attributed to chronic fluoride treatment. The fluoride produces marked alteration in the fine structure of ameloblast from teeth of young rats, such as large confluent distensions of the endoplasmic reticulum and swelling of isolated mitochondria, in particular on the morphology of the rough-surfaced endoplasmic reticulum. A graded series of alterations to these organelles were produced, and the severity of the changes would seem to be dependent on dose and time. This experimental data suggested that exposure prolonged of animal to high level of fluoride appears to induce morphological changes in the normal appositional growth and initial mineralization of enamel created during amelogenesis.

• Journal of Veterinary Clinics
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• v.16 no.1
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• pp.42-49
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• 1999

The reproductive effect of $Telazol^{\circledR}$ was studied in pregnant rats. Two different doses (20 or 40 mg/kg/day) were injected on days one of 3, 5 or 8 of pregnancy and 3 consecutive days of 3~5 or 5~7 in pregnant rats. On days 8 or 21, the rats were anesthetized, the cesarean section was performed, the uterus was carefully examined, and the numbers of corpora lutea, implantation sites and viable fetuses, fetal and placental weights and pre-and post-implantation losses in rats were surveyed. Simultaneously the concentrations of sodium and potassium of the plasma, uterine and amniotic fluids were determined. And gestation period in pregnant rats, postnatal offspring survival and body weight gains were evaluated. Administration of $Telazol^{\circledR}$ did not exert a bad influence upon body weight gains in pregnant rats. Reproductive indices were normal. The concentrations of sodium and potassium of the plasma, uterine and amniotic fluids in pregnant rats remained unchanged. Gestation period of rats, postnatal offspring survival and body weight gains were normal. It is concluded that $Telazol^{\circledR}$ is devoided of significant adverse reproductive effects in pregnant rats.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.6
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• pp.597-603
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• 1999

Caldesmon (CaD), one of microfilament-associated proteins, plays a key role in microfilament assembly in mitosis. We have investigated the effects of overexpression of the high molecular weight isoform of CaD (h-CaD) on the physiology of vascular smooth muscle cells (VSMCs). Rat aortic VSMCs were stably transfected with plasmids carrying a full length human h-CaD cDNA under control of cytomegalovirus promoter. The majority of the overexpressed h-CaD appears to be localized predominantly on cytoskeleton structures as determined by detergent lysis. The overexpression of h-CaD, however, does not decrease the level of endogenous low molecular weight isoform of CaD. h-CaD overexpressing VSMCs (h-CaD/VSMCs) show a decreased growth rate than that of vector-only transfected cells when determined by $[^3H]thymidine$ uptake and cell counting after fetal bovine serum (FBS) stimulation. h-CaD/VSMCs were smaller than vector-transfected cells by 18% in cell diameter. These data suggest that overexpression of h-CaD can inhibit the poliferation and the cell volume of VSMCs stimulated by growth factors and that the gene therapy with h-CaD may be helpful to prevent the conditions associated with hypertrophy and/or hyperplasia of VSMCs after arterial injuries.

• Archives of Pharmacal Research
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• v.19 no.2
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• pp.116-121
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• 1996

Antisense oligonucleotides seem to provide a promising new tool for the therapy. Choi et al. (1995) reported antisense phosphorothioate oligonucleotides (PS-ODN, 25 mer) complementary to TGF-.betha. mRNA designed for scar formation inhibitor to eliminate scars, which was caused by undesired collagen deposition due to overexpression of TGF-.betha., in wounded skin. PS-ODN were evaluated in vitro for skin penetration using normal and tape-stripped damaged rat skin. The in vitro skin transports were carried out with partially modified PS-ODN (6S) and fully modified PS-ODN (25S). The cumulative amount of PS-ODN (6S) penetrated through normal rat skin was $0.234{\pm}0.041{\mu}g/cm^2$ and that of tape-stripped damaged rat skin was $1.077{\pm}0.301{\mu}g/cm^2$ over 8 hrs. PS-ODN (25S) can not be found in receptor medium through normal skin due to high molecular weight (Mol.Wt.=8,000) and polyanionic charge. However, the cumulative amount of PS-ODN (25S) penetrated across damaged rat skin in PBS was $0.340{\pm}0.296{\mu}g/cm^2$ over 8 hrs. The absense of dermis raised the cumulative amount of PS-ODN (6S) penetrated through rat skin. And the fluxes of PS-ODN (6S) and PSODN (25S) at 8hrs across damaged rat skin were $134.63{\pm}37.67{\mu}g/cm^2$ h, and $42.50{\pm}36.95ng/cm^2$ h, respectively. While PS-ODN (25S) was stable in 10% heat inactivated fetal bovine serum (FBS) during 24 hrs, PS-ODN (6S) was less stable than PS-ODN (25S), but was markedly stable than unmodified phosphodiester. It is suggested that the cumulative amount of PS-ODN (6S) penetrated through damaged rat skin is larger than that of PS-ODN (25S) since the former is easier to degrade by nuclease than the latter and then is apt to penetrate into skin. Thus, PS-ODN represents a logical candidate for further evaluation due to the potential for delivery into the wounded skin.

• Journal of Periodontal and Implant Science
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• v.34 no.4
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• pp.771-780
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• 2004

Chronic exposure to high levels of manganese (Mn) leads a pronounced and debilitating disorder known as manganism. Research on the toxic manifestation of manganese have focused primarily on its neurological effects because exposure to high levels of the metal produces a distinct and irreversible extrapyramidal dysfunction resembling the dystonic movements associated with Parkinson's physiological and biochemical systems in the body. The purpose of this study is to determine the effects of Mn on mineralization in primary rat calvarial cells. The experimental groups were in concentration of 0, 10, 30 and 60 ${\mu}M$. The results were as follows: 1. ALP activity was decreased in concentration of 30 and 60 ${\mu}M$ (p<0.01). 2. Bone nodule formation was depressed in concentration of 30 and 60 ${\mu}M$ at day 14 and 21 (p<0.01). 3. RT-PCR results showed an altered expression of bone matrix proteins. These result suggested that manganese might decrease or alter the expression of the osteoblast phenotype.

• Journal of Periodontal and Implant Science
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• v.35 no.2
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• pp.277-288
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• 2005

There is a potential role of collagenase-3 in alveolar bone loss and periodontal disease progression, we need to develope or find chemotherapeutic drugs or herbal agents which may regulate the expression of MMP-13. Ginseng saponin, one of the major components of Korea ginseng(panax ginseng) root, has many various biologic effects, such as cytotoxic effect, tumoricidal effects, cytokine regulations, and protein biosynthesis effect. The purpose of this study was to determine the effects of Korea red ginseng saponin on MMP-13 gene expression in osteoblasts. The experimental groups were cultured with ginseng saponin in concentration of 1.0, 10, 25, 50, 100, 250 and $500{\mu}g/ml$ for MTT assay. Primary rat calvarial cells were pre-treated for 1 hour with ginseng saponin(100 ${\mu}g/ml$) and then stimulated with $IL-1{\beta}(1.0ng/ml)$ and PTH(10 nM). MMP-13 gene expression was evaluated by RT-PCR. The results were as follows: Ginseng saponin was cytotoxic to osteoblast at concentration exceeding $250{\mu}g/ml$ for longer than 24 hours in tissue culture(p<0.01). In RT-PCR analysis, steady state MMP-13 mRNA levels were increased approximately 350% by $IL-1{\beta}$, and 400% by PTH when normalized to untreated control. $IL-1{\beta}-indued$ MMP-13 mRNA expression was reduced 50% by pretreatment with ginseng saponin. But ginseng saponin didn't inhibit MMP-13 expression from PTH stimulated cells. This results suggest that ginseng saponin Inhibit $IL-1{\beta}-indued$ MMP-13 mRNA expression.

• Korean Journal of Veterinary Research
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• v.43 no.3
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• pp.383-392
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• 2003

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are important regulators on the development of maternal tissues during pregnancy. This study was performed to examine the relationship between maternal IGFs/IGFBPs system (i.e: IGF-I, II, their receptors, and IGFBPs) in pre- and post-partum rats. The liver and kidney are important organs for the synthesis of IGFs and IGFBPs in adults. The levels of materanal IGFs and IGFBPs in serum, liver, and kidney were examined at 14 and 21 days of gestation and at 3, 7, 11, and 14 days after birth. The expression of IGFs and their receptors mRNA was also examined in fetal and maternal rat liver, kidney. IGF-I concentrations in maternal serum and liver were decreased during pregnancy. However, IGF-I concentration in maternal kidney was increased, having maximal effect at 14 days of gestation. IGF-I concentrations were decreased in serum, liver, and kidney of postpartum rat, compared to control (p < 0.05). On the other hand, IGF-II concentrations in serum, liver, and kidney were increased during pregnancy (p<0.05) and gradually decreased to control level in postpartum period. The levels of IGFBP-3 and IGFBP-2 are expressed in serum, liver, and kidney. However, IGFBP-3 is mainly expressed in serum and liver, and IGFBP-2 in kidney. The levels of IGFBP-3 and IGFBP-2 in maternal serum were markedly decreased during pregnancy and gradually recovered to control level during postpartum period by western ligand blotting. However, there was no change of IGFBP-3 and IGFBP-2 levels by western immunoblotting. The levels of IGFBP-3 and IGFBP-2 in maternal liver and kidney also showed the same pattern of serum, although the main IGFBP is different. In normal rat serum, IGF-I 150 kDa and 50 kDa carrier proteins were detected. The level of IGF-I 150 kDa carrier proteins in pregnant rat was decreased compared to normal rat, but that of 50 kDa carrier proteins was increased. IGFBP-3 protease activity was identified in pregnant rat serum and maternal placenta, and it was inhibited by EDTA ($Ca^{2+}$ chelating agent) and aprotinin (serine proteinase inhibitor). Taken together, these results suggest that the changes of IGFs and IGFBPs in maternal rats are regulated by liver and kidney IGFs and their receptors mRNA during the pregnancy.

• Journal of Life Science
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• v.10 no.5
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• pp.529-532
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• 2000

Prostaglandin $E_2$(PG$E_2$) is an abundant eicosanoid in bone that has been implicated in a number of pathological states associated with bone loss, and is also known to stimulate matric metalloproteinase-1 systhesis and secretion in rat and human osteoblast cells, although the intracellular reaction remain unclear. Interleukin-1$\beta$ (IL-1$\beta$) is a cytokine that plays a critical role in bone remodelling and appears to act as a downstream effector of most bone-resorbing agents. However, it is still interesting to examine whether PG$E_2$ regulates IL-1$\beta$ expression by mouse osteoblasts or not. Here we demonstrate that PG$E_2$is a potent inducer of IL-1$\beta$ production by fetal osteoblasts.