• Journal of the korean academy of Pediatric Dentistry
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• v.28 no.1
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• pp.54-66
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• 2001

The aim of this study was to investigate the fluoride release and some mechanical properties including 3-point bending strength, amount of abrasion, surface hardness, water sorption/solubility and cytotoxicity of the newly developed composite resins containing 8, 16, 24 wt% $SrF_2$ glass filler (VF8, VF16, VF24) and four commercially available composite resins, Heliomolar(HE), Verdonfil(VE), Z100(ZH) and Aelitefil(AE). To investigate cytotoxic effect, agar overlay assay was done. Amount of fluoride released into distilled water was measured over a 62-days period from VF8, VF16, VF24 and HE. Results were as follows: 1. Experimental composite resins showed similar mechanical properties to commercial composite resins, but 3-point bending strength and surface hardness of experimental composite resins were inferior to ZH. 2. Over a 62-day Period, the amount of fluoride released was ordered: VF24>VF16>VF8>HE. In experimental composite resins, the amount of fluoride released was 9-23 times greater than HE and seemed to be proportional to the content of $SrF_2$ glass filler. 3. Experimental composite resins and all control composite resins showed mild cytotoxicity. This study showed significantly greater fluoride release from newly developed composite resins than control(HE) and addition of $SrF_2$ glass filler did not decrease mechanical properties or increase cytotoxicity of composite resin. The results from this study imply that newly developed composite resin have adequate mechanical properites, mild cytotoxicity and some potential for secondary caries prevention.

• Tuberculosis and Respiratory Diseases
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• v.40 no.1
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• pp.16-22
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• 1993

Background: The Microbicidal and cytotoxic activities of neutrophils are to a large extent dependent on a burst of oxidative metabolism which generates superoxide anion, hydrogen peroxide, and other reactive products of oxygen. The respiratory burst of PMN is initiated by intracellular calcium mobilization that follows immune or particular stimulation and is very sensitive to modulation by c-AMP or adenosine. Despite its antagonism against adenosine, earlier study has demonstrated potent theophylline inhibition of the PMN respiratory burst at variable ranges of blood concentrations of theophylline in the healthy normal volunteers and in the septic animals pretreated or early post-treated with aminophylline (AMPH) or pentoxifylline. However it is unclear whether theophylline inhibits the superoxide generation or not in the established human sepsis caused by acute pneumonia, as taking into consideration of the fact that full activation of neutrophils have occurred within minutes after the septic insult in the animal experiments. Methods: We measured the $O_2$ generation of peripheral arterial neutrophils obtained from 11 human septic subjects caused by acute pneumonia before and 1 hour after completion of continuous AMPH infusion. Patients were identified and studied within 48 hour of admission. All subjects were administered an intravenous loading and maintenance dose of AMPH. The generation of $O_2$ was measured at a discrete time point (60 min) by the reduction of ferricytochrome c.PMA (10 ${\mu}g/ml$) was used as a stimulating agent. PMNs were isolated at a concentration of $2{\times}10^6$ cells/ml. The arterial oxygen tension, blood pressure and heart rates were also checked to evaluate the systemic effects of AMPH in the acute pneumonia. Results: The mean serum concentration of AMPH at 60 minutes was $8.8{\pm}0.6{\mu}g/ml$. Sixty minutes after AMPH infusion the generatition of $O_2$ was decreased from $0.076{\pm}0.034$ to $0.013{\pm}0.004$(OD) (p<0.05) and from $0.177{\pm}0.044$ to $0.095{\pm}0.042$(OD) (p<0.01) in the resting and stimulated PMNs respectively. $PaO_2$ was not changed after AMPH infusion. Conclusion: AMPH may compromise host defense by significant inhibition of neutrophil release of superoxide anion and it had no effect on improving $PaO_2$ in the acute pneumonia.

• The korean journal of orthodontics
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• v.23 no.2 s.41
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• pp.229-248
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• 1993

[ $Interferon-\gamma$ ] has been suggested as a cytokine of connective tissue stabilizer. In addition, it has also been demonstrated that this cytokine inhibited bone remodeling activities of the bone derived cells. In order to illuminate the effects of this cytokine in orthodontic force induced bone remodeling, it was administered to primary cultured periodontal ligament cells which have been known to have some osteoblast like characteristics. $Interferon-\gamma$ slightly decreased $[^3H]thymidine$ incorporation rate without a significant change in the total cellular DNA content up to 1000 U/ml, which meant these doses were not cytotoxic to the cell. Total protein synthesis was not influenced by various concentration of interferon-y whether it was determined by the $[^3H]proline$ incorporation rate or by the Lowry smethod. The effect of $interferon-\gamma$ on the individual protein was, however, differential, ie, it increased $[^3H]proline$ incorporation into the noncollagenous protein marginally, while it decreased $[^3H]proline$ incorporation into the collagen, so that it caused dose-dependent suppression of the relative collagen synthesis. On the contrary, the fibronectin synthesis determined by the ELISA was increased by 1000 U/ml of $interferon-\gamma$. The differential effects of the interferon-y on the collagen and fibronectin synthesis exhibited not only their protein level but also the steady state mRNA level. $Interferon-\gamma$ decreased steady state level of ${\alpha}1(I)$ procollagen mRNA significantly, while showing no significant changes in the fibronectin mRNA level. In addition to this, it was also found that indomethacin did not affect on the $interferon-\gamma$ induced collagen decrease in this cell, which meant prostaglandins were not involed in the process of $interferon-\gamma$ induced collagen decrease. So it can be concluded that the incubation of periodontal ligament cells with 1000 U/ml of $interferon-\gamma$ for 24 hr showed differential effects on the type I collagen and fibronectin gene expression. The decrease in relative collagen synthesis in the protein level was related with decrease in the steady state level of mRNA, while the increase in the fibronectin synthesis in the protein level was not correlated with the mRNA level.

• Korean Journal of Food Science and Technology
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• v.31 no.3
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• pp.838-847
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• 1999

Based on the results that the extract of Korean mistletoe (KM-110) has immunological and anti-tumor activities and its main component is lectin called KML-U, this study was carried out to investigate the immunostimulatory and anti-tumor activities of FKM-110, fermented KM-110 with lactobacillus, as a basic study for the development of functional food with anti-tumor activity. The amount of lectin after fermentation determined by ELISA was varied with the fermentation time and kinds of lactobacillus. Cytotoxic effects of FKM-110 on the various tumor cells was significant and dependent on the concentration of KML-U and the kinds of lactobacillus. FKM-110 stimulated macrophage and resulted in the secretion of some cytokines such as IL-1 and $IFN-{\gamma}$, but this effect was not correlated with the concentration of lectin. FKM-110 fermented with Marshall Lactobacillus casei showed the most potent antitumor activity in experimental and spontaneous metastasis models. When yoghurt produced with KM-110, Marshall Lactobacillus casei and skim milk was administered orally to mouse, the metastasis of tumor cells was significantly inhibited.

• Journal of Animal Science and Technology
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• v.46 no.4
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• pp.563-570
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• 2004

The insulin-like growth factor(IGF) system, consisting of IGFs-I and -II ligands and their receptors and six IGF-binding proteins(IGFBPs), plays an important role in survival, proliferation and differentiation of a variety of cell types. Lithium is a known modulator of survival and proliferation of many cell types in vitro. The present study was undertaken to investigate the relationship between LiCI-induced changes in cell survival and growth and the expression of the IGF system components in C6 rat glioma cell line which, besides IGF-I and its receptor, is known to express IGFBP-3 as its major IGF carrier. When C6 cells were cultured for 24h in the absence or presence of 2mM or 5mM LiCl in a 10% serwn-containing medium, the viability and the number of cells were not affected by added lithium. In 72-h culture, however, C6 cells clearly exhibited a dose-dependent response to added LiCl. The cells cultured for 72h in the presence of 0, 2mM and 5mM LiCl exhibited a typical mitotic, a growth-arrested and an apoptotic appearances, respectively. Moreover, the apoptotic cells were accompanied by reduced expression of IGF-I, IGF-I receptor and IGFBP-3 as examined by semi-quantitative reverse transcription-polymerase chain reaction. Interestingly, blockade of IGFBP-3 mRNA translation by addition of 101${\mu}M$ IGFBP-3 anti-sense oligodeoxyribonucleotide in serum-free, 24-h culture resulted in a decrease in the number of cells as well as relative abundance of the target mRNA. In summary, results suggest that the cytotoxic effect of lithium in C6 cell is likely to be mediated, in part, by suppression by this agent of the expression of the IGF system components. In this regard, IGFBP-3 may play at least a 'permissive' role in normal proliferation of this cell.

• Journal of Life Science
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• v.20 no.1
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• pp.103-112
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• 2010

Pemetrexed has demonstrated clinical activity in non-small cell lung cancer (NSCLC) as well as other solid tumors. It transports into the cells via reduced folate carrier (RFC) and is polyglutamated by folypolyglutamate synthetase (FPGS). Pemetrexed directly inhibits several folate-dependent enzymes such as thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). We investigated the effects of genetic variations and the expression of RFC, FPGS, TS and DHFR enzymes on drug sensitivity to pemetrexed in NSCLC cells. Polymorphisms in RFC, FPGS, and DHFR were genotyped in four NSCLC cells - A549, PC14, HCC-1588, and H226. Real-time RT-PCR and Western blot was performed to evaluate mRNA transcripts and protein of these genes. The cytotoxicity of pemetrexed was measured by SRB assay. In PC14 and H226 cells, increased mRNA expressions of RFC and FPGS were associated with higher cytotoxicity to pemetrexed. 2R/2R genotype of TS and its increased mRNA expression were associated with drug resistance to pemetrexed in A549 cells, whereas 3R/3R genotype in TS with decreased mRNA expression was associated with higher sensitivity in H226 cells. After pemetrexed treatment, an inverse change of DHFR mRNA and protein expression was found. The strongest linkage disequilibrium (LD) was discovered between-1726C>T and -1188A>C SNP of DHFR gene. Our findings suggest the cytotoxic effect of pemetrexed may be associated with genetic polymorphisms and the expression level of genes involved in pemetrexed metabolisms in NSCLC cells.

• Journal of Veterinary Clinics
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• v.20 no.1
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• pp.1-6
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• 2003

Immunoenhancing effects of conjugated linoleic acid (CLA) isomers (l0t-l2c CLA, 9c-11t CLA, CLA mixture, 9c-11c CLA and 9t-11t CLA) on chemotactic activity of porcine peripheral blood polymorphonuclear cells (PMN) were examined. The chemotactic activity of PMN was evaluated by a modified Boyden chamber assay. CLA isomers at higher concentration of 50 to 200$\mu$M exhibited a low viability of cells by trypan blue exclusion. CLA isomers were used at concentration of 20uM showing no cytotoxic effect and high cell viability. CLA isomers themselves were not active or slight chemotactic for PMN. But culture supernatant from mononuclear cells (MNC) treated with 10t-12c CLA, 9c-11t CLA and CLA mixture except for 9c-11c. CLA and 9t-11t CLA enhanced remarkably chemotactic activity or porcine PMN PMN migration by culture supernatant from MNC treated with CLA mixture was found to be true chemotaxis by checkboard assay. This migration was also induced by porcine recombinant interleukin (rIL)-8. PMN chemotaxis caused both culture supernatant from MNC treated with CLA mixture and porcine rIL-8 was inhibited in a dose-dependent manner by addition of anti-porcine IL-8 polyclonal antibody. Therefore, these results strongly suggested that CLA (10t-12c CLA, 9c-11t CLA and CLA mixture) could stimulate porcine MNC to release and IL-8 like chemotactic activity.

• Restorative Dentistry and Endodontics
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• v.31 no.1
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• pp.36-49
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• 2006

The purpose of this study was to compare the cytotoxicity by MTT test and genotoxicity by Ames test of new calcium phosphate-based root canal sealers (CAPSEAL I, CAPSEAL II) with commercially available resin-based sealers (AH 26, AH Plus) , zinc oxide eugenol-based sealers (Tubliseal EWT, Pulp Canal Sealer EWT), calcium hydroxide-based sealer (Sealapex), and tricalcium phosphate based sealers (Sankin Apatite Root Canal Sealer I, II, III). According to this study, the results were as follows : 1. The extracts of freshly mixed group showed higher toxicity than those of 24 h set group in MTT assay (p<0.001). 2. CAPSEAL I and CAPSEAL II were less cytotoxic than AH 26, AH Plus, Tubliseal EWT, Pulp Canal Sealer EWT Sealapex and SARCS II in freshly mixed group (p<0.01). 3. AH 26 in freshly mixed group showed mutagenicity to TA98 and TA100 with and without S9 mix and AH Plus extracts also were mutagenic to TA100 with and without S9 mix. 4. Tubliseal EWT, Pulp Canal Sealer EWT and Sealapex in freshly mixed group were mutagenic to TA100 with S9 mix. 5. Among those of 24 h set groups the extracts of SARCS II were mutagenic to TA98 with and without S9 mix and AH 26 showed mutagenic effects to TA98 with S9 mix. 6. No mutagenic effect of CAPSEAL I and CAPSEAL II was detected. 7. There is no statistically significant difference between CAPSEAL I and CAPSEAL II at MTT assay and Ames test in both freshly mixed group and 24 h set group.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.4
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• pp.486-492
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• 2011

This study was designed to evaluate the effect of hot water extract (ESW) and 70% ethanol extract (ESE) from Euphorbia supina Rafin on LPS-stimulated inflammatory response in RAW 264.7 macrophages. Upon investigation at concentrations up to $1000\;{\mu}g$/mL, ESW and ESE did not have any cytotoxic effects on RAW 264.7 macrophages. ESW induced inhibition of 21.6%~54.8% of nitric oxide (NO) production at 100~1000${\mu}g$/mL, and $PGE_2$ production was inhibited up to 25.7%~38.2% at 250~1000${\mu}g$/mL, proportional to the ESW concentrations. ESW induced inhibition of 66.1% and 54.3% of IL-6 production at 250 and $1000\;{\mu}g$/mL, respectively. ESE (100~1000${\mu}g$/mL) induced inhibition of 38.3%~77.5% of NO, 40%~94.7% of $PGE_2$, and 43.9%~89.4% of IL-6 production, proportional to the ESE concentrations. Only 44.1% of IL-10 production was inhibited at a concentration of $500\;{\mu}g$/mL. ESE induced an increase in TNF-${\alpha}$ production at a concentration of 100 and $250\;{\mu}g$/mL, whereas at high concentrations (500 and $1000\;{\mu}g$/mL), ESE induced inhibition of 19.2% and 92.4% of TNF-${\alpha}$ production, respectively. In conclusion, concentrations of more than $500\;{\mu}g$/mL ESE demonstrated effective immune-modulating activity through inhibition of NO, $PGE_2$, IL-6, IL-10, or TNF-${\alpha}$ production, as it relates to the macrophage's immuno-activity; therefore, ESE has potential as a good candidate substance for reduction of inflammatory responses.

• Journal of Life Science
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• v.17 no.10
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• pp.1447-1451
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• 2007

Through the screening of marine natural compounds that inhibit cancer cell proliferation, we previously reported that pectenotoxin-2 (PTX-2) isolated from marine sponges exhibits selective cytotoxicity against several cell lines in p53-deficient tumor cells compared to those with functional p53. However, the molecular mechanisms of its anti-proliferative action on malignant cell growth are not completely known. To further explore the mechanisms of its anti-cancer activity and to test whether the status of p53 in liver cancer cells correlates with their chemo-sensitivities to PTX-2, we used two well-known hepatocarcinoma cell lines, p53-deficient Hep3B and p53-wild type HepG2. We have demonstrated that PTX-2 markedly inhibits Hep3B cell growth and induces apoptosis whereas HepG2 cells are much more resistant to PTX-2 suggesting that PTX-2 seems to act by p53-independent cytotoxic mechanism. The apoptosis induced by PTX-2 in Hep3B cells was associated with the modulation of DNA fragmentation factor (DFF) family proteins, up-regulation of pro-apoptotic Bcl-2 family members such as Bax and Bcl-xS and activation of caspases (caspase-3, -8 and -9). Blockade of the caspase-3 activity by caspase-3 inhibitor, z-DEVD-fmk, prevented the PTX-2-induced growth inhibition in Hep3B cells. Moreover, treatment with PTX-2 also induced phosphorylation of AKT and extracellular-signal regulating kinase (ERK), but not c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MARK). Specific inhibitors of PI3K inhibitor (LY294002) and ERK1/2 inhibitor (PD98059) significantly blocks PTX-2-induced-anti-proliferative effects, whereas a JNK inhibitor (SP600125) and a p38 MAPK inhibitor (SB203580) have no significant effects demonstrating that the pro-apoptotic effect of PTX-2 mediated through activation of AKT and ERK signal pathway in Hep3B cells.