• Toxicological Research
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• v.26 no.4
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• pp.261-266
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• 2010

In the workplace, the arsenic is used in the semiconductor production and the manufacturing of pigments, glass, pesticides and fungicides. Therefore, workers may be exposed to airborne arsenic during its use in manufacturing. The purpose of this study was to evaluate the potential toxicity of particulate matters (PMs) doped with arsenic (PMs-Arsenic) using a rodent model and to compare the genotoxicity in various concentrations and to examine the role of PMs-Arsenic in the induction of signaling pathway in the lung. Mice were exposed to PMs $124.4{\pm}24.5\;{\mu}g/m^3$ (low concentration), $220.2{\pm}34.5\;{\mu}g/m^3$ (middle concentration), $426.4{\pm}40.3\;{\mu}g/m^3$ (high concentration) doped with arsenic $1.4\;{\mu}g/m^3$ (Low concentration), $2.5\;{\mu}g/m^3$ (middle concentration), $5.7\;{\mu}g/m^3$ (high concentration) for 4 wks (6 h/d, 5 d/wk), respectively in the whole-body inhalation exposure chambers. To determine the level of genotoxicity, Chromosomal aberration (CA) assay in splenic lymphocytes and Supravital micronucleus (SMN) assay were performed. Then, signal pathway in the lung was analyzed. In the genotoxicity experiments, the increases of aberrant cells were concentration-dependent. Also, PMs-arsenic caused peripheral blood micronucleus frequency at high concentration. The inhalation of PMs-Arsenic increased an expression of phosphorylated Akt (p-Akt: protein kinase B) and phpsphorylated mammalian target of rapamycin (p-mTOR) at high concentration group. Taken together, inhaled PMs-Arsenic caused genotoxicity and altered Akt signaling pathway in the lung. Therefore, the inhalation of PMs-Arsenic needs for a careful risk assessment in the workplace.

• Parasites, Hosts and Diseases
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• v.55 no.3
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• pp.295-304
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• 2017

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-$1{\beta}$, IL-6, IFN-${\gamma}$, LT-${\alpha}$, and TNF-${\alpha}$ were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-$1{\beta}$-511C/T, IL-6-174G/C, IFN-${\gamma}$+874T/A, LT-${\alpha}$+252A/G, and TNF-${\alpha}$-308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-${\alpha}$+252A/G and TNF-${\alpha}$-308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-${\gamma}$+874T/A were significantly higher than the variants in CCA cases. IFN-${\gamma}$+874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6-174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.

• Journal of Life Science
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• v.30 no.6
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• pp.542-549
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• 2020

A previous study reported that Ulmus macrocarpa Hance water extract (UME) can improve hyperlipid metabolism and the involvement of suppressed lipid synthesis through adenosine monophosphate-activated protein kinase (AMPK) pathway regulation was suggested. Further exploration of the lipid metabolism between liver and peripheral tissue was necessary to confirm that work, and so this study aimed to extend the possibility that UME can regulate serum lipids. After a 6-week in vivo trial of oral administration of UME to rats with induced hyperlipidemia, serum levels of triglyceride (TG) and total cholesterol (TC) were seen to decrease while HDL cholesterol increased. The UME administrations also decreased the TC and TG levels from the control in liver analysis. However, the suggestion that UME regulates the AMPK pathway to improve hyperlipid states through the suppression of hepatic lipogenesis seems to be only one part of the extract's effect. Indeed, serum concentrations of apolipoproteins A and B were returned to baseline levels of the control group in response to UME administration whilst the liver lipid content was much reduced; this cannot occur through the suggested suppression of hepatic lipogenesis alone. Therefore, a possible mechanism of UME could be that it improves blood circulation by modulating serum lipid levels through both the prior stimulation of lipid oxidation and the suppression of hepatic lipogenesis.

• Journal of Life Science
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• v.11 no.2
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• pp.181-189
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• 2001

Cytokines are hormone-like proteins which mediate and regulast inflammatory and immune responses. Transforming growth factor -$\beta$1(TGF-$\beta$) plays an important role in the control of the immune response and wound healing, and in the development o various tissues and organs, Nitric oxide(NO) is major messenger molecule regulating immune function and blood vessel dilation and serving as a neurotransmitter in the brain and peripheral nervous system. Also, NO is to be a potent mutagen that cause mutation in the p53 tumor suppressor gene in early phases of human gastric carcinogenesis. The purpose of this study was to investigate the effect of Helicobacter phlori lystes, lipopolysaccharide (LPS), and Staphylococcus enterotoxin B(SEB) on production of TGF-$\beta$1 and NO by human fibroblasts. Primary cultured human fibroblasts were incubated with H. pylori lysates(Hp), LPs, SEB, Hp+LPS, Hp+SEB, Hp+LPS+SEB. Cultured supernatants that were collected at 24, 48 and 72 hr were assessed for TGF-$\beta$1 by enzyme-linked immunosorbent assay and NO production by quantification of nitrite ion. TGF-$\beta$1 production in fibroblasts exposed with Hp, LPS or SEB for 48 hrs was enhanced, but for 72 hrs inhibited. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB was lowered in comparison with single exposure of Hp in cases of 24 and 48 hrs incubation, but for 72 hrs decreased in Hp vaculoating toxin(+), increased in Hp vacuolating toxin(-). No production in fibroblasts increaed at all doses of LPS. But its production by exposure of SEB increased or decreased according to dose and incubation time. Also, NO production by Hp vacuolating toxin(+) increased at all doses, but its production by Hp vacuolating toxin(-) decreased. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB decreased in comparison with single exposure Hp Therefore, quantities pf TGB-$\beta$1 and NO released by human fibroblasts shows differences according to kinds of stimulants. Also, in care stimulated with same kinds of stimulants, its productions exhibit quantitative differences according to exposure times. These results suggest that the decreased of TGF-$\beta$1 in fibroblasts by mixed exposure with Hp producing vacuolating toxin and bacterial toxins such as LPS and SEB may effect negatively in healing of host tissue and increased of NO by infection oh H. pylori may related to the increased susceptibility for human gastric carcinogenesis.

• Journal of fish pathology
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• v.27 no.1
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• pp.47-56
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• 2014

Propolis is a beehive product with a very complex chemical composition, widely used in folk medicine because of its several therapeutic activities. This study was conducted to measure the efficacy of propolis on non-specific defense reactions, specific immune response, and protection levels against pathogen challenge with Streptococcus iniae. in vitro and in vivo. In vitro, the phagocytic activity and NBT assay of peripheral blood leukocytes (PBL) were evaluated in a various propolis extractsconcentrations (0, 10, 50, 100, 150, 250 and $500{\mu}g/ml$). The optimal concentration showing activation of propolis extracts was determined to $100{\mu}g/ml$. In vivo, they were divided into four groups (PBS, propoli extractss, vaccine, propolis extracts + vaccine) in vivo. Fish were received i.p. injection of either PBS or propolis extracts, and in the presence or absence of formalin inactivated S. iniae ($1{\times}10^8$ CFU/fish), respectively. The level of haematocrit is not affected among experimental groups. The phagocytic activity and the NBT reduction activities of head kidney phagocyte were markedly (p<0.05)augmented in the propolis extracts groups than in the PBS-control group, respectively. The level of serum lysozyme activity was significantly (p<0.05) increased in the propolis extracts treated groups than in the PBS-control group. The agglutinin titer was significantly (p<0.05) enhanced in the vaccine+propolis extracts group than in the vaccine group, but there was no difference between PBS-control and propolis treated group. The results of the present study suggest that propolis extracts seems to be a promising compounds of non-specific immune stimulator, also being able to use a good adjuvant.

• Korean Journal of Food Science and Technology
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• v.38 no.5
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• pp.717-719
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• 2006

A randomized, double blind, placebo-controlled human intervention study involving 62 healthy volunteers was performed to investigate the effects of Keumsa sangwhang (Phellinus linteus) mushroom extracts (KPLE) on natural killer (NK) cell activity in peripheral blood. The volunteers were randomly distributed into two groups, one receiving KPLE (3.3 g/day) and the other a placebo by oral administration for 8 weeks. In this study, the number of NK cells did not increase with KPLE administration, however the cytotoxic activity of NK cells against the Jurkat leukemia cell line increased significantly. This result suggests that administration of KPLE induces cell-mediated immunity by increasing NK cell activity in humans.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1137-1144
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• 2012

Introduction: Recent studies have shown that circulating tumor cells (CTCs) play potential roles as diagnostic and prognostic biomarkers with various cancer types. The aim of this study was to comprehensively and quantitatively summarize the evidence for the use of CTCs to predict the survival outcome of lung cancer patients. Materials and Methods: Relevant literature was identified using Medline and EMBASE. Patients' clinical characteristics, overall survival (OS) and progression-free survival (PFS) together with CTC positive rates at different time points (before, during and after treatment) were extracted. A meta-analysis was performed to clarify the prognostic role of CTCs and the correlation between the CTC appearance and clinical characteristics. Results: A total of 12 articles containing survival outcomes and clinical characteristics and 15 articles containing only clinical characteristics were included for the global meta-analysis. The hazard ratio (HR) for OS predicted by pro-treatment CTCs was 2.61 [1.82, 3.74], while the HR for PFS was 2.37 [1.41, 3.99]. The HR for OS predicted by post-treatment CTCs was 4.19 [2.92, 6.00], while the HR for PFS was 4.97 [3.05, 8.11]. Subgroup analyses were conducted according to histological classification and detection method. Odds ratio (OR) showed the appearance of pro-treatment CTCs correlated with the lymph node status, distant metastasis, and TNM staging, while post-treatment CTCs correlated with TNM staging only. Conclusion: Detection of CTCs in the peripheral blood indicates a poor prognosis in patients with lung cancer.

• Clinical and Experimental Reproductive Medicine
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• v.31 no.2
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• pp.141-147
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• 2004

Objective: To investigate the association between endometriosis and polymorphisms of N-acetyl transferase 2 (NAT2), glutathione S-transferase M1 (GSTM1), and cytochrome P450 (CYP) 1A1 genes in Korean infertile patients. Materials and Methods: A total of 303 infertile patients who had undertaken diagnostic laparoscopy during January, 2001 through December, 2003 at Samsung Cheil Hospital enrolled in this study. The patients were grouped according to laparoscopic findings: minimal to mild endometriosis (group I: n=147), moderate to severe endometriosis (group II: n=57), normal pelvic cavity (n=99). Peripheral blood was obtained and genomic DNA was extracted. The genotypes of each genes were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). For NAT2, RFLP was used to detect the wild type (wt) and mutant (mt) alleles, enabling classification into slow (mt/mt) or fast (wt/wt or wt/mt) acetylation genotypes. For GSTM1, PCR was used to distinguish active (+/- or +/+) from null (-/-) genotypes. For CYP1A1, MspI digestion was used to detect the wild type (A1A1), heterozygote (A1A2) or mutant (A2A2) genotypes. Result: The genotype frequencies of NAT2 slow acetylator was 12.8%, 10.9%, 12.8% in group I, group II and control, respectively. The genotype frequencies of GSTM1 null mutation was 55.3%, 41.8%, 53.2% in group I, group II and control, respectively. The genotype frequencies of CYP1A1 MspI polymorphism was 16.3%, 9.1%, 18.1% in group I, group II and control, respectively. No significant difference was observed between endometriosis and normal controls in the genotype frequencies of the NAT2, GSTM1, CYP1A1 MspI polymorphism. Conclusion: The NAT2, GSTM1, CYP1A1 gene polymorphism may not be associated with the susceptibility of endometriosis in Korean women.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.29 no.3
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• pp.134-149
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• 2016

Objectives : Gal-Geun-Tang (GT) has been described from SANGHAN in Korean traditional medicine and known to act against cold, fever, hypertension, and nasal catarrh. However, little has yet been learned about the effect of GT on immune function. In the current study, in vitro and in vivo immunomodulatory activity of GT (water extract) was investigated.Methods : Water extract of GT induced in vitro proliferation of spleen cells and significantly increased their proliferative responses during anti-CD3 activation. Using purified splenic T and B cells, it was revealed that GT has a mitogenic activity to B cells and promotes their proliferation induced by lipopolysaccharide, whereas T cell proliferation was not triggered and GT was rather inhibitory to T cell activation caused by anti-CD3 antibody. In the presence of antigen presenting cells (APC), GT addition resulted in a significant increase of IFNγ and IL-4, but not IL-2, production. However, addition of high concentration (1,000㎍/㎖) of GT led to a marked reduction in T cell cytokine production and under such condition, GT facilitated apoptosis of T cells when examined by flow cytometry with propidium iodide staining.Results : In vivo immunomdulation of GT was also investigated using a mouse model. Following keyhole limpet hemocyanin (KLH) immunization, GT (1 ㎎/day) was orally administered for 9 days. Cell numbers in thymus, spleen and peripheral blood were not altered by GT administration, indicating that such dose is not immunotoxic. Cell numbers in draining lymph nodes (LN) and ex vivo Ag-specific proliferation of LN cells were significantly elevated by GT administration. However, any preferential stimulation of T or B and CD4⁺ or CD8⁺ T cell subpopulations was not observed in a flow cytometric analysis of LN cells. This result shows that GT does not promote in vivo B cell proliferation while GT enhances Ag-specific proliferation of LN cells, unlike what was observed in vitro.Conclusions : For a further understanding of in vivo immunomodulatory activity of GT, ex vivo cytokine production of LN cells obtained from KLH-immunized mice was evaluated. Ag-specific IFNγ production was significantly higher in GT-treated mice when compared to PBS-treated control mice. In contrast, IL-4 production in GT-treated group was comparable to control group unlike to in vitro data. In addition, GT administration did not result in any significant differences in serum levels of Ig (IgM, IgG1 and IgG2a) between GT-treated and control groups. Taken together, these data strongly support that GT promotes immune response, more profoundly type 1 helper T cell (Th1) activity and GT may be applicable for treatment of intracellular parasite infection such as viral diseases.

• Journal of The Korean Dental Society of Anesthesiology
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• v.13 no.1
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• pp.1-7
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• 2013

Background: Intravenous sedation is effective for dental patients who are anxious. Recently, target-controlled infusion (TCI) has begun to be used widely to administer and titrate propofol and remifentanil during sedation. To investigate the effect and safety of the pharmacologic agents used in anesthetic department, we performed a retrospective study. Methods: Retrospective study of a series of dental procedure under intravenous sedation performed in department of anesthesiology in Dental Hospital of Dankook University was carried out with propofol or propofol/remifentanil between January and August 2011 and January and April 2012. All patients received oxygen by nasal cannula. The average propofol and remifentanil target was 0.5 ${\mu}g/ml$ and 1.0 ng/ml, respectively using a TCI pump. The average peripheral oxygen saturation ($SpO_2$), heart rate, blood pressure, respiratory rate, nasal end-tidal $CO_2$ were recorded at 5-10 minute intervals. The age, gender, weight, procedure and sedation time, type of procedure were also recorded. Results: We included 22 cases of 19 adults (group A) and 6 cases of children (group B). In group A, 4 patients received propofol (group A-P), and 15 patients received propofol with remifentanil (group A-PR). In group B, 6 patients received propofol only. The mean age of group A was 41.1 years old and that of group B was 9.5 years old. No clinically significant complications were noted. There were no case of de-saturation <90%. The median respiratory rate was 13.1 (range 6 to 36) in group A and 19 (range 13 to 25) in group B. The median end tidal $CO_2$ was 36.7 mmHg(range 8 mmHg to 56 mmHg) in group A and 41.7 mmHg (range 30 mmHg to 53 mmHg) in group B. Conclusions: Based on our results, dental sedation using propofol/remifentanil in adult and propofol in children with TCI pump seems to appear as a safe and effective procedure while performing dental procedure.