• Journal of The Korean Society of Clinical Toxicology
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• v.19 no.2
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• pp.100-109
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• 2021

Purpose: The purpose of this study was to investigate effect of N-acetylcysteine (NAC) on the injury of putative parvalbumin positive interneurons defined by molecular marker and hippocampal long-term potentiation (LTP), a marker of neural plasticity following acute carbon monoxide (CO) poisoning. Methods: Adult Sprague-Dawley rats were exposed to 1100 ppm CO for 40 minutes followed by 3000 ppm CO for 20 minutes. Animals received daily intraperitoneal injection of NAC (150 mg/kg) for 5 days after CO exposure. Changes in learning and spatial memory were evaluated by Y-maze test 5 days after the poisoning. In vivo LTP in hippocampal CA1 area was evaluated by using extracellular electrophysiological technique. Immunohistochemical staining were adopted to observe expressional damages of parvalbumin (PV) immunoreactive interneurons in the hippocampus following the poisoning. Results: Acute CO intoxication resulted in no changes in memory performance at Y-maze test but a significant reduction of LTP in the in hippocampal CA1 area. There was also a significant reduction of PV (+) interneurons in the hippocampal CA1 area 5 days after CO poisoning. Daily treatment of NAC significantly improved hippocampal LTP impairment and reduced immunoreactivity for PV in the hippocampus following the acute CO poisoning. Conclusion: The results of this study suggest that reduction of hippocampal LTP and PV (+) interneurons in the hippocampus is sensitive indicator for brain injury and daily NAC injections can be the alternative therapeutics for the injury induced by acute CO poisoning.

• Nutrition Research and Practice
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• v.13 no.2
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• pp.95-104
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• 2019

BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to $12.5-50{\mu}g/mL$ extract. However, absence of XBP1 or $IRE1{\alpha}$ in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an $IRE1{\alpha}$-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.

• Radiation Oncology Journal
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• v.29 no.2
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• pp.91-98
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• 2011

Purpose: To assess the usefulness of implanted fiducial markers in the setup of hypofractionated radiotherapy for prostate cancer patients by comparing a fiducial marker matched setup with a pelvic bone match. Materials and Methods: Four prostate cancer patients treated with definitive hypofractionated radiotherapy between September 2009 and August 2010 were enrolled in this study. Three gold fiducial markers were implanted into the prostate and through the rectum under ultrasound guidance around a week before radiotherapy. Glycerin enemas were given prior to each radiotherapy planning CT and every radiotherapy session. Hypofractionated radiotherapy was planned for a total dose of 59.5 Gy in daily 3.5 Gy with using the Novalis system. Orthogonal kV X-rays were taken before radiotherapy. Treatment positions were adjusted according to the results from the fusion of the fiducial markers on digitally reconstructed radiographs of a radiotherapy plan with those on orthogonal kV X-rays. When the difference in the coordinates from the fiducial marker fusion was less than 1 mm, the patient position was approved for radiotherapy. A virtual bone matching was carried out at the fiducial marker matched position, and then a setup difference between the fiducial marker matching and bone matching was evaluated. Results: Three patients received a planned 17-fractionated radiotherapy and the rest underwent 16 fractionations. The setup error of the fiducial marker matching was $0.94{\pm}0.62$ mm (range, 0.09 to 3.01 mm; median, 0.81 mm), and the means of the lateral, craniocaudal, and anteroposterior errors were $0.39{\pm}0.34$ mm, $0.46{\pm}0.34$ mm, and $0.57{\pm}0.59$ mm, respectively. The setup error of the pelvic bony matching was $3.15{\pm}2.03$ mm (range, 0.25 to 8.23 mm; median, 2.95 mm), and the error of craniocaudal direction ($2.29{\pm}1.95$ mm) was significantly larger than those of anteroposterior ($1.73{\pm}1.31$ mm) and lateral directions ($0.45{\pm}0.37$ mm), respectively (p<0.05). Incidences of over 3 mm and 5 mm in setup difference among the fractionations were 1.5% and 0% in the fiducial marker matching, respectively, and 49.3% and 17.9% in the pelvic bone matching, respectively. Conclusion: The more precise setup of hypofractionated radiotherapy for prostate cancer patients is feasible with the implanted fiducial marker matching compared with the pelvic bony matching. Therefore, a less marginal expansion of planning target volume produces less radiation exposure to adjacent normal tissues, which could ultimately make hypofractionated radiotherapy safer.

• Journal of Environmental Health Sciences
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• v.35 no.3
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• pp.153-161
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• 2009

The purpose of this paper is to evaluate 1) blood lead levels of workers at auto repair shops as Biological Exposure Indices (BEI) of toxic substances such as lead and toluene that are produced during automotive painting process, 2) the differences depending on personal characteristics of workers who have been exposed to toluene by using urine hippuric acid concentration as a marker and 3) the correlation between the concentration of hazardous chemicals in each workplace and the BEL. All subjects were male with a mean age of 36.2 years. In terms of age, most were in the 30 to 40 age group (13 persons, 48.1%). In relation to the length of work experience, the highest proportion had experience of 10 years of less (18 persons, 66.7%). Twenty three workers were cigarette smokers (85.2%) while 4 (14.8%) were non-smokers. In addition, more than 80% of the workers drank alcohol. Dust concentration and toluene exposure during automotive painting showed no significant difference with age, length of work experience, smoking and drinking while a significant difference (p<0.05) has been detected between lead concentration and smoking. The geometric mean of dust concentration, lead concentration and toluene concentration were $0.38mg/m^3,\;0.0021mg/m^3$ and 1.08ppm respectively. In addition, the geometric mean of blood lead levels and urine hippuric acid concentration were $1.70{\mu}g/dl$ and 0.25g/g respectively, which were lower than the standard levels suggested by the Ministry of Labor. To determine the influential factors on blood lead and urine hippuric acid concentrations, a correlation analysis has been conducted with variables of air, lead and toluene concentrations, age, length of work experience and amount of cigarette smoking. According to the analysis, a relatively high correlation (p<0.01) has been observed between air lead concentration and biological sample concentration.

• Molecular & Cellular Toxicology
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• v.1 no.3
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• pp.164-171
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• 2005

Toxicological studies have an object of detecting adverse effects of a chemical on an organism based on observed toxicity marker (i.e., serum biochemical markers and chemical-specific gene expression) or phenotypic outcome. To date, most toxicogenomic studies concentrated on hepatic toxicity. cDNA microarray analysis enable discrimination of the responses in animals exposed to different classes of hepatotoxicants. In an effort to further characterize the mechanisms of 2, 3, 7, 8,-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin)-mediated toxicity, comprehensive temporal-responsive microarray analyses were performed on hepatic tissue from Sprague-Dawley rats treated with TCDD. Hepatic gene expression profiles were monitored using custom DNA chip containing 490 cDNA clones related with toxicology. Gene expression analysis identified 26 features which exhibited a significant change. In this study, we observed that the genes related with oxidative stress in rats exposed to Dioxin, such as CYPIIA3 and glutathione S-transferase, were up-regulated at 24hr after exposure. In this study, we carried out to discover novel evidence for previously unknown gene expression patterns related to mechanism of hepatic toxicity in rats exposed to dioxin, and to elucidate the effects of dioxin on the gene expression after exposure to dioxin.

• Korean Journal of Biological Psychiatry
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• v.22 no.4
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• pp.205-215
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• 2015

Objectives Sex hormones exposure during the prenatal period has an effect on cerebral lateralization. Male brains are thought to be more lateralized than female brains. Bipolar disorder was known to show abnormalities in cerebral laterality whose characteristics could be estimated by electroencephalography (EEG) coherences. We studied sex-related differences of EEG coherences between healthy controls and patients with bipolar disorder to examine the sex effects in the genesis of bipolar disorder. Methods Participants were 25 patients with bipolar disorder (11 male, 14 female) and 46 healthy controls (23 male, 23 female). EEG was recorded in the eyes closed resting state. To examine dominant EEG coherence associated with sex differences in both groups within five frequency bands (delta, theta, alpha, beta, and gamma) across several brain regions, statistical analyses were performed using analysis of covariance. Results Though statistically meaningful results were not found, some remarkable findings were noted. Healthy control females showed more increased interhemispheric coherences than control males in gamma frequency band. There were no differences in the intrahemispheric coherences between the healthy control males and females. In patients with bipolar disorder, female dominant pattern in interhemispheric coherences was attenuated compared with healthy control. Conclusions Sex differences of EEG coherences, which could be a marker for cerebral laterality, were attenuated in patients with bipolar disorder compared with healthy controls. These results imply that abnormal sex hormone exposure during early development might play some role in the pathogenesis of bipolar disorder.

• Toxicological Research
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• v.20 no.4
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• pp.329-337
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• 2004

Primiphos-methyl and methidathion as organophosphorus (OP) pesticides were tested for their immunotoxic effects on Balb/c mice. Three dose levels of primiphos-methyl (10, 60, or 120 mg/kg/day) and methidathion (0.5, 2.5 or 5.0 mg/kg/day) were administered orally in the mice for 4 weeks. After, changes in body weight gain, relative weight of spleen and thymus, viable splenic cell numbers, surface marker on immune cell, and proliferation activity were investigated. Results showed that neither Pirimiphos-methyl nor methidathion dosages changed significantly body weight, relative thymus and spleen weight, and thymus and spleen cellularities of the mice, but high dose treatment (120 mg/kg) of pirimiphos-methyl significantly decreased relative spleen weight and spleen cellularity of the mice. No alterations were observed in changes of LPS-proliferation response of splenocytes by exposure to any dose of pirimiphos-methyl and methidathion. However, pirimiphos-methyl dosages reduced ConA-proliferation response of splenocytes and both methidathion and pirimiphos-methyl decreased the ability of antibody production to SRBC. The results indicate that 28 days exposure to the high dose of pirimiphos-methyl suppress the function of splenic T and B cell function, and methidathion reduce the immune responsibility of B cell in mice without the changes in lymphoid organ weight or viability of splenocytes. Pirimiphos-methyl is more immunotoxic than methidathion although this has higher general toxicity than that.

• Korean Journal of Veterinary Research
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• v.46 no.1
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• pp.35-41
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• 2006

Vitellogenin (Vtg), a phospholipoglycoprotein precursor of egg yolk is synthesized and secreted from the liver in response to estrogens in female fish. Vtg is normally undetectable in the blood of male fish, but can be induced by exposure to chemicals possessing estrogenic activity. Thus, the presence of Vtg in blood of male fish can serve as a useful biomarker for assessing previous exposure to estrogenic compounds. In the present study, Vtg was abnormally expressed in Rhynchocypris oxycephalus using estradiol benzoate ($E_2$). As the result, it was found that the level of Vtg in blood from R. oxycephalus was increased by treated quantity of $E_2$ with dose-effect manner. Monoclonal antibodies were generated against Vtg of R. oxycephalus. The hybridoma were screened with an enzyme immunoassay for the production of specific anti-Vtg antibodies. Five positive cell lines with a high specificity were selected. Monoclonal antibodies against vtg of R. oxycephalus that was developed in this study, may be a useful bio-indicator for the detection of estrogenic contamination in the aquatic ecosystem.

• Annals of Occupational and Environmental Medicine
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• v.35
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• pp.34.1-34.8
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• 2023

Background: Hydrogen sulfide is a toxic substance that humans can be exposed to occupationally, and cases of hydrogen sulfide poisoning of workers in industrial sites are commonly reported. However, there have been no cases of poisoning of the public due to an unauthorized discharge of wastewater, so it is important to describe this incident. Case presentation: In a small village in Jeollanam-do, Republic of Korea, accounts of a terrible stench had been reported. A 26-year-old man who lived and worked in a foul-smelling area was taken to the emergency room with a headache, dizziness, nausea, and repeated syncope. A subsequent police and Ministry of Environment investigation determined that the cause of the stench was the unauthorized discharge of 9 tons of wastewater containing hydrogen sulfide through a stormwater pipe while the villagers were sleeping. The patient had no previous medical history or experience of symptoms. Leukocytes and cardiac markers were elevated, an electrocardiogram indicated biatrial enlargement, left ventricular hypertrophy, and corrected QT interval prolongation. Myocardial hypertrophy was detected on a chest computed tomography scan, and hypertrophic cardiomyopathy was confirmed on echocardiography. After hospitalization, cardiac marker concentrations declined, symptoms improved, and the patient was discharged after 7 days of hospitalization. There was no recurrence of symptoms after discharge. Conclusions: We suspect that previously unrecognized heart disease manifested or was aggravated in this patient due to exposure to hydrogen sulfide. Attention should be paid to the possibility of unauthorized discharge of hydrogen sulfide, etc., in occasional local incidents and damage to public health. In the event of such an accident, it is necessary to have government guidelines in place to investigate health impact and follow-up clinical management of exposed residents.

• Food Science and Preservation
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• v.21 no.6
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• pp.859-865
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• 2014

This study was conducted to analyze the hydrocarbons and 2-alkylcyclobutanones as marker compounds in walnuts after the walnuts' exposure to ${\gamma}$ irradiation. The samples were irradiated with gamma rays at 0, 1, 3, 5, 7, and 10 kGy doses. The lipids were extracted via soxhlet extraction using hexane, and were separated by florisil column and identified via gas chromatography / mass spectrometry (GC/MS). The hydrocarbons that were detected were 8-heptadecene ($C_{17:1}$) and 1,7-hexadecadiene ($C_{16:2}$) from oleic acid and 8,11-heptadecadiene ($C_{17:2}$) and 1,7,10-hexadecatriene ($C_{16:3}$) from linoleic acid. The 2-alkylcyclobutanones that were detected were 2-dodecylcyclobutanone (DCB) from palmitic acid, 2-tetradecylcyclobutanone (TCB) from stearic acid, 2-(5'-tetradecenyl)cyclobutanone (TECB) from oleic acid, and 2-(5',8'-tetradecadienyl)cyclobutanone (5',8'-TCB) from linoleic acid. The correlation between the irradiation dose and the concentrations of the hydrocarbons and 2-alkylcyclobutanones in the walnuts was found to be linear. The radio-induced hydrocarbons and 2-alkylcyclobutanones were clearly detected in the irradiated walnuts at 1 kGy and above, but not in the non-irradiated ones. The major hydrocarbons obtained after irradiation were 8-heptadecene from oleic acid and 8,11-heptadecadiene and 1,7,10-hexadecatriene from linoleic acid, and the major 2-alkylcyclobutanones were TECB from oleic acid and 5',8'-TCB from linoleic acid. Therefore, these major compounds were concluded to be the marker compounds for determining the irradiated and non-irradiated samples.