• Toxicological Research
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• 제34권4호
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• pp.343-354
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• 2018

Aluminum oxide nanoparticles ($Al_2O_3$ NPs) are among the most widely used nanomaterials; however, relatively little information about their risk identification and assessment is available. In the present study, we aimed to investigate the potential toxicity of $Al_2O_3$ NPs following repeated inhalation exposure in male Sprague-Dawley rats. Rats were exposed to $Al_2O_3$ NPs for 28 days (5 days/week) at doses of 0, 0.2, 1, and $5mg/m^3$ using a nose-only inhalation system. During the experimental period, we evaluated the clinical signs, body weight change, hematological and serum biochemical parameters, necropsy findings, organ weight, and histopathology findings. Additionally, we analyzed the bronchoalveolar lavage fluid (BALF), including differential leukocyte counts, and aluminum contents in the major organs and blood. Aluminum contents were the highest in lung tissues and showed a dose-dependent relationship in the exposure group. Histopathology showed alveolar macrophage accumulation in the lungs of rats in the $5mg/m^3$ group during exposure and recovery. These changes tended to increase at the end of the recovery period. In the BALF analysis, total cell and neutrophil counts and lactate dehydrogenase, tumor necrosis factor-${\alpha}$, and interleukin-6 levels significantly increased in the 1 and $5mg/m^3$ groups during exposure. Under the present experimental conditions, we suggested that the no-observed-adverse-effect level of $Al_2O_3$ NPs in male rats was $1mg/m^3$, and the target organ was the lung.

• Korean Journal of Veterinary Research
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• 제37권4호
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• pp.855-862
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• 1997

Ivermectin is a synthetic derivative of the naturally occurring avermectin $B_{1a}$ (22, 23-dihydroavermectin $B_{1a}$) and $B_{1b}$ (22, 23-dihydroavermectin $B_{1b}$), It is widely used as antiparasitic and pesticidal agents because of its remarkably potent and broad spectrum of antiparasitic activity. Although the drug has shown excellent anthelmintic effects, development of toxicosis in some animals such as the Collie species of dog is well documented. However, no studies have been reported on the toxic effects of the drug in Korean native animals such as the Jindo dog. The toxic effect of ivermectin was evaluated in 25 Jindo dogs divided into five groups which were orally administered with ivermectin at dosage levels of $200{\mu}g/kg$, $300{\mu}g/kg$, $600{\mu}g/kg$ and $2,500{\mu}g/kg$ of body weight, respectively. Toxic signs were not observed in the groups receiving $200{\mu}g/kg$ and $300{\mu}g/kg$ B.W. ivermectin. One dog developed mild clinical signs of toxicosis in the group receiving $600{\mu}g/kg$ dosage of ivermectin. In the group with $2,500{\mu}g/kg$ dosage, all dogs developed mild (salivation, drooling, vomiting, mydriasis, and/or confusion) and/or moderate (ataxia and tremors) clinical signs of toxicosis. Hematologic changes were not observed in the groups receiving $200{\mu}g/kg$, $300{\mu}g/kg$ and $600{\mu}g/kg$ B.W. ivermectin. In the groups receiving $2,500{\mu}g/kg$ B.W., total erythrocyte counts, total and differential leukocyte counts and hemoglobin levels were not affected by drug. Aspartate aminotransferase levels were increased after administration of ivermectin, while serum cholesterol and blood glucose levels were decreased.

• Environmental Analysis Health and Toxicology
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• 제28권
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• pp.14.1-14.9
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• 2013

Objectives This study was conducted to determine whether nano-sized carbon black exposure results in greater damage in high fat diet-induced overweight rats than normal weight ones and to identify the possible causes of any differences. Methods Two groups of Sprague-Dawley rats allocated by body weight (normal and overweight) were exposed to aerosolized nano-sized carbon black for 6 hours a day, 5 days per week over a 4-week period. Differential cell counts, lactate dehydrogenase (LDH) activities and albumin concentrations were measured in bronchoalveolar lavage (BAL) fluid, and histopathological findings in the lungs were evaluated. Tumor necrosis factor-alpha (TNF-${\alpha}$) and interleukin (IL)-6 were measured in BAL fluid and supernatants of lipopolysaccharide(LPS)-stimulated lymphocyte culture. Results Rats exposed to high concentrations of nano-sized carbon black showed significantly increased (p <0.05) polymorphonuclear leukocyte number and LDH activity in the BAL fluid from both overweight and normal rats. Mild histopathological changes were observed in normal rats irrespective of carbon black concentrations. However, severe histological scores were found in overweight rats ($1.75{\pm}0.46$, $2.25{\pm}0.46$, and $2.88{\pm}0.35$ after low, medium, and high concentration exposures). Proinflammatory cytokine levels of TNF-${\alpha}$ and IL-6 were significantly higher in the supernatant of LPS-stimulated lymphocytes of overweight rats, whereas there was no significant difference in the BAL fluid between normal and overweight rats. Conclusions Inflammation and damage to lungs exposed to nano-sized carbon black was more severe in high fat diet-induced overweight rats compared to normal rats.

• Asian Pacific Journal of Cancer Prevention
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• 제15권10호
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• pp.4217-4224
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• 2014

Cholangiocarcinoma (CCA), a slow growing but highly metastatic tumor, is highly prevalent in Northeast Thailand. Specific tests that predict prognosis of CCA remain elusive. The present study was designed to investigate whether peripheral blood leukocyte (PBL) transcriptional profiles might be of use as a prognostic test in CCA patients. Gene expression profiles of PBLs from 9 CCA and 8 healthy subjects were conducted using the Affymetrix HG_U133 Plus 2.0 GeneChip. We indentified informative PBLs gene expression profiles that could reliably distinguish CCA patients from healthy subjects. Of these CCA specific genes, 117 genes were up regulated and 60 were down regulated. The molecular and cellular functions predicted for these CCA specific genes according to the Gene Ontology database indicated differential PBL expression of host immune response and tumor progression genes (EREG, TGF ${\beta}1$, CXCL2, CXCL3, IL-8, and VEGFA). The expression levels of 9 differentially expressed genes were verified in 36 CCA vs 20 healthy subjects. A set of three tumor invasion related genes (PLAU, CTSL and SERPINB2) computed as "prognostic index" was found to be an independent and statistically significant predictor for CCA patient survival. The present study shows that CCA PBLs may serve as disease predictive clinically accessible surrogates for indentifying expressed genes reflective of CCA disease severity.

• Tuberculosis and Respiratory Diseases
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• 제53권2호
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• pp.183-189
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• 2002

Churg-Strauss syndrome(CSS) is a systemic vascular disorder that has an unknown cause with multiorgan involvement and diverse presentations. The three main histologically distinct phases were necrotizing vasculitis, tissue eosinophilia and extravascular granulomas. A diagnosis of CSS can be made on four or more of the following six criteria : 1) asthma, 2) peripheral eosinophilia >10% on the differential leukocyte count, 3) mononeuropathy (including multiple) or polyneuropathy, 4) paranasal sinus abnormalities, 5) nonfixed pulmonary infiltrates and 6) biopsy evidence of extravascular eosinophils in the skin, the nerves, or the lungs. CSS has a good prognosis with systemic steroid therapy. The 5 year survival is approximately 70%. We experienced a 66-year-old man who presented with cough, sputum, edema and numbness in both legs. He presented with all of the 6 CSS criteria. A nerve and muscle biopsy confirmed the diagnosis. Here, we report this case with a review of the relevant literatures.

• Genomics & Informatics
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• 제21권2호
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• pp.18.1-18.11
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• 2023

Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell-derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55⁺) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.

• Tuberculosis and Respiratory Diseases
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• 제60권5호
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• pp.516-522
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• 2006

Background : In contrast to tuberculous pleurisy, tuberculous empyema is a chronic active infectious disease of the pleural cavity that is frequently accompanied by cavitary or advanced pulmonary lesions. The condition requires long-term anti-tuberculous medication with external drainage. The clinical features and treatment outcome of tuberculous empyema are unclear despite the high prevalence of tuberculosis in Korea. Methods : From January 1991 through April 2004, 17 patients diagnosed with tuberculous empyema in Kyungpook National University Hospital were enrolled in this study. Their medical records and chest radiographs were reviewed. Results : Twelve patients(71%) had a history of tuberculosis and six of the 12 patients were under current anti-tuberculous medication. Productive cough, fever, and dyspnea were the main complaints. There was no predominance between the right and left lungs. Nine patients(53%) had far-advanced pulmonary tuberculosis, two(12%) had a cavitary lesion, and seven(41%) had a pyopneumothorax on the chest radiograph. All eight cases in whom the data of pleural fluid WBC differential count was available showed polymorphonuclear leukocyte predominance. Eight patients(47%) had other bacterial infections as well. The overall rates of a positive sputum AFB smear and culture for M. tuberculosis were 71% and 64%, respectively. The positive AFB smear and culture rates for M. tuberculosis from the pleural fluid were 33% and 36%, respectively. Twelve of the 16 patients(75%) were treated successfully. Three underwent additional surgical intervention. Two patients (12%) died during treatment. Conclusion : Tuberculous empyema is frequently accompanied by advanced pulmonary lesions, and polymorphonuclear leukocytes are predominant in the pleural fluid. Other accompanying bacterial infections in the pleural cavity are also common in tuberculous empyema patients. Therefore, tuberculous empyema should be considered in differential diagnosis of patients with polymorphonuclear leukocyte-predominant pleural effusion. In addition, more active effort will be needed to achieve a bacteriological diagnosis in the pleural fluid.

• Tuberculosis and Respiratory Diseases
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• 제59권4호
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• pp.361-367
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• 2005

Background : Differential diagnosis of lymphocytic pleural effusion is difficult even with many laboratory findings. Nitric oxide(NO) level is higher in the sputum or exhaled breath of patients with active pulmonary tuberculosis than in those without tuberculosis. In addition, there are some reports about the increased level of NO metabolites in body fluids of cancer patients. However, there is no data on the NO levels in the pleural fluid of patients with tuberculous pleurisy. Method : The serum and pleural fluid NO in the patients with acute lymphocytic pleural effusion were analyzed. Results : Of total 27 patients, there were 14 males and average age of patients was 48 years. The final diagnosis was tuberculous pleurisy in 17 cases and malignant pleural effusion in 10. The pleural fluid NO level was $540.1{\pm}116.4{\mu}mol$ in the tuberculous pleurisy patients and $383.7{\pm}71.0{\mu}mol$ in the malignant pleural effusion patients. The serum NO level was $624.7{\pm}142.0{\mu}mol$ in tuberculous pleurisy patients and $394.4{\pm}90.4{\mu}mol$ in malignant pleural effusion patients. There was no significant difference in the serum and pleural fluid NO level between the two groups. The NO level in the pleural fluid showed a significant correlations with the pleural fluid neutrophil count, the pleural fluid/serum protein ratio, and pleural fluid/serum albumin ratio (p<0.05 in each). The protein concentration, leukocyte and lymphocyte count in the pleural fluid were significantly higher in the tuberculous pleurisy patients than the malignant pleural effusion patients (p<0.05 in each). Conclusion : NO is not a suitable marker for a differential diagnosis of lymphocytic pleural effusion. However, the NO level in the pleural fluid might be associated with the neutrophil recruitment and protein leakage in the pleural space.

• Journal of Life Science
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• 제16권5호
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• pp.840-849
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• 2006

Severe brain injuries induced by toxin pose one of the most important problems on our health care because of their high morbidity and mortality, are implicated to leucocyte infiltration more premature or immature brain than mature brain. Chemokines are the induction meditators for infiltration of inflammatory cells to the inflammation sites. In order to study the mechanism of leucocyte infiltration, the expression of several chemokines, MCP-1, $MIP-1{\alpha}$ and MIP-2 was studied in lipopolysaccharide(LPS)-stimulated neonatal and adult brain. One week old Sprague-Dawley rats or adult male rats weighing 300-350 g were used for the experiment. After anesthetization, $1\;{\mu}l$ LPS (0.5 mg/ml) subsequently was injected in the right caudate nucleus of the brain with stereotaxic frame. Animals were sacrificed at 6 hours, 24 hours, and 72 hours after injection. The present study was carried out using RT-PCR for the mRNA and immunohistochemistry for the expression of the proteins. In the neonatal rat brain, prominent interstitial edema with significant accumulation of leukocytes was detected at 24 and 72 hours after LPS injection. A semiquantitative analysis of RT-PCR revealed that the MCP-1, $MIP-1{\alpha}$, and MIP-2 mRNA expression peaked at 24 hours in neonatal and adult rat brain. Neonatal rats showed about 2.6, 1.4, and 1.2 times more expression of the MCP-1, $MIP-1{\alpha}$, and MIP-2 than that of the adult rats in the brain tissue. Immunohistochemical analysis also showed that MCP-1 immunoreactivity was paralleled with the RT-PCR results. MCP-1 protein was significantly detected at 24 and 72 hours in the brain parenchyma. $MIP-1{\alpha}$protein was highly expressed at 24 hours. The results of leukocyte infiltration in H&E stain was parallelled with that of the immunohistochemistry. Chemokine proteins were markedly detected at 24 hours after injection of LPS and neutrophil influx into intraparenchymal was prominent at 24 hours. These results suggest that the leukocyte infiltration in the intracranial infection may be controlled by mechanisms influenced by chemokine producing cells in the central nervous system such as microglia, astrocyte and endothelial cell.

• Asian-Australasian Journal of Animal Sciences
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• 제23권1호
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• pp.52-60
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• 2010

This experiment was conducted on 60 Hanwoo calves comprising five feed additive groups, with 12 calves in each group, to determine the effects of additives at pre- and post-weaning on growth performance and blood profile. The groups were control, antibiotic (Neomycin 110 ppm), illite (2%), fermented green tea probiotics (FGTP, 0.5%), and mixed additives (FGTP 0.25%, illite 1% and licorice 0.1%). The calves were offered experimental pellet feeds ad libitum and after one month were supplied with imported timothy hay. They moved freely within the group and suckled their mother' milk during the pre-weaning stage (birth to 3 months) and were separated from their dam during the post-weaning stage (4-5 months). During the pre-weaning stage, the highest average daily gain (ADG) was recorded in the antibiotic- and mixed additive-fed groups followed by FGTP, control and illite groups. In the post-weaning stage, significantly higher total weight gain and ADG were recorded in both the FGTP and mixed additive groups compared to the other groups (p<0.05). Feed efficiency of mixed additive- and illite-fed calves were almost similar with antibiotic-fed calves compared to the other two groups, but the ADG was lowest in illite-fed calves during the pre-weaning stage. In contrast, post-weaning calves fed FGTP and mixed additives showed better feed efficiency. The values of hematological indices, differential leukocyte count, blood proteins and immunoglobulin among the additive-fed calves were not significantly different (p>0.05), although hemoglobin and hematocrit values were lower in FGTP compared to control, but similar in mixed additive and antibiotic groups. These results indicate no detrimental effects of feed additives on the blood profile of calves at both pre- and post-weaning age. Serum albumin in post-weaning calves of all feed additive groups were similar but significantly lower (p<0.05) than in the control group. Post-weaning, IgM was significantly lower (p<0.05) in illite-fed calves compared to other treatment groups, but there was no difference at pre-weaning. Considering all factors, the mixed feed additives and FGTP can be the replacement feed formula for antibiotic for Hanwoo beef calf production, especially when used post- weaning.