• Toxicological Research
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• v.22 no.2
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• pp.95-102
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• 2006

Exposure to soluble nickel compound produces toxic effects on immune system, but the mechanism of action remains to be elucidated. Differential gene expression was studied to understand the potential molecular mechanism responsible for acute toxicity induced by nickel acetate in spleen cells. We exposed mouse spleen cells to nickel acetate with a nontoxic dose ($40{\mu}M$) and then extracted total RNA at 6 h and 12 h after exposure. The RNA was hybridized onto 10K mouse oligonucleotide microarrays, and data were analyzed using GeneSpring 7.1. Nickel had a modest effects on expression of many genes, in the range of 1.3-3 fold. The expression profile showed time-dependent changes in expression levels of differentially expressed genes, including some important genes related to cell cycle, apoptosis and DNA repair. In hierarchical cluster analysis of duplicate experiments, 111 genes were screened out. Out of these, 44 genes showing time- dependent up-regulation (>1.5 fold) and 38 genes showing down-regulation (>1.5 fold) at all time points were chosen for further analysis. The change in the expression of three genes (GPX1, GADD45B and FAIM) after nickel treatment was validated using RT-PCR. As a rule, a number of genes appear to be coordinately regulated between cell survival and cell death from nickel toxicity. In conclusion, changes in the gene profile in the spleen after nickel treatment are complex and genes with diverse functions are modulated. These findings will be contributed to the understanding of the complicated biological effects of nickel.

• Toxicological Research
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• v.16 no.4
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• pp.302-309
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• 2000

The purpose of this study is to investigate toxic effects of iso-butylalcohol (iBA) in Sprague-Dawley (SD) rats under the exposure of 6 hours a day, 5 days a week for 13 weeks by inhalation, and to evaluate the occupational safety of iBA in comparison with the permissible exposure level (PEL) stipulated by the Occupational Safety and Health Administration (OSHA). iBA did not induce any abnormal changes from the aspects of clinical signs, feed consumption, ophthalmic test, urinalysis, hematology and blood chemistry during and at the terminal of the inhalation toxicity tests. We did not find any abnormal findings in the gross and microscopic observations due to the inhalation of iBA. There was no alteration in relative organ weights by the inhalation of iBA. No observed adverse effect level (NOAEL) of iBA was considered to be more than 3,000 ppm in rats under the inhalation of 6 hours a day, 5 days a week for 13 weeks. Fifty ppm of iBA, the PEL regulated by OSHA, is too conservative for working places. As iBA showed no abnormal observations in all the experimental parameters at any concentration under this experimental condition, we suggest that 150 ppm is safe enough for the PEL of iBA in the working areas, even taking into onsideration that OSHA lowered the PEL to 50 ppm for fear of the probable risk of its skin irritation.

• Reproductive and Developmental Biology
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• v.33 no.1
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• pp.55-61
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• 2009

The epididymis in the male reproductive tract is the site where spermatozoa produced from the testis become mature. The epididymis is divided into 4 different segments, initial segment and caput, corpus, and caudal epididymis, depending upon functional and morphological features. Aquaporins (Aqps) are water channel molecules, which are present in the epididymis and play a major role in removal of epididymal water, resulting in creation of microenvironment for sperm maturation and concentration of sperms. Nandrolone decanoate (ND) is a synthetic anabolic-androgenic steroid, which is used to treat clinical diseases and improve physical ability and appearance. Even though it is well determined that the ND causes the male infertility by affecting the testis, little is known the effect of the ND on the epididymis. The present study was focused to examine the effect of ND at different treatment doses and periods on expression of Aqp1 and Aqp9 genes in the epididymis of pubertal rats. Results showed that mRNA expression of Aqp1 and Aqp9 genes among the parts of the epididymis was differentially regulated by ND treatment doses. In addition, treatment periods of ND caused differential expression of Aqp1 and Aqp9 mRNAs among segments of the epididymis. Therefore, it is believed that male infertility induced by ND could be resulted not only from malfunction of the testis but also from aberrant gene expression of Aqp1 and Aqp9 in the epididymis.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.5
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• pp.754-760
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• 2007

The effect of dehydrated food waste product (DFWP) inclusion in diets of Taiwan native chickens on the growth performance, carcass traits, clinical blood chemistry and nutrient digestibility was investigated with 320 male Taishi Native Chickens (Taishi No. 13). They were randomly allocated into four levels of DFWP inclusion (0, 5, 10, or 20%) treatment. Each treatment had 80 chickens with four replicates. At 15 weeks of age, 8 chickens were selected from each group for the nutrient digestibility trial. The results showed that body weight gain during the 0 to 4 week period decreased as the feed intake and feed conversion rate (FCR) increased linearly with increasing level of DFWP inclusion. During the 4 to 8 week period, greater body weight gains were recorded for the birds on the 5% DFWP inclusion level than for the control (p<0.05). During 8 to16 weeks, the feed intake and FCR increased linearly (p<0.05). Interestingly too, results of the carcass analysis showed that DFWP inclusion up to 20% in the diet significantly decreased the relative abdominal fat weight but increased the relative proventriculus and gizzard weights of the birds. However, other carcass parameters, meat quality and sensory scores were not significantly influenced by the dietary DFWP inclusion levels (p>0.05). Higher serum aspartate aminotransferase, ${\gamma}$-glutamyltransferase activity and crude protein digestibility, and lower gross energy digestibility were observed in the 20% DFWP group compared to the control (p<0.05). Dietary DFWP inclusion was inappropriate during the 0 to 4 week period. During 4 to 8 weeks, there was no adverse effect on chicken performance in the 20% group. There was no disadvantage on carcass properties and in the meat panel test. This result would not affect consumer determination.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.107-115
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• 2017

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the "fit for purpose" application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in $C_{max}$ of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.

• Journal of Microbiology and Biotechnology
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• v.24 no.10
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• pp.1346-1353
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• 2014

In the present study, an anthraquinone derivative, questinol was successfully isolated from the broth extract of the marine-derived fungus Eurotium amstelodami for the first time. The structure of questinol was determined based on the analysis of the MS and NMR spectral data as well as comparison of those data with the published data. Moreover, the anti-inflammatory effect of questinol in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was investigated. The results showed that questinol did not exhibit cytotoxicity in LPS-stimulated RAW 264.7 cells up to $200{\mu}M$. Questinol could significantly inhibit NO and $PGE_2$ production at indicated concentrations. Questinol was also found to inhibit the production of pro-inflammatory cytokines, including TNF-${\alpha}$, IL-1${\beta}$, and IL-6. Furthermore, the western blot analysis showed that questinol suppressed the expression level of iNOS in a dose-dependent manner. However, questinol could slightly inhibit the expression of COX-2 at the concentration of $200{\mu}M$. Therefore, our study suggests that questinol might be selected as a promising agent for the prevention and therapy of inflammatory disease.

• Journal of Veterinary Clinics
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• v.26 no.1
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• pp.54-57
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• 2009

A 5-month-old intact female Siberian Husky dog was presented for evaluation of severely enlarged maxilla. Abnormalities in CBC, serum chemistry and urinalysis indicated purulent inflammation and renal failure. Cytologic examination of the swollen maxilla showed a mixed population of multinucleated giant cells and round to polygonal to spindle shaped cells either individualized or aggregated. Both type of cells showed moderate anisokaryosis, and anisocytosis, prominent nucleolus or multiple nucleoli, and coarse chromatin. On histopathology maxilla and turbinate were diffusely expanded and replaced by variably dense fibrous connective tissue, and the kidneys showed changes consistent with renal dysplasia. Based on these findings, the diagnosis of fibrous osteodystrophy due to renal dysplasia and fibrosis was made. Despite the supportive care, the dog continued to decline and was euthanized.

• Journal of Veterinary Clinics
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• v.31 no.4
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• pp.316-318
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• 2014

A 3-year-old castrated male domestic shorthair cat was presented with a chief complaint of sudden onset of intermittent seizures occurring five times a day. Physical examination revealed the copper colored iris and loss of menace response at both eyes. Abnormalities of blood works and serum chemistry revealed mild erythrocytosis, severe microcytosis, and threefold increase in ALT activity. Additional liver function tests results were increased bile acid and $NH_3$ concentration. Radiographic study revealed multifocal nodules of the liver and an extrahepatic shunt was noted by ultraonography, which was confirmed by computed tomography as multiple extrahepatic shunts. The cat was scheduled for surgery applying an ameloid ring to occlude the shunt gradually. Diazepam and lactulose were instituted to the patient. However, clinical signs worsened despite medical management with shortened interval of seizures and the patient died due to cardiac arrest.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3753-3757
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• 2016

Background: The aim of this study was to investigate whether electrochemotherapy is a clinically and cost-effective treatment option against skin tumors. Materials and Methods: We performed an analysis of the current literature based on database searches in PubMed/MEDLINE and we included articles till July 2012. Terms used for the search were 'electrochemotherapy', 'skin cancer', 'recurrence', and 'cutaneous and subcutaneous tumors'. Only papers published in English were included. In addition, we performed an analysis of the cost effectiveness of the method. Results: The combination of physics and chemistry is the foundation for electrochemotherapy and its efficacy, independent of the tumor histology. Clinical data showed that ECT is well tolerated and can be used in difficult cases without other available treatment options. The analysis also showed that the treatment is feasible and cost-effective. Conclusions: Electrochemotherapy is a clinically efficient safe and cost-effective treatment and clinicians should not hesitate to use it as alternative therapeutic modality or as palliative treatment.

• Journal of Periodontal and Implant Science
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• v.47 no.4
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• pp.194-210
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• 2017

Purpose: The aim of the present study was to evaluate the healing of post-extraction sockets following alveolar ridge preservation clinically, radiologically, and histologically. Methods: Overall, 7 extraction sockets in 7 patients were grafted with demineralised bovine bone mineral and covered with a porcine-derived non-crosslinked collagen matrix (CM). Soft tissue healing was clinically evaluated on the basis of a specific healing index. Horizontal and vertical ridge dimensional changes were assessed clinically and radiographically at baseline and 6 months after implant placement. For histological and histomorphometric analysis, bone biopsies were harvested from the augmented sites during implant surgery 6 months after the socket preservation procedure. Results: Clinically, healing proceeded uneventfully in all the sockets. A trend towards reduced horizontal and vertical socket dimensions was observed from baseline to the final examination. The mean width and height of resorption were 1.21 mm (P=0.005) and 0.46 mm (P=0.004), respectively. Histologically, residual xenograft particles ($31.97%{\pm}3.52%$) were surrounded by either newly formed bone ($16.02%{\pm}7.06%$) or connective tissue ($50.67%{\pm}8.42%$) without fibrous encapsulation. The CM underwent a physiological substitution process in favour of well-vascularised collagen-rich connective tissue. Conclusions: Socket preservation using demineralised bovine bone mineral in combination with CM provided stable dimensional changes of the alveolar ridge associated with good reepithelialisation of the soft tissues during a 6-month healing period.