• Neonatal Medicine
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• v.17 no.2
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• pp.181-192
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• 2010

Purpose: Current studies have demonstrated the neuroprotective effects of dizocilpine (MK-801) in many animal models of brain injury, including hypoxic-ischemic (HI) encephlopathy, trauma and excitotoxicity, but limited data are available for those during the neonatal periods. Here we investigated whether dizocilpine can protect the developing rat brain from HI injury via anti-apoptosis. Methods: In an in vitro model, embryonic cortical neuronal cell culture of Sprague-Dawley (SD) rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with dizocilpine (HD). The N group was prepared in 5% $CO_2$ incubators and the other groups were placed in 1% $O_2$ incubators (94% N2, 5% $CO_2$) for 16 hours. In an in vivo model, left carotid artery ligation was done in 7-day-old SD rat pups. The animals were divided into six groups; hypoxia (N), hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with dizocilpine (HD). Hypoxia was made by exposure to a 2 hour period of hypoxic incubator (92% N2, 8% $O_2$). Results: In the in vitvo and in vivo models, the expressions of Bcl-2 in the hypoxia groups were reduced compared to the normoxia group. whereas those in the dizocilpine-treated group were increased compared to the hypoxia group. However. the expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were revealed reversely. Conclusion: Dizocilpine has neuroprotective property over perinatal HI brain injury via anti-apoptosis.

• Korean Journal of Environmental Biology
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• v.38 no.2
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• pp.271-277
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• 2020

Toxicities to many organs caused by humidifier disinfectants have been reported. Recently, humidifier disinfectants have been reported to cause cardiovascular, embryonic, and hepatic toxicities. This study was designed to investigate the toxic mechanism of humidifier disinfectants and compare toxicity in a cellular model and a zebrafish animal model. Because brain toxicity and skin toxicity have been less studied than other organs, we evaluated toxicity in a human dermal cell line and zebrafish under various concentrations of humidifier disinfectants that included polyhexamethyleneguanidine phosphate (PHMG), oligo-[2-(2-ethoxy)-ethoxyethyl-guanidinium-chloride] (PGH) and methylchloroisothiazolinone/methylisothiazolinone (CMIT/MIT). A human dermal fibroblast cell line was treated with disinfectants (0, 2, 4, 6, 8, and 16 mg L^-1) to compare their cytotoxicity. The fewest PHMG-treated cells survived (up to 33%), while 49% and 40% of the PGH- and CMIT/MIT-treated cells, respectively, survived. The quantification of oxidized species in the media revealed that the PHMG-treated cells had the highest MDA content of around 28 nM, while the PGH- and CMIT/MIT-treated cells had 13 and 21 nM MDA, respectively. As for brain toxicity, treatment of the zebrafish tank water with CMIT/MIT (final 40 mg L^-1) for 30 min resulted in a 17-fold higher production of reactive oxygen species (ROS) than in the control. Treatment with PGH or PHMG (final 40 mg L^-1) resulted in 15- and 11-fold higher production, respectively. The humidifier disinfectants (PHMG, PGH, and CMIT/MIT) showed severe dermal cell toxicity and brain toxicity. These toxicities may be relevant factors in understanding why some children have language disorders, motor delays, and developmental delays from exposure to humidifier disinfectants.

• Journal of Chest Surgery
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• v.39 no.7 s.264
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• pp.520-526
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• 2006

Background: The clinical application of cryosurgery the management of lung cancer is limited because the response of lung at low temperature is not well understood. The purpose of this study is to investigate the response of the pulmonary tissue at extreme low temperature. Material and Method: After general anesthesia the lungs of twelve Mongrel dogs were exposed through the fifth intercostal space. Cryosurgical probe (Galil Medical, Israel) with diameter 2.4 mm were placed into the lung 20 mm deep and four thermosensors (T1-4) were inserted at 5 mm intervals from the cryoprobe. The animals were divided into group A (n=8) and group B (n=4). In group A the temperature of the cryoprobe was decreased to $-120^{\circ}C$ and maintained for 20 minutes. After 5 minutes of thawing this freezing cycle was repeated. In group B same freezing temperature was maintained for 40 minutes continuously without thawing. The lungs were removed for microscopic examination on f day after the cryosurgery. In four dogs of the group A the lung was removed 7 days after the cryosurgery to examine the delayed changes of the cryoinjured tissue, Result: In group A the temperatures of T1 and T2 were decreased to the $4.1{\pm}11^{\circ}C\;and\;31{\pm}5^{\circ}C$ respectively in first freezing cycle. During the second freezing period the temperatures of the thermosensors were decreased lower than the temperature during the first freezing time: $T1\;-56.4{\pm}9.7^{\circ}C,\;T2\;-18.4{\pm}14.2^{\circ}C,\;T3\;18.5{\pm}9.4^{\circ}C\;and\;T4\;35.9{\pm}2.9^{\circ}C$. Comparing the temperature-distance graph of the first cycle to that of the second cycle revealed the changes of temperature-distance relationship from curve to linear. In group B the temperatures of thermosensors were decreased and maintained throughout the 40 minutes of freezing. On light microscopy, hemorrhagic infarctions of diameter $18.6{\pm}6.4mm$ were found in group A. The infarction size was $14{\pm}3mm$ in group B. No viable cell was found within the infarction area. Conclusion: The conductivity of the lung is changed during the thawing period resulting further decrease in temperature of the lung tissue during the second freezing cycle and expanding the area of cell destruction.

• Neonatal Medicine
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• v.18 no.1
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• pp.59-69
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• 2011

Purpose: Current studies have demonstrated the neuroprotective effects of 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) in many animal models of brain injury, including hypoxic-ischemic (HI) encephlopathy, trauma and excitotoxicity, but limited data are available for those during the neonatal periods. Here we investigated whether CNQX can protect the developing rat brain from HI injury via mediation of nitric oxide synthase. Methods: In an in vivo model, left carotid artery ligation was done in 7-day-old Sprague-Dawley (SD) rat pups. The animals were divided into six groups; normoxia (N), hypoxia (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), HO treated with vehicle (HV), and HO treated with CNQX at a dose of 10 mg/kg (HC). Hypoxia was made by exposure to a 2 hr period in the hypoxic chamber (92% $N_2$, 8% $O_2$). In an in vitro model, embryonic cortical neuronal cell culture of SD rats at 18-day gestation was done. The cultured cells were divided into three groups: normoxia (N), hypoxia (H), and hypoxia treated with CNQX (HC). The N group was prepared in 5% $CO_2$ incubators and the other groups were placed in 1% $O_2$) incubators (94% $N_2$, 5% $CO_2$) for 16 hr. Results: In the in vitvo and in vivo models, the expressions of iNOS and eNOS were reduced in the hypoxia group when compared to the normoxia group, whereas they were increased in the CNQX-treated group compared to the hypoxia group. In contrast, the expression of nNOS was showed reversely. Conclusion: CNQX has neuroprotective property over perinatal HI brain injury via mediation of nitric oxide synthase.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.19 no.3
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• pp.219-226
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• 1986

To confirm the application of a newer in vitro assays to determining the nutritional value of marine crustaceans (mainly shrimps and crabs), which have been considered to be highly nutritive depending on their levels of the essential amino acids and digestibility, their C-PERs and DC-PERs were determined and studied the factors influencing their in vitro results. Four species of seawater shrimps and 2 species of seawater crabs were used in this experiment. The in vitro digestibilities showed $83{\sim}86\%$ for raw shrimps and the trypsin indigestibile substrate content (TIS) was ranged from 1.32 to 3.33 mg/g solid expressed quantitatively as mg of purified soybean trypsin inhibitor. The smaller size of shrimps revealed a greater in vitro digestibility and a lower contents of TIS. It was noted that the in vitro digestibility of raw blue crab meat was around $85\%$ while boiled tenner crab meat showed $86\%$ or above, and the leg meat had the greatest in vitro digestibility in the various parts of crab meats. The poor in vitro digestibilities for shrimp's and crab's meat, compared with that of the other seafoods as noted in previous reports, suggest that the drop in pH, due to the change in their freshness during harvesting and frozen storage, resulted in underestimating their digestibilities using four-enzyme digestion technique. The lysine contents in all samples were higher than that of ANRC casein but they contained a slightly lower sulfur-containing amino acids than those in ANRC casein. But the other EAA, such as valine, tyrosine and phenylalanine, were found to be a half as little as that in casein and played a key-factor in calculation of C-PER or DC-PER. It was observed that the value of C-PER and DC-PER for all samples ranged from 2.1 to 2.4, and the predicted digestibilities showed $90\%$ or above in all samples. It was a different results from the fact that the animal proteins bear a higher values and predicted digestibilities than those of C-PER values. The lack of correlation between C-PER and DC-PER values is attributable to the fact that the lower content of valine, tyrosine and phenylalanine, and drop in pH owing to the changes of freshness in marine crustacea proteins. Therefore, if a newer in vitro digestion technique-which are taken into account the pH drop before digestion, TIS content and released free amino acids and/or peptides-developed, C-PER assays can provide more advantages in assessing the protein nutritional value of marine crustacea than any other in vitro assays.

• Journal of Life Science
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• v.24 no.12
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• pp.1339-1344
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• 2014

Inflammatory bowel disease is an immune disorder associated with chronic mucosal inflammation and severe ulceration in the gastrointestinal tract. Antibodies against proinflammatory cytokines, including TNF${\alpha}$, are currently used as promising therapeutic agents against the disease. Stabilization of the transcript is a crucial post-transcriptional process in the expression of proinflammatory cytokines. In the present study, we assessed the expression and histological distribution of the HuR protein, an important transcript stabilizer, in tissues from experimental animals and patients with Crohn's disease. The total and cytosolic levels of the HuR protein were enhanced in the intestinal epithelia from dextran sodium sulfate (DSS)-treated mice compared to those in control tissues from normal mice. Moreover, the expression of HuR was very high only in the mucosal and glandular epithelium, and the relative localization of the protein was sequestered in the lower parts of the villus during the DSS insult. The expression of HuR was significantly higher in mucosal lesions than in normal-looking areas. Consistent with the data from the animal model, the expression of HuR was confined to the mucosal and glandular epithelium. These results suggest that HuR may contribute to the post-transcriptional regulation of proinflammatory genes during early mucosal insults. More mechanistic investigations are warranted to determine the potential use of HuR as a predictive biomarker or a promising target against IBD.

• Journal of Embryo Transfer
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• v.20 no.3
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• pp.255-269
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• 2005

This study was aimed to investigate genetic relationships, variables, and correlations between economic traits and metabolic materials in serum components according to bleeding periods and breeding locations for the castrated and not castrated Hanwoo cattle at National Livestock Research Institute. Analysis of variance for serum hormones and metabolic materials showed significant differences by breeding locations except for testosterone and globulin. Statistical differences for serum components were detected by birth year except for cortisol, total protein, globulin and creatinine, and by castration except for total protein and BUN. All the serum components were tended to have sire effects except for testosterone resulting in some degree of additive gene actions. Breeding locations showed statistical significances for carcass weight and back fat thickness, but not in carcass rate, KPH, live weight and transportation weight loss. Effects of breeding locations and castration were significant for all weight measurement periods except for 9 month and 6 month, respectively. A significant sire effect was observed in all weight measurements. Least squared means for concentration of serum components by breeding year, season and castration were not significant. High concentration of cortisol, creatinine and triglyceride and low concentration of IGF-1 and glucose were detected in castrated cattle. Concentration of testosterone with castrated cattle was $5.2\%$ corresponding to non castrated cattle. Estimation of heritabilities of serum components using a sire model with restricted maximum likelihood were ranged 0.07 to 0.58. High heritabilities were estimated for total protein, albumin, globulin, cortisol, creatinine and BUN were 0.53, 0.54, 0.42, 0.45, 0.58 and 0.54, respectively. Low heritabilities were estimated fur calcium, testosterone and IGF-1 for 0.07, 0.15 and 0.12, respectively. Heritabilities for carcass weight, back fat thickness, meat yield index, KPH, and IMF were estimated as 0.39, 0.45, 0.30 0.13, and 0.93. Heritabilities of weights on 18, 12, 9, 6, and 24 month were estimated as 0.78, 0.76, 0.62, 0.58 and 0.58. Estimated heritabilities for average daily gain on 6${\~}$2, 12${\~}$18, and 18${\~}$24 month were 0.80, 0.75 and 0.19, respectively.

• Neonatal Medicine
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• v.16 no.2
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• pp.221-233
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• 2009

Purpose: Erythropoietin (EPO) has neuroprotective effects in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity. Current studies have demonstrated the neuroprotective effects of EPO, but limited data are available for the neonatal periods. Here in we investigated whether recombinant human EPO (rHuEPO) can protect the developing rat brain from HI injury via modulation of NMDA receptors. Methods: In an in vitro model, embryonic cortical neuronal cell cultures from Sprague-Dawley (SD) rats at 19-days gestation were established. The cultured cells were divided into five groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated (H+E1, H+ E10, and H+E100) groups. To estimate cell viability and growth, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was done. In an in vivo model, left carotid artery ligation was performed on 7-day-old SD rat pups. The animals were divided into six groups; normoxia control (NC), normoxia Sham-operated (NS), hypoxia-ischemia only (H), hypoxia-ischemia+vehicle (HV), hypoxia-ischemia+rHuEPO before a HI injury (HE-B), and hypoxia-ischemia+rHuEPO after a HI injury (HE-A). The morphologic changes following brain injuries were noted using hematoxylin and eosin (H/E) staining. Real-time PCR using primers of subunits of NMDA receptors (NR1, NR2A, NR2B, NR2C and NR2D) mRNA were performed. Results: Cell viability in the H group was decreased to less than 60% of that in the N group. In the H+E1 and H+E10 groups, cell viability was increased to >80% of the N group, but cell viability in the H+E100 group did not recover. The percentage of the left hemisphere area compared the to the right hemisphere area were 98.9% in the NC group, 99.1% in the NS group, 57.1% in the H group, 57.0% in the HV group, 87.6% in the HE-B group, and 91.6% in the HE-A group. Real-time PCR analysis of the expressions of subunits of NMDA receptors mRNAs in the in vitro and in vivo neonatal HI brain injuries generally revealed that the expression in the H group was decreased compared to the N group and the expressions in the rHuEPO-treated groups was increased compared to the H group. Conclusion: rHuEPO has neuroprotective property in perinatal HI brain injury via modulation of N-methyl-D-aspartate receptors.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.3
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• pp.177-185
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• 2006

Purpose: Purpose of this study is to synthesize $^{99m}Tc$-labeled transferrin for injection imaging and to compare it with $^{67}Ga$-titrate for the detection of infectious foci. Materials and methods: Succinimidyl 6-hydrazino-nicotinate hydrochloride-chitosan-transferrin (Transferrin) was synthesized and radiolabeled with $^{99m}Tc$. Labeling efficiencies of $^{99m}Tc$-Transferrin were determined at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 8 hr. Biodistribution and imaging studies with $^{99m}Tc$-Transferrin and $^{67}Ga$-citrate were performed in a rat abscess model induced with approximately $2{\times}10^8$ colony forming unit of Staphylococcus aureus ATCC 25923. Results: Successful synthesis of Transferrin was confirmed by mass spectrometry. Labeling efficiency of $^{99m}Tc$-Transferrin was $96.2{\pm}0.7%,\;96.4{\pm}0.5%,\;96.6{\pm}1.0%,\;96.9{\pm}0.5%,\;97.0{\pm}0.7%\;and\;95.5{\pm}0.7%$ at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 8 hr, respectively. The injected dose per tissue gram of $^{99m}Tc$-Transferrin was $0.18{\pm}0.01\;and\;0.18{\pm}0.01$ in the lesion and $0.05{\pm}0.01\;and\;0.04{\pm}0.01$ in the normal muscle, and lesion-to-normal muscle uptake ratio was $3.7{\pm}0.6\;and\;4.7{\pm}0.4$ at 30 min and 3 hr, respectively. On image, lesion-to-background ratio of $^{99m}Tc$-Transferrin was $2.18{\pm}0.03,\;2.56{\pm}0.11,\;3.08{\pm}0.18,\;3.77{\pm}0.17,\;4.70{\pm}0.45\;and\;5.59{\pm}0.40$ at 10 min, 30 min, 1 hr, 2 hr, 4 hr and 10 hr and those of $^{67}Ga$-citrate was $3.06{\pm}0.84,\;4.12{\pm}0.54\;and\;4.55{\pm}0.74 $ at 2 hr, 24 hr and 48 hr, respectively. Conclusion: Transferrin is successfully labeled with $^{99m}Tc$, and its labeling efficiency was higher than 95% and stable for 8 hours. $^{99m}Tc$-Transferrin scintigraphy showed higher image quality in shorter time compared to $^{67}Ga$-citrate image. $^{99m}Tc$-transferrin is supposed to be useful in the detection of the infectious foci.

• Journal of Biomedical Engineering Research
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• v.25 no.5
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• pp.421-430
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• 2004

Clinically, it is almost impossible for a physician to distinguish subtle changes of frequency spectrum by using a stethoscope alone especially in the early stage of thrombus formation. Considering that reliability of mechanical valve is paramount because the failure might end up with patient death, early detection of valve thrombus using noninvasive technique is important. Thus the study was designed to provide a tool for early noninvasive detection of valve thrombus by observing shift of frequency spectrum of acoustic signals with computer aid diagnosis system. A thrombus model was constructed on commercialized mechanical valves using polyurethane or silicon. Polyurethane coating was made on the valve surface, and silicon coating on the sewing ring of the valve. To simulate pannus formation, which is fibrous tissue overgrowth obstructing the valve orifice, the degree of silicone coating on the sewing ring varied from 20％, 40％, 60％ of orifice obstruction. In experiment system, acoustic signals from the valve were measured using microphone and amplifier. The microphone was attached to a coupler to remove environmental noise. Acoustic signals were sampled by an AID converter, frequency spectrum was obtained by the algorithm of spectral analysis. To quantitatively distinguish the frequency peak of the normal valve from that of the thrombosed valves, analysis using a neural network was employed. A return map was applied to evaluate continuous monitoring of valve motion cycle. The in-vivo data also obtained from animals with mechanical valves in circulatory devices as well as patients with mechanical valve replacement for 1 year or longer before. Each spectrum wave showed a primary and secondary peak. The secondary peak showed changes according to the thrombus model. In the mock as well as the animal study, both spectral analysis and 3-layer neural network could differentiate the normal valves from thrombosed valves. In the human study, one of 10 patients showed shift of frequency spectrum, however the presence of valve thrombus was yet to be determined. Conclusively, acoustic signal measurement can be of suggestive as a noninvasive diagnostic tool in early detection of mechanical valve thrombosis.