• Toxicological Research
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• 제11권2호
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• pp.315-327
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• 1995

Diverse neurotoxic insults result in proliferation and hypertrophy of astrocytes, a subtype of glia in central nervous system. The hallmark of this response, often terms "reactive gliosis", is the enhanced expression of the major intermediate filament protein of castrocytes, glial fibrillary acidic protein (GFAP). These changes in the astrocytes suggest that GFAP may be a useful biochemical indicator of neurotoxicity. To investigate this possibility, we administered intra-peritoneally prototype nerotoxicants, metharnphetamine (MAP, 5 mg/kg), cocaine (30 mg/kg), N-buthyl benzenesulfonamide (NBBS, 300 mg/kg) and trimethytin (TMT, 8 mg/kg) to Wistar Rats and then assessed the effects of these agents on content of GFAP, which were determined by Sandwish ELISA and evaluated with neurotoxic symptoms, and quantitative changes of imrnunoreactivity of GFAP by light microscopic image analysis in specific regions. We found that assay of GFAP revealed time- and region-dependant patterns of neurotoxicity. The GFAP immunoreactivity of rat brain was increased in substantia nigra and hippocampus by MAP, NBBS and TMT; in roedial septal nucleus and nucleus accurnbens, it was also increased by RrBBS. Sandwich ELISA showed that GFAP levels of cerebrum in all groups on days 3 and 7 and that of brainstem(including cerebellum) in MAP, NBBS groups on day 1 and 3 were increased. A review of the background, design and results of these experiments are presented in this paper. Our findings indicate that GFAP is a sensitive and specific biomarker of neurotoxicity.otoxicity.

• 한국가금학회지
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• 제33권2호
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• pp.159-164
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• 2006

본 연구는 사료와 음수에 함유된 염분 수준이 육계 초기 병아리에 미치는 영향을 조사하기 위하여 실시하였다. 1일령 초생추(Hubbard)를 공시하여 14일 동안 시험을 수행하였다. 시험 1에서, 사료내 염분 함량은 0, 0.25, 0.5, 0.75, 1.0, 2.0, 3.0, 4.0%로 조절하여 8처리구 처리구당 3반복, 반복당 12수씩 총 288수에 급여하였고, 시험 2에서, 음수내 염분 함 량은 0, 0.1, 0.2, 0.5, 1.0%로 조절하여 5처리구 처리구당 3반복, 반복당 12수씩 총 180수에 공급하였다. 시험 1의 경우에, 사료 섭취량과 증체량은 사료내 염분 함량이 증가할수록 감소하는 경향이었다. 특히 4% 처리구에서 각각 481 g과 168 g으로 가장 낮았으며, 폐사율은 75%로 가장 높았다. 시험 2의 경우에는, 음수 1% 처리구에서 사료 섭취량과 증체량은 각각 427 g과 162 g이었고, 폐사율은 77.8%로 가장 높았다. 염 중독 증상을 나타낸 닭들은 갈증, 식욕부진, 기립불능, 졸림, 경련 등을 나타내었고, 부검 소견에서는 복수증, 심낭수종, 심비대, 각종 장기의 출혈 등이 나타났다. 이상의 결과로 육계 초기에서 사료내 염분 함량이 3%, 음수내 염분 함량은 1% 이상에서 뚜렷한 생산성의 저하는 물론 생리 해부학적인 염분중독 증상이 나타남을 알 수 있다.

• Asian-Australasian Journal of Animal Sciences
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• 제13권2호
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• pp.155-160
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• 2000

In order to understand the effects of sex or age on cellular characteristics of adipocytes from Hanwoo and sheep, samples were obtained from omental, subcutaneous, intermuscular and intramuscular adipose tissue depots of bulls, steers, heifers and cows in Hanwoo, and perirenal, omental and subcutaneous adipose tissues of fetal lambs, suckling lambs and wethers in sheep. In case of Hanwoo, mean diameter, surface area and volume of adipocytes from each depot were obtained by multisizer II (Coulter Co., UK). Osmium-fixed adipocytes were sized and counted using $560{\mu}m$ aperture. For samples obtained from sheep, cellularity was measured by using microscope and MCV program of Texas Instrument. Bulls had less subcutaneous and kidney fat than steers even though their slaughter and carcass weight were heavier. The amounts of fat from cows were greater in subcutaneous, kidney and internal organs than heifers. Steers had larger adipocytes in subcutaneous, intermuscular and intramuscular adipose tissues than bulls, although the differences were significant only for the subcutaneous adipose tissue depots. Adipocytes appeared to be largest in omental and smallest in intramuscular adipose tissue, although there were no significant differences among tissues. In a comparison of heifers and cows, significant site effects (p<0.05) were shown in adipocyte diameter, surface area and volume, and adipocyte appeared to be largest in omental tissue. Statistical difference (p<0.05) was only shown in cell volume of intramuscular tissue which was higher in cow than heifer. Intramuscular adipose tissue tended to have relatively greater numbers of cells per gram tissue and reflect lesser maturity of intramuscular adipose tissue relative to other adipose tissues. In sheep, regardless of adipose tissue depots, wethers had the greater adipocyte diameters than those at any other growth stage of sheep. Within adipose depots, the ranking of cell size was the greatest in the omental tissue of wether and the lowest in the renal and subcutaneous adipose tissue depots of fetal lamb. The cell size of adipocyte became larger with age, especially from fetal to suckling lamb due to a rapid hypertrophy of both perirenal and subcutaneous adipocytes during the suckling period.

• Journal of Ginseng Research
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• 제28권2호
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• pp.111-119
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• 2004

자연발생적 고혈압 흰쥐에 STZ로 당뇨를 유발한 고혈압-당뇨 질환모델에서 고려홍삼 조사포닌분획과 비사포닌 분획간의 신장보호 활성을 비교해 보았다. STA 65mg/kg용량을 투여한 후 3일에 네 그룹으로 나누어 본 실험에 임하였다. 신장비대에 대한 저해 활성을 비교해 보았을 때 GTS와 GNS 각각 12, 13% 억제 활성을 나타내었고 두 군간에는 유의적인 차이를 보이지 않았다. 한편 요 중 요소질소의 배설은 GNS 투여군에서는 69% 증가(p＜0.05)한 반면 GTS 투여군은 31%만이 증가하였다. 혈중 포도당, 콩 콜레스테롤 및 중성지방의 경우는 고혈압-당뇨 대조군과 비교시 홍삼투여군 두군 모두에서 유의한 차이를 발견할 수 없었다. 반면 oxidative stress를 저해하는 효소인 SOD 활성에 있어서는 GNS투여군에서 대조군에 비해 17%유의하게 상승하는 활성을 보여주었다. 신장비대의 지표인 TGG-$\beta$1, fibronectin그리고 upstream의 MEPK인 p-38, ERK 등의 발현을 그룹간 비교해 본 결과 모든 지표에서 비사포닌 분획이 사포닌 분획에 비해 우수한 억제활성을 나타내었다. TGF-$\beta$1의 mRNA 및 단백질의 발현을 살펴보았을 때 GNS 투여군은 각각 33%, 91% 억제활성을 나타낸 반면 GTS 투여군은 각각 5%, 65% 억제활성을 나타내었다. Fibronectin 단백질의 발현에서도 GNS 투여군은 87% 억제 활성을 나타낸 반면 GTS 투여군은 28% 저해활성을 나타내었다. 본 실험의 결과를 종합해보면 고려홍삼의 신장보호 활성은 사포닌 분획보다는 비사포닌 분획에 함유된 성분에 의해 일어나는 효과가 아닌가 추측된다.

• Archives of Reconstructive Microsurgery
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• 제15권1호
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• pp.17-25
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• 2006

Twelve cases in eleven patients with segmental bone defects were treated with contralateral fibula free flap and ipsilateral island fibula flap in an antegrade, retrograde or bidirectional flow fashion. Five cases were managed with free flaps and seven were with ipsilateral fibula island transfer. Among seven cases, antegrade fashion was three, retrograde was three, and bidirectional was one. All patients were related with open tibial fractures and its sequelae except one who had open foot bone fracture. According to Gustilo's classification, ten patients were type IIIb and one was type IIIc. Basically, antegrade-flow flaps based on the peroneal vessels as in the conventional free flap were used for the proximal or middle one-third tibial defects. On the contrary, retrograde-flow flaps based on the communicating branch between the peroneal and posterior tibial vessels were used for the middle or distal one-third of the tibia. Bidirection-flow flap based on intact peroneal vessels were used for the middle portion of the tibia. The patients who have undergone ipsilateral fibula island flap had one of the following problems: a previously failed free flap, below-knee amputation of the opposite leg because of open tibial fracture, refusal to use the contralateral sound leg, or poor general condition to stand a lengthy operation. Six of the patients who have got ipsilateral fibula island flap also had an associated fibula fracture on the same leg, which was ultimately used as one of the osteotomy sites. The follow-up period was from 1 to 10 years. Two cases of free flap were failed: one patient had below-knee amputation and the other patient had ipsilateral fibula transfer. Other cases were successful and excellent hypertophy of the transferred fibula was achieved. Time to bone union ranged from 4 to 11 months. Time to full weight bearing was from 5 to 13 months after surgery. All of the transferred fibulas showed hypertrophy after weight bearing. In one case, stress fracture was developed during ambulation, which was healed conservatively. Nonunion occurred in two cases, which were treated with a long leg cast and cancellous bone graft, respectively. Length discrepancy of the legs was noted. The limb was shorter by an average 0.5 cm in three cases, longer by 1.1 cm in one case. In the case of island fibula transfer, limited arc of rotation was not a problem. Other disabling complications were not seen. We believe that these diverse modalities using a vascularized fibula will make us more comfortable to handle major bone defects.

• Applied Microscopy
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• 제25권4호
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• pp.26-51
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• 1995

The present study was designed to examine effect of long term weight-training on aging atrophy in the rat skeletal muscle. Male rats of 8, 15, and 24 month old were used. Each age groups included control and weight-training for 5 months by using body press apparatus. The histo- and cytochemical, ultrastructural and stereological changes in aging skeletal muscles of the rat were observed in the present study. During the training period the body weight and muscular weight in all groups except the rectus femoris and the gastrocnemius in young age groups remained constant, but muscular weights were increased in the rectus femoris and the gastrocnemius muscles in young age groups. In trained rat, the volume density of muscle fiber type IIA and IIB were increased, but those of type IIC was decreased. Type I remained constant in 8 and 15 month old age groups, but reduced in the tibialis anterior and the gastrocnemius muscles in the 24 month old groups. Some histotological and ultrastructural changes associated with age were found: numerical increase of cytiplasmic vacuoles, lysosomes, lipofuscins, and irregularity of myofibrils. At 24 month old groups some unusual formation of contraction band and muscle splitting were observed. After weight-training, ultrastructural degenerative changes occured in the type I muscle fiber, such as splitting of muscle fiber, disorganization of myofilaments, swelling of mitochondria, accumulation of many lipid droplets, appearance of many lysosomes and residual bodies and necrotic fibers, in the old age groups. But, in the type II muscle fibers hypertrophy of muscle fiber appeared without any noticible damage as the type I. The activities of $Mg^{++}$ -ATPase decreased with age and this enzyme activities in the trained rat were significantly decreased with age. Activities of the acid phosphatase were increased with age and significantly in the trained rat. In stereological analysis, volume density of the myofibrils and the tubular system were increased, on the other hand there mitochondrial capacity was decreased. These experimental results suggested that old rats are not susceptible to be affected by weight-training as young rats, and that physical capacity of the rats must be considered when old rats are exercised for training.

• Applied Microscopy
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• 제38권3호
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• pp.213-219
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• 2008

신경계통의 가소성은 신경세포의 변화에 의해 이루어질 뿐 아니라 신경아교세포의 변화에 의해서도 이루어진다. 신경아교세포 중 별아교세포는 신경세포의 기능을 조절하므로 정상적인 뇌의 기능을 유지하는데 매우 중요하다. 뇌에서 편도복합체는 위험 혹은 유해한 일련의 감각정보를 받아들이는 구역으로 받아들인 일련의 이와 같은 정보를 통합하고 변환시켜 공포라는 감정을 만들어낸다. 이런 과정은 편도복합체 신경세포에서 분비되는 신경전달물질의 균형변화에 의해 이루어지며, 신경전달물질의 조절에 별아교세포가 관여하므로 본 연구에서는 출생 전 스트레스와 성장 후에 받은 스트레스가 편도복합체 별아교세포의 세포체에 어떤 영향을 미치는지 조사하였다. 이를 위해 흰쥐를 스트레스를 받지 않은 대조군 (CON), 성장 후 스트레스를 받은 군 (CONR), 출생 전 스트레스를 받은 군 (PNS), 출생 전 스트레스와 성장 후 스트레스를 모두 받은 군 (PNSR)으로 구분하였다. 별아교세포는 GFAP 항체를 이용한 면역조직화학 염색을 시행하여 확인하였으며, methylene blue/azure II로 대조 염색하였다. Neurolucida 프로그램을 이용하여 계측한 별아교세포의 세포체는 일부 편도복합체 신경핵에서 출생 전 스트레스를 받은 PNS군이 대조군에 비하여 면적이 증가하였으며, 이런 경향은 출생 전 스트레스를 받고 다시 성장 후 스트레스를 받은 PNSR군에서 더욱 증가하였다. 따라서 흰쥐의 편도복합체에 분포하는 별아교세포는 스트레스에 영향을 받아 비대해지는 경향을 보인 것으로 나타났으며, 출생 전 스트레스가 성장 후에도 영향을 미치는 것으로 사료된다.

• 동의생리병리학회지
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• 제20권2호
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• pp.442-448
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• 2006

To obtain the 50% lethal dose (LD50), approximated lethal dose (ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study like repeat dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male ICR mouse according to KFDA Guideline 1999-61 [KFDA, 1999] at a dosage level of 2,000, 1,000, 500, 250 and $125\;mg/kg/10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. After 2 or 3 days of dosing, 1 or 2 animals in 2,000 and 1,000 mg/kg-dosing groups were died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and they were recovered to normal within 4 days after dosing in case of survivors. A significant decrease of body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group from 1 days after dosing compared to those of vehicle control group. A significant decrease of body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. LD50 in this study was detected as 2,242.42 mg/kg. ALD in this study was detected as 1,000 mg/kg and the target organ was considered as the heart and kidney.

• Toxicological Research
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• 제20권1호
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• pp.83-88
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• 2004

The present study was carried out to investigate the potential adverse effects of CKD-602 by a 5-day repeated intravenous dose in Sprague-Dawley rats. The test article, CKD-602, was administered intravenously to male and female rats at dose levels of 0.07, 0.22, 0.67, 2.0 and 6.0 mg/kg/day for 5 days consecutively. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period after cessation of the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. There were 2 and 5 treatment related deaths in the 0.67 and 2.0 mg/kg/day dose groups of both genders, respectively. Treatment related clinical signs, including hair loss, skin paleness, decreased locomotor activity, emaciation, and changes in stool were observed in a dose-dependent manner from the third day after initiation of the injection. Decrease or suppression of body weight was also observed dose-dependently in males and females of the treated groups. Gross postmortem examinations revealed a dose-dependent increase in the incidence and severity of atrophy or hypertrophy and white membrane formation in the spleen, atrophy of the thymus, diffuse white spots and paleness of the liver, paleness of the lung, kidney and adrenal gland, and dark red discoloration and dark red contents in the alimentary tract. Based on these results, it was concluded that the 5-repeated intravenous injection of CKD-602 to male and female rats resulted in increased incidence of abnormal clinical signs and death, decreased or suppressed body weight, and increased incidence of abnormal gross findings. In the present experimental conditions, the $LD_{50}$ value was 2.07 (95% confidence limit not specified) mg/kg/day in both genders and the $LD_{10}$ value was 1.72 (95% confidence limit not specified) mg/kg/day in both genders.

• Journal of Chest Surgery
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• 제33권10호
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• pp.777-784
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• 2000

Congenital aortic stenosis in children is characterized by "excessive" left ventricular hypertrophy with reduced left ventricular systolic wall stress that allows for supernormal ejection performance. We hypothesized that left ventricular wall stress was decreased immediately after surgical correction of pure congenital aortic stenosis. Also measuring postoperative left ventricular wall stress was a useful noninvasive measurement that allowed direct assessment for oxygen consumption of myocardium than measuring the peak systolic pressure gradient between ascending aorta and left ventricle for the assessment of surgical results. Material and Method: Between September 1993 and August 1999, 8 patients with isolated congenital aortic stenosis who underwent surgical correction at Yonsei cardiovascular center were evaluated. There were 6 male and 2 female patients ranging in age from 2 to 11 years(mean age, 10 years). Combined Hemodynamic-Ultrasonic method was used for studying left ventricular wall stress. We compared the wall stress peak systolic pressure gradient and ejection fraction preoperatively and postoperatively. Result: After surgical correction peak aortic gradient fell from 58.4${\pm}$17.6, to 23.7${\pm}$17.7 mmHg(p=0.018) and left ventricular ejection fraction decreased but it is not statistically significant. In the consideration of some factors that influence left ventricular end-systolic wall stress excluding one patient who underwent reoperation for restenosis of left ventricular outflow tract left ventricular end-systolic pressure and left ventricular end-systolic dimension were fell from 170.6${\pm}$24.3 to 143.7${\pm}$27.1 mmHg and from 1.78${\pm}$0.4 to 1.76${\pm}$0.4 cm respectively and left ventricular posterior wall thickness was increased from 1.10${\pm}$0.2, to 1.27${\pm}$0.3cm but it was not statistically singificant whereas left ventricular end-systolic wall stress fell from 79.2${\pm}$24.9 to 57.1${\pm}$27.6 kdynes/cm2(p=0.018) in 7 patients. For one patient who underwent reoperation peak aortic gradient fell from 83.0 to 59.7 mmHg whereas left ventricular end-systolic wall stress increased from 67.2 to 97.0 kdynes/cm2 The intervals did not change significnatly. Conclusion ; We believe that probably some factors that are related to left ventricular geometry influenced the decreased left ventricular wall stress immediately after surgical correction of isolated congenital aortic stenosis. Left ventricular wall stress is a noninvasive measurement and can allow for more direct assesment than measuring peak aortic gradient particularly in consideration of the stress and oxygen consumption of the myocardium therefore we can conclude it is a useful measurement for postoperative assessment of congenital aortic stenosis.