• 대한수의학회지
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• 제44권1호
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• pp.7-13
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• 2004

Severe hypertension (>180 mmHg) develops in spontaneously hypertensive rats (SHR) after 12 wk-old; however, it is not clear whether what kinds of molecular mechanism leads to altered cardiac performance following developmental stages in SHR. Also, although the effect of calcineurin (Cn) to promote cardiomyocyte hypertrophy in vivo and in vitro is established, its overall necessity as a hypertrophic mediator is currently an area of ongoing debate. Thus, we have examined i) body weight and blood pressure, ii) differences of expression and distribution of signaling molecules such as Cn, protein kinase B/Akt (PKB/Akt), and extracellular signal-regulated kinase (ERK) between SHR and their age-matched control Wistar-Kyoto (WKY) rats following developmental stages. In 16 wk-old SHR compared with WKY, 2-dimentional echocardiography showed cardiac enlargement and hypertrophy of left ventricle, significantly. Taken together, we suggest that Cn is associated with hereditary cardiac hypertrophy, the process being related to the molecular signaling mechanisms involving PKB/Akt and ERK.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 제4회 추계심포지움
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• pp.171-172
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• 1996

Cocaine is a powerful reinforcer that has become a popular drug of abuse in man. CNS effects that are related to the abuse of cocaine include feeling of well-being and euphoria. Brain dopamine systems are thought to mediate reinforcement and it is often assumed that cocaine's inhibition of dopamine uptake is the mechanism underlying its reinforcing effects. With increase in cocaine use among general population in recent years, adverse effects of the drug have occurred in all social strata and age groups. Therefore, it has been recognized that the epidemic of cocaine abuse is a growing major concerning public health. One of the most troubling aspects of cocaine abuse is its use by pregnant women. Drug abuse during pregnancy puts two lives at risk. Cocaine produces toxic effects on the fetus at concerntrations that are apparently nontoxic to the mother. Not only does cocaine cross the placenta via diffusion and via rapid penetration to mucous membranes, due to its high lipid solubility, but cocaine can also be found in breast milk, the effects of the cocaine can persist long after the child is born. Although it is known that prenatal cocaine exposure is associated with developmental risk to the fetus ana newborn, few studies have been conducted to assess the mechanisms whereby either short-term or long-term administration of cocaine can exert its harmful effects on the mother or the child. Therefore, it was our great interest to investigate the pharmacological and neurobehavioral changes in offspring that are prenatally exposed to cocaine.

• 한국식품영양과학회지
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• 제34권4호
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• pp.466-475
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• 2005

본 연구에서는 인공 사육 모델 시스템과 인공 쥐용 분유를 이용하여 출생 직후 12시간 이내에 엄마 쥐들로부터 신생 쥐를 분리하여 n-3 지방산 결핍분유와 n-3 지방산 적절분유로 3주 동안 사육한 후(이유기) 각각 장기들을 취하고 또한 성숙 쥐(15 wks)의 뇌, 망막, 간을 취하여 뇌 성장 발달 과정 동안 n-3지방산 결핍이 이들 장기들의 지방산조성 변화에 미치는 영향을 알아보고자 한다. 이유기와 성숙기 쥐의 뇌 지방산 조성은 n-3 지방산 적절군과 대조군과 비교했을 때, n-3지방산 결핍군의 경우 n-6지방산의 함량은 높았으나 (p<0.05), 총 monounsaturated 지방산과 총 n-3 지방산의 함량은 낮았고(p<0.05), 총 saturated 지방산의 경우는 변화가 없었다. 기대했듯이 뇌 DHA의 경우 n-3 지방산 결핍군은 n-3 지방산 적절군과 대조군에 비해 이유기 때 $50\%$, 성숙기에는 $70\%$까지 감소하였고 반면 n-6 계열인 DPAn-6의 함량은 상당히 증가하였음을 살펴볼 수가 있었다. 이유기의 망막의 총 saturated 지방산과 총 monounsaturated 지방산에는 식이군 사이에 변화가 없었고 22:4n-6, DPAn-6와 총 n-6 지방산의 함량은 n-3 지방산 결핍군에서 n-3 지방산 적절군과 대조군에 비해 증가하였으나(p<0.05), 22:5n-3, DHA와 총 n-3 지방산의 함량은 상당히 감소하였음을 관찰할 수가 있었다(p<0.05). 성숙 쥐 망막의 지방산조성의 경우 20:4n-6, 22:4n-6, 22:5n-6와 총 n-6 지방산의 함량은 n-3 지방산 결핍군에서 n-3 지방산 적절군과 대조군에 비해 증가하였으나(p<0.05), 22:5n-3, DHA와 총 n-3 지방산의 함량은 상당히 감소하였다(p<0.05). 특히 n-3 결핍군의 망막 DHA는 이유기 때 $57\%$ 감소에서 성숙기에 $63\%$까지 감소하였다. (p<0.05). 간의 경우, 이유기의 n-3 지방산 결핍군의 DHA는 $65\%$ 감소한 반면 간의 DPAn-6는 $59\%$ 증가하였다. 흥미로운 것은 이유기의 간 지방산 조성과는 대조적으로 성숙기의 n-3 지방산 결핍군의 18:2n-6, 20:3n-6, 20:4n-6와 22:4n-6 지방산 함량이 현저히 감소된 것과는 달리 DPAn-6의 함량이 n-3 지방산 적절군보다 $143\%$까지 증가되었음 관찰할 수 가 있었다(p<0.05). 이상의 장기들의 n-3지방산 결핍군은 이유기와 성숙기에서 DPAn-6/DHA비와 n-6/n-3비 또한 n-3 지방산 적절군과 대조군에 비해 컸으나(p<0.05) DPAn-6와 DHA의 합에는 변화가 없었다. 따라서 뇌 성숙 발달 과정동안 n-3 지방산 결핍은 뇌의 DHA의 결핍을 초래하고 이러한 비정상적인 조건에서 DPAn-6의 증가를 유발하였으며 이러한 지방산 조성의 변화와 공간과 후각에 기초를 하는 기억 학습 능력 저하의 관련성에 대해서는 앞으로 연구가 진행되어져야 할 것으로 사료되어진다.

• Food Science and Biotechnology
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• 제15권1호
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• pp.122-127
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• 2006

The effects of fermented chaga mushroom (Inonotus obliquus) powder on the lipid concentrations and the activities of liver marker enzymes of serum in genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats were investigated. Rats were fed a semisynthetic diet supplemented with 50 g/kg chaga mushroom powder (CM) or 50 g/kg fermented chaga mushroom powder (FCM) for 8 weeks (26 to 34 weeks of age). Nondiabetic Long-Evans Toknshima Otsuka (LETO) rats were used as age-matched nondiabetic control animals. Water consumption was significantly higher in the OLETF control than the LETO rats. Water consumption in the FCM-fed OLETF rats tended to be less than in both the OLETF control and CM-fed OLETF rats. Serum concentrations of triglycerides and total cholesterol were significantly higher in the OLETF control rats than in the LETO rats while within the OLETF rat groups, the consumption of FCM resulted in a significantly lower serum triglyceride concentration and slightly lowered serum total cholesterol concentration when compared to the OLETF control and CM-fed rats. The alanine aminotransferase (ALT) activity was significantly higher in the OLETF control than in the LETO rats, but this difference was significantly reduced compared to the CM-fed rats and essentially no difference in the ALT levels was observed between the LETO and OLETF-FCM rats. This observation suggests an adaptive effect of the fermented chaga mushroom in liver function. Livers of the LETO rats showed no histopathological changes, whereas those of the OLETF control rats were characterized by many fat depositions in the central zone of the hepatocytes. The livers of the OLETF CM-fed rats showed less fatty changes compared to the OLETF control rats and fat deposition in the hepatocytes was nearly absent. These results suggest that orally ingested fermented chaga mushroom has a potential beneficial effect on the complications known to occur in the obesity-related non-insulin dependent diabetes mellitus (NlDDM) OLETF rat.

• Journal of Ginseng Research
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• 제29권2호
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• pp.100-106
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• 2005

The number of reporting the effects on ginseng's physiological, pharmacological, and behavioral effects has been increased every year. Major active components of Panax ginseng, are the ginsenosides, which are mainly triterpenoid dammarane derivatives. 3-Nitropropionic acid (3-NP) is blown to induce cellular energy deficit and oxidative stress related neurotoxicity via an irreversible inhibition of the mitochondrial enzyme succinate dehydrogenase (SDH). Intraperitoneal injection of 3-NP produces striatal degeneration. Aged animals was more vulnerable to 3-NP than young animal. We used three different ages of 5-, 8-, and 26-week-old rats. 3-NP alone treatment induced striatal lesion and increased lesion volume with age-dependent manner in 5-, 8-, and 26-week-old rats by $30.2{\pm}5.8$, $v$, and $51.3{\pm}8.4mm^3$, respectively. However, pretreatment of GTS (100 mg/kg/day) before 3-NP reduced striatal lesion in 5-,8-, and 26-week-old rats by $3.15{\pm}6.1$, $8.89{\pm}1.9$, and $27.3{\pm}5.6mm^3$, respectively. Pretreatment of GTS also significantly increased survival rate in 5-week-old rats (3-NP alone: GTS +3-NP = $40.4{\pm}6.3$: $72.5{\pm}9.5\%$) than 8-week-old rats (3-NP alone: GTS + 3-NP : $13.5{\pm}5.2\%$ : $45.1{\pm}3.1\%$). In 26-week-old rats, 3-NP alone treated group died on day 18, whereas GTS +3-NP-treated group prolonged lifespan to 30 days. Thus, pretreatment of GTS before administration of 3-NP extended lifespan in all ages. The present results indicate that aged animals are more vulnerable to 3-NP and GTS pretreatment protected 3-NP-induced striatal damage in different ages of animals.

• 한국약용작물학회지
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• 제15권5호
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• pp.352-356
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• 2007

The present study was investigated the anti-oxidative effects of aloe vera ingestion on brain and kidney in aged rats by monitoring several oxidative-related parameters. Male specific pathogen-free Fischer 344 rats were randomly divided into four groups of five rat each: Group A was fed test chow without aloe supplementation; Group B was fed a diet containing a 1% freeze-dried aloe filet; Group C was fed a diet containing a 1% charcoal-processed, freeze-dried aloe filet; and Group D was fed a diet containing a charcoal-processed, freeze-dried, whole leaf aloe in drinking water. Analyses of tissues were done at 4 months and 16 months of age. Results showed that a long-term intake of aloe, regardless of the preparation used, enhanced antioxidant defenses against lipid peroxidation, as indicated by reduced phosphatidylcholine hydroperoxide levels in both brain and kidney. The additional benefit of aloe intake on the anti-oxidative action was evidenced by enhanced superoxide dismutase and catalase activity in all aloe-ingested groups. Another beneficial effect of aloe shown in this study, although not an anti-oxidative parameter, was its cholesterol-lowering effect as detected in brain and kidney with significant decreases at age16 months of aloe-fed rats. Based on these findings, we conclude that a long-term dietary aloe supplementation modulated the anti-oxidative defense systems and cholesterol level.

• The Korean Journal of Physiology and Pharmacology
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• 제12권1호
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• pp.7-12
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• 2008

OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium $(K_{ATP})$ channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of $K_{ATP}$ channels, insulin receptor ${\beta}$-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that $K_{ATP}$-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on $K_{ATP}$ channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects.

• 생명과학회지
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• 제29권8호
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• pp.888-894
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• 2019

류마티스관절염(rheumatoid arthritis)과 골관절염(osteoarthritis) 같은 관절질환은 연골세포(chondrocytes) 감소와 관절연골(articular cartilage)의 분해를 수반한다. 최근, 연골세포의 활성과 연골 항상성(cartilage homeostasis)에 염증성 ROS (reactive oxygen species) burst 및 나이와 관련된 산화적 스트레스(oxidative stress)의 증가와 관련된 연구가 활발히 진행되고 있다. 본 연구는 관절연골로부터 분리한 연골세포의 노화 과정과 나이대별 관절연골에서 항산화 인자들(antioxidants)의 변화를 조사함으로써, 연골세포와 관절연골의 노화 과정 동안 산화적 스트레스로부터 조직을 보호하는 항산화 인자들의 역할을 규명하는데 목적이 있다. 쥐의 관절연골로부터 분리한 연골세포의 연속 계대배양을 통한 노화 과정에서 산화적 스트레스가 증가함을 관찰하였다. 그리고, 노화 유도한 연골세포는 세포내 총 glutathione (GSSG/GSH) 양과 항산화 효소 superoxide dismutase (SOD)와 heme oxygenase-1 (HO-1)의 발현이 증가하였다. 다음으로, 나이대별 쥐로부터 분리한 관절연골에서 항산화 인자의 발현을 분석하였다. 항산화 인자 glutathione의 양은 40주령에서 발현이 가장 높게 관찰되었으며 72주령에 다소 감소하였고, SOD와 HO-1의 발현은 나이대별로 현저히 증가되는 경향을 보였다. 이를 종합해 볼 때, 세포내 항산화 인자들은 과도한 양의 ROS에 반응하여 연골세포의 노화와 나이와 관련된 관절연골의 퇴화 과정에서 중요한 역할을 하는 것으로 보인다.

• The Journal of Korean Physical Therapy
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• 제20권1호
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• pp.57-65
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• 2008

Purpose: Heat shock proteins (HSPs) are a group of proteins that are activated when cells are exposed to a variety of environmental stresses, such as infection, inflammation, exposure to toxins, starvation, hypoxia, brain injury, or water deprivation. The activation of HSPs by environmental stress plays a key role in signal transduction, including cytoprotection, molecular chaperone, anti-apoptotic effect, and anti-aging effects. However, the precise mechanism for the action of small HSPs, such as HSP27 and mitogen-activated protein kinases (MAPKs: extracellular-regulated protein kinase 1/2 (ERK1/2), p38MAPK, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), is not completely understood, particularly in application of cell stimulators including platelet-derived growth factor (PDGF), angiotensin II (AngII), tumor necrosis factor $\alpha$ (TNF$\alpha$), and $H_2O_2$. This study examined the relationship between stimulators-induced enzymatic activity of HSP27 and MAPKs from rat smooth and skeletal muscles. Methods: 2-dimensional electrophoresis (2DE) and matrix assisted laser desorption ionizationtime-of-flight/time-of-flight (MALDI-TOF/TOF) analysis were used to identify HSP27 from the intact vascular smooth and skeletal muscles. Three isoforms of HSP27 were detected on silver-stained gels of the whole protein extracts from the rat aortic smooth and skeletal muscle strips. Results: The expression of PDGF, AngII, TNF$\alpha$, and $H_2O_2$-induced activation of HSP27, p38MAPK, ERK1/2, and SAPK/JNK was higher in the smooth muscle cells than the control. SB203580 (30${\mu}$M), a p38MAPK inhibitor, increased the level of HSP27 phosphorylation induced by stimulators in smooth muscle cells. Furthermore, the age-related and starvation-induced activation of HSP27 was higher in skeletal muscle cells (L6 myoblast cell lines) and muscle strips than the control. Conclusion: These results suggest, in part, that the activity of HSP27 and MAPKs affect stressors, such as PDGF, AngII, TNF$\alpha$, $H_2O_2$, and starvation in rat smooth and skeletal muscles. However, more systemic research will be needed into physical therapy, including thermotherapy, electrotherapy, radiotherapy and others.

• Journal of Korean Neurosurgical Society
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• 제65권2호
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• pp.204-214
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• 2022

Objective : Osteoporosis result from age-related decline in the number of osteoblast progenitors in the bone marrow. Probiotics have beneficial effects on the host, when administered in appropriate amounts. This study investigated the effects of probiotics expressing specific genes, especially the effects of genetically modified bone morphogenetic protein (BMP)-2-expressing Lactobacillus plantarum CJNU 3003 (LP) on ovariectomized rats. Methods : Twenty-eight female Wistar rats (250-300 g, 12 weeks old) were divided into four groups : the sham (control), the ovariectomy (OVX)-induced osteoporosis group (OVX), the OVX and LP (OVX/LP), OVX and genetically modified BMP-2-expressing LP (OVX/LP with BMP) groups. The three groups underwent bilateral OVX and two of these groups were administered two different types of LP via oral gavage daily. At 16 weeks post-OVX, blood was collected from the heart and the bilateral tibiae were extracted and were scanned by ex-vivo micro-computed tomography and stained with hematoxylin-and-eosin (H&E) and Masson's trichrome stain for pathological assessment. The serum levels of osteocalcin (OC), rat C-telopeptide of type I collagen (CTX-I), BMP-2, and receptor activator of nuclear factor-ĸB ligand (RANKL) were measured. Results : The 3D-micro-computed tomography images showed that the trabecular structure in the OVX/LP with BMP group was maintained compared with OVX and OVX/LP groups. No significant differences were detected in trabecular thickness (Tb.Th) between control and OVX/LP with BMP groups (p>0.05). Furthermore, a tendency toward increased BMD, trabecular bone volume, Tb.Th, and trabecular number and decreased trabecular separation was found in rats in the OVX/LP with BMP groups when compared with the OVX and OVX/LP groups (p>0.05). The H&E and Masson's trichrome stained sections showed a thicker trabecular bone in the OVX/LP with BMP group compared with the OVX and OVX/LP groups. There was no difference in serum levels of OC, CTX and RANKL control and OVX/LP with BMP groups (p>0.05). In contrast, significant differences were found in OC and CTX-1 levels between the OVX and OVX/LP with BMP groups (p<0.05). Conclusion : Our results showed that the expression of genetically modified BMP-2 showed inhibition effect for bone loss in a rat model of osteoporosis.