• Clinical and Experimental Pediatrics
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• v.48 no.8
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• pp.865-870
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• 2005

Purpose : The use of growth hormone(GH) to promote growth in normal short children without classical GH deficiency is controversial. Numerous foreign studies have shown the effects of GH therapy in children with idiopathic short stature(ISS) whereas few has been interested in Korea. Therefore, this study is designed to investigate the effects of GH therapy on ISS by observing correlations and changes among various growth parameters such as, insulin-like growth factor-I(IGF-I) and insulin-like growth factor binding protein-3(IGFBP-3). Methods : This study was conducted retrospectively with 15 children with ISS in Chungbuk National University Hospital in Korea. Mean age was $11.44{\pm}2.81$ and the children were treated with 0.66 IU/kg/wk dosage of GH for 1 or 2 years. Also, the growth parameters before and after the GH therapy were observed. Results : Height standard deviation score(HT-SDS) was increased from $-1.85{\pm}0.70$ to $-1.58{\pm}0.56$ at 1 year and to $-1.21{\pm}0.37$ at 2 years after GH therapy. Predicted adult height standard deviation score(PAH-SDS) was also increased from $-2.10{\pm}0.52$ to $-1.67{\pm}0.59$ at 1 year, and to $-0.96{\pm}0.60$ at 2 years. Serum IGF-I and IGFBP-3 levels were significantly increased after 1 year and marginally increased after 2 years of GH therapy. Conclusion : It is concluded that GH therapy has growth promoting effect. The significant increase in IGF-I and IGFBP-3 levels during the GH therapy suggests that IGF-I and IGFBP-3 are useful predictors of response to the use of GH therapy. It is expected that larger patient samples would provide more reliable information about the effect of GH therapy.

• Journal of Life Science
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• v.16 no.5
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• pp.734-739
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• 2006

This study investigated the hepatoprotective effects of mesangi (Capsosiphon fulvecens) in carbon tetrachloride $(CCI_4)$-induced liver injury. Thirty healthy male Sprague-Dawley rats were divided into three groups : the normal (Normal), $CCI_4$-treated $(CCI_4)$, and mesangi-treated (Exp-CF) groups. Administration of $CCI_4$ increased the levels of GOT, GPT, and LDH in serum, while the levels were significantly decreased by the addition of mesangi. Higher levels of HDL-cholesterol were found in the Normal and Exp-CF groups, which has lower levels of total and LDL-cholesterol. Administration of $CCI_4$ also increased IGFBP-1 expression in serum, but it was decreased in the Exp-CF group. This suggests that $CCI_4$ is involved in the change in IGFBP-1 expression via its hepatotoxicity. The results indicate that mesangi has a hepatoprotective effect in rats given $CCI_4$.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.9
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• pp.1244-1251
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• 2008

The aim of the present study was to delineate the expression and secretion of insulin-like growth factor (IGF) system components by pig liver cells. Hepatocytes were prepared from 3-wk-old weanling piglets following a two-step collagenase perfusion procedure, after which the cells were incubated for 24 or 48 h at a density of $2{\pm}10^5$ cells per 35-mm dish in 2-ml Williams' medium E. The cells were found to express the genes encoding IGF-I, IGF-binding proteins (IGFBPs)-2 and -3 and acid-labile subunit (ALS) by reverse transcription-polymerase chain reaction (RT-PCR) following the culture. However, IGF-I was localized to hepatocytes by immunohistochemical analysis, whereas IGFBP-3 was localized to endothelial cells, but not to hepatocytes. This indicated that the IGFBP-3 gene expression detected by RT-PCR was likely to have been contributed by unidentified non-parenchymal cells that had not been removed during the hepatocyte preparation. The conditioned culture medium (CCM) of the cells contained immunoreactive IGF-I and IGF-II, with the latter being seven-fold more abundant than the former. The CCM also contained 43-, 40-, 34-, 31-kDa doublet and 26-kDa IGFBPs as examined by Western ligand blotting. The 40-, 34- and 31-kDa doublet IGFBPs were approximately three-fold as abundant as the 43- and 26-kDa IGFBPs. Moreover, the 43- and 40-kDa doublet and the 34-kDa IGFBPs were immunoprecipitable with IGFBP-3 and IGFBP-2 antibodies, respectively. Overall, these results are similar to those known in the rat, which suggests that the IGF system components are likely to be expressed and secreted in pig liver in a manner similar to that in rat liver.

• Clinical and Experimental Pediatrics
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• v.49 no.5
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• pp.552-557
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• 2006

Purpose : The recent results observed in precocious puberty and the hope that interrupting puberty might increase adult height have led to an attempt to use GnRH agonist(GnRHa) in children with premature puberty and a poor growth prognosis. We aimed to analyze the growth promoting effect of GnRHa in girls with early puberty and low predicted adult height(PAH). Methods : Thirty six girls were recruited. They were grouped according to the GnRHa treatment period(group 1>6 mo, n=18; group 2<6 mo, n=18). The following variables were analyzed before and after GnRHa treatment : chronological age(CA), bone age(BA), ${\Delta}age$(CA-BA), height, target height (TH), PAH, serum IGF-1, IGFBP-3. Results : Duration of the GnRHa treatment was $0.89{\pm}0.81yr$($1.37{\pm}0.92yr$ in group 1, and $0.41{\pm}0.08yr$ in group 2). Before treatment, none of the variables were different between the two groups. There were no differences in the following variables the between two groups at the end of treatment : CA, BA, ${\Delta}age$, PAH, serum IGF-1, IGFBP-3. But, growth velocity(GV) and PAH increment during treatment were significantly reduced in group 1. Compared with initial PAH, PAH at the end of treatment was significantly increased($3.7{\pm}3.2cm$). The last serum levels of IGF-1 and IGFBP-3 were lower than those before treatment. Conclusion : Even though last PAH didn't approach TH, short term GnRHa administration in early puberty with low predicted PAH was somewhat effective. But, GnRHa administration suppressed the growth hormone-IGF-1 axis. Therefore, it is recommended that growth hormone(GH) should be used in combination with GnRHa.

• Tuberculosis and Respiratory Diseases
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• v.58 no.2
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• pp.120-128
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• 2005

Background : Insulin-like growth factor binding protein (IGFBP)-3 regulates non-small cell lung cancer(NSCLC) cell proliferation in vitro and in vivo by inhibiting IGF-mediated signaling pathways. To have better strategies for the treatment of lung cancer, we analyzed the combining effects of adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and SCH66336, a farnesyl transferase inhibitor (FTI) designed to block Ras-mediated proliferative signaling pathways. Methods : To measure the combining effects of Ad5CMV-BP3 and SCH66336 on the proliferation of NSCLC cells, human NSCLC cell lines (H1299, H596, A549, H460, and H358), SCH66336, recombinant adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and athymic nude mice were used in these experiments. Results : The combination of Ad5CMV-BP3 and SCH66336 produced a synergistic enhancement in antiproliferative effects over a range of clinically achievable concentrations in a variety of NSCLC cell lines. Furthermore, we observed a significant reduction in growth of NSCLC xenograft induced in athymic nude mice. Conclusion : In conclusion, this study demonstrated for the first time that the FTI SCH66336 synergizes with IGFBP-3 and enhances its apoptotic activity in NSCLC cells in vitro and in vivo. The combined treatment of Ad5CMV-BP3 and SCH66336 raises the possibility of using this regimen in clinic for the treatment of NSCLC.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.8
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• pp.1180-1185
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• 2009

Two experiments were carried out to study the effects of dietary energy level on nutrient digestion, nitrogen (N) utilization, growth performance, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-3 (IGFBP-3) in plasma, liver and longissimus dorsi muscle in growing-finishing pigs. In experiment 1 (Exp 1), 15 castrated male pigs (Duroc${\times}$Landrace${\times}$Large White) (Body weight, BW, 55.6${\pm}$1.8 kg) were divided into three groups and fed rations containing 13.33, 14.87 and 17.35 MJ digestible energy (DE)/kg as treatments I, II and III, respectively, using soybean oil as an energy source. The experiment lasted 8 days and faecal and urinary samples were collected during the last 3 days. The results showed that the digestibility of dry matter (DM), energy and N was increased from treatments I to III (p<0.01). N-retention and N-retention rate were not influenced by dietary DE level (p>0.05). In experiment 2 (Exp 2), 36 female pigs (Duroc${\times}$Landrace${\times}$Large White) (BW 41.5${\pm}$3.8 kg) were divided into three groups. The pigs were fed with the same three rations used in Exp 1 for 60 days. At the end of Exp 2, eight pigs were selected from each group for blood sampling and 4 pigs for slaughter trial. The results indicated that average daily feed intake (ADFI) and N-intake were significantly decreased (p<0.01), and DE intake (p<0.01) and average daily gain (ADG) (p<0.05) were increased. IGF-I and IGFBP-3 in plasma were increased (p<0.05). No significant differences in IGF-I and IGFBP-3 in liver and longissimus dorsi muscle were found between different treatments. It was concluded that higher dietary DE level improved nutrient digestibility, ADG and feed/gain ratio when soybean oil was used as an energy source in the ration of growing-finishing pigs. No significant differences were found in Nretention and IGF-I and IGFBP-3 in liver and longissimus dorsi muscle between different treatments.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.3
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• pp.379-384
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• 2010

The principal objective of this experiment was to determine the effects of dietary betaine on IGF-I, IGFBP-3 and IGFBP-1 secretion and IGF-I mRNA gene expression in the serum and liver of laying hens. A total of 72 ISA-Brown laying hens were fed with four different levels of betaine (0, 300, 600, 1,200 ppm) based on a corn-soybean meal diet containing 2,800 kcal/kg of metabolizable energy (ME) and 16% crude protein (CP) for four weeks. The results indicated significantly higher serum and liver IGF-I concentrations in the laying hens fed with 600 and 1,200 ppm betaine (p<0.05) compared to controls. IGF-I gene expression in liver showed a statistically correlated increase in 600 and 1,200 ppm betaine-fed groups as compared to the controls (p<0.05). Serum IGFBP-3 concentrations were elevated significantly in the groups fed 600 ppm of betaine. However, the secretion of IGFBP-1 in the liver of laying hens fed on 600 and 1,200 ppm of betaine was significantly lower than in the controls (p<0.05). The results of this experiment showed that dietary betaine supplementation plays a pivotal role in changes of the IGFs system in laying hens.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.31 no.5
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• pp.774-778
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• 1998

The effect of insulin-like growth factor-I (IGF-I) on circulating insulin-like growth factor binding proteins (IGFBPs) in the Korean rockfish, Sebastes schlegeli, was assessed after injected of recombinant human IGF-I (6 $\mu$g/100 g body weight). Growth and metabolic status of each fish were assessed by determing body length and body weight changes, and serum glucose concentration. Serum IGF binding proteins concentrations were assessed by the Western ligand blot procedure using $^{125}I$-labeled human IGF-I tracer. The fish received IGF-I were Heavier than the saline-injected control fish after 2 weeks of treatment. Plasma IGFBP-3 concentration inclosed, but plasma IGFBP-1 and glucose levels decreased significantly after administration. Taken together, the findings of this study suggest that human IGF-I is biologically active in Korean rockfish and may be of significance in metabolic and growth-related processes.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.5
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• pp.659-665
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• 2000

A nitrogen (N) balance trial was conducted to examine the effect of N deprivation on subsequent N retention, blood urea nitrogen (BUN) and IGF-I levels and the ratio of IGF binding protein (IGFBP)-3 to IGFBP-l and -2. Pigs in treatment (T) 1 were given diet A (2.39% N) and those in T2 and T3 were given diet B (1.31% N) and excreta were collected (period 1 (P1)). Pigs in T1 continued to receive diet A while diets for T2 and T3 were changed to diets A and C (2.74% N), respectively. The excreta were collected for two more periods (P2 and P3). During P1, pigs in T2 and T3 retained 50% less N (p<0.001) than those in T1. However, pigs provided T2 (p<0.01) and T3 (p<0.05) retained more N than those assigned to T1 during P2. Pigs in T3 tended to retain more (p=0.10) N than those receiving T2 for the same period. The BUN values were lower (p<0.05) for pigs assigned to T2 and T3 than T1 during P1 and P2. Both IGF-I and IGFBP ratios of pigs assigned to T1 were higher (p<0.05) than those given T2 and T3 during P1 but no differences were found during P2 and P3.

• Journal of Nutrition and Health
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• v.35 no.2
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• pp.192-200
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• 2002

Conjugated linoleic acid (CLA) is a collective term for positional and geometric isomers of octadecadienoic acid in which the double bonds are conjugated. CLA has anticancer activity in a variety of animal cancer models, and cis-9, trans-11 (c9t11) and trans-10, cis-12(t10c12) CLA are the most predominant isomers present in the synthetic preparations utilized in these animal studies. To compare the ability of c9t11, t10c12 and an isomeric mixture of CLA to inhibit TSU-Prl cell growth, cells were incubated in a serum-free medium with various concentrations of these fatty acids. The isomeric mixture inhibited cell growth in a dose-dependent manner (1-3 $\mu$M) with a 41 $\pm$ 1% inhibition observed at 3 $\mu$M concentration after 48 hours. T10c12 also inhibited cell proliferation in a dote-dependent manner, However, the efficacy and potency of this isomer was much greater than that of the isomeric mixture with a 49 $\pm$ 2% inhibition observed at 0.3 $\mu$M concentration after 48 hours. By contrast, c9t11 slightly increased cell proliferation. To determine whether the growth-inhibiting effect of CLA is related to the changes in production of insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) by these cells, serum-free conditioned media were collected. Immunoblot analysis of conditioned media using a monoclonal anti-IGF-II antibody showed that both the isomeric mixture and t10c12 inhibited secretion of both mature 7,500 Mr and higher Mr forms of pro IGF-II, whereas c9t11 had no effect. Ligand blot analysis with 125I-IGF-II revealed the presence of two types of IGFBPs : 24,000 Mr IGFBP-4 and 30,000 Mr IGFBP-6. The production of IGFBP-4 slightly decreased at the highest concentrations of the isomeric mixture and t10c12. These results indicate that CLA inhibits human prostate cancer cell growth, an effect largely due to the action of t10c12. The growth inhibition may result, at least in part, from decreased production of IGF-II and IGFBP-4 by these cells.