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Effects of Aqueous Azadirachta indica Extract on Hepatotoxicity in Rats (수용성 님추출물이 랫드의 간 독성에 미치는 영향)

  • Park, Kyung-Hun;Yoon, Hyunjoo;Han, Beom Seok;Lee, Je-Bong;Jeong, Mi Hye;Cho, Namjun;Om, Ae Son;Paik, Min-Kyoung
    • Korean Journal of Environmental Agriculture
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    • v.33 no.4
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    • pp.395-402
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    • 2014
  • BACKGROUND: Azadirachta indica Extract(AIE) containing azadirachtin as active ingredient have been used worldwide as environment-friendly organic material having pest control properties. However, the extracts prepared with different solvent and from different plant site is very diverse and have different toxicity. METHODS AND RESULTS: In this study, the four week repeated oral dose toxicity test of aqueous AIE in Sprague-Dawley rats was carried out to investigate the toxic effect of liver, main toxicity target organ of AIE. The male and female rats were divided into 4 groups, respectively; control(0 g/Kg bw), low-dose group(0.5 g/Kg bw), middle-dose(1.0 g/Kg bw) and high-dose group(2.0 g/Kg bw). As a results, relative liver weight increased with dose-dependent of AIE(p<0.05). Serum LDH in all AIE-treated groups were significantly lower than the control in male rats(p<0.05). However, serum GOT and GPT were significantly increased in all male AIE-treated groups in male rats(p<0.05) and, in particular, increase of serum GPT in dose-dependent manner raise the possibility of liver damage. Even through serum GLU was increased significantly in high-dose group in male rats compared to control, there were no significant differences of urinary GLU among all groups(p<0.05). In addition, histopathological examination of the liver did not reveal any lesions in all AIE-treated groups. CONCLUSION: In conclusion, 4 weeks of the repeated oral administration of AIE 2.0 g/Kg to rats has resulted no toxic response in liver. Therefore, AIE was no indicated to have any toxic effect in the SD rats, when it was orally administrated below the dosage 2.0 g/Kg/day for 4weeks.

Effects of Donor Somatic Cell Conditions on In Vitro Development of Nuclear Transplanted Porcine Embryos (돼지 공여세포의 조건이 핵이식 수정란의 체외발달에 미치는 영향)

  • 홍승표;박준규;이명열;이지삼;정장용
    • Journal of Embryo Transfer
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    • v.16 no.3
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    • pp.213-221
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    • 2001
  • This study was conducted to examine in vitro developmental ability of porcine embryos after somatic cell nuclear transfer. The porcine ear fell was cultured in vitro for confluency in serum-starvation condition(TCM-199 + 0.5% FBS) far 3~6 days of cell confluency. The zona pellucida of IVM oocytes were partially drilled using laser system. Single somatic cell was individually transferred into enucleated oocytes. And the reconstructed embryos were electrically fused(single DC 1.9kv/cm, 30$\mu$ sec) with 0.3M mannitol. After electrofusion, embryos were activated(single AC 5v/mm, 5sec) and cultured in HCSU-23 medium containing 10% FBS at 39$^{\circ}C$, 5% $CO_2$ in air for 6 to 8 days. The fusion rate of donor cells was 45.6, 36.8 and 46.1% in 3~4, 5~6 days of serum starvation and non serum starvation(N-S), and were 52.7. 53.0 and 51.7% in 1~2. 5~6 and 13~14 passages of donor cell culture, respectively. No significant difference was found in the fusion rate of donor cells by the duration of serum starvation treatment or the number of donor cell passages. By the size of donor cells, however, the fusion rate was significantly higher(P<0.05) for reconstructed embryos derived from 25r $\mu$m $\geq$ site of donor cells (65.3%) than that of 25~30$\mu$ m(42.5%) or 30$\mu$ m(45.5%)$\leq$ cells. The cleavage rate was significantly (P<0.05) higher in 3~4 darts of serum starvation treatment(67.1%) than that in N-S (50.7%) or 5~6 days of starvation(57.1%). The activation rate by the size of donor cells in fused oocytes was 56.5, 68.8 and 58.5%, respectively, and was not significant.

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Feasibility of Off-Pump Coronary Artery Bypass Grafting Using Bilateral Skeletonized Internal Thoracic Arteries (양측 내흉동맥을 이용한 관상동맥 우회술의 임상적 분석)

  • Lee, Jun-Wan;Lee, Jae-Won;Kim, Jong-Woo;Choo, Suk-Joong;Song, Hyun;Rheu, Sang-Wan;Kim, Jong-Wook;Park, Jong-Bin;Song, Meong-Gun
    • Journal of Chest Surgery
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    • v.36 no.10
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    • pp.728-733
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    • 2003
  • Background: The aim of the current study was to assess the effects of total arterial myocardial revascularization (TAMR) with bilateral internal mammary arteries. Material and Method: 139 consecutive patients who underwent off pump coronary artery bypass surgery from January 2000 to December 2001 were included in the current retrospective study. Patients were divided into those receiving bilateral internal mammary artery, BITA (n=85) and those receiving single internal mammary artery, SITA (n=54). Result: There was only one death in each group. No significant differences were noted in the total ICU and hospital stay; 2.4$\pm$1.7 and 11.2$\pm$17.7 days, in the BITA group, respectively and 2.8$\pm$2.7 and 9.7$\pm$7.1 days in the SITA group, respectively (P>0.05). The mean number of distal anastomosis of 3.9$\pm$0.7 was slightly higher in the SITA group compared to the SITA group, which was 3.1$\pm$0.8. Myocardial infarction occurred in 7 patients (BITA group: 2, SITA group: 5) and deep sternal infection necessitating reoperation occurred in 4 patients (BITA group: 3, SITA group: 1). Coronary angiogram was performed in the immediate postoperative period in 104 patients (BITA group: 64/85, SITA group: 40/54). Of these patients, stenosis in the LAD anastomosis site occurred in 4 patients (BITA group: 2, SITA group: 2). A total of 8 anastomotic sites were stenotic in the entire series of which percutaneous intervention was performed in 3 patients and none required reoperative coronary artery bypass. Conclusion: The results of the current data did not show a significant difference in patiency rate with bilateral internal mammary artery use for CABG supporting the feasibility of its use as a viable alternative method for TAMR.

Investigation on Inhibitory Effect of ErmSF N-Terminal End Region Peptide on ErmSF Methyltansferase Activity In Vivo Through Development of Co-Expression System of Two Different Proteins in One Cell (서로 다른 두 단백질의 세포 내 동시 발현 체계의 개발을 통한 ErmSF에서 특이적으로 발견되는 N-Terminal End Region (NTER)을 포함하는 펩타이드의 생체내에서의 ErmSF 활성 억제 효과 검색)

  • Jin, Hyung-Jong
    • Korean Journal of Microbiology
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    • v.47 no.3
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    • pp.200-208
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    • 2011
  • Most problematic antibiotic resistance mechanism for MLS (macrolide-lincosamide-streptogramn B) antibiotics encountered in clinical practice is mono- or dimethylation of specific adenine residue at 2058 (E. coli coordinate) of 23S rRNA which is performed by Erm (erythromycin ribosome resistance) protein through which bacterial ribosomes reduce the affinity to the antibiotics and become resistant to them. ErmSF is one of the four gene products produced by Streptomyces fradiae to be resistant to its own antibiotic, tylosin. Unlike other Erm proteins, ErmSF harbors idiosyncratic long N-terminal end region (NTER) 25% of which is comprised of arginine well known to interact with RNA. Furthermore, NTER was found to be important because when it was truncated, most of the enzyme activity was lost. Based on these facts, capability of NTER peptide to inhibit the enzymatic activity of ErmSF was sought. For this, expression system for two different proteins to be expressed in one cell was developed. In this system, two plasmids, pET23b and pACYC184 have unique replication origins to be compatible with each other in a cell. And expression system harboring promoter, ribosome binding site and transcription termination signal is identical but disparate amount of protein could be expressed according to the copy number of each vector, 15 for pACYC and 40 for pET23b. Expression of NTER peptide in pET23b together with ErmSF in pACYC 184 in E. coli successfully gave more amounts of NTER than ErmSF but no inhibitory effects were observed suggesting that there should be dynamicity in interaction between ErmSF and rRNA rather than simple and fixed binding to each other in methylation of 23S rRNA by ErmSF.

Retrieval of Pollen Optical Depth in the Local Atmosphere by Lidar Observations (라이다를 이용한 지역 대기중 꽃가루의 광학적 두께 산출)

  • Noh, Young-Min;Lee, Han-Lim;Mueller, Detlef;Lee, Kwon-Ho;Choi, Young-Jean;Kim, Kyu-Rang;Choi, Tae-Jin
    • Korean Journal of Remote Sensing
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    • v.28 no.1
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    • pp.11-19
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    • 2012
  • Air-borne pollen, biogenically created aerosol particle, influences Earth's radiative balance, visibility impairment, and human health. The importance of pollens has resulted in numerous experimental studies aimed at characterizing their dispersion and transport, as well as health effects. There is, however, limited scientific information concerning the optical properties of airborne pollen particles contributing to total ambient aerosols. In this study, for the first time, optical characteristics of pollen such as aerosol backscattering coefficient, aerosol extinction coefficient, and depolarization ratio at 532 nm and their effect to the atmospheric aerosol were studied by lidar remotes sensing technique. Dual-Lidar observations were carried out at the Gwangju Institute of Science & Technology (GIST) located in Gwagnju, Korea ($35.15^{\circ}E$, $126.53^{\circ}N$) for a spring pollen event from 5 to 7 May 2009. The pollen concentration was measured at the rooftop of Gwangju Bohoon hospital where the building is located 1.0 km apart from lidar site by using Burkard trap sampler. During intensive observation period, high pollen concentration was detected as 1360, 2696, and $1952m^{-3}$ in 5, 6, and 7 May, and increased lidar return signal below 1.5km altitude. Pollen optical depth retrieved from depolarization ratio was 0.036, 0.021, and 0.019 in 5, 6, and 7 May, respectively. Pollen particles mainly detected in daytime resulting increased aerosol optical depth and decrease of Angstrom exponent.

Histological Changes in Rat Testis by Injection of Hypertonic Saline (고장성 식염수 주사에 의한 흰쥐 정소의 해부학적 변화)

  • Kwak, Byung-Kuk;Lee, Chul-Sang;Lee, Sung-Ho
    • Development and Reproduction
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    • v.14 no.4
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    • pp.281-286
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    • 2010
  • Recent evidence has revealed that the intratesticular injection of hypertonic saline(20%) resulted in a chemically castrated state such as nadir testosterone levels in rats. To confirm the efficacy of this simple saline-injection method further, we investigated the changes in the gross and microscopic anatomy of testis. Our study comprised three groups; intact(control) group, orchidectomy group and saline-injection (experimental) group. Single dose of hypertonic saline (sterilized, $750{\mu}{\ell}/testis$) were directly administered into both testis of adult rats (about 300 g BW). Bilateral orchidectomy was performed at the same day of saline injection. Following 30 days post-injection, reproductive tissues were surgically removed, weighed and fixed for histological examination. The body weights were not changed in both orchidectomy group and saline-injection group when compared to those in intact group. The wet weights of testis were significantly decreased in saline-injection group when compared to those in intact group. The wet weights of epididymis and seminal vesicle and prostate were significantly decreased in orchidectomy group and saline-injection group when compared to those in intact group. Macroscopically, the testes exerted slight atrophy and the tunica albuginea seemed to be intact in saline injection group. Histologically, however, larger parts of testicular tissue underwent necrosis and were barely recognizable after hematoxylin-eosin staining. In the same section, only the opposite part of the injection site was stained showing abnormal state of cell layers mostly fibrosis and infiltrated leukocytes. Sloughing of immature germ cells from the basement membrane along with shedding cells in the intraluminal space was notable in most seminiferous tubules from the saline injected testis. The present study confirmed that the direct injection of hypertonic saline into testis can induce a castration-like, testosterone-depriving effects on accessory sex organs. Our findings suggest that the efficacy of this less expensive and minimally invasive method seems to be almost even with that of conventional orchidectomy and chemical castration, though more in-depth evaluation should be supported.

Study on the Methodology of the Microbial Risk Assessment in Food (식품중 미생물 위해성평가 방법론 연구)

  • 이효민;최시내;윤은경;한지연;김창민;김길생
    • Journal of Food Hygiene and Safety
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    • v.14 no.4
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    • pp.319-326
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    • 1999
  • Recently, it is continuously rising to concern about the health risk being induced by microorganisms in food such as Escherichia coli O157:H7 and Listeria monocytogenes. Various organizations and regulatory agencies including U.S.FPA, U.S.DA and FAO/WHO are preparing the methodology building to apply microbial quantitative risk assessment to risk-based food safety program. Microbial risks are primarily the result of single exposure and its health impacts are immediate and serious. Therefore, the methodology of risk assessment differs from that of chemical risk assessment. Microbial quantitative risk assessment consists of tow steps; hazard identification, exposure assessment, dose-response assessment and risk characterization. Hazard identification is accomplished by observing and defining the types of adverse health effects in humans associated with exposure to foodborne agents. Epidemiological evidence which links the various disease with the particular exposure route is an important component of this identification. Exposure assessment includes the quantification of microbial exposure regarding the dynamics of microbial growth in food processing, transport, packaging and specific time-temperature conditions at various points from animal production to consumption. Dose-response assessment is the process characterizing dose-response correlation between microbial exposure and disease incidence. Unlike chemical carcinogens, the dose-response assessment for microbial pathogens has not focused on animal models for extrapolation to humans. Risk characterization links the exposure assessment and dose-response assessment and involve uncertainty analysis. The methodology of microbial dose-response assessment is classified as nonthreshold and thresh-old approach. The nonthreshold model have assumption that one organism is capable of producing an infection if it arrives at an appropriate site and organism have independence. Recently, the Exponential, Beta-poission, Gompertz, and Gamma-weibull models are using as nonthreshold model. The Log-normal and Log-logistic models are using as threshold model. The threshold has the assumption that a toxicant is produce by interaction of organisms. In this study, it was reviewed detailed process including risk value using model parameter and microbial exposure dose. Also this study suggested model application methodology in field of exposure assessment using assumed food microbial data(NaCl, water activity, temperature, pH, etc.) and the commercially used Food MicroModel. We recognized that human volunteer data to the healthy man are preferred rather than epidemiological data fur obtaining exact dose-response data. But, the foreign agencies are studying the characterization of correlation between human and animal. For the comparison of differences to the population sensitivity: it must be executed domestic study such as the establishment of dose-response data to the Korean volunteer by each microbial and microbial exposure assessment in food.

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The Effects of Dimethyl Sulfoxide and Sodium Thiosulfate for the Prevention of Tissue Necrosis due to Extravasaion of Mitomycin-C (혈관외로 유출된 Mitomycin-C에 의한 조직괴사 예방을 위한 Dimethyl Sulfoxide와 Sodium Thiosulfate의 효과)

  • Woo, Sang-Hyun;Choi, Byung-Cheol;Kim, Ki-Hyung;Seul, Jung-Hyun;Jung, Tae-Eun
    • Journal of Yeungnam Medical Science
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    • v.13 no.2
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    • pp.243-250
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    • 1996
  • Extravasation of toxic chemotherapeutic agents cause severe skin ulceration and necrosis which often need secondary surgical intervention. Still, there were not established antidote agent in case of extravasation with mitomycin-c. Dimethyl sulfoxide is known as an effective chemical scavenger of toxic hydroxyl free radical and sodium thiosulfate also was demonstrated significant protector from mitomycin-c induced ulceration by a few experimental studies. Author investigated necrotic area of mitomycin-c injected site and compare to the effectiveness of topical treatment with dimethyl sulfoxide and intradermal injection of sodium thiosulfate according to starting times, forty five mice were divided into 3 groups. Control group(n=5) had no treatment after subcutaneous injection of mitomycin-c. Experimental group I and II were 20 mice treated dimethyl sulfoxide and sodium thiosulfate, respectively. Depending on the starting time of treatment, group I and II were subdivided into 1, 2, 3 and 4 as immediate, 6 hours, 12 hours and 24 hours after mitomycin-c injection. Histologic studies of the necrotic area and survival area after treatment were performed using hematoxylin-eosin staining. The mean necrotic area of group I was significantly decreased depending on the starting time of treatment compared with control group(p<0.01). The results means there was no necrosis area which was treated with topical sodium thiosulfate within 6 hours, and it showed also significant decrease of necrosis area within 24 hours. There was also no necrosis area in group II-1 and significant decrease of necrosis area II-2 and III-3. But, effctiveness of intradermal injection of sodium thiosulfate was not found in group II-4 which was started after 24 hours. Hisotolgic findings showed a bland coagulative necrosis without inflammatory changes and no granulation tissue. The significant difference that cytoplasmic loss of subcutaneous fat and decrease number of hair follicles between two groups resulted from the methods of treatment by topical application and intradermal injection. In conclusion, immediate treatments with topical dimethyl sulfoxide or intradermal injection of sodium thiosulfate signifcantly prevents necrosis by extravasation of mitomycin-c.

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Studies on the Fracture Healing in the Alloxan treated Rabbits (Alloxan 투여 가토(家兎)에 대한 골절치유 실험)

  • Kim, Sung-Joon
    • The Korean Journal of Pharmacology
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    • v.7 no.1
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    • pp.53-65
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    • 1971
  • It is well known that diabetes mellitus is associated with metabolic derangements, such as hyper-glycemia, ketosis, glycosuria, and also widespread alterations in the blood vessels, kidneys, eyes, peripheral nerves and heart. It is also recognized that healing of skin wound is delayed in diabetics. In bone, according to Aegerter, osteopenia develops in diabetes mellitus and it is chiefly ascribed to overutilization of protein. Shim claims that total blood flow to the entire skeletal system is approximately 4 to 8 percent of resting cardiac output and blood supply to the skeletal system would be decreased on account of secondary arteriosclerotic changes in the diabetics. An adequate blood supply is an essential factor in the healing process of fracture, and disturbed blood flow, either local or systemic, will invariably delay union of the fragments or the fragments from being fused. As the author has encountered several cases of diabetics in whom healing of fracture was delayed or incomplete, this experimental study was undertaken to elucidate the effects of hyperglycemia and diabetes mellitus on the healing process of fracture. In this experiment adult albino rabbits, weighing about 2 kg. were used and divided into 6 groups. The femur of each animal was fractured surgically, and then the healing process of fracture was periodically checked by radiography at an interval of one week for a period of 6 weeks. Thereafter, all the rabbits were killed to obtain tissue preparation of the femur. The experimental groups were as follows; 1) Control group: Six rabbits sustained a surgical fracture to the femur, without being given any other treatment or drug. 2) Alloxan-treated group: For inducing diabetes, alloxan was given intravenously to 17 rabbits in various dose as follows; to 7 of them 40 mg/kg, to 6 rabbits 80 mg/kg and to 4 rabbits 120 mg/kg of body weight, respectively. 3) Insulin-treated group: Protamine-zinc insulin was injected subcutaneously to each of 6 rabbits in a daily dose of 1 unit per kilogram of body weight. 4) Group treated with insulin after alloxan: Four rabbits were given 80 mg of alloxan once and than 1 unit of insulin per kilogram of body weight daily. Another 5 rabbits were injected 1 unit of insulin per kg of body weight daily following administration of alloxan in a dose of 120 mg/kg. 5) Homotransplantation group: Following intravenous injection of alloxan in a dose of 120 mg/kg, 10 rabbits underwent homotransplantation of a short bone segment to the femur. Five of them were subsequently given 1 unit/kg of insulin daily. 6) Sugar-treated group: six rabbits were fed $15{\sim}20$ gm of sugar daily throughout the period of experiment. The results obtained are summarized as follows; 1. Blood sugar level and damage to the pancreatic islet increased proportionately when alloxan was given to the rabbits in various doses. No appreciable change could be observed in the islets when the blood sugar level was altered by either oral administration of sugar or subcutaneous injection of insulin. 2. Comparing with the control group, healing of fracture was delayed in the alloxan-treated group, while callus formation and periosteal reaction were shown to be more prominent in this group and subsequently, the ultimate osseous tissue formed at the fracture site was significantly smaller in amount and less compact. These findings were more marked as the amount of alloxan increased. 3. Administration of insulin prevented the delay in healing process of fracture in the rabbits with alloxan-induced hyperglycemia. In this case, the course and progression of fracture healing were almost similar to those of control group. 4. Union between the host bone and the fragment transplanted from other rabbit of the same species was more delayed in the group treated with alloxan alone than in the group to which insulin was administered after development of alloxan-induced diabetes. In both groups periosteal new bone developed from the ends of the host bone, above and below the transplanted fragment, and directly fused with failure of periosteal callus to bridge the adjacent ends of the host bone and the transplanted fragment. 5. The healing process of fracture was not inhibited by alteration in blood sugar level when the blood sugar was abnormally increased by excessive sugar intake or lowered by administration of insulin alone. The healing of fracture in these groups progressed similarly as in the control group. In brief summary, it appears that the healing process of fracture would be definitely disturbed in diabetic state brought about by damage to the pancreatic islet. As such an inhibition could be overcome with insulin, it seems that insulin plays an important role in healing of fracture, but alteration in blood sugar level alone does not modify healing process of fracture to significant degree.

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Insulin-like growth factor가 소장 점막 세포 증식에 미치는 영향

  • 윤정한
    • Proceedings of the Korean Nutrition Society Conference
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    • 1995.11b
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    • pp.11-34
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    • 1995
  • Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

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