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factor-I
Kinds of factor-I Terms modified by factor-I Selected AbstractsSERUM INSULIN-LIKE GROWTH FACTOR-I AND INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-3 FOLLOWING CHEMOTHERAPY FOR ADVANCED BREAST CANCERANZ JOURNAL OF SURGERY, Issue 11 2003Ian M. Holdaway Background: Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) appear to influence the growth of breast cancer cells in vitro, and epidemiological studies suggest higher serum IGF-I levels increase the risk of breast cancer. IGF-I and IGFBP-3 have therefore been measured in women with advanced breast cancer to determine if changes in serum levels predict the response to treatment by chemotherapy. Methods: Serum IGF-I and IGFBP-3 levels were measured in 14 patients before and after 1 week of chemotherapy. Changes in serum levels were compared with duration of survival. Results: Mean basal serum levels of IGF-I and IGFBP-3 were not significantly different between patients with advanced breast cancer and controls or women with early breast cancer. Serum IGFBP-3 fell significantly 1 week after initiation of chemotherapy. Patient survival was not significantly related to baseline IGF-I or IGFBP-3 levels, but when the fall in serum levels 1 week after starting treatment was expressed either as absolute change or as a percentage of baseline, those individuals with a decrease in IGFBP-3 greater than the median had significantly poorer survival (median survival 5.5 months vs 18 months). These results were independent of other prognostic variables such as previous disease-free survival, and were also unaffected by the change in serum albumin with treatment. The fall in IGF-I and IGFBP-3 with chemotherapy mainly occurred in those with hepatic metastases, but prediction of survival was explained solely by the extent of the fall in IGFBP-3. Conclusions: This preliminary study has shown that serum IGFBP-3 falls significantly following initiation of chemotherapy and the extent of reduction significantly predicts the response to treatment. [source] CHARACTERIZATION OF THE ACUTE CARDIOVASCULAR EFFECTS OF INTRAVENOUSLY ADMINISTERED INSULIN-LIKE GROWTH FACTOR-I IN CONSCIOUS SPRAGUE-DAWLEY RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2006Nga Cao SUMMARY 1Insulin-like growth factor (IGF)-I has acute effects on cardiovascular function, including a well-characterized vasodilator response in isolated arteries. In addition to increasing the release of nitric oxide, IGF-I also has effects on a variety of other signalling pathways that affect vascular tone, in particular interactions with the sympathetic nervous system and the renin,angiotensin,aldosterone system. We sought to characterize the effects of intravenous IGF-I on blood pressure and on responses to noradrenaline (NA), angiotensin II, acetylcholine and dobutamine. 2Administration of IGF-I administration caused small decreases in mean arterial pressure (5.4 ± 1.5%) and responsiveness to the prazosin-sensitive vasoconstrictor effects of NA (a 2.1 ± 0.6-fold increase in ED50; n = 40; P < 0.01) and both effects were maximal at 200 µg/kg IGF-I. In addition, IGF-I significantly increased pulse pressure increases induced by low doses of dobutamine (from an increase in pulse pressure of 9.9 ± 1.2 to 13.4 ± 1.9 mmHg; n = 39; P < 0.05). Administration of IGF-I had no significant effect on responses to AngII or ACh. 3Intravenous administration of IGF-I receptor antisense oligonucleotides (400 µg/kg) abolished the effects of IGF-I on NA-induced vasoconstriction (n = 11; P < 0.05), whereas administration of a mismatch oligonucleotide did not. 4These data indicate that the maximal effects of exogenously administered IGF-I include modest direct vasodilation and inhibition of constrictor responses to NA and an increase in the effect of dobutamine on pulse pressure. The magnitude of these effects was less than what previous in vitro studies and those performed in anaesthetized animals may have indicated likely. 5The modest magnitude of the dilator effects of IGF-I observed in conscious rats in vivo in the present study suggests that IGF-I is unlikely to be a major player in regulating vascular tone in normotensive animals. [source] Premenopausal Breast Cancer: Estrogen Receptor Status and Insulin-Like Growth Factor-I (IGF-I), Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3), and LeptinTHE BREAST JOURNAL, Issue 4 2009Jennifer Eng-Wong MD No abstract is available for this article. [source] Effects of in utero exposure to 2,2,,4,4,,5,5,-hexachlorobiphenyl (PCB 153) on somatic growth and endocrine status in rat offspringCONGENITAL ANOMALIES, Issue 4 2008Kenichi Kobayashi ABSTRACT Exposure to polychlorobiphenyl (PCB) mixtures at an early stage of development has been reported to affect endocrine glands; however, little is known about the precise toxicological properties of individual PCB. The present study was undertaken to determine whether prenatal exposure to 2,2,,4,4,,5,5,-hexachlorobiphenyl (PCB 153), a di- ortho -substituted non-coplanar congener, affects postnatal development in rat offspring. Pregnant Sprague-Dawley rats (Crj: CD (SD) IGS) were given PCB 153 (0, 16, or 64 mg/kg/day) orally from gestational day (GD) 10 through GD 16, and developmental parameters in the male and female offspring were examined. We found no dose-dependent changes in body weight, body length (nose,anus length), tail length, or the weights of kidneys, testes, ovaries and uterus in offspring at 1 or 3 weeks of age. Liver weights were increased in the PCB 153,treated groups, although we observed a significant difference only in males. Anogenital distance was unaffected in the PCB 153,treated groups. We observed a significant dose-dependent decrease in the plasma concentrations of thyroxine and tri-iodothyronine, whereas those of thyroid-stimulating hormone were not significantly changed. In addition, there were no dose-dependent changes in plasma concentrations of growth hormone and insulin-like growth factor-I in any dose group. These findings suggest that prenatal exposure to PCB 153 (GD 10,16, 16,64 mg/kg/day) may alter the thyroid status in rat offspring to some extent without affecting somatic growth or its related hormonal parameters. [source] Pubertal maturation modifies the regulation of insulin-like growth factor-I receptor signaling by estradiol in the rat prefrontal cortexDEVELOPMENTAL NEUROBIOLOGY, Issue 8 2008Amaya Sanz Abstract The transition from adolescence to adulthood is accompanied by substantial plastic modifications in the cerebral cortex, including changes in the growth and retraction of neuronal processes and in the rate of synaptic formation and neuronal loss. Some of these plastic changes are prevented in female rats by prepubertal ovariectomy. The ovarian hormone estradiol modulates neuronal differentiation and survival and these effects are in part mediated by the interaction with insulin-like growth factor-I (IGF-I). In this study, we have explored whether the activation by estradiol of some components of IGF-I receptor signaling is altered in the prefrontal cortex during puberty. Estradiol administration to rats ovariectomized after puberty resulted, 24 h after the hormonal administration, in a sustained phosphorylation of Akt and glycogen synthase kinase 3, in the prefrontal cortex. However, this hormonal effect was not observed in animals ovariectomized before puberty. These findings suggest that during pubertal maturation there is a programming by ovarian hormones of the future regulatory actions of estradiol on IGF-I receptor signaling in the prefrontal cortex. The modification in the regulation of IGF-I receptor signaling by estradiol during pubertal maturation may have implications for the developmental changes occurring in the prefrontal cortex in the transition from adolescence to adulthood. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] The role of IGF-I and its binding proteins in the development of type 2 diabetes and cardiovascular diseaseDIABETES OBESITY & METABOLISM, Issue 3 2008Vivienne A. Ezzat Patients with insulin resistance and type 2 diabetes have an excessive risk of cardiovascular disease (CVD); this increased risk is not fully explained by traditional risk factors such as hypertension and dyslipidaemias. There is now compelling evidence to suggest that abnormalities of insulin-like growth factor-I (IGF-I) and one of its binding proteins, insulin-like growth factor-binding protein-1 (IGFBP-1), occur in insulin-resistant states and may be significant factors in the pathophysiology of CVD. We reviewed articles and relevant bibliographies following a systematic search of MEDLINE for English language articles between 1966 and the present, using an initial search strategy combining the MeSH terms: IGF, diabetes and CVD. Our aim was first to review the role of IGF-I in vascular homeostasis and to explore the mechanisms by which it may exert its effects. We also present an overview of the physiology of the IGF-binding proteins, and finally, we sought to summarize the evidence to date describing the changes in the insulin/IGF-I/IGFBP-1 axis that occur in type 2 diabetes and CVD; in particular, we have focused on the potential vasculoprotective effects of both IGF-I and IGFBP-1. We conclude that this system represents an interesting and novel therapeutic target in the prevention of CVD in type 2 diabetes. [source] Appraising the mitogenicity of insulin analogues relative to human insulin,response to: Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and anti-apoptotic activity in cultured cancer cells.DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2010Diabetes Metab Res Rev 2009; 25(1): 4 Abstract Interest in mitogenic and potentially carcinogenic effects of insulin and insulin analogues has been renewed by several recent publications that have examined the relationship between cancer and insulin analogues. Actions mediated through the insulin-like growth factor-I receptor in a hyperinsulinaemic state have been implicated mechanistically. Both type 2 diabetes and endogenously elevated insulin-like growth factor-I have been epidemiologically linked to malignancies. Therefore, in vitro mitogenic effects and binding affinities of the various analogues have been analysed. A recent publication by Weinstein et al. studied the in vitro mitogenic and anti-apoptotic activities of insulin analogues, and their conclusion asserts that insulins glargine, detemir, and lispro displayed proliferative and anti-apoptotic effects in a number of malignant cell lines. However, their conclusions are not supported by the data which are not complete and lack clear statistical significance. This data should be interpreted cautiously in light of all other presently available scientific evidence. Prospective, randomized clinical trials will best address any direct relationship between insulin analogues and cancer. Until those studies are designed and completed, clinicians should consider the demonstrated strong benefit of glycaemic control in balance with any alleged risk. Copyright © 2010 John Wiley & Sons, Ltd. [source] The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2009Swapnil N. Rajpathak Abstract This review addresses the possible role of the insulin-like growth factor (IGF)-axis in normal glucose homoeostasis and in the etiopathogenesis of type 2 diabetes. IGF-I, a peptide hormone, shares amino acid sequence homology with insulin and has insulin-like activity; most notably, the promotion of glucose uptake by peripheral tissues. Type 2 diabetes as well as pre-diabetic states, including impaired fasting glucose and impaired glucose tolerance, are associated cross-sectionally with altered circulating levels of IGF-I and its binding proteins (IGFBPs). Administration of recombinant human IGF-I has been reported to improve insulin sensitivity in healthy individuals as well as in patients with insulin resistance and type 2 diabetes. Further, IGF-I may have beneficial effects on systemic inflammation, a risk factor for type 2 diabetes, and on pancreatic ,-cell mass and function. There is considerable inter-individual heterogeneity in endogenous levels of IGF-I and its binding proteins; however, the relationship between these variations and the risk of developing type 2 diabetes has not been extensively investigated. Large prospective studies are required to evaluate this association. Copyright © 2009 John Wiley & Sons, Ltd. [source] Impact of microcystin containing diets on physiological performance of Nile tilapia (Oreochromis niloticus) concerning stress and growth,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2010Andrea Ziková Abstract Diets containing Microcystis with considerable amounts of the cyanotoxin microcystin-LR (MC-LR) were fed to determine their impact on the physiological performance of the omnivorous Nile tilapia (Oreochromis niloticus) with regard to stress and growth performance. Four different diets were prepared based on a commercial diet (control, MC-5% [containing 5% dried Microcystis biomass], MC-20% [containing 20% dried Microcystis biomass], and Arthrospira-20% [containing 20% dried Arthrospira sp. biomass without toxin]) and fed to female Nile tilapia. Blood and tissue samples were taken after 1, 7, and 28 d, and MC-LR was quantified in gills, muscle, and liver by using high-performance liquid chromatography (HPLC). Only in the liver were moderate concentrations of MC-LR detected. The stress hormone cortisol and glucose were analyzed from plasma, suggesting that all modified diets caused only minor to moderate stress, which was confirmed by analyses of hepatic glycogen. In addition, the effects of the different diets on growth performance were investigated by determining gene expression of hypophyseal growth hormone (GH) and hepatic insulin-like growth factor-I (IGF-I). For all diets, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) demonstrated no significant effect on gene expression of the major endocrine hormones of the growth axis, whereas classical growth data, including growth and feed conversion ratio, displayed slight inhibitory effects of all modified diets independent of their MC-LR content. However, no significant change was found in condition or hepatosomatic index among the various diets, so it seems feasible that dried cyanobacterial biomass might be even used as a component in fish diet for Nile tilapia, which requires further research in more detail. Environ. Toxicol. Chem. 2010;29:561,568. © 2009 SETAC [source] Reduced growth hormone receptor immunoreactivity in osteoclasts adjacent to the erupting molar in the incisor-absent (osteopetrotic) ratEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 6 2003Anne L. Symons First molars fail to erupt in the incisor-absent (ia/ia) rat because of a defect in osteoclast function. Growth factors that regulate local bone metabolism include growth hormone (GH), insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF) and interleukin-1 alpha (IL- 1,). Since osteoclast function may be affected by these factors, the aim of this study was to determine the distribution of GH receptor (GHr), IGF-I, EGF and IL-1,, in osteoclasts located occlusal to the erupting first molar, in the ,eruption pathway', in normal and ia/ia rats. Sagittal sections of the first molar and adjacent bone from 3- and 9-d-old animals were examined. Osteoclasts were identified using tartrate-resistant acid phosphatase (TRAP). The TRAP-positive osteoclast cell numbers were higher in ia/ia animals at 3 and 9 days-of-age. In the ia/ia group, fewer osteoclasts were GHr- and IGF-I-positive at 3 d of age, and at 9 d of age fewer osteoclasts were GHr-positive. In the ia/ia rat, defective osteoclast function failed to resorb bone to provide an eruption pathway for the lower first molar. The expression of GHr, and to some degree IGF-I, by these osteoclasts was reduced, which may be related to their ability to differentiate and function. [source] Adult-onset deficiency in growth hormone and insulin-like growth factor-I alters oligodendrocyte turnover in the corpus callosumGLIA, Issue 10 2009Kun Hua Abstract Growth hormone (GH) and insulin-like growth factor-I (IGF-I) provide trophic support during development and also appear to influence cell structure, function and replacement in the adult brain. Recent studies demonstrated effects of the GH/IGF-I axis on adult neurogenesis, but it is unclear whether the GH/IGF-I axis influences glial turnover in the normal adult brain. In the current study, we used a selective model of adult-onset GH and IGF-I deficiency to evaluate the role of GH and IGF-I in regulating glial proliferation and survival in the adult corpus callosum. GH/IGF-I-deficient dwarf rats of the Lewis strain were made GH/IGF-I replete via twice daily injections of GH starting at postnatal day 28 (P28), approximately the age at which GH pulse amplitude increases in developing rodents. GH/IGF-I deficiency was initiated in adulthood by removing animals from GH treatment. Quantitative analyses revealed that adult-onset GH/IGF-I deficiency decreased cell proliferation in the white matter and decreased the survival of newborn oligodendrocytes. These findings are consistent with the hypothesis that aging-related changes in the GH/IGF-I axis produce deficits in ongoing turnover of oligodendrocytes, which may contribute to aging-related cognitive changes and deficits in remyelination after injury. © 2008 Wiley-Liss, Inc. [source] Insulin-like growth factor-I, liver function, and hypogonadism in rats with experimentally induced cirrhosisHEPATOLOGY, Issue 6 2000Inma Castilla-Cortazar M.D. No abstract is available for this article. [source] Effects of aging on early B- and T-cell developmentIMMUNOLOGICAL REVIEWS, Issue 1 2005Hyeyoung Min Summary:, Lymphocyte production in the bone marrow and the thymus is reduced during aging, but why this decline occurs has not been fully elucidated. The ability to isolate hematopoietic stem and progenitor cells using sophisticated flow cytometric strategies and to manipulate them in vitro and in vivo has provided insights into the effects of aging on primary lymphopoiesis. These analyses have showed that intrinsic changes in hematopoietic precursors that affect their proliferative potential are one factor that contributes to the age-related decline in B- and T-cell production. This and other age-related defects may be exacerbated by changes in the lymphopoietic support potential of the bone marrow and thymic microenvironments as well as by age-induced fluctuations in the production of various endocrine hormones. Particular attention with regard to the latter point has focused on changes in the production of sex steroids, growth hormone, and insulin-like growth factor-I. The present review summarizes recent studies of how age-related perturbations affect primary lymphopoiesis and highlights how the data necessitate the reevaluation of a number of existing paradigms. [source] Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian womenINTERNATIONAL JOURNAL OF CANCER, Issue 11 2007Yngve Bremnes Abstract The associations between endogenous sex hormone levels and breast cancer risk in postmenopausal women are well established. Mammographic density is a strong risk factor for breast cancer, and possibly an intermediate marker. However, the results from studies on the associations between endogenous sex hormones and mammographic density are conflicting. The authors examined the associations between circulating levels of sex hormones, sex hormone binding globulin (SHBG) and prolactin and mammographic densities among postmenopausal women not currently using postmenopausal hormone therapy (HT). The authors also examined if insulin-like growth factor-I (IGF-I) levels influenced the association between estrogen and mammographic density. Altogether, 722 postmenopausal participants in the Norwegian governmental mammographic screening program had endogenous hormone concentrations measured. Mammograms were classified according to percent and absolute mammographic density using a previously validated computer-assisted method. After adjustment for age, number of children, age at menopause, body mass index and HT use, both plasma concentrations of SHBG (p -trend = 0.003) and estrone (p -trend = 0.07) were positively associated with percent mammographic density. When the analyses were stratified according to median IGF-I concentration, the weak association between estrone and mammographic density was strengthened among women with IGF-I levels below median, while the association disappeared among women with over median IGF-I levels (p for interaction = 0.02). In summary, the authors found a positive association between plasma SHBG levels and mammographic densities among 722 postmenopausal Norwegian women not currently using HT. Further, the authors found a positive but weak association between plasma estrone concentration and mammographic density, which appeared to be modified by IGF-I levels. © 2007 Wiley-Liss, Inc. [source] Growth factors in periodontal regenerationINTERNATIONAL JOURNAL OF DENTAL HYGIENE, Issue 2 2009S Raja Abstract:, Inflammatory periodontal disease is an almost ubiquitous disorder in the adult population. Cases or sites with moderate to advanced disease often continue to show signs of inflammation after non-surgical approach. Our current understanding of periodontal healing is based on a hypothesis by Melcher who proposed that the cell type that repopulates the exposed root surface at the periodontal repair site will define the nature of the attachment/repair that take place. If mesenchymal cells from periodontal ligament/perivascular region of the bone proliferate and colonize the root surface, regeneration occurs. Growth factors are natural cell products that are released or activated when cell division is needed. This action typically occurs during such events as wound healing or tissue regeneration. Activated platelets at the wound margins release several growth factors such as platelet-derived growth factor (PDGF), transforming growth factor (TGF)-,, epidermal growth factor etc. Cells adjacent to the injured site also are induced to release growth factors such as insulin-like growth factor-I, PDGF, TGF-, and TGF-, within a few hours after injury. In periodontal regeneration, the coronal re-establishment of the periodontal ligament (PDL) is required together with corresponding cementum and supporting alveolar bone. Thus, agents which promote periodontal ligament fibroblast (PLF) proliferation and migration as well as collagen biosynthesis would appear to be mediators for enhancing new PDL formation. When combinations or cocktails of different factors are used, greater repair is achieved than when individual factors are applied. [source] Treatment of osteopenia and osteoporosis in anorexia nervosa: A systematic review of the literatureINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 3 2009Philip S. Mehler MD Abstract Objective: To systematically review the evidence supporting treatment of osteopenia and osteoporosis in patients with anorexia nervosa (AN). Data sources: We identified controlled clinical studies of interventions for low bone mass in AN via searches of MEDLINE; the Cochrane Library; EMBASE; PsycINFO; and cumulative index to nursing and allied health literature. Outcomes of interest were changes in bone mineral density and fracture incidence. Results: Six randomized controlled trials (RCTs) and two cohort trials examined five classes of medical therapy on bone mineral density outcomes. One RCT of bisphosphonates showed no benefit and a second flawed RCT showed some benefit; one RCT showed a benefit of insulin-like growth factor-I; none of the five trials evaluating estrogen therapy showed benefit. Discussion: Although patients with AN are often losing bone mass when they should be optimizing bone growth, there is no good evidence to guide medicinal interventions. Therefore, early detection and weight restoration are of utmost importance whereas ongoing trials define effective therapies. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2009 [source] Growth Hormone Administration and Exercise Effects on Muscle Fiber Type and Diameter in Moderately Frail Older PeopleJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2001James V. Hennessey MD OBJECTIVE: Reduced muscle mass and strength are characteristic findings of growth hormone deficiency (GHD) and aging. We evaluated measures of muscle strength, muscle fiber type, and cross sectional area in response to treatment with recombinant human growth hormone (rhGH) with or without a structured resistance exercise program in frail older subjects. DESIGN: Placebo-controlled, randomized, double blind trial. SETTING: Outpatient clinical research center at an urban university-affiliated teaching hospital. PARTICIPANTS: Thirty-one consenting older subjects (mean age 71.3 ± 4.5 years) recruited as a subset of a larger project evaluating rhGH and exercise in older people, who underwent 62 quadricep-muscle biopsies. INTERVENTION: Random assignment to a 6-month course of one of four protocols: rhGH administered subcutaneously daily at bedtime, rhGH and a structured resistance exercise program, structured resistance exercise with placebo injections, or placebo injections only. MEASUREMENTS: Muscle biopsy specimens were obtained from the vastus lateralis muscle. Isokinetic dynamometry strength tests were used to monitor individual progress and to adjust the weights used in the exercise program. Serum insulin-like growth factor-I (IGF-I) was measured and body composition was measured using a Hologic QDR 1000W dual X-ray densitometer. RESULTS: The administration of rhGH resulted in significant increase in circulating IGF-I levels in the individuals receiving rhGH treatment. Muscle strength increased significantly in both the rhGH/exercise (+55.6%, P = .0004) as well as the exercise alone (+47.8%, P = .0005) groups. There was a significant increase in the proportion of type 2 fibers between baseline and six months in the combined rhGH treated subjects versus those not receiving rhGH (P = .027). CONCLUSIONS: Our results are encouraging in that they suggest an effect of growth hormone on a specific aging-correlated deficit. IGF-I was increased by administrating rhGH and muscle strength was increased by exercise. The administration of rhGH to frail older individuals in this study resulted in significant changes in the proportions of fiber types. Whether changes in fiber cross-sectional area or absolute number occur with long-term growth hormone administration requires further study. [source] Metabolic and luteal function in winter-calving Spanish beef cows as affected by calf management and breedJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3 2010J. Álvarez-Rodríguez Summary This experiment aimed at evaluating the effect of calf management and breed on the metabolic and luteal function of post-partum beef cows fed at maintenance. Fifty multiparous cows, 22 Parda de Montańa (PA) and 28 Pirenaica (PI), were assigned to either suckling once-daily for 30 min (RESTR) or ad libitum (ADLIB) from the day after calving. Blood samples were collected to analyse metabolites [non-esterified fatty acids (NEFA), ,-hydroxybutyrate, total protein and urea)], insulin-like growth factor-I (IGF-I) and progesterone (P4) at different intervals. Cows from RESTR maintained their live-weight (LW) over the first 3 months post-partum, whereas ADLIB cows lost nearly 4% LW. Both genotypes showed similar LW gains during this period (p > 0.10). Calf daily gains were lower in RESTR than in ADLIB treatment (p < 0.05), but similar across breeds (p > 0.10). Milk and lactose production were lower in RESTR cows than in ADLIB (p < 0.05). Milk and protein yield were greater in PA than in PI breed (p < 0.05). Serum NEFA, total protein and urea were higher in PI cows suckling ADLIB than in the rest (p < 0.05). Cows from PI breed had greater NEFA values than PA ones on the first week post-partum (p < 0.001). Circulating IGF-I was not affected by suckling frequency, breed nor their interaction (p > 0.10). Suckling frequency, but not breed, affected the interval from calving to first ovulation (p < 0.001), being shorter in RESTR than in ADLIB cows. In conclusion, the ad libitum suckling practice improved cow milk yield and offspring gain compared to once-daily suckling for 30 min from the day after calving, at the expense of impairing the onset of cyclicity. The effect of calf management was confounded with breed on the studied blood biochemical constituents, but any of these metabolites influenced the role of endocrine IGF-I in these genotypes. [source] Biodegradable poly(D,L -lactide) coating of implants for continuous release of growth factorsJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 4 2001G. Schmidmaier Abstract Local application of growth factors like insulin like growth factor-I (IGF-I) and transforming growth factor-beta 1 (TGF-,1) from a biodegradable thin layer of poly(D,L -lactide) (PDLLA) coated implants could stimulate fracture healing. A new "cold coating technique" for metallic implants was established to produce a biodegradable coating with a high mechanical stability that provides a continuous release of incorporated growth factors. The properties of this bioactive coating were investigated in vitro and in vivo. Scanning electron microscope analysis revealed a coating thickness of in average 14.8 ,m on titanium and 10.7 ,m on steel wires. Intramedullary implantation and extraction experiments depicted a loss of PDLLA coating from titanium and steel implants of less than 5%. After explantation of the implants, the coating displayed a complete and regular layer without any defects of PDLLA uncovering the metallic surface. Smear tests demonstrate that the coating can be performed under sterile conditions. The PDLLA depicted a reduction of about 8% within 6 weeks in vitro and in vivo. The growth factors were incorporated in a stable form and demonstrated a loss of stability of less than 3% within 42 days and less than 5% within one year. In an elution experiment, 54% IGF-I and 48% TGF-,1 were released within the first 48 h. After 42 days, 76% of IGF-I and 71% of TGF-,1 were detected in the elution fluid by ELISA. Comparable results were obtained in the in vivo experiments after 42 days. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 449,455, 2001 [source] Transcriptional and proteolytic regulation of the insulin-like growth factor-I system of equine articular chondrocytes by recombinant equine interleukin-1,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2006Ryan M. Porter Interleukin-1 (IL-1) and insulin-like growth factor-I (IGF-I), which have opposing effects on matrix metabolism within articular cartilage, are thought to play prominent roles in the pathogenesis of osteoarthritis. To better understand the link between these anabolic (IGF-I) and catabolic (IL-1) stimuli, we examined exogenous IL-1 regulation of the IGF-I signaling system of articular chondrocytes (ACs). Equine ACs from non-arthritic stifle joints were expanded in monolayer culture, encapsulated for 10 days in alginate beads, and stimulated as high-density monolayers with recombinant equine IL-1, (0, 1, 10 ng/ml) for 48 h. IL-1, enhanced expression of IGF-IR levels, as determined by both [125I]-IGF-I binding studies and Western blotting, while reducing the concentration of endogenous IGF-I detected in conditioned media by radioimmunoassay. Western ligand blotting revealed that chondrocytes primarily secreted IGF binding proteins (IGFBPs) with molecular weights of 28,30 and 32,34 kDa, which were identified as IGFBPs 5 and 2, respectively, and that IL-1, treatment diminished IGFBP-2, the prominent homolog in conditioned media. Northern blot analysis suggested IL-1, regulation of IGF-I and, to some extent, IGF-IR was mediated by transcription; however, the cytokine did not affect IGFBP-2 expression. To test for evidence of proteolysis by matrix metalloproteinases (MMPs), additional cultures were co-incubated with inhibitors for MMPs 2/9, 3, and 8. IGFBP-2 suppression was partially reversed by gelatinase (MMP-2/9) inhibition. In summary, these findings further delineate the role of IL-1 as a key regulator of the IGF-I system within articular cartilage, demonstrating that regulation occurs through both direct (transcriptional) and indirect (proteolytic) mechanisms. J. Cell. Physiol. 209: 542,550, 2006. © 2006 Wiley-Liss, Inc. [source] Insulin-like growth factor (IGF) binding protein-3 regulation of IGF-I is altered in an acidic extracellular environmentJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2001Kimberly E. Forsten While extracellular acidification within solid tumors is well-documented, how reduced pH impacts regulation of insulin-like growth factor-I (IGF-I) has not been studied extensively. Because IGF-I receptor binding is affected by IGF binding proteins (IGFBPs), we examined how pH impacted IGFBP-3 regulation of IGF-I. IGF-I binding in the absence of IGFBP-3 was diminished at reduced pH. Addition of IGFBP-3 reduced IGF-I cell binding at pH 7.4 but increased surface association at pH 5.8. This increase in IGF-I binding at pH 5.8 corresponded with an increase in IGFBP-3 cell association. This, however, was not due to an increase in affinity of IGFBP-3 for heparin at reduced pH although both heparinase III treatment and heparin addition reduced IGFBP-3 enhancement of IGF-I binding. An increase in IGF-I binding to IGFBP-3, though, was seen at reduced pH using a cell-free assay. We hypothesize that the enhanced binding of IGF-I at pH 5.8 is facilitated by increased association of IGFBP-3 at this pH and that the resulting cell associated IGF-I is IGFBP-3 and not IGF-IR bound. Increased internalization and nuclear association of IGF-I at pH 5.8 in the presence of IGFBP-3 was evident, yet cell proliferation was reduced by IGFBP-3 at both pH 5.8 and 7.4 indicating that IGFBP-3-cell associated IGF-I does not signal the cell to proliferate and that the resulting transfer of bound IGF-I from IGF-IR to IGFBP-3 results in diminished proliferation. Solution binding of IGF-I by IGFBP-3 is one means by which IGF-I-induced proliferation is inhibited. Our work suggests that an alternative pathway exists by which IGF-I and IGFBP-3 both associate with the cell surface and that this association inhibits IGF-I-induced proliferation. © 2001 Wiley-Liss, Inc. [source] LDL-apheresis up-regulates VEGF and IGF-I in patients with ischemic limbJOURNAL OF CLINICAL APHERESIS, Issue 3 2003Shuzo Kobayashi Abstract Although it is known that LDL-apheresis improves ischemic limb seen in patients with peripheral arterial occlusive disease (PAOD), the underlying mechanism(s) still remains unknown. We studied whether vascular endothelial growth factor (VEGF) and/or insulin-like growth factor-I (IGF-I) levels correlated with improvement of ischemic limbs after LDL-apheresis. Sixteen patients with PAOD (13 men, 3 women) were enrolled in our study. LDL-apheresis was performed 10 times (treated plasma 3,000 ml) for 5 weeks. Serum level of VEGF significantly increased from 262 ± 171 pg/ml to 306 ± 165 pg/ml before and after LDL-apheresis (P < 0.05). This value further increased up to 441 ± 175 pg/ml 3 months after the end of this therapy (P < 0.01, compared with the basal value and P < 0.05, compared with the value at the end of 10-times session). Increased levels of VEGF paralleled increases in the ankle-brachial pressure index (ABI). After 10-times therapy, IGF-I significantly decreased (P < 0.05), but increased over the basal value 3 months after this therapy. Plasma fibrinogen statistically decreased and remained low for 3 months. The favorable effects of LDL-apheresis may be ascribed to up-regulation of VEGF and IGF-I associated with decreased fibrinogen levels. J. Clin. Apheresis, 18:115,119, 2003. © 2003 Wiley-Liss, Inc. [source] Growth factors and cytokines in autologous platelet concentrate and their correlation to periodontal regeneration outcomesJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2006M. Christgau Abstract: Aim: To determine the concentration of naturally available biologic mediators in autologous platelet concentrates and their correlation with periodontal regeneration outcomes. Material and methods: In 25 patients with two intra-bony defects each, an autologous platelet concentrate (APC) was prepared by a laboratory thrombocyte apheresis technique pre-operatively. Both defects were treated using a bioresorbable guided tissue regeneration-membrane in combination with tricalciumphosphate (TCP). In the test defect, APC was additionally applied. In the APC, platelets were counted and the levels of growth factors and cytokines were determined by ELISA. Correlations between the platelet counts or the growth factor/cytokine levels and the potential clinical and radiographic regeneration outcomes due to APC were calculated after 3, 6, and 12 months. Results: The APC contained 2.2 × 106 platelets/,l, which was 7.9 times more than in the venous blood. Transforming growth factor- ,1 (TGF- ,1), insulin-like growth factor-I (IGF-I), platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were found in the APC, whereas interleukin-1, (IL-1,), IL-6, tumor necrosis factor , (TNF,), IL-4, and IL-10 were not detectable. The regression analysis showed a weak correlation between the platelet counts or the growth factor levels and the clinical and radiographic regeneration outcomes (r20.4). Conclusion: Autologous platelet concentrate contains relatively high concentrations of PDGF-AB, PDGF-BB, TGF- ,1, and IGF-I, but their potential influence on periodontal regeneration remains unclear. [source] Activation of the PI3K/Akt signal transduction pathway and increased levels of insulin receptor in protein repair-deficient miceAGING CELL, Issue 1 2005Christine Farrar Summary Protein l -isoaspartate (d -aspartate) O -methyltransferase is an enzyme that catalyses the repair of isoaspartyl damage in proteins. Mice lacking this enzyme (Pcmt1,/, mice) have a progressive increase in brain size compared with wild-type mice (Pcmt1+/+ mice), a phenotype that can be associated with alterations in the PI3K/Akt signal transduction pathway. Here we show that components of this pathway, including Akt, GSK3, and PDK-1, are more highly phosphorylated in the brains of Pcmt1,/, mice, particularly in cells of the hippocampus, in comparison with Pcmt1+/+ mice. Examination of upstream elements of this pathway in the hippocampus revealed that Pcmt1,/, mice have increased activation of insulin-like growth factor-I (IGF-I) receptor and/or insulin receptor. Western blot analysis revealed an approximate 200% increase in insulin receptor protein levels and an approximate 50% increase in IGF-I receptor protein levels in the hippocampus of Pcmt1,/, mice. Higher levels of the insulin receptor protein were also found in other regions of the adult brain and in whole tissue extracts of brain, liver, heart and testes of both juvenile and adult Pcmt1,/, mice. There were no significant differences in plasma insulin levels for adult Pcmt1,/, mice during glucose tolerance tests. However, they did show higher peak levels of blood glucose, suggesting a mild impairment in glucose tolerance. We propose that Pcmt1,/, mice have altered regulation of the insulin pathway, possibly as a compensatory response to altered glucose uptake or metabolism or as an adaptive response to a general accumulation of isoaspartyl protein damage in the brain and other tissues. [source] Influences of the environment on the endocrine and paracrine fish growth hormone,insulin-like growth factor-I systemJOURNAL OF FISH BIOLOGY, Issue 6 2010M. Reinecke Insulin-like growth factor-I (IGF-I) is a key component of the complex system that regulates differentiation, development, growth and reproduction of fishes. The IGF-I gene is mainly expressed in the liver that represents the principal source of endocrine IGF-I but also in numerous other organs where the hormone most probably acts in an autocrine,paracrine manner. The primary stimulus for synthesis and release of IGF-I is growth hormone (GH) from the anterior pituitary. Thus, in analogy to mammals, it is usual to speak of a fish ,GH,IGF-I axis'. The GH,IGF-I system is affected by changes in the environment and probably represents a target of endocrine disrupting compounds (EDC) that impair many physiological processes in fishes. Thus, the review deals with the influences of changes in different environmental factors, such as food availability, temperature, photoperiod, season, salinity and EDCs, on GH gene expression in pituitary, IGF-I gene expression in liver and extrahepatic sites and the physiological effects resulting from the evoked alterations in endocrine and local IGF-I. Environmental influences certainly interact with each other but for convenience of the reader they will be dealt with in separate sections. Current trends in GH,IGF-I research are analysed and future focuses are suggested at the end of the sections. [source] Fasting modulates metabolic responses to cortisol, GH and IGF-I in Arctic charr hepatocytesJOURNAL OF FISH BIOLOGY, Issue 6 2005Ř. Aas-Hansen Hepatocytes in primary culture from fed and 2 month fasted Arctic charr Salvelinus alpinus were exposed to physiological doses of either cortisol, salmon growth hormone (GH), salmon insulin-like growth factor-I (IGF-I) or a combination of salmon GH and salmon IGF-I. Fasting significantly lowered medium glucose levels compared to the fed fish, but had no significant effects on hepatocyte glycogen content or on the activities of enzymes involved in the intermediary metabolism. Cortisol treatment had no effect on hepatocyte glycogen content or on the enzyme activities investigated, but resulted in a significant increase in medium glucose concentration in hepatocytes isolated from fasted, but not fed fish. GH and IGF-I treatments, both singly and in combination, significantly increased the glycogen content of hepatocytes isolated from fed fish, with less pronounced effects on hepatocytes isolated from fasted fish. The combination of GH and IGF-I significantly increased lactate dehydrogenase activity regardless of the feeding state and significantly reduced the phosphenolpyruvate carboxykinase activity and medium glucose concentration in hepatocytes isolated from fed fish. Further, GH and IGF-I significantly increased the activities of alanine aminotransferase and aspartate aminotransferase in hepatocytes isolated from fasted fish, but not fed fish. There were no effects of GH, IGF-I, or their combination, on glucose 6-phosphate dehydrogenase or 3-hydroxyacyl-CoA dehydrogenase activities. The results demonstrated that nutritional status of the animal modulates hepatocyte responsiveness to metabolic hormones, and suggested a role for GH and IGF-I in hepatic glycogen conservation. [source] Divergence of mucosal and motor effects of insulin-like growth factor (IGF)-I and LR3IGF-I on rat isolated ileum following abdominal irradiationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2000R Fraser Abstract Background and Aims: In addition to its beneficial effects on small intestinal mucosal development and repair, insulin-like growth factor (IGF)-I has also been reported to improve neural function in toxic neuropathies. It has recently been recognized that enteric neural abnormalities contribute to the small intestinal dysmotility observed during and after abdominal radiotherapy for gynecological and pelvic malignancy. The aim of the present study was to evaluate the effects of IGF-I (5 mg/kg per day) and the more potent analog LR3IGF-I (5 mg/kg per day) on neurally mediated ileal dysmotility following irradiation. Methods: Intestinal motor activity was recorded from 6,8 cm segments of explanted rat ileum using a miniaturized manometric technique during arterial perfusion with oxygenated fluorocarbon solution. Studies were performed 4 days after treatment with 10 Gy abdominal irradiation. At the time of irradiation, all rats underwent implantation of an osmotic mini-pump that contained 100 mmol/L acetic acid vehicle (n = 8), IGF-I (n = 8) or LR3IGF-I (n = 7). For each experiment, the total number of pressure waves, high-amplitude long-duration (defined as > 20 mmHg, > 6 s; HALD) pressure waves and long bursts (> 20) of pressure waves were determined. Ileal segments from 12 non-irradiated rats were used as controls for manometric studies. In radiotherapy treated animals, the degree of mucosal damage was determined using a standardized histologic scoring system. Results: The HALD pressure waves were infrequent in non-irradiated rats but occurred in all irradiated animals. Insulin-like growth factor-I and LR3IGF-I had no effect on the frequency, amplitude or migration characteristics of HALD pressure waves compared with vehicle. Histologic damage was reduced in animals that received IGF-I and LR3IGF-I compared with vehicle-treated animals. Conclusions: In radiation enteritis, IGF-I has no effect on neurally mediated small intestinal dysmotility while improving mucosal histology. The disparity between these results suggests that parallel but separate pathologic processes underlie mucosal and motor abnormalities in radiation enteritis. [source] IGFBP-1 levels in adult women born small for gestational age suggest insulin resistance in spite of normal BMIJOURNAL OF INTERNAL MEDICINE, Issue 1 2004A. Kistner Abstract. Objective., Impaired fetal development may contribute to decreased insulin sensitivity. This study was designed to characterize serum markers of insulin resistance in adults born small for date or born prematurely. Study design., Fifty subjects, all women, were evaluated at a mean age ± SD of 26 ± 2 years (range: 23,30 years). They were allocated to three groups: (i) born fullterm with birth weight <2600 g (n = 18) (small for gestational age, SGA), (ii) born before gestational week 32 (n = 15) (ex-preterm), and (iii) controls, born fullterm with appropriate birth weight (n = 17). Anthropometric data as well as fasting serum samples of plasma B-glucose, serum lipids, insulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) levels were determined. Results., In the SGA group final height was lower and they weighed less compared with the controls. Fasting insulin and glucose levels did not differ amongst the groups. Triglycerides were lower in the SGA group and in the ex-preterm group compared with the controls (P < 0.05). The SGA group showed lower IGFBP-1 levels compared with the controls median 17 (range 3,121) vs. 26 (7,67) ,g L,1; P < 0.05]. The IGF-I levels in the SGA, ex-preterm and control groups were 212 ± 58, 259 ± 37 and 216 ± 32 ,g L,1, respectively, corresponding to a mean SD score of ,0.8 ± 1.0, 0.1 ± 0.6 and ,0.6 ± 0.6. Conclusion., As IGFBP-1 is a marker of insulin sensitivity, the low levels observed in adult women with normal BMI, born small for date, suggest relative insulin resistance in spite of normal BMI. [source] Sustained low-dose growth hormone therapy optimizes bioactive insulin-like growth factor-I level and may enhance CD4 T-cell number in HIV infectionJOURNAL OF MEDICAL VIROLOGY, Issue 2 2010Ove Andersen Abstract High-dose recombinant human growth hormone (rhGH) (2,6,mg/day) regimes may facilitate T-cell restoration in patients infected with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART). However, high-dose rhGH regimens increase insulin-like growth factor-I (IGF-I) to supra-physiological levels associated with severe side effects. The present study investigated whether lower doses of rhGH may improve T-cell restoration in patients infected with HIV following an expedient response of total and bioactive (i.e., free) IGF-I. A previous 16-week pilot-study included six HIV-infected patients on stable HAART to receive rhGH 0.7,mg/day, which increased total (+117%, P,<,0.01) and free (+155%, P,<,0.01) IGF-I levels. The study was extended to examine whether continuous use of low-dose rhGH (0.7,mg/day until week 60; 0.4,mg/day from week 60 to week 140) would maintain expedient IGF-I levels and improve CD4 T-cell response. Total and free IGF-I increased at week 36 (+97%, P,<,0.01 and +125%, P,<,0.01, respectively) and week 60 (+77%, P,=,0.01 and +125%, P,<,0.01) compared to baseline levels (161,±,15 and 0.75,±,0.11,µg/L). CD4 T-cell number increased at week 36 (+15%, P,<,0.05) and week 60 (+31%, P,=,0.01) compared to baseline levels (456,±,55,cells/µL). Following rhGH dose reduction, total IGF-I and CD4 T-cell number remained increased at week 88 (+44%, P,=,0.01 and +33%, P,<,0.01) and week 140 (+46%, P,=,0.07 and +36%, P,=,0.02) compared to baseline levels. These data support the notion that low-dose rhGH regimens may increase expediently total and bioactive IGF-I and improve T-cell restoration in patients infected with HIV on HAART. J. Med. Virol. 82:197,205, 2010. © 2009 Wiley-Liss, Inc. [source] Transcriptional activation of human mu-opioid receptor gene by insulin-like growth factor-I in neuronal cells is modulated by the transcription factor RESTJOURNAL OF NEUROCHEMISTRY, Issue 6 2008Andrea Bedini Abstract The human mu-opioid receptor gene (OPRM1) promoter contains a DNA sequence binding the repressor element 1 silencing transcription factor (REST) that is implicated in transcriptional repression. We investigated whether insulin-like growth factor I (IGF-I), which affects various aspects of neuronal induction and maturation, regulates OPRM1 transcription in neuronal cells in the context of the potential influence of REST. A series of OPRM1-luciferase promoter/reporter constructs were transfected into two neuronal cell models, neuroblastoma-derived SH-SY5Y cells and PC12 cells. In the former, endogenous levels of human mu-opioid receptor (hMOPr) mRNA were evaluated by real-time PCR. IGF-I up-regulated OPRM1 transcription in: PC12 cells lacking REST, in SH-SY5Y cells transfected with constructs deficient in the REST DNA binding element, or when REST was down-regulated in retinoic acid-differentiated cells. IGF-I activates the signal transducer and activator of transcription-3 signaling pathway and this transcription factor, binding to the signal transducer and activator of transcription-1/3 DNA element located in the promoter, increases OPRM1 transcription. We propose that a reduction in REST is a critical switch enabling IGF-I to up-regulate hMOPr. These findings help clarify how hMOPr expression is regulated in neuronal cells. [source] | |||||||||||||||||||||||||||||||