Insulin-like growth factor-I (IGF-I) is a growth hormone that acts as a key modulator of the growth axis. Serum and plasma concentrations of IGF-I have been linked to economically important traits in beef cattle. In order to determine whether concentrations of IGF-I differed among breeds of beef cattle, plasma samples from purebred and crossbred animals were analyzed. Two calf crops were derived from three-breed diallel matings using temperate and tropically-adapted breeds of cattle. The breeds consisted of temperate Bos taurus (A; Angus), tropical Bos indicus (B; Brahman), and tropical Bos taurus (R; Romosinuano). Plasma samples were obtained from 10 heifers and 10 steers of each breed-type at weaning, and two dates post-weaning. Concentrations of IGF-I were determined by radioimmunoassay (RIA). Breed differences were observed (P < 0.001). Relative to the temperate Bos taurus breed, IGF-I was greater in tropically-adapted breed-types. In an effort to select for the improvement of economically important traits, experiments were performed to explore the possible use of concentration of IGF-I and temperament assessment as tools for selection. Using a Calan gate system, 3 Brahman heifer crops were fed during70-day trials. Performance and feed intake data were collected to determine feed efficiency. Temperament, determined by exit velocity and pen score, was evaluated at weaning. Serum samples were taken at weaning and days 0 and 70 of each trial. Concentrations of IGF-I and cortisol were determined by RIA. Correlations including IGF-I were weak (P > 0.05). Temperament had no significant effect on RFI but may affect ADG. In an attempt to examine the relationship between IGF-I and RFI, body weight and feed intake data were collected during individual finishing phase feeding trials, on steers at El Reno, OK. The breeds consisted of temperate Bos taurus (A; Angus), tropical Bos indicus (B; Brahman), and tropical Bos taurus (R; Romosinuano). Plasma samples were obtained from 10 steers of each breed-type at weaning and days 0 and 60 of each finishing phase. Concentrations of IGF-I were determined by RIA. Correlations between IGF-I and RFI were weak (P > 0.05). Breed and year significantly influenced RFI (P < 0.01).

Em nossos dias, a Cirurgia e Traumatologia Buco-Maxilo-Facial busca novas terapêuticas tendo como meta uma rápida reparação, osteointegração e regeneração dos tecidos ósseos e periodontais. Uma diminuição do tempo de reparação em fraturas e cirurgias ortognáticas, uma reparação normal de defeitos ósseos de tamanho crítico sem a utilização de enxertos e a redução do tempo de osteointegração de implantes possibilitará redução da morbidade, dos custos e uma reabilitação protética com menor período de tempo. Uma alternativa recente é a utilização de Fatores de Crescimento Semelhante a Insulina (IGFs) para a estimulação da proliferação e reparação tecidual. Os resultados observados na revisão de literatura indicam que as futuras terapias com IGFs propiciarão um avanço em relação à velocidade de reparação óssea, reparação em defeitos ósseos de tamanho crítico e em implantes imediatos. / In our days, the Oral and Maxillofacial Surgery search new techniques to goal a quick repair, osteointeration and regeneration of bone and periodontal tissues. A diminution of time healing of bone fractures and ortognatic surgery, a normal healing in critics bone defects without grafts and a decrease time of osteointegration will make possible a low morbidity and a rapid protetic rehabilitation. An newly alternative is the use of Insulin Like Growth Factor (IGFs) to estimulate the tissue proliferation and healing. The results discovered in literature review indicate that future therapies with IGFs provide an advance in speed of bone healing, healing critical bone defects and immediate implants.

Em nossos dias, a Cirurgia e Traumatologia Buco-Maxilo-Facial busca novas terapêuticas tendo como meta uma rápida reparação, osteointegração e regeneração dos tecidos ósseos e periodontais. Uma diminuição do tempo de reparação em fraturas e cirurgias ortognáticas, uma reparação normal de defeitos ósseos de tamanho crítico sem a utilização de enxertos e a redução do tempo de osteointegração de implantes possibilitará redução da morbidade, dos custos e uma reabilitação protética com menor período de tempo. Uma alternativa recente é a utilização de Fatores de Crescimento Semelhante a Insulina (IGFs) para a estimulação da proliferação e reparação tecidual. Os resultados observados na revisão de literatura indicam que as futuras terapias com IGFs propiciarão um avanço em relação à velocidade de reparação óssea, reparação em defeitos ósseos de tamanho crítico e em implantes imediatos. / In our days, the Oral and Maxillofacial Surgery search new techniques to goal a quick repair, osteointeration and regeneration of bone and periodontal tissues. A diminution of time healing of bone fractures and ortognatic surgery, a normal healing in critics bone defects without grafts and a decrease time of osteointegration will make possible a low morbidity and a rapid protetic rehabilitation. An newly alternative is the use of Insulin Like Growth Factor (IGFs) to estimulate the tissue proliferation and healing. The results discovered in literature review indicate that future therapies with IGFs provide an advance in speed of bone healing, healing critical bone defects and immediate implants.

Insulin-like growth factor-I (IGF-I) is a mitogenic polypeptide that induces proliferation and activation of kinase pathways in MCF-7 breast cancer cells. The role of estrogen receptor α (ERα) in mediating responses induced by IGF-I was investigated in cells transfected with small inhibitory RNA for ERα (iERα) or cotreated with the pure antiestrogen ICI 182780. The results showed that IGF-I-dependent phosphorylation of Akt and MAPK, induction of G1–S-phase progression and enhanced expression of cyclin D1 and cyclin E were dependent on ERα. Moreover, these IGF-I-induced responses were also inhibited by the antiestrogen ICI 182780, suggesting that the effects of ICI 182780 as an inhibitor of IGF-I induced responses in breast cancer cells are primarily related to downregulation of ERα. Chemoprotective phytochemicals exhibit multiple activities and interact with several cellular receptors, including the aryl hydrocarbon receptor (AhR). We investigated the AhR agonist/antagonist activities of the following flavonoids: chrysin, phloretin, kaempferol, galangin, naringenin, genistein, quercetin, myricetin, luteolin, baicalein, daidzein, apigenin, and diosmin, in MCF-7 breast cancer cells, HepG2 human liver cells and mouse Hepa-1 cells. The dietary phytochemicals exhibited substantial cell context–dependent AhR agonist as well as antagonist activities, and these are factors that must be considered in risk assessment of overall exposures to AhR agonists. Halogenated aromatic hydrocarbons (HAHs) such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8- pentachlorodibenzo-p-dioxin (PeCDD), 3,3’,4,4’,5-pentachlorobiphenyl (PCBP), 2,3,7,8- tetrachlorodibenzofuran (TCDF) and 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) bind and activate the aryl hydrocarbon receptor (AhR). It has been assumed that these compounds only differ in their potencies. The SAhRM-like activity of the 5 HAHs was investigated by determining ligand structure dependent differences in their induction of CYP1A1 and interactions of the AhR with a series of coactivators in a mammalian two-hybrid assay in three AhR-responsive cell lines, including mouse Hepa-1, Human HEK293 and human Panc1 cells. There were multiple structure-dependent differences in activation of luciferase activity in these cell lines transfected with VP-AhR and six different GAL4-coactivator chimeras and a GAL4-response element-luciferase promoter construct. The results show that HAHs selectively interact with coactivators and these interactions are dependent on cell-context, and even among HAHs, these compounds exhibit selective receptor modulator activity.

Objectif Ce travail se veut une contribution à l’amélioration de la santé des enfants du Burkina Faso et de l’Afrique en général. Il vise à l’identification de meilleures stratégies de diagnostic et de pronostic des enfants atteints de malnutrition. Méthodes · Dans une première étape, nous avons validé une méthode permettant la quantification de l’IGF-I à partir de sang prélevé sur papier buvard chez des enfants de moins de cinq ans, dont les valeurs d’IGF-I sont très basses. Une collecte des échantillons de sang sur tube (sérum), sur papier buvard à la température de 4 °C et sur papier buvard à la température ambiante (30-35 °C) a été réalisée auprès de 13 enfants burkinabè âgés de 0 à 59 mois qui ont consulté au service de Pédiatrie du CHU Yalgado Ouedraogo de Ouagadougou et au Centre Médical de Kossodo à Ouagadougou. Les mesures de l’IGF-I ont été effectuées sur IGF-I RIA, après séparation des protéines porteuses en utilisant la chromatographie sur Sep-Pack. · Nous avons ensuite réalisé une étude transversale en population auprès générale auprès de 400 enfants en bonne santé apparente à Ouagadougou (Burkina Faso). La collecte de sang s’est faite sur papier buvard. · Enfin, nous avons mené une étude de cohorte auprès des enfants admis dans 2 centres de réhabilitation et d’éducation nutritionnelle à Ouahigouya dans le Nord du Burkina Faso. Les enfants ont été suivis de l’admission à leur sortie et les données anthropométriques ainsi que des échantillons de sang sur papier buvard ont été collectés à l’admission, au 7ème Jour et au 14ème Jour. Résultats · L’étude de validation a montré qu’il existe une excellente corrélation entre les taux sériques d’IGF-I et les taux d’IGF-I sur papier buvard conservés à 4 °C ou à la température ambiante d’une zone tropicale (30 – 35 °C). · L’étude transversale en population a permis d’obtenir les valeurs de référence de l’IGF-I chez les enfants de moins de 5 ans au Burkina Faso. Les concentrations moyennes d’IGF-I sont plus élevées chez les filles que chez les garçons. De la naissance à 24 mois, l’IGF-I décroît et après 24 mois, il y a une augmentation de l’IGF-I chez les filles comme chez les garçons. · Les résultats de l’étude de cohorte en milieu hospitalier ont montré des valeurs de l’IGF-I très basses à l’admission. Ensuite, nous avons observé une augmentation des valeurs d’IGF-I au 7ème jour et cette augmentation a continué jusqu’au 14ème jour. Une corrélation significative a été observée entre le gain pondéral et le gain d’IGF-I au 7ème jour et au 14ème jour. Conclusion Les études que nous avons réalisées démontrent qu’il est possible d’utiliser le papier buvard pour la collecte des échantillons de sang dans le cadre des études épidémiologiques dans les pays où les contraintes matérielles ne permettent pas toujours de maintenir une chaîne de froid efficace pour la conservation des échantillons sanguins et chez de très jeunes enfants chez lesquels il est très malaisé d’obtenir des échantillons de sang par ponction veineuse. Les valeurs de référence de l’IGF-I établies peuvent être utiles pour le diagnostic et la surveillance nutritionnels ainsi que pour les évaluations des pathologies endocriniennes chez les enfants de moins de 5 ans dans le contexte d’un pays tropical comme le Burkina Faso. Mais des études complémentaires pourraient mettre en évidence la valeur pronostic d’une récupération faible ou importante de l’IGF-I après un épisode de malnutrition sévère. Il est plausible que la perte plus ou moins importante d’un potentiel de croissance lors d’une période de malnutrition sévère soit un indicateur de mauvais développement à l’adolescence ou à l’âge adulte.

Insulin-like growth factor-I (IGF-I) is a mitogenic polypeptide that induces proliferation and activation of kinase pathways in MCF-7 breast cancer cells. The role of estrogen receptor α (ERα) in mediating responses induced by IGF-I was investigated in cells transfected with small inhibitory RNA for ERα (iERα) or cotreated with the pure antiestrogen ICI 182780. The results showed that IGF-I-dependent phosphorylation of Akt and MAPK, induction of G1–S-phase progression and enhanced expression of cyclin D1 and cyclin E were dependent on ERα. Moreover, these IGF-I-induced responses were also inhibited by the antiestrogen ICI 182780, suggesting that the effects of ICI 182780 as an inhibitor of IGF-I induced responses in breast cancer cells are primarily related to downregulation of ERα. Chemoprotective phytochemicals exhibit multiple activities and interact with several cellular receptors, including the aryl hydrocarbon receptor (AhR). We investigated the AhR agonist/antagonist activities of the following flavonoids: chrysin, phloretin, kaempferol, galangin, naringenin, genistein, quercetin, myricetin, luteolin, baicalein, daidzein, apigenin, and diosmin, in MCF-7 breast cancer cells, HepG2 human liver cells and mouse Hepa-1 cells. The dietary phytochemicals exhibited substantial cell context–dependent AhR agonist as well as antagonist activities, and these are factors that must be considered in risk assessment of overall exposures to AhR agonists. Halogenated aromatic hydrocarbons (HAHs) such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8- pentachlorodibenzo-p-dioxin (PeCDD), 3,3’,4,4’,5-pentachlorobiphenyl (PCBP), 2,3,7,8- tetrachlorodibenzofuran (TCDF) and 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) bind and activate the aryl hydrocarbon receptor (AhR). It has been assumed that these compounds only differ in their potencies. The SAhRM-like activity of the 5 HAHs was investigated by determining ligand structure dependent differences in their induction of CYP1A1 and interactions of the AhR with a series of coactivators in a mammalian two-hybrid assay in three AhR-responsive cell lines, including mouse Hepa-1, Human HEK293 and human Panc1 cells. There were multiple structure-dependent differences in activation of luciferase activity in these cell lines transfected with VP-AhR and six different GAL4-coactivator chimeras and a GAL4-response element-luciferase promoter construct. The results show that HAHs selectively interact with coactivators and these interactions are dependent on cell-context, and even among HAHs, these compounds exhibit selective receptor modulator activity.

Successful synaptic transmission at the neuromuscular junction depends on the precise alignment of the nerve terminals with the postsynaptic specialization of the muscle fiber. It is increasingly apparent that this precision is achieved during development and maintained in the adult through signals exchanged between motoneurons and their target muscle fibers that serve to coordinate their spatial and temporal differentiation. Several aspects of neuronal differentiation appear to be dependent on retrograde signals from the target and studies about synaptic modulation have now focused attention on the characterization of proteins that mediate retrograde signals regulating the organization and function of nerve terminals. According to the published evidences, we find Insulin-like growth factor-I (IGF-I ) might be one of these potential factors. The acute application of IGF-I, a factor which has been addressed to widely express in developing myocyte, dose-dependently enhances the spontaneous acetylcholine secretion at developing neuromuscular synapses in Xenopus cell culture using whole-cell patch clamp recording. The IGF-I-induced potentiating effect is not abolished when calcium is eliminated from culture medium or bath application of pharmacological calcium channel blocker cadmium, indicating calcium influx through voltage-activated calcium channels are not required. We further define the roles of intracellular Ca2+ stores in IGF-I-induced synaptic potentiation. To approach this problem, Ca2+-ATPase inhibitor thapsigargin were initially used to deplete internal Ca2+ stores. IGF-I no longer elicited any changes in SSC frequency in thapsigargin-treated synapses suggesting that an increase in [Ca2+]i due to Ca2+ release from intracellular Ca2+ stores may contribute to the facilitation of transmitter release induced by IGF-I. Application of membrane-permeable inhibitors of IP3-induced Ca2+ release 2-aminoethoxydiphenyl borate (2-APB) or Xestospongin C (XeC) effectively occluded the increase of SSC frequency elicited by IGF-I. Furthermore, pretreatment of the cultures with ryanodine receptor antagonist 8-(dethylamino) octyl 3, 4, 5-trimethoxybenzoate (TMB-8) also blocked the IGF-I effects indicating that IGF-I activates IP3 and/or ryanodine pathway to initiate calcium release from intracellular stores which subsequently potentiate transmitter release. Treating cells with inhibitors of phosphoinositide-3 kinase (wortmannin and LY294002) and Phospholipase C-g (U73122), but not inhibitor of MAP kinase (PD98059) abolishes IGF-1-induced potentiation of synaptic transmission. Inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) by KN-62 effectively blocks the effect of IGF-I. Taken collectively, our results obtained suggest that IGF-I potentiates neurotransmitter secretion by stimulating Ca2+ release from IP3 and ryanodine sensitive intracellular calcium stores via activate PI3 and/or PLC-g signaling cascades, which leading to an activation of CaMKII-dependent transmitter release.

No description available.

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Evaluating the growth axis of an ancient species such as the Shovelnose Sturgeon Scaphirhynchus platorynchus can aid in understanding the divergence of growth factors among a vast evolutionary span of vertebrates. It is hypothesized, that similar to teleosts and tetrapods, growth hormone (GH) mediates and stimulates the anabolic actions of insulin-like growth factor I (IGF-I) and insulin-like growth factor II (IGF-II) in sturgeon. Using Shovelnose Sturgeon as a model, the objectives of this research were to identify the acute and chronic effects of exogenous recombinant bovine GH (rbGH) on IGF-I and IGF-II gene expression and investigate the roles IGF's have on whole animal growth and nutrient partitioning in the presence of chronic rbGH administration. In the first experiment, fish were injected with five different concentrations of rbGH (0, 30, 60, 120, 240 μg/g body weight (BW) rbGH)) and sampled at five time points (6, 12, 24, 36, 48-h post-injection). Hepatic and muscle tissue specimens were rapidly excised following euthanasia for mRNA isolation and quantitative real-time polymerase chain reaction (qRT-PCR) analysis of IGF expression. qRT-PCR analysis indicated hepatic IGF-I and IGF-II expression was significantly higher than muscle IGF-I expression, and IGF-II was not expressed in muscle. The highest rbGH concentration (240 μg/g BW) significantly increased hepatic IGF-I and IGF-II mRNA and muscle IGF-I mRNA expression levels at 48 hours post injection. After 6 weeks of bi-weekly rbGH administration in a second experiment, fish injected with rbGH at 240 μg/g BW gained significantly more length and weight than fish injected with the sham (0 μg rbGH; sesame oil), and whole body proximate analysis revealed rbGH treated fish had significantly higher amounts of protein. This research aids in understanding the regulatory and evolutionary principles of the vertebrate somatotropic axis through characterizing the endocrine regulation of growth in Scaphirhynchus sturgeon.