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Mitogenic Potential (mitogenic + potential)
Selected AbstractsActivation of human platelet-rich plasmas: effect on growth factors release, cell division and in vivo bone formationCLINICAL ORAL IMPLANTS RESEARCH, Issue 5 2007Yanik Roussy Abstract Objectives: Aims of this controlled study were to determine the effects of activated human platelet-rich plasmas (PRPs) on early and mature bone formation in vivo, and to characterize the effect of PRP activation on growth factors release and endothelial cell division in vitro. Material and methods: PRPs were prepared from four volunteers with the platelet concentrate collector system (PCCS) system and activated with three concentrations of calcium and thrombin. Platelet-derived growth factor (PDGF)-BB, vascular endothelial growth factor (VEGF), transforming growth factor , (TGF-,) and interleukin-1, (IL-1,) levels released in supernatants were measured by ELISA, at time 0, 1h, 24h and 6 days following PRP activation. Mitogenic potential of PRP supernatants were tested on endothelial cells in vitro, and the effects of activated human PRPs on bone formation in vivo were measured in athymic rats by micro-CT analyses. Results: Activation of PRPs with calcium and thrombin triggered an immediate release of VEGF, PDGF-BB and TGF-, and a delayed release of IL-1, in PRP supernatants. Higher endothelial cell division was observed with supernatants from activated PRPs than from non-activated PRPs. Positive correlations were observed between VEGF levels and endothelial cell division and bone formation. A negative correlation was also found between PDGF-BB concentration and bone formation. However, early and mature bone formations with activated PRPs did not significantly differ from the ones obtained in the control group. Conclusions: Activation of PRPs with calcium and thrombin regulates growth factors release and endothelial cell division in vitro. However, activated PRPs does not improve the early or mature bone formations in vivo in this athymic rat model. [source] Novel insulin analogues and its mitogenic potentialDIABETES OBESITY & METABOLISM, Issue 6 2006Ivana Zib Abstract:, Insulin analogues were developed to modify the structure of the human insulin molecule in order to more accurately approximate the endogenous secretion of insulin. With the help of recombinant technology and site-directed mutagenesis, the insulin molecule can be modified to either delay or shorten absorption time, providing better insulin treatment options and facilitating the achievement of glycaemic goals. Changing the structure of the insulin molecule, however, may significantly alter both its metabolic and mitogenic activity. Multiple factors such as residence time on the receptor, dissociation rate, rate of receptor internalization and the degree of phosphorylation of signalling proteins can affect the mitogenic potencies of insulin analogues. Changes in the structure of the insulin have raised concern about the safety of the insulin analogues. For example, questions have emerged about the relationship between the use of insulin lispro and insulin glargine and the progression of diabetic retinopathy. Two studies have shown progression of retinopathy with the use of insulin lispro. However, others have not confirmed these results, and causality could not be proven as progression of retinopathy can occur with rapid improvement in glycaemic control, and methods of assessments among studies were not consistent. Therefore, we examine the metabolic and mitogenic characteristics of the three insulin analogues, insulin lispro, insulin aspart and insulin glargine, that are currently on the market, as well as the two insulin analogues, insulin glulisine and insulin detemir, that are soon going to be available for clinical use. [source] Insulin glargine and receptor-mediated signalling: clinical implications in treating type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2007Derek Le Roith Abstract Most patients with type 2 diabetes mellitus will eventually require insulin therapy to achieve or maintain adequate glycaemic control. The introduction of insulin analogues, with pharmacokinetics that more closely mimic endogenous insulin secretion, has made physiologic insulin replacement easier to achieve for many patients. However, there are also concerns regarding alteration of binding affinities for the insulin receptor (IR) or insulin-like growth factor-1 receptor (IGF-1R) may increase the mitogenic potential of some analogues. Therefore, this article will review the relevant preclinical and clinical data to assess the mitogenic potential of insulin glargine, a basal insulin analogue, compared with regular human insulin (RHI). Searches of the PubMed database were performed using terms that included ,IR,' ,insulin-like growth factor-1,' ,IGF-1R,' ,type 2 diabetes mellitus,' and ,insulin glargine.' Original articles and reviews of published literature were retrieved and reviewed. Although one study reported increased binding affinity of insulin glargine for the IGF-1R and increased mitogenic potential in cells with excess IGF-1Rs (Saos/B10 osteosarcoma cells), most in vitro binding-affinity and cell-culture studies have demonstrated behaviour of insulin glargine comparable to that of RHI for both IR and IGF-1R binding, insulin signalling, and metabolic and mitogenic potential. Currently published in vivo carcinogenic studies and human clinical trial data have shown that insulin glargine is not associated with increased risk for either cancer or the development or progression of diabetic retinopathy. Copyright © 2007 John Wiley & Sons, Ltd. [source] Differential erbB signaling in astrocytes from the cerebral cortex and the hypothalamus of the human brainGLIA, Issue 4 2009Ariane Sharif Abstract Studies in rodents have shown that astroglial erbB tyrosine kinase receptors are key regulatory elements in neuron,glia communication. Although both astrocytes and deregulation of erbB functions have been implicated in the pathogenesis of many common human brain disorders, erbB signaling in native human brain astrocytes has never been explored. Taking advantage of our ability to perform primary cultures from the cortex and the hypothalamus of human fetuses, we conducted a thorough analysis of erbB signaling in human astrocytes. We showed that human cortical astrocytes express erbB1, erbB2, and erbB3, whereas human hypothalamic astrocytes express erbB1, erbB2, and erbB4 receptors. Ligand-dependent activation of different erbB receptor heterodimeric complexes in these two populations of astrocytes translated into different morphological and proliferative responses. Although morphological plasticity was more pronounced in hypothalamic astrocytes than in cortical astrocytes, the former showed a lower mitogenic potential. Decreasing erbB4 expression via siRNA-mediated gene knockdown revealed that erbB4 constitutively restrains basal proliferative activity in hypothalamic astrocytes. We further show that treatment of human astrocytes with a protein kinase C activator results in rapid tyrosine phosphorylation of erbB receptors that involves cleavage of endogenous membrane bound erbB ligands by metalloproteinases. Together, these results indicate that erbB signaling in primary human brain astrocytes is functional, region-specific, and can be activated in a paracrine and/or autocrine manner. In addition, by revealing that some aspects of astroglial erbB signaling are different between human and rodents, our results provide a molecular framework to explore the potential involvement of astroglial erbB signaling deregulation in human brain disorders. © 2008 Wiley-Liss, Inc. [source] | ||||||||||