Conditional Genetic Elimination of Hepatocyte Growth Factor in Mice Compromises Liver Regeneration after Partial Hepatectomy

Hepatocyte growth factor (HGF) has been shown to be indispensable for liver regeneration because it serves as a main mitogenic stimulus driving hepatocytes toward proliferation. We hypothesized that ablating HGF in adult mice would have a negative effect on the ability of hepatocytes to regenerate. Deletion of the HGF gene was achieved by inducing systemic recombination in mice lacking exon 5 of HGF and carrying the Mx1-cre or Cre-ERT transgene. Analysis of liver genomic DNA from animals 10 days after treatment showed that a majority (70-80%) of alleles underwent cre-induced genetic recombination. Intriguingly, however, analysis by RT-PCR showed the continued presence of both unrecombined and recombined forms of HGF mRNA after treatment. Separation of liver cell populations into hepatocytes and non-parenchymal cells showed equal recombination of genomic HGF in both cell types. The presence of the unrecombined form of HGF mRNA persisted in the liver in significant amounts even after partial hepatectomy (PH), which correlated with insignificant changes in HGF protein and hepatocyte proliferation. The amount of HGF produced by stellate cells in culture was indirectly proportional to the concentration of HGF, suggesting that a decrease in HGF may induce de novo synthesis of HGF from cells with residual unrecombined alleles. Carbon tetrachloride (CCl4)-induced regeneration resulted in a substantial decrease in preexisting HGF mRNA and protein, and subsequent PH led to a delayed regenerative response. Thus, HGF mRNA persists in the liver even after genetic recombination affecting most cells; however, PH subsequent to CCl4 treatment is associated with a decrease in both HGF mRNA and protein and results in compromised liver regeneration, validating an important role of this mitogen in hepatic growth. © 2013 Nejak-Bowen et al

Testosterone mediates satellite cell activation in denervated rat levator ani muscle

Denervation stimulates quiescent satellite cells in skeletal muscle to reenter the cell cycle. In the androgen-sensitive rat levator ani muscle (LA), this mitotic response to loss of neural input fails to occur in castrated animals. To elucidate the role of androgens in denervation-induced satellite cell proliferation, the denervated LA of castrated rats (Group A) was compared with that of animals infixed with testosterone implants after castration (Group B). Mean myofiber cross-sectional areas (Group A: 362.95 Μm 2 ± 27.74; Group B: 403.13 Μm 2 ± 53.87) and linear nuclear densities (Group A: 74.07 mm −1 ± 17.58; Group B: 104.13 mm −1 ± 4.06) were similar ( P > 0.05) in both groups. The androgen-deprived myofibers of Group A, however, had a significantly lower nuclear content (271.0 ± 74.91 vs. 1,285.80 ± 81.74 in Group B; P < 0.05) on account of their considerably shorter mean length (3.44 mm ± 0.29 vs. 12.31 mm ± 0.92 in Group B; P < 0.05). The proportional representation of satellite cells in hormone-replaced, denervated muscle was more than twice that in the untreated group (Group B: 5.15 ± 0.83% vs. Group A: 2.28 ± 0.23%; P < 0.05). In absolute terms, the satellite cell number in Group B was approximately an order of magnitude greater than in Group A (408.4 × 10 3 vs. 38.08 × 10 3 ). The results confirm the absence of testosterone as the factor responsible for the inability of satellite cells in the LA of castrated rats to respond mitotically to the withdrawal of neural input after denervation. Anat Rec 263:19–24, 2001. © 2001 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34289/1/1072_ftp.pd

Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery)

Bone morphogenetic proteins (BMPs) are cytokines with a strong effect on bone and cartilage growth and with important roles during embryonic patterning and early skeletal formation. BMPs have promising potential for clinical bone and cartilage repair, working as powerful boneinducing components in diverse tissue-engineering products. Synthetic polymers, natural origin polymers, inorganic materials and composites may be used as carriers for the delivery of BMPs. Carriers range from nanoparticles to complex three-dimensional (3D) scaffolds, membranes for tissue-guided regeneration, biomimetic surfaces and smart thermosensitive hydrogels. Current clinical uses include spinal fusion, healing of long bone defects and craniofacial and periodontal applications, amongst others. BMP-2 and BMP-7 have recently received approval by the US Food and Drug Administration (FDA) for specific clinical cases, delivered in absorbable collagen sponges. Considering the expanding number of publications in the field of BMPs, there are prospects of a brilliant future in the field of regenerative medicine of bone and cartilage with the use of BMPs

Jozef Vercoullie (1857-1937)

Blanquaert E. Jozef Vercoullie (1857-1937). In: Revue belge de philologie et d'histoire, tome 16, fasc. 1-2, 1937. pp. 556-560

Comment améliorer l'autonomie des patients sous anticoagulants injectables en ambulatoire

Les thérapies anticoagulantes pour prévenir et guérir la thromboembelie veineuse ont beaucoup évolué ces dernières années. L'arrivée sur le marché d'héparine de bas poids moléculaire, présentant moins de risques pour le patient que les héparines non fractionnées, a permis la prise en charge en ambulatoire de la thromboembolie veineuse. La prévalence et les coûts engendrés par la thromboembolie veineuse justifient l'utilisation des anticoagulants injectables de plus en plus sur le marché de ville non seulement pour améliorer la qualité de vie des patients mais aussi pour diminuer les dépenses de santé publique. L'industrie pharmaceutique, ne s'adressant plus seulement au médecin mais aussi au patient, essaie de trouver de nouvelles solutions pour répondre au mieux à ses besoins et à ses attentes. Les systèmes d'injection actuellement proposés dans le domaine de l'anticoagulothérapie ne permettent pas à la totalité des patients de recevoir leur traitement en complète autonomie. En effet, nombre de patients restent dépendants en partie ou en totalité d'une infirmière à domicile. Les nouvelles technologies ou formulations futures pourraient-elles offrir l'opportunité d'accroitre l'autonomie des patients pour assurer leur traitement anticoagulant ?TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Convective and radiative heat flux prediction of Huygens's Entry on Titan

The present paper focuses on the convective and radiative heat flux predictions required for the post-delta Flight Acceptance Review consolidation of the Huygens entry profile and, in particular, the desired flight path angle at entry interface. This consolidation effort has concluded on the appropriateness of the probe's thermal protection system design under the nominal and dispersed entry conditions considered and has supported the positive decision for Huygens's release from its carrier, Cassini, in December 2004. The related predictions are based on the atmospheric model of Yelle as implemented during the Huygens recovery effort (2002–2004) by the companies Alcatel and European Aeronautic Defence and Space, Les Mureaux and subsequent variations thereof. The atmospheric model (with emphasis on chemical composition, gravity wave, and wind profiles) has been updated before probe release during the Titan flybys in October 2004 and the final preentry predictions reported here have been performed with the atmospheric model resulting from the observations recorded during the second Titan flyby and the preflight trajectory baselined during the delta Flight Acceptance Review in February 2004. The results obtained clearly support the appropriateness of the thermal protection system design and the decision for probe release

Glycosaminoglycans mimetics potentiate the clonogenicity, proliferation, migration and differentiation properties of rat mesenchymal stem cells.

Contains fulltext : 108052.pdf (publisher's version ) (Open Access)Successful use of stem cell-based therapeutic products is conditioned by transplantation of optimized cells in permissive microenvironment. Mesenchymal stem cell (MSC) fates are tightly regulated by humoral factors, cellular interactions and extracellular matrix (ECM) components, such as glycosaminoglycans (GAG), which are complex polysaccharides with structural heterogeneity. During osteogenesis, a temporally controlled expression of particular GAG species is required to interact with specific growth promoting and differentiating factors to regulate their biological activities. As a comparative tool to study natural GAG, we used structurally and functionally related synthetic GAG mimetics. One of these compounds [OTR(4120)] was previously shown to stimulate bone repair in rat models. Here, we demonstrate that structurally distinct GAG mimetics stimulate differentially clonogenicity, proliferation, migration and osteogenic phenotype of MSC in vitro, according to their specific chemical signature, underlying the role of sulfate and acetyl groups in specific interactions with heparin binding factors (HBF). These effects are dependent on FGF-2 interactions since they are inhibited by a FGF receptor 1 signaling pathway blocker. These data suggest that the in vivo [OTR(4120)] bone regenerative effect could be due to its ability to induce MSC migration and osteogenic differentiation. To conclude, we provide evidences showing that GAG mimetics may have great interest for bone regeneration therapy and represent an alternative to exogenous growth factor treatments to optimize potential therapeutic properties of MSC.01 maart 201