Hepatic steatosis is a major risk factor in ischemia-reperfusion (I/R). IGF-binding proteins (IGFBPs) modulate IGF-I action by transporting circulating IGF-I to its sites of action. Epidermal growth factor (EGF) stimulates IGF-I synthesis in vitro. We examined the effect of IGF-I and EGF treatment, separately or in combination, on the vulnerability of steatotic livers to I/R. Our results indicated that I/R impaired IGF-I synthesis only in steatotic livers. Only when a high dose of IGF-I (400 microg/kg) was given to obese animals did they show high circulating IGF-I:IGFBP levels, increased hepatic IGF-I levels, and protection against damage. In lean animals, a dose of 100 microg/kg IGF-I protected nonsteatotic livers. Our results indicated that the combined administration of IGF-I and EGF resulted in hepatic injury parameters in both liver types similar to that obtained by IGF-I and EGF separately. IGF-I increased egf expression in both liver types. The beneficial role of EGF on hepatic I/R injury may be attributable to p38 inhibition in nonsteatotic livers and to PPAR gamma overexpression in steatotic livers. In conclusion, IGF-I and EGF may constitute new pharmacological strategies to reduce the inherent susceptibility of steatotic livers to I/R injury.

The intervertebral disc exhibits a complex inelastic response characterized by relaxation, hysteresis during cyclic loading and rate dependency. All these inelastic phenomena depend on osmotic interactions between disc tissues and their surrounding chemical environment. Coupling between osmotic and inelastic effects is not fully understood, so this article aimed to study the influence of chemical conditions on the inelastic behaviour of the intervertebral disc in response to different modes of loading. A total of 18 non-frozen 'motion segments' (two vertebrae and the intervening soft tissues) were dissected from the cervical spines of mature sheep. The motion segments were loaded in tension, compression and torsion at various loading rates and saline concentrations. Analysis of variance showed that saline concentration significantly influenced inelastic effects in tension and especially in compression (p \ 0.05), but not in torsion. Opposite effects were seen in tension and compression. An interpretation of the underlying osmo-inelastic mechanisms is proposed in which two sources of inelastic effects are identified, that is, extracellular matrix rearrangements and fluid exchange created by osmosis.

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The aim of this article is to provide some insights on the osmo-inelastic response under stretching of annulus fibrosus of the intervertebral disc. Circumferentially oriented specimens of square cross section, extracted from different regions of bovine cervical discs (ventral-lateral and dorsal-lateral), are tested under different strain-rates and saline concentrations within normal range of strains. An accurate optical strain measuring technique, based upon digital image correlation, is used in order to determine the full-field displacements in the lamellae and fibers planes of the layered soft tissue. Annulus stress–stretch relationships are measured along with full-field transversal strains in the two planes. The mechanical response is found hysteretic, rate-dependent and osmolarity-dependent with a Poisson’s ratio higher than 0.5 in the fibers plane and negative (auxeticity) in the lamellae plane. While the stiffness presents a regional-dependency due to variations in collagen fibers content/orientation, the strain-rate sensitivity of the response is found independent on the region. A significant osmotic effect is found on both the auxetic response in the lamellae plane and the stiffness rate-sensitivity. These local experimental observations will result in more accurate chemo-mechanical modeling of the disc annulus and a clearer multi-scale understanding of the disc intervertebral function.