Additionally, specific receptors on the spermatozoon head bind to ZP3 ligands located on the surface of the ZP, which locks the sperm’s head onto the oocyte. Both mechanisms are important cofactors in the initial sperm penetration into the ZP, which is required for successful fertilization of the oocyte, but it is unclear which forces-mechanical thrust or biochemical binding-are more influential at this stage. To address Selleck CH5183284 this question, we developed a biomechanical sperm-oocyte contact model, which is based on the Johnson-Kendall-Roberts model adopted from the contact mechanics theory. The modeling predicted that during the early stage of penetration into the ZP,

biochemical binding forces acting on spermatozoa, which are swimming at a (normal) velocity of 100 mu m/s are similar to 4.2-times to similar to 16.7-times less than the mechanically-generated propulsive forces. In a simulated pathology of a low number of properly functioning receptors (50 out of 300 receptors/mu m(2)), the biochemical binding forces are similar to 63-times less than the propulsive forces for the normally swimming sperm. It is suggested

that such dominance of the propulsive forces over the biochemical binding forces can prevent efficient binding of spermatozoa to the ZP of the oocyte due to continuous movement of the sperm (which is not necessarily perpendicular to the ZP surface, and can cause sliding of sperm over the ZP). Thus, our theoretical CFTRinh-172 in vitro analysis indicates that a sufficiently large density of receptors to ZP3 ligands on the sperm head is critical at the stage of early sperm-oocyte contact, in order to allow an efficient acrosome reaction to follow, so that the spermatozoon can start penetrating into the ZP. (C) 2011 Elsevier Ltd. All rights reserved.”
“We have demonstrated previously that nicotine affords neuroprotective and anti-inflammatory Pitavastatin datasheet effects against intracerebral hemorrhage (ICH)-associated neuropathological changes. The present study was undertaken to clarify whether subtype-specific

agonists of nicotinic acetylcholine receptors (nAChRs) could preserve tissue integrity in mouse ICH model in vivo. ICH was induced by unilateral injection of collagenase into the striatum of male C57BL/6 mice. Daily intraperitoneal injection of alpha 7 nAChR agonist PNU-282987 (3-10 mg/kg) for 3 days, starting from 3 h after induction of ICH, significantly increased the number of surviving neurons in the central and the peripheral regions of hematoma at 3 days after ICH. In contrast, alpha 4 beta 2 nAChR agonist RJR-2403 (2-10 mg/kg) given in the same regimen showed no significant effect. PNU-282987 and RJR-2403 did not affect either the size of hemorrhage or the extent of brain edema associated with ICH. PNU-282987 decreased the number of activated microglia/macrophages accumulating in the perihematoma region at 3 days after ICH, in a dose-dependent manner.