Mechanical and structural characterisation of the dural venous sinuses.

The dural venous sinuses play an integral role in draining venous blood from the cranial cavity. As a result of the sinuses anatomical location, they are of significant importance when evaluating the mechanopathology of traumatic brain injury (TBI). Despite the importance of the dural venous sinuses in normal neurophysiology, no mechanical analyses have been conducted on the tissues. In this study, we conduct mechanical and structural analysis on porcine dural venous sinus tissue to help elucidate the tissues' function in healthy and diseased conditions. With longitudinal elastic moduli values ranging from 33 to 58 MPa, we demonstrate that the sinuses exhibit higher mechanical stiffness than that of native dural tissue, which may be of interest to the field of TBI modelling. Furthermore, by employing histological staining and a colour deconvolution protocol, we show that the sinuses have a collagen-dominant extracellular matrix, with collagen area fractions ranging from 84 to 94%, which likely explains the tissue's large mechanical stiffness. In summary, we provide the first investigation of the dural venous sinus mechanical behaviour with accompanying structural analysis, which may aid in understanding TBI mechanopathology.

Piezoelectricity in the Intervertebral disc.

Lower back pain is a major global health challenge that can often be caused by degeneration of the Intervertebral Disc (IVD). While IVD biomechanics are a key factor in the degenerative cycle, many mechanotransduction pathways remain unknown, in particular the electro-mechanical coupling in the loaded tissue. However, despite evidence for a role in the mechanically-induced remodelling of similar tissue, piezoelectricity has been overlooked in the IVD. In this study, we investigate the piezoelectric properties of the Annulus Fibrosus (AF) and the Nucleus Pulposus (NP) by measuring the direct piezoelectric effect of mechanically-induced electrical potential change. To verify these findings, we conducted Piezoresponse Force Microscopy (PFM) to measure the inverse effect of electrically-induced deformation. We demonstrate that, for the first time, piezoelectricity is generated throughout the IVD. Piezoelectric effects were greater in the AF than the NP, owing to the organised collagen networks present. However, the piezoresponse found in the NP indicates piezoelectric properties of non-collagenous proteins that have not yet been studied. The voltage generated by longitudinal piezoelectricity in-vivo has been calculated to be ~1 nV locally, indicating that piezoelectric effects may directly affect cell alignment in the AF and may work in conjunction with streaming potentials throughout the IVD. In summary, we have highlighted an intricate electro-mechanical coupling that appears to have distinct physiological roles in the AF and NP. Further study is required to elucidate the cell response and determine the potential role of piezoelectric effects in regeneration and preventative measures from degeneration.

Synthesis and structure-activity relationship of 2-amino-3-heteroaryl-quinoxalines as non-peptide, small-molecule antagonists for interleukin-8 receptor.

Interleukin-8 modulation is implicated in many inflammatory and cancer diseases. Starting from a mass-screening hit, the synthesis and structure-activity relationship of 2-amino-3-heteroarylquinoxalines as non-peptide, small molecule interleukine-8 receptor antagonists have been developed. The optimized derivatives, PD 0210293 (13y) and PD 0220245 (13r), show inhibition of both IL-8 receptor binding and IL-8-mediated neutrophil chemotaxis.