Effect of Local Neck Anatomy on Localized One-Dimensional Measurements of Arterial Stiffness: A Finite-Element Model Study.

Cardiovascular diseases (CVD) are the most prevalent cause of death in the Western World, and their prevalence is only expected to rise. Several screening modalities aim at detecting CVD at the early stages. A common target for early screening is common carotid artery (CCA) stiffness, as reflected in the pulse wave velocity (PWV). For assessing the CCA stiffness using ultrasound (US), one-dimensional (1D) measurements along the CCA axis are typically used, ignoring possible boundary conditions of neck anatomy and the US probe itself. In this study, the effect of stresses and deformations induced by the US probe, and the effect of anatomy surrounding CCA on a simulated 1D stiffness measurement (PWVus) is compared with the ground truth stiffness (PWVgt) in 60 finite-element models (FEM) derived from anatomical computed tomography (CT) scans of ten healthy male volunteers. Based on prior knowledge from the literature, and from results in this study, we conclude that it is safe to approximate arterial stiffness using 1D measurements of compliance or pulse wave velocity, regardless of boundary conditions emerging from the anatomy or from the measurement procedure.

Prolonged somatostatin therapy may cause down-regulation of SSTR-like GPCRs on Schistosoma mansoni.

BACKGROUND & OBJECTIVES: Chemotherapy with praziquantel remains the only control measure to Schistosoma mansoni infections to date. The neuropeptide hormone somatostatin gives relief from gastrointestinal disturbances, liverpathology, and reduces egg production in S. mansoni infected mice, suggesting an interaction of somatostatin with the parasite rather than with the host alone. Using antibodies directed to epitopes of the seven somatostatin transmembrane receptors (SSTRs), the presence of SSTRs (or proteins that contain these epitopes) was shown on both worm- and egg-stages of S. mansoni. The present study was undertaken to investigate whether SSTRs on S. mansoni displayed homo/heterodimerisation properties as well as agonist induced down-regulation. RESULTS: Somatostatin therapy was effective after two days of treatment with no further reduction in pathology after five days of therapy. Immunohistochemistry performed on parasite sections showed reactivity of the anti-SSTR antibodies to the tegument and internal parts of adult S. mansoni worms. SDS-PAGE-Western blotting identified protein bands of 70-100 and 200-250 kDa molecular weight. Upon carboxymethylation of the sulfhydryl groups of proteins in the worm lysate, a reduction in density of the protein band at 200-250 kDa and an increase in density of the protein band at 70-100 kDa were noted. This suggested that a substantial amount of the proteins detected on the blot are present as a homo/heterodimer. A protein microarray was used to investigate whether somatostatin therapy induced receptor down- or up-regulation on the adult worm of S. mansoni. Slides spotted with primary anti-SSTR antibody were exposed to lysates of worms collected from infected C3H mice that received none, two days or five days somatostatin treatment, followed by a secondary anti-SSTR antibody coupled to a fluorophore. Comparison of the different samples in terms of parasite dilution till when the fluorescence was detectable, and the fluorescence intensity, proved that the proteins detected in the parasite worm have been down-regulated after five days of somatostatin treatment. CONCLUSION: SSTR-like GPCRs are being expressed by adult S. mansoni worms and extended somatostatin treatment may cause down-regulation of these receptors, thus reducing the therapeutic capacities of this neuropeptide. However, the presence of SSTRs on S. mansoni has not yet been proven on a genetic basis. Cross-reactivity of anti-SSTR antibodies with other G-protein coupled receptors (GPCR) thus cannot yet be excluded.