The response of living tissue to injury is a central component in the planning of all surgical procedures. The wound-healing process is typically divided into three phases (inflammatory, proliferative, and remodeling) and is a complex process in which a multitude of cellular and humoral components interact to restore a wound defect. Platelets and their released cytokines and growth factors are pivotal in the modulation of this entire process. Although several techniques may be used to achieve hemostasis after initial injury, few initiate and actually accelerate tissue regeneration. Both platelet gel and fibrin glue are effective hemostatic agents. Platelet gels, unlike fibrin glue, have a high concentration of platelets that release the bioactive proteins and growth factors necessary to initiate and accelerate tissue repair and regeneration. In particular, two growth factors that play a major role in platelet gels are platelet-derived growth factor, a powerful chemoattractant, and transforming growth factor beta, which significantly increases and stimulates the deposition of extracellular matrix. In creating a platelet gel, autologous blood is centrifuged to produce a concentrate high in both platelets and plasma. This concentrate can be applied to wounds, providing hemostasis, adhesion, and enhanced wound healing. Recent techniques for the autologous concentrating process have been streamlined, and now platelet gels are clinically accessible to most physicians. Platelet gels have global applications in surgery and are especially useful for the soft tissue and bony reconstructions encountered in facial plastic and reconstructive surgery. In these applications, their use has been associated with a decrease in operative time, necessity for drains and pressure dressings, and incidence of complications. When applied to bony reconstruction it provides adhesion for the consolidation of cancellous bone and comminuted fracture segments.

In the shark, C-type natriuretic peptide (CNP) is the only cardiac natriuretic hormone identified and is a potent activator of Cl− secretion in the rectal gland, an epithelial organ of this species that contains cystic fibrosis transmembrane conductance regulator (CFTR) Cl−channels. We have cloned an ancestral CNP receptor (NPR-B) from the shark rectal gland that has an overall amino acid identity to the human homologue of 67%. The shark sequence maintains six extracellular Cys present in other NPR-B but lacks a glycosylation site and a Glu residue previously considered important for CNP binding. When shark NPR-B and human CFTR were coexpressed in Xenopusoocytes, CNP increased the cGMP content of oocytes (EC50 12 nM) and activated CFTR Cl− channels (EC50 8 nM). Oocyte cGMP increased 36-fold (from 0.11 ± 0.03 to 4.03 ± 0.45 pmol/oocyte) and Cl− current increased 37-fold (from −34 ± 14 to −1,226 ± 151 nA) in the presence of 50 nM CNP. These findings identify the specific natriuretic peptide receptor responsible for Cl− secretion in the shark rectal gland and provide the first evidence for activation of CFTR Cl− channels by a cloned NPR-B receptor.

Based on our experience, resorbable plates appear to be safe, easy to contour and apply, as well as effective for a wide range of head and neck reconstructive applications. In addition, the shortcomings of permanently retained plates such as plate migration, bone growth restriction, and imaging artifact are avoided.

Adenosine receptors (ADORs) are G-protein coupled purinoceptors that have several functions including regulation of chloride secretion via CFTR in human airway and kidney. We cloned an ADOR from Squalus acanthias (shark) that likely regulates CFTR in the rectal gland. Phylogenic- and expression- analyses indicate that elasmobranch ADORs are non-olfactory, and appear to represent extant predecessors of mammalian ADORs. We therefore designate the shark ADOR as the A0 receptor. We co-expressed A0 with CFTR in Xenopus laevis oocytes and characterized the coupling of A0 to the chloride channel. Two electrode voltage clamping was performed and current-voltage (I-V) responses were recorded to monitor CFTR status. Only in A0- and CFTR- co-injected oocytes did adenosine analogs produce a significant concentration-dependent activation of CFTR consistent with its electrophysiological signature. A pharmacological profile for A0 was obtained for ADOR agonists and antagonists that differed markedly from all mammalian ADOR subtypes (agonists: R-PIA > S-PIA > CGS21680 > CPA > 2ClADO > CV1808 = DPMA > NECA) and (antagonists: DPCPX > PD115199 > 8PT > CGC > CGS15943). Structures of human ADORs permitted a high-confidence homology model of the shark A0 core which revealed unique structural features of ancestral receptors. We conclude: (1) A0 is a novel and unique adenosine receptor ancestor by functional and structural criteria; (2) A0 likely activates CFTR in vivo and this receptor activates CFTR in oocytes indicating an evolutionary coupling between ADORs and chloride secretion; and (3) A0 appears to be a non-olfactory evolutionary ancestor of all four mammalian ADOR subtypes.