A nonolfactory shark adenosine receptor activates CFTR with unique pharmacology and structural features.

Adenosine receptors (ADORs) are G protein-coupled purinoceptors that have several functions including regulation of chloride secretion via cystic fibrosis transmembrane conductance regulator (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 nonolfactory and appear to represent extant predecessors of mammalian ADORs. We therefore designate the shark ADOR as the A0 receptor. We coexpressed 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-coinjected 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-phenyl-isopropyl adenosine (R-PIA) > S-phenyl-isopropyl adenosine (S-PIA) > CGS21680 > N6-cyclopentyladenosine (CPA) > 2-chloroadenosine (2ClAdo) > CV1808 = N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA) > N-ethyl-carboxyl adenosine (NECA); and antagonists: 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) > PD115199 > 1,3-dimethyl-8-phenylxanthine (8PT) > CGS15943]. Structures of human ADORs permitted a high-confidence homology model of the shark A0 core that revealed unique structural features of ancestral receptors. We conclude that 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 nonolfactory evolutionary ancestor of all four mammalian ADOR subtypes.

The efficacy of resorbable plates in head and neck reconstruction.

OBJECTIVE/HYPOTHESIS: The advent of malleable macroporous resorbable plates has allowed the surgeon a greater range of reconstructive options and has decreased the morbidity of conventional plating procedures. Completely malleable after warming to 55 degrees C, resorbable plates can readily conform to most morphologic appearances of fractures or defects and provide rigid fixation when cooled. The plating systems used in head and neck reconstruction are described. STUDY DESIGN: Nine patients were selected for reconstruction using a resorbable plating system. The resorbable system was tested under a variety of clinical situations including frontal sinus fractures (three patients), midface fractures (two patients), mandibular defects (two patients), and laryngeal fractures (two patients). METHODS: Each case was evaluated for rigidity of fixation, and ease of plate contouring and application. Furthermore, the postoperative functional and cosmetic results and complications were contrasted between the resorbable plating systems and each surgeon's vast experience with traditional plating systems. RESULTS: The resorbable plating system was found to be as effective as traditional plating systems with respect to rigidity of fixation, functional results, and complications. In addition, the resorbable system was far easier to contour and, consequently, to apply, while producing higher cosmetic satisfaction after plate resorption than traditional plating. CONCLUSIONS: 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.

Current applications of platelet gels in facial plastic surgery.

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.