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P2Y receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on P2Y Receptors [3, 5, 189]) are activated by the endogenous ligands ATP, ADP, UTP, UDP, UDP-glucose and adenosine. The eight mammalian P2Y receptors are activated by distinct nucleotides: P2Y1, P2Y11, P2Y12 and P2Y13 are activated by adenosine-nucleotides; P2Y2, P2Y4 can be activated by both adenosine and uridine nucleotides, with some species-specific differences; P2Y6 is mainly activated by UDP; P2Y14 is preferentially activated by sugar-uracil nucleotides. The missing numbers in the receptor nomenclature refer either to non-mammalian orthologs or receptors having some sequence homology to P2Y receptors but for which there is no functional evidence of responsiveness to nucleotides [380]. Based on their G protein coupling P2Y receptors can be divided into two subfamilies: P2Y1, P2Y2, P2Y4, P2Y6 and P2Y11 receptors couple via Gq proteins to stimulate phospholipase C followed by increases in inositol phosphates and mobilization of Ca2+ from intracellular stores. P2Y11 receptors couple in addition to Gs proteins followed by increased adenylate cyclase activity. In contrast, P2Y12, P2Y13, and P2Y14 receptors signal primarily through activation of Gi proteins and inhibition of adenylate cyclase activity or control of ion channel activity [380]. Clinically used drugs acting on these receptors include the dinucleoside polyphosphate diquafosol, agonist of the P2Y2 receptor subtype, approved in Japan and South Korea for the management of dry eye disease [238], and the P2Y12 receptor antagonists prasugrel, ticagrelor and cangrelor, all approved as antiplatelet drugs [52, 320].

P2Y receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on P2Y Receptors [3, 5, 192]) are activated by the endogenous ligands ATP, ADP, uridine triphosphate, uridine diphosphate and UDP-glucose. The relationship of many of the cloned receptors to endogenously expressed receptors is not yet established and so it might be appropriate to use wording such as 'uridine triphosphate-preferring (or ATP-, etc.) P2Y receptor' or 'P2Y1-like', etc., until further, as yet undefined, corroborative criteria can be applied [47, 110, 190, 383, 396]. Clinically used drugs acting on these receptors include the dinucleoside polyphosphate diquafosol, agonist of the P2Y2 receptor subtype, approved in Japan for the management of dry eye disease [241], and the P2Y12 receptor antagonists prasugrel, ticagrelor and cangrelor, all approved as antiplatelet drugs [53, 323].

P2Y receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on P2Y Receptors [3, 5]) are activated by the endogenous ligands ATP, ADP, uridine triphosphate, uridine diphosphate and UDP-glucose. The relationship of many of the cloned receptors to endogenously expressed receptors is not yet established and so it might be appropriate to use wording such as 'uridine triphosphate-preferring (or ATP-, etc.) P2Y receptor' or 'P2Y1-like', etc., until further, as yet undefined, corroborative criteria can be applied [46, 109, 187, 375, 388].Clinically used drugs acting on these receptors include the dinucleoside polyphosphate diquafosol, agonist of the P2Y2 receptor subtype, approved in Japan for the management of dry eye disease [236], and the P2Y12 receptor antagonists prasugrel, ticagrelor and cangrelor, all approved as antiplatelet drugs [52, 316].

An important role for adenosine diphosphate (ADP)-induced platelet activation and aggregation was proposed more than 40 years ago. The clinical use of clopidogrel, a prodrug of an irreversible P2Y (12) antagonist, has further proved the relevance of inhibiting signaling via the platelet-specific P2Y (12) ADP receptor in the prevention of cardiovascular events. Pharmacological studies at AstraZeneca R&D Charnwood have identified direct, selective, and competitive P2Y (12) antagonists, including cangrelor (also known as AR-C69931MX), which is suitable for intravenous administration, and AZD6140, which is suitable for oral administration. In preclinical use, these compounds predictably and effectively inhibited platelet aggregation without significant increases in bleeding time. In clinical use, these compounds may have significant advantages over current antiplatelet agents. This article summarizes preclinical and clinical data on cangrelor and AZD6140 and discusses the potential of these compounds as novel antiplatelet therapies.

This study integrates surface hail reports with concurrent radar measurements. It employs polarization techniques, corrected for propagation effects, to detect hail within rain storms. For two decades, S-band polarization diversity radar was employed in central Alberta, Canada, to study severe storms. The radar normally transmitted circularly polarized radiation. It measured the four parameters commonly used to describe echoes received by circularly polarized weather radars: namely, equivalent reflectivity factor Ze, circular depolarization ratio CDR, degree of common hydrometcor alignment ORTT, and their apparent orientation angle ALD. It was shown that circular polarization estimates of differential reflectivity ZDRc are comparable to those more commonly derived using dual-linear polarization radars. Low-level radar measurements were compared to well documented and carefully timed ground-based observations of precipitation collected by a mobile truck crew. The case studies were analyzed to esta...

Objective— Reperfusion therapy for myocardial infarction is limited by a significant reocclusion rate and less optimal myocardial tissue perfusion due to excessive platelet accumulation and recruitment at the sites of vascular injury. We assessed the influence of a selective P2Y 12 -receptor antagonist (AR-C69931MX), in conjunction with thrombolytic therapy, on the prevention of platelet aggregation and thrombus formation. Methods and Results— A canine coronary electrolytic injury thrombosis model was used. Tissue-type plasminogen activator (t-PA; 1 mg/kg in phase I, 0.5 mg/kg in phase II in the AR-C69931MX group, and 1 mg/kg in the placebo group in phase I and II) was administered 30 minutes after thrombus formation; either saline or AR-C69931MX (4 μg · kg −1 · min −1 ) was given to all animals intravenously 10 minutes before t-PA administration for a total of 2 hours. All animals received heparin (80 U/kg) as an intravenous bolus followed by a continuous infusion of 17 U · kg −1 · h −1 . Myocardial tissue perfusion was evaluated by use of the colored microsphere technique and real-time myocardial contrast echocardiography. The incidences of reocclusion and cyclic flow variation were significantly decreased in the AR-C69931MX group ( P P Conclusions— The adjunctive administration of AR-C69931MX blocked ADP-mediated platelet aggregation and recruitment and prevented platelet-mediated thrombosis, resulting in prolongation of reperfusion time and a decrease in reocclusion and cyclic flow variations. Importantly, myocardial tissue perfusion was significantly improved in the P2Y 12 antagonist group.

Polarization is a fundamental descriptor of electromagnetic waves and, as such, has received the attention of scientists for over three centuries, beginning with the discovery of double refraction in crystals by Bartolinus and the discovery of polarized light by Huygens in the seventeenth century. Dramatic advances in the understanding of optics and electricity occurred thereafter, particularly throughout the nineteenth century, culminating in Maxwell’s classic formulation of the electromagnetic theory, Hertz’ extensive experiments on radiation fields, and Lord Rayleigh’s investigations in electromagnetic scattering. These laid the groundwork for the development of radio, radar, and all that was to come in telecommunications during the twentieth century.

Ultraviolet erythema in the guinea pid has been in use for many years as a model for assessing the anti-inflammatory potency of non-steroidal anti-inflammatory agents, the degree of erythema usually being estimated about 2 h after u.v. exposure. Using a suction blister technique for obtaining tissue fluid from erythemic and normal skin of the guinea pig we have shown that prostaglandin output in ultraviolet-irradiated skin increases rapidly during the first 2 h after irradiation, at which time the erythema reaches near-maximal development. Flurbiprofen, a potent non-steroidal anti-inflammatory agent, almost totally prevents the appearance of prostaglandins in the blister fluid and significantly reduces the degree of erythema in the skin during this early period. However, in flurbiprofen-treated animals, although prostaglandin synthesis is also suppressed at 4 to 5 h after exposure and is still partially suppressed at 17 h, a well developed erythema nevertheless appears by 4 h. This indicates the appearance of one or more non-prostaglandin mediators in the later stages of the reaction.