Albiglutide improved fasting plasma glucose and postprandial glucose with a favorable safety profile in subjects with type 2 diabetes. Albiglutide's long half-life may allow for once-weekly or less frequent dosing.

Albiglutide has a half-life that favours once weekly or less frequent dosing with an acceptable safety/tolerability profile in non-diabetic subjects.

Neuiropeptide Y (NPY) is one of the most abundant peptide transmitters in the mammalian brain. In the periphery it is costored and coreleased with norepinephrine from sympathetic nerve terminals. However, the physiological functions of this peptide remain unclear because of the absence of specific high-affinity receptor antagonists. Three potent NPY receptor antagonists were synthesized and tested for their biological activity in in vitro, ex vivo, and in vivo functional assays. We describe here the effects of these antagonists inhibiting specific radiolabeled NPY binding at Y1 and Y2 receptors and antagonizing the effects of NPY in human erythroleukmia cell intracellular calcium mobilization, perfusion pressure in the isolated rat kidney, and mean arterial blood pressure in anesthetized rats.Neuropeptide Y (NPY) is a 36-amino acid peptide with an N-terminal tyrosine and a C-terminal tyrosine amide, first isolated from porcine brain by Tatemoto et al. in 1982 (1). NPY has been found to be an abundant mammalian neuropeptide, widely distributed throughout the central and peripheral nervous systems (2-4). On the basis of the pharmacological effects observed in experimental animals after central or peripheral administration of NPY, the peptide has tentatively been implicated in the regulation of a wide variety of biological functions such as vascular tone, feeding behavior, mood, and hormone secretion among others (for a review see ref. 5). At least two NPY receptor subtypes have been described based on the relative affinity of different NPY agonists: NPY-Y1 receptors require essentially the full NPY sequence of amino acids (see Fig. 1) for activation and have high affinity for the analog [Leu31,Pro34]NPY, whereas NPY-Y2 receptors can be activated by NPY and the shorter C-terminal fragment, NPY13-36, but have low affinity for [Leu31,Pro34]NPY (6,7). A third subtype (NPY-Y3) that recognizes all three of the above peptides but is insensitive to the NPY homolog, peptide YY, has been proposed (8, 9). Direct demonstration of a physiological and pathophysiological role for NPY has been hampered by the lack of specific, high-affinity NPY receptor antagonists. Receptor antagonists based on modified Cterminal fragments of NPY (10) Peptide Synthesis. Peptides were synthesized by the solidphase method. Compound 2 was obtained by oxidation of the reduced monomer and purification of the dimer by HPLC. Compound 3 was synthesized by using standard solid-phase synthesis. Compound 4 was synthesized by coupling BOC-Lglutamic acid fluorenylmethyl ester and a-Boc 3-FmOC-Ldiamino propionic acid in position 8 and 6, respectively. Dimerization was achieved on the resin by treatment with piperidine followed by a coupling reagent. Detailed synthesis is described in the compounds' patent publication (15).Binding Assays.[3H]NPY binding to rat brain membranes was done as described (16) except that incubations were terminated by filtration on a Brandel cell harvester through a Whatman GF/B filter, previously soaked overnight in 0.3% po...

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Peptide analogs of neuropeptide Y (NPY) with a Tyr-32 and Leu-34 replacement resulted in the decapeptide TyrIleAsnLeuIleTyrArgLeuArgTyr-NH2 (9; Table 1) and a 3700-fold improvement in affinity at Y2 (rat brain; IC50 = 8.2 +/- 3 nM) receptors when compared to the native NPY(27-36) C-terminal fragment. In addition, compound 9 was an agonist at Y1 (human erythroleukemia (HEL) cell; ED50 = 8.8 +/- 0.5 nM) receptors with potency comparable to that of NPY(1-36) (ED50 = 5 nM). Molecular dynamics and 1H-NMR were used to propose a solution structure of decapeptide 9 and for subsequent analog design. The replacement of Leu with Pro at position 4 of decapeptide 9 afforded an antagonist of NPY in HEL cells (18, TyrIleAsnProIleTyrArgLeuArgTyr-NH2; IC50 = 100 +/- 5 nM). Deletion of the N-terminal tyrosine of 18 resulted in a 10-fold improvement in antagonistic activity with a parallel 4-fold decrease in Y2 affinity. This potent antagonist may provide further insight into the physiological role(s) for NPY in the mammalian and peripheral nervous system.

In ED patients with suspected PE, the CT angiogram frequently provides evidence suggesting an important alternative diagnosis to PE. Pulmonary infiltrate suggesting pneumonia was the most common non-PE finding.

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The phototoxicity of argon laser irradiation was studied in aqueous suspensions of Porphyromonas endodontalis (American Type Culture Collection [ATCC] 35406), Porphyromonas gingivalis (ATCC 33277), Prevotella denticola (ATCC 33184) and two strains of Prevotella intermedia (ATCC 15033 and 49046), all "black-pigmented bacteria," BPB, that accumulate cellular porphyrins. Several of these species have been implicated in the etiology of periodontal disease. Non-black-pigmented bacteria were also studied to test the specificity of irradiation as a potential photodynamic treatment for periodontal infections. Cell suspensions were irradiated with an argon laser at fluences of 20-200 J/cm2. When cultured in hemin-supplemented media, ATCC 15033 was the most sensitive to irradiation. However, a second strain of the same species (ATCC 49046) was resistant. The photosensitivity of other species ranked ATCC 33277 > 35406 = 33184 = 35496. When hemin was replaced in media by hemoglobin, ATCC 33277 became resistant to irradiation. Protoporphyrin IX content in BPB cells was shown not to be a major factor determining photosensitivity. Oxygen was required during irradiation for BPB species to be affected. Non-black-pigmented bacteria were much less sensitive to irradiation than BPB.