The Soft X-ray Telescope (SXT) of the SOLAR-A mission is designed to produce X-ray movies of flares with excellent angular and time resolution as well as full-disk X-ray images for general studies. A selection of thin metal filters provide a measure of temperature discrimination and aid in obtaining the wide dynamic range required for solar observing. The co aligned SXT aspect telescope will yield optical images for aspect reference, white-light flare and sunspot studies, and, possibly, helioseismology. This paper describes the capabilities and ckaracteristics of the SXT for scievtiflc observing.

Interleukin-23 (IL-23) and IL-17 are cytokines currently being targeted in clinical trials. Although inhibition of both of these cytokines is effective for treating psoriasis, IL-12 and IL-23 p40 inhibition attenuates Crohn's disease, whereas IL-17A or IL-17 receptor A (IL-17RA) inhibition exacerbates Crohn's disease. This dichotomy between IL-23 and IL-17 was effectively modeled in the multidrug resistance-1a-ablated (Abcb1a(-/-)) mouse model of colitis. IL-23 inhibition attenuated disease by decreasing colonic inflammation while enhancing regulatory T (Treg) cell accumulation. Exacerbation of colitis by IL-17A or IL-17RA inhibition was associated with severe weakening of the intestinal epithelial barrier, culminating in increased colonic inflammation and accelerated mortality. These data show that IL-17A acts on intestinal epithelium to promote barrier function and provide insight into mechanisms underlying exacerbation of Crohn's disease when IL-17A or IL-17RA is inhibited.

Galanin is a 29-aa neuropeptide with a complex role in pain processing. Several galanin receptor subtypes are present in dorsal root ganglia and spinal cord with a differential distribution. Here, we describe a generation of a specific galanin R2 (GalR2) agonist, AR-M1896, and its application in studies of a rat neuropathic pain model (Bennett). The results show that in normal rats mechanical and cold allodynia of the hindpaw are induced after intrathecal infusion of low-dose galanin (25 ng per 0.5 l͞h). The same effect is seen with equimolar doses of AR-M1896 or AR-M961, an agonist both at GalR1 and GalR2 receptors. In allodynic Bennett model rats, the mechanical threshold increased dose-dependently after intrathecal injection of a high dose of AR-M961, whereas no effect was observed in the control or AR-M1896 group. No effect of either of the two compounds was observed in nonallodynic Bennett model rats. These data indicate that a low dose of galanin has a nociceptive role at the spinal cord level mediated by GalR2 receptors, whereas the antiallodynic effect of high-dose galanin on neuropathic pain is mediated by the GalR1 receptors. Thus, a selective GalR1 agonist may be used to treat neuropathic pain.alanin is a 29-aa (30 aa in humans) neuropeptide (1). It has a wide distribution in the nervous system and may be involved in a variety of physiological and pathophysiological activities (2), including pain signaling (3-5). Galanin is upregulated in dorsal root ganglion (DRG) neurons in many animal models based on peripheral nerve injury, including complete axotomy (6, 7), complete nerve constriction injury (8-10), as well as partial nerve ligation (9, 10). In agreement, enhanced immunoreactive galanin release was also found in the superficial dorsal horn ipsilateral to sciatic nerve injury (11).Galanin's role in pain signaling is complex, and early studies revealed inhibitory (12-15) and at low doses excitatory (16-18) effects of galanin, as well as enhanced inhibition after nerve injury (17,19). It also has been proposed that galanin after nerve injury may contribute to neuropathic pain (9), and recently infusion of low doses of galanin resulted in a decrease in pain threshold (20,21).Three galanin receptors have been identified and cloned (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34), and all of the three subtype mRNAs are expressed within DRGs and spinal cord with different distribution patterns, expression levels, and response to peripheral nerve injury (4, 34-38). All three known receptors belong to the superfamily of G protein-coupled transmembrane receptors, and they use different transduction signaling pathways (see ref. 34). The multitude of receptors may at least in part underlie the diversity and opposing views on the apparent functional roles of galanin in pain processing at the spinal level.A problem in the field has been the lack of specific and efficient drugs affecting galaninergic mechanisms. However, Bartfai and colleagues (39) ]Gal(1-16)-NH 2 , which has high affinity and functional a...

No abstract

Chronic enalapril treatment of dogs with naturally occurring, moderate to severe MR significantly delayed onset of CHF, compared with placebo, on the basis of number of CHF-free days, number of dogs free of CHF at days 500 and study end, and increased time to a combined secondary endpoint of CHF-all-cause death. Improvement in the primary endpoint, CHF-free survival, was not significant. Results suggest that enalapril modestly delays the onset of CHF in dogs with moderate to severe MR.

No abstract

No abstract

The design, synthesis, and pharmacological evaluation of a novel class of delta opioid receptor agonists, N, N-diethyl-4-(phenylpiperidin-4-ylidenemethyl)benzamide (6a) and its analogues, are described. These compounds, formally derived from SNC-80 (2) by replacing the piperazine ring with a piperidine ring containing an exocyclic carbon carbon double bond, were found to bind with high affinity and exhibit excellent selectivity for the delta opioid receptor as full agonists. 6a, the simplest structure in the class, exhibited an IC(50) = 0.87 nM for the delta opioid receptors and extremely high selectivity over the mu receptors (mu/delta = 4370) and the kappa receptors (kappa/delta = 8590). Rat liver microsome studies on a selected number of compounds show these olefinic piperidine compounds (6) to be considerably more stable than SNC-80. This novel series of compounds appear to interact with delta opioid receptors in a similar way to SNC-80 since they demonstrate similar SAR. Two general approaches have been established for the synthesis of these compounds, based on dehydration of benzhydryl alcohols (7) and Suzuki coupling reactions of vinyl bromide (8), and are herewith reported.