Anti-neuroinflammatory effects of GPR55 antagonists in LPS-activated primary microglial cells

Background: Neuroinflammation plays a vital role in Alzheimer’s disease and other neurodegenerative conditions. Microglia are the resident mononuclear immune cells of the central nervous system, and they play essential roles in the maintenance of homeostasis and responses to neuroinflammation. The orphan G-protein-coupled receptor 55 (GPR55) has been reported to modulate inflammation and is expressed in immune cells such as monocytes and microglia. However, its effects on neuroinflammation, mainly on the production of members of the arachidonic acid pathway in activated microglia, have not been elucidated in detail. Methods: In this present study, a series of coumarin derivatives, that exhibit GPR55 antagonism properties, were designed. The effects of these compounds on members of the arachidonic acid cascade were studied in lipopolysaccharide (LPS)-treated primary rat microglia using Western blot, qPCR, and ELISA. Results: We demonstrate here that the various compounds with GPR55 antagonistic activities significantly inhibited the release of PGE₂ in primary microglia. The inhibition of LPS-induced PGE₂ release by the most potent candidate KIT 17 was partially dependent on reduced protein synthesis of mPGES-1 and COX-2. KIT 17 did not affect any key enzyme involved on the endocannabinoid system. We furthermore show that microglia expressed GPR55 and that a synthetic antagonist of the GPR receptor (ML193) demonstrated the same effect of the KIT 17 on the inhibition of PGE₂. Conclusions: Our results suggest that KIT 17 is acting as an inverse agonist on GPR55 independent of the endocannabinoid system. Targeting GPR55 might be a new therapeutic option to treat neurodegenerative diseases with a neuroinflammatory background such as Alzheimer’s disease, Parkinson, and multiple sclerosis (MS)

Vorrichtung und Verfahren zur kontinuierlichen Gasphasenabscheidung unter Atmosphaerendruck und deren Verwendung

WO 2007033832 A2 UPAB: 20070517 NOVELTY - In a device for continuous atmospheric pressure gas phase deposition onto substrates, comprising a reaction chamber (1) with two opposite open sides, along which the substrates are transported to close the chamber, and front and back walls (relative to the transport direction) connected by opposite side walls, each side wall has at least two process gas inlets (2) and outlets (3), at least parts of which are alternately located in the transport direction. DETAILED DESCRIPTION - INDEPENDENT CLAIMS are included for: (1) a gas phase deposition reactor, comprising a heating furnace in which at least two devices as above are located in parallel or in series; and (2) a deposition method using the apparatus, in which the gas supply is controlled so that, during deposition on the substrate, parasitic deposits on the apparatus are inhibited and/or removed. USE - The substrates to be coated are specifically of silicon, ceramic or glass (including corresponding composites or laminate systems) (all claimed). Typically the apparatus and method are used for epitaxial deposition of silicon layers (using a gaseous mixture of chlorosilanes and hydrogen), e.g. for use in solar cells. ADVANTAGE - The alternating arrangement of gas inlets and outlets causes gas streams to pass through the apparatus in a countercurrent manner, so that parasitic coatings in the apparatus are minimized or completely eliminated (or continuously cleaned off during operation). Continuous operation without interruptions is thus possible, so that markedly increased throughputs can be obtained. The number of parallel substrates passed through the apparatus and the length of the deposition zone can be increased

Light-Induced Step-Growth Polymerization of AB-Type Photo-Monomers at Ambient Temperature

We introduce two AB-type monomers able to undergo a facile catalyst-free photoinduced polycycloaddition of photocaged dienes, enabling rapid Diels–Alder ligations under UV-irradiation (λ_max = 350 nm) at ambient temperature, closely adhering to Carother’s equation established by a careful kinetic study (17800 g mol^–1 < <i>M</i>_w < 24700 g mol^–1). The resulting macromolecules were in-depth analyzed via size exclusion chromatography (SEC) and nuclear magnetic resonance (NMR) spectroscopy. Additionally, SEC hyphenated to high resolution-electrospray ionization-mass spectrometry (HR-ESI-MS) enabled the careful mapping of the end group structure of the generated polymers. Furthermore, we demonstrate that both monomer systems can be readily copolymerized. The study thus demonstrates that Diels–Alder ligation resting upon photocaged dienes is a powerful tool for accessing step-growth polymers