Sedative-hypnotic and muscle relaxant activities of propoxazepam in animal models and investigation on possible mechanisms

Analgesic (for both neuropathic and nociceptive pain) and anticonvulsant action of 7-bromo-5-(o-chlorophenyl)-3- propoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one (propoxazepam) make it perspective for further studying. Objectives: Propoxazepam was evaluated for sedative-hypnotic-like activity in mice and involved mechanisms in a battery of tests: acute oral toxicity, motor coordination and muscle relaxation studies. Materials and Methods: Acute toxicity (rats) and thiopental-induced sleeping (mice) were determined as motor coordination and muscle relaxation. Results: As relatively nontoxic substance (LD50>5000 mg/kg) propoxazepam belong to fifth category according to GHS toxicity classification. At high doses (700, 1100 and 1300 mg/kg, i.p.) a delay in the righting reflex was observed but not a total loss. The results indicated that substance induces hypnotic effects. Because propoxazepam produces any effect on rotarod test, seems that its effects on sleeping time and sleep latency are mediated by affecting motor movement. Conclusion: Based on previous results and present data, it should be presumed that GABAergic mechanisms may be involved in the potentiating effect of propoxazepam on thiopental-induced sleeping time and sleep latency in mice. Propoxazepam potentiates sleep induced by hypnotics like thiopental, but can not induce hypnosis by itself

Individual SWCNT Transistor with Photosensitive Planar Junction Induced by Two-Photon Oxidation

The fabrication of planar junctions in carbon nanomaterials is a promising way to increase the optical sensitivity of optoelectronic nanometer-scale devices in photonic connections, sensors, and photovoltaics. Utilizing a unique lithography approach based on direct femtosecond laser processing, a fast and easy technique for modification of single-walled carbon nanotube (SWCNT) optoelectronic properties through localized two-photon oxidation is developed. It results in a novel approach of quasimetallic to semiconducting nanotube conversion so that metal/semiconductor planar junction is formed via local laser patterning. The fabricated planar junction in the field-effect transistors based on individual SWCNT drastically increases the photoresponse of such devices. The broadband photoresponsivity of the two-photon oxidized structures reaches the value of 2 × 107 A W−1 per single SWCNT at 1 V bias voltage. The SWCNT-based transistors with induced metal/semiconductor planar junction can be applied to detect extremely small light intensities with high spatial resolution in photovoltaics, integrated circuits, and telecommunication applications.Peer reviewe

Deficiency of TLR4 homologue RP105 aggravates outward remodeling in a murine model of arteriovenous fistula failure

Abstract Arteriovenous access dysfunction is a major cause of morbidity for hemodialysis patients. The pathophysiology of arteriovenous fistula (AVF) maturation failure is associated with inflammation, impaired outward remodeling (OR) and intimal hyperplasia. RP105 is a critical physiologic regulator of TLR4 signaling in numerous cell types. In the present study, we investigated the impact of RP105 on AVF maturation, and defined cell-specific effects of RP105 on macrophages and vascular smooth muscle cells (VSMCs). Overall, RP105−/− mice displayed a 26% decrease in venous OR. The inflammatory response in RP105−/− mice was characterized by accumulation of anti-inflammatory macrophages, a 76% decrease in pro- inflammatory macrophages, a 70% reduction in T-cells and a 50% decrease in MMP-activity. In vitro, anti-inflammatory macrophages from RP105−/− mice displayed increased IL10 production, while MCP1 and IL6 levels secreted by pro-inflammatory macrophages were elevated. VSMC content in RP105−/− AVFs was markedly decreased. In vitro, RP105−/− venous VSMCs proliferation was 50% lower, whereas arterial VSMCs displayed a 50% decrease in migration, relative to WT. In conclusion, the impaired venous OR in RP105−/− mice could result from of a shift in both macrophages and VSMCs towards a regenerative phenotype, identifying a novel relationship between inflammation and VSMC function in AVF maturation