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《Bioorganic & medicinal chemistry letters》2014,24(7):1846-1850
Two novel small molecule gonadotropin-releasing hormone (GnRH) receptor antagonists (12 and 13) of the furamide-class were synthesized and evaluated in vitro for their receptor binding affinities for the rat GnRH receptor. Radiolabeling with no carrier added fluorine-18 of the appropriate precursors was investigated in a one-step reaction. Log P (Octanol/PBS pH 7.4) and serum stability of the compounds were investigated. The antagonists showed low nM affinity for the rat GnRH receptor. 18F-radiolabled compounds were obtained in high radiochemical purity (>95%) and specific activity (>75 GBq/μmol). These findings suggest this class of compounds holds promise as potential probes for PET targeting of GnRH-receptor expression. 相似文献
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We generalize the results of multiyear studies of the level of antioxidative activity of lipids isolated from tissues of laboratory rodents of different species and lines. A classification of lipids according to their ability to inhibit thermal autooxidation of methyl oleate is proposed. The involvement of lipids in low-temperature autooxidation reactions at the radical initiation and chain propagation stages was proved using the model developed. In addition to antioxidative activity, the initial content of peroxides in lipids, determined by their degree of unsaturation, and the antiperoxide activity of lipids are proposed for quantitative estimation of the kinetic characteristics of lipids of mammalian tissues. The dependence of effects on the rate of radical initiation in the system is shown, which is determined by the influence of the physicochemical properties of lipids on the coordination of relationships and balance of biochemical functions in biological objects differing in the intensity of oxidation processes. 相似文献
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Kevin Boylan Cui Yang† Julia Crook‡ Karen Overstreet Michael Heckman‡ Yong Wang§ David Borchelt† Gerry Shaw†§ 《Journal of neurochemistry》2009,111(5):1182-1191
Levels of neurofilament subunits, potential biomarkers of motor axon breakdown, are increased in amyotrophic lateral sclerosis (ALS) patient's CSF but data on blood are not available. We measured blood levels of the phosphorylated axonal form of neurofilament H (pNF-H) by ELISA in transgenic rodent models of superoxide dismutase 1 (SOD1) ALS, and in 20 ALS patients and 20 similar aged controls monthly for 4 months. All symptomatic rodent ALS models showed robust levels of blood pNF-H, while control rodents or mice transgenic for unmutated SOD1 showed no detectable blood pNF-H. Average pNF-H levels in the G93A SOD1 mouse progressively increased from day 74 through death (day ∼130). Median blood pNF-H level in ALS patients was 2.8-fold higher than controls ( p < 0.001). Median ALSFRS-R declined a median of 0.8 pt/month ( p < 0.001); higher baseline pNF-H level appeared to be associated with faster ALSFRS-R decline over 4 months ( p = 0.087). The median rate of decline in ALSFRS-R was 1.9 pt/month in patients with baseline pNF-H levels above the median pNF-H value of 0.53 ng/mL; ALSFRS-R declined at a median of 0.6 pt/month in patients below this level. The pNF-H levels were relatively stable month to month in individual patients, raising questions regarding the molecular pathogenesis of ALS. Baseline control human pNF-H levels were higher in men than women and increased minimally over time. These data suggest that blood pNF-H can be used to monitor axonal degeneration in ALS model rodents and support further study of this protein as a potential biomarker of disease prognosis in ALS patients. 相似文献
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《Bioorganic & medicinal chemistry》2016,24(7):1419-1430
Parkinson’s disease (PD) is a common chronic degenerative disease of the central nervous system. Due to a rapidly aging society worldwide, PD morbidity is on the rise; however, the treatment of PD with conventional drugs carries serious adverse reactions and cannot fix the root cause of PD, the degeneration of dopaminergic neurons, which limits conventional drug usage in clinical practice. In recent years, research on the pathogenesis of PD and its clinical manifestations has led to the discovery of an increasing number of novel targets in PD, including several small molecule targeted compounds. In this paper, we analyze and summarize the most recently published PD literature and review several recently discovered novel targets in PD and their small molecule targeted pharmacologically active agents based on their mechanisms of action and pharmacodynamic profiles. 相似文献
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Summary The distributions of small cardioactive peptide (SCP)- and FMRFamide-like immunoreactivities in the central nervous system of the medicinal leech Hirudo medicinalis were studied. A subset of neurons in the segmental ganglia and brains was immunoreactive to an antibody directed against SCPB. Immunoreactive cell bodies were regionally distributed throughout the nerve cord, and occurred both as bilaterally paired and unpaired neurons. The majority of the unpaired cells displayed a tendency to alternate from side to side in adjacent ganglia. A small number of neurons were immunoreactive only in a minority of nerve cords investigated. Intracellular injections of Lucifer yellow dye and subsequent processing for immunocytochemistry revealed SCP-like immunoreactivity in heart modulatory neurons but not in heart motor neurons. FMRFamide-like immunoreactivity was also detected in cell bodies throughout the central nervous system. A subset of neurons contained both SCP- and FMRFamide-like immunoreactivities; others stained for only one or the other antigen. These data suggest that an antigen distinct from FMRFamide is responsible for at least part of the SCP-like immunoreactivity. This antigen likely bears some homology to the carboxyl terminal of SCPA and SCPB. 相似文献
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