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排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Brian Cox James Duffy Victor Zdorichenko Corentin Bellanger Jessica Hurcum Benoît Laleu Kevin I. Booker-Milburn Luke D. Elliott Michael Robertson-Ralph Christopher J. Swain Stephen J. Bishop Irene Hallyburton Mark Anderson 《ACS medicinal chemistry letters》2020,11(12):2497
We utilized synthetic photochemistry to generate novel sp3-rich scaffolds and report the design, synthesis, and biological testing of a diverse series of amides based on the 1-(amino-methyl)-2-benzyl-2-aza-bicyclo[2.1.1]hexane scaffold. Preliminary antimalarial screening of the library provided promising compounds with activity in the 1–5 μM range with an enhanced hit rate. Further evaluation (solubility, drug metabolism and pharmacokinetics (DMPK), and toxicity) of a selected compound (9) suggested that this series represents an excellent opportunity for further optimization with the framework offering multiple opportunities for the addition of uniquely vectorally positioned extra functionality. 相似文献
992.
Christopher C. Waller Sumudu A. Weththasinghe Lauren McClure Adam T. Cawley Craig Suann Emily Suann Emma Sutherland Elliot Cooper Alison Heather Malcolm D. McLeod 《Drug testing and analysis》2020,12(6):752-762
Hemapolin (2α,3α‐epithio‐17α‐methyl‐5α‐androstan‐17β‐ol) is a designer steroid that is an ingredient in several “dietary” and “nutritional” supplements available online. As an unusual chemical modification to the steroid A‐ring could allow this compound to pass through antidoping screens undetected, the metabolism of hemapolin was investigated by an in vivo equine drug administration study coupled with GC‐MS analysis. Following administration of synthetically prepared hemapolin to a thoroughbred horse, madol (17α‐methyl‐5α‐androst‐2‐en‐17β‐ol), reduced and dihydroxylated madol (17α‐methyl‐5α‐androstane‐2β,3α,17β‐triol), and the isomeric enone metabolites 17β‐hydroxy‐17α‐methyl‐5α‐androst‐3‐en‐2‐one and 17β‐hydroxy‐17α‐methyl‐5α‐androst‐2‐en‐4‐one, were detected and confirmed in equine urine extracts by comparison with a library of synthetically derived reference materials. A number of additional madol derivatives derived from hydroxylation, dihydroxylation, and trihydroxylation were also detected but not fully identified by this approach. A yeast cell‐based androgen receptor bioassay of available reference materials showed that hemapolin and many of the metabolites identified by this study were potent activators of the equine androgen receptor. This study reveals the metabolites resulting from the equine administration of the androgen hemapolin that can be incorporated into routine GC‐MS antidoping screening and confirmation protocols to detect the illicit use of this agent in equine sports. 相似文献
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Burel R. Goodin Tarek Kronfli Christopher D. King Toni L. Glover Kimberly Sibille Roger B. Fillingim 《Journal of behavioral medicine》2013,36(2):165-174
Greater dispositional optimism has been related to less severe pain; however, whether optimism is associated with endogenous pain modulation has not yet been examined. The beneficial effects of dispositional optimism often vary according to cultural dynamics. Thus, assessing optimism–pain relationships across different ethnic groups is warranted. This study sought to examine the association between optimism and conditioned pain modulation (CPM), and test whether this association differs according to ethnicity. Optimism and CPM were assessed in a sample of healthy, ethnically diverse young adults. CPM was determined by comparing pressure pain thresholds obtained before and during exposure to a cold pressor task. All participants completed a validated measure of dispositional optimism. Greater reported optimism was significantly associated with enhanced CPM, and the strength of this association did not vary according to individuals’ ethnic background. These findings suggest that an optimistic disposition may potentiate endogenous pain inhibition. 相似文献
998.
Holly Turula Corinne J. Smith Finn Grey Katherine A. Zurbach Christopher M. Snyder 《European journal of immunology》2013,43(5):1252-1263
Both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) establish persistent infections that induce the accumulation of virus‐specific T cells over time in a process called memory inflation. It has been proposed that T cells expressing T‐cell receptors (TCRs) with high affinity for HCMV‐derived peptides are preferentially selected after acute HCMV infection. To test this in the murine model, small numbers of OT‐I transgenic T cells, which express a TCR with high affinity for the SIINFEKL peptide, were transferred into congenic mice and recipients were challenged with recombinant MCMV expressing SIINFEKL. OT‐I T cells were selectively enriched during the first 3 weeks of infection. Similarly, in the absence of OT‐I T cells, the functional avidity of SIINFEKL‐specific T cells increased from early to late times postinfection. However, even when exceedingly small numbers of OT‐I T cells were transferred, their inflation limited the inflation of host‐derived T cells specific for SIINFEKL. Importantly, subtle minor histocompatibility differences led to late rejection of the transferred OT‐I T cells in some mice, which allowed host‐derived T cells to inflate substantially. Thus, T cells with a high functional avidity are selected shortly after MCMV infection and continuously sustain their clonal dominance in a competitive manner. 相似文献
999.
Jeroen N. Stoop Christopher A. Tibbitt Willem van Eden John H. Robinson Catharien M. U. Hilkens 《Immunology》2013,138(1):68-75
Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic inflammation of the synovial joints. Collagen‐induced arthritis (CIA) and proteoglycan‐induced arthritis (PGIA) are mouse models of inflammatory arthritis; CIA is a T helper type 17 (Th17) ‐dependent disease that is induced with antigen in complete Freund's adjuvant, whereas PGIA is Th1‐mediated and is induced using antigen in dimethyldioctadecyl‐ammonium bromide (DDA) as an adjuvant. To investigate whether the type of adjuvant determines the cytokine profile of the pathogenic T cells, we have compared the effect of CFA and DDA on T‐cell responses in a single arthritis model. No differences in incidence or disease severity between aggrecan‐T‐cell receptor transgenic mice immunized with aggrecan in either CFA or DDA were observed. Immunization with CFA resulted in a higher proportion of Th17 cells, whereas DDA induced more Th1 cells. However, the levels of interleukin‐17 (IL‐17) produced by T cells isolated from CFA‐immunized mice after antigen‐specific stimulation were not significantly different from those found in DDA‐immunized mice, indicating that the increased proportion of Th17 cells did not result in significantly higher ex vivo IL‐17 levels. Hence, the choice of adjuvant can affect the overall proportions of Th1 and Th17 cells, without necessarily affecting the level of cytokine production or disease incidence and severity. 相似文献
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