A Phase I, Two-part, Single-center, Open-label, Drug-drug Interaction Study to Assess the Effect of Voriconazole (Part 1) and Quinidine (Part 2) on the Pharmacokinetics of a Single Dose of Repotrectinib (BMS-986472) in Healthy Participants

The purpose of this study is to evaluate the effects of coadministration of voriconazole or quinidine on the pharmacokinetics (PK) of repotrectinib in healthy male and female (individual not of childbearing potential [INOCBP]) participants.

开始日期2024-08-26

申办/合作机构

Bristol Myers Squibb Co.

100 项与 SCNA x α-adrenergic receptor 相关的临床结果

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100 项与 SCNA x α-adrenergic receptor 相关的转化医学

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0 项与 SCNA x α-adrenergic receptor 相关的专利（医药）

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项与 SCNA x α-adrenergic receptor 相关的文献（医药）

2024-10-01·Cell Reports Medicine

The sympathetic nervous system drives hyperinflammatory responses to Clostridioides difficile infection

Article

作者: Petri, William A ; Naz, Farha ; Leslie, Jhansi L. ; Leslie, Jhansi L ; Thompson, Brandon ; Tyus, David ; Uddin, Md Jashim ; Petri, William A.

Clostridioides difficile infection (CDI) is a leading cause of hospital-acquired infections in the United States, known for triggering severe disease by hyperactivation of the host response. In this study, we determine the impact of the sympathetic nervous system (SNS) on CDI disease severity. Mouse models of CDI are administered inhibitors of SNS activity prior to CDI. Chemical sympathectomy or pharmacological inhibition of norepinephrine synthesis greatly reduces mortality and disease severity in the CDI model. Pharmacological blockade or genetic ablation of the alpha 2 adrenergic receptor ameliorates intestinal inflammation, disease severity, and mortality rate. These results underscore the role of the SNS and the alpha 2 adrenergic receptor in CDI pathogenesis and suggest that targeting neural systems could be a promising approach to therapy in severe disease.

2022-08-03·Rheumatology2区 · 医学

Interplay between genetics and lifestyle on pain susceptibility in women with fibromyalgia: the al-Ándalus project

2区 · 医学

Article

作者: Martínez-González, Luis J ; Geenen, Rinie ; Álvarez-Gallardo, Inmaculada C ; Aparicio, Virginia A ; Álvarez-Cubero, María J ; Gavilán-Carrera, Blanca ; Guerrero-González, Juan M ; Ruiz, Jonatan R ; Estévez-López, Fernando ; Camiletti-Moirón, Daniel ; Segura-Jiménez, Víctor ; Soriano-Maldonado, Alberto ; Salazar-Tortosa, Diego ; Acosta-Manzano, Pedro ; Delgado-Fernández, Manuel

AbstractObjectivesIt is widely acknowledged that the experience of pain is promoted by both genetic susceptibility and environmental factors such as engaging in physical activity (PA), and that pain-related cognitions are also important. Thus, the purpose of the present study was to test the association of 64 polymorphisms (34 candidate genes) and the gene–gene, gene–PA and gene–sedentary behaviour interactions with pain and pain-related cognitions in women with FM.MethodsSaliva samples from 274 women with FM [mean (s.d.) age 51.7 (7.7) years] were collected for extracting DNA. We measured PA and sedentary behaviour by accelerometers for a week, pain with algometry and questionnaires, and pain-related cognitions with questionnaires. To assess the robustness of the results, a meta-analysis was also performed.ResultsThe rs6311 and rs6313 polymorphisms (5-hydroxytryptamine receptor 2A, HTR2A) were individually related to algometer scores. The interaction of rs4818 (catechol-O-methyltransferase, COMT) and rs1799971 (opioid receptor μ gene, OPRM1) was related to pain catastrophizing. Five gene–behaviour interactions were significant: the interactions of sedentary behaviour with rs1383914 (adrenoceptor alpha 1A, ADRA1A), rs6860 (charged multivesicular body protein 1A, CHMP1A), rs4680 (COMT), rs165599 (COMT) and rs12994338 (SCN9A) on bodily pain subscale of the Short Form 36. Furthermore, the meta-analysis showed an association between rs4680 (COMT) and severity of FM symptoms (codominant model, P-value 0.032).ConclusionThe HTR2A gene (individually), COMT and OPRM1 gene–gene interaction, and the interactions of sedentary behaviour with ADRA1A, CHMP1A, COMT and SCN9A genes were associated with pain-related outcomes. Collectively, findings from the present study indicate a modest contribution of genetics and gene–sedentary behaviour interaction to pain and pain catastrophizing in women with FM. Future research should examine whether reducing sedentary behaviour is particularly beneficial for reducing pain in women with genetic susceptibility to pain.

2020-06-01·The American Journal of Pathology2区 · 医学

Sympathetic Nerves Positively Regulate Eosinophil-Driven Allergic Conjunctivitis via α1-Adrenergic Receptor Signaling

2区 · 医学

Article

作者: Huang, Shuoya ; He, Jingxin ; Wang, Yuming ; Yu, Ruoxun ; Xue, Yunxia ; Chen, Xinwei ; Li, Zhijie ; Wu, Mingjuan ; Liu, Jun ; Fu, Ting ; Li, Fanying

Eosinophils are a major cause of tissue injury in allergic conjunctivitis. The biological nature of eosinophils in the conjunctiva and the mechanisms that control eosinophils' responses in allergic conjunctivitis are currently not completely understood. This study reports that conjunctival eosinophils comprise two populations-Siglec-F^int and Siglec-F^hi-in different life stages. Siglec-F^int eosinophils partly expressed CD34 and were in the immature (or steady) state. Siglec-F^hi eosinophils did not express CD34, sharply increased in number after short ragweed (SRW) pollen challenge, and were in the mature (or activated) state. Moreover, chemical sympathectomy by 6-hydroxydopamine reduced the recruitment and activation of eosinophils, whereas the activation of the sympathetic nerve system (SNS) with restraint stress accelerated the recruitment and activation of eosinophils in SRW-induced conjunctivitis. It was also found that two eosinophil populations expressed alpha-1a-adrenergic receptors (α1a-ARs); in SRW-induced conjunctivitis, treatment with an α1a-AR antagonist decreased eosinophil responses, whereas treatment with an α1a-AR agonist aggravated eosinophil responses. Thus, eosinophil responses in conjunctivitis are regulated by the SNS via α1a-AR signaling. SNS inputs or α1a-AR function may be potential targets for the treatment of allergic conjunctivitis.