Orosomucoid polymorphisms influence plasma drug binding in humans; however, canine variants and their effect on drug plasma protein binding have not yet been reported. In this study, the orosomucoid gene (ORM1) was sequenced in 100 dogs to identify the most common variant and its allele frequency determined in 1,464 dogs (from 64 breeds and mixed-breed dogs). Plasma protein binding extent of amitriptyline, indinavir, verapamil, and lidocaine were evaluated by equilibrium dialysis using plasma from ORM1 genotyped dogs (n = 12). Free and total drug plasma concentrations were quantified by liquid chromatography-mass spectrometry. From the five polymorphisms identified in canine ORM1, two were nonsynonymous. The most common was c.70G>A (p.Ala24Thr) with an allele frequency of 11.2% (n = 1464). Variant allele frequencies varied by breed, reaching 74% in Shetland Sheepdogs (n = 21). Free drug fractions did not differ significantly (p > .05; Mann-Whitney U) between plasma collected from dogs with c.70AA (n = 4) and those with c.70GG (n = 8) genotypes. While c.70G>A did not affect the extent of plasma protein binding in our study, the potential biological and pharmacological implication of this newly discovered ORM1 variant in dogs should be further investigated.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819641 | PMC |
| http://dx.doi.org/10.1111/jvp.12899 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dichotomitin promotes osteoblast differentiation and improves osteoporosis by inhibiting oxidative stress.
J Orthop Surg Res
January 2025
Research Institute of Orthopedics, The Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Objective: Osteoporosis is a systemic disease with high morbidity and significant adverse effects. Increasing evidence supports the close relationship between oxidative stress and osteoporosis, suggesting that treatment with antioxidants may be a viable approach. This study evaluated the antioxidant properties of dichotomitin (DH) and its potential protective effects against osteoporosis.
View Article and Find Full Text PDFCord blood platelet-rich plasma: proteomics analysis for ophthalmic applications.
Clin Proteomics
January 2025
Ophthalmology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli, 1, 00168, Rome, Italy.
Our objective is to determine the protein and complements constituents of Cord blood Platelet-rich plasma (CB-PRP), based on the hypothesis that it contains beneficial components capable of arresting or potentially decelerating the advancement of atrophic age-related macular degeneration (dry-AMD), with the support of radiomics. Two distinct pools of CB-PRP were assessed, each pool obtained from a total of 15 umbilical cord-blood donors. One aliquot of each pool respectively was subjected to proteomic analysis in order to enhance the significance of our findings, by identifying proteins that are shared between the two sample pools and gaining insights into the pathways they are associated with.
View Article and Find Full Text PDFSustained virologic suppression of multidrug-resistant HIV in an individual treated with anti-CD4 domain 1 antibody and lenacapavir.
Nat Med
January 2025
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
The clinical management of people with multidrug-resistant (MDR) human immunodeficiency virus (HIV) remains challenging despite continued development of antiretroviral agents. A 58-year-old male individual with MDR HIV and Kaposi sarcoma (KS) was treated with a new antiretroviral regimen consisting of anti-CD4 domain 1 antibody UB-421 and capsid inhibitor lenacapavir. The individual experienced delayed but sustained suppression of plasma viremia and a substantial increase in the CD4 T cell count.
View Article and Find Full Text PDFCommon biomarkers of idiopathic pulmonary fibrosis and systemic sclerosis based on WGCNA and machine learning.
Sci Rep
January 2025
Harbin Medical University, Harbin, Heilongjiang Province, China.
Interstitial lung disease (ILD) is known to be a major complication of systemic sclerosis (SSc) and a leading cause of death in SSc patients. As the most common type of ILD, the pathogenesis of idiopathic pulmonary fibrosis (IPF) has not been fully elucidated. In this study, weighted correlation network analysis (WGCNA), protein‒protein interaction, Kaplan-Meier curve, univariate Cox analysis and machine learning methods were used on datasets from the Gene Expression Omnibus database.
View Article and Find Full Text PDFPlasma proteomic signatures of social isolation and loneliness associated with morbidity and mortality.
Nat Hum Behav
January 2025
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
The biology underlying the connection between social relationships and health is largely unknown. Here, leveraging data from 42,062 participants across 2,920 plasma proteins in the UK Biobank, we characterized the proteomic signatures of social isolation and loneliness through proteome-wide association study and protein co-expression network analysis. Proteins linked to these constructs were implicated in inflammation, antiviral responses and complement systems.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!