A new radioligand-binding assay (RBA) is described for the detection of insulin/proinsulin-specific antibodies using 35S-labeled proinsulin produced by a cell-free reticulocyte extract. Direct use of the crude expression product in the RBA was not feasible because the protein failed to fold properly (or had incorrectly paired disulphide bridges) and purification was hindered by interfering by-products. A refolding protocol and a chromatographic procedure were devised that readily allowed production of purified and immunochemically competent 35S-labeled proinsulin. The new RBA was compared with the reference test, in which the tracer was standard 125I-insulin. The analysis included sera from 41 diabetic patients and 25 healthy controls. Twenty-six (63.4%) and 29 (70.7%) patients scored positive by RBA using 35S-PI and 125I-insulin, respectively. The methods showed a satisfactory correlation with r(2)=0.77 and a slope not significantly different from unity (m=1.16+/-0.10; 95% confidence interval). Since the nuclide used in the assay is 35S, the procedure is compatible with standard assays for GADA and IA-2A, and thus may permit combined assays for the major early markers of autoimmune diabetes.
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http://dx.doi.org/10.1016/s0022-1759(03)00197-2 | DOI Listing |
Obesity is a global health crisis, with its prevalence particularly severe in the United States, where over 42% of adults are classified as obese. Obesity is driven by complex molecular and tissue-level mechanisms that remain poorly understood. Among these, angiogenesis-primarily mediated by vascular endothelial growth factor (VEGF-A)-is critical for adipose tissue expansion but presents unique challenges for therapeutic targeting due to its intricate regulation.
View Article and Find Full Text PDFJ Neurochem
January 2025
College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea.
The α4β2 nicotinic acetylcholine receptor (nAChR), an ionophore, has been suggested to signal through metabotropic pathways and interact with other receptor families, such as dopamine receptors. In this study, the interaction between α4β2 nAChR and dopamine receptors was investigated through in vivo and in vitro studies. Nicotine exposure in adolescent rats is known to induce a sustained increase in nicotine's rewarding effects which was assessed by conditioned place preference (CPP) assay.
View Article and Find Full Text PDFBehav Brain Res
February 2025
Laboratory of Neuropharmacology, Department of Physiological Sciences. Institute of Biological Sciences. University of Brasilia, ZIP 70910-900, Brasilia-DF, Brazil.
Pathological anxiety is among the most common psychiatric disorders. Despite advancements, predominant pharmacological treatments can lead to physical, chemical, and psychological dependence. Venoms of arthropods are important sources of neuroactive peptides with potential therapeutic applications for the treatment of neurological disorders.
View Article and Find Full Text PDFMolecules
November 2024
Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, 30-688 Kraków, Poland.
Autism spectrum disorder is a complex neurodevelopmental disorder. The available medical treatment options for autism spectrum disorder are very limited. While the etiology and pathophysiology of autism spectrum disorder are still not fully understood, recent studies have suggested that wide alterations in the GABAergic, glutamatergic, cholinergic, and serotonergic systems play a key role in its development and progression.
View Article and Find Full Text PDFChemMedChem
November 2024
Novartis Biomedical Research, Global Discovery Chemistry, Novartis Campus, WSJ-88.10.110, 4056, Basel, Switzerland.
We describe the identification of a candidate positron emission tomography (PET) imaging agent for the NLRP3 protein. NLRP3 plays a critical role in the immune system and has proven a difficult target for the development of imaging agents due to its low and cell-specific expression profile. A recently described series of pyridazine-based inhibitors, with improved permeability and brain-penetration properties, was used as a starting point for the development of a suitable PET imaging agent.
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