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Visualizing the DNA Damage Response in Purkinje Cells Using Cerebellar Organotypic Cultures.

J Vis Exp

December 2024

The David and Inez Myers Laboratory for Cancer Genetics, Department of Human Molecular Genetics and Biochemistry, Faculty of Health and Medical Sciences, School of Medicine, Tel Aviv University;

Cerebellar Purkinje cells (PCs) exhibit a unique interplay of high metabolic rates, specific chromatin architecture, and extensive transcriptional activity, making them particularly vulnerable to DNA damage. This necessitates an efficient DNA damage response (DDR) to prevent cerebellar degeneration, often initiated by PC dysfunction or loss. A notable example is the genome instability syndrome, ataxia-telangiectasia (A-T), marked by progressive PC depletion and cerebellar deterioration.

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Background: The impact of protein-bound uremic toxins, specifically indoxyl sulfate (IS) on peritoneal dialysis (PD) complications remains controversial. This study aimed to explore the link between serum total IS (tIS) levels, proinflammatory cytokines in serum and peritoneal dialysis effluent (PDE), and PD technique survival.

Methods: In this prospective cohort study, 84 patients were followed up for three years and analyzed.

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Prednisolone pharmacokinetics in dogs with protein-losing enteropathy.

J Vet Intern Med

December 2024

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.

Background: It is unknown if glucocorticoid malabsorption contributes to the approximate 50% treatment failure rate in dogs with protein-losing enteropathy (PLE).

Objective: To compare pharmacokinetics (PK) of orally administered prednisolone in dogs with PLE vs healthy controls.

Animals: Fourteen dogs with well-characterized PLE and 7 control dogs.

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The analysis of protein-bound glycans has gained significant attention due to their pivotal roles in physiological and pathological processes like cell-cell recognition, immune response, and disease progression. Routine methods for glycan analysis are challenged by the very similar physicochemical properties of their carbohydrate components. As an alternative, lectins, which are proteins that specifically bind to glycans, have been integrated into biosensors for glycan detection.

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Alternate Sampling Matrices for Therapeutic Drug Monitoring of Immunosuppressants.

Ther Drug Monit

February 2025

Department of Clinical Pharmacology, The Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Woodville South, SA, Australia ; and.

Background: Immunosuppressant (IS) therapeutic drug monitoring (TDM) relies on measuring mostly pharmacologically inactive erythrocyte-bound and/or plasma protein-bound drug levels. Variations in hematocrit and plasma protein levels complicate interpretation of blood calcineurin inhibitor (CNI) and inhibitors of the molecular target of rapamycin (mTORi) concentrations. Variable binding of mycophenolic acid (MPA) to albumin similarly complicates its TDM in plasma.

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