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Chronotropic effects of milrinone in a guinea pig ex vivo model: a pilot study to screen for new mechanisms of action.

J Cardiovasc Pharmacol

January 2025

Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Positive inotropic responses upon administration of milrinone, an inhibitor of the phosphodiesterase enzyme (PDE), involve a well-pronounced positive chronotropic effect. Here we tested whether milrinone evokes this chronotropic response solely by PDE inhibition or by a concerted action that involve additional pharmacological targets. Milrinone stimulated increases in heart rate were studied in right atrial preparations of guinea pig in the presence or absence of inhibitors of putative ancillary molecular pathways or ion channels: i.

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Lower body negative pressure (LBNP) has been used for decades in humans to model arterial baroreceptor unloading and represents a powerful tool for evaluating cardiovascular responses to orthostatic challenges. However, LBNP studies in animals have been limited to conditions of anesthesia or sedation, where cardiovascular reflexes are altered. Given the consequent uncertainties, the usefulness of LBNP studies in these preclinical models has been severely hampered.

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Background/aim: Glioblastoma multiforme (GBM) is the most common and aggressive form of primary malignant tumors in the central nervous system of adults. In practice, all patients with GBM experience relapse, and treatment options become limited following first-line therapy. We previously reported a new, successful treatment approach for a GBM patient, implemented in direct conjunction with surgical intervention.

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Wnt signaling is a critical pathway implicated in cancer development, with Frizzled proteins, particularly FZD10, playing key roles in tumorigenesis and recurrence. This study focuses on the potential of repurposed FDA-approved drugs targeting FZD10 as a therapeutic strategy for nasopharyngeal carcinoma (NPC). The tertiary structure of human FZD10 was constructed using homology modeling, validated by Ramachandran plot and ProQ analysis.

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