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Design, Synthesis, and Pharmacological Evaluation of Nonsteroidal Tricyclic Ligands as Modulators of GABA Receptors.
J Med Chem
January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen DK-2100, Denmark.
GABA receptors (GABARs) are the major elements of inhibitory neurotransmission in the central nervous system (CNS). They are established targets for regulation by endogenous brain neuroactive steroids (NASs) such as pregnanolone. However, the complexity of de novo synthesis of NAS derivatives has hindered attempts to circumvent the principal limitations of using endogenous NASs, including selectivity and limited oral bioavailability.
View Article and Find Full Text PDFEpidemiological trends and healthcare disparities in onychomycosis: An analysis of the All of Us research program.
PLoS One
January 2025
Division of Dermatology, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Onychomycosis is a common, difficult to treat nail disorder. Our objective was to explore disparities in current clinical management practices for onychomycosis in patients from underrepresented groups and with specific comorbidities. We conducted a cross-sectional study using the All of Us (AoU) research program.
View Article and Find Full Text PDFSafety of hyperbaric oxygen therapy in non-emergent patients with a history of seizures: A retrospective cohort study.
PLoS One
January 2025
Hyperbaric Medicine Unit, Toronto General Hospital, Toronto, Ontario, Canada.
Background: Hyperbaric oxygen therapy (HBOT) is well established as a treatment for various medical conditions. However, it poses a risk of oxygen toxicity, which can cause seizures particularly in individuals with pre-existing seizure disorders. Consequently, seizure disorders are considered a relative contraindication to HBOT.
View Article and Find Full Text PDFTRAIL agonists rescue mice from radiation-induced lung, skin or esophageal injury.
J Clin Invest
January 2025
Laboratory of Translational Oncology and Translational Cancer Therapeutics, Warren Alpert Medical School of Brown University, Providence, United States of America.
Radiotherapy can be limited by pneumonitis which is impacted by innate immunity, including pathways regulated by TRAIL death receptor DR5. We investigated whether DR5 agonists could rescue mice from toxic effects of radiation and found two different agonists, parenteral PEGylated trimeric-TRAIL (TLY012) and oral TRAIL-Inducing Compound (TIC10/ONC201) could reduce pneumonitis, alveolar-wall thickness, and oxygen desaturation. Lung protection extended to late effects of radiation including less fibrosis at 22-weeks in TLY012-rescued survivors versus un-rescued surviving irradiated-mice.
View Article and Find Full Text PDFSelective progesterone receptor modulators for the treatment of dysmenorrhea: an update.
Expert Opin Pharmacother
January 2025
Department of Obstetrics and Gynecology, University of Florence, Careggi University Hospital, Florence, Italy.
Introduction: Dysmenorrhea is a painful symptom associated with uterine contractions and menstrual bleeding and is treated by administering analgesic drugs. Since progesterone receptors (PRs) have a major role in regulating uterine tissues (myometrium and endometrium) oral contraceptives are used off-label for treating primary or secondary dysmenorrhea. The development of selective progesterone receptor modulators (SPRMs) a class of synthetic steroids with agonistic, antagonistic, or mixed effects in targeting PRs in different tissues stimulated their possible clinical use for treating secondary dysmenorrhea related to uterine diseases (endometriosis, adenomyosis, uterine fibroids).
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