Tularemia is a zoonotic disease caused by Francisella tularensis. We aimed to explicate the clinical and laboratory findings of 27 consecutive tularemia patients who were included into the study. The average duration between onset of symptoms and diagnosis was 19.1 +/- 7.3 days. Sore throat (100%), fever (93%) and myalgia (100%) were the most frequently observed symptoms, while lymphadenopathy (100%), pharyngeal hyperemia (85%), tonsillitis (74%), and rash (7%) were the most frequently observed physical findings. Treatment failed in 6 patients: 1/13 streptomycin- (changed to doxycycline + streptomycin), 1/7 ciprofloxacin- (changed to streptomycin), and 4/7 gentamicin- (changed to streptomycin) receiving patients who had longer duration to treatment (26.5 +/- 2.9 days) than the 21 successfully treated cases (17.0 +/- 6.8 days). Tularemia should to be taken into account in the differential diagnosis in cases having tonsillopharyngitis and cervical lymphadenopathy without response to beta lactam/macrolide-group antibiotics in rural areas. We believe that streptomycin should be the first-line antibiotic in the treatment of pediatric tularemia cases, but it should be supported by comprehensive studies with larger patient series.
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Cancers (Basel)
December 2024
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Triple-negative breast cancers (TNBCs) typically have a greater immune cell infiltrate and are more likely to respond to immune checkpoint inhibition (ICI) than ER+ or HER2+ breast cancers. However, there is a crucial need to optimize combining chemotherapy strategies with ICI to enhance overall survival in TNBC. Therefore, we developed a high-throughput co-culture screening assay to identify compounds that enhance CD8+ T-cell-mediated tumor cell cytotoxicity.
View Article and Find Full Text PDFMol Pharmacol
February 2024
Departments of Anesthesiology (K.L., S.J.M., J.S.D.), Pharmacology (K.L., C.H., J.D.B., U.R., O.B., C.W.L., J.S.D.), Pediatrics (E.L.S.), and Biochemistry (J.A.B.), Vanderbilt University Medical Center, Nashville, Tennessee and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee (J.A.B., E.L.D., J.S.D.)
Vascular smooth muscle K channels critically regulate blood flow and blood pressure by modulating vascular tone and therefore represent attractive drug targets for treating several cardiovascular disorders. However, the lack of potent inhibitors that can selectively inhibit Kir6.1/SUR2B (vascular K) over Kir6.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
July 2023
Department of Chemistry, University of Manchester, Manchester, M13 9PL, UK.
We report the modulation of reactivity of nitrogen dioxide (NO ) in a charged metal-organic framework (MOF) material, MFM-305-CH in which unbound N-centres are methylated and the cationic charge counter-balanced by Cl ions in the pores. Uptake of NO into MFM-305-CH leads to reaction between NO and Cl to give nitrosyl chloride (NOCl) and NO anions. A high dynamic uptake of 6.
View Article and Find Full Text PDFBioorg Med Chem Lett
May 2023
Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address:
Kir6.2/SUR1 is an ATP-regulated potassium channel that acts as an intracellular metabolic sensor, controlling insulin and appetite-stimulatory neuropeptides secretion. In this Letter, we present the SAR around a novel Kir6.
View Article and Find Full Text PDFAssay Drug Dev Technol
April 2023
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Antagonists of the serotonin receptor 2B (5-HT) have shown great promise as therapeutics for the treatment of pulmonary arterial hypertension, valvular heart disease, and related cardiopathies. Herein, we describe a high-throughput screen campaign that led to the identification of highly potent and selective 5-HT antagonists. Furthermore, selected compounds were profiled for their predicted ability to cross the blood-brain barrier.
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