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https://www.selleckchem.com/products/dorsomorphin-2hcl.html Aberrant expression ratio of Cl- transporters, NKCC1 and KCC2, is implicated in several brain conditions. NKCC1 inhibition by the FDA-approved diuretic drug, bumetanide, rescues core symptoms in rodent models and/or clinical trials with patients. However, bumetanide has a strong diuretic effect due to inhibition of the kidney Cl- transporter NKCC2, creating critical drug compliance issues and health concerns. Here, we report the discovery of a new chemical class of selective NKCC1 inhibitors and the lead drug candidate ARN23746. ARN23746 restores the physiological intracellular Cl- in murine Down syndrome neuronal cultures, has excellent solubility and metabolic stability, and displays no issues with off-target activity in vitro. ARN23746 recovers core symptoms in mouse models of Down syndrome and autism, with no diuretic effect, nor overt toxicity upon chronic treatment in adulthood. ARN23746 is ready for advanced preclinical/manufacturing studies toward the first sustainable therapeutics for the neurological conditions characterized by impaired Cl- homeostasis. To examine if a 5-day challenge with penicillin improves the diagnostic sensitivity compared with a single full dose in children with mild skin reactions. Subjects referred with suspected allergy to penicillin were consecutively included. Irrespectively of the morphology of the index reaction and the result of specific IgE, all subjects underwent a two-step titrated drug provocation test (DPT) with the culprit drug followed by a 5-day challenge at home. Children and adolescents aged 0-18 years referred to allergic workup for penicillin hypersensitivity at two paediatric Danish centres. Only subjects with non-severe skin reactions were included. A total of 305 subjects were included and 22 (7%) of the DPTs were positive. Three subjects reacted within 1 hour of the first full dose and nine reacted 1-8 hours after the first full dose. Additional 10 po

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