However, when plasma blood volume is low and ADH is released the aquaporins that are opened are also permeable to urea. This allows urea to leave the collecting duct into the medulla, creating a hyperosmotic solution that "attracts" water. Urea can then re-enter the nephron and be excreted or recycled again depending on whether ADH is still present or not. The single effect describes the fact that the ascending thick limb of the loop of Henle is not permeable to water but is permeable to sodium chloride. This allows for a countercurrent exchange system whereby the medulla becomes increasingly concentrated, but at the same time setting up an osmotic gradient for water to follow should the aquaporins of the collecting duct be opened by ADH. Blood pressure
Although the kidney cannot directly sense blood, long-term regulation of blood pressure predominantly depends upon the kidney. This primarily occurs through maintenance of the extracellular fluid compartment, the size of which depends on the plasma sodium concentration. Renin is the first in a series of important chemical messengers that make up the renin–angiotensin system. Changes in renin ultimately alter the output of this system, principally the hormones angiotensin II and aldosterone. Each hormone acts via multiple mechanisms, but both increase the kidneys absorption of sodium chloride, thereby expanding the extracellular fluid compartment and raising blood pressure. When renin levels are elevated, the concentrations of angiotensin II and aldosterone increase, leading to increased sodium chloride reabsorption, expansion of the extracellular fluid compartment, and an increase in blood pressure.
In 2016, Impact Biomedicines acquired the rights to fedratinib from Sanofi and continued its development for the treatment of myelofibrosis and polycythemia vera. In January 2018, the drugs rights were transferred to Celgene with their purchase of Impact Biomedicines.Fedratinib was approved for medical use in the United States in August 2019.The U.S. Food and Drug Administration (FDA) granted the application for fedratinib priority review and orphan drug designations. The FDA granted the approval of Inrebic to Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation. References
External links
"Fedratinib". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT01437787 for "Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis (JAKARTA)" at ClinicalTrials.gov