The parvocellular neurosecretory neurons of the hypothalamus release corticotropin-releasing hormone (CRH), which is sent to the anterior pituitary. Here the pituitary releases adrenocorticotropic hormone (ACTH), which ultimately stimulates the release of cortisol. In relation to anxiety, the amygdala activates this circuit, while the hippocampus is responsible for suppressing it. Glucocorticoid receptors in the hippocampus monitor the amount of cortisol in the system and through negative feedback can tell the hypothalamus to stop releasing CRH.Studies on mice engineered to have high concentrations of CRH showed higher levels of anxiety, while those engineered to have no or low amounts of CRH receptors were less anxious. In people with phobias, therefore, high amounts of cortisol may be present, or there may be low levels of glucocorticoid receptors or even serotonin (5-HT). Disruption by damage
For the areas in the brain involved in emotion—most specifically fear— the processing and response to emotional stimuli can be altered when one of these regions is damaged. Damage to the cortical areas involved in the limbic system, such as the cingulate cortex or frontal lobes, has resulted in extreme emotion changes. Other types of damage include Klüver–Bucy syndrome and Urbach–Wiethe disease. In Klüver–Bucy syndrome, a temporal lobectomy, or removal of the temporal lobes, results in changes involving fear and aggression. Specifically, the removal of these lobes results in decreased fear, confirming its role in fear recognition and response. Damage to both side (Bilateral damage) of the medial temporal lobes is known as Urbach–Wiethe disease.
Luspatercept, sold under the brand name Reblozyl, is a medication used for the treatment of anemia in beta thalassemia and myelodysplastic syndromes.The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses
Luspatercept is indicated for the treatment of adults with transfusion-dependent anemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts, who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy.Luspatercept is indicated for the treatment of adults with transfusion-dependent anaemia associated with beta thalassaemia. Side effects
Possible adverse effects include temporary bone pain, joint pains (arthralgias), dizziness, elevated blood pressure (hypertension) and elevated uric acid levels (hyperuricemia). There was also an increased risk of thrombosis (blood clots) in patients who have risk factors for thrombosis who are taking luspatercept. Structure and mechanism
Luspatercept is a recombinant fusion protein derived from human activin receptor type IIb (ActRIIb) linked to a protein derived from immunoglobulin G. It binds TGF (transforming growth factor beta) superfamily ligands to reduce SMAD signaling. The reduction in SMAD signaling leads to enhanced erythroid maturation. History
Phase III trials evaluated the efficacy of luspatercept for the treatment of anemia in the hematological disorders beta thalassemia and myelodysplastic syndromes.It was developed by Acceleron Pharma in collaboration with Celgene.The U.S. Food and Drug Administration (FDA) granted approval for luspatercept–aamt in November 2019, for the treatment of anemia (lack of red blood cells) in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.