does glutathione kill cancer cells and Thioredoxin Antioxidant Pathways Synergize to Drive Initiation and Progression EMT

Dihexa (also known as PNB-0408) is an experimental small molecule derived from angiotensin IV. It was engineered to cross the blood–brain barrier and has shown synaptogenic effects in preclinical models. The often-quoted

Frequent heart rate monitoring is required to identify tachycardia which may indicate a further drop in Hb Repeat FBC within 6-12 hours to detect ongoing haemolysis Monitor reticulocyte count and bilirubin Additional investigations will be guided by blood film findings eg Coombs test (direct antiglobulin test), blood group and antibody screening (BGAB), G6PD assay and Eosin-5 maleimide red cell staining (diagnosis of hereditary spherocytosis) Sickle cell anaemia See Sickle cell disease Hypoplastic/aplastic anaemia Causes Acute leukaemia, aplastic anaemia, infiltrative disorders Drugs (eg cytotoxics, chloramphenicol, sulfonamides) Viral infection Severe nutritional deficiencies (vitamin B12 or folate deficiency), however usually children present with macrocytic red cells Reticulocyte count is usually low Differential diagnosis based on FBC results Consider bone marrow infiltration if neutrophils and/or platelets also decreased If isolated anaemia with low reticulocyte count with normal platelet and neutrophil counts, consider transient erythroblastopenia of childhood (TEC) or congenital forms (eg Diamond-Blackfan anaemia) Bone marrow aspirate is usually required for diagnosis Chronic disease Normochromic normocytic anaemia can be seen with chronic inflammation and chronic disease such as renal disease Reticulocyte count may be low Platelet count may be elevated Further investigation (eg UEC, LFT and ESR) may be indicated depending on clinical features Blood loss Normochromic normocytic anaemia can be seen with acute blood loss Reticulocyte count may be normal or elevated Correlate with any bleeding symptoms Macrocytic anaemia Vitamin B12 and folate deficiency Can be associated with failure to thrive or neurodevelopmental problems (regression, seizures, irritability, poor feeding) Vitamin B12 deficiency may be seen in exclusively breast-fed infants of mothers with vitamin B12 deficiency, children with a vegan or vegetarian diet, pernicious anaemia and metabolic disorders Characteristic blood film findings include teardrop red cells and hypersegmented neutrophils and often neutropenia or thrombocytopenia Requires urgent investigation with red cell folate and active vitamin B12 If low active vitamin B12 suggest serum homocysteine and urine methylmalonic acid Treatment must be commenced urgently, particularly if neurological symptoms or regression Other causes of red cell macrocytosis with or without anaemia Myelodysplasia Medications eg anticonvulsants, immunosuppressants and zidovudine Liver disease Hypothyroidism Consider consultation with local paediatric team when Children have red flag features Consider transfer when Children require care beyond the level of comfort of the local hospital For emergency advice and paediatric or neonatal ICU transfers, see Retrieval Services Consider discharge when Cause for anaemia is identified and follow up is arranged Parent information Iron intake (Royal Children’s Hospital Melbourne) Iron for children (Queensland Health) Additional notes Other features on the blood film appearance that prompt further investigation

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Combination regimens that sensitize lesions—by increasing iron availability within lesions or dampening compensatory antioxidant pathways—may allow meaningful dose reductions of Erastin-class agents