Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SUMMARY: In patients with pathologically altered erythrocytes, red blood cell exchange is a very efficient therapeutic measure without important side effects. With increasing migration more patients with e.g. severe malaria or sickle cell anemia have to be treated. In minor or bidirectional ABO-mismatched stem cell transplantations after reduced intensity conditioning, hemolysis can be prevented by prophylactic erythrocytapheresis. Other rare indications for red blood cell exchange are advanced erythropoietic protoporphyria and babesiosis. Sickle cell anemia can be treated with hydroxyurea. Transfusions are administered when necessary, but this results in iron overload in the long term. An expensive but safe and very efficient treatment alternative is red blood cell exchange. In cases with stroke, acute chest syndrome and other severe complications, erythrocytapheresis reproducibly breaks the vicious circle of sickling and increasing oxygen deficiency. At the same time one can aim at an exact end hematocrit. In severe malaria, erythrocytapheresis both reduces parasite load to the designated extent and reconstitutes reduced oxygen transport capacity without serious adverse effects. Here we describe our experience of erythrocytapheresis in long-term prophylaxis of complications in sickle cell anemia and sickle cell thalassemia patients. The documentation of improved iron balance was carried out by liver susceptometry.
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PMID:Erythrocytapheresis: Do Not Forget a Useful Therapy! 2154 7

Many red cell polymorphisms are a result of selective pressure by the malarial parasite. Here, we add another red cell disease to the panoply of erythrocytic changes that give rise to resistance to malaria. Erythrocytes from individuals with erythropoietic protoporphyria (EPP) have low levels of the final enzyme in the heme biosynthetic pathway, ferrochelatase. Cells from these patients are resistant to the growth of Plasmodium falciparum malarial parasites. This phenomenon is due to the absence of ferrochelatase and not an accumulation of substrate, as demonstrated by the normal growth of P falciparum parasites in the EPP phenocopy, X-linked dominant protoporphyria, which has elevated substrate, and normal ferrochelatase levels. This observation was replicated in a mouse strain with a hypomorphic mutation in the murine ferrochelatase gene. The parasite enzyme is not essential for parasite growth as Plasmodium berghei parasites carrying a complete deletion of the ferrochelatase gene grow normally in erythrocytes, which confirms previous studies. That ferrochelatase is essential to parasite growth was confirmed by showing that inhibition of ferrochelatase using the specific competitive inhibitor, N-methylprotoporphyrin, produced a potent growth inhibition effect against cultures of P falciparum. This raises the possibility of targeting human ferrochelatase in a host-directed antimalarial strategy.
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PMID:Red cells from ferrochelatase-deficient erythropoietic protoporphyria patients are resistant to growth of malarial parasites. 2541 39