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Dimethylarginines: Endogenous Inhibitors of Nitric Oxide Synthesis in Children with Falciparum Malaria

Weinberg, Joe Brice, Yeo, Tsin W., Mukemba, Jackson P., Florence, Salvatore M., Volkheimer, Alicia D., Wang, Hao, Chen, Youwei, Rubach, Matthew, Granger, Donald L., Mwaikambo, Esther D. and Anstey, Nicholas M. (2014). Dimethylarginines: Endogenous Inhibitors of Nitric Oxide Synthesis in Children with Falciparum Malaria. Journal of Infectious Diseases,210(6):913-922.

Document type: Journal Article
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IRMA ID cmartelxPUB184
Title Dimethylarginines: Endogenous Inhibitors of Nitric Oxide Synthesis in Children with Falciparum Malaria
Author Weinberg, Joe Brice
Yeo, Tsin W.
Mukemba, Jackson P.
Florence, Salvatore M.
Volkheimer, Alicia D.
Wang, Hao
Chen, Youwei
Rubach, Matthew
Granger, Donald L.
Mwaikambo, Esther D.
Anstey, Nicholas M.
Journal Name Journal of Infectious Diseases
Publication Date 2014
Volume Number 210
Issue Number 6
ISSN 0022-1899   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-84906754006
Start Page 913
End Page 922
Total Pages 10
Place of Publication United States of America
Publisher Oxford University Press
HERDC Category C1 - Journal Article (DIISR)
Abstract Background.
Nitric oxide (NO) bioavailability is impaired in children and adults with severe falciparum malaria (SM). Asymmetric-dimethylarginine (ADMA) limits NO production by inhibiting NO synthase and is increased in adult SM. The role of ADMA in the pathogenesis of childhood SM is unknown.

We studied Tanzanian children ages 4–8 years with malaria. Plasma levels of arginine, arginase, cell-free hemoglobin, ADMA, symmetric-dimethylarginine (SDMA), histidine-rich protein-2, and angiopoietin-2 were measured.


ADMA was low in children with SM relative to controls. Nevertheless, arginine and arginine:ADMA ratios were very low in SM. SDMA was high in children with SM. With treatment, arginine and the arginine:ADMA ratio normalized, but SDMA did not. Arginine:ADMA ratios, but not arginine, were significantly and inde­pendent­ly inversely associated with lactate and angiopoietin-2. Plasma arginase was not elevated in those with malaria, and plasma free hemoglobin was elevated only in patients with cerebral malaria.


In contrast to adults, plasma ADMA is reduced in SM in children, but hypoargininemia is more severe. Arginine bioavailability (reflected by low arginine:ADMA ratios) is therefore comparably low in SM in children as in adults. Therapies to increase NO bioavailability in malaria may be useful as adjunctive treatment of severe malaria in children.
Keywords Falciparum malaria
Nitric oxide
Asymmetric dimethylarginine
Symmetric dimethylarginine
Angiopoeitin 2
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Created: Wed, 19 Aug 2015, 12:35:37 CST