Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production

Bert K. Lopansri; Nicholas M. Anstey; J. Brice Weinberg; Gregory J. Stoddard; Maurine R. Hobbs; Marc C. Levesque; Esther D. Mwaikambo; Donald L. Granger

doi:10.1016/S0140-6736(03)12564-0

Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production

Bert K. Lopansri, Nicholas M. Anstey, J. Brice Weinberg, Gregory J. Stoddard, Maurine R. Hobbs, Marc C. Levesque, Esther D. Mwaikambo, Donald L. Granger

Global and Tropical Health

Research output: Contribution to journal › Article › peer-review

154 Citations (Scopus)

Abstract

Nitric oxide (NO) production and mononuclear cell NO synthase 2 (NOS2) expression are high in healthy Tanzanian children but low in those with cerebral malaria. Factors that downregulate NOS2 also diminish factors involved in cellular uptake and biosynthesis of L-arginine, the substrate for NO synthesis. We therefore postulated that L-arginine concentrations would be low in individuals with cerebral malaria. We measured concentrations of L-arginine in cryopreserved plasma samples from Tanzanian children with and without malaria. L-arginine concentrations were low in individuals with cerebral malaria (mean 46 μmol/L, SD 14), intermediate in those with uncomplicated malaria (70 μmol/L, 20), and within the normal range in healthy controls (122 μmol/L, 22; p<0·0001). Analysis by logistic regression showed that hypoargininaemia was significantly associated with cerebral malaria case-fatality. Hypoargininaemia may contribute to limited NO production in children with cerebral malaria and to severe disease.

Original language	English
Pages (from-to)	676-678
Number of pages	3
Journal	Lancet
Volume	361
Issue number	9358
DOIs	https://doi.org/10.1016/S0140-6736(03)12564-0
Publication status	Published - 22 Feb 2003

Bibliographical note

Funding Information:
The main support for this project was provided by a grant from The Thrasher Research Fund (Award number 02815-4), Salt Lake City, UT, USA. Other support was from the ASTMH, the VA Research Service, and the NIH/NIAID. The funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

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SDG 3 Good Health and Well-being

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title = "Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production",

abstract = "Nitric oxide (NO) production and mononuclear cell NO synthase 2 (NOS2) expression are high in healthy Tanzanian children but low in those with cerebral malaria. Factors that downregulate NOS2 also diminish factors involved in cellular uptake and biosynthesis of L-arginine, the substrate for NO synthesis. We therefore postulated that L-arginine concentrations would be low in individuals with cerebral malaria. We measured concentrations of L-arginine in cryopreserved plasma samples from Tanzanian children with and without malaria. L-arginine concentrations were low in individuals with cerebral malaria (mean 46 μmol/L, SD 14), intermediate in those with uncomplicated malaria (70 μmol/L, 20), and within the normal range in healthy controls (122 μmol/L, 22; p<0·0001). Analysis by logistic regression showed that hypoargininaemia was significantly associated with cerebral malaria case-fatality. Hypoargininaemia may contribute to limited NO production in children with cerebral malaria and to severe disease.",

author = "Lopansri, \{Bert K.\} and Anstey, \{Nicholas M.\} and Weinberg, \{J. Brice\} and Stoddard, \{Gregory J.\} and Hobbs, \{Maurine R.\} and Levesque, \{Marc C.\} and Mwaikambo, \{Esther D.\} and Granger, \{Donald L.\}",

note = "Funding Information: The main support for this project was provided by a grant from The Thrasher Research Fund (Award number 02815-4), Salt Lake City, UT, USA. Other support was from the ASTMH, the VA Research Service, and the NIH/NIAID. The funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report.",

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doi = "10.1016/S0140-6736(03)12564-0",

language = "English",

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AU - Lopansri, Bert K.

AU - Anstey, Nicholas M.

AU - Weinberg, J. Brice

AU - Stoddard, Gregory J.

AU - Hobbs, Maurine R.

AU - Levesque, Marc C.

AU - Mwaikambo, Esther D.

AU - Granger, Donald L.

N1 - Funding Information: The main support for this project was provided by a grant from The Thrasher Research Fund (Award number 02815-4), Salt Lake City, UT, USA. Other support was from the ASTMH, the VA Research Service, and the NIH/NIAID. The funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

PY - 2003/2/22

Y1 - 2003/2/22

N2 - Nitric oxide (NO) production and mononuclear cell NO synthase 2 (NOS2) expression are high in healthy Tanzanian children but low in those with cerebral malaria. Factors that downregulate NOS2 also diminish factors involved in cellular uptake and biosynthesis of L-arginine, the substrate for NO synthesis. We therefore postulated that L-arginine concentrations would be low in individuals with cerebral malaria. We measured concentrations of L-arginine in cryopreserved plasma samples from Tanzanian children with and without malaria. L-arginine concentrations were low in individuals with cerebral malaria (mean 46 μmol/L, SD 14), intermediate in those with uncomplicated malaria (70 μmol/L, 20), and within the normal range in healthy controls (122 μmol/L, 22; p<0·0001). Analysis by logistic regression showed that hypoargininaemia was significantly associated with cerebral malaria case-fatality. Hypoargininaemia may contribute to limited NO production in children with cerebral malaria and to severe disease.

AB - Nitric oxide (NO) production and mononuclear cell NO synthase 2 (NOS2) expression are high in healthy Tanzanian children but low in those with cerebral malaria. Factors that downregulate NOS2 also diminish factors involved in cellular uptake and biosynthesis of L-arginine, the substrate for NO synthesis. We therefore postulated that L-arginine concentrations would be low in individuals with cerebral malaria. We measured concentrations of L-arginine in cryopreserved plasma samples from Tanzanian children with and without malaria. L-arginine concentrations were low in individuals with cerebral malaria (mean 46 μmol/L, SD 14), intermediate in those with uncomplicated malaria (70 μmol/L, 20), and within the normal range in healthy controls (122 μmol/L, 22; p<0·0001). Analysis by logistic regression showed that hypoargininaemia was significantly associated with cerebral malaria case-fatality. Hypoargininaemia may contribute to limited NO production in children with cerebral malaria and to severe disease.

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DO - 10.1016/S0140-6736(03)12564-0

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SN - 0140-6736

VL - 361

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JO - Lancet

JF - Lancet

IS - 9358

ER -

Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production

Abstract

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