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Impaired nitric oxide bioavailability and l-arginine–reversible endothelial dysfunction in adults with falciparum malaria

Overview of attention for article published in The Journal of Experimental Medicine, October 2007
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Title
Impaired nitric oxide bioavailability and l-arginine–reversible endothelial dysfunction in adults with falciparum malaria
Published in
The Journal of Experimental Medicine, October 2007
DOI 10.1084/jem.20070819
Pubmed ID
Authors

Tsin W. Yeo, Daniel A. Lampah, Retno Gitawati, Emiliana Tjitra, Enny Kenangalem, Yvette R. McNeil, Christabelle J. Darcy, Donald L. Granger, J. Brice Weinberg, Bert K. Lopansri, Ric N. Price, Stephen B. Duffull, David S. Celermajer, Nicholas M. Anstey

Abstract

Severe falciparum malaria (SM) is associated with tissue ischemia related to cytoadherence of parasitized erythrocytes to microvascular endothelium and reduced levels of NO and its precursor, l-arginine. Endothelial function has not been characterized in SM but can be improved by l-arginine in cardiovascular disease. In an observational study in Indonesia, we measured endothelial function using reactive hyperemia-peripheral arterial tonometry (RH-PAT) in 51 adults with SM, 48 patients with moderately severe falciparum malaria (MSM), and 48 controls. The mean RH-PAT index was lower in SM (1.41; 95% confidence interval [CI] = 1.33-1.47) than in MSM (1.82; 95% CI = 1.7-2.02) and controls (1.93; 95% CI = 1.8-2.06; P < 0.0001). Endothelial dysfunction was associated with elevated blood lactate and measures of hemolysis. Exhaled NO was also lower in SM relative to MSM and controls. In an ascending dose study of intravenous l-arginine in 30 more patients with MSM, l-arginine increased the RH-PAT index by 19% (95% CI = 6-34; P = 0.006) and exhaled NO by 55% (95% CI = 32-73; P < 0.0001) without important side effects. Hypoargininemia and hemolysis likely reduce NO bioavailability. Endothelial dysfunction in malaria is nearly universal in severe disease, is reversible with l-arginine, and likely contributes to its pathogenesis. Clinical trials in SM of adjunctive agents to improve endothelial NO bioavailability, including l-arginine, are warranted.

Mendeley readers

The data shown below were compiled from readership statistics for 121 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Colombia 1 <1%
Malaysia 1 <1%
Indonesia 1 <1%
Brazil 1 <1%
Canada 1 <1%
Belgium 1 <1%
Spain 1 <1%
Japan 1 <1%
Unknown 113 93%

Demographic breakdown

Readers by professional status Count As %
Researcher 24 20%
Student > Ph. D. Student 22 18%
Student > Master 19 16%
Student > Bachelor 15 12%
Student > Postgraduate 6 5%
Other 18 15%
Unknown 17 14%
Readers by discipline Count As %
Medicine and Dentistry 43 36%
Agricultural and Biological Sciences 21 17%
Biochemistry, Genetics and Molecular Biology 10 8%
Immunology and Microbiology 9 7%
Pharmacology, Toxicology and Pharmaceutical Science 4 3%
Other 14 12%
Unknown 20 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 December 2007.
All research outputs
#8,793,373
of 14,018,082 outputs
Outputs from The Journal of Experimental Medicine
#8,729
of 9,548 outputs
Outputs of similar age
#113,561
of 211,730 outputs
Outputs of similar age from The Journal of Experimental Medicine
#54
of 70 outputs
Altmetric has tracked 14,018,082 research outputs across all sources so far. This one is in the 24th percentile – i.e., 24% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,548 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.7. This one is in the 2nd percentile – i.e., 2% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 211,730 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 70 others from the same source and published within six weeks on either side of this one. This one is in the 10th percentile – i.e., 10% of its contemporaries scored the same or lower than it.