Nitric oxides in plasma, urine, and cerebrospinal fluid in patients with severe falciparum malaria.

It has been suggested that nitric oxide (NO) plays an important role in the pathogenesis of severe falciparum malaria. Since NO has a very short half-life, nitrate and nitrite (NOx) levels, stable metabolites of NO, are used as measures of NO production. We measured plasma NOx levels in 24 adults with severe falciparum malaria on the Thai-Burmese border. After correction for renal function, there was no correlation between plasma NOx levels, or the total amount of NOx excreted in the urine, and disease severity. Plasma NOx levels decreased after the first 48 hr in all patients (P = 0.007), suggesting decreased NO production. The NOx levels in cerebrospinal fluid (CSF) correlated well with plasma NOx levels, but these did not show a correlation with coma depth, and were not significantly different from those in a healthy control group. These findings do not support the hypothesis that excessive NO production contributes to the pathogenesis of severe falciparum malaria. However, local changes in NO production, e.g., in the central nervous system, might not be reflected in the total NOx production or NOx levels in the CSF.

[1]  T. Agbenyega,et al.  Plasma nitrogen oxides and blood lactate concentrations in Ghanaian children with malaria. , 1997, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[2]  I. Clark,et al.  Serum creatinine levels and reactive nitrogen intermediates in children with cerebral malaria in Papua New Guinea. , 1997, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[3]  S. Moncada The biology of nitric oxide , 1997 .

[4]  K. Rockett,et al.  Does malarial tolerance, through nitric oxide, explain the low incidence of autoimmune disease in tropical Africa? , 1996, The Lancet.

[5]  N. Anstey,et al.  Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression , 1996, The Journal of experimental medicine.

[6]  P. Kremsner,et al.  Enhanced production of reactive nitrogen intermediates in human and murine malaria. , 1995, Parasitology today.

[7]  K. Silamut,et al.  A simple method for assessing quinine pre-treatment in acute malaria. , 1995, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[8]  P. Libby,et al.  Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. , 1995, The Journal of clinical investigation.

[9]  S. Lundin,et al.  Conversion of inhaled nitric oxide to nitrate in man , 1995, British journal of pharmacology.

[10]  B. Nelson,et al.  Nitric oxide: cytokine-regulation of nitric oxide in host resistance to intracellular pathogens. , 1994, Immunology letters.

[11]  S. Milstien,et al.  Cerebrospinal Fluid Nitrite/Nitrate Levels in Neurologic Diseases , 1994, Journal of neurochemistry.

[12]  S. Hoffman,et al.  Nitric oxide-mediated antiplasmodial activity in human and murine hepatocytes induced by gamma interferon and the parasite itself: enhancement by exogenous tetrahydrobiopterin , 1994, Infection and immunity.

[13]  A. Nussler,et al.  Patients with Plasmodium falciparum malaria and Plasmodium vivax malaria show increased nitrite and nitrate plasma levels. , 1994, Journal of Infectious Diseases.

[14]  A. Nussler,et al.  Nitric oxide in cerebral malaria. , 1994, The Journal of infectious diseases.

[15]  B. Aggarwal,et al.  In vivo induction of nitrite and nitrate by tumor necrosis factor, lymphotoxin, and interleukin-1: possible roles in malaria , 1992, Infection and immunity.

[16]  J. Schrader,et al.  Control of coronary vascular tone by nitric oxide. , 1990, Circulation research.

[17]  L. Rickman,et al.  RAPID DIAGNOSIS OF MALARIA , 1989, The Lancet.

[18]  G. Schwedt,et al.  Kinetic studies on nitrite and nitrate in rats by ion-pair chromatography. , 1988, Clinica chimica acta; international journal of clinical chemistry.

[19]  J. Radomski,et al.  Concentrations of nitrate in normal human urine and the effect of nitrate ingestion. , 1978, Toxicology and applied pharmacology.

[20]  H. H. Mitchell,et al.  THE ORIGIN OF THE NITRATES IN THE URINE , 1916 .

[21]  W Graninger,et al.  High plasma levels of nitrogen oxides are associated with severe disease and correlate with rapid parasitological and clinical cure in Plasmodium falciparum malaria. , 1996, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[22]  P. López-Jaramillo,et al.  The L-arginine: nitric oxide pathway. , 1993, Current opinion in nephrology and hypertension.

[23]  World malaria situation in 1991. , 1993, Canada communicable disease report = Releve des maladies transmissibles au Canada.

[24]  I. Clark,et al.  Proposed link between cytokines, nitric oxide and human cerebral malaria. , 1991, Parasitology today.