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)

To investigate the kinetics of monocyte/macrophage activation in falciparum malaria we determined urinary neopterin values serially in experimentally infected volunteers. Three subjects who had been immunized with irradiated sporozoites via mosquito bites served as controls. These individuals remained aparasitaemic, afebrile and without a rise in neopterin after challenge by infective mosquitoes. Four non-immune subjects developed Plasmodium falciparum parasitaemia, fever (3 of 4) and sharp rises in neopterin. Parasite densities reached 10-100 parasitized erythrocytes per microliter before elevations in temperature or neopterin levels were detected. Onset of fever preceded the rise in neopterin excretion by one day. Prompt chemotherapy was associated with the clearance of parasites from the blood and the return of temperature and neopterin levels to normal.
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PMID:Urinary neopterin in volunteers experimentally infected with Plasmodium falciparum. 144 Jul 69

In order to evaluate the relationship between fever and macrophage activation in vivax malaria, serum interferon-gamma (IFN-gamma) and urinary neopterin concentrations were determined in Thai adults with Plasmodium vivax parasitaemia. Magnitude of fever, after controlling for parasite density, was found to be positively correlated with both IFN-gamma (r = 0.47) and neopterin (r = 0.57). In the 26 febrile patients, neopterin excretion increased further during the first two days of chemotherapy (P = 0.0002). Mean neopterin values for both groups had fallen to within the normal range by the sixth day post-treatment. Thus, the fever of vivax malaria was associated with IFN-gamma induced macrophage activation, as reflected by neopterin excretion.
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PMID:Macrophage activation in vivax malaria: fever is associated with increased levels of neopterin and interferon-gamma. 181 Dec 17

Neopterin is a biochemical marker of cellular mediated immune reactions and may be used in elucidating the cause of acute renal failure. 9 patients (6 males, 3 females) aged 23 to 56 years suffering from a severe form of the disease were examined. A continuous arteriovenous hemofiltration was used as a treatment with exchanging 29.2 +/- 2.0 (14-65) kg of fluid during 24 hours. The patients' diet included protein and amino acids of 1.2-1.5 g/kg of body weight, 35-45 Kcal/kg of body weight per 24 hours with meal and parenteral infusions. 4 patients died. Contents of neopterin in the plasma of the healthy equaled to 6.8 +/- 03 (3.4-11.3) nmol/l (radioimmunoassay; Henning; Berlin, GmbH). In patients with acute renal failure plasma neopterin contents were increased, i.e. 130.0 +/- +/- 9.6 (48.2-200.2) nmol/l and in two thirds of the cases and correlated with creatinine levels (r = + 0.60 +/- 0.17; p less than 0.05; n = 23), thus showing a simultaneous influence of anuria and continuous arteriovenous hemofiltration on a neopterin pool amount at the same time, in patients with tropical malaria and hemotransfusion shocks (2 cases), the neopterin contents were extremely high and did not correlate with the creatinine level. During continuous hemofiltration at a rate of 21.6 +/- 1.3 (15.9-36.9) ml/min neopterine clearance was 17.2 +/- 2.1 (6.7-36.2) ml/min. Neopterin hyperproduction after blood transfusion suggests an immune conflict as a possible cause of acute renal failure.
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PMID:[The level of neopterin in the plasma of patients with acute kidney failure during treatment with continuous arteriovenous hemofiltration]. 187 25

Macrophage activation during acute falciparum malaria in 71 Thai adults was investigated by measuring urinary neopterin and serum interferon-gamma (IFN-gamma). Neopterin, a product of IFN-gamma-activated macrophages, was elevated in 94% of patients upon admission (day 0, prior to treatment) and in all at some time during the period of study. Neopterin levels tended to rise further (days 1-5) before falling back towards the normal range as patients recovered following effective chemotherapy (days 6-8). IFN-gamma was measured in 32 patients and found to be directly related to neopterin concentration. Both neopterin and IFN-gamma values were highest in patients experiencing a first malaria infection. Among those with histories of prior malaria, neopterin and IFN-gamma levels were inversely related to the number of previous infections. Morbidity, as assessed by degree and duration of fever, was directly related to neopterin concentration. This longitudinal study quantitatively describes the extent and duration of macrophage activation in falciparum malaria. The data also suggest that with repeated malaria infection and antigen exposure, there is a progressive decrease or possibly suppression of the T cell-macrophage interaction mediated by IFN-gamma.
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PMID:Macrophage activation in falciparum malaria as measured by neopterin and interferon-gamma. 211 22

Numerical alterations of circulating lymphocytes were investigated in 37 Brazilian patients with uncomplicated Plasmodium falciparum malaria and in a group of 15 healthy controls. The number of CD4+ T helper/inducer cells was significantly lower in patients than controls, whereas absolute numbers of CD8+ suppressor/cytotoxic T cells did not differ between the groups. TNF and neopterin levels were markedly increased in the plasma of patients and remained slightly elevated after chemotherapy with clindamycin. Neopterin, but not TNF levels, were significantly correlated with parasitaemia. TNF was inversely related to monocyte counts. Interferon gamma could not be detected in the plasma of control subjects and was observed in only one patient. We conclude that in uncomplicated falciparum malaria the distribution of phenotypes of circulating lymphocytes are altered slightly and that the high plasma levels of TNF and neopterin indicate excessive release of these molecules by activated macrophages and the activation of cellular immune mechanisms during the infection.
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PMID:Immunological alterations in uncomplicated Plasmodium falciparum malaria. Relationship between parasitaemia and indicators of macrophage activation. 257 70

In vitro, neopterin, a pyrazino-[2, 3-d]-pyrimidine compound, is produced by human monocytes-macrophages following induction by either supernatants from activated T lymphocytes or by recombinant gamma interferon. In vivo, its determination in urine or serum provides a sensitive and specific test for the activation grade of cell-mediated immune reactions. Urinary neopterin levels were measured in 128 Tanzanian individuals (age 6 months to 54 years) with parasitologically proven malaria. Levels in a subgroup of 117 previously untreated patients were compared with those previously reported from 19 untreated malarial patients from Bangkok, Thailand (age 7 to 62 years). The influence of concomitant variables such as age, fever, parasitaemia, duration of symptoms and local endemicity of malaria upon neopterin excretion levels was analysed. In the Thai patients, levels were considerably higher than in Tanzanian subjects of similar age. Among the Tanzanian patients, an overwhelming influence of age was detected, children showing extremely high neopterin excretion levels. The other variables did not influence neopterin levels significantly. Our findings are in accord with recent data on the prevalence and mean titres of antibodies to the circumsporozoite protein of Plasmodium falciparum, which indicate that in endemic areas acquired humoral immunity develops slowly with increasing age, while prevalence and severity of disease decline.
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PMID:The dependence of cell-mediated immune activation in malaria on age and endemicity. 332 84

Lysates of Plasmodium falciparum parasitized human erythrocytes stimulate U937 cells to secrete neopterin during a 48 hr co-culture period. Neopterin secretion by U937 cells was enhanced by the addition of human interferon gamma (IFN-gamma). Several P. falciparum antigens, 'FC27' (a synthetic 'S' antigen), Ag16 (a recombinant 'S' antigen) and Ag44/RHOP3 (a recombinant merozoite rhoptry protein), also activated U937 cells to neopterin secretion and produced a similar effect on peripheral blood mononuclear cells (PBMC) from 2 of 3 normal healthy donors cultured with the antigens for 7 days. Plasma from six Nigerian malaria patients contained high neopterin concentrations ranging from 5.06 to 14.17 ng/ml. This preliminary pilot study lends support for further investigation incorporating a larger number of malaria patients and further culture experiments with U937 cells and PBMC with the aim of defining the cause and source of the large quantities of plasma neopterin produced in this infection.
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PMID:Malaria antigens stimulate neopterin secretion by PBMC and U937 cells. 760 65

Neopterin levels in plasma were measured during a longitudinal study of 75 patients living in an area endemic for malaria. The maximum levels were observed in August/September, the period of peak transmission of the disease. During the dry season, levels remain elevated. No relationship was found between the level of neopterin and the individual's immune status against malaria. Tumor necrosis factor (TNF), activated T lymphocytes subpopulations, soluble interleukin 2 receptors, and anti-circumsporozoite protein antibodies were not correlated with neopterin levels during the period of peak transmission. In contrast, neopterin levels were correlated with anti-Plasmodium falciparum antibodies detected by immunofluorescence. It was concluded that, in a population of chronic parasite carriers subjected to repeated infestations, neopterin was a good indicator of slowly acquired immunity in stable transmission area, but it poorly reflected acute immune responses.
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PMID:Neopterin levels in plasma during a longitudinal study in an area endemic for malaria. 850 Feb 75

To determine if iron chelation therapy alters immune responses in children with cerebral malaria, we retrospectively measured mean serum levels of neopterin, interleukin-4 (IL-4), and IL-6 in children who received desferrioxamine B or placebo for three days in addition to quinine-based therapy. Mean levels of neopterin, IL-4, and IL-6 were elevated above the expected normal range on admission. Neopterin correlated significantly with the degree of anemia, IL-4 with the duration of fever prior to admission, and IL-6 with parasite density. Serial measurements of cytokines and neopterin were performed over four days in 39 children, 21 randomized to receive desferrioxamine B and 18 to receive placebo. Mean concentrations of neopterin did not change significantly in either group while levels of IL-4 increased significantly in the placebo group (P = 0.04) but remained unchanged in the desferrioxamine B group. Interleukin-6 concentrations decreased markedly in both groups (P < 0.025). Stable IL-4 levels in children given desferrioxamine B may represent an inhibition of the T helper lymphocyte-2 (TH-2) response resulting from a strengthened TH-1 response associated with iron chelation therapy. Any effect of iron chelation on immunity in the setting of severe malaria will have to be confirmed in future prospective investigations.
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PMID:Serum neopterin, interleukin-4, and interleukin-6 concentrations in cerebral malaria patients and the effect of iron chelation therapy. 861 42

Plasma levels of nitrogen oxide (NO), neopterin and C-reactive protein (CRP) were compared in 3 groups of Gabonese patients with Plasmodium falciparum malaria before and after therapy: adults with uncomplicated malaria, children with uncomplicated malaria, and children with severe malaria. Plasma levels of all 3 molecules were significantly higher in severe malaria than in uncomplicated malaria. High levels of neopterin and CRP during the acute phase of malaria significantly correlated with slow parasitological and clinical cure after therapy. In contrast, high NO plasma levels during the acute phase of malaria predicted accelerated cure. These findings provide further evidence for the protective role of NO in malaria. However, as NO levels were highest in severe disease, overproduction may be harmful for the patients.
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PMID:High plasma levels of nitrogen oxides are associated with severe disease and correlate with rapid parasitological and clinical cure in Plasmodium falciparum malaria. 919 81


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