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)

Nitric oxide (NO)-related activity has been shown to be protective against Plasmodium falciparum in vitro. It has been hypothesized, however, that excess NO production contributes to the pathogenesis of cerebral malaria. The purpose of this study was to compare markers of NO production [urinary and plasma nitrate + nitrite (NOx)], leukocyte-inducible nitric oxide synthase type 2 (NOS2), and plasma TNF-alpha and IL-10 levels with disease severity in 191 Tanzanian children with and without malaria. Urine NOx excretion and plasma NOx levels (corrected for renal impairment) were inversely related to disease severity, with levels highest in subclinical infection and lowest in fatal cerebral malaria. Results could not be explained by differences in dietary nitrate ingestion among the groups. Plasma levels of IL-10, a cytokine known to suppress NO synthesis, increased with disease severity. Leukocyte NOS2 antigen was detectable in all control children tested and in all those with subclinical infection, but was undetectable in all but one subject with cerebral malaria. This suppression of NO synthesis in cerebral malaria may contribute to pathogenesis. In contrast, high fasting NOx levels and leukocyte NOS2 in healthy controls and asymptomatic infection suggest that increased NO synthesis might protect against clinical disease. NO appears to have a protective rather than pathological role in African children with malaria.
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PMID:Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression. 876 Aug 9

Autoimmune disease is generally rare in tropical rural populations. Plasma concentrations of nitrite plus nitrate (reactive nitrogen intermediates), reflecting high nitric-oxide production somewhere in the body, can be high in patients who have cerebral malaria, but even higher in symptom-free parasitised individuals, who are termed malaria-tolerant. We propose that the nitric oxide causing high serum levels of reactive nitrogen intermediates in malaria-tolerant individuals is generated in macrophages during the establishment and maintenance of malarial tolerance, and makes autoimmune disease rare in many tropical rural populations by minimising proliferation of autoreactive T cells. Conversely, innately low levels of nitric-oxide generation in these populations, selected by malarial disease in tropical areas, could rationalise their high frequency of autoimmune disease and hypertension when living in western societies.
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PMID:Does malarial tolerance, through nitric oxide, explain the low incidence of autoimmune disease in tropical Africa? 902 7

To determine whether iron chelation modulates nitric oxide (NO) formation and cell-mediated immune effector function in children with cerebral malaria, serum concentrations were measured of the stable end products of NO, nitrite and nitrate (NO2-/NO3-), interleukin (IL)-4, -6, and -10, and neopterin in 39 Zambian children enrolled in a placebo-controlled trial of desferrioxamine B and quinine therapy. Mean concentrations of NO2-/NO3- increased significantly over 3 days in children receiving desferrioxamine plus quinine but not in those given placebo and quinine. Neopterin levels declined significantly with placebo but not with desferrioxamine. IL-4 levels increased progressively in the placebo group and ultimately decreased in the desferrioxamine group, but the trends were not statistically significant. IL-6 and IL-10 levels were elevated initially and decreased significantly in both groups over 3 days. These data are consistent with the hypothesis that iron chelation therapy in children with cerebral malaria strengthens Th1-mediated immune effector function involving increased production of NO.
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PMID:Modulatory potential of iron chelation therapy on nitric oxide formation in cerebral malaria. 898 27

We have shown previously that at the time of peak primary parasitaemia of P. chabaudi infection in NIH mice, significant levels of nitric oxide are produced, detectable as nitrate in the serum, and that these contribute to the protective immune response to infection. Here, we demonstrate that following reinfection, mice show a markedly diminished ability to produce nitrate. However, if mice are treated with L-NG-monomethyl arginine specifically to block nitric oxide metabolism during the primary infection, and are then reinfected, production of nitrate is restored to levels approaching those attained at peak primary parasitaemia. These experiments, together with others we have reported, indicate that whereas nitric oxide appears to play a significant role in control of the primary parasitaemia of P. chabaudi infection, it performs no such function during subsequent patent parasitaemias. Furthermore, they suggest that factors as yet unknown may regulate nitric oxide activity during malaria infection, such that under normal circumstances its production comes under strict control. This is exemplified by the observation that after the burst of nitric oxide activity that coincides with peak primary parasitaemia, there follows a prolonged period of immunological tolerance during which nitrate levels remain low even at secondary challenge infection. This tolerized state is lifted only several months after initial infection, when the nitric oxide activity at reinfection appears to correlate with the size of the parasite challenge and the presence of a patent parasitaemia. The implications of these findings for protective immunity to malaria, malarial immunosuppression, and immunoregulation in general, are discussed.
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PMID:Kinetics of nitric oxide production during infection and reinfection of mice with Plasmodium chabaudi. 922 97

Nitric oxide is an important host defence molecule as well as being a mediator in many pathophysiological processes. To investigate its role in severe malaria, we measured plasma nitrate and nitrite concentrations in 70 children with malaria (54 with severe malaria) and 48 control subjects (33 with medical conditions and 15 surgical patients). We related these measurements to plasma lactate concentrations, an established marker of disease severity in malaria. Plasma lactate levels were significantly elevated in patients with deep coma (P = 0.0007) and those with a fatal outcome, but mean nitrogen oxide concentrations were not significantly different in the 2 outcome categories and were not related to depth of coma (P > 0.5). In patients whose cerebrospinal fluid (CSF) was examined, lactate concentrations were elevated in fatal cases (geometric mean 8.2 mmol/L, n = 5) compared with survivors (3.4 mmol/L, n = 13; P = 0.032); corresponding CSF nitrogen oxide concentrations were 10.7 microM in fatal cases compared with 12.5 microM in survivors (P = 0.5). Plasma nitrogen oxide concentrations were negatively correlated with admission parasitaemia (r = -0.41, n = 70; P < 0.0001). In our population, elevations of plasma lactate, but not nitrite or nitrate, reflected disease severity in malaria.
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PMID:Plasma nitrogen oxides and blood lactate concentrations in Ghanaian children with malaria. 923 Dec 1

Serum from 41 of 92 children admitted to Madang Hospital, Papua New Guinea, with cerebral malaria, previously assessed for serum levels of reactive nitrogen intermediates (RNI: nitrate plus nitrite), were re-assessed for creatinine levels on the day of admission. Further analysis of RNI levels on day 21 compared to day 0 was carried out. Children with the highest RNI levels on admission, and with the longest duration of coma, did not have elevated creatinine levels. The highest levels of creatinine occurred among those with the lightest coma and creatinine levels were similar in those with short (< 48 h) and long (> 48 h) duration of coma. Between days 0 and 21, RNI decreased in 30 of 57 children, increased in 23, and did not change in 4. There was a significant relationship between the decrease in RNI relative to the level of RNI on admission and the duration of coma. For children with a coma duration < 48 h (48/57), there was no difference between the numbers showing an increase or a decrease in RNI level, but 6 of the 9 children with coma duration > 48 h showed a decrease in RNI greater than 50% of the RNI levels on admission. None of these 9 children had elevated creatinine levels. Elevated RNI levels in severe cases were thus not associated with renal function in these children in Papua New Guinea.
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PMID:Serum creatinine levels and reactive nitrogen intermediates in children with cerebral malaria in Papua New Guinea. 923 Dec 2

Previous studies have reported increased serum concentrations of nitrite/nitrate - the degradation products of nitric oxide - in Plasmodium vivax malaria and uncomplicated Plasmodium falciparum malaria. In all these studies, however, nitrite/nitrate has been measured spectrometrically using Griess reagent which carries major disadvantages in the determination of serum nitrite/nitrate. The method does not allow an exact differentiation of nitrite and biogenic amines that are physiologically present in plasma. In the present study we introduce high-performance liquid chromatography as a new, accurate and cost effective method for determination of serum nitrite/nitrate levels. Significantly increased nitrate concentrations were found in malaria patients and serum values remained above normal levels for at least 21 days. It could be shown that our HPLC method is a sensitive and cost-effective method for direct determination of nitrite/nitrate in serum samples, which is not influenced by the presence of biogenic amines.
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PMID:Measurement of serum nitrite/nitrate concentrations using high-performance liquid chromatography. 979 32

We have discovered that the mosquito Anopheles stephensi, a natural vector of human malaria, limits parasite development with inducible synthesis of nitric oxide (NO). Elevated expression of A. stephensi NO synthase (NOS), which is highly homologous to characterized NOS genes, was detected in the midgut and carcass soon after invasion of the midgut by Plasmodium. Early induction is likely primed by bacterial growth in the blood meal. Later increases in A. stephensi NOS expression and enzyme activity occurred at the beginning of sporozoite release. Circulating levels of nitrite/nitrate, end-products of NO synthesis, were significantly higher in Plasmodium-infected mosquitoes. Dietary provision of the NOS substrate L-arginine reduced Plasmodium infections in A. stephensi. In contrast, dietary provision of a NOS inhibitor significantly increased parasite numbers in infected mosquitoes, confirming that A. stephensi limits Plasmodium development with NO.
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PMID:The mosquito Anopheles stephensi limits malaria parasite development with inducible synthesis of nitric oxide. 957 47

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.
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PMID:Nitric oxides in plasma, urine, and cerebrospinal fluid in patients with severe falciparum malaria. 974 51

The purpose of this study was to evaluate nitric oxide (NO) activity in patients with uncomplicated malaria. Lipopolysaccharide and gamma interferon (IFN-gamma) are potent inducers of NO by inducing production of NO synthase. NO activity was determined by measuring serum levels of nitrite/nitrate (metabolic end products of NO), and IFN-gamma in patients with uncomplicated malaria, mostly caused by Plasmodium falciparum. Neither serum levels of nitrite/nitrate nor of IFN-gamma were significantly increased in patients with uncomplicated malaria, especially in patients with P. falciparum infection, and in those with high parasitaemia. These results show that NO cannot play a role in uncomplicated malaria, and it is still debatable if NO production in this infection has beneficial or detrimental effects.
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PMID:Levels of circulating nitrate/nitrite and gamma interferon not increased in uncomplicated malaria. 979 89


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