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)

In recent years, cell-mediated immunity against malaria has been the subject of intensive investigation either in humans from malaria endemic areas, or experimental models. Cellular immune mechanisms have been regarded as secondary to humoral immunity but, there is increasing evidence that shows its critical role in protection against blood stage plasmodium parasites. In the context of a large humoral-cellular interaction, T helper lymphocytes and monocytes/macrophages may play a key role in the elimination of plasmodial blood stages, particularly P. falciparum. IL-2, IL-4, IL-5, IFN-gamma cytokines secreted principally by CD4+ T lymphocytes and oxygen and nitrogen radicals produced by activated macrophages, are involved in the control of plasmodial infection. The spleen also plays a very important function in the anti-malarial protection by its increased capacity for filtration/destruction of parasitized red blood cells and by induction of B and T memory lymphocytes. Successful vaccination against malaria needs a choice of plasmodial antigens or B and T immunodominants epitopes able to stimulate plasmodium-specific lymphocytes and functional modification in the spleen.
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PMID:[Cell-mediated immunity and protection against blood stages of Plasmodium falciparum]. 812 17

The in vitro production of reactive nitrogen intermediates (RNI) by murine macrophages was evaluated in response to heat-stable malaria antigen and cytokines. Malaria antigen, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) induced RNI production in macrophages in a dose-dependent way. RNI production steadily increased over a 2-day period and was enhanced when the malaria antigen was co-incubated with IFN-gamma and/or TNF. RNI production induced by either IFN-gamma or malaria antigen or a combination of the two was suppressed by pentoxifylline in a dose-dependent manner. Pentoxifylline did not significantly influence TNF-induced RNI production. L-N-monomethyl arginine reduced malaria antigen, IFN-gamma and TNF-induced RNI production when these reagents were used in combination or alone. An anti-TNF monoclonal antibody (mAb) reduced IFN-gamma-induced RNI production, but did not significantly alter the malaria antigen-induced RNI synthesis by macrophages. The influence of inhibitors of nitric oxide synthase, L-N-monomethyl arginine and N omega-nitro-L-arginine, was studied in experimental cerebral malaria. They did not exert any significant effect on the development of cerebral malaria in Plasmodium berghei ANKA-infected CBA/J mice.
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PMID:Malaria antigen and cytokine-induced production of reactive nitrogen intermediates by murine macrophages: no relevance to the development of experimental cerebral malaria. 847 17

The production of reactive oxygen intermediates (ROI) by host macrophages has long been recognized as an important defense mechanism against microorganisms. More recently, reactive nitrogen intermediates (RNI), also produced by activated macrophages, have been shown to be part of the host's first line of defense against malaria. In the present in-vitro study we have investigated the effects of antimalarial drugs on RNI production by murine macrophages stimulated by interferon-gamma (IFN-gamma) and/or malaria antigen, and on ROI production induced by phorbol myristate acetate. At concentrations exceeding the peak serum levels achieved with therapeutic dosages, chloroquine, in a dose-dependent manner, inhibited IFN-gamma- and malaria antigen-induced RNI production. Quinine, at a concentration of 10 mg/L also caused a significant reduction in IFN-gamma and malaria antigen-induced RNI synthesis; this concentration was well within the therapeutic range. High concentrations of artelinate significantly inhibited IFN-gamma-induced RNI production but clindamycin had no effect on RNI synthesis. In contrast, halofantrine, in concentrations attainable with therapeutic dosages, significantly enhanced IFN-gamma-induced RNI production. ROI production by murine macrophages was unaffected by the antimalarial drugs over the same concentration ranges. It remains to be determined whether these in-vitro effects of antimalarial drugs on RNI production also influence the clinical and parasitological response in patients with malaria.
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PMID:Interference by antimalarial drugs with the in-vitro production of reactive nitrogen intermediates by murine macrophages. 848 72

Serum transcobalamin II (TCII) levels were determined in 56 patients with P. falciparum malaria infection. They were divided into 3 groups: severe (malarial parasite > 5% or patients with cerebral malaria or renal insufficiency), moderate (1-5% infection without complications) and mild (1% infection). Elevated serum TCII values were found only in patients with severe malaria infection. These values correlated directly with parasitemia, blood urea nitrogen and creatinine, but were not correlated with alkaline phosphatase. As 17 patients with azotemia had elevated serum TCII levels while other 3 patients with normal BUN and creatinine concentrations had serum TCII levels within the normal limits. These findings indicated that malarial patients with renal insufficiency had increased serum TCII. A possible mechanism is the reduced TCII-B12 that filtered through the glomeruli due to the reduced renal blood flow with the decreased its uptake by proximal tubular cells resulting in the decreased degradation of TCII by the tubular lysosomal enzymes. Determination of serum TCII level may be used as an indicator of renal function in malarial patients with renal insufficiency.
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PMID:Serum transcobalamin II levels in patients with malaria infection. 852 19

After Anopheles stephensi mosquitoes with salivary infection of Plasmodium vivax were put in environments with temperatures of 30 +/- 1 degrees C, 26 +/- 1 degrees C or 13 +/- 1 degrees C for 5 d, their glands were aseptically dissected and sporozoites were collected and inoculated into HepG2-A16 cell monolayers. Seven days post-inoculation the cultured materials were harvested and the exoerythrocytic schizonts and hypnozoites were observed under the microscope by using immunoperoxidase staining technique. The results showed that the sporozoite developing rate of 30 +/- 1 degrees C group and 13 +/- 1 degrees C group was significantly lower than that of 26 +/- 1 degrees C group (0.33%, 0.35% and 0.75% respectively). The proportion of hypnozoites in the total number of EE forms was the highest in the low temperature group (62.5%) compared with 26 +/- 1 degrees C and 30 +/- 1 degrees C group (40.1% and 42.7% respectively). Suggesting that the low environmental temperature first affected the viability of tachysporozoites or the phenotype of sporozoites and thus resulted in heightened hypnozoite rate. This is parallel to the epidemiological data that in the regions of high latitute vivax malaria with long incubation period was more frequently observed. When the sporozoites within the body of mosquito were cryopreserved at -70 degrees C or in liquid nitrogen for 24 h or 5 d respectively, the proportion of hypnozoite increased 87.4% and 82.4%, respectively. However, cryopreservation did not inactivate all of the tachysporozoites, indicating that the resistance to ultralow temperature in bradysporozoite was much greater than that in tachysporozoites. Aging of sporozoites decreased their developing rate and the exoerythrocytic (EE) schizonts were found to grow sluggishly and asynchronously, indicating that the size of EE schizont and the age of sporozoites are in negative correlation. Meantime, proportion of the hyponozoite decreased significantly.
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PMID:[Effect of environmental temperature, cryopreservation and aging on Plasmodium vivax sporozoites developing into exoerythrocytic stages]. 855 88

When murine peritoneal macrophages were loaded in vitro with Plasmodium vinckei hemozoin and stimulated with opsonized zymosan for 90 min or with lipopolysaccharide and/or murine interferon-gamma for 24 hr, significant decreases in the production of oxygen radicals and nitrogen oxides, respectively, could be detected by comparison with macrophages without hemozoin. Moreover, nonradioactive in situ hybridization and immunohistologic analysis in liver sections of P. vinckei-infected mice with more than 60% parasitemia showed that liver cells were still expressing considerable levels of inducible nitric oxide synthase in the late phase of murine malaria, but most of the liver macrophages presenting accumulation of malaria pigment were negative in this analysis. These results further indicate that malaria pigment accumulation may be responsible for toxicity and impairment of macrophage functions during murine malaria.
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PMID:Effects of Plasmodium vinckei hemozoin on the production of oxygen radicals and nitrogen oxides in murine macrophages. 868 81

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

Serum levels of reactive nitrogen intermediates (RNI; nitrate plus nitrite) were measured in 92 patients with cerebral malaria in the Madang Province of Papua New Guinea. RNI levels were compared to disease severity and clinical outcome, and correlated with both the depth of coma on admission and its duration. Median levels were higher among children with deeper coma than among those with lighter coma (35.6 microM vs. 16.7 microM; P = 0.008) and also among children with longer duration of coma (72 h; 59.3 microM vs. 19.3 microM; P = 0.004). RNI levels also correlated with clinical outcome, fatal cases having significantly higher RNI levels than survivors (41.2 microM vs. 18.5 microM; P = 0.014). Thus, high RNI levels are associated with indices of disease severity and may predict outcome in children with cerebral malaria. These data are consistent with the hypothesis that nitric oxide is involved in the pathogenesis of coma in human cerebral malaria.
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PMID:Association between serum levels of reactive nitrogen intermediates and coma in children with cerebral malaria in Papua New Guinea. 919 81

Plasmodium berghei ANKA infected C57B1/6 mice develop cerebral malaria at a parasitaemia of 15-25%. When parasitaemia reached 10%, P. berghei infected mice were treated with artemether, chloroquine or clindamycin in order to prevent the occurrence of cerebral malaria. Artemether and chloroquine were highly efficient. Functional tests revealed that zymosan stimulated spleen cells from untreated mice with cerebral malaria showed a slight decrease in their capacity to produce reactive oxygen intermediates (ROI) when compared with naive mice. After artemether or chloroquine treatment, the ROI production was significantly enhanced. The interferon-gamma induced production of reactive nitrogen intermediates (RNI) was slightly elevated in mice with cerebral malaria, but markedly elevated in artemether or chloroquine treated mice when compared with naive mice. Moreover, high levels of inducible nitric oxide synthase gene expression could be detected by in-situ hybridization in spleen sections of mice which had been treated with artemether or chloroquine. These findings suggest that increased production of ROI and RNI after chemotherapy may play a protective role for the host during malaria.
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PMID:Upregulation of reactive oxygen and nitrogen intermediates in Plasmodium berghei infected mice after rescue therapy with chloroquine or artemether. 885 61

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


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