Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production and function of nitric oxide during the early phase of blood-stage infection with Plasmodium chabaudi AS was analyzed using two inbred strains of mice that differ in the level of resistance to this parasite. Northern blot analysis of in vivo expression of inducible nitric oxide synthase (iNOS) revealed that early during infection resistant C57BL/6 mice, which clear the infection by 4 wk, have higher levels of iNOS mRNA in the spleen than susceptible A/J mice. In contrast, susceptible A/J mice have significantly increased levels of iNOS mRNA in the liver later in the course of infection just before death occurs. Splenic macrophages recovered from resistant C57BL/6 mice on day 7 postinfection express iNOS mRNA which is up-regulated following overnight stimulation of the cells with LPS. Furthermore, during the first week postinfection, splenic macrophages recovered from resistant hosts produce significantly higher levels of nitrite (NO2-) in vitro in response to LPS than similarly stimulated macrophages from susceptible A/J mice. Increased levels of nitrate (NO3-) were only detected in serum of resistant C57BL/6 mice at the time of peak parasitemia. Treatment with the iNOS inhibitor, aminoguanidine, reduced NO3- levels in serum of C57BL/6 mice and eliminated resistance of these hosts to P. chabaudi AS malaria without affecting parasitemia. These results demonstrate that the ability to produce high amounts of nitric oxide (NO) early during infection with blood-stage P. chabaudi AS correlates with resistance, but that NO may not be involved in parasite killing. Moreover, the tissue site of NO production, that is, spleen vs liver, appears to be critical and correlates with resistance vs susceptibility to P. chabaudi AS malaria, respectively.
 ...
PMID:Nitric oxide expression in the spleen, but not in the liver, correlates with resistance to blood-stage malaria in mice. 759 44

The haemoprotozoan parasite, Babesia canis, is the cause of an economically important and potentially life-threatening disease of dogs in South Africa, the pathophysiology of which is incompletely understood. Available literature is reviewed, with emphasis on the pathophysiology of the anaemia and complications of babesiosis. The remainder of the review explores the possibility that pathophysiological mechanisms currently being investigated in human malaria and bovine babesiosis (in which, as in canine babesiosis, an intra-erythrocytic parasite causes multi-systemic pathology) might also be active in B. canis infections. The entity referred to as the multiple organ dysfunction syndrome is discussed as a proposed mechanism within which apparently unrelated aspects of babesiosis form a predictable pattern. The molecular mediators of multiple organ dysfunction, including cytokines, nitric oxide and free oxygen radicals, are generated by host tissues, and are now under active study to help elucidate the pathophysiology of malaria. The similarities between the manifestations of different diseases in different host species can be explained by the concept that the disease process is largely mediated by these molecules, generated by the host in response to the parasite, rather than arising directly from the parasite itself. The current direction of malaria research provides a basis for future research into the pathophysiology of canine babesiosis.
 ...
PMID:The pathophysiology of canine babesiosis: new approaches to an old puzzle. 759 23

The effects of IL-12 administration on the development of protective immunity to blood-stage Plasmodium chabaudi AS were analyzed. Treatment of susceptible A/J mice on the day of infection and for 5 days postinfection with various doses 0.025-0.3 microgram) of rIL-12 significantly decreased the peak parasitemia level, but only treatment with 0.1 microgram resulted in increased survival. Treatment of resistant B6 mice with 0.1 microgram of rIL-12 using the same regimen also significantly decreased the peak parasitemia level, but 40% of the animals died. Treatment of these mice with anti-IL-12 mAb resulted in a more severe course of infection, but survival was not significantly altered. The mechanism of IL-12-induced resistance was examined in A/J mice during infection. Compared with spleen cells from untreated mice, cells from IL-12-treated mice produced significantly higher levels of IFN-gamma spontaneously as well as in response to Con A or Ag stimulation on day 7 postinfection. Significantly higher levels of INF-gamma and TNF-alpha were found in the sera of IL-12-treated mice, which correlated with high levels of the nitric oxide (NO) metabolite, NO3-. Furthermore, CD4+T cell depletion was found to abrogate IL-12-induced resistance. Administration of neutralizing mAb against IFN-gamma or TNF-alpha to IL-12-treated mice showed that simultaneous depletion of both cytokines resulted in 100% mortality. The role of NO was investigated by administration of aminoguanidine, a selective inhibitor of cytokine-inducible nitric oxide synthase, to IL-12-treated mice. Significantly increased mortality was observed following treatment twice daily with 9 mg of aminoguanidine, but there was no effect on parasitemia. In conclusion, these results demonstrate that IL-12 regulates the development of resistance to P. chabaudi AS via a CD4+ Th1 response, which involves the cytokines IFN-gamma and TNF-alpha, and is in part NO dependent. Therefore, IL-12, given in the appropriate dose, may be useful in the induction of protective immunity to blood-state malaria.
 ...
PMID:IL-12-induced protection against blood-stage Plasmodium chabaudi AS requires IFN-gamma and TNF-alpha and occurs via a nitric oxide-dependent mechanism. 765 Mar 84

Experimental primary infection with Plasmodium berghei in rats is known to be influenced by several cytokines. Dietary supplementation of n-3 fatty acids has been shown to influence cytokine production capacity and to protect mice from cerebral malaria. We investigated the effect of dietary fish oil (FO) supplementation on cytokine and nitric oxide production and liver schizont development in male brown Norway rats. Control groups were fed either a corn oil-supplemented diet (CO) or standard lab chow (LC). After six weeks on either diet, rats given supplementary FO had a significantly lower production of interleukin-1 (IL-1) and IL-6 after stimulation with lipopolysaccharide, and also had significantly lower numbers of liver schizonts compared with CO- or LC-fed animals. We conclude that in rats, an FO-supplemented diet reduces the production capacity of IL-1 and IL-6 and inhibits schizont development after intravenous inoculation of P. berghei sporozoites. Fish oil did not influence nitric oxide production by peritoneal macrophages.
 ...
PMID:Inhibition of Plasmodium berghei liver schizont development and reduction of cytokine production capacity in rats by dietary fish oil supplementation. 767 26

Intraperitoneal injection of recombinant Interleukin 12 (rIL-12) at 30 ng/day for 5 days beginning 1 to 2 days before sporozoite challenge or administration of a single dose of 150 ng of rIL-122 days before challenge protected 100% of BALB/c mice against challenge with 10(2) Plasmodium yoelii sporozoites. rIL-12-induced protection was eliminated in all mice by administration of a monoclonal antibody against interferon gamma and in 50% of mice by administration of NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthase. rIL-12 protected BALB/c mice treated with cytotoxic anti-CD4 and anti-CD8 monoclonal antibodies, as well as T-cell- and B-cell-deficient severe combined immunodeficiency mice. These data suggest that rIL-12 stimulates non-B, non-T cells to produce interferon gamma that kills intrahepatic parasites by stimulating nitric oxide production. If rIL-12 proves to be well tolerated by humans, our findings support consideration of rIL-12 as an immunoprophylactic against malaria.
 ...
PMID:Interleukin 12 induction of interferon gamma-dependent protection against malaria. 793 13

Reports linking human malarial illness and pathology with serum tumor necrosis factor (TNF) levels are now common, although the association is not always precise. Possible reasons for this discrepancy include the reported variation in levels of interleukin-1 (IL-1), a cytokine known to synergize with TNF. We have examined the extent of synergy between recombinant human TNF and either recombinant human IL-1 alpha or recombinant human IL-1 beta in producing hypoglycemia and increasing plasma levels of nitric oxide in malaria (Plasmodium vinckei)-infected CBA mice. Very low concentrations of either IL-1 alpha or IL-1 beta, with negligible effects on their own, greatly enhanced the effectiveness of TNF in bringing about these changes. In particular, synergy in generating nitric oxide, a mediator argued to induce cerebral malaria, was profound. Thus, variation in generation of IL-1 during infection provides one explanation for the poor correlation sometimes encountered between serum TNF levels and clinical condition.
 ...
PMID:Tumor necrosis factor and interleukin-1 synergy in the context of malaria pathology. 802 67

We have tested the hypothesis that nitric oxide may be responsible for the immunosuppression reported during malaria infections. We first showed that reactive nitrogen intermediates, which indicate nitric oxide generation, were increased in the plasma of Plasmodium vinckei-infected mice. We next found that Concanavalin A-induced proliferation of spleen cells from these mice was reduced compared with that observed in uninfected animals. The addition of NG-methyl-L-arginine (L-NMMA) for the duration of the cultures restored the malarial proliferative response to normal. We then tested the effect of oral L-NMMA on the proliferative response of P. chabaudi-infected mice to a human red blood cell lysate. The secondary response to this antigen, measured as spleen cell proliferation in vitro ten days after immunization and when there was no discernible parasitaemia, remained normal in L-NMMA-treated P. chabaudi mice, but was decreased in the untreated infected mice. These results suggest a role for nitric oxide in malarial immunosuppression.
 ...
PMID:Possible role of nitric oxide in malarial immunosuppression. 807 68

CD4+ T cells play a major role in protective immunity against the blood stage of malaria, but the mechanism of protection is unclear. By adoptive transfer of cloned T cell lines, direct evidence is provided that both TH1 and TH2 subsets of CD4+ T cells can protect mice against Plasmodium chabaudi chabaudi infection. TH1 cells protect by a nitric oxide-dependent mechanism, whereas TH2 cells protect by the enhancement and accelerated production of specific immunoglobulin G1 antibody.
 ...
PMID:The role of TH1 and TH2 cells in a rodent malaria infection. 810 Mar 66

To analyze whether nitric oxide may be involved in the pathogenesis of the mouse cerebral malaria (CM), nitrate and nitrite were first measured in urines of Plasmodium species infected mice. The CM-susceptible CBA/J mice were infected with either Plasmodium berghei or Plasmodium chabaudi, and the CM-resistant BALB/c mice were infected with P. berghei. No increased levels of nitrate and nitrite were detected in urine of mice infected with Plasmodium whatever the time of monitoring. In contrast, the nitrite level was found to be increased in the urine of C3H/HeJ mice infected with Trypanosoma cruzi, used as a positive control for nitrate excretion in urine. Two analogs of L-arginine, the L-NG-monomethyl-arginine acetate hydrate (L-NMMA) and N omega-nitro-L-arginine, which inhibit the nitric oxide synthase were used. CBA/J mice infected with P. berghei and treated ip with the analogs developed full neurological symptoms. Even administered intracranially, L-NMMA did not reverse CM. The role of nitric oxide in the CM pathogenesis of the mouse model is discussed.
 ...
PMID:Plasmodium berghei: is nitric oxide involved in the pathogenesis of mouse cerebral malaria? 834

To investigate the effect of the heme moiety of malaria pigment, hemozoin, on phagocyte functions, mouse macrophages were fed with insoluble beta-hematin, the synthetic heme-polymer chemically identical to the native pigment, or the soluble monomer, hematin. Production of inflammatory cytokines, interleukin 1 (IL1), tumor necrosis factor alpha (TNF alpha), and nitric oxide (NO) was assayed in the supernatants after stimulation with lipopolysaccharide. The results indicate that both beta-hematin and hematin induce a dose-dependent inhibition of macrophage production of TNF alpha and NO, but not of IL1. One-hour pretreatment with soluble hematin inhibited production of cytotoxic mediators by more than 50% compared to controls, while 6-hr exposure was necessary for insoluble beta-hematin to induce the same level of inhibition. However, the same treatment did not modify the production of TNF alpha and NO by mouse microglia cell lines. The inhibition was partially counterbalanced by adding sulphydryl group donors such as 2-mercaptoethanol, glutathione, or N-acetyl-cysteine during the preincubation time. The results of the present study confirm the inhibitory role of malaria pigment and show that such effect is due to the heme moiety and may be selective for the production of cytotoxic mediators by specific phagocytes. The implications of these findings in the control of malaria infection and disease and in the pathogenesis of severe malaria are discussed.
 ...
PMID:The heme moiety of malaria pigment (beta-hematin) mediates the inhibition of nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide-stimulated macrophages. 854 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>