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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the state of ferriprotoporphyrin IX (FP) in malaria pigment, mouse erythrocytes infected with Plasmodium berghei NYU-2 parasites were lysed by hypotonic shock, and hemoglobin and other soluble material were removed by extensive washing. The amount of FP recovered in the insoluble pellet was 2.1 mumol/ml of packed infected erythrocytes, of which approximately 1% was attributable to hemoglobin contamination. This crude preparation then was digested with a nonspecific protease from Streptomyces griseus and extracted with chloroform/methanol. The residue of insoluble dark brown material had the spectral and solubility properties characteristic of the FP of malaria pigment, and various different preparations contained from 82 to 99% of FP by weight. By elemental analysis, highly purified preparations contained no chlorine and had an oxygen content consistent with 1 mol of hydroxyl/mol of FP (oxygen content: calculated, 12.6%; found, 12.5%). In comparison to hematin purchased from Sigma, which had a measured oxygen content of 14.7%, the low oxygen form of hematin purified from malaria pigment was remarkably less soluble in ethanol, 3% sodium bicarbonate, and chloroform.
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PMID:The state of ferriprotoporphyrin IX in malaria pigment. 311 78

Cell-mediated immunity to malaria may involve macrophages, the monokines that mediate endotoxicity, and reactive oxygen species. Since interferon-gamma activates macrophages to release reactive oxygen species, and tumor necrosis factor-alpha (TNF-alpha) helps both to mediate endotoxicity and to induce leukocytes to secrete reactive oxygen, we monitored the effects of administering recombinant forms of these cytokines on Plasmodium chabaudi adami infections in mice. We also fed infected mice a diet containing 0.75% butylated hydroxyanisole, a scavenger of free radicals. Infections were suppressed by daily i.p. injections of 5 x 10(4) U of recombinant mouse interferon-gamma from day -1 or by recombinant human TNF released from i.p. osmotic pumps at the rate of 6 x 10(3) U/hr. Degenerate intraerythrocytic parasites (crisis forms) were evident much sooner in the course of the suppressed infections, and parasitemias fell correspondingly earlier. The butylated hydroxyanisole diet, in contrast, enhanced the infections. In these mice crisis forms were seen later, and at higher parasitemias, than they normally occur. These observations are consistent with the concept that T cell-dependent, macrophage-derived mediators are central to the type of malarial immunity that kills parasites inside circulating red cells. They also suggest, but do not prove, that both TNF and reactive oxygen species are involved, and that the role of TNF may be more indirect, although no less important, than that of reactive forms of oxygen.
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PMID:Inhibition of murine malaria (Plasmodium chabaudi) in vivo by recombinant interferon-gamma or tumor necrosis factor, and its enhancement by butylated hydroxyanisole. 311 10

NBT-test for circulating neutrophils and monocytes in the blood of mice inoculated with Plasmodium berghei, strain N or LNK-65, have been performed. Within the first 24 h of the infection, before the onset of the recordable parasitemia or in the course of the subsequent six days (depending of the strain used for inoculation) a 50-100% reduction in NBT-positive cells was observed. This demonstrates the ability of malaria parasite to suppress the oxygen-dependent enzyme system in circulating phagocytes, neutrophils and monocytes of the host blood. The results of NBT-test could be utilized for the investigation of immunological disorders and also for the differential diagnosis of malarial infection.
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PMID:[The nitroblue tetrazolium reduction test in evaluating the function of the circulating leukocytes in mice with experimental malaria]. 328 42

Zymosan-activated and non-activated human polymorphonuclear neutrophils (PMN) were added to in-vitro cultures of the human malaria parasite Plasmodium falciparum in microtitre wells. Microscopic counting of parasites in Giemsa-stained smears showed that at a PMN:RBC ratio of 1:150, the same as occurs in human malaria, parasites in wells with zymosan-activated neutrophils were suppressed 65%. Determination of parasite nucleic acid synthesis by 3H-hypoxanthine incorporation showed that in wells with PMN:RBC ratio of 1:150 parasite viability was only 22% of control. Various oxygen scavengers were tested for ability to reverse the effects of activated neutrophils on parasite development. Superoxide dismutase (20 mg/ml) and catalase (50 mg/ml) had no effect; tryptophan protected the parasites to a moderate degree while histidine alleviated suppression of parasite development to the greatest extent. This suggests that singlet oxygen is the most effective neutrophil product in killing or suppressing the growth of parasites. We also observed that non-activated neutrophils were activated by parasites and/or their products resulting in killing of newly-released parasites.
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PMID:Evidence for a neutrophil-mediated protective response in malaria. 328 Nov 2

Dexamethasone has recently been shown to block the production of cachectin (implicated in the pathogenesis of cerebral malaria) if administered prior to endotoxin induction of mouse macrophages. Using the hamster cheek pouch-cerebral malaria model, we tested the hypothesis that dexamethasone is effective as a therapeutic agent in severe malaria if given before some yet undefined trigger point in the disease. Infected hamsters were treated with dexamethasone (0.7 mg/kg) daily on days 7-12, 4-12, or 1-12 post-challenge. When treatment was started on day 1, whole body oxygen consumption (used as a measure of erythrocyte transport to sites of diffusion) on day 12 was greater than (P less than 0.05) that of infected control animals, though the degree of anemia was no different in treated and untreated groups. Furthermore, treatment produced a reduction in monocyte accumulation, capillary malfunction, and monocyte/red blood cell aggregate formation observable in the cheek pouch in vivo and a similar reduction in monocyte presence, capillary pathologic change, and multifocal hemorrhage in the brain on postmortem. These data suggest that mediator(s), whose production can be blocked by pretreatment with dexamethasone, are involved in the pathogenesis of disease leading to death of the Plasmodium berghei infected hamster.
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PMID:Pathologic activity of Plasmodium berghei prevented but not reversed by dexamethasone. 328 90

Nitroblue tetrazolium (NBT) reduction by polymorphonuclear leukocytes (PMN) has been employed for the detection of specific opsonizing antibodies against Plasmodium falciparum in sera from individuals exposed to malaria parasites. Specific antibody-antigen complex is known to trigger the metabolic activation of normal PMN, as measured by NBT-test. In the sera from 16 out of 17 patients tested the NBT-reduction of normal PMN was, in the presence of P. falciparum antigen, significantly higher than that obtained with pooled normal serum from individuals without malaria background. This enhancement was more pronounced in the presence of complement. NBT-reduction was elevated to a lower extent when human anti-P. falciparum sera were substituted with anti-P. vivax or P. ovale sera. Furthermore, no enhancement was noted when red blood cells lysate was used as antigen. The results indicated the presence of specific opsonizing antibodies against P. falciparum in the patient sera. Oxygen-derived free radicals formed by PMN during the stimulation are suggested as the neutrophil mediated protection against malaria.
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PMID:Detection and semiquantitative determination of antibodies against Plasmodium falciparum in human blood serum: NBT-reduction by polymorphonuclear leukocytes. 329 16

Pathophysiological significance of hypoxia in malarial infection was investigated in mice infected with Plasmodium berghei NK65. Intraperitoneal inoculation of mice with 1 X 10(7) parasitized red blood cells resulted in death of the hosts 6-7 days later. Anaemia of infected animals developed on day 4 after inoculation and oxygen affinity of whole blood, measured as P50 act pH, increased simultaneously. This change may be a physiological adaptive response to a reduction in oxygen delivery to the tissues to day 5. However, the blood oxygen supply on day 6 appeared to be deteriorating and this is thought to be an important factor contributing to the death of the host. The value of adenylate energy charge in red cells during malarial infection, however, was comparatively well-maintained. Allopurinol stimulated the multiplication of malaria parasites and seems to have induced collapse in host-parasite balance more rapidly. Decrease in blood pH and in blood oxygen transport may be important factors for the pathogenesis of the allopurinol-treated hosts.
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PMID:Pathophysiology of hypoxia in mice infected with Plasmodium berghei. 330 17

Reversed-phase h.p.l.c. was used to detect 2,4-dinitrophenylhydrazine-reactive carbonyl products, which excludes malonaldehyde, in malaria-parasite (Plasmodium vinckei)-infected murine red blood cells (RBCs). A number of alkanals, 4-hydroxyalk-2-enals and alka-2,4-dienals were tentatively identified by comparison with authentic standards. The formation of 4-hydroxynon-2-enal, deca-2,4-dienal and hexanal was greater in P. vinckei-infected RBCs than in their uninfected counterparts and was increased by the presence of t-butyl hydroperoxide. Several of these aldehydes have previously been shown to be toxic to various types of cells, including P. falciparum, in vitro. The iron chelator desferrioxamine and the free-radical scavenger butylated hydroxyanisole inhibited the formation of these aldehydes. These experiments demonstrate that products of lipid peroxidation other than malonaldehyde are formed during the exposure of malaria-infected RBCs in vitro to drugs that generate reactive oxygen species and have anti-parasitic activity. The formation of products of this type during the natural course of malaria infection may have implications for the mechanisms underlying intra-RBC parasite death and the tissue damage associated with the disease.
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PMID:Detection of short-chain carbonyl products of lipid peroxidation from malaria-parasite (Plasmodium vinckei)-infected red blood cells exposed to oxidative stress. 334 16

Many parasites--including the causative agents of malaria, Chagas' disease and schistosomiasis--are more susceptible to reactive oxygen species (ROS) than their hosts are. This is manifested by one or more of the following criteria: 1. Susceptibility of the parasite to ROS in vitro; 2. macrophage-based defense mechanisms against the parasite in vivo; 3. successful therapy using agents which lead to oxidative stress; 4. selection advantage (with respect to parasite infections) of human populations whose antioxidant capacity is impaired by a gene defect or by strong oxidants in their staple food. Our laboratory is involved in developing inhibitors against antioxidant enzymes thus mimicking natural experiments. Since glutathione reductase is a protein of known atomic structure the methods of drug design by receptor fit (DDRF) can be applied for this enzyme. Another promising target enzyme is trypanothione reductase which was found so far only in trypanosomatids, and specifically, not in their hosts. Consequently the trypanothione pathway may be a general target in the design of drugs against diseases caused by trypanosomes and leishmanias.
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PMID:Oxidative stress as a defense mechanism against parasitic infections. 350 42

Interaction between human neutrophils (polymorphonuclear leukocytes [PMN]) and Plasmodium falciparum in the natural defense of the host remains to be elucidated. In patients with acute malaria, oxygen consumption (QO2) of PMN at rest and after stimulation by zymosan was significantly increased compared with that in the controls. With 10% immune serum, both QO2 and chemiluminescence of normal PMN were significantly increased after stimulation by a P. falciparum erythrocyte culture. This activation was not observed with a nonparasitized erythrocyte culture and was correlated with parasitemia. Immune serum and complement were required to trigger this metabolic activation of normal PMN. With normal serum or heat-inactivated immune serum, a parasitized erythrocyte culture did not significantly stimulate QO2 or chemiluminescence of normal PMN. The classical complement pathway was essential for this stimulation, whereas the alternate pathway was less involved. Hyperimmune sera from subjects residing in endemic areas were more able to trigger the metabolic burst than were immune sera from subjects from other sources. The use of synchronous cultures showed that PMN were more stimulated by cultures rich in merozoites than by the same cultures which contained only intraerythrocytic forms. Giemsa staining showed granules of hemozoin and occasional merozoites or parasitized erythrocytes within PMN. This increase in production of activated oxygen radicals could damage intra-or extraphagocytic parasitic forms. As P. falciparum is sensitive to oxidant stress and PMN is the phagocyte with the most intense metabolic burst, the role of PMN in defense against malaria should be considered.
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PMID:Role of immune serum and complement in stimulation of the metabolic burst of human neutrophils by Plasmodium falciparum. 351 35


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