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

Oxidative stress has been incriminated as a deleterious factor in the development of malaria parasites. Various chemical reductones which can undergo cyclic oxidation and reduction, such as ascorbate have been shown to cause oxidative stress to red blood cells. This, naturally-occurring and redox-active compound, can induce the formation of active oxygen derived species, such as superoxide radicals (.O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). The formation of the hydroxyl radical, the ultimate deleterious species, is mediated by the redox-active and available transition metals iron and copper in the Haber-Weiss reaction. During the development of the parasite, hemoglobin is progressively digested and a concurrent release of high levels of iron-containing breakdown products takes place within the red blood cell. Indications for the progressive increase in redox-active iron during the growth of P. falciparum have been recently found in our lab: a) adventitious ascorbate proved highly detrimental to the parasite when added to the mature forms. In contrast, if the parasitized erythrocytes were in the early phase following invasion, and only low levels of iron-containing structures had been liberated, then the observed effect was a small promotion of parasite development. b) erythrocytes containing mature parasites were more potent than erythrocytes containing ring forms as a source for redox-active iron in the ascorbate-driven metal-mediated degradation of DNA. The addition of extracts from parasitized erythrocytes and ascorbate to DNA caused a dose and time dependent DNA degradation. Non-infected erythrocytes had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of oxidant stress by iron available in advanced forms of Plasmodium falciparum. 206 Aug 37

For most living organisms, heat shock represents an unusual stress situation, but for parasites that are transmitted between invertebrate vectors and mammalian hosts it is a frequent physiological occurrence. Because of the extraordinary conservation of heat shock proteins (HSPs) and their potential immunogenicity, much attention has recently focused on the role of HSPs in infection and immunity. In parasites, HSPs appear to play specific functions in differentiation, in protection from the host cell's killing mechanisms, including oxygen free radicals, and even in virulence. In this article, Barbara Polla uses the example of malaria to illustrate the possible role of HSPs in host-parasite relationships.
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PMID:Heat shock proteins in host-parasite interactions. 206 77

The negative consequences of parasitic infection (virulence) were examined for two lizard malaria parasite-host associations: Plasmodium agamae and P. giganteum, parasites of the rainbow lizard, Agama agama, in Sierra Leone, West Africa; and P. mexicanum in the western fence lizard, Sceloporus occidentalis, in northern California. These malaria species vary greatly in their reproductive characteristics: P. agamae produces only 8 merozoites per schizont, P. giganteum yields over 100, and P. mexicanum an intermediate number. All three parasites appear to have had an ancient association with their host. In fence lizards, infection with malaria is associated with increased numbers of immature erythrocytes, decreased haemoglobin levels, decreased maximal oxygen consumption, and decreased running stamina. Not affected were numbers of erythrocytes, resting metabolic rate, and sprint running speed which is supported by anaerobic means in lizards. Infected male fence lizards had smaller testes, stored less fat in preparation for winter dormancy, were more often socially submissive and, unexpectedly, were more extravagantly coloured on the ventral surface (a sexually dimorphic trait) than non-infected males. Females also stored less fat and produced smaller clutches of eggs, a directly observed reduction in fitness. Infected fence lizards do not develop behavioural fevers. P. mexicanum appears to have broad thermal buffering abilities and thermal tolerance; the parasite's population growth was unaffected by experimental alterations in the lizard's body temperature. The data are less complete for A. agama, but infected lizards suffered similar haematological and physiological effects. Infected animals may be socially submissive because they appear to gather less insect prey, possibly a result of being forced into inferior territories. Infection does not reduce clutch size in rainbow lizards, but may lengthen the time between clutches. These results are compared with predictions emerging from several models of the evolution of parasite virulence. The lack of behavioural fevers in fence lizards may represent a physiological constraint by the lizards in evolving a thermal tolerance large enough to allow elimination of the parasite via fever. Such constraints may be important in determining the outcome of parasite-host coevolution. Some theory predicts low virulence in old parasite-host systems and higher virulence in parasites with greater reproductive output. However, in conflict with this argument, all three malarial species exhibited similar high costs to their hosts.
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PMID:Virulence of lizard malaria: the evolutionary ecology of an ancient parasite-host association. 223 62

Two cases of cerebral malaria with hyperkinetic shock are reported. The first case concerned a 39-year-old european male who was not taking any prophylactic anti-malarial drugs. After having had headache and fever for a week, he was admitted to the intensive care unit (ICU) in coma and with jaundice. His initial systolic blood pressure was 60 mmg, with a central venous pressure (CVP) of -3 cmH2O. Five-hundred ml of modified fluid gelatin increased the CVP without raising the blood pressure. Haemodynamic investigations revealed a cardiac index (CI) = 5.2 l.min-1.m-2, peripheral arterial resistances (Rsa) = 290 dyn.s.cm-5, oxygen consumption (VO2) = 120 ml.min-1.m-2. Despite treatment with dopamine and dobutamine, the patient died 3 h after his admission, with a CI of 1.9 l.min-1.m-2. The second patient was a 14-year-old senegalese girl, admitted in circumstances similar to the first case. Initial haemodynamic investigations gave the following figures: CI 6.5 l.min-1.m-2, Rsa = 476 dyn.s.cm-5, VO2 = 174 ml.min-1.m-2. Recovery was obtained with fluid replacement therapy and dopamine. In the absence of another associated infectious disease, the plasmodial origin of the septic shock would seem to be the most likely in both cases. Pathophysiological mechanisms of these algid forms of malaria remain enigmatic. Various factors are discussed: cytoadherence of erythrocytes infected with Plasmodium falciparum, immunological disturbances, or a specific endotoxin.
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PMID:[Hyperkinetic shock and cerebral malaria]. 224 Jul

Malaria associated with complications or a fatal outcome is almost always caused by Plasmodium falciparum. The mortality due to this disease parallels the degree of parasitemia. Successful use of exchange blood transfusion as a therapeutic adjunct for this infection was first reported in 1974, although the efficacy of this procedure has not been established by randomized, controlled trials. The rationale for this form of therapy is based on: (1) rapid reduction in the parasite load by direct removal; (2) decreased risk of severe intravascular hemolysis and its consequences (disseminated intravascular coagulation and renal dysfunction); (3) improved rheology with transfused blood and reduced microcirculatory sludging; and (4) improved oxygen-carrying capacity with transfused erythrocytes. We describe a case of severe falciparum malaria and review the literature describing the use of exchange transfusion for treatment of this infection.
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PMID:Exchange transfusion as an adjunct to the treatment of severe falciparum malaria: case report and review. 192 97

In response to malaria infection, phagocytes, such as macro-phages and neutrophils, produce superoxide and thence the other reactive oxygen species (ROS) with which to kill the parasites. Excess ROS is normally eliminated by the body's natural scavenger molecules; however, in the event of a vast excess of ROS, as may be the case in acute as well as chronic malaria patients, the natural scavengers may be overwhelmed. We hypothesize that unscavenged ROS in malaria patients causes DNA damage in normal host cells which, if unrepaired or incorrectly repaired, could result in oncogene activation and eventually lead to cancer. An epidemiologic study may be warranted in malaria-endemic regions to investigate the possible relationship between malaria infection and cancer risk.
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PMID:Reactive oxygen production against malaria--a potential cancer risk factor. 237 89

The CD36 leukocyte differentiation antigen, recognized by MAbs OKM5 and OKM8 and found on human monocytes and endothelial cells, has been implicated as a sequestration receptor for erythrocytes infected with the human malaria parasite Plasmodium falciparum (IRBC). CD36 is also expressed on platelets and appears to be identical to platelet glycoprotein IV. We investigated receptor activation of monocytes and platelets by anti-CD36 MAbs and by IRBC. Incubation of human monocytes with anti-CD36 MAbs or IRBC resulted in stimulation of the respiratory burst as measured by reduction of nitroblue tetrazolium and generation of chemiluminescence. Incubation of human platelets with anti-CD36 MAbs resulted in platelet activation as measured by aggregation or ATP secretion. Activation of monocytes and platelets required appropriate intracellular transmembrane signaling and was inhibited by calcium antagonists or by specific inhibitors of protein kinase C or guanine nucleotide binding proteins. Soluble CD36 inhibited binding of IRBC to both monocytes and platelets, suggesting that these interactions are mediated by the CD36 receptor. Using a cytochemical electron microscopic technique, the presence of reactive oxygen intermediates was identified at the interface between human monocytes and IRBC. These data provide support for the hypothesis that reactive oxygen intermediates produced by monocytes when IRBC ligands interact with cell surface receptors may play a role in the pathophysiology of falciparum malaria.
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PMID:Activation of monocytes and platelets by monoclonal antibodies or malaria-infected erythrocytes binding to the CD36 surface receptor in vitro. 247 69

The role of splenic leukocyte oxidative activity and macrophage activation in the development of protective immunity was examined during acute Plasmodium chabaudi adami malaria. Splenic leukocyte oxidative activity was compared in infected BALB/c and P/J mice; the latter are known to suffer from defects in macrophage function. Phorbol myristate acetate-stimulated chemiluminescence and superoxide anion production by splenic leukocytes from infected BALB/c mice were found to be increased dramatically, while the response of splenic leukocytes from infected P/J mice was elevated only minimally. Hydrogen peroxide release was slightly increased in splenic leukocytes from infected BALB/c mice but remained essentially unchanged in those from infected P/J mice. Macrophage function was assessed on the basis of measurements of tumoricidal activity. Splenic macrophages from uninfected BALB/c mice displayed significant tumoricidal activity against L929 target cells. As a result of splenomegaly during infection, tumoricidal activity, when calculated on a per-spleen basis, was increased further in infected BALB/c mice. In contrast, the tumoricidal activity of splenic macrophages from P/J mice was minimal, regardless of infection. Despite these differences, both strains of mice developed malarial infections that resolved within 16 days. Thus, while the production of reactive oxygen radicals by splenic leukocytes and the phenomenon of macrophage activation have traditionally been associated with the resolution of malarial infection, this study failed to establish a correlation between these parameters and the development of protective immunity to blood-stage infection with P. chabaudi adami.
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PMID:Reassessment of the role of splenic leukocyte oxidative activity and macrophage activation in expression of immunity to malaria. 255 11

Malaria parasites are very vulnerable to oxidant stress during the part of their life cycle when they inhabit erythrocytes. As the infection progresses they also activate macrophages, one consequence of which is extracellular release of reactive oxygen species. For these reasons free radicals are frequently discussed in the literature on antimalarial drugs, malarial immunity, and disease pathogenesis. They are also central to arguments explaining how the genetic mutations that lead to sickle cell disease, thalassemia and glucose-6-phosphate dehydrogenase have become so common in tropical regions. This review summarizes how these links between free radicals and this disease came to be understood, and the present state of the field.
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PMID:Some roles of free radicals in malaria. 266 64

A/J and CBA/H mice infected with Plasmodium berghei ANKA, a murine model of cerebral malaria, were used to see whether antioxidants influenced the outcome of this disease. Untreated, infected mice died 7 to 9 days after infection, often with cerebral symptoms. Haemorrhages, mononuclear infiltration and oedema were present in the central nervous system (CNS). Feeding a diet containing 0.75% (w/w) butylated hydroxyanisole (BHA) greatly altered the course of this disease. Death was delayed by up to 2 weeks and mice appeared healthy at parasitaemias that would have caused cerebral symptoms and death had they been on a conventional diet. BHA-fed mice showed few or no cerebral symptoms at a time at which control mice were clearly affected, and greatly reduced haemorrhages, mononuclear infiltration and oedema when the CNS was examined. Similar, but more consistent, protective effects were seen after administration of BHA by repeated injections or in osmotic pumps. The combination of superoxide dismutase and catalase, coupled to polyethylene glycol, when administered intravenously also protected mice against death from cerebral complications. Permeability of the blood-brain barrier was monitored by the use of 125I-labelled bovine serum albumin, 51Cr-labelled erythrocytes and the dye Evans blue, all of which are normally excluded from the CNS. Infected mice on control diet showed an increase in Evans blue staining and 125I and 51Cr retention in the CNS tissue itself. Feeding the diet containing BHA reduced these indices of increased blood-brain barrier permeability. In view of the potent radical scavenging activity of BHA in many other systems it is likely, but unproven, that this is its main role here. The protective effect of superoxide dismutase and catalase lends support to the idea that reactive oxygen species are involved in the pathology of experimental cerebral malaria.
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PMID:Antioxidants can prevent cerebral malaria in Plasmodium berghei-infected mice. 266 24


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