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

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.
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PMID:The pathophysiology of canine babesiosis: new approaches to an old puzzle. 759 23

Pathogenic organism can be considered as pro-oxidant agents because they produce cell death and tissue damage. In addition organism can be eliminated by specific cell defense mechanism which utilize in part, reactive oxygen radicals formed by oxidative stress responses. The cause of the necessarily defense process results in cell damage thereby leading to development of inflammation, a characteristic oxidative stress situation. This fact shows the duality of oxidative stress in infections and inflammation: oxygen free radicals protect against microorganism attack and can produce tissue damage during this protection to trigger inflammation. Iron, a transition metal which participates generating oxygen free radicals, displays also this duality in infection. We suggest also that different infectious pathologies, such as sickle cell anemia/malaria and AIDS, may display in part this duality. In addition, it should be noted that oxidative damage observed in infectious diseases is mostly due the inflammatory response than to the oxidative potential of the pathogenic agent, this last point is exemplified in cases of respiratory distress and in glomerulonephritis. This review analyzes these controversial facts of infectious pathology in relation with oxidative stress.
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PMID:[Oxidative stress and infectious pathology]. 779 23

We describe the haemodynamic and oxygen transport response in a patient undergoing exchange transfusion for severe falciparum malaria. We found that exchange transfusion produced a significant increase in left ventricular stroke work index, systemic oxygen delivery and oxygen consumption. This potentially beneficial effect of exchange transfusion has not been reported previously.
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PMID:Haemodynamic and oxygen transport response during exchange transfusion for severe falciparum malaria. 782 13

The role of oxidative stress resulting from production of reactive oxygen species and/or from suppression of the cellular antioxidant capacity in parasitic infections is shortly reviewed. The experimental part of the paper deals with the glutathione (GSH)--glutathione reductase (GR) system, a cornerstone of intracellular antioxidant defence mechanisms. For studying this system in parasitic diseases such as malaria new or modified methods are required. Total glutathione comprising GSH and glutathione disulphide (GSSG) in blood samples was assayed as follows. One volume of blood (> or = 10 microliters) is mixed with two volumes of 5% sulphosalicylic acid; after centrifugation (5 min, 10000 g), 10 microliters of supernatant is taken for spectrophotometric analysis using the 5,5'-dithiobis(2-nitrobenzoate) (DTNB)-glutathione recycling assay. When compared with the original method, the procedure reported here is more sensitive, less time-consuming, avoids unfavourable pH-values and leads to a sample which when frozen is stable for months. In a pilot study, the method was applied to 14 patients suffering from malaria caused by Plasmodium falciparum. The concentrations of erythrocyte glutathione were significantly decreased in the patients (1.42 +/- 0.47 mM, mean +/- SD) when compared to age- and sex-matched controls (2.11 +/- 0.45 mM, P < 0.01). The findings are contrasted with P. falciparum cultures in vitro where glutathione levels are known to be elevated. Based on the characteristics of GR a concept of determining the redox state of single cells is introduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Redox processes in malaria and other parasitic diseases. Determination of intracellular glutathione. 786 69

Recognition of the central role of iron in the generation of toxic, oxygen-derived species through the Haber-Weiss reaction, the ability of desferrioxamine (DFX) to prevent the damage associated with free radical generation in reperfusion injury, and its inhibitory effect on cell proliferation by inactivation of the iron dependent enzyme ribonucleotide reductase, resulted in an increasing number of studies exploring the novel therapeutic applications of iron chelating drugs: (a) Animal models of reperfusion injury have shown that DFX is able to decrease post-anoxic damage to the brain and heart as manifested in decreased infarct size and improved functional recovery. Iron chelators may be particularly useful in improving the preservation of organs intended for transplantation such as the heart, lung or kidney. (b) Anthracycline cardiotoxicity is aggravated by iron and inhibited by iron chelators. Because the mechanism of its antineoplastic effect differs from its cardiotoxic effect, it is possible to inhibit anthracycline cardiotoxicity without interfering with therapeutic efficacy. In vivo and in vitro animal studies have yielded encouraging results but much additional experimental work is still required before iron chelating therapy may be advocated for use in patients on anthracycline therapy. (c) Cell proliferation can be inhibited by iron chelators through the reversible inhibition of ribonucleotide reductase, a rate-limiting enzyme in DNA synthesis. This may be exploited for the treatment of malignant disease, and preliminary studies have already shown that DFX in combination with multidrug chemotherapy is effective in controlling neuroblastoma and other tumours. However, the contribution of DF to the overall clinical effect is unclear. Prospective controlled clinical studies are required in order to establish whether the antiproliferative, or cell synchronizing properties of DFX may be of practical usefulness in the control of malignant disease. (d) Control of protozoal infection: Experimental in vivo and in vitro models have shown that malarial infection may be inhibited by iron chelating therapy. This useful effect of DFX and other iron chelators is most probably related to ribonucleotide reductase inhibition. Clinical studies of asymptomatic P. falciparum malaria and of cerebral malaria have shown both an accelerated rate of parasite clearance and earlier recovery from coma. These observations lend new meaning to the term 'nutritional immunity' and open new channels for exploring the possibility of controlling infection by means of selective intracellular iron deprivation. Experimental models for studying the effect of iron chelators on other intracellular pathogens such as Toxoplasma gondii, Chlamydia psittaci, or Mycobacterium tuberculosis should be established.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Control of disease by selective iron depletion: a novel therapeutic strategy utilizing iron chelators. 788 Nov 62

Malaria causes a number of clinical complications, including diarrhoea. There are relatively few reports on the frequency of diarrhoea in malaria, but diarrhoea attributable to malaria is thought to be more common among children and nonimmune adults with hyperparasitaemia. The reported incidence of diarrhoea during malaria varies from 5 to 38%. The pathological changes in patients infected with malaria are very complex and involve many organs, including the small bowel. However, the causes of gastrointestinal manifestations during malaria are still not clear, and the mechanism of diarrhoea during malaria is likely to be multifactorial. Massive gastrointestinal bleedings with multiple foci of mucosal haemorrhage have also been observed. Tumor necrosis factor has been implicated in malaria and free oxygen radicals which can cause tissue injury in the liver, pancreas and intestine are enhanced during malaria infection; this can result in various disorders of the digestive system including diarrhoea and intestinal bleeding. Prostaglandins and cyclic AMP may also be involved in the development of diarrhoea in malaria.
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PMID:Malaria as a cause of diarrhoea--a review. 794 65

High levels of interleukin 1 alpha (IL-1 alpha) were detected in vitro, in murine peritoneal macrophages stimulated with Plasmodium vinckei exogenous antigens, and in vivo, in sera of P. vinckei-parasitized mice. Moreover, high production of IL-1 alpha mRNA could be detected by in situ hybridization analysis in spleen sections of mice during the course of P. vinckei malaria. The observed IL-1 alpha gene expression in the spleen was associated with the accumulation of F4/80+ macrophages in the red pulp and in the marginal zone of follicles, as well as with the relative proportions of Mac-1+ cells in the spleen and the capacity of spleen cells to produce reactive oxygen intermediates during murine malaria.
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PMID:Splenic interleukin 1 gene expression is associated with accumulation of macrophages and oxygen radical production in Plasmodium vinckei malaria. 796 3

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

Mefloquine (MQ) is highly effective in the treatment and prophylaxis of chloroquine-resistant Plasmodium falciparum malaria. Despite its widespread use, scant information is available on the transplacental profile and time course of MQ transfer across the human placenta. Six human placentas were perfused with human plasma for 180 min using recirculating maternal and fetal circuits. The viability of the placental preparation was validated measuring oxygen and carbon dioxide balance and the rates of glucose consumption and lactate production. MQ data were compared with antipyrine, a routine marker in placental perfusions. Disappearance of MQ from the maternal circulation after a dose of 0.8 mg/liter was biexponential, with a first, rapid distribution phase into the placental tissue. The apparent first-order distribution (lambda 1) and elimination (lambda z) rate constants were 0.043 +/- 0.014 min-1 and 0.020 +/- 0.007 min-1, respectively. The fetomaternal mass ratio became constant (0.46 +/- 0.07) after 120 min of perfusion and the time needed to achieve equal concentrations on both sides of the placenta was 178 +/- 31 min. MQ clearance was 3.36 +/- 0.38 ml/min. About 40% of the MQ maternal dose was recovered in tissue and 11% appeared in the fetal circulation. These data provide support for using MQ in pregnant women for both the treatment and prophylaxis of Plasmodium malaria, although comparison with other compounds are needed.
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PMID:Mefloquine transfer during in vitro human placenta perfusion. 816 35

Polymorphonuclear leukocytes are armed with an impressive arsenal of bactericidal agents that allow these cells to play a vital role in host defense against invading pathogens. However, these same agents can produce extensive cellular damage in host tissues when leukocytes are activated during inflammatory conditions. Recognition of this fact, when coupled with the observation that leukocyte adhesion to post-capillary venules is a critical first step in the inflammatory process, has led to the development of the concept that inhibition of neutrophil-endothelial cell adhesion (NECA) may represent a novel therapeutic strategy for the prevention of leukocyte-dependent injury in inflammatory conditions. Indeed, pharmacological or immunologic inhibition of NECA reduces cellular injury, dysfunction, and necrosis induced by ischemia/reperfusion, circulatory shock and resuscitation, organ transplantation, cardiopulmonary bypass, frostbite, and thermal trauma. NECA also appears to play an important role in the pathobiology of airway inflammation and asthma, pulmonary oxygen toxicity, arthritis, bacterial meningitis, and cerebral malaria. The aim of this review is to summarize the evidence implicating NECA in the pathogenesis of these inflammatory conditions.
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PMID:Role of neutrophil-endothelial cell adhesion in inflammatory disorders. 819 53


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