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)

Peripheral gangrene, characterized by distal ischemia of the extremities, is a rare complication in patients with falciparum malaria. Patients with this complication have generally undergone early amputation of the affected areas. In this report, we describe 3 adult Thai patients presented at the Hospital for Tropical Diseases, Bangkok, with high grade of fever ranged 6-9 days, jaundice, acute renal failure, respiratory failure, alteration of consciousness and shock. Two patients had gangrene developed at the lower extremities on day 1 of hospitalization and 1 patient had gangrene developed on day 3. Blood smears revealed hyperparasitemia with Plasmodium falciparum. These patients were diagnosed as having severe malaria with peripheral gangrene. The resolution of gangrene was successfully achieved by treatment with artesunate and conservative treatment in 2 of 3 cases.
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PMID:Peripheral gangrene in patients with severe falciparum malaria: report of 3 cases. 1680 62

Although neurological symptoms associated with cerebral malaria (CM) are largely reversible, recent studies suggest that lasting neurological sequelae can occur. This may be especially true for children, in whom persistent deficits include problems with memory and attention. Because the malaria parasite is not thought to enter the brain parenchyma, lasting deficits are likely related to factors including the host response to disease. Studies with a rodent model, and with human postmortem tissue, suggest that glial activation occurs with CM. In this review, the authors will highlight studies focused on such activation in CM. Likely causes will be discussed, which include ischemia and activation of blood brain barrier endothelial cells. The potential consequences of glial activation will also be discussed, highlighting the possibility that glial-derived proteinases contribute to structural damage of the central nervous system (CNS). Of note, for the purposes of this focused review, glial activation will refer to the activation of astrocytes and microglial cells; discussion of oligodendroglial cells will not be included. In addition, although events thought to be critical to the pathogenesis of CM and glial activation will be covered, a comprehensive review of cerebral malaria will not be presented. Excellent reviews are already available, including Coltel et al (2004; Curr Neurovasc Res 1: 91-110), Medana and Turner (2006; Int J Parasitol 36: 555-568), and Hunt et al (2006; Int J Parasitol 36: 569-582).
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PMID:Glial activation and matrix metalloproteinase release in cerebral malaria. 1745 43

Severe falciparum malaria (SM) is associated with tissue ischemia related to cytoadherence of parasitized erythrocytes to microvascular endothelium and reduced levels of NO and its precursor, l-arginine. Endothelial function has not been characterized in SM but can be improved by l-arginine in cardiovascular disease. In an observational study in Indonesia, we measured endothelial function using reactive hyperemia-peripheral arterial tonometry (RH-PAT) in 51 adults with SM, 48 patients with moderately severe falciparum malaria (MSM), and 48 controls. The mean RH-PAT index was lower in SM (1.41; 95% confidence interval [CI] = 1.33-1.47) than in MSM (1.82; 95% CI = 1.7-2.02) and controls (1.93; 95% CI = 1.8-2.06; P < 0.0001). Endothelial dysfunction was associated with elevated blood lactate and measures of hemolysis. Exhaled NO was also lower in SM relative to MSM and controls. In an ascending dose study of intravenous l-arginine in 30 more patients with MSM, l-arginine increased the RH-PAT index by 19% (95% CI = 6-34; P = 0.006) and exhaled NO by 55% (95% CI = 32-73; P < 0.0001) without important side effects. Hypoargininemia and hemolysis likely reduce NO bioavailability. Endothelial dysfunction in malaria is nearly universal in severe disease, is reversible with l-arginine, and likely contributes to its pathogenesis. Clinical trials in SM of adjunctive agents to improve endothelial NO bioavailability, including l-arginine, are warranted.
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PMID:Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria. 1795 70

Adherence of parasitized erythrocytes to activated endothelium causes microvascular obstruction, tissue ischemia, and clinical complications in severe malaria (SM); however, the mechanisms leading to endothelial activation remain unclear. The angiogenic factors, angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) are modulators of endothelial activation, with Ang-2 release from Weibel-Palade bodies (WPBs) being regulated by endothelial nitric oxide (NO). We explored the relationships between endothelial NO bioavailability, Ang-2, VEGF, tissue perfusion, and clinical outcomes in SM. We measured plasma Ang-2 and VEGF, together with biomarkers of severity from 146 adults with and without SM, in parallel with longitudinal measures of endothelial function by using reactive hyperemia peripheral arterial tonometry (a measure of endothelial NO bioavailability). Regression was used to relate concentrations of Ang-2/VEGF with malaria disease severity, biomarkers of perfusion, endothelial activation, and parasite biomass. The longitudinal relationship between Ang-2 and endothelial function was assessed by using a mixed-effects model. Ang-2 concentrations were elevated in SM and associated with increased venous lactate, plasma intercellular cell adhesion molecule-1 concentrations, parasite biomass, and mortality. In contrast, VEGF concentrations were inversely associated with these biomarkers. Ang-2 concentrations were significantly better predictors of death than venous lactate (P = 0.03). Recovery of endothelial function was associated with falling concentrations of Ang-2. Ang-2 release from endothelial cells with reduced NO bioavailability is likely to contribute to endothelial activation, sequestered parasite biomass, impaired perfusion, and poor outcome in severe falciparum malaria. Agents that improve endothelial NO, reduce WPB exocytosis, and/or antagonize Ang-2 may have therapeutic roles in SM.
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PMID:Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. 1895 36

Several diseases, such as malaria, sickle cell disease, and ischemia/reperfusion may cause excessive formation of hemin, which may in turn trigger hemolysis. A variety of drugs and diseases leading to hemolysis triggers suicidal erythrocyte death or eryptosis, i.e., cell membrane scrambling and cell shrinkage. Eryptosis is elicited by increased cytosolic Ca(2+) activity and by ceramide. The present study explored whether hemin stimulates eryptosis. Cell membrane scrambling was estimated from annexin V-binding to phosphatidylserine exposed at the cell surface, cell shrinkage from forward scatter in fluorescence-activated cell sorter analysis, cytosolic Ca(2+) activity from Fluo3 fluorescence and ceramide formation from fluorescence-labeled antibody binding. Exposure to hemin (1-10 microM) within 48 h significantly increased annexin V-binding, decreased forward scatter, increased cytosolic Ca(2+) activity, and stimulated ceramide formation. In conclusion, hemin stimulates suicidal cell death, which may in turn contribute to the clearance of circulating erythrocytes and thus to anemia.
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PMID:Hemin-induced suicidal erythrocyte death. 1918 15

A dysregulated host immune response, as opposed to the intrinsic virulence of a microbial pathogen induces a large part of the pathology seen in infectious diseases. However, current therapies are designed to target the pathogen rather than the underlying pathogenic mechanisms responsible for the manifestation of the pathology. Recent studies have highlighted the role of endothelial cell alteration in the pathology induced in sepsis and cerebral malaria. The endothelial onslaught described, is similar to that seen during ischemia reperfusion in stroke. Protecting endothelial cell membranes during sepsis and cerebral malaria, using citicoline in the same way as in stroke, has thus emerged as a new strategy that needs to be evaluated urgently. Citicoline is a natural compound that is registered for use in ischemic stroke, head trauma and neurological disorders. It enters the phosphatidylcholine synthesis pathway as a rate-limiting step and is involved in the modulation of a large number of metabolic pathways and neurotransmitter levels, and also in the biosynthesis of phospholipids in neuronal membranes. This short review highlights the potential role of citicoline as part of adjunct therapy in the treatment of infectious diseases.
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PMID:Citicoline (CDP-choline): What role in the treatment of complications of infectious diseases. 1940 Nov 46

This paper reviews our studies concerning imaging analysis of the brain in a primate model of cerebral malaria. To elucidate the clinical features of cerebral malaria, we performed positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) scanning and magnetic resonance imaging (MRI) of the brain in Japanese macaques (Macaca fuscata) infected with Plasmodium coatneyi, a primate model of severe human malaria with cerebral involvement. On FDG-PET scanning, we observed diffuse and heterogeneous reduction of metabolism in the cerebral cortex in the acute phase of malaria infection. Although the monkey exhibited severe clinical signs, MR imaging did not reveal any significant changes during the course of infection. Histopathologic examination frequently revealed preferential sequestration of PRBCs in the cerebral and cerebellum capillaries, but neither parenchymal injury nor neuronal necrosis was found in the tissues. These results suggest that heterogeneous metabolic reduction and lack of abnormalities on MRI in the acute phase of CM may be due to any avoidance mechanisms from ischemia caused by sequestration. This may be one reason why more than half of CM patients have no neurological sequelae following recovery.
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PMID:Imaging analysis of the brain in a primate model of cerebral malaria. 1946 18

In tropical countries, malaria and hypertension are common diseases of pregnancy. They have physiopathologic similarities such as placental ischemia, endothelial dysfunction, and production of proinflammatory cytokines. Recent findings suggested their possible link. The authors conducted a case-control study to explore the relation between malaria and hypertension at Guediawaye, a hypoendemic malarial setting in Senegal. Cases were pregnant women admitted to the delivery unit for hypertension. Controls were pregnant women admitted for normal delivery, without any history of hypertension or proteinuria during the present pregnancy. Malarial infection was determined by placental tissue examination. From January to December 2002, 77 cases of gestational hypertension, 113 cases of preeclampsia, 59 cases of eclampsia, and 241 controls were enrolled. Placental malarial infection (PMI) was present in 14 cases (6.3%) and in 15 controls (6.2%). The prevalence of PMI was 4.6% for eclampsia, 4.0% for preeclampsia, and 11.6% for gestational hypertension. In multivariate analysis, PMI appeared to be an independent risk factor for gestational hypertension (adjusted odds ratio = 2.7, 95% confidence interval: 1.0, 7.6). The authors found an association between PMI and nonproteinuric hypertension in women living in a malaria-hypoendemic area. The exact significance of such relation should be clarified in further studies in different settings of malarial endemicity.
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PMID:Placental malarial infection as a risk factor for hypertensive disorders during pregnancy in Africa: a case-control study in an urban area of Senegal, West Africa. 1967 49

Rapid advances in the field of nanotechnology promise revolutionary improvements in the diagnosis and therapy of neuroinflammatory disorders. An array of iron oxide nano- and microparticle agents have been developed for in vivo molecular magnetic resonance imaging (mMRI) of cerebrovascular endothelial targets, such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and the glycoprotein receptor GP IIb/IIIa expressed on activated platelets. Molecular markers of glioma cells, such as matrix metalloproteinase-2 (MMP-2), and markers for brain tumor angiogenesis, such as alpha (v) beta (3) integrin (alpha(v)beta(3)), have also been successfully targeted using nanoparticle imaging probes. This chapter provides an overview of targeted, iron oxide nano- and microparticles that have been applied for in vivo mMRI of the brain in experimental models of multiple sclerosis (MS), brain ischemia, cerebral malaria (CM), brain cancer, and Alzheimer's disease. The potential of targeted nanoparticle agents for application in clinical imaging is also discussed, including multimodal and therapeutic approaches.
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PMID:Chapter 4 - Applications of nanotechnology in molecular imaging of the brain. 2030 29

Malaria is one of the most common causes of febrile illness in travelers. Coinfections with bacterial, viral, and fungal pathogens may not be suspected unless a patient fails to respond to malaria treatment. Using novel immunohistochemical and molecular techniques, Plasmodium falciparum, Clostridium perfringens, and Candida spp. coinfections were confirmed in a German traveler to Haiti. Plasmodium falciparum-induced ischemia may have increased this patient's susceptibility to C. perfringens and disseminated candidiasis leading to his death. When a patient presents with P. falciparum and shock and is unresponsive to malaria treatment, secondary infections should be suspected to initiate appropriate treatment.
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PMID:Fatal Plasmodium falciparum, Clostridium perfringens, and Candida spp. Coinfections in a Traveler to Haiti. 2033 63


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