Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemokines are a superfamily of small proteins secreted primarily by leukocytes and related by a conserved four-cystein motif. In the present study we investigated the serum levels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) and interleukin-8 (IL-8). MIP-1 alpha is a neutrophil chemotactic protein important in acute and chronic inflammation. Recent studies demonstrated that MIP-1 alpha may also act as potent inhibitor of hemopoetic stem cell proliferation, which may be important in the development of prolonged anemia in patients suffering from Plasmodium falciparum malaria. IL-8 serum concentrations correlate with severity and outcome of infectious diseases. Moreover, recent reports indicate that IL-8 plays a major role in fatal gram-negative sepsis. It was the aim of this study to investigate the time course of MIP-1 alpha and IL-8 concentrations in patients suffering from acute P. falciparum infection. Blood samples of 20 patients suffering from severe P. falciparum malaria were investigated. MIP-1 alpha and IL-8 concentrations were determined using ELISA technique at admission, on Days 7, 14, 21, and 28. Maximal concentrations of MIP-1 alpha and IL-8 were found on Day 14, at a time when parasites were not detected in the smears. The serum levels of IL-8 on the day of admission were correlated to the parasite count. No correlation was seen between the hematokrit values and the MIP-1 alpha concentrations at any time.
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PMID:Serum concentrations of MIP-1 alpha and interleukin-8 in patients suffering from acute Plasmodium falciparum malaria. 760 66

Some clinical manifestations of severe malaria resemble those of sepsis and there may be mediators of the host response that are common to both sepsis and malaria. Phospholipase A2 (PLA2), a proinflammatory enzyme whose expression is induced by tumor necrosis factor (TNF), has been implicated in the pathogenesis of complications of the sepsis syndrome. We examined levels of circulating PLA2 in Plasmodium falciparum malaria and studied the association of PLA2 with disease severity. Plasma PLA2 and TNF were measured in 75 Malawian children with P. falciparum malaria. The mean (SD) plasma PLA2 activity in children with acute malaria was 53,804 (37,256) units/ml as compared with 424 (349) units/ml in 34 healthy controls (P < 0.00001). The mean PLA2 activity in 45 convalescent patients was 2,546 (7,372) units/ml (P < 0.00001). In 48 patients with pretreatment PLA2 activity less than 60,000 units/ml, mortality was 8.3%, while in 27 patients with pretreatment PLA2 levels greater than 60,000 units/ml, mortality was 33.3% (P = 0.008). There were significant correlations between PLA2 and TNF (r = 0.471, P < 0.01), density of parasitemia (r = 0.443, P < 0.0001) and a decrease in hematocrit (r = 0.352, P < 0.005). These data show that P. falciparum malaria is associated with a markedly increased circulating PLA2, especially in patients with severe disease, as manifested by high parasite burden, anemia, coma, and death.
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PMID:Increased serum phospholipase A2 activity in Malawian children with falciparum malaria. 821 74

Fatal Plasmodium falciparum malaria is accompanied by systemic endothelial activation. To study endothelial activation directly during malaria and sepsis in vivo, the expression of cell adhesion molecules on dermal microvascular endothelium was examined in skin biopsies and correlated with plasma levels of soluble (circulating) ICAM-1, E-selectin, and VCAM-1 and the cytokine tumor necrosis factor (TNF)-alpha. Skin biopsies were obtained from 61 cases of severe malaria, 42 cases of uncomplicated malaria, 10 cases of severe systemic sepsis, and 17 uninfected controls. Systemic endothelial activation, represented by the up-regulation of inducible cell adhesion molecules (CAMs) on endothelium and increased levels of soluble CAMs (sCAMs), were seen in both severe and uncomplicated malaria and sepsis when compared with uninfected controls. Plasma levels of sICAM-1, sVCAM-1, and sE-selectin correlated positively with the severity of malaria whereas TNF-alpha was raised nonspecifically in malaria and sepsis. Immunohistochemical evidence of endothelial activation in skin biopsies did not correlate with sCAM levels or disease severity. This indicates a background of systemic endothelial activation, which occurs in both mild and severe malaria and sepsis. The levels of sCAMs in malaria are thus not an accurate reflection of endothelial cell expression of CAMs in a particular vascular bed, and other factors must influence their levels during disease.
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PMID:Systemic endothelial activation occurs in both mild and severe malaria. Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity. 962 52

Falciparum malaria remains a major killer in developing countries, particularly for African children. The sequestration of parasitized erythrocytes in the deep microvasculature is mostly mediated by their cytoadherence to activated endothelium. Proinflammatory cytokines and particularly tumor necrosis factor contribute to severe disease but the pathophysiology of coma remains poorly understood. In young children, features of severe malaria include severe anemia, hypoglycemia and cerebral malaria. Half of the children with neurological impairment actually have raised intracranial pressure, and seizures are extremely common. Clinical respiratory distress usually reflects severe lactic acidosis. In non immune adults, pictures of severe sepsis with shock, acute renal failure and respiratory distress syndrome are common and often associated with bacterial coinfection. Although chemotherapy of malaria is challenged by the continuing evolution of antimalarial resistance, quinine remains the first-line drug for severe disease. The optimization of symptomatic management of severe malaria remains a major concern in developing countries.
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PMID:[Severe malaria]. 978 Oct 74

Levels of procalcitonin (ProCT) have been found to be elevated in individuals with severe bacterial infections such as sepsis and peritonitis, and this correlates well with the severity of the disease. Recently, increased levels have been described in melioidosis and Plasmodium falciparum malaria. In this study ProCT levels were measured in 27 Thai patients with complicated malaria before and during/after treatment with artesunate and mefloquine. Initial parasite counts averaged 290,680/microl (range = 533-1,147,040). On admission, ProCT levels were elevated in all but one patient (median = 40 ng/ml, range = 0.04-662, normal values < 0.5 ng/ml). With treatment, levels decreased to 1.3 ng/ml (range = 0.01-6.5). Nitrite/nitrate levels in patients were higher than in controls throughout the study. The ProCT levels correlated with initial parasite density (P < 0.05), which is a marker of disease severity, and with nitrite/nitrate levels (P < 0.05). Based on the changes of ProCT levels over the course of the disease a possible role in the acute-phase reaction seems likely.
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PMID:Serum procalcitonin levels in severe Plasmodium falciparum malaria. 988 89

Falciparum malaria remains a major killer in developing countries, particularly for African children. Moreover, France is the leading European country in term of incidence of imported malaria. Parasitized erythrocytes, which can form rosettes or auto-agglutinate, are sequestrated in the deep microvasculature and stick to activated endothelium by the mean of various receptors. Activation of T lymphocytes and macrophages induces secretion of proinflammatory cytokines, including tumour necrosis factor, which contributes to severe disease. However, the pathophysiology of coma remains poorly understood. In nonimmune adults, besides cerebral malaria, pictures of severe sepsis with shock, acute renal failure and respiratory distress syndrome are common. Although chemotherapy of malaria is challenged by the continuing evolution of antimalarial resistance, quinine remains the first-line drug for severe imported disease. In addition, early symptomatic management in the intensive care unit setting is of paramount importance. Prevention of severe imported malaria lays on prophylactic measures during travel, as well as adequate management of uncomplicated disease after return. In developing countries, early and adequate treatment of uncomplicated disease using cheap alternatives to classical compounds should contribute to "roll back" malaria, particularly in sub-Saharan Africa.
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PMID:[Severe malaria]. 1134 66

Falciparum malaria is a complex disease with no simple explanation, affecting organs where the parasite is rare as well as those organs where it is more common. We continue to argue that it can best be understood in terms of excessive stimulation of normally useful pathways mediated by inflammatory cytokines, the prototype being tumor necrosis factor (TNF). These pathways involve downstream mediators, such as nitric oxide (NO) that the host normally uses to control parasites, but which, when uncontrolled, have bioenergetic failure of patient tissues as their predictable end point. Falciparum malaria is no different from many other infectious diseases that are clinically confused with it. The sequestration of parasitized red blood cells, prominent in some tissues but absent in others with equal functional loss, exacerbates, but does not change, these overriding principles. Recent opportunities to stain a wide range of tissues from African pediatric cases of falciparum malaria and sepsis for the inducible NO synthase (iNOS) and migration inhibitory factor (MIF) have strengthened these arguments considerably. The recent demonstration of bioenergetic failure in tissue removed from sepsis patients being able to predict a fatal outcome fulfils a prediction of these principles, and it is plausible that this will be demonstrable in severe falciparum malaria. Understanding the disease caused by falciparum malaria at a molecular level requires an appreciation of the universality of poly(ADP-ribose) polymerase-1 (PARP-1) and Na(+)/K(+)-ATPase and the protean effects of activation by inflammation of the former that include inactivation of the latter.
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PMID:The pathophysiology of falciparum malaria. 1288 13

Severe Plasmodium falciparum malaria encompasses a complex syndrome affecting many organs and causing physiological perturbations that have many features in common with children with sepsis. Among these, metabolic acidosis has emerged as a central feature of severe malaria and is the best independent predictor of a fatal outcome in both adults and children. There is now clear evidence that intravascular hypovolaemia (shock) is common in children with malarial acidosis. How it should be treated presents a therapeutic dilemma because acidosis often coexists with impaired consciousness (cerebral malaria). We summarize the results of recent clinical trials examining the safety and efficacy of volume expansion in children with 'cerebral malaria' complicated by acidosis.
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PMID:Acidosis of severe falciparum malaria: heading for a shock? 1563 35

A 56-year-old man presented to a peripheral hospital in New Zealand with severe Plasmodium falciparum malaria with cerebral involvement and subsequently developed multi-system organ failure. Activated protein C was used in an attempt to stop the cascade of events into multi-organ failure. Severe infection with P. falciparum is life-threatening and appears to activate a hypercoagulable state similar to that of severe sepsis. Activated protein C is currently used in the treatment of severe sepsis and may provide a new adjuvant therapy for severe P. falciparum malaria.
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PMID:The use of activated protein C in severe Plasmodium falciparum malaria. 1759 Nov 42

Falciparum malaria infection influences blood coagulation by various interacting pathobiological mechanisms, the most important being the overwhelming response of the host to sepsis resulting in a cytokine storm. In addition, the parasite infects the red cells leading to changes in the red cell phospholipid composition which supports blood coagulation. Red cells infected with Plasmodium falciparum also adhere to deeper tissue capillary endothelium leading to profound damage to endothelial cells leading to further activation. This results in widespread consumption of platelets and activation of blood coagulation which at times culminates in a clinically and pathologically detectable disseminated intravascular coagulation (DIC). Monocyte-macrophage system also gets activated in this infection compounding the hypercoagulable state. Heavy parasitaemia leading to occlusion of hepatic microcirculation leads to abnormalities in synthesis and secretion of coagulation factors and their inhibitors. Drugs used in the treatment for falciparum malaria can cause thrombocytopaenia, bone marrow suppression and haemolytic anaemia, all of which can interfere indirectly with blood coagulation. Microparticle formation from platelets, red cells and macrophages also causes widespread activation of blood coagulation, and this recently observed mechanism is the focus of intense research in many other inflammatory and neoplastic conditions where there is activation of blood coagulation system. Thus, in severe falciparum malaria, there is activation of blood coagulation system along with thrombocytopaenia, even before widespread DIC and coagulation failure occur.
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PMID:Blood coagulation in falciparum malaria--a review. 1806 97


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