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

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

There is now wide acceptance of the concept that the similarity between many acute infectious diseases, be they viral, bacterial, or parasitic in origin, is caused by the overproduction of inflammatory cytokines initiated when the organism interacts with the innate immune system. This is also true of certain noninfectious states, such as the tissue injury syndromes. This review discusses the historical origins of these ideas, which began with tumor necrosis factor (TNF) and spread from their origins in malaria research to other fields. As well the more established proinflammatory mediators, such as TNF, interleukin-1, and lymphotoxin, the roles of nitric oxide and carbon monoxide, which are chiefly inhibitory, are discussed. The established and potential roles of two more recently recognized contributors, overactivity of the enzyme poly(ADP-ribose) polymerase 1 (PARP-1) and the escape of high-mobility-group box 1 (HMGB1) protein from its normal location into the circulation, are also put in context. The pathogenesis of the disease caused by falciparum malaria is then considered in the light of what has been learned about the roles of these mediators in these other diseases, as well as in malaria itself.
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PMID:Pathogenesis of malaria and clinically similar conditions. 1525 91

Chloroquine is an antimalarial drug that has been used in the treatment and prophylaxis of malaria since the 1950s. The present study was undertaken to examine the effects of chloroquine on Bcap-37 human breast cancer cells' growth, cell cycle modulation, apoptosis induction, and associated molecular alterations in vitro. The chloroquine treatment decreased the viability of Bcap-37 cells in a concentration- and time-dependent manner, which correlated with G(2)/M phase cell cycle arrest. The chloroquine-mediated cell cycle arrest was associated with a decrease in protein levels/activity of polo-like kinase 1 (Plk1), phosphorylated cell division cycle 25C (Cdc25C), phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated Akt. The chloroquine-treated Bcap-37 cells exhibited a marked decrease in the level of mitochondrial transmembrane potential (DeltaPsim), which was accompanied by the activation of caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Exposure of Bcap-37 cells to chloroquine also resulted in the induction of spindle abnormalities. In conclusion, the findings in this study suggested that chloroquine might have potential anticancer efficacy, which could be attributed, in part, to its proliferation inhibition and apoptosis induction of cancer cells through modulation of apoptosis and cell cycle-related proteins expressions, down-regulation of mitochondrial transmembrane potential (DeltaPsim), and induction of spindle abnormalities.
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PMID:Cell growth inhibition, G2/M cell cycle arrest, and apoptosis induced by chloroquine in human breast cancer cell line Bcap-37. 1908 25

As a derivative of artemisinin, dihydroartemisinin is effective in the treatment of malaria. Dihydroartemisinin has been identified to possess inhibitory effects in numerous types of animal model with tumors, indicating that it has an antineoplastic effect. The aim of the present study was to analyze the potential anticancer effects of dihydroartemisinin, particularly its effect on apoptosis of colon cancer cells. In the present study, it was identified that dihydroartemisinin inhibited cell viability, promoted cell apoptosis, increased B-cell lymphoma-2-associated X-protein expression, increased caspase-3/9 activities, decreased poly(ADP-ribose) polymerase levels, decreased phosphorylation of extracellular-signal-regulated kinase, and increased phosphorylation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase in colon cancer cells. Conversely, the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was suppressed by dihydroartemisinin in colon cancer cells. These results demonstrate that the potential anticancer effects of dihydroartemisinin may increase apoptosis of colon cancer cells through targeting JAK2/STAT3 signaling.
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PMID:Dihydroartemisinin increases apoptosis of colon cancer cells through targeting Janus kinase 2/signal transducer and activator of transcription 3 signaling. 2943 95