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

We have earlier shown that recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and methionine-enkephalin co-treatment can protect mice from malaria. We now report the bioimmunotherapeutic effect of rmGM-CSF and a synthetic enkephalin fragment peptide Tyr-Gly-Gly (TGG) co-treatment on blood-induced Plasmodium berghei infection in Swiss mice. Mice were completely aparasitimic following co-treatment with rmGM-CSF (10.0 microg/kg) and TGG (2.0 mg/kg x 3 per day, intraperitoneally (i.p.)) starting from day -1 to day +4; however, in monotherapy, neither of these agents showed any detectable bioimmunotherapeutic effect. Curiously, similar co-treatment with rmGM-CSF (10.0 microg/kg) and higher doses of TGG (10.0 mg/kg) did not protect the mice. The combined bioimmunotherapeutic effect of these agents was abrogated by the separate administration each of rabbit neutralizing anti-rmGM-CSF antibody, non-selective opioid receptor antagonist naltrexone (10.0 mg/kg x 6 per day, i.p.), and silica (3.0 mg per mouse, intravenously (i.v.)). The peritoneal and splenic macrophages from the protected mice showed a significant (P<0.05) increase in their pool-size and the phagocytic activity, ex vivo. Furthermore, the protected mice, as compared to the unprotected ones, showed a significant (P<0.05) maximum increase in their serum nitrate and nitrite, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) levels in their splenic homogenates, on the day before the beginning of the resolution of parasitaemia. Selective inhibitors of both inducible (aminoguanidine) and all forms (L-N(G)-monomethyl arginine) of nitric oxide (NO) synthase, significantly (P<0.05) augmented the mortality of co-treated mice, suggesting the role of NO in protection. These data show that, in P. berghei-infected mice, co-treatment with rmGM-CSF and conditional doses of TGG can impart protection, apparently through partly NO-dependent and macrophage-mediated mechanism(s).
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PMID:Bioimmunotherapy of rodent malaria: co-treatment with recombinant mouse granulocyte-macrophage colony-stimulating factor and an enkephalin fragment peptide Tyr-Gly-Gly. 1515 86

Malaria transmission is dependent upon many hydrology-driven ecological factors that directly affect the vectorial competence, including the presence of suitable habitats for the development of anopheline larvae. Larval habitats were identified and characterized at three malaria endemic villages (Ban Khun Huay, Ban Pa Dae, and Ban Tham Seau) in Mae Sot district, Tak Province, in northwestern Thailand between July 2002 and June 2003. The Global Positioning System (GPS) was used to provide precise locational data for the spatial distribution of anopheline mosquito larvae and their habitats. Ten habitat categories were identified. Eighteen adult Anopheles species were identified from larvae in all the surveyed habitats. An. minimus was the most common species throughout the year. The relationship between eight abiotic variables (temperature, hardness, carbon dioxide, dissolved oxygen, nitrate, phosphate, silica and pH) and the abundance of four major species of malaria vectors (An. (Cel.) dirus, An. (Cel.) minimus, An. (Cel.) maculatus, and An. (Cel.) sawadwongporni), and six species of non-vectors (An. (Cel.) kochi, An. (Cel.) jamesii, An. (Ano.) peditaeniatus, An. (Ano.) barbirostris, An. (Ano.) campestris, and An (Cel.) vagus) larvae was investigated. The results from the multiple regression models suggest that hardness, water temperature and carbon dioxide are the best predictor variables associated with the abundance of An. minimus larvae (p < 0.001); water pH for An. dirus larvae (p < 0.001); temperature and pH for An. kochi larvae (p < 0.01); temperature and silica concentration for An. jamesii larvae (p < 0.001); dissolved oxygen and silica concentration for An. campestris larvae (p < 0.001); and pH and silica concentration for An. vagus larvae (p < 0.001). We could not identify key environmental variables for An. maculatus, An. sawadwongporni, An. peditaeniatus, and An. barbirostris.
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PMID:Water quality and breeding habitats of anopheline mosquito in northwestern Thailand. 1590 41

Nitric oxide (NO) has toxic properties against Plasmodium falciparum. While high blood levels have been associated with protection against severe malarial disease, they may also contribute to the pathophysiology of cerebral malaria and severe anaemia. Promoter variants in the inducible nitric oxide synthase (iNOS) gene have been shown to influence NO concentrations and disease manifestation. However, findings are conflicting. We examined associations of plasma NO metabolites (NOx) with symptoms of severe malaria, particularly malarial anaemia and cerebral malaria, and with iNOS promoter variants. In 210 Ghanaian children with severe malaria, we measured plasma nitrite, nitrate, and S-nitrosothiol, and genotyped the iNOS promoter variants -954G-->C, -1173C-->T, and the -2.5 kb (CCTTT)(n) microsatellite. NOx levels decreased with age. In young children (<24 months), high NOx was associated with reduced parasite density. This was not seen in patients of 24-48 months of age and reversed in older children. Subgroup analysis revealed that in children with severe anaemia but without cerebral involvement (prostration, impaired consciousness, convulsions), high NOx levels correlated with low parasitaemia (P = 0.02). In these children, elevated NOx levels were also associated with the iNOS-954C-->T/(CCTTT)(8) haplotype (P = 0.03). No association between NOx or iNOS genotypes and cerebral malaria was observed. Our findings suggest that in young children with severe malaria NOx reduces parasitaemia. This effect wanes at higher ages and may reflect a predominance of unspecific immune responses to infection in early childhood. This finding may have importance for the understanding of associations between iNOS variants and severe malaria in regions of differing disease manifestation.
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PMID:Age-dependent effect of plasma nitric oxide on parasite density in Ghanaian children with severe malaria. 1596 Jul 6

We provide a global assessment, with detailed multi-scale data, of the ecological and toxicological effects generated by inorganic nitrogen pollution in aquatic ecosystems. Our synthesis of the published scientific literature shows three major environmental problems: (1) it can increase the concentration of hydrogen ions in freshwater ecosystems without much acid-neutralizing capacity, resulting in acidification of those systems; (2) it can stimulate or enhance the development, maintenance and proliferation of primary producers, resulting in eutrophication of aquatic ecosystems; (3) it can reach toxic levels that impair the ability of aquatic animals to survive, grow and reproduce. Inorganic nitrogen pollution of ground and surface waters can also induce adverse effects on human health and economy. Because reductions in SO2 emissions have reduced the atmospheric deposition of H2SO4 across large portions of North America and Europe, while emissions of NOx have gone unchecked, HNO3 is now playing an increasing role in the acidification of freshwater ecosystems. This acidification process has caused several adverse effects on primary and secondary producers, with significant biotic impoverishments, particularly concerning invertebrates and fishes, in many atmospherically acidified lakes and streams. The cultural eutrophication of freshwater, estuarine, and coastal marine ecosystems can cause ecological and toxicological effects that are either directly or indirectly related to the proliferation of primary producers. Extensive kills of both invertebrates and fishes are probably the most dramatic manifestation of hypoxia (or anoxia) in eutrophic and hypereutrophic aquatic ecosystems with low water turnover rates. The decline in dissolved oxygen concentrations can also promote the formation of reduced compounds, such as hydrogen sulphide, resulting in higher adverse (toxic) effects on aquatic animals. Additionally, the occurrence of toxic algae can significantly contribute to the extensive kills of aquatic animals. Cyanobacteria, dinoflagellates and diatoms appear to be major responsible that may be stimulated by inorganic nitrogen pollution. Among the different inorganic nitrogenous compounds (NH4+, NH3, NO2-, HNO2NO3-) that aquatic animals can take up directly from the ambient water, unionized ammonia is the most toxic, while ammonium and nitrate ions are the least toxic. In general, seawater animals seem to be more tolerant to the toxicity of inorganic nitrogenous compounds than freshwater animals, probably because of the ameliorating effect of water salinity (sodium, chloride, calcium and other ions) on the tolerance of aquatic animals. Ingested nitrites and nitrates from polluted drinking waters can induce methemoglobinemia in humans, particularly in young infants, by blocking the oxygen-carrying capacity of hemoglobin. Ingested nitrites and nitrates also have a potential role in developing cancers of the digestive tract through their contribution to the formation of nitrosamines. In addition, some scientific evidences suggest that ingested nitrites and nitrates might result in mutagenicity, teratogenicity and birth defects, contribute to the risks of non-Hodgkin's lymphoma and bladder and ovarian cancers, play a role in the etiology of insulin-dependent diabetes mellitus and in the development of thyroid hypertrophy, or cause spontaneous abortions and respiratory tract infections. Indirect health hazards can occur as a consequence of algal toxins, causing nausea, vomiting, diarrhoea, pneumonia, gastroenteritis, hepatoenteritis, muscular cramps, and several poisoning syndromes (paralytic shellfish poisoning, neurotoxic shellfish poisoning, amnesic shellfish poisoning). Other indirect health hazards can also come from the potential relationship between inorganic nitrogen pollution and human infectious diseases (malaria, cholera). Human sickness and death, extensive kills of aquatic animals, and other negative effects, can have elevated costs on human economy, with the recreation and tourism industry suffering the most important economic impacts, at least locally. It is concluded that levels of total nitrogen lower than 0.5-1.0 mg TN/L could prevent aquatic ecosystems (excluding those ecosystems with naturally high N levels) from developing acidification and eutrophication, at least by inorganic nitrogen pollution. Those relatively low TN levels could also protect aquatic animals against the toxicity of inorganic nitrogenous compounds since, in the absence of eutrophication, surface waters usually present relatively high concentrations of dissolved oxygen, most inorganic reactive nitrogen being in the form of nitrate. Additionally, human health and economy would be safer from the adverse effects of inorganic nitrogen pollution.
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PMID:Ecological and toxicological effects of inorganic nitrogen pollution in aquatic ecosystems: A global assessment. 1678 74

Malaria, a disease accounting for more than one million deaths per year, is caused by intraerythrocytic growth of Plasmodia. Parasitemia may be blunted by suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and phosphatidylserine exposure. Triggers of eryptosis include lead nitrate (Pb(NO3)2). As shown here, Pb(NO3)2 (> or = 10 microM) increased phosphatidylserine exposure of Plasmodium falciparum-infected human erythrocytes, an effect significantly more marked than in noninfected cells. Pb(NO3)2 treatment accelerated the clearance of erythrocytes from circulating blood. Parasitemia in Plasmodium berghei-infected mice was significantly decreased and mouse survival significantly enhanced by 100 microM Pb(NO3)2 (20 ppm) in drinking water. The treatment significantly increased reticulocyte number but did not significantly decrease erythrocyte number in noninfected mice and in infected animals mainly triggered the disappearance of P. berghei harbouring erythrocytes. In conclusion, Pb(NO3)2 accelerates eryptosis and subsequent clearance of infected erythrocytes and thus favourably influences the course of malaria.
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PMID:Lead decreases parasitemia and enhances survival of Plasmodium berghei-infected mice. 1788 70

Malaria remains an important health problem in tropical countries like Brazil. Thrombocytopenia is the most common hematological disturbance seen in malarial infection. Oxidative stress (OS) has been implicated as a possible mediator of thrombocytopenia in patients with malaria. This study aimed to investigate the role of OS in the thrombocytopenia of Plasmodium vivax malaria through the measurement of oxidant and antioxidant biochemical markers in plasma and in isolated platelets. Eighty-six patients with P. vivax malaria were enrolled. Blood samples were analyzed for total antioxidant and oxidant status, albumin, total protein, uric acid, zinc, magnesium, bilirubin, total thiols, glutathione peroxidase (GPx), malondialdehyde (MDA), antibodies against mildly oxidized low-density lipoproteins (LDL-/nLDL ratio) and nitrite/nitrate levels in blood plasma and GPx and MDA in isolated platelets. Plasma MDA levels were higher in thrombocytopenic (TCP) (median 3.47; range 1.55-12.90 micromol/L) compared with the non-thrombocytopenic (NTCP) patients (median 2.57; range 1.95-8.60 micromol/L). Moreover, the LDL-/nLDL autoantibody ratio was lower in TCP (median 3.0; range 1.5-14.8) than in NTCP patients (median 4.0; range 1.9-35.5). Finally, GPx and MDA were higher in the platelets of TPC patients. These results suggest that oxidative damage of platelets might be important in the pathogenesis of thrombocytopenia found in P. vivax malaria as indicated by alterations of GPx and MDA.
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PMID:The role of platelet and plasma markers of antioxidant status and oxidative stress in thrombocytopenia among patients with vivax malaria. 1894 18

To assess the hypothesis that nitric oxide (NO) is critical in the pathogenesis of cerebral malaria, we analyzed those single nucleotide polymorphisms (SNPs) and microsatellite (MS) of the promoter region of inducible nitric oxide synthase (iNOS) gene which are known to enhance the NO production in vivo. A total of 428 (204 severe, 224 mild) adult patients living in the eastern part of India were analyzed. The single nucleotide substitutions -954G-->C was found to be very rare, and -1173C-->T was absent in this population. But interestingly, longer forms of MS were found to be significantly associated with severe malaria (OR = 2.89, 95% CI = 1.955-4.295, P < 0.0001), and the linear regression analysis revealed that the risk of severe malaria significantly increases as the summed repeat number in an individual increase (OR = 1.16, P = 0.0013). Further, the median plasma level of nitrate/nitrite (NOx) was observed to be high in mild patients compared to severe patients, and the level of parasitemia was significantly low among mild patients than severe ones. These findings suggest that the CCTTT repeats in iNOS may play a key role in the pathogenesis of severe malaria.
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PMID:The CCTTT pentanucleotide microsatellite in iNOS promoter influences the clinical outcome in P. falciparum infection. 1915 66

To explore the hypothesis that susceptibility to cerebral malaria is influenced by genetic variation in endothelial nitric oxide synthase (eNOS), we genotyped three commonly defined polymorphic loci of eNOS, Glu(298)-->Asp, intron 4 variable number of tandem repeat region, and T-786-->C, in 244 patients (mean age, 36.2 years) with mild malaria and 194 patients (mean age, 35.6 years) with severe malaria belonging to same ethnic group in Orissa, an eastern Indian state. We found that there was an association of the Glu(298)-->Asp substitution (P = 0.0037; odds ratio, 1.95; 95% confidence interval, 1.2 to 3.0) and a single unique haplotype defined by "C-b-Asp" (P(corrected) = 0.0024) for protection against cerebral malaria. Further, the median plasma level of nitrite-nitrate was found to be increased in individuals with the Glu(298)-->Asp substitution and was significantly higher in the mild malaria group (P <or= 0.0001), but the increase was not significant in the severe malaria group (P = 0.0528). These findings suggest that the Glu(298)-->Asp substitution and the "C-b-Asp" haplotype may enhance eNOS expression and NO production, which leads to protection against cerebral malaria. These findings may increase our understanding of the pathogenesis of malaria.
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PMID:Endothelial nitric oxide synthase gene polymorphisms and Plasmodium falciparum infection in Indian adults. 1936 39

Glutathione reductase (GR), is responsible for the existence of GSH molecule, a crucial antioxidant against oxidative stress reagents. The antimalarial activities of some redox active compounds are attributed to their inhibition of antioxidant flavoenzyme glutathione reductase, and inhibitors are therefore expected to be useful for the treatment of malaria. Twelve organic nitrate derivatives were synthesized and treated with human erythrocyte GR. The molecules were identified as strong GR inhibitors and novel antimalaria candidates.
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PMID:In vitro inhibition of human erythrocyte glutathione reductase by some new organic nitrates. 1944 20

The global rate of heavy metal pollution is rapidly increasing in various habitats. Anopheles malaria vector species (Diptera: Culicidae) appear to tolerate many aquatic habitats with metal pollutants, despite their normal proclivity for 'clean' water (i.e. low levels of organic matter). Investigations were conducted to establish whether there are biological costs for tolerance to heavy metals in Anopheles gambiae Giles sensu stricto and to assess the potential impact of heavy metal pollution on mosquito ecology. Anopheles gambiae s.s. were selected for cadmium, copper or lead tolerance through chronic exposure of immature stages to solutions of the metals for three successive generations. Biological costs were assessed in the fourth generation by horizontal life table analysis. Tolerance in larvae to cadmium (as cadmium chloride, CdCl(2)), copper [as copper II nitrate hydrate, Cu(NO(3))(2) 2.5 H(2)O] and lead [as lead II nitrate, Pb(NO(3))(2)], monitored by changes in LC(50) concentrations of the metals, changed from 6.07 microg/L, 12.42 microg/L and 493.32 microg/L to 4.45 microg/L, 25.02 microg/L and 516.69 microg/L, respectively, after three generations of exposure. The metal-selected strains had a significantly lower magnitude of egg viability, larval and pupal survivorship, adult emergence, fecundity and net reproductive rate than the control strain. The population doubling times were significantly longer and the instantaneous birth rates lower in most metal-selected strains relative to the control strain. Our results suggest that although An. gambiae s.s. displays the potential to develop tolerance to heavy metals, particularly copper, this may occur at a significant biological cost, which can adversely affect its ecological fitness.
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PMID:Biological cost of tolerance to heavy metals in the mosquito Anopheles gambiae. 2037 78


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