Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Making use of a model pair Aedes aegypti--Plasmodium gallinaceum, the authors assess the susceptibility of mosquito female survivors to malaria agent after treatment of larvae with various bioactive substances. Eight binary combinations of 6 preparations have been tried: dimilin and uvemon, insect development regulators; fundosol and copper sulfate, fungicides; phytobacteriomicin (PBM), a larvicidal antibiotic; bactoculicide, a bacterial agent. Combinations of PBM with compounds differing by their mechanisms of action were found to inhibit the specific effect of PBM on the vector, PBM specific effect consisting in depression of mosquito susceptibility to P. gallinaceum. PBM combinations with some agents may alter other parameters of the vector potential: combinations of copper sulfate or uvemon with low concentrations of PBM potentiated the larvicidal effect, and PBM mixtures with fungicides reduces the activity of female attacks.
 ...
PMID:[The susceptibility of mosquitoes for Plasmodium gallinaceum in the joint use of biologically active substances]. 143 76

Tumor necrosis factor and related cytokines are thought to be implicated in cell-mediated immunity and pathophysiology in malaria, but their mechanism of action has not been ascertained. Tumor necrosis factor has been reported to generate nitric oxide in vitro, so we have measured levels of this molecule and its products in the plasma of mice after they have received an injection of tumor necrosis factor, lymphotoxin, interleukin-1, gamma interferon, or interleukin-6, all of which have been reported to be increased in malaria. Total reactive nitrogen intermediate levels in plasma were assayed spectrophotometrically after exposing plasma to a copper-cadmium-zinc catalyst to convert nitrate to nitrite and then to Griess reagent. Tumor necrosis factor, lymphotoxin, and interleukin-1 all induced reactive nitrogen intermediates in vivo, with interleukin-1 showing the most activity. Tumor necrosis factor was then examined more closely. It induced more reactive nitrogen intermediates in malaria-infected mice than in normal mice, and appreciably more was in the form of nitrate than was in the form of nitrite. NG-methyl-L-arginine inhibited the in vivo generation of reactive nitrogen intermediates by tumor necrosis factor in a dose-dependent manner, implying that these molecules were arginine derived. These results are consistent with the possibility that tumor necrosis factor, lymphotoxin, and interleukin-1 may contribute to host pathology and parasite suppression through generation of nitric oxide.
 ...
PMID:In vivo induction of nitrite and nitrate by tumor necrosis factor, lymphotoxin, and interleukin-1: possible roles in malaria. 150 Jan 82

Micromolar concentrations of diethyldithiocarbamic acid (DDC) kill fungi, bacteria and malaria. DDC forms chelates with copper and the microbicidal effectiveness of this drug is enhanced greatly by small amounts of copper. DDC, in the presence of at least 1 molar equivalent of copper, also causes lysis of human erythrocytes. To explore the cytocidal actions of DDC and copper, we have used human erythrocytes and Escherichia coli as models. We found that: (1) the combination of DDC and copper also lysed E. coli spheroplasts, suggesting a possible common mechanism of hemolytic and microbicidal action; (2) higher ratios of drug: metal (greater than 4:1) diminished hemolytic and, as observed earlier, microbicidal effects; (3) cobalt, known to suppress the microbicidal effects of DDC:Cu, also prevented red cell lysis; (4) despite the necessary involvement of copper in DDC-mediated hemolysis, there was no evidence of oxidative damage to erythrocytes, and both lysis of erythrocytes and killing of E. coli were undiminished in the absence of oxygen; (5) the DDC:Cu chelate preferentially located in organic solvents and in membranes of erythrocytes. The chelate was quite soluble in chloroform but much less so in a C-16 hydrocarbon (hexadecane) which resembled erythrocyte membrane lipid. In hexadecane and at greater than 10(-4) M DDC and 5 x 10(-5) copper, an amphipathic drug:metal complex accumulated at the organic:aqueous interface; and (6) this amphipathic complex may permeabilize the lipid bilayer, causing leakage of ions and cell water and eventuating in colloid osmotic lysis. Red cells and E. coli exposed to the chelate showed early loss of intracellular rubidium (86Rb+). Furthermore, lysis of erythrocytes and E. coli spheroplasts was suppressed by the inclusion of either dextran or sucrose. Thus, it appears that DDC:Cu chelates are cytocidal by virtue of concentrating in the lipid bilayer and, perhaps, forming amphipathic complexes which disrupt membrane integrity. Drugs with similar behavior hold promise for therapy of malaria because metals capable of forming such complexes may accumulate within parasitized red cells.
 ...
PMID:Hemolytic and microbicidal actions of diethyldithiocarbamic acid. 184 82

Oxidative stress has been incriminated as a deleterious factor in the development of malaria parasites. Various chemical reductones which can undergo cyclic oxidation and reduction, such as ascorbate have been shown to cause oxidative stress to red blood cells. This, naturally-occurring and redox-active compound, can induce the formation of active oxygen derived species, such as superoxide radicals (.O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). The formation of the hydroxyl radical, the ultimate deleterious species, is mediated by the redox-active and available transition metals iron and copper in the Haber-Weiss reaction. During the development of the parasite, hemoglobin is progressively digested and a concurrent release of high levels of iron-containing breakdown products takes place within the red blood cell. Indications for the progressive increase in redox-active iron during the growth of P. falciparum have been recently found in our lab: a) adventitious ascorbate proved highly detrimental to the parasite when added to the mature forms. In contrast, if the parasitized erythrocytes were in the early phase following invasion, and only low levels of iron-containing structures had been liberated, then the observed effect was a small promotion of parasite development. b) erythrocytes containing mature parasites were more potent than erythrocytes containing ring forms as a source for redox-active iron in the ascorbate-driven metal-mediated degradation of DNA. The addition of extracts from parasitized erythrocytes and ascorbate to DNA caused a dose and time dependent DNA degradation. Non-infected erythrocytes had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Induction of oxidant stress by iron available in advanced forms of Plasmodium falciparum. 206 Aug 37

The effects of ascorbate and copper on the development of Plasmodium falciparum were studied in two modes: pretreatment of uninfected erythrocytes followed by infection by P. falciparum and treatment of parasitized erythrocytes. Pretreatment of G6PD(+) cells with ascorbate caused a slight enhancement in parasite development, while in G6PD(-) cells a suppressive effect on the plasmodia was demonstrated. Copper alone interfered with parasite growth in both cell types. The combination of copper and ascorbate arrested parasite maturation, an effect which was more pronounced in G6PD(-) cells. Synergism between copper and ascorbate was better demonstrated following the treatment of infected erythrocytes: while ascorbate alone supported parasite development and copper alone had only a marginal suppressive effect, the combination of copper and ascorbate yielded a marked inhibition of parasite growth. Ascorbate proved destructive to the parasites in the presence of adventitious copper, or on the second day of the parasite life cycle. In these cases it acted as a pro-oxidant, while in other systems, in particular in the presence of a chelator, ascorbate acted as an antioxidant and promoted parasite growth. The understanding of the role of transition metals and free radicals in parasite development and injury could shed light on novel approaches to fight malaria.
 ...
PMID:Deleterious synergistic effects of ascorbate and copper on the development of Plasmodium falciparum: an in vitro study in normal and in G6PD-deficient erythrocytes. 268 84

Administration of a combination of chloroquine and the copper-lysine complex, copper(lysine)(2), an inhibitor of microsomal monooxygenases, considerably decreased the parasitaemia level of mice infected with a chloroquine-resistant strain of Plasmodium berghei. When given separately, chloroquine and the complex had no antimalarial effect. Use of a combination of monooxygenase inhibitors and chloroquine therefore appears to be a promising addendum to the chemotherapy of malaria caused by chloroquine-resistant parasites.
 ...
PMID:Suppression of the chloroquine resistance of Plasmodium berghei by treatment of infected mice with a microsomal monooxygenase inhibitor. 311 94

A survey was carried out to establish baseline anthropometric and health data in the Wopkaimin, a small group of Mountain Ok-speaking hunter-horticulturalists who live in a remote and isolated part of the Highland fringe of Papua New Guinea, where a major gold and copper mine is being developed. Malaria is hyperendemic in the region and infant mortality has been estimated at approximately 230 per thousand. A 79% sample of the population was examined and the results of the anthropometric survey are reported. Wopkaimin childrens' heights and weights are well below the 50th percentile of British standards throughout growth; at maturity boys' weights and girls' heights and weights are at or below the 3rd percentile, and boys' weights are just above the 10th percentile. Wopkaimin children lag far behind British children in percentage of adult height achieved at all ages, and appear to attain maturity at least four years later. This relatively slow growth and short adult stature may represent an adaptive response to chronic nutritional deprivation, for which there is evidence from skinfold thickness and arm circumference measurements. Younger adults are significntly taller, heavier, fatter and more muscular than older adults; possible explanations for this are discussed. Within the sample, individuals living in villages less than a day's walk from the mine town are significantly taller, heavier and fatter than those living further away, and there are also similar significant anthropometric differences between employed and unemployed men. Ready food availability which has come with the mine development appears to be the most likely explanation for these differences. A continuing study of changing patterns of health and nutrition in the area has been initiated.
 ...
PMID:The Ok Tedi Health and Nutrition Project, Papua New Guinea: physique, growth and nutritional status of the Wopkaimin of the Star Mountains. 382 99

GTP cyclohydrolase (EC 3.5.4.16), the first enzyme in the pteridine pathway leading to the de novo formation of folic acid, has been identified and isolated from the human malaria parasite, Plasmodium falciparum. The enzyme was purified 200-fold by high performance size-exclusion chromatography on a TSK-G-3000 SW protein column. The molecular weight was estimated at 300 000. Optimal enzyme activity was observed at pH 8.0 and 42 degrees C. The Km for GTP was 54.6 microM. Products of the enzyme reaction were identified as the carbon-8 of GTP and D-erythro-dihydroneopterin triphosphate. ATP was a competitive inhibitor (Ki = 600 microM) of the enzyme. Activity of the enzyme was Mg2+-independent, whereas Mn2+, Cu2+ and Hg2+ (5 mM) were inhibitory. GTP cyclohydrolase activity was also identified in a murine parasite, Plasmodium berghei, and a simian parasite, Plasmodium knowlesi. Activity of the enzyme in P. knowlesi, an intrinsically synchronous quotidian parasite, was found to be dependent on the stage of parasite development.
 ...
PMID:Guanosine triphosphate cyclohydrolase in Plasmodium falciparum and other Plasmodium species. 390 34

Between July 1974 and June 1978 the diagnosis of haemolytic anaemia was made in 267 patients. Thalassaemia major was the leading cause (40-50%) every year except in 1977, when a sharp rise in drug induced haemolysis in G-6-PD deficient patients (61.3%) was encountered. This was possible due to an increase in incidence of vivax malaria and the use of anti-malarial drugs in that year. Abnormal haemoglobins were noted in 9.7% of the total number of patients. Hereditary spherocytosis, autoimmune haemolytic anaemias and paroxysmal nocturnal haemoglobinuria formed a minor cause. Others included copper sulphate poisoning, snake bite, hornet sting and Plasmodium falciparum infection.
 ...
PMID:Spectrum of haemolytic anaemias in Punjab, North India. 721 Jan 70

In the course of an investigation of hexosamine catabolism in the human malaria parasite, Plasmodium falciparum, it became apparent that a basic understanding of the relevant enzymatic reactions in the host erythrocyte is lacking. To acquire the necessary basic knowledge, we have determined the activities of several enzymes involved in hexosamine metabolism in normal human red blood cells. In the present communication we report the results of studies of glucosamine 6-phosphate deaminase (GlcN6-P) using a newly developed sensitive radiometric assay. The mean specific activity in extracts of fresh erythrocytes assayed within 4h of collection was 14.7 nmol/h/mg protein, whereas preparations from older erythrocytes that had been stored at 4 degrees C for up to 4 weeks had a mean specific activity of 6.2 nmol/h/mg. Characterization of the deaminase by chromatofocusing gave a pI of 8.55. The enzyme was optimally active at pH 9.0 and had a Km of 41 microM. The metal chelators EDTA and EGTA were non-inhibitory; however, inhibition was observed in the presence of metal ions, especially Cu2+, Ni2+ and Zn2+. In addition, the deaminase was also inhibited by several sugar phosphates including the reaction product, fructose 6-phosphate.
 ...
PMID:Glucosamine 6-phosphate deaminase in normal human erythrocytes. 757 55


1 2 3 4 5 6 Next >>