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)

Plasmodium falciparum contains a family of 21-base-long repetitive DNA sequences in its genome. A 21-base synthetic DNA oligomer, formerly labelled with phosphorus-32 for autoradiographic detection of P falciparum DNA, was covalently coupled to alkaline phosphatase for histochemical detection. The conjugate (PFR1-AP) detected purified P falciparum DNA with a sensitivity and specificity equal to that of 32P-labelled probes after 2-day exposures. PFR1-AP did not detect host DNA or DNA of other Plasmodium species. In African blood specimens PFR1-AP specifically detected P falciparum infections of 100 parasites/microliter. This sensitive, rapid, nonisotopic probe will allow more widespread use of DNA hybridisation in the diagnosis of malaria.
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PMID:Use of enzyme-linked synthetic DNA in diagnosis of falciparum malaria. 288 32

Mefloquine is currently the drug-of-choice for malaria prophylaxis among military personnel. Four active duty military personnel receiving 250 mg mefloquine per week were killed in the line of duty under combat conditions. Samples of blood, bile, liver, kidney, muscle, brain, spleen and lung were submitted to the Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, for routine toxicologic analysis. Qualitative screening revealed only the presence of ethanol (< 25 mg/dl, probably attributable to postmortem formation) and mefloquine. Quantitation of mefloquine was performed using an HP 5880 gas chromatograph equipped with a nitrogen/phosphorus detector. The column was an HP-5 cross-linked 5% phenyl methyl silicone fused silica capillary column (15 m x 0.25 mm i.d. x 0.25 microns film thickness). The temperature program began at 110 degrees C, was held for 1 min and ramped at 20 degrees C/min to 200 degrees C, held for 1 min and then ramped at 10 degrees C/min to 280 degrees C and held for 10 min. Mefloquine elutes with a relative retention time similar to that of the tricyclic antidepressants. No postmortem data concerning mefloquine concentrations or tissue distribution was available. Quantitated blood concentrations in the presented cases were greater than the expected therapeutic values indicating the possibility of postmortem redistribution of this drug. No mefloquine overdoses were identified in the literature making comparison to the postmortem therapeutic concentrations impossible at this time.
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PMID:Mefloquine distribution in postmortem cases. 795 78

We have previously shown that infection with Plasmodium yoelii malaria or injection of extracts from malaria-parasitized red cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in mice made moderately diabetic with streptozotocin. Inositol phosphoglycans (IPGs) are released outside cells by hydrolysis of membrane-bound glycosylphosphatidylinositols (GPIs), and act as second messengers mediating insulin action. The C57BL/Ks-db/db and C57BL/6J-ob/ob mice offer good models for studies on human obesity and Type 2 diabetes. In the present study, we show that a single iv injection of IPG-A or IPG-P extracted from P. yoelii significantly (P < 0.02) lowers the blood glucose in STZ-diabetic, db/db, and in ob/ob mice for at least 4--6 h. Using rat white adipocytes, IPG-P increased lipogenesis by 20--30% in the presence and absence of maximal concentrations of insulin (10(-8) M) (P < 0.01) and stimulated pyruvate dehydrogenase (PDH) phosphatase in a dose-related manner. Both IPG-A and IPG-P inhibited c-AMP-dependent protein kinase (PKA) in a dose-related manner. Compositional analysis of IPGs after 24 h hydrolysis revealed the presence of myo-inositol, phosphorus, galactosamine, glucosamine, and glucose in both IPG-A and IPG-P. However, hydrolysis of IPGs for 4 h highlighted differences between IPG-A and IPG-P. There are some functional similarities between P. yoelii IPGs and those previously described for mammalian liver. However, this is the first report of the hypoglycemic effect of IPGs in murine models of Type 2 diabetes. We suggest that IPGs isolated from P. yoelii, when fully characterized, may provide structural information for the synthesis of new drugs for the management of diabetes mellitus.
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PMID:Reversal of type 2 diabetes in mice by products of malaria parasites. II. Role of inositol phosphoglycans (IPGs). 1146 Nov 92

The reaction of 2-nitrobenzaldehyde with methyl propiolate and ammonium acetate in acetic acid yields 2,6-dinor-nifedipine (1a) and the isomeric rac. 1,4-dihydropyridine (DHP) 1b. The DHP 1 are dehydrogenated both chemically and by anodic oxidation using a rotating platinum electrode (RPE) by means of differential pulse voltammetry (DPV) affording the corresponding pyridines 2a, b. Compound 1a is more stable, while compound 1b is less stable than nifedipine. Irradiation of the DHP 1 with UV-A light forms the nitrosophenyl-pyridines 3, which cyclize after addition of conc. hydrochloric acid to yield the chloro substituted hydroxamic acids 4a, b. The hydroxamic acids 4c, d are obtained treating 2a, b with zinc in acetate buffer pH 4.6. The hydroxamic acids 4b, d demonstrate only a moderate inhibition of 5-lipoxygenase (5-LOX) of human whole blood compared with the activity of the reference compound zileutone. The formation of 15-HETE is also inhibited. Compound 4a reduces the activity of cyclooxygenase. The lactames 5, obtained from the hydroxamic acids 4 by desoxygenation with phosphorus trichloride, react with phosphoryl chloride to give compounds 6, representing educts for potential agents against malaria.
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PMID:[Benzo[c][2,7]naphthyridines from 2,6-dinor-nifedipine and its dimethyl 2,5-dicarboxylate isomer]. 1496 15

Although acidocalcisomes have been well characterized morphologically in other apicomplexan parasites, no such characterization has been done in Plasmodium spp. Here, we report that Plasmodium falciparum merozoites possess electron-dense organelles rich in phosphorus and calcium, as detected by X-ray microanalysis of intact cells, which are similar to the acidocalcisomes of other apicomplexans, but of more irregular form. In agreement with these results malaria parasites possess large amounts of short- and long-chain polyphosphate (polyP), which are associated with acidocalcisomes in other organisms. PolyP levels were highest in the trophozoite stage of the parasite. Treatment of isolated trophozoites with chloroquine resulted in a significant hydrolysis of polyP. Taken together, these results provide evidence that acidocalcisomes from Plasmodium falciparum do not differ significantly from acidocalcisomes of other apicomplexan parasites.
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PMID:Polyphosphate content and fine structure of acidocalcisomes of Plasmodium falciparum. 1552 30

Anthropogenic land use changes often alter natural patterns of disease transmission. The goal of this study was to determine whether phosphorus input from sugarcane, Saccharum officinarum L., cultivation in northern Belize could pose a significant environmental impact on malaria transmission by changing vegetation structure and composition of wetlands and associated larval habitats. Our primary focus was on the increased dominance of cattail, Typha domingensis Pers., a favored habitat for Anopheles vestitipennis Dyar & Knab. A land cover classification based on satellite imagery was used to select 20 marshes impacted by agricultural runoff and 20 marshes surrounded by forest (nonimpacted). A 100-m transect was established into each of the 40 marshes. Water, vegetation, and larval sampling were conducted at the 0-, 10-, 25-, 50-, and 100-m locations along the transect. Analyses of larval density data indicated that Anopheles albimanus Wiedemann was negatively correlated with percentage of cover of Typha (R2 = 0.39, P < 0.001) but positively correlated with sparse Eleocharis cellulosa Torr. (rush) cover (R2 = 0.19, P < 0.05) and presence of cyanobacterial mats (CBM) (R2 = 0.33, P < 0.0001). An. vestitipennis was found to be positively correlated with percentage of cover of Typha (R2 = 0.19, P < 0.001). Canonical correspondence analysis identified CBM and light as the variables associated with the presence of An. albimanuts larvae, Typha cover with An. vestitipennis larvae, and Eleocharis and absence of light with Anopheles crucians (Wiedemann). A positive correlation also existed between marshes adjacent to agricultural activities and presence of An. vestitipennis (R2 = 0.37, P < 0.05). These results indicate that marshes in proximity to agricultural fields are conducive for Typha growth, thereby providing habitat for the more efficient malaria vector
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PMID:Distribution of Anopheles albimanus, Anopheles vestitipennis, and Anopheles crucians associated with land use in northern Belize. 1673 24

Hypophosphatemia occurs in 40 to 60% of patients with acute malaria, and in many other conditions associated with elevations of body temperature. To determine the prevalence and causes of hypophosphatemia in patients with malaria, we retrospectively studied all adults diagnosed with acute malaria during a 12-year period. To validate our findings, we analyzed a second sample of malaria patients during a subsequent 10-year period. Serum phosphorus correlated inversely with temperature (n = 59, r = -0.62; P<0.0001), such that each 1 degrees C increase in body temperature was associated with a reduction of 0.18 mmol/L (0.56 mg/dL) in the serum phosphorus level (95% confidence interval: -0.12 to -0.24 mmol/L [-0.37 to -0.74 mg/dL] per 1 degrees C). A similar effect was observed among 19 patients who had repeat measurements of serum phosphorus and temperature. In a multiple linear regression analysis, the relation between temperature and serum phosphorus level was independent of blood pH, PCO2, and serum levels of potassium, bicarbonate, calcium, albumin, and glucose. Our study demonstrates a strong inverse linear relation between body temperature and serum phosphorus level that was not explained by other factors known to cause hypophosphatemia. If causal, this association can account for the high prevalence of hypophosphatemia, observed in our patients and in previous studies of patients with malaria. Because hypophosphatemia has been observed in other clinical conditions characterized by fever or hyperthermia, this relation may not be unique to malaria. Elevation of body temperature should be added to the list of causes of hypophosphatemia.
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PMID:Fever as a cause of hypophosphatemia in patients with malaria. 1815 56

Natural products containing carbon-phosphorus bonds (phosphonic and phosphinic acids) have found widespread use in medicine and agriculture. Recent years have seen a renewed interest in the biochemistry and biology of these compounds with the cloning of the biosynthetic gene clusters for several family members. This review discusses the commonalities and differences in the molecular logic that lie behind the biosynthesis of these compounds. The current knowledge regarding the metabolic pathways and enzymes involved in the production of a number of natural products, including the approved antibiotic fosfomycin, the widely used herbicide phosphinothricin (PT), and the clinical candidate for treatment of malaria FR-900098, is presented. Many of the enzymes involved in the biosynthesis of these compounds catalyze chemically and biologically unprecedented transformations, and a wealth of new biochemistry has been revealed through their study. These investigations have also suggested new strategies for natural product discovery.
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PMID:Biosynthesis of phosphonic and phosphinic acid natural products. 1948 22

Worldwide increases in human and wildlife diseases have challenged ecologists to understand how large-scale environmental changes affect host-parasite interactions. One of the most profound changes to Earth's ecosystems is the alteration of global nutrient cycles, including those of phosphorus (P) and especially nitrogen (N). Along with the obvious direct benefits of nutrient application for food production, anthropogenic inputs of N and P can indirectly affect the abundance of infectious and noninfectious pathogens. The mechanisms underpinning observed correlations, however, and how such patterns vary with disease type, have long remained conjectural. Here, we highlight recent experimental advances to critically evaluate the relationship between environmental nutrient enrichment and disease. Given the interrelated nature of human and wildlife disease emergence, we include a broad range of human and wildlife examples from terrestrial, marine, and freshwater ecosystems. We examine the consequences of nutrient pollution on directly transmitted, vector-borne, complex life cycle, and noninfectious pathogens, including West Nile virus, malaria, harmful algal blooms, coral reef diseases, and amphibian malformations. Our synthetic examination suggests that the effects of environmental nutrient enrichment on disease are complex and multifaceted, varying with the type of pathogen, host species and condition, attributes of the ecosystem, and the degree of enrichment; some pathogens increase in abundance whereas others decline or disappear. Nevertheless, available evidence indicates that ecological changes associated with nutrient enrichment often exacerbate infection and disease caused by generalist parasites with direct or simple life cycles. Observed mechanisms include changes in host/vector density, host distribution, infection resistance, pathogen virulence or toxicity, and the direct supplementation of pathogens. Collectively, these pathogens may be particularly dangerous because they can continue to cause mortality even as their hosts decline, potentially leading to sustained epidemics or chronic pathology. We suggest that interactions between nutrient enrichment and disease will become increasingly important in tropical and subtropical regions, where forecasted increases in nutrient application will occur in an environment rich with infectious pathogens. We emphasize the importance of careful disease management in conjunction with continued intensification of global nutrient cycles.
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PMID:Linking environmental nutrient enrichment and disease emergence in humans and wildlife. 2034 28

It is now being realized that irradiation products of natural bioactive agents can also be beneficially utilized to impart value addition in agriculture by converting these bioactive agents into more useful form. Polysaccharides, such as sodium alginate, have proven to be wonderful growth promoting substances in their depolymerized form for various plants. Artemisinin has been increasingly popular as an effective and safe alternative therapy against malaria; also proved effective against the highly adaptable malaria parasite, which has already become resistant to many other drugs. The drug artemisinin can be extracted from the leafy tissues of Artemisia annua. Therefore, experiments were conducted with an aim to evaluate artemisinin production and overall plant development though depolymerized sodium alginate application and nutrient supply. In the present study, sodium alginate, irradiated by Co-60 gamma rays together with various phosphorus doses, was used to study their effect on growth, physiological and biochemical processes and production of artemisinin in A. annua. Among various applied doses of phosphorus fertilizer, P40 (40 kg Pha(-1)) together with ISA80 (80 mg L(-1)) significantly improved all the parameters studied. Increase in plant height as well as weight was noted at this treatment. Dry leaf yield, artemisinin concentration in leaves and artemisinin yield was also significantly enhanced by the treatment.
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PMID:Effect of irradiated sodium alginate and phosphorus on biomass and artemisinin production in Artemisia annua. 2490 72


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