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)

Previous studies have shown depressed serum corrected calcium and phosphate concentrations in acute falciparum malaria. To characterize malaria-associated disturbances in mineral homoeostasis further, serum ionized calcium and intracellular phosphate were measured in 18 patients (10 with falciparum malaria, 8 with vivax malaria) and 10 healthy controls. Six patients (4 falciparum, 2 vivax) had admission serum ionized calcium concentrations below the absolute control range (< 1.15 mmol/litre) and a further six (3 falciparum, 3 vivax) developed ionized hypocalcaemia during treatment. The patients with falciparum malaria had the lowest values at presentation (median [95% confidence intervals in brackets]: 1.17 [1.12-1.23] vs. 1.20 [1.18-1.24] mmol/litre in controls, P = 0.035) in the presence of depressed simultaneous serum parathormone concentrations (1.2 [0.6-1.9] vs. 1.6 [1.1-2.6] pmol/litre; P = 0.05). Admission serum phosphate concentrations were lower in the malaria patients (P = 0.007 vs. controls), especially in those with falciparum malaria (0.85 [0.7-1.1] vs. 1.2 [1.1-1.3] mmol/litre in controls; P = 0.002); patients with falciparum malaria also had significantly lower intracellular phosphate than controls (0.74 [0.58-0.90] vs. 0.88 [0.66-1.04] mmol/litre red cells; P = 0.047). There was a weak association between serum corrected and ionized calcium in the malaria patients (rs = 0.31, n = 18, P > 0.1), but serum and intracellular phosphate correlated significantly (rs = 0.71, n = 17, P < 0.001) with a regression line slope of 0.49 and intercept of 0.27 mmol/litre of red cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum ionized calcium, serum and intracellular phosphate, and serum parathormone concentrations in acute malaria. 846 94

This study was designed to confirm that low dietary riboflavin does not contribute to the flavin-deficient red blood cells commonly found in subjects in Ferrara Province, northern Italy. In this area it is primarily an inherited characteristic believed to have been selected for by malaria, which was endemic from the 12th century. In parallel with assessment of daily riboflavin intake (DRI), flavin adenine dinucleotide-dependent glutathione reductase (EGR) and flavin mononucleotide-dependent pyridoxine phosphate oxidase (PPO) were measured in beta-thalassemic heterozygotes, their normal relatives, and normal spouses (representative of the normal population). In all of these groups there is a high incidence of deficiency of these flavin enzymes. We found that the majority had an adequate riboflavin intake and there was no significant correlation of EGR and PPO activities with DRI. Thus, interpretation of low EGR activity is discussed with reference to studies of EGR done to detect nutritional riboflavin deficiency in countries where there is malnutrition and endemic malaria.
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PMID:Low red blood cell glutathione reductase and pyridoxine phosphate oxidase activities not related to dietary riboflavin: selection by malaria? 848 Jun 84

A sensitive, selective and rapid reversed-phase high-performance liquid chromatographic method was developed for the simultaneous analysis of dapsone, monoacetyldapsone and pyrimethamine in human whole blood and plasma. The procedure involved extraction of the compounds and the internal standard, monopropionyldapsone, with tert.-butylmethyl ether under alkaline conditions. A newly marketed column, Supelcosil LC-ABZ (Supelco, 15 cm x 4.6 mm I.D.), was employed. The mobile phase, consisting of acetonitrile-methanol-phosphate buffer (2:1:7, v/v/v), was delivered at a flow-rate of 1.2 ml/min, and ultraviolet absorbance was monitored at 286 nm. The limit of determination using a 150-microliters sample was 10 ng/ml (40 nM) for dapsone and pyrimethamine and 8 ng/ml (28 nM) for monoacetyldapsone. Given that only a small amount of blood is required in this method, it could now be applied in studies involving blood level monitoring and pharmacokinetics in children on Maloprim (dapsone-pyrimethamine) prophylaxis in malaria endemic areas.
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PMID:Simultaneous determination of dapsone, monoacetyldapsone and pyrimethamine in whole blood and plasma by high-performance liquid chromatography. 849 23

Phospholipid-containing antigens of malaria parasites stimulate macrophages to secrete tumour necrosis factor (TNF), induce hypoglycaemia and are toxic to mice. This TNF induction is inhibited by antisera made against the antigens, the inhibitory activity of which can be removed specifically by adsorption to phosphatidylinositol (PI) liposomes. Although the same was true of antisera made against PI, the inhibitory activity of antisera made against some other phospholipids appeared to be directed against a common determinant, probably the phosphate ester head group. We have shown previously that the activity of all the antisera was associated mainly with IgM and was not boosted by repeated injections of the antigens. To try and induce a secondary response against the parasite antigens using non-toxic molecules, mice were immunized with various phosphorylated compounds coupled to keyhole limpet haemocyanin (KLH). Three injections of PI-KLH or of phosphatidylserine (PS) coupled to KLH induced significantly higher titres of inhibitory antibody than one; furthermore, the inhibitory activity was mainly in the IgG fraction. The antisera did not inhibit TNF induction by lipopolysaccharide (LPS) or lipoteichoic acid. However, antisera against PS-KLH, though not PI-KLH, inhibited the induction of TNF by the phospholipid, platelet-activating factor (PAF). These antisera, and antisera from mice immunized with phospho-threonine or galactosamine-1-phosphate conjugated to KLH, contained inhibitory antibodies of differing specificities. Mice immunized with PI-KLH, PS-KLH or phospho-threonine-KLH did not develop hypoglycaemia when challenged with the parasite toxic antigens. These results indicate that the antigenicity of non-toxic analogues can be dramatically enhanced by coupling to a protein carrier.
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PMID:Phospholipids coupled to a carrier induce IgG antibody that blocks tumour necrosis factor induction by toxic malaria antigens. 850 34

The pathways of glucose utilization for energy production in the malaria parasite, Plasmodium falciparum, have been studied extensively. Little is known, however, about the reactions by which glucose is converted into complex carbohydrates in the parasite, and knowledge of the catabolism of these substances is likewise scanty. The present investigation was undertaken to determine whether the parasites possess a key enzyme of glucosamine catabolism, i.e. glucosamine 6-phosphate deaminase (EC 5.3.1.40), which catalyses the conversion of the sugar phosphate to fructose 6-phosphate and ammonia. Lysates of Plasmodium-infected erythrocytes had substantially higher deaminase activity than control samples from normal erythrocytes, and an even higher specific activity was observed in extracts of isolated parasites, amounting to 20-40 times that of uninfected cells. Anion exchange chromatography indicated that the parasite deaminase eluted in a retarded position when compared to the elution profile of the erythrocyte enzyme. The charge difference suggested by these findings was established more directly by chromatofocusing, which indicated pI values of 6.85 and 8.55 for the parasite and erythrocyte deaminases, respectively. Other differences were also observed, notably a greater thermolability on the part of the parasite enzyme. These results indicated that the parasites synthesize a specific deaminase that is distinct from the normal erythrocyte enzyme. Studies on synchronized parasite cultures further indicated that the parasite deaminase is developmentally regulated, because a dramatic increase in activity levels occurred during the later stages of parasite development.
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PMID:Glucosamine 6-phosphate deaminase in Plasmodium falciparum. 855 58

We review here some recent data about glucose-6-phosphate dehydrogenase (G6PD), the first and key regulatory enzyme of the pentose phosphate pathway. New evidence has been presented to suggest that malaria is a selective agent for G6PD deficiency, which is the most common enzymopathy in man, and that G6PD deficiency, generally considered to be a mild and benign condition, is significantly disadvantageous in certain environmental conditions. At the molecular level, the enzyme structure has recently been elucidated and mechanisms regulating G6PD gene expression have been determined. A G6PD knock-out mutation introduced in mouse cells makes them exquisitely sensitive to oxidative stress, indicating that this ubiquitous metabolic enzyme has a major role in the defence against oxidative stress, even in eukaryotic nucleated cells, which have several alternative routes for providing the same protection. Because of the high prevalence of G6PD deficiency in many populations, it is expected that these findings will prompt further studies to ascertain the putative role of G6PD deficiency in conditions such as carcinogenesis and ageing.
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PMID:A new lease of life for an old enzyme. 876 Mar 36

Along the western shore of Lake Kivu in eastern Zaire, Katana health zone's primary health care (PHC) development plan established a pilot community trial in 1987 in 12 villages. It concerned community health workers (CHW) who provide chloroquine phosphate (25 mg/kg) treatment over 3 days for episodes of fever (i.e., presumed malaria attacks). A socioeconomically comparable area about 30 km south of the intervention area with the same malarial ecology and malariometric indices served as the control area. Malaria treatment continued to be offered at the health center only in the control area. Both areas were peninsulas. Villagers selected a literate volunteer to serve as the malaria CHW. CHWs received 2 weeks of in-service training in the area's health center. They charged no consultation fees. Malaria prevalence and incidence fell 50% in the intervention area, a significant decline. The crude parasitological index and high parasitemia index declined by 5- and 6-fold, respectively, in the intervention area compared to 2-fold in the control area. Even though mortality rates fluctuated in both areas, they remained essentially the same in both areas. The population in the intervention area had adopted important health care behavior. For example, the number of malaria episodes that remained untreated decreased 7%, while it increased 8% in the control area. In the intervention area, the number of cases treated at home and by the CHW increased 16% and use of the informal private sector fell markedly (-23%). Thus, more than 65% of malaria episodes were treated at the community level. There were problems revolving around the non-comprehensiveness of CHWs' care and their unclear position in the health care system. The major problems concerned the lack of a long-term commitment to CHWs on the part of the health care system and the failure to achieve real community participation. Even though malaria morbidity and parasitological indices were reduced and health care behavior improved, the problems compromised the sustainability of the intervention.
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PMID:Using community health workers for malaria control: experience in Zaire. 882 65

The frequency and clinical characteristics of plasmodium infection were reported in 420 renal transplant recipients who were followed in the Transplantation Unit and Out-Patient Clinic of the Medical School of Istanbul. Plasmodium infection was diagnosed in eleven (9 male, 2 female) of the 420 patients (2.6%). Ten of the patients were transplanted in India, and one in our institution. The mean duration between the transplantation and the diagnosis of malaria was 21.7 + 44.4 days in patients who were transplanted in India. All of the patients were taking triple immunosuppressive drugs (CsA, AZA, PRED). Plasmodium falciparum was diagnosed in 6 patients, P vivax in 1 patient and P malariae in 1 patient. Also mixed infection with P falciparum and P malariae was diagnosed in 3 patients. After definite diagnosis, the patients were hospitalized. Chloroquine phosphate plus primaquine phosphate was administered for P vivax infection, whereas chloroquine phosphate alone was given for P falciparum and P malariae infection as a first line antimalarial therapy. As a result of therapy, infection improved clinically and the plasmodia disappeared rapidly from the thick blood film in 10 of the patients. Severe hemolysis and acute renal failure developed in one patient, who improved after hemodialysis therapy and exchange transfusions. It was concluded that malaria is quite a frequent infection of transplant recipients who get their allografts from donors living in high-risk areas, and all transplant recipients having this kind of transplantations should be suspected and examined for malaria. This may help to diagnose and treat the complication in the early period, thus resulting in an improved prognosis for this potentially life-threatening complication of the posttransplant period.
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PMID:Posttransplant malaria. 895 86

The major pathways of glucose metabolism in the malaria parasite, Plasmodium falciparum, have now been elucidated, and the structures and properties of parasite-specific enzymes are presently being investigated. Little is known, however, about the enzymes catalysing monosaccharide interconversions in the parasite. In the present investigation we have examined the pathway of N-acetylglucosamine catabolism which, in higher organisms, involves the following reaction sequence: N-acetylglucosamine -->N-acetylglucosamine 6-phosphate-->glucosamine 6-phosphate-->fructose 6-phosphate. Assay of the specific kinase (E.C. 2.7.1.59) catalysing the phosphorylation of the sugar showed that the enzyme is present in Plasmodium extracts as well as in normal human erythrocytes; specific activities of 7.2 and 5.3 nmol/h/mg protein were measured for the parasite and erythrocyte extracts, respectively, N-Acetylglucosamine 6-phosphate deacetylase (E.C. 3.5.1.25), catalysing the second reaction, was also detected in both normal and Plasmodium-infected erythrocytes. At 75% parasitaemia, the deacetylase activity was close to 3 times higher than that of normal control cells. The erythrocyte deacetylase was purified approximately 16,000-fold by chromatography on DE52 cellulose, chromatofocusing, and size exclusion chromatography. Attempts to purify the parasite enzyme by the same procedures were unsuccessful due to loss of activity. A partially purified erythrocyte deacetylase preparation (eluted from DE52 cellulose) had a pH optimum of 7.5, a pI of 6.0, as indicated by chromatofocusing, and a K(m) of 29 microM. In conjunction with previous investigations, the present study indicated that all three enzymes required for N-acetylglucosamine utilization are present in Plasmodium parasites as well as in normal erythrocytes.
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PMID:N-acetylglucosamine kinase and N-acetylglucosamine 6-phosphate deacetylase in normal human erythrocytes and Plasmodium falciparum. 898 40

Sixty-nine children aged between 6 and 60 months with parasitologically proven Plasmodium falciparum malaria were treated with chloroquine (2.5 mg/kg) in the Children's Emergency Room of the University of Calabar Teaching Hospital (UCTH) in 1993. Thirty subjects (mean age 27.8 months) and 39 (mean age 29.5 months) received chloroquine phosphate suppository (Pharma Deko) and chloroquine sulphate syrup (May & Baker), respectively. The World Health Organization (WHO) 14-day in vivo field test was used in evaluating the response to treatment. In both treatment groups the responses were similar. Overall, parasitological cure occurred in 24 subjects (34.8%) and in the remaining 45 subjects (65.2%) treatment failed (chloroquine resistance). This level of chloroquine resistant Plasmodium falciparum (CRPF) is higher than 53.6% reported in this centre in 1989. Furthermore, in the present study the proportion of RII (46.4%) is significantly higher than 21.4% (P < 0.02) obtained in 1989. Our findings show a worsening of CRPF in Calabar with RII being the main contributor. This observation indicates the need for continued surveillance of the response of P. falciparum to chloroquine and alternative antimalarials as a means of evolving an effective treatment policy for malaria.
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PMID:Chloroquine-resistant Plasmodium falciparum among children in Calabar, south eastern Nigeria. 922 7


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