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)

Marasmus and kwashiorkor are clinically distinct manifestations of severe malnutrition. This study tested the hypothesis that rates of whole-body protein synthesis and breakdown are higher in marasmus than in kwashiorkor during acute infection. We measured whole-body protein kinetics using stable isotope tracers in eight children with marasmus and acute infection (pneumonia or malaria) to determine the rate of appearance of urea and leucine in plasma. Serum concentrations of total protein, albumin, and C-reactive protein were also measured. These findings were compared with those reported previously for 13 children with kwashiorkor (including marasmic kwashiorkor) and acute infection who were studied with the same methods. HIV infection was present in 10 of 21 children. Rates of protein breakdown and synthesis were higher in marasmus than in kwashiorkor (227 +/- 59 compared with 103 +/- 30 micromol leucine x kg(-1) x h(-1) and 216 +/- 60 compared with 97 +/- 30 micromol leucine x kg(-1) x h(-1), P < 0.001). The concentration of globulin (total protein minus albumin) was higher in marasmus than kwashiorkor (40 +/- 17 compared with 25 +/- 7 g/L, P < or = 0.01), but C-reactive protein was not different (73 +/- 79 compared with 83 +/- 89 mg/L). HIV infection and body composition did not explain the differences between marasmus and kwashiorkor. The accelerated rate of protein turnover in children with marasmus and acute infection requires further investigation.
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PMID:Whole-body protein kinetics in marasmus and kwashiorkor during acute infection. 962 94

The ionophore properties of cationomycin and monensin were studied on human erythrocytes by measuring Na+ influx by 23Na NMR and concomitant K+ efflux by potentiometry in the presence of increasing amounts of serum. Both ion currents (Na+ or K+) decreased linearly with the reciprocal of serum amount. The serum effects on ion currents were stronger with cationomycin than with monensin. Assuming this decreased transport activity was due to drug binding to serum proteins, a partition coefficient between the protein and the membrane phase was determined for each ionophore by using a novel model. This partition coefficient is about 30 times higher for cationomycin than for monensin; the same result was obtained with purified human serum albumin, indicating that albumin may be the major ionophore binding protein of serum. In parallel, we also measured IC50 for 50% in vitro growth inhibition of Plasmodium falciparum, the agent of malaria. In the presence of increasing serum concentrations, the antimalarial activity was decreased for both ionophores. Serum effect was less severe for monensin than for cationomycin, in agreement with the weaker interaction of monensin with proteins as shown from the partition coefficient values. A correlation was established between the ion transport currents (sodium and potassium) and the IC50 measured on P. falciparum in the presence of the various concentrations of serum. The relative value of the ion transport currents (expressed as percentage of control in absence of serum) can be indicative of the ionophore unbound fraction in the medium.
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PMID:Cationomycin and monensin partition between serum proteins and erythrocyte membrane: consequences for Na+ and K+ transport and antimalarial activities. 1006 60

Kidney function was studied in 80 Gambian children with cerebral malaria, 73 children with mild malaria, and in 19 children with other febrile illnesses. Serum creatinine was measured, and the excretion in urine of immunoglobulin G, transferrin, albumin and alpha 1 microglobulin was determined. Twenty-five percent of children with cerebral malaria, and 4% of children with mild malaria had an elevated serum creatinine above 62 mumol/l. Increased urinary protein excretion was frequent: 53% of children with cerebral malaria had a glomerulo-tubular pattern of protein excretion, and 46% a tubular pattern. Median albuminuria was 68 mg/l in children with cerebral malaria, 18 mg/l in children with mild malaria, and 9 mg/l in febrile children with other diseases (P < 0.0001). There was no significant association between the proteinuria and height of fever or the degree of parasitaemia, and there was no significant association between death and signs of renal impairment. Renal involvement is common in children with malaria in The Gambia, with prerenal, glomerular, and tubulo-interstitial factors contributing. It is more pronounced in children with cerebral malaria than in those with mild malaria. However, renal dysfunction is relatively mild and does not indicate a worse prognosis.
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PMID:Renal involvement in Gambian children with cerebral or mild malaria. 1040 76

To assess the extent of oxidative stress in erythrocytes of patients with acute Plasmodium falciparum malaria, erythrocyte thiobarbituric acid-reactive substance (ETBAR), and intracellular, membrane and extracellular antioxidants were estimated in 102 cases of P. falciparum malaria and 50 control subjects. The mean concentration of ETBAR was significantly higher (P < 0.001) and many of the antioxidants were significantly lower in patients than controls. Among the erythrocyte antioxidants, catalase, reduced glutathione (GSH) and tocopherol were significantly lower in the patients (P < 0.05, 0.001, 0.001, respectively). Erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were not reduced to a statistically significant level. Similarly, the plasma antioxidants ascorbate and albumin were significantly lower (P < 0.001) but not urate. ETBAR correlated inversely with erythrocyte GSH and tocopherol (P < 0.001), and plasma ascorbate and albumin (P < 0.001) but not with the erythrocyte enzymic antioxidants. However, on multiple regression analysis only tocopherol correlated strongly with ETBAR, followed by GSH and plasma ascorbate. ETBAR also correlated well with haemolytic indices such as haemoglobin, plasma unconjugated bilirubin and haptoglobin concentrations (P < 0.001, for all). On follow-up after 2 weeks, ETBAR and different antioxidants reached near control levels. These observations indicate an enhanced oxidative stress on erythrocytes in acute falciparum malaria that may contribute substantially to haemolysis and anaemia.
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PMID:Evidence for erythrocyte lipid peroxidation in acute falciparum malaria. 1049 92

Pulmonary complication is a rare manifestation of childhood malaria and isolated pleural effusion without pulmonary edema has never been reported in children. We report here an 11-year-old boy who suffered from cerebral malaria and massive right pleural effusion. The patient was treated with intravenous artesunate, albumin, and other supportive treatments. He recovered completely after eight days. The clinical and laboratory courses suggested that the plasma leakage played a role in the pathogenesis of pleural effusion.
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PMID:Pleural effusion in childhood falciparum malaria. 1102 91

CBA/T6 and DBA/2J mice inoculated with Plasmodium berghei ANKA (PbA) develop cerebral involvement 6-8 days post-inoculation, from which the CBA mice almost invariably die and the DBA mice recover. Dexamethasone (DXM; 80 mg/kg) given to inoculated CBA mice twice, on day 3 and again within 48 h, reduced the cerebral symptoms and prevented death from cerebral malaria. Plasma tumour necrosis factor (TNF) levels, which increased at the time of the cerebral symptoms, were also reduced in these DXM-treated mice. Intravenously administered Evans Blue, a dye which binds to albumin, diffused extensively across the blood-brain barrier only during the period of cerebral symptoms, in proportion to the severity of the cerebral symptoms and the disease. In PbA-infected CBA mice, cerebral symptoms and the amounts of Evans Blue diffusing into the brain tissue were both reduced by DXM treatment, but only if the steroid was given on day 3 and again within 48 h. Endotoxin injected intravascularly into PbA-infected DBA mice after day 5 resulted in an exaggeration of cerebral symptoms and death between days 6 and 9. Plasma TNF and the amount of Evans Blue in the brain parenchyma increased above normal levels in these mice. Endotoxin injections had only minor effects on the severity of the cerebral symptoms in PbA-infected CBA mice and did not cause the animals to die sooner.
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PMID:Effects of endotoxin and dexamethasone on cerebral malaria in mice. 1102 8

Cerebral malaria (CM) is a serious complication of Plasmodium falciparum infection. Binding of parasitized erythrocytes to cerebral endothelium plays a key role in disease pathogenesis. Central nervous system signs and symptoms (coma, seizures, raised intracranial pressure) predominate in African children, whereas in adults, multiorgan system failure is more common. In this study we investigated whether changes in blood-brain barrier (BBB) structure and function are compatible with the signs and symptoms observed in Malawian children with CM. Immunohistochemistry on autopsy brain tissues from eight cases of CM showed activation of endothelial cells and macrophages, and disruption of endothelial intercellular junctions in vessels containing sequestered parasitized erythrocytes, but no gross leakage of plasma proteins. Examination of the partition of albumin between circulating plasma and the cerebrospinal fluid from 72 cases of CM showed subtle but measurable changes compatible with impaired BBB function in malaria. These findings suggest that BBB breakdown occurs in areas of parasite sequestration in CM in African children.
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PMID:Blood-brain barrier function in cerebral malaria in Malawian children. 1144 19

In a study performed in Tamale, in the Northern region of Ghana, cystatin C, a new and sensitive indicator of the glomerular filtration rate (GFR), was used to estimate the frequency of renal dysfunction in 78 children with uncomplicated, Plasmodium falciparum malaria. The excretion in urine of albumin, immunoglobulin G and alpha1-microglobulin was also investigated. Plasma concentrations of cystatin C were found to be elevated in 17% of the children, indicating subclinical impairment of renal function. As most (85%) of the children had glomerular as well as tubular patterns of proteinuria, it appears that both glomerulonephritis and damage to tubular cells often occur in P. falciparum malaria.
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PMID:Renal dysfunction in children with uncomplicated, Plasmodium falciparum malaria in Tamale, Ghana. 1283 20

Cassia singueana (Family: Fabaceae) is used in northern Nigeria for the treatment of acute malaria attack. We investigated the activities of the methanol extract of the root bark of this plant against rodent plasmodia infection, nociception, pyrexia and inflammation in mice and rats. The studies were carried out using acetic acid-induced writhing, hot plate algesia, rodent plasmodia (Plasmodium berghei) in mice; formalin test, yeast-induced pyrexia and egg-albumin-induced inflammation in rats. The results showed that the extract exhibited significant antinociceptive, antipyretic and antiplasmodial activity in all the models used. Phytochemical screening of the extract revealed the presence of phenols, saponins, tannins and some traces of anthraquinones. The LD50 of the extract was established to be 847+/-30 mg/kg, i.p. in mice. The observed pharmacological activities might be the scientific basis for the folkloric use of the plant in treating acute malaria attack. The study also paves way for the possible development of it, as a phytodrug against malaria.
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PMID:Studies on the use of Cassia singueana in malaria ethnopharmacy. 1296 53

The elucidation of factors inducing the growth of Plasmodium falciparum can provide critical information about the developmental mechanisms of this parasite and open the way to search for novel targets for malaria chemotherapy. The ability of components of a growth-promoting factor derived from bovine serum and various related substances to sustain growth of P. falciparum was characterized. A simple total lipid fraction (GFS-C) containing non-esterified fatty acids (NEFAs) as essential factors was noted to promote the parasite's growth. Various proteins from a variety of animals were tested, indicating the importance not only of GFS-C, but also of specific proteins, such as bovine and human albumin, in the parasite growth. Several combinations of the NEFAs tested sustained low parasite growth. Among various phospholipids and lysophospholipids tested, lysophosphatidylcholine containing C-18 unsaturated fatty acids was found to sustain the complete development of the parasite in the presence of bovine albumin. Several other lysophospholipids can partially support growth of P. falciparum.
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PMID:Investigating serum factors promoting erythrocytic growth of Plasmodium falciparum. 1563 34


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