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)

The aim of the present study was to measure the changes in resting energy expenditure (REE) induced by malaria and to assess to what extent they are related to fever and nutritional status. The REE of 19 Gambian children (mean age +/- SEM, 9 +/- 1 y; weight, 24 +/- 2 kg; expected weight for height 86 +/- 1%) were measured with a hood system at repeated intervals at the onset of malaria crisis (test A), 3 to 4 d after therapy (test B), and 14 to 21 d later (test C). Axillary temperature averaged 39.2 +/- 0.1, 36.6 +/- 0.1, and 36.7 +/- 0.1 degrees C in the tests A, B, and C, respectively. REE in test A was significantly higher than REE in test B (223 +/- 10 versus 174 +/- 8 kJ/kg.d, p less than 0.0001), but in test C (169 +/- 8 kJ/kg.d), it did not differ from that observed in test B. The percentage of increase in REE was significantly correlated with the difference in axillary temperature (r = 0.46, p less than 0.05); the slope of the regression line indicated an increase of 6.9% in REE/degree C of fever. Furthermore, the individual increase in REE/degree C was correlated to the percentage of weight for height of the children (r = 0.54, p less than 0.05), indicating that the child's nutritional status influences the magnitude of the hypermetabolism due to fever. We concluded that Gambian children suffering from an acute episode of malaria have an increase in REE averaging 30%; however, REE promptly returns to baseline value a few days after the beginning of therapy.
 ...
PMID:Effect of malaria and fever on energy metabolism in Gambian children. 154 35

Thirteen patients suffering from acute malaria attack and thirteen apparently healthy human volunteers (control) were used for the study. Platelet aggregation was determined by platelet count ratio technique in which a reduction in platelet count ratio signified an increase in platelet aggregation. Platelet count ratio in acute malaria patients was 0.75 +/- 0.03 (SEM). Platelet count ratio in subjects used as control was 0.88 +/- 0.02. This value was significantly higher than the former (P less than 0.001). Platelet count ratio correlated negatively with the degree of parasitaemia (r = -0.71; P less than 0.01). ADP, a platelet aggregating drug, also reduced platelet count ratio in rats significantly. Acute malaria attack therefore enhances platelet aggregation in vivo.
 ...
PMID:In vivo platelet aggregation in acute malaria. 168 3

To determine if iron chelation therapy has activity against human malaria, we administered desferrioxamine B in amounts of 100 mg/kg per day by continuous 72-hour subcutaneous infusions to 28 volunteers with asymptomatic Plasmodium falciparum infection in a randomized, double-blind, placebo-controlled crossover trial. Peripheral blood concentrations of P falciparum ring forms were determined at 12-hour intervals in all subjects and serum concentrations of desferrioxamine B + ferrioxamine (the iron complex of desferrioxamine B) were measured in 26 subjects. Geometric mean concentrations of asexual intraerythrocytic parasites decreased with both chelator and placebo treatment, but the decrement with desferrioxamine B was significantly greater than that with placebo (P less than .006) during both the initial and crossover periods. Compared with placebo, desferrioxamine B treatment was associated with an almost 10-fold enhancement of the rate of parasite clearance during both phases of the trial (P less than .007). Mean +/- SEM steady state concentrations of desferrioxamine B + ferrioxamine were 6.90 +/- 0.60 mumol/L at 36 hours and 7.72 +/- 0.68 mumol/L at 72 hours; in vitro, the ID50 has been reported to be approximately 4 to 20 mumol/L. No drug toxicity was detected. Parasitemia recurred in 19 of 24 participants followed-up over 1 to 6 months. We conclude that desferrioxamine B enhances the clearance of P falciparum parasitemia and that iron chelation may provide a new strategy to be developed for the treatment of malaria.
 ...
PMID:Iron chelation with desferrioxamine B in adults with asymptomatic Plasmodium falciparum parasitemia. 163 34

To investigate the role of hemodynamics in the adherence of Plasmodium falciparum-infected erythrocytes to cerebral endothelium in vivo, we investigated cytoadherence of parasitized erythrocytes to human umbilical vein endothelial cells (HUVEC) under shear conditions in vitro. At 1.0 dyne/cm2 shear stress, parasitized red blood cell (RBC) adherence to HUVEC ranged from 9.9 +/- 1.0 (+/- SEM) to 75.2 +/- 4.8 RBC/mm2 (mean +/- SEM: 35.1 +/- 2.8 RBC/mm2) and was 13-fold greater than uninfected erythrocyte adherence to HUVEC (range 0.1 +/- 0.1 to 6.7 +/- 1.6 RBC/mm2, mean +/- SEM 2.8 +/- 0.8 RBC/mm2). Only erythrocytes infected with trophozoites and schizonts adhered to HUVEC under shear conditions. Parasitized erythrocyte adherence to HUVEC decreased from 28.4 +/- 2.7 RBC/mm2 to 12.7 +/- 2.4 RBC/mm2 when shear stress was increased from 1.0 to 2.0 dynes/cm2. At 4.0 dynes/cm2, parasitized erythrocyte adherence decreased further to 2.0 +/- 1.3 RBC/mm2. In falciparum malaria patients, endothelial cytoadherence predominates in the microcirculation. Therefore, we also investigated adherence of parasitized erythrocytes to human dermal microvascular endothelial cells (MEC). At 1.0 dyne/cm2, cytoadherence of P. falciparum-infected erythrocytes to MEC ranged from 7.9 +/- 1.1 to 60.0 +/- 2.4 RBC/mm2 (mean +/- SEM: 23.0 +/- 1.7 RBC/mm2) and was 10-fold greater than uninfected erythrocyte cytoadherence to MEC (mean +/- SEM: 2.2 +/- 0.6 RBC/mm2). These data indicate that P. falciparum-infected erythrocytes adhere to human umbilical vein and microvascular endothelial cells under shear stress conditions typical of the postcapillary venules in vivo, and that cytoadherence is specific for parasitized erythrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cytoadherence of Plasmodium falciparum-infected erythrocytes to human umbilical vein and human dermal microvascular endothelial cells under shear conditions. 195 67

Chloroquine and ammonium chloride, by virtue of their basic properties, have been shown to raise endocytic and lysosomal pH and thereby interfere with normal iron metabolism in a variety of cell types, including mononuclear phagocytes. Cellular iron metabolism is of critical importance to Legionella pneumophila, an intracellular bacterial pathogen whose capacity to multiply in human mononuclear phagocytes is dependent upon the availability of intracellular iron. In view of this, we have studied the effects of chloroquine and ammonium chloride on L. pneumophila intracellular multiplication in human monocytes. Chloroquine, at a concentration of 20 microM, and ammonium chloride, at a concentration of 20 mM, inhibited L. pneumophila intracellular multiplication by 1.4 +/- 0.2 (SEM) logs and 1.5 +/- 0.2 logs, respectively. Chloroquine- and ammonium chloride-induced inhibition of L. pneumophila intracellular multiplication was completely reversed by iron nitrilotriacetate, an iron compound which is soluble in the neutral to alkaline pH range, but not by iron transferrin, which depends upon acidic intracellular conditions to release iron. Chloroquine had no major direct effect on L. pneumophila multiplication in artificial media except at extremely high concentrations (15,000-fold that which inhibited L. pneumophila multiplication in mononuclear phagocytes), and inhibition at such concentrations was not reversed by iron nitrilotriacetate. This study demonstrates that chloroquine and ammonium chloride inhibit the intracellular multiplication of L. pneumophila by limiting the availability of iron to the bacterium. It is possible that such a mechanism of action underlies chloroquine's antimicrobial effect against other intracellular pathogens, such as the agents of malaria and tuberculosis.
 ...
PMID:Chloroquine inhibits the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. A potential new mechanism for the therapeutic effect of chloroquine against intracellular pathogens. 205 29

To investigate the role of tumor necrosis factor in Plasmodium falciparum infections, we measured serum concentrations of this cytokine in 65 Malawian children with severe falciparum malaria. Of these children (mean age, 5.3 years), 55 were unconscious and 10 had hypoglycemia at presentation. Although there was considerable overlap, the mean (+/- SEM) initial serum concentration of tumor necrosis factor was significantly higher in the 10 patients who died (709 +/- 312 pg per milliliter) than in the 55 who survived (184 +/- 32 pg per milliliter; P less than 0.02). The mortality rate increased with the concentration of tumor necrosis factor: at a level of less than 100 pg per milliliter, 1 of 24 patients died; at 100 to 500 pg per milliliter, 6 of 34 patients; and at more than 500 pg per milliliter, 3 of 7 patients. High concentrations of tumor necrosis factor were also associated with hypoglycemia (P less than 0.02), hyperparasitemia (P less than 0.002), age under three years (P less than 0.03), and severity of illness as measured by a prognostic index (P less than 0.0005). The highest serum concentrations of tumor necrosis factor were found in patients who died shortly after admission. The concentrations in cerebrospinal fluid were within the normal range in all patients. In serum samples obtained from 38 convalescent patients, the concentration of tumor necrosis factor declined to a mean of 16 +/- 3 pg per milliliter. We conclude that the level of tumor necrosis factor is frequently increased in patients with severe falciparum malaria, particularly in those with cerebral malaria or hypoglycemia. To determine whether it is important in the pathogenesis of the signs and symptoms of the disease requires further study.
 ...
PMID:Tumor necrosis factor and disease severity in children with falciparum malaria. 265 27

Life threatening hypoglycaemia has been closely associated with the use of quinine, but the effect of quinidine and the synthetic antimalarials on the homoeostasis of glucose has not been investigated. In volunteers given a fixed dose of 500 mg base and patients with malaria given a quinidine loading dose (15 mg base/kg) mean (SEM) plasma insulin concentrations rose from 6.1 (1.5) mU/l to 10.9 (4.4) mU/l (p less than 0.02) and 10.4 (2.0) mU/l to 18.5 (5.3) mU/l (p less than 0.04), respectively. Plasma glucose concentrations fell from 4.5 (1.1) mmol/l (81 (20) mg/100 ml) to 4.0 (0.3) mmol/l (72 (5) mg/100 ml) in volunteers (p less than 0.04) and from 5.7 (1.3) mmol/l (102 (23) mg/100 ml) to 4.8 (1.6) mmol/l (86 (29) mg/100 ml) in patients (p less than 0.05). One of two patients with cerebral malaria and acute renal failure became profoundly hypoglycaemic (plasma glucose concentration 1.4 mmol/l (25 mg/100 ml), plasma insulin concentration 3.1 mU/l). Hypoglycaemia may occur in any severely ill fasting patient given parenteral quinidine. The other antimalarials tested, chloroquine, amodiaquine, mefloquine, and halofantrine, did not stimulate the release of insulin, an important advantage that should be taken into account when treatment is chosen for Plasmodium falciparum malaria.
 ...
PMID:Hypoglycaemia and antimalarial drugs: quinidine and release of insulin. 308 30

A reversed-phase high performance liquid chromatography method was developed to simultaneously estimate serum concentrations of dapsone (DDS), monoacetyldapsone (MADDS), and pyrimethamine (PYR) in 34 young adult Chinese men after they had taken the sixth weekly dose of Maloprim for malaria prophylaxis. Serum concentrations of DDS, MADDS, and PYR after 24 h were (mean +/- SEM) 374 +/- 31.3, 310 +/- 30.4, and 121 +/- 7.9 ng/ml, respectively. The 72-h serum concentrations of DDS, MADDS, and PYR were (mean +/- SEM) 134 +/- 21.6, 115 +/- 17.9, and 80 +/- 7.2 ng/ml, respectively. Serum concentrations of DDS and MADDS in many subjects after 120 h were less than 20 ng/ml, while mean +/- SEM concentration of PYR was 53 +/- 5.6 ng/ml. Acetylator phenotyping of the subjects showed that there were 31 (91%) fast acetylators, three (9%) intermediate acetylators, and no slow acetylators.
 ...
PMID:Simultaneous estimation of serum concentrations of dapsone, monoacetyldapsone, and pyrimethamine in Chinese men on maloprim for malaria prophylaxis using reversed-phase high performance liquid chromatography. 390 34

Children two to nine years old from an area of holoendemic malaria in northern Liberia had mean HbA2 and haematocrit values significantly (P less than 0.001) lower than others from a neighbouring town where malaria is hypoendemic. After regular administration of chloroquine over two years to 38 children living in a holoendemic village, their mean HbA2 rose from 2.1%, SE +/- 0.04, to 2.6%, SE +/- 0.08 (P less than 0.001) and their mean haematocrit from 0.348, SEM +/- 0.004, to 0.382, SE +/- 0.004 (P less than 0.001), values similar to those of children from the neighbouring town. In another village where chloroquine was not given regularly, mean HbA2, haematocrit and malariometric indices were little changed at the end of the two-year period. We conclude that persistent malarial parasitaemia was the main factor in the relatively low values of the village children. Although it is not clear how malaria depresses HbA, the findings were consistent with the hypothesis that chronic malaria induces iron-deficiency.
 ...
PMID:The effect of persistent malarial infections on haemoglobin A2 levels in Liberian children. 400 95

Previous studies have suggested that malaria induces changes in erythrocytic membrane permeability and susceptibility to osmotic lysis. The present study investigated erythrocytic transport of sodium with cells from Rhesus monkeys infected with Plasmodium knowlesi. Red blood cell sodium concentration was significantly elevated in 37 parasitized animals (21.8+/-1.2 mM; mean +/-SEM), as compared to 23 control animals (10.0+/-0.38 mM). The cellular sodium increased with the density of parasitemia and the cellular potassium decreased in proportion to the elevation of sodium. Nonparasitized as well as parasitized erythrocytes possessed this abnormality of cation metabolism. Effective chloroquine therapy reversed the changes over a period of 4 days. Active sodium outflux rate constants were depressed in animals with malaria (0.202+/-0.012), as compared to controls (0.325+/-0.027). Passive sodium influx rate constants were higher in infected monkeys (0.028+/-0.002) than in control animals (0.019+/-0.002). The cross incubation of malarial plasma with normal red blood cells induced a 22% diminution in active sodium outflux but no changes were observed in sodium influx. It is concluded that malaria alters erythrocytic sodium transport in all erythrocytes. The elevated intracellular sodium concentration is the net result of decreased sodium outflux and increased sodium influx. The plasmodium organism or the affected host may produce a circulating substance that is deleterious to erythrocytic membrane cation transport.
 ...
PMID:Alterations of red blood cell sodium transport during malarial infection. 497 61


1 2 3 4 5 Next >>