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

South African canine babesiosis is caused by the virulent Babesia canis rossi. In recent years, this common disease has been detected in 12% of dogs presented at the outpatients' division of the University of Pretoria's (Onderstepoort) Veterinary Academic Hospital, and 31% of the affected dogs have been hospitalized as seriously ill. Of these hospitalized cases, 50% had severe anaemia at presentation, 32% had moderate anaemia and 18% were non-anaemic (often polycythaemic), frequently with central-nervous-system signs or multiple organ failure. A retrospective survey of 662 hospitalized cases revealed that the haematology, clinical biochemistry and patient profile (signalment) of the severely anaemic dogs were distinct from those of the non-anaemic, indicating that the babesiosis in these two groups of dogs should be viewed as two different disease in terms of the postulated, underlying, 'pathomechanisms'. The severely anaemic dogs exhibited hypoxic hepatic disease and an increase in serum urea (without a concomitant increase in creatinine), seldom had profound electrolyte imbalances and tended to have a much more profound leucocytosis, consisting of a left-shifted inflammatory leucogram, with higher numbers of circulating metamyelocytes, lymphocytosis and monocytosis. In contrast, the non-anaemic dogs exhibited severe azotaemia (which could be of renal or pre-renal origin) and often showed a marked electrolyte disturbance (reflecting acid-base abnormalities) and a very mild leucocyte response; such dogs often presented as leucopenic, many being lymphocytopenic. These results indicate that the severely anaemic dogs had developed haemolytic disease (possibly immune-mediated), whereas the non-anaemic dogs had developed an acute and overwhelming inflammatory response. The mean age of the non-anaemic dogs (2.66 years) was less than the dogs in the 'severe anaemia group' (0.83 years). Dogs belonging to the traditional fighting breeds (bull terriers, pit bull terriers and Staffordshire bull terriers) were noticeably over-represented in the non-survivors of the acute inflammatory response, possibly indicating an underlying genetic basis for the different presentations. It is evident that the inflammatory-response disease presentation, which is similar to complicated falciparum malaria in humans, amy serve as an animal model for the disease.
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PMID:Canine babesiosis in South Africa: more than one disease. Does this serve as a model for falciparum malaria? 968 1

One hundred and four adult cases of cerebral malaria (73 male, 31 female) were studied between July 1995 to June 1996 in Chittagong Medical College Hospital. Diagnosis of cerebral malaria was based on unrousable coma or any neurological manifestation in a febrile patient with asexual Plasmodium falciparum in blood film. Intermittent fever (83%), vomiting (80%), headache (75%), convulsion (60%) and history of travel or residence in malaria endemic area were important features noted in patients with cerebral malaria. Most of the patients (69%) were admitted within 25 to 48 hours following unconsciousness. The factors are more common in cases with high mortality with diastolic blood pressure (DBP) below 60 mm of Hg, anaemia, persistence of Glasgow Coma Score below 5 on day 2, high parasite count at presentation, proteinuria and high level of serum urea. Out of 104 cases of cerebral malaria 66 patients (63.5%) recovered without sequelae, 34 patients (32.7%) died and 4 patients (3.8%) recovered with some residual sequelae. Establishment of intensive care unit in tertiary level hospitals is necessary to take appropriate measure for severe cerebral malaria cases for reduction of mortality.
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PMID:Cerebral malaria--a study of 104 cases. 992 81

To establish the effects of chloroquine on kidney function we monitored renal parameters in age and sex matched control subjects and patients who presented with acute transient fever. The patients were immediately treated with chloroquine diphosphate in the recommended dosage. Blood samples for creatinine, urea, Na+ and K+ determinations were collected before treatment (Day 0), on the 3rd day of treatment (Day 3) and two days after the last dose of chloroquine (Day 5). 24 h urine collections were collected for five consecutive days from the second day of treatment. Spot urine samples showed the absence of blood cells, bilirubin, glucose, protein and ketones. Examination of thick blood smears over three days did not reveal any forms of malaria parasites. Urinary tract infection in the patients was also excluded. Therefore, these patients were a suitable group to assess the effects of chloroquine on renal function. The blood pressure in females and males decreased significantly after two days of chloroquine treatment compared with Day 0. The plasma concentration of creatinine in females and females was increased by chloroquine 2 days after the last dose by comparison with the Day 0 (females, 66 +/- 2 mumol/L versus 83 +/- 2 mumol/L n = 20, p < 0.01 and males, 78 +/- 6 mumol/L versus 81 +/- 9 mumol/L, n = 20, p < 0.01). This was paralleled by a reduction in urinary creatinine excretion during the same period (females 15 +/- 1 mg/kg body weight/24 h versus 12 +/- 1 mg/kg body weight/24 h and males 23 +/- 3 mg/kg/24 h versus 18 +/- 2 mg/kg/24 h, p < 0.01 in both instances). Urinary urea excretion in females was reduced from 290 +/- 6 mumol/kg/24 h to 215 +/- 5 mumol/kg/24 h 2 days after treatment. The results of the study suggest that the effects of chloroquine in patients with acute transient fever include lowered urinary urea and creatinine excretion.
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PMID:Chloroquine influences renal function in rural Zimbabweans with acute transient fever. 1008 79

The Plasmodium falciparum cysteine protease falcipain is required for the degradation of hemoglobin by erythrocytic malaria parasites. In prior studies, peptidyl inhibitors of falcipain blocked hemoglobin degradation and development by cultured parasites and one of these compounds, when administered parenterally, cured Plasmodium vinckei-infected mice. We now report an evaluation of orally administered peptidyl inhibitors of falcipain in a mouse malaria model. In studies with a fluoromethyl ketone, orally administered morpholine urea-phenylalanine-homophenylalanine-fluoromethyl ketone delayed the progression of murine malaria. In studies of a new series of vinyl sulfones, a set of related compounds demonstrated marked inhibition of falcipain and of parasite biological activities in vitro. One of these compounds, N-methyl piperazine urea-leucine-homophenylalanine-2-naphthalene vinyl sulfone, cured about 40% of mice when administered orally twice-a-day for four days. Our results suggest that peptidyl inhibitors of falcipain have promise as antimalarial chemotherapeutic agents.
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PMID:Antimalarial effects in mice of orally administered peptidyl cysteine protease inhibitors. 1035 42

Chloroquine-resistant Plasmodium falciparum is endemic in many areas. Saudi Arabia was considered to have chloroquine-susceptible P. falciparum. During the 1997-1998 season, an outbreak of malaria occurred in the southwestern region. Over a 4-month period, 32 cases (6.2%) of 520 malaria admissions met the World Health Organization criteria for cerebral malaria. The mean patient age was 28 years. Thirteen male and 19 female patients were admitted in coma. The mean duration of coma was 4.3 days; the case fatality rate was 41%. Compared with those who recovered, patients who died had a lower mean admission diastolic blood pressure and hemoglobin level, higher mean blood urea nitrogen and blood glucose levels, and thrombocytopenia. Logistic regression analysis identified treatment with quinine rather than chloroquine to be associated with survival. These findings show the potential of P. falciparum to emerge as chloroquine resistant in previously susceptible areas, resulting in significant morbidity and mortality in spite of sophisticated medical care.
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PMID:Chloroquine-resistant Plasmodium falciparum cerebral malaria in a chloroquine-susceptible area. 1051 45

Falciparum malaria is a disease of tropical climates which affects 270 million people annually and has an overall mortality of 1%. While the incidence of acute renal failure in malaria is less than 1%, mortality is reported to be as high as 45% in those with renal failure. We report the clinical course and outcome in 5 patients with falciparum malaria-induced acute renal failure treated at the Singapore General Hospital between June and July 1997. All 5 males, with mean age of 35.2 +/- 13.1 years, were admitted with history of fever and reported travel to a known malarious zone. Mean laboratory parameters upon admission included serum creatinine 725 +/- 515 mumol/L and serum urea 47 +/- 31 mmol/L. Three patients with hypotension on admission were started on haemodiafiltration, of whom 2 were subsequently converted to haemodialysis as their haemodynamics improved. Two remaining patients were started on intermittent bicarbonate haemodialysis. The overall mortality in our series was 20%, with 1 patient having died of complications of adult respiratory distress syndrome, disseminated intravascular coagulation and multiorgan failure. The remaining 4 survived and recovered their renal function. The single patient mortality occurred in the patient with admission serum creatinine of 1632 mumol/L, a value significantly higher than that of the 4 patients who survived (mean serum creatinine, 499 +/- 106 mumol/L, P < 0.002). These results suggest that falciparum malaria associated with acute renal failure is associated with a high morbidity, but early presentation and intervention with appropriate antimalarial and renal replacement therapy is associated with improved survival and recovery of renal function.
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PMID:A case series of falciparum malaria-induced acute renal failure. 1056 76

Parasite-encoded membrane proteins translocated to the surface of infected erythrocytes or in specialized vesicles underneath (Maurer's clefts) play a key role in the asexual life cycle of Plasmodium falciparum (a malaria-causing protozoan), by mediating key steps such as red blood cell invasion, sequestration of infected cells in microcapillaries, and red blood cell rupture. A large-scale analysis of these membrane proteins would therefore be of great help to gain knowledge of the different stages of the Plasmodium falciparum life cycle. In order to be able to detect and identify parasite-encoded proteins directed to the red blood cell membrane, we first defined the conditions required for optimal extraction and separation of normal red blood cell ghost proteins by two-dimensional gel electrophoresis. These conditions included the use of urea, thiourea and new zwitterionic detergents in the extraction and isoelectric focusing media. The optimized conditions were then applied to analyze normal and P. falciparum-infected red blood cell ghosts. Several protein spots were found only in infected ghosts and are expected to represent parasite-encoded proteins. These proteins are currently under investigation.
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PMID:Analysis of membrane proteins by two-dimensional electrophoresis: comparison of the proteins extracted from normal or Plasmodium falciparum-infected erythrocyte ghosts. 1061 87

For many years the study of Red Blood Cell (RBC) deformability has been limited to specialised hematological research institutes and this has hampered a widespread clinical testing of this dynamic RBC property. Consequently, the clinical relevance of such in vitro measurements has remained questionable now for a considerable time. The recent availability of the LORCA, a routinely applicable and computer assisted instrument for this purpose, opens now the possibility to evaluate RBC deformability on a large scale in various pathological situations associated with impaired microcirculatory flow. In this communication we present our clinical experience obtained thusfar with this instrument. Besides the effect of physiological aging of normal RBC, the results of a clinical study on malaria tropica, case studies of hereditary elliptocytosis, Smith-Lemli-Opitz syndrome (a cholesterol biosynthesis defect), the treatment of sickle cell crisis with hydroxy-urea as well as the clinical intervention with Cyclosporin, are collected. In conclusion, it can be stated that the limited clinical experience with the LORCA as is reported here, yields sufficient evidence about the clinical potential of this technique.
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PMID:Clinical potential of in vitro measured red cell deformability, a myth? 1071 55

The malaria parasite Plasmodium falciparum has an unusual organization of its secretory compartments. As an approach to a functional identification of auxiliary proteins involved in secretion, a parasite line was generated by drug selection that is resistant to brefeldin A, an inhibitor of the secretory pathway. In the resistant line, neither protein secretion nor parasite viability were affected by the drug. The analysis of a sec7 domain, a conserved structure of guanine nucleotide exchange factors (ARF-GEF) required for the activation of ADP-ribosylation factors, revealed a single methionine-isoleucine substitution in the resistant parasite line. ARF-GEFs are key molecules in the formation of transport vesicles and the main targets of brefeldin A. The methionine residue in this position of sec7 domains is highly conserved and confers brefeldin A sensitivity. Unlike other eukaryotes that have multiple ARF-GEFs, the plasmodial genome encodes a single sec7 domain. This domain shows a distinct structural difference to all sec7 domains analysed so far; two conserved subdomains that are essential for protein function are separated in the plasmodial protein by an insertion of 146 amino acids.
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PMID:A point mutation in an unusual Sec7 domain is linked to brefeldin A resistance in a Plasmodium falciparum line generated by drug selection. 1155 94


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