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)

In China, increasing emphasis has been laid in recent years on research on natural products. About 140 new drugs have been developed from Chinese medicinal plants. For example, anisodamine possesses good effects in the treatment of septic shock and morphine addiction; 3-n-butylphthalide isolated from seeds of celery was shown to be a new cerebral anti-ischemic agent; indirubin was identified as an anti-leukemic drug with no inhibition of bone marrow; huperzine is a potent and reversible inhibitor of acetylcholinesterase (AChE) and its selective action is superior to that of donepezil; clausenamide was shown to be a potassium channel blocker, its nootropic effect was 50-100 times more potent than that of piracetam; bicyclol was synthesized from schizandrin C isolated from Fructus schizandrae. It has remarkable hepatoprotective and certain anti-hepatitis virus actions; salvianolic acid B is a very strong antioxidant agent with potential anti-dementia effects; yingzhaosu A and artemisinin are anti-malaria drugs containing a peroxide ring which is very rarely seen in natural substances.
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PMID:New drugs derived from medicinal plants. 1218 62

A case of failed peritoneal dialysis in a 5-year-old male nephrotic who developed acute renal failure following severe P. falciparum malaria infection is presented. Peritoneal dialysis (PD) failure was sequel to undetected severe dehydration which occurred during the diuretic phase of the acute renal failure. Pre-dialysis plasma potassium, bicabonate, urea and creatinine concentrations were 6.0mmol/L, 13mmol/L, 28mmol/L and 900mmol/L respectively, after about 22 hours of PD, the plasma K+, HCO-3 Ur and Cr were 5.7mmol/L, 15mmol/L, 32mmol/L and 1,090mml/L respectively. The peritoneal dialysate Ur concentration (3.5mmol and peritoneal Ur clearance (1.85ml/min/1.73m2) were grossly inadequate. There was also, intradialysis hyperglycaemia (12mmol/L owing to massive absorption of peritoneal dialysate solution which contains high concentration of glucose. Hyperglycaemia was corrected with 0.25 units/kg/dose of soluble insulin intravenously, he had two doses. Owing to similarity of clinical and biochemical features of dehydration and ARF, all efforts must be made to exclude dehydration before embarking on PD in patients with renal failure. Failure to exclude dehydration, led to PD failure in this patient.
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PMID:Failed peritoneal dialysis in a dehydrated nephrotic child, in acute renal failure: a case report. 1250 Dec 70

Our study demonstrates the capacity of FR160, a catechol iron chelator, to reach and accumulate into infected Plasmodium falciparum erythrocytes and parasites (cellular accumulation ratio between 12 and 43). Steady-state FR160 accumulation is obtained after 2 hr of exposure. After 2 hr exposure, it reaches intracellular levels that are 4- to 10-fold higher in infected red blood cells than those attained in normal erythrocytes. There is quite a good correlation between the accumulation of chloroquine and FR160 in the different strains (r=0.939) and in the IC(50) values (r=0.719). In contrast, the accumulation of FR160 and its activity is poorly correlated (r=0.500), suggesting that activity of FR160 may be independent of its penetration into infected erythrocytes. The mechanism of accumulation is yet unknown but based on inhibitor studies, the uptake of FR160 seems to be not associated with the calcium pump or channel, the potassium channel or the Na(+)/H(+) exchanger. Combinations of FR160 with verapamil, diltiazem, clotrimazole, amiloride, diazoxide, 4-aminopyridine, and picrotoxin should be avoided (antagonistic effects). The potent in vitro activity of FR160 on chloroquine-resistant strains or isolates, its lower toxicity against Vero cells, its mechanisms of action, its capacity to reach rapidly and accumulate into infected erythrocytes suggest that FR160 holds much promise as a new structural lead and effective antimalarial agent or at least a promising adjuvant in treatment of malaria.
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PMID:Cellular uptake of a catechol iron chelator and chloroquine into Plasmodium falciparum infected erythrocytes. 1269 76

In Paramecium, cAMP formation is stimulated by a potassium conductance, which is an intrinsic property of the adenylyl cyclase. We cloned a full-length cDNA and several gDNA fragments from Paramecium and Tetrahymena coding for adenylyl cyclases with a novel domain composition. A putative N-terminal ion channel domain contains a canonical S4 voltage-sensor and a canonical potassium pore-loop located C-terminally after the last transmembrane span on the cytoplasmic side. The adenylyl cyclase catalyst is C-terminally located. DNA microinjection of a green fluorescent protein (GFP)-tagged construct into the macronucleus of Paramecium resulted in ciliary localization of the expressed protein. An identical gene coding for an ion-channel adenylyl cyclase was cloned from the malaria parasite Plasmodium falciparum. Expression of the catalytic domain of the latter in Sf9 cells yielded an active homodimeric adenylyl cyclase. The occurrence of this highly unique subtype of adenylyl cyclase appears to be restricted to ciliates and apicomplexa.
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PMID:Adenylyl cyclases from Plasmodium, Paramecium and Tetrahymena are novel ion channel/enzyme fusion proteins. 1460 82

The cardiotoxicity of halofantrine was a major concern during the past decade. Other old antimalarials (quinine, mefloquine, etc.) and more recent drugs may carry a similar risk. Studies of ventricular repolarization and myocardial cells can throw light on these adverse effects. Studies of QT dispersion measured on the surface electrocardiogram and of QT dynamicity and variability (QT/RR slope) during long-term Holter recording help to identify patients at risk of drug-induced ventricular arrhythmia. Such electrocardiographic investigations have shown that quinine, mefloquine and artemisinin derivatives do not alter ventricular repolarization. In contrast, halofantrine significantly increases QT dispersion and the QT regression slope. At the cellular level, most major antimalarial drugs inhibit potassium channels, which are regulated by the LQT1 and HERG genes responsible for the congenital long-QT syndrome. We propose new recommendations for the use of these drugs in the treatment and prevention of malaria.
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PMID:[Effects of antimalarial drugs and cardiomyocytes. Pathogenic approach and new therapeutic recommendations]. 1700 71

Artemisia annua became a valuable agricultural crop after the World Health Organization recommended artemisinin as a component of ACT (artemisinin-combination based therapies) for malaria in 2001. A cloned, greenhouse-grown, A. annua (Artemis) subjected to an acidic soil and macronutrient deficit was evaluated for artemisinin production. Lack of lime (L) and macronutrients (N, P, and K) reduced leaf biomass accumulation. When L was provided (pH 5.1), the highest average leaf biomass was achieved with the "complete" (+N, +P, +K, and +L) treatment (70.3 g/plant), and the least biomass was achieved with the untreated (-N, -P, -K, and -L) treatment (6.18 g/plant). The nutrient least required for biomass accumulation per plant (g) was K (49.0 g), followed by P (36.5 g) and N (14.3 g). The artemisinin concentration (g/100 g) was significantly higher (75.5%) in -K plants when compared to plants under the complete treatment (1.62 vs 0.93%). Although the artemisinin total yield (g/plant) was 21% higher in -K plants, it was not significantly different from plants under the complete treatment (0.80 vs 0.66 g/plant). There were no marked treatment effects for concentration (g/100 g) or yield (g/plant) of both dihydroartemisinic acid and artemisinic acid, although higher levels were achieved in plants under the complete or -K treatments. There was a positive and significant correlation between artemisinin and both artemisinic acid and dihydroartemisin acid, in g/100 g and g/plant. This is the first report where potassium deficiency significantly increases the concentration (g/100 g) of artemisinin. Thus, under a mild potassium deficiency, A. annua farmers could achieve similar gains in artemisinin/ha, while saving on potassium fertilization, increasing the profitability of artemisinin production.
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PMID:Nutrient deficiency in the production of artemisinin, dihydroartemisinic acid, and artemisinic acid in Artemisia annua L. 1729 13

It was reported that there was a case of severe malaria patient with jaundice who presented with arrhythmia (premature ventricular contraction) while getting quinine infusion was reported. A man, 25 years old, was admitted to hospital with high fever, chill, vomiting, jaundice. The patient was fully conscious, blood pressure 120/80 mmHg, pulse rate 100 x/minute, regular. On admission, laboratory examination showed Plasmodium falciparum (++++), total bilirubin 8.25 mg/dL, conjugated bilirubin 4.36 mg/dL, unconjugated bilirubin 3.89 mg/dL, potassium 3.52 meq/L Patient was diagnosed as severe malaria with jaundice and got quinine infusion in dextrose 5% 500 mg/8 hour. On the second day the patient had vomitus, diarrhea, tinnitus, loss of hearing. After 30 hours of quinine infusion the patient felt palpitation and electrocardiography (ECG) recording showed premature ventricular contraction (PVC) > 5 x/minute, trigemini, constant type--sinoatrial block, positive U wave. He was treated with lidocaine 50 mg intravenously followed by infusion 1500 mg in dextrose 5%/24 hour and potassium aspartate tablet. Quinine infusion was discontinued and changed with sulfate quinine tablets. Three hours later the patient felt better, the frequency of PVC reduced to 4 - 5 x/minute and on the third day ECG was normal, potassium level was 3.34 meq/L. He was discharged on 7th day in good condition. Quinine, like quinidine, is a chincona alkaloid that has anti-arrhythmic property, although it also pro-arrhythmic that can cause various arrhythmias, including severe arrhythmia such as multiple PVC. Administration of parenteral quinine must be done carefully and with good observation because of its pro-arrhythmic effect, especially in older patients who have heart diseases or patients with electrolyte disorder (hypokalemia) which frequently occurs due to vomiting and or diarrhea in malaria cases.
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PMID:Quinine-induced arrhythmia in a patient with severe malaria. 1729 7

(2SR,6RS,7RS)-4-Dialkylaminobicyclo[2.2.2]octan-2-ols and several of their esters have shown promising activity against the causative organisms for malaria and sleeping sickness. The base-catalyzed epimerization of the alcohols was carried out by different methods giving their (2RS,6RS,7RS)-isomers. Best results were obtained by the consecutive use of potassium tert-butoxide and sodium. The isomeric alcohols were converted to selected esters. All new compounds were tested for their activity against Trypanosoma brucei rhodesiense (STIB 900) and a multiresistant strain of Plasmodium falciparum. The antitrypanosomal activity and the cytotoxicity were in general increased. The most active antitrypanosomal agents were the benzoate 8b and the 4-chlorobenzoate 9b of the 4-pyrrolidino series. The nicotinate 10a and the isonicotinate 11a showed the highest antiplasmodial activities.
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PMID:Epimers of bicyclo[2.2.2]octan-2-ol derivatives with antiprotozoal activity. 1769 58

Malaria sporozoites migrate through several cells prior to a productive invasion that involves the formation of a parasitophorous vacuole (PV) where sporozoites undergo transformation into Exo-erythorcytic forms (EEFs). The precise mechanism leading to sporozoite activation for invasion is unknown, but prior traversal of host cells is required. During cell migration sporozoites are exposed to large shifts in K(+) concentration. We report here that incubation of sporozoites to the intracellular K(+) concentration enhances 8-10 times the infectivity of Plasmodium berghei and 4-5 times the infectivity of Plasmodium yoelli sporozoites for a hepatocyte cell line, while simultaneously decreasing cell passage activity. The K(+) enhancing effect was time and concentration dependent, and was significantly decreased by K(+) channel inhibitors. Potassium-treated P. berghei sporozoites also showed enhanced numbers of EEFs in non-permissive cell lines. Treated sporozoites had reduced infectivity for mice, but infectivity was enhanced upon Kupffer cell depletion. Transcriptional analysis of K(+) treated and control sporozoites revealed a high degree of correlation in their levels of gene expression, indicating that the observed phenotypic changes are not due to radical changes in gene transcription. Only seven genes were upregulated by more than two-fold in K(+) treated sporozoites. The highest level was noted in PP2C, a phosphatase known to dephosphorylate the AKT potassium channel in plants.
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PMID:Exposure of Plasmodium sporozoites to the intracellular concentration of potassium enhances infectivity and reduces cell passage activity. 1771 5

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


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