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)

Chloroquine chemotherapy of malaria fever induces severe generalised pruritus in a large proportion of black Africans. In a double blind, placebo controlled, randomised, parallel group study in 28 historically chloroquine pruritus-reactor (R+) patients, with malaria, we evaluated the prophylactic and the palliative antipruritic actions of prednisolone (5 mg) or niacin (50 mg). There was a significant prophylactic effect of both drugs on the pruritogenecity of chloroquine as well as significant reduction in the area under the pruritus intensity-time curve, AUC(0-72 h) by niacin. The salutary effect both of niacin and prednisolone on chloroquine pruritogenecity resulted neither, in the mitigation of malaria parasite clearance, nor in the clinical amelioration following antimalaria therapy.
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PMID:The effects of prednisolone and niacin on chloroquine-induced pruritus in malaria. 180 57

Research has not provided unequivocal support for the recommendation to continue breastfeeding until children reach at least age 24 months. In many circumstances, breastfeeding duration is chosen or conditioned by factors other than scientific evidence and recommendations. Even in communities where breastfeeding into the second year is the norm, a significant number of toddlers are weaned before the recommended age. The research reported here was conducted in a rural community of western Kenya. We prospectively followed a cohort of 264 children for 6 months (mean age at baseline, 14.1 +/- 2.4 months) to examine the effect of variable breastfeeding duration on length and weight gain. We found that breastfeeding was positively associated with growth in a manner that we inferred to be causal, the effect being stronger on linear growth than on weight gain. This was despite the fact that in a cohort where 95% were breastfeeding at baseline, the prevalence of stunting (height-for-age below -2 standard deviations of the WHO-NCHS reference) was already 48%. The present paper examines the socioeconomic characteristics, sanitation, morbidity, and complementary feeding practices that define the context of this apparently contradictory relationship. The population was poor, no household had running water, and malaria is endemic in the study area. Complementary feeding was initiated for 93% of the cohort before age 3 months. The weaning diet was bulky (77% energy from carbohydrate), and high in phytate content ([phytate]:[zinc] molar ratio, 28). Diet quality, judged by diversity and animal source food intake, was low. Several micronutrient intakes were below current recommendations, including riboflavin (63%), niacin equivalents (64%), calcium (72%), iron (74%) and zinc (33%). Based on a locally defined socioeconomic status scale, children in higher SES households were breastfed for a shorter duration than were children from poorer households. Sanitation and water consumption modified the effect of breastfeeding duration on growth: the effect was stronger in the absence of a pit latrine and at low water consumption. Our results support the recommendation to sustain breastfeeding in the second year, particularly in economically depressed environments with inadequate sanitation and water supplies.
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PMID:Breastfeeding and growth in rural Kenyan toddlers. 1106 68

(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

Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite utilized as a redox cofactor and enzyme substrate in numerous cellular processes. Elevated NAD+ levels have been observed in red blood cells infected with the malaria parasite Plasmodium falciparum, but little is known regarding how the parasite generates NAD+. Here, we employed a mass spectrometry-based metabolomic approach to confirm that P. falciparum lacks the ability to synthesize NAD+ de novo and is reliant on the uptake of exogenous niacin. We characterized several enzymes in the NAD+ pathway and demonstrate cytoplasmic localization for all except the parasite nicotinamidase, which concentrates in the nucleus. One of these enzymes, the P. falciparum nicotinate mononucleotide adenylyltransferase (PfNMNAT), is essential for NAD+ metabolism and is highly diverged from the human homolog, but genetically similar to bacterial NMNATs. Our results demonstrate the enzymatic activity of PfNMNAT in vitro and demonstrate its ability to genetically complement the closely related Escherichia coli NMNAT. Due to the similarity of PfNMNAT to the bacterial enzyme, we tested a panel of previously identified bacterial NMNAT inhibitors and synthesized and screened twenty new derivatives, which demonstrate a range of potency against live parasite culture. These results highlight the importance of the parasite NAD+ metabolic pathway and provide both novel therapeutic targets and promising lead antimalarial compounds.
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PMID:Targeting NAD+ metabolism in the human malaria parasite Plasmodium falciparum. 2474 74