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Query: UMLS:C0024530 (malaria)
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Insecticide bioassays and biochemical microtitre assays were compared for detection of resistance to the organophosphate insecticides malathion and fenitrothion, using inbred laboratory strains of malaria vectors Anopheles albimanus Wiedemann, An.arabiensis Patton and An.stephensi Liston. With susceptible mosquitoes, the LT100 values determined from bioassays corresponded closely with times taken to abolish the activity of acetylcholinesterase activity in biochemical assays: approximately 2 h for malathion and 3 h for fenitrothion. Resistant strains of all three anophelines showed longer survival correlated with prolonged acetylcholinesterase activity. An.albimanus strains with insensitive acetylcholinesterase survived bioassays with discriminating doses of 1 h exposure to 5% malathion or 1% fenitrothion and were judged as resistant. It is concluded that enzyme-specific microassays provide a reliable means of detecting resistant individuals, with practical advantages over bioassays which do not reveal the resistance mechanism and require large numbers of healthy mosquitoes.
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PMID:A generalized approach to detection of organophosphate resistance in mosquitoes. 142 79

In Turkey, the mosquito Anopheles sacharovi has been under field selection pressure sequentially with DDT, dieldrin, malathion and pirimiphosmethyl over a period of 30 years for the purpose of malaria control. In 1984, the field population of An.sacharovi in the malarious Cukurova plain of Adana Province contained an altered acetylcholinesterase-based resistance gene giving broad spectrum resistance against organophosphorus and carbamate insecticides. The cross-resistance spectrum from this mechanism conferred resistance to malathion but not to the organophosphorus insecticide pirimiphos-methyl. Over the 6 years that pirimiphos-methyl has been applied for malaria vector control in this area, the frequency of the altered acetylcholinesterase resistance gene has declined, although in 1989 and 1990 it was still present at measurable frequencies in An.sacharovi from Cukurova. In addition to the acetylcholinesterase resistance mechanism there is evidence of an increased level of glutathione S-transferase in some of the An.sacharovi populations tested. This is known to be correlated with DDT resistance in other anophelines. In Turkish An.sacharovi, DDT resistance and elevated glutathione S-transferase occur in the same populations at similar frequencies. The continued prevalence of resistance to DDT and dieldrin, long after the 1971 cessation of DDT spraying for malaria control in Turkey, suggests that the DDT resistance gene has insufficient reduced fitness associated with it to have been lost from the field population during the past two decades. The implications of the slow decline in resistance gene frequencies in this field population are discussed in relation to mathematical models for managing resistance.
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PMID:Insecticide resistance gene frequencies in Anopheles sacharovi populations of the Cukurova plain, Adana Province, Turkey. 146 99

1. The acetylcholinesterase (AChE) gene from the important malaria vector Anopheles stephensi has been isolated by homology to the Drosophila acetylcholinesterase gene. 2. The complete sequence and intron-exon organization has been determined. The encoded protein has 69% identity to Drosophila AChE and 38 and 36% identity to Torpedo AChE and human butyrylcholinesterase, respectively.
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PMID:The acetylcholinesterase gene of Anopheles stephensi. 190 15

The phospholipid and fatty acid compositions of the host infected erythrocyte plasma membrane (IEPM) have been determined for erythrocytes infected with the human malaria parasite Plasmodium falciparum. IEPM were prepared by selective lysis of the host erythrocyte (but not of the parasite membranes) with 0.1% saponin, followed by differential centrifugation. The purity of the IEPM was determined by measuring the membrane-specific enzyme markers acetylcholinesterase, glutamate dehydrogenase and lactate dehydrogenase, and by immunoelectron microscopy using monoclonal antibodies specific for human erythrocyte glycophorin A (4E7) and for a 195 kDa parasite membrane glycoprotein (Pf6 3B10.1). Both approaches demonstrated that the host erythrocyte plasma membrane preparation was free from contamination by parasite membranes. During intra-erythrocytic development of the parasite, the phospholipid composition of the erythrocyte membrane was strikingly altered. IEPM contained more phosphatidylcholine (38.7% versus 31.7%) and phosphatidylinositol (2.1% versus 0.8%) and less sphingomyelin (14.6% versus 28.0%) than normal uninfected erythrocytes. Similar alterations in phospholipid composition were determined for erythrocyte membranes of parasitized cells isolated by an alternative method utilizing polycationic polyacrylamide microbeads (Affigel 731). The total fatty acid compositions of the major phospholipids in IEPM were determined by g.l.c. The percentage of polyunsaturated fatty acids in normal erythrocyte phospholipids (39.4%) was much higher than in phospholipids from purified parasites (23.3%) or IEPM (24.0%). The unsaturation index of phospholipids in IEPM was considerably lower than in uninfected erythrocytes (107.5 versus 161.0) and was very similar to that in purified parasites (107.5 versus 98.5). Large increases in palmitic acid (C16:0) (from 21.88% to 31.21%) and in oleic acid (C18:1) (from 14.64% to 24.60%), and major decreases in arachidonic acid (C20:4) (from 17.36% to 7.85%) and in docosahexaenoic acid (C22:6) (from 4.34% to 1.8%) occurred as a result of infection. The fatty acid profiles of individual phospholipid classes from IEPM resembled in many instances the fatty acid profiles of parasite phospholipids rather than those of uninfected erythrocytes. Analysis of IEPM from P. falciparum-infected erythrocytes (trophozoite stage) revealed that, during intra-erythrocytic maturation of the parasite, the host erythrocyte phospholipid composition was markedly refashioned. These alterations were not dependent on the method used to isolate the IEPM, with similar results obtained using either a saponin-lysis method or binding to Affigel beads. Since mature erythrocytes have negligible lipid synthesis and metabolism, these alterations must occur as a result of parasite-directed metabolism of erythrocyte lipids and/or trafficking of lipids between the parasite and erythrocyte membranes.
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PMID:Modification of host cell membrane lipid composition by the intra-erythrocytic human malaria parasite Plasmodium falciparum. 200 Dec 27

Serum cholinesterase (CHE) and acetylcholinesterase (ACHE) in cerebrospinal fluid (CSF) were determined simultaneously in 30 patients with P. falciparum cerebral malaria. Nineteen patients (63%) had low serum CHE and mean value of this serum enzyme in 30 patients was significantly lower than that of non-infected group. CSF ACHE levels were found to be significantly lower than those of normal subjects reported earlier. Post-treatment in the hospital for one week, both serum CHE and CSF ACHE levels in 9 convalescent subjects increased significantly. These findings indicated that both serum CHE and CSF ACHE levels were depressed in patients with cerebral malaria and increased on recovery.
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PMID:Acetylcholinesterase activities in cerebrospinal fluid of patients with Plasmodium falciparum cerebral malaria. 391 1

Baseline entomological surveillance was carried out in a rural area of The Gambia during the rainy season in 1988, one year before the implementation of a malaria control programme using insecticide-impregnated nets and targeted chemoprophylaxis in villages with a primary health care (PHC) system. Mosquito collections took place in 6 pairs of settlements each with untreated bed nets; within each pair there was a large PHC village with a resident village health worker (VHW) and traditional birth attendant (TBA) and a smaller non-PHC village without either a VHW or a TBA. The most common vectors in the study area were Anopheles gambiae sensu stricto and, to a lesser extent, An. arabiensis. These mosquitoes were found in appreciable numbers for at least 4 months of the year (geometric mean/bedroom/night = 32.5, 95% confidence interval 18.2-57.3). Numbers of mosquitoes collected in PHC villages or non-PHC villages were not significantly different. Greater numbers of mosquitoes were found in villages closer to the River Gambia than in those further away. Evidence for DDT resistance due to elevated glutathione S-transferase activity was found in one of the 12 villages, but there was no evidence of resistance to organophosphate or carbamate insecticides as suggested by the low esterase levels and carbamate sensitive acetylcholinesterase.
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PMID:A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 3. Entomological characteristics of the study area. 821 5

Present status of insecticide resistance was investigated in two major vectors of malaria; An. culicifacies and An. subpictus, collected from a high malaria transmission area in Sri Lanka during 1996/1998. Adult and larval bioassays were carried out to obtain log-probit mortality lines for malathion, propoxur, permethrin and chlorpyrifos. Respective LD50 values were 4.45%, 0.002%, 0.16% and 0.001% for An. culicifacies and 0.66%, 0.004%, 0.004% and 0.04% for An. subpictus. Adults were also tested for WHO standard discriminating dosages of malathion, propoxur, permethrin, DDT, cypermethrin, deltamethlin and lambda cyhalothrin. Both populations were highly resistant to DDT. An. culicifacies was more resistant to malathion and An. subpictus was more resistant to chlorpyrifos. About 25% of both populations were resistant to permethrin. An. culicifacies was susceptible to propoxur, deltamethrin and lambda cyhalothrin and An. subpictus to cypermethrin and lambda cyhalothrin. Adult mosquitos were individually tested for their insecticide detoxifying enzyme activities and altered target-site, acetylcholinesterase. High general esterase activity indicated the presence of amplified esterase genes in both populations. Native gel electrophoresis resolved one elevated esterase isoenzyme, with high affinity to organophosphates, from each species. Malathion carboxylesterase mechanism was present in both populations. Higher glutathione-S-transferase activity was marked in An. subpictus. Synergistic studies showed the possible involvement of monooxygenases in resistance in both species. Acetylcholinesterase activity of approximately 80% of both populations was not inhibited by a standard dosage of propoxur. Low resistance to carbamates shows that the impact of agricultural pesticides is not significant in the development of resistance especially in An. culicifaies. Pyrethroids, other than permethrin, can be successfully used in vector control programs. Carbamates will be an alternative.
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PMID:Insecticide cross-resistance spectra and underlying resistance mechanisms of Sri Lankan anopheline vectors of malaria. 1077 52

Anopheles pseudopunctipennis, one of the primary vectors of malaria in the southwest of Colombia, was evaluated for susceptibility to the 3 major insecticide groups (organophosphates, pyrethroids, and carbamates) by bioassay and biochemical assay. Larval populations, which were collected principally from irrigation channels in agricultural areas, where the intensity of insecticide use varied, were utilized to establish susceptibility for the 1st time in this species. The baselines for each population showed a range of biological susceptibility to the insecticides evaluated, but overall no resistance was detected according to standards established by the World Health Organization. The high sensitivity of biochemical microassays enabled the detection of a small proportion of mosquitoes with higher levels of nonspecific esterases and mixed-function oxidases from 2 areas where agricultural application of organophosphate and pyrethroid insecticides had been heavy. These differences were not sufficient to affect susceptibility as measured by bioassay. No evidence of insensitive acetylcholinesterase was observed. Absence of resistance in areas that have experienced heavy insecticide application could be explained by genetic drift, by gene flow from areas without insecticide pressure, by manner of exposure to the insecticides, or by recent changes in agricultural activities that decreased insecticide use. Baseline values were established that serve as provisional susceptibility thresholds for applying simple Centers for Disease Control and Prevention biochemical assay and bioassay methods to larvae of this anopheline species.
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PMID:Insecticide susceptibility in Anopheles pseudopunctipennis from Colombia: comparison between bioassays and biochemical assays. 1119 20

Cholinesterase inhibition is considered a specific biomarker of exposure and effect for organophosphorous pesticides. Its use for monitoring has been hindered, particularly in tropical countries where organophosphates are widely used for malaria and dengue control, because of the frequent lack of suitable controls. An in vitro technique is proposed as a biochemical method for monitoring pollutant mixtures in sediment toxicity tests. Brain homogenate from the fish Oreochromis niloticus is used as the enzyme source. Optimum incubation time, extraction solvent and effect of crude oil on acetylcholinesterase (AChE) are reported. The method described was used in sediments from two Mexican lagoons, located in an oil extraction area where pesticides are used in agriculture and vector control campaigns. AChE inhibitions from 3 to 21% were found in these lagoons, even in the presence of high concentrations of petroleum.
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PMID:Environmental monitoring using acetylcholinesterase inhibition in vitro. A case study in two Mexican lagoons. 1146 Jul 18

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


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