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Chiral separation of pyrethroic acids with single isomer permethyl monoamino beta-cyclodextrin selector.

Enantiomers and diastereomers of chrysanthemic, permethrinic, and deltamethrinic pyrethroic acids were separated from each other, using positively ionizable permethyl monoamino beta-cyclodextrin (PMMAbetaCD). The highest chiral resolution value was 20.0. The optimum conditions of separation were found to be 16 mM PMMAbetaCD concentration and pH 6.5, where analytes and selector were in oppositely ionized states. Selectivity of PMMAbetaCD proved to be the best among the cyclodextrin derivatives studied.

Cyclodextrins↗

Influence of (hydroxy)alkylamino substituents on enantioseparation ability of single-isomer amino-beta-cyclodextrin derivatives in chiral capillary electrophoresis.

A family of single-isomer amino-beta-cyclodextrin (amino-beta-CD) derivatives containing an amino or (hydroxy)alkylamino group in one of the primary positions has been synthesized. The steric effect and hydrogen bond forming ability of the different substituents on enantioseparation of acidic enantiomers has been studied by capillary electrophoresis (CE). Three enantiomeric model compounds (mandelic acid, cis-permethrinic acid, and cis-deltamethrinic acid) having significantly different apparent complex stability constants with beta-CD were applied in the experiments. Dependence of separation selectivity, resolution as well as mobility difference on chiral selector concentration (0.1-20 mM, pH 6.0) was investigated. Each amino-beta-CD showed higher enantioselectivity than the native beta-CD. One hydroxyalkyl group attached to the primary amino N-atom significantly increased both the enantioselectivity and the resolution compared to the primary amino-beta-CD, while two hydroxyalkyl moieties decreased them due to the predominance of steric hindrance. The value of the apparent complex stability constants obtained suited well the mobility difference model (by Wren). On the other hand, the optimum selector concentrations calculated according to the model were slightly lower than the experienced concentrations giving the maximum enantioresolution of enantiomers.

Electrophoresis, Capillary↗

The effect of insecticide on adipokinetic hormone titre in the insect body.

The effect of an insecticide, permethrin (Ambush 25 EC), on the titre of two adipokinetic hormones in the central nervous system (CNS) and haemolymph of the firebug Pyrrhocoris apterus (L) was tested. Doses of 2.5, 12.5 and 25 ng of the insecticide elicited no significant effect on the titre of the adipokinetic peptides in CNS, but caused their dramatic elevation in the haemolymph of both macropterous and reproductive brachypterous bugs. Changes in diapausing brachypterous bugs were minimal and not significant. Using high-performance liquid chromatography (HPLC) and competitive ELISA, both adipokinetic peptides of P apterus (Pyrap-AKH and Peram-CAH-II) were identified and quantified in the CNS of all experimental groups. The ratios of the two peptides in the CNS of the bugs used were affected by insecticide treatment, but in all three groups of bugs the Pyrap-AKH level remained dominant. The insecticide-treated bugs were compared with those exposed to forced running (shaking) and dark shock. Both factors also acted as stressors and enhanced the titre of adipokinetic peptides in the haemolymph but had no effect on hormone titre in CNS. The results indicate an involvement of adipokinetic peptides in the response of insect to various stressors including insecticides.

Animals↗

Functional and evolutionary consequences of pyrethroid resistance mutations in S6 transmembrane segments of a voltage-gated sodium channel.

Pyrethroids are a class of voltage-dependent sodium channel modifiers widely used as insecticides for control of disease vectors and agricultural pests. Many insect populations have developed resistance to pyrethroids linked to nervous system insensitivity and structural mutations in neuronal sodium channels. Pyrethroid resistant strains of the moth Heliothis virescens carry single point mutations leading to amino acid substitutions in either transmembrane segment I-S6 (V421M) or II-S6 (L1029H) of the para-homologous sodium channel. We analyzed the consequences of V421M and L1029H mutations constructed in the Drosophila para sodium channel heterologously expressed in Xenopus oocytes, and found that both mutations confer channel insensitivity to permethrin, with the L1029H mutation having a more pronounced effect. Both mutations also modify the intrinsic voltage-dependent gating properties of the channel, but L1029H less so than V421M. These results suggest that mutation V421M exacts a higher fitness cost than L1029H, providing a plausible explanation for genetic succession observed in field strains, where V421M was replaced by L1029H during the past decade.

Amino Acid Sequence↗

Duration of repellency of various synthetic and plant-derived preparations for Culicoides imicola, the vector of African horse sickness virus.

Objectives of the study were threefold: to find a safer and longer lasting repellent of the biting midge Culicoides imicola than di-ethyl toluamide (DEET), to examine whether the current recommendations in Israel for application of repellents during an outbreak of C. imicola-borne pathogens are justified; and to examine whether plant-derived preparations that have no known detrimental side effects are potential replacements of synthetic repellents. Of the seven repellents tested, those inferior to DEET were: oregano and Herbipet which showed a slight non-significant repellency for 2 h and 1 h respectively and Stomoxin which showed significant (P < 0.05) repellency for only 1 h. As the active ingredient of Stomoxin is permethrin, this suggests that recommendations to spray animals with this insecticide to prevent the spread of C. imicola-borne pathogens are not useful. Tri-Tec14 showed significant (P < 0.05) repellency with respect to controls for 2 h only, but performed similarly to, or slightly better than DEET. The repellents clearly superior to DEET were: the plant-derived material Ag1000 that repelled significantly (P < 0.05) with respect to controls for up to 4 h following a similar pattern to but somewhat more strongly than DEET, and pyrethroid-T which exerted significant (P < 0.05) repellency for 9 h. Pyrethroid-T proved to be the best repellent tested and if sprayed nightly it might provide protection from C. imicola-borne pathogens.

African Horse Sickness↗

Location of a gene conferring DDT resistance but no pyrethroid cross-resistance in larvae of Anopheles stephensi.

In larvae of Anopheles stephensi, DDT resistance of 30 to 40-fold, involving no cross-resistance to pyrethroids, showed fully dominant monofactorial inheritance. The gene, termed DDT, is located 36.6 cross-over units from the morphological mutant, black larvae (Bl), on chromosome III. A polygenic system, which confers a 17-fold reduction in susceptibility to knockdown by the pyrethroid, permethrin, also makes a minor contribution to DDT resistance. It was not possible to block DDT resistance with the dehydrochlorinase inhibitor DMC.

Animals↗

Occupational exposure to organophosphorus insecticides and synthetic pyrethroid.

Dermal and respiratory exposure to pirimiphosmethyl, dimethoate and permethrin were determined for applicators and operators in greenhouse tomato spraying operations. Dermal exposure is several times higher than the degree of respiratory exposure. Dermal exposure in terms of different parts of the body shows significant differences. For applicators the exposure of hands, arms and legs is the greatest, and the operators are the most exposed on their hands and to a small extent on legs. This fact should be taken into account when providing the workers with suitable protective clothing. The carefully selected technology of spraying also has great significance in decreasing the degree of exposure. Because of the chronic toxicity of dimethoate, all possible methods should be taken to reduce exposure.

Agricultural Workers' Diseases↗

Inhibition of monoamine oxidase-A of rat brain by pyrethroids--an in vitro kinetic study.

An in vitro kinetic study on inhibition of the monoamine oxidase-A (MAO-A) of the rat brain by two pyrethroids, namely permethrin (PM) and cypermethrin (CPM), has shown that PM and CPM competitively inhibit MAO-A by altering both the Michaelis-Menten constant (Km) and the maximum velocity (Vmax). Inhibitor constant values (Ki) indicated that CPM was a more effective inhibitor of MAO-A than PM. Both PM and CPM caused maximum inhibition of MAO-A at neutral pH. CPM significantly elevated the activation energy values of MAO-A as compared to those of PM.

Animals↗

The susceptibility of the poultry red mite, Dermanyssus gallinae (De Geer, 1778), to some acaricides under laboratory conditions.

Toxicity of 14 selected acaricides was tested for a laboratory strain of female D. gallinae. The most toxic were carbaryl (LC50 = 5.0 micrograms/m2), deltamethrin (LC50 = 7.8 micrograms/m2), bendiocarb (LC50 = 11.1 micrograms/m2), and permethrin (LC50 = 12.6 micrograms/m2). High level resistance to DDT in D. gallinae was recorded, with factors of resistance at LC50/LC90 reaching 57/73.

Animals↗

Efficacy of various synthetic pyrethroid-impregnated encasement materials against house dust mite under laboratory conditions.

The acaricidal activity of synthetic pyrethroid and benzyl benzoate against Dermatophagoides pteronyssinus was examined in the laboratory, using a specially designed test set up. On the basis of median lethal dose (LD50) values, the compound found to be most toxic to D. pteronyssinus was benzyl benzoate (LD50 = 50 mg/m2), followed by permethrin (LD50 = 76.7 mg/m2), deltamethrin (LD50 = 146.7 mg/m2), esbioallenthrin (LD50 = 186.6 mg/m2) and lamdacyhalothrin (LD50 = 756.6 mg/m2). Very low toxicity was observed with bifenthrin (LD50 = 5157.8 mg/m2). A laboratory control trial was also carried out to compare the acaricidal activity (residual effect) of four pyrethroids impregnated on woven and non-woven encasement materials against house dust mites during a 4-month period. Of the pyrethroids used in this study, esbioallenthrin demonstrated the highest acaricidal activity, and of the pyrethroid impregnated materials, the non-woven encasement material was more effective than the woven encasement material.

Animals↗

Interactions of pyrethroids with phosphatidylcholine liposomal membranes.

Interactions of several pyrethroids with membrane lipids in the form of dipalmitoylphosphatidylcholine (DPPC) liposomes have been studied using fluorescent membrane probes. Fluorescence anisotropy values and lifetimes (determined by phase-shift and demodulation techniques) of the fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene, were decreased in gel phase liposomes by pyrethroids at concentrations on the order of 10 microM. The pyrethroids containing a cyano substituent were also observed to cause collisional quenching of diphenylhexatriene fluorescence. Pyrethroids differed in their effectiveness at lowering the phase transition temperature of DPPC, and in their ability to broaden the temperature range of this transition. The fluorescence intensity of DPPC-incorporated chlorophyll a was used to monitor the pretransition of DPPC and the lateral diffusion of a membrane component located in the polar headgroup region. Permethrin did not affect chlorophyll a fluorescence intensity at any temperature. It may be concluded from these results that pyrethroids are preferentially located in the interior hydrophobic regions of the lipid bilayer, and that these compounds can disorder hydrocarbon packing in the bilayer core. However, polar headgroups were not disordered, and diffusion of membrane components in the polar headgroup region was not altered.

Allethrins↗

Insecticide impregnation can restore the efficiency of torn bed nets and reduce man-vector contact in malaria endemic areas.

Three trials with torn bed nets impregnated with permethrin and deltamethrin were made under field conditions at the Soumousso Field Station and the Vallée du Kou rice-field area, both in Burkina Faso, and the Djoumouna fish pond area in the Congo Republic. Even a considerably torn correctly impregnated bed net could be an useful method for limiting human-anopheline contacts. But bed nets in poor condition, i.e. too little impregnated and too much torn, cannot protect the users against anopheline bites. Protection increases with insecticide concentration, but at a high dosage insecticide could have more a repellent than a killing effect. Therefore a balance has to be found for the optimum rate of insecticide treatment of bed nets to obtain a real reduction in malaria transmission and morbidity, in every epidemiological situation.

Animals↗

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 5. Design and implementation of the trial.

A large-scale malaria intervention programme using insecticide-treated bed nets and chemoprophylaxis administered to children was introduced into a rural area of The Gambia. The operation was carried out using the existing primary health care (PHC) service in the region. Training of the village health workers, sensitization of the communities, and implementation of net impregnation and the drug delivery programme are described. This delivery system resulted in over 90% of nets being treated with insecticide and 80% of children receiving over 90% of their tablets during the rainy season. There was considerable variation in the distribution of permethrin on a bed net and between individual nets, which is likely to facilitate the spread of insecticide resistance in the local mosquito populations. Bed nets made from heavier fabrics tended to absorb more insecticide than those made from lighter materials. Four months after dipping, 89% of the insecticide had been lost from treated nets. This was probably due mainly to women washing their nets, an activity carried out on average once every 2 months during the rainy season. The high number of insecticide-treated bed nets in the study area demonstrated that a malaria control programme operated through a PHC system can be implemented successfully.

Antimalarials↗

Bed nets for the prevention of malaria and anaemia in pregnancy.

A prospective comparison of the antimalarial efficacy of bed nets was conducted with 341 pregnant women living in a mesoendemic malarious area of the Thai-Burmese border. Women in 3 adjacent study sites were allocated at random to receive either a single size permethrin-impregnated bed net (PIB), a non-impregnated bed net (NIB), or to a control group who used either their own family size non-impregnated bed net (FNIB) or no net. In one study site, but not the other 2, PIB significantly reduced parasite densities and, together with FNIB, reduced the incidence of malaria in pregnancy from 56% to 33% (relative risk = 1.67, confidence interval = 1.07-2.61, P = 0.03, allowing for parity). Anaemia proved a more sensitive marker of bed net antimalarial efficacy than parasite rates. The incidence of anaemia (haematocrit < 30%) at all study sites was significantly lower at delivery in the PIB (27%) and FNIB groups (21%) than in the NIB group (41%) or those using no net (56%). This suggests that a significant proportion of the malaria in pregnancy in this mesoendemic area was sub-patent. Both patent Plasmodium falciparum parasitaemia and anaemia were associated with a reduction in birth weight. Infant mortality was high (16%) and strongly associated with prematurity, low birth weight and maternal anaemia. PIB were well tolerated and had no apparent adverse effect on the pregnancy or infant development. Although the overall effect of bed nets on patent parasitaemia was marginal, they were associated with a significant reduction in maternal malaria-associated anaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Insecticide-impregnated bed nets reduce malaria transmission in rural Zanzibar.

There has been concern that impregnated bed nets are an insufficiently powerful method to control malaria in areas with very high perennial transmission, as in the humid lowland parts of tropical Africa. We carried out a 'cross-over' trial among children under 5 years of age in 2 villages in rural Zanzibar. In 1989, one village was supplied with newly permethrin-impregnated bed nets whereas the other served as unprotected control. In 1992, when those nets had lost their insecticidal activity and were badly torn, the village which had previously been the control was given newly impregnated bed nets. Each time, reinfection with Plasmodium falciparum was measured after initially clearing the parasites by administering a therapeutic dose of sulfadoxine/pyrimethamine. The introduction of bed nets led to a 74-78% reduction in the weekly rate of reinfection with malaria parasites, in all age groups. The nets apparently also affected perceived clinical symptoms, haemoglobin levels, and the mosquito sporozoite rate.

Animals↗

The effect of insecticide-treated bed nets on mortality of Gambian children.

Insecticide treatment of bed nets ("mosquito nets") may be a cheap and acceptable method of reducing the morbidity and mortality caused by malaria. In a rural area of The Gambia, bed nets in villages participating in a primary health-care (PHC) scheme were treated with permethrin at the beginning of the malaria transmission season. Additionally, children aged 6 months to 5 years were randomised to receive weekly either chemoprophylaxis with maloprim or a placebo throughout the malaria transmission season. We measured mortality in children in PHC villages before and after the interventions described, and compared this with mortality in villages where no interventions occurred (non-PHC villages). About 92% of children in PHC villages slept under insecticide-treated bed nets. In the year before intervention, mortality in children aged 1-4 years was lower in non-PHC villages. After intervention, the overall mortality and mortality attributable to malaria of children aged 1-4 in the intervention villages was 37% and 30%, respectively, of that in the non-PHC villages. Among children who slept under treated nets, we found no evidence of an additional benefit of chemoprophylaxis in preventing deaths. Insecticide-treated bed nets are simple to introduce and can reduce mortality from malaria.

Antimalarials↗

Laboratory toxicity of potential blackfly larvicides on some African fish species in the Onchocerciasis Control Programme area.

The Onchocerciasis Control Programme of the World Health Organization uses larvicides to fight against the aquatic stages of the vector Simulium damnosum s.l., and thereby interrupt transmission of the disease. Since the appearance of resistance to Abate and chlorphoxim in certain cytotypes of the vector, the efficacy of many possible replacement insecticides has been tested and the impact of the best of them (permethrin, cyphenothrin, pyraclofos, and carbosulfan) on the aquatic fauna evaluated.

Africa, Western↗

A quantitative assessment of pyrethroid-induced paraesthesia in the guinea-pig flank model.

Pyrethroids are known to induce cutaneous effects in man which are distinct from the classical irritation and vascular responses. These effects are characterised by transient facial burning and tingling sensations. The aetiology of this cutaneous effect is related to the ability of pyrethroids to produce trains of nerve impulses in afferent nerves by prolonging the opening of the neuronal sodium channel. The veratrum alkaloids which are structurally dissimilar to the pyrethroids are known to affect the sodium channel in a similar manner. Using the guinea-pig flank model which has been developed to study this cutaneous phenomenon we have constructed dose-response curves to three structurally related pyrethroids (permethrin, cypermethrin and deltamethrin) and to a mixture of veratrum alkaloids (veratrine). In addition we have examined the time course over which these chemicals elicit a response.

Animals↗