Acaricides resistance in ticks : selection, diagnosis, mechanisms, and mitigation

Ticks are blood-feeding ecto-parasites that have a cosmopolitan distribution in tropical and subtropical regions of the world. Ticks cause economic losses in the form of reduced blood, meat and dairy products, as well as pathogen transmission. Different acaricides such as organochlorines, organophosphates, formamidines (e.g. amitraz), synthetic pyrethroids, macrocyclic lactones, fipronil, and fluazuron are currently used sequentially or simultaneously to control tick infestations. Most acaricide treatments now face increasingly high chances of failure, due to the resistance selection in different tick populations against these drugs. Acaricide resistance in ticks can be developed in different ways, including amino acid substitutions that result in morphological changes in the acaricide target, metabolic detoxification, and reduced acaricide entry through the outer layer of the tick body. The current literature brings a plethora of information regarding the use of different acaricides for tick control, resistance selection, analysis of mutations in target sites, and resistance mitigation. Alternatives such as synergistic use of different acaricides, plant-derived phytochemicals, fungi as biological control agents, and anti-tick vaccines have been recommended to avoid and mitigate acaricide resistance. The purpose of this review was to summarize and discuss different acaricides applied for tick control, their mechanisms of action and resistance selection, genetic polymorphisms in their target molecules, as well as the approaches used for diagnosis and mitigation of acaricide resistance, specifically in Rhipicephalus microplus ticks

The comparative metabolism and toxicity of the pyrethroid insecticide cypermethrin in vertebrates

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β4 Peptide Mediated Voltage-gated Sodium Channel Resurgent Currents of Human Nav1.5 Sodium Channel Expressed in Hek293 Cells Increase after Exposure to Pyrethroid Insecticides Permethrin and Cypermethrin

Voltage-gated sodium channels (VGSCs) are transmembrane proteins responsible for the initiation of action potentials in excitable tissues by selectively allowing sodium ions (Na+) to flow through the cell membrane. VGSC resurgent currents occur when an open channel blocker from the β4 subunit interacts with the α subunit, transiently blocking the movement of Na+ across the membrane. VGSC subtype Nav1.5 channels are expressed in cardiac tissue and irregularities in their activity can lead to pathophysiological conditions like arrhythmias that can lead to death. Pyrethroid insecticides have been used widely in agriculture, vector control and households around the world for decades and since this is the case, human exposure to these products has increased dramatically. It is important to understand the effects of these insecticides on humans, including how these insecticides affect the heart. This thesis highlights the effects of pyrethroids on β4 peptide mediated Nav1.5 VGSC resurgent currents. The aims of this thesis were to 1) determine Nav1.5 channel activity and if activity changes with exposure to the vehicle (DMSO) used to dilute pyrethroids; 2) investigate the β4 peptide’s effect on these Nav1.5 currents and if resurgent currents are produced; 3) investigate Nav1.5 channel activity when exposed to pyrethroids; and 4) investigate β4 peptide mediated VGSC resurgent current activity after exposure to pyrethroids. Standard whole-cell electrophysiology was used to determine electrophysiological and pharmacological properties of WT Nav1.5 currents. Results from these experiments showed that 1) Nav1.5 channel activity follows established understanding of VGSC: when depolarized a rapid and transient inward current is produced followed by a rapid inactivation; 2) DMSO did not affect activation and inactivation pattern; 3) the β4 peptide produced resurgent currents in Nav1.5; 4) pyrethroids alter electrophysiological properties of Nav1.5 by prolonging inactivation; and 5) β4 peptide mediated resurgent currents are larger after exposure to pyrethroids. Overall, this thesis answers important questions regarding effects of pyrethroids on the cardiac VGSC and has implications for effects on health and highlights the necessity to be mindful of how pyrethroids are used in the future

Electronic Structure and Molecular Docking Studies of an anti-HIV Drug: Stavudine

337–339For anti HIV activity, Stavudine (or D4T or Zerit) is an important nucleoside reverse transcriptase inhibitor (NRTI). Molecular geometry of this compound has been optimized by DFT B3LYP/6–31G (d,p) method using Gaussian 03 software package. In order to examine global reactivity descriptors of the drug molecule, Frontier orbital analysis has been carried out. Using molecular docking inhibition activity of the drug against HIV-1 reverse transcriptase (6AN2) has been investigated. Attempts have been made to elucidate the chemical and biological properties of the drug