Characterization of molecular and kinetic properties of two acetylcholinesterases from the Colorado potato beetle, Leptinotarsa decemlineata.

The molecular and biochemical properties of two acetylcholinesterases (LdAChE1 and LdAChE2) from the Colorado potato beetle, Leptinotarsa decemlineata, were investigated in this study. Polyacrylamide gel electrophoresis in conjunction with western blotting with LdAChE1- or LdAChE2-specific antibodies suggested that LdAChE1 exists in a soluble form, whereas LdAChE2 exists in both soluble and amphiphilic forms with a glycophosphatidylinositol anchor. Both LdAChEs exist as homodimers with each monomer connected with a disulfide bond. LdAChE1 was the most highly expressed in the thorax followed by the head, leg, and abdomen, whereas LdAChE2 was the most highly expressed in the head, followed by the thorax, leg, and abdomen. The overall expression levels of LdAChE1, however, were higher than those of LdAChE2 in all examined tissues. Kinetic analysis using recombinant LdAChE1 and LdAChE2 showed that LdAChE2 has a 4.8-fold higher catalytic efficiency toward acetylthiocholine iodide compared to LdAChE1. LdAChE2 was more sensitive to organophosphorus and carbamate insecticides than LdAChE1. The addition of irreversibly phosphorylated LdAChE1 via paraoxon titration significantly reduced LdAChE2 inhibition by insecticides and glycoalkaloids, suggesting a sequestration role of soluble LdAChE1 in the chemical defense against xenobiotics. Taken together, LdAChE2 may be the main enzyme for synaptic transmission, thus serving as a toxicologically more relevant target, whereas the soluble LdAChE1 may function as a bioscavenger.

Chronic exposure to field-realistic doses of imidacloprid resulted in biphasic negative effects on honey bee physiology.

There have been many investigations on the negative effects of imidacloprid (IMD) on honey bees. IMD is known to disrupt honey bee physiology and colony health at a relatively low concentration compared to other pesticides. In this study, honey bee colonies were chronically exposed to field-realistic concentrations (5, 20, and 100 ppb) of IMD, and the body weight, flight performance, carbohydrate reserve, and lipid contents of forager bees analyzed. Transcriptome analyses followed by quantitative PCR were also conducted for both nurse and forager bees to elucidate any changes in energy metabolism related to phenotypic disorders. The body weights of newly emerged and nurse bees showed decreasing tendencies as the IMD concentration increased. In forager bees, however, IMD induced a biphasic change in body weight: body weight was decreased at the lower concentrations (5 and 20 ppb) but increased at the higher concentration (100 ppb). Nevertheless, the flight capability of forager bees significantly decreased in a concentration-dependent manner. The effects of IMD on target gene transcription in forager bees showed biphasic patterns between low (5 and 20 ppb) and high (100 ppb) concentrations. Nurse bees showed typical features of premature transition to foragers in a concentration-dependent manner. When exposed to low concentrations, forager bees exhibited downregulation of genes involved in carbohydrate and lipid metabolism and in the insulin/insulin-like growth factor signaling pathway, upregulation of transporter activity, and a dose-dependent body weight reduction, which were similar to insulin resistance and diabetic symptoms. However, increased lipid metabolism and decreased energy metabolism with body weight gain were observed at high IMD concentration. Considered together, these results suggest that field-realistic doses of IMD alter honey bee energy metabolism in distinctly different ways at low and high concentrations, both of which negatively affect honey bee colony health.

High efficacy of a dimeticone-based pediculicide following a brief application: in vitro assays and randomized controlled investigator-blinded clinical trial.

BACKGROUND: Increasing resistance of head lice against neurotoxic agents and safety concerns have led to the search for treatment alternatives. Dimeticones with a physical mode of action are safe, and bear a reduced risk for the development of resistance. METHODS: We performed in vitro bioassays to assess pediculicidal and ovicidal activities of a new dimeticone-based product, and a randomized controlled clinical trial to assess efficacy, following 10 min application. Of 153 individuals screened, 100 participants with active head louse infestations were randomly assigned to treatment with either a dimeticone-based test product, or a 0.5% permethrin-based reference product (50 participants per group). Participants received two topical applications of either the test (10 min) or reference products (45 min) at days 0 and 7 or 8. Outcome measures included the efficacies of treatment and their safety, as well as global and local tolerability at baseline, and days 1, 7, and 10. RESULTS: After 10 min exposure, all lice treated with the dimeticone test product were classified as non-viable in the in vitro assay. Ovicidal activity after treatment of eggs with the dimeticone test product was 96.8%. In the clinical trial, 96 patients completed all study visits. In the full analysis set (FAS) population, on day 1 after one application, 98% of patients were cured in the test group, as compared to 84% cured in the reference group. All participants in both groups were free of head lice on day 10, following two applications (100% cure rate). In total, 42 adverse events (AEs) in 23 patients of both treatment groups were recorded, with the majority of AEs classified as mild. CONCLUSIONS: We have shown a high level of pediculicidal and ovicidal activity, and clinical efficacy and safety, of a brief application of a new dimeticone-based product. The short application time and reduced risk for the development of resistance are key drivers for improved patients' compliance. TRIAL REGISTRATION: EU Clinical Trials Register EudraCT  2016-004635-20 . Registered 14 November 2016.

4,4'-Dichlorodiphenyltrichloroethane (DDT) and 4,4'-dichlorodiphenyldichloroethylene (DDE) inhibit myogenesis in C2C12 myoblasts.

BACKGROUND: Most countries have banned the use of 4,4'-dichlorodiphenyltrichloroethane (DDT). However, owing to its extremely high lipophilic characteristics, DDT and its metabolite 4,4'-dichlorodiphenyldichloroethylene (DDE) are ubiquitous in the environment and in many types of food. The positive correlation between exposure to insecticides, including DDT and DDE, and weight gain, resulting in impaired energy metabolism in offspring following perinatal DDT and DDE exposure, was previously reported. Therefore the influence of DDT and DDE on myogenesis using C2C12 myoblasts was investigated in this study. RESULTS: DDT and DDE decreased myotube formation dose- and time-dependently. Among myogenic regulatory factors, DDT and DDE mainly decreased MyoD1 and Myf5 expression. DDT and DDE treatment also altered Myostatin expression, phosphorylation of protein kinase B, p70 ribosomal protein S6 kinase, forkhead box O protein 3 and mammalian target of rapamycin, resulting in attenuation of myotube formation. CONCLUSION: These results may have significant implications for understanding the effects of developmental exposure of DDT and DDE on myogenesis and development of obesity and type 2 diabetes later in life. © 2017 Society of Chemical Industry.

Management of Head Louse Infestations in the United States-A Literature Review.

UNLABELLED: Head lice are a source of scalp irritation, social disruption, and loss of school time. Health care providers need authoritative information to help avoid the costs and risks of ineffective treatment. A review was completed to provide relevant information on infestation treatments available in the United States. Three major biomedical databases were searched from 1985, when current products were first available, to 2014, focusing on U.S. REPORTS: A total of 579 references remained after duplicates were removed. A search of the U.S. Food and Drug Administration website and labels of approved products were reviewed. A marked decline in the effectiveness of permethrin and synergized pyrethrins was found, probably because of resistance arising from widespread and indiscriminate use, and the emergence of knockdown resistance mutations. The potential toxicity of lindane in the setting of readily available, safer, and more effective alternatives, should limit its use. Prescription products shown to be safe and effective with a single application, without nit combing, are topical ivermectin, malathion, and spinosad, whereas benzyl alcohol requires two applications. Home remedies such as mayonnaise, and essential oils, have not been demonstrated to be safe or effective, and may carry potential for severe adverse events. The high risk of failure of over-the-counter treatments in eliminating head louse infestations drives a need for health care provider recognition of the limitations of current treatments and for judicious use of treatments that remain effective.