Kyong Sup Yoon

4,4′-Dichlorodiphenyltrichloroethane (DDT) and 4,4′-dichlorodiphenyldichloroethylene (DDE) promote adipogenesis in 3T3-L1 adipocyte cell culture

4,4-Dichlorodiphenyltrichloroethane (DDT), a chlorinated hydrocarbon insecticide, was extensively used in the 1940s and 1950s. DDT is mainly metabolically converted into 4,4-dichlorodiphenyldichloroethylene (DDE). Even though most countries banned DDT in the 1970s, due to the highly lipophilic nature and very stable characteristics, DDT and its metabolites are present ubiquitously in the environment, including food. Recently, there are publications on relationships between exposure to insecticides, including DDT and DDE, and weight gain and altered glucose homeostasis. However, there are limited reports regarding DDT or DDE and adipogenesis, thus we investigated effects of DDT and DDE on adipogenesis using 3T3-L1 adipocytes. Treatment of DDT or DDE resulted in increased lipid accumulation accompanied by increased expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome-proliferator activated receptor-γ (PPARγ), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), adipose triglyceride lipase, and leptin. Moreover, treatment of DDT or DDE increased protein levels of C/EBPα, PPARγ, AMP-activated protein kinase-α (AMPKα), and ACC, while significant decrease of phosphorylated forms of AMPKα and ACC were observed. These finding suggest that increased lipid accumulation caused by DDT and DDE may mediate AMPKα pathway in 3T3-L1 adipocytes.

Fipronil promotes adipogenesis via AMPKα-mediated pathway in 3T3-L1 adipocytes

Emerging evidence suggests that organochlorine, organophosphorus and neonicotinoid insecticide exposure may be linked to the development of obesity and type 2 diabetes. However, there is no knowledge of the potential influence of fipronil, which belongs to the phenylpyrazole chemical family, on obesity. Thus, the goal of this study was to determine the role of fipronil in adipogenesis using 3T3-L1 adipocytes. Fipronil treatment, at 10xa0μM, increased fat accumulation in 3T3-L1 adipocytes as well as promoted key regulators of adipocyte differentiation (CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor gamma-γ), and key regulators of lipogenesis (acetyl-CoA carboxylase and fatty acid synthase). The activation of AMPKα with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) abolished effects of fipronil on increased adipogenesis. These results suggest that fipronil alters adipogenesis and results in increased lipid accumulation through a AMPKα-mediated pathway.

Quantitative Sequencing for the Determination of Kdr-Type Resistance Allele (V419L, L925I, I936F) Frequencies in Common Bed Bug (Hemiptera: Cimicidae) Populations Collected from Israel

ABSTRACT n Human bed bug infestations have dramatically increased worldwide since the mid-1990s. A similar phenomenon was also observed in Israel since 2005, when infestations were reported from all over the country. Two single nucleotide polymorphisms (V419L and L925I) in the bed bug voltagesensitive sodium channel confer kdr-type resistance to pyrethroids. Using quantitative sequencing (QS), the resistance allele frequencies of Israeli bed bug populations from across the country were determined. Genomic DNAwas extracted from samples of 12 populations of bed bugs collected from Israel and DNA fragments containing the V419L or L925I and I936F mutations sites were PCR amplified. The PCR products were analyzed by QS and the nucleotide signal ratios calculated and used to predict the resistance allele frequencies of the unknown populations. Results of the genetic analysis show that resistant nucleotide signals are highly correlated to resistance allele frequencies for both mutations. Ten of the 12 tested populations had 100% of the L925I mutation and 0% of the V419L mutation. One population was heterogeneous for the L925I mutation and had 0% of the V419L mutation and another population was heterogeneous for the V419L mutation and had 100% of the L925I mutation. I936F occurred only at low levels. These results indicate that bed bugs in Israel are genetically resistant to pyrethroids. Thus, pyrethroids should only be used for bed bug management with caution using effective application and careful monitoring procedures. Additionally, new and novel-acting insecticides and nonchemical means of controlling bed bugs should be explored.

Expansion of the Knockdown Resistance Frequency Map for Human Head Lice (Phthiraptera: Pediculidae) in the United States Using Quantitative Sequencing

Abstract Pediculosis is a prevalent parasitic infestation of humans, which is increasing due, in part, to the selection of lice resistant to either the pyrethrins or pyrethroid insecticides by the knockdown resistance (kdr) mechanism. To determine the extent and magnitude of the kdr-type mutations responsible for this resistance, lice were collected from 138 collection sites in 48 U.S. states from 22 July 2013 to 11 May 2015 and analyzed by quantitative sequencing. Previously published data were used for comparisons of the changes in the frequency of the kdr-type mutations over time. Mean percent resistance allele frequency (mean % RAF) values across the three mutation loci were determined from each collection site. The overall mean % RAF (±SD) for all analyzed lice was 98.3 ± 10%. 132/138 sites (95.6%) had a mean % RAF of 100%, five sites (3.7%) had intermediate values, and only a single site had no mutations (0.0%). Forty-two states (88%) had a mean % RAF of 100%. The frequencies of kdr-type mutations did not differ regardless of the human population size that the lice were collected from, indicating a uniformly high level of resistant alleles. The loss of efficacy of the Nix formulation (Prestige Brand, Tarrytown, NY) from 1998 to 2013 was correlated to the increase in kdr-type mutations. These data provide a plausible reason for the decrease in the effectiveness of permethrin in the Nix formulation, which is the parallel increase of kdr-type mutations in lice over time.

Comparison of the proliferation and excretion of Bartonella quintana between body and head lice following oral challenge

Human body and head lice are highly related haematophagous ectoparasites but only the body louse has been shown to transmit Bartonella quintana, the causative agent of trench fever. The mechanisms by which body lice became a vector for B. quintana, however, are poorly understood. Following oral challenge, green fluorescent protein‐expressing B. quintana proliferated over 9 days postchallenge with the number of bacteria being significantly higher in whole body vs. head lice. The numbers of B. quintana detected in faeces from infected lice, however, were approximately the same in both lice. Nevertheless, the viability of B. quintana was significantly higher in body louse faeces. Comparison of immune responses in alimentary tract tissues revealed that basal transcription levels of peptidoglycan recognition protein and defensins were lower in body lice and the transcription of defensin 1 was up‐regulated by oral challenge with wild‐type B. quintana in head but not in body lice. In addition, the level of cytotoxic reactive oxygen species generated by epithelial cells was significantly lower in body lice. Although speculative at this time, the reduced immune response is consistent with the higher vector competence seen in body vs. head lice in terms of B. quintana infection.

Permethrin alters glucose metabolism in conjunction with high fat diet by potentiating insulin resistance and decreases voluntary activities in female C57BL/6J mice

Permethrin, a type 1 pyrethroid insecticide, was previously reported to promote adipogenesis in 3T3-L1 adipocytes and insulin resistance in C2C12 muscle cells; however, the effects of permethrin exposure on glucose and lipid metabolisms inxa0vivo remain unknown. The purpose of this study was to investigate the effects of permethrin exposure on glucose and lipid homeostasis as well as voluntary movement in female mice in response to dietary fat. We tested three doses of permethrin (50, 500, & 5000xa0μg/kg body weight/day) in low fat diet-fed (4% w/w of diet) and high fat diet-fed (20% w/w of diet) female C57BL/6xa0J mice for twelve weeks. Our results demonstrated that permethrin treatment potentiated high fat diet-induced insulin resistance as indicated by insulin tolerance tests, glucose tolerance tests, and homeostasis model assessment - insulin resistance (HOMA-IR) without altering weight or fat mass. Permethrin treatment significantly decreased voluntary movement and elevated blood glucose and insulin levels. Western blot results further showed that permethrin impaired insulin signaling via the Akt signaling pathway in the gastrocnemius muscle. Taken together, these results suggest that oral administration of permethrin potentiated high fat diet-induced insulin resistance, possibly increasing the risk of type 2 diabetes without altering weight gain in female C57BL/6xa0J mice.

Ovicidal Efficacy of Abametapir Against Eggs of Human Head and Body Lice (Anoplura: Pediculidae)

Abstract Studies were undertaken to determine the ovicidal efficacy of 5,5′-dimethyl-2,2′ -bipyridyl (abametapir) against eggs of both human head and body lice. Head lice eggs of different ages (0–2, 3–5, and 6–8-d-old eggs) were exposed to varying concentrations of abametapir in isopropanol and concentration-dependent response relationships established based on egg hatch. One hundred percent of all abametapir-treated eggs failed to hatch at the 0.74 and 0.55% concentrations, whereas 100% of 6–8-d-old head louse eggs failed to hatch only at the 0.74% concentration. The LC50 value for abametapir varied, depending on the age of the head lice eggs, from ∼0.10% recorded for 0–2-d-old eggs and increasing to ∼0.15% for 6–8-d-old eggs. Abametapir was also evaluated once formulated into a lotion referred to as Xeglyze (0.74% abametapir) and serial dilutions made. Ovicidal efficacies were determined against head lice eggs 0–8-d-old. Results indicated 100% ovicidal activity at the 0.74, 0.55, 0.37, and 0.18% concentrations. Additional studies undertaken using body lice eggs also demonstrated that abametapir was 100% ovicidal against eggs of all ages when evaluated at a concentration of 0.37 and 0.55%. Given that ovicidal activity is a critical component of any effective treatment regime for louse control, the data presented in this study clearly demonstrate the ability of abametapir to inhibit hatching of both head and body louse eggs as assessed in vitro.

Body Lice: From the Genome Project to Functional Genomics and Reverse Genetics

In 2010, the initial annotations of the genomes of the body louse (Pediculus humanus humanus Linnaeus) and its primary endosymbiont, “Candidatus Riesia pediculicola,” were completed. The body louse had the smallest genome of any insect sequenced to that point. Prior to the proposal for the sequencing project, there was a dearth of information about louse genes, with no more than around 500–600 inferred open reading frames in public databases. Since the publishing of this genome project, the field of louse genomics has experienced significant advances in our understanding of the taxonomic relationship and the differences in vector competence between head and body lice. To date, the louse system has emerged as a model system to understand xenobiotic induction responses. Finally, a louse RNAi-based reverse genetic system has been developed with the potential to study the functional role of louse genes in vector competence.

In Vitro and In Vivo Evaluation of Infestation Deterrents Against Lice

ABSTRACT n The human head louse is a cosmopolitan ectoparasite and frequently infests many people, particularly school-age children. Due to widespread pyrethroid resistance and the lack of efficient resistance management, there has been a considerable interest in the protection of uninfested people and prevention of reinfestation by disrupting lice transfer. In this study, two nonclinical model systems (in vitro and in vivo) were used to determine the efficacy of the infestation deterrents, Elimax lotion and Elimax shampoo, against human head lice or poultry chewing lice, respectively. With in vitro assessments, female head lice exhibited significantly higher avoidance responses to hair tufts treated with either of the test formulations, which led to significantly higher ovipositional avoidance when compared with female lice on control hair tufts. Additionally, both formulations were determined to be competent infestation deterrents in a competitive avoidance test in the presence of a known attractant (head louse feces extract). In in vivo assessments using a previously validated poultry model, Elimax shampoo was determined to be an efficacious deterrent against poultry chewing lice within Menopon spp. and Menacanthus spp.

Exposure to permethrin promotes high fat diet-induced weight gain and insulin resistance in male C57BL/6J mice

Permethrin is a pyrethroid pesticide that was previously reported to promote fat accumulation and insulin resistance in vitro. A recent study in female mice also found that permethrin could promote high fat-induced insulin resistance. The effects of permethrin on glucose and lipid metabolisms in male mice, however, remain unknown. The purpose of this study was to investigate the effects and interactions of permethrin exposure (50, 500, and 5000 μg/kg body weight/day) and dietary fat (low fat, 4% w/w; high fat, 20% w/w) on development of obesity and insulin resistance in male C57BL/6J mice. Our results showed that permethrin treatment significantly increased body weight, fat mass, and insulin resistance with high fat diet, but not with low fat diet, without influencing energy intake. Permethrin treatment also significantly increased serum levels of insulin, glucose, leptin, triglycerides and cholesterol. Further results showed that permethrin inhibited AMP-activated protein kinase in white adipose tissue. These results suggest that permethrin interacts with dietary fat to alter lipid and glucose metabolisms in male C57BL/6J mice.