Made available in DSpace on 2016-07-18T17:53:17Z (GMT). No. of bitstreams: 1 Francislaine.pdf: 394781 bytes, checksum: a0d56232957fee86543512d568bcec4c (MD5) Previous issue date: 2015-12-18 / Tea is an extremely popular drink, being the second most commonly consumed in the world. People ingest teas on average two to three times a day, the majority being derived from the Camellia sinensis plant. The beneficial health effects of the consumption of tea from this plant are well known, such as the prevention of cancer, cardiovascular disease and osteoporosis. Despite this, little is known about the action of white tea on reproduction. It is important to evaluate the possible consequences of consumption on luteal and endometrial development since the main catechin, epigallocatechin gallate (EGCG), present in the tea influences the gene expression of VEGF in tumors and this is an important angiogenic factor in the reproductive organs. This study aimed to verify the effects of prolonged intake of white tea on the relative abundance of VEGF mRNA and its receptors, as well as in cell proliferation in the endometrium of superovulated rats. For this purpose, the rats were divided into two groups, control group (n = 30), which received water, and white tea intake group (n = 30). The ovaries and uteri were collected from 10 animals in each group at the end of every month, for three consecutive months, stored in Trizol in a freezer at -80 ° C and the relative abundance of VEGF mRNA, Flt-1 and KDR were subsequently evaluated. In addition, the uteri were histologically analyzed using the silver staining method to detect cell proliferation. The data were evaluated for the assumption of normality (Shapiro-Wilk) and statistical comparisons were performed using the unpaired t test between groups at different collection moments (p <0.05). The relative abundance of VEGF mRNA and its receptors was changed by the tea consumption and there were a lower number of nucleolar organizer regions in endometrial cells. It was concluded that prolonged consumption of white tea interferes the expression of the VEGF system genes in the corpus luteum and decreases cell proliferation in the endometrium of Wistar rats. / O chá é uma das bebidas mais populares e a segunda mais consumida no mundo. A população ingere chás em média, de duas a três vezes ao dia, sendo em sua maioria oriundos da planta Camellia sinensis. São bem conhecidos os efeitos benéficos para a saúde do consumo dos chás provenientes dessa planta, como a prevenção de câncer, de doença cardiovascular e da osteoporose. Apesar disso, pouco se sabe sobre a ação do chá branco na reprodução, sendo importante avaliar as possíveis consequências do seu consumo no desenvolvimento luteal e endometrial. Visto que a principal catequina, a epigalocatequina galato (EGCG) presente neste chá influencia a expressão gênica do Vegf em tumores e este é um importante fator angiogênico dos órgãos reprodutivos, este estudo teve como objetivo verificar o efeito da ingestão do chá branco sobre a abundância relativa do mRNA do Vegf e dos seus receptores,sobre a proliferação celular do endométrio de ratas superovuladas. Para tanto, as ratas foram distribuídas em dois grupos, grupo controle (n=30) que recebeu água e grupo com ingestão de chá branco (n=30). Os ovários e os úteros foram coletados ao final de cada mês de ingestão de chá branco ou água de 10 animais de cada grupo, durante três meses consecutivos, sendo os ovários armazenados em trizol no freezer a -80ºC e posteriormente a abundância relativa de mRNA do Vegf, do Flt-1 e do Kdr foram avaliadas. Além disso, os úteros foram analisados histologicamente pelo método de coloração de prata para detecção de proliferação celular. Os dados foram avaliados quanto ao pressuposto de normalidade (Shapiro-Wilk) e as comparações estatísticas foram realizadas por meio dos testes t não pareado entre os grupos nos diferentes momentos de colheitas (p<0,05). A abundância relativa de mRNA do Vegf e dos seus receptores foi alterada pelo consumo de chá e houve um menor número de regiões organizadoras de nucléolo nas células do endométrio. Conclui-se que a ingestão prolongada de chá branco altera a expressão dos genes do sistema Vegf no corpo lúteo e diminui a proliferação celular do endométrio de ratas Wistar.

The cardiovascular system is the first functional organ to develop during embryogenesis. As the embryo reaches above a certain size, passive diffusion of gases and nutrients is no longer compatible with efficient growth. During embryogenesis, endothelial progenitor cells (angioblasts) are recruited from the primitive streak mesoderm and instructed to express vascular endothelial growth factor receptor-2 (VEGFR-2). This thesis examines the roles played by VEGFR-2 in the events through which a subpopulation of embryonic stem (ES) cells differentiate into endothelial cells and form the vasculature. We show that ES cells gene targeted for VEGFR-2 (flk1-/-) develop immature endothelial cells (ECs), precursors, when differentiated in vitro as embryoid bodies (EBs). The flk1-/- ECs are unresponsive to VEGF-stimulation and consistently fail to form vessels. However, when co-cultured with wild type ES cells in chimeric EBs, flk1-/- endothelial precursors are guided by wild type ECs to form transient, chimeric vascular structures. Use of lentivirus in an add-back approach allowed reconstitution of VEGFR-2 expression in flk1-/- ES cells, and rescue of vasculogenesis and sprouting angiogenesis. We propose that recruitment to the endothelial lineage is not dependent on VEGFR-2, although this receptor tyrosine kinase appears indispensible for EC integrity, survival and for differentation of endothelial precursors into mature ECs formating a stable vasculature. Neuropilin-1 (NRP1) and heparan sulfate proteoglycans (HSPGs) function as co-receptors for VEGFs. The co-receptors influence, qualitatively and quantitatively, the intracellular signal relayed by VEGFR-2 but it is unclear how. We examined the contribution of NRP1 to VEGFR-2 signaling in EB cultures, in zebrafish and in mice. Only NRP1-binding VEGFs were able to promote sprouting angiogenesis and formation of properly branched vascular tubes, supported by pericytes. Downstream of VEGFR-2/NRP1 activation, we identified recruitment of p38MAPK in signal transduction regulating sprouting angiogenesis.

Submitted by Marco Antônio de Ramos Chagas (mchagas@ufv.br) on 2017-07-06T13:14:32Z No. of bitstreams: 1 texto completo.pdf: 281782 bytes, checksum: 55a6b921ddc9e16a34e099872f6b9ef1 (MD5) / Made available in DSpace on 2017-07-06T13:14:32Z (GMT). No. of bitstreams: 1 texto completo.pdf: 281782 bytes, checksum: 55a6b921ddc9e16a34e099872f6b9ef1 (MD5) Previous issue date: 2001-02-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Este estudo foi conduzido com o objetivo de detectar a resistência a seis inseticidas e os prováveis mecanismos bioquímicos de resistência em populações de Sitophilus zeamais, oriundas de seis estados brasileiros. Os bioensaios foram feitos em frascos de 20 ml que foram impregnados por toda a sua área interna, com inseticida ou sinergista. Os bioensaios de detecção de resistência foram feitos utlizando as concentrações letais para 95% dos indivíduos, CL 95 , para a população padrão de susceptibilidade de cada inseticida, obtidas através de análise de próbite. Os resultados destes testes mostraram seis populações resistentes. A população de Cristalina-GO apresentou resistência apenas a cipermetrina, o mesmo acontecendo com a população de Nova Andradina-MS. Já a populaç ão de Jacarezinho-PR se mostrou resistente a todos os inseticidas piretróides testados: deltametrina, cipermetrina e permetrina. A população de Penápolis/Barbosa-SP apresentou resistência à cipermetrina, ao clorpirifós metílico e ao pirimifós metílico. Na população de Fátima do Sul-MS foi detectada resistência apenas para clorpirifós metílico. A população de São José do Rio Preto-SP se mostrou resistente a cipermetrina e pirimifós metílico. Para os bioensaios com os sinergistas trifenil fosfato (TPP), butóxido de piperonila (PBO) e dietil maleato (DEM), foram aplicadas nas populações resistentes as CL 95 para a população padrão de susceptibilidade dos inseticidas combinados com os sinergistas. Os resultados destes bioensaios mostraram que os compostos TPP e DEM bloquearam a resistência a cipermetrina nas populações de Cristalina-GO, Nova Andradina-MS, Penápolis/Barbosa-MS e São José do Rio Preto-SP. Estes compostos e o PBO também ocasionaram a perda da resistência a clorpirifós metílico nas populações de Fátima do Sul-MS e Penápolis/Barbosa- SP. Os resultados dos bioensaios com PBO também mostraram que este composto provocou um aumento na resistência a cipermetrina nas populações de Cristalina-GO e Nova Andradina-MS; o mesmo efeito foi constatado para o inseticida pirimifós metílico nas populações de Penápolis/Barbosa e São José do Rio Preto. Este estudo mostrou evidências de que os mecanismos bioquímicos de resistência baseados nas glutationa-S-transferase, inibidas pelo DEM, e esterases, inibidas pelo TPP, atuaram de forma mais frequente do que as monoxigenases dependentes do citocromo P-450, cuja ação é suprimida pelo PBO. Além do envolvimento destas enzimas na resistência de S. zeamais a inseticidas, é provável a ocorrência de insensibilidade ao sítio de ação na resistência da população de Jacarezinho-PR a piretróides. / This study was carried out with the objective of detecting the resistance to six insecticides and the possible biochemical mechanisms of resistance in populations of Sitophilus zeamais , from six Brazilian states. The bioassay was carried out in 20 mL vials which were impregnated with insecticide or sinergist on their inner walls. The bioassay of resistance detection was carried out using the LC 95 for the susceptible standard population and each insecticide. The results of these tests showed six resistant populations. The Cristalina-GO population just showed resistance to the cypermethrin, like the population from Nova Andradina-MS. The Jacarezinho population showed resistance to all of the tested pyrethroids: deltamethrin, cypermethrin and permethrin. The population from Penápolis/Barbosa-SP showed resistance to cypermethrin, chlorpirifos methyl and pirimiphos methyl. For the population of Fátima do Sul- MS, only resistance to chlorpyrifos methyl was detected. The São José do Rio Preto-SP population showed resistance to cypermethrin and pirimiphos methyl. Bioassays with the sinergists triphenyl phosphate (TPP), piperonyl butoxide (PBO) and diethyl maleate (DEM) were carried out using the LC 95 of the standard susceptible population for the insecticides combined with the sinergists. The results of these bioassays showed that TPP and DEM are able to suppress cypermetrin resistance in the population of Cristalina-GO, Nova Andradina-MS, Penápolis/Barbosa-MS and São José do Rio Preto-SP. All three sinergists provided suppression of the resistance to chlorpyrifos methyl resistance in the population of Fátima do Sul-MS and Penápolis/Barbosa-SP. The results of the bioassays with PBO also showed that this synergist antagonizes the insecticide action increasing its resistance to cypermetrin in the populations of Cristalina-GO and Nova Andradina-MS. The same effect was observed for the insecticide pirimiphos methyl in the population from Penápolis/Barbosa-SP and São José do Rio Preto -SP. This study provided preliminary evidence of a major involvement of biochemical mechanisms of resistance based on enhanced detoxification activity of the glutathione-S- transferases enzyme group inhibited by DEM, and of the esterases, enzyme group inhibited by TPP, with a minor involvement of the cytochrome P-450 dependent monoxigenases, whose action is suppressed by PBO. Besides the likely involvement of these enzymes in S. zeamais resistance, there also seems to occur site of action insensibility leading to pyrethroid resistance in the population from Jacarezinho-PR. / Dissertação importada do Alexandria

Submitted by Jaqueline Silva (jtas29@gmail.com) on 2014-10-20T19:00:58Z No. of bitstreams: 2 Dissertação - Francesca Guaracyaba Garcia Chapadense - 2014.pdf: 2109065 bytes, checksum: 072f238fcfb1e81ef119c284c7367100 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2014-10-20T19:01:08Z (GMT) No. of bitstreams: 2 Dissertação - Francesca Guaracyaba Garcia Chapadense - 2014.pdf: 2109065 bytes, checksum: 072f238fcfb1e81ef119c284c7367100 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-10-20T19:01:08Z (GMT). No. of bitstreams: 2 Dissertação - Francesca Guaracyaba Garcia Chapadense - 2014.pdf: 2109065 bytes, checksum: 072f238fcfb1e81ef119c284c7367100 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-04-10 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Organophosphorus and Pyrethroids are widely used in Brazil in the control of Aedes aegypti. Excessive use of these insecticides has resulted in the evolution of insecticide-resistant mosquito populations. The present study aimed to evaluate resistance to temephos and deltamethrin of A. aegypti populations from three districts in Goiânia-GO, Brazil (Finsocial, Sudoeste and Jardim America), to and to identify mutations in the kdr resistance-associated sodium channel gene pyrethroid. The collections were made using Ovitraps. The Dose-Response Bioassays were performed according to the WHO. Determined the lethal concentration (LC50 and LC95) for the three populations of the two compounds and their resistance ratios (RR) compared with the susceptible Rockefeller strain. DNA from 30 individuals of each population, and was extracted by using the allele-specific PCR, by dissociation curve to search Phe1534Cys polymorphism site, and Real-Time PCR and polyacrylamide gel for detection of gene polymorphism Val1016Ile kdr. In addition to the substitutions at sites identified individually, they were detected occurring concurrently. The Finsocial, Sudoeste and Jardim América, populations showed, RR95 of 5.1; 4.9 and 5.3 for temephos RR95 and 112.6, 64.7 and 75.9 for deltamethrin, respectively. The Phe1534Cys polymorphism was found in all populations having an allelic frequency: 1.0, 1.0 and 0.98 for Vila Finsocial, Sudoeste and Jardim América. The Val1016Ile polymorphism was detected and showed allele frequency of 0.47, 0.72 and 0.53 respectively in Vila Finsocial, Sudoeste and Jardim América. All populations showed concurrent evaluated polymorphisms occurring in the ratio of 0.25, 0.577 and 0.393 for Vila Finsocial, Southwest and Jardim America. We conclude that even after eight years of disuse of temephos in the region, the larvae of A. aegypti also show resistance to the compound, preventing his return. The deltamethrin is a measure of ineffective management for vector control in Goiânia-GO and mutations involved in the mechanism of resistance to pyrethroids are present at high level in all tested populations, jeopardizing the effectiveness of the main tool for vector control dengue virus. / Organofosforados e piretroides são amplamente utilizados no Brasil no controle de Aedes aegypti. O uso excessivo desses inseticidas resultou na evolução de populações de mosquitos resistentes aos compostos. O estudo teve como objetivo avaliar a resistência de populações de A. aegypti de três bairros de Goiânia-GO (Finsocial, Sudoeste e Jardim América), ao temefós e à deltametrina e identificar mutações no gene do canal de sódio kdr associadas à resistência a piretroides. As coletas foram realizadas utilizando armadilhas do tipo Ovitrampas. Os bioensaios Dose-Resposta para temefós e deltametrina foram realizados de acordo com a OMS. Determinou-se a Concentração Letal (CL50 e CL95) para as três populações aos dois compostos e suas respectivas Razões de Resistência (RR), por comparação à cepa suscetível Rockefeller. O DNA de 30 indivíduos de cada população foi extraído e através do uso do PCR alelo-específica, por curva de dissociação, para pesquisa do polimorfismo sítio Phe1534Cys, e do PCR em Tempo Real e gel de poliacrilamida, para detecção do polimorfismo Val1016Ile do gene kdr. Além das substituições identificadas individualmente nos sítios, as mesmas foram detectadas ocorrendo em simultaneidade. As populações Finsocial, Sudoeste e Jardim América, mostraram, RR95 de 5,1; 4,9 e 5,3 para o temefós e RR95 de 112,6, 64,7 e 75,9 para deltametrina, respectivamente. O polimorfismo Phe1534Cys foi encontrado em todas as populações apresentando uma freqüência alélica de: 1,0, 1,0 e 0,98, para Vila Finsocial, Sudoeste e Jardim América. O polimorfismo Val1016Ile foi detectado e apresentou frequência alélica de 0,47, 0,72 e 0,53, respectivamente em Vila Finsocial, Sudoeste e Jardim América. Todas as populações avaliadas apresentaram polimorfismos simultâneos ocorrendo na proporção de 0,25, 0,577 e 0,393, para Vila Finsocial, Sudoeste e Jardim América. Conclui-se que mesmo após oito anos de desuso do temefós na região, as larvas de A. aegypti apresentam ainda resistência ao composto, impossibilitando seu retorno. A deltametrina representa uma medida de controle ineficaz para o controle do vetor em Goiânia-GO e as mutações envolvidas no mecanismo de resistência a piretroides estão presentes em alto nível em todas as populações avaliadas, pondo em risco a eficácia da principal ferramenta de controle do vetor do vírus da dengue.

Atherosklerotische Arterien unterliegen strukturellem Umbau und chronischer Inflammation, die von einer dynamischen Entwicklung von Vasa vasorum (VV) begleitet wird. Die Beteiligung von Leukozyten und von vaskulären Vorläuferzellen an der Neovaskularisierung sowie die intimale Hyperplasie stehen im Zentrum der Atheroskleroseforschung. Damit verbundene Erkenntnisse könnten neue therapeutische Ansätze ermöglichen. Die vorliegende Arbeit befaßt sich mit der morphologischen Verteilung von Leukozyten (CD45, CD68, Mastzellen) und von Zellen mit Vorläufermarkern (CD34, CD117, VEGFR-2) in menschlichen Coronararterien mit verschiedenen atherosklerotischen Schweregraden. Mittels immunhistologischer Technik wurden Intima und Adventitia untersucht und die Ergebnisse zu den atherosklerotischen Schweregraden und der Neovaskularisierung korreliert. In Intima, Adventitia und dem perivaskulären Fettgewebe hat die Dichte der CD45+ Lymphozyten ihr Maximum im atherosklerotischen Grad 3. Dabei konnte sowohl in der Intima als auch in der Adventitia gezeigt werden, daß eine lineare Korrelation der CD45+ Lymphozyteninfiltration und VV-Dichte vorliegt. Es wurden zwei unterschiedliche Entzündungsmuster festgestellt. Beide zeigen in Grad 3 eine Zunahme der Zelldichten. In Grad 4-5 fällt die Dichte des einen Musters (CD45+, VEGFR-2+, VV) jedoch ab, während die Dichte des anderen Musters (CD34+, CD68+, Tryptase+, CD117+) in Grad 4-5 keine Veränderung aufweist. Die Ergebnisse deuten darauf hin, daß Leukozyten und vaskuläre Vorläuferzellen im Verlauf der Atherogenese wechselnde Funktionen wahrnehmen können. Sie nehmen offensichtlich VV als Eintrittspforte in die Gefäßwand.

Atherosklerotische Arterien unterliegen strukturellem Umbau und chronischer Inflammation, die von einer dynamischen Entwicklung von Vasa vasorum (VV) begleitet wird. Die Beteiligung von Leukozyten und von vaskulären Vorläuferzellen an der Neovaskularisierung sowie die intimale Hyperplasie stehen im Zentrum der Atheroskleroseforschung. Damit verbundene Erkenntnisse könnten neue therapeutische Ansätze ermöglichen. Die vorliegende Arbeit befaßt sich mit der morphologischen Verteilung von Leukozyten (CD45, CD68, Mastzellen) und von Zellen mit Vorläufermarkern (CD34, CD117, VEGFR-2) in menschlichen Coronararterien mit verschiedenen atherosklerotischen Schweregraden. Mittels immunhistologischer Technik wurden Intima und Adventitia untersucht und die Ergebnisse zu den atherosklerotischen Schweregraden und der Neovaskularisierung korreliert. In Intima, Adventitia und dem perivaskulären Fettgewebe hat die Dichte der CD45+ Lymphozyten ihr Maximum im atherosklerotischen Grad 3. Dabei konnte sowohl in der Intima als auch in der Adventitia gezeigt werden, daß eine lineare Korrelation der CD45+ Lymphozyteninfiltration und VV-Dichte vorliegt. Es wurden zwei unterschiedliche Entzündungsmuster festgestellt. Beide zeigen in Grad 3 eine Zunahme der Zelldichten. In Grad 4-5 fällt die Dichte des einen Musters (CD45+, VEGFR-2+, VV) jedoch ab, während die Dichte des anderen Musters (CD34+, CD68+, Tryptase+, CD117+) in Grad 4-5 keine Veränderung aufweist. Die Ergebnisse deuten darauf hin, daß Leukozyten und vaskuläre Vorläuferzellen im Verlauf der Atherogenese wechselnde Funktionen wahrnehmen können. Sie nehmen offensichtlich VV als Eintrittspforte in die Gefäßwand.

The regulation of muscle stem cell (MuSC) asymmetric division plays an essential role in controlling the growth and repair of skeletal muscle. Perturbations in MuSC function have been demonstrated in disease and aging contexts such as Duchenne’s Muscular Dystrophy (DMD) and sarcopenia. We developed and optimized a high content analysis platform combining lineage tracing, myofiber culture, imaging, and bioinformatic analysis to determine modulators of muscle stem cell division. We discover kinase domain receptor (KDR) as a positive modulator of MuSC asymmetric division and confirmed its expression in satellite cells by ddPCR and immunofluorescence. Knockdown of KDR significantly reduces the numbers of asymmetric divisions, whereas ligand stimulation of KDR increases the numbers of asymmetric divisions. KDR signaling is impaired in dystrophin- deficient satellite cells and requires a polarized cell environment established by the dystrophin glycoprotein complex (DGC) to direct asymmetric division. Mice lacking KDR in MuSCs exhibit reduced numbers of satellite cells due to precocious differentiation, and deficits in regeneration consistent with impaired asymmetric division and reduced generation of progenitors. Therefore, our experiments identify KDR signaling as playing an essential role in MuSC function in muscle regeneration. These findings further our understanding of muscle stem cell biology, and in particular, the role of asymmetric division under homeostatic and regenerative conditions.

<p>Bed bugs (<i>Cimex lectularius</i> L.) are globally important human ectoparasites. Their management necessitates the use of multiple control techniques. Plant-derived essential oils are extracts from aromatic plants that represent one of the alternative control measures for bed bug control, in addition to mechanical options and synthetic pesticides. However, there is limited information available on the efficacy and toxicology of plant essential oils against bed bugs. This project was designed with the aim to provide in-depth information on efficacy, toxicology and mode-of-action of essential oils and their insecticidal constituents in bed bugs. Initially, I evaluated topical and fumigant toxicity of fifteen essential oil components against adult male bed bugs of the Harlan strain (an insecticide susceptible strain). Neurological effects of the six most toxicologically active compounds were also determined. In both topical and fumigant bioassays, carvacrol and thymol were the most active compounds. Spontaneous electrical activity measurements of the bed bug nervous system demonstrated neuroinhibitory effects of carvacrol, thymol and eugenol, whereas linalool and bifenthrin (a pyrethroid class insecticide) produced excitatory effects. Further, I evaluated the efficacy and neurological impacts of a mixture of three neuroinhibitory compounds; carvacrol, eugenol and thymol in 1:1:1 ratio against adult male bed bugs of the Harlan strain. This mixture of monoterpenoids as well as the mixture of synthetic insecticides exhibited a synergistic affect in topical bioassays. In electrophysiology experiments, the monoterpenoid mixture led to higher neuroinhibitory effects, whereas a mixture of synthetic insecticides caused higher neuroexcitatory effects in comparison to single compounds. </p> <p>In the next objective of my dissertation, I compared the efficacy of five plant essential oils (thyme, oregano, clove, geranium and coriander), their major components (thymol, carvacrol, eugenol, geraniol and linalool) and EcoRaider^® (commercial product) between pyrethroid susceptible (Harlan) and field collected (Knoxville) bed bug populations. Initially, I found that the Knoxville strain was 72,893 and 291,626 fold resistant to topically applied deltamethrin (a pyrethroid class insecticide) compared to the susceptible Harlan strain at the LD₂₅ and LD₅₀ lethal dose levels, respectively. Synergist bioassays and detoxification enzyme assays showed that the Knoxville strain possesses significantly higher activity of cytochrome P450 and esterase enzymes. Further, Sanger sequencing revealed the presence of the L925I mutation in the voltage gated sodium channel gene. The Knoxville strain, however, did not show any resistance to plant essential oils, their major components or EcoRaider^® in topical bioassays (resistance ratios of ~ 1). In the final objective, I evaluated the efficacy of binary mixtures of above-mentioned essential oils or their major components or EcoRaider^® with deltamethrin in susceptible and resistant bed bugs. In topical application bioassays, binary mixtures of essential oils or their major components or EcoRaider^® and deltamethrin at the LD₂₅ dose caused a synergistic increase in toxicity in resistant bed bugs. Further, I studied the inhibitory effects of major essential oil components on detoxification enzyme activities (cytochrome P450s, esterases and glutathione transferases). Detoxification enzyme assays conducted using protein extracts from bed bugs pre-treated with essential oil constituents showed that these compounds significantly inhibited cytochrome P450 activity in the resistant strain, but esterase and glutathione transferase activity were unaffected. No inhibition of detoxification enzyme activities was observed in the Harlan strain bed bugs pre-treated with essential oil constituents.</p> <p>In conclusion, my dissertation research has created the foundation for utilization of natural products for bed bug management by (i) describing the efficacy of plant essential oils and their components against bed bugs, (ii) discovering synergistic interactions between essential oil components at the nervous system level, (iii) determining susceptibility of deltamethrin-resistant bed bugs to plant essential oils and their constituents and (iv) identifying synergistic effects of essential oils or their components on toxicity of pyrethroid insecticides and underlying mechanisms of this synergistic interaction. </p> <br>