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Weidemann, Annchen. "The role of fructose restriction in addition to dietary modifications for weight loss and lifestyle improvement, on fertility outcome and other markers of metabolic syndrome (MS), in obese women with polycystic ovarian syndrome (PCOS)." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71878.
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Thesis (MNutr)--Stellenbosch University, 2012.ENGLISH ABSTRACT: The role of fructose restriction in addition to dietary modifications for weight loss and lifestyle improvement, on fertility outcome and other markers of metabolic syndrome, in obese women with polycystic ovarian syndrome (PCOS) Introduction: At the time at which the current study was undertaken no data, as yet, existed on whether restriction of fructose, while treating obese patients with PCOS for weight loss, improves the clinical symptoms and metabolic/anthropometric profile so as to promote fertility. Objectives: To evaluate the baseline intake of fructose, as well as the effect of restricting fructose intake from fruit and soft beverages to less than 20 g daily, as well as to provide guidelines for weight loss on anthropometric measurements, for improving subjective clinical symptoms, and for promoting fertility outcome in obese patients with PCOS, who seek to become fertile. Methods: The study was conducted in the Tygerberg Hospital Infertility Clinic, as an experimental cohort. Patients with a body mass index (BMI) higher than 27, seeking fertility after diagnosis with PCOS, were referred for dietary consultation, and followed up 3 monthly over 1 year. At each visit anthropometric measurements and a detailed dietary history were taken and a questionnaire for clinical symptoms was completed. Results: Baselinely, 86 patients were included in the study. Averages for weight and BMI were 99.8 ± 24.3 kg and 39.2 ± 8.7kg/m2, respectively. Average baseline daily fructose intake was 167 ± 116.8g. At baseline, significant relationships were shown between fructose intake and burning feet (ρ=0.02) and frequent waking (ρ=0.02), with a trend towards nightly eating (ρ=0.07). The dropout rate after visit 1 was 50%, with a further dropout of 41% after visit 2. After 3 visits (n=18), fructose intake significantly reduced (ρ=0.018), with the significant relationships with clinical symptoms having disappeared by visit 2. After 3 visits (n=18), both weight and BMI decreased significantly (ρ=0.017) and (ρ=0.019), respectively. Fructose was tested as a covariate to BMI, with high significance (ρ=0.006) in said population group. Conclusion: Dietary intervention to reduce fructose intake proved significant for weight loss and BMI after 3 visits. Reduced fructose intake was associated with reduced clinical symptoms. With fructose being a significant covariate to BMI, it can be concluded that fructose overconsumption could possibly contribute to both clinical symptoms and elevated BMI in said study population.
AFRIKAANSE OPSOMMING: Die rol wat die beperking van fruktose speel bykomend tot dieetaanpassings en lewenstylverbetering vir gewigsverlies by oorgewig vroue met polisistiese ovariële sindroom (PCOS) in die uitkoms van fertiliteit en ander merkers van metaboliese sindroom. Inleiding: Met die aanvang van hierdie studie was daar is geen data beskikbaar oor die invloed van die beperking van fruktose in die dieet van oorgewig pasiënte met PCOS wat vir gewigsverlies behandel word nie. Dit was ook nie bekend of laasgenoemde pasiënte se kliniese simptome en metaboliese/antropometriese profiel sou verbeter met die beperking van fruktose sodat fertiliteit by hierdie pasiënte terselfdertyd ook bevorder word nie. Doelwitte: Die evaluering van die aanvanklike inname van fruktose, sowel as die beperking van fruktose afkomstig van eetbare vrugte en versoete drankies en sap tot ’n inname van minder as 20 g daagliks, tesame met riglyne vir gewigsverlies. Die uitkoms hiervan is bepaal deur antropometriese metings, die verbetering in subjektiewe kliniese simptome en die fertiliteituitkoms by oorgewig pasiënte wat hulp met fertiliteit verlang. Metodes: Die studie het as ’n eksperimentele kohort by die Infertiliteitskliniek by Tygerberg Hospitaal plaasgevind. Pasiënte wat na diagnose met PCOS fertiliteitsbehandeling verlang het en ’n BMI hoër as 27 gehad het , is vir dieetbehandeling verwys en driemaandeliks oor ’n tydperk van een jaar opgevolg. Tydens elke besoek is antropometriese metings en ’n omvattende dieetgeskiedenis geneem en ’n vraelys oor kliniese simptome ingevul. Resultate: Aanvanklik is 86 pasiënte by die studie ingesluit. Gemiddeldes vir gewig en BMI was 99.8 ± 24.3 kg en 39.2 ± 8.7 kg/m2 respektiewelik. Gemiddelde aanvanklike daaglikse inname van fruktose was 167 ± 116.8 g. Oorspronklik het betekenisvolle verhoudings tussen fruktose en die volgende bestaan: brandvoete (ρ=0.02) en veelvuldige episodes van nagtelike wakkerheid (ρ=0.02), met ’n neiging na nagtelike etery (ρ=0.07). Die uitvalsyfer na een besoek was 50% met ’n verdere uitvalsyfer van 41% na die tweede besoek. Na drie besoeke (n=18) het sowel die gewig as die BMI betekenisvolle afname getoon (ρ= 0.017) en (ρ=0.019), respektiewelik. Fruktose is as ’n belangrike kovariant vir BMI (ρ= 0.006) vir hierdie populasiegroep geïdentifiseer. Gevolgtrekking: Dieetintervensie vir die vermindering van die inname van fruktose was beduidend vir gewigsverlies en afname in BMI na drie besoeke. Verminderde fruktose-inname het gelei tot die vermindering van kliniese simptome. Met fruktose as beduidende kovariant vir BMI kan die gevolgtrekking gemaak word dat die oor-inname van fruktose by hierdie studiepopulasie waarskynlik tot sowel kliniese simptome as BMI bygedra het.
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Braga, Ana Maria Cheble Bahia. "Dioxinas, furanos e PCBs em leite humano no Brasil." [s.n.], 2003. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310590.
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Orientadores: Angelo Zanaga Trape, Thomas Manfred KraussTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-05T19:02:29Z (GMT). No. of bitstreams: 1 Braga_AnaMariaChebleBahia_D.pdf: 1900359 bytes, checksum: 79e7312e2649cd6e41634906f1302f41 (MD5) Previous issue date: 2003
Resumo: O presente estudo é pioneiro no Brasil e ganha relevância tendo em vista as várias possíveis fontes antropogênicas de PCBs, PCDDs e PCDFs ainda não mapeadas, da ocorrência de acidentes com exposição a produtos clorados em populações brasileiras e da presença, de detecção recente, na ração animal aqui produzida e exportada para a Europa. O objetivo principal foi avaliar a exposição da população geral, utilizando-se o leite humano como bioindicador, com vistas a subsidiar ações de prevenção e controle de emissões destes poluentes para o meio ambiente, como forma efetiva de minimizar a exposição humana. Sendo também parte da terceira rodada dos estudos de exposição organizada pela OMS, a metodologia utilizada seguiu seu protocolo já validado. Em cada uma das 10 áreas amostradas, nas diferentes regiões do país, foram coletadas 10 amostras individuais, conformando uma amostra composta que foi enviada para análise no laboratório de referência da OMS na Alemanha. As amostras de leite humano foram coletadas, em sua maioria, em bancos de leite humano integrantes da Rede Nacional de Bancos de Leite Humano, usando critérios pré-definidos para a seleção das mães doadoras. Ao nível mundial, dos 24 países participantes do estudo, as concentrações encontradas no Brasil foram as mais baixas. Propõe-se um programa de monitoramento destas substâncias e outros Poluentes Orgânicos Persistentes em leite humano e em amostras ambientais como ação preventiva e de controle, incrementando o conhecimento a respeito da ocorrência destes compostos no Brasil, para subsidiar o gerenciamento das substâncias químicas e os acordos internacionais como a Convenção de Estocolmo
Abstract: The presented research is pioneer in brazil and its relevance is due to the various unmapped possible anthropogenic sources of PCBs, PCDDs and PCDFs, to the occurrence of accidents with chlorinated products exposing brazilian populations and the recent episode related to the presence of such contaminants in feedstuff exported to europe. The main objective of this study was to evaluate the exposure of the general population considering human milk as good indicator. Moreover, the study may subsidize future preventing actions and emission control of these pollutants to the environment as an effective manner to minimize human exposure. being also part of the third round of exposure studies organized by WHO, the used methodology followed the validated WHO¿s protocol, as well. In each of the ten sampled areas from different brazilian regions, it was collected ten individual samples to form one pooled sample which was sent to the WHO¿s reference laboratory in Germany. Human milk samples were mostly collected from human milk banks which are part of the National Human Milk Bank Network. Donors were selected considering the prior defined eligibility criteria. On worldwide level, the concentrations found in brazil were the lowest among the 24 participant countries. A monitoring program of these substances e others Persistent Organic Pollutants in human milk and environmental samples is proposed as prevention and control actions. Besides extending the knowledge about the occurrence of these compounds in Brazil, the study may subsidize international programs such as the Stockholm Convention and improve the management of chemical substances
Doutorado
Saude Ambiental
Doutor em Saude Coletiva
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Juan, Ching-yi Amy. "Studies on the intake and behaviour of PCBs in humans." Thesis, Lancaster University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274223.
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Perumal, Kuppusamy Senthilkumar. "Telomerase and telomere dysregulation in Polychlorinated Biphenyl (PCB) exposed human skin keratinocytes." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/2957.
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Polychlorniated Biphenyls (PCBs), a group of 209 individual congeners, are ubiquitous environmental pollutants and classified as probable human carcinogens. Hallmarks of aging and carcinogenesis are changes in telomerase activity and telomere length. I hypothesize that PCBs modulate telomerase activity and telomeres via interference in gene regulation and generation of reactive oxygen species (ROS) resulting in the dysregulation of cell growth. To explore this possibility, I exposed human skin keratinocytes (HaCaT) to a synthetic airborne PCB mixture (CAM) and individual congeners, i.e. PCB28, PCB52, PCB126 and PCB153. To mimic the chronic human exposure to PCBs and the slow process of carcinogenesis, a long term exposure period of 48 days and beyond was employed. All PCB congeners and CAM reduced telomerase activity, telomere length and cell growth. Among all PCBs, PCB126 had the most pronounced effect with reduction in telomerase activity, telomere length, hTERT and hTR gene expression and cell growth, while increasing TRF1 & TRF2 gene expression. PCB126 elicited an increase in CYP1A1 mRNA, CYP1A1 activity, DHE and DCFH oxidation levels from days 6 to 48, suggesting that increased ROS might be a causative factor for the reduction in telomerase activity and telomere length. However, transduction with hTERT and hTR subunits partly rescued telomerase activity, while treatment with PEG-catalase did not rescue telomerase activity suggesting that telomerase subunits play an important role on PCB126 induced effects on telomerase activity and telomere length. Since cells with shortened telomeres may escape crisis through telomerase reactivation, PCB126 treatment was continued until day 90. A change in growth behavior was observed from day 54 to 90, with cells recovering the proliferation rate, and increasing c-Myc, hTERT, and hTR gene expression level, re-activating telomerase activity and re-elongating telomere length. TRF1 & 2 gene expression started to decrease after day 66. From day 78, no increase in CYP1A1mRNA and its activity as well as CYP1B1, ALDH3A1, UGT1A1 and AhRRmRNA was observed suggesting that the AhR response pathway may have been altered. This study shows for the first time that PCBs initially reduce telomerase activity, telomere length, and cell growth, and can later lead to telomerase re-activation, telomere lengthening and increased cell growth with modulation of the AhR receptor pathway. This observation has broad implications for chronic PCB exposure scenarios.
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Khabazbashi, Sara. "Analytical Standard Free Semi-Quantification of OH-PCBs in human blood serum samples." Thesis, Karlstads universitet, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-84442.
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Grimm, Fabian Alexander. "Toxicological and therapeutic implications of interactions between polychlorinated biphenyl sulfates and human transthyretin." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/4635.
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In recent years, lower-chlorinated, airborne congeners of polychlorinated biphenyls (PCBs) have evolved as an emerging class of potentially hazardous environmental contaminants. Previous work has demonstrated that sulfation is a major metabolic pathway for these PCBs in vitro and in vivo; however, their metabolic fate and toxicities have not been explored. Hypothyroxinemia is among the most prevalent adverse health effects associated with PCB exposure in human populations and is an assumed cause of a variety of neurodevelopmental effects observed in infants following prenatal PCB exposure. The displacement of L-thyroxine (T4) from binding sites on transthyretin (TTR), a major T4 transport protein and trans-placental carrier of thyroid hormones, is thought to be a significant contributing factor in PCB-induced hypothyroxinemia. Structural similarities between sulfated metabolites of PCBs and T4 led to the central hypothesis that PCB sulfates are bioactive metabolites that exhibit high affinity binding to T4 binding sites on human TTR. An examination of the ability of six lower-chlorinated PCB sulfates to bind to human TTR in vitro, as well as subsequent computational modeling, revealed that these compounds interact with the high-affinity binding site in a non-covalent manner and with affinities comparable to T4. Corroborating evidence for the binding of PCB sulfates stems from their ability to inhibit the formation of TTR amyloid fibrils through stabilization of the protein's native conformation. Fibrillar TTR aggregates are the cause of amyloidoses like senile systemic amyloidosis, familial amyloid polyneuropathy and familial amyloid cardiomyopathy. All PCB sulfates examined were effective inhibitors of TTR fibrillogenesis with equal or higher efficiencies than some of the best previously described inhibitors. In vivo exposure of male Sprague-Dawley rats to a model PCB sulfate, 4-PCB 11 sulfate, resulted in rapid and widespread distribution of the metabolite to various organs, including the brain. Consequently, there is a strong indication for a potential role of PCB sulfates in thyroid disruption and inter-tissue transport of PCBs, and the binding of PCB sulfates to TTR may also provide structural information for improved design of anti-amyloid therapeutics. To date there are no analytical procedures for the quantification of PCB sulfates available, and exposure levels in human populations remain unknown. This study provides, for the first time, evidence that PCB sulfates, if present in human serum samples, are not extracted by current standard protocols for the analysis of PCBs and their metabolites. Consequently, PCB sulfates may have been overlooked in the past decades resulting in potential underestimation of total PCB exposure levels in exposed populations. Based on this finding, an efficient approach for the quantitative extraction of PCB sulfates from a variety of biological samples was developed. This procedure, coupled with quantitative mass spectrometry, has been validated for the future screening of human serum samples, and it was successfully applied to determine the tissue distribution and elimination profile of 4-PCB 11 sulfate in male Sprague-Dawley rats.
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Boulay, Hillary Michelle. "The effect of cisplatin on the role of proprotein convertases (PCs) in human ovarian cancer cells." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27319.
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Proprotein convertases (PCs) have been implicated in cancer progression as well as cell survival, although their role in ovarian cancer and drug sensitivity is largely unknown. Of all the PCs, PC4 has the most restricted expression; present only in reproductive tissues (testis, ovary and placenta). The expression and regulation of PC4 were investigated using a pair of cisplatin-sensitive and -resistant cell lines as an in vitro model of ovarian cancer. PC4 is expressed in the ovarian cancer cell lines as well as in tumours from patients diagnosed with the disease. Over-expression of PC4 in chemosensitive cells attenuated cisplatin (CDDP)-induced apoptosis, while inhibition of PC4 activity or down-regulation of PC4 by siRNA sensitized chemoresistant cells to the apoptotic effects of CDDP. Furthermore, current data suggests that the role of PC4 in chemoresistance may be mediated through the processing and activation of IGF-II. These data demonstrate for the first time that PC4 is anti-apoptotic and imply its involvement in the chemoresistance of human ovarian cancer cells.
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Hazrati, Sadegh. "The signiflcance of indoor air as a source of human exposure to polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs)." Thesis, University of Birmingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.633125.
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In order to investigate the significance of indoor air as a source of human exposure to PBDEs and PCBs, 94 indoor microenvironments from 4 major indoor environment categories (i.e. offices, homes, public environments, and cars) were monitored in the West Midlands area between 2003 and 2005. Seasonal and within building variability in PCB and PBDE concentrations were studied by monitoring 8 indoor environments for a period of 12 months. The impact of contaminated indoor air on PCB and PBDE concentrations in outdoor air was also evaluated using both chiral techniques and a simple box model. The average concentration of 2PCB in homes, offices, and public indoor environments combined was 11.65 ng m"3 (median = 3.54 ng m"3 ), ranging from 0.49 to 101.8 ng m'3 . The most contaminated indoor environment category was public environments, followed by offices, homes, and cars. The average concentration of ZPBDE for all indoor *% <5 __ microenvironments studied was 0.269 ng m", ranging from 0.004 to 8.2 ng m" . Excluding cars, this figure for all other indoor microenvironments combined ranged from 0.004 to 1.416 ng m" 3 with average value of 0.109 ng m" 3 . Unlike PCBs, cars were identified as the most contaminated indoor microenvironment category studied with an average concentration of 0.709 ng m'3 . Based on records of time activity patterns and concentrations of PCBs and PBDEs found in indoor environments, the relative significance of inhalation exposure to ZPCB compared to diet ranged from 3.3 to 66.2% (average = 30.6%) for adults and from 0.98 to 20% (average = 7.4%) for toddlers. This figure for ZPBDE was between 0.2 and 15.3% (average = 2.3%) for adults and between 0.04 and 3.9% (average = 0.59%) for toddlers. The results obtained from monitoring 8 selected indoor microenvironments revealed that PCB and PBDE concentrations in warmer months are generally higher than those measured in colder months. Concentrations of some PCB and PBDE congeners also showed statistically significant (p<0.05) seasonal variations in some monitoring locations. The highest ZPCB concentrations were found in buildings constructed between 1950 and 1979 (average EPCB = 19.9 ng m" 3 and SD = 5 ng m"3 ) followed by those constructed prior to 1950 (average SPCB = 5.8 ng m' 3 and SD = 4 ng m' 3 ) and post 1979 (average EPCB = 2 ngm" 3 , and SD = 1.8 ng m" 3 ). ZPCB concentrations in buildings constructed in 1950-1979 were statistically significantly higher than those built post 1979 (pO.OOl). Concentrations of the major PBDE congeners were significantly positively correlated with the construction year of the buildings (p<0.05). However, although concentrations of PBDEs in one office fell appreciably following replacement of a PC manufactured in 1998 with one manufactured in 2003; no significant relationships were detected between concentrations of either PCBs or PBDEs and room contents such as numbers of PCs, other items of electronic equipment, or items of PUF-containing furniture. This suggests that the influence of room contents on the contamination of indoor environments with such compounds is complex, and that factors such as the age of electronic equipment and room ventilation may play an important role. Chiral signatures of PCBs in indoor air were essentially racemic with average EF values of 0.496 ± 0.003, 0.500 ± 0.003, and 0.500 ± 0.004 for PCBs 95, 136, and 149, respectively. EF values of all PCB atropisomers in one office microenvironment in monthly samples taken over a 12 month monitoring period displayed no statistically significant variations between warmer months and colder months (p>0.10). Direct comparison of EFs in indoor air, outdoor air, and soil for chiral PCBs revealed that on average >80% of atmospheric concentrations of PCB 95, 136, and 149 at the EROS monitoring site is derived from the ventilation of contaminated indoor air, which is consistent with the results obtained using a simple box model in the West Midlands. Applying the box model for PBDEs revealed an estimate of daily mass flux of 9.98x10 8 ng ZPBDE from indoor to outdoor air, which provides a predicted concentration of ~5 pg EPBDE m" 3 in outdoor air. This value is line with observed values reported elsewhere for the West Midlands, and suggests that ventilation of indoor air makes a significant contribution to outdoor air contamination with PBDEs.
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Magan, Christopher L. "Human health risk characterization for dietary exposure to polychlorinated biphenyls (PCBs) in fish from the Columbia Basin Irrigation Project a probabilistic approach /." Pullman, Wash. : Washington State University, 2009. http://www.dissertations.wsu.edu/Thesis/Spring2009/c_magan_041709.pdf.
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Thesis (M.S. in environmental science)--Washington State University, May 2009.Title from PDF title page (viewed on May 28, 2009). "School of Earth and Environmental Sciences." Includes bibliographical references (p. 56-63).
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Rodriguez, Eric Alberto. "Hydroxylated and sulfated metabolites of lower chlorinated PCBs bind with high affinity to human serum albumin and exhibit selective toxicity to neuronal cells." Diss., University of Iowa, 2016. https://ir.uiowa.edu/etd/3175.
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Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants that have been associated with a myriad of negative human health effects. These man-made compounds were used throughout most of the 20th century and although their intentional production has since been banned and their use limited to closed systems, their prevalence in the environment remains a factor in disease states for exposed populations. The worldwide levels of PCBs has been declining, however, there is evidence for renewed sources of these compounds. The presence of PCBs with lower numbers of chlorine atoms (LC-PCBs) have been verified as unintentional byproducts in paints and pigments, the decomposition of PCB waste, or the recycling or disposal attempts of PCB-laden materials. While exposure to the higher chlorinated congeners (HC-PCBs) is often attributed to the consumption of contaminated water or fatty animal meat, a significant route of exposure to the airborne LC-PCBs is through inhalation. These semi-volatile compounds have been detected in high quantities in both indoor and outdoor air in urban and rural communities, and their presence is pronounced in older buildings (e.g., homes and schools). When compared to HC-PCBs, LC-PCBs are more highly susceptible to metabolic transformations, and recently their sulfated metabolites have gained much interest. Although the sulfation of xenobiotics often is considered a route for their removal from the body, a previous study of Sprague-Dawley rats treated with 4-chlorobiphenyl (PCB 3) resulted in the substantial formation of sulfated metabolites (i.e., hydroxylation followed by sulfation of the LC-PCB). This metabolic route accounted for more than half of the treatment dose. Furthermore, LC-PCB sulfates have been shown to bind to the human serum protein, transthyretin, in vitro.
Of the health effects associated with PCB exposure, neurotoxicity has been well established through various laboratory and epidemiological studies. It is proposed that the dopaminergic system lies at the core of the observed cognitive, motor, and intellectual dysfunction observed in exposed populations, especially in children exposed perinatally. Interestingly, PCB exposure has been linked to Parkinson's disease (PD) etiology, which is marked by a substantial loss of dopaminergic neurons.
This thesis describes studies on the binding of selected LC-PCBs and their hydroxylated and sulfated metabolites to human serum albumin (HSA), the most abundant protein in human serum. The displacement of fluorescent probes, selective for the two major drug binding sites of HSA, indicates that LC-PCB sulfates generally bind to HSA with such affinity that is equal to or greater than that for the LC-PCBs or OH-LC-PCBs This work also included a study of the selective toxicity of these compounds to dopaminergic neuronal cells. The selective toxicity of these compounds was studied in a series of immortalized cell lines (i.e., two neuronal cell lines: the rat midbrain-derived N27 cell line, the human neuroblastoma-derived SH-SY5Y cell line, and the human liver-derived HepG2 cell line). The assessment of toxicity by MTT reduction and LDH release in these cellular models indicated that hydroxylated and sulfated metabolites of LC-PCBs exhibited toxicity that was selective to neuronal cells and, in most cases, selective for the dopaminergic neuronal cells. Furthermore, HPLC analysis of the distribution of the compounds from the extracellular medium into the cellular milieu indicated that the observed toxicity may be due in some cases to selective transport and further metabolism. This work contributes to understanding the neurotoxicity of LC-PCB hydroxylated and sulfated metabolites and the role that binding to serum proteins may play in it. Furthermore, it emphasizes the need for future studies on the effects that metabolism, particularly sulfation, may play in the disposition of LC-PCB congeners as it pertains to their metabolism, retention, and toxic effects.
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Sandau, Courtney Douglas. "Analytical chemistry of hydroxylated metabolites of PCBs and other halogenated phenolic compounds in blood and their relationship to thyroid hormone and retinol homeostasis in humans and polar bears." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ57637.pdf.
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Sandau, Courtney Douglas Carleton University Dissertation Chemistry. "Analytical chemistry of hydroxylated metabolites of PCBs and other halogenated phenolic compounds in blood and their relationship to thyroid hormone and retinol homeostasis in humans and polar bears." Ottawa, 2000.
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Geng, Dawei. "Gas chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry methods for the determination of environmental contaminants." Doctoral thesis, Örebro universitet, Institutionen för naturvetenskap och teknik, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-51727.
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The recent developments and improvements of instrumental methods for the analyses of the environmental contaminants, especially the persistent organic pollutants (POPs), have made it possible to detect and quantify these at very low concentrations in environmental and biotic matrices. The main objective of this thesis is to demonstrate the capability of the atmospheric pressure chemical ionization technique (APCI), using gas chromatography coupled to tandem mass spectrometry for the determination of a wide range of environmental contaminants, including the POPs regulated by Stockholm Convention, such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), but also the derivates of PBDEs and novel brominated flame retardants (NBFRs). The APCI was operated in charge transfer condition, preferably producing molecular ions. Multiple reaction monitoring (MRM) experiments were optimized by adjusting cone voltage, collision energy and dwell time. Optimization of source parameters, such as gas flows and temperatures was also performed. Low concentration standards were analyzed, achieving a visible chromatographic peak for 2 fg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) demonstrating the excellent sensitivity of the system. Adequate linearity and repeatability were observed for all the studied compounds. The performance of APCI methods was validated against the conventional methods using gas chromatography coupled to high resolution mass spectrometry for chlorinated compounds in a wide range of matrices including environmental, air, human and food matrices. The GC-APCI-MS/MS method was successfully applied to a set of 75 human serum samples to study the circulating levels of POPs in epidemiologic studies. Moreover the method was utilized to establish temporal trends of POPs in osprey eggs samples collected during the past five decades.
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Augulyte, Lijana. "Use and Development of Diffusive Samplers to Analyse the Fate of Polycyclic Aromatic Compounds, Polychlorinated Biphenyls and Pharmaceuticals in Wastewater Treatment Processes." Doctoral thesis, Umeå : Department of Chemistry, Umeå University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1912.
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Alhaddad, Abdolrauf Gawad. "Balanced antennas for mobile handset applications : simulation and measurement of balanced antennas for mobile handsets, investigating specific absorption rate when operated near the human body, and a coplanar waveguide alternative to the balanced feed." Thesis, University of Bradford, 2012. http://hdl.handle.net/10454/5512.
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The main objectives of this research are to investigate and design low profile antennas for mobile handsets applications using the balanced concept. These antennas are considered to cover a wide range of wireless standards such as: DCS (1710-1880 MHz), PCS (1850-1990 MHz), UMTS (1920-2170 MHz), WLAN (2400-2500 MHz and 5000-5800 MHz) and UWB frequency bands. Various antennas are implemented based on built-in planar dipole with a folded arm structure. The performance of several designed antennas in terms of input return loss, radiation patterns, radiation efficiency and power gain are presented and several remarkable results are obtained. The measurements confirm the theoretical design concept and show reasonable agreement with computations. The stability performance of the proposed antenna is also evaluated by analysing the current distribution on the mobile phone ground plane. The specific absorption rate (SAR) performance of the antenna is also studied experimentally by measuring antenna near field exposure. The measurement results are correlated with the calculated ones. A new dual-band balanced antenna using coplanar waveguide structure is also proposed, discussed and tested; this is intended to eliminate the balanced feed network. The predicted and measured results show good agreement, confirming good impedance bandwidth characteristics and excellent dual-band performance. In addition, a hybrid method to model the human body interaction with a dual band balanced antenna structure covering the 2.4 GHz and 5.2 GHz bands is presented. Results for several test cases of antenna locations on the body are presented and discussed. The near and far fields were incorporated to provide a full understanding of the impact on human tissue. The cumulative distribution function of the radiation efficiency and absorbed power are also evaluated.
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Alhaddad, A. G. "Balanced antennas for mobile handset applications. Simulation and Measurement of Balanced Antennas for Mobile Handsets, investigating Specific Absorption Rate when operated near the human body, and a Coplanar Waveguide alternative to the Balanced Feed." Thesis, University of Bradford, 2012. http://hdl.handle.net/10454/5512.
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The main objectives of this research are to investigate and design low profile antennas
for mobile handsets applications using the balanced concept. These antennas are
considered to cover a wide range of wireless standards such as: DCS (1710¿1880 MHz),
PCS (1850¿1990 MHz), UMTS (1920¿2170 MHz), WLAN (2400¿2500 MHz and 5000
¿ 5800 MHz) and UWB frequency bands. Various antennas are implemented based on
built-in planar dipole with a folded arm structure.
The performance of several designed antennas in terms of input return loss, radiation
patterns, radiation efficiency and power gain are presented and several remarkable
results are obtained. The measurements confirm the theoretical design concept and show
reasonable agreement with computations. The stability performance of the proposed
antenna is also evaluated by analysing the current distribution on the mobile phone
ground plane. The specific absorption rate (SAR) performance of the antenna is also
studied experimentally by measuring antenna near field exposure. The measurement
results are correlated with the calculated ones.
A new dual-band balanced antenna using coplanar waveguide structure is also proposed,
discussed and tested; this is intended to eliminate the balanced feed network. The
predicted and measured results show good agreement, confirming good impedance
bandwidth characteristics and excellent dual-band performance.
In addition, a hybrid method to model the human body interaction with a dual band
balanced antenna structure covering the 2.4 GHz and 5.2 GHz bands is presented.
Results for several test cases of antenna locations on the body are presented and
discussed. The near and far fields were incorporated to provide a full understanding of
the impact on human tissue. The cumulative distribution function of the radiation
efficiency and absorbed power are also evaluated.UK Engineering and Physical Sciences Research Council (EPSRC)
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Cachada, Anabela Ferreira de Oliveira. "Organic contaminants in urban soils: major inputs and potential risks." Doctoral thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/14130.
Full textAbstract:
Doutoramento em QuímicaUrban soil quality may be severely affected by hydrophobic organic contaminants (HOCs), impairing environmental quality and human health. A comprehensive study was conducted in two contrasting Portuguese urban areas (Lisbon and Viseu) in order to assess the levels and potential risks of these contaminants, to identify sources and study their behaviour in soils. The concentrations of HOCs were related to the size of the city, with much higher contamination levels observed in Lisbon urban area. Source apportionment was performed by studying the HOCs profiles, their relationship with potentially toxic elements and general characteristics of soil using multivariate statistical methods. Lisbon seems to be affected by nearby sources (traffic, industry and incineration processes) whereas in Viseu the atmospheric transport may be playing an important role. In a first tier of risk assessment (RA) it was possible to identify polycyclic aromatic hydrocarbons (PAHs) in Lisbon soils as a potential hazard. The levels of PAHs in street dusts were further studied and allowed to clarify that traffic, tire and pavement debris can be an important source of PAHs to urban soils. Street dusts were also identified as being a potential concern regarding human and environmental health, especially if reaching the nearby aquatic bodies. Geostatistical tools were also used and their usefulness in a RA analysis and urban planning was discussed. In order to obtain a more realistic assessment of risks of HOCs to environment and human health it is important to evaluate their available fraction, which is also the most accessible for organisms. Therefore, a review of the processes involved on the availability of PAHs was performed and the outputs produced by the different chemical methods were evaluated. The suitability of chemical methods to predict bioavailability of PAHs in dissimilar naturally contaminated soils has not been demonstrated, being especially difficult for high molecular weight compounds. No clear relationship between chemical and biological availability was found in this work. Yet, in spite of the very high total concentrations found in some Lisbon soils, both the water soluble fraction and the body residues resulting from bioaccumulation assays were generally very low, which may be due to aging phenomena. It was observed that the percentage of soluble fraction of PAHs in soils was found to be different among compounds and mostly regulated by soil properties. Regarding bioaccumulation assays, although no significant relationship was found between soil properties and bioavailability, it was verified that biota-to-soil bioaccumulation factors were sample dependent rather than compound dependent. In conclusion, once the compounds of potential concern are targeted, then performing a chemical screening as a first tier can be a simple and effective approach to start a RA. However, reliable data is still required to improve the existing models for risk characterization.
A qualidade dos solos urbanos pode ser afetada por contaminantes orgânicos hidrofóbicos (HOCs), prejudicando a saúde ambiental e humana. Este trabalho consistiu em estudar duas áreas urbanas contrastantes (Lisboa e Viseu), com o objetivo de avaliar os níveis de HOCs nos solos e os seus potenciais riscos para a saúde humana e para o ambiente. Pretendia-se ainda identificar as fontes e estudar o comportamento destes contaminantes no solo. Foi possível relacionar as concentrações de HOCs com o tamanho da cidade, sendo os níveis de contaminação muito mais elevados em Lisboa. A identificação das fontes destes contaminantes foi feita através do estudo dos respetivos perfis e da relação com elementos potencialmente tóxicos, utilizando métodos estatísticos multivariados. Lisboa parece ser afetada por fontes próximas (tráfego, indústria e incineração) enquanto em Viseu o transporte atmosférico aparenta ter um papel mais importante. Num primeiro nível da avaliação de risco (RA), foi possível identificar os hidrocarbonetos aromáticos policíclicos (PAHs) nos solos de Lisboa como um perigo potencial. Os níveis de PAHs em poeiras das ruas de Lisboa foram também estudados e permitiram clarificar que o tráfego e os detritos de pneus e de pavimento podem também ser uma importante fonte destes compostos. Utilizaram-se e discutiram-se ferramentas de geoestatística assim como a respetiva utilidade em RA e em planeamento urbano. De modo a obter uma avaliação mais realista dos riscos de HOCs é importante avaliar a fração disponível, que é também a mais acessível para os organismos. Deste modo, foi feita uma avaliação dos processos envolvidos na disponibilidade de PAHs e também dos resultados obtidos pelos diferentes métodos químicos. A adequação dos métodos químicos para prever a biodisponibilidade de PAHs em solos naturalmente contaminados ainda não foi demonstrada, sendo especialmente difícil para os compostos de elevado peso molecular. No presente trabalho também não foi possível estabelecer uma relação significativa entre a disponibilidade química e a biodisponibilidade. No entanto, apesar das elevadas concentrações totais encontradas em alguns solos de Lisboa, tanto a fração solúvel em água como os resíduos acumulados nos ensaios de bioacumulação foram, em geral, muito baixos, o que estará relacionado com os fenómenos de envelhecimento destes contaminantes nos solos. Observou-se que a fração solúvel de PAHs depende do composto em causa e é regulada pelas propriedades do solo. Apesar de não se terem observado correlações entre as propriedades do solo e a biodisponibilidade, observou-se que os fatores de bioacumulação dependem mais da amostra do que do composto. Em conclusão: após a identificação dos contaminantes de interesse uma avaliação química baseada nos teores totais pode ser uma abordagem eficaz no primeiro nível da RA, mas no entanto é necessário melhorar os modelos existentes para a caracterização do risco.
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Lutz, Elizabeth Anne. "Effects of Modified Cyclosporine A on Posterior Capsule Opacification Formation and Corneal Endothelial Cell Viability in an Ex Vivo Model." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1371477702.
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Tuck, Astrud Rebecca Rose. "Investigation into the expression and localisation of c-kit and the regulation of kit ligand gene expression in the adult human ovary." Thesis, 2013. http://hdl.handle.net/2440/80602.
Full textAbstract:
Folliculogenesis is a complex process that is central to the ovary’s primary function, the production of healthy oocytes. One of the essential ligand/receptor pairs that mediates folliculogenesis is kit ligand (KITL), a granulosa-derived cytokine growth factor, and its receptor, c-kit. Since their discovery two decades ago, the KITL/c-kit system has been extensively studied in animal models, in particular the mouse, in which it has been demonstrated to be crucial for normal folliculogenesis and fertility. To date, little investigation into KITL and c-kit has been performed in the adult human ovary. Previously, this laboratory showed abnormally increased KITL protein levels in human polycystic ovaries (PCO) compared to non-PCO, suggesting that KITL may contribute to several PCO phenotypes according to the range of actions KITL has been shown to have in animal folliculogenesis. Thus, this thesis aimed to characterise KITL and c-kit expression and localisation in the adult human ovary, including polycystic ovaries, and examined regulation of KITL gene expression by endocrine and intraovarian factors. To perform these studies, human ovarian tissues were obtained. These included granulosa cell subtypes cumulus and mural granulosa cells from women undergoing assisted reproductive technology treatment at infertility clinics, fresh ovarian cortex from the Royal Adelaide Hospital and archival paraffin-embedded human ovarian tissue from the Institute of Medical and Veterinary Sciences. The human granulosa tumour cell line, KGN, was also used as a model. KITL and c-kit isoforms were demonstrated to be present in the human ovary throughout follicle development. KITL-2 was shown to be expressed primarily by granulosa cells representing preantral follicles, while KITL-1 was the predominant isoform expressed in preovulatory granulosa cells, suggesting that KITL-2 may play a greater role during early follicle development which then diminishes in preovulatory follicles with increased KITL-1 levels. Both c-kit mRNA isoforms were found to be present in human ovarian cortex. Examination of c-kit localisation throughout follicle development by immunohistochemistry revealed that all follicular cell types in preantral and antral follicles expressed c-kit protein. This may suggest that KITL has an unknown autocrine function in granulosa cells unique to the human ovary, as animals models have previously demonstrated c-kit staining to be confined to the theca layer and the oocyte. c-kit staining patterns were found to be different in PCO compared to non-PCO preantral and antral follicles, suggesting a potential involvement for c-kit in PCO pathology. Collectively these results suggest, as demonstrated in various animal models, that the KITL/c-kit system is present in the human ovary and may have some involvement in the mediation of human folliculogenesis. Regulation of KITL gene expression was examined using KGN and cumulus cells. Based on previous studies, the candidate regulatory factors that were examined included androgen receptor (AR), endocrine factor follicle-stimulating hormone (FSH), theca-derived factor keratinocyte growth factor (KGF) and oocyte-secreted factors bone morphogenetic factor-15 (BMP-15) and growth differentiation factor-9 (GDF-9). Of these candidate factors, GDF-9 was found to directly decrease KITL gene expression in KGN cells and cumulus cells via ALK 4/5/7 receptors. There was also some evidence for a slight reversal of the GDF-9 effect on KITL expression by the addition of the potent androgen 5α-dihydrotestosterone (DHT). The results of these studies indicated KITL gene expression is regulated by GDF-9 in human granulosa cells and are consistent with observations of negative regulation of KITL expression in mouse granulosa cells. Evidence shown in this thesis suggests that the ratio of KITL isoforms in granulosa cells changes throughout human folliculogenesis. Follicular target cells for KITL signalling were found to include granulosa cells, theca cells and the oocyte, suggesting that the KITL/c-kit system may have potential roles throughout human folliculogenesis as demonstrated in animal models. Furthermore, this thesis has demonstrated that GDF-9 directly regulates KITL gene expression in human granulosa cells. From these results, this thesis proposes an in vivo model in which abnormally low levels of GDF-9, shown by a previous study to be characteristic of PCOS oocytes, results in increased KITL levels and this effect may be further exacerbated by the reversal of GDF-9 inhibition by excess androgen. This thesis has provided a greater understanding of the molecular mechanisms involved in human folliculogenesis which may be of use in future therapeutic strategies and diagnosis in assisted reproductive technology, and provide a basis for understanding human ovarian function and ovarian disease.Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2013
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McIlvenna, Luke. "Polycystic Ovary Syndrome and Insulin Resistance: Dysregulation of Transforming Growth Factor Beta Signalling and the Effects of Exercise Training." Thesis, 2021. https://vuir.vu.edu.au/42295/.
Full textAbstract:
Polycystic Ovary Syndrome (PCOS) is primarily thought of as a reproductive condition, although it has profound effects on metabolic health, with 38-80% of women with PCOS presenting with insulin resistance. This underlying insulin resistance occurs independently of obesity and has negative effects on other features of the condition. The identification of peripheral insulin resistance in PCOS occurred in 1989, and despite several advances in this area, the molecular mechanisms responsible for peripheral insulin resistance in women with PCOS remain unclear. In addition, interventional studies from women with PCOS have identified impaired responses to insulin-sensitizing therapies. A possible explanation for the underlying insulin resistance and poor response to insulin-sensitizing treatments may be the dysregulation of Transforming Growth Factor-beta (TGF-beta) signalling. The dysregulation of TGF-beta signalling is responsible for remodelling in the ovarian tissues and reproductive dysfunction. Due to the systemic action of TGF-beta signalling, it may be conceivable that these effects extend beyond the reproductive tissues to the peripheral tissues. This presents a possible mechanism that could contribute to the development of insulin resistance in women with PCOS. Understanding the underlying mechanisms of insulin resistance will allow for improvements in diagnosis and for targeted therapies to be developed, which are currently lacking for women with PCOS. The overall aim of this thesis was to determine if dysregulated TGF-beta signalling plays a role in skeletal muscle insulin resistance and can influence metabolic responses to exercise in women with PCOS. This was achieved through a combination of in vivo and in vitro studies focusing on skeletal muscle metabolism.
Study 1 explored the role of TGF-beta ligands, TGF-beta 1 and Anti-müllerian hormone (AMH), on glucose uptake and insulin signalling in myotubes from women with PCOS and healthy controls. In line with previous studies, we showed that in vivo metabolic phenotype was not accurately retained in cultured myotubes from women with PCOS, suggesting that a combination of the in vivo environmental factors and intrinsic defects lead to the development of insulin resistance. TGF-beta 1 and AMH had distinct metabolic effects. TGF-beta 1 increased basal and insulin-stimulated glucose uptake, while AMH decreased glucose uptake and PI3K-p110 expression, which was accompanied by an increase in inhibitory IRS-1ser312 phosphorylation. Study 2 assessed the response of myotubes from women with PCOS and healthy controls to an in vitro model of contraction with and without TGF-beta 1 or AMH. It was found that myotubes from women with PCOS and healthy controls display minimal differences in exercise-induced signalling transduction. Myotubes from healthy women showed an increase in the phosphorylation of p38 MAPK and CREB, which appeared to be absent in the myotubes from women with PCOS. The TGF-beta ligands AMH and TGF-beta 1 do not appear to influence in vitro skeletal muscle exercise-like signalling responses.
In Study 3, a cross-sectional approach was used to assess skeletal muscle TGF-beta and insulin signalling in women with PCOS compared to overweight and lean controls. Insulin sensitivity, as determined by euglycemic–hyperinsulinemic clamp, confirmed previous findings that women with PCOS have a significant reduction in insulin sensitivity compared to controls. This insulin resistance occurred in the absence of any identifiable defects in skeletal muscle insulin signalling and did not appear to be related to TGF-beta signalling. Women with PCOS had greater levels of basal phosphorylation of p38 MAPK, suggesting that excessive reactive oxygen species and/or inflammation may contribute to insulin resistance.
In Study 4, overweight women with PCOS participated in a 12-week exercise training intervention. We aimed to determine if changes in insulin sensitivity following 12 weeks of moderate or high-intensity exercise training were related to aberrant TGF-beta signalling and collagen deposition in the skeletal muscle. Exercise training of high and moderate intensities resulted in improvements in insulin sensitivity and cardiorespiratory fitness, with the metabolic benefits being more noticeable following the high-intensity intervention. Improvements in insulin sensitivity occurred independently of changes in body composition, TGF-beta signalling and other clinical measures.
Collectively, the results from these studies demonstrate the role of TGF-beta ligands and signalling dysregulation in skeletal muscle metabolism in vitro. However, these findings do not appear to translate in vivo where insulin sensitivity was not related to TGF-beta signalling in women with or without PCOS. There was no apparent evidence of dysregulation of TGF- beta signalling or insulin signalling in women with PCOS. Furthermore, improvements in insulin sensitivity following 12 weeks of high- or moderate-intensity exercise training occurred independently of changes in TGF-beta signalling.
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"Dioxinas, furanos e PCBs em leite humano no Brasil." Tese, Biblioteca Digital da Unicamp, 2003. http://libdigi.unicamp.br/document/?code=vtls000376714.
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Kennedy, Katherine Margaret. "Molecular methods for evaluating the human microbiome." Thesis, 2014. http://hdl.handle.net/10012/8230.
Full textAbstract:
In human microbiome analysis, sequencing of bacterial 16S rRNA genes has revealed a role for the gut microbiota in maintaining health and contributing to various pathologies. Novel community analysis techniques must be evaluated in terms of bias, sensitivity, and reproducibility and compared to existing techniques to be effectively implemented. Next- generation sequencing technologies offer many advantages over traditional fingerprinting methods, but this extensive evaluation required for the most efficacious use of data has not been performed previously. Illumina libraries were generated from the V3 region of the 16S rRNA gene of samples taken from 12 unique sites within the gastrointestinal tract for each of 4 individuals. Fingerprint data were generated from these samples and prominent bands were sequenced. Sequenced bands were matched with OTUs within their respective libraries. The results demonstrate that denaturing gradient gel electrophoresis (DGGE) represents relatively abundant bacterial taxa (>0.1%) beta-diversity of all samples was compared using Principal Coordinates Analysis (PCoA) of UniFrac distances and Multi-Response Permutation Procedure (MRPP) was applied to measure sample cluster strength and significance; indicator species analysis of fingerprint bands and Illumina OTUs were also compared. The results demonstrate overall similarities between community profiling methods but also indicate that sequence data were not subject to the same limitations observed with the DGGE method (i.e., only abundant taxa bands are resolved, unable to distinguish disparate samples). In addition, the effect of stochastic fluctuations in ???????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????? differ for DGGE and next-generation sequencing. I compared pooled and individual reactions for samples of high and low template concentration for both Illumina and DGGE using the combined V3-V4 region of the 16S rRNA gene, and demonstrated that template concentration has a greater impact on reproducibility than pooling. This research shows congruity between two disparate molecular methods, identifies sources of bias, and establishes new guidelines for minimizing bias in microbial community analyses.
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Weiß, N., A. Stegemann, Marwa A. T. A. Elsayed, Karin U. Schallreuter, T. A. Luger, K. Loser, D. Metze, C. Weishaupt, and M. Böhm. "Inhibition of the prohormone convertase subtilisin-kexin isoenzyme-1 induces apoptosis in human melanoma cells." 2014. http://hdl.handle.net/10454/7065.
Full textAbstract:
noProhormone convertases (PCs) are endoproteases that process many substrates in addition to hormone precursors. Although overexpression of PCs is linked to carcinogenesis in some solid tumors, the role of subtilisin-kexin isoenzyme-1 (SKI-1) in this context is unknown. We show that SKI-1 is constitutively expressed in human pigment cells with higher SKI activity in seven out of eight melanoma cell lines compared with normal melanocytes. SKI-1 immunoreactivity is also detectable in tumor cells of melanoma metastases. Moreover, tissue samples of the latter display higher SKI-1 mRNA levels and activity than normal skin. From various stimuli tested, 12-O-tetradecanoylphorbol-13-acetate and tunicamycin affected SKI-1 expression. Importantly, SKI-1 inhibition by the cell-permeable enzyme inhibitor decanoyl-RRLL-chloromethylketone (dec-RRLL-CMK) not only suppressed proliferation and metabolic activity of melanoma cells in vitro but also reduced tumor growth of melanoma cells injected intracutaneously into immunodeficient mice. Mechanistic studies revealed that dec-RRLL-CMK induces classical apoptosis of melanoma cells in vitro and affects expression of several SKI-1 target genes including activating transcription factor 6 (ATF6). However, ATF6 gene silencing does not result in apoptosis of melanoma cells, suggesting that dec-RRLL-CMK induces cell death in an ATF6-independent manner. Our findings encourage further studies on SKI-1 as a potential target for melanoma therapy.
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Coombs, Andrea Pauline. "Marine mammals and human health in the Eastern Bering Sea : using an ecosystem-based food web model to track PCBs." Thesis, 2004. http://hdl.handle.net/2429/15476.
Full textAbstract:
The comprehensive changes that have occurred in the Bering Sea over the last 30 years
have prompted a wide range of studies to better understand the ecosystem as a whole.
One set of studies has used the Ecopath with Ecosim (EwE) modelling software to
synthesise existing biological data and gain insight into how the ecosystem was before
and after the system-wide changes. This modelling framework provides a means for
tracing contaminants through the ecosystem, and evaluating the role that persistent
organic pollutants (POPs) may have played in the changing dynamics of the eastern
Bering Sea. Using the EwE software, the likely pathways of PCB flow within the eastern
Bering Sea were identified and health implications of contaminant exposure for Steller
sea lions, other species of marine mammals, and humans were evaluated. The base EwE
model was refined from existing models and validated with traditional stock assessment
data. Ecotracer (a component of the EwE software) tracked the bioaccumulation of
contaminants moving through the system with biomass. The models estimated
contaminant concentrations for species and functional groups that have not previously
been measured. Results suggest that PCB concentrations for most species in the eastern
Bering Sea have remained below threshold levels associated with negative reproduction
and survival effects. However, these concentrations may have subtle effects on adults and
more serious effects on foetuses and nursing young, which could inhibit the recovery of
Steller sea lions and other species that have declined in the eastern Bering Sea. Although
the benefits of traditional foods appear to continue to outweigh the risks posed by
contaminants for humans, PCB exposure and dietary intake for many Alaska Natives
subsisting on marine mammals is above the USEPA Daily Reference Dose. Results
extend the existing eastern Bering Sea models and are important in terms of management
alternatives for marine mammals and human health. They also synthesise evidence
regarding the presence, extent, and movement of PCBs throughout the system. The
refined eastern Bering Sea models are useful tools for exploring different scenarios and
hypotheses, to inform resource managers, and to further our understanding of this
ecosystem.
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Nyberg, Elisabeth. "Improved Assessment in Environmental Monitoring of POPs : Using monitoring data from the aquatic ecosystem and human milk." Doctoral thesis, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-134769.
Full textAbstract:
The thesis deals with several aspects of monitoring of persistent organic contaminants (POPs) in biological matrices, for example choice of sample, sampling design, and statistical treatment of data both for temporal and spatial trends and for compliance towards a set target value. The efficiency has been evaluated through statistical power analyses. Contaminant data from more than 4 decades from the Swedish National Monitoring Programs for monitoring of contaminants in biota (marine, freshwater and human health), has been quantitatively evaluated both temporally and spatially and for compliance. The aim was also to evaluate the suitability of different matrices, i.e. herring (Clupea harengus), guillemot (Uria aalge) egg, cod (Gadus morhua), perch (Perca fluviatilis), eelpout (Zoarces viviparous), blue mussel (Mytilus edulis), pike (Esox lucius), Arctic char (Salvelinus alpinus) and human milk, for monitoring of POPs with the overall aim to improve the assessment within monitoring programs. The results show that variation can be reduced by using pooled samples including more specimens but fewer chemical analyses, which in turn generate a higher statistical power to a lower cost, at least in cases where the cost of collection and sampling is considerably lower than the cost of chemical analysis. However, there are also a number of advantages using individual samples, such as information of sample variance and maximum value, which allows the choice of an appropriate central measure and direct adjustment of confounding factors. Generally, the levels of polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs) and hexachlorobenzene (HCB) have decreased both in marine and freshwater biota but concentrations are still higher in the Baltic compared to e.g. the North Sea. The levels of dioxinlike-PCBs and polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans (PCDD/Fs) have decreased in human milk over time, but not to the same extent in fish and guillemot egg from the Baltic and the freshwater environment. This may be explained by the dietary advice developed by the Swedish Food Administration with the goal that girls, reproductive aged, and pregnant women should eat less food containing high levels of PCDD/Fs. Thus the levels in milk could continue to decrease at the same rate although the temporal trend in the environment has slowed down or leveled out. The most essential regarding the choice of species and matrices for contaminant monitoring, is that the species and organ fit the purpose of the monitoring.
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Ya-Hsin, Chou, and 周雅炘. "Effects of polychlorinated biphenyls (PCBs) on the induction of cell toxicity, DNA damage and altered gene expression by 17β-estradiol in human breast carcinoma cell lines." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/10203183548422254988.
Full textAbstract:
碩士國立中興大學
環境工程學系
93
The objective of this research is to investigate the effects of polychlorinated biphenyls (PCBs) (i.e. PCB126 and PCB153), on the induction of imbalances in gene expression, formation of reactive oxygen species (ROS), oxidative DNA damage and cell toxicity by 17β-estradiol (E2) in human breast cancer cell lines, including estrogen receptor α (ERα)(+)/MCF-7 and ERα(-)/MDA-MB-231 cells. Results indicated that E2, PCB126, and PCB153 induced concentration- and time-dependent increases in cytotoxic response in both MCF-7 and MDA-MB-231 cells. The extent of cytotoxic response in human breast cancer cells was greater for PCB153 than for PCB126 in these two cell lines. The data also showed that at non-cytotoxic concentrations, E2 induces concentrations-dependent increases in intracellular levels of ROS in MDA-MB-231 cells. Pretreatment with PCB126 did not alter the induction of ROS by E2 in MDA-MB-231 cells. α-Naphthoflavone (a CYP1A1/1B1 inhibitor) completely blocked the E2-induced increases in the amount of intracellular ROS in MDA-MB-231 cells pretreatment of PCB126 (20 μM) and PCB mixture [PCB126 (20μM)+PCB153 (1μM)]. In contrast, induction of ROS formation by E2 in MDA-MB-231 cells was inhibited with pretreatment of PCB153. Additionally, E2 did not induce increases in intracellular ROS in MCF-7 cells. However, when cells were pretreated with PCB153, increases in intracellular ROS was detected in E2-treated MCF-7 cells. Further investigation indicated that E2 induces decreases in intracellular NAD(P)H and NAD+ by PARP-1 [poly(ADP-ribose) polymerase-1] activation through formation of DNA strand breaks in MDA-MB-231 cells at physiologically relevant concentration (1-10 nM). Pretreatment with PCB126 did not alter the E2-induced PARP-1 activation in MDA-MB-231 cells. In contrast, pretreatment of PCB153 inhibits the E2-induced PARP-1 activation in MDA-MB-231 cells. When MCF-7 cells were exposed to E2 (0.1 nM-10 nM) alone, we did not observe decreases in intracellular NAD(P)H, whereas pretreatment of cells with PCB153 significantly reduces intracellular NAD(P)H in MCF-7 cells exposed to E2. Results from semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay indicated that E2 induced increases in the expression of CYP1A1, CYP1B1, and hOGG1, XRCC1 genes in MDA-MB-231 cells. Pretreatment of PCB153 inhibits the E2-induced CYP1A1, CYP1B1, hOGG1 and XRCC1 gene expression in MDA-MB-231 cells. PCB153 and E2 alone induced increases in the expression of CYP1A1 and CYP1B1 in MCF-7 cells. Pretreatment of PCB153 increases the E2-induced CYP1A1 gene expression in MCF-7 cells. PCB153 alone can inhibits the hOGG1 and XRCC1 gene expression in MCF-7 cels. This result suggests that exposure to PCB153 alters gene expression in the disposition of estrogen and DNA repair. In conclusions, this evidence suggests that both planar and non-planar PCB congeners modulate different profile of estrogen-induced formation of ROS, DNA lesions, and cell toxicity in human breast cancer cells. The data also suggests that the status of estrogen receptor a may play a role in modulating the E2-mediated induction of oxidative DNA lesions and cell toxicity in human breast cancer cells.
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Huang, Ching-Lung, and 黃景隆. "Effects of metabolic activation and altered gene expression on the induction of oxidative stress, DNA damage, and cell toxicity in human breast cancer cells by polychlorinated biphenyls (PCBs)." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/34040164716643403534.
Full textAbstract:
碩士國立中興大學
環境工程學系
93
The objective of this research is to examine the effects of metabolic activation and altered gene expression on the induction of oxidative stress, DNA damage, and cell toxicity by polychlorinated biphenyls (PCBs), including PCB52 and PCB77, in human ERα(++)/MCF-7, ERα(+)/T47D and ERα(-)/MDA-MB-231 breast cancer cells. Results indicated that both PCB52 and PCB77 induced concentration- and time-dependent increases in cytotoxic response in MCF-7, T47D, and MDA-MB-231 cells. The extent of cytotoxic response induced by these two PCB congeners in human breast cancer cells was greater for PCB52 than for PCB77. Additionally, the reduction in the number of viable cells exposed to PCBs was primarily mediated by apoptosis. Further, α-naphthoflavone, resveratrol, and metyrapone blocked the PCB52-induced cell toxicity in T47D and MDA-MB-231 cells, but not in MCF-7 cells. The data also showed that PCB52 and PCB77 induced significant increases in intracellular levels of reactive oxygen species (ROS) in MCF-7, T47D, and MDA-MB-231 cells, particularly in MDA-MB-231 cells. In addition, when cells were exposed to PCBs at non-cytotoxic concentration, we observed that PCB52 (1 mM) and PCB77 (10 mM) alone or mixture did not induce decreases in intracellular NAD(P)H in MCF-7 cells. In contrast, both PCB52 and PCB77 induced decreases in intracellular NAD(P)H and NAD＋ through formation of DNA strand breaks and poly(ADP-ribose)polymerase-1 activation in T47D and MDA-MB-231 cells. Antagonism was detected in T47D and MDA-MB-231 cells exposed to PCB52/PCB77 mixture. Further, results from semi-quantitative reverse-transcription polymerase chain reaction (semi-quantitative RT-PCR) analyses indicated that exposure to PCB77 (10 mM) induced increases in the expression of CYP1A1, hAPE, and XRCC1 whereas PCB52 (1 mM) alone induced increases in the expression of hOGG1, hAPE, and XRCC1. Similar observation was also detected in MCF-7 cells exposed to PCB52/PCB77 mixture. On the other hand, both PCB52 (10 mM) and PCB77 (10 mM) induced increases in the expression of CYP1A1 and XRCC1 genes whereas PCB52/PCB77 mixture induced increases in the expression of CYP1A1 in MDA-MB-231 cells. Overall, this evidence indicates that both PCB52 and PCB77 may induce ROS formation and imbalances in the expression of genes responsible for the DNA repair process and apoptosis in MCF-7 cells. In contrast, PCB52 and PCB77 are likely to mediate the induction of ROS formation, DNA strand breaks, and cell toxicity through futile cycling and/or redox cycling in MDA-MB-231 cells. The data also suggests that the status of estrogen receptor a may play a role in modulating the PCB-induced DNA damage and cytotoxic response in human breast cancer cells.