A doença hepática associada a sobrecarga de ferro pode ocorrer devido a causas genéticas ou secundárias. Esse estudo avaliou pacientes com hepatopatia crônica com sobrecarga de ferro submetidos à pesquisa das mutações HFE no período de 2007-2009 e classificou como portadores de hemocromatose hereditária HFE (HH-HFE) aqueles que apresentavam as mutações C282Y/C282Y ou C282Y/H63D e como sobrecarga de ferro não HFE aqueles que apresentavam outras mutações no gene HFE como C282Y/-, H63D/- e H63D/H63D ou pacientes sem qualquer uma dessas mutações mencionadas. Os objetivos do estudo foram 1) analisar e correlacionar os aspectos fenotípicos e genotípicos de grupo de indivíduos com doença hepática crônica e sobrecarga de ferro; 2) caracterizar o quadro clínico, laboratorial e anatomopatológico, em busca de achados compatíveis com o fenótipo de hemocromatose; 3) Correlacionar o quadro clínico com as mutações no gene HFE. Foram analisados 108 indivíduos portadores de hepatopatia crônica selecionados a partir de saturação de transferrina (ST) > 45% e ferritina sérica > 350 ng/mL. Foram estudados e comparados 16 pacientes no grupo HH-HFE com 92 no grupo sobrecarga de ferro não HFE. Da casuística geral, a idade média ao diagnóstico da doença foi de 46,69 anos (16-77), com 70,73% constituída por indivíduos de cor branca, 77,57% do sexo masculino e 64,8% tinham cirrose hepática. A frequência de cirrose hepática não diferiu entre os grupos, entretanto, artropatia, carcinoma hepatocelular, diabetes e osteoporose foram mais frequentes no grupo HH- HFE (53,8% x 15,9%, 31,2% x 7,06%, 56,2% x 30%, 72,7% x 32,1%, respectivamente, p < 0,05). Os pacientes com mutações HFE diagnósticas de HH apresentaram maior chance de ter carcinoma hepatocelular (OR= 5,0, p= 0,032) quando comparados com os portadores de outros genótipos HFE e aqueles sem mutação. Os níveis de ST, ferro e ferritina também foram maiores naquele grupo, bem como os graus de siderose 3 e 4 (p= 0,026). A ST foi a variável que se correlacionou independentemente com o diagnóstico das mutações C282Y/C282Y e C282Y/H63D. A frequência de fatores de risco para sobrecarga de ferro não diferiu entre os grupos. Observou-se, entretanto, que no grupo HH-HFE havia maior número de pacientes sem qualquer fator de risco detectado (p= 0,019). Níveis de ST > 82% apresentaram maior valor preditivo negativo para o diagnóstico de HH-HFE do que os de ferritina, ferro, capacidade total de ligação de ferro e de transferrina. Concluímos que os portadores de HH-HFE têm maiores graus de sobrecarga de ferro quando comparados ao grupo de sobrecarga de ferro não-HFE; em indivíduos com doença hepática crônica. ST > 82% tem maior acurácia para diagnóstico de HH-HFE; portadores de mutações C282Y em homozigose ou em heterozigose composta com H63D têm maior chance de apresentar carcinoma hepatocelular do que os portadores de outras mutações no gene HFE e pacientes sem mutação / Chronic liver disease related to iron overload may occur due to genetic or secondary causes. This study analyzed patients with chronic liver diseases and iron overload who were tested for HFE mutations from 2007 to 2009. Patients with C282Y/C282Y or C282Y/H63D mutations were diagnosed with HFE hereditary hemochromatosis (HFE-HH) and those with other HFE genotypes (C282Y/-, H63D/- or H63D/H63D) or individuals without HFE mutations (wild type) were designed as non-HFE iron overload. The aims of this study were: 1) to analyze and to establish correlations between phenotypic and genotypic aspects of individuals with chronic liver disease and with iron overload; 2) to charachterize the clinical manifestations, laboratory and histological findings consistent with the phenotype of hemochromatosis; 3) to verify associations between clinical manifestations and HFE mutations. One hundred and eight patients with chronic liver diseases and with iron overload, defined as transferrin saturation (TS) > 45% and serum ferritin levels > 350 ng/mL were included. Sixteen patients had HH-HFE and were compared with 92 patients with non-HFE iron overload group. The average of age at diagnosis was 46.69 years (16-77), 70.73% were Caucasians, 77.57% were male and 64.8% had hepatic cirrhosis. The proportion of hepatic cirrhosis was similar in both groups, nevertheless arthropathy, hepatocellular carcinoma, diabetes and osteoporosis were more frequent in the HFE-HH group (53,8% x 15,9%, 31,2% x 7,06%, 56,2% x 30%, 72,7% x 32,1%, respectively, p < 0,05). The HFE C282Y/C282Y or C282Y/ H63D genotypes had a higher chance to develop hepatocellular carcinoma (OR= 5.0, p= 0.032) when compared with the other HFE genotypes and with those wild type. The levels of TS, serum iron and ferritin were greater in HFE-HH group, as well as hepatic siderosis grade 3 and 4 (p= 0.026). TS was the biochemical marker of iron overload with the higher independent correlation with the presence of C282Y/C282Y and C282Y/H63D mutations. The frequency of risk factors for iron overload was not different between the groups, however, in HFE-HH group a greater number of patients without any risk factor was detected (p= 0.019). TS > 82% had a higher predictive negative value for diagnosing HFE-HH when compared to the levels of ferritin, serum iron, total iron binding capacity and transferrin. We concluded that the HFE-HH patients had a greater iron overload than patients with chronic liver diseases with non-HFE iron overload. TS > 82% had more accuracy to diagnose HFE-HH. The carriers of C282Y/C282Y or C282Y/H63D mutations had a higher probability to develop hepatocellular carcinoma, when compared to the patients with HFE genotypes and patients wild type

A doença hepática associada a sobrecarga de ferro pode ocorrer devido a causas genéticas ou secundárias. Esse estudo avaliou pacientes com hepatopatia crônica com sobrecarga de ferro submetidos à pesquisa das mutações HFE no período de 2007-2009 e classificou como portadores de hemocromatose hereditária HFE (HH-HFE) aqueles que apresentavam as mutações C282Y/C282Y ou C282Y/H63D e como sobrecarga de ferro não HFE aqueles que apresentavam outras mutações no gene HFE como C282Y/-, H63D/- e H63D/H63D ou pacientes sem qualquer uma dessas mutações mencionadas. Os objetivos do estudo foram 1) analisar e correlacionar os aspectos fenotípicos e genotípicos de grupo de indivíduos com doença hepática crônica e sobrecarga de ferro; 2) caracterizar o quadro clínico, laboratorial e anatomopatológico, em busca de achados compatíveis com o fenótipo de hemocromatose; 3) Correlacionar o quadro clínico com as mutações no gene HFE. Foram analisados 108 indivíduos portadores de hepatopatia crônica selecionados a partir de saturação de transferrina (ST) > 45% e ferritina sérica > 350 ng/mL. Foram estudados e comparados 16 pacientes no grupo HH-HFE com 92 no grupo sobrecarga de ferro não HFE. Da casuística geral, a idade média ao diagnóstico da doença foi de 46,69 anos (16-77), com 70,73% constituída por indivíduos de cor branca, 77,57% do sexo masculino e 64,8% tinham cirrose hepática. A frequência de cirrose hepática não diferiu entre os grupos, entretanto, artropatia, carcinoma hepatocelular, diabetes e osteoporose foram mais frequentes no grupo HH- HFE (53,8% x 15,9%, 31,2% x 7,06%, 56,2% x 30%, 72,7% x 32,1%, respectivamente, p < 0,05). Os pacientes com mutações HFE diagnósticas de HH apresentaram maior chance de ter carcinoma hepatocelular (OR= 5,0, p= 0,032) quando comparados com os portadores de outros genótipos HFE e aqueles sem mutação. Os níveis de ST, ferro e ferritina também foram maiores naquele grupo, bem como os graus de siderose 3 e 4 (p= 0,026). A ST foi a variável que se correlacionou independentemente com o diagnóstico das mutações C282Y/C282Y e C282Y/H63D. A frequência de fatores de risco para sobrecarga de ferro não diferiu entre os grupos. Observou-se, entretanto, que no grupo HH-HFE havia maior número de pacientes sem qualquer fator de risco detectado (p= 0,019). Níveis de ST > 82% apresentaram maior valor preditivo negativo para o diagnóstico de HH-HFE do que os de ferritina, ferro, capacidade total de ligação de ferro e de transferrina. Concluímos que os portadores de HH-HFE têm maiores graus de sobrecarga de ferro quando comparados ao grupo de sobrecarga de ferro não-HFE; em indivíduos com doença hepática crônica. ST > 82% tem maior acurácia para diagnóstico de HH-HFE; portadores de mutações C282Y em homozigose ou em heterozigose composta com H63D têm maior chance de apresentar carcinoma hepatocelular do que os portadores de outras mutações no gene HFE e pacientes sem mutação / Chronic liver disease related to iron overload may occur due to genetic or secondary causes. This study analyzed patients with chronic liver diseases and iron overload who were tested for HFE mutations from 2007 to 2009. Patients with C282Y/C282Y or C282Y/H63D mutations were diagnosed with HFE hereditary hemochromatosis (HFE-HH) and those with other HFE genotypes (C282Y/-, H63D/- or H63D/H63D) or individuals without HFE mutations (wild type) were designed as non-HFE iron overload. The aims of this study were: 1) to analyze and to establish correlations between phenotypic and genotypic aspects of individuals with chronic liver disease and with iron overload; 2) to charachterize the clinical manifestations, laboratory and histological findings consistent with the phenotype of hemochromatosis; 3) to verify associations between clinical manifestations and HFE mutations. One hundred and eight patients with chronic liver diseases and with iron overload, defined as transferrin saturation (TS) > 45% and serum ferritin levels > 350 ng/mL were included. Sixteen patients had HH-HFE and were compared with 92 patients with non-HFE iron overload group. The average of age at diagnosis was 46.69 years (16-77), 70.73% were Caucasians, 77.57% were male and 64.8% had hepatic cirrhosis. The proportion of hepatic cirrhosis was similar in both groups, nevertheless arthropathy, hepatocellular carcinoma, diabetes and osteoporosis were more frequent in the HFE-HH group (53,8% x 15,9%, 31,2% x 7,06%, 56,2% x 30%, 72,7% x 32,1%, respectively, p < 0,05). The HFE C282Y/C282Y or C282Y/ H63D genotypes had a higher chance to develop hepatocellular carcinoma (OR= 5.0, p= 0.032) when compared with the other HFE genotypes and with those wild type. The levels of TS, serum iron and ferritin were greater in HFE-HH group, as well as hepatic siderosis grade 3 and 4 (p= 0.026). TS was the biochemical marker of iron overload with the higher independent correlation with the presence of C282Y/C282Y and C282Y/H63D mutations. The frequency of risk factors for iron overload was not different between the groups, however, in HFE-HH group a greater number of patients without any risk factor was detected (p= 0.019). TS > 82% had a higher predictive negative value for diagnosing HFE-HH when compared to the levels of ferritin, serum iron, total iron binding capacity and transferrin. We concluded that the HFE-HH patients had a greater iron overload than patients with chronic liver diseases with non-HFE iron overload. TS > 82% had more accuracy to diagnose HFE-HH. The carriers of C282Y/C282Y or C282Y/H63D mutations had a higher probability to develop hepatocellular carcinoma, when compared to the patients with HFE genotypes and patients wild type

Les transfusions de culots globulaires sont une pratique fréquente aux soins intensifs; elles sont associées à de nombreuses complications. Ce travail s'intéresse à l'une d'entre elles, celle qui occasionne le plus de décès, la surcharge volémique liée à la transfusion (Transfusion-Associated Circulatory Overload - TACO). Dans une première étude, nous avons tenté de déterminer l’impact des critères diagnostiques pris en compte dans la définition adulte du TACO dans une population de soins intensifs pédiatriques. Cette définition a été appliquée à 136 patients de soins intensifs pédiatriques durant leur séjour. Nous avons obtenu des taux d’incidence du TACO très variables (entre 1,5 et 76%) selon la manière d’interpréter les critères diagnostiques proposés. Notre seconde étude a consisté en une revue exploratoire de la littérature concernant le TACO aux soins intensifs adultes et pédiatriques, peu importe le type de produit sanguin labile transfusé. Neuf études ont rencontré nos critères d’inclusion, à savoir décrire au moins un des critères suivants : l’incidence, les facteurs de risque ou les conséquences du TACO. Huit études étaient observationnelles. Seules trois études étudiaient la population pédiatrique. Les résultats montrent une incidence cumulée de TACO plus élevée aux soins intensifs (5,5%) que dans la population générale. Les principaux facteurs de risque chez l'adulte sont liés à la balance liquidienne préexistante, aux caractéristiques de la transfusion elle-même et aux comorbidités déjà présentes chez le patient. En outre, le TACO adulte est associé à une augmentation de la durée de séjour à l'hôpital. Les études pédiatriques incluses ne rapportaient aucune donnée sur les facteurs de risque et les conséquences du TACO dans cette population. Ce travail a permis de montrer que la définition actuelle du TACO n’est pas applicable à la population des soins intensifs pédiatriques. Le TACO aux soins intensifs est peu présent dans la littérature scientifique malgré sa fréquence et les risques qu’il présente; d’autres études sont indispensables pour en améliorer sa compréhension. Nous évoquerons certaines voies de recherche qui permettraient une meilleure connaissance de cette complication potentiellement mortelle des transfusions. / Red blood cell transfusions are common practice in intensive care and lead to many adverse reactions. This research project is focused on the most frequent fatal complication: transfusion-associated circulatory overload (TACO). In our first study, we tried to determine the impact of the diagnostic criteria of the adult definition of TACO in a pediatric intensive care population. The definition was applied to 136 pediatric intensive care patients during their stay. We obtained highly variable incidence rates (from 1.5 to 76%) depending on the interpretation of the diagnostic criteria. Our second study is a scoping review of the literature about TACO in intensive care, both adult and pediatric, regardless of the type of labile blood product transfused. Nine studies met our inclusion criteria, namely, to describe at least one of the following criteria: incidence, risk factors or outcomes of TACO. Eight studies were observational. Only three studies were conducted in pediatric population. The results showed a pooled incidence of TACO which is higher (5.5%) in intensive care than in the general population. The main risk factors in the adult population were related to the positive pre-existing fluid balance, the characteristics of the transfusion itself and the patients’ preexisting comorbidities. Furthermore, the results showed an association between TACO in adult intensive care and an increased length of stay. None of the included pediatric study reported data on risk factors or outcomes. This research demonstrates that the current TACO definition is not applicable for the pediatric intensive care population. There is limited literature about TACO in intensive care despite its occurrence rate and the associated risks; other studies are therefore necessary to enhance its comprehension. We will touch on potential research pathways that would lead to a better understanding of this deadly transfusion complication.

The mining environment is one of the largest contributors to the South African economy and provides employment and a livelihood to many South African households. However; the mining environment is one of the most hazardous and production-driven environments in South Africa and worldwide, often leaving households without their primary provider, as a result of accidents. The objective of this study was to investigate the relationship between work stressors, job insecurity, union support, job satisfaction and safety motivation and -behaviour, also to determine whether the levels of job satisfaction mediate the relationship between work stressors, job insecurity, union support and safety motivation and -behaviour. The role conflict scale (Rizzo, House, & Lirtzman, 1970), role overload (qualitative and quantitative) scale (Beehr, Walsh, & Taber, 1976; Sverke, Hellgren, & Öhrming, 1999), job insecurity scale (Hellgren, Sverke, & Isaksson, 1999), union support scale (Shore, Tetrick, Sinclair, & Newton, 1994), job satisfaction scale (Hellgren, Sjöberg & Sverke, 1997), safety motivation scale (Neal, Griffin, & Hart, 2000), safety behaviour scale (Neal et al., 2000) and a biographical questionnaire were administered to employees (N = 260) from the mining industry. A cross-sectional survey design was utilised. The scales demonstrated acceptable levels of internal consistency. Increased levels of work stressors and job insecurity were found to be associated with decreased levels of job satisfaction. Also, increased levels of perceived union support were associated with increased levels of job satisfaction and safety motivation and -behaviour. Finally, it was found that job satisfaction mediates the relationship between union support and safety motivation and -behaviour. Recommendations were made to be applied in practice, as well as for future research. / MCom (Industrial Psychology), North-West University, Potchefstroom Campus, 2015

The mining environment is one of the largest contributors to the South African economy and provides employment and a livelihood to many South African households. However; the mining environment is one of the most hazardous and production-driven environments in South Africa and worldwide, often leaving households without their primary provider, as a result of accidents. The objective of this study was to investigate the relationship between work stressors, job insecurity, union support, job satisfaction and safety motivation and -behaviour, also to determine whether the levels of job satisfaction mediate the relationship between work stressors, job insecurity, union support and safety motivation and -behaviour. The role conflict scale (Rizzo, House, & Lirtzman, 1970), role overload (qualitative and quantitative) scale (Beehr, Walsh, & Taber, 1976; Sverke, Hellgren, & Öhrming, 1999), job insecurity scale (Hellgren, Sverke, & Isaksson, 1999), union support scale (Shore, Tetrick, Sinclair, & Newton, 1994), job satisfaction scale (Hellgren, Sjöberg & Sverke, 1997), safety motivation scale (Neal, Griffin, & Hart, 2000), safety behaviour scale (Neal et al., 2000) and a biographical questionnaire were administered to employees (N = 260) from the mining industry. A cross-sectional survey design was utilised. The scales demonstrated acceptable levels of internal consistency. Increased levels of work stressors and job insecurity were found to be associated with decreased levels of job satisfaction. Also, increased levels of perceived union support were associated with increased levels of job satisfaction and safety motivation and -behaviour. Finally, it was found that job satisfaction mediates the relationship between union support and safety motivation and -behaviour. Recommendations were made to be applied in practice, as well as for future research. / MCom (Industrial Psychology), North-West University, Potchefstroom Campus, 2015

Internal marketing and internal communication are essential tools to align em-ployees’ mindsets with the necessary tasks which bring about employee satis-faction and organisational prosperity. Electronic newsletters serve as an internal marketing communication medium which can convey the necessary information to employees regarding the organisation’s goals and objectives. They also act as a medium to build relationships with employees and encourage improved service delivery and customer-oriented employee mindsets. Employees’ willingness to make use of electronic newsletters for the purpose of disseminating organisational information is an indication of employees’ acceptance of the organisational information and use thereof in performing organisational tasks successfully as the organisation intends. The purpose of the current study was to determine employees’ acceptance of electronic newsletters, as an internal marketing communication medium, in order to disseminate organisational information which contributes to the attainment of organisational goals, objectives and success. An empirical study was conducted to determine employees’ acceptance of elec-tronic newsletters by means of an adapted technology acceptance model, self-administered, e-mail survey disseminated to employees of a higher education institution. The study followed a quantitative research approach, utilising re-gression in the analysis of the data. Based on the research results, employees do accept the electronic newsletter for the dissemination of organisational information, albeit with suggestions on how it can be better utilised in future. / Business Management / M. Com (Business Management)

Heart failure contributes to nearly 60,000 deaths per year in the USA and is often caused by hypertension and preceded by the development of left ventricular hypertrophy (LVH). LVH is usually accompanied by intensive interstitial and perivascular fibrosis which may contribute to arrhythmogenic sudden cardiac death. Emerging evidence indicates that LV dysfunction in patients and animal models of cardiac hypertrophy is closely associated with perivascular inflammation. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of pressure-overload-induced LVH: transverse aortic constriction (TAC). Early perivascular inflammation was indicated by accumulation of macrophages and T lymphocytes 24 hours post-TAC and which peaked at day 7. Coronary luminal platelet deposition was observed along with macrophages and lymphocytes at day 3. Also, LV protein levels of VEGF and MCP-1 were significantly increased. Consistent with lymphocyte accumulation, cardiac expression of IL-10 mRNA was elevated. Furthermore, circulating platelet-leukocyte aggregates tended to be higher after TAC, compared to sham controls. Platelets have been shown to modulate perivascular inflammation and may facilitate leukocyte recruitment at sites of inflamed endothelium. Therefore, we investigated the impact of thrombocytopenia in the response to TAC. Immunodepletion of platelets decreased early perivascular accumulation of T lymphocytes and IL-10 mRNA expression, and altered subsequent coronary artery remodeling. The contribution of lymphocytes was examined in Rag1-/- mice, which displayed significantly more intimal hyperplasia and perivascular fibrosis compared to wild-type mice following TAC. Collectively, our studies support a role of early perivascular accumulation of platelets and T lymphocytes in pressure overload-induced inflammation which will contribute to long-term LV remodeling. One potential mechanism for inflammatory cells to modulate their environment and affect surrounding cells is through release of cargo stored in granules. To determine the contribution of granule release from inflammatory cells in the development of LVH, we used Unc13dJinx (Jinx) mice, which contain a single point mutation in Unc13d gene resulting in defects in Munc13-4. Munc13-4 is a limiting factor in vesicular priming and fusion during granule secretion. Therefore, Jinx mice have defects in degranulation of platelets, NK cells, cytotoxic T lymphocytes, neutrophils, mast and other cells. With the use of bone marrow transplantation, Jinx chimeric mice were created to determine whether the ability of hematopoietic cells to secrete granule contents affects the development of LVH. Wild-type mice (WT) that were transplanted with WT bone marrow (WT>WT) and WT mice that received Jinx bone marrow (Jinx>WT) developed LVH and a classic fetal reprogramming response early after TAC (7 days), but at later times (5 weeks), Jinx>WT mice failed to sustain the cardiac hypertrophic response observed in WT>WT mice. No difference in cardiac fibrosis was observed at early or late times. Repetitive injection of WT platelets or platelet releasate restored cardiac hypertrophy in Jinx>WT mice. These results suggest that sustained LVH in the setting of pressure overload depends on factor(s) secreted, likely from platelets. In conclusion, our studies demonstrate that platelets and lymphocytes are involved in early perivascular inflammation post-TAC, which may contribute to later remodeling in the setting of LVH. Factors released from hematopoietic cells, including platelets, in a Munc13-4-dependent manner are required to promote cardiac hypertrophy. These findings focus attention on modulating perivascular inflammation and targeting granule cargo release to prevent the development and consequences of LVH.

Recently, technological developments have affected most lifestyles, especially with the growth in Internet usage. Internet applications highlight the E-commerce capabilities and applications which are now available everywhere; they receive a great number of users on a 24-7 basis because online services are easy to use, faster and cheaper to acquire. Thus E-commerce web sites have become crucial for companies to increase their revenues. This importance has identified certain effective requirements needed from the performance of these applications. In particular, if the web server is overloaded, poor performance can result, due to either a huge rate of requests being generated which are beyond the server's capacity, or due to saturation of the communication links capacity which connects the web server to the network. Recent researches consider the overload issue and explore different mechanisms for managing the performance of E-commerce applications under overload condition. This thesis proposes a formal approach in order to investigate the effects of the extreme load and the number of dropped requests on the performance of E- III commerce web servers. The proposed approach is based on the class-based priority scheme that classifies E-commerce requests into different classes. Because no single technique can solve all aspects of overload problems, this research combines several techniques including: admission control mechanism, session-based admission control, service differentiation, request scheduling and queuing model-based approach. Request classification is based on the premise that some requests (e.g. buy) are generally considered more important than others (e.g. browse or search). Moreover, this research considers the extended models from Priority Scheduling Mechanism (PSM). These models add a new parameter, such as a review model or modify the basic PSM to low priority fair model, after the discovery of ineffectiveness with low priority customers or to add new features such as portal models. The proposed model is formally specified using the π-calculus in early stage of models design and a multi-actor simulation was developed to reflect the target models as accurately as possible and is implemented as a Java-based prototype system. A formal specification that captures the essential PSM features while keeping the performance model sufficiently simple is presented. Furthermore, the simplicity of the UML bridges the gap between π-calculus and Java programming language. IV There are many metrics for measuring the performance of E-commerce web servers. This research focuses on the performance of E-commerce web servers that refer to the throughput, utilisation, average response time, dropped requests and arrival rate. A number of experiments are conducted in order to test the performance management of the proposed approaches.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Student Number : 9902006N - MSc(Med) Dissertation - School of Medicine - Faculty of Health Sciences / Hepatocellular carcinoma (HCC) is the most common primary malignant tumour of the liver. Aflatoxin B1 (AFB1) is a potent hepatocarcinogen, and dietary iron overload has been shown to contribute to HCC development in black africans. Both are well studied hepatotoxins. The aim of this study was to use a Wistar rat model over a 12 month period to investigate synergy and the extent thereof between AFB1 ingestion and dietary iron overload. 25ug/day of AFB1, reconstituted in DMSO, was administered by gavaging the animals, over a period of 10 days with a 2 day interval in between. The chow diet was supplemented with 0.75% (w/w) ferrocene iron. Experimental subjects were divided into 4 groups. Group 1 was fed the normal chow diet. Group 2 was fed 0.75% (w/w) ferrocene iron alone. Group 3 was gavaged 250μg AFB1 alone. Group 4 was fed the 0.75% (w/w) ferrocene iron and gavaged 250μg AFB1. A number of assays were conducted to investigate synergy. Colorimetric assays were used to measure serum iron, total-iron binding capacity, ALT, AST, GGT, nitrite production, lipid peroxidation and hydroxyproline concentrations. ELISA’s were used to determine ferritin, 8-isoprostane and 8-hydroxyguanosine concentrations. Nontransferrin bound iron was measured using an HPLC method. A chemiluminescent assay was used to measure superoxide anion production. Cytokines were measured using a suspension array system. Mutagenicity was assessed using the Ames mutagenicity assay using salmonella typhimirium strains TA97, TA98, TA100 and TA102. Iron profiling indicated that iron overloading occurred with the ingestion of the ferrocene diet. Biomarkers of oxidative stress, as illustrated by the measurement of 8-hydroxyguanosine and lipid peroxidation, showed additive synergistic effects between the two carcinogens. The anti-inflammatory interleukin-10 was shown to be markedly elevated with the co-administration of the two carcinogens, indicating the elevated inflammatory processes. Additive synergistic effects were noted in terms of the liver disease marker ALT. The salmonella typhimirium strain TA102 used in the Ames mutagenicity test showed increased colony counts with respect to the coadministration of carcinogens (P<0.05), although no synergistic effect was noted. In a few of the presented parameters, the AFB1 group was not significantly different to the control group, although significant differences between the Fe group and the Fe + AFB1 groups were noted. The implication of which is that the presence of AFB1 is increasing the activity of Fe as a carcinogen, thereby acting as a co-carcinogen. Examples of such parameters illustrating this are presented in the results section including serum ALT, serum nitrite, liver and serum lipid peroxidation, liver and serum 8-hydroxyguanosine, some of the mutagenicity assays, and interleukin-10. The conclusion of this study suggests that AFB1 acts as a co-carcinogen in the presence of iron overloading, implying that a synergistic relationship between these two toxins exists.