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Using a Modified Lymphocyte Genome Sensitivity (LGS) Test or TumorScan Test to Detect Cancer at an Early Stage in Each IndividualAnderson, Diana, Najafzadeh, Mojgan, Scally, Andy J., Jacob, B.K., Griffith, John, Chaha, R., Linforth, R., Soussaline, M., Soussaline, F. 12 October 2018 (has links)
Yes / Our previous case-control study observed isolated lymphocytes from 208 individuals and determined the differences in the sensitivity to genomic damage of lymphocytes derived from cancer patients, pre/suspect cancer patients and healthy volunteers using the Comet assay (Anderson et al, 2014). We adapted the LGS technique using a slightly different method and examined 700 more blood samples from 598 patients with cancer or suspected cancer and 102 healthy individuals. To help increase the sensitivity of the test and detect cancer at the level of each individual, we joined with the IMSTAR team who analysed our cells with their fully automated Pathfinder™ cell reader-analyser system. With this reading and analysis system 4,000 to 10,000 cells were able to be read per slide. The new test which is called TumorScan is a highly sensitive test to detect any cancer at an early stage through the response of the white blood cells to UV treatment. These patient blood samples have also been collected at the stage before confirming diagnosis and treatment. There were four of these individuals with cancer who had received anti-cancer treatment. The results from these patients showed a reverse pattern compared to non-treated cancer patients and followed the pattern seen in healthy individuals. The results are consistent with the early results as reported in the above 2014 paper. Given the results from these samples were in a particularly challenging subgroup, whose cancer status was difficult to distinguish, the data suggest that the technique using the TumorScan system could exceed the area under the ROC curve >93% obtained in the earlier study on a group basis, whereas this present study was to detect cancer at an early stage in each individual. / Department of Research and Knowledge Transfer at the University of Bradford, Bradford, UK
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Ingestão alimentar, perfil vitamínico e dano de DNA em crianças e adolescentes do município de Ribeirão Preto / Food intake, vitamin status and DNA damage in children and adolescents from Ribeirão PretoBarros, Tamiris Trevisan de 08 February 2018 (has links)
O objetivo deste estudo é descrever o dano de DNA através das variáveis Tail Moment e Tail Intensity e investigar a associação entre o dano do DNA, padrão alimentar e concentrações plasmáticas de vitaminas em crianças e adolescentes em Ribeirão Preto (São Paulo, Brasil). Estudantes de 9 a 13 anos foram selecionados de três escolas de Ribeirão Preto (São Paulo, Brasil), totalizando uma amostra de 120 indivíduos. A coleta de dados incluiu antropometria, composição corporal, avaliação da ingestão utilizando um questionário de frequência alimentar (QFA) e o Índice de Qualidade da Dieta Revisado (IQD-R) e coleta de sangue para a dosagem de vitaminas e determinação do dano do DNA pelo método de eletroforese em gel de célula única - comet assay. Os indivíduos foram divididos em dois grupos opostos de dano do DNA usando duas técnicas distintas: análise de k-cluster e classificação por escala de dano. Padrões de ingestão de nutrientes também foram gerados, utilizando robust sparse k-means cluster, e associados com o dano de DNA. Para análise utilizaram-se os testes T de Student, Mann-Whitney e ANCOVA. Na primeira análise, o cluster 1 (n = 73), com menor dano de DNA, apresentou maior consumo de vegetais verdes escuros e alaranjados (p = 0,047), vegetais totais (p = 0,041) e carnes, ovos e leguminosas (p = 0,022), através do IQD-R, e um escore de IQD total maior (p = 0,030), indicando melhor qualidade de dieta em comparação ao cluster 2 (n = 47), de maior dano de DNA. O cluster 2 apresentou maior consumo de laticínios, em comparação ao cluster 1 (p = 0,008). Em relação a vitaminas plasmáticas, o cluster 1 apresentou maior concentração de riboflavina (p = 0,004). No segundo método de divisão, o grupo 1 (n = 108), com menor dano de DNA, apresentou maior concentração de retinol (p = 0,010), beta-caroteno (p = 0,017) e riboflavina (p = 0,046), após teste de ANCOVA ajustado para o índice de massa corporal (IMC) em comparação ao grupo 2 (n = 12). Na divisão por padrão alimentar, o cluster 2 (n = 58), com menor consumo de aminoácidos e micronutrientes, apresentou maior consumo de energia (p = 0,001) e uma tendência de maior dano do DNA (p = 0,063) em relação ao cluster 1 (n = 27), com maior ingestão de nutrientes. Estes achados corroboram a literatura, afirmando o papel protetor de vitaminas e antioxidantes contra o dano do DNA. / The aim of this study is to describe the DNA damage using values of Tail Moment and Tail Intensity and investigate the association between DNA damage, dietary pattern and vitamin status in children and adolescents in Ribeirão Preto (São Paulo, Brazil). 9 to 13 year old students were selected from three schools in the city of Ribeirão Preto (São Paulo, Brazil), totalizing a sample of 120 subjects. Data collection included anthropometry, body composition, assessment of food intake using a food frequency questionnaire (FFQ), quality of diet through Revised Health Eating Index (HEI-R), and blood sampling for vitamins dosage and determination of DNA damage with single cell gel electrophoresis - comet assay. The subjects were divided into two opposing groups according to DNA damage using two different methods: k-cluster analysis and classification by scale of damage. Nutrients intake patterns were also generated through robust sparse k-means cluster and associated with DNA damage. The statistical analysis were performed using Student\'s T test, Mann-Whitney test and ANCOVA. In the first analysis, cluster 1 (n = 73), with less DNA damage presented higher intake of dark green and orange vegetables (p = 0,047), total vegetables (p = 0,041), meat, eggs and legumes (p = 0,022), assessed through HEI, as well as a higher total HEI-R level (p = 0,030), indicating higher quality of diet compared to cluster 2 (n = 47), with increased DNA damage. Cluster 2 presented a higher intake of milk and dairy products, compared to cluster 1 (p = 0,008). In relation to vitamins plasma levels, cluster 1 presented higher levels of riboflavin (p = 0,004). In the second method of division, group 1 (n = 108), with less DNA damage, presented higher levels of retinol (p = 0,010), beta-carotene (p = 0,017) and riboflavin (p = 0,046), after ANCOVA teste adjusted for body mass index (BMI) compared to group 2 (n = 12). In the division by dietary pattern, cluster 2 (n = 58) with a lower consumption of amino acids and micronutrients had higher energy intake (p = 0,001) and a tendency of higher DNA damage (p = 0,063) compared to cluster 1(n = 27), with higher intake of nutrients. These findings corroborate the literature, asserting protective role of vitamins and antioxidants against DNA damage.
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Ingestão alimentar, perfil vitamínico e dano de DNA em crianças e adolescentes do município de Ribeirão Preto / Food intake, vitamin status and DNA damage in children and adolescents from Ribeirão PretoTamiris Trevisan de Barros 08 February 2018 (has links)
O objetivo deste estudo é descrever o dano de DNA através das variáveis Tail Moment e Tail Intensity e investigar a associação entre o dano do DNA, padrão alimentar e concentrações plasmáticas de vitaminas em crianças e adolescentes em Ribeirão Preto (São Paulo, Brasil). Estudantes de 9 a 13 anos foram selecionados de três escolas de Ribeirão Preto (São Paulo, Brasil), totalizando uma amostra de 120 indivíduos. A coleta de dados incluiu antropometria, composição corporal, avaliação da ingestão utilizando um questionário de frequência alimentar (QFA) e o Índice de Qualidade da Dieta Revisado (IQD-R) e coleta de sangue para a dosagem de vitaminas e determinação do dano do DNA pelo método de eletroforese em gel de célula única - comet assay. Os indivíduos foram divididos em dois grupos opostos de dano do DNA usando duas técnicas distintas: análise de k-cluster e classificação por escala de dano. Padrões de ingestão de nutrientes também foram gerados, utilizando robust sparse k-means cluster, e associados com o dano de DNA. Para análise utilizaram-se os testes T de Student, Mann-Whitney e ANCOVA. Na primeira análise, o cluster 1 (n = 73), com menor dano de DNA, apresentou maior consumo de vegetais verdes escuros e alaranjados (p = 0,047), vegetais totais (p = 0,041) e carnes, ovos e leguminosas (p = 0,022), através do IQD-R, e um escore de IQD total maior (p = 0,030), indicando melhor qualidade de dieta em comparação ao cluster 2 (n = 47), de maior dano de DNA. O cluster 2 apresentou maior consumo de laticínios, em comparação ao cluster 1 (p = 0,008). Em relação a vitaminas plasmáticas, o cluster 1 apresentou maior concentração de riboflavina (p = 0,004). No segundo método de divisão, o grupo 1 (n = 108), com menor dano de DNA, apresentou maior concentração de retinol (p = 0,010), beta-caroteno (p = 0,017) e riboflavina (p = 0,046), após teste de ANCOVA ajustado para o índice de massa corporal (IMC) em comparação ao grupo 2 (n = 12). Na divisão por padrão alimentar, o cluster 2 (n = 58), com menor consumo de aminoácidos e micronutrientes, apresentou maior consumo de energia (p = 0,001) e uma tendência de maior dano do DNA (p = 0,063) em relação ao cluster 1 (n = 27), com maior ingestão de nutrientes. Estes achados corroboram a literatura, afirmando o papel protetor de vitaminas e antioxidantes contra o dano do DNA. / The aim of this study is to describe the DNA damage using values of Tail Moment and Tail Intensity and investigate the association between DNA damage, dietary pattern and vitamin status in children and adolescents in Ribeirão Preto (São Paulo, Brazil). 9 to 13 year old students were selected from three schools in the city of Ribeirão Preto (São Paulo, Brazil), totalizing a sample of 120 subjects. Data collection included anthropometry, body composition, assessment of food intake using a food frequency questionnaire (FFQ), quality of diet through Revised Health Eating Index (HEI-R), and blood sampling for vitamins dosage and determination of DNA damage with single cell gel electrophoresis - comet assay. The subjects were divided into two opposing groups according to DNA damage using two different methods: k-cluster analysis and classification by scale of damage. Nutrients intake patterns were also generated through robust sparse k-means cluster and associated with DNA damage. The statistical analysis were performed using Student\'s T test, Mann-Whitney test and ANCOVA. In the first analysis, cluster 1 (n = 73), with less DNA damage presented higher intake of dark green and orange vegetables (p = 0,047), total vegetables (p = 0,041), meat, eggs and legumes (p = 0,022), assessed through HEI, as well as a higher total HEI-R level (p = 0,030), indicating higher quality of diet compared to cluster 2 (n = 47), with increased DNA damage. Cluster 2 presented a higher intake of milk and dairy products, compared to cluster 1 (p = 0,008). In relation to vitamins plasma levels, cluster 1 presented higher levels of riboflavin (p = 0,004). In the second method of division, group 1 (n = 108), with less DNA damage, presented higher levels of retinol (p = 0,010), beta-carotene (p = 0,017) and riboflavin (p = 0,046), after ANCOVA teste adjusted for body mass index (BMI) compared to group 2 (n = 12). In the division by dietary pattern, cluster 2 (n = 58) with a lower consumption of amino acids and micronutrients had higher energy intake (p = 0,001) and a tendency of higher DNA damage (p = 0,063) compared to cluster 1(n = 27), with higher intake of nutrients. These findings corroborate the literature, asserting protective role of vitamins and antioxidants against DNA damage.
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Quantifizierung von DNA-Schäden an adhaerenten Zelllinien nach Bestrahlung mit 188 Re- bzw. Röntgenstrahlung unter Zugabe von Methimazol, Nicotinamid und Perchlorat durch den Comet AssayKahmann, Cindy 20 August 2008 (has links) (PDF)
Dissertationsschrift zur Erlangung eines doctor medicinae (Dr.med.) der Medizinischen Fakultät Carl Gustav Carus der Technischen Universität Dresden
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The effect of fumigants on earthworms (Eisenia andrei) and soil microbial communities / Tanya Christina FouchéFouché, Tanya Christina January 2015 (has links)
Biofumigation is an important crop protection practice that uses a plant’s natural defence mechanisms to control agricultural crop pathogens and diseases. Glucosinolates are volatile compounds found in most Brassica species and when hydrolysed, it forms a range of natural toxins including isothiocyanates that act as biofumigants. Research suggests that biofumigation is a good alternative to chemical fumigants as it is effective in controlling plant pests but with lower health and environmental risks. Several studies have confirmed the effectiveness of the breakdown products, especially isothiocyanates, as fungicidal, bactericidal and nematicidal products against a series of plant pests. However, very little information is available on the effects of glucosinolates and its breakdown products on non-target and beneficial soil organisms. Negative effects on beneficial soil organisms can have serious negative impacts on soil quality especially when essential ecosystem functions such as nutrient cycling and soil bioturbation are affected.
Three biofumigants, broccoli, mustard and oilseed radish, and two chemical fumigants, metham sodium and cadusafos, were investigated for possible effects on non-target and essential soil organisms such as earthworms and the soil microbial community. Sublethal endpoints, including growth and reproductive success of the earthworms, were monitored. The genotoxicity of the biologically active compounds found in the fumigants, towards earthworms, was evaluated by means of the comet assay. The DNA damage was quantified by tail intensity parameters. Furthermore, the changes in the soil microbial community function and structure were evaluated by means of community level physiological profiling (CLPP) and phospholipid fatty acid (PLFA) analyses respectively. All exposures were done in artificial soil prepared according to the OECD standard guidelines.
In the biofumigant treated soils, results varied and different effects were observed on the non-target soil organisms. Broccoli reduced cocoon production and the number of hatchlings while mustard induced more DNA strand breaks in earthworm cells compared to the control. All the biofumigants stimulated microbial growth but broccoli and oilseed radish changed the microbial functional diversity. Mustard had no lasting effect on the functional diversity but altered the microbial community structure.
The chemical fumigants had a marked negative impact on the survival, growth, reproduction and the genotoxicity of the earthworms with metham sodium causing greater harm than cadusafos. The effects on the microbial community varied. Both chemicals had an inhibitory effect on the microbial growth in terms of the viable biomass determined by PLFA and the average well colour development in the Biolog™ Ecoplates. No lasting effects were
observed in the community structure. Overall, cadusafos had a more pronounced effect on the microbial community functional diversity than metham sodium.
Results indicated that each bioindicator species illustrates effects at their own level of organisation / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2015
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The effect of fumigants on earthworms (Eisenia andrei) and soil microbial communities / Tanya Christina FouchéFouché, Tanya Christina January 2015 (has links)
Biofumigation is an important crop protection practice that uses a plant’s natural defence mechanisms to control agricultural crop pathogens and diseases. Glucosinolates are volatile compounds found in most Brassica species and when hydrolysed, it forms a range of natural toxins including isothiocyanates that act as biofumigants. Research suggests that biofumigation is a good alternative to chemical fumigants as it is effective in controlling plant pests but with lower health and environmental risks. Several studies have confirmed the effectiveness of the breakdown products, especially isothiocyanates, as fungicidal, bactericidal and nematicidal products against a series of plant pests. However, very little information is available on the effects of glucosinolates and its breakdown products on non-target and beneficial soil organisms. Negative effects on beneficial soil organisms can have serious negative impacts on soil quality especially when essential ecosystem functions such as nutrient cycling and soil bioturbation are affected.
Three biofumigants, broccoli, mustard and oilseed radish, and two chemical fumigants, metham sodium and cadusafos, were investigated for possible effects on non-target and essential soil organisms such as earthworms and the soil microbial community. Sublethal endpoints, including growth and reproductive success of the earthworms, were monitored. The genotoxicity of the biologically active compounds found in the fumigants, towards earthworms, was evaluated by means of the comet assay. The DNA damage was quantified by tail intensity parameters. Furthermore, the changes in the soil microbial community function and structure were evaluated by means of community level physiological profiling (CLPP) and phospholipid fatty acid (PLFA) analyses respectively. All exposures were done in artificial soil prepared according to the OECD standard guidelines.
In the biofumigant treated soils, results varied and different effects were observed on the non-target soil organisms. Broccoli reduced cocoon production and the number of hatchlings while mustard induced more DNA strand breaks in earthworm cells compared to the control. All the biofumigants stimulated microbial growth but broccoli and oilseed radish changed the microbial functional diversity. Mustard had no lasting effect on the functional diversity but altered the microbial community structure.
The chemical fumigants had a marked negative impact on the survival, growth, reproduction and the genotoxicity of the earthworms with metham sodium causing greater harm than cadusafos. The effects on the microbial community varied. Both chemicals had an inhibitory effect on the microbial growth in terms of the viable biomass determined by PLFA and the average well colour development in the Biolog™ Ecoplates. No lasting effects were
observed in the community structure. Overall, cadusafos had a more pronounced effect on the microbial community functional diversity than metham sodium.
Results indicated that each bioindicator species illustrates effects at their own level of organisation / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2015
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In vitro chemically-induced DNA damage in cancer patients and healthy individuals : the effect of genotoxic compounds in cells from polyposis coli, colon cancer patients and healthy individualsKurzawa-Zegota, Malgorzata January 2011 (has links)
In the present study DNA damage was measured in peripheral blood lymphocytes from polyposis coli and colorectal cancer patients, treated with different dietary and environmental compounds and compared with lymphocytes from healthy individuals. In addition, confounding factors such as age, gender, alcohol intake and smoking habits were taken into consideration. The assays used in this study included the Comet assay, the Micronucleus assay, the Micronucleus-FISH assay and the sister chromatid exchange assay. The food mutagens, PhIP and IQ, as well as titanium dioxide nanoparticles (TiO2 NPs) induced a dose dependent increase in the DNA damage and chromosomal abnormalities in all tested groups regardless of confounding factors. Prior to experiments physicochemical characterisation of nanoparticles was conducted. In the presence of the flavonoids, quercetin and rutin that were acting in an antioxidant manner, the DNA damage resulting from the highest doses of food mutagens was significantly reduced. Thus, dietary supplementation with flavonoid-rich vegetables and fruits may prove very effective in protection against oxidative stress. The polyposis coli and colon cancer patients were more susceptible to food mutagens, PhIP and IQ, as well as TiO2 NPs, and in the majority of cases had a higher level of DNA damage in the Comet assay and higher cytogenetic damage in the Micronucleus assay. In the final project, twelve frequently encountered (NewGeneris) chemical compounds were evaluated to establish their damaging potential in lymphocytes and spermatozoa from healthy donors. The highest damage was produced by DNA reactive aldehydes, food mutagens and benzo[a]pyrene when assessed with the neutral and alkaline Comet assay with and without metabolic activation.
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DNA damage and repair detected by the comet assay in lymphocytes of African petrol attendants : a pilot study / G.S. KeretetseKeretetse, Goitsemang Salvation January 2007 (has links)
Petrol attendants are exposed to petrol volatile organic compounds (VOCs) which may have genotoxic and carcinogenic effects. The single cell gel electrophoresis assay (comet assay) is a method highly sensitive to DNA damage induced by environmental and occupational exposure to carcinogenic and mutagenic agents. The aim of this study was to evaluate the level of exposure of petrol attendants to petrol VOCs and also to determine their effect on DNA damage and repair in lymphocytes of African petrol attendants. The exposed group consisted of 20 subjects, randomly selected from three petrol stations. A control group of 20 unexposed subjects was also chosen and matched for age and smoking habits with the exposed group. Sorbent tubes were used to assess personal exposure of petrol attendants. The comet assay was used to investigate the basal DNA damage and repair capacity in isolated lymphocytes of petrol attendants and control subjects. Blood samples were taken from the petrol attendants at the end of their 8 hour working shift and also from the control subjects. The petrol attendants were found to be exposed to levels of petrol VOCs lower than the occupational exposure limit (OEL) for constituent chemicals. A significant relationship was found between the volume of petrol sold during the shift and the average concentrations of benzene, toluene and the total VOCs measured. However, relative humidity had a negative correlation with the average concentrations of benzene, toluene, xylene and the total VOCs. Significantly higher basal DNA damage was observed with the exposed group compared to the control group. The period of exposure influenced the level of DNA damage and the calculated repair capacity. Smoking and age had a significant influence on the level of DNA damage. DNA repair capacity was delayed in smokers of both exposed and non-exposed group. / Thesis (M.Sc. (Occupational Hygiene))--North-West University, Potchefstroom Campus, 2008.
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Exercise and DNA damage and repair in middle aged men / Matthew Andrew AikmanAikman, Matthew Andrew January 2007 (has links)
Regular physical activity (PA) leads to an increased quality of life by means of certain
physiological adaptations. Regular PA is beneficial to the human body and its functionality,
including the physiological, biochemical and even psychological modalities. During PA an
increased burden is placed on all physiological mechanisms due to the increased energy demand,
resulting in an adaptation of the physiological systems. Currently the biochemical mechanisms
by which these adaptations occur are not well understood or defined.
During the flow of electrons through the electron transport chain in the mitochondria free
radicals and reactive oxygen species (ROS) are produced. PA results in increased ROS
production. The relationship of different exercise intensities and ROS production with resulting
DNA damage is unclear. These free radicals and ROS disturb the pro-oxidant anti-oxidant
balance resulting in oxidative stress. When this balance is disturbed oxidative stress could lead to
potential oxidative damage, Oxidative damage occurs in lipid, protein and nucleic acid
macromolecules. ROS can attack DNA bases or deoxyribose residues to produce damaged bases
and/or single and double strand breaks. When the DNA is regarded and the damages are
replicated it could cause mutations or apoptosis, affecting the cell function and physiology.
The purpose of this study was to investigate the influence of different aerobic intensities on
oxidative DNA damage and repair in middle aged men by means of the Comet assay. Five PA
males and five physically inactive males were assigned to an experimental and control group
respectively. The subjects did not differ significantly at baseline. The VO2-max of each subject
was determined at baseline. Subjects were then randomly assigned to 60, 70, 80 and 90% of
individual baseline VO2-max intensities for an acute exercise intervention of 30 minutes on a
bicycle ergometer. Blood sampling was done at baseline, post-exercise and 24 hours post-exercise
for oxygen radical absorbance capacity (ORAC) and hydroperoxide analysis (dROM).
Peripheral blood was obtained for DNA damage testing by means of Comet analysis at baseline,
post-exercise, 5, 15, 30 minutes, and also 6, 12, 24, 48 and 72 hours after exercise. The results
obtained indicated that subjects who regularly participate in PA had an increased baseline
reading of ORAC and dROM values. ORAC levels after each acute exercise session increased,
with the highest increase in the control group, with a decrease in the direction of baseline
readings 24 hours post exercise. A biphasic damage-repair cycle over the 72 hour period was
observed with the Comet analysis. The most damaged cells occur directly after acute exercise.
The highest incidence of DNA damage over a 72 hour period was observed at 70% VO2-max,
with the least amount of damage after 90% VO2-max.
In conclusion the study indicates stress proteins or other kinds of physiological reaction to
minimize the damaging effect of oxidative stress, is in place to restore the cell's homeostasis.
Thus PA results in the development of oxidative DNA damage. To minimize DNA damage the
optimal intensity for acute physical exercise is between 70-80% VO2-max. At higher intensities
the release of stress proteins are initiated to buffer the damaging effect of oxidative stress and to
restore homeostasis. / Thesis (M.Sc. (Human Movement Science))--North-West University, Potchefstroom Campus, 2007.
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Einfluss einer fortgesetzten Benfotiamintherapie auf die Konzentration zirkulierender Advanced Glycation Endproducts, proinflammatorischer Zytokine und DNA-Läsionen bei Hämodialysepatienten / Influence of a prolonged therapy with benfotiamine on the concentration of circulating advanced glycation endproducts, proinflammatory cytokines and DNA-lesions at hemodialysis patientsWinkler, Michaela January 2007 (has links) (PDF)
Der Einsatz der Vitamin B 1 Vorstufe Benfotiamin hat sich im Tiermodell durch Verhinderung oder gar Aufhebung typischer diabetischer Folgeschäden wie Ne- phropathie, Retinopathie und Neuropathie ausgezeichnet. Diese Wirkung wird unter anderem der Aktivitätssteigerung des Enzyms Transketolase zugeschrie- ben, welches auch bei Dialysepatienten ohne diabetische Grunderkrankung sup- primiert ist. Das Ziel der vorliegenden Arbeit war, die Auswirkungen einer ora- len Benfotiaminsubstitution auf den Stoffwechsel von Langzeithämodialysepati- enten zu untersuchen. Die 15 rekrutierten Patienten mit und ohne Diabetes mel- litus erhielten über einen Zeitraum von 2 Monaten eine Dosis von 300 mg/d Benfotiamin, die in den folgenden 2 Monaten bis maximal 450 mg/d gesteigert wurde. Um einen Eindruck über den Verlauf der Entzündungssituation und des oxidativen Stresses zu gewinnen, wurden im Patientenvollblut AGEs und pro- inflammatorische Zytokine gemessen. Außerdem wurden peripheren Lympho- zyten mit Hilfe des alkaline Comet-Assay und des Mikrokerntestes auf DNA- Schädigungen analysiert. In beiden Patientengruppen lässt die Senkung der Mi- krokernraten den Schluss zu, dass Benfotiamin DNA-Schäden und somit eventu- ell das Krebsrisiko reduziert. Dieses vielversprechende Ergebnis korreliert jedoch nicht mit dem Resultat des Comet-Assay. Da hier der relative DNA-Schaden ten- dentiell ansteigt, sollte es Ziel weiterer Studien sein, diesen Sachverhalt an ei- nem größeren Patientenkollektiv mit Kontrollgruppen zu überprüfen. Eventuell ist letzteres Testsystem wegen seiner hohen Sensitivität in diesem Fall nicht op- timal geeignet. Außerdem sollte gezielt auf die beobachtete schnellere und stär- kere Mikrokernsenkung der diabetischen Patienten eingegangen werden, da die- se in der vorliegenden Studie zahlenmäßig unterrepräsentiert waren. Positiv zu bewerten ist der leichte CRP-Abfall sowie der Anstieg des Gesamtproteins und Albumin im Serum, was auf eine Reduktion der Mikroinflammation und oder eine verbesserte Ernährungssituation hinweist. Andererseits spricht der Anstieg des Neopterin- und Interleukin 6-Spiegels gegen die Veränderung des Inflamma- tionsstatus. Entgegen der Erwartung ließ sich in dieser Studie keine Reduktion der zirkulierenden AGEs und AOPPs im Serum erzielen. Um eine Reduktion des oxidativen Stresses besser beurteilen zu können, sollten in Folgestudien direkte und leicht veränderliche Marker wie der Glutathionspiegel verwendet werden. Zusammenfassend reduzierte Benfotiamin bei Hämodialysepatienten mit und ohne Diabetes mellitus DNA-Schäden in peripheren Lymphozyten bei unver- änderter Inflammationssituation und steigerte die Plasmaproteinkonzentration. Dies wurde eventuell durch Reduktion von oxidativem Stress und oder Beein- flussung seiner Ursachen wie Reduktion von Urämietoxinen erreicht.Weitere kli- nische Studien sind notwendig, um dieses vielversprechende Medikament in der täglichen Praxis einsetzen zu können. Besonders vorteilhaft ist seine gute Verträg- lichkeit auch in hoher Dosierung. Darüber hinaus soll das Präparat auch neuro- patische Schmerzen reduzieren, die sich bei Dialysepatienten häufig manifestie- ren, und wirkt somit multikausal. / It has been shown in animal models, that Benfotiamine, a precursor of the vitamine B1, prevents typical complications of diabets, like nephropathy, retinopathy and neuropathy. This effect is attributed to the increased activity of the enzyme trankelotase. The latter is also suppressed in patients of the hemodialysis program who are not diabetic. The goal of this thesis was to show the effects of an oral administration of benfotiamine on longterm hemodialysis patients. Fifteen patients were treated with 300 mg per day of benfotiamine which was increased in the following two months to 450 mg per day. The patient group consisted of a sub-group of diabetic and non-diabetic individuals. Advanced glycation endproducts (AGEs) and proinflammatory cytocines were measured in patients full-blood to show the impact on the inflammation and the oxidative stress situation. The DNA-damage in peripheral lymphocytes was determined using the alkaline comet-assay and the micronucleus-assay. The rate of micronuclei was diminished in both patient groups which could be attributed to the reduction of DNA-damage by benfotiamine and so eventually to a reduced risk of cancer. However, this result does not agree with the comet-assay experiments. The relative DNA-damage increased in the course of the study and so seems to be unaffected by the benfotiamine therapy. This may be attributed to the high sensitivity of the comet-assay technique. Therefore, further investigations with a bigger patient group in a double-blind study are necessary. Additionally, there should be a greater focus on diabetic patients that showed a faster and increased reduction of micronuclei which were underrepresentated in this study. The slight reduction of CRP and the increased protein and serum-albumine concentration correlates to a better nutritional status. On the other hand, the increasing neopterine and interleukine 6 level do not agree to the changes in the inflammatory situation. Against all expectations there was no reduction of AGEs and AOPPs in patients serum. Following studies should focus on rapidly changing direct markers like the glutathione level. In summary, benfotiamine reduces DNA-damage in peripheral lymphocytes in hemodialysis patients with or without diabetes. The plasma protein concentration was increased but unexpectedly the inflammatory situation was stable. These effects may be due to a reduction of oxidative stress or its causes like diminished ureamic toxines. One of Benfotiamines advantages is its good tolerance, even in increased dosages. Furthermore it seems to diminish neuropathic pain which is frequent in hemodialysis patients. However, more clinical studies are neccessary for a use in daily practice.
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