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Rôle des acides gras polyinsaturés alimentaires dans l'homéostasie lipidique de la rétine en conditions physiologiques et pathologiques liées au vieillissement / Role of dietary polyunsaturated fatty acids in the retina lipid homeostasia in physiological and pathological conditions associted with agingThierry, Magalie 19 November 2014 (has links)
La rétine est constituée de l’association d’un tissu neurosensoriel et de l’épithélium pigmentaire rétinien (EPR). Malgré la présence d’une barrière hémato-rétinienne, la rétine est contrainte aux changements de son milieu environnant, incluant les modifications du régime alimentaire et les stress environnementaux. Au cours du vieillissement, les échanges de nutriments et l’élimination des déchets métaboliques et cellulaires au travers de l’EPR diminuent. La dégénérescence maculaire liée à l’âge (DMLA) et la rétinopathie diabétique (RD) sont les pathologies rétiniennes les plus prévalentes dans les populations occidentales avant et après l’âge de 50 ans, respectivement. L’atrophie géographique et la DMLA néovasculaire constituent les stades avancés des maculopathies liées à l’âge. La RD affecte 60% des patients atteints de diabète de type 2 (T2D) dans les 15 années suivant l’apparition de la pathologie. Par ailleurs, les facteurs alimentaires interfèrent avec le développement de la DMLA et du T2D. Considérant l’épidémie mondiale de T2D d’une part, et l’allongement de l’espérance de vie d’autre part, les dépenses médico-sociales relatives à la prise en charge des patients atteints de T2D ou de DMLA sont à même de devenir un enjeu socioéconomique majeur. Le syndrome métabolique (SMet) est un des principaux facteurs de risque du T2D. Il peut ainsi être suggéré que limiter le développement du SMet pourrait potentiellement limiter l’incidence du T2D et de ses complications. Dans ce contexte, la consommation d’acides gras polyinsaturés à longue chaîne (AGPI-LC) de type oméga 3 fait partie des recommandations nutritionnelles pour la population afin de prévenir l’apparition du SMet et du T2D. Par ailleurs, une alimentation riche en AGPI-LC omega-3 est également associée à la réduction du risque de DMLA. En revanche, l’association entre T2D, RD et DMLA reste controversée, bien que quelques études basées sur des grandes cohortes rapportent une prévalence de DMLA augmentée chez les patients atteints de diabète ou de RD. Nos objectifs ont été d’évaluer premièrement si un SMet constituait un environnement favorable au développement des complications de type néovasculaires dans la rétine, et de tester secondairement l’efficacité d’AGPI-LC omega-3 dans la réduction des conséquences de ce SMet sur la rétine. Pour atteindre cet objectif, des rats ont été nourris avec un régime diabétogène enrichi en fructose afin de provoquer un SMet. Une néovascularisation choroïdienne a ensuite été induite en utilisant un modèle d’impacts laser au fond d’œil. Nous nous sommes intéressés tout d’abord à l’effet de ce régime à court terme et avons mis en évidence une diminution de la sensibilité des photorécepteurs de type cônes après 8 jours de régime, ainsi qu’une modification de l’expression des gènes et en particulier des sous-familles de cristallines. Ensuite, nos études se sont portées sur les effets de régime enrichi en fructose à long terme jusqu’à 6 mois. Le développement d’un SMet a été illustré par une augmentation de la masse grasse, une hyperinsulinémie, une hyperleptinémie et l’installation d’une stéatose hépatique. Ces rats ont développé une néovascularisation choroïdienne exacerbée après 1 et 3 mois de régime associée à une surexpression de facteurs pro-angiogéniques tels que VEGF et leptine .Une infiltration de macrophages dans la rétine et/ou l’activation des cellules microgliales résidentes a également été détectée. Les données électrorétinographiques ont suggéré une diminution de la sensibilité des photorécepteurs de type bâtonnets ainsi qu’une altération des fonctionnalités des cellules de la rétine interne à 6 mois. Dans un second temps, l’efficacité des AGPI-LC omega-3 (EPA+DHA) dans le but de réduire les conséquences du SMet dans la rétine a été testée. Nos données mettent en évidence qu’une forte dose d’EPA+DHA n’a cependant pas amélioré le SMet chez le rat. / The retina is the association of the neurosensory tissue and the retinal pigment epithelium (RPE). Despite the presence of the blood retinal barrier, the retina is submitted to changes of the external milieu, including dietary modulation and environmental stresses. With advanced age, the exchanges of nutrients and elimination of cellular and metabolic wastes via the RPE become limited. Age-related Macular Degeneration (AMD) and Diabetic Retinopathy (DR) are the most prevalent retinal pathologies in Western adult populations before and after the age of 50 years, respectively. Geographic atrophy and neovascular AMD are advanced stages of age-related maculopathies. DR afflicts 60% of type 2 diabetic (T2D) patients in the first 15 years of the disease. Dietary factors interfere in the development of both AMD and T2D. Accounting the worldwide epidemics of T2D in the one hand, and the improvement of life expectancy in the other hand, medical care to the patients is expected to worsen the socioeconomic burden of both T2D and AMD. Metabolic syndrome (MetS) is one of the major risk factor for T2D. Lowering the development of MetS would potentially lessen the incidence of T2D, and its complications. The daily intake of omega 3 long chain polyunsaturated fatty acids (LC-PUFA) is now recommended by health agencies for the prevention of MetS. Meanwhile dietary omega 3 LC-PUFA are associated with reduced risk of AMD. The association between T2D, DR, and AMD remains controversial, although large-scale population-based studies have reported increased prevalence of AMD in patients with diabetes or DR. Our objectives were first to evaluate whether MetS would represent a favorable environment for the development of neovascular complications in the retina, and second to test the efficacy of omega 3 LC-PUFA to reduce the consequences of MetS in the retina. For that purpose, a pro-diabetogenic high fructose diet was fed to rats to induce MetS and choroidal neovascularization was triggered by laser impacts in the eye fundus. We focused first on short term diet periods, and showed impairment on cone photoreceptor sensitivity after 8 days, as well as changes in gene expression in relation to crystallin sub-families. A long term - up to 6 months - fructose diet period triggered MetS as illustrated by body fat increase, hyperinsulinemia, hyperleptinemia and liver steatosis. Rats exhibited exacerbated laser-induced choroidal neovascularization after 1 and 3 months of feeding, that was associated with up-regulation of genes coding pro-angiogenic factors such as VEGF and leptin, as well as infiltration of macrophages and/or activation of retinal microglia. Electroretinographic data showed decreased sensitivity of rod photoreceptors and inner retinal cell functionality at 6 months of feeding. In a second time, the efficacy of dietary omega 3 LC-PUFA (EPA plus DHA) to reduce the consequences of MetS in the retina was tested. Our data showed that a high dose of EPA+DHA in rats did not improve MetS. Furthermore, side effects were generated as illustrated by localized atrophy in the retina submitted to the combination of laser-impacts, and normal light exposure. These works allowed us to suggest that MetS generated a favorable environment in the retina for the development of neovascular complications. Meanwhile, the sensitivity of cones and rods was impaired by MetS. Accounting the deleterious long term effects of omega 3 LC-PUFA in the retina, caution may be taken while recommending massive supplementation with omega 3 LC-PUFA in the context of MetS.
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Purification and Characterization of glpX-Encoded Fructose 1,6-Bisphosphatase, a New Enzyme of the Glycerol 3-Phosphate Regulon of Escherichia coliDonahue, Janet Lee 01 May 2000 (has links)
In Escherichia coli, the utilization of glycerol and sn-glycerol 3-phosphate is mediated by gene products of the glp regulon. The regulon encompasses five operons, including the glpFKX operon. Although glpF and glpK encode glycerol diffusion facilitator and glycerol kinase,respectively, the function of glpX was unknown. In the present work, we show that glpX encodes a fructose 1,6-bisphosphatase (FBPase), which catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and phosphate. The purified FBPase was dimeric, dependent on Mn2+ for activity and exhibited an apparent Km of 35 μM for fructose 1,6-bisphosphate. The enzyme was inhibited by ADP, ATP and phosphate and activated by PEP.
The attributes of the glpX-encoded FBPase were different from those of the previously characterized E. coli FBPase encoded by fbp. Mutants deleted in fbp (Δfbp) display a growthnegative phenotype on gluconeogenic carbon sources such as glycerol, indicating the inability of chromosomal glpX+ to complement Δfbp. However, a Δfbp mutation was complemented by overexpression of glpX+. In contrast, a glpX mutant exhibited a growth-positive phenotype on glycerol, glucose or fructose media. Surprisingly, a double mutant strain glpX pfkA (6-phosphofructokinase I) was more inhibited in growth on glucose and glycerol media than the pfkA parent. Carbohydrate metabolism in the pfkA background may be affected by the glpXmediated change in fructose 6-phosphate/fructose 1,6-bisphosphate levels. FBPase activities of soluble proteins separated by non-denaturing PAGE were visualized, showing a novel (third) FBPase, perhaps encoded by the glpX homolog, yggF. / Master of Science
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Effects of corn sweeteners on cookie qualityCurley, Lynn Patricia January 2011 (has links)
Typescript (photocopy). / Digitized by Kansas Correctional Industries
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Pre-exercise feedings of glucose, fructose, or sucrose: effects on fuel homeostasis in ratsAddington, Elizabeth Elaine. January 1985 (has links)
Call number: LD2668 .T4 1985 A32 / Master of Science
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Engineering a fungal β-fructofuranosidaseTrollope, Kim Mary 04 1900 (has links)
Thesis (PhD)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: β-fructofuranosidases are hydrolytic enzymes that act on sucrose to yield the products glucose and fructose. Under high substrate conditions these enzymes display fructosyltransferase activity which results in the synthesis of fructooligosaccharides (FOS). Some enzymes display higher propensities for FOS synthesis than others, with the determinants of this activity remaining unclear. The consumption of FOS produces a prebiotic effect that positively alters the composition of the colonic microflora, and as a result is linked to improved human and animal health. The increased demand for FOS has necessitated the industrial production of these nutraceuticals. In enzymatic sucrose biotransformation processes operating at high substrate loading and temperatures between 50 and 60°C, β-fructofuranosidase activity is negatively influenced by glucose product inhibition and thermal instability.
The aim of this study was therefore to engineer the Aspergillus japonicus β-fructofuranosidase, FopA, to improve a FOS synthesis bioprocess. A dual approach was employed to engineer FopA so as to increase the probability of obtaining an improved enzyme variant(s). A random mutagenesis approach was applied to harness the potential of the randomness of introduced mutations as precise structural knowledge of the enzyme regions involved in the phenotypic presentation of product inhibition, specific activity and thermal stability was unavailable. A semi-rational approach afforded the additional opportunity to reduce the number of variants to be screened, yet theoretically increased the functional content of the library. This study details the development of a method to rapidly quantify FOS using Fourier transform mid infrared attenuated total reflectance spectroscopy and multivariate data analysis. The method offers improvements over conventionally used high performance liquid chromatography in terms of reduced sample analysis times and the absence of toxic waste products. This is the first report on the direct screening of an enzyme variant library for FOS synthesis to identify improved variants and will significantly support future engineering of β-fructofuranosidases using random mutagenesis approaches. The random mutagenesis approach yielded a variant displaying limited relief from glucose inhibition. At the peak difference in performance, the variant produced 28% more FOS from the same amount of sucrose, when compared to the parent. The semi-rational approach, using a combined crystal structure and evolutionary-guided approach, yielded a four amino acid combination variant displaying improved specific activity and thermostability that was able to reduce the time to completion of an industrial-like FOS synthesis reaction by 26%. The positive outcome of the semi-rational approach showed that engineering loops regions in an enzyme is a feasible strategy to improve both specific activity and thermostability, most probably due to the modification of enzyme structural flexibility.
A bioinformatic tool that enables the identification of β-fructofuranosidases displaying high-level FOS synthesis from protein sequence alone was also developed during the study. These investigations revealed conserved sequence motifs characteristic of enzymes displaying low- and high-level FOS synthesis and a structural loop, unique to the latter group, that were readily applicable identifiers of FOS synthesis capacity. The tool presented may also be useful to improve the understanding of the structure-function relationships of β-fructofuranosidases by facilitating the identification of variations in groups of enzymes that have been functionally sub-classified. / AFRIKAANSE OPSOMMING: β-fruktofuranosidases is hidrolitiese ensieme wat op sukrose inwerk en glukose en fruktose as produkte vorm. Onder toestande met hoë substraatkondisies vertoon hierdie ensieme fruktosieltransferase-aktiwiteit wat tot die sintese van frukto-oligosakkariede (FOS) lei. Sommige ensieme neig na ʼn hoër FOS-sintese as ander, maar die bepalende faktore vir hierdie aktiwiteit is nog onbekend. Die verbruik van FOS veroorsaak ʼn prebiotiese effek wat die samestelling van kolon mikroflora positief beïnvloed en met verhoogde mens- en dieregesondheid verbind word. Die verhoogde aanvraag vir FOS het die industriële produksie van hierdie nutraseutiese middel genoodsaak. Tydens ensiemgedrewe sukrose-biotransformasieprosesse by hoë substraatladings en temperature tussen 50 en 60 °C, word β-fruktofuranosidase-aktiwiteit negatief deur glukose produkonderdrukking en termiese onstabiliteit beïnvloed.
Die doel van hierdie studie was dus om die Aspergillus japonicus β-fruktofuranosidase, FopA, vir ʼn verbeterde FOS-sintese bioproses te manipuleer. ʼn Tweeledige benadering is vir FopA manipulasie gevolg om die waarskynlikheid van verbeterde variant(e) te verhoog. ʼn Lukrake mutagenese benadering, wat die potensiaal van ingevoegde mutasie ewekansigheid inspan, is in die lig van onvoldoende akkurate kennis van die strukturele gedeeltes betrokke by produkinhibisie-, spesifieke aktiwiteit- en termiese stabiliteit fenotipes gevolg. Die toepassing van ʼn semi-rasionele benadering het ook geleentheid vir die sifting van ʼn kleiner variantbibioloteek geskep, terwyl die funksionele inhoud teoreties verhoog word. Die studie beskryf die ontwikkeling van ʼn metode vir die vinnige kwantifisering van FOS, gebaseer op Fourier transform middel infrarooi geattenueerde totale refleksie spektroskopie en meerveranderlike data-analise. Dit is die eerste melding van ʼn direkte sifting van ʼn ensiemvariantversameling vir FOS-sintese om verbeterde variante te identifiseer, en kan die toekomstige manipulasie van β-fruktofuranosidases deur middel van lukrake mutagenese-benaderings beduidend ondersteun. Die lukrake mutagenese-benadering het ʼn variant met beperkte opheffing van glukose-onderdrukking gelewer. By die punt waar die prestasie die meeste verskil, het die variant 28% meer FOS vanaf dieselfde hoeveelheid sukrose geproduseer in vergelyking met die ouer-ensiem. Die semi-rasionele benadering, gegrond op ʼn kombinasie van kristalstruktuur en evolusionêre-geleide benaderings, het ʼn vier-aminosuurkombinasie variant met hoër spesifieke aktiwiteit en termostabiliteit gelewer wat die voltooiingstyd van ʼn tipiese industriële FOS sintesereaksie met 26% kon verkort. Die positiewe uitkoms van die semi-rasionele benadering het aangedui dat manipulasie van die lusgedeeltes in ʼn ensiem ʼn lewensvatbare strategie is om beide spesifieke aktiwiteit en termostabiliteit te verbeter, moontlik as gevolg van wysigings in die buigsaamheid van die ensiemstruktuur.
ʼn Bioïnformatika-hulpmiddel vir die identifikasie van β-fruktofuranosidases met hoë vlakke van FOS-sintese op grond van proteïenvolgordes is ook tydens die studie ontwikkel. Motiewe met gekonserveerde volgordes kenmerkend van lae- en hoë-vlak FOS-produserende ensieme en ʼn strukturele lus, uniek tot die laasgenoemde groep, is tydens die ondersoek onthul wat as maklike identifiseerders van FOS-sintesekapasiteit kan dien. Die voorgestelde hulpmiddel kan ook nuttig wees om die struktuur-funksie-verwantskap van β-fruktofuranosidases beter te verstaan deur die identifikasie van variasie in ensiemgroepe wat funksioneel gesubklassifiseer is.
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A study of fructose-1, 6-diphosphatase: some properties including ascorbate inhibition.李蘊盈, Lam, Wan-ying. January 1972 (has links)
published_or_final_version / Biochemistry / Master / Master of Philosophy
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Kinetic and Chemical Mechanism of Pyrophosphate-Dependent PhosphofructokinaseCho, Yong Kweon 12 1900 (has links)
Data obtained from isotope exchange at equilibrium, exchange of inorganic phosphate against forward reaction flux, and positional isotope exchange of 18O from the (βγ-bridge position of pyrophosphate to a (β-nonbridge position all indicate that the pyrophosphate-dependent phosphofructokinase from Propionibacterium freudenreichii has a rapid equilibrium random kinetic mechanism. All exchange reactions are strongly inhibited at high concentrations of the fructose 6-phosphate/Pi and MgPPi/Pi substrate-product pairs and weakly inhibited at high concentrations of the MgPPi/fructose 1,6-bisphosphate pair suggesting three dead-end complexes, E:F6P:Pi, E:MgPPi:Pi, and E:FBP:MgPPi. Neither back-exchange by [32p] nor positional isotope exchange of 18O-bridge-labeled pyrophosphate was observed under any conditions, suggesting that either the chemical interconversion step or a step prior to it limits the overall rate of the reaction. Reduction of the pyridoxal 5'-phosphate-inactivated enzyme with NaB[3H]4 indicates that about 7 lysines are modified in free enzyme and fructose 1,6-bisphosphate protects 2 of these from modification. The pH dependence of the enzyme-reactant dissociation constants suggests that the phosphates of fructose 6-phosphate, fructose 1,6-bisphosphate, inorganic phosphate, and Mg-pyrophosphate must be completely ionized and that lysines are present in the vicinity of the 1- and 6-phosphates of the sugar phosphate and bisphosphates probably directly coordinated to these phosphates. The pH dependence of kinetic parameters suggests that the enzyme catalyzes its reaction via general acid-base catalysis with the use of a proton shuttle. The base is required unprotonated in both reaction directions. In the direction of fructose 6-phosphate phosphorylation the base accepts a proton from the hydroxyl at C-l of F6P and then donates it to protonate the leaving phosphate. The maximum velocity of the reaction is pH independent in both reaction directions while V/K profiles exhibit pKs for binding groups (including enzyme and reactant functional groups) as well as pKs for enzyme catalytic groups. These data suggest that reactants bind only when correctly protonated and only to the correctly protonated form of the enzyme.
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A high fructose diet alters affective-like behavior and metrics of synaptic mitochondrial function differentially in male and female ratsKloster, Alix H 01 January 2019 (has links)
Fructose consumption has become a normalized part of the standard American diet over the past 40 years. While fructose consumption is a known risk factor of metabolic syndrome, there is increasing evidence that fructose consumption influences brain and behavior. Recently, more interest has been focused on mitochondrial dysfunction as a potential link between metabolic stress and modifications of the central nervous system. Mitochondria are in the unique position of both regulating and being vulnerable to alterations in energy homeostasis. Sex-differences are well categorized in the presentation of metabolic symptoms associated with excessive fructose consumption. Thus, it is important to characterize sex-specific outcomes in the arena of brain and behavior in order to develop better strategies for mitigating the effects of fructose consumption. Therefore, I determined the extent to which a high fructose diet modified physiological outcomes, serum corticosterone, and affective-like behavior in male and female rats. In addition, I examined the potential of excessive fructose consumption to modify synaptic mitochondrial respiration at baseline and following an acute stress experience. In males, serum corticosterone was increased following an acute stress event, and this increase was modified by diet. Fructose consumption resulted in decreased affective-like behavior in the open field test and synaptic mitochondrial respiration was altered by both diet and acute stress experience. In females, fructose consumption altered weight and caloric efficiency. Females demonstrated increased depressive-like behavior in a forced swim test. Corticosterone concentrations were only increased by acute stress experience, and synaptic mitochondrial function was modified by diet in groups that underwent an acute stressor.
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Kohlenhydratmalassimilation bei der Hashimotothyreoiditis / Evidence of impaired carbohydrate assimilation in euthyroid patients with Hashimoto's thyroiditisHeckl, Steffen January 2014 (has links) (PDF)
Die autoimmune Thyreoiditis nach Hashimoto stellt aktuell eine der häufigsten Autoimmunerkrankungen eines Organs und die häufigste Ursache der Hypothyreose dar. Die Hashimotothyreoiditis (HT) weist eine hohe Prävalenz und Inzidenz auf. Es existieren Hinweise, dass die Inzidenz der HT aus noch nicht geklärten Gründen gestiegen sein könnte.
Die Kohlenhydrate Fruktose, Laktose und Sorbitol werden in der Lebensmittelproduktion umfassend eingesetzt. Insbesondere die industrielle Verwendung sowie der weltweite Konsum von Fruktose und Laktose unterlagen in den letzten Jahrzehnten einer rasanten Steigerung, obwohl ein hoher Prozentsatz der Bevölkerung zur Malassimilation jener Kohlenhydrate prädisponiert ist.
In einer internistischen Praxis (Praxis Frau Dr. med. I. Heckl, Bad Homburg) zeigte sich, dass HT-Patienten trotz verifizierter Euthyreose vermehrt über gastrointestinale Symptome berichteten. Unter anderem wurden eine bakterielle Fehlbesiedelung des Dünndarmes und eine Zöliakie ausgeschlossen. In der weiteren Abklärung durch die Praxis Dr. I. Heckl wurde eine deutliche Häufung der Malassimilation der Kohlenhydrate Fruktose, Laktose oder Sorbitol unter euthyreoten HT-Patienten ersichtlich. In Abhängigkeit von einer konsequenten Nahrungsumstellung normalisierten sich regelmäßig das Befinden der Patienten sowie die sonographischen, die serologischen und die laborchemischen Marker der HT, sodass man einen ursächlichen Zusammenhang empirisch vermuten konnte.
Im Rahmen einer prospektiven Studie sollte dieser neu beobachtete Zusammenhang zwischen der HT und der Kohlenhydratmalassimilation in der Klinik und Poliklinik für Nuklearmedizin der Universität Würzburg untersucht werden.
In einem unizentrischen Fall-Kontroll-Studiendesign wurden 45 euthyreote HT-Patienten und 38 schilddrüsengesunde Kontrollpersonen auf das Vorliegen einer Kohlenhydratmalassimilation mittels des Wasserstoffatemtests (H2-Atemtest) untersucht. Alle Probanden erhielten einen Fruktose-H2-Atemtest sowie einen Laktose-H2-Atemtest inklusive einer kapillären Blutglukosemessung. Im Falle eines positiven Ergebnisses des Fruktose-H2-Atemtests wurde ein Glukose-H2-Atemtest zum Ausschluss einer bakteriellen Fehlbesiedelung des Dünndarmes durchgeführt. Lieferte der Fruktose-H2-Atemtest ein negatives Ergebnis, so folgte ein H2-Atemtest mit Sorbitol. Das Auftreten gastrointestinaler Symptome während der Testdurchführung wurde dokumentiert. Symptomfragebögen und semiquantitative Ernährungsfragebögen im retrospektiven Design dienten der Erfassung alltäglicher Symptome und Ernährungsgewohnheiten. Blutproben dienten der Messung von Schilddrüsenhormonen, Schilddrüsenautoantikörpern, Gewebstransglutaminase-Antikörpern und Antiparietalzell-Autoantikörpern.
Unter den euthyreoten HT-Patienten konnte ein signifikant häufigeres Auftreten der Fruktose- sowie der Laktosemalassimilation im Vergleich zu den schilddrüsengesunden Kontrollpersonen demonstriert werden. Die Fruktosemalassimilation wurde bei den HT-Patienten mit 48,9% signifikant häufiger als in der Kontrollgruppe nachgewiesen (p=0,035). Im Kontrollgruppenkollektiv hatte eine Fruktosemalassimilation lediglich bei 26,3% der Probanden bestanden. Eine Laktosemalassimilation wurde bei den HT-Patienten mit 42,2% signifikant häufiger als im Kontrollkollektiv diagnostiziert, welches in 21,1% der Fälle eine Laktosemalassimilation aufwies (p=0,04). Insgesamt lag eine Fruktose- und / oder Laktosemalassimilation bei 73,3% der HT-Patienten und bei 42,1% der Kontrollgruppenprobanden vor. Somit vertrugen nur 26,7% der Fallgruppe, jedoch 57,9% der Kontrollgruppe beide Kohlenhydrate (p=0,004). Hinsichtlich der Prävalenz der Sorbitolmalassimilation oder eines positiven Glukose-H2-Atemtestes kam kein signifikanter Unterschied zur Darstellung. Die Auswertung der Ernährungsfragebögen zeigte für beide Kollektive eine vergleichbare durchschnittliche Konsummenge der jeweiligen Kohlenhydrate auf.
Gastrointestinale Symptome waren während des Laktose-H2-Atemtests sowie während des Fruktose-H2-Atemtests jeweils in der Fallgruppe signifikant häufiger anzutreffen als in der Kontrollgruppe. Auch im Hinblick auf das Alltagsleben beschrieben die euthyreoten HT-Patienten signifikant häufiger unter den folgenden Symptomen zu leiden: Weicher Stuhlgang, Oberbauchschmerzen, Meteorismus, laute Darmgeräusche, „Kugelbauch“, Sodbrennen, Schleimauflagerungen des Stuhlgangs, Obstipation, Müdigkeit, postprandiale Kraftlosigkeit, Depressionen, Heißhunger auf Süßes, Migräne, Konzentrationsmangel und eine vermehrte Infektanfälligkeit.
Zur Kausalität des hier erstmals beschriebenen Zusammenhangs existieren mehrere Hypothesen. Die Einteilung der HT-Patienten gemäß ihrer Schilddrüsenautoantikörper-Titer in Subkollektive ergab keinen Hinweis auf einen Einfluss der Aktivität des Autoimmungeschehens auf die Häufigkeit der Kohlenhydratmalassimilation. Es steht zur Diskussion, ob die HT zur Entstehung einer Kohlenhydratmalassimilation führen, oder ob eine vorbestehende Kohlenhydratmalassimilation, im Sinne eines neu identifizierten Risikofaktors, zur Genese einer HT prädisponieren könnte.
In der vorliegenden Studie konnte erstmalig eine signifikante Häufung der Kohlenhydratmalassimilation bei euthyreoten HT-Patienten aufgezeigt werden. Vor dem Hintergrund der weitreichenden lebensmittelindustriellen Verwendung und des hohen Konsums der Kohlenhydrate Fruktose, Laktose und Sorbitol sowie der hohen Prävalenz und Inzidenz der HT, ergibt sich eine hohe Relevanz des hier nachgewiesenen Zusammenhangs. In der differenzialdiagnostischen Abklärung gastrointestinaler Beschwerden bei euthyreoten HT-Patienten nimmt die hier beschriebene Assoziation zwischen der HT und der Kohlenhydratmalassimilation einen besonderen Stellenwert ein. Die Kohlenhydratmalassimilation verkörpert einen neuen, sowohl klinisch, als auch potentiell pathogenetisch relevanten Aspekt der Hashimotothyreoiditis. / Background/Objectives:
Hashimoto’s thyroiditis (HT) represents a wide-spread autoimmune disease. In euthyroid patients with HT, an impaired assimilation of common carbohydrates has been observed. Our objectives were to compare the frequency of (1) fructose (FM), lactose (LM) and sorbitol malassimilation (SM), (2) gastrointestinal symptoms (GS) following carbohydrate ingestion and (3) recurrent GS relevant to the participants’ daily lives.
Subjects/Methods:
We conducted a prospective case–control study of 45 ambulatory patients with HT and 38 healthy volunteers, matched with regard to age, gender and area of origin. Hydrogen breath tests with fructose, lactose, sorbitol and glucose were performed, the lactose testing additionally comprising measurements of capillary blood glucose (cBG). GS during the tests and recurrent GS concerning the participants’ daily lives were assessed. A food-frequency questionnaire was administered.
Results:
FM was diagnosed in 48.9% of patients compared with 26.3% of the control group (P=0.035). In all, 42.2% of patients with HT and 21.1% of healthy controls showed LM (P=0.04). FM and/or LM was present in 73.3% of the patients and in 42.1% of healthy controls (P=0.004). GS after the ingestion of fructose (P=0.003) or lactose (P=0.025) and recurrent GS were significantly more prevalent in the case group. The consumption of free fructose, lactose or sorbitol did not differ.
Conclusions:
Carbohydrate malassimilation and gastrointestinal complaints are frequent in euthyroid patients with HT, leading to novel clinical and pathophysiological considerations and concepts.
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Synthesis of sialyl mimetics as biological probesPhan, Tho Van January 2004 (has links)
Abstract not available
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