Thesis (doctoral)--Rijksuniversiteit te Utrecht.

Childhood micronutrient deficiencies have negative effects on cognition. Little is known about the effects of combined consumption of micronutrients and sugar on growth and cognitive function. The aim of this thesis was to 1) investigate the effects of micronutrients and sugar, alone and in combination, in a beverage, on growth and cognition in South African children and 2) review recent evidence on iron status and anaemia prevalence in South African children since the National Food Consumption Survey-Fortification Baseline-2005 (NFCS-FB-2005). Children (n = 408, 6−11 years) were randomly allocated to a beverage containing 1) micronutrients with sugar, 2) micronutrients with non-nutritive sweetener, 3) no micronutrients with sugar, or 4) no micronutrients with non-nutritive sweetener for 8.5 months. Cognition was assessed using sub-tests from the Kaufman Assessment Battery for Children-II. Growth was assessed as weight-for-age (WAZ), height-for-age and body-mass-index-for-age z-scores. Relevant internet search engines identified studies reporting iron status of South African children after 2005. Secondary analysis was conducted on NFCS-FB-2005 provincial data for children 7−9 years old. Positive intervention effects were observed for micronutrients (0.76; 95% CI: 0.10, 1.42) and sugar (0.71; 95% CI: 0.05, 1.37) on Atlantis (measure learning ability), and sugar on Rover (measure simultaneous processing) (0.72; 96% CI: 0.08, 1.35) test scores. Attenuating micronutrient x sugar interactions were observed on Atlantis, Number Recall (measure sequential processing) and Rover test performance. Micronutrients or sugar alone lowered WAZ. In combination, this effect was attenuated (significant micronutrient x sugar interaction). Four studies from four different provinces were identified. All reported lower anaemia prevalence than the NFCS-FB-2005 (KwaZulu-Natal (11.5% vs 14.4%), North West (6.9% vs 27%) Western Cape (17.2% vs 18.8%) and Northern Cape (5.4% vs 22.2%). A beverage fortified with micronutrients or added sugar had beneficial effects on cognition, but a lowering effect on WAZ in the children. Unexpectedly, the combination of micronutrients and sugar attenuated these effects. In the identified studies, anaemia prevalence in school-aged children was lower than reported in the NFCS-FB-2005. / Thesis (PhD (Nutrition))--North-West University, Potchefstroom Campus, 2013.

Childhood micronutrient deficiencies have negative effects on cognition. Little is known about the effects of combined consumption of micronutrients and sugar on growth and cognitive function. The aim of this thesis was to 1) investigate the effects of micronutrients and sugar, alone and in combination, in a beverage, on growth and cognition in South African children and 2) review recent evidence on iron status and anaemia prevalence in South African children since the National Food Consumption Survey-Fortification Baseline-2005 (NFCS-FB-2005). Children (n = 408, 6−11 years) were randomly allocated to a beverage containing 1) micronutrients with sugar, 2) micronutrients with non-nutritive sweetener, 3) no micronutrients with sugar, or 4) no micronutrients with non-nutritive sweetener for 8.5 months. Cognition was assessed using sub-tests from the Kaufman Assessment Battery for Children-II. Growth was assessed as weight-for-age (WAZ), height-for-age and body-mass-index-for-age z-scores. Relevant internet search engines identified studies reporting iron status of South African children after 2005. Secondary analysis was conducted on NFCS-FB-2005 provincial data for children 7−9 years old. Positive intervention effects were observed for micronutrients (0.76; 95% CI: 0.10, 1.42) and sugar (0.71; 95% CI: 0.05, 1.37) on Atlantis (measure learning ability), and sugar on Rover (measure simultaneous processing) (0.72; 96% CI: 0.08, 1.35) test scores. Attenuating micronutrient x sugar interactions were observed on Atlantis, Number Recall (measure sequential processing) and Rover test performance. Micronutrients or sugar alone lowered WAZ. In combination, this effect was attenuated (significant micronutrient x sugar interaction). Four studies from four different provinces were identified. All reported lower anaemia prevalence than the NFCS-FB-2005 (KwaZulu-Natal (11.5% vs 14.4%), North West (6.9% vs 27%) Western Cape (17.2% vs 18.8%) and Northern Cape (5.4% vs 22.2%). A beverage fortified with micronutrients or added sugar had beneficial effects on cognition, but a lowering effect on WAZ in the children. Unexpectedly, the combination of micronutrients and sugar attenuated these effects. In the identified studies, anaemia prevalence in school-aged children was lower than reported in the NFCS-FB-2005. / Thesis (PhD (Nutrition))--North-West University, Potchefstroom Campus, 2013.

Diamond-Blackfan anemia (DBA) is a rare congenital syndrome that presents with ane- mia and selective deficiency of erythroid precursors, while other blood lineages are usu- ally unaffected. Approximately half of the patients display additional somatic anoma- lies and growth retardation. The therapy is mostly symptomatic and is dominated by corticosteroids, other modalities include regular blood transfusions or hematopoietic stem cell transplantation. At the beginning of this work, only two DBA causal genes were known, RPS19 and RPS24, being mutated in approximately 1/4 of all DBA patients. The goals of this work were to study the consequences of the known DBA causal mutations on cellular level and to find novel DBA causal genes. To date, over a half of DBA patients have been reported to carry a mutation in one of nine known DBA causal genes, including RPS17, RPL11 and RPL5, that are reported in this dissertation. All confirmed DBA causal genes encode for ribosomal proteins (RPs) that were essential for ribosome assembly. We further hypothesized a non- ribosomal protein participating in this process might be involved in DBA pathogenesis, too. In one DBA patient, we identified a rare sequence variant in one such candidate, a protein arginine methyltransferase 3 (PRMT3). We reported that the patient PRMT3...

Diamond-Blackfan anemia (DBA) is a rare congenital syndrome that presents with ane- mia and selective deficiency of erythroid precursors, while other blood lineages are usu- ally unaffected. Approximately half of the patients display additional somatic anoma- lies and growth retardation. The therapy is mostly symptomatic and is dominated by corticosteroids, other modalities include regular blood transfusions or hematopoietic stem cell transplantation. At the beginning of this work, only two DBA causal genes were known, RPS19 and RPS24, being mutated in approximately 1/4 of all DBA patients. The goals of this work were to study the consequences of the known DBA causal mutations on cellular level and to find novel DBA causal genes. To date, over a half of DBA patients have been reported to carry a mutation in one of nine known DBA causal genes, including RPS17, RPL11 and RPL5, that are reported in this dissertation. All confirmed DBA causal genes encode for ribosomal proteins (RPs) that were essential for ribosome assembly. We further hypothesized a non- ribosomal protein participating in this process might be involved in DBA pathogenesis, too. In one DBA patient, we identified a rare sequence variant in one such candidate, a protein arginine methyltransferase 3 (PRMT3). We reported that the patient PRMT3...

Diploma work was concentrated on the evaluation of two metabolic profiles on the milch cows of Holstein breed on the basic of compilated nutritive rations for individual phases of lactation. The metabolic tests were evaluated in the milch cows in the period of making cow milk, the top of lactation and the second phase of lactation. The balance of nutriments was counted out in the nutritive rations. The haemotological and biochemical parameters, macromineral and urinary profiles were evaluated in the metabolic profiles. The work in the both metabolic profiles evidenced the reduced number of erythrocytes which can be connected with the occurence of anaemia. In the period of the top of lactation it is possible to speculate about an energetical deficit with regard to the low content of triacylglycerols. In the profile tests the presence of ketone bodies substances in urine was found out in the period of making cow milk. This finding connects with the negative energetic balance that occurrs in the course of the first two months after calving. Within of mineral profile an attention should be paid to especially the content of calcium, which was reduced in the both profiles. In comparison with the profiles perfomed in 2011 we find out that reached modifications of the nutrive ration and the increase in the content of main nutriments, which shoved in the milch cows by improvement of metabolic effects. Neverthless in breeding of the milch cows the increased emphasis should be put on the period of making cow milk and the recommendation for prevention from anaemia or other disorders is carrying out of the selective metabolic test.

Iron is an essential element for human organism, because it cooperates as a cofactor of enzymes in many metabolic pathways. Iron is a component of hemoglobin, and thus it is indispensable for the oxygen transport to tissues. It can exist as a ferrous or ferric form. However, ferrous iron paticipates in reactions in which highly reactive hydroxyl group can be formed. This product is harmful for the organism. Non-heme iron is taken up to the circulation through duodenal enterocyte. Iron excretion is carried out only by desquamation of the enterocytes or by bleeding. Therefore, iron intake must be strictly regulated. Iron overloading is observed in some chronic diseases (hereditary hemochromatosis, alcohol liver disease). In contrary, iron depletion can be a case of iron deficiency anemia. The aim of this master thesis is to determine the expression of iron transport molecules in duodenum in chronic diseases which originate due to disturbances of iron intake regulation. We determine the expression of molecules of iron transport (DMT1, Dcytb, ferroportin, hephaestin) on mRNA level by qPCR and on protein level by western blot. The level of serum hepcidin was determined by ELISA. Our results show an increased expression of mRNA of transporters DMT1 and ferroportin as well as ferrireductase Dcytb and ferroxidase...

Une méthode de réaction de polymérisation en chaîne en temps réel (t-PCR), permettant de déterminer dès 12 semaines d'aménorrhée (SA) le statut RhD dun foetus à partir d'ADN libre dans le plasma maternel, a été mise au point dans notre laboratoire. Cette technique est appliquée en routine clinique depuis novembre 2002 aux patientes RhD négatif dans le cadre de leur suivi immuno-hématologique. Ce développement ainsi quune première évaluation portant sur 218 grossesses et 223 nouveau-nés ont été rapportés dans un travail original publié dans le J Gynecol Obstet Biol Reprod en 2005 (Minon et al. 2005). La qualité de la prédiction du statut RhD ftal a permis d'envisager l'extension du génotypage à toute patiente RhD négatif. En parallèle, différentes PCR conventionnelles ont été développées pour rechercher les gènes RHD silencieux. Lexistence de variants non fonctionnels du gène RHD - principalement trouvés dans les populations africaine et asiatique - a conduit à amplifier des segments spécifiques du gène RHD fonctionnel (séquences des exons 4 et 5) en plus dune séquence de lexon 10, afin déviter les faux positifs. Toutefois, un résultat faux positif inhabituel, lié en fait à la présence d'un greffon rénal chez l'une de nos patientes, a fait l'objet d'une publication dans Transfusion en 2006 (Minon et al. 2006). La place du génotypage foetal RHD a été réfléchie dans un contexte plus général de prise en charge et de prévention de l'alloimmunisation foeto-maternelle anti-D. Cette réflexion a permis de définir de nouvelles stratégies qui ont été décrites dans la Revue Médicale de Liège en 2006 (Minon et al. 2006). Une synthèse de notre activité tant régionale que nationale entre 2002 et 2006 a été récemment publiée dans Transfusion en 2008 (Minon et al. 2008). Elle reprend l'étude de 563 patientes et de leurs 581 nouveau-nés. Notre expérience dans les grossesses gémellaires y est rapportée. Les pièges (faux positifs et négatifs) de la technique sont abordés et des moyens de prévention pour les éviter sont proposés. Elle a été loccasion dune discussion assez exhaustive sur le génotypage RHD foetal à partir du sang maternel. La faible expression de l'antigène D chez certaines mamans pose un double problème: le premier est lié à la présence d'un gène RHD maternel "intact" qui invalide la recherche du gène RHD foetal dans le plasma. Le second est lié à la confusion induite dans lesprit de l'obstétricien par la présence d'un gène RHD maternel « normal » mais associé à une expression faible de l'antigène D, la patiente étant par ailleurs connue sérologiquement D négative. Sur ce sujet déjà épineux viennent se greffer les particularités des variants D partiels. Une nouvelle stratégie a été définie afin d'orienter l'obstétricien dans le suivi immuno-hématologique et la prophylaxie par anti-D des patientes présentant un D variant (D faible et/ou D partiel). Cette nouvelle approche concerne aussi la politique transfusionnelle à adopter en matière de sang D phéno-compatible. Cette discussion fait partie intégrante de notre sujet et reprendra notre expérience reposant maintenant sur plus de 700 déterminations de RHD ftal réalisées depuis 2007. L'extension du génotypage RHD à toutes les patientes RhD négatif encourage nos équipes à réaliser de manière systématique une prévention par immunoglobulines anti-D à 28 semaines daménorrhée (SA) chez les patientes Rh D négatif dont le foetus est RHD positif. L'introduction de cette prophylaxie modifie le suivi immuno-hématologique obstétrical traditionnel et fait l'objet d'une publication sous presse dans Acta Clinica Belgica (Minon et al. 2008). En corollaire de notre travail, nous avons démontré la fiabilité de la prédiction du sexe foetal par la recherche du gène SRY utilisé comme contrôle interne de la présence de DNA foetal dans le plasma maternel lorsque le foetus est de sexe masculin.