Folate intake in North America has drastically increased over the past decade due to folic acid fortification and widespread supplemental use. The role of folate in breast cancer is highly controversial and the effects of folic acid supplementation on breast cancer patients are currently unknown. An animal study was performed to determine the effects of folic acid supplementation on the progression of the mammary tumors in the DMBA-carcinogen model. Folic acid supplementation was associated with more rapid sentinel tumor progression and with higher sentinel tumor weight, volume, and area, although no clear dose-responsive relationship was observed. Folic acid supplementation was associated with an increased expression of proapoptotic protein PARP and decreased expression of proliferation protein PCNA. These data suggest that folic acid supplementation may promote the progression of established mammary tumors. Whether or not folic acid supplementation may adversely affect the outcome of patients with breast cancer warrants further studies.

Folate intake in North America has drastically increased over the past decade due to folic acid fortification and widespread supplemental use. The role of folate in breast cancer is highly controversial and the effects of folic acid supplementation on breast cancer patients are currently unknown. An animal study was performed to determine the effects of folic acid supplementation on the progression of the mammary tumors in the DMBA-carcinogen model. Folic acid supplementation was associated with more rapid sentinel tumor progression and with higher sentinel tumor weight, volume, and area, although no clear dose-responsive relationship was observed. Folic acid supplementation was associated with an increased expression of proapoptotic protein PARP and decreased expression of proliferation protein PCNA. These data suggest that folic acid supplementation may promote the progression of established mammary tumors. Whether or not folic acid supplementation may adversely affect the outcome of patients with breast cancer warrants further studies.

Is Supplemental Leucine Intake Associated with Enhanced Post Exercise Muscle Protein Synthesis and Attenuated Muscle Protein Breakdown? Knight AD, Benardot D, Thompson W, and Henes ST Introduction: The role of individual amino acids on protein synthesis and their impact on physical performance is of high importance to athletes and to those studying the science of sports nutrition. Leucine, one of three branched-chain amino acids, is a frequently researched amino acid because of its potential stimulatory effect on muscle protein synthesis (MPS) following exercise in humans. Purpose: Although there have been many studies conducted on leucine’s muscle stimulatory effect, questions remain as to the efficacy and feasibility of leucine as an MPS catalyst. Contributing to these questions are the widely varied dosing and timing strategies that different researchers have employed. It is the purpose of this thesis, therefore, to assess the differences in study protocols and shed light on the potential effectiveness on leucine as a MPS stimulator. Central to this issue is whether supplemental leucine intake is associated with enhanced post exercise MPS and, if so, what associated factors, including timing and level of intake, are most likely to influence this effect. Methods: A comprehensive review of the literature on leucine and its effect on MPS was performed. Studies were organized into similar topics, with an assessment and summary of effect produced for each topic area. A general conclusion was made that was based on the summary of each topic area. Results: Leucine is involved in protein metabolism regulation through its role in stimulating the mammalian target of rapamycin (mTOR) signaling cascade and by indicating energy and amino acid availability. It functions to initiate MPS and decrease muscle protein breakdown by downregulating the ubiquitin-proteasome system, lysosomal activity, and/or increasing circulating insulin. Conclusions: Supplementation with the amino acid leucine effectively enhances MPS and attenuates muscle protein degradation in humans following bouts of physical exertion. Leucine intake in amounts greater than that found in ~20g whole protein saturates MPS and increases leucine oxidation. For this reason, an upper limit of leucine intake should be established. While leucine successfully increases MPS, it remains unclear whether this translates to enhanced physical performance, an area that requires more studies to be conducted.

There has been limited investigation as to whether a predominantly forage-based diet can provide adequate amounts of limiting amino acids (AA) to horses. The first objective was to determine if AA supplementation of AA believed to be limiting to protein synthesis in forage-based diets would affect measures of whole-body protein metabolism in sedentary mature horses. The effect of forage type (timothy or alfalfa) and AA supplementation (lysine, threonine or histidine) on plasma urea nitrogen (PUN) and AA concentrations and measures of whole-body phenylalanine kinetics were evaluated. There was no effect of either forage type or AA supplement on rates of whole-body protein synthesis (P > 0.05). The second objective was to determine the effects of either timothy or alfalfa hay supplemented with either a high or low protein ration balancer on measures of whole-body protein metabolism in yearling horses. The effect of forage type and the ration balancer protein level on concentrations of PUN, plasma AA and measures of wholebody phenylalanine kinetics were evaluated. There was no effect of treatment on average daily gain (P = 0.18). When horses consumed the alfalfa-based diets, rates of phenylalanine flux, oxidation and use for protein synthesis were greater than when they consumed timothy-based diets (P < 0.05). Phenylalanine use for protein synthesis was not affected by the protein level of the ration balancer (P = 0.3). Yearling horses achieve greater rates of protein synthesis when fed alfalfa-based diets, compared to timothy-based diets, supplemented with a low protein ration balancer.

Thesis (M.Sc.) --University of Limpopo, 2009 / Two experiments were conducted to determine the effect of dietary ascorbic acid supplementation levels on productivity, carcass characteristics and mortality of Venda chickens. The first experiment determined the effect of dietary ascorbic acid supplementation levels on productivity and mortality rate of 175 unsexed Venda chickens between 1 and 6 weeks old. The second experiment determined the effect of dietary ascorbic acid supplementation levels on productivity, carcass characteristics and mortality rate of 140 female Venda chickens between 8 and 13 weeks old. A Completely Randomized Design was used in both experiments. The treatments ranged from 0 to 2000 mg of ascorbic acid per kg DM feed. A quadratic equation was used to determine levels of ascorbic acid supplementation for optimum feed intake, feed conversion ratio, growth rate, live weight and breast meat yield. Feed conversion ratio, growth rate and live weight were optimized at different levels of 1050, 1301 and 1500 mg of ascorbic acid per kg DM feed, respectively, during the starter phase. Similarly, feed conversion ratio, growth rate, live weight and breast meat yield were optimized at different levels of 1000, 1250, 1482 and 769 mg of ascorbic acid per kg DM feed, respectively, during the grower phase. Dietary feed intake in both phases was not optimized within the range of values of ascorbic acid supplementation used in this experiment. The results indicate that at each growth phase, different levels of ascorbic acid supplementation optimized feed conversion ratio, growth rate and live weight of Venda chickens. However, level of ascorbic acid supplementation for optimum breast meat yield was lower than those for feed conversion ratio, growth rate and live weight. These findings have implications on ration formulation for Venda chickens.

A Fissura Oral (FO) é uma malformação craniofacial comum na espécie humana e sua etiologia é complexa com aspectos genéticos e ambientais envolvidos na sua formação. Por ser uma malformação de prevalência variável, estudos de associação em populações distintas são necessários, principalmente em populações heterogêneas como no Brasil. A suplementação com ácido fólico está envolvida na redução do risco de recorrência para algumas malformações, mas a natureza da reação entre a ingestão do ácido fólico, a interação entre os genes da rota metabólica e o seu efeito nas concentrações de folato é pouco caracterizada. Além disso, existem poucos estudos envolvendo um grande número de genes e a suplementação com ácido fólico a longo prazo. O objetivo desse trabalho foi estudar o papel dos genes MSX1 e IRF6 e região 8q24 em indivíduos com fissuras orais não sindrômicas de diferentes regiões do Brasil e analisar o efeito da suplementação com ácido fólico e dos polimorfismos nos genes da rota metabólica do folato nos níveis de folato séricos e eritrocitários. Nossos resultados mostram associação positiva entre o alelo 4 do polimorfismo de repetição CA (MSX1) e FO, alelo A da variante rs987525 (8q24) foi associado com FL/P e o haplótipo G/A (rs2235371/rs642961) do gene IRF6 associado com o aumento do risco para FL/P. Dos 23 genes da rota metabólica do ácido fólico estudados, 5 (FPGS, FOLR1, FOLR2, SHMTI e MTHFR) foram relacionados com os níveis de folato sérico e eritrocitário. As variantes rs7033913 (FPGS), rs11235462 (FOLR1) e rs2276048 (FOLR2) foram associadas com os níveis de folato sérico após suplementação. Os polimorfismos rs2168781 e rs2461837 (SHMT1) foram relacionados com os níveis de folato eritrocitário basal e o rs1801131(MTHFR) com os níveis de folato eritrocitário durante a suplementação. Conhecer a etiologia das fissuras orais e entender os efeitos da suplementação e de variantes dos genes da rota do folato nos níveis basais de folato é essencial tanto para auxiliar no manejo clínico através de uma medicina personalizada quanto para aconselhamento genético. / Oral cleft (OC) is a common craniofacial malformation. The etiology is complex and involves genetic and environmental factors. OC have a variable prevalence and association studies are needed in different populations, especially in heterogeneous populations as the Brazilian. Folic acid supplementation reduce the recurrence risk for some malformation, but the reaction between folic acid intake, the interaction between genes of metabolic pathway and effect on folate concentrations is poorly characterized. Furthermore, there are few studies with a large number of genes and long-term folic acid supplementation. The aim was to analyze the role of MSX1 and IRF6 gene and 8q24 region in individuals with non-syndromic oral clefts in different regions of Brazil and to analyze the effect of folic acid supplementation in folate pathway genes and correlate to levels of serum and red blood cell (RBC) folate. Our results have shown a positive association between the CA repeat polymorphism 4 allele (MSX1) and OC, between rs987525 A allele (8q24) and CL/P and the G/A haplotype (rs2235371 / rs642961) of IRF6 associated with increased risk of CL/P. The 23 folate pathway genes studied, 5 (FPGS, FOLR1, FOLR2, SHMTI and MTHFR) were correlated to serum and red blood cell (RBC) folate levels. The variants rs7033913 (FPGS), rs11235462 (FOLR1) and rs2276048 (FOLR2) were associated to serum folate levels after supplementation. Polymorphisms in SHMT1 (rs2168781 and rs2461837) were associated with basal RBC folate while MTHFR (rs1801131) were associated with RBC folate levels during supplementation. Understanding of oral cleft etiology and folate gene pathway will assist clinic management and genetic counseling since folate is involved in important biologic processes.

A Fissura Oral (FO) é uma malformação craniofacial comum na espécie humana e sua etiologia é complexa com aspectos genéticos e ambientais envolvidos na sua formação. Por ser uma malformação de prevalência variável, estudos de associação em populações distintas são necessários, principalmente em populações heterogêneas como no Brasil. A suplementação com ácido fólico está envolvida na redução do risco de recorrência para algumas malformações, mas a natureza da reação entre a ingestão do ácido fólico, a interação entre os genes da rota metabólica e o seu efeito nas concentrações de folato é pouco caracterizada. Além disso, existem poucos estudos envolvendo um grande número de genes e a suplementação com ácido fólico a longo prazo. O objetivo desse trabalho foi estudar o papel dos genes MSX1 e IRF6 e região 8q24 em indivíduos com fissuras orais não sindrômicas de diferentes regiões do Brasil e analisar o efeito da suplementação com ácido fólico e dos polimorfismos nos genes da rota metabólica do folato nos níveis de folato séricos e eritrocitários. Nossos resultados mostram associação positiva entre o alelo 4 do polimorfismo de repetição CA (MSX1) e FO, alelo A da variante rs987525 (8q24) foi associado com FL/P e o haplótipo G/A (rs2235371/rs642961) do gene IRF6 associado com o aumento do risco para FL/P. Dos 23 genes da rota metabólica do ácido fólico estudados, 5 (FPGS, FOLR1, FOLR2, SHMTI e MTHFR) foram relacionados com os níveis de folato sérico e eritrocitário. As variantes rs7033913 (FPGS), rs11235462 (FOLR1) e rs2276048 (FOLR2) foram associadas com os níveis de folato sérico após suplementação. Os polimorfismos rs2168781 e rs2461837 (SHMT1) foram relacionados com os níveis de folato eritrocitário basal e o rs1801131(MTHFR) com os níveis de folato eritrocitário durante a suplementação. Conhecer a etiologia das fissuras orais e entender os efeitos da suplementação e de variantes dos genes da rota do folato nos níveis basais de folato é essencial tanto para auxiliar no manejo clínico através de uma medicina personalizada quanto para aconselhamento genético. / Oral cleft (OC) is a common craniofacial malformation. The etiology is complex and involves genetic and environmental factors. OC have a variable prevalence and association studies are needed in different populations, especially in heterogeneous populations as the Brazilian. Folic acid supplementation reduce the recurrence risk for some malformation, but the reaction between folic acid intake, the interaction between genes of metabolic pathway and effect on folate concentrations is poorly characterized. Furthermore, there are few studies with a large number of genes and long-term folic acid supplementation. The aim was to analyze the role of MSX1 and IRF6 gene and 8q24 region in individuals with non-syndromic oral clefts in different regions of Brazil and to analyze the effect of folic acid supplementation in folate pathway genes and correlate to levels of serum and red blood cell (RBC) folate. Our results have shown a positive association between the CA repeat polymorphism 4 allele (MSX1) and OC, between rs987525 A allele (8q24) and CL/P and the G/A haplotype (rs2235371 / rs642961) of IRF6 associated with increased risk of CL/P. The 23 folate pathway genes studied, 5 (FPGS, FOLR1, FOLR2, SHMTI and MTHFR) were correlated to serum and red blood cell (RBC) folate levels. The variants rs7033913 (FPGS), rs11235462 (FOLR1) and rs2276048 (FOLR2) were associated to serum folate levels after supplementation. Polymorphisms in SHMT1 (rs2168781 and rs2461837) were associated with basal RBC folate while MTHFR (rs1801131) were associated with RBC folate levels during supplementation. Understanding of oral cleft etiology and folate gene pathway will assist clinic management and genetic counseling since folate is involved in important biologic processes.

A Fissura Oral (FO) é uma malformação craniofacial comum na espécie humana e sua etiologia é complexa com aspectos genéticos e ambientais envolvidos na sua formação. Por ser uma malformação de prevalência variável, estudos de associação em populações distintas são necessários, principalmente em populações heterogêneas como no Brasil. A suplementação com ácido fólico está envolvida na redução do risco de recorrência para algumas malformações, mas a natureza da reação entre a ingestão do ácido fólico, a interação entre os genes da rota metabólica e o seu efeito nas concentrações de folato é pouco caracterizada. Além disso, existem poucos estudos envolvendo um grande número de genes e a suplementação com ácido fólico a longo prazo. O objetivo desse trabalho foi estudar o papel dos genes MSX1 e IRF6 e região 8q24 em indivíduos com fissuras orais não sindrômicas de diferentes regiões do Brasil e analisar o efeito da suplementação com ácido fólico e dos polimorfismos nos genes da rota metabólica do folato nos níveis de folato séricos e eritrocitários. Nossos resultados mostram associação positiva entre o alelo 4 do polimorfismo de repetição CA (MSX1) e FO, alelo A da variante rs987525 (8q24) foi associado com FL/P e o haplótipo G/A (rs2235371/rs642961) do gene IRF6 associado com o aumento do risco para FL/P. Dos 23 genes da rota metabólica do ácido fólico estudados, 5 (FPGS, FOLR1, FOLR2, SHMTI e MTHFR) foram relacionados com os níveis de folato sérico e eritrocitário. As variantes rs7033913 (FPGS), rs11235462 (FOLR1) e rs2276048 (FOLR2) foram associadas com os níveis de folato sérico após suplementação. Os polimorfismos rs2168781 e rs2461837 (SHMT1) foram relacionados com os níveis de folato eritrocitário basal e o rs1801131(MTHFR) com os níveis de folato eritrocitário durante a suplementação. Conhecer a etiologia das fissuras orais e entender os efeitos da suplementação e de variantes dos genes da rota do folato nos níveis basais de folato é essencial tanto para auxiliar no manejo clínico através de uma medicina personalizada quanto para aconselhamento genético. / Oral cleft (OC) is a common craniofacial malformation. The etiology is complex and involves genetic and environmental factors. OC have a variable prevalence and association studies are needed in different populations, especially in heterogeneous populations as the Brazilian. Folic acid supplementation reduce the recurrence risk for some malformation, but the reaction between folic acid intake, the interaction between genes of metabolic pathway and effect on folate concentrations is poorly characterized. Furthermore, there are few studies with a large number of genes and long-term folic acid supplementation. The aim was to analyze the role of MSX1 and IRF6 gene and 8q24 region in individuals with non-syndromic oral clefts in different regions of Brazil and to analyze the effect of folic acid supplementation in folate pathway genes and correlate to levels of serum and red blood cell (RBC) folate. Our results have shown a positive association between the CA repeat polymorphism 4 allele (MSX1) and OC, between rs987525 A allele (8q24) and CL/P and the G/A haplotype (rs2235371 / rs642961) of IRF6 associated with increased risk of CL/P. The 23 folate pathway genes studied, 5 (FPGS, FOLR1, FOLR2, SHMTI and MTHFR) were correlated to serum and red blood cell (RBC) folate levels. The variants rs7033913 (FPGS), rs11235462 (FOLR1) and rs2276048 (FOLR2) were associated to serum folate levels after supplementation. Polymorphisms in SHMT1 (rs2168781 and rs2461837) were associated with basal RBC folate while MTHFR (rs1801131) were associated with RBC folate levels during supplementation. Understanding of oral cleft etiology and folate gene pathway will assist clinic management and genetic counseling since folate is involved in important biologic processes.

No description available.

Thesis (M.Sc. (Animal Production)) --University of Limpopo, 2007 / Two experiments were conducted to evaluate the effect of time of initiation of feeding after hatching and influence of dietary lysine and ascorbic acid supplementation on productivity, carcass characteristics and mortality of Ross 308 broiler chickens. The first experiment examined the effect of time of initiation of feeding after hatching and influence of dietary lysine supplementation during realimentation on productivity, carcass characteristics and mortality of Ross 308 broiler chickens during the winter period. Three hundred and sixty unsexed Ross 308 broiler chickens with an initial weight of 30 ± 2 g per bird were assigned to twelve treatments with three replications of ten birds each in a 4 (times of initiation of feeding) x 3 (lysine supplemental levels) factorial, complete randomized design. At each time of initiation of feeding after hatching during the starter and grower stages, the diets were isocaloric and isonitrogenous but with three different lysine supplementation levels. Lysine supplementation started three days after hatching. Time of initiation of feeding above 36 hours after hatching resulted in growth retardation and high mortality rate. More than 50 % of the birds died between one and three days of age when initiation of feeding after hatching was above 36 hours. However, the birds ‘caught-up’ at the latest within eight days of realimentation. This compensatory growth could be explained in terms of higher intakes. Lysine supplementation during realimentation reduced the number of days of ‘catch-up’ irrespective of time of initiation of feeding after hatching. Generally, the higher the level of lysine supplementation, the lower was the number of days of ‘catch-up’ upon realimentation. Thereafter, time of initiation of feeding after hatching and lysine supplementation had no effect (P>0.05) on live weight, feed intake, growth rate, feed conversion ratio, diet digestibility, nitrogen content of breast meat, dressing %, carcass characteristics and mortality of Ross 308 broiler chickens. The second experiment examined the effect of time of initiation of feeding after hatching and influence of dietary ascorbic acid supplementation on productivity, carcass characteristics and mortality of Ross 308 broiler chickens during the summer period. Six v hundred and seventy five unsexed Ross 308 broiler chickens with an initial weight of 32 ± 2 g per bird were assigned to fifteen treatments with three replications of fifteen birds each in a 3 (times of initiation of feeding) x 5 (ascorbic acid supplemental levels) factorial, complete randomized design. Ascorbic acid supplementation started 3 days after hatching. An average of 18 % and 31 % of the birds died between one and three days of age when initiation of feeding after hatching was above 36 hours. However, the birds ‘caught-up’ within ten days of realimentation irrespective of time of initiation of feeding after hatching. This compensatory growth could be explained in terms of reduced maintenance requirement and possibly, increased efficiency of growth. Following ‘catch-up’, ascorbic acid supplementation during realimentation lowered (P<0.05) mortality rate and improved growth rates irrespective of time of initiation of feeding after hatching. Growth rate increased incrementally with increasing levels of ascorbic acid supplementation within each time of initiation of feeding after hatching. Improved growth rate in the ascorbic acid supplemented birds resulted in improved live weight in comparison with those without ascorbic acid supplementation at 21 days of age and continued until 42 days of age. Live weight increased incrementally with increasing levels of ascorbic acid supplementation within each time of initiation of feeding after hatching. Similarly, increasing ascorbic acid supplementation within each time of initiation of feeding after hatching increased dressing percentage and breast meat yield at 42 days old. However, ascorbic acid supplementation had no effect (P>0.05) on feed intake of the birds irrespective of time of initiation of feeding after hatching. In both experiments, mortality was positively and strongly correlated with time of initiation of feeding after hatching while live weight was negatively and strongly correlated with time of initiation of feeding after hatching. It is concluded that time of initiation of feeding above 36 hours after hatching is not desirable, mainly because of its effect on mortality. However, lysine supplementation in the diet of broiler chickens subjected to delayed initiation of feeding after hatching might play a key role in accelerating the rate of ‘catch-up’ growth response. vi It is also concluded that the beneficial effect of ascorbic acid supplementation could be exploited in reducing mortality rate and improving growth rates in broiler chickens subjected to delayed initiation of feeding after hatching. / the National Research Foundation