The ability of human growth hormone (hGH) to alleviate the effects of zinc deficiency on growth was investigated in the rat. Human GH treatment had no significant effect on food consumption, growth parameters or plasma IGF-I. Food consumption, tail length, liver weight, and tibia weight were significantly lower in the zinc deficient group. Body weight was significantly reduced in the zinc deficient and pair fed groups compared to the control. A significant interaction between zinc and hGH was found for tibial epiphyseal cartilage width but there were no significant differences between the groups receiving hGH and the respective shams. Tissue zinc content and plasma alkaline phosphatase were significantly decreased by the dietary zinc deficiency. Plasma zinc was higher in the groups receiving hGH. Significant interactions between zinc and hGH was found for liver iron, tibial zinc, and tibial copper. Copper and iron showed a competitive interaction with zinc and were lower in the rats receiving the control diet. Both lowered zinc and food intake contributed to the effects of the zinc deficiency; however, these effects were not equally distributed. Food intake had the greater effect on growth and plasma IGF-I while tissue mineral content showed a greater effect for zinc intake.

A crucial requirement for the stepwise, continued growth of a brain tumor is the acquisition of a blood supply from the host, i.e. angiogenesis. The mechanisms of copper activity linked to neovascular and neoplastic growth are largely unknown. Copper ion was shown to be a cofactor for angiogenesis. / We tested the effect of copper depletion achieved by a low copper diet and a copper chelator D-penicillamine, on the intracerebral growth of two experimental brain tumors. We developed in in vivo brain tumor model using the VX2 carcinoma. Implantation of 5 $ times$ 10$ sp5$ VX2 carcinoma cells into the parietal lobe of normocupremic rabbits consistently yielded large hemorrhagic, necrotic, vascularized tumors. The cortical surface revealed numerous, hypertrophied, tortuous new vessels with feeding arteries and draining veins similar to the angioarchitecture of malignant human brain tumors. We report here that copper depletion prevents tumor neovascularization and restricts tumor growth of the VX2 carcinoma in the rabbit brain. Low copper diet and penicillamine are both necessary to achieve angiogenic inhibition. We also tested the effect of copper depletion on the 9L gliosarcoma. We observed that invasive growth of the tumor was blocked in rats depleted of copper. Electron microscopy revealed the absence of cytoplasmic extensions, including pseudopodia, by contrast, in normocupremic controls, cytoplasmic extensions, typical of mobile cells, invaded the surrounding neuropil. Our findings link the activity of copper in vascular and neoplastic growth. / We found an increase in the peritumoral brain water content in the copper depleted animals and that copper depletion by itself in nontumor implanted animal has no effect on brain water content. / Because of the ability to pharmacologically suppress capillary growth induced by the VX2 carcinoma, we could test the relative contribution of breakdown of the blood-brain barrier compared with that of angiogenesis in the appearance of contrast enhancement in computed tomographic examinations. We conclude from our data that tumor neovascularization, in our brain tumor model, is the key determinant for the appearance of contrast enhancement. / The same protocol used in the brain failed to prevent tumor neovascularization and growth of the VX2 carcinoma in the muscle of the rabbit thigh indicating the crucial role played by the milieu (muscle versus brain) for the growth of malignant tumor. In the same manner, lung metastases were not prevented.

Study Objective. To assess the dietary intakes of children with Attention Deficit Hyperactivity Disorder (ADHD); including macro- and micronutrient intake, the percentage of low nutrient density foods in the diet, as well as specific biochemical and anthropometric parameters. Design. Observational study. Setting. Provincial ADHD Program of BC, Children’s’ Hospital, Vancouver, BC. Sample. 44 children aged 6 - 12 years with ADHD, treatment-naïve or stable on medication for 6 months or longer. Main Results. ADHD Children were taller and heavier than population norms, and significantly taller than previously reported in ADHD. Of children aged 6-8 years, 28% were below the Estimate Average Requirement (EAR) for zinc and 61% of children aged 9-12 years were below the EAR for zinc. In addition, 28% of children aged 6-8 years and 39% of children aged 9-12 years were below the EAR for copper. Only 2% of children in the sample were below lab normal cutoffs for ferritin; however, 73% had serum zinc values below lab normal cut-offs and 23% had serum copper below lab normal cutoffs. Overall prevalence of serum zinc below the 2.5 percentile was 23% compared to 2% from National Health and Nutrition Examination Survey II (NHANES) data. Additionally, mean serum copper was significantly lower than NHANES II data. Mean energy intake was comparable to mean Estimated Energy Requirement (EER) based on the age, gender, height, weight and physical activity of subjects. In addition, mean dietary intake of Low Nutrient Density foods was not significantly different from NHANES II data and there was no significant difference in energy intake or the proportion of daily energy from protein, fat, and carbohydrate than what is observed from CCHS data. Medication treatment for ADHD was not associated with altered dietary intake or nutrient status. Conclusion. Results are suggestive of low zinc status in ADHD.

Marginal zinc deficiency (MZD) exists in children of industrialized societies and can impair growth and development. Presently there are no data available on its global prevalence. It is believed that MZD is one of the most common hidden deficiencies throughout the world. This is partly because of the lack of sensitivity and specificity of serum zinc, the most commonly used biomarker of zinc status, to detect MZD . This deficiency in children is always accompanied by a decrease in hair zinc . Although in research settings hair zinc is a recognized biomarker of MZD in children, health practitioners do not presently use it. These cross-sectional studies were designed to examine the hair zinc status of preschoolers in Vancouver . They also aimed at exploring some dietary and non-dietary factors associated with hair zinc status in an attempt to construct and validate a screening tool for detection of MZD. Our first study indicated a mean hair zinc of 75±30 μg/g, with 46% below the cutoff (<70μg/g) for a group (n=87) of low-income preschoolers (Chapter II). Among these children we observed negative associations between the hair zinc and consumption of dairy (R² =0.09, P=0 .01) and milk (R² =0.08, P=0.01), being described as "often sick" (R² =0.55, P=0 .00) and "eating unhealthy" (R² =0.16 P=0.00), and prolonged breastfeeding (R² =0.11, P=0.01). Our citywide survey (n=719) indicated a mean hair zinc of 116±43 μg/g with 17% below the cutoff (Chapter III). Logistic regression analysis indicated sex, age, maternal education, the number of adults at home, consumption frequency of milk, "scores of activity level", "being described as frequently sick" and "taking supplements containing iron" as the significant predictors of hair zinc status . However, the final model had 16% sensitivity while having 98 .3% specificity, indicating its lack of usefulness as a screening tool. Our study provides important information on the hair zinc status of Vancouver preschoolers. Although we did not accomplish our primary goal of constructing and validating a screening tool, we did identify some factors in children and their environment associated with hair zinc, which may help in better understanding of hair zinc as a biomarker of MZD .

Magistro baigiamajame darbe daugiausia akcentuojama Lietuvos konvergencijos programa ir įsipareigojimai siekiant tapti Ekonominės ir pinigų sąjungos nare. Atkūrus nepriklausomybę Lietuvoje įvyko daug fiskalinės politikos formavimo bei jos vykdymo, valstybės finansų sistemos grandžių, biudžetinius santykius reglamentuojančios teisinės bazės permainų. Nuo 2004 m. Lietuvai tapus Europos Sąjungos nare yra laikomasi nuostatos, jog visos valstybės narės privalo derinti ekonominę ir valiutų kurso politiką. Todėl pagrindinis Lietuvos fiskalinės politikos uždavinys – tiksliai nustatyti biudžetinius prioritetus ir skatinti ekonomikos augimą. Tai suteiks galimybes išleisti tik tiek lėšų, kiek gaunama, ir stengti sutaupyti, o ne skolintis. / In work basically there was an accent on the Lithuanian program of convergence and the obligation in aspiration to become a member of the economic and monetary union. After declaration about independence of Lithuania following reforms have been accepted: about formation of fiscal policy, about distribution of public finances, about legal base regulating the state budget.Since 2004, after the introduction of Lithuania into the European Union, Lithuania as well as other members of the union is obliged should to coordinate economy and a rate of exchange among themselves. Therefore the main task of fiscal policy of Lithuania - to define priorities of the budget and aspires to the general growth of economy. It will allow, to counterbalance charges and incomes of the state and to avoid credits.

MTHFD is a folate-dependent trifunctional protein comprised of three activities: N$ sp5$,N$ sp{10}$-methylenetetrahydrofolate dehydrogenase, N$ sp5$,N$ sp{10}$-methenyltetrahydrofolate cyclohydrolase and N$ sp{10}$-formyltetrahydrofolate synthetase. The enzymes catalyse the sequential interconversion of tetrahydrofolate derivatives required for purine, methionine and thymidylate synthesis. A Chinese hamster ovary cell line, reported to have reduced cyclohydrolase activity, was studied to characterize the nature of its mutation. / Enzymatic assays showed reduced activities of all three enzymes. Immunoblotting and immunoprecipitation of radiolabelled cell extracts indicated that the gene product was greatly reduced or absent in the mutant. Southern analysis showed no differences between normal and mutant cells, indicating that the defect was not due to a major gene rearrangement. RNA analysis, by Northern blotting and by RNA amplification using the polymerase chain reaction, showed that a mRNA for MTHFD of normal size was present in mutant cells. These results suggest that the mutation is post-transcriptional and that it disrupts the synthesis of MTHFD.

Prolidase deficiency (McKusick 26413) is a rare autosomal recessive disorder characterized by iminodipeptiduria, skin lesions and mental retardation. The enzyme prolidase hydrolyzes dipeptides containing C-terminal proline or hydroxyproline. / The results presented here indicate that prolidase plays a major role in the recycling of dipeptide bound proline. Control fibroblasts were able to use iminodipeptides in lieu of proline to sustain normal growth and protein synthesis whereas prolidase deficient cells were not. / Iminodipeptides added to the media of control and mutant cells showed no adverse effects on protein synthesis or cell growth. These results are consistent with a mechanism of biochemical pathology in which proline deprivation caused by the enzyme deficit is the cause of damage to skin cells. / Prolidase regulation by product and substrate was studied. A two fold decrease of prolidase activity was observed in fibroblasts grown in excess proline. However, cells grown in medium in which iminodipeptides replaced proline showed no significant difference in prolidase activity.

No description available.

The SLC30A2 zinc transporter has been investigated due to its important role in zinc secretion into human milk. SLC30A2 is expressed in mammary epithelial cells, and the presence of genetic variations in this transporter could cause low zinc transport into the milk, leading to Transient Neonatal Zinc Deficiency (TNZD) in newborns. Through bioinformatics analysis 22 SNPs were identified. Therefore, we aim to identify the functional changes caused by 4 SNPs. By subcloning the SLC30A2 open reading frames into the Gateway expression plasmid tagged with red and green fluorescent proteins (mCherry, tGFP). Four SNPs were introduced by mutagenesis and tagged with mCherry. We transfected individual plasmids into mammary epithelial cells (HC11) and observed cellular targeting using epifluorescent imaging. The most common variants located to secreting endosomes and membrane in HC11 cells. Incorrect targeting of SLC30A2 causes mislocalization. It may be possible to identify mothers carrying risk genotypes for infant zinc deficiency.

Access to abstract restricted until 05/2017. / Access to thesis restricted until 05/2017. / Department of Family and Consumer Sciences