Background: Folate and cobalamin are essential cofactors for homocysteine (HCY) metabolism. Hyperhomocysteinemia, a multifactorial condition, may reflect B vitamin deficiency and is associated with increased risk of cardiovascular disease, thrombosis, and neurodegenerative and chronic gastrointestinal diseases in humans. Hyperhomocysteinemia has been reported in Greyhounds with suspected chronic enteropathy. Objectives: To evaluate the frequencies of and the association between hypofolatemia and hyperhomocysteinemia in Greyhounds. Animals: Data and serum samples from 559 Greyhounds. Methods: Nested case-control study. The frequency of hypofolatemia in Greyhounds was determined by a laboratory database search. The relationship between hyperhomocysteinemia (measured by gas chromatography-mass spectrometry) and hypocobalaminemia and hypofolatemia was evaluated, and its frequency compared between healthy Greyhounds and Greyhounds with thrombosis or chronic diarrhea. Results: Hypofolatemia was identified in 172 of 423 (41%) Greyhounds and was more common in hypo- than in normocobalaminemic dogs (49% vs. 35%; P = .0064). Hyperhomocysteinemia was detected in 53 of 78 (68%) of Greyhounds, being more common in hypo- than in normofolatemic dogs (88% vs. 59%; P = .0175). All healthy Greyhounds, 21 of 30 (70%) of dogs with chronic diarrhea and 6 of 8 (75%) of those with thrombosis, were hyperhomocysteinemic. Serum HCY concentrations were inversely correlated with serum folate concentration (q = -0.28; P = .0386) and were positively associated with serum albumin concentration (q = 0.66; P = .0022). Conclusions and Clinical Relevance: Hyperhomocysteinemia occurs frequently in the Greyhound population. Its association with hypofolatemia suggests decreased intracellular availability of B vitamins, but the functional implications warrant further investigation. Hyperhomocysteinemia in Greyhounds potentially may serve as a spontaneous canine model to further investigate hyperhomocysteinemia in humans.

Aging increases the risk of both vitamin D deficiency and metabolic syndrome. Vitamin D deficiency and metabolic syndrome may be related, although there are mixed findings. Furthermore, literature suggests other factors such as physical fitness activity and smoking behavior are associated with Vitamin D deficiency and the development of metabolic syndrome. A number of studies have documented associations between Vitamin D levels and physical fitness activities, while other studies found correlations between Vitamin D levels, metabolic syndrome, and smoking behavior. However, no previous study has examined the links between physical fitness activity, smoking behavior, Vitamin D levels, and the risks for metabolic syndrome. The purpose of this study was to examine if smoking behavior and physical fitness activity moderated the relationship between Vitamin D deficiency and metabolic syndrome among older individuals. The research problem was addressed through the use of retrospective data collected from the National Health and Nutrition Examination Survey (NHANES) 2005-2006. This study utilized a quantitative, retrospective, cross-sectional design employing regression and correlational analysis to determine that Vitamin D deficiency (p = 0.02) predicts metabolic syndrome (n = 1570). However, neither physical activity (p = 0.99) nor smoking behavior (p = 0.23) moderated the relationship between Vitamin D deficiency and metabolic syndrome (n = 1570). The results of the study could give practitioners a better understanding and insights into the different risk factors to metabolic syndrome among older individuals, which can eventually enable primary and secondary prevention interventions.

[Truncated abstract] Vitamin E is comprised of a family of tocopherols (TOH) and tocotrienols. The most studied of these is [alpha]-tocopherol ([alpha]-TOH), as this form is retained within the body and any deficiency of vitamin E is corrected with this supplement. [alpha]-TOH is a lipid-soluble antioxidant required for the preservation of cell membranes and potentially acts as a defense against oxidative stress. Individuals who have a primary vitamin E deficiency such as low birth weight infants, secondary vitamin E deficiency due to fat malabsorption such as in abetalipoproteinaemia, or a genetic defect in TOH transport require supplementation. There is debate as to whether vitamin E supplementation in other patient groups is required. Vitamin E supplementation has been recommended for persons with FHBL, a rare disorder of lipoprotein metabolism that leads to low serum [alpha]-TOH and decreased LDL cholesterol and apolipoprotein B concentrations. We examined the effect of truncated apoB variants on vitamin E metabolism and oxidative stress in persons with heterozygous FHBL. We used HPLC with electrochemical detection to measure [alpha]- and [gamma]-TOH in serum, erythrocytes, and platelets, and GC-MS to measure urinary F2-isoprostanes and TOH metabolites as markers of oxidative stress and TOH intake, respectively. Erythrocyte [alpha]-TOH was decreased, but we observed no differences in lipid-adjusted serum TOHs, erythrocyte [gamma]-TOH, platelet [alpha]- or [gamma]-TOH, urinary F2-isoprostanes, or TOH metabolites. Taken together, our findings do not support the recommendation that persons with heterozygous FHBL should receive vitamin E supplementation. ... Sesame lignans are natural components of sesame seed oil and there is evidence that these lignans can inhibit CYP450 enzymes, in particular, those responsible for vitamin E metabolism. We hypothesised that sesame seed ingestion would increase serum [gamma]-TOH, lower plasma lipids and inhibit platelet function in human subjects with at least one cardiovascular risk factor. We used HPLC with electrochemical detection to measure [alpha]- and -TOH in serum and GC-MS to measure F2-isoprostanes and TOH metabolites as markers of oxidative stress and TOH intake, respectively. We used high-sensitive C-reactive protein as a measure of systemic inflammation. Platelet function was assessed using the PFA-100 platelet aggregation assay. Although serum [gamma]-TOH increased by 17%, we observed no effect on lipid metabolism, markers of inflammation, oxidative stress or platelet function following treatment with ~25 g/day sesame seeds for five weeks. Our findings challenge the hypothesis that sesame seed ingestion provides beneficial cardiovascular effects. In summary, we have studied the metabolism and transport of both [alpha]- and [gamma]-TOH in humans to evaluate the requirements for supplementation and the effects of vitamin E on platelet function and CYP3A4 activity. Specialised techniques using HPLC were developed to measure serum and cellular TOH concentrations both in supplemented and un-supplemented individuals. We also used GCMS to provide a sensitive, accurate assessment of TOH metabolites and midazolam pharmacokinetics in humans after vitamin E supplementation. We have examined the role vitamin E has on important biochemical endpoints, with emphasis on the implications for TOH supplementation in subjects at risk of CVD.

<p>In hyperparathyroidism (HPT) raised serum concentrations of ionized calcium is caused by increased secretion of parathyroid hormone (PTH) by parathyroid tumors. Active vitamin D, 1α,25-dihydroxyvitamin D₃, is known to suppress PTH secretion and to reduce proliferation of parathyroid tumor cells.</p><p>The aim of this thesis was to examine expression of vitamin D hydroxylating enzymes, regulating the activation and inactivation of vitamin D and to study effects of vitamin D analogues, in parathyroid tumors and breast cancer.</p><p>The vitamin D activating enzyme, CYP27B1/25-hydroxyvitamin D₃ 1α-hydroxylase (1α-hydroxylase) and the vitamin D inactivating enzyme CYP24A1/25-hydroxyvitamin D₃ 24-hydroxylase (24-hydroxylase) were expressed in parathyroid tumors and breast cancer. </p><p>The parathyroid tumors had raised expression levels of 1α-hydroxylase and reduced levels of 24-hydroxylase in comparison to normal parathyroid glands, indicating ability for endogenous activation of vitamin D. The expression of 1α-hydroxylase may be of therapeutic advantage for local activation of non-1α-hydroxylated vitamin D analogues in tumor cells, thereby reducing unwanted hypercalcemic effects. </p><p>Three of five selected low calcemic vitamin D analogues had as efficient PTH suppressing effect, in bovine parathyroid cells, as three vitamin D analogues used clinically for treatment of secondary HPT.</p><p>The non-1α-hydroxylated vitamin D analogue EB1285 showed antiproliferative and PTH suppressive effects as well as transcriptional activity in parathyroid and breast tumor cells, respectively.</p><p>Ketoconazole, an inhibitor of vitamin D hydroxylating enzymes, suppressed PTH secretion and potentiated the effect of vitamin D analogues. Combined treatment with vitamin D analogues and specific 24-hydroxylase inhibitors may be important for future therapy. </p>

In hyperparathyroidism (HPT) raised serum concentrations of ionized calcium is caused by increased secretion of parathyroid hormone (PTH) by parathyroid tumors. Active vitamin D, 1α,25-dihydroxyvitamin D3, is known to suppress PTH secretion and to reduce proliferation of parathyroid tumor cells. The aim of this thesis was to examine expression of vitamin D hydroxylating enzymes, regulating the activation and inactivation of vitamin D and to study effects of vitamin D analogues, in parathyroid tumors and breast cancer. The vitamin D activating enzyme, CYP27B1/25-hydroxyvitamin D3 1α-hydroxylase (1α-hydroxylase) and the vitamin D inactivating enzyme CYP24A1/25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) were expressed in parathyroid tumors and breast cancer. The parathyroid tumors had raised expression levels of 1α-hydroxylase and reduced levels of 24-hydroxylase in comparison to normal parathyroid glands, indicating ability for endogenous activation of vitamin D. The expression of 1α-hydroxylase may be of therapeutic advantage for local activation of non-1α-hydroxylated vitamin D analogues in tumor cells, thereby reducing unwanted hypercalcemic effects. Three of five selected low calcemic vitamin D analogues had as efficient PTH suppressing effect, in bovine parathyroid cells, as three vitamin D analogues used clinically for treatment of secondary HPT. The non-1α-hydroxylated vitamin D analogue EB1285 showed antiproliferative and PTH suppressive effects as well as transcriptional activity in parathyroid and breast tumor cells, respectively. Ketoconazole, an inhibitor of vitamin D hydroxylating enzymes, suppressed PTH secretion and potentiated the effect of vitamin D analogues. Combined treatment with vitamin D analogues and specific 24-hydroxylase inhibitors may be important for future therapy.

Orientador: Gabriel Hessel / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-10T23:58:17Z (GMT). No. of bitstreams: 1 Saron_MargarethLopesGalvao_D.pdf: 3406733 bytes, checksum: 734ea37c3690fa8925b87a9129e6019a (MD5) Previous issue date: 2008 / Resumo: As doenças hepáticas crônicas podem induzir à má-absorção de lipídios e vitaminas lipossolúveis e levar ao comprometimento do estado nutricional. O objetivo da pesquisa foi determinar os níveis séricos de vitaminas lipossolúveis (A, D e E) em crianças e adolescentes com atresia biliar (AB) e hepatite auto-imune (HAI) e verificar a relação com o estado nutricional e indicadores laboratoriais e clínicos. O estudo foi transversal e controlado e foram avaliados os pacientes com HAI (n=25) e AB (n=24), e um grupo controle (n=53) pareado por sexo e idade. Os níveis séricos das vitaminas A, D e E foram determinados pela técnica de cromatografia líquida de alta eficiência. Além disso, foi realizada a avaliação antropométrica e a classificação dos pacientes na pontuação de Child-Pugh. Foram empregados os testes de Mann-Whitney, o coeficiente de correlação de Spearman e análise de variância, sendo considerada diferença significativa se p<0,05. Em relação às vitaminas, no grupo controle, constatou-se que os níveis séricos das vitaminas A e E variaram com a idade. Os níveis séricos das vitaminas A, D e E foram maiores no grupo controle em relação aos pacientes com AB e HAI, em conjunto ou separadamente. Em relação ao grupo AB, não foi observado diferença significativa nos níveis séricos das vitaminas A, D e E nos pacientes com ou sem colestase. Os pacientes com AB e HAI, em conjunto, classificados em Child C e Child B apresentaram os menores níveis séricos das vitaminas A e E comparados ao Child A. O déficit nutricional mais grave foi observado nos pacientes com AB com colestase. Verificou-se no grupo AB e HAI em conjunto a correlação do Peso/Idade (P/I), Prega Cutânea Triciptal (PCT), Prega Cutânea Subescapular (PCSE), Circunferência Braquial (CB), Área Adiposa Braquial (AAB) com as vitaminas A e E. Além destes indicadores a vitamina E também se correlacionou com Estatura/Idade (E/I), Índice de Massa Corporal (IMC), Área Muscular Braquial (AMB) e Soma das Pregas Cutâneas (SPG) nos pacientes com HAI e AB, em conjunto. Pode-se concluir que, foi observada deficiência das vitaminas A, D e E nos pacientes com AB e HAI. Quanto maior a gravidade da doença menores foram os níveis séricos das vitaminas A e E, nos pacientes com AB e HAI, em conjunto. Essa mesma relação da gravidade da doença ocorreu para as vitaminas A e D nos pacientes com HAI. Com relação ao estado nutricional, os pacientes com AB, principalmente com colestase, apresentaram maior comprometimento nutricional. Houve correlação diretamente proporcional, principalmente da vitamina E com todas as variáveis antropométricas do grupo de AB e HAI em conjunto / Abstract: The chronic liver diseases can cause malabsorption of lipids and fat-soluble vitamins, leading to a deficient nutritional status. The aim of research was: to evaluate the relation between serum levels of fat-soluble vitamins (A, D and E) on chidren and adolescents with biliary atresia (BA) and auto-immune hepatitis (AIH) with the nutritional status and with laboratorial and clinic indicators. The study was transversal controlled, which were evaluated patients with AIH (n=25) and BA (n=24) and a control group (n=53) lined up by sex and age. The determination of serum levels of vitamins A, D and E was carried out by high performance liquid chromatography. Anthropometrics evaluation and classification of patients on Child-Pugh scale were also used. It was used the Mann-Whitney test, the correlation coefficient of Spearman and variance analysis for data analysis, which was considered significant difference if p< 0.05. Have been evidenced that serum levels of vitamins A and E in healthful group were changed with age. The serum levels of vitamins A, D and E were higher in the healthful group when compared with the patients with BA and AIH together or isolated. No difference in the serum levels of vitamins A, D and E was noted in the BA group with or without cholestasis. The patients with BA and AIH together grouped and classified in Child C and Child B presented the lowest serum levels of vitamins A and E when compared to the patients classified in Child A. The nutritional deficit more intense was observed in the patients with BA and cholestasis. It was verified in the BA and AIH groups together a correlation weight/age (W/A), Triceps Skinfold Thickness (TST), Subscapular Skinfold Thickness (SST), Midarm Circunference (MC) and Midarm Fat Area (MFA), with the vitamins A and E. Besides indicators, the vitamin E was also correlated with Stature/Age (S/A), Body Mass Index (BMI), Midarm Muscle Area (MMA) and SKinfold Sum (SFS) for patients with AIH and BA together. In conclusion, have been observed deficiency of vitamins A, D and E in patients with AB and AIH. For higher serevity of disease, the serum levels of vitamins A e E are lower for patients with AB and AIH together. This same relation occurs for vitamins A and D for patients with AIH. When the nutrition status is evaluated, the patients with AB and cholestasis presented the highest nutritional deficiency. There is a correlation directly proportional, mainly of vitamin E with the anthropometric variables of the AB and AIH groups together / Doutorado / Saude da Criança e do Adolescente / Doutor em Saude da Criança e do Adolescente

Vitamin D deficiency is common in individuals diagnosed with HIV and is known for its detrimental health effects. Its recognition as a potent immune-modulator with possible immune health implications in HIV disease progression was the main impetus for this study. The association between Vitamin D and CD4 count falls short of being consistent and is too weak to allow conclusions. Similarly, the literature is inconsistent with regard to the impact of Vitamin D supplementation on CD4. This observational, retrospective chart review study aimed to explore the relationship between Vitamin D deficiency and CD4 count/percent, and to evaluate whether changes in Vitamin D levels after supplementation corresponds with significant changes in CD4 count/percent in a cohort of African American, HIV-infected men who attended an HIV clinic in southeast Michigan (N = 70). The conceptual framework was based on the role of Vitamin D in regulating the immune responses through Vitamin D nuclear receptors on the CD4 cells. It postulated that an increase in Vitamin D level might enhance immune function, promote cellular anti-inflammatory state, and decelerate CD4 destruction. Data analysis included descriptive statistics, bivariate correlation, logistic and linear regression, t test, repeated measures ANOVA, and ANCOVA. Findings of the study did not support the hypotheses of significant correlation between Vitamin D and CD4 count (p = 0.458) and percent (p = 0.776), or of any impact of supplementation on CD4 count (p = 0.216) and percent (p = 0.918). Social change implications include providing health professionals, researchers, and policymakers with knowledge to tailor health promotion interventions aiming to reduce Vitamin D deficiency in favor of improving the overall health of HIV patients, especially high-risk groups such as African American HIV-infected patients.

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Call number: LD2668 .T4 1931 G51

LD2668 .T4 1941 S62 / Master of Science