Assessment of executive function before and after vitamin D replacement in vulnerable adults who self-neglect

Purpose: Self-neglect (SN) is the inability to maintain self-care needs. It is thought that older adults who have impaired executive function (EF) develop the inability to do self-care and to protect themselves. The specific aims were to (1) determine the feasibility of using multiple EF measures with community-dwelling elders with SN, (2) identify changes in EF between baseline and 5-months in community-dwelling elders with SN who receive 50,000 IU or 400 IU of oral vitamin D monthly and (2) explore changes in specific dimensions of EF between the groups. ^ Methods: Fifty adults, 65 years of age and older, were recruited from Adult Protective Services with confirmed SN. A research nurse administered the following tests at baseline and five-months: Delis-Kaplan Card Sort Test (D-KEFS), Executive Interview (EXIT 25), CLOX Drawing Test (CLOX I, II), Trails Making Test A and B (TMT A & B) and the Mini-Mental State Examination (MMSE). Demographic data was collected at baseline and serum 25-OHD levels were collected at baseline and five-months. ^ Results: Older adults with SN were more likely to fail the CLOX1 and D-KEFS, while passing the MMSE, CLOX II, TMT A & B and the EXIT 25. At five-months, the only statistically significant difference between groups was in the TMT A & B test scores; the control group did better than the treatment group. There was a non-significant increase in serum vitamin D levels for both groups and no difference between groups. ^ Conclusions: Results from this study provide support that individuals who SN will complete a battery of EF tests and that they exhibit the following impairments consistent with executive dysfunction: 'concept generation', 'planning', 'inhibition', and 'spatial working memory'. Utilizing only one EF measure in individuals with intact cognition may result in unidentification of individuals with executive dysfunction, thus delaying necessary treatment. Future studies should attempt to determine different etiologies of executive dysfunction and determine if early treatment can prevent or reverse SN. ^ Key Words: Self-neglect, Executive Dysfunction, Executive Function, Adult Protective Services, Community-dwelling, Vitamin D ^

Vitamin A supplementation in very low birth weight infants

PURPOSE: In United States, the percentage of Extremely Low Birth Weight (ELBW) born for year 2006 was 0.8% (approximately 32,000 babies) & Very Low Birth Weight (VLBW) 1.48% (1). ELBW babies account for nearly half (49%) of the infant mortality for United States. Very Low birth weight infants are at a significant risk for high mortality and morbidity due to their multi system involvement and predisposition to lung prematurity and impaired immune function. One of the common causes cited is Vitamin A deficiency (2, 3).The purpose of this study is to look at published literature on Vitamin A supplementation in very low birth weight (VLBW) infants. ^ RESEARCH DESIGN: Systematic review of literature of published articles meeting the pre-defined criteria. ^ PROCEDURE: Studies included in this review were those which looked at very low birth weight infants defined as birth weight<1500gms. All experimental studies were reviewed. Studies looking at the effect of Vitamin A supplementation in comparison with a placebo or by itself in varying dosing regimens as an intervention were reviewed. Vitamin A deficiency and its manifestations were of interest. We used key words such as "very low birth weight", "mortality", "Vitamin A", "retinol" and "supplementation" in our search. ^ RISKS & POTENTIAL BENEFITS: We do not see any potential risks associated with this study. The potential benefit is recommendation for future studies based on the review of literature available currently. ^ IMPORTANCE OF KNOWLEDGE THAT MAY REASONABLY BE EXPECTED TO RESULT: The systematic review of literature of all experimental studies in VLBW infants showed uniform correlation of parenteral Vitamin A dosing and high plasma concentrations achieved. The recommended dosage for use is 5000 IU 3 times/week given intramuscularly for 4 weeks to prevent CLD. Higher doses have not shown benefit, with a potential for toxicity, while lower doses are inadequate. There is no role of use of Vitamin A in closure of patent ductus arteriosus & reducing mortality. However, it is important to state that the number of studies done so far is limited with small sample sizes. There is a need in the future for experimental studies to ascertain the role of Vitamin A to improve outcomes in VLBW. Atleast, one more RCT should be conducted using the dosage recommended above to make this a standard practice.^

(Table 1) Retinol (vitamin A) and alpha-tocopherol (vitamin E) concentration in polar bear (Ursus maritimus) kidney

Vitamins A and E content of inner organs, among these the kidneys, are increasingly being used as an indicator of adverse effects caused to the organism by e.g. environmental contaminants. In general, only a renal sub sample is used for analyses, and it is thus essential to know which part of the organ to sample in order to get a representative value for this important biomarker. The aim here was to assess the distribution of vitamins A (retinol) and E (alpha-tocopherol) within the polar bear multireniculate kidney (i.e. polar vs. medial position) and also within the cortex vs. medulla of each separate renculi. The results showed no significant difference between the medial and polar renculi with regards to either retinol (p = 0.44) or alpha-tocopherol (p = 0.75). There were, however, significant differences between cortex and medulla for both vitamins (retinol, p = 0.0003; alpha-tocopherol, p<0.0001). The kidney cortex contained higher values of both vitamins than the medulla; on average 29% more retinol and 57% more alpha-tocopherol. Mean concentrations in the medulla was 2.7 mg/kg for retinol and 116 mg/kg for alpha-tocopherol, and in the cortex 3.5 mg/kg for retinol and 182 mg/kg for alpha-tocopherol. These results clearly indicate that one should take precautions when analyzing retinol and alpha-tocopherol in polar bear kidneys. Prior to analysis, the renculi should be separated into medulla and cortex. The results indicated no significant differences between renculi from different parts of the kidney.

CO2 and vitamin B12 interactions determine bioactive trace metal requirements of a subarctic Pacific diatom

Phytoplankton growth can be limited by numerous inorganic nutrients and organic growth factors. Using the subarctic diatom Attheya sp. in culture studies, we examined how the availability of vitamin B(12) and carbon dioxide partial pressure (pCO(2)) influences growth rate, primary productivity, cellular iron (Fe), cobalt (Co), zinc (Zn) and cadmium (Cd) quotas, and the net use efficiencies (NUEs) of these bioactive trace metals (mol C fixed per mol cellular trace metal per day). Under B(12)-replete conditions, cells grown at high pCO(2) had lower Fe, Zn and Cd quotas, and used those trace metals more efficiently in comparison with cells grown at low pCO(2). At high pCO(2), B(12)-limited cells had ~50% lower specific growth and carbon fixation rates, and used Fe ~15-fold less efficiently, and Zn and Cd ~3-fold less efficiently, in comparison with B(12)-replete cells. The observed higher Fe, Zn and Cd NUE under high pCO(2)/B(12)-replete conditions are consistent with predicted downregulation of carbon-concentrating mechanisms. Co quotas of B(12)-replete cells were 5- to 14-fold higher in comparison with B(12)-limited cells, suggesting that >80% of cellular Co of B(12)-limited cells was likely from B(12). Our results demonstrate that CO(2) and vitamin B(12) interactively influence growth, carbon fixation, trace metal requirements and trace metal NUE of this diatom. This suggests the need to consider complex feedback interactions between multiple environmental factors for this biogeochemically critical group of phytoplankton in the last glacial maximum as well as the current and future changing ocean.

Influence of soy oil source and supplementation of the diet with vitamin E and vi tamin C on performance and egg quality of Single Comb White Leghourn lyaing hens from forty four to fity six weeks of age

Two experiments (Exp.) were conducted to determine the AME content of refined soybean oil (SO), recycled soybean oil (RSO), and acidulated soybean oil soapstocks (ASO) and the effects of inclusion of vitamin E and vitamin C in diets containing 3.5% of these soy oils on performance and egg quality of Hy-line hens from 44 to 56 wks of age.

Evolution and treatment of vitamin B12 deficiency as a risk factor for (cognitive and functional) neurodegenerative diseases in institutionalized elderly = Evolución y tratamiento de la deficiencia de vitamina B12 como factor de riesgo de enfermedades neurodegenerativas (cognitivas y funcionales) en las personas mayores institucionalizadas.

Prevalence of vitamin B12 deficiency is very common in elderly people and can reach values as high as 40.5% of the population. It can be the result of the interaction among several factors. Vitamin B12 deficiencies have been associated with neurological, cognitive deterioration, haematological abnormalities and cardiovascular diseases that have an important influence on the health of the elderly and their quality of life. It is necessary to approach the problems arisen from the lack of data relative to them. The main objective of this thesis was to analyse the evolution of vitamin B12 status and related parameters, lipid and haematological profiles and their relationship to health risk factors, and to functional and cognitive status over one year and to determine the effect of an oral supplementation of 500 μg of cyanocobalamin for a short period of 28 days. An additional objective was to analyze the possible effects of medicine intakes on vitamin B status. Three studies were performed: a) a one year longitudinal follow-up with four measure points; b) an intervention study providing an oral liquid supplement of 500 μg of cyanocobalamin for a 28 days period; and c) analysis of the possible effect of medication intake on vitamin B status using the ATC classification of medicines. The participants for these studies were recruited from nursing homes for the elderly in the Region of Madrid. Sixty elders (mean age 84 _ 7y, 19 men and 41 women) were recruited for Study I and 64 elders (mean age 82 _ 7y, 24 men and 40 women) for Study II. For Study III, baseline data from the initially recruited participants of the first two studies were used. An informed consent was obtained from all participants or their mentors. The studies were approved by the Ethical Committee of the University of Granada. Blood samples were obtained at each examination date and were analyzed for serum cobalamin, holoTC, serum and RBC folate and total homocysteine according to laboratory standard procedures. The haematological parameters analyzed were haematocrit, haemoglobin and MCV. For the lipid profile TG, total cholesterol, LDL- and HDLcholesterol were analyzed. Anthropometric measures (BMI, skinfolds [triceps and subscapular], waist girth and waist to hip ratio), functional tests (hand grip, arm and leg strength tests, static balance) and MMSE were obtained or administered by trained personal. The vitamin B12 supplement of Study II was administered with breakfast and the medication intake was taken from the residents’ anamnesis. Data were analyzed by parametric and non-parametric statistics depending on the obtained data. Comparisons were done using the appropriate ANOVAs or non-parametric tests. Pearsons’ partial correlations with the variable “time” as control were used to define the association of the analyzed parameters. XIII The results showed that: A) Over one year, in relationship to vitamin B status, serum cobalamin decreased, serum folate and mean corpuscular volumen increased significantly and total homocysteine concentrations were stable. Regarding blood lipid profile, triglycerides increased and HDL-cholesterol decreased significantly. Regarding selected anthropometric measurements, waist circumference increased significantly. No significant changes were observed for the rest of parameters. B) Prevalence of hyperhomocysteinemia was high in the elderly studied, ranging from 60% to 90 % over the year depending on the cut-off used for the classification. LDL-cholesterol values were high, especially among women, and showed a tendency to increase over the year. Results of the balance test showed a deficiency and a tendency to decrease; this indicates that the population studied is at high risk for falls. Lower extremity muscular function was deficient and showed a tendency to decrease. A highly significant relationship was observed between the skinfold of the triceps and blood lipid profile. C) Low cobalamin concentrations correlated significantly with low MMSE scores in the elderly studied. No correlations were observed between vitamin B12 status and functional parameters. D) Regarding vitamin B12 status, holo-transcobalamin seems to be more sensitive for diagnosis; 5-10% of the elderly had a deficiency using serum cobalamin as a criterion, and 45-52% had a deficiency when using serum holotranscobalamin as a criterion. E) 500 μg of cyanocobalamin administered orally during 28 days significantly improved vitamin B12 status and significantly decreased total homocysteine concentrations in institutionalized elderly. No effect of the intervention was observed on functional and cognitive parameters. F) The relative change (%) of improvement of vitamin B12 status was higher when using serum holo-transcobalamin as a criterion than serum cobalamin. G) Antiaenemic drug intake normalized cobalamin, urologic drugs and corticosteroids serum folate, and psychoanaleptics holo-transcobalamin levels. Drugs treating pulmonary obstruction increased total homocysteine concentration significantly. H) The daily mean drug intake was 5.1. Fiftynine percent of the elderly took medication belonging to 5 or more different ATC groups. The most prevalent were psycholeptic (53%), antiacid (53%) and antithrombotic (47%) drugs.

Influence of liposoluble vitamin status on health parameter and physical fitness in European adolescents = Influencia del estado en vitaminas liposolubles en parámetros de salud y condición física en adolescentes europeos

La adolescencia es un período de crecimiento y desarrollo crítico e importante para la adquisición de hábitos saludables, en los que tanto la alimentación como la actividad física tienen un papel destacado. Junto con el primer año de vida, los requerimientos de energía y nutrientes son mayores que en cualquier otro periodo. Dentro de la nutrición, las vitaminas se ven involucradas en múltiples procesos celulares y tisulares, y sus deficiencias se vinculan a enfermedades crónicas degenerativas en la edad adulta como las cardiovasculares, cáncer, diabetes y osteoporosis, pero cuyos factores de riesgo se establecen a edades más tempranas. Las concentraciones sanguíneas de vitaminas están influenciadas en gran medida por la ingesta dietética, pero existen otros factores del individuo, entre los que cabe citar la composición corporal, la actividad física y condición física que, junto a la genética, podrían desempeñar un papel crucial. La presente memoria de Tesis Doctoral tiene como objetivo analizar el estado en vitaminas liposolubles y su relación con diversos factores de salud, entre los que destacan la composción corporal, hábitos dietéticos, actividad física y condición física en adolescentes Europeos. El trabajo está basado en los datos del estudio HELENA (“Healthy Lifestyle in Europe by Nutrition in Adolescence”). Se han analizado un total de 1089 adolescentes procedentes de diez ciudades en nueve paises europeos. Los principales resultados de este trabajo indican; a) La existencia de un estado deficiente en vitaminas liposolubles en adolescentes Europeos, especialmente de vitamina D, que alcanza valores del 80%. b) La estación del año, la latitud, el índice de masa corporal, la condición física, la ingesta de calcio dietético, los suplementos vitamínicos y la edad son las variables más relacionadas con el estado de vitamina D. c) A su vez, la capacidad cardiorrespiratoria puede predecir los niveles de vitamina D en los chicos, mientras que la fuerza muscular y masa magra parecen influir en los niveles de vitamina D en las chicas. La grasa corporal y el índice de masa corporal se correlaccionan negativamente con los niveles de vitamina D, especialmente en chicos. d) Un estado de vitamina D óptimo provoca una mejora de la masa ósea sólo cuando se tiene un nivel adecuado de actividad física. e) Se identifica la necesidad de establecer un consenso sobre los rangos aceptables y puntos de corte para las concentraciones sanguíneas de estas vitaminas en este grupo de población, ya que los actuales están extrapolados de la población adulta ABSTRACT Adolescence is a critical period of physiological growth and development as well as for the acquisition of healthy behaviors where both diet and physical activity play a major role. Apart from the first year of life, both energy and nutrient requirements are greatest during adolescence and the way to spend this energy by movement is also crucial. Vitamins are specifically involved in multiple cellular and tissue processes, and there is increasing evidence that deficiencies at these early ages could contribute to risk factors of chronic diseases like cardiovascular and cerebrovascular disease, cancer, diabetes and osteoporosis in adulthood, regardless data are scarce for younger ages. Vitamin concentrations are largely influenced by diet but other individual factors like body composition, physical activity or fitness together with genetics could play also an important role. The current thesis analyzes the liposoluble vitamin status in European adolescents and their relation with several health related factors, like body composción, dietary intake, physical activity and fitness. The work is based on data from the HELENA study ("Healthy Lifestyle in Europe by Nutrition in Adolescence"), for which a total of 1089 adolescents from ten different cities, in nine European countries were recruited. The main outcomes of this thesis are: a) There is a high liposoluble vitamin deficiency prevalence in European adolescents, specifically for vitamin D, which is presenting almost 80% of the adolescents. b) Season, latitude, BMI, fitness, dietary calcium intake, supplements intake and age are highly related to 25(OH)D concentrations found in European adolescents. c) Cardiorespiratory fitness may predict 25(OH)D concentrations in male adolescents, whereas upper limbs muscular strength and FFM may predict 25(OH)D concentrations in young females. Fat mass and BMI are inversely related to 25(OH)D concentrations, especially in males. d) The effect of 25(OH)D concentrations on bone mineral content in adolescents depends on physical activity levels. e) There is a need to establish a consensus on acceptable ranges and cut-offs of blood concentrations of these vitamins during adolescence, as currently they are extrapolated from adults.

Dietary xylanase increases hepatic vitamin E concentration of chickens fed wheat based diet

The study examined the effect of xylanase supplementation on apparent metabolizable energy (AME) and hepatic vitamin E and carotenoids in broiler chickens fed wheat based diets. A total of one hundred forty four male Ross 308 chickens were used in this study. Birds were randomly assigned to 3 dietary treatments (8 cages per treatment of 6 male broilers each) for 14 days from 7 to 21 day old. The control treatment was based on wheat-soyabean meal and was either unsupplemented or supplemented with either 1000 or 2000 xylanase units per kg diet. Orthogonal polynomial contrasts were used to test linear response to dietary xylanase activity. There was a positive linear relationship (P < 0.05) between dietary AME and doses of supplementary xylanase. A linear relationship (P < 0.05) was also observed between dosage of xylanase supplementation and hepatic vitamin E concentration and retention. In conclusion, xylanase supplementation improved dietary AME and increased hepatic vitamin E concentration which may have positive effects on the antioxidative status of the birds.

Genetic evidence for the role of GDP-mannose in plant ascorbic acid (vitamin C) biosynthesis

Vitamin C (l-ascorbic acid; AsA) acts as a potent antioxidant and cellular reductant in plants and animals. AsA has long been known to have many critical physiological roles in plants, yet its biosynthesis is only currently being defined. A pathway for AsA biosynthesis that features GDP-mannose and l-galactose has recently been proposed for plants. We have isolated a collection of AsA-deficient mutants of Arabidopsis thaliana that are valuable tools for testing of an AsA biosynthetic pathway. The best-characterized of these mutants (vtc1) contains ≈25% of wild-type AsA and is defective in AsA biosynthesis. By using a combination of biochemical, molecular, and genetic techniques, we have demonstrated that the VTC1 locus encodes a GDP-mannose pyrophosphorylase (mannose-1-P guanyltransferase). This enzyme provides GDP-mannose, which is used for cell wall carbohydrate biosynthesis and protein glycosylation as well as for AsA biosynthesis. In addition to genetically defining the first locus involved in AsA biosynthesis, this work highlights the power of using traditional mutagenesis techniques coupled with the Arabidopsis Genome Initiative to rapidly clone physiologically important genes.

Manipulation of the membrane binding site of vitamin K-dependent proteins: Enhanced biological function of human factor VII

Recent studies suggested that modification of the membrane contact site of vitamin K-dependent proteins may enhance the membrane affinity and function of members of this protein family. The properties of a factor VII mutant, factor VII-Q10E32, relative to wild-type factor VII (VII, containing P10K32), have been compared. Membrane affinity of VII-Q10E32 was about 20-fold higher than that of wild-type factor VII. The rate of autoactivation VII-Q10E32 with soluble tissue factor was 100-fold faster than wild-type VII and its rate of activation by factor Xa was 30 times greater than that of wild-type factor VII. When combined with soluble tissue factor and phospholipid, activated factor VII-Q10E32 displayed increased activation of factor X. Its coagulant activity was enhanced in all types of plasma and with all sources of tissue factor tested. This difference in activity (maximum 50-fold) was greatest when coagulation conditions were minimal, such as limiting levels of tissue factor and/or phospholipid. Because of its enhanced activity, factor VII-Q10E32 and its derivatives may provide important reagents for research and may be more effective in treatment of bleeding and/or clotting disorders.

Propeptide and glutamate-containing substrates bound to the vitamin K-dependent carboxylase convert its vitamin K epoxidase function from an inactive to an active state

The vitamin K-dependent γ-glutamyl carboxylase catalyzes the posttranslational conversion of glutamic acid to γ-carboxyglutamic acid in precursor proteins containing the γ-carboxylation recognition site (γ-CRS). During this reaction, glutamic acid is converted to γ-carboxyglutamic acid while vitamin KH2 is converted to vitamin K 2,3-epoxide. Recombinant bovine carboxylase was purified free of γ-CRS-containing propeptide and endogenous substrate in a single-step immunoaffinity procedure. We show that in the absence of γ-CRS-containing propeptide and/or glutamate-containing substrate, carboxylase has little or no epoxidase activity. Epoxidase activity is induced by Phe-Leu-Glu-Glu-Leu (FLEEL) (9.2 pmol per min per pmol of enzyme), propeptide, residues −18 to −1 of proFactor IX (3.4 pmol per min per pmol of enzyme), FLEEL and propeptide (100 pmol per min per pmol of enzyme), and proPT28 (HVFLAPQQARSLLQRVRRANTFLEEVRK, residues −18 to +10 of human acarboxy-proprothrombin), (5.3 pmol per min per pmol of enzyme). These results indicate that in the absence of propeptide or glutamate-containing substrate, oxygenation of vitamin K by the carboxylase does not occur. Upon addition of propeptide or glutamate-containing substrate, the enzyme is converted to an active epoxidase. This regulatory mechanism prevents the generation of a highly reactive vitamin K intermediate in the absence of a substrate for carboxylation.

Targeted ablation of the vitamin D receptor: An animal model of vitamin D-dependent rickets type II with alopecia

Vitamin D, the major steroid hormone that controls mineral ion homeostasis, exerts its actions through the vitamin D receptor (VDR). The VDR is expressed in many tissues, including several tissues not thought to play a role in mineral metabolism. Studies in kindreds with VDR mutations (vitamin D-dependent rickets type II, VDDR II) have demonstrated hypocalcemia, hyperparathyroidism, rickets, and osteomalacia. Alopecia, which is not a feature of vitamin D deficiency, is seen in some kindreds. We have generated a mouse model of VDDR II by targeted ablation of the second zinc finger of the VDR DNA-binding domain. Despite known expression of the VDR in fetal life, homozygous mice are phenotypically normal at birth and demonstrate normal survival at least until 6 months. They become hypocalcemic at 21 days of age, at which time their parathyroid hormone (PTH) levels begin to rise. Hyperparathyroidism is accompanied by an increase in the size of the parathyroid gland as well as an increase in PTH mRNA levels. Rickets and osteomalacia are seen by day 35; however, as early as day 15, there is an expansion in the zone of hypertrophic chondrocytes in the growth plate. In contrast to animals made vitamin D deficient by dietary means, and like some patients with VDDR II, these mice develop progressive alopecia from the age of 4 weeks.

Cloning and characterization of the mouse vitamin D receptor promoter

The gene encoding the mouse vitamin D receptor has been cloned. A new exon 1 has been found that changes the numbering established for the human VDR gene. Exons 2 and 3 in the human VDR gene (coding for the zinc fingers 1 and 2, respectively) are named exons 3 and 4 in the mouse vitamin D receptor. The 1.5-kb 5′-flanking region of the new exon 1 was analyzed and revealed the presence of putative cis-acting elements. Despite the absence of a TATA box, this 5′-flanking region contains several characteristics of a GC-rich promoter including four Sp1 sites present in tandem and two CCAAT boxes. Interestingly, the Sp1 site that is the most proximal to the new exon 1 overlaps a perfect site for Krox-20/24. Krox-20 is a transcription factor involved in brain development, and also in bone remodeling. In luciferase reporter gene expression assays, we showed that sequences from this 5′-flanking region elicit high transactivation activity. Furthermore, in the NIH 3T3 cell line, a 3- to 5-fold increase in response to forskolin treatment (an activator of adenylate cyclase and in turn of protein kinase A pathway) was observed.

Vitamin A in serum is a survival factor for fibroblasts

Murine 3T3 cells arrest in a quiescent, nondividing state when transferred into medium containing little or no serum. Within the first day after transfer, fibroblasts can be activated to proliferate by platelet-derived growth factor (PDGF) alone; cells starved longer than 1 day, however, are activated only by serum. We demonstrate that endogenous vitamin A (retinol) or retinol supplied by serum prevents cell death and that retinol, in combination with PDGF, can fully replace serum in activating cells starved longer than 1 day. The physiological retinol derivative 14-hydroxy-4,14-retro-retinol, but not retinoic acid, can replace retinol in rescuing or activating 3T3 cells. Anhydroretinol, another physiological retinol metabolite that acts as a competitive antagonist of retinol, blocks cell activation by serum, indicating that retinol is a necessary component of serum. It previously has been proposed that activation of 3T3 cells requires two factors in serum, an activation factor shown to be PDGF and an unidentified survival factor. We report that retinol is the survival factor in serum.