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Biomedical subjects

Connie M Weaver

Publications and source records attributed to Connie M Weaver.

35 records · Page 2Linked to original sources

Vitamin D requirements: current and future.

The requirements for vitamin D were last set in 1997 by the Food and Nutrition Board of the Institute of Medicine. Intakes were assumed to come from diet, and values were based on achievement of adequate vitamin D status and on observed values to prevent seasonal variations in parathyroid hormone concentrations. Serum 25-hydroxyvitamin D concentrations were considered the best indicator of vitamin D adequacy, because the production of 25-hydroxyvitamin D is not regulated. Normal ranges were obtained from reference populations, but the values varied widely with age and geographic region. Revised recommendations should take into consideration appropriate functional measures for multiple tissues and disease risks. Vitamin D-calcium interdependencies must be taken into account. Higher intakes of both vitamin D and calcium can reduce bone resorption, and higher concentrations of one nutrient might compensate for insufficiency in the other. Better ways to assess vitamin D (and calcium) inputs are needed. Food composition databases are incomplete for both vitamin D and calcium, especially in this era of food fortification, and are complicated by the poor quality control for vitamin D fortification. Upper levels of vitamin D intake were set at 50 microg/d (2000 IU/d) for all ages. Some individuals would require higher levels than these to achieve serum 25-hydroxyvitamin D concentrations for optimal calcium absorption. So much new information on vitamin D and health has been collected since the requirements were set in 1997 that this nutrient is likely the most in need of revised requirements.

Adolescent↗

Nondigestible oligosaccharides increase calcium absorption and suppress bone resorption in ovariectomized rats.

Nondigestible oligosaccharides (NDO) including inulin and fructooligosaccharides (FOS) have been reported to stimulate calcium absorption. Here we report the effect of a mixture of inulin and FOS (Raftilose Synergy 1, Orafti) on calcium and bone metabolism in ovariectomized (OVX) rats. OVX rats (6 mo old) were fed a semipurified diet for 3 mo in our animal care laboratory for stabilization after ovariectomy. They were then divided into two groups (n = 13/group) and fed either a control or a NDO-supplemented diet (55 g/kg) for 21 d. Catheters were placed in their jugular veins. After 2 d, a tracer ((45)Ca) was administered by gavage or i.v. and blood was sampled for up to 300 min. Urine and fecal samples were collected for 4 d after (45)Ca administration. Femurs were measured for bone mineral density (BMD), breaking strength, and total calcium. Calcium absorption, femoral calcium content, BMD, and bone balance (V(bal)) were significantly increased (P < 0.05) by NDO, whereas the bone resorption rate relative to the bone formation rate was significantly depressed by NDO. We conclude that feeding NDO at 5.5 g/100 g for 21 d has a positive effect on calcium absorption and retention in ovariectomized rats.

Absorption↗

Cluster analysis of mass spectrometry data reveals a novel component of SAGA.

The SAGA histone acetyltransferase and TFIID complexes play key roles in eukaryotic transcription. Using hierarchical cluster analysis of mass spectrometry data to identify proteins that copurify with components of the budding yeast TFIID transcription complex, we discovered that an uncharacterized protein corresponding to the YPL047W open reading frame significantly associated with shared components of the TFIID and SAGA complexes. Using mass spectrometry and biochemical assays, we show that YPL047W (SGF11, 11-kDa SAGA-associated factor) is an integral subunit of SAGA. However, SGF11 does not appear to play a role in SAGA-mediated histone acetylation. DNA microarray analysis showed that SGF11 mediates transcription of a subset of SAGA-dependent genes, as well as SAGA-independent genes. SAGA purified from a sgf11 Delta deletion strain has reduced amounts of Ubp8p, and a ubp8 Delta deletion strain shows changes in transcription similar to those seen with the sgf11 Delta deletion strain. Together, these data show that Sgf11p is a novel component of the yeast SAGA complex and that SGF11 regulates transcription of a subset of SAGA-regulated genes. Our data suggest that the role of SGF11 in transcription is independent of SAGA's histone acetyltransferase activity but may involve Ubp8p recruitment to or stabilization in SAGA.

Acetyltransferases↗

Yeast Asc1p and mammalian RACK1 are functionally orthologous core 40S ribosomal proteins that repress gene expression.

Translation of mRNA into protein is a fundamental step in eukaryotic gene expression requiring the large (60S) and small (40S) ribosome subunits and associated proteins. By modern proteomic approaches, we previously identified a novel 40S-associated protein named Asc1p in budding yeast and RACK1 in mammals. The goals of this study were to establish Asc1p or RACK1 as a core conserved eukaryotic ribosomal protein and to determine the role of Asc1p or RACK1 in translational control. We provide biochemical, evolutionary, genetic, and functional evidence showing that Asc1p or RACK1 is indeed a conserved core component of the eukaryotic ribosome. We also show that purified Asc1p-deficient ribosomes have increased translational activity compared to that of wild-type yeast ribosomes. Further, we demonstrate that asc1Delta null strains have increased levels of specific proteins in vivo and that this molecular phenotype is complemented by either Asc1p or RACK1. Our data suggest that one of Asc1p's or RACK1's functions is to repress gene expression.

Adaptor Proteins, Signal Transducing↗

Calcium bioavailability and kinetics of calcium ascorbate and calcium acetate in rats.

The objective was to investigate the bioavailability and mechanism of calcium absorption of calcium ascorbate (ASC) and calcium acetate (AC). A series of studies was performed in adult Sprague-Dawley male rats. In the first study, each group of rats (n = 10/group) was assigned to one of the five test meals labeled with (45)Ca: (i) 25 mg calcium as heated ASC or (ii) unheated ASC, (iii) 25 mg calcium as unheated AC, (iv) 3.6 mg Ca as unheated ASC, or (v) unheated AC. Femur uptake indicated better calcium bioavailability from ASC than AC at both calcium loads. A 5-min heat treatment partly reduced bioavailability of ASC. Kinetic studies were performed to further investigate the mechanism of superior calcium bioavailability from ASC. Two groups of rats (n = 10/group) received oral doses of 25 mg Ca as ASC or AC. Each dose contained 20 micro Ci (45)Ca. Two additional groups of rats (n = 10/group) received an intravenous injection (iv) of 10 micro Ci (45)Ca after receiving an unlabeled oral dose of 25 mg calcium as ASC or AC. Sequential blood samples were collected over 48 hrs. Urine and fecal samples were collected every 12 hrs for 48 hrs and were analyzed for total calcium and (45)Ca content. Total calcium and (45)Ca from serum, urine, and feces were fitted by a compartment kinetics model with saturable and nonsaturable absorption pathways by WinSAAM (Windows-based Simulation Analysis and Modeling). The difference in calcium bioavailability between the two salts was due to differences in saturable rather than passive intestinal absorption and not to endogenous secretion or calcium deposition rate. The higher bioavailability of calcium ascorbate was due to a longer transit time in the small intestine compared with ASC.

Absorption↗

Sodium retention in black and white female adolescents in response to salt intake.

Increased sodium (Na(+)) retention in blacks could be related to the high prevalence of hypertension in adult blacks. Na(+) retention in response to controlled dietary Na(+) has not been rigorously compared in the different race groups. The present study assessed Na(+) retention in 22 black and 14 white girls, 11-15 yr old, during 3 wk on a low (1.3 g, 57 mmol)- and during 3 wk on a high (4 g, 172 mmol)-Na(+) diet in a randomized order, crossover design. Subjects were matched by postmenarcheal age and weight. After a 1-wk equilibration period, the mean daily Na(+) retention was 357 +/- 69 mg (15.5 +/- 3.0 mmol) in blacks and 239 +/- 37 mg (10.4 +/- 1.6 mmol) in whites on the low-Na(+) diet and 991 +/- 138 mg (43.1 +/- 6.0 mmol) in blacks vs. 334 +/- 90 mg (14.5 +/- 3.9 mmol) in whites (P < 0.001) on the high-Na(+) diet. The greater Na(+) retention in blacks was not accompanied by an increase in fecal or sweat Na(+) excretion. Blood pressure and weight did not increase despite the Na(+) retention, and thus, the retained Na(+) appeared to reside in a nonextracellular compartment that we speculate to be bone. In summary, black girls showed greater Na(+) retention compared with white girls. The difference in Na(+) handling may contribute to underlying racial differences in susceptibility to hypertension.

Adolescent↗

Calcium and vitamin D.

Calcium and vitamin D are essential for bone maintenance and for treatment-induced bone augmentation. Deficiencies of both nutrients are very common in the age group most afflicted by osteoporosis. Calcium enhancement of estrogen's effects now have been clearly demonstrated. Additionally, all currently approved bone active agents have been tested only in the presence of extra calcium, and newer anabolic agents create a skeletal need for mineral that will require even higher levels of calcium repletion. Prudent nutritional support for osteoporosis prevention and treatment consists of 30 to 40 mmol Ca/d together with sufficient vitamin D to maintain serum 25(OH)D levels above 80 nmol/L (i.e., approximately 25 microg vitamin D/d).

Bone and Bones↗

Comparison of 24 hour whole body versus patch tests for estimating body surface electrolyte losses.

PURPOSE: To compare dermal electrolyte loss between whole body and regional patch methods in women during 24-h. METHODS: Dermal loss was collected in 6 healthy women mean age 27 +/- 4 years, while consuming 936 mg/d sodium, 1764 mg/d potassium, 696 mg/d calcium, and 152 mg/d magnesium. Twenty-four hour whole body dermal loss was collected using cotton suits by a washdown procedure. Twenty-four hour patch loss was collected from 8 patches placed on the legs, arms, and back. RESULTS: Dermal loss from whole body was 108 +/- 110 mg/d sodium, 133 +/- 87 mg/d potassium, 103 +/- 22 mg/d calcium, and 35 +/- 13 mg/d magnesium. Electrolyte content from the 8 patches was similar among sites and ranged from 1.01-1.41 mg/d sodium, 0.35-0.83 mg/d potassium, 1.0-1.45 mg/d calcium, and 0.43-0.49 mg/d magnesium. Projections from patches to whole body by the ratio of body surface area appear to overestimate actual whole body losses by 3.2X for sodium and calcium, 3.6X for magnesium, and 1.3X for potassium. CONCLUSIONS: Regional patch methods are more appropriate for relative comparisons than for accurately determining total daily dermal electrolyte losses.

Adult↗

Absorption of calcium fumarate salts is equivalent to other calcium salts when measured in the rat model.

Calcium absorption from fumarate salts (calcium fumarate and calcium malate fumarate), which have recently been considered for use as sources for food and beverage enrichment, was compared to that from calcium citrate malate, calcium citrate, and calcium carbonate. Salts were instrinsically labeled with 45Ca and orally administered to Sprague-Dawley rats. Fractional absorption of calcium from each salt was determined using the femur uptake model. Fractional absorption from the five salts (0.30-0.27) was not significantly different (p > 0.05). Thus, when measured in the rat model, calcium from calcium fumarate and calcium malate fumarate is absorbed equally well as compared to other salts, which are common calcium sources in many foods, beverages, and supplements.

Absorption↗

Calcium absorption from three salts and CaSO(4)-fortified bread in premenopausal women.

Two studies were conducted to measure calcium absorption from calcium sulfate fortified bread and three salts (calcium lactate, calcium carbonate, and calcium sulfate) in healthy premenopausal women using a crossover design. In study I, calcium fractional absorption levels from the three salts labeled with a stable isotope, 44Ca, were not significantly different (0.039-0.47) as determined by the fecal recovery method. In a second study, absorption of 45Ca from CaSO(4)-fortified labeled bread or labeled milk was measured in serum exactly 5 h postingestion. Fractional calcium absorption was slightly but significantly greater from fortified bread than from milk (mean within subject difference = 0.0675 +/- 0.016). Calcium sulfate is a bioavailable fortificant for white bread that compares favorably with milk and two other salts.

Adsorption↗

Biomarkers of bone health appropriate for evaluating functional foods designed to reduce risk of osteoporosis.

Osteoporosis is a growing global problem. The health care costs and decreased productivity and quality of life are staggering. Much research is invested in life-style approaches to build peak bone mass during growth to prevent osteoporosis as well as to treat the disease in later life. Functional foods have enjoyed a niche in bone health. Foods fortified with Ca are most popular. Other bone nutrients such as vitamin D, Mg and vitamin K are sometimes added. Future products are likely to include enhancers of Ca absorption such as inulin or whey proteins. Dietary factors that reduce urinary Ca loss (plant proteins) or suppress bone resorption (possibly phyto-oestrogens) are also gaining attention. Methodologies for evaluating the effectiveness of functional foods on bone health include measures of bone quality such as bone densitometry or measures of Ca metabolism, particularly absorption. Biochemical markers for bone turnover are less satisfactory for diet-related effects. Use of a rare isotope, 41Ca, and accelerator mass spectrometry offers a new approach for assessing the ability of functional foods to suppress bone resorption.

Biomarkers↗

Adolescence: the period of dramatic bone growth.

Adolescence is a period of rapid skeletal growth during which nearly half of the adult skeletal mass is accrued. This life stage is a window of opportunity for influencing peak bone mass and reducing the risk of osteoporosis later in life. Endocrine factors that may influence peak bone mass include insulin-like growth factor-1, which regulates skeletal growth, and gonadotropic hormones, which stimulate epiphyseal maturation. Estrogen deficiency and amenorrhea can reduce skeletal mass. Weight-bearing exercise can increase bone mass. Appropriate mineralization of the skeleton requires adequate dietary intakes of minerals involved in the formation of hydroxyapatite; the most likely to be deficient is calcium.

Adolescent↗

MyPyramid food intake pattern modeling for the Dietary Guidelines Advisory Committee.

Modeling analyses using the MyPyramid intake patterns were conducted in collaboration with the 2005 Dietary Guidelines Advisory Committee in response to their research questions and to determine likely effects of possible recommendations on overall dietary adequacy. Scenarios modeled included the feasibility of using the food patterns for lacto-ovo-vegetarian diets, of varying fat levels within the patterns, and of increasing dietary flexibility through food group substitutions. Food pattern modeling was a useful tool to identify possible impacts on diet quality of potential Dietary Guidelines recommendations. Modeling analyses can help researchers explore the overall effect of specific dietary recommendations on intake patterns.

Databases, Factual↗