Calcium-41: a technology for monitoring changes in bone mineral.

The rare, long-lived radiotracer, 41Ca, measured by accelerator mass spectrometry in the urine or serum following incorporation into the bone provides an ultra-sensitive tool to assess changes in bone calcium balance in response to an intervention. Changes in bone balance can be followed for years with one small dose that is both radiologically and biologically non-invasive. Sequential interventions can be compared, with greater precision than they can with biochemical markers of bone turnover and with greater power than with bone densitometry. This method is especially useful to screen interventions over a period of weeks. The development and validation of this tool and its applications are reviewed. Mini abstract: Use of 41Ca measured in the urine or blood by accelerator mass spectrometry to assess bone balance provides a tool to compare the relative efficacy of multiple interventions. This perspective provides insights in the use of this novel method and comparisons with more traditional methods for evaluating the efficacy of interventions.

Association of adenovirus 36 infection with adiposity and inflammatory-related markers in children.

CONTEXT: Although animal studies suggest that adenovirus 36 (Ad36) infection is linked to obesity and systemic inflammation, human data are scant and equivocal. OBJECTIVE: Associations of Ad36 infection with total body adiposity and inflammatory-related markers were determined in 291 children aged 9-13 years (50% female, 49% black). DESIGN: Fasting blood samples were measured for presence of Ad36-specific antibodies and TNF-α, IL-6, vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1). Fat mass and fat-free soft tissue mass were measured by dual-energy X-ray absorptiometry. RESULTS: The overall prevalence of Ad36 seropositivity [Ad36(+)] was 42%. There was a higher percentage of Ad36(+) children in the highest tertiles of TNF-α and IL-6 compared with their respective middle and lowest tertiles (both P < .03). There was also a trend toward a higher prevalence of Ad36(+) children in the highest tertile of VEGF compared with tertiles 1 and 2 (P = .05). Multinomial logistic regression, adjusting for age, race, sex, and fat-free soft tissue mass, revealed that compared with children with the lowest TNF-α, IL-6, and VEGF levels (tertile 1), the adjusted odds ratios for Ad36(+) were 2.2 [95% confidence interval (CI) 1.2-4.0], 2.4 (95% CI 1.4-4.0), and 1.8 (95% CI 1.0-3.3), respectively, for those in the highest TNF-α, IL-6, and VEGF levels (tertile 3). No association was observed between Ad36(+) and greater levels of fat mass or MCP-1 (all P > .05). CONCLUSIONS: In children, our data suggest that Ad36(+) may be associated with biomarkers implicated in inflammation but not with greater levels of fat mass.

Validation of urinary calcium isotope excretion from bone for screening anabolic therapies for osteoporosis.

SUMMARY: Urinary excretion of calcium tracers in labeled individuals decreases in response to antiresorptive therapy, providing a tool to rapidly screen potential therapies. Using teriparatide, we demonstrate in this study that anabolic therapy also decreases tracer excretion, confirming that this method can also be used to screen potential anabolic therapies. INTRODUCTION: Changes in urinary excretion of calcium tracers from a labeled skeleton may be a rapid and sensitive method to screen potential therapies for osteoporosis. This method has been used to screen antiresorptive therapies, but the effect of anabolic therapies on tracer excretion is unknown. METHODS: Eight-month-old female Sprague Dawley rats (n = 11) were given 50 µCi (45)Ca iv. After a 1-month equilibration period, baseline urinary (45)Ca excretion and total bone mineral content (BMC) were measured. Rats were then treated with 30 µg/kg teriparatide sc per day, a bone anabolic agent, for 80 days. Urine was collected throughout the study and analyzed for (45)Ca and total Ca, and BMC was measured at the beginning and end of the study. RESULTS: Teriparatide decreased urinary (45)Ca excretion by 52.1 % and increased BMC by 21.7 %. The change in bone calcium retention as determined by the ratio of (45)Ca to total Ca excretion in urine from day 6 through 15 of teriparatide treatment was significantly correlated (p = 0.036) with the change in BMC after 80 days of teriparatide treatment. CONCLUSION: Urinary excretion of calcium tracers from labeled bone is an effective method to rapidly screen potential anabolic therapies for osteoporosis.

Microbial community structure during fluoranthene degradation in the presence of plants.

AIMS: To investigate bacterial and fungal community structure during degradation of varying concentrations (0-5000 mg kg(-1) ) of the polycyclic aromatic hydrocarbon (PAH) fluoranthene in the presence or absence of tomato plants. METHOD AND RESULTS: Fluoranthene amended or unamended growing media, with or without a plant, were incubated in pots in a glasshouse for 30 days. Fluoranthene concentration was quantified using GC-FID, while bacterial and fungal community structure was investigated using trflp and arisa, respectively. The abundance of two ring hydroxylating dioxygenase genes was measured using qPCR. More fluoranthene was degraded in the presence of tomato plants at 500 and 5000 mg fluoranthene kg(-1) (P < 0·001), and it had a toxic effect on plant growth. Bacterial and fungal community composition in the rhizosphere was significantly different from that in nonrhizospheric and unplanted samples. The influence of fluoranthene on bacterial communities overcame that of the plant root such that community composition in rhizosphere and planted nonrhizospheric samples was broadly similar when fluoranthene was present. PAH-RHDα-GP genes were more abundant than PAH-RHDα-GN genes in all treatments. PAH-RHDα-GN abundance was unaffected by either PAH concentration or growing medium type, while the abundance of PAH-RHDα-GP was greatest in the rhizosphere. CONCLUSIONS: Plants promoted microbial growth and diversity and led to increases in abundance of Gram-positive dioxygenase genes, correlated with increased degradation of fluoranthene. SIGNIFICANCE AND IMPACT OF THE STUDY: This work contributes to knowledge in the broad area of biodegradation and also provides useful information for the design of future bioremediation strategies.

Calcium and vitamin D intake maintained from preovariectomy independently affect calcium metabolism and bone properties in Sprague Dawley rats.

UNLABELLED: The interaction of habitual Ca and vitamin D intake from preovariectomy to 4 months postovariectomy on bone and Ca metabolism was assessed. Higher Ca intake suppressed net bone turnover, and both nutrients independently benefitted trabecular structure. Habitual intake of adequate Ca and ~50 nmol/L vitamin D status is most beneficial. INTRODUCTION: Dietary strategies to benefit bone are typically tested prior to or after menopause but not through menopause transition. We investigated the interaction of Ca and vitamin D status on Ca absorption, bone remodeling, Ca kinetics, and bone strength as rats transitioned through estrogen deficiency. METHODS: Sprague Dawley rats were randomized at 8 weeks to 0.2 or 1.0 % Ca and 50, 100, or 1,000 IU (1.25, 2.5, or 25 µg) vitamin D/kg diet (2 × 3 factorial design) and ovariectomized at 12 weeks. Urinary (45)Ca excretion from deep-labeled bone was used to assess net bone turnover weekly. Ca kinetics was performed between 25 and 28 weeks. Rats were killed at 29 weeks. Femoral and tibiae structure (by µCT), dynamic histomorphometry, and bone Ca content were assessed. RESULTS: Mean 25(OH)D for rats on the 50, 100, 1,000 IU vitamin D/kg diet were 32, 54, and 175 nmol/L, respectively. Higher Ca intake ameliorated net bone turnover, reduced fractional Ca absorption and bone resorption, and increased net Ca absorption. Tibial and femoral trabecular structures were enhanced independently by higher Ca and vitamin D intake. Tibial bone width and fracture resistance were enhanced by higher vitamin D intake. Dynamic histomorphometry in the tibia was not affected by either nutrient. A Ca × vitamin D interaction existed in femur length, tibial Ca content, and mass of the soft tissue/extracellular fluid compartment. CONCLUSIONS: Adequate Ca intake and serum 25(OH)D level of 50 nmol/L provided the most benefit for bone health, mostly through independent effects of Ca and vitamin D.

A randomized trial of vitamin D3 supplementation in children: dose-response effects on vitamin D metabolites and calcium absorption.

CONTEXT: Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D3 in healthy children are unknown. OBJECTIVE: Our objective was to examine the dose-response effects of supplemental vitamin D3 on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes. DESIGN: Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D3 (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope 44Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption. RESULTS: The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from -10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)2D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D. CONCLUSION: Large increases in serum 25(OH)D with vitamin D3 supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children.

Body size and pubertal development explain ethnic differences in structural geometry at the femur in Asian, Hispanic, and white early adolescent girls living in the U.S.

UNLABELLED: Variation in structural geometry is present in adulthood, but when this variation arises and what influences this variation prior to adulthood remains poorly understood. Ethnicity is commonly the focus of research of skeletal integrity and appears to explain some of the variation in quantification of bone tissue. However, why ethnicity explains variation in skeletal integrity is unclear. METHODS: Here we examine predictors of bone cross sectional area (CSA) and section modulus (Z), measured using dual-energy X-ray absorptiometry (DXA) and the Advanced Hip Analysis (AHA) program at the narrow neck of the femur in adolescent (9-14 years) girls (n=479) living in the United States who were classified as Asian, Hispanic, or white if the subject was 75% of a given group based on parental reported ethnicity. Protocols for measuring height and weight follow standardized procedures. Total body lean mass (LM) and total body fat mass (FM) were quantified in kilograms using DXA. Total dietary and total dairy calcium intakes from the previous month were estimated by the use of an electronic semi-quantitative food frequency questionnaire (eFFQ). Physical activity was estimated for the previous year by a validated self-administered modifiable activity questionnaire for adolescents with energy expenditure calculated from the metabolic equivalent (MET) values from the Compendium of Physical Activities. Multiple regression models were developed to predict CSA and Z. RESULTS: Age, time from menarche, total body lean mass (LM), total body fat mass (FM), height, total calcium, and total dairy calcium all shared a significant (p<0.05), positive relationship with CSA. Age, time from menarche, LM, FM, and height shared significant (p<0.05), positive relationships with Z. For both CSA and Z, LM was the most important covariate. Physical activity was not a significant predictor of geometry at the femoral neck (p≥0.339), even after removing LM as a covariate. After adjusting for covariates, ethnicity was not a significant predictor in regression models for CSA and Z. CONCLUSION: Variability in bone geometry at the narrow neck of the femur is best explained by body size and pubertal maturation. After controlling for these covariates there were no differences in bone geometry between ethnic groups.

Warming experiments underpredict plant phenological responses to climate change.

Warming experiments are increasingly relied on to estimate plant responses to global climate change. For experiments to provide meaningful predictions of future responses, they should reflect the empirical record of responses to temperature variability and recent warming, including advances in the timing of flowering and leafing. We compared phenology (the timing of recurring life history events) in observational studies and warming experiments spanning four continents and 1,634 plant species using a common measure of temperature sensitivity (change in days per degree Celsius). We show that warming experiments underpredict advances in the timing of flowering and leafing by 8.5-fold and 4.0-fold, respectively, compared with long-term observations. For species that were common to both study types, the experimental results did not match the observational data in sign or magnitude. The observational data also showed that species that flower earliest in the spring have the highest temperature sensitivities, but this trend was not reflected in the experimental data. These significant mismatches seem to be unrelated to the study length or to the degree of manipulated warming in experiments. The discrepancy between experiments and observations, however, could arise from complex interactions among multiple drivers in the observational data, or it could arise from remediable artefacts in the experiments that result in lower irradiance and drier soils, thus dampening the phenological responses to manipulated warming. Our results introduce uncertainty into ecosystem models that are informed solely by experiments and suggest that responses to climate change that are predicted using such models should be re-evaluated.

Simple isotopic method using oral stable or radioactive tracers for estimating fractional calcium absorption in adult women.

UNLABELLED: We extended a simple oral method for estimating fractional calcium absorption determined by double isotopic methods using radioactive or stable isotope across wide age of adult women. Fractional calcium absorption can be estimated by using either a radioactive or stable oral isotope across the entire age spectrum of adult women. INTRODUCTION: A method for estimating fractional calcium absorption using a single serum collection following a single oral radioactive isotopic tracer has been validated against a classical double isotopic tracer ratio method in adults. Our goal was to extend this simplified method to include use of stable isotopes and a broad age range. METHODS: We used our database of 56 observations from 26 white adult women aged 19-67 years receiving either radioactive or stable isotopes. Reference values for fractional calcium absorption were determined from 24-h double isotopic ratios in serum and urine and from full kinetic modeling. RESULTS: Equations for estimating fractional calcium absorption were developed from isotopic enrichment in serum and urine from an oral tracer and measures of body size using the multiple linear regression analysis. Equations using a 4- to 6-h sample following an oral dose of either a stable or radioactive isotope corrected for body size were highly correlated with the reference values for fractional calcium absorption across different aged populations (r > 0.8, p < 0.001). CONCLUSION: Fractional calcium absorption can be estimated by a single oral tracer method using either radioactive or stable calcium isotopes across the entire age spectrum in healthy white adult women.

Validation of a simple isotope method for estimating true calcium fractional absorption in adolescents.

UNLABELLED: We validated a single oral isotope method for estimating fractional calcium absorption determined by double isotope methods in adolescents. Developed equations with an oral isotope including a single blood draw or spot urine collection can be used to evaluate fractional calcium absorption in adolescents which allows flexibility in developing protocols. INTRODUCTION: This study was designed to develop and validate a simpler, less expensive single oral isotope method for determining fractional calcium (Ca) absorption in adolescents. METHODS: We used our database of 31 observations from ten white and 12 black adolescent girls aged 10-15 years who participated in metabolic and kinetic studies. Tracer data following oral ((44)Ca) and intravenous (IV, (42)Ca) administration of calcium stable isotopes and samples in serum and urine from various time points up to 4 days were used to develop methods using multiple regression analysis based on a single measurement of enriched stable isotope/tracee defined as tracer/tracee (TT) in serum (TT(serum)) or urine (TT(urine)). Reference values for fractional calcium absorption were from oral/IV stable isotope ratios in 24-h serum or urine and full kinetic modeling. RESULTS: The strongest equation using a single blood sample had R (2) = 0.94 (p < 0.001): fractional Ca absorption = 1.3340(4-h TT(serum))(0.7872) BSA(1.7132)e ((-0.01652 PMA)), where BSA is body surface area and PMA is post-menarcheal age. The strongest equation using a single urine sample had R (2) = 0.95 (p < 0.001): fractional Ca absorption = 2.3088 (5-12 h TT(urine))(0.8208) BSA(1.5260)e ((-0.01850 PMA)). Equations were also developed with Tanner score. An external data set of Asian adolescent boys and girls was used to validate the equations. CONCLUSION: Equations using an oral isotope and a single blood draw or urine collection for determining fractional calcium absorption were successfully validated in healthy, non-obese white and black adolescent girls aged 10-15 years. The equations well-predicted fractional calcium absorption in Asian adolescent boys and girls.

Bone-seeking labels as markers for bone turnover: validation of urinary excretion in rats.

UNLABELLED: Urinary excretion of tritiated tetracycline ((3)H-TC) and (41)Ca tracers was validated as reflecting skeletal disappearance of these bone-seeking tracers as a direct measure of bone turnover following ovariectomy in rats. INTRODUCTION: Tritiated tetracycline ((3)H-TC) and Ca tracers have been used to measure bone resorption in animal models, but urinary excretion of these labels has not been directly compared to skeletal turnover. We aimed to evaluate the use of bone-seeking labels by comparing label release into urine with label in the skeleton when bone turnover was perturbed following ovariectomy. METHODS: Sixty-four 6-month-old ovariectomized (OVX) rats were randomized to one of eight groups in a 2 × 4 design that differed in time of (3)H-TC and (41)Ca administration following ovariectomy (1 month, when bone turnover would be accelerated following estrogen depletion or 3 months when bone loss due to OVX had slowed down) and time of euthanasia (1 week, 1 month, 3 months, and 6 months post-dose). Twenty-four-hour urine pools over two to four consecutive days and total skeleton were collected and recovered for the assessment of (3)H-TC and (41)Ca. RESULTS: Urinary (3)H-TC levels reflected skeletal (3)H-TC levels (r = 0.93; p < 0.0001) over a wide range of bone turnover rates in response to an intervention. Urinary (41)Ca and (3)H-TC excretion were highly correlated (r = 0.95, p < 0.0001). CONCLUSION: This study confirms that bone-seeking label excretion into the urine directly measures bone turnover.

Antiresorptive effects of phytoestrogen supplements compared with estradiol or risedronate in postmenopausal women using (41)Ca methodology.

INTRODUCTION: Reduction of ovarian estrogen secretion at menopause increases net bone resorption and leads to bone loss. Isoflavones have been reported to protect bone from estrogen deficiency, but their modest effects on bone resorption have been difficult to measure with traditional analytical methods. METHODS: In this randomized-order, crossover, blinded trial in 11 healthy postmenopausal women, we compared four commercial sources of isoflavones from soy cotyledon, soy germ, kudzu, and red clover and a positive control of oral 1 mg estradiol combined with 2.5 mg medroxyprogesterone or 5 mg/d oral risedronate (Actonel) for their antiresorptive effects on bone using novel (41)Ca methodology. RESULTS: Risedronate and estrogen plus progesterone decreased net bone resorption measured by urinary (41)Ca by 22 and 24%, respectively (P < 0.0001). Despite serum isoflavone profiles indicating bioavailability of the phytoestrogens, only soy isoflavones from the cotyledon and germ significantly decreased net bone resorption by 9% (P = 0.0002) and 5% (P = 0.03), respectively. Calcium absorption and biochemical markers of bone turnover were not influenced by interventions. CONCLUSIONS: Dietary supplements containing genistein-like isoflavones demonstrated a significant but modest ability to suppress net bone resorption in postmenopausal women at the doses supplied in this study over a 50-d intervention period.

Bone mineral and predictors of bone mass in white, Hispanic, and Asian early pubertal girls.

Differences in bone among racial/ethnic groups may be explained by differences in body size and shape. Previous studies have not completely explained differences among white, Asian, and Hispanic groups during growth. To determine racial/ethnic differences and predictors of bone mass in early pubertal girls, we measured bone mineral content (BMC) in white, Hispanic, and Asian sixth-grade girls across six states in the United States. We developed models for predicting BMC for the total-body, distal radius, total-hip, and lumbar spine for 748 subjects. For each of the bone sites, the corresponding area from dual-energy X-ray absorptiometry (DXA) was a strong predictor of BMC, with correlations ranging 0.78-0.98, confirming that larger subjects have more BMC. Anthropometric measures of bone area were nearly as effective as bone area from DXA at predicting BMC. For total-body, distal radius, lumbar spine, and total-hip BMC, racial/ethnic differences were explained by differences in bone area, sexual maturity, physical activity, and dairy calcium intake. Bone size explained most of the racial/ethnic differences in BMC, although behavioral indicators were also significant predictors of BMC.

Simple aspiration versus intercostal tube drainage for primary spontaneous pneumothorax in adults.

BACKGROUND: In the management of primary spontaneous pneumothorax, simple aspiration is technically easier to perform. A systematic review may better define the clinical effectiveness and safety of simple aspiration compared to intercostal tube drainage in the management of primary spontaneous pneumothorax. OBJECTIVES: To compare the clinically efficacy and safety of simple aspiration and intercostal tube drainage in the management of primary spontaneous pneumothorax. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2006), MEDLINE (1966 to August 2006), and EMBASE (1980 to August 2006). We searched Current Controlled Trials metaRegister of Clinical Trials (compiled by Current Science) (August 2006). We checked the reference lists of trials and contacted trial authors . We imposed no language restriction. SELECTION CRITERIA: Randomized controlled trials comparing simple aspiration with intercostal tube drainage in adults aged 18 and over with primary spontaneous pneumothorax. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. No statistical methods were necessary because only one study met the inclusion criteria. MAIN RESULTS: Of the 1239 publications obtained from the search strategy, we examined six studies. Five studies were excluded, and one study of 60 participants was eligible for inclusion. There was no difference in immediate success rate of simple aspiration when compared with intercostal tube drainage in the management of primary spontaneous pneumothorax (relative risk (RR) = 0.93; 95% confidence interval (CI) 0.62 to 1.40). There was no significant difference in the early failure rate between the two interventions: RR 1.12 (95% CI 0.59 to 2.13). Simple aspiration reduced the proportion of patients hospitalized (RR = 0.52; 95% CI 0.36 to 0.75). There was no significant difference between the two interventions with regard to the following outcome measures: duration of hospitalization (weighted mean difference = 1.09; 95% CI 2.18 to 0.00); number of participants undergoing any procedure for lung pleurodesis within one year (RR = 0.95; 95% CI 0.41 to 2.22);and one year success rate (RR = 1.02; 95% CI 0.75 to 1.38). AUTHORS' CONCLUSIONS: There is no significant difference between simple aspiration and intercostal tube drainage with regard to: immediate success rate, early failure rate, duration of hospitalisation, one year success rate and number of patients requiring pleurodesis at one year. Simple aspiration is associated with a reduction in the per cent of patients hospitalized when compared with intercostal tube drainage.

Soy isoflavones do not affect bone resorption in postmenopausal women: a dose-response study using a novel approach with 41Ca.

INTRODUCTION: The purpose of this 3-way crossover study was to identify the effective dose of soy protein isolate enriched with isoflavones for suppressing bone resorption in postmenopausal women using a novel, rapid assessment of antibone resorbing treatments. METHODS: Thirteen postmenopausal women (>or=6 yr since menopause) were predosed with 41Ca iv. After a 200-d baseline period, subjects were given 43 g soy protein/d that contained 0, 97.5, or 135.5 mg total isoflavones in randomized order. The soy protein isolate powder was incorporated into baked products and beverages. Each 50-d intervention phase was preceded by a 50-d pretreatment phase for comparison. Serum isoflavone levels and biochemical markers were measured at the end of each phase. Twenty-four-hour urine samples were collected approximately every 10 d during each phase for 41Ca/Ca analysis by accelerator mass spectrometry. RESULTS: Serum isoflavone levels reflected the amount of isoflavones consumed in a dose-dependent manner. None of the isoflavone levels had a significant effect on biochemical markers of bone turnover, urinary cross-linked N teleopeptides of type I collagen and serum osteocalcin, or bone turnover as assessed by urinary 41Ca/Ca ratios. CONCLUSIONS: Soy protein with isoflavone doses of up to 135.5 mg/d did not suppress bone resorption in postmenopausal women. This is the first efficacy trial using the novel technique of urinary 41Ca excretion from prelabeled bone.

Using functional data analysis to summarise and interpret lactate curves.

John Tukey used the term exploratory data analysis (EDA) to describe a philosophy for analyzing data where graphical and numerical summaries are used to uncover interesting structures. The applied statistician today has a much more sophisticated set of methods to use when applying the EDA philosophy. One such collection of methods is functional data analysis (FDA), which was used to explore the structure of lactate curves. A principal components analysis and plots of the second derivatives provide new intuitive endurance markers which correlates highly with other numerical summaries of lactate curves that have been suggested in the literature.

Parathyroid hormone is associated with decreased fat mass in young healthy women.

OBJECTIVE: To investigate the relationship of parathyroid hormone (PTH) with dietary calcium and changes in body composition. DESIGN: Cross-sectional and 1-year longitudinal trial. SUBJECTS: Normal-weight young women (age: 18-31), 155 subjects analyzed at baseline, and data for 41 subjects analyzed prospectively between baseline and 12 months. MEASUREMENTS: Levels of fasting serum calcium and PTH, intakes of calcium (3-day diet records), and total body weight and body composition (dual energy X-ray absorptiometry). RESULTS: Baseline dietary calcium, regardless of whether unadjusted or adjusted for energy intake, did not predict baseline levels of fasting serum PTH. Change in dietary calcium also did not predict change in serum PTH. However, log PTH was significantly correlated with body fat mass (R = 0.27), but not lean mass at baseline (n = 155), independent of serum calcium (corrected R = 0.25). Further, 12-month changes (n = 41) in log PTH positively predicted the 12-month change in body weight (R = 0.32) and body fat (R = 0.32), but not lean mass even when controlled for age or change in serum calcium. CONCLUSION: Fasting serum PTH was associated with increased fat mass, in both cross-sectional and prospective analysis. Thus, serum PTH may play a role in the regulation of body fat mass in young women.

Predicting toxicity equivalents in fish tissue.

Toxicity equivalents is a measure of "dioxin-like" toxicity contributed by polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (dioxins), and polychlorinated dibenzofurans (furans). Calculation of toxicity equivalents require the use of analytical procedures that are expensive and slow, making them impractical for routine analysis. U.S. Environmental Protection Agency National Fish Tissue Study (2003) data were used to determine the most significant predictors of toxicity equivalents with multiple regression analysis. The strongest predictive model (P < 0.0001, R2 = 0.97) included five compounds (PCB-118; PCB-126; 2,3,7,8-TCDD; 1,2,3,6,7,8-HxCDD; 2,3,4,7,8-PeCDF). However, the required lower limit of detection for an analytical method measuring these congeners is 0.1 ppt and would not provide much benefit over the current analytical method. An alternative model (P < 0.0001, R2 = 0.68) that included three PCBs (PCB-138, PCB-153, PCB-118) would require a limit of detection of 1,000 ppt and be more practical. This research demonstrates that the measurement of selected compounds can be used to estimate toxicity equivalents and consequently serve as the impetus for the development of lower cost, rapid analytical methods for analysis of fish.

Effects of subclinical infection on plasma retinol concentrations and assessment of prevalence of vitamin A deficiency: meta-analysis.

BACKGROUND: Vitamin A deficiency adversely affects child morbidity and survival. This deficiency is estimated by measurement of plasma retinol concentrations, but because plasma retinol is reduced by clinical and subclinical infection, this proxy measure can lead to overestimation. Infection and trauma are accompanied by rises in concentrations of acute-phase proteins in plasma. We aimed to estimate vitamin A deficiency more accurately by measuring changes in plasma retinol and acute-phase proteins associated with subclinical infection or convalescence. METHODS: We analysed data for concentrations of plasma retinol and one or more acute-phase proteins (alpha1-acid-glycoprotein, alpha1-antichymotrypsin, C-reactive protein, or serum amyloid A) from 15 studies of apparently healthy individuals. We generated summary estimates of differences in retinol concentrations for incubation, early, and late convalescent phases of infection between people with none and those with one or more raised acute-phase proteins. We compared these groups in two, three, and four group analyses. We also compared a subgroup of apparently healthy preschool (1-5 years) children with results from all other studies. FINDINGS: For all four proteins, retinol values were much higher in people with normal concentrations of protein, than in individuals with raised concentrations (16% higher for alpha1-antichymotrypsin, 18% for alpha1-acid-glycoprotein, 25% for C-reactive protein, and 32% for serum amyloid A). Estimates of the reduction in plasma retinol for individuals with infection compared with healthy individuals, were 13% (incubation), 24% (early convalescent), and 11% (late convalescent). Estimates of vitamin A deficiency in individuals with no raised acute-phase proteins (healthy group) were much the same as those obtained by adjustment of plasma retinol concentrations in the whole group using acute-phase proteins. INTERPRETATION: We recommend that surveys to estimate vitamin A deficiency should include measurements of serum C-reactive protein and alpha1-acid-glycoprotein concentrations. Information about acute-phase proteins will enable plasma retinol concentrations to be corrected where sub-clinical infection exists, and the healthy sub-group to be identified.