Are milk and alternatives and fruit and vegetable intakes during adolescence associated with cortical and trabecular bone structure, density, and strength in adulthood?

We investigated the impact of food group intake during adolescence on bone structure and strength during adulthood. In females, we found a beneficial effect of adolescent milk and alternatives and fruit and vegetable intake on adult radius shaft and distal tibia bone structure, respectively. No association was observed in males. INTRODUCTION: The purpose of this study was to investigate whether adolescents with high intake of milk and alternatives (M&A) or fruit and vegetables (F&V) had better adult bone structure and strength compared to those with low intake levels. METHODS: We analyzed data from 47 males and 69 females enrolled in the Pediatric Bone Mineral Accrual Study (PBMAS 1991-2011), who had one peripheral quantitative computed tomography scan at age 29 ± 2 years. We measured radius and tibia shaft total area (ToA), cortical area (CoA), cortical content (CoC), cortical density, bone strength (SSIp), and muscle area, as well as distal radius and tibia ToA, total density, trabecular area, trabecular content, trabecular density, and bone strength (BSIc). Sequential 24-h recalls were used to assess M&A and F&V intake; participants were grouped for their mean intake during adolescence (low = bottom quartile, moderate = middle quartiles, high = top quartile) and were compared using multivariate analysis of covariance while adjusting for adult height, muscle area, physical activity, energy and calcium intake and adolescent energy intake, and physical activity. RESULTS: Females with high M&A intake compared to low M&A intake group (mean 3.8 vs. 1.3 servings/day, respectively) had greater adult ToA (14 %, p < 0.05), CoA (15 %, p < 0.01), and CoC (16 %, p < 0.01) at radius shaft. Females with moderate F&V intake compared to low F&V intake group (mean 3.7 vs. 2.1 servings/day, respectively) had greater adult ToA (8.5 %, p < 0.05) at distal tibia. CONCLUSION: Higher intake of M&A or F&V during adolescence had a long-term beneficial effect on bone structure in females, an association not observed in males.

Heritable variation in heat shock gene expression: a potential mechanism for adaptation to thermal stress in embryos of sea turtles.

The capacity of species to respond adaptively to warming temperatures will be key to their survival in the Anthropocene. The embryos of egg-laying species such as sea turtles have limited behavioural means for avoiding high nest temperatures, and responses at the physiological level may be critical to coping with predicted global temperature increases. Using the loggerhead sea turtle (Caretta caretta) as a model, we used quantitative PCR to characterise variation in the expression response of heat-shock genes (hsp60, hsp70 and hsp90; molecular chaperones involved in cellular stress response) to an acute non-lethal heat shock. We show significant variation in gene expression at the clutch and population levels for some, but not all hsp genes. Using pedigree information, we estimated heritabilities of the expression response of hsp genes to heat shock and demonstrated both maternal and additive genetic effects. This is the first evidence that the heat-shock response is heritable in sea turtles and operates at the embryonic stage in any reptile. The presence of heritable variation in the expression of key thermotolerance genes is necessary for sea turtles to adapt at a molecular level to warming incubation environments.

Survival, quality-adjusted survival, and other clinical end points in older advanced non-small-cell lung cancer patients treated with albumin-bound paclitaxel.

BACKGROUND: This analysis compared the quality-adjusted survival and clinical outcomes of albumin-bound paclitaxel+carboplatin (nab-PC) vs solvent-based paclitaxel+carboplatin (sb-PC) as first-line therapy in advanced non-small-cell lung cancer (NSCLC) in older patients. METHODS: Using age-based subgroup data from a randomised Phase-3 clinical trial, nab-PC and sb-PC were compared with respect to overall response rate (ORR), overall survival (OS), progression-free survival (PFS), quality of life (QoL), safety/toxicity, and quality-adjusted time without symptoms or toxicity (Q-TWiST) with ages ⩾60 and ⩾70 years as cut points. RESULTS: Among patients aged ⩾60 years (N=546), nab-PC (N=265) significantly increased ORR and prolonged OS, despite a non-significant improvement in PFS, vs sb-PC (N=281). Nab-PC improved QoL and was associated with less neuropathy, arthralgia, and myalgia but resulted in more anaemia and thrombocytopenia. Nab-PC yielded significant Q-TWiST benefits (11.1 vs 9.8 months; 95% CI of gain: 0.2-2.6), with a relative Q-TWiST gain of 10.8% (ranging from 6.4% to 15.1% in threshold analysis). In the ⩾70 years age group, nab-PC showed similar, but non-significant, ORR, PFS, and Q-TWiST benefits and significantly improved OS and QoL. CONCLUSION: Nab-PC as first-line therapy in older patients with advanced NSCLC increased ORR, OS, and QoL and resulted in quality-adjusted survival gains compared with standard sb-PC.

Increased expression of Hsp70 and Hsp90 mRNA as biomarkers of thermal stress in loggerhead turtle embryos (Caretta Caretta).

The survival and viability of sea turtle embryos is dependent upon favourable nest temperatures throughout the incubation period. Consequently, future generations of sea turtles may be at risk from increasing nest temperatures due to climate change, but little is known about how embryos respond to heat stress. Heat shock genes are likely to be important in this process because they code for proteins that prevent cellular damage in response to environmental stressors. This study provides the first evidence of an expression response in the heat shock genes of embryos of loggerhead sea turtles (Caretta caretta) exposed to realistic and near-lethal temperatures (34°C and 36°C) for 1 or 3 hours. We investigated changes in Heat shock protein 60 (Hsp60), Hsp70, and Hsp90 mRNA in heart (n=24) and brain tissue (n=29) in response to heat stress. Under the most extreme treatment (36°C, 3h), Hsp70 increased mRNA expression by a factor of 38.8 in heart tissue and 15.7 in brain tissue, while Hsp90 mRNA expression increased by a factor of 98.3 in heart tissue and 14.7 in brain tissue. Hence, both Hsp70 and Hsp90 are useful biomarkers for assessing heat stress in the late-stage embryos of sea turtles. The method we developed can be used as a platform for future studies on variation in the thermotolerance response from the clutch to population scale, and can help us anticipate the resilience of reptile embryos to extreme heating events.

Potential importance of transition metals in the induction of DNA damage by sperm preparation media.

STUDY QUESTION: What are the mechanisms by which the preparation of spermatozoa on discontinuous density gradients leads to an increase in oxidative DNA damage? SUMMARY ANSWER: The colloidal silicon solutions that are commonly used to prepare human spermatozoa for assisted reproduction technology (ART) purposes contain metals in concentrations that promote free radical-mediated DNA damage. WHAT IS KNOWN ALREADY: Sporadic reports have already appeared indicating that the use of colloidal silicon-based discontinuous density gradients for sperm preparation is occasionally associated with the induction of oxidative DNA damage. The cause of this damage is however unknown. STUDY DESIGN, SIZE, DURATION: This study comprised a series of experiments designed to: (i) confirm the induction of oxidative DNA damage in spermatozoa prepared on commercially available colloidal silicon gradients, (ii) compare the levels of damage observed with alterative sperm preparation techniques including an electrophoretic approach and (iii) determine the cause of the oxidative DNA damage and develop strategies for its prevention. The semen samples employed for this analysis involved a cohort of >50 unselected donors and at least three independent samples were used for each component of the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: The setting was a University biomedical science laboratory. The major techniques employed were: (i) flow cytometry to study reactive oxygen species generation, lipid peroxidation and DNA damage, (ii) computer-aided sperm analysis to measure sperm movement and (iii) inductively coupled mass spectrometry to determine the elemental composition of sperm preparation media. MAIN RESULTS AND THE ROLE OF CHANCE: Oxidative DNA damage is induced in spermatozoa prepared on PureSperm(®) discontinuous colloidal silicon gradients (P < 0.001 versus repeated centrifugation) because this medium contains metals, particularly Fe, Al and Cu, which are known to promote free radical generation in the immediate vicinity of DNA. This damage can be significantly accentuated by reducing agents, such as ascorbate (P < 0.001) and inhibited by selective chelation (P < 0.001). This problem is not confined to PureSperm(®); analysis of additional commercial sperm preparation media revealed that metal contamination is a relatively constant feature of such products. LIMITATIONS, REASONS FOR CAUTION: While the presence of metals, particularly transition metals, may exacerbate the levels of oxidative DNA damage seen in human spermatozoa, the significance of such damage has not yet been tested in suitably powered clinical trials. WIDER IMPLICATIONS OF THE FINDINGS: The results explain why the preparation of spermatozoa on discontinuous colloidal silicon gradients can result in oxidative DNA damage. The results are of immediate relevance to the development of safe, effective protocols for the preparation of spermatozoa for ART purposes. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the Australian Health and Medical Research Council. One of the authors (R.J.A.) has had a consultantship with a biotechnology company, NuSep, interested in the development of electrophoretic methods of sperm preparation. He has no current financial interest in this area. None of the other authors have a conflict of interest to declare.

Could capsaicinoids help to support weight management? A systematic review and meta-analysis of energy intake data.

OBJECTIVE: Capsaicinoids are a group of chemicals naturally occurring in chilli peppers with bioactive properties that may help to support weight management. The aim of the present study was to conduct a meta-analysis investigating the potential effects of capsaicinoids on energy intake, to clarify previous observations and form evidence-based conclusions about possible weight management roles. METHODS: Medical databases (Medline, Web of Knowledge and Scopus) were systematically searched for papers. Search terms were: 'capsaicin(*)' or 'red pepper' or 'chilli(*)' or 'chili(*)' with 'satiety' or 'energy intake'. Of the seventy-four clinical trials identified, 10 were included, 8 of which provided results suitable to be combined in analysis (191 participants). From the studies, 19 effect sizes were extracted and analysed using MIX meta-analysis software. RESULTS: Data analysis showed that capsaicinoid ingestion prior to a meal reduced ad libitum energy intake by 309.9kJ (74.0kcal) p<0.001 during the meal. Results, however, should be viewed with some caution as heterogeneity was high (I(2)=75.7%). Study findings suggest a minimum dose of 2mg of capsaicinoids is needed to contribute to reductions in ad libitum energy intake, which appears to be attributed to an altered preference for carbohydrate-rich foods over foods with a higher fat content. CONCLUSIONS: Meta-anlysis findings suggest that daily consumption of capsaicinoids may contribute to weight management through reductions in energy intake. Subsequently, there may be potential for capsaicinoids to be used as long-term, natural weight-loss aids. Further long-term randomised trials are now needed to investigate these effects.

Vitamin D metabolism, functions and needs: from science to health claims.

BACKGROUND: Vitamin D is a nutrient long considered as essential for skeletal health but is now attracting interest from medical and nutritional communities as knowledge emerges of its biological function and its association with decreased risk of many chronic diseases. RESULTS: A question emerges: How much more vitamin D do we need for these new functions of vitamin D? This review discusses vitamin D physiology and hypovitaminosis D and presents two vitamin D dietary policies: that according to regulatory authorities and that of nutrition scientists. Scientific evidence suggests that 25(OH)D serum levels should be over 75 nmol/L; otherwise, there is no beneficial effect of vitamin D on long-latency diseases. Current regulatory authority recommendations are insufficient to reach this level of adequacy. Observational and some prospective data show that vitamin D has a role in the prevention of cancer as well as immunity, diabetes and cardiovascular and muscle disorders, which supports the actions of 1α,25(OH)2D at cellular and molecular levels. The recent assessments done by the European Food Safety Authority should lead to new health claims. CONCLUSIONS: Vitamin D, through food fortification and supplementation, is a promising new health strategy and thus provides opportunities for food industry and nutrition researchers to work together towards determining how to achieve this potential health benefit.

Influence of zinc and zinc chelator on HT-29 colorectal cell line.

Trace elements are involved in many key pathways involving cell cycle control. The influence of zinc and zinc chelator (TPEN) on transcription levels of the main zinc transporters (ZnT1 and ZIP1) in the HT-29 colorectal cell line has not been reported. Proliferation of HT-29 cells was measured using the methylene blue assay after exposure to zinc (two concentrations), TPEN (two concentrations), or a combination of zinc and TPEN (simultaneously and sequentially) for 4 h, 8 h, and 24 h. The transcription levels of ZnT1, ZIP1, vascular endothelial growth factor (VEGF), and caspase-3 were determined using reverse transcriptase real-time polymerase chain reaction (RT-PCR) after exposure of cells to zinc and TPEN. The zinc content in the substrate (medium used for culture) was determined using atomic absorption spectrometry. TPEN decreased cellular proliferation causing complete cell death by 8 h. Zinc had a protective effect against short periods of exposure to TPEN. There was no correlation between the transcripts of main zinc transporters and the zinc content in the substrate. The zinc content in the substrate remained constant after varying periods of cell culture. TPEN decreased the transcript levels of caspase-3 and VEGF, which are surrogate markers for apoptosis and angiogenesis. Zinc chelation of HT-29 cells causes cell death. Zinc appears to be protective for short periods of exposure to TPEN but has no protective effect on prolonged exposure. HT-29 cells are not able to counteract the effect of intracellular chelation of zinc by altering zinc transport. Further research into the mechanisms of these findings is necessary and may lead to novel therapeutic options.

Plutonium and other radionuclides persist across marine-to-terrestrial ecotopes in the Montebello Islands sixty years after nuclear tests.

Since the 1956 completion of nuclear testing at the Montebello Islands, Western Australia, this remote uninhabited island group has been relatively undisturbed (no major remediations) and currently functions as high-value marine and terrestrial habitat within the Montebello/Barrow Islands Marine Conservation Reserves. The former weapons testing sites, therefore, provide a unique opportunity for assessing the fate and behaviour of Anthropocene radionuclides subjected to natural processes across a range of shallow-marine to island-terrestrial ecological units (ecotopes). We collected soil, sediment and biota samples and analysed their radionuclide content using gamma and alpha spectrometry, photostimulated luminescence autoradiography and accelerator mass spectrometry. We found the activity levels of the fission and neutron-activation products have decreased by ~hundred-fold near the ground zero locations. However, Pu concentrations remain elevated, some of which are high relative to most other Australian and international sites (up to 25,050 Bq kg-1 of 239+240+241Pu). Across ecotopes, Pu ranked from highest to lowest in the following order: island soils > dunes > foredunes > marine sediments > and beach intertidal zone. Low values of Pu and other radionuclides were detected in all local wildlife tested including endangered species. Activity concentrations ranked (highest to lowest) terrestrial arthropods > terrestrial mammal and reptile bones > algae > oyster flesh > whole crab > sea turtle bone > stingray and teleost fish livers > sea cucumber flesh > sea turtle skin > teleost fish muscle. The three detonations (one from within a ship and two from 30 m towers) resulted in differing contaminant forms, with the ship detonation producing the highest activity concentrations and finer more inhalable particulate forms. The three sites are distinct in their 240/239Pu and 241/239Pu atom ratios, including the Pu transported by natural process or within migratory living organisms.

Vitamin D status and its association with parathyroid hormone concentrations in women of child-bearing age living in Jakarta and Kuala Lumpur.

OBJECTIVE: To describe the vitamin D status of women living in two Asian cities,--Jakarta (6 degrees S) and Kuala-Lumpur (2 degrees N), to examine the association between plasma 25-hydroxyvitamin D and parathyroid hormone (PTH) concentrations, and to determine a threshold for plasma 25-hydroxyvitamin D above which there is no further suppression of PTH. Also, to determine whether dietary calcium intake influences the relationship between PTH and 25-hydroxyvitamin D. DESIGN: Cross-sectional. SETTING: Jakarta, Indonesia and Kuala Lumpur, Malaysia. PARTICIPANTS: A convenience sample of 504 non-pregnant women 18-40 years. MAIN MEASURES: Plasma 25-hydroxyvitamin D and PTH. RESULTS: The mean 25-hydroxyvitamin D concentration was 48 nmol/l. Less than 1% of women had a 25-hydroxyvitamin D concentration indicative of vitamin D deficiency (<17.5 nmol/l); whereas, over 60% of women had a 25-hydroxyvitamin D concentration indicative of insufficiency (<50 nmol/l). We estimate that 52 nmol/l was the threshold concentration for plasma 25-hydroxyvitamin D above which no further suppression of PTH occurred. Below and above this concentration the slopes of the regression lines were -0.18 (different from 0; P=0.003) and -0.01 (P=0.775), respectively. The relation between vitamin D status and parathyroid hormone concentration did not differ between women with low, medium or high calcium intakes (P=0.611); however, even in the highest tertile of calcium intake, mean calcium intake was only 657 mg/d. CONCLUSION: On the basis of maximal suppression of PTH we estimate an optimal 25-hydroxyvitamin D concentration of approximately 50 nmol/l. Many women had a 25-hydroxyvitamin D below this concentration and may benefit from improved vitamin D status.

Food fortification for bone health in adulthood: a scoping review.

Food fortification can deliver essential micronutrients to large population segments without modifications in consumption pattern, suggesting that fortified foods may be formulated for populations at risk for fragility fractures. This scoping review determined the extent to which randomized controlled studies have been carried out to test the impact of fortified foods on bone outcomes, searching PubMed for all studies using the terms 'fortified AND bone', and 'fortification AND bone'. Studies were restricted to English language, published between 1996 and June 2015. From 360 articles, 24 studies met the following criteria: human study in adults ⩾18 years (excluding pregnancy or lactation); original study of a fortified food over time, with specific bone outcomes measured pre- and post intervention. Six studies involved adults <50 years; 18 involved adults ⩾50 years. Singly or in combination, 17 studies included calcium and 16 included vitamin D. There were 1 or 2 studies involving either vitamin K, magnesium, iron, zinc, B-vitamins, inulin or isoflavones. For adults <50 years, the four studies involving calcium or vitamin D showed a beneficial effect on bone remodeling. For adults ⩾50 years, n=14 provided calcium and/or vitamin D, and there was a significant bone turnover reduction. No consistent effects were reported in studies in which addition of vitamin K, folic acid or isoflavone was assessed. Results from this scoping review indicate that up to now most studies of fortification with bone health have evaluated calcium and/or vitamin D and that these nutrients show beneficial effects on bone remodeling.

Involvement of homocysteine, homocysteine thiolactone, and paraoxonase type 1 (PON-1) in the etiology of defective human sperm function.

This study reports, for the first time, the significant (p ≤ 0.01) accumulation of homocysteine residues in low density, defective sperm suspensions isolated from patients attending an infertility clinic. This overabundance of homocysteine was not related to a deficiency in folate availability but may have been a reflection of the oxidative stress that characterizes such defective sperm populations. Direct addition of the homocysteine cyclic congener, homocysteine thiolactone, to human spermatozoa resulted in the rapid induction of mitochondrial reactive oxygen species (ROS) generation (p < 0.001), the stimulation of lipid peroxidation (p < 0.01), the promotion of tyrosine phosphorylation (p < 0.001), and the suppression of sperm motility (p < 0.001) in the absence of any significant impact on DNA integrity. The parent homocysteine molecule was less active and took 24 h to stimulate mitochondrial ROS production possibly because of the need to convert this compound to the corresponding thiolactone before it could exert a measureable biological effect. Thiolactone was also effective in suppressing the carboxymethylation of key proteins in the sperm tail, which are thought to be involved in the regulation of sperm movement. The major enzyme responsible for removing thiolactone from proteins, paraoxonase (PON-1), was shown to be a major target for alkylation by lipid aldehydes, such as 4-hydroxynonenal, generated as a consequence of oxidative stress. Exposure of human spermatozoa to such aldehydes resulted in a dose-dependent accumulation of homocysteine in spermatozoa (p < 0.03). These results suggest that one of the consequences of oxidative stress in mammalian spermatozoa is the inhibition of PON-1, which then enhances the availability of homocysteine thiolactone to interact with the epsilon-amino group of lysine residues on sperm proteins, triggering a raft of significant biological changes in these cells that ultimately compromise sperm function.

Analysis of the effects of polyphenols on human spermatozoa reveals unexpected impacts on mitochondrial membrane potential, oxidative stress and DNA integrity; implications for assisted reproductive technology.

The need to protect human spermatozoa from oxidative stress during assisted reproductive technology, has prompted a detailed analysis of the impacts of phenolic compounds on the functional integrity of these cells. Investigation of 16 individual compounds revealed a surprising variety of negative effects including: (i) a loss of mitochondrial membrane potential (Δψm) via mechanisms that were not related to opening of the permeability transition pore but associated with a reduction in thiol expression, (ii) a decline in intracellular reduced glutathione, (iii) the stimulation of pro-oxidant activity including the induction of ROS generation from mitochondrial and non-mitochondrial sources, (iv) stimulation of lipid peroxidation, (v) the generation of oxidative DNA damage, and (vi) impaired sperm motility. For most of the polyphenolic compounds examined, the loss of motility was gradual and highly correlated with the induction of lipid peroxidation (r=0.889). The exception was gossypol, which induced a rapid loss of motility due to its inherent alkylating activity; one consequence of which was a marked reduction in carboxymethyl lysine expression on the sperm tail; a post-translational modification that is known to play a key role in the regulation of sperm movement. The only polyphenols that did not appear to have adverse effects on spermatozoa were resveratrol, genistein and THP at doses below 100µM. These compounds could, therefore, have some therapeutic potential in a clinical setting.

Properties of strand displacement synthesis by Moloney murine leukemia virus reverse transcriptase: mechanistic implications.

Previous results indicated that Moloney murine leukemia virus reverse transcriptase is capable of extensive synthesis under conditions where it must simultaneously displace a downstream non-template DNA strand. To investigate more fully the mechanistic basis for displacement synthesis and to characterize the activity with natural viral templates, displacement and non-displacement synthesis were compared under a variety of conditions using the viral long terminal repeat plus strand as the template. Although the rates of both displacement and non-displacement synthesis varied regionally over the template, on the average, displacement synthesis was slower by a factor of approximately 3 to 4. Surprisingly, with one particular primer situated downstream of the tRNA primer binding site, displacement synthesis was found to be at least tenfold more processive than non-displacement synthesis, approaching a value of 500 nucleotides. The sequence features associated with pausing during the two modes of synthesis are different in both nucleotide preference and position relative to the enzyme, suggesting that the enzyme contacts the DNA differently under the two modes of synthesis. It was found that pausing during displacement synthesis did not reflect those local regions of DNA with a predicted high degree of thermal stability. Moreover, the very similar effects of temperature on the rates of displacement and non-displacement synthesis make unlikely a strictly passive mechanism of displacement synthesis whereby breathing of the downstream duplex is sufficient for advancement of the polymerase. Together, these results suggest a mechanism of displacement synthesis in which reverse transcriptase actively participates in the process of strand separation in front of the translocating polymerase.

Calcium accretion in girls and boys during puberty: a longitudinal analysis.

The primary purpose of this study was to estimate the magnitude and variability of peak calcium accretion rates in the skeletons of healthy white adolescents. Total-body bone mineral content (BMC) was measured annually on six occasions by dual-energy X-ray absorptiometry (DXA; Hologic 2000, array mode), a BMC velocity curve was generated for each child by a cubic spline fit, and peak accretion rates were determined. Anthropometric measures were collected every 6 months and a 24-h dietary recall was recorded two to three times per year. Of the 113 boys and 115 girls initially enrolled in the study, 60 boys and 53 girls who had peak height velocity (PHV) and peak BMC velocity values were used in this longitudinal analysis. When the individual BMC velocity curves were aligned on the age of peak bone mineral velocity, the resulting mean peak bone mineral accrual rate was 407 g/year for boys (SD, 92 g/year; range, 226-651 g/year) and 322 g/year for girls (SD, 66 g/year; range, 194-520 g/year). Using 32.2% as the fraction of calcium in bone mineral, as determined by neutron activation analysis (Ellis et al., J Bone Miner Res 1996;11:843-848), these corresponded to peak calcium accretion rates of 359 mg/day for boys (81 mg/day; 199-574 mg/day) and 284 mg/day for girls (58 mg/day; 171-459 mg/day). These longitudinal results are 27-34% higher than our previous cross-sectional analysis in which we reported mean values of 282 mg/day for boys and 212 mg/day for girls (Martin et al., Am J Clin Nutr 1997;66:611-615). Mean age of peak calcium accretion was 14.0 years for the boys (1.0 years; 12.0-15.9 years), and 12.5 years for the girls (0.9 years; 10.5-14.6 years). Dietary calcium intake, determined as the mean of all assessments up to the age of peak accretion was 1140 mg/day (SD, 392 mg/day) for boys and 1113 mg/day (SD, 378 mg/day) for girls. We estimate that 26% of adult calcium is laid down during the 2 adolescent years of peak skeletal growth. This period of rapid growth requires high accretion rates of calcium, achieved in part by increased retention efficiency of dietary calcium.

Association between urinary potassium, urinary sodium, current diet, and bone density in prepubertal children.

BACKGROUND: Our understanding of the role of nutrients in bone development in children is limited. OBJECTIVE: We examined the associations between urinary potassium, urinary sodium, usual dietary intake, and bone mineral density (BMD) in prepubertal children. DESIGN: This was a cross-sectional study of 330 boys and girls aged 8 y. Urinary measures were assessed in a single, timed, overnight urine specimen. Usual diet was assessed with a food-frequency questionnaire completed by a parent or guardian. BMD at the femoral neck, lumbar spine, and total body was measured by dual-energy X-ray absorptiometry. RESULTS: Urinary potassium correlated significantly with BMD at all sites (femoral neck: r = 0.20, P < 0.001; lumbar spine: r = 0.19, P = 0.001; total body: r = 0.24, P < 0.001). After adjustment for confounders (primarily lean body mass), this association was lower in magnitude but remained significant at 2 sites with a consistent trend at the third (femoral neck: P = 0.15; lumbar spine: P = 0.046; total body: P = 0.028). Urinary sodium was not associated with BMD at any site. No nutrient or food intake estimate was associated with BMD, although urinary potassium correlated significantly with potassium intake (r = 0.14, P = 0.016) and fruit and vegetable intake (r = 0.12, P = 0.033). CONCLUSIONS: Urinary potassium was associated with both dietary intake and BMD independent of lean body mass in these well-nourished, calcium-replete young children. These findings should be confirmed in further longitudinal studies. Nevertheless, this association is likely to represent dietary intake of potassium and suggests that measurement of urinary potassium is superior to food-frequency questionnaires for assessing potassium intake in this age group.

Calciuric effects of protein and potassium bicarbonate but not of sodium chloride or phosphate can be detected acutely in adult women and men.

An acute load test was used to test the influence of dietary factors on urinary calcium excretion. In study 1, 10 fasting premenopausal women consumed test meals providing a moderate amount of protein (MP; 23 g), MP plus 23 mmol KHCO3 (MP+K), MP plus 23 mmol NaCl (MP+Na), and a high amount of protein (HP; 53 g), HP plus 70 mmol KHCO3 (HP+K), and HP plus 70 mmol NaCl (HP+Na). Protein was casein:lactalbumin (80:20), except for the treatments with added sodium chloride, to which only casein was added. In study 2, the effects of HP and HP plus 50 mmol KHCO3 (HP+K) were compared with those of MP or MP plus 7.5 mmol phosphate (MP+Pi), equaling the additional phosphate of HP, in 10 adult men. Subjects completed all treatments in random order. In study 1, the peak of calcium excretion was at 3 h for all treatments, except for HP+K, which indicated an acute hypocalciuric effect of potassium. Unexpectedly, there was no hypercalciuric effect of adding sodium chloride, nor was urine sodium increased. In study 2, calcium excretion was significantly higher with HP than with MP+Pi but not with MP at 3 h, indicating an acute hypercalciuric effect of protein alone. A hypocalciuric effect of potassium (HP+K compared with HP) but not of phosphate (MP compared with MP+Pi) was seen. An acute load test measuring changes 3 h postload was appropriate for examining the calciuric effects of protein and potassium bicarbonate, but not those of sodium chloride or phosphate in adults.

Bone mineral and calcium accretion during puberty.

We measured bone mineral content (BMC) and estimated calcium accretion in children to provide insight into dietary calcium requirements during growth. Anthropometric measurements were done semiannually and whole-body BMC was measured annually by dual-energy X-ray absorptiometry for 4 y in 228 children (471 scans in 113 boys and 507 scans in 115 girls). Mean values for BMC, skeletal area, and height were calculated for 1-y age groups from 9.5 to 19.5 y of age. Cross-sectional analysis of the pooled data gave peak height velocity and peak BMC velocity (PBMCV) and the ages at which these occurred (13.3 y in boys and 11.4 y in girls). PBMCV did not peak until 1.2 y after peak height velocity in boys and 1.6 y after peak height velocity in girls. Within 3 y on either side of PBMCV, boys had consistently higher BMC and BMC velocity compared with girls and the discrepancy increased steadily through puberty. Three years before PBMCV, BMC values in girls were 69% of those in boys; 3 y after peak height velocity this proportion fell to 51%. PBMCV was 320 g/y in boys and 240 g/y in girls. Under the assumption that bone mineral is 32.2% calcium, these values corresponded to a daily calcium retention of 282 mg in boys and 212 mg in girls. Individual values could be much greater. In one boy in a group of six subjects for whom there were enough data for individual analysis through puberty, PBMCV was 555 g Ca/y or 490 mg Ca/d. Such high skeletal demands for calcium require large dietary calcium intakes and such requirements may not be met immediately in some children.

Evidence for two distinct types of postsynaptic alpha-adrenoceptor in vascular smooth muscle in vivo.

1 The effects of the highly selective alpha(1)-adrenoceptor antagonist, prazosin, and the relatively selective alpha(2)-adrenoceptor antagonist, yohimbine, on the pressor responses to intravenous injections of phenylephrine and noradrenaline have been examined in anaesthetized cats and pithed rats in an attempt to determine whether alpha(1)- and alpha(2)-adrenoceptors are located postsynaptically on vascular smooth muscle.2 In anaesthetized cats prazosin caused a much greater reduction in the pressor responses to phenylephrine than to noradrenaline or splanchnic nerve stimulation (after adrenalectomy). Yohimbine was of similar potency in reducing the pressor responses to each stimulus.3 A differential blocking activity of prazosin against intra-arterial injections of phenylephrine and noradrenaline was also demonstrated in the blood-perfused cat hind limb. As in the whole animal, prazosin was more potent against phenylephrine than noradrenaline. A similar, though less marked, effect was seen in the mesenteric circulation, but not in the renal circulation, where prazosin was almost equipotent in reducing responses to phenylephrine and noradrenaline.4 In pithed rats prazosin was a potent, competitive antagonist of phenylephrine, but had little effect against noradrenaline; only the responses to high doses of noradrenaline were reduced by prazosin. Yohimbine was approximately equipotent as an antagonist of phenylephrine and noradrenaline. In the anococcygeus muscle, prazosin was as potent an antagonist of noradrenaline as it was of phenylephrine on vascular smooth muscle.5 The results suggest that there are two types of alpha-adrenoceptor in the vasculature of cats and rats. Phenylephrine produces pressor responses by stimulating one type of postsynaptic alpha-adrenoceptor that is blocked by prazosin and yohimbine; these are alpha(1)-adrenoceptors. Noradrenaline exerts some of its effect via these receptors but most of its effect appears to be exerted through prazosin-insensitive receptors. The latter receptors appear to differ from alpha(2)-adrenoceptors.

The inhibitory effect of dietary calcium on iron bioavailability: a cause for concern?

Increased intake of calcium has been recently recommended by a National Institutes of Health (NIH) Consensus Development Panel on Optimal Calcium Intake. However, high intakes of dietary calcium can inhibit iron absorption if both are present in the same meal. The mechanism for the calcium-iron interaction is not known. A recent study has demonstrated that separating foods high in calcium from meals high in iron can prevent some of the calcium-induced inhibition of iron absorption. The feasibility of changing the nature of meals or the timing of calcium supplementation to adjust for this phenomenon is untested.