Effect of increasing dietary calcium through supplements and dairy food on body weight and body composition: a meta-analysis of randomised controlled trials

This meta-analysis of randomised controlled trials assessed the effect of Ca on body weight and body composition through supplementation or increasing dairy food intake. Forty-one studies met the inclusion criteria (including fifty-one trial arms; thirty-one with dairy foods (n 2091), twenty with Ca supplements (n 2711). Ca intake was approximately 900 mg/d higher in the supplement groups compared with control. In the dairy group, Ca intake was approximately 1300 mg/d. Ca supplementation did not significantly affect body weight (mean change ( - 0&middot;17, 95 % CI - 0&middot;70, 0&middot;37) kg) or body fat (mean change ( - 0&middot;19, 95 % CI - 0&middot;51, 0&middot;13) kg) compared to control. Similarly, increased dairy food intake did not affect body weight ( - 0&middot;06, 95 % CI - 0&middot;54, 0&middot;43) kg or body fat change ( - 0&middot;36, 95 % CI - 0&middot;80, 0&middot;09) kg compared to control. Sub-analyses revealed that dairy supplementation resulted in no change in body weight (nineteen studies, n 1010) ( - 0&middot;32, 95 % CI - 0&middot;93, 0&middot;30 kg, P= 0&middot;31), but a greater reduction in body fat (thirteen studies, n 564) ( - 0&middot;96, 95 % CI - 1&middot;46, - 0&middot;46 kg, P < 0&middot;001) in the presence of energy restriction over a mean of 4 months compared to control. Increasing dietary Ca intake by 900 mg/d as supplements or increasing dairy intake to approximately 3 servings daily (approximately 1300 mg of Ca/d) is not an effective weight reduction strategy in adults. There is, however, an indication that approximately 3 servings of dairy may facilitate fat loss on weight reduction diets in the short term.

Studies of the human lymphocyte P2Z receptor and its activation of phospholipase D

Extracellular adenosine 5′-triphosphate (ATP) is an agonist for the P2Z receptor of human leukaemic lymphocytes and opens a Ca ²⁺-selective ion channel, which also conducts Ba²⁺, Sr²⁺ and the small fluorescent dye, ethidium⁺. A wide range of receptor agonists, many of which raise cytosolic [Ca<sup>2+] activate phospholipase D (PLD). In the present study, it was shown that both ATP and 3′-O-(4-benzoylbenzoyl)-ATP (BzATP) stimulated PLD activity in a concentration-dependent manner, and the inhibitory effects of suramin, oxidised ATP, extracellular Na⁺ and Mg²⁺ suggested that the effect of these agonists is mediated by P2Z receptors. The role of divalent cations in ATP-stimulated PLD activity was investigated. Several agonists (eg ATP, thapsigargin, ionomycin) stimulated a rise in cytosolic [Ca<sup>2+] in human lymphocytes, but only ATP and ionomycin stimulated PLD activity. When Ca<sup>2+ influx was prevented by EGTA, the majority of ATP-stimulated and all of ionomycin-stimulated PLD activity was inhibited. Preloading cells with the Ca<sup>2+ chelator, BAPTA, reduced cytosolic [Ca<sup>2+] and, paradoxically, ATP-stimulated PLD activity was potentiated. ATP-stimulated PLD activity was supported by both Ba²⁺ and Sr²⁺ when they were substituted for extracellular Ca<sup>2+. Furthermore, both ATP-stimulated PLD activity and ATP-stimulated ¹³³Ba²⁺ influx showed a linear dependence on extracellular [Ba²⁺]. Thus it was concluded that ATP stimulated PLD activity in direct proportion to the influx of divalent cations through the P2Z ion channel and this PLD activity was insensitive to changes in bulk cytosolic [Ca<sup>2+]. The calmodulin (Ca<sup>2+/CaM) inhibitor, trifluoperazine (TFP) inhibited ionomycin- and ATP-stimulated PLD activity and ATP-stimulated apoptosis, but had no effect on PLD activity already activated by ATP. However, TFP inhibited ATP-stimulated Ca<sup>2+, Ba²⁺ and ethidium⁺ fluxes, at concentrations below those which inhibit Ca<sup>2+/CaM, suggesting that TFP inhibits the P2Z receptor. Similarly, the isoquinolinesulphonamide, KN-62, a selective inhibitor of Ca<sup>2+/CaM-dependent protein kinase II (CaMKII), also prevented ATP-stimulated apoptosis, but had no effect on pre-activated PLD. In addition, KN-62, and an analogue, KN-04, which has no effect on CaMKII, potently inhibited ATP-stimulated Ba²⁺ influx (IC₅₀ 12.7 ± 1.5 and 17.3 ± 2.7 nM, respectively), ATP-stimulated ethidium⁺ uptake (IC₅₀ 13.1 ± 2.6 and 37.2 ± 8.9 nM, respectively), ATP-stimulated phospholipase D activity (50% inhibition 5.9 ± 1.2 and 9.7 ± 2.8 nM, respectively) and ATP-induced shedding of the surface adhesion molecule, L-selectin (IC₅₀ 31.5 ± 4.5 and 78.7 ± 10.8 nM, respectively). They did not inhibit phorbol ester- or ionomycin-stimulated PLD activity or phorbol ester-induced L-selectin shedding. Neither KN-62 nor KN-04 (both 500 nM) have any effect on UTP-stimulated Ca<sup>2+ transients in fura-2-loaded human neutrophils, a response which is mediated by the P2Y₂ receptor, neither did they inhibit ATP-stimulated contractile responses mediated by the P2X₁ receptor of guinea pig urinary bladder. Thus, KN-62 and KN-04 are almost equipotent as P2Z inhibitors with IC₅₀s in the nanomolar, indicating that their actions cannot be due to CaMKII inhibition, but rather that they are potent and direct inhibitors of the P2Z receptor. Extracellular ATP-induced shedding of L-selectin from lymphocytes into the medium is a Ca<sup>2+-independent response. L-selectin is either cleaved by a metalloproteinase or a PLD with specificity for glycosylphosphatidylinositol (GPI). The novel hydroxamic acid-based zinc chelator, Ro-31-9790 blocks ATP-induced L-selectin shedding, but was without effect on ATP-induced Ba²⁺ influx or ATP-stimulated PLD activity. Furthermore, another zinc chelator, 1,10-phenanthroline, an inhibitor of a GPI-PLD, potentiated rather than inhibited ATP-stimulated PLD activity, suggesting that ATP-induced L-selectin shedding and ATP-stimulated PLD activity are independent of each other. Although extracellular ATP is the natural ligand for the lymphocyte P2Z receptor, it is less potent than BzATP in stimulating Ba²⁺ influx. Concentration-response curves for BzATP- and ATP-stimulated ethidium⁺ influx gave EC₅₀s 15.4 ± 1.4 µM and 85.6 ± 8.8 µM, respectively. The maximal response to ATP was only 69.8 ± 1.9% of that for BzATP. Hill coefficients were 3.17 ± 0.24 and 2.09 ± 0.45 for BzATP and ATP respectively, suggesting greater positive cooperativity for BzATP than for ATP in opening the P2Z-operated ion channel. A rank order of agonist potency of BzATP > ATP = 2MeSATP > ATPγS was observed for agonist-stimulated ethidium⁺ influx, while maximal influxes followed a rank order of BzATP > ATP > 2MeSATP > ATPγS. When ATP (300 -1000 µM) was added simultaneously with 30 µM BzATP (EC₉₀), it reduced both ethidium⁺ and Ba²⁺ fluxes by 30 - 40% relative to values observed with BzATP alone. KN-62, previously shown to be a specific inhibitor of the lymphocyte P2Z receptor, was a less potent antagonist of BzATP-induced fluxes than ATP, when maximal concentrations of both agonists (50 and 500 µM respectively) were used. However, when BzATP (18 µM) was used at a concentration equiactive with a maximally effective ATP concentration, KN-62 showed the same inhibitory potency for both agonists. The ecto-ATPase antagonist, ARL-67156, inhibited both ATP- and BzATP-stimulated Ba²⁺ influx, suggesting that the lower efficacy of ATP compared with BzATP was not due to preferential hydrolysis of ATP. Thus, the natural ligand, ATP, is a partial agonist for the P2Z receptor while BzATP is a full agonist. Moreover the competitive studies show that only a single class of P2-receptor (P2Z class) is expressed on human leukaemic lymphocytes. Both ATP- and BzATP-stimulated PLD activity were significantly inhibited (P < 0.05) when cells were suspended in iso-osmotic choline Cl medium. Choline⁺ was found to be a permeant for the P2Z ion channel, since ATP induced a large uptake of [¹⁴C]choline⁺ (60 to 150 µmol/ml intracellular water) during a 5 min incubation, which remained in the cells for several hours, and ATP was used to load cells with these levels of choline⁺. Intracellular choline⁺ inhibited ATP-, BzATP-, PMA- and ionomycin-stimulated PLD activity. Brief exposure of lymphocytes to ATP increased the subsequent basal rate of ethidium⁺ uptake, and this was prevented by intracellular choline⁺. It is proposed that P2Z-mediated Ca<sup>2+ influx in lymphocytes activates PLD leading to significantly changes of the phospholipid composition of the plasma membrane, which subsequently produces a permeability lesion, which in turn contributes to cell death.

Biodegradable Mg-Zr-Ca alloys for bone implant materials

Mg&ndash;Zr&ndash;Ca alloys were developed for new biodegradable bone implant materials. The microstructure and mechanical property of the Mg&ndash;xZr&ndash;yCa [x=0&middot;5, 1&middot;0% and y=1&middot;0, 2&middot;0% (wt-% hereafter)] alloys were characterised by optical microscopy, compressive and hardness tests. The in vitro cytotoxicity of the alloys was assessed using osteoblast-like SaOS₂ cells. The corrosion behaviour of these alloys was evaluated by soaking the alloys in simulated body fluid (SBF) and modified minimum essential medium (MMEM). Results indicated that the mechanical properties of the Mg&ndash;Zr&ndash;Ca are in the range of the mechanical properties of natural bone. The corrosion rate and biocompatibility decreases with the increase in the Ca content in the Mg&ndash;Zr&ndash;Ca alloys. The solutions of SBF and MMEM with the immersion of the Mg&ndash;Zr&ndash;Ca alloys show strong alkalisation. The Zr addition to the Mg&ndash;Zr&ndash;Ca alloys leads to an increase in the corrosion resistance, compressive strength and the ductility of the alloys, and a decrease in the elastic modulus of the Mg&ndash;Zr&ndash;Ca alloys.

The effects of progressive resistance training combined with a whey-protein drink and vitamin D supplementation on glycaemic control, body composition and cardiometabolic risk factors in older adults with type 2 diabetes: study protocol for a randomized c

While physical activity, energy restriction and weight loss are the cornerstone of type 2 diabetes management, less emphasis is placed on optimizing skeletal muscle mass. As muscle is the largest mass of insulin-sensitive tissue and the predominant reservoir for glucose disposal, there is a need to develop safe and effective evidence-based, lifestyle management strategies that optimize muscle mass as well as improve glycaemic control and cardiometabolic risk factors in people with this disease, particularly older adults who experience accelerated muscle loss.

Collagen type-I leads to in vivo matrix mineralization and secondary stabilization of Mg-Zr-Ca alloy implants

Biodegradable magnesium-zirconia-calcium (Mg-Zr-Ca) alloy implants were coated with Collagen type-I (Coll-I) and assessed for their rate and efficacy of bone mineralization and implant stabilization. The phases, microstructure and mechanical properties of these alloys were analyzed using X-ray diffraction (XRD), optical microscopy and compression test, respectively, and the corrosion behavior was established by their hydrogen production rate in simulated body fluid (SBF). Coll-I extracted from rat tail, and characterized using fourier transform infrared (FT-IR) spectroscopy, was used for dip-coating the Mg-based alloys. The coated alloys were implanted into the femur bones of male New Zealand white rabbits. In vivo bone formation around the implants was quantified by measuring the bone mineral content/density (BMC/BMD) using dual-energy X-ray absorptiometry (DXA). Osseointegration of the implant and new bone mineralization was visualized by histological and immunohistochemical analysis. Upon surface coating with Coll-I, these alloys demonstrated high surface energy showing enhanced performance as an implant material that is suitable for rapid and efficient new bone tissue induction with optimal mineral content and cellular properties. The results demonstrate that Coll-I coated Mg-Zr-Ca alloys have a tendency to form superior trabecular bone structure with better osteoinduction around the implants and higher implant secondary stabilization, through the phenomenon of contact osteogenesis, compared to the control and uncoated ones in shorter periods of implantation. Hence, Coll-I surface coating of Mg-Zr-Ca alloys is a promising method for expediting new bone formation in vivo and enhancing osseointegration in load bearing implant applications.

Seasonal timing of the spring departure of waders from the Banc D'Arguin, Mauritania

The northward departure of 13 wader species was studied in the Baie d' Aouatif, Bane d'Arguin, Mauritania, in the springs of 1985, 1986 and 1988. Waders left the area in the late afternoon. Wind speed and direction were registered near ground level (all years) and at altitudes up to 5 km (in 1988). A total of 31 000 waders were observed heading northwards, with those species wintering locally in largest numbers being most common. The majority of wader species showed fairly short periods of departure and unimodal departure peaks. Redshank and Dunlin departed over extended periods. Average departure dates of species correlated positively with the estimated midpoints of ranges in breeding latitude (ca. 2 d per 0 latitude).  Since winds at ground level did not correlate with winds at higher altitudes, and since it is likely that the departing waders traveled at great heights, it was not surprising that there is no correlation between the average afternoon tail wind vector at ground level and the daily departure intensity. We suggest that the timing ofdeparture from the Bane d'Arguin is largely under internal, instead of under direct environmental, control.