Is a lower dose of vitamin D supplementation enough to increase 25(OH)D status in a sunny country?

Calcium and vitamin D are essential nutrients for bone metabolism Vitamin D can either be obtained from dietary sources or cutaneous synthesis. The study was conducted in subtropic weather; therefore, some might believe that the levels of solar radiation would be sufficient in this area. To evaluate calcium and vitamin D supplementation in postmenopausal women with osteoporosis living in a sunny country. A 3-month controlled clinical trial with 64 postmenopausal women with osteoporosis, mean age 62 +/- A 8 years. They were randomly assigned to either the supplement group, who received 1,200 mg of calcium carbonate and 400 IU (10 mu g) of vitamin D(3,) or the control group. Dietary intake assessment was performed, bone mineral density and body composition were measured, and biochemical markers of bone metabolism were analyzed. Considering all participants at baseline, serum vitamin D was under 75 nmol/l in 91.4% of the participants. The concentration of serum 25(OH)D increased significantly (p = 0.023) after 3 months of supplementation from 46.67 +/- A 13.97 to 59.47 +/- A 17.50 nmol/l. However, the dose given was limited in effect, and 86.2% of the supplement group did not reach optimal levels of 25(OH)D. Parathyroid hormone was elevated in 22.4% of the study group. After the intervention period, mean parathyroid hormone tended to decrease in the supplement group (p = 0.063). The dose given (400 IU/day) was not enough to achieve 25(OH)D concentration, considered optimal for bone health.

Treadmill Training Increases SIRT-1 and PGC-1 alpha Protein Levels and AMPK Phosphorylation in Quadriceps of Middle-Aged Rats in an Intensity-Dependent Manner

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Low serum levels of 25-hydroxyvitamin D (25-OHD) in children with autism

Objective: To confirm previous evidence suggesting an association between autism and low vitamin D serum levels. Methods: This preliminary exploratory study assessed the circulating levels of 25-hydroxyvitamin D (25-OHD) in pediatric patients with autism and in typically developing controls from Juiz de Fora, Brazil. Results: Serum levels of 25-OHD were lower in children with autism (26.48 ± 3.48 ng mL-1) when compared to typically developing subjects (40.52 ± 3.13 ng mL-1) (p < 0.001). Conclusion: Our findings attest to the importance of vitamin supplementation during pregnancy and in the treatment of children with autism, who tend to present low vitamin D consumption rates.

Rapid effects of 1alpha,25-dihydroxyvitamin D3 on osteoblasts: Studies of membrane transducers that affect calcium signals

1,25-dihydroxyvitamin D3 [1,25(OH)2D 3] exerts pleiotropic effects on osteoblasts via both long-term nuclear receptor-mediated and rapid membrane-initiated pathways during bone remodeling and mineral homeostasis. This study explored the membrane transducers that mediate rapid effects of 1,25(OH)2D3 on osteoblasts, including sphingomyelinase (SMase) and L-type voltage sensitive calcium channels (VSCCs). ^ It was previously demonstrated that 1,25(OH)2D3 stimulates transmembrane influx of Ca2+ through VSCCs in ROS 17/2.8 osteoblasts, however the molecular identity of 1,25(OH)2D 3-regulated VSCC has not been known. In this study, on the basis of in vitro tests of three unique ribozymes specifically cleaving a1C mRNA, I transfected ROS 17/2.8 cells with vectors coding recombinant ribozyme modified with U1 snRNA structure, and successfully selected stable clonal cells in which the expression of a1C was strikingly reduced. Ca2+ influx studies in these cells compared to control transfectants showed selective attenuation of depolarization- and 1,25(OH)2D3-regulated Ca2+ responses. These results allow us to conclude that the cardiac ( a1C ) subtype of the L-type VSCC is the major membrane transducer of Ca 2+ influx in osteoblasts. ^ I also demonstrated that 1,25(OH)2D3 induces a rapid hydrolysis of membrane sphingomyelin (SM) in ROS 17/2.8 cells, with the concomitant generation of ceramide, detectable at 15 minute, and maximal at 1 hour after addition. Sphingosine, sphingosine-1-phosphate (SPP) and sphingosylphosphorylcholine (SPC), downstream products of SM hydrolysis, but not ceramide, elicit Ca 2+ release from intracellular stores. Considering ceramide, sphingosine, and SPP as second messengers modulating intracellular kinases or phosphatases, these findings implicate sphingolipid-signaling pathways in transducing rapid effects of 1,25(OH)2D3 on osteoblasts. In structure/function analyses of sphingolipid signaling, it was observed that psychosine elicits Ca2+ release from intracellular stores. This challenges the dogma that sphingosine phosphorylation permits mobilization of Ca2+ , because psychosine is a sphingosine analog galactosylated at 1-carbon, preventing phosphorylation at that site. Psychosine is the pathological metabolite found in patients with Krabbe's disease, suggesting that psychosine disrupts the physiological sphingolipid signaling by chronic release of Ca2+ from intracellular stores. ^ Slower SM turnover than Ca2+ influx through VSCCs in response to 1,25(OH)2D3 demonstrates ceramide does not mediate the 1,25(OH)2D3-induced Ca2+ signaling, a conclusion endorsed further by the failure of ceramide to induce Ca 2+ signaling. ^

Bericht der Central-Abtheilung über den Gesetzentwurf wegen Ausschreibung einer Zwangs-Anleihe: Der geringe Erfolg der am 25. April d. J., auf den Grund der dazu von dem vereinigten Landtage in der Sitzung vom 10. April ...

Welsch (Projektbearbeiter): Der Gesetzentwurf über die Ausschreibung einer zu 3 1/3 % verzinslichen Zwangsanleihe zwecks Beschaffung des Betrages von 15 Millionen Talern wird von den Abteilungen der Nationalversammlung mit sechs gegen zwei Stimmen angenommen

(Table 3) Carbon and oxygen isotopic data of carbonates from Core SLR 37-1, HYC 25-1 and an aragonite crust from station DR 35-1

An area of massive barite precipitations was studied at a tectonic horst in 1500 m water depth in the Derugin Basin, Sea of Okhotsk. Seafloor observations and dredge samples showed irregular, block- to column-shaped barite build-ups up to 10 m high which were scattered over the seafloor along an observation track 3.5 km long. High methane concentrations in the water column show that methane expulsion and probably carbonate precipitation is a recently active process. Small fields of chemoautotrophic clams (Calyptogena sp., Acharax sp.) at the seafloor provide additional evidence for active fluid venting. The white to yellow barites show a very porous and often layered internal fabric, and are typically covered by dark-brown Mn-rich sediment; electron microprobe spectroscopy measurements of barite sub-samples show a Ba substitution of up to 10.5 mol% of Sr. Rare idiomorphic pyrite crystals (1%) in the barite fabric imply the presence of H2S. This was confirmed by clusters of living chemoautotrophic tube worms (1 mm in diameter) found in pores and channels within the barite. Microscopic examination showed that micritic aragonite and Mg-calcite aggregates or crusts are common authigenic precipitations within the barite fabric. Equivalent micritic carbonates and barite carbonate cemented worm tubes were recovered from sediment cores taken in the vicinity of the barite build-up area. Negative ?13C values of these carbonates (>?43.5? PDB) indicate methane as major carbon source; ?18O values between 4.04 and 5.88? PDB correspond to formation temperatures, which are certainly below 5°C. One core also contained shells of Calyptogena sp. at different core depths with 14C-ages ranging from 20 680 to >49 080 yr. Pore water analyses revealed that fluids also contain high amounts of Ba; they also show decreasing SO42- concentrations and a parallel increase of H2S with depth. Additionally, S and O isotope data of barite sulfate (?34S: 21.0-38.6? CDT; ?18O: 9.0-17.6? SMOW) strongly point to biological sulfate reduction processes. The isotope ranges of both S and O can be exclusively explained as the result of a mixture of residual sulfate after a biological sulfate reduction and isotopic fractionation with 'normal' seawater sulfate. While massive barite deposits are commonly assumed to be of hydrothermal origin, the assemblage of cheomautotrophic clams, methane-derived carbonates, and non-thermally equilibrated barite sulfate strongly implies that these barites have formed at ambient bottom water temperatures and form the features of a Giant Cold Seep setting that has been active for at least 49 000 yr.

Down-regulation of NF-kappa B protein levels in activated human lymphocytes by 1,25-dihydroxyvitamin D3.

The effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2)D3], a steroid hormone with immunomodulating properties, on nuclear factor kappa B (NF-kappa B) proteins was examined in in vitro activated normal human lymphocytes by Western blot analysis. Over a 72-hr period of activation, the expression of the 50-kDa NF-kappa B, p50, and its precursor, p105, was increased progressively. When cells were activated in the presence of 1,25(OH)2D3, the levels of the mature protein as well as its precursor were decreased. The effect of the hormone on the levels of p50 was demonstrable in the cytosolic and nuclear compartments; it required between 4 and 8 hr and was specific, as 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were ineffective. Besides p50, 1,25(OH)2D3 decreased the levels of another NF-kappa B protein, namely c-rel. In addition, 1,25(OH)2D3 decreased the abundance of a specific DNA-protein complex formed upon incubation of nuclear extracts from activated lymphocytes with a labeled NF-kappa B DNA binding motif. Further, 1,25(OH)2D3 inhibited the transcriptional activity of NF-kappa B in Jurkat cells transiently transfected with a construct containing four tandem repeats of the NF-kappa B binding sequence of the immunoglobulin kappa light chain gene linked to the chloramphenicol acetyltransferase reporter gene. These observations demonstrate directly that there is de novo synthesis of NF-kappa B during human lymphocyte activation and suggest that this process is hormonally regulated.

Crystal structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin.

We report the 1.8-A crystal structure of the CD11a I-domain with bound manganese ion. The CD11a I-domain contains binding sites for intercellular adhesion molecules 1 and 3 and can exist in both low- and high-affinity states. The metal-bound form reported here is likely to represent a high-affinity state. The CD11a I-domain structure reveals a strained hydrophobic ridge adjacent to the bound metal ion that may serve as a ligand-binding surface and is likely to rearrange in the absence of bound metal ion. The CD11a I-domain is homologous to domains found in von Willebrand factor, and mapping of mutations found in types 2a and 2b von Willebrand disease onto this structure allows consideration of the molecular basis of these forms of the disease.

The crystal structure of an N-terminal two-domain fragment of vascular cell adhesion molecule 1 (VCAM-1): a cyclic peptide based on the domain 1 C-D loop can inhibit VCAM-1-alpha 4 integrin interaction.

Vascular cell adhesion molecule 1 (VCAM-1) represents a structurally and functionally distinct class of immunoglobulin superfamily molecules that bind leukocyte integrins and are involved in inflammatory and immune functions. X-ray crystallography defines the three-dimensional structure of the N-terminal two-domain fragment that participates in ligand binding. Residues in domain 1 important for ligand binding reside in the C-D loop, which projects markedly from one face of the molecule near the contact between domains 1 and 2. A cyclic peptide that mimics this loop inhibits binding of alpha 4 beta 1 integrin-bearing cells to VCAM-1. These data demonstrate how crystallographic structural information can be used to design a small molecule inhibitor of biological function.

Metal-insulator transition in Nd(1-x) Eu(x) NiO(3) probed by specific heat and anelastic measurements

Oxides RNiO(3) (R - rare-earth, R not equal La) exhibit a metal-insulator (MI) transition at a temperature T(MI) and an antiferromagnetic (AF) transition at T(N). Specific heat (C(P)) and anelastic spectroscopy measurements were performed in samples of Nd(1-x)Eu(x)NiO(3), 0 <= x <= 0.35. For x - 0, a peak in C(P) is observed upon cooling and warming at essentially the same temperature T(MI) - T(N) similar to 195 K, although the cooling peak is much smaller. For x >= 0.25, differences between the cooling and warming curves are negligible, and two well defined peaks are clearly observed: one at lower temperatures that define T(N), and the other one at T(MI). An external magnetic field of 9 T had no significant effect on these results. The elastic compliance (s) and the reciprocal of the mechanical quality factor (Q(-1)) of NdNiO(3), measured upon warming, showed a very sharp peak at essentially the same temperature obtained from C(P), and no peak is observed upon cooling. The elastic modulus hardens below T(MI) much more sharply upon warming, while the cooling and warming curves are reproducible above T(MI). Conversely, for the sample with x - 0.35, s and Q(-1) curves are very similar upon warming and cooling. The results presented here give credence to the proposition that the MI phase transition changes from first to second order with increasing Eu doping. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3549615]

Calcium absorption in postmenopausal osteoporosis: Benefit of HRT plus calcitriol, but not HRT alone, in both malabsorbers and normal absorbers

In a randomized trial involving 71 postmenopausal osteoporotic women with vertebral compression fractures, radiocalcium absorption studies using the Ca-45 single isotope method (alpha) were performed at baseline and after 8 months of treatment with either continuous combined hormone replacement therapy (HRT, as piperazine estrone sulfate 0.625-0.937mg daily +/- medroxyprogesterone acetate 2.5 mg daily depending on uterine status) or HRT plus calcitriol 0.25 mu g twice daily. A calcium supplement of 600 mg nocte was given to only those women who had a daily calcium intake of less than 1 g per day at baseline, as assessed by recalled dietary intake. There was a significant decrease 0.74 (+/- 0.35 SD) to 0.58 (+/- 0.22), Delta alpha = -0.17 (+/- 0.26), p<0.0005] in alpha at 8 months compared with baseline in the HRT-treated group, but a significant increase [0.68 (+/- 0.31) to 0.84 (+/- 0.27), Delta alpha = +0.16 (+/- 0.30), p<0.003] in the HRT-plus-calcitriol treated patients, resulting in alpha being significantly higher after 8 months in the latter group than in the HRT-only group. Although 72% of the patients had been supplemented with calcium between the first and second studies, separate analyses revealed that the change in calcium intake had not affected the result. Further breakdown of the groups into baseline 'normal' absorbers (alpha greater than or equal to 0.55) and 'malabsorbers' (alpha <0.55) revealed that alpha decreased with HRT treatment only in the normal absorbers, and remained stable in the malabsorbers. Conversely, following HRT plus calcitriol treatment, alpha increased only in the malabsorbers, the normal absorbers in this group remaining unchanged. In conclusion, our data show that HRT, of the type and dose used in this study, did not produce an increase in absorption efficiency; it was in fact associated with a fall. increased absorption efficiency cannot be achieved unless calcitriol is used concurrently, and then only in patients with malabsorption. Calcitriol also had a significant effect in normal absorbers in that it prevented the decline in alpha seen with HRT alone, and thus should be considered in all patients with postmenopausal osteoporosis treated with HRT.

Central substance P NK(1) receptors are involved in fever induced by LPS but not by IL-1 beta and CCL3/MIP-1 alpha in rats

Substance P (SP) is a neuropeptide that can modulate inflammatory mediator release through activation of NK(1) receptors (NK(1)R). Some studies have also suggested the involvement of SP in lipopolysaccharide (LPS)-induced fever. However, the precise contribution of this neuropeptide to the pathways activated during fever is unknown. In this study we investigated the effect of a selective NK(1)R antagonist, SR140333B, on the febrile response induced by LPS and cytokines. Our results show that the systemic injection of SR140333B did not modify the fever induced by LPS at a dose that is able to reduce protein extravasation induced by SP in the skin. On the other hand, intracerebroventricular administration of 5R140333B significantly reduced the fever induced by peripheral injection of LPS. These data emphasize an important role for SP in the central nervous system during the febrile response to LPS, and are reinforced by the fact that intracerebroventricular injection of SP also induced fever in a dose-dependent manner in captopril-treated rats. Considering that the febrile response can result from the generation of several endogenous pyrogens, among them interleukin (IL)-1 beta and macrophage inflammatory protein-1 alpha (CCL3/MIP-1 alpha), we also examined the effect of SR140333B on the fever induced by these cytokines which act through prostaglandin-dependent and independent mechanisms, respectively. Surprisingly, SR140333B did not modify the febrile response to IL-1 beta or CCL3/MIP-1 alpha. Altogether these data suggest that the central action of SP is essential for LPS-, but not for IL-1 beta- or CCL3/MIP-1 alpha-induced fever. (C) 2011 Elsevier B.V. All rights reserved.