Higher dietary calcium intakes are associated with reduced risks of fractures, cardiovascular events, and mortality: a prospective cohort study of older men and women

The aim of this population-based, prospective cohort study was to investigate long-term associations between dietary calcium intake and fractures, non-fatal cardiovascular disease (CVD), and death from all causes. Participants were from the Melbourne Collaborative Cohort Study, which was established in 1990 to 1994. A total of 41,514 men and women (∼99% aged 40 to 69 years at baseline) were followed up for a mean (SD) of 12 (1.5) years. Primary outcome measures were time to death from all causes (n = 2855), CVD-related deaths (n = 557), cerebrovascular disease-related deaths (n = 139), incident non-fatal CVD (n = 1827), incident stroke events (n = 537), and incident fractures (n = 788). A total of 12,097 participants (aged ≥50 years) were eligible for fracture analysis and 34,468 for non-fatal CVD and mortality analyses. Mortality was ascertained by record linkage to registries. Fractures and CVD were ascertained from interview ∼13 years after baseline. Quartiles of baseline energy-adjusted calcium intake from food were estimated using a food-frequency questionnaire. Hazard ratios (HR) and odds ratios (OR) were calculated for quartiles of dietary calcium intake. Highest and lowest quartiles of energy-adjusted dietary calcium intakes represented unadjusted means (SD) of 1348 (316) mg/d and 473 (91) mg/d, respectively. Overall, there were 788 (10.3%) incident fractures, 1827 (9.0%) incident CVD, and 2855 people (8.6%) died. Comparing the highest with the lowest quartile of calcium intake, for all-cause mortality, the HR was 0.86 (95% confidence interval [CI] 0.76-0.98, ptrend  = 0.01); for non-fatal CVD and stroke, the OR was 0.84 (95% CI 0.70-0.99, ptrend  = 0.04) and 0.69 (95% CI 0.51-0.93, ptrend  = 0.02), respectively; and the OR for fracture was 0.70 (95% CI 0.54-0.92, ptrend  = 0.004). In summary, for older men and women, calcium intakes of up to 1348 (316) mg/d from food were associated with decreased risks for fracture, non-fatal CVD, stroke, and all-cause mortality.

Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest

The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8), or no exercise (control n = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest (p ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6-24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control (p = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels.

Trabecular and cortical bone density and architecture in women after 60 days of bed rest using high-resolution pQCT: WISE 2005

Prolonged bed rest is used to simulate the effects of spaceflight and causes disuse-related loss of bone. While bone density changes during bed rest have been described, there are no data on changes in bone microstructure. Twenty-four healthy women aged 25 to 40 years participated in 60 days of strict 6-degree head-down tilt bed rest (WISE 2005). Subjects were assigned to either a control group (CON, n = 8), which performed no countermeasures; an exercise group (EXE, n = 8), which undertook a combination of resistive and endurance training; or a nutrition group (NUT, n = 8), which received a high-protein diet. Density and structural parameters of the distal tibia and radius were measured at baseline, during, and up to 1 year after bed rest by high-resolution peripheral quantitative computed tomography (HR-pQCT). Bed rest was associated with reductions in all distal tibial density parameters (p < 0.001), whereas only distal radius trabecular density decreased. Trabecular separation increased at both the distal tibia and distal radius (p < 0.001), but these effects were first significant after bed rest. Reduction in trabecular number was similar in magnitude at the distal radius (p = 0.021) and distal tibia (p < 0.001). Cortical thickness decreased at the distal tibia only (p < 0.001). There were no significant effects on bone structure or density of the countermeasures (p ≥ 0.057). As measured with HR-pQCT, it is concluded that deterioration in bone microstructure and density occur in women during and after prolonged bed rest. The exercise and nutrition countermeasures were ineffective in preventing these changes.

Kinetic Analysis of Substrate Utilization by Native and TNAP-, NPP1-, or PHOSPHO1-Deficient Matrix Vesicles

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prospecção geofísica em ocorrência de cobre localizada na bacia sedimentar do Camaquã (RS)

Estudos de pesquisa mineral são fundamentais para o reconhecimento e a incorporação de novas reservas. Esse trabalho apresenta os resultados de aplicação do método geofísico da eletrorresistividade numa ocorrência mineralizada em carbonatos de cobre, por meio da técnica de caminhamento elétrico em arranjo azimutal. A área de estudos está inserida na bacia sedimentar do Camaquã, formada por um conjunto de unidades estratigráficas sedimentares e vulcanogênicas, onde são descritas diversas ocorrências cupríferas. A presença de azurita e malaquita em fraturas e zonas de maior porosidade em arenito encaixante define a geologia local. Os modelos de inversão revelam anomalias circulares de resistividade moderada para até 25m abaixo da ocorrência aflorante e anomalias de baixa resistividade em profundidades abaixo de 25m, além de áreas adjacentes com alta resistividade. Indicadores de mineralização descritos para ocorrências de cobre estudadas, no âmbito da bacia sedimentar do Camaquã, ocorrem na área de estudos e permitem caracterização em termos de resistividade elétrica. Áreas com silicificação apresentam alta resistividade, enquanto que valores intermediários são atribuídos a zonas com carbonatação e, finalmente, áreas de baixa resistividade, provavelmente, indicam concentrações de sulfetos disseminados.

Kinetic characterization of hypophosphatasia mutations with physiological substrates

We have analyzed 16 missense mutations of the tissue-nonspecific AP (TNAP) gene found in patients with hypophosphatasia. These mutations span the phenotypic spectrum of the disease, from the lethal perinatal/infantile forms to the less severe adult and odontohypophosphatasia. Site-directed mutagenesis was used to introduce a sequence tag into the TNAP cDNA and eliminate the glycosylphosphatidylinositol (GPI)-anchor recognition sequence to produce a secreted epitope-tagged TNAP (setTNAP). The properties of GPI-anchored TNAP (gpiTNAP) and setTNAP were found comparable. After introducing each single hypophosphatasia mutation, the setTNAP and mutant TNAP cDNAs were expressed in COS-1 cells and the recombinant flagged enzymes were affinity purified. We characterized the kinetic behavior, inhibition, and heat stability properties of each mutant using the artificial substrate p-nitrophenylphosphate (pNPP) at pH 9.8. We also determined the ability of the mutants to metabolize two natural substrates of TNAP, that is, pyridoxal-5'-phosphate (PLP) and inorganic pyrophosphate (PPi), at physiological pH. Six of the mutant enzymes were completely devoid of catalytic activity (R54C, R54P, A94T, R206W, G317D, and V365I), and 10 others (A16V, A115V, A160T, A162T, E174K, E174G, D277A, E281K, D361V, and G439R) showed various levels of residual activity. The A160T substitution was found to decrease the catalytic efficiency of the mutant enzyme toward pNPP to retain normal activity toward PPi and to display increased activity toward PLP. The A162T substitution caused a considerable reduction in the pNPPase, PPiase, and PLPase activities of the mutant enzyme. The D277A mutant was found to maintain high catalytic efficiency toward pNPP as substrate but not against PLP or PPi. Three mutations ( E174G, E174K, and E281K) were found to retain normal or slightly subnormal catalytic efficiency toward pNPP and PPi but not against PLP. Because abnormalities in PLP metabolism have been shown to cause epileptic seizures in mice null for the TNAP gene, these kinetic data help explain the variable expressivity of epileptic seizures in hypophosphatasia patients.

Polarização induzida aplicada no estudo de ocorrencia de cobre localizada a nordeste de Caçapava do Sul (RS)

Mineral research works are fundamentals for recognition and incorporation of new reserves. This paper present an integrated analysis of geologic and metallogenetics data, with results gotten from the application of the Induced Polarization geophysical method, in an copper ore occurrence, inserted in Camaquã sedimentary basin, situated in northeast of Caçapava do Sul city (RS). In area ocurr arkosean arenites average coarse, the intensely silicified and recrystallized, pertaining to Passo da Promessa Formation. The presence of azurita and malachite in breakings and high porosity zones of the host rock characterizes the mineral occurrence in surface, located in the crossing two fault families. The inversion models indicate the predominance of high chargeability in vulcanics tuff, rock of high porosity in relation to the andesites and metaconglomerates gifts in the area. The strong structural control of the mineral occurrence associated the high chargeability in volcanic tuff is indications of the hydrothermal fluid access by means of faults, until rocks with great porosity, where it occurred disseminations of copper sulfides in depth and carbonates in surface.

Correlação entre dados geofísicos e geológicos em ocorrência de cobre localizada na bacia sedimentar do Camaquã - RS

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caracterização geofísica no Gabro Santa Catarina, São Sepé (RS)

Geophysical methods are widely used in mineral exploration for several types of mineral deposits. When combined with direct studies as geochemistry, a substantial increase in the probability of ore discovery is possible in mineral exploration activities. Electrical geophysical methods are particularly promising in studies related to the search of sulphides due to the contrast of physical properties electric resistivity and chargeability. This paper presents the results obtained from the application of Resistivity (DC) and Induced Polarization methods, through the electrical profiling technique, aiming at evaluating the potential mineral of a gabbro intruded in a metasedimentary sequence, in an area where several occurrences of gold and copper were described. This gabbro is ranked on the Basic-Ultrabasic stratiform bodies, which gather peridotites, gabbros, and layered anortosites. Three radial lines of electrical profiling were performed, spaced of 60° and crossing at the area center, with readings of electric resistivity and chargeability in Wenner-Schlumberger array. The association of low resistivity and high chargeability areas has allowed defining potentially mineralized zones related to structures that condition the drainage net in the gabbro domain. Grains of gold detected through geochemical prospection of alluvial sediments dowstream from the gabbro may have originated from leaching of ores deposited in fractures through the action of river waters within the gabbro domain, possibly consisting of sulphides and gold.

Aquisição e interpretação de dados geofísicos e geológicos em mina de manganês supergênicos na região de Itapira (SP)

The mineral sector is of utmost importance for Brazilian economic growth, an area which depends on basic geological research to enlarge known deposits and in process of mining, besides discovering new occurrences and mineral deposits. This set of activities is named mineral research, which planning involves economy concepts, market demands and use of methods and techniques for geological evaluation, direct and indirect. This paper aim at performing geophysical detailing on occurrences of supergenic manganese located in the northwest portion of the State of São Paulo, Itapira, for spatial dimensioning of mineral targets, besides the attempt to correlate among the content on physical parameter measured by geophysics. The lack of scientific publications by Brazilian researchers in this theme, availability of previous studies for the selected targets, commercial importance of the mineral goods for the Brazilian Trade Balance, justify the performance of the present research project

Resposta dos tecidos periodontais aos cimentos de silicato tricálcico associado ao óxido de zircônio ou óxido de nióbio usados no selamento de perfurações de furca em molares de ratos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Resposta dos tecidos periodontais aos cimentos de silicato tricálcico associado ao óxido de zircônio ou óxido de nióbio usados no selamento de perfurações de furca em molares de ratos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)