Clinical calcium最新文献

In the past decade, the various types of genetically-encoded optogenetic tools using blue-light sensitive LOV2 domain have been developed and applied in a wide range of areas including neuroscience field. Recently, we succeeded in developing a photoactivatable inhibitory peptide, a genetically-encoded light inducible CaMKⅡ inhibitory peptide. Using this new optogenetic tool, we found that the 1 min of CaMKⅡ activation is sufficient for triggering structural plasticity of synapses(spines)in hippocampal neurons. Furthermore, using passive avoidance test, we found that transient CaMKⅡ activity, but not sustained activity, is only required for fear memory formation/maintenance in amygdala of mice.

Rheumatoid arthritis is a systemic autoimmune disease characterized by inflammation and joint damage that causes significant morbidity and mortality. Rapid and appropriate intervention using disease-modifying anti-rheumatic drugs(DMARDs)is prerequisite to halt joint destruction and long-term functional disabilities. Recent progress in the treatment strategy has brought about paradigm shift for the management of the disease, namely, the combined use of methotrexate, a synthetic DMARD, and a biologic DMARD targeting TNF, IL-6 and T cells has revolutionized treatment of rheumatoid arthritis. Clinical remission is now realistic targets for the treatment, achieved by a large proportion of rheumatoid arthritis patients, which leads to structural remission without damage in bone and cartilage as well as functional remission. Furthermore, orally available small but strong molecules targeting Janus kinase(JAK)are emerging. When DMARDs are prescribed, appropriate selection of DMARDs, adequate screening, regular monitoring and systemic management are required.

Milk has been historically recognized as having great nutritional value;its high nutrient density per energy makes it useful for individuals recovering from malnutrition among others. Milk is composed of an excellent ratio of essential amino acids, with an amino acid score of 100, and enhances the protein content when served with a meal. Additionally, not only is milk rich in calcium, but the absorption rate of calcium contained in the meal increases when milk is served with a meal. Instead of consuming nutritional supplements to make up for a lack of nutrients in the diet, Milk is a representative food that highlights the nutritional value of taking one food in combination with other foods. Moreover, milk costing as little as 100 contains high nutrient density, making it an economically efficient food.

In Japan, nutrition education programs to prevent osteoporosis and osteoporotic fractures have focused primarily on increasing dietary calcium intake and recommended the consumption of milk and dairy products. However, the effect of milk and dairy product consumption on bone density loss or fracture incidence in Japanese has rarely been evaluated in randomized controlled studies. In the present study, we reviewed the literature investigating the consumption of milk and dairy products in relation to bone density and fracture risk. The results showed that milk and dairy product consumption had only a modest effect in the prevention of midlife bone loss and subsequent fractures. However, given that infrequent(once weekly or less)consumption of milk may be associated with an increased risk of femoral neck fracture, and that Japanese generally have a lower calcium intake, it is still necessary to encourage elderly and younger adults to increase their consumption of milk and dairy products to promote bone health.

An assessment of the association between the intake of milk or dairy products and bone density or the risk of fractures on the basis of epidemiological studies revealed the following findings:(1)a sufficient prepubertal intake of milk or dairy products could contribute to the increased bone growth and maximized peal bone mass because the intake of calcium in the corresponding stage in Japan is inadequate;(2)adequate milk intake could contribute to the maintenance of peal bone mass among menstruating adult females and the decrease of bone loss in postmenopausal females. Adequate milk intake could contribute to the decrease of aging-induced bone loss in elderly males, though there is no sufficient scientific evidence;and(3)a meta-analysis indicated no correlation between the increased milk intake and decreased risks of hip fractures in the elderly. As the intake of milk or dairy products in the Japanese elderly is rather less than that reported by the meta-analysis, the minimal intake of milk or dairy products is anticipated to elevate the risk of fractures in middle-aged or elderly males and females although the scientific evidence is inadequate.

Rheumatoid arthritis(RA)is one of the systemic autoimmune diseases characterized by progressive joint destruction with chronic synovitis. In the synovium, activated osteoclasts with plenty of inflammatory cytokines and metalloproteinases induce bone and cartilage destruction. Anti-cyclic citrullinated protein antibodies(ACPA)was recognized not only as a diagnostic marker but also as direct inducer of synovitis. In addition, environmental factors and background of daily life also contribute to the pathogenesis of RA, especially smoking and periodontitis are considered to be important factors for disease activities.

Incretins are gastro-intestinal hormones released from enteroendocrine cells in response to food intake. Incretins such as glucose-dependent insulinotropic peptide(GIP)and glucagon-like peptide 1(GLP-1)modulate glucose homeostasis by regulating glucose-dependent insulin release from pancreatic βcells. Dipeptidyl peptidase-4(DPP-4)inhibitors and GLP-1 receptor agonists are incretin-based drugs that have been used for the management of hyperglycemia and obesity in patients with type 2 diabetes mellitus. Although experimental studies have shown that incretin improves bone quality and increases bone mass in rodents, further studies are necessary to clarify the effect of incretin-based drugs on bone mineral density and risk of fractures in humans.

Calcimimetics are widely used for severe secondary hyperparathyroidism in hemodialysis patients. Two clinical studies showed that cinacalcet, one of calcimimetics, has possibility to reduce the risk of fracture in hemodialysis patients. Although the mechanism in which calcimimetics reduce the risk of fracture in hemodialysis patients remains unclear, improvement of severe secondary hyperparathyroidism may cause the reduction of fracture risk. However, the optimal intact PTH levels for reducing the risk of fracture in hemodialysis patients is not known. In addition, since calcium-sensing receptor also exists in bone, calcimimetics may have direct effects on bone.

Vitamin D are taken from sunlight exposure and foods, such as oil rich fish. Serum 25-hydroxyvitamin D concentration is most appropriate marker to assess nutritional vitamin D status. On the other hand, 1,25-dihydroxyvitamin D is a clinical marker of disorders in calcium metabolism. To detect vitamin D deficiency and insufficiency, high-throughput and high-sensitive automated measurement system of 25OHD has been developed, and added in health insurance listing. Several methods of 25OHD concentration measurement have been developed based on biochemical or physicochemical such as LC-MS/MS.

FGF23 is an "endocrine FGF" mainly secreted by osteocytes. FGF23 exerts its action through binding to an FGF receptor isoform, FGFR1c, using α-Klotho as a co-receptor. The main physiological function of FGF23 is to suppress phosphate reabsorption and active vitamin D production in the proximal tubule of the kidney, thereby lowering serum concentration of inorganic phosphate. In recent years, however, FGF23 has been shown to contribute to various pathological processes including cardiac hypertrophy via a distinct mode of action in a Klotho-independent manner. This review summarizes such pleiotropic actions of FGF23.