Biomedical subjects
Naoyuki Yao
Publications and source records attributed to Naoyuki Yao.
Management of calcium, phosphorus and bone metabolism in dialysis patients using sevelamer hydrochloride and vitamin D therapy.
Abnormalities of mineral metabolism, including those of calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) in patients on maintenance hemodialysis induce severe bone involvement, which manifests as renal osteodystrophy. Recently, vascular calcification caused by abnormal mineral metabolism has been attracting attention because cardiovascular diseases (CVD) are a major cause of death in hemodialysis patients. Since 2000, the treatment standard for overt secondary hyperparathyroidism (SHPT) in our facilities has shifted from conventional or pulse therapy with oral vitamin D3 (VitD) to intravenous pulse therapy with maxacalcitriol or calcitriol. After selecting the criterion of overt SHPT as intact-PTH>500 pg/mL, the proportion of overt SHPT cases among all hemodialysis patients decreased from 12% at the start of intravenous pulse treatment to 6.4% after 4 years' treatment. However, the number of patients who had an interruption to pulse treatment because of hypercalcemia and/or hyperphosphatemia was high and it became a bottleneck for the continuation of the therapy. The major cause of hypercalcemia is considered to be Ca load derived from oral calcium carbonate. In Japan, sevelamer hydrochrolide (SH), which does not contain Ca, has been available commercially since 2003 and potentially should enable a reduction in the incidence of overt SHPT during long-term intravenous treatment when combined with careful adjustment of the dose of VitD and strict monitoring of Ca and P level concentrations. In this study, we found that the proportion of patients who satisfy the recommended serum concentrations of Ca and P reported by K/DOQI guideline was low irrespective of the serum concentration of intact-PTH. The aortic calcification index was high in the patient group with lower intact-PTH level concentration, probably because of reduced Ca and P buffering ability associated with reduced bone turnover. We consider that VitD treatment with SH might give better control of the intact-PTH level concentration within the range recommended by the K/DOQI guideline.
[Sevelamer hydrochloride and vitamin D for controlling serum calcium, phosphorus and bone metabolism in patients undergoing hemodialysis].
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[Calcium channel blocker for protection against hypertensive target-organ damage].
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Roles of calcineurin and calcium/calmodulin-dependent protein kinase II in pressure overload-induced cardiac hypertrophy.
Calcineurin and calcium/calmodulin-dependent protein kinase (CaMK) II have been suggested to be the signaling molecules in cardiac hypertrophy. It was not known, however, whether these mechanisms are involved in cardiac hypertrophy induced by pressure overload without the influences of blood-derived humoral factors, such as angiotensin II. To elucidate the roles of calcineurin and CaMK II in this situation, we examined the effects of calcineurin and CaMK II inhibitors on pressure overload-induced expression of c-fos, an immediate-early gene, and protein synthesis using heart perfusion model. The hearts isolated from Sprague-Dawley rats were perfused according to the Langendorff technique, and then subjected to the acute pressure overload by raising the perfusion pressure. The activation of calcineurin was evaluated by its complex formation with calmodulin and by its R-II phosphopeptide dephosphorylation. CaMK II activation was evaluated by its autophosphorylation. Expression of c-fos mRNA and rates of protein synthesis were measured by northern blot analysis and by 14C-phenylalanine incorporation, respectively. Acute pressure overload significantly increased calcineurin activity, CaMK II activity, c-fos expression and protein synthesis. Cyclosporin A and FK506, the calcineurin inhibitors, significantly inhibited the increases in both c-fos expression and protein synthesis. KN62, a CaMK II inhibitor, also significantly prevented the increase in protein synthesis, whereas it failed to affect the expression of c-fos. These results suggest that both calcineurin and CaMK II pathways are critical in the pressure overload-induced acceleration of protein synthesis, and that transcription of c-fos gene is regulated by calcineurin pathway but not by CaMK II pathway.