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Biomedical subjects

Eriko Kinugasa

Publications and source records attributed to Eriko Kinugasa.

15 recordsLinked to original sources
PubMed2005

Combination therapy with sevelamer hydrochloride and calcium carbonate in Japanese patients with long-term hemodialysis: alternative approach for optimal mineral management.

Calcium (Ca) overload by Ca-containing phosphorus (P) binder has been suggested to be implicated in the pathogenesis of soft tissue and vascular calcification, which contribute to increased morbidity and mortality of cardiovascular disease in patients undergoing dialysis. Recently, a noncalcium P binder, sevelamer hydrochloride (sevelamer), has become available in Japan. However, Japanese patients undergoing dialysis might be less tolerant of sevelamer treatment, and it is likely to cause hypocalcemia because their dietary Ca intake is less than that in European and American patients. We evaluated the effects of combination therapy with sevelamer and calcium carbonate (CC) on mineral metabolism in Japanese hemodialysis patients, as an alternative form of P management. A total of 210 hemodialysis patients were enrolled, and were given a small dose of sevelamer (0.75-1.5 g/day) on CC treatment. Sevelamer dose was gradually increased, while CC decreased during 24 weeks. Five patients discontinued sevelamer treatment because of severe constipation, anorexia, and parathyroidectomy for severe secondary hyperparathyroidism. After 24 weeks, the dose of sevelamer was significantly increased to 3.29 g/day (initial dose: 1.47 g/day), while CC was decreased by 54%. Adjusted serum Ca significantly decreased (9.63 +/- 0.57-9.45 +/- 0.67 mg/dL; P = 0.0012), although serum P increased (5.89 +/- 1.32-6.25 +/- 1.32 mg/dL; P = 0.017). Serum intact PTH (iPTH) significantly increased in patients with a low or normal iPTH level (< or =300 pg/mL), while it did not change in patients with secondary hyperparathyroidism (>300 pg/mL). The results suggest that the therapeutic regimen is more tolerant and reduces Ca load in Japanese hemodialysis patients while avoiding hypocalcemia. In addition, the mitigated Ca overload could improve PTH hyposecretion in patients with adynamic bone disease, which is associated with soft tissue calcification and higher mortality in uremia.

Antacids↗
PubMed2005

[Apoptosis: a possible mechanism of suppressing parathyroid hyperplasia by calcimimetics].

The mechanism through which calcimimetic compounds suppress parathyroid cell growth has not been fully elucidated. We investigated the effect of the calcimimetic compound (NPS R-568:R568) on the parathyroid cell growth in vitro. Whole parathyroid glands of subtotally nephrectomized rats fed high phosphorus diet for 8 weeks were used in this study. Fresh rat parathyroid glands were incubated in a media (phosphorus concentration is 1.0 mM and calcium is 1.25 mM) with R-568 (10-4 M) or calcitriol (10-7 M) or vehicle for 6 hours. Medium PTH level was significantly decreased in both R568-treated group and calcitriol-treated group compared with either vehicle-treated group, or no-treated group. While TUNEL-positive cells were similar in calcitriol-treated group compared with both vehicle-treated and no-treated groups, they were significantly increased in R568-treated group compared with other three groups. These results suggest that calcimimetic compounds, NPS R-568 reduces PTH secretion and induces apoptosis of hyperfunctional parathyroid cell in vitro.

Aniline Compounds↗
PubMed2005

[Serum amyloid protein A was a useful marker for steroid tapering in a case of MPO-ANCA-associated vasculitis].

A 55-year-old man was admitted complaining of hemosputa, fever and dyspnea. The chest radiographs and computed tomography showed a diffuse alveolar filling pattern; suggesting alveolar hemorrhage. Laboratory data demonstrated renal dysfunction with hematuria and proteinuria and serum MPO-ANCA was also elevated. Respiratory failure progressed rapidly within two days. Steroid pulse therapy and plasmapheresis was performed. Thereafter, symptoms and chest radiograph findings improved dramatically. However proteinuria persisted as steroid administration was tapered. Renal biopsy demonstrated gromeluronephritis and interstitial lymphocyte infiltration. After administering a second course of steroid semi-pulse therapy, her proteinuria improved. C-reactive protein and MPO-ANCA decreased to normal levels after the initial steroid therapy, but serum amyloid A protein (SAA) gradually elevated. The second course of steroid pulse therapy normalized SAA, and proteinuria improved. Based on these findings, SAA seems to be a more sensitive marker for steroid tapering than either CRP or MPO-ANCA.

Anti-Inflammatory Agents↗
PubMed2004

Calcimimetic compound upregulates decreased calcium-sensing receptor expression level in parathyroid glands of rats with chronic renal insufficiency.

The reduced expression level of the calcium-sensing receptor (CaR) is attributed to the hyposensitivity of parathyroid cells to extracellular calcium concentration [Ca2+]o, which plays a crucial role in the pathogenesis of secondary hyperparathyroidism (SHPT) in patients and rats with chronic renal insufficiency (CRI). Calcimimetic compounds have been demonstrated to improve the decreased sensitivity of CaR to extracellular calcium concentration and to suppress both parathyroid hormone (PTH) oversecretion and parathyroid cell proliferation. However, the effect of calcimimetics on the reduced CaR expression level in parathyroid cells in CRI remains unclarified. The aim of this investigation was to examine the effect of the calcimimetic compound NSP R-568 (R-568) on the CaR expression in the parathyroid cells of rats with experimental CRI. Subtotally nephrectomized rats were fed a high-phosphorus diet for 8 (n = 12; Nx-8 group) or 9 wk (n = 11; Nx-9 group) to induce severe SHPT. Another group of uremic rats were fed a high-phosphorus diet for 8 wk and then orally administered R-568 (100 micromol/kg body wt) once a day for 7 d (n = 11; Nx+R-568 group). Sham-operated rats that were fed a standard diet for 9 wk were used as controls (n = 8). R-568 treatment induced a significant reduction in plasma PTH level with significant decrease in serum calcium and without change in serum phosphorus concentration. Serum 1,25(OH)2D3 level was not affected by R-568 administration. CaR mRNA and protein levels in the Nx-8 and Nx-9 groups significantly decreased compared with those in the controls; however, no significant difference in these parameters was observed between the Nx-8 and Nx-9 groups. In the Nx+R-568 group, CaR mRNA and protein levels significantly increased compared with those in either the Nx-8 or Nx-9 group. R-568 was effective in reducing the number of proliferating cell nuclear antigen-positive cells along with parathyroid gland growth suppression in the Nx+R-568 group compared with that in the Nx-9 group. The results suggest that the calcimimetic compound R-568 upregulates decreased CaR expression, and the upregulation possibly has an enhancement effect on PTH secretion and parathyroid cell hyperplasia through the improved sensitivity of CaR to [Ca2+]o.

Analysis of Variance↗
PubMed2004

[Pathogenesis of secondary hyperparathyroidism and renal bone disease].

Patients with chronic renal disease (CKD)almost always develop secondary hyperparathyroidism (SHPT) due to hypocalcemia, phosphate retention, and abnormalities in vitamin D (VD) metabolism. Concomitant decreases in VD receptor and calcium sensing receptor in the parathyroid glands render them more resistant to the action of VD and calcium, and accelerate parathyroid cell growth. Several types of bone diseases are known to occur in CKD patients. Excessive secretion of parathyroid hormone (PTH) due to SHPT causes high-turnover bone disease, called osteitis fibrosa. Among low-turnover bone disease (LTBD), osteomalacia which is characterized by calcification defect is often complicated with VD deficiency and/or aluminum accumulation. Recently, frequency of adynamic bone disease caused by PTH suppression, another type of LTBD, is increasing probably due to calcium salts as phosphate binder with or without VD treatment.

Aluminum↗
PubMed2003

Management of secondary hyperparathyroidism of dialysis patients.

Hyperphosphatemia, vitamin D deficiency, and resulted hypocalcemia have been regarded as classical pathogeneses of secondary hyperparathyroidism. These factors have been treated by the administration of phosphorus binder and vitamin D derivatives. However, these therapies have not brought about a successful result for the prevention and treatment of secondary hyperparathyroidism. The reason could be mainly attributed to the hypercalcemia that results from the administration of calcium salts as a phosphorus binder and the calcemic action of vitamin D. To prevent hypercalcemia, non-calcium containing phosphorus binder (sevelamer hydrochloride) and vitamin D analogues, which suppress PTH secretion with minimum calcemic action, have been developed. These new vitamin D analogues include 19-nor-1-alpha, 25-dihydroxyvitamin D2 (paricalcitol), 1-alpha-hydroxyvitamin D2 (doxercalciferol), 22oxa-calcitriol (maxacalcitol) and F6-calcitriol (falecalcitriol). Furthermore, calcimimetics that stimulate calcium-sensing receptor of parathyroid cells as calcium and suppress PTH secretion are now under clinical trial. Percutaneous direct injection therapy of vitamin D, vitamin D analogue or calcimimetics into parathyroid gland has also been reported. The combination of these new strategies is expected to effectively and safely suppresses secondary hyperparathyroidism that has been resistant to conventional medical treatments.

Ethanol↗
PubMed2003

New strategies for the treatment of secondary hyperparathyroidism.

Classic pathogeneses of secondary hyperparathyroidism (2HPT), hyperphosphatemia, vitamin D deficiency, and hypocalcemia, have been treated by the administration of phosphorus binders and vitamin D derivatives. However, these therapies have not brought about a successful result. The main reason could be attributed to hypercalcemia resulting from the administration of calcium salts as a phosphorus binder and the calcemic action of vitamin D. To prevent hypercalcemia, non-calcium-containing phosphorus binders and vitamin D analogues, which suppress parathyroid hormone (PTH) secretion with minimum calcemic action, have been developed. Furthermore, calcimimetics that stimulate the calcium-sensing receptor of parathyroid cells and suppress PTH secretion are now under clinical trial. Direct injection therapy of vitamin D analogues or calcimimetics into the parathyroid gland also has been reported. These new strategies are expected to effectively and safely suppress 2HPT, which has been resistant to conventional medical treatments.

Animals↗
PubMed2002

Effects of 1,25-dihydroxy-22-oxavitamin D(3) on parathyroid gland function in haemodialysis patients with secondary hyperparathyroidism.

Secondary hyperparathyroidism (2HPT) is characterized by an abnormal threshold for suppression of parathyroid hormone (PTH) secretion by serum ionized Ca (ICa). It is therefore critical to examine the threshold of PTH secretion in chronic renal failure patients in relation to the physiopathological conditions and the severity of 2HPT. The effect of 1,25-dihidroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) on parathyroid gland function was investigated in six haemodialysis patients with 2HPT. OCT was administered three times a week for 26 consecutive weeks. The maximum serum PTH (PTHmax), the minimum serum PTH (PTHmin), and ICa concentration required to inhibit 50% of PTHmax were estimated based on the model formula of the sigmoid curve describing the relationship between ICa and intact-PTH levels. The sigmoid ICa-PTH curves displayed a downward shift at 12 and 26 weeks of OCT treatment. Parathyroid gland function, as reflected by both PTHmax and PTHmin, decreased over time. A steep slope was found at 12 and 26 weeks, compared with that at the start of OCT treatment. There were no marked changes in the set point of calcium. Hypercalcaemia and elevated creatine phosphokinase, probably due to OCT therapy, were observed during the study period. In view of the findings that the sigmoid ICa-PTH curve displayed a downward shift, that both PTHmax and PTHmin decreased, and that functional mass of the parathyroid gland was reduced, OCT appears to be useful in ameliorating parathyroid gland function, contributing to the management of 2HPT.

Adult↗
PubMed2002

Diagnostic significance of serum soluble transferrin receptors in various anemic diseases: the first multi-institutional joint study in Japan.

Serum soluble transferrin receptor (sTfR) has been reported to be higher in patients with iron deficiency or with elevated erythropoiesis. In the present study, serum sTfR was measured in various anemic diseases and their clinical significance was examined in a multi-institutional joint study. Serum sTfRs in patients with the following anemic diseases were markedly higher than those in normal healthy adults: non-treated iron deficiency anemia (IDA) (9.13 +/- 7.04 mg/l, n = 52, p < 0.0001), anemia of chronic disorders (ACD) (3.45 +/- 1.38 mg/l, n = 20, p < 0.0001), hemolytic anemia (HA) (5.57 +/- 3.26 mg/l, n = 17, p < 0.0001), and myelodysplastic syndrome (MDS) (4.03 +/- 2.83 mg/l, n = 20, p < 0.0001). There were significant differences between IDA and ACD (p < 0.0001), between aplastic anemia (AA) (1.58 +/- 1.26 mg/l, n = 16) and MDS (p < 0.001), and between AA and MDS with refractory anemia (MDS-RA) (4.16 +/- 3.40 mg/l, n = 9) (p < 0.02). In patients with chronic renal failure (CRF), serum sTfR levels and serum sTfR/log serum ferritin ratios (sTfR/F index) were compared in the two classified groups according to Muirhead's criteria, as IDA and non-IDA groups with or without recombinant human erythropoietin (rHuEPO) treatment. Significantly high levels of both serum sTfR (p < 0.0001) and the sTfR/F index (p < 0.0001) were observed in IDA without rHuEPO treatment. Especially in CRF with rHuEPO treatment, the sTfR/F index showed marked elevation in the IDA group (p < 0.0001) compared with serum sTfR (p < 0.001), indicating more diagnostic efficacy of the sTfR/F index for CRF with IDA. In conclusion, the serum sTfR concentration is a useful diagnostic tool for discrimination between IDA and ACD, and between AA and MDS-RA, and for the detection of iron deficiency in CRF patients in the Japanese population.

Adult↗
PubMed2002

[Vitamin D and its analogs in the treatment of secondary hyperparathyroidism (2nd HPT) associated with end stage renal disease (ESRD)].

Management of 2nd HPT in ESRD patients consists of administration of vitamin D (VD) and phosphate control. VD possesses not only suppressive effect on parathyroid hormone (PTH) secretion via increase in serum calcium, but also shows direct suppressive action on transcription of PTH mRNA and parathyroid cell growth, especially in high dose intermittent administratin (pulse therapy). However, hypercalcemia, a major side effect of VD pulse therapy, have limited the effective usage of VD, especially in patients with severe hyperparathyroidism. Several new VD analogs have been developed that specifically target parathyroid cells while having less calcemic action, and currently approved for clinical use.

English Abstract↗
PubMed2002

[New insight into phosphate metabolism].

Phosphate (P) homeostasis has long been considered to be closely linked with calcium metabolism regulated by calcium-regulating hormones, such as PTH and 1,25-dihydroxyvitamin D(3). The regulation of P is controlled mainly by three factors, absorption in the intestine, redistribution among intracellular, extracellular, and osseous compartments, and reabsorption in the kidney. Renal P reabsorption in the proximal tubule is a key process through sodium-dependent P cotransport, which is regulated mainly by dietary phosphate intake and PTH. Recently, it has been suggested that some putative P-regulating factors might play an important role in the pathogenesis of hypophosphatemic disorders, including TIO, ADHR, and XLH. This review focuses primarily on P regulatory mechanism and some candidates for putative humoral P-regulating factors.

English Abstract↗