Comparative study of the usefulness of a novel insulin therapy in Japanese patients with Type 2 diabetes for concomitant use of an oral antidiabetic agent with twice-daily dosing either of insulin aspart, biphasic insulin aspart-30, or insulin detemir: Two times Insulin injection Combined with oral therapy Efficacy Study (TWICE study).

Objectives: It is common to treat type 2 diabetes by regular injections of insulin. We compared the efficacy and safety of twice-daily administration of short-acting, premixed, and long-acting insulins.

Methods: This was a multi-center, randomized, open-label, 52-week study.

Level of urinary liver-type fatty acid-binding protein is associated with cardiac markers and electrocardiographic abnormalities in type-2 diabetes with chronic kidney disease stage G1 and G2.

Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was ≥60 mL/min/1.

[Assessment of the treatment of glucocorticoid-induced osteoporosis].

Glucocorticoid-induced osteoporosis (GIOP) is known as a serious adverse side effect during long-term glucocorticoid treatment. Several clinical guidelines are available to whom and how we should start to treat GIOP. However, the assessment of the treatment of GIOP is still controversial.

Oral alendronate can suppress bone turnover but not fracture in kidney transplantation recipients with hyperparathyroidism and chronic kidney disease.

Post-transplantation bone diseases negatively affect the quality of life of solid organ recipients. Secondary or tertiary hyperparathyroidism is a frequent complication in kidney transplantation (KTx) recipients. Treatment with immunosuppressive agents including glucocorticoids can lead to deterioration in bone metabolism in these patients.

High prevalence of hypovitaminosis D in pregnant Japanese women with threatened premature delivery.

Serum 25-hydroxyvitamin D (25-OHD) concentrations are thought to accurately reflect vitamin D stores, and vitamin D deficiency causes secondary hyperparathyroidism, irreversible bone loss, and increased risk of fracture. Recent studies suggest that decrease of serum 25-OHD level in mothers could increase the risk of preeclampsia, cesarean section, and craniotabes. Furthermore, this deficiency may affect bone mass and the incidence of neuromuscular diseases of their children in the future.

Phosphate overload induces podocyte injury via type III Na-dependent phosphate transporter.

Uptake of P(i) at the cellular membrane is essential for the maintenance of cell viability. However, phosphate overload is also stressful for cells and can result in cellular damage. In the present study, we investigated the effects of the transgenic overexpression of type III P(i) transporter Pit-1 to explore the role of extracellular P(i) in glomerular sclerosis during chronic renal disease.

Local microbleeding facilitates IL-6- and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells.

Cognate antigen recognition by CD4(+) T cells is thought to contribute to the tissue specificity of various autoimmune diseases, particularly those associated with class II MHC alleles. However, we show that localized class II MHC-dependent arthritis in F759 mice depends on local events that result in the accumulation of activated CD4(+) T cells in the absence of cognate antigen recognition. In this model, transfer of in vitro polarized Th17 cells combined with the induction of experimental microbleeding resulted in CCL20 production, the accumulation of T cells in the joints, and local production of IL-6.

Effects of transgenic Pit-1 overexpression on calcium phosphate and bone metabolism.

The type III inorganic phosphate (Pi) transporter Pit-1 was previously found to be preferentially expressed in developing long bones. Several studies also described a regulation of its expression in cultured bone cells by osteotropic factors, suggesting a role of this transporter in bone metabolism. In the present study, we investigated the effects of the transgenic overexpression of Pit-1 in Wistar male rats on calcium phosphate and bone metabolism.

Sphingomyelins in four ascidians, Ciona intestinalis, Halocynthia roretzi, Halocynthia aurantium, and Styela clava.

Sphingomyelin is rarely found in lower animals, while sphingophospholipid is a characteristic of higher animals. In this study, sphingomyelin was first isolated and characterized from ascidian Ciona intestinalis. Ascidian sphingomyelin was prepared using ion exchange (QAE-Sphadex-A25) and silicic acid (Florisil and Iatrobeads) column chromatographies.

[Biochemical markers of bone turnover. New aspect. Biochemical markers of bone turnover in long term treatment with bisphosphonate].

Bisphosphonates (BPs) are now widely used for the prevention of osteoporotic fracture. The elevation of bone turnover markers (BTM) is an independent risk factor for the bone fracture, and their significant decrease with BPs treatment is considered to reflect BPs' efficacy to "adjust" bone turnover. A large-scale study so far showed that BPs continuously suppress both BTM levels and the incidence of fracture as long as 7 to 10 years, though possible deterioration of bone strength with long-term severe suppression of BTM has been pointed out.

Effects of prostaglandin D2 on Na-dependent phosphate transport activity and its intracellular signaling mechanism in osteoblast-like cells.

Inorganic phosphate (Pi) transport probably represents an important function of bone-forming cells in relation to extracellular matrix mineralization. In the present study, we investigated the effect of prostaglandin D2 (PGD2) on Pi transport activity and its intracellular signaling mechanism in MC3T3-E1 osteoblast-like cells. PGD2 stimulated Na-dependent Pi uptake time- and dose-dependently in MC3T3-E1 cells during their proliferative phase.

[Etidronate for treatment of osteoporosis].

The treatment with anti-resorptive agents including bisphosphonates and selective estrogen receptor modulators (SERM) has clinical relevance to reduce osteoporotic fractures in postmenopausal women. Among them, etidronate has a unique mechanism to suppress osteoclastic activity, and could be used to treat long-term immobilized patients, to whom other bisphosphonates or SERM are not available because of their adverse effects. In addition, intermittent therapy regimen (two weeks every three months) and less gastroesophageal reflux disorder may be suitable for some patients.

Pharmacological topics of bone metabolism: recent advances in pharmacological management of osteoporosis.

The prevention of osteoporotic fracture is an essential socioeconomical priority, especially in the developed countries including Japan. Estrogen, selective estrogen-receptor modulators (SERMs), and bisphosphonate are potent inhibitors of bone resorption; and they have clinical relevance to reduce osteoporotic fractures in postmenopausal women. However, we can prevent at most 50% of vertebral fractures with these agents.

Vasopressin stimulates Na-dependent phosphate transport and calcification in rat aortic smooth muscle cells.

We investigated the effect of arginine vasopressin (AVP) on inorganic phosphate (Pi) transport in A-10 rat aortic vascular smooth muscle cells (VSMCs). AVP time- and dose-dependently stimulated Na-dependent Pi transport in A-10 cells. This stimulatory effect of AVP on Pi transport was markedly suppressed by V1 receptor antagonist.