Eldecalcitol Induces Minimodeling-Based Bone Formation and Inhibits Sclerostin Synthesis Preferentially in the Epiphyses Rather than the Metaphyses of the Long Bones in Rats.

This study aimed to examine minimodeling-based bone formation between the epiphyses and metaphyses of the long bones of eldecalcitol (ELD)-administered ovariectomized rats. Sixteen-week-old female rats were divided into four groups: sham-operated rats receiving vehicle (Sham group), ovariectomized (OVX) rats receiving vehicle (Vehicle group), or ELDs (30 or 90 ng/kg BW, respectively; ELD30 and ELD90 groups). ELD administration increased bone volume and trabecular thickness, reducing the number of osteoclasts in both the epiphyses and metaphyses of OVX rats.

Interleukin-6: evolving role in the management of neuropathic pain in neuroimmunological disorders.

Background: Neuropathic pain in neuroimmunological disorders refers to pain caused by a lesion or disease of the somatosensory system such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MS and NMOSD are autoimmune disorders of the central nervous system, and ≥ 50% of patients with these disorders experience chronic neuropathic pain. The currently available medications for the management of neuropathic pain have limited effectiveness in patients with MS and NMOSD, and there is an unmet medical need to identify novel therapies for the management of chronic neuropathic pain in these patients.

Prolonged Duration of Erythropoiesis-Stimulating Agents' Action Delays Disease Progression in Anti-Thy 1 Antibody-Induced Chronic Glomerulonephritis Rats.

Background: Although erythropoiesis-stimulating agents (ESAs) exert renoprotective effects in renal disease models, it has not been revealed whether the prolonged duration of action of ESAs contributes to their renoprotective effects.

Objective: We examined whether the prolonged duration of ESAs' action contributes to their renoprotective effects by comparing a divided administration of a short-acting ESA, epoetin beta (EPO), or a single administration of a long-acting ESA, epoetin beta pegol (continuous erythropoietin receptor activator; C.E.

Anti-IL-6 Receptor Antibody Inhibits Spontaneous Pain at the Pre-onset of Experimental Autoimmune Encephalomyelitis in Mice.

Chronic pain is a significant symptom in patients with autoimmune encephalomyelitis, such as multiple sclerosis and neuromyelitis optica. The most commonly used animal model of these diseases is experimental autoimmune encephalomyelitis (EAE). We previously reported that evoked pain, such as mechanical allodynia, was improved by an anti-IL-6 receptor antibody in EAE mice.

Sequential Treatment with Eldecalcitol After PTH Improves Bone Mechanical Properties of Lumbar Spine and Femur in Aged Ovariectomized Rats.

Parathyroid hormone (PTH) analogs have a powerful anabolic effect on bone and are used in the treatment of patients with severe osteoporosis. However, there are limitations to how long they can be safely administered. Withdrawal of PTH results in the cancelation of its effects, necessitating subsequent treatment to maintain the bone quantity and quality.

Anti-IL-6 receptor antibody improves pain symptoms in mice with experimental autoimmune encephalomyelitis.

Background And Aims: Chronic pain is a prevalent symptom in patients with autoimmune encephalomyelitis such as multiple sclerosis and neuromyelitis optica. Although IL-6 is involved in various inflammatory and immune diseases, the roles of IL-6 in autoimmune-related pain have not been clarified. Therefore, we examined the effect of anti-IL-6 receptor antibody (MR16-1) on the pain sensitivity of experimental autoimmune encephalomyelitis (EAE) mice.

Eldecalcitol, an Active Vitamin D Derivative, Prevents Trabecular Bone Loss and Bone Fragility in Type I Diabetic Model Rats.

Diabetes mellitus is known to adversely affect the bones and be associated with increased fracture risk. We examined whether eldecalcitol (ELD), an active vitamin D derivative, could inhibit the diabetic bone loss in streptozotocin-induced type I diabetic rats. ELD (10, 20, or 40 ng/kg), alfacalcidol (ALF; 25, 50, or 100 ng/kg), or vehicle was administered 5 times per week for 12 weeks from 1 week after diabetes induction.

Obesity does not diminish the efficacy of IL-6 signalling blockade in mice with collagen-induced arthritis.

Objectives: Obese rheumatoid arthritis patients often have higher disease activity and a poorer response to treatment than do non-obese patients. The present study aims to clarify the influence of obesity on the action of IL-6 and to evaluate the efficacy of IL-6 signalling blockade in arthritis with obesity.

Methods: Mice were fed a high-fat diet for 5 weeks, and the influence of this diet on macrophages and type II collagen-induced arthritis was investigated.

Intermittent Ibandronate Maintains Bone Mass, Bone Structure, and Biomechanical Strength of Trabecular and Cortical Bone After Discontinuation of Parathyroid Hormone Treatment in Ovariectomized Rats.

Although parathyroid hormone (PTH) expresses an anabolic effect on bone mass, the increased bone mass disappears once PTH treatment is withdrawn. Therefore, sequential treatment with anti-bone-resorptive agents is required to maintain bone mass after PTH treatment. We examined the effect of sequential treatment with ibandronate (IBN), a nitrogen-containing bisphosphonate, following PTH in ovariectomized (OVX) rats.

Epoetin beta pegol ameliorates flow-mediated dilation with improving endothelial nitric oxide synthase coupling state in nonobese diabetic rats.

Background/aims: Patients with diabetic nephropathy have a high cardiovascular mortality. Epoetin beta pegol (continuous erythropoietin receptor activator, C.E.

Eldecalcitol prevents endothelial dysfunction in postmenopausal osteoporosis model rats.

Postmenopausal women have high incidence of cardiovascular events as estrogen deficiency can cause endothelial dysfunction. Vitamin D is reported to be beneficial on endothelial function, but it remains controversial whether vitamin D is effective for endothelial dysfunction under the treatment for osteoporosis in postmenopausal women. The aim of this study was to evaluate the endothelial protective effect of eldecalcitol (ELD) in ovariectomized (OVX) rats.

Epoetin beta pegol prevents endothelial dysfunction as evaluated by flow-mediated dilation in chronic kidney disease rats.

Chronic kidney disease (CKD) patients have a poor prognosis due to cardiovascular disease. Anemia and endothelial dysfunction are important risk factors for cardiovascular events in CKD patients, and treatment with erythropoiesis-stimulating agent (ESA) has been reported to improve the quality of life in CKD patients. In this study, we evaluated the effect of anemia correcting dose of epoetin beta pegol (continuous erythropoietin receptor activator; C.

Treatment with the combination of ibandronate plus eldecalcitol has a synergistic effect on inhibition of bone resorption without suppressing bone formation in ovariectomized rats.

Bisphosphonates are widely used in the treatment of osteoporosis and contribute to the reduction of bone fractures. Ibandronate (IBN) is a highly potent, nitrogen-containing bisphosphonate, which is administered orally or intravenously at extended dosing intervals. Vitamin D or active vitamin D3 derivatives are also used in the treatment of osteoporosis, and are often used in combination with other drugs.

Nicorandil prevents sirolimus-induced production of reactive oxygen species, endothelial dysfunction, and thrombus formation.

Sirolimus (SRL) is widely used to prevent restenosis after percutaneous coronary intervention. However, its beneficial effect is hampered by complications of thrombosis. Several studies imply that reactive oxygen species (ROS) play a critical role in endothelial dysfunction and thrombus formation.

Vitamin D receptor signaling enhances locomotive ability in mice.

Bone fractures markedly reduce quality of life and life expectancy in elderly people. Although osteoporosis increases bone fragility, fractures frequently occur in patients with normal bone mineral density. Because most fractures occur on falling, preventing falls is another focus for reducing bone fractures.

Nicorandil suppresses urinary protein excretion and activates eNOS in Dahl salt-sensitive hypertensive rats.

Background: Hypertension is a risk factor common to both chronic kidney disease and cardiovascular disease. Nicorandil is widely used for the treatment of angina. We investigated the benefits of nicorandil with respect to renal dysfunction in Dahl salt-sensitive hypertensive (DS) rats.

GATA-4 transcription factor regulates cardiac COX-2 expression induced by nicorandil in left ventricle of rats.

Background And Aims: Cardioprotective effects induced by delayed ischemic preconditioning and by nicorandil are mediated via expression of cardioprotective factors such as COX-2. The present study was undertaken to evaluate whether nicorandil could induce COX-2 in rats and to elucidate its mode of induction pharmacologically.

Methods And Results: Three hours after administration of nicorandil (10 mg/kg, p.

Nicorandil ameliorated hypertensive renal injury without lowering blood pressure in spontaneously hypertensive rats.

Proteinuria, a symptom of hypertensive renal injury, is a powerful predictor of mortality in chronic kidney disease patients with hypertension. The present study investigated whether a nonhypotensive dose of nicorandil could decrease hypertensive renal injury in male spontaneously hypertensive rats (SHR). Nicorandil (15 mg/kg/day, for 20 weeks) was administered in the drinking water to rats from 11 weeks old.

22-Oxacalcitriol prevents progression of endothelial dysfunction through antioxidative effects in rats with type 2 diabetes and early-stage nephropathy.

Background: Vitamin D deficiency is associated with endothelial dysfunction in type 2 diabetes patients, but the effectiveness of vitamin D supplementation remains controversial. We assessed whether 22-oxacalcitriol (OCT) could prevent endothelial dysfunction in type 2 diabetes mellitus (DM) rats.

Methods: DM rats with early-stage nephropathy were treated for 10 weeks with OCT (0.

Paclitaxel-induced endothelial dysfunction in living rats is prevented by nicorandil via reduction of oxidative stress.

Paclitaxel-eluting stents dramatically reduce rates of in-stent restenosis; however, paclitaxel is known to lead to endothelial dysfunction. Protective effects of nicorandil on paclitaxel-induced endothelial dysfunction by examining flow-mediated dilation (FMD) were investigated in anesthetized rats. After 7-day osmotic infusion of paclitaxel (5 mg/kg per day), FMD was measured by high-resolution ultrasound in the femoral artery of living rats.

Nicorandil prevents endothelial dysfunction due to antioxidative effects via normalisation of NADPH oxidase and nitric oxide synthase in streptozotocin diabetic rats.

Background: Nicorandil, an anti-angina agent, reportedly improves outcomes even in angina patients with diabetes. However, the precise mechanism underlying the beneficial effect of nicorandil on diabetic patients has not been examined. We investigated the protective effect of nicorandil on endothelial function in diabetic rats because endothelial dysfunction is a major risk factor for cardiovascular disease in diabetes.

Left ventricular hypertrophy is associated with inflammation in sodium loaded subtotal nephrectomized rats.

The pathological influences of inflammation on left ventricular hypertrophy (LVH) were studied in subtotal nephrectomized (SNx) rats after 0.3% NaCl loading for 5 weeks. We found that mild hypertension, increased plasma levels of creatinine, inorganic phosphate, asymmetric dimethylarginine (ADMA), and parathyroid hormone (PTH) were observed in the present SNx rats without LVH.

Nicorandil improves glomerular injury in rats with mesangioproliferative glomerulonephritis via inhibition of proproliferative and profibrotic growth factors.

Recent clinical studies on chronic kidney disease (CKD) reported that renal dysfunction was a critical risk factor for cardiovascular events (CVE), which lead us to reconsider the effect of cardioprotective agents on the kidney. Glomerulonephritis, which is the major cause of CKD, is characterized by mesangial cell proliferation and extracellular matrix deposition. Nicorandil, a therapeutic drug for angina and acute heart failure, have been reported to show antiproliferative activity in mesangial cells.

An orally active motilin receptor antagonist, MA-2029, inhibits motilin-induced gastrointestinal motility, increase in fundic tone, and diarrhea in conscious dogs without affecting gastric emptying.

The pharmacological properties of MA-2029, a selective and competitive motilin receptor antagonist, were investigated in conscious dogs after oral administration. Gastrointestinal contractile activity was recorded by chronically implanted force transducers. The proximal gastric volume was measured with a barostat under constant pressure.

Nicorandil, a potassium channel opener and nitric oxide donor, improves the frequent urination without changing the blood pressure in rats with partial bladder outlet obstruction.

Objective: It was studied to determine if nicorandil can improve frequent urination in rats with partial bladder outlet obstruction (BOO) without changing the blood pressure.

Materials And Methods: Voiding behavior was observed 6 to 8 d after obstruction in female rats with BOO that loaded 30 ml/kg of water. A drug was administered orally.