A novel RORγt inhibitor is a potential therapeutic agent for the topical treatment of psoriasis with low risk of thymic aberrations.

Background: Retinoic acid receptor-related orphan receptor gamma t (RORγt) has critical roles in the development, maintenance and function of interleukin (IL)-17-producing cells and is a highly attractive target for the treatment of IL-17-mediated autoimmune disease, particularly psoriasis. On the other hand, RORγt is also critical for controlling apoptosis during thymopoiesis, and genetic RORγt ablation or systematic RORγt inhibition cause progressive thymic aberrations leading to T cell lymphomas.

Objective: We investigated whether topical administration of our novel RORγt inhibitor, S18-000003 has therapeutic potential for psoriasis with low risk of thymic aberrations.

[Association between osteoporosis and atherosclerosis in dyslipidemia.].

Age-related osteoporosis and atherosclerosis is promoted by life style-related diseases such as dyslipidemia and diabetes mellitus. Common factors pathophysiologically involved in both osteoporosis and vascular calcification include senescent cells and osteoprotegerin(OPG). Dyslipidemia may impair both osteoclast and osteoblast function,thereby causing osteoporosis.

[Bone and calcium metabolism associated with malignancy. Malignancy-associated hypercalcemia.].

Hypercalcemia is a poor prognostic factor and can be a direct cause of death in patients with malignancy. Here we provide a brief overview of pathology, etiology and management of malignancy associated hypercalcemia(MAH). MAH can be divided into two categories:humoral hypercalcemia of malignancy(HHM)caused by a systemic soluble factor secreted by the tumor;and local osteolytic hypercalcemia(LOH)in which tumor cells in situ enhance bone resorption.

[Treatment of malignancy associated hypercalcemia].

Malignancy associated hypercalcemia (MAH) is a paraneoplastic syndrome that impairs the quality of life and that can be a direct cause of death. MAH is classified into two major categories : humoral hypercalcemia of malignancy (HHM) and local osteolytic hypercalcemia (LOH) . Bisphosphonates are the gold standard of treatment for MAH, because enhanced resorption causing a massive calcium mobilization from bone plays a central role in the pathogenesis of MAH.

Osteoporosis is highly prevalent in Japanese males with chronic obstructive pulmonary disease and is associated with deteriorated pulmonary function.

Osteoporosis has recently been recognized as a major comorbidity in chronic obstructive pulmonary disease (COPD). We conducted a cross-sectional study in a cohort of 136 Japanese males with COPD to evaluate the prevalence of vertebral fracture (VF) and to explore its relationship with pulmonary function parameters. VFs were present in 108 (79.

[Anti-Dickkopf1 (Dkk1) antibody as a bone anabolic agent for the treatment of osteoporosis].

Wnt/β-catenin signaling pathway plays an important role in bone metabolism. This signal is subject to strict regulation, involving endogenous soluble inhibitors. Dkk1 is a member of family of secreted protein which functions in head induction during Xenopus embryogenesis.

Cytosolic phospholipase A2 alpha inhibitor, pyrroxyphene, displays anti-arthritic and anti-bone destructive action in a murine arthritis model.

Objective: The aim of this study is to verify the crucial role of cytosolic phospholipase A2 alpha (cPLA2 alpha) in the pathogenesis of collagen-induced arthritis in mice and to determine the anti-arthritic effects of pyrroxyphene, a cPLA2 alpha inhibitor.

Methods: Pyrroxyphene was administered (p.o.

[Pharmacological profiles of benzodiazepinergic hypnotics and correlations with receptor subtypes].

We examined the behavioral pharmacological properties of six benzodiazepine (omega) receptor ligands including brotizoram, nitrazepam, quazepam, rilmazafone, zolpidem and zopiclone and the binding of these drugs with omega receptor subtypes. Behavioral tests were performed at the time of the maximal effects induced by each drug following its oral administration to mice. All of these drugs dose-dependently induced impairment of motor coordination as rotarod performance and potentiation of thiopental-induced anesthesia as hypnotic effect.

Inhibitory effects of glucocorticoids on rat eosinophil superoxide generation and chemotaxis.

Eosinophil infiltration into inflammatory tissues and the subsequent release of inflammatory mediators are the hallmarks of several inflammatory allergic diseases. Although there have been a considerable number of publications on anti-inflammatory effects of glucocorticoids, little is known about whether glucocorticoids affect the activation of eosinophils directly. We studied the effects of three glucocorticoids, mometasone furoate, dexamethasone and beclomethasone dipropionate, on superoxide generation and the chemotaxis of rat eosinophils.

The role of histamine H(1) receptors in late-phase reaction of allergic conjunctivitis.

The role of histamine H(1) receptors in the late-phase reaction of allergic conjunctivitis was studied using histamine H(1) receptor-deficient mice. To clarify the eosinophil infiltration, which is a reliable indicator of late-phase reaction, eosinophil peroxidase activity in the conjunctiva was measured. Mice were actively immunized with ovalbumin, and conjunctivitis was induced by topical instillation of ovalbumin.