ABSTRACT
Chronic kidney disease (CKD) is associated with a high incidence of fractures. However, the pathophysiology of this disease is not fully understood, and limited therapeutic interventions are available. This study aimed to determine the impact of type 1 angiotensin II receptor blockade (AT-1RB) on preventing CKD-related fragility fractures and elucidate its pharmacological mechanisms. AT-1RB use was associated with a lower risk of hospitalization due to fractures in 3276 patients undergoing maintenance hemodialysis. In nephrectomized rats, administration of olmesartan suppressed osteocyte apoptosis, skeletal pentosidine accumulation, and apatite disorientation, and partially inhibited the progression of the bone elastic mechanical properties, while the bone mass was unchanged. Olmesartan suppressed angiotensin II-dependent oxidation stress and apoptosis in primary cultured osteocytes in vitro. In conclusion, angiotensin II-dependent intraskeletal oxidation stress deteriorated the bone elastic mechanical properties by promoting osteocyte apoptosis and pentosidine accumulation. Thus, AT-1RB contributes to the underlying pathogenesis of abnormal bone quality in the setting of CKD, possibly by oxidative stress. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Subject(s)
Renal Insufficiency, Chronic , Uremia , Animals , Bone Density , Bone and Bones , Humans , Rats , Receptors, Angiotensin , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Uremia/complications , Uremia/drug therapyABSTRACT
Verification of the dose control method for Tokaimura criticality accident was performed. Personal dose estimation for accident termination was performed based on measurements of dose rate taken before the work commenced, but the personal dose to workers as a result of the termination work was found to be approximately 50 times higher than the previous estimation. For this report, the doses are reevaluated based on the results of close range measurements from 40 to 100 m, and the results were found to agree with the actual personal doses within the uncertainty of its determination 60-80 %. Therefore, the work can likely be done safely by taking into account factors such as annual dose limits and the guideline dose constraints for works in high-level neutron radiation fields.
