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Abstract Purpose  To examine the mechanisms of the alteration of serum uric acid level by angiotensin II receptor blockers (ARBs), the effects of ARBs on renal uric acid transporters, including OAT1, OAT3, OAT4, and MRP4, were evaluated. Materials and Methods  Uptakes of uric acid by OAT1-expressing Flp293 cells, by Xenopus oocytes expressing OAT3 or OAT4, and by membrane vesicles from Sf9 cells expressing MRP4 were evaluated in the presence or absence of ARBs. Results  All ARBs inhibited uptake of uric acid or estrone-3-sulfate by OAT1, OAT3 and OAT4 in concentration dependent manners. Among them, the IC50 values of valsartan, olmesartan and pratosartan for OAT3 were comparable to clinically observed unbound maximum plasma concentration of ARBs. Candesartan, losartan, and telmisartan inhibited ATP-dependent uptake of uric acid by MRP4 at 10 μM. The IC50 value of losartan for MRP4 was comparable to the estimated kidney tissue concentration of losartan. No ARBs showed trans-stimulatory effects on the uptake of estrone-3-sulfate by OAT4. Conclusion  Valsartan, olmesartan, and pratosartan could inhibit the OAT3-mediated uric acid secretion in clinical situations. Furthermore losartan could inhibit ATP-dependent uric acid secretion by MRP4. These effects may explain partially the alteration of serum uric acid level by ARBs. [ABSTRACT FROM AUTHOR]

Distant metastasis of primary squamous cell carcinoma (SCC) of the thyroid gland is rare and, to the best of our knowledge, cardiac metastasis has not been reported to date. A 57-year-old man underwent surgery and adjuvant chemoradiotherapy for stage IVA SCC of the thyroid gland. After 3 months, the patient was admitted to the Kyushu University Hospital (Fukuoka, Japan) with subcutaneous hematomas of the left thigh and lower leg, and he was diagnosed with cardiac and mediastinal lymph node metastases of SCC of the thyroid gland with severe disseminated intravascular coagulation (DIC). Echocardiography revealed a mass, 52 mm in greatest diameter, protruding from the interventricular septum towards the right ventricle. Weekly administration of paclitaxel and concurrent irradiation of the cardiac and lymph node metastases were performed. Eighteen days after the initiation of chemoradiotherapy, the DIC and hematomas had significantly improved, and the cardiac metastasis was stable. However, 2 months after admission, the patient developed dyspnea and multiple nodular shadows appeared to be spreading in the subpleura of the lungs bilaterally, which were initially suspected to be pulmonary tumor embolisms. Prednisolone and subsequent administration of lenvatinib were not effective and the patient succumbed to respiratory failure. Severe DIC caused by extremely rare cardiac metastasis of SCC of the thyroid gland was effectively controlled by chemoradiotherapy. However, intensive local control appears to be required for this condition. [ABSTRACT FROM AUTHOR]