Dynamic change and preventive role of stress response via Keap1-Nrf2 during renal crystal formation.

Oxidative stress is a major risk factor for calcium oxalate nephrolithiasis. Reports suggest that oxidative stress response is induced in animals and humans with kidney stones. Keap1, Nrf2, and HO-1 are known as oxidative stress mediators. However, the association between oxidative stress response and stone formation is unclear. In this study, we analyzed oxidative stress response from the acute to the crystal formation phase when crystal formation was applied to renal crystal mice model and bioimaging mice and investigated the effect on crystal formation. In renal tissues, after glyoxylate administration, HO-1 increased for up to 6 h and returned to baseline at 24 h. This was observed following each daily dose until five days after the crystallization phase; however, the range of increase was attenuated. The possibility that Nrf2 activity influenced the number of crystals was considered in the experiment. Crystal formation increased in Nrf2-deficient mice and could be reduced by Nrf2 activators. In conclusion, the oxidative stress response via the Keap1-Nrf2 pathway may contribute to crystal formation. Particularly, this pathway may be a prospective target for drug development to prevent and cure nephrolithiasis.

[CLINICAL STUDY OF THE PROSTATE CANCERS WITH A SERUM PROSTATE SPECIFIC ANTIGEN LEVEL OF MORE THAN 100 ng/ml AT THE FIRST DIAGNOSIS].

In patients with prostate cancer high serum prostate specific antigen (PSA) at diagnosis was generally regarded as a strong impression of advanced disease with distant metastasis and poor prognosis. (Objective) We reported a retrospective study of prognostic factor and Overall survival (OS) in patients with prostate specific antigen (PSA) level of greater than 100 ng/ml (PSA≥100 ng/ml). (Subjects and methods) Between January 2002 and December 2015, 60 patients were diagnosed prostate cancer with PSA≥100 ng/ml and performed hormonal monotherapy at Kanazawa Medical University hospital. We evaluated initial PSA level, Gleason score, Gleason Grading Group, clinical stage, site of metastasis, PSA nadir level, Time to PSA nadir (TTN), serum Hemoglobin (Hb) level, serum C-Reactive Protein (CRP) level, serum Lactate Dehydrogenase (LDH) level, serum Alkaline Phosphatase (ALP) level, clinical passage and survival time. (Results) The median age of the patients was 73 years old (54-90) and the initial PSA levels ranged from 100 ng/ml to 15,823 ng/ml (median 390).Prognostic factors of overall survival were site of metastasis, Gleason score, Gleason Grading Group, PSA nadir level, TTN, serum CRP level, serum LDH level and serum ALP level at the diagnosis. In multivariate analysis serum LDH level remained an independent predictor of OS.