Comparing these IC(50) values with intratubular concentrations of unbound drugs in humans, it is thought that URAT1 is a target molecule of uricosuric drugs, including 6-hydroxybenzbromarone, probenecid, indomethacin and salicylate, to inhibit urate reabsorption in vivo. In addition, a cell line that stably expressing URAT1 could be a useful tool for the development of uricosuric drugs.

Abstract:Our objective was to determine the incidence of inguinal hernia (IH) after surgery for prostatic diseases. Medical records of 395 patients who underwent radical retropubic prostatectomy (RRP; n = 155), open simple prostatectomy (OP; n = 35), or transurethral resection of the prostate (TURP; n = 205) at the Chibaken Saiseikai Narashino Hospital from April 2000 to March 2007 were retrospectively evaluated. The incidence of IH was 23.9% in the RRP group, 18.9% in the OP group, and 2% in the TURP group. Overall, 91.9% in the RRP and 83.3% in the OP group developed an IH within 2 years postoperatively. The laterality of IH after open surgery was mainly on the right side. Subclinical IH were seen in 25% of RRP cases. The existence of subclinical IH was the only significant risk factor for postoperative IH in this analysis. Furthermore, OP and RRP procedures significantly increased the risk of postoperative IH compared with TURP. The hernia-free ratios were significantly lower after RRP and OP than after TURP (vs RRP: P < 0.001; vs OP: P < 0.001). Our findings confirm that a lower abdominal incision itself is associated with postoperative IH in patients undergoing prostate surgery. Attention must be paid to pre-existing subclinical IH through careful preoperative assessment. Patients should be followed for more than 2 years due to the high incidence of postoperative IH.

Cystinuria is caused by the inherited defect of apical membrane transport systems for cystine and dibasic amino acids in renal proximal tubules. Mutations in either SLC7A9 or SLC3A1 gene result in cystinuria. The mutations of SLC7A9 gene have been identified mainly from Italian, Libyan Jewish, North American, and Spanish patients. In the present study, we have analyzed cystinuria cases from oriental population (mostly Japanese). Mutation analyses of SLC7A9 and SLC3A1 genes were performed on 41 cystinuria patients. The uptake of 14C-labeled cystine in COS-7 cells was measured to determine the functional properties of mutants. The protein expression and localization were examined by Western blot and confocal laser-scanning microscopy. Among 41 patients analyzed, 35 were found to possess mutations in SLC7A9. The most frequent one was a novel missense mutation P482L that affects a residue near the C-terminus end of the protein and causes severe loss of function. In MDCK II and HEK293 cells, we found that P482L protein was expressed and sorted to the plasma membrane as well as wild type. The alteration of Pro482 with amino acids with bulky side chains reduced the transport function of b(0,+)AT/BAT1. Interestingly, the mutations of SLC7A9 for Japanese cystinuria patients are different from those reported for European and American population. The results of the present study contribute toward understanding the distribution and frequency of cystinuria-related mutations of SLC7A9.

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