Freel RW, Morozumi M, Hatch M. Parsing apical oxalate exchange in Caco-2BBe1 monolayers: siRNA knockdown of SLC26A6 reveals the role and properties of PAT-1. Am J Physiol Gastrointest Liver Physiol 297: G918 -G929, 2009. First published August 27, 2009 doi:10.1152/ajpgi.00251.2009.-The purpose of this investigation was to quantitate the contribution of the anion exchanger PAT-1 (putative anion transporter-1), encoded by SLC26A6, to oxalate transport in a model intestinal epithelium and to discern some characteristics of this exchanger expressed in its native environment. Control (Con) Caco-2 BBe1 monolayers, 6 -8 days postseeding, were compared with those transfected with a small interfering RNA targeted to SLC26A6 (A6KD). Radiotracer and Ussing chamber techniques were used to determine the transepithelial unidirectional fluxes of Ox 2Ϫ , Cl Ϫ , and SO 4 2Ϫ whereas fluorometric/BCECF measurements of intracellular pH were used to assess HCO 3 Ϫ exchange. PAT-1 was functionally targeted to the apical membrane, and SLC26A6 knockdown reduced PAT-1 protein (Ͼ60%) and mRNA (Ͼ75%) expression in A6KD. No net flux of Ox 2Ϫ , Cl Ϫ , or SO 4 2Ϫ was detected in Con or A6KD monolayers, yet the unidirectional fluxes in A6KD were reduced 50, 35, and 15%, respectively. Cl Ϫ -dependent HCO 3 Ϫ efflux from A6KD was reduced 50% compared with Con. The difference between Con and A6KD properties represents that mediated solely by PAT-1, and by this approach we found that PAT-1-mediated oxalate influx and efflux are inhibited equally by mucosal DIDS (EC 50 ϳ5 M) and that mucosal Cl Ϫ inhibits oxalate uptake with an EC50 Ͻ 20 mM. Transepithelial Cl Ϫ gradients supported large, DIDS-sensitive net absorptive or secretory fluxes of oxalate in a direction opposite that of the imposed Cl Ϫ gradient. The overall symmetry of PAT-1-mediated oxalate exchange suggests that vectorial oxalate transport observed in vivo is principally dependent on the magnitude and direction of counterion gradients. chloride; bicarbonate; sulfate; intestine; transport; anion flux; nephrolithiasis; putative anion transporter-1; small interfering RNA CALCIUM OXALATE NEPHROLITHIASIS is a relatively common disorder that may result from an imbalance in oxalate input (absorption from dietary sources and endogenous hepatic oxalogenesis) and oxalate output (renal excretion, intestinal secretion) (12). Intestinal epithelia play an important role in oxalate homeostasis by mediating bidirectional and net oxalate transport in a segment-specific manner (11, 12). Recent interest in identifying possible mediators of oxalate transport has been successfully focused on anion exchanger proteins encoded by the SLC26A family of genes (1,3,23). For example, the protein encoded by SLC26A6 (PAT-1, putative anion transporter-1; also referred to as CFEX, chloride-formate exchanger) has been shown to be an important mediator of oxalate secretion in the mouse ileum (10) and duodenum (13), since SLC26A6 knockout mice excrete less oxalate enterically and develop hyperoxaluria, which can promot...

The predominance of osteoblastic change with resorption may lead to bone remodeling in metastatic lesions, and osteoclasts may play an important role in bone metastasis from prostate cancer.

Calcium oxalate supersaturation of the blood is associated with deposition of crystals in various tissues. We measured the serum levels of oxalate, citrate, calcium, and magnesium to estimate their saturation in 112 hemodialysis patients without primary hyperoxaluria and two boys with primary hyperoxaluria. Serum levels of oxalate and citrate were determined by high-performance capillary electrophoresis, while calcium and magnesium were measured by ICP spectroscopy. The serum levels of oxalate, citrate, calcium, and magnesium were 44.9+/-16.5, 138.1+/-54.9 micromol/l, 2.30+/-0.28, and 1.07+/-0.18 mmol/l, respectively, while the levels in patients with primary hyperoxaluria were 83.9+/-34.3, 197.9+/-63.5 micromol/l, 2.53+/-0.15, and 1.14+/-0.34 mmol/l, respectively. Serum calcium oxalate saturation (SS), as calculated by the Equil program, was significantly correlated with the serum oxalate level. Most patients showed metastable supersaturation (1

The TaqI t allele of the VDR gene may be a risk factor for severe stone disease and recurrent stones.

Abstract:The incidence of stonestreet formation after extracorporeal shock wave lithotripsy (ESWL) rises with increasing stone burden. However, stonestreet after ESWL is often experienced even in stones smaller than 20 mm. To examine whether the non-contrast helical computed tomography (CT) data could predict stonestreet formation in these stones, 53 radiopaque stones of 5-20 mm treated with ESWL were evaluated. Maximal dimension was measured on plain radiograph. From an attenuation value histogram graphed from the CT data, total stone volume and mean attenuation value were calculated. Seven stonestreets longer than 25 mm developed. There was no significant difference in maximal dimension and total stone volume between stones that did and stones that did not develop stonestreet. Mean attenuation value was the sole significant predictive factor. Application of mean attenuation value with cut-off level of 650 HU would anticipate stonestreet formation with a sensitivity of 85.7% and a specificity of 71.7%. The estimated risk of stonestreet formation is high in the treatment of stones with higher mean attenuation value.