Defect in parathyroid-hormone-induced luminal calcium absorption in connecting tubules of Klotho mice.

Background: Homozygous Klotho mutant mice (KL(-/-) mice) exhibit multiple phenotypes resembling human ageing. Increases in the ratio of urinary calcium to urinary creatinine (uCa/uCr) and in serum Ca concentration and decreases in urinary Cr excretion and serum parathyroid hormone (PTH) concentration were reported; however, precise information about renal Ca handling was not reported in these animals.

Methods: We evaluated the PTH-induced increase in intracellular Ca(2+) concentration ([Ca(2+)]i) in cells of isolated perfused connecting tubules (CNTs) of KL(-/-) mice.

Drug interaction between St John's Wort and quazepam.

Aim: St John's Wort (SJW) enhances CYP3A4 activity and decreases blood concentrations of CYP3A4 substrates. In this study, the effects of SJW on a benzodiazepine hypnotic, quazepam, which is metabolized by CYP3A4, were examined.

Methods: Thirteen healthy subjects took a single dose of quazepam 15 mg after treatment with SJW (900 mg day(-1)) or placebo for 14 days.

Chronopharmacology of oxacalcitriol in 5/6 nephrectomized rats.

We previously reported on the merits of the chronopharmacological effects of 1,25(OH) 2 vitaminD3 in 5/6 nephrectomized rats (Tsuruoka et al, Life Scineces 2002; 71: 1809-1820). In this study, the chronopharmacological effect of 22-oxacalcitriol (OCT), a newly developed active vitaminD3 analogue with less calcemic activity, was evaluated by a single and repeated dosing of the drug. The 5/6 nephrectomized animals were kept in rooms with a 12-h light/dark cycle.

Subclinical alteration of taste sensitivity induced by candesartan in healthy subjects.

Aims: There have been case reports of taste disturbance for the angiotensin II receptor blockers losartan and valsartan, but not for candesartan. This study was undertaken to examine whether candesartan causes taste disturbance.

Methods: Candesartan cilexetil (4 mg day(-1)) or vehicle was given to healthy volunteers (n = 8) for 7 days in a randomized, double-blind, placebo-controlled, cross-over design with a 2-week washout period.

Nitric oxide production modulates cyclosporin A-induced distal renal tubular acidosis in the rat.

Cyclosporine A (CsA) causes distal renal tubular acidosis (dRTA) in humans and rodents. Because mice deficient in nitric-oxide (NO) synthase develop acidosis, we examined how NO production modulated H+ excretion during acid loading and CsA treatment in a rat model. Rats received CsA, L-arginine (L-Arg), or N omega-nitro-L-arginine methyl ester (L-NAME), or combinations of CsA and L-NAME or L-Arg, followed by NH4Cl (acute acid load).

Dosing time-dependent variation in the hypocalcemic effect of calcitonin in rat.

Dosing time-dependent variation in the hypocalcemic effect of salmon calcitonin was examined in rats under a 12-h light-dark cycle. In both a single-dosing study with normal rats and a repeated-dosing study with hypercalcemic rats (induced by chronic vitamin-D dosing), we consistently observed that the hypocalcemic effect of calcitonin was greater when the drug was given at 14 h after lights on than that at 2 h after lights on. The reduction in urinary deoxypyridinoline excretion, a marker of bone resorption, was also greater when calcitonin was given at 14 h after lights on.

Inhibition of Rho-kinase reduces renal Na-H exchanger activity and causes natriuresis in rat.

Rho-kinase regulates the actin cytoskeleton and therefore modulates transport. The role of Rho-kinase in Na-H exchanger (NHE) activity of rat proximal convoluted tubules (PCTs) was investigated using (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632), a specific inhibitor of Rho-kinase. In spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats, apical and basolateral NHE activities were determined by measuring cell pH recovery following luminal NH4+ prepulse and basolateral sodium removal, respectively.

Specific therapy of digoxin intoxication in dogs by hybrid kidney overexpressing multidrug resistance protein.

Background: We have recently developed a unique hybrid artificial kidney, where the proximal tubular cell line, over-expressing multidrug resistance protein, MDR-1 (PCTL-MDR), was cultured on hollow fibers. While this module efficiently removed digoxin in vitro, its efficacy in vivo remained to be determined.

Methods: The system was scaled up by connecting 10 similar modules in parallel, with the MDR-1 (PCTL-MDR) overexpressed proximal tubular cell line cultured as in our previous study.

Time of day improves efficacy and reduces adverse reactions of vitamin D3 in 5/6 nephrectomized rat.

Time-dependent differences in adverse reactions and efficacy by a repeated administration of 1,25(OH)2 vitamin D3 (vit D, 0.3 microg/Kg/day for 12 weeks) were examined in 5/6 nephrectomized rats under a condition of 12-hour light-dark cycle. The 5/6 nephrectomy increased serum concentrations of phosphate, osteocalcin and PTH, and urinary excretions of phosphate and deoxypyridinoline (DPD) while the maneuver reduced serum Ca concentration and its urinary excretion.

Vitamin E-bonded hemodialyzer improves neutrophil function and oxidative stress in patients with end-stage renal failure.

We evaluated the biocompatibility of a newly developed vitamin E hemodialyzer (CL-EE; Terumo Co Ltd, Tokyo, Japan) by neutrophil function and oxidant stress in patients with end-stage renal failure in a randomized crossover study. Ten patients underwent hemodialysis using either the CL-EE or a control dialyzer membrane identical to the CL-EE except for vitamin E binding for 12 weeks in a crossover fashion after a 1-month washout period with hemophane membranes. White blood cell counts, serum oxidized low-density lipoprotein (Ox-LDL) levels, and malondialdehyde (MDA) levels during hemodialysis sessions were measured at the initiation and end of the CL-EE and control trials.