Claudin-14 Gene Polymorphisms and Urine Calcium Excretion.

BACKGROUND AND OBJECTIVES: Claudin-16 and -19 are proteins forming pores for the paracellular reabsorption of divalent cations in the ascending limb of Henle loop; conversely, claudin-14 decreases ion permeability of these pores. Single-nucleotide polymorphisms in gene coding for claudin-14 were associated with kidney stones and calcium excretion. This study aimed to explore the association of claudin-14, claudin-16, and claudin-19 single-nucleotide polymorphisms with calcium excretion. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective observational study of 393 patients with hypertension who were naïve to antihypertensive drugs, in whom we measured 24-hour urine calcium excretion; history of kidney stones was ascertained by interview; 370 of these patients underwent an intravenous 0.9% sodium chloride infusion (2 L in 2 hours) to evaluate the response of calcium excretion in three different 2-hour urine samples collected before, during, and after saline infusion. Genotypes of claudin-14, claudin-16, and claudin-19 were obtained from data of a previous genome-wide association study in the same patients. RESULTS: Thirty-one single-nucleotide polymorphisms of the 3' region of the claudin-14 gene were significantly associated with 24-hour calcium excretion and calcium excretion after saline infusion. The most significant associated single-nucleotide polymorphism was rs219755 (24-hour calcium excretion in GG, 225±124 mg/24 hours; 24-hour calcium excretion in GA, 194±100 mg/24 hours; 24-hour calcium excretion in AA, 124±73 mg/24 hours; P<0.001; calcium excretion during saline infusion in GG, 30±21 mg/2 hours; calcium excretion during saline infusion in GA, 29±18 mg/2 hours; calcium excretion during saline infusion in AA, 17±11 mg/2 hours; P=0.03). No significant associations were found among claudin-16 and claudin-19 single-nucleotide polymorphisms and calcium excretion and between claudin-14, claudin-16, and claudin-19 single-nucleotide polymorphisms and stones. Bioinformatic analysis showed that one single-nucleotide polymorphism at claudin-14 among those associated with calcium excretion may potentially influence splicing of transcript. CONCLUSIONS: Claudin-14 genotype at the 3' region is associated with calcium excretion in 24-hour urine and after the calciuretic stimulus of saline infusion.

Anion Gap as a Determinant of Ionized Fraction of Divalent Cations in Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Circulating levels of anions that bind to magnesium and calcium are often altered in patients with CKD. However, it is unknown how these alterations affect the ionized fraction of magnesium and calcium. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This cross-sectional study involved patients on maintenance hemodialysis and patients not on dialysis who visited the outpatient department of nephrology. We collected whole-blood samples to measure ionized magnesium and calcium concentrations. Adjusted anion gap was calculated as an integrative index of unmeasured anions. RESULTS: A total of 118 patients on hemodialysis and 112 patients not on dialysis were included. Although the prevalence of hypermagnesemia defined by total magnesium was much higher in patients on hemodialysis than in patients not on dialysis (69% versus 12%; P<0.001), the prevalence of hypermagnesemia defined by ionized magnesium did not differ significantly (13% versus 18%; P=0.28). Among patients on hemodialysis with high total magnesium, 83% had normal or low ionized magnesium. Consequently, the mean ionized fraction of magnesium in patients on hemodialysis was significantly lower than that in patients not on dialysis (51% versus 63%; P<0.001). Similarly, the mean ionized fraction of calcium in patients on hemodialysis was lower than that in patients not on dialysis (55% versus 56%; P<0.001). In patients on hemodialysis who had a higher adjusted anion gap than patients not on dialysis (mean [SD]: 14.1 [2.2] versus 5.1 [3.1]), the ionized fractions of magnesium and calcium were inversely associated with the adjusted anion gap. Furthermore, the anion gap significantly improved predictions of ionized magnesium and calcium in patients on hemodialysis. CONCLUSIONS: Anions that accumulate in patients on hemodialysis contribute to the lower ionized fraction of magnesium and calcium. Equations that incorporate the anion gap provide better predictions of ionized magnesium and calcium in patients on hemodialysis.

The experimental study on MR diffusion and perfusion-weighted imaging during permanent focal cerebral ischemia in rabbits,comparison with the changes of intracellular Ca~(2+) in brain slice / 中华放射学杂志

Objective Calcium overload has important effect on cell injury in the ischemic stroke MR DWI/PWI mismatch may display the ischemic penumbra We try to explain the relationship between the characters of MR DWI/PWI and intracellular Ca 2+ in the different ischemic region through the model of focal cerebral ischemia Methods Twenty-eight rabbits underwent permanent middle cerebral artery occlusion (MCAo) From 0 5 h to 36 h after the onset of occlusion, diffusion-, perfusion-, and T 2-weighted MR imaging were performed to generate ADC, CBF, CBV parameters and anatomic images After the MR scanning, the same brain slices were incubated with Fluo-3/AM followed by the examination using laser confocal scanning microscope (LCSM) At different ischemic time, fluorescence intensity (FI) of the intracellular Ca 2+ in the DWI/PWI match region and mismatch one was recorded FI match /FI contralateral and FI mismatch /FI contralateral were produced and analyzed Results (1) MR outcome: The DWI/PWI match was located in the lateral caudoputamen and the DWI/PWI mismatch was mainly located in the frontoparietal cortex At 0 5 h after MCAo, CBF and CBV of lateral caudoputamen and frontoparietal cortex in the affected side deceased marked and the rCBF and rCBV of lateral caudoputamen were less then that of frontoparietal cortex in all groups ( t =-11 74, P

Berberine-induced Changes of Mitochondria Membrane Potential and Free Intracellular Calcium of HaCaT Cells / 中华皮肤科杂志

Objective To study the effects on berberine hydrochloride on the mitochondria membrane potential and free intracellular calcium of HaCaT cells, and elucidate the mechanism of action of berberine on keratinocytes. Methods Rhodamine-123 fluorescence (very sensitive to mitochondria membrane potential) and Fluo-3/AM fluorescence (suitabe to detect free intracellular calcium in single HaCaT cell) were measured by laser scanning confocal technique. Results Fluo-3/AM fluorescence intensity of HaCaT cells was persistently increased after treating with berberine at concentrations of 5 ? 10-5M, 2.5 ? 10-5M and 1.25 ? 10-5M, and significant differences were observed as compared with the PBS control. The intensity of rhodamine-123 fluorescence in HaCaT cells was decreased immediately when exposed to berberine, with significant difference from that of the PBS control. Conclusions It is suggested that berberine could increase free intracellular calcium and decrease mitochondria membrane potential of HaCaT cells, induce overload of intracellular calcium, influence energy metabolism, and then inhibit the proliferation of keratinocytes.