NKCC2 surface expression in mammalian cells: down-regulation by novel interaction with aldolase B.

Apical bumetanide-sensitive Na(+)-K(+)-2Cl(-) co-transporter, termed NKCC2, is the major salt transport pathway in kidney thick ascending limb. NKCC2 surface expression is subject to regulation by intracellular protein trafficking. However, the protein partners involved in the intracellular trafficking of NKCC2 remain unknown.

Gated blood pool tomoscintigraphy with 4-dimensional optical flow motion analysis quantifies left ventricular mechanical activation and synchronization.

Background: Gated blood pool tomoscintigraphy has the unique capacity to accurately assess myocardial motion in paced patients. Our goal was to develop a precise radionuclide angiography analysis of cardiac dynamics to evaluate ventricular synchronization in patients undergoing biventricular pacing.

Methods And Results: On the basis of a 4-dimensional deformable motion estimation algorithm, we developed a protocol allowing estimation of motion fields after gated blood pool tomoscintigraphy.

Tissue kallikrein-deficient mice display a defect in renal tubular calcium absorption.

Renal tubular calcium (RTCa) transport is one of the main factors that determine serum Ca concentration and urinary Ca excretion. The distal convoluted and connecting tubules reabsorb a significant fraction (10%) of filtered Ca. These tubule segments also synthesize in large abundance tissue kallikrein (TK), a major kinin-forming enzyme.

Genetic ablation of Rhbg in the mouse does not impair renal ammonium excretion.

NH(4)(+) transport by the distal nephron and NH(4)(+) detoxification by the liver are critical for achieving regulation of acid-base balance and to avoid hyperammonemic hepatic encephalopathy, respectively. Therefore, it has been proposed that rhesus type B glycoprotein (Rhbg), a member of the Mep/Amt/Rh NH(3) channel superfamily, may be involved in some forms of distal tubular acidosis and congenital hyperammonemia. We have tested this hypothesis by inactivating the RHbg gene in the mouse by insertional mutagenesis.

Bone status in primary hyperparathyroidism assessed by regional bone mineral density from the whole body scan and QUS imaging at calcaneus.

To assess the bone mineral density status in primary hyperparathyroidism (PHPT), we studied 64 females with PHPT and 17 healthy women. Regional BMD (arms, trunk, legs) from the whole body scan and conventional sites (lumbar spine, femur, radius) were assessed by DXA. Quantitative ultrasound (QUS) imaging measurements were performed at calcaneus.

Inactivation of the Na-Cl co-transporter (NCC) gene is associated with high BMD through both renal and bone mechanisms: analysis of patients with Gitelman syndrome and Ncc null mice.

Unlabelled: Chronic thiazide treatment is associated with high BMD. We report that patients and mice with null mutations in the thiazide-sensitive NaCl cotransporter (NCC) have higher renal tubular Ca reabsorption, higher BMD, and lower bone remodeling than controls, as well as abnormalities in Ca metabolism, mainly caused by Mg depletion.

Introduction: Chronic thiazide treatment decreases urinary Ca excretion (UVCa) and increases BMD.

Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function.

Recent recommendations emphasize the need to assess kidney function using creatinine-based predictive equations to optimize the care of patients with chronic kidney disease. The most widely used equations are the Cockcroft-Gault (CG) and the simplified Modification of Diet in Renal Disease (MDRD) formulas. However, they still need to be validated in large samples of subjects, including large non-U.

Regulation of the Cl-/HCO3- exchanger AE2 in rat thick ascending limb of Henle's loop in response to changes in acid-base and sodium balance.

The Cl(-)/HCO(3)(-) exchanger AE2 is believed to be involved in transcellular bicarbonate reabsorption that occurs in the thick ascending limb of Henle's loop (TAL). The purpose of this study was to test whether chronic changes in acid-base status and sodium intake regulate AE2 polypeptide abundance in the TAL of the rat. Rats were subjected to 6 d of loading with NaCl, NH(4)Cl, NaHCO(3), KCl, or KHCO(3).

The Cl-/HCO3- exchanger pendrin in the rat kidney is regulated in response to chronic alterations in chloride balance.

Pendrin (Pds; Slc26A4) is a new anion exchanger that is believed to mediate apical Cl(-)/HCO(3)(-) exchange in type B and non-A-non-B intercalated cells of the connecting tubule and cortical collecting duct. Recently, it has been proposed that this transporter may be involved in NaCl balance and blood pressure regulation in addition to its participation in the regulation of acid-base status. The purpose of our study was to determine the regulation of Pds protein abundance during chronic changes in chloride balance.

Angiotensin II inhibits NaCl absorption in the rat medullary thick ascending limb.

NaCl reabsorption in the medullary thick ascending limb of Henle (MTALH) contributes to NaCl balance and is also responsible for the creation of medullary interstitial hypertonicity. Despite the presence of angiotensin II subtype 1 (AT(1)) receptors in both the luminal and the basolateral plasma membranes of MTALH cells, no information is available on the effect of angiotensin II on NaCl reabsorption in MTALH and, furthermore, on angiotensin II-dependent medullary interstitial osmolality. MTALHs from male Sprague-Dawley rats were isolated and microperfused in vitro; transepithelial net chloride absorption (J(Cl)) as well as transepithelial voltage (V(te)) were measured.

What keeps serum calcium levels stable?

Many body functions require that serum calcium levels remain stable over time. This stability is provided by cooperation among three organs: two effectors, the bone and the kidney, which control calcium movements into and out of the extracellular compartment, and the parathyroid glands, which produce and release parathyroid hormone (PTH). PTH acts on the bone and renal tubule.

Normocalcemic primary hyperparathyroidism: evidence for a generalized target-tissue resistance to parathyroid hormone.

Primary hyperparathyroidism (PHPT) is usually characterized by fasting hypercalcemia associated with inappropriately high PTH concentration. Nevertheless, cases of proven PHPT have been reported in normocalcemic patients. The purpose of the study was to investigate the mechanism(s) of persistent normocalcemia in PHPT.

Urinary measurement of Na+/H+ exchanger isoform 3 (NHE3) protein as new marker of tubule injury in critically ill patients with ARF.

Background: It has been shown that apical sodium transporters of the renal tubule can be detected by immunoblotting of urine membrane fraction from rats. We raised the hypothesis that protein levels of the Na+/H+ exchanger isoform 3 (NHE3), the most abundant apical sodium transporter in renal tubule, should be increased in urine of patients presenting with acute renal failure (ARF) with severe tubular cell damage and thus might be a noninvasive marker of acute tubular necrosis (ATN).

Methods: Sixty-eight patients admitted to the intensive care unit were studied prospectively (54 patients with ARF, 14 controls without renal dysfunction).

Basal asynchrony and resynchronization with biventricular pacing predict long-term improvement of LV function in heart failure patients.

Biventricular pacing (BiV) is emerging for patients with dilated cardiomyopathy (DCM) and asynchrony. We measured basal asynchrony and early resynchronization by radionuclide angioscintigraphy (RNA) in order to predict long-term evolution of ventricular function after BiV. Thirty-four patients (NYHA Class III-IV,65.

Angiotensin II stimulates NHE3 activity by exocytic insertion of the transporter: role of PI 3-kinase.

Background: Low-concentration angiotensin II (Ang II) stimulates Na+/H+ exchanger 3 (NHE3) activity in renal proximal tubule mainly via angiotensin II type 1 (AT1) receptors. The mechanisms that mediate the increase in NHE3 activity elicited by Ang II remain incompletely settled.

Methods: To assess a potential role of NHE3 trafficking in the Ang II effect, NHE3 activity was measured by H+-driven initial rate of 22Na uptake resistant to 50 micromol/L of the Na+/H+ exchange inhibitor cariporide (HOE642), and sensitive to 300 micromol/L ethyl isopropyl amiloride (EIPA), in a model of cultured proximal tubular cells (MKCC), in which functional apical NHE3 and AT receptors are normally present.

Differentiated thick ascending limb (TAL) cultured cells derived from SV40 transgenic mice express functional apical NHE2 isoform: effect of nitric oxide.

Studying the apical Na/H exchanger NHE2 is difficult in the intact thick ascending limb (TAL) because of its weak expression and transport activity compared with the co-expressed NHE3. From a mouse transgenic for a recombinant plasmid adeno-SV(40) (PK4), we developed an immortalized TAL cell line, referred to as MKTAL, which selectively expresses NHE2 protein and activity. The immortalized cells retain the main properties of TAL cells.

Circulating vasopressin levels in septic shock.

Objective: To assess the frequency of vasopressin deficiency in septic shock.

Design: Prospective cohort study.

Setting: Intensive care unit at Raymond Poincaré University Hospital.

RhBG and RhCG, the putative ammonia transporters, are expressed in the same cells in the distal nephron.

Two nonerythroid homologs of the blood group Rh proteins, RhCG and RhBG, which share homologies with specific ammonia transporters in primitive organisms and plants, could represent members of a new family of proteins involved in ammonia transport in the mammalian kidney. Consistent with this hypothesis, the expression of RhCG was recently reported at the apical pole of all connecting tubule (CNT) cells as well as in intercalated cells of collecting duct (CD). To assess the localization along the nephron of RhBG, polyclonal antibodies against the Rh type B glycoprotein were generated.

pH dependence of Na+/myo-inositol cotransporters in rat thick limb cells.

Background: To balance medullary interstitium hypertonicity generated by transepithelial NaCl absorption, medullary thick ascending limb (MTAL) cells accumulate myo-inositol (MI). Expression of Na+-MI cotransporter (SMIT) mRNA in TAL is correlated with the NaCl absorption rate. Our present study aimed to determine the plasma membrane location and functional properties of the Na+-MI cotransporter in MTAL cells.

Sleep/wake cycles in the dark: sleep recorded by polysomnography in 26 totally blind subjects compared to controls.

Objectives: To evaluate subjective sleep difficulties and nocturnal sleep with polysomnography in 26 completely blind subjects, living in normal social environments and to compare the findings with those of matched controls.

Methods: Twenty-six blind individuals with no light perception and free-running melatonin rhythms, as assessed by measurements of urinary and salivary 6-sulfatoxymelatonin, were polygraphically monitored. Actigraphy and Braille sleep logs were obtained from the individuals for 14 days.

Medical and socio-professional impact of insomnia.

Study Objectives: Insomnia, a highly prevalent disorder with direct and indirect economic and professional consequences, affects daytime functioning, behavior, and quality of life. Several studies have shown that insomnia affects the workforce and is associated with an increased risk of accidents. Insomnia may also play a role in other disorders.

Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome.

The extracellular Ca(2+)-sensing receptor (CaSR) plays an essential role in extracellular Ca(2+) homeostasis by regulating the rate of parathyroid hormone (PTH) secretion and the rate of calcium reabsorption by the kidney. Activation of the renal CaSR is thought to inhibit paracellular divalent cation reabsorption in the cortical ascending limb (cTAL) both directly and indirectly via a decrease in NaCl transport. However, in patients with autosomal dominant hypocalcemia (ADH), caused by CaSR gain-of-function mutations, a defect in tubular NaCl reabsorption with renal loss of NaCl has not been described so far.

Expression of RhCG, a new putative NH(3)/NH(4)(+) transporter, along the rat nephron.

Two non-erythroid members of the erythrocyte Rhesus (Rh) protein family, RhBG and RhCG, have been recently cloned in the kidney. These proteins share homologies with specific NH(3)/NH(4)(+) transporters (Mep/Amt) in primitive organisms and plants. When expressed in a Mep-deficient yeast, RhCG can function as a bidirectional NH(3)/NH(4)(+) transporter.

The luminal membrane of rat thick limb expresses AT1 receptor and aminopeptidase activities.

Background: Endogenous intratubular angiotensin II (Ang II) supports an autocrine tonic stimulation of NaCl absorption in the proximal tubule, and its production may be regulated independently of circulating Ang II. In addition, endogenous Ang II activity may be regulated at the brush border membrane (BBM), by the rate of aminopeptidase A and N (APA and APN) activities and the rate of Ca2+-independent phospholipase A2 (PLA2-dependent endocytosis and recycling of the complex Ang II subtype 1 (AT1) receptor (AT1-R). The aim of the present study was to look for subcellular localization of AT1-R, and APA and APN activities in the medullary thick ascending limb of Henle (mTAL), as well as search for an asymmetric coupling of AT1-R to signal transduction pathways.