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Moshe Levi

Publications and source records attributed to Moshe Levi.

32 records · Page 2Linked to original sources
PubMed2004

Regulation of NaPi-IIa mRNA and transporter protein in chronic renal failure: role of parathyroid hormone (PTH) and dietary phosphate (Pi).

Chronic renal failure (CRF) is associated with a high fractional phosphate excretion (FEPi), secondary hyperparathyroidism, and resistance to parathyroid hormone (PTH). This study was undertaken to characterize the role of PTH and dietary Pi in the regulation of PTH/PTH-related peptide receptor (PTHrP-R) mRNA and NaPi-IIa mRNA and protein in CRF. The following groups of rats were studied: (1) sham-operated (control); (2) CRF: 6 weeks after 5/6 nephrectomy (NPX); (3) NPX and parathyroidectomy (NPX + PTX); (4) NPX rats fed a low-Pi diet (NPX + LP); (5) sham-operated rats fed a low-Pi diet (control + LP); (6) sham-operated after PTX (control + PTX). Expression of NaPi-IIa mRNA and PTH/PTHrP-R mRNA was determined in the renal cortex by Northern hybridization. NaPi-IIa protein abundance was determined in cortical brush border membranes by immunoblotting. In NPX rats creatinine clearance decreased to 40 +/- 4%, PTH/PTHrP-R mRNA to 52.1 +/- 2% and NaPi-IIa mRNA to 41.2 +/- 5.5% of control. The PTH/PTHrP-R and NaPi-IIa mRNA in the NPX + PTX and NPX + LP group was similar to that in NPX. NaPi-IIa protein abundance was reduced in NPX compared with control, but was increased dramatically in NPX + PTX and NPX + LP compared to NPX, paralleled by a decrease in FEPi. These findings suggest that the elevated FEPi in CRF is maintained by decreased NaPi-IIa mRNA and NaPi-IIa protein abundance. In contrast, the observed decrease in FEPi with PTX or LP diet in CRF is mediated, at least partly, by increased NaPi-IIa protein abundance with no change in NaPi-IIa mRNA, suggesting post-transcriptional regulation of the NaPi-IIa transporter.

Administration, Oral↗
PubMed2004

Advanced glycation end products and oxidative stress are increased in chronic allograft nephropathy.

BACKGROUND: The histologic picture of chronic allograft nephropathy (CAN) resembles early arteriosclerotic lesion. Oxidative stress and advanced glycation end products (AGES) have been implicated in the pathogenesis of atherosclerosis and progression of renal disease. METHODS: The authors serially measured the plasma malonyldialdehyde (MDA), carbonyl protein (CP), pentosidine, and argpyramidine levels in 11 postrenal transplant patients with normal renal function (KPT) and 10 patients with biopsy proven CAN at 1, 3, 6, 9 through 12, and 18 through 24 months posttransplant. Data were also obtained in 16 controls and 13 patients with chronic renal failure (CRF). RESULTS: Although serum creatinine, MDA, CP, pentosidine, and argpyrimidine levels decreased during follow-up in KPT, it progressively increased in patients with CAN. The mean serum creatinine level was higher in patients with CRF (3.3 +/- 0.8 mg/dL [291.7 +/- 70.7 micromol/L]) and CAN (2.4 +/- 1.1 mg/dL [212.1 +/- 96.6 micromol/L]) than in controls (1.2 +/- 0.3 mg/dL [105.8 +/- 26.7 micromol/L]) and KPT patients (1.2 +/- 0.2 mg/dL [109.7 +/- 17.7 micromol/L]; P < 0.001). Markers of oxidative stress and AGEs measured at 18 to 24 months posttransplant in patients with CAN were higher than in KPT, controls, and CRF patients. MDA (nmol/mL) was significantly higher in patients with CAN (1.30 +/- 0.30) compared with controls (0.53 +/- 0.12), KPT (0.52 +/- 0.15), and CRF (0.74 +/- 0.27) groups (P < 0.001). Plasma CP (nmol/mg protein) in patients with CAN (4.3 +/- 1.00) was higher than in controls (1.90 +/- 0.69) and KPT (2.62 +/- 1.00) groups at the same time-point (P < 0.001), but comparable with CRF (2.69 +/- 1.20). Plasma pentosidine (pmol/micromol protein) level in patients with CAN (19.69 +/- 5.05) was higher compared with controls (2.49 +/- 0.86), CRF (13.10 +/- 3.68), and KPT (14.32 +/- 6.28) groups (P < 0.001). Plasma argpyrimidine (pmol/10 micromol protein) was higher in patients with CAN (123.8 +/- 17.9) compared with controls (4.81 +/- 1.91), CRF (56.92 +/- 29.67), and KPT (31.1 +/- 11.1; P < 0.001) groups. CONCLUSION: Oxidative stress and AGEs are increased in patients with CAN, which cannot be explained by the decline in renal function alone. Oxidative stress and AGEs may be one among the nonimmune mediators of CAN.

Adult↗
PubMed2004

Spatial-temporal studies of membrane dynamics: scanning fluorescence correlation spectroscopy (SFCS).

Giant unilamellar vesicles (GUVs) have been widely used as a model membrane system to study membrane organization, dynamics, and protein-membrane interactions. Most recent studies have relied on imaging methods, which require good contrast for image resolution. Multiple sequential image processing only detects slow components of membrane dynamics. We have developed a new fluorescence correlation spectroscopy (FCS) technique, termed scanning FCS (i.e., SFCS), which performs multiple FCS measurements simultaneously by rapidly directing the excitation laser beam in a uniform (circular) scan across the bilayer of the GUVs in a repetitive fashion. The scan rate is fast compared to the diffusion of the membrane proteins and even small molecules in the GUVs. Scanning FCS outputs a "carpet" of timed fluorescence intensity fluctuations at specific points along the scan. In this study, GUVs were assembled from rat kidney brush border membranes, which included the integral membrane proteins. Scanning FCS measurements on GUVs allowed for a straightforward detection of spatial-temporal interactions between the protein and the membrane based on the diffusion rate of the protein. To test for protein incorporation into the bilayers of the GUVs, antibodies against one specific membrane protein (NaPi II cotransporter) were labeled with ALEXA-488. Fluorescence images of the GUVs in the presence of the labeled antibody showed marginal fluorescence enhancement on the GUV membrane bilayers (poor image contrast and resolution). With the application of scanning FCS, the binding of the antibody to the GUVs was detected directly from the analysis of diffusion rates of the fluorescent antibody. The diffusion coefficient of the antibody bound to NaPi II in the GUVs was approximately 200-fold smaller than that in solution. Scanning FCS provided a simple, quantitative, yet highly sensitive method to study protein-membrane interactions.

Antigen-Antibody Complex↗
PubMed2004

Recovery of renal tubule phosphate reabsorption despite reduced levels of sodium-phosphate transporter.

BACKGROUND: The acute effect of parathyroid hormone (PTH) on phosphate transport has been reported to be mediated by rapid downregulation of sodium-phosphate transporter (NaPi-IIa) protein, but the association was observed with pharmacological doses of PTH. OBJECTIVE: To explore the effects of physiological doses of PTH on NaPi-IIa protein and its relationship to phosphate transport. METHODS: Acute clearance studies were performed in parathyroidectomized rats given a bolus i.v. physiological dose (1 microg) of bovine PTH(1-34) and NaPi-IIa protein concentrations were examined at different time intervals. RESULTS: Fractional excretion of phosphate increased from 0.031+/-0.006 (mean+/-S.E.) to 0.238+/-0.059 (P<0.01 compared with baseline and compared with controls) at 40 min and returned to control values by 120 min. Urinary cAMP concentrations were increased at 20 min only. Superficial cortex brush-border membrane (BBM) NaPi-IIa protein was decreased from baseline at both 40 and 120 min (P<0.01) and did not recover at 240 min (P<0.01 compared with baseline and compared with controls). CONCLUSION: These results confirm that PTH, even in physiological dosage, causes a rapid decrease in BBM NaPi-IIa, but subsequent recovery of phosphate reabsorption is poorly correlated with BBM concentrations of NaPi-IIa protein. This suggests that transport mechanisms other than NaPi-IIa are important in renal phosphate reabsorption.

Absorption↗
PubMed2003

Central control of renal sodium-phosphate (NaPi-2) transporters.

Regulation of phosphate (Pi) reabsorption occurs through the up- and downregulation of the renal type-II sodium Pi cotransporters (NaPi-2). Recently, renal NaPi2-type expression has been identified in areas of the brain. The present study determined whether brain NaPi-2 is regulated by dietary Pi and whether the behavioral and renal adaptations to low-dietary Pi are controlled centrally. NaPi-2-like expression in the third ventricle (3V) and amygdala of juvenile Wistar rats was regulated by dietary Pi, as in the kidneys. When cerebrospinal fluid (CSF) Pi concentration was elevated by 3V injections of Pi in rats fed low-Pi diet (LPD), the behavioral and renal adaptations to LPD were abolished. Most importantly, NaPi-2 expression was markedly reduced not only in the brain, but also renal proximal tubules, despite the low plasma Pi milieu. This was confirmed by the significant reduction in the transport maximum for Pi (from 8.1+/-0.2 in LPD + veh 3V to 1.7+/-0.1 micromol Pi/ml glomerular filtration rate in LPD + 3V Pi, P < 0.001). These findings indicate that NaPi-2-like transporters in the brain are regulated by both dietary Pi and CSF Pi concentrations, and most significantly, that the central Pi milieu can regulate renal NaPi-2 expression. We hypothesize that central 3V NaPi-2 transporters may act as Pi sensors and help regulate both brain and whole body Pi homeostasis.

Adaptation, Physiological↗
PubMed2003

Hyperkalemia with concomitant watery diarrhea: an unusual association.

Four patients presented to the emergency room with life-threatening hyperkalemia and concomitant watery diarrhea. Hypovolemia, acidosis, and renal insufficiency were present in all 4 cases. In 2 patients, hyperkalemia followed initiation of angiotensin-converting enzyme (ACE) inhibitor therapy, whereas 1 patient experienced hyperkalemia after a dose increase of an ACE inhibitor, and the fourth patient was on continuous ACE-inhibitor therapy at the time of the hyperkalemia episode. Two of the 3 patients with functioning kidneys required hemodialysis to correct the hyperkalemia, whereas the other patient was on long-term hemodialysis therapy. In the 2 patients in whom transtubular potassium (K+) gradients were available, their values ranged far below normal, indicating tubular failure to secrete K+. This abnormality was attributed to decreased distal delivery of sodium and water and to renin/angiotensin II/aldosterone blockade. It has been proposed that aldosterone blockade impairs the capacity of the colonic epithelial cells to secrete K+. In all 4 patients the watery diarrhea ceased in parallel with the correction of serum K+ to normal values. It is suggested that hyperkalemia, most likely by stimulating intestinal motility, induced the watery diarrhea in all 4 patients. The watery diarrhea, however, failed to compensate for the renal tubular failure to secrete K+.

Aged↗
PubMed2003

Effect of high protein diet on stone-forming propensity and bone loss in rats.

BACKGROUND: High protein diets are believed to cause kidney stone formation and bone loss, but the mechanisms mediating these changes are unknown. The purpose of this study was to create an animal model of animal protein excess and to evaluate the response of kidney and bone to the dietary protein load. METHODS: Rats (12 per group) were pair-fed with a high (48%) and low (12%) casein diets that were otherwise identical in their content of sodium, potassium, calcium, phosphorus, and magnesium. RESULTS: Compared with the low casein group, the high casein group delivered a substantial acid load during 59 days of study, since it significantly decreased urinary pH, and increased urinary ammonium, titratable acidity, and net acid excretion. Animals on high casein diet also had higher urinary volumes. On the high casein diet, urinary calcium excretion was significantly higher and urinary citrate excretion and concentration was significantly lower. On the high casein diet, urinary saturation of calcium phosphate was higher. Serum calcitriol concentration did not significantly differ between the two groups. Histomorphometric analysis of femur procured after 59 days on the diet showed marked increase in bone resorption in the high casein group. Hypocitraturia was associated with increased activity of sodium-citrate cotransporter in renal cortical brush-border membranes (BBM) in the high casein group. CONCLUSION: Both the kidney and bone contribute to the pathogenesis of hypercalciuria during high casein diet in rats. Hypocitraturia is probably renal in origin. This rat model will be useful in elucidating the mechanisms by which high protein intake increases the risk of nephrolithiasis and bone loss in human beings.

Acid-Base Equilibrium↗
PubMed2003

Localized irregularities in hemoglobin flow and oxygenation in calf muscle in patients with peripheral vascular disease detected with near-infrared spectrophotometry.

PURPOSE: Near-infrared spectrophotometry is used to measure flow, concentration, and oxygenation of hemoglobin in arterioles, capillaries, and venules several centimeters deep in tissue. The purpose of this study was to investigate the distribution of flow, concentration, and oxygenation of hemoglobin in calf muscle in patients with documented peripheral arterial occlusive disease (PVD), patients with risk factors for PVD,and healthy younger subjects at rest. METHOD: With a frequency-domain near-infrared spectrophotometer and a specially designed probe, we generated maps at 22 locations simultaneously of hemoglobin flow, concentration, and oxygenation, with the venous occlusion method. Eight legs of 7 patients with diagnosed PVD (PVD group), 10 legs of 8 patients with normal ankle-brachial index but with risk factors for PVD (RF group), and 16 legs of 8 healthy subjects (H group) were studied. RESULTS: Global mean values were significantly (P <.05) different between the three groups for oxygen consumption (PVD group, 0.027 +/- 0.009 mL/100 g/min; RF group, 0.038 +/- 0.017 mL/100 g/min; H group, 0.022 +/- 0.020 mL/100 g/min), venous oxygen saturation (PVD, 59.7% +/- 15.4%; RF, 69.6% +/- 10.5%; H, 80.8% +/- 4.5%), and, at 60 s of venous occlusion, concentration changes in oxyhemoglobin (PVD, 4.48 +/- 3.25 micromol/L; RF, 8.44 +/- 2.33 micromol/L; H, 6.85 +/- 4.57 micromol/L), deoxyhemoglobin (PVD, 3.60 +/- 0.73 micromol/L; RF, 4.39 +/- 1.30 micromol/L; H, 2.36 +/- 1.79 micromol/L), and total hemoglobin (PVD, 8.07 +/- 3.83 micromol/L; RF, 12.83 +/- 2.75 micromol/L; H, 9.21 +/- 6.34 micromol/L). No significant difference was found between the three groups for hemoglobin flow (PVD, 0.92 +/- 0.69 micromol/100 mL/min; RF, 1.68 +/- 0.50 micromol/100 mL/min; H, 1.44 +/- 1.17 micromol/100 mL/min) and blood flow (PVD, 0.45 +/- 0.28 mL/100 g/min; RF, 0.77 +/- 0.21 mL/100 g/min; H, 0.62 +/- 0.50 mL/100 g/min). All parameters featured a distribution dependent on location. CONCLUSION: Mean value for venous oxygen saturation was higher in healthy subjects compared to patients with documented PVD. In patients with PVD, areas of lower oxygenation were clearly discernible. At distal locations of calf muscle, significant correlations between reduced hemoglobin flow, venous oxygen saturation, oxyhemoglobin, and total hemoglobin and reduced ankle-brachial index were found. Maps revealed localized irregularities in oxyhemoglobin, total hemoglobin, and venous oxygen saturation in patients with PVD. Near-infrared spectrophotometry is a noninvasive bedside technique that can enable determination of blood flow and oxygenation in tissue and may provide a method for evaluating patients with PVD.

Adult↗
PubMed2003

Effect of rocaltrol on bone mass in patients with pulmonary disease treated with corticosteroids.

The aim of this study was to evaluate the effect of calcitriol on bone mass in patients with corticosteroid induced osteoporosis. Thirty-seven patients (26 females, 11 males, mean age 66.4 years) with pulmonary disease under long-term treatment with corticosteroids (5-10 mg prednisolone daily) and osteopenia/osteoporosis verified by dual-energy x-ray absorptiometry (DEXA) measurement were enrolled into the study. Rocaltrol was prescribed to 30/37 of the patients, the rest of the patients (6 females, 1 male) served as controls. In the treatment group, there was a slight increase of bone mass in the hip and lumbar vertebrae (L1-L4), whereas the control group showed a decrease of bone mass (change rate of bone mass in patients +0.8% and +1.0%, respectively, vs. -1.9% and -0.3%, respectively, in the control group). The preliminary results of our study suggest a beneficial role for the treatment of corticosteroid induced osteoporosis with Rocaltrol, which is well-tolerated by patients and cost-efficient in patient management.

Absorptiometry, Photon↗
PubMed2002

Role of sterol regulatory element-binding protein 1 in regulation of renal lipid metabolism and glomerulosclerosis in diabetes mellitus.

Diabetic renal disease is associated with lipid deposits in the kidney. The purpose of our study was to determine whether there is altered regulation of the sterol regulatory element-binding proteins (SREBPs) in the diabetic kidney and whether SREBPs mediate the abnormal renal lipid metabolism and diabetic renal disease. In streptozotocin-induced diabetes in the rat, there were marked increases in SREBP-1 and fatty acid synthase (FAS) expression, resulting in increased triglyceride (TG) accumulation. Treatment of diabetic rats with insulin prevented the increased renal expression of SREBP-1 and the accumulation of TG. The role of hyperglycemia in the up-regulation of SREBP-1 was confirmed in renal cells cultured in a high glucose media. High glucose induced increased expression of SREBP-1a and -1c mRNA, SREBP-1 protein, and FAS, resulting in increased TG content. To determine a direct role for SREBP in mediating the increase in renal lipids and glomerulosclerosis, we studied SREBP-1a transgenic mice with increased renal expression of SREBP-1. The increase in SREBP-1 was associated with increased expression of FAS and acetyl CoA carboxylase, resulting in increased TG content, increased expression of transforming growth factor beta1 and vascular endothelial growth factor, mesangial expansion, glomerulosclerosis, and proteinuria. Our study therefore indicates that renal SREBP-1 expression is increased in diabetes and that SREBP-1 plays an important role in the increased lipid synthesis, TG accumulation, mesangial expansion, glomerulosclerosis, and proteinuria by increasing the expression of transforming growth factor beta and vascular endothelial growth factor.

Animals↗
PubMed2002

Hemodynamic changes during hemodialysis: role of nitric oxide and endothelin.

BACKGROUND: Etiology of dialysis induced hypotension and hypertension remains speculative. There is mounting evidence that nitric oxide (NO) and endothelin (ET-1) may play a vital role in these hemodynamic changes. We examined the intradialytic dynamic changes in NO and ET-1 levels and their role in the pathogenesis of hypotension and rebound hypertension during hemodialysis (HD). METHODS: The serum nitrate + nitrite (NT), fractional exhaled NO concentration (FENO), L-arginine (L-Arg), NGNG-dimethyl-L-arginine (ADMA) and endothelin (ET-1) profiles were studied in 27 end-stage renal disease (ESRD) patients on HD and 6 matched controls. The ESRD patients were grouped according to their hemodynamic profile; Group I patients had stable BP throughout HD, Group II had dialysis-induced hypotension, and Group III had intradialytic rebound hypertension. RESULTS: Pre-dialysis FENO was significantly lower in the dialysis patients compared to controls (19.3 +/- 6.3 vs. 28.6 +/- 3.4 ppb, P < 0.002). Between the experimental groups, pre-dialysis FENO was significantly higher in Group II (24.1 +/- 6.7 ppb) compared to Group I (17.8 +/- 5.6 ppb) and Group III (16.1 +/- 4.2 ppb; P < 0.05). Post-dialysis, FENO increased significantly from the pre-dialysis values (19.3 +/- 6.3 vs. 22.6 +/- 7.9 ppb; P=0.001). Pre-dialysis NT (34.4 +/- 28.2 micromol/L/L) level was not significantly different from that of controls (30.2 +/- 12.3 micromol/L/L). Serum NT decreased from 34.4 +/- 28.2 micromol/L/L at initiation of dialysis to 10.0 +/- 7.4 micormol/L/L at end of dialysis (P < 0.001). NT concentration was comparable in all the three groups at all time points. Pre-dialysis L-Arg (105.3 +/- 25.2 vs. 93.7 +/- 6.0 micromol/L/L; P < 0.05) and ADMA levels were significantly higher in ESRD patients (4.0 +/- 1.8 vs. 0.9 +/- 0.2 micromol/L/L; P < 0.001) compared to controls. Dialysis resulted in significant reduction in L-Arg (105.3 +/- 25.2 vs. 86.8 +/- 19.8 micromol/L/L; P < 0.005) and ADMA (4.0 +/- 1.8 vs. 1.6 +/- 0.7 micromol/L/L; P < 0.001) concentrations. Pre-dialysis ET-1 levels were significantly higher in ESRD patients compared to the controls (8.0 +/- 1.9 vs. 12.7 +/- 4.1 pg/mL; P < 0.002), but were comparable in the three study groups. Post-dialysis ET-1 levels did not change significantly in Group I compared to pre-dialysis values (14.3 +/- 4.3 vs.15.0 +/- 2.4 pg/mL, P=NS). However, while the ET-1 concentration decreased significantly in Group II (12.0 +/- 4.0 vs. 8.7 +/- 1.8 pg/mL, P < 0.05), it increased in Group III from pre-dialysis levels (12.8 +/- 3.8 vs. 16.7 +/- 4.5 pg/mL, P=0.06). CONCLUSION: Pre-dialysis FENO is elevated in patients with dialysis-induced hypotension and may be a more reliable than NT as a marker for endogenous NO activity in dialysis patients. Altered NO/ET-1 balance may be involved in the pathogenesis of rebound hypertension and hypotension during dialysis.

Adult↗
PubMed2002

Upregulation of autocrine-paracrine renin-angiotensin systems in chronic renovascular hypertension.

INTRODUCTION: The mechanism by which hypertension is maintained in renovascular hypertension remains poorly defined. Because plasma angiotensin II does not correlate with blood pressure in RVH, we postulated that activation of tissue-specific autocrine-paracrine renin-angiotensin systems may upregulate local production of angiotensin II and maintain hypertension in chronic RVH. METHODS: RVH was induced with a two-kidney one-clip (2K1C) rat model. Animals were killed at 1 or 12 weeks after surgery (acute or chronic RVH). Angiotensin II was quantitated with radioimmunoassay. Angiotensin II-type 1 (AT(1)) receptor density was determined with immunoblotting and immunohistochemistry. RESULTS: Blood pressure was significantly elevated in 2K1C animals compared with sham animals at 1 week (141 +/- 5 mm Hg versus 98 +/- 3 mm Hg; P <.0005) and at 12 weeks (164 +/- 14 mm Hg versus 110 +/- 7 mm Hg; P <.0005) after surgery. No significant difference was seen in plasma angiotensin II levels between 2K1C and control animals during acute (38.2 +/- 6.5 fmol/mL versus 27.6 +/- 6.8 fmol/mL; P = not significant) or chronic (40.1 +/- 17.4 fmol/mL versus 27.1 +/- 6.5 fmol/mL; P = not significant) RVH. During acute RVH, intrarenal angiotensin II was significantly increased in both the clipped (126.0 +/- 16.2 fmol/g versus 62.0 +/- 6.2 fmol/g; P <.005) and unclipped (78.9 +/- 6.3 fmol/g versus 39.9 +/- 2.5 fmol/g; P <.05) kidneys of 2K1C animals compared with control animals. Increased intrarenal angiotensin II levels persisted in chronic RVH in the clipped (147.4 +/- 37.7 fmol/g versus 59.2 +/- 8.7 fmol/g; P <.05) and unclipped (130.8 +/- 31.8 fmol/g versus 63.0 +/- 11.0 fmol/g; P <.05) kidneys of 2K1C animals compared with controls. Adrenal angiotensin II content of 2K1C animals was unchanged in acute RVH (493.7 +/- 51.4 fmol/g versus 522.6 +/- 80.5 fmol/g; P = not significant) but increased nearly three-fold over control animals during chronic RVH (1129.0 +/- 149.3 fmol/g versus 400.6 +/- 59.1 fmol/g; P <.0005). No significant difference in AT(1) receptor density was noted in renal tubules of clipped and unclipped kidneys or in the adrenal glands of 2K1C animals during acute or chronic RVH compared with control animals. CONCLUSION: Tissue angiotensin II production is upregulated in the kidneys and adrenal glands in chronic RVH, and AT(1) receptor density is maintained in these tissues, providing a potential mechanism for maintenance of hypertension in RVH.

Adrenal Glands↗