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Biomedical subjects

M Allon

Publications and source records attributed to M Allon.

At least 37 records · Page 2Linked to original sources
PubMed1996

The role of cytosolic calcium in chronic adaptation to phosphate depletion in opossum kidney cells.

Chronic dietary phosphate restriction is associated with up-regulation of sodium-dependent phosphate (Na/Pi) cotransport by renal proximal tubular epithelial cells in association with increases in Na/Pi cotransporter mRNA and protein. We investigated whether changes in cytosolic calcium mediate this adaptive response in opossum kidney cells, a continuous line of renal epithelial cells. After 24 h of phosphate depletion, steady-state cytosolic calcium levels were increased; this increase was observed at physiologic levels of phosphate restriction and was prevented by the calcium channel blocker verapamil. Chronic phosphate depletion was also associated with parallel increases in Na/Pi cotransport activity, Na/Pi cotransporter mRNA, and Na/Pi cotransporter protein, all of which were blocked in verapamil-treated cells. Actinomycin D, at a dose that prevented the increase in NaPi-4 mRNA during phosphate depletion, also prevented the increase in Na/Pi cotransport activity. Incubation with the calcium ionophore ionomycin or A23187 reproduced the increase in Na/Pi cotransporter mRNA in phosphate-replete cells. Conversely, chelation of cytosolic calcium by quin-2/AM prevented the increase in Na/Pi cotransporter mRNA in phosphate-depleted cells. The effect of an increase in cytosolic calcium was specific for the Na/Pi cotransporter as mRNA levels for the sodium-dependent glucose transporter were not affected. Our observations suggest that chronic phosphate restriction increases steady-state cytosolic calcium, which, in turn, increases transcription of Na/Pi cotransporter mRNA, thereby stimulating Na/Pi cotransport activity.

Animals↗
PubMed1996

Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol.

Acute treatment of hyperkalemia in patients with end-stage renal disease requires temporizing measures to shift potassium rapidly from the extracellular to the intracellular fluid compartments until hemodialysis can be initiated. Whereas insulin and albuterol are effective in lowering plasma potassium acutely, bicarbonate by itself is not. Bicarbonate administration may, however, potentiate the effects of insulin and albuterol on plasma potassium. Using a prospective cross-over design, we investigated the acute effects of (1) isotonic bicarbonate, (2) isotonic saline, (3) insulin + bicarbonate, (4) insulin + saline, (5) albuterol + bicarbonate, and (6) albuterol + saline on plasma potassium as well as blood bicarbonate and pH in nondiabetic hemodialysis patients. After obtaining a baseline blood sample, the subjects received one of the six treatment protocols, with plasma potassium measured every 15 minutes over 1 hour. Neither isotonic bicarbonate nor isotonic saline decreased plasma potassium significantly (-0.03 +/- 0.06 mmol/L v -0.01 +/- 0.10 mmol/L at 60 minutes; P = 0.60). Intravenous insulin decreased plasma potassium by a similar degree when given in conjunction with bicarbonate or saline (-0.81 +/- 0.05 mmol/L v -0.85 +/- 0.06 mmol/L at 60 minutes; P = 0.65). Likewise, nebulized albuterol decreased plasma potassium by a similar degree when given with bicarbonate or saline (-0.71 +/- 0.16 mmol/L v -0.53 +/- 0.15 mmol/L at 60 minutes; P = 0.18). The three protocols that included bicarbonate administration resulted in significant increases in blood bicarbonate (P < 0.005) and pH (P < 0.01), whereas the three protocols that included saline did not affect blood bicarbonate or pH. These observations suggest that bicarbonate administration does not potentiate the potassium-lowering effects of insulin or albuterol in hemodialysis patients.

Adrenergic beta-Agonists↗
PubMed1995

Adaptation to phosphate depletion in opossum kidney cells.

Dietary phosphate restriction produces an adaptive increase in renal tubular Na/Pi cotransport. A similar adaptation occurs during phosphate depletion in opossum kidney cells, a continuous line of cultured renal epithelial cells. We investigated the cellular changes associated with adaptation to phosphate depletion in OK cells, in isolation from the complex systemic changes that occur with in vivo phosphate restriction. Phosphate depletion for up to 24 hours was associated with increases in Na/Pi cotransport activity, Na/Pi cotransporter mRNA, and Na/Pi cotransporter protein. Moreover, the increases in Na/Pi cotransport, and Na/Pi cotransporter mRNA and protein occurred at physiologically relevant degrees of phosphate restriction. The experimental results suggest that increases in Na/Pi cotransporter mRNA and protein may mediate the increase in Na/Pi cotransport activity in OK cells during phosphate depletion.

Acclimatization↗
PubMed1995

Effect of albuterol treatment on subsequent dialytic potassium removal.

End-stage renal disease patients presenting with severe hyperkalemia are frequently treated with albuterol to lower their plasma potassium acutely, until emergent hemodialysis can be initiated. Such treatment stimulates potassium shifts from the extracellular to the intracellular fluid compartments. The resulting reduction of potassium concentration gradient between the blood and dialysate may potentially attenuate the efficacy of potassium removal during the ensuing hemodialysis treatment. To evaluate the effect of prior albuterol treatment on dialytic potassium removal, seven chronic hemodialysis patients were studied prospectively on two separate occasions. In one study the patients received 20 mg nebulized albuterol 30 minutes before dialysis; in the control study, albuterol treatment was omitted. Plasma potassium decreased 30 minutes after albuterol treatment (-0.84 +/- 0.06 mmol/L; P < 0.001) and remained unchanged in the corresponding period of the control experiment. Plasma potassium decreased during dialysis in both experimental protocols, but was significantly lower throughout dialysis in the albuterol study, as compared with the control study. Cumulative dialytic potassium removal was significantly lower following albuterol pretreatment compared with the control experiment (29.0 +/- 5.7 mmol v 49.6 +/- 7.0 mmol; P < 0.001). These observations suggest that acute albuterol therapy in patients with end-stage renal disease may substantially decrease potassium removal in the ensuing hemodialysis session. This may lead to rebound hyperkalemia several hours after the dialysis treatment.

Adult↗
PubMed1995

Hyperkalemia in end-stage renal disease: mechanisms and management.

Clinical investigations in the past few years have enhanced the understanding of the mechanisms of hyperkalemia in patients with ESRD. The results of these studies have led to modifications in the acute treatment and prevention of hyperkalemia in this patient population. They have confirmed the efficacy of intravenous insulin, while raising doubts about the utility of intravenous bicarbonate, for the acute treatment of hyperkalemia. Moreover, the beta-adrenergic agonist albuterol has been shown to be a useful adjunct to insulin for acutely lowering plasma potassium. Finally, there has been enhanced recognition of nondietary factors that can predispose to hyperkalemia in patients with ESRD, including prolonged fasting and the use of nonselective beta-adrenergic blockers. These new insights may improve the clinical management of hyperkalemia in patients with renal failure.

Humans↗
PubMed1993

Effect of insulin-plus-glucose infusion with or without epinephrine on fasting hyperkalemia.

Extrarenal potassium disposal is an important defense against hyperkalemia in patients with end-stage renal disease. Both insulin and epinephrine are important modulators of this process. Hemodialysis patients are prone to developing hyperkalemia during fasting. We tested the hypothesis that the infusion of physiologic doses of insulin prevents fasting hyperkalemia in hemodialysis patients, both by a direct stimulation of extrarenal potassium disposal, as well as by augmenting the potassium-lowering effect of epinephrine. Ten stable, nondiabetic maintenance hemodialysis patients were studied prospectively in a Clinical Research Center. They were fasted for 18 hours, followed by an acute infusion of epinephrine at 0.01 microgram/kg/min, in the absence or presence of prior beta-blockade with propranolol. Serial measurements of plasma potassium, insulin and glucose were obtained. The patients were restudied under the same experimental protocols, while receiving a continuous infusion of insulin with dextrose. The plasma potassium increased by 0.58 +/- 0.13 mmol/liter (P = 0.002) after 18 hours of fasting. Administration of insulin with dextrose at a dose that doubled the plasma insulin levels within the physiologic range (9.3 +/- 1.1 vs. 20.2 +/- 2.3 mU/liter, P < 0.002), completely prevented the rise in plasma potassium (+0.06 +/- 0.13 mmol/liter, P = 0.64). Epinephrine did not significantly change the plasma potassium during fasting alone (+0.05 +/- 0.09 mmol/liter, P = 0.59), whereas it lowered the potassium significantly (-0.16 +/- 0.04 mmol/liter, P = 0.003) when the subjects were receiving insulin with glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Calcitriol stimulates Na(+)-Pi cotransport in a subclone of opossum kidney cells (OK-7A) by a genomic mechanism.

Calcitriol (CT) stimulates Na(+)-Pi cotransport in a subclone of opossum kidney cells (OK-7A) by a genomic mechanism. An experimental model of renal proximal tubular cells in which CT affects Na(+)-Pi cotransport would be useful for examining the mechanisms of this effect. This study evaluated the effect of CT on Na(+)-Pi cotransport in opossum kidney (OK) cells. CT had no effect on Na(+)-Pi cotransport in wild-type OK cells and in the OK-B, OK-H, and OK-P subclones. In contrast, CT at physiological concentrations stimulated Na(+)-Pi cotransport in the OK-7A subclone; the effect was dose related with a 52% increase at 10(-11) M CT, as well as a maximal twofold stimulation at 10(-9) M. CT (10(-11) M) increased the maximum uptake for Na(+)-Pi cotransport (Vmax = 3.55 +/- 0.16 vs. 2.51 +/- 0.17 nmol.mg protein-1.5 min-1, P < 0.01), without affecting the apparent Michaelis constant (Km = 30.6 +/- 1.0 vs. 30.8 +/- 0.7 microM). The stimulatory effect on Na(+)-Pi cotransport was specific for CT and did not occur with 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3, or 1 beta,25-dihydroxyvitamin D3. At 10(-11) M CT, the stimulation of Na(+)-Pi uptake in OK-7A cells was maximal at 3 h; it was completely abolished by preincubation with actinomycin D or cycloheximide. Both calphostin C, an inhibitor of protein kinase C (PKC), or prolonged incubation with phorbol 12-myristate 13-acetate, to downregulate the PKC pathway, partially inhibited the stimulatory effect of CT on Na(+)-Pi cotransport in OK-7A cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The kidney in sarcoidosis.

Sarcoidosis has been associated with a wide spectrum of renal manifestations, including disordered calcium metabolism, nephrocalcinosis, nephrolithiasis, granulomatous interstitial nephritis, and glomerulonephritis. In some patients, two or more manifestations of renal sarcoidosis may coexist. The case of a young patient with sarcoidosis who presented with hypercalcemia and acute renal failure is discussed. Despite normalization of the serum calcium with intravenous fluids and corticosteroids, his renal insufficiency persisted. A diagnostic renal biopsy was performed to determine the etiology of his renal failure and was helpful in the selection of optimal medical therapy.

Adult↗
PubMed1992

Exclusion of linkage between hypokalemic periodic paralysis (HOKPP) and three candidate loci.

Hypokalemic periodic paralysis (HOKPP) is an autosomal dominant neuromuscular disorder characterized by flaccid paralysis accompanied by lowered serum potassium levels. We have tested polymorphic markers linked to the adult skeletal muscle sodium channel (SCN4A) locus at 17q23-q25, the T-cell receptor beta (TCRB) locus at 7q35, and the H-Ras cellular proton-cogene locus (HRAS) at 11p15.5 for linkage with the affected phenotype in a single multigenerational pedigree. No evidence for genetic linkage to HOKPP was found at any of the candidate loci.

Chromosome Mapping↗
PubMed1992

Effects of insulin and glucose on renal phosphate reabsorption: interactions with dietary phosphate.

Both insulin deficiency and glycosuria are known to inhibit the tubular reabsorption of phosphate. This inhibition has previously been evaluated either in the fasted state or on a normal phosphate diet. The goal of this study was to evaluate how dietary phosphate depletion affected the relative effects of insulin deficiency and glycosuria on the tubular reabsorption of phosphate. Rats were maintained on either a low- (0.03%) or normal (0.8%) phosphate diet. After 5 days, one half of the animals in each group received streptozotocin to induce short-term insulin deficiency, whereas the other half received vehicle alone. Two days later, sodium-dependent phosphate uptake by renal brush border membrane vesicles (BBMV) was evaluated in each of the four experimental groups. The effect of glucose on phosphate uptake was determined by the addition of varying concentrations of glucose (between 0 and 32 mmol/L) to the extravesicular transport fluid. BBMV phosphate uptake was about threefold higher in the nondiabetic rats fed a low-phosphate diet as compared with the nondiabetic animals maintained on a normal phosphate diet. In rats maintained on a low-phosphate diet, streptozotocin treatment prevented the increase in BBMV phosphate transport; in contrast, in animals fed a normal phosphate diet, streptozotocin treatment had no effect on BBMV phosphate transport. Extravesicular glucose significantly inhibited phosphate transport in a dose-related manner, regardless of dietary phosphate or insulin status. Because fasting mimics the catabolic state associated with insulin deficiency, BBMV phosphate transport was also measured in rats fasted for 48 h after the administration of streptozotocin or vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Adrenergic modulation of extrarenal potassium disposal in men with end-stage renal disease.

In normal subjects, beta-adrenergic stimulation lowers the serum potassium, whereas alpha-stimulation raises it. Epinephrine, a mixed alpha and beta agonist, acutely lowers the blood potassium in normal subjects, but not in patients with end-stage renal disease. This study was designed to determine whether the resistance to the hypokalemic effect of epinephrine in dialysis patients is due to a blunted beta-adrenergic response, or to an augmented alpha-adrenergic response. The infusion of epinephrine at low doses (0.01 microgram/kg/min) produced a significant increase in serum potassium in hemodialysis patients (+0.21 +/- 0.07 mmol/liter, P less than 0.05), as compared to a nonsignificant decrease (-0.06 +/- 0.04 mmol/liter) in normal subjects. Epinephrine at high physiologic doses (0.04 microgram/kg/min) failed to significantly change the serum potassium in the dialysis patients (-0.10 +/- 0.14 mmol/liter), but substantially lowered serum potassium in the controls (-0.64 +/- 0.10 mmol/liter, P less than 0.001). There was no significant correlation (r = 0.03) between the baseline serum potassium concentration and the magnitude of change during epinephrine infusion. Epinephrine infusion (0.04 microgram/kg/min) during beta-blockade with propranolol produced a greater rise in serum potassium in the dialysis patients as compared to the controls (+0.69 +/- 0.11 vs. +0.32 +/- 0.11 mmol/liter, P less than 0.05). Epinephrine infusion (0.01 microgram/kg/min) during alpha-blockade with phentolamine resulted in similar changes in serum potassium in dialysis patients and in normal control (-0.10 +/- 0.12 vs. -0.10 +/- 0.06 mmol/liter). Moreover, phentolamine reversed the increase in serum potassium observed in dialysis patients during the infusion of epinephrine following beta-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effects of maleic acid on renal phosphorus transport: role of dietary phosphorus.

The effects of maleic acid on renal phosphate (Pi) transport were examined by clearance and brush-border membrane vesicle (BBMV) transport studies. In normal rats, maleic acid 50 mg.kg body wt-1.h-1 increased the phosphaturia (P less than 0.001). Intraperitoneal administration of a similar dose of maleic acid decreased the BBMV uptake of Pi but not glucose. In rats fed a low-phosphate diet (0.03%), the maleic acid-induced phosphaturia was blunted, but the inhibitory effect on the BBMV transport of Pi persisted. In chronic parathyroidectomized rats fed a low-phosphate diet, where the filtered load of Pi was higher than in the previous groups, the phosphaturia was abolished, but the inhibition of the BBMV transport of Pi was sustained. Both the in vitro incubation of BBMVV and in vivo administration of maleic acid were associated with a competitive inhibition of Pi transport. These studies indicate that the maleic acid-induced phosphaturia is expressed at the apical membrane entry step of Pi, and the enhanced distal tubular reabsorption accounts for the lack of phosphaturia in dietary Pi deprivation.

Animals↗
PubMed1991

Renal adaptation to dietary phosphate restriction in rats. Interactions with insulin and calcitriol.

Insulin may contribute to the increase in tubular reabsorption of phosphate during dietary phosphate restriction. Moreover, insulin is required for the stimulation of calcitriol under this experimental condition. To evaluate whether calcitriol plays a role in the antiphosphaturic effect of insulin during phosphate restriction, phosphate uptake was measured in brush border membrane vesicles (BBMVs) obtained from the following six experimental groups of rats: normal (0.8%)-phosphate diet for 1 wk, low (0.03%)-phosphate diet for 1 wk, normal-phosphate diet for 1 wk and streptozocin 48 h before the experiment, low-phosphate diet for 1 wk and streptozocin 48 h before the experiment, low-phosphate diet and streptozocin and exogenous insulin, and low-phosphate diet and streptozocin and exogenous calcitriol. BBMV phosphate uptake was higher in the nondiabetic rats on a low-phosphate diet than in the controls on a normal-phosphate diet. BBMV phosphate uptake was not different between diabetic rats on a normal-phosphate diet than in nondiabetic controls on the same diet. In contrast, BBMV was significantly lower in diabetic rats on a low-phosphate diet than in nondiabetic controls on the same diet. Exogenous insulin but not calcitriol restored the increase in BBMV phosphate uptake in diabetic rats on a low-phosphate diet. Plasma calcitriol levels were increased threefold in nondiabetic rats fed a low-phosphate diet. Streptozocin-induced diabetes abolished the adaptive increase in plasma calcitriol. Exogenous insulin and calcitriol administration to diabetic rats on a low-phosphate diet resulted in similar increases in plasma calcitriol levels. These results suggest that, during dietary phosphate restriction, insulin stimulates renal phosphate retention independently of its effect on calcitriol.

Acclimatization↗
PubMed1990

Effect of soluble and immobilized plasmin on fibrinogen and platelets.

Plasmin was immobilized on collageno-elastic tubes (CET) using carbodiimide as the cross-linking agent. The effects of plasmin-CET grafts and corresponding soluble plasmin on fibrinogen, thrombin-mediated fibrinogen activation, and platelet activity, were investigated. There was a significant increase in fibrinogen deposition on plasmin-CETs over non-plasmin (i.e. control) CETs. Furthermore, exposure of fibrinogen to plasmin CETs enhances its deposition to control grafts situated downstream. Plasmin-bound CETs retained higher platelet deposition when preliminarily coated with fibrinogen. Finally, plasmin exerted a positive effect on thrombin-mediated fibrinogen activation at low plasmin concentrations. A mechanistic hypothesis aimed at interpreting this finding is proposed.

Animals↗
PubMed1990

Insulin in the acute renal adaptation to dietary phosphate restriction in the rat.

Dietary phosphate restriction produces a rapid increase in tubular reabsorption of phosphate. To evaluate whether insulin is important in the acute renal adaptation following a low phosphate meal, four groups of conscious rats were studied by renal clearance methods, following a single meal by gavage. Group A received a normal (0.8%) phosphate meal, followed by saline infusion; Group B, a low (0.03%) phosphate meal, followed by saline infusion; Group C, a low phosphate meal, followed by infusion of somatostatin to suppress endogenous insulin secretion; and Group D, a low phosphate meal, followed by infusion of somatostatin plus insulin. Baseline plasma phosphate, insulin, glomerular filtration rate, and fractional excretion of phosphate were similar in all four groups. Following a low phosphate meal in Groups B, C, and D, there was a decrease in plasma phosphate, as compared with Group A. Whereas fractional excretion of phosphate decreased when plasma phosphate fell in Group B, administration of somatostatin (Group C) prevented the drop in fractional excretion of phosphate, despite a lower plasma phosphate. The addition of exogenous insulin (Group D) restored the antiphosphaturic effect of the low phosphate meal. These results suggest that insulin contributes to the acute decrease in phosphate excretion following a low phosphate meal.

Adaptation, Physiological↗