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D Rubinger

Publications and source records attributed to D Rubinger.

At least 19 recordsLinked to original sources
PubMed1992

Assessment of combined 24,25(OH)2D3 and 1 alpha (OH)D3 therapy for bone disease in dialysis patients.

An increasing body of experimental data suggests a role for 24,25(OH)2D3 in bone metabolism. The present study was carried out to assess a possible therapeutic role of this vitamin D metabolite in renal osteodystrophy. Twenty-two chronic dialysis patients, most of whom were previously maintained on 1 alpha (OH)D3 therapy, received additional treatment with 10 micrograms/day 24,25(OH)2D3 and were compared to 19 patients receiving 1 alpha (OH)D3 alone. Analysis of transiliac bone biopsies obtained at study entry and following 10-16 months of treatment revealed that the combined therapy produced a decrease in bone turnover. Specifically, the addition of 24,25(OH)2D3 inhibited an increase in trabecular bone volume (BV/TV) and suppressed osteoclastic parameters. Thus BV/TV increased from 26.2 +/- 8.6 to 32.1 +/- 7.5% (p < 0.01) in the 1 alpha (OH)D3 group, but it remained unchanged in the combined therapy group. In contrast, the eroded surface (ES/BS), the osteoclast surface (Oc.S/BS), and the osteoclast numbers were significantly suppressed in patients receiving both 24,25(OH)2D3 and 1 alpha (OH)D3, as compared with those receiving 1 alpha (OH)D3 alone (p < 0.01, p < 0.01, and p < 0.001, respectively). These improvements were independent of changes in 1 alpha (OH)D3 dosage. The extent of bone aluminium deposits was unrelated to the administration of 24,25(OH)2D3 or to its effect. 24,25(OH)2D3 therapy was not associated with any adverse effects.

24,25-Dihydroxyvitamin D 3↗
PubMed1992

Indomethacin and sodium retention in the rat: role of inhibition of prostaglandin E2 synthesis.

1. To further explore the Na(+)-retaining effect of indomethacin along the whole length of the nephron, the Na(+)-K(+)-ATPase activity of isolated tubules from indomethacin-pretreated rats was compared with that of tubules isolated from intact rats and exposed directly to prostaglandin E2. 2. Indomethacin increased Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (+24%, P < 0.001 versus control), proximal straight tubule (+75%, P < 0.001 versus control), medullary thick ascending limb (+68%, P < 0.001 versus control), cortical thick ascending limb (+7%, not significant) and cortical collecting duct (+18%, P < 0.025 versus control). In contrast, in the distal convoluted tubule indomethacin decreased Na(+)-K(+)-ATPase activity by -42% (P < 0.001 versus control). 3. Indomethacin also strongly increased Na(+)-K(+)-ATPase activity in the cortical collecting duct of adrenalectomized rats. 4. In isolated tubules from control rats, prostaglandin E2 reduced Na(+)-K(+)-ATPase activity in the proximal convoluted tubule (-33%, P < 0.05), proximal straight tubule (-60%, P < 0.001), medullary thick ascending limb (-43%, P < 0.001), cortical thick ascending limb (-25%, P < 0.001) and cortical collecting duct (-45%, P < 0.001) and in the distal convoluted tubule, prostaglandin E2 increased Na(+)-K(+)-ATPase activity (+32%, P < 0.05). 5. That these changes in Na(+)-K(+)-ATPase activity in indomethacin-pretreated rats and prostaglandin E2-treated controls are similar in magnitude but occur in opposite directions suggests that the response to indomethacin is mediated by inhibition of prostaglandin E2 synthesis in the nephron. In the cortical collecting duct the effect of indomethacin is aldosterone-independent.

Adrenalectomy↗
PubMed1991

24,25(OH)2D3 affects the calcemic effects of 1,25(OH)2D3 by mechanisms independent of intestinal calcium absorption.

To better define the interaction between 1,25(OH)2D3 and 24,25(OH)2D3 in different states of renal function, the fractional absorption of Ca45 (FCa45) and plasma calcium (PCa) were determined in rats with intact kidneys and in rats with reduced renal mass after 5/6 nephrectomy. The two series of experiments were performed in control animals, and in rats treated with: 1) 1,25(OH)2D3, 54 ng/rat/day, 2) 24,25(OH)2D3 in the same dose, and 3) 1,25 and 24,25(OH)2D3 in the same (and equal) doses. In all animals 1,25(OH)2D3 administration was associated with a significant increase in PCa and in FCa45. In rats with normal renal function, however, 24,25(OH)2D3 enhanced and in rats with reduced renal mass it suppressed the hypercalcemic effect of 1,25(OH)2D3. These variations in PCa were not associated with further alteration in FCa45 which was similar after 1,25(OH)2D3 and after combined 1,25 and 24,25(OH)2D3 in normal rats and in rats with chronic renal failure. FCa45 was found to be of the same magnitude in rats with normal renal function and in rats with reduced renal mass. These results confirm previous findings of normal intestinal absorption of Ca in mild to moderate renal failure. The above data suggest that 24,25(OH)2D3 used in an equivalent dose does not influence the intestinal effects of 1,25(OH)2D3. Therefore, the interaction of 1,25 with 24,25(OH)2D3 in rats with intact kidneys or with reduced renal mass occurs at extra-intestinal sites.

24,25-Dihydroxyvitamin D 3↗
PubMed1991

Unusual causes of I-131 metaiodobenzylguanidine uptake in non-neural crest tissue.

Three patients with clinical suspicion of pheochromocytoma were studied with metaiodobenzylguanidine (MIBG) labeled with I-123 or I-131. In these three patients, marked uptake of the radiopharmaceutical was demonstrated in tissues that were subsequently proven not to be of neural crest origin. Furthermore, extensive biochemical evaluations and long-term followup definitively excluded pheochromocytoma in all three. Therefore, these three cases represent unexpected "false-positive" MIBG uptake.

3-Iodobenzylguanidine↗
PubMed1991

A simple test of intestinal absorption of calcium in rats.

We have developed a simple test of fractional calcium absorption in rats using oral 45Ca. The tracer was administered via a gastric tube, each animal receiving 0.15 microgram 45Ca with calcium glubionate as a carrier. Plasma radioactivity was determined at 30, 60, 90 and 120 min and expressed as percent dose in extracellular fluid. The fractional absorption of 45Ca was also expressed as 'area under the curve' (F45Ca) calculated by Simpson's approximation for each rat. The fractional absorption of calcium was determined in fasting and nonfasting fed animal subsets, each subset including control and rats treated with 1,25(OH)2D3. After 1,25(OH)2D3 administration, a significant increase in plasma calcium was seen in both fasting and fed animals. The fractional absorption of calcium was significantly higher in 1,25(OH)2D3-treated fasting as compared with control rats. In these animals, a positive correlation was found between F45Ca and plasma calcium. In contrast, in fed rats, the determined fractional absorption of calcium was similar in control and after 1,25(OH)2D3 administration. These results point to the use of orally administered 45Ca as a technically easy method for calcium absorption which can be used in most laboratories. In fasting animals it is sensitive enough for the evaluation of the effect of promoters of calcium absorption. The different findings in fed and fasting states may be related to the transmural processes which regulate the intestinal absorption of calcium.

Animals↗
PubMed1990

Effect of indomethacin in vivo and PGE2 in vitro on MTAL Na-K-ATPase of the rat kidney.

We have previously shown that prostaglandin synthesis inhibition in rats which reduces urinary excretion of PGE2 and sodium, is associated with increased Na-K-ATPase activity in renal medulla. To further characterize this interaction studies were performed in isolated segments of medullary thick ascending limb of Henle's loop (MTAL) in rats. The effect of pretreatment with indomethacin in vivo and incubation with PGE2 in vitro on MTAL Na-K-ATPase activity was studied. Pretreatment of rats with indomethacin increased Na-K-ATPase of the MTAL from 37.2 +/- 2.0 x 10(-11) mol/mm/min in controls to 62.7 +/- 2.2 (p less than 0.001) while Mg-ATPase was only slightly decreased. Incubation of MTAL Na-K-ATPase from indomethacin pretreated rats with increasing concentration of PGE2 in vitro dose dependently inhibited MTAL Na-K-ATPase activity with no effect on Mg-ATPase. Baseline Na-K-ATPase was 62.7 +/- 2.2 in MTAL from indomethacin pretreated rats and decreased to 36.9 +/- 1.4 (p less than 0.001) with 1 microM of PGE2, to 26.5 +/- 2.3 (p less than 0.001) with 10 microM PGE2 and to 22.0 +/- 1.0 (p less than 0.001) with 100 microM PGE2. 100 microM PGE2 in the incubation medium inhibited MTAL Na-K-ATPase of intact rats from 37.2 +/- 2 to 21.3 +/- 1.2 (p less than 0.001) and completely abolished the indomethacin induced increase in MTAL Na-K-ATPase. The results of this study show stimulation of MTAL Na-K-ATPase by pretreatment with indomethacin in vivo and, direct inhibition of MTAL Na-K-ATPase by PGE2 in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Renal sodium handling and stimulation of medullary Na-K-ATPase during blockade of prostaglandin synthesis.

The effect of suppression of prostaglandin synthesis on renal sodium handling and microsomal Na-K ATPase was studied in control and indomethacin treated intact rats maintained on a normal sodium diet (series A) and chronically salt loaded (series B). Indomethacin administration resulted in a decreased GFR and a significantly depressed urinary excretion and an increased fractional reabsorption of sodium in animals fed the normal sodium diet or chronically salt loaded. In rats maintained on a normal Na diet, the activity of the renal medullary Na-K ATPase after indomethacin was 206.3 +/- 6.4 ug Pi/mg protein, i.e. significantly higher as compared with the enzyme activity in the medullary renal fraction from control animals in which it averaged 148 +/- 7.79 ug Pi/mg protein (p less than 0.001). While after chronic salt load a similar increment in the activity of renal medullary Na-K ATPase was observed, no additional stimulation was elicited by subsequent indomethacin administration. The addition of exogenous PGE2, 0.1 mM to microsomal fractions obtained from kidneys of normal rats, was associated with a moderate suppression of the medullary Na-K-ATPase activity, from a basal level of 170 +/- 16 to 151.3 +/- 13 umol Pi/mg protein/hr (p less than 0.005). In isolated segments of medullary thick ascending limb of Henle's loop (MTAL) addition of PGE2 to the incubation medium resulted in a significant inhibition of Na-K ATPase from 37.2 +/- 2 to 21.25 +/- 1.17 x 10(-11) mol/mm/min (p less than 0.0001). These findings suggest that the increased renal Na reabsorption after inhibition of PG synthesis might be related, at least partly, to stimulation of medullary Na-K ATPase. In parallel, the reported natriuretic effect of prostaglandins might imply a direct inhibitory effect of these mediators on renal Na-K ATPase.

Animals↗
PubMed1990

The influence of 24,25(OH)2D3 on the calcemic effect of 1,25(OH)2D in rats with chronic renal failure is parathyroid hormone dependent.

Previous studies from our laboratory have shown that 24,25(OH)2D3 attenuates the calcemic effect of 1,25(OH)2D3 in rats with reduced renal mass. This study was undertaken to clarify the role of parathyroid hormone in this response. Adult rats (n = 27) with reduced renal mass after parathyroidectomy with an initial plasma calcium of 3.7 +/- 0.1 mEq/liter were divided into four groups: (i) control rats and rats treated with (ii) 24,25(OH)2D3, (iii) 1,25(OH)2D3, and (iv) both 1,25 and 24,25(OH)2D3. After 4 days significant hypercalcemia was seen in PTX animals receiving 1,25(OH)2D3 alone or in combination with 24,25(OH)2D3. Plasma calcium in the combined therapy rats (7.42 +/- 0.22 mEq/liter) was significantly higher than in those treated with 1,25(OH)2D3 alone (6.68 +/- 0.22 mEq/liter, P less than 0.05). After 8 days, plasma calcium was higher in the rats treated with 1,25(OH)2D3 but was of same magnitude in those treated with 1,25(OH)2D3 alone or in combination with 24,25(OH)2D3. In contrast, in a subset of rats (n = 35) with reduced renal mass but intact parathyroid glands similarly treated with the vitamin D metabolites, a blunted calcemic response was seen after the combination of 1,25(OH)2D3 with 25,25(OH)2D3 administration alone. These results show that in rats with reduced renal mass, 24,25(OH)2D3 attenuates the calcemic effect of 1,25(OH)2D3 only in the presence of intact parathyroid glands. The different calcemic responses to 1,25 or combined 1,25 and 24,25(OH)2D3 in intact or parathyroidectomized rats with chronic renal insufficiency may result from different interaction between the vitamin D metabolites and the parathyroid hormone, presumably at the level of bone.

24,25-Dihydroxyvitamin D 3↗
PubMed1990

25-Hydroxycholecalciferol and 1,25-dihydroxycholecalciferol enhances phosphaturia in rats with reduced renal mass: evidence for a PTH-dependent mechanism.

To evaluate the acute effect of 25-hydroxycholecalciferol [25(OH)D3] on renal handling of phosphate in rats with reduced renal mass, clearance studies were performed in the following groups of five sixth (5/6) nephrectomized (NPX) animals: (1) rats with intact parathyroids infused 25(OH)D3 (5/6 NPX + 25(OH)D3), (2) rats with intact parathyroids which received the vitamin D vehicle only (5/6 NPX). A separate subgroup of animals received 1,25-dihydroxycholecalciferol [1,25(OH)2D3] [5/6 NPX + 1,25(OH)2D3], (3) parathyroidectomized (PTX) rats infused 25(OH)D3 [5/6 NPX-PTX + 25(OH)D3], and (4) PTX rats infused the vehicle only (5/6 NPX-PTX). In group 1 [5/6 NPX + 25(OH)D3] the final fractional excretion of phosphate (CP/CIn) was significantly higher, i.e., 0.281 +/- 0.016, as compared to that of control animals (group 2, 5/6 NPX) in which the final CP/CIn averaged 0.195 +/- 0.016 (p less than 0.005). There was no difference, however, in the urinary cAMP excretion between these two groups. A similar phosphaturic effect was seen in rats infused 1,25(OH)2D3. After parathyroidectomy, however, the final CP/CIn was similar in rats receiving 25(OH)D3 [group 3, 5/6 NPX-PTX + 25(OH)D3] and in those receiving the vehicle alone (group 4, 5/6 NPX-PTX). In vitro studies on renal cortical adenylate cyclase activity in kidney remnants from the rats with reduced renal mass failed to demonstrate blunting of PTH activation of the enzyme by 25(OH)D3 or by 1,25(OH)2D3 as seen in kidneys from the control intact animals. These experiments demonstrate a phosphaturic response to 25(OH)D3 without parallel change in urinary cAMP in 5/6 NPX with intact parathyroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1989

Oncogenous osteomalacia: a case study.

A case of oncogenous osteomalacia due to a fibrosarcoma of the maxilla is reported, with a 19 year course before treatment. Metabolic studies of calcium and phosphorus were performed 3 and 19 years after the first symptomology. There was a negative balance for both phosphorus and calcium with low serum levels of 1,25-dihydroxyvitamin D which were corrected by resection of the tumor. Portions of the tumor were cultured and the supernatant did not affect phosphorus transport by a proximal tubule kidney cell line. Other portions were injected into athymic nude mice where they resulted in hypophosphatemia and phosphaturia, thus confirming the endocrine nature of the oncogenous osteomalacia factor.

Adult↗
PubMed1989

Renal transplantation is not contraindicated in asymptomatic carriers of hepatitis B surface antigen.

Recent reports showing that the presence of positive tests for hepatitis B surface antigen (HBsAg) is associated with prohibitively high morbidity and mortality suggest that such patients should not be considered for kidney transplantation. The clinical outcome and serology including hepatitis B DNA assays of 11 patients who were HBsAg-positive at the time of transplantation, as well as the hepatic complications in all 200 kidney transplantations during the same period, were analyzed. In the 11 HBsAg-positive patients, no clinical or laboratory evidence suggesting deterioration in liver function over a mean follow-up period of 8.0 +/- 1.7 years was found. Of six patients with fatal or severe chronic liver disease, only one was HBsAg-positive at the time of transplantation and showed no deterioration over 9 years. Two immunosuppressed patients developed anti-HBs antibodies after acute hepatitis B infection. A review of the literature leads to the conclusion that previous reports of poor patient prognosis may represent patients who first showed HBsAg positivity after transplantation or who had preexisting HBsAg-related liver disease. The present findings suggest that asymptomatic patients with positive tests for HBsAg should not be excluded from kidney transplantation programs.

Adult↗
PubMed1989

Effect of heparin on cortical adenylate cyclase activity and on urinary excretion of 3',5'-adenosine monophosphate in rat.

The effect of heparin on the renal adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP) system was studied in vitro in renal cortical membrane preparations and in vivo on hormone-stimulated nephrogenous cAMP excretion. The heparin dose dependently inhibited basal and hormone-stimulated rat renal cortical AC activity. The heparin concentration causing 50% inhibition was 45 micrograms/ml for the basal activity and 33 and 85 micrograms/ml for the parathyroid hormone (PTH) and glucagon-stimulated activities, respectively. PTH- and glucagon-stimulated AC activity was inhibited by the non-antithrombotic heparinoid, N-acetylated N-disulfated heparin, but not by a structural analogue of heparin, dextran sulfate. Forskolin- and Mn2(+)-stimulated AC activity was also inhibited by heparin, while NaF stimulated activity was resistant to it. Increasing Mg2+ concentration did not affect the inhibition of basal and PTH-stimulated AC activity by heparin. The urinary excretion of nephrogenous cAMP was determined in parathyroidectomized rats treated with glucagon (group 1), glucagon and heparin (group 2), heparin alone (group 3) and control (group 4). Glucagon induced a significant increase in nephrogenous cAMP excretion. The urinary excretion of nephrogenous cAMP, however, was significantly lower in group 2 (receiving glucagon and heparin) than in group 1 (receiving glucagon alone). There were no significant changes in nephrogenous cAMP in groups 3 and 4. These results suggest that heparin is a potent inhibitor of renal AC in vivo and in vitro. Taken together, our data point out the catalytic unit of the AC system as the site of heparin interaction.

Adenylyl Cyclase Inhibitors↗
PubMed1988

Noninvasive assessment of skin iron content in hemodialysis patients. An index of parenchymal tissue iron content?

Iron overload has been described in patients undergoing chronic hemodialysis. The present study was undertaken to evaluate a rapid, noninvasive method for determination of skin iron by the technique of diagnostic x-ray spectrometry (DXS). Thirty-five patients receiving chronic hemodialysis treatment entered the study and were compared with 25 normal controls. Since pathological skin iron deposition occurs mainly at the dermal-epidermal junction in the basal cells of the epidermis, measurements were made in the thenar eminence representing mainly epidermal tissue (FeE), and in the forearm representative mainly of dermis (FeD). The mean +/- SD FeE iron concentrations were equivalent to 14.5 +/- 8.8 and 18.2 +/- 10.2 parts per million wet weight tissue (ppm) and both were significantly higher than in normal controls in which they averaged 9.2 +/- 2.5 ppm (P less than 0.005) and 10.2 +/- 3.2 ppm (P less than 0.001), respectively. There was significant positive correlation between individual skin iron determinations with the total number of blood transfusions received, the rate of blood transfusion, and with serum ferritin levels. Bone marrow hemosiderin was examined in six patients and showed a similar trend. Despite correlation only with indirect indices of tissue iron, our findings suggest that DXS may serve as a reliable quick method for noninvasive estimation of nonreticuloendothelial tissue iron deposition in hemodialysis patients suspected of having transfusional iron overload. The method may be valuable in monitoring the effects of chelation therapy.

Adult↗
PubMed1988

Impaired production and decreased urinary excretion of adenosine 3',5'-monophosphate in primary hyperparathyroidism with vitamin D deficiency.

Increased urinary excretion of cAMP is a common finding in patients with primary hyperparathyroidism. We report a patient with hypercalcemia, primary hyperparathyroidism, vitamin D deficiency and high nephrogenous cAMP that fell to low levels during the course of a protracted illness. Surgical removal of a large parathyroid cystic adenoma was associated with a decrease in plasma calcium. Because of the relatively low nephrogenous cAMP with high plasma iPTH the biological activity of the fluid aspirated from the adenoma was examined. Acute clearance studies were performed in parathyroidectomized rats and their response to the parathyroid fluid was compared with the response of synthetic PTH. Similar phosphaturic responses to PTH and the aspirated fluid were recorded and were preceded by similar increments in nephrogenous cAMP. Thus the discrepancy between the high plasma calcium, high PTH and the low nephrogenous cAMP seen in our patient was related to impaired cAMP production by the renal adenylate cyclase. There was no evidence for a hormone with a different biological activity. The impaired formation of cAMP may reflect a combined result of several factors including downregulation of renal adenylate cyclase, phosphate depletion and vitamin D deficiency state.

Adenoma↗
PubMed1988

Effect of intravenous glucagon on the urinary excretion of adenosine 3',5'-monophosphate in man and in rats. Evidence for activation of renal adenylate cyclase and formation of nephrogenous cAMP.

To examine the effect of glucagon in vivo on renal formation and excretion of cAMP, clearance studies were performed in patients with hypoparathyroidism and in parathyroidectomized rats. Four patients with idiopathic hypoparathyroidism and 2 patients with pseudohypoparathyroidism were studied during an intravenous glucagon infusion (20 micrograms/kg body weight). In all patients, glucagon induced a significant increase in nephrogenous cAMP and a 2- to 3-fold increase in fractional excretion of phosphate. The average increase in nephrogenous cAMP was from a baseline of 784 +/- 229 to 18,748 +/- 3,842 pmol/100 ml glomerular filtrate (GF) (p less than 0.01) and occurred 30-60 min after the beginning of the glucagon infusion. The effect of intravenous glucagon, given as a bolus, was further examined in parathyroidectomized rats. Glucagon elicited a significant increase in the urinary excretion of the nucleotide. The excreted cAMP was compared with its filtered load for each urine collection period. In the first two collections, 0-15 and 15-30 min, the filtered load of cAMP was higher than its urinary excretion. During the following periods, 30-90 min, the excreted urinary cAMP exceeded by far its filtered load, suggesting a net nephrogenous contribution to the excretion of the nucleotide. Infusion of exogenous cAMP to parathyroidectomized rats induced significant increments in the filtered load and urinary excretion of the nucleotide. Tubular secretion of extrarenal cAMP could not be detected during the cAMP infusion. These results provide evidence supporting in vivo a possible parathyroid-independent formation of nephrogenous cAMP after glucagon administration, in men and in rats. The glucagon-induced increase in nephrogenous cAMP seems to account, at least partly, for some of the renal actions of this hormone.

Adenylyl Cyclases↗
PubMed1987

The regional cerebral blood flow in patients under chronic hemodialytic treatment.

Regional cerebral blood flow (rCBF) was measured by the xenon-133 inhalation method in an unselected group of nine chronic hemodialysis patients before and after a single hemodialytic treatment. All patients underwent neurological, neuropsychological, and biochemical evaluations on the same occasions. Predialysis rCBF values did not differ from those obtained in age-matched normal controls. Following hemodialysis, there was a mild reduction in the rCBF by a mean of 7 +/- 2.6% (p = 0.02). The posthemodialysis rCBF reduction was not associated with any neurological or cognitive dysfunction. The causes of hemodialysis-induced rCBF decreases are unknown, but increased blood viscosity and biochemical changes, such as urea reduction and blood alkalinization, may play a role.

Adult↗