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Biomedical subjects

M M Popovtzer

Publications and source records attributed to M M Popovtzer.

At least 73 records · Page 4Linked to original sources
PubMed1990

Glycerol-induced acute renal failure in the rat: the protective effect of unilateral nephrectomy.

Studies were performed to evaluate the effect of unilateral nephrectomy on glycerol-induced acute renal failure in the rat. Normal rats were subjected to either sham uninephrectomy (n = 43) or right uninephrectomy (n = 53). The functional compensation of the remaining kidney was followed after 1 and 2 weeks. Fourteen days after the operation, acute renal failure was induced by injection of 50% glycerol solution to both groups. Uninephrectomised rats developed a lesser degree of renal failure compared to sham-operated rats. Forty-eight hours after glycerol injection, PCr of uninephrectomised rats was 260 +/- 22 mumol/l compared with 338 +/- 26 in sham-operated rats (P less than 0.0125) and CCr in uninephrectomised rats was greater (0.10 +/- 0.01 ml/min vs 0.07 +/- 0.01; P less than 0.025) in sham rats. Uninephrectomised rats had significantly greater recovery of CCr compared to sham rats at 24 h (20.1% +/- 2.3 vs 13.1% +/- 2.2, P less than 0.025) and at 48 h (32.1% +/- 3.3 vs 19.2% +/- 3.3, P less than 0.005) after glycerol injection. FENa was significantly less in uninephrectomised rats: 0.96 +/- 0.16% vs 2.25 +/- 0.05% (P less than 0.025) in sham rats 24 h post glycerol. Urinary excretion of K+ was greater in rats following uninephrectomy compared to sham rats both after 24 h and 48 h post glycerol (P less than 0.01), accompanied by lower plasma potassium (P less than 0.05). A correlation coefficient (r) of 0.793 was observed between urinary potassium excretion rate and percentage recovery of CCr.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
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

Opposite effects of diabetes on nephrotoxic and ischemic acute tubular necrosis.

The effect of streptozotocin-induced diabetes mellitus on two different models of acute tubular necrosis (ATN), was studied: (i) the nephrotoxic model of HgCl2-induced ATN and (ii) the ischemic model of renal artery clamping for 60 min. Induction of ATN with HgCl2 in normal rats decreased CrCl from 0.67 +/- 0.05 to 0.1 +/- 0.019 ml/min (P less than 0.001) after 24 hr, and it deteriorated further to 0.03 +/- 0.013 ml/min after 48 hr; whereas, in the diabetic rats, HgCl2 decreased CrCl from 0.98 +/- 0.11 only to 0.31 +/- 0.037 ml/min (P less than 0.0001), but CrCl recovered to 0.50 +/- 0.08 ml/min after 48 hr. Bilateral clamping of renal arteries for 60 min in control and diabetic rats extremely decreased CrCl in both groups. Twenty-four hours after clamping, two of nine rats from the diabetic group died, whereas none from the control group died. Forty-eight hours after clamping, all nine rats from the diabetic group died, whereas only two rats from the control group died, and in the four surviving rats CrCl recovered slightly. Our study shows that streptozotocin-induced diabetes could not confer a general protection against ATN. It was protective against a nephrotoxic insult but aggravated the ischemic insult. An attempt to reconcile these discrepant effects is made in the Discussion.

Acute Kidney Injury↗
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

The in vivo and in vitro effect of calmodulin antagonists on the renal actions of 25(OH) vitamin D3 in the rat.

Previous work from this laboratory has demonstrated that 25(OH) vitamin D3 [25(OH)D3] acutely suppresses the phosphaturic action of parathyroid hormone (PTH) and interferes with the PTH-induced activation of adenylate cyclase (AC). Calmodulin inhibitors block vitamin D-induced Ca2+ transport in the gut and phosphorus uptake in renal BBMV's. We have examined whether calmodulin antagonists affect the renal action of 25(OH)D3. Acute clearance experiments were performed in PTH-infused parathyroidectomized rats receiving 25(OH)D3 after pretreatment with trifluoperazine (TFP) or promethazine (P). In vitro PTH-induced activation of renal AC was also studied in membrane preparations from pretreated rats in the presence of 25(OH)D3. 25(OH)D3 reduced the PTH-stimulated increase in fractional excretion of phosphorus (CP/CIn) from 0.292 +/- 0.024 to 0.195 +/- 0.018 (p less than 0.005) and urinary cAMP from 149.3 +/- 20.3 to 78.1 +/- 10.4 pmol/min (p less than 0.01) and also blunted AC activation in vitro. TFP but not P abolished the effects of 25(OH)D3 both in vivo and in vitro. R 24571 also abolished the in vitro effect of 25(OH)D3. Thus, (1) TFP abolishes both the antiphosphaturic and the AC/cAMP-related actions of 25(OH)D3, (2) P does not have these effects, and (3) R 24571 abolishes the in vitro effect of 25(OH)D3. These results suggest that the antiphosphaturic effect of 25(OH)D3 acting via the AC/cAMP system may be calmodulin dependent.

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

Inhibition of thick ascending limb Na+-K+-ATPase activity in salt-loaded rats by furosemide.

To evaluate the role of increased thick ascending limb Na+-K+-ATPase activity in rats undergoing hypertonic salt loading, the following groups of rats were studied: 1) control rats, 2) rats receiving an oral hypertonic Na load for 7 days, and 3) rats receiving the same oral Na load as in group 2 plus a daily injection of 10 mg/100 g of furosemide ip for 7 days. Salt loading (group 2) was associated with increased glomerular filtration rate (GFR) and hence an increased filtered load of sodium. Plasma aldosterone levels were markedly decreased. Na+-K+-ATPase was unchanged in the proximal tubule [convoluted (PC) and straight (PS)], increased in the thick ascending limb of Henle's loop [outer medullary (OMTAL) and cortical (CTAL)] and decreased in the distal nephron [distal convoluted tubule (DCT) and cortical collecting duct (CCD)]. The renal corticomedullary gradient of solutes was markedly increased in the salt-loaded group. Salt loading plus furosemide for 7 days (group 3) was associated with severe dehydration and hypernatremia. GFR as well as plasma aldosterone levels were unchanged compared with control. Na+-K+-ATPase was significantly increased in the proximal tubule (PC and PS), markedly decreased in the thick ascending limb of Henle's loop (OMTAL and CTAL), increased in the DCT and unchanged in the CCD. The increase in the corticomedullary gradient caused by salt loading per se was abolished by treatment of salt-loaded rats with furosemide. These results indicate that treatment with furosemide prevents the preservation of water balance and of normal body fluid tonicity in rats undergoing hypertonic Na loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Improvement of immune-complex nephritis associated with hepatitis B surface antigen excess.

A case of hypocomplementemic membranoproliferative glomerulonephritis was studied during remission of nephrosis induced by high doses of corticosteroids. Hepatitis B surface antigen (HBsAg) and immune complexes were detected in serum and glomeruli. Anti-hepatitis-B surface antibody, undetectable in serum by conventional radioimmunoassays was identified in circulating immune complexes (CIC). On two occasions, improvement in renal function coincided paradoxically with an extreme increase in serum HBsAg levels as well as with marked elevation of CIC. We suggest that, as previously observed in animal models of glomerulonephritis, extreme antigen excess may inhibit glomerular deposition of immune complexes.

Antigen-Antibody Complex↗
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

Nephrogenic diabetes insipidus, cystinosis, and vitamin D.

We describe a patient with early diagnosed cystinosis who presented with nephrogenic diabetes insipidus in addition to proximal tubular dysfunction. Another feature in this patient was abnormally low serum concentration of 24,25 dihydroxy vitamin D3 (24,25(OH)2D3) with normal 25 hydroxy vitamin D3 (25(OH)D3) and relatively low 1,25 dihydroxy vitamin D3 (1,25(OH)2D3).

Child, Preschool↗
PubMed1988

Colchicine does not interfere with the antiphosphaturic effect of 25(OH) vitamin D3 in the rat.

The effect of colchicine pretreatment on the antiphosphaturic action of 25(OH)vitamin D3 (25[OH]D3) was examined in parathyroidectomized (PTX), parathyroid-hormone (PTH)-infused rats by acute clearance studies. The following groups were studied: group 1, colchicine-pretreated PTX rats; group 2, colchicine-pretreated PTX rats receiving PTH infusion; group 3, colchicine-pretreated PTH-infused PTX rats receiving intravenous 25(OH)D3 with pretreated PTH-infused PTX rats serving as controls. The effect of 25(OH)D3 on PTH-activated renal adenylate cyclase [AC] from colchicine-pretreated rats was studied in vitro. In group 1, fractional excretion of phosphate (Cp/CIn) after colchicine was 0.102 +/- 0.011 vs. 0.029 +/- 0.005 in controls (p less than 0.001). In group 2, PTH increased Cp/CIn from 0.074 +/- 0.026 to 0.184 +/- 0.028 (p less than 0.05) in colchicine-pretreated animals and from 0.018 +/- 0.006 to 0.213 +/- 0.034 in controls (p less than 0.0025). In group 3, 25(OH)D3 decreased Cp/CIn from 0.344 +/- 0.022 to 0.235 +/- 0.026 (p less than 0.005) and UcAMP from 103.7 +/- 12.4 to 69.0 +/- 9.6 (p less than 0.025). In vitro PTH activation of AC was blunted in colchicine-pretreated rats; however, the response to 25(OH)D3 was intact. Histological changes compatible with microtubule disruption were found in proximal tubules of kidneys from colchicine-pretreated rats. These results show that colchicine alters the response to PTH but it does not affect the antiphosphaturic action of 25(OH)D3, suggesting that this action is not mediated via cytoplasmic microtubules.

Adenylyl Cyclases↗
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↗
PubMed1988

Antinuclear antibody-negative systemic lupus erythematosus (SLE) and severe renal involvement: close correlation between disease activity and appearance of circulating anticoagulant.

A 16-year-old girl meeting the criteria for SLE is described. Salient features of the clinical course included active glomerulonephritis with dense subepithelial deposits on electron microscopy, pulmonary embolism, axillary vein thrombosis, arthritis, serositis and fever. Disease activity correlated with the presence of lupus anticoagulant as measured by VDRL and partial thromboplastin time (PTT). Her serum was consistently negative to ANA, anti-DS-DNA, anti-SS-DNA, ENA, anti-Ro, anti-La, and LE cells for the entire 4-year course. She responded remarkably to prednisone and azathioprine. Reappearance of VDRL and elevated PTT preceded exacerbation of disease activity and served as a serological guide for modifying medical treatment.

Adolescent↗