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Biomedical subjects

S Sabatini

Publications and source records attributed to S Sabatini.

At least 109 records · Page 6Linked to original sources
PubMed1984

Effect of lanthanum on urinary acidification and sodium transport by the turtle and toad bladder.

Lanthanum has been extensively used to evaluate the role of extracellular and membrane-bound calcium on several aspects of cell function. In the present study we evaluated the effect of mucosal or serosal addition of lanthanum on Na and H+ transport by the turtle bladder, in vitro, to gain insight concerning the role of calcium on these processes. Mucosal addition of lanthanum was associated with a decrease in Na transport and H+ secretion. The inhibition was of rapid onset, achieving a maximal inhibition at 10(-3) M for H+ secretion and 5 X 10(-4) for Na transport. The effect was rapidly and totally reversible with the removal of lanthanum. The mucosal effect of lanthanum addition was observed only at pH 7.4 for H+ secretion and at pH 7.4, 6.4, and 5.4 for Na transport. Agents capable of 'screening' the negative change of membrane proteins, such as cadmium or zinc, could neither elicit nor prevent the effect of lanthanum on H+ secretion. The effect of serosal addition of lanthanum on H+ or Na transport was different from that observed with mucosal addition; it was of slow onset, smaller magnitude, partially reversible, and only elicited by high concentrations (10 mM) of lanthanum. Serosal addition of lanthanum caused an early increase and a late decrease in radioactive calcium efflux. Mucosal addition of lanthanum caused an increase in calcium efflux. The data demonstrate that lanthanum inhibits Na and H+ transport in the turtle bladder and suggest that the mechanism of action of lanthanum is the result of either displacement of membrane-bound calcium or altered cell membrane permeability to calcium.

Animals↗
PubMed1983

Reaction of beef plasma and lentil seedlings Cu-amine oxidases with phenylhydrazine.

The reaction of copper amine oxidases from beef plasma and lentil seedlings with hydrazine derivatives has been studied. A 1:1 stoichiometry was always found for the irreversible binding to the dimeric proteins. The formation of the adduct does not require the presence of oxygen or copper. Substrates compete with hydrazine derivatives for the binding to the enzymes. The binding of hydrazines and of substrate has different effects on the EPR spectra of enzymic copper.

Amine Oxidase (Copper-Containing)↗
PubMed1983

The acidosis of chronic renal failure.

The acidosis of chronic renal failure is not due to bicarbonate wastage per se; rather, bicarbonate reabsorption per nephron is markedly enhanced. The ability to lower the urine pH is preserved. While overall ammonium production may be decreased in chronic renal failure, both ammonium production and excretion are markedly increased when expressed per remaining nephron. Titratable acid excretion in chronic renal failure is essentially maximal, owing to the effect of parathyroid hormone on phosphate excretion by the kidney. Thus, it appears that the acidosis of chronic renal failure is solely the consequence of the reduction in functional renal mass. Extrarenal buffering may contribute substantially to the maintenance of a near normal acid-base status in patients with marked reduction in glomerular filtration rate. That homeostasis is so well preserved until glomerular filtration rate falls to approximately 10 per cent of normal is remarkable; the price, however, may be considerable. Prolonged acidosis may magnify the tendency of renal failure to cause osteodystrophy. An obvious treatment for the acidosis of renal failure is exogenous alkali therapy. Most clinicians withhold alkali therapy until the bicarbonate concentration falls below 20 mEq per L. If the acidosis cannot be safely corrected with exogenous therapy, dialysis should be initiated.

Acidosis↗
PubMed1983

Role of urinary concentrating ability in the generation of toxic papillary necrosis.

We studied the pathogenesis of chemically induced papillary necrosis in six groups of rats. Papillary necrosis was produced by a single injection of 2-bromoethylamine hydrobromide (BEA), 50 mg, i.v.; the animals were followed for 7 to 10 days after the administration of the compound. Following BEA, heterozygous Brattleboro rats developed all the functional and morphologic lesions of papillary necrosis that we previously described in Sprague-Dawley rats. They were unable to maintain sodium balance when dietary sodium was withdrawn. Homozygous Brattleboro rats, on the other hand, developed none of the manifestations of papillary necrosis (that is, animals with central diabetes insipidus were protected completely from the nephrotoxic effects of BEA). They adapted normally to a zero sodium diet. Chronic administration of vasopressin to homozygous Brattleboro rats fully restored the toxic effects of BEA. Lowering urinary concentrating ability by inducing a water diuresis in Sprague-Dawley rats completely protected against BEA-induced papillary necrosis. Decreasing papillary solute concentration by furosemide or increasing urine flow after abrupt withdrawal of vasopressin to homozygous Brattleboro rats did not protect against BEA-induced papillary necrosis. We conclude that the combination, but not either alone, of increased urine flow and decreased papillary solute concentration protects against the development of BEA-induced papillary necrosis.

Animals↗
PubMed1983

[Substances inhibiting monoamine oxidase. II. Inhibition of bovine plasma amine oxidase by N-cyclopropyltryptamines].

In this paper, we report the inhibition constants obtained with N-cyclopropyl-5,6-dimethoxytryptamine and with N-cyclopropyl-6,7-dimethoxytryptamine on the activity of beef plasma amineoxidase. The inhibition constants are respectively: 0.3 x 10(-3) M and 0.65 x 10(-3) M. A dixon graph of the enzymic oxidation of benzylamine indicates a non-competitive inhibition of the enzyme by these dimethoxytryptamines.

5-Methoxytryptamine↗
PubMed1982

The effects of chronic papillary necrosis on acid excretion.

Complete papillary necrosis in rats can be induced within 1 month following a single injection of 2-bromoethylamine hydrobromide (BEA) (50 mg, i.v.). Utilizing a combination of clearance and balance techniques the effects of complete absence of the papilla was examined as regards urinary acidification, whole kidney glomerular filtration rate (GFR), single nephron GFR, and morphology. Whole kidney GFR was not different from control, however, the percent filtering juxtamedullary nephrons was markedly diminished (87.2 +/- 2.1 vs. 31.5 +/- 3.6% filtering, control vs. BEA, respectively, P less than 0.001) and significantly reduced in the superficial nephrons (80.6 +/- 3.6 vs. 62.2 +/- 6.1% filtering, control vs. BEA, respectively, P less than 0.05). There was a significant decrease in juxtamedullary single nephron GFR and an increase in the superficial single nephron GFR as assessed by the quantitative Hanssen's technique in the animals with chronic papillary necrosis. Complete papillary necrosis was associated with normal arterial bicarbonate concentration, pH, and plasma electrolyte concentrations. At the same degree of acidemia (induced by NH4Cl administration) minimal urinary pH, ammonium excretion, and titratable acid excretion were not different than seen in age matched controls. The response to Na2SO4 infusion and phosphate infusion was the same in both groups of animals. The urine-blood (U-B)pCO2, and index of urinary acidification, was identical in BEA and control animals. Scanning electron microscopy showed scarring of the juxtamedullary glomeruli one month after BEA. The papilla was sloughed and lying free in the renal pelvis in every experimental animal. These data demonstrate that complete papillary necrosis is not associated with acidosis nor a defect in urinary acidification.

Absorption↗
PubMed1982

Serosal Na/Ca exchange and H+ and Na+ transport by the turtle and toad bladders.

A Na/Ca exchange system has been described in the plasma membrane of several tissues and seems to regulate the concentration of calcium in cytosol. Replacement of extracellular Na by sucrose increases calcium uptake into and decreases calcium efflux from the cell, leading to an increase in cytosolic calcium. The effect of an increase in cytosolic calcium mediated by the Na/Ca exchange system on H+ and Na transport in the turtle and toad bladder was investigated by replacing serosal Na isosmotically by sucrose or choline. Replacement of serosal by sucrose was associated with a significant inhibition of H+ secretion or Na transport which was reversible by addition of NaCl. Replacement of mucosal Na by sucrose failed to alter H+ secretion. Removal of serosal Na was associated with a significant increase in 45Ca uptake which could be blocked by pretreatment with lanthanum chloride. Pretreatment with lanthanum chloride blunted the inhibitory effect of replacement of serosal Na by sucrose on H+ and Na transport, thus suggesting that the increase in calcium uptake and the inhibition of transport are causally related. Under anaerobic conditions the rate of H+ or Na transport are linked to the rate of lactate production. The inhibition of Na or H+ transport by removal of serosal Na was accompanied by a proportional decrease in lactate production, thus suggesting that an increase in cytosolic calcium does not inhibit transport by uncoupling glycolysis from transport. Replacement of serosal Na by sucrose did not alter the force of the H+ or Na pump but led to an increase in resistance of the active pathway of H+ and Na transport. The inhibition of Na transport by replacement of serosal Na with sucrose could be reversed by addition of amphotericin B, an agent which increases luminal permeability to Na, thus suggesting that decreased Na entry across the apical membrane is the mechanism responsible for the inhibition of Na transport. The results of the present studies strongly suggest that an increase in cytosolic calcium through the serosal Na/Ca exchange system inhibits H+ and Na transport in the turtle and toad bladder probably by increasing the resistance of the luminal membrane.

Amphotericin B↗
PubMed1982

Distal acidification in the rabbit: role of diet and blood pH.

A distal acidification defect is said to exist in rabbits because this species does not achieve a normal urine minus blood (U-B) PCO2 gradient in response to sodium bicarbonate infusion. This observation contrasts with data derived from studies in isolated rabbit cortical collecting tubules that have shown an acidifying capacity when the tubules were obtained from acidotic animals. The present study was designed to examine the role of diet and blood pH on distal acidification in the rabbit. Maximal alkalinization of the urine by acute sodium bicarbonate infusion was associated with a low U-B PCO2 gradient (0.7 +/- 2.1 mmHg). Rabbits made acidotic by ammonium chloride administration for 1 wk achieved a substantial U-B PCO2 gradient (29 +/- 5 mmHg) in response to neutral sodium phosphate infusion. To further evaluate the role of blood pH on the ability to raise U-B PCO2 gradient, rabbits and rats made acidotic by chronic ammonium chloride administration were studied. Neutral sodium phosphate was then infused to stimulate distal acidification. At comparable levels of urinary phosphate concentration and blood pH, acidotic rabbits were able to achieve a U-B PCO2 (50 +/- 7 mmHg) comparable with that of acidotic rats (48 +/- 8.3 mmHg). These data show that the failure of rabbits to raise U-B PCO2 gradient can be partially corrected by prior exposure to acid in the diet and further corrected by maintaining the blood pH within the acidotic range.

Acidosis↗
PubMed1982

Metabolic and hormonal factors influencing extrarenal buffering of an acute acid load.

This study evaluates metabolic and hormonal factors influencing extrarenal buffering of an acute acid load. Phosphate deprivation of 2 weeks duration was associated with enhanced extrarenal acid buffering. The enhanced extrarenal buffering capacity of phosphate deprivation was not dependent on the presence of parathyroid glands. Parathyroid hormone administration to phosphate-deprived rats promoted a further enhancement of the buffering capacity of an acid load. Blood pH and HCO3 during acid loading were not significantly different between control and diphosphonate-treated rats and between phosphate-deprived rats and phosphate-deprived rats treated with diphosphonate. The mortality rate, however, was significantly higher in diphosphonate-treated rats than in rats not receiving the drug suggesting that diphosphonate blunts the buffering of an acid load in both control and phosphate-deprived rats. Chronic vitamin D administration and acute administration of arginine vasopressin in pharmacologic doses were associated with significant enhancement of buffering capacity as compared to control rats. Thyrocalcitonin administration to intact but not thyroparathyroidectomized rats was associated with diminished capacity to buffer an acid load. These data demonstrate that the buffering of an acute acid load is influenced by a number of dietary and hormonal factors probably acting at the level of the bone.

Acid-Base Equilibrium↗
PubMed1981

Drug-induced papillary necrosis: electrolyte excretion and nephron heterogeneity.

The functional expression of papillary necrosis was investigated in rats following administration of 2-bromoethylamine hydrobromide (BEA). The percentage of filtering superficial and juxtamedullary nephrons was assessed using the qualitative Hanssen technique. There was a marked decrease in the percentage of filtering juxtamedullary nephrons 24 h after the induction of papillary necrosis (as compared with control rats), which was blunted in salt-loaded animals. The percentage of filtering superficial nephrons was the same in all three groups. BEA administration to normal rats was associated with a significant increase in sodium, chloride, phosphate, and calcium excretion. BEA administration to rats on a chloride-restricted diet was associated with chloride wastage. These animals also failed to adapt to a low chloride diet as late as 7 days after the administration of BEA. The phosphaturia observed in intact rats treated with BEA was abolished by parathyroidectomy. BEA-treated rats were able to adapt to a low phosphate diet and to a low magnesium diet. These data demonstrate that papillary necrosis is associated with profound impairment of juxtamedullary nephron filtration and with chloride wastage. In the absence of the papillary structures adaptation to phosphorus or magnesium deprivation is still possible.

Animals↗
PubMed1981

Factors influencing vascular hyporesponsiveness to angiotensin II.

Bartter's syndrome is characterized, in part, by hyporesponsiveness to the pressor effect of exogenous angiotensin II (AII). This has been attributed to volume contraction, hypokalemia, and/or increased prostaglandin (PG) levels. In order to investigate factors responsible for a diminished response to the pressor effect of AII, rats were made hypokalemic or volume contracted and hypokalemic (VCHK) by dietary restriction. AII sensitivity was examined by determining the dose of AII required to raise the mean arterial pressure 20 mm Hg. When compared with control rats. VCHK and hypokalemic rats were significantly less sensitive to AII. VCHK rats were significantly less sensitive to AII than hypokalemic rats. Both experimental groups were similarly hypokalemic, but plasma renin activity (PRA) of VCHK only was greater than control values. In VCHK rats, acute K+ restoration partially corrected AII hyporesponsiveness, although plasma K+ increased to normal. In VCHK rats, acute volume expansion with normal saline similarly achieved only partial correction of AII hyporesponsiveness although PRA values fell to the control range. Simultaneous K+ restoration and volume expansion to VCHK rats successfully restored AII sensitivity to the control range. Dietary sodium, chloride, and potassium restriction did not increase urinary excretion to PGE2. Indomethacin (5 mg/kg, iv) given acutely to VCHK rats did not significantly after baseline hyporesponsiveness to AII. Norepinephrine vascular sensitivity was not affected by either volume contraction or hypokalemia. These data demonstrate that volume contraction and hypokalemia individually depress exogenous AII sensitivity in the rat and do so by separate and additive mechanisms. Furthermore, these mechanisms appear to be independent of PG.

Angiotensin II↗