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Biomedical subjects

S Sabatini

Publications and source records attributed to S Sabatini.

At least 91 records · Page 5Linked to original sources
PubMed1987

Effect of parathyroid hormone on transport by toad and turtle bladder.

We recently demonstrated that parathyroid hormone (PTH) inhibited both vasopressin- and cyclic AMP-stimulated water transport in the toad bladder. This was associated with an increase in calcium uptake by isolated epithelial cells. We postulated that PTH exerts its action on H2O transport by directly stimulating calcium uptake. The current study was designed to compare the effects of PTH and the calcium ionophore, A23187, on H2O and Na transport and H+ secretion in toad and turtle bladders. In toad bladder, PTH and A23187 decreased arginine vasopressin (AVP)-stimulated H2O flow and short-circuit current (SCC) after 60 min serosal incubation. In turtle bladder A23187 decreased SCC to 79.3 +/- 3.6% of base line (P less than 0.05), and significantly decreased RSCC as well. PTH had no effect on SCC or H+ secretion in turtle bladders. Both PTH and A23187 increased 45Ca uptake in toad bladder epithelial cells; only A23187 increased 45Ca uptake in the turtle bladder. The different action of PTH in these two membranes, compared with that of the calcium ionophore, illustrates the selectivity of PTH on membrane transport. PTH increases calcium uptake and decreases transport only in a hormone-sensitive epithelium, whereas the ionophore works in virtually all living membranes. The mode of action of these two agents to increase calcium uptake is, therefore, likely different.

Animals↗
PubMed1987

Calcium transport in turtle bladder.

Unidirectional 45Ca fluxes were measured in the turtle bladder under open-circuit and short-circuit conditions. In the open-circuited state net calcium flux (JnetCa) was secretory (serosa to mucosa) and was 388.3 +/- 84.5 pmol.mg-1.h-1 (n = 20, P less than 0.001). Ouabain (5 X 10(-4) M) reversed JnetCa to an absorptive flux (serosal minus mucosal flux = -195.8 +/- 41.3 pmol.mg-1.h-1; n = 20, P less than 0.001). Amiloride (1 X 10(-5) M) reduced both fluxes such that JnetCa was not significantly different from zero. Removal of mucosal sodium caused net calcium absorption; removal of serosal sodium caused calcium secretion. When bladders were short circuited, JnetCa decreased to approximately one-third of control value but remained secretory (138.4 +/- 54.3 pmol.mg-1.h-1; n = 9, P less than 0.025). When ouabain was added under short-circuit conditions, JnetCa was similar in magnitude and direction to ouabain under open-circuited conditions (i.e., absorptive). Tissue 45Ca content was approximately equal to 30-fold lower when the isotope was placed in the mucosal bath, suggesting that the apical membrane is the resistance barrier to calcium transport. The results obtained in this study are best explained by postulating a Ca2+-ATPase on the serosa of the turtle bladder epithelium and a sodium-calcium antiporter on the mucosa. In this model, the energy for calcium movement would be supplied, in large part, by the Na+-K+-ATPase. By increasing cell sodium, ouabain would decrease the activity of the mucosal sodium-calcium exchanger (or reverse it), uncovering active calcium transport across the serosa.

Amiloride↗
PubMed1987

Effect of parathyroid hormone fragments on calcium transport in toad bladder.

Parathyroid hormone (PTH) has a variety of biologic effects which are both dependent and independent on activation of adenylate cyclase. We studied the effects of intact PTH and PTH fragments on water flow and Ca transport in isolated toad bladder sacs. As reported previously by us, PTH (1-84) significantly stimulated basal water flow in isolated toad bladder sacs. Synthetic PTH 1-34, 44-68, 53-84 and 65-84 (1 microgram/ml) had no effect on basal water flow after a 60-min incubation period. Intact PTH (1-84) and synthetic 1-34 PTH significantly inhibited both arginine-vasopressin and cyclic AMP-stimulated water flow. Synthetic PTH 44-68, 53-84 and 65-84 (1 microgram m/ml) had no effect on arginine-vasopressin or cyclic AMP-stimulated water flow after a 60-min incubation. Intact PTH (1-84) and synthetic 1-34 PTH significantly stimulated 45Ca uptake without affecting 45Ca efflux. Synthetic PTH 44-68, 53-84 and 65-84 had no effect on either 45Ca uptake or 45Ca efflux. Although these results suggest that the intact hormone is required for the maximal effect of PTH on water flow, substantial activity resides in the amino terminal fragment of the hormone. No activity per se resides in the carboxy terminal portion of the hormone as regards water flow. Alterations in Ca transport appear to mediate the effect of PTH on water flow. These effects are independent of activation of adenylate cyclase because these hormones also inhibit cyclic AMP-stimulated water flow.

Animals↗
PubMed1987

[Substances inhibiting amine oxidases. III. Synthesis and amine oxidase inhibition of imidazoquinoline derivatives].

The activity of copper and FAD dependent amine oxidases was tested with some derivatives of 3H-imidazo[4,5-h]quinoline and its isomers 3H-imidazo[4,5-f]quinoline, the chemistry of which is described in the literature (1), and Ki calculated. The methyl derivative of 3H-imidazo[4,5-f]quinoline was found to activate the copper bovine serum enzyme, but inhibits the FAD mitochondrial enzyme.

Animals↗
PubMed1986

Hemodialysis clearance of metronidazole and its metabolites.

Metronidazole is now being used with increasing frequency for various infectious conditions in patients with renal failure. It is commonly administered to septic patients who have developed acute renal failure requiring hemodialysis. The hemodialysis clearances of metronidazole and its metabolites were evaluated in nine renal failure patients on maintenance hemodialysis. The mean +/- standard deviation clearance and the extraction ratio were 106.9 +/- 16.3 ml/min and 0.65 +/- 0.08, respectively, when regenerated cellulose dialysis membrane was used. The clearance and the extraction ratio with the use of cuprophan membrane were 72.1 +/- 17.3 ml/min and 0.44 +/- 0.12, respectively. The clearances and extraction ratios for the metabolites were similar to those of the parent drug. For both metronidazole and the hydroxy metabolite, the clearance and the extraction ratio demonstrated a statistically significant difference between the regenerated cellulose membrane and the cuprophan membrane. In summary, metronidazole and its metabolites were found to be highly dialyzable with different clearances depending on the specific type of membrane used. However, owing to the relatively wide therapeutic index of the drug, dosage supplementation may be necessary only in seriously ill patients to ensure therapeutic effect.

Acute Kidney Injury↗
PubMed1986

Parathyroid hormone inhibits water flow in the isolated toad bladder.

These experiments studied the effect of parathyroid hormone (PTH) (1-84) on water and Ca transport in isolated toad bladder sacs and toad bladder epithelial cells. Serosal addition of PTH significantly inhibited maximal water flow induced by vasopressin or exogenous cyclic AMP. This effect was seen over a wide range of concentrations, with the threshold for the effect occurring at 1 ng/ml. Pretreatment of the toad bladder sacs with prostaglandin inhibitors (indomethacin or ibuprofen, 1 X 10(-6) M) or preincubation in low-Ca medium (0.089 mM) abolished the effect of PTH on vasopressin-stimulated water flow. Pretreatment of the toad bladders with lanthanum (5 X 10(-5) M) also abolished the effect of PTH on vasopressin-stimulated water flow. Synthetic PTH (1-34) inhibited vasopressin-stimulated water flow only at a high concentration (1 microgram/ml). PTH increased 45Ca uptake by toad bladder epithelial cells but had no effect on 45Ca efflux. These results demonstrate that PTH inhibits water transport beyond the generation of cyclic AMP. That the effect of PTH was abolished in a low-Ca medium or by pretreatment with lanthanum suggests that cell Ca uptake is required for the effect of PTH on water transport. That prostaglandin inhibitors also block the effect of PTH on vasopressin-stimulated water flow suggests that prostaglandin synthesis is required for the effect. These data suggest that the effect of PTH on water flow is mediated by an increased cellular uptake of Ca that stimulates prostaglandin release. Prostaglandin release, in turn, appears to mediate the inhibitory effect of PTH on vasopressin-stimulated water transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The use of drugs in renal failure.

We have tried to emphasize specific variables that impact upon the use of drugs in the patient with renal disease. These variables are complex, often interrelated, and if neglected by the physician will surely lead to unwarranted drug reactions and serious harm to the patient. We have purposely limited the tables of "Selected Pharmacologic Agents" to a few prototypic drugs from each class, emphasizing the newer agents recently introduced in clinical medicine. We strongly recommend that as new drugs are used, the original literature be consulted for verification.

Analgesics↗
PubMed1985

Effect of cyclic AMP on acidification in the isolated turtle bladder.

Cyclic AMP (10 mM) has been demonstrated to inhibit hydrogen ion secretion in the isolated turtle bladder. These experiments were designed to study the effect of cyclic AMP on hydrogen ion secretion in the isolated turtle bladder using both the pH stat and the reverse short circuit current techniques. Sodium transport was measured as the short circuit current. Studies were carried out at 0% CO2 and 1% CO2 at pH 7.4. Cyclic AMP (10 mM) was added to either the serosal or mucosal solutions, and hydrogen ion secretion was measured from 0 to 120 min. In the presence or absence of carbon dioxide, cyclic AMP and dibutyryl cyclic AMP had no effect on hydrogen ion secretion in fasted turtles. The addition of theophylline (10 mM) to the serosal solution, with or without cyclic AMP had no effect on proton secretion. Sodium transport was unchanged from control following serosal or mucosal addition of 10 mM cyclic AMP in the presence or absence of carbon dioxide. In chronically bicarbonate-loaded turtles proton secretion was the same as control fasted turtles. In these animals, however, serosal administration of 10 mM cyclic AMP significantly stimulated bicarbonate secretion. Stimulation of bicarbonate secretion occurred in the presence of a 20 mM bicarbonate gradient. When there was no bicarbonate gradient, cyclic AMP was without effect; cyclic AMP had no effect on bicarbonate permeability when measured in the presence of acetazolamide. These results indicate that cyclic AMP has no effect on hydrogen ion secretion or sodium transport in the isolated turtle bladder when studied at two different rates of acidification (0 and 1% CO2). Cyclic AMP appears to stimulate active bicarbonate secretion.

Acetazolamide↗
PubMed1985

Treatment of acute cyanide intoxication with hemodialysis.

A dramatic response was noted in a patient at our hospital who received hemodialysis therapy for severe acidosis secondary to an unknown toxin, subsequently identified as cyanide. We were unable to find any information concerning the hemodialysis clearance and extraction ratio of cyanide; thus, we studied the effect of hemodialysis in dogs receiving a constant infusion of cyanide with and without a simultaneous infusion of thiosulfate. The hemodialysis clearance of cyanide in the presence of thiosulfate was 38.3 +/- 5.4 ml/min with an extraction ratio of 0.43 +/- 0.06 (n = 4). Hemodialysis was found to increase the lethal dose of cyanide without thiosulfate infusion, and a further increase was noted with the thiosulfate infusion. Thiosulfate promotes mitochondrial metabolism of cyanide to thiocyanate. The end product, thiocyanate, is quickly removed by hemodialysis. We believe that the demonstrated effectiveness of hemodialysis in the treatment of acute cyanide intoxication is related not only to the hemodialysis clearance of cyanide, but also to the removal of its metabolic end product, thiocyanate. Based on our observations, we feel that hemodialysis is an effective adjunct in the treatment of acute cyanide intoxication.

Acidosis↗
PubMed1985

Cellular mechanisms of drug-induced papillary necrosis.

2-Bromoethylamine hydrobromide (BEA) causes complete papillary necrosis within 24-hr of i.v. administration. The mechanism of this effect is unknown. To characterize further the effect of BEA in transporting epithelia, the urinary bladders of toads and turtles were exposed to varying concentrations of BEA in vitro. In the toad bladder, both cyclic AMP- and vasopressin-stimulated water flow were significantly inhibited after 3 hr of exposure to BEA at a concentration as low as 2.5 X 10(-4) g/ml; after 1 and 2 hr no effect on water transport was observed. Serosal administration of BEA to both toad and turtle bladders significantly inhibited sodium transport to 54% of control at the end of 3 hr. The effect on sodium transport was seen as early as 10 min. The threshold for the effect on sodium transport occurred at a concentration less than that observed for water transport. By contrast, BEA had no effect on hydrogen ion secretion in the isolated turtle bladder over a wide range of concentrations. In fact, after 1 hr, BEA significantly stimulated hydrogen ion secretion. In homogenates of stripped turtle bladder mucosa, BEA significantly inhibited total Na-K adenosine triphosphatase and ouabain sensitive Na-K adenosine triphosphatase. Thus, in anuran membranes, BEA inhibits water and sodium transport but has no effect on acidification. These results suggest that its action in vivo may be related to alterations in cell volume regulation resulting from inhibition of sodium transport rather than a nonspecific toxic effect on the inner medullary epithelium.

Animals↗
PubMed1985

Evidence for voltage regulation of carbonic anhydrase-independent acidification in turtle bladder.

Despite 100% reabsorption of renal carbonic anhydrase activity, 70% of filtered bicarbonate is still reabsorbed. Recent data suggest that one of the mechanisms mediating carbonic anhydrase-independent bicarbonate reabsorption is the generation of favorable concentration gradients across the distal nephron following inhibition of carbonic anhydrase activity. Additional work suggests that the generation of favorable voltage gradients across the cortical collecting tubule may also mediate carbonic anhydrase-independent bicarbonate reabsorption. These studies were performed in turtle bladder to examine this issue. Acidification in this membrane was measured over a range of mucosa-negative potential difference of from 0 to 100 mV in the presence and absence of carbonic anhydrase activity. Under both conditions there was a linear increase in acidification as the potential difference increased. The rate of increase, however, was slightly less than 50% in the bladders subjected to carbonic anhydrase inhibition as compared to those with intact carbonic anhydrase activity. These data demonstrate that favorable electrical gradients enhance carbonic anhydrase-independent acidification as do favorable concentration gradients. We suggest that carbonic anhydrase-independent bicarbonate reabsorption in the kidney is mediated by a combination of favorable concentration and electrical gradients.

Acetazolamide↗
PubMed1984

Oxygraphic assay of 3,4-dihydroxyphenylalanine decarboxylase activity by coupled reaction with free and immobilized serum amine oxidase.

An oxygraphic method for the assay of 3,4-dihydroxyphenylalanine (Dopa) decarboxylase activity which makes use of the coupled reactions of Dopa decarboxylase with serum amine oxidase is presented. Both free and immobilized amine oxidases were utilized. The assay is simple, rapid, and allows a continuous monitoring of the reaction. The kinetic parameters for Dopa decarboxylase obtained with the coupled assay do not significantly differ from those obtained by standard methods.

Amine Oxidase (Copper-Containing)↗
PubMed1984

Recent results on the active site of amine oxidases.

A preparation of bovine plasma amine oxidase, containing only one copper ion per molecule, was obtained by treatment with diethyldithiocarbamate. The enzyme preparation still retained full activity. Thus, only one of the two copper ions contained in the enzyme molecule appears to be involved in the catalytic process.

Amine Oxidase (Copper-Containing)↗
PubMed1984

Pathophysiology of drug-induced papillary necrosis.

Papillary necrosis, a common cause of renal failure, is a life-threatening pathophysiologic event which may have a multiplicity of mechanisms. The primary functional lesions are salt wastage, impairment of urinary concentrating ability, polyuria, and imbalances of potassium, calcium and phosphate homeostasis; urinary acidification is completely normal. Papillary necrosis is associated with a profound decrease in juxtamedullary nephron glomerular filtration rate, in addition to damage to the papillary collecting duct. 2-Bromoethylamine hydrobromide (BEA) has proved to be a useful tool in elucidating the generation of this important clinical syndrome.

Acids↗