PubMed Health⌕ Search

Biomedical subjects

S Sestini

Publications and source records attributed to S Sestini.

At least 37 records · Page 2Linked to original sources
PubMed1998

First-pass cerebral extraction of benzamide-derivative radiotracers for SPECT.

Central dopaminergic receptors are widely studied for their importance in the pathophysiology of neurological and psychiatric diseases. We have investigated the cerebral delivery kinetics of three dopaminergic ligands in rats through the use of an indicator fractionation method to measure the tracer's regional influx rate constant with respect to regional blood flow. The aim is to collect the in vivo kinetic parameters of the radioligand cerebral distribution, which are necessary if, dealing with SPECT and "trapped" tracers, one wishes to analyse data using a graphical approach.

Animals↗
PubMed1997

Comparison of baseline-nitrate technetium-99m sestamibi with rest-redistribution thallium-201 tomography in detecting viable hibernating myocardium and predicting postrevascularization recovery.

OBJECTIVES: This study aimed to define the optimal criteria for detecting viable myocardium with rest-redistribution thallium-201 (Tl-201) or baseline-nitrate technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) using discriminant analysis and to compare the accuracy of the two tracers in predicting postrevascularization recovery. BACKGROUND: Rest-redistribution Tl-201 imaging is currently used for detection of myocardial viability, but the optimal variables for territory classification have not yet been defined. Although Tc-99m sestamibi is reportedly less effective than Tl-201, its reliability can be increased by injecting it during nitrate infusion. METHODS: In 35 patients with left ventricular (LV) dysfunction, tracer activity within asynergic coronary territories was quantified on rest and redistribution Tl-201 and baseline and nitrate Tc-99m sestamibi SPECT. Asynergic territory viability was evaluated on the basis of the postrevascularization functional outcome. RESULTS: Percent activity within asynergic territories was significantly influenced by their viability (p < 0.005) and the type of acquisition (p < 0.0001) but not by the tracer used. Discriminant analysis identified redistribution Tl-201 activity and nitrate-induced Tc-99m sestamibi activity change as the two most significant predictors of postrevascularization recovery. The discriminant function defined for Tl-201, including redistribution activity and reversibility, correctly classified 38 of 56 asynergic territories, whereas that for Tc-99m sestamibi, including nitrate-induced activity change and activity in nitrate images, correctly classified 43 territories. CONCLUSIONS: Redistribution activity is more important than reversibility when differentiating viable from nonviable territories using rest-redistribution Tl-201. In Tc-99m sestamibi SPECT, nitrate-induced activity changes are particularly useful in identifying myocardial viability. Baseline-nitrate Tc-99m sestamibi SPECT appears no less effective than rest-redistribution Tl-201 in predicting postrevascularization recovery.

Adult↗
PubMed1997

Cardiovascular and renal effects of low-dose atrial natriuretic peptide in compensated cirrhosis.

OBJECTIVES: Patients with cirrhosis and ascites have high plasma levels of atrial natriuretic peptide (ANP). Pharmacological doses of this hormone usually worsen systemic hemodynamics of cirrhotic patients. We assessed whether ANP influences cardiovascular homeostasis and renal function in patients with compensated cirrhosis at plasma levels comparable to those observed in patients with cirrhosis and ascites. METHODS: Radionuclide angiocardiography was performed in eight compensated cirrhotic patients during placebo (three periods of 15 min each) and ANP infusion (2, 4, and 6 pmol/kg.min for 15 min each), together with appropriate blood and urine sampling, to evaluate left ventricular diastolic, systolic, and stroke volume, heart rate, cardiac output, arterial pressure, peripheral vascular resistance, creatinine clearance, urinary sodium excretion, plasma renin activity, plasma aldosterone, norepinephrine and hematocrit. RESULTS: The infusion increased plasma ANP up to levels (52.03 +/- 2.29 pmol/L) comparable with those observed in 35 patients with ascites (46.42 +/- 1.57 pmol/ L). This increment was associated with significant reductions in left ventricular end diastolic volume, stroke volume, cardiac index (from 3.7 +/- 0.7 to 3.1 +/- 0.5 L/min.m2, p < 0.05) and mean arterial pressure (from 96.7 +/- 6.5 to 88.5 +/- 9.5 mmHg, p < 0.05), while heart rate and hematocrit significantly increased. Peripheral vascular resistance did not change. These hemodynamic effects occurred despite significant increases in plasma renin activity and norepinephrine. ANP also induced increases in creatinine clearance, urinary sodium excretion, and fractional sodium excretion. CONCLUSIONS: Low-dose ANP affected cardiovascular homeostasis and renal sodium handling in compensated cirrhosis, suggesting that this hormone may be involved in the pathophysiology of systemic hemodynamic and renal functional abnormalities of cirrhosis.

Aldosterone↗
PubMed1996

Enzymatic activities affecting exogenous nicotinamide adenine dinucleotide in human skin fibroblasts.

The fate of nicotinamide adenine dinucleotide (NAD), AMP, and ADP-ribose supplied to intact human skin fibroblasts was monitored, and the concentrations of intra- and extracellular pyridine and purine compounds were determined by HPLC analysis. Two enzymatic activities affecting extracellular NAD were detected on the plasma membrane, one hydrolyzing the pyrophosphoric bond and yielding nicotinamide mononucleotide (nucleotide pyrophosphatase) and the other cleaving the glycoside link and releasing nicotinamide (NAD-glycohydrolase). No AMP or ADP-ribose was found in the extracellular medium of cells incubated with NAD, the former being completely catabolized to hypoxanthine and the latter degraded to adenine and hypoxanthine.

Adenosine Diphosphate Ribose↗
PubMed1995

Purine and pyridine nucleotide metabolism in the erythrocytes of patients with Rett syndrome.

The possible involvement of purine and pyridine metabolism in Rett syndrome, a neurodegenerative disorder of unknown aetiology affecting females, was investigated. The levels of purine and pyridine nucleotides and their metabolites were determined by HPLC in the erythrocytes and plasma of 31 Rett patients and of 17 age-matched controls. Nucleotide production rate from extracellular precursors was determined in intact cells and enzyme activities were assayed in crude lysates using the same HPLC method. Decreased plasma nicotinamide concentrations and lower erythrocyte activities of hypoxanthine phosphoribosyl transferase, adenine phosphoribosyl transferase and phosphoribosylpyrophosphate synthetase were observed in Rett children compared with age-matched controls, while the production rate of IMP from hypoxanthine and of total pyridine nucleotides from nicotinic acid by intact erythrocytes was significantly increased. No significant difference was found in any of the other parameters examined. These findings give a new contribution to the knowledge of the biochemical alterations in Rett syndrome and encourage further investigations in the nucleotide field.

Adolescent↗
PubMed1993

Nicotinamide mononucleotide adenylyltransferase activity in human erythrocytes.

Nicotinamide mononucleotide adenylyltransferase (NMN-AT) activity has not hitherto been demonstrated in human red blood cells, owing to its low activity. Since it is usually located in the nucleus, the possibility of finding it in human erythrocytes was excluded. Here we report the first demonstration and characterization of NMN-AT in human red blood cells, by an HPLC method. The enzyme is Mg2+ dependent, with a Km of 0.303 mM for nicotinamide mononucleotide and 0.103 mM for ATP, and a Vmax of 346 nmol g Hb-1 h-1. The crude preparation is also active on nicotinic acid mononucleotide, producing nicotinic acid adenine dinucleotide. NMN-AT activity is inhibited by nicotinic acid mononucleotide, and nicotinic acid adenylyltransferase is inhibited by nicotinamide mononucleotide. Fiftyfold purification of NMN-AT was achieved by DEAE-Toyopearl chromatography, and the kinetic characteristics were determined. The partially purified preparation maintained its nicotinic acid adenylyltransferase activity. These findings are discussed in light of the regulation of NAD metabolism in human red blood cells.

Adenosine Triphosphate↗
PubMed1990

Importance of nicotinamide as an NAD precursor in the human erythrocyte.

The effect of variation in the concentration of inorganic phosphate and of the pyridine precursors nicotinamide (NAm) and nicotinic acid (NA) on pyridine nucleotide synthesis was studied using intact human erythrocytes. A wide range of incubation times was employed. The results showed that under physiological conditions the rate of synthesis of NAD from NAm exceeded that from NA twofold, while the reverse situation pertained at higher and unphysiological substrate levels. The two pathways had different regulation points. For NAm the rate-limiting factor was the initial step, namely its conversion into the mononucleotide, while for NA it lay at the second step, conversion of NA mononucleotide (NAMN) to its adenine dinucleotide. At physiological substrate levels the uptake of NA and conversion to NAMN were rapid, while the uptake and conversion of NAm were time dependent. This process was stimulated significantly by inorganic phosphate only for NAm. These results indicate that while NA is the predominant precursor of human erythrocyte NAD at high (unphysiological) substrate and phosphate levels, NAm is more efficient as an NAD precursor under physiological conditions, suggesting an important and hitherto unrecognized role for nicotinamide in NAD synthesis in vivo.

Adenosine Diphosphate↗
PubMed1990

Further insight into NAD synthesis in human erythrocytes: significance and relevance.

The cellular levels of NAD and its rate of synthesis from nicotinic acid (NA) were found to decrease from reticulocyte-rich fractions to mature erythrocytes separated on a density gradient. Decreased activity of NA-phosphoribosyltransferase in crude lysates was also observed from young to mature cells, while the uptake of extracellular NA did not show any difference. Impaired NAD synthesis, more likely than progressive breakdown, is suggested to cause NAD decrease during erythrocyte maturation.

Cell Survival↗
PubMed1987

Nucleotide synthesis in human erythrocyte: correlations between purines and pyridines.

The regulation of erythrocyte synthesis of nicotinate and adenine nucleotides has been investigated. Some effectors of the two committed enzymes, nicotinate- and adenine phosphoribosyltransferases, have been identified on crude lysates and on partially purified preparations of the former. Enzyme characteristics have been correlated with the nucleotide synthesis achieved in intact cells incubated in suitable mediums containing (14-C)-nicotinate or adenine. Inorganic phosphate, Mg ions and adenine nucleotides proved to be important effectors of pyridine synthesis, whose products, in turn, do not influence adenine nucleotide production. The production of pyridine nucleotides is little lower than that of adenine nucleotides in intact cells, even if adenine phosphoribosyl-transferase activity appears to be much more limited, inside the cell, than nicotinate phosphoribosyltransferase.

Adenine Nucleotides↗
PubMed1986

Purine and pyridine nucleotide production in human erythrocytes.

Human erythrocyte adenyl and pyridine nucleotide production has been tested in cell-free lysates and in intact cells. The main products obtained in cells incubated with adenine and nicotinic acid are adenosine triphosphate and nicotinate mononucleotide, respectively, under any experimental condition used (incubation time, base concentration). Adenine-phosphoribosyltransferase activity determined in crude lysates is about 100 times higher than nicotinate-phosphoribosyltransferase activity, while cellular adenyl nucleotide production is only three times higher than that of pyridine nucleotide. A strong intracellular regulation for the former, but not latter, synthetic process is thus suggested. Intact erythrocyte nicotinate nucleotide production is inhibited by adenine, while nicotinate-phosphoribosyltransferase activity is not. The possible regulation by adenyl nucleotides is discussed in light of the modulating action of ATP on nicotinate-phosphoribosyltransferase activity. The kinetic characteristics of both adenine- and nicotinate-phosphoribosyltransferases, determined on crude lysates, are reported.

Adenine Nucleotides↗