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Biomedical subjects

S Boschi

Publications and source records attributed to S Boschi.

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

Hemodynamic and humoral effects of chronic antihypertensive treatment with fenquizone: importance of aldosterone response.

The effects of 1-year antihypertensive treatment with the diuretic fenquizone were evaluated in 16 patients with mild essential hypertension. During treatment with placebo, after 2, 4, 24, and 52 weeks of treatment we measured blood pressure, heart rate, forearm blood flow (FBF) and vascular resistance (FVR) at rest and after 10 minutes ischemia, and forearm venous distensibility. Subjects whose diastolic blood pressure after fenquizone was reduced at least 10% were classified as responders. On this basis, 56% of patients after 1 month and 68% after 1 year responded to fenquizone. Responders, in comparison to nonresponders, were characterized by a greater increase in FBF and a greater decrease in FVR. The reduction in diastolic blood pressure was significantly related to the fall in FVR whereas no correlation was found between blood pressure and venous compliance changes. Nonresponders had a PRA increase similar to that observed in responders but they showed a much greater increase in aldosterone, whose changes were inversely related to modifications of both FVR and blood pressure. Our results demonstrate that chronic therapy with fenquizone causes a reduction of FVR, and that nonresponders have an exaggerated rise in aldosterone. This observation further reinforces the hypothesis that factors influencing the secretion of aldosterone are important determinants of the antihypertensive mechanism of diuretics.

Adult↗
PubMed1990

Evidence for increased intracellular transport of m-sarcolysine (alkylating moiety) when combined with two amino acid analogs (PTT-119).

PTT-119 is an antineoplastic agent in which an alkylating moiety, m-sarcolysine, is linked to two amino acid analogs. Previous studies showed a higher "in vitro" cytotoxicity of PTT-119 when compared to free m-sarcolysine; the mechanisms of this enhanced activity are not completely understood. In this study we incubated peripheral blood cells from 8 chronic lymphocytic leukemia patients with both m-sarcolysine and equimolar concentrations of PTT-119, measuring the intracellular concentration of the alkylating moiety. We observed a significantly higher intracellular concentration of m-sarcolysine in cells incubated with the peptide-bound drug than with the free drug (58.3 +/- 39.6 versus 4.4 +/- 1.9 ng/10(6) cells; P = 0.013). This observation could explain the higher cytotoxic activity of PTT-119 and the lack of cross-resistance with melphalan.

Amino Acids↗
PubMed1990

Short-term plasma renin activity suppression by saline and release of a plasma endogenous Na/K ATPase inhibitor in essential hypertension.

The present study was conducted in 15 essential hypertensives to evaluate the modifications of plasma levels of an endogenous Na/K ATPase inhibitor, blood pressure, forearm hemodynamics and plasma renin activity (PRA) elicited by an intravenous saline infusion (0.9% NaCl at the mean rate of 0.22 mL/min/kg body weight for 2 h). The response to saline was determined in the whole hypertensive population as well as in two subgroups of patients classified according to their rate of PRA suppression in response to volume expansion by comparison with normotensive controls (Normal- and Low-suppressors: N-S, L-S). Over the whole group of hypertensive patients, NaCl load provoked an increase in Na/K ATPase inhibitory activity, measured by enzyme-coupled assay, which was linearly related to PRA decline (r = 0.73) and to the increase in mean blood pressure (r = 0.57). These effects were clearly enhanced by considering L-S patients alone. Urinary Na/K ratio after saline infusion was significantly higher in L-S as result of a lesser potassium excretion in this subgroup. Our results support the hypothesis that acute volume expansion with saline causes an increase in plasma levels of an endogenous sodium pump inhibitor with hemodynamic effects and whose release is related to the individual handling of infused fluids and to the degree of renin-angiotensin-aldosterone suppression.

Adult↗
PubMed1990

Alarm reaction and serum K+ in hypertensive patients.

The effect of serum K+ of the alarm reaction induced by the participation to an experimental noninvasive study was evaluated in 35 subjects with borderline hypertension and in 18 essential hypertensives. A group of 44 inpatients undergoing routine blood sampling served as a control. Serum K+, blood pressure and heart rate were measured before (casual) and after (baseline) 20 min of rest in the recumbent position. Baseline serum K+ values were significantly higher than casual values in patients participating to the experimental protocol while no change was observed in inpatients undergoing routine blood sampling. The increase in serum K+ induced by relaxation was significantly related to heart rate decrease (r = 0.73). After relaxation 75% of patients had an increase in serum K+ with a change greater than 10% in about 35% of patients. In a subgroup of patients who repeated the same test three times, the alarm reaction was still evident and not reproducible within each patient. These data suggest that when potassium levels are measured in outpatients undergoing diagnostic or experimental procedures falsely reduced levels can be found in a large proportion of subjects.

Adult↗
PubMed1990

[Determination of oxidative phenotype in a sample population and correlation with the pharmacokinetics of propafenone].

UNLABELLED: Propafenone, like other cardioactive drugs (metoprolol, propranolol, encainide) is submitted to oxidative metabolism, evaluable by assessment of debrisoquine oxidative capacity. Two phenotypes have been described: extensive and poor oxidizers, with interethnic differences in the prevalence of poor oxidizers. Aims of this study were: 1) to assess the oxidative phenotype in a sample of the Italian population and 2) to evaluate the relationships between oxidative capacity and propafenone pharmacokinetics or pharmacodynamics. The ratio between debrisoquine (D) and 4-hydroxy-debrisoquine (4-OH-D) in the urines after D administration (10 mg) was employed to characterize oxidative phenotype in 90 subjects (42 arrhythmia patients and 48 healthy volunteers). In 10 patients, extensive oxidizers of debrisoquine, we studied propafenone (P) and 5-hydroxy-propafenone (5-OH-P) kinetics after acute oral administration (450 mg) and chronic oral treatment (300 mg tid for 2 weeks), followed by wash out. RESULTS: 1) the prevalence of poor oxidizers (D/4-OH-D ratio greater than 12.6) in our population resulted to be 6.6%, like in other studies in Caucasians; 2) propafenone kinetics was strictly related to oxidative capacity since D/4-OH-D ratio strictly correlated with the ratio of P and 5-OH-P areas under curve in acute (r = 0.91) and in chronic administration (r = 0.90) and with P half-life in acute (r = 0.82) and in chronic administration (r = 0.82); 3) QRS widening both during chronic treatment and after acute administration correlated with oxidative capacity (r = -0.78 and -0.68 with D/4-OH-D ratio respectively) and with 5-OH-P areas under curve (r = 0.84 and 0.70 respectively); it did not correlate with P areas under curve. In conclusion both kinetics and electrophysiological effects of propafenone strictly correlate with oxidative capacity, even in extensive oxidizers. Thus even a small reduction in oxidative capacity may have relevant consequences during propafenone oral treatment.

Adult↗
PubMed1989

Tocainide and metoprolol: an efficacious therapeutic combination in the treatment of premature ventricular beats.

A double-blind crossover study was performed in 20 patients to verify the efficacy of tocainide plus metoprolol in patients with premature ventricular contractions (PVCs) class Lown greater than or equal to 2 (mean frequency greater than or equal to 30/h) judged as being "stable" by at least three basal 24-h Holter ECGs with PVC variation of less than +/- 25%. All 20 patients were submitted to a placebo period; and all were subsequently randomized to therapy with tocainide 1800 mg/day or metoprolol 200 mg/day for 15 days and then to tocainide 1800 mg + metoprolol 200 mg/day or tocainide 1200 mg + metoprolol 200 mg/day for 15 days, followed by a crossover of the two combination treatments. At steady state in every stage we controlled for plasma levels of the drugs, a 24-h Holter recording, and a 12-lead ECG. A modified Lown score was evaluated together with the Lown class. Tocainide (mean plasma level 3.3 +/- 0.7 micrograms/ml) was efficacious in 3 of 8 patients, the modified Lown score decreased from 63 +/- 32 (placebo period) to 42 +/- 27 (p less than 0.01) and Lown 4B arrhythmias were abolished in 3 of 4 patients. Metoprolol (mean plasma level 97.4 +/- 89.6 ng/ml) was efficacious in 2 of 10 patients; the modified Lown score and Lown classes did not change significantly. Administration of tocainide 1200 mg + metoprolol 200 mg obtained a positive response in 9 of 12 patients, the modified Lown score decreased significantly compared with placebo (from 53 +/- 31 to 32 +/- 30, p less than 0.01) and Lown 4B arrhythmias were abolished in 2 of 5 cases. Tocainide 1800 mg plus metoprolol 200 mg was scarcely tolerated owing to neurologic and gastroenteric side effects, and only three patients completed this stage with no better antiarrhythmic results compared to the lower dose. In conclusion, the combination of tocainide at 1200 mg and metoprolol 200 mg is well tolerated, efficacious in a high percentage of patients, and superior to single drug therapy in patients with stable PVCs.

Administration, Oral↗
PubMed1989

Peripheral hemodynamic and humoral effects of oral zofenopril calcium (SQ. 26,991) in patients with congestive heart failure.

In 14 patients with congestive heart failure (CHF) of various grade (NYHA class 2-4) the effects of zofenopril calcium (SQ 26,991) on blood pressure and forearm circulation were studied by venous occlusion plethysmography. Changes in plasma renin activity (PRA), aldosterone, Atrial natriuretic factor (ANF) and arginine-vasopressin (AVP) were also measured. Two hours after oral administration of 7.5 mg of zofenopril we observed a decrease in blood pressure, heart rate, and forearm vascular resistance along with an increase in venous distensibility. Zofenopril also decreased ANP levels in a manner directly related to peripheral venodilatation (r = .64; P less than .05) and modified arginine-vasopressin (AVP) proportionally to the fall in blood pressure observed in response to drug administration (%SBP/%AVP: r = .64, P less than .05; %DBP/%AVP: r = .67, P less than .05). Hemodynamic and humoral responses to zofenopril occurred without any significant unwanted adverse reaction, even in patients with greater pressor reduction. We conclude that oral acute zofenopril administration, in patients with congestive heart failure, causes an arterial and venous forearm vasodilatation which is probably involved in the acute changes in plasma levels of ANF and AVP observed after drug administration.

Administration, Oral↗
PubMed1989

Plasma concentrations of atrial natriuretic factor in normal pregnancy and early puerperium.

The atrial natriuretic factor (ANF) and parameters related to renal sodium handling and renal function were evaluated in 92 normotensive pregnant women at different gestational ages (1st group: 7th-13th week, 2nd group: 14th-20th week; 3rd group: 21st-27th week; 4th group: 28th-34th week; 5th group: greater than 34th week), in 15 normotensive non-pregnant women and in 15 normotensive women 6 days after spontaneous delivery at the end of a normal pregnancy. ANF did not differ significantly between the 5 groups of pregnant women while, concurrently with a further increase in plasma volume (as shown by our data) it was significantly higher in late pregnancy (3rd and 5th groups) than in the non-pregnant women. ANF in post-partum women was significantly higher than in non-pregnant and pregnant women. Only in post-partum women was ANF significantly directly related to sodium excretion. Even though ANF does not seem to play an important role in water and sodium excretion in pregnancy in comparison with other hormones such as progesterone, oestriol and aldosterone, the higher levels of ANF in late pregnancy probably represent a compensatory increase when a given threshold of plasma volume (and therefore of atrial stretch) is reached. However ANF does seem to play a more important role in the induction of diuresis and natriuresis in early puerperium.

Adult↗
PubMed1988

Erythrocyte Na-K-ATPase membrane activity in obese patients fed over a long-term period with a very-low-calorie diet.

In a search for the role of long-term hypocaloric feeding on the expression of the erythrocyte Na pump in obesity, we examined three groups of subjects. Group 1 consisted of 10 obese subjects who had been under treatment for a long period of time with a very-low-calorie diet (500 kcal/d) while group 2 consisted of 10 age-, sex-, and body mass index-matched obese subjects on their usual diet; in the third group, 12 normal-weight subjects on a free diet served as controls. There was no difference between the groups in the number of erythrocyte binding sites per cell. On the contrary, the Na-K-ATPase activity was significantly lower in the obese group 1 (0.35 +/- 0.09 mumol Pi x mg protein-1 x h-1) compared to that observed in the obese group 2 (0.42 +/- 0.07, P less than .05) and in control subjects (0.45 +/- 0.06, P less than .05). Sex, duration of hypocaloric feeding, and the amount of weight loss before the study in the obese group 1 seemed not to be related to the Na pump parameters. We conclude that long-term severe hypocaloric feeding may be a factor in altered erythrocyte Na-K-ATPase in obese individuals.

Adult↗
PubMed1988

Impaired vasodilator capacity and exaggerated pressor response to isometric exercise in subjects with family history of hypertension.

The nature of the cardiovascular response to isometric exercise is still debated. An adequate blood supply to exercising muscles at the onset of contraction seems to be an important factor controlling the extent of pressor response to isometric contraction. In comparison to normotensive subjects without familiar hypertensive history (F-), normotensive subjects with family history of hypertension (F+) have a reduced peripheral vasodilator capacity which impairs the possibility to adjust the muscular blood flow during exercise. An enhanced pressor response to handgrip test was observed in F+ and this hyperresponsivity was inversely related to the extent of forearm vasodilation capacity and largely prevented by the pretest increase of blood flow in exercising muscles. Our results suggest the importance of local vasodilating capacity as a determinant of reflex pressor response to isometric exercise.

Adult↗
PubMed1988

Importance of plasma renin activity suppression and venous distensibility on pressor and natriuretic responses to intravenous salt load in borderline hypertension.

Cardiopulmonary receptors influence renin release in a variety of physiological situations and in a fashion related to the degree of peripheral venous distensibility. We studied two groups of borderline hypertensives (BHTs) with different capacities to suppress plasma renin activity in response to saline infusion (0.20 mL/kg/per minute for 2 hours). Those BHTs with low suppressive capacity (L-supp) showed an increased venous distensibility in comparison with those with high suppressive capacity (H-supp). Saline infusion led to a significant increase in blood pressure only in L-supp BHTs, which was associated with enhanced 24-hour postloading natriuresis and raised plasma levels of an Na/K ATPase inhibitor (+12.2%). This result underlines the importance of venous distensibility as a determinant of pressor and humoral response to acute volume expansion.

Adenosine Triphosphatases↗
PubMed1988

Characterization of a Na+/K+-ATPase inhibitor from human plasma: preliminary data.

The role of an endogenous sodium pump inhibitor in the pathogenesis of hypertension has been reported in several papers. Unfortunately, because of the unknown structure and lack of biochemical characterization, some discrepancies have arisen. In this study we report a method to obtain extracts from human plasma that are able to inhibit Na+/K+-ATPase in vitro. Preliminary characterization was carried out, which showed that the extracts are able to inhibit Na+/K+-ATPase, pNPPase, and [3H]ouabain binding to red blood cells. The enzyme inhibition is not due to vanadate, FFA, or bivalent cations, and it seems to be reversible, dose-dependent, and largely prevented in E1 conformation of the enzyme. These results seem to support the hypothesis that human plasma contains a sodium pump inhibitor with many characteristics of a "ouabainlike" compound.

Blood Chemical Analysis↗
PubMed1988

Cellular ionic composition at the prehypertensive phase of essential hypertension.

This article reviews the data from literature regarding cell sodium and potassium content in young subjects at risk of developing essential hypertension (subjects with family history of hypertension or with borderline hypertension). The studies performed with red blood cells have produced conflicting results: approximately one-half of these studies have found an increase in intracellular Na+ in subjects with family history of hypertension (genetic normotensives) whereas the other studies found no difference. The reasons for these discrepancies are discussed. Studies with leukocytes gave more univocal results and the majority of these studies found an increase in intracellular Na+ in many genetic normotensives. These observations emphasize that it is possible to find a high intracellular Na+ in subjects with normal blood pressure. Longitudinal studies are need to clarify whether subjects with high Na+ are those who will develop hypertension. The data from our studies suggest that subjects with high Na+, even if they are normotensive, exhibit an exaggerated pressor response to mental and physical activities and that a reduction in dietary salt content produces a parallel decrease in intracellular sodium and in pressor reactivity. The data on borderline hypertension are even more scarce than those on genetic normotensives and the different classification criteria produce results which are frequently not comparable. Our studies showed that in borderline subjects not only intracellular Na+ can be increased, but also intracellular K+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Ciclosporin A: correlation of blood levels with acute graft-versus-host disease after bone marrow transplantation.

Thirty patients undergoing allogeneic bone marrow transplantation (BMT) for hematologic malignancies received ciclosporin A (CS-A) as prophylaxis of graft-versus-host disease (GVHD). CS-A trough levels were determined in whole blood by radioimmunoassay (RIA); results were not used to adjust the CS-A dosage. Neither the dose of CS-A administered nor the CS-A concentration and fluctuation of blood levels during the first 15 days after BMT correlated with acute GVHD. Conversely in the 13 patients with acute GVHD, CS-A concentrations in the 10 days prior to the onset of the disease were increasingly lower with increasing severity of GVHD. Moreover, patients without GVHD had higher CS-A concentrations in a matched period of time. Upon withdrawal of CS-A treatment, 7 patients developed GVHD. There was no possibility to predict who would do so, but the analysis of CS-A disappearance profiles indicates that effective CS-A concentrations might be lower during long-term treatment than the concentrations required early after transplant. Despite these relationships, CS-A concentration is of little predictive value in the individual patient because of the considerable overlap among patients.

Acute Disease↗