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Biomedical subjects

T Di Perri

Publications and source records attributed to T Di Perri.

At least 37 records · Page 2Linked to original sources
PubMed1995

QTc interval prolongation during infusion with dipyridamole or adenosine.

The aim of our study was to discover whether there was a relationship between the QTc interval prolongation on the standard 12-lead electrocardiogram (ECG) and provoked myocardial ischemia. Since the increase of adenosine plasma levels, obtained either with adenosine or dipyridamole (an adenosine reuptake inhibitor) infusion, has been used to test the coronary artery reserve in patients affected by coronary artery disease, the QTc interval modifications during dipyridamole or adenosine echocardiographic stress test were evaluated. Twenty-five patients admitted to our Institute for evaluation of chest pain of suspected myocardial origin underwent an echocardiographic dipyridamole stress test (0.84 mg/kg over 10 min) after discontinuation of antianginal treatment. Of these patients, 10 underwent an echocardiographic adenosine stress test (scalar doses of 50, 75, 100, 140 micrograms/kg/min) after 48-72 h. The Bazett formula was used to evaluate the QTc interval. After dipyridamole and adenosine administration, a significant prolongation of the QTc interval was observed only in those patients who had positive test results. Our data suggested that QTc interval prolongation during pharmacological stress tests might be considered a marker of myocardial ischemia.

Adenosine↗
PubMed1995

Pharmacokinetics and pharmacodynamics of neutrophil-associated ciprofloxacin in humans.

OBJECTIVE: To study the possibility that the penetration of the antibiotic ciprofloxacin into polymorphonuclear leukocytes (PMN) may be associated with some changes in cell reactivity. DESIGN: Superoxide anion and chemiluminescence generation induced by formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) were studied ex vivo in 12 healthy volunteers (mean age, 53.15 +/- 16.3 years; mean body weight, 71.23 +/- 6.9 kg) at fixed intervals up to 72 hours from the administration of a single oral dose of 250 mg ciprofloxacin. Cytosolic free calcium levels ([Ca2+]i) in resting and stimulated cells were also evaluated. The dynamic parameters of the effects on PMNs were compared with the kinetic profile of the drug in plasma and in PMNs. RESULTS: Superoxide generation induced by the stimulating agents increased significantly, reaching a peak after 12 hours (+116% [p < 0.001] for fMLP and +66% [p < 0.05] for PAF). Similarly, chemiluminescence production showed a threefold increase in the response to the stimulating agents 12 hours after drug administration (p < 0.001). The increase in [Ca2+]i in stimulated PMNs was significantly potentiated (p < 0.001). The mathematic analysis of the effects of ciprofloxacin showed that time to maximal activity was between 10.4 hours (PAF-dependent [Ca2+]i increase), and 15 hours (fMLP-induced superoxide anion and chemiluminescence production). The ratio of PMNs to plasma ciprofloxacin concentration increased progressively, from 0.5 at 30 minutes to 10.4 after 24 hours. In addition, time to maximal activity and half-life differed in PMNs and in plasma (4.66 versus 1.90 hours and 13.03 versus 7.28 hours, respectively). CONCLUSIONS: Ciprofloxacin administration induced a long-lasting enhancement of PMN reactivity to fMLP and PAF. The levels of the drug in the cells were greater and more sustained in the time than those in plasma.

Adult↗
PubMed1995

Increase in plasma levels of adenosine and adenine nucleotides after intravenous infusion of buflomedil in humans.

To clarify the mode of action of the vasoactive agent buflomedil, we evaluated plasma levels of adenosine and adenine nucleotides after intravenous (i.v.) infusion in humans of 50, 100, and 200 mg of the drug in 20 min. Buflomedil induced an increase of the same order of magnitude in plasma levels of adenosine and adenine nucleotides. Maximal adenosine increase (84%) was observed at the end of the infusion period, whereas peak plasma levels of ATP and ADP (69 and 55%, respectively) and of AMP (61%) were detected 10 and 5 min after discontinuation of infusion, respectively. Although the exact mode of action of buflomedil at the molecular level remains unclear, some indirect findings suggest that the increase in adenosine may be due to enhanced release rather than to inhibition of cell uptake. Because such activity of buflomedil consists of enhancement of physiologic mechanisms of vasodilation and tissue protection occurring in the course of ischemic events, new pharmacologic perspectives for the drug may arise.

Adenine Nucleotides↗
PubMed1995

An equivalence study of the safety and efficacy of a fixed-dose combination of perindopril with indapamide versus fixed-dose combinations of captopril with hydrochlorothiazide and enalapril with hydrochlorothiazide in the treatment of hypertension.

OBJECTIVE: The aim of this multicenter, randomly allocated, double-blind, parallel-group study was to evaluate the equivalence of three fixed-dose combination drugs in mild to moderate hypertension: perindopril + indapamide (4 + 1.25 mg), captopril + hydrochlorothiazide (50 + 25 mg) and enalapril + hydrochlorothiazide (20 + 12.5 mg). PATIENTS AND METHODS: After a single-blind, 4-week, placebo run-in phase, 527 patients (mean +/- SD age 54.5 +/- 1.2 years) with a supine diastolic blood pressure of 101.2-101.7 mmHg were randomly assigned to one of the three treatments for 8 weeks. The main evaluation criteria were diastolic blood pressure and serum potassium concentration. Equivalence was assessed on an intention-to-treat basis, using Schuirmann's method, which involves performing two one-tailed statistical tests on the data. Thirty-five patients were withdrawn from the study but there were no differences between groups in the reasons for withdrawal. RESULTS: Diastolic blood pressure decreased by between 13.1 and 14.2 mmHg in the three groups. The 90% confidence intervals for the differences between perindopril + indapamide and the other treatments were -1.1, +1.7 mmHg for captopril + hydrochlorothiazide and -0.4, +2.6 mmHg for enalapril + hydrochlorothiazide. Schuirmann's test was highly statistically significant (P<0.001 for perindopril + indapamide versus captopril + hydrochlorothiazide; P<0.002 for perindopril + indapamide versus enalapril + hydrochlorothiazide), so that the two one-sided hypotheses that the treatments were not equivalent were rejected at the nominal level of alpha = 0.05. Similarly, the safety of the treatments was equivalent in terms of serum potassium. The 90% confidence intervals of the differences between perindopril + indapamide and the other treatments were -8.7, -1.6% for captopril + hydrochlorothiazide (P = 0.004) and -1.5, +2.7% for enalapril + hydrochlorothiazide (P<0.001). CONCLUSIONS: We conclude that the safety and efficacy of perindopril + indapamide, captopril + hydrochlorothiazide and enalapril + hydrochlorothiazide were equivalent after 8 weeks of treatment in patients with mild to moderate hypertension.

Adolescent↗
PubMed1994

Calcium infusion induces myocardial ischaemia in patients with coronary artery disease by a mechanism possibly adenosine mediated.

In the first part of the study five healthy volunteers were submitted to i.v. infusion of 0.2 mM.kg-1 b.w. of calcium gluconate over 20 min. Total calcium (atomic absorption method), ionized calcium (ion-selective electrode method) and adenosine (HPLC technique) were measured at the following times: 0 (basal), 5, 10, 15, 20 (end of infusion), 25, 30, 35, and 50 min. The increase in total and ionized calcium serum levels was associated with a significant increase in adenosine plasma levels (from 207 +/- 41 to 362 +/- 63 nM.l-1, P < 0.001). Since the increase in adenosine plasma levels, obtained either with adenosine or dipyridamole (an adenosine reuptake inhibitor), has been used to test the coronary reserve in coronary artery disease (CAD) patients, in the second part of the study we compared the effects of calcium infusion with dipyridamole in 15 subjects. Pharmacological stress tests were evaluated by monitoring two-dimensional echocardiography and ECG. Ten patients had positive results with both the dipyridamole stress test and the calcium infusion. Our results show that calcium infusion induces an increase in adenosine plasma levels that can elicit a dipyridamole-like coronary steal, thus suggesting the central role of extracellular adenosine in myocardial ischaemia.

Adenosine↗
PubMed1993

Pharmacokinetics of exogenous adenosine in man after infusion.

The plasma kinetics of adenosine was investigated in healthy volunteers after a 1 minute infusion of 2.5, 5 and 10 mg (38.79 and 148 micrograms.kg-1 respectively) and after infusion of 200 micrograms.kg-1 in 10 min followed by 400 micrograms.kg-1 in 10 min. As the dose in the 1 min infusion study was increased the mean CL of adenosine decreased (10.7, 4.70 and 4.14 l.min-1, respectively), its mean half-life increased (0.91, 1.24 and 1.86 min, respectively), and the mean volume of distribution did not show any clear trend (8-13 l). After the 20 minute infusion the plasma level of adenosine reached a peak value comparable to that observed after infusion of 5 mg in 1 min (about 0.5 micrograms.ml-1), but the mean clearance and half-life were significantly different (12.1 l.min-1 and 0.63 min respectively). In all the subjects the plasma concentration of adenosine had returned to the baseline value in 5-15 min after the end of the infusion.

Adenosine↗
PubMed1993

A simple computational approach to model parameter estimation.

The desire to describe biological data using mathematical models has led to the rapid development of various analytical techniques for model identification and parameter estimation. The procedures used may be non-linear and complex, and require long calculation periods. Thus, the aid of a personal computer renders efficient the application of these rather complicated procedures. In this study we developed a simple identification programme for heparan sulfate pharmacodynamics which can be easily and rapidly implemented on a personal computer. The programme is based on an iterative algorithm performing a non-linear regression analysis by the least-square method. This programme was applied to a clinical measured variables with which it was possible to quantify the pharmacodynamic effect of heparan sulfate.

Aged↗
PubMed1993

Inhibition of neutrophil function in vitro by heparan sulfate.

The profibrinolytic and antithrombotic glycosaminoglycan heparan sulfate (HS) was tested in vitro on some neutrophil functions induced by several stimuli. HS 1-500 micrograms/ml was able to significantly inhibit, in a dose-dependent fashion, superoxide anion generation, lysozyme and beta-glucuronidase release from neutrophils stimulated with the formylated oligopeptide fMLP, the ionophore A23187, and Platelet Activating Factor. Such an effect could represent an additional therapeutical benefit in those pathological conditions in which neutrophil activation contributes to tissue injury and vascular damage.

Amino Acid Sequence↗
PubMed1993

Pharmacokinetics and pharmacodynamics of dermatan sulfate after intravenous and intramuscular administration to healthy volunteers.

The pharmacokinetics and pharmacodynamics of dermatan sulfate (DS) was investigated in healthy volunteers (two groups, namely group A: 6 subjects, group B: 8 subjects). The subjects of group A received 100 mg of DS both i.v. and i.m. and the subjects of group B received 400 mg of DS both i.v. and i.m. in two different days. The resulting anticoagulant activities were assessed by the activated partial thromboplastin time (aPTT) and the pharmacokinetic parameters were calculated from the plasma concentrations of DS measured by a chromogenic assay. The plasma concentrations of DS were fitted by linear and non-linear elimination models (i.e. assuming that the drug elimination follows Michaelis-Menten kinetics). Some evidence of non-linear kinetics was given by the observation that the mean terminal half-life and clearance estimated by the linear model were not independent of the i.v. dose (0.83 +/- 0.1 and 1.74 +/- 0.21 hours and 4.94 +/- 0.64 and 2.67 +/- 0.27 l/h after 100 and 400 mg i.v. respectively. Moreover the mean half-lives estimated after i.m. administrations were much higher than the values estimated after the i.v. dose (2.03 +/- 0.74 and 3.54 +/- 1.3 hours after 100 and 400 mg) and linear models failed to fit simultaneously the DS plasma concentrations after both the administration routes. Using the linear model, the mean drug bioavailability after i.m. administration was estimated to be about 30% and 80% after the 100- and the 400-mg dose respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Action of 2-acetoxy-trifluoromethylbenzoic acid (Triflusal) on platelet function after repeated oral administration in man: a pharmacological clinical study.

The efficacy and safety of Triflusal capsules given to patients at thrombogenetic risk because of platelet hyperaggregation were investigated in a controlled study involving 15 patients (9 males and 6 females, mean age 65.7 years) who were given 300 mg/day of Triflusal during the first 5 days and 600 mg/day during the following 5 days. Subsequently, after 7 days of wash-out all these patients received placebo for 10 days, one capsule for the first 5 days and 2 capsules for the following 5 days. The platelet antiaggregant activity of the drug was evaluated by means of Born's platelet activation test. Specific tests were also made to assess the effect of this substance on platelet release and the coagulation system. The safety was evaluated by measuring the most important clinical chemistry and clinical haematology indexes of haematopoietic, hepatic, renal and metabolic functions. Arterial blood pressure and heart rate values were also recorded. All the 15 patients completed the study. It was found that the Triflusal treatment led to a significant mean reduction of the indexes chosen as markers of thrombophilia or platelet hyperaggregation in vivo. It did not affect the normal haemostatic-coagulation process and was well tolerated by the patients. The subsequent placebo treatment did not induce any platelet antiaggregant effects.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Inhibition of neutrophil function in vitro by nimesulide. Preliminary evidence of an adenosine-mediated mechanism.

Nimesulide (CAS 51803-78-2) is a methane sulphoanilide derivative provided with specific anti-inflammatory activity. In human polymorphonuclear leucocytes (PMNs), the activity of nimesulide has been suggested to be based on the inhibition of the oxidative burst. However, the effect of the compound on PMNs function seems to be very complex. In order to give a major insight into the mechanism of action of nimesulide, the effect of the drug was studied in vitro on human PMNs functions, such as free radical generation and enzyme release, and on cytosolic free calcium levels, following the activation with specific stimuli. Moreover, the hypothesis that nimesulide could act by interfering with the adenosine cell receptor system was also evaluated. Nimesulide (1-50 mumol/l showed a dose-dependent inhibitory activity on superoxide anion and chemiluminescence production from PMNs stimulated with the oligopeptide fMLP, the ionophore A23187, and the phorbol ester PMA. Enzyme release was significantly reduced, when fMLP and A23187 represented the stimulating agents, while no effect at all was observed with PMA. Studies with the fluorescent calcium chelating dye FURA 2/AM showed that nimesulide was able to reduce free cytosolic calcium increase produced by fMLP and the ionophore ionomycin. The preincubation of cells with the specific adenosine receptor antagonist theophylline was able to significantly reverse the inhibitory activity of nimesulide, either on free radical production and enzyme release, and on free cytosolic calcium increase sustained by fMLP and the ionophores.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1992

Pharmacodynamics of salmon calcitonin in humans: new markers of pharmacological activity.

In order to define the pharmacodynamic profile of salmon calcitonin (sCT) in humans, several markers of the biological activity of the drug have been studied, namely cAMP, adenosine and pO2 in venous blood, and the cytosolic free calcium level in circulating cells. Different dosages and routes of administration (1.5 IU.kg-1 and 0.75 IU kg-1 IM, and 1.5 IU.kg-1 via nasal spray) were compared. sCT caused an increase in cAMP, adenosine and pO2, and a decrease in cytosolic free calcium in neutrophils, lymphocytes and platelets. The peak times of all these parameters ranged between 109 and 182 min, and 101 and 168 min after IM and nasal spray administration respectively. There was greater variability in the values after IM than nasal spray of administration of sCT. It is concluded that adenosine and pO2 in venous blood, and cytosolic free calcium in circulating cells are valuable markers of the activity of sCT and that sCT decreases the cytosolic free calcium level in neutrophils, lymphocytes and platelets. Pharmacodynamic analysis of the biological effects of the drug is highly reliable and valuable in predicting its pharmacological profile. sCT administration via a nasal spray is able to produce significant biological effects, although they are less marked than after IM dosing.

Adenosine↗
PubMed1992

Isradipine in the treatment of peripheral occlusive vascular disease of the lower limbs: a pilot study.

The long-term effects of isradipine on peripheral occlusive vascular disease of the lower limbs were investigated in 23 normotensive patients with stable Fontaine stage IIa disease and with an absolute pain-free interval (treadmill speed 4 km/h, no incline) of 300 - 700 m, and Doppler ankle - arm arterial pressure index of less than 0.80 in at least one leg. Using a double-blind, parallel-group design, patients received either 2.5 mg isradipine twice daily or placebo for 12 months. Both isradipine (n = 11) and placebo (n = 12) increased the absolute pain-free interval mean values; the increases were not significantly different. Similar trends were observed in the mean values for relative pain-free interval and ankle--arm arterial pressure index. In a subgroup of patients with a baseline absolute pain-free interval of greater than 500 m, isradipine (n = 6) significantly (P less than 0.001) increased both the absolute and the relative pain-free intervals and increased the ankle--arm arterial pressure index compared with placebo (n = 7). The favourable effects of long-term isradipine treatment suggest that isradipine could positively interfere with factors involved in the progression of atherosclerotic lesions or improve collateral vessel flow.

Antihypertensive Agents↗
PubMed1992

Effectiveness and tolerability of nimesulide in the treatment of osteoarthritic elderly patients.

One important point in the treatment of osteoarthritis is to control the pain that accompanies the persistent inflammatory conditions. Because of the chronic nature of the disease, drugs with a good ratio of effectiveness to tolerability must be used. In the following double-blind study the effects of nimesulide, a non-steroidal antiinflammatory drug, were compared with those of placebo in 40 elderly osteoarthritic patients, during and after a treatment cycle of 90 days with two 100-mg tablets a day. The reduction of spontaneous and motion-induced pain and of morning stiffness seen at the various check-ups attested the good effectiveness of nimesulide. Functional status as a whole was improved, and it was found that the concomitant weekly intake of an analgesic (paracetamol) treatment could be decreased during the 3 months of the study. The tolerability of nimesulide was good.

Aged↗