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Biomedical subjects

M Nazzari

Publications and source records attributed to M Nazzari.

At least 19 recordsLinked to original sources
PubMed1992

Hemodialysis with defibrotide: effects on coagulation parameters.

In a crossover study conducted with eight uremic patients maintained on hemodialysis, the Authors compared the effects of heparin (100 IU/kg at the start of dialysis) and defibrotide (400 mg at the start, repeated at 2 hours of ongoing dialysis) on the parameters of blood coagulation (VIII:C, AT III, TAT, PC antigen and activity, PS, and FPA), each being assessed before dialysis and at 2, 3 and 4 hours of the ongoing procedure. Heparin-assisted dialysis resulted in a significant rise of VIII:C and AT III; with defibrotide, instead, there was evidence of thrombin activation (increased FPA and TAT). PC levels were raised with both dialysis modalities; however, PC activity and PS levels were increased only in defibrotide-assisted dialysis. There were no adverse reactions or evidence of fibrin formation. These results confirm the antithrombotic activity of defibrotide in the course of dialysis and indicate that this action is independent of thrombin neutralization.

Antithrombin III↗
PubMed1992

Effect of sulglycotide treatment on cell kinetics alterations induced by aspirin in humans.

The effect on gastric epithelial cell proliferation of small doses of aspirin was evaluated in 9 healthy volunteers, with or without administration of sulglycotide, a sulfated glycopeptide with cytoprotective properties. Cell kinetics study was performed by incubation of gastric biopsies with bromodeoxyuridine (BrdU) and immunohistochemistry. A decrease of BrdU-labeling index and a shortening of the height of gastric columns were observed after treatment with aspirin and placebo. No variations were observed after treatment with aspirin and sulglycotide. A decrease of the epithelial cell renewal could be one of the damaging effects of aspirin on the gastric mucosa. The treatment with sulglycotide seems to be effective to prevent this alteration.

Adult↗
PubMed1991

[The prevention of deep venous thrombosis in patients undergoing an internal arteriovenous fistula intervention].

Twenty patients, submitted to internal arteriovenous fistula procedure, were randomly assigned to one of the following treatments: defibrotide 400 mg b.i.d. IM (starting the day before surgery and continuing for the following 7 days); calcium heparin 5,000 IU t.i.d. SC (since the day of surgery and for the following 7 days). No deep venous thrombosis or thrombosis of the fistula were noticed during both treatments and no side effects were observed. In the defibrotide group, ELT showed a significant decrease (-40%) attesting an improvement of fibrinolysis without a plasminogen abatement. These findings indicate that defibrotide represent an effective alternative to calcium heparin for antithrombotic prophylaxis of A-V fistula in uremic patients.

Arteriovenous Shunt, Surgical↗
PubMed1991

Deficient fibrinolytic response in patients with Raynaud's phenomenon and its correction with defibrotide.

Twenty outpatients presenting with Raynaud's phenomenon secondary to clinical or preclinical inflammation of connective tissue were treated orally with defibrotide 400 mg three times daily or a matching placebo in a randomized double-blind study. The test product defibrotide (a polydeoxyribonucleic acid compound of animal origin with demonstrated profibrinolytic activity when administered parenterally) was administered orally for 3 weeks in order to explore its effects on the parameters of extrinsic fibrinolysis before and after venous stasis. The antigen of t-PA and its inhibitor PAI, free and total, and the biologic activity of PAI were assayed in basal conditions and after treatment. Although a marked increase of t-PA was seen with the active treatment, PAI activity was significantly reduced by defibrotide. Immunoreactive PAI was not significantly modified by treatment, even though it dropped considerably after venous stasis in the defibrotide group. Thus, the disturbance of endothelial function that seems to occur in vasculitis and in Raynaud's phenomenon secondary to inflammation of connective tissue (or so suspected to be) would constitute the basis of a disturbance of fibrinolysis, which oral defibrotide seems able to correct. Further studies are warranted to define the clinical effectiveness of this treatment in patients with Raynaud's phenomenon.

Adult↗
PubMed1990

A multicenter double-blind study of sulglycotide versus sucralfate in nonulcer dyspepsia.

Nonulcer dyspepsia remains to this date a clinical disease entity that is diagnosed and treated empirically by considering such patients potential ulcer carriers and treating them accordingly with H2 antagonists. The purpose of this study was to assess the therapeutic effectiveness of sulglycotide in patients with nonulcer dyspepsia in a random double-blind trial vs sucralfate. One hundred and eighty-seven consecutive patients with nonulcer dyspepsia were treated with sulglycotide (oral, 200 mg t.i.d. for 6 weeks, n = 93) or with sucralfate (oral, 1 g t.i.d. for the same length of time, n = 94). Drug effectiveness was evaluated in terms of apparent clinical symptom modifications, fiberoptic endoscopy findings and histological aspects of biopsy specimens. Both treatments resulted in prompt abatement of the clinical complaints of nonulcer dyspepsia and the improvement of macroscopic gastritis at endoscopy. These results confirm the usefulness of cytoprotective drugs in nonulcer dyspepsia characterized by gastroduodenal inflammation.

Double-Blind Method↗
PubMed1990

Kinetics of anti-Xa activity during combined defibrotide-heparin administration in hemodialysis.

Defibrotide, a polydesoxyribonucleotide derivative with antithrombotic and fibrinolytic activity, capable of inducing the release of PGI2 from vascular endothelia, was proposed as an alternative to standard heparin coverage during blood dialysis for patients at risk of bleeding. The original procedure featured the preliminary washing of the dialysis circuit with heparin, which was then recirculated and eliminated, and the two drugs, heparin and defibrotide, are known to interact with each other. The purpose of this present study was to explore the ex-vivo heparin activity (assessed as anti-Xa activity) in diverse hemodialysis models using defibrotide (800 mg intravenous, in 4 bolus injections) and various dosages of heparin. Anti-Xa activity is negligible in dialysis conducted with defibrotide alone. When the circuit was prewashed with heparin (5000 and 2500 IU), there was evident anti-Xa activity (0.3-0.5 U/ml) in the first 30-60 minutes of dialysis; continuous heparin infusion (500 U/hour) resulted in high anti-Xa activity levels at the end of dialysis. Thus the best hemodialysis procedure for patients at high risk of bleeding should be one utilizing only defibrotide, or defibrotide plus small amounts of calcium heparin infused at the rate of 500 U/hour for not more than two hours.

Drug Interactions↗
PubMed1989

[A multicenter study of defibrotide in the prevention of deep venous thrombosis. Final results].

In an open multicenter comparative study aimed at the evaluation of the efficacy of defibrotide and calcium heparin in the prophylaxis of postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE) an evaluation has been made on 4810 patients. 2810 patients received defibrotide (800 mg/die: 400 mg b.i.d. or 200 mg q.i.d. by IV route); 2000 patients received calcium heparin (500 IU b.i.d. or t.i.d. by SC route) till the 7th post-operative day. The diagnosis of DVT or pulmonary embolism (PE) was made according to clinical routine criteria. The incidence of DVT has been 33/2810 (1.17%) in the defibrotide group and 47/2000 (2.35%) in the heparin group (chi 2 p = 0.002), while the cases of suspected or ascertained PE have been respectively 15/2810 (0.53%) and 23/2000 (1.15%) (p = 0.025). The post-operative course was totally normal in both groups; no significant adverse reactions were noticed. The obtained results suggest the effectiveness of defibrotide as an alternative to heparin in the prevention of post-operative DVT.

Adult↗
PubMed1988

Lack of effect of a single-dose of sulglicotide on the bioavailability of diclofenac.

The bioavailability of diclofenac (D) was assessed in 12 healthy volunteers treated orally with single doses of 100 mg (retard formulation) and subsequently retreated with the same dose of (D) plus sulglicotide (S) 200 mg. (D) blood levels were measured by GLC in samples collected after 1, 2, 4, 6, 8, 12, 24 h. No relevant difference was seen in (D) bioavailability after (S) administration; after 8 h plasma levels of (D) were slightly higher after (S) (p less than 0.05), but this difference can be considered incidental only. Thus, sulglicotide does not interfere with the bioavailability of diclofenac, and can be administered concurrently with the latter to prevent possible gastric injury by the antiinflammatory drug.

Adult↗
PubMed1988

[Defibrotide in the prevention of deep venous thrombosis in general surgery. Preliminary results of a multicenter study].

In an open multicenter comparative study aimed at the evaluation of the efficacy of defibrotide in the prophylaxis of postsurgical deep vein thromboses (DVT) an ad interim evaluation has been made on 2626 patients thus far enrolled. 1323 had received defibrotide (200 mg q.i.d. by IV route from day -1 to day +7th postoperative), 941 calcium heparin (5000 IU b.i.d. or t.i.d. by SC route from day 0 to day +7 postoperative) and 362 other treatments (antiaggregating agents, placebo or no therapy). This group has not been included in the final evaluation, due to its limited size. The diagnosis of DVT or pulmonary embolism (PE) was made according to clinical routinary criteria. The incidence of DTV has been 15/1323 (1.13%) in the defibrotide group and 21/941 (2.23%) in the heparin group (chi-square, p = 0.056) while the cases of suspected or ascertained PE have been respectively 3/1323 (0.22%) and 10/941 (1.06%) (p = 0.02). The incidence of adverse effects with defibrotide was less than 1%; occasional cases of increased serum transaminase levels were seen with heparin. These preliminary results supports the effectiveness of defibrotide in the prevention of post-surgery DVT, its effects being similar or more prominent than those of calcium heparin, currently regarded as the standard medication.

Adult↗
PubMed1988

A pilot evaluation of the effect of defibrotide in patients affected by peripheral arterial occlusive disease.

This was a random double-blind study versus placebo designed to assess the effectiveness and tolerability of defibrotide in patients with chronic peripheral vascular disease (PVD), Leriche stage II. A total of 20 male outpatients (mean age 58.8 years) were selected and treated with placebo for 2 weeks (run-in period), and then allocated randomly to treatment with defibrotide (200 mg/day, intramuscular, n = 10) or matched placebo (n = 10) for 90 days. Before intake and at 15, 30, 60, and 90 days of treatment, each patient received a Doppler ultrasound examination of the lower limbs, and the residual perfusion index (Winsor) was calculated at rest and immediately after a symptom-limited treadmill test. Absolute walking distance was measured in addition. Blood samples were taken for routine laboratory tests before intake and at 30 and 90 days of treatment. All patients completed the trial without adverse effects; no meaningful alterations of laboratory test returns were detected. Patients receiving defibrotide showed a significant increase of the Winsor index after exercise at 90 days versus basal (mean 0.47 +/- 0.04 vs. 0.43 +/- 0.05, p less than 0.05), and a parallel increase of walking distance (basal 288 +/- 42.3 m vs. 368 +/- 46.6 at 60 days, p less than 0.05, and 407 +/- 64.3 m at 90 days, p less than 0.01). No improvement was seen in the placebo group. These preliminary results suggest that defibrotide may prove beneficial to patients with PVD; further studies are needed to find the most appropriate dosage regime.

Arterial Occlusive Diseases↗
PubMed1988

Lack of influence of sulglycotide on naproxen bioavailability in healthy volunteers.

We explored the bioavailability and kinetics of naproxen (N) in 12 healthy volunteers treated orally with single doses of 500 mg and retreated after a washout period with the same dose of N plus sulglycotide (S) 200 mg. Naproxen blood levels were measured by high-performance liquid chromatography (HPLC) in samples collected at 0.5, 1, 2, 4, 8, 12, and 24 h of dosing with N or with N + S. No statistically significant difference in terms of naproxen blood levels emerged as the product was administered alone or concurrently with sulglycotide. Peak plasma concentrations and AUC values were 71 +/- 3.16 micrograms/ml and 685 +/- 27 micrograms/ml/h, respectively for N alone, and 72.5 +/- 2.85 micrograms/ml and 651 +/- 28 micrograms/ml/h, respectively for N + S. The difference was not significant. Similarly, the kinetic behavior of naproxen was not modified by the simultaneous presence of sulglycotide, as shown by the t1/2 beta-values obtained with N alone (8.39 +/- 0.31 h) and with N + S (7.93 +/- 0.30 h), and likewise by the distribution volumes at equilibrium (7.63 +/- 0.42 and 7.9 +/- 0.38, respectively), Cmax (63.3 +/- 2.86 and 60.4 +/- 2.9 micrograms/ml, respectively) and tmax (0.95 +/- 0.06 and 1.10 +/- 0.10 h, respectively). From these findings it seems legitimate to claim that sulglycotide can be administered concurrently with naproxen to prevent possible gastric injury by the anti-inflammatory agent thanks to its wellknown antiulcer and cytoprotective activity on the gastric mucosa, without any undue interference with the absorption (hence effectiveness) of naproxen.

Adult↗
PubMed1987

[Prevention of deep venous thrombosis with defibrotide in chest surgery. Controlled multicenter study versus heparin].

The effectiveness and tolerability of defibrotide in the prevention of post-surgery deep vein thrombosis (DVT) were compared with those of heparin in a multicentric randomized controlled study. One hundred-eight-four both sexes patients submitted to thoracic surgery were randomly allocated to defibrotide (400 mg b.i.d. by IV route, n = 94) or to calcium heparin (5000 I.U. t.i.d. s.c., n = 90); both treatments were started the day before the operation and withdrawn when patients were allowed to stand up (i.e., after 7 days). No patients developed DVT in the defibrotide group, while a single case of DVT was detected in the heparin group; furthermore, a more prominent bleeding was observed in the latter, in the early post-operative period (normal bleeding: 2nd day: defibrotide 70/92 pts, heparin 53/90 pts, p less than 0.02; 3rd day: defibrotide 87/92 pts, heparin 76/90 pts, p less than 0.05, chi 2 test), while the healing rate of surgical wounds was similar in the two groups. No relevant modifications in laboratory parameters were seen throughout the observation period. Thus, these preliminary data suggest that defibrotide is at least as effective as heparin in the prevention of post-thoracic surgery DVT and that the former drug has a possibly better tolerability profile, due to a lesser tendency to bleeding.

Adult↗
PubMed1987

Double-blind comparison of once-daily bopindolol and atenolol for mild-to-moderate hypertension.

In order to compare the medium term antihypertensive effectiveness and tolerability of atenolol with those of bopindolol (LT 31-200), a new non-selective beta-blocker with slight PAA (partial agonist activity), a randomized double-blind study was performed. Thirty-one outpatients with mild-to-moderate essential hypertension (WHO stage I-II) were enrolled and after a placebo run-in randomly allocated to bopindolol (1 to 4 mg/day) or atenolol (50 to 200 mg/day). The dose was titrated according to the individual pressor responses, and thereafter it was kept constant until the end of the treatment (12 weeks). Both drugs induced statistically significant decreases in SBP, DBP and HR, both in resting conditions and during an ergometric test. Accordingly, most patients achieved the main goal of the therapy, i.e., supDBP less than or equal to 90 mmHg, 11/15 (74%) with bopindolol versus 8/13 (62%) with atenolol. There were no significant differences between the effects of the two compounds. Resting airway resistance (expressed as Peak Expiratory Flow) was not influenced by the treatments. The antihypertensive efficacy was still evident after 12 months in 8 patients who were evaluated for non-comparative long-term effectiveness of bopindolol monotherapy, and improvements in plasma lipid profiles were also observed. Side effects were relatively mild and transient, with two patients in the atenolol group discontinuing therapy (one for inefficacy and one because of undesirable reactions) and one dropped out in the bopindolol group (late evidence of not fulfilling inclusion criteria).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

Humoral and hemodynamic effects of nitrendipine versus clonidine in patients with essential hypertension.

A single-blind, randomized controlled study was conducted to assess and compare the antihypertensive effectiveness and the effects on glucose tolerance and renin-angiotensin-aldosterone balance of nitrendipine (Bay e 5009), a new dihydropyridine calcium antagonist, and clonidine. Twenty-six outpatients with uncomplicated mild to moderate essential hypertension were randomly allocated to receive 20 mg of nitrendipine or 0.25 mg of clonidine (slow-release formulation) daily for five weeks. One patient in the clonidine group dropped out. Both treatments significantly reduced systolic and diastolic blood pressures with negligible modifications in heart rate. However, diastolic blood pressure was reduced significantly more (P less than 0.001) with nitrendipine. Accordingly, 12 of 13 patients given nitrendipine attained the goal of diastolic pressure less than or equal to 90 mmHg, according to criteria of the Hypertension Detection and Follow-up Program, while only three of 12 patients in the clonidine group achieved this goal. Side effects were mild and transient in both treatment groups. No definite trends in plasma renin activity or plasma aldosterone concentration, or in blood glucose or immunoreactive insulin (measured both in fasting conditions and after an oral glucose tolerance test), were evident when baseline and posttreatment values were compared. The results of this study suggest that nitrendipine is an effective and safe antihypertensive agent and is devoid of adverse effects on glucose tolerance and renin-aldosterone homeostasis.

Blood Glucose↗