Search PubMed⌕ Search

Biomedical subjects

M Barbanti

Publications and source records attributed to M Barbanti.

At least 37 records · Page 2Linked to original sources
PubMed1996

A new series of 6-chloro-2,3-dihydro-4(1H)-quinazolinone derivatives as antiemetic and gastrointestinal motility enhancing agents.

New 6-chloro-2,3-dihydro-4(1H)-quinazolinones (24-27) have been synthesized and evaluated for gastrointestinal prokinetic and antiemetic activities in comparison with structurally related benzamides (21-22) and 6-chloro-2,3-dihydro-(1H)-1,3-benzoxazolin-4-ones (28). Their key pharmacophoric element has been defined as a 6-membered ring replacing the "virtual ring" arising from the hydrogen bond between amidic nitrogen and methoxy group in metoclopramide (1) and structurally related benzamides (2-10). Variations of heterocycle linking groups have pointed out that a lipophilic aromatic group in position 1 plays an important role for pharmacological properties, while the steric restriction and the modification of the side-chain nucleophilicity are uneffective both for the in vitro and in vivo activity. Some of these compounds very effectively enhance gut peristaltic activity in vitro (rabbit jejunum), increase gastric emptying of a semisolid meal (in rats), and inhibit cisplatin-induced emesis (in pigeons), favourably comparing with cisapride.

Animals↗
PubMed1995

Pharmacology of desmin (low molecular weight dermatan sulphate) in healthy volunteers following intravenous bolus administration of different dosages (200, 400, 800 mg).

Eight healthy volunteers (6 males, 2 females, mean age 31.6 yrs), were administered--on three separate days--200, 400 and 800 mg of a new low molecular weight Dermatan sulphate (Desmin), given as a single i.v. bolus (2 min.) injection. Before each administration and 10, 20, 30 min., 1, 2, 4, 8, 12, 24 hours after, blood samples were drawn and the following coagulative assays performed: aPTT (activated Partial Thromboplastin Time), TT (Thrombin Time), anti Xa (Xa Factor inhibition), Heptest, Stachrom D.S.. Furthermore, a kinetic analysis was performed on the activity curves calculated on the Heptest and Stachrom data. Plasma peak values and half lives of the parameters checked showed a clear dose-effect relationship. aPTT and TT showed very short-lasting variations and the inhibition of Factor Xa was moderate, but significant. The most evident and specific effects of Desmin were those on Heptest and Stachrom D.S.: both tests were influenced in a clear-cut and dose-dependent way, mainly as a consequence of the action of Desmin on HCII, with partially different kinetic patterns. A series of in vitro experiments proved an anti Xa effect of Desmin, mediated by antithrombin III, well above the possible interference of the small (< 1%) heparin contaminants in Desmin. An even more marked anti Xa activity was seen in the in vivo study, an observation so far unrecognized for this type of drug: some possible interpretations of this fact are discussed.

Adult↗
PubMed1995

Desmin 370, a low molecular weight dermatan sulfate, reduces the weight of preformed thrombi in rats made afibrinogenemic by ancrod.

Desmin 370 (D370), a low molecular weight dermatan sulfate, has been shown to induce a marked reduction of the weight of preformed venous thrombi in rats and rabbits by mechanisms that appeared largely independent of inhibition of thrombus accretion. In order to provide further support for such a mechanism, we exploited the defibrinating capacity of ancrod to obtain a thrombosis model characterized by the lack of thrombus growth and thus sensitive only to agents promoting thrombus lysis. Thrombus formation in anesthetized rats was induced by vena cava ligature. Injection of ancrod (5 U/kg) 5 h after induction of venous stasis caused a more than 95% reduction in plasma fibrinogen and prevented thrombus accretion as indicated by the lack of thrombus weight increase during the 3 h experimental period (12.2 +/- 0.6 vs 14.5 +/- 1 as compared to 12.6 +/- 0.6 vs 19.6 +/- 0.8, p < 0.01, in control rats) and by the almost complete (> 90%) inhibition of 125I-fibrin(ogen) binding to thrombi. Moreover, when ancrod was given 1 h before vena cava ligature, no thrombi were formed within 2 h whereas at the same time interval visible thrombi were present in all control rats. Administration of D370 (10 mg/kg) to thrombus bearing rats, 1 h after induction of afibrinogenemia, resulted in a significant reduction in thrombus weight (43% after 2 h, p < 0.01) which was only slightly lower than that recorded in normofibrinogenemic rats (54%). Enhancement of plasma fibrinolytic activity by ancrod had no influence on thrombus lysis and was not all affected by administration of D370.(ABSTRACT TRUNCATED AT 250 WORDS)

Ancrod↗
PubMed1994

The HLA class I-CML association revisited taking into account the two forms of gene fusion in the Philadelphia chromosome. A multicenter study.

CML patients possess either a b3-a2 or a b2-a2 fusion between the BCR and ABL genes. Depending on the type of fusion, two different series of non-self potentially immunogenic peptides may be produced. If they are presented by HLA class I molecules and recognized by cytotoxic CD8 lymphocytes, individuals could be more susceptible or resistant to leukemic cells bearing one or the other form of fusion according to their HLA class I phenotype. To test this point, the frequencies of HLA-A and HLA-B alleles were compared between b3-a2 and the b2-a2 CML patients. In essence, no difference was found whose significance could withstand correction for multiple comparisons.

Base Sequence↗
PubMed1993

Therapeutic effect of a low molecular weight dermatan sulphate (Desmin 370) in rat venous thrombosis--evidence for an anticoagulant-independent mechanism.

We evaluated the capacity of a low molecular weight dermatan sulphate (D370) to prevent thrombus formation and to induce a reduction of a stabilized thrombus in a rat venous thrombosis model. Injection of D370, 10 min before induction of venous stasis (prevention model), prevented thrombus formation in a dose-dependent way (ED50: 2.3 mg/kg). When given to rats 6 h after induction of venous stasis (therapeutic model), D370 caused a time- and dose-dependent reduction in thrombus size (60% to 70% reduction 2 h after injection of 10 mg/kg). At comparable antithrombotic dosages (i.e. minimum dose giving complete inhibition of thrombus formation), heparin (0.5 mg/kg) only caused 40% reduction of a preformed thrombus while hirudin (1 mg/kg) was virtually ineffective (less than 10% reduction in weight). All three compounds inhibited 125I-fibrin(ogen) deposition on 6-h aged thrombi by more than 85%, suggesting that D370 and, to a lesser extent, heparin reduce thrombus size via mechanisms other than inhibition of thrombus accretion. The involvement of a fibrinolysis-mediated mechanism in the D370-induced effect is suggested by the following. EACA (1 g/kg), when given to thrombus-bearing control animals, did not influence thrombus weight. However, when administered before D370 treatment, it prevented the expected reduction in thrombus weight by more than 80%, without influencing the effect of D370 on 125I-fibrin(ogen) accumulation onto preexisting thrombi. D370 injection caused neither an enhancement of fibrinolytic activity nor a reduction of PAI in plasma. In vitro, D370 (200 microns/ml) was unable to potentiate the spontaneous or PA-induced lysis of 125I-fibrinogen labelled blood, plasma, or purified fibrin clots.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

A quantitative cytochemical study on the pathogenesis of streptozotocin-induced epithelial tumors in rat kidney.

We investigated the development of early neoplastic lesions preceding the appearance of kidney epithelial tumors in rats treated with a single iv injection of 35 mg/kg of streptozotocin (STZ). Most of these lesions were associated with segments of atrophied and regenerative nephrons surrounded by a thick basal membrane that appear precociously in chronic progressive nephropathy. Cytochemical periodic acid-Schiff, Alcian blue, and colloidal iron reactions did not indicate an excessive storage of glycogen or acid mucopolysaccharides in early neoplastic lesions and tumors. Quantitative cytochemistry of mitochondrial succinate, alpha-glycerophosphate, and reduced nicotinamide adenine dinucleotide-dehydrogenases revealed a shift in metabolism toward glycolysis in atrophied and regenerative nephrons as well as in early neoplastic lesions and tumors. These correlative cytomorphological and cytochemical findings raise the possibility that changes associated with the initial stages of chronic progressive nephrosis may provide favorable conditions for the selective growth of STZ-initiated cells that generate focal collections of proliferating cells and then progress to tumor growth. Tumor prevalence was remarkably constant in animals sacrificed 33, 48, and 54 wk after treatment, suggesting that the prominent inflammatory and scarring reaction later developing in the course of progressive nephrosis might contribute to control the growth of STZ-induced cancer.

Adenoma↗
PubMed1993

Pharmacodynamic effects of single and repeated doses of oral sulodexide in healthy volunteers. A placebo-controlled study with an enteric-coated formulation.

Eight male and 8 female healthy volunteers, aged on average 32 +/- 6 years, underwent a randomized, crossover study, aimed at comparing the activity on some fibrinolysis and coagulation parameters of 100 and 200 mg/day of oral sulodexide, administered as enteric-coated tablets. After the single and the repeated (for 7 days) administration of the two daily dosages, the Fibrin Plates test, the Heptest, the Plasminogen Activator Inhibitor test (as to both activity and antigen level) and the activated Partial Thromboplastin Time were checked during the first 6 hours after administration. The pro-fibrinolytic and antithrombotic activity of sulodexide was confirmed to be significant with both dosage schemes and potentiated by repeated administrations. On the other hand, the absence of any influence on aPTT confirmed the lack of interference of the drug, after oral administration, on the intrinsic pathway of coagulation. No adverse reactions or events were observed.

Administration, Oral↗
PubMed1992

Antithrombotic and thrombolytic activity of sulodexide in rats.

We evaluated the ability of sulodexide, an extracted glycosaminoglycan, to prevent thrombus formation and to reduce a stabilized thrombus in a rat venous thrombosis model (vena cava ligature). Injection of sulodexide 10 min before induction of venous stasis, prevented thrombus formation in a dose-dependent manner (median effective dose 0.55 mg/kg). When given to rats with 6-h-old thrombi, sulodexide caused a marked reduction in thrombus size which reached 70% after 2 h with the highest dose tested (2 mg/kg). The effect of sulodexide on established thrombi appears to be due, at least in part, to a fibrinolysis-mediated mechanism, since it was significantly inhibited by epsilon-aminocaproic acid, a well-known antifibrinolytic drug. Treatment with sulodexide did not noticeably affect plasma levels of plasminogen activator and its specific inhibitor. We also showed that fluorescein-labelled sulodexide, when given to animals with 6-h-old thrombi, was present within the thrombi harvested 2 h later, but was then absent from blood. The fluorescence was mainly located in areas filled with amorphous material, that was identified as fibrin by staining with phosphotungstic acid-hematoxylin. No fluorescein-labelled material could be detected in rats treated with fluorescein alone. These findings indicate that, besides preventing venous thrombus formation, sulodexide is able to promote thrombus dissolution by a mechanism that is partly related to local fibrinolysis stimulation.

Animals↗
PubMed1990

Protein C deficiency in insulin-dependent diabetes: a hyperglycemia-related phenomenon.

In 30 insulin-dependent diabetic patients protein C (PC) antigen and PC activity were significantly lower than those of matched control healthy subjects. An inverse correlation between fasting plasma glucose and both PC concentration and activity was present in diabetics, while a direct correlation between PC concentration and PC activity was observed. Induced hyperglycemia in diabetic and normal subjects was able to decrease both PC antigen levels and PC activity, and heparin reversed in part this effect. In diabetic patients euglycemia obtained by insulin infusion restored to normal the depressed PC levels. Heparin did not alter both the basal PC concentration and activity in healthy controls. These data stress the major role of hyperglycemia in determining PC decrease in diabetics, and suggest that PC reduction is probably associated to hyperglycemia-enhanced thrombin formation.

Adult↗
PubMed1990

Evidence for a hyperglycaemia-dependent decrease of antithrombin III-thrombin complex formation in humans.

In the presence of increased levels of fibrinopeptide A, decreased antithrombin III biological activity, and thrombin-antithrombin III complex levels are seen in diabetic patients. Induced-hyperglycaemia in diabetic and normal subjects decreased antithrombin III activity and thrombin-antithrombin III levels, and increased fibrinopeptide A plasma levels, while antithrombin III concentration did not change; heparin was shown to reduced these phenomena. In diabetic patients, euglycaemia induced by insulin infusion restored antithrombin III activity, thrombin-antithrombin III complex and fibrinopeptide A concentrations; heparin administration had the same effects. These data stress the role of a hyperglycaemia-dependent decrease of antithrombin III activity in precipitating thrombin hyperactivity in diabetes mellitus.

Adult↗
PubMed1990

Non-enzymatic glycation reduces heparin cofactor II anti-thrombin activity.

The effects of non-enzymatic glycation on heparin cofactor II activity, at glucose concentrations which might be expected in physiological or diabetic conditions have been evaluated in this study. Radiolabelled glucose incorporation was associated with a loss of heparin cofactor anti-thrombin activity. The heparin cofactor heparin and dermatan sulfate-dependent inhibition of thrombin was significantly reduced, showing a remarkable decrease of the maximum second order rate constant. This study shows that heparin cofactor can be glycated at glucose concentrations found in the blood, and that this phenomenon produces a loss of heparin cofactor-antithrombin activity. These data suggest, furthermore, a possible link between heparin cofactor glycation and the pathogenesis of thrombosis in diabetes mellitus.

Antithrombins↗
PubMed1990

The role of hyperglycaemia-induced alterations of antithrombin III and factor X activation in the thrombin hyperactivity of diabetes mellitus.

Factor X concentration and factor X activation, antithrombin III anti-Xa activity and plasma concentration, and fibrinopeptide A were measured in 20 diabetic patients and 20 normal subjects. Although factor X activation (81.3 +/- 2.2 vs 97.3 +/- 2.1%, p less than 0.01; mean +/- SE) and antithrombin III activity (76.5 +/- 2.2 vs 96.3 +/- 1.8%, p less than 0.01) were reduced in the diabetic patients, fibrinopeptide A concentration was increased (3.7 +/- 0.4 vs 1.7 +/- 0.2 ng ml-1, p less than 0.01). The ratio of factor X activation to antithrombin III anti-factor Xa activity was increased in the diabetic patients (1.10 +/- 0.01 vs 1.01 +/- 0.02, p less than 0.01). Induced hyperglycaemia was able to mimic all these abnormalities, without changing factor X or antithrombin III concentration. The results suggest that in vivo hyperglycaemia produces a decrease of factor X activation, but at the same time increases fibrinopeptide A formation due to a greater decrease of antithrombin III anti-Xa activity.

Adult↗
PubMed1990

Possible role for increased C4b-binding-protein level in acquired protein S deficiency in type I diabetes.

In this study, total protein S (PS) immunological levels, free-PS and C4b-binding-protein (C4bBP) concentrations, and PS functional activity were investigated in insulin-dependent (type I) diabetic patients and compared with nondiabetic subjects. Mean total PS antigen concentration was not different between diabetic patients and nondiabetic subjects, whereas free-PS levels and PS functional activity were significantly reduced in diabetic patients. C4bBP was increased in diabetic patients and correlated with HbA1 levels. This study shows that type I diabetic patients have depressed free PS and PS activity despite the presence of normal total PS concentration and suggests that this phenomenon is probably linked to the increase of circulating C4bBP.

Adult↗