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Biomedical subjects

G Benoni

Publications and source records attributed to G Benoni.

At least 37 records · Page 2Linked to original sources
PubMed1997

Study on paradoxical effects of NSAIDs on platelet activation.

We recently described a stimulatory effect of high doses (> 100 mumol/L) diclofenac on platelet adhesion. In this study we extend our research to the possible biochemical mechanisms of the observed effects, to other non steroidal anti-inflammatory drugs (NSAIDs) (flurbiprofen, indomethacin, acetylsalicylic acid, ibuprofen, nitrofenac and nitroflurbiprofen) and to the effect of high doses diclofenac and flurbiprofen on platelet aggregation. We observed that high doses of diclofenac and of flurbiprofen, but not of the other tested NSAIDs, increased platelet adhesion at doses ranging from 100 to 500 mumol/L, an effect completely removed by the 12-lipoxygenase-inhibitor nordihydroguaiaretic acid. Moreover, they had no pro-aggregating effect, inhibiting platelet aggregation induced by 10 mumol/L arachidonic acid and dose-dependently increasing the [Ca2+]i. Finally, whereas no basal nitric oxide release by washed platelets was detected, when platelets were incubated by 500 mumol/L diclofenac or flurbiprofen, the production of nitric oxide, as measured by amounts of nitrite released, was 4.4 +/- 0.5 and 3.8 +/- 0.4 pmol/5 x 10(8) platelets/min, respectively. Our data indicate that high doses diclofenac and flurbiprofen are promoters of the early phases of platelet activation, probably through the 12-lipoxygenase pathway.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Role of endogenous and exogenous nitric oxide on intestinal mucosa and microflora in the rat.

In the present study the effects of exogenous and endogenous nitric oxide (NO) on intestinal bacteria and on the intestinal tissue integrity have been investigated in healthy rats and in rats receiving bacterial endotoxin (LPS). A segment of jejunum was taken in order to evaluate tissue damage and hematoxylin-eosin staining; microbiological studies were carried out collecting stool samples. Administration of LPS (5 mg kg-1 i.v.) induced a moderate jejunal damage, which was completely prevented by NG-nitro-L-arginine methyl ester (L-NAME), 5 mg kg-1 s.c.), thus suggesting a damage of endogenous NO on the intestinal mucosa; sodium nitroprusside (SNP, 10 mg kg-1 os) reduced significantly jejunal damage induced by LPS. Endogenous NO produced by the administration of LPS resulted to be cytotoxic for all examined aerobic and anaerobic bacteria, while exogenous NO, released from SNP, showed an inhibitory effect only on Entero. faecalis and E. coli growth. From our data, it seems reasonable to conclude that high local levels of NO are required in order to observe jejunal damage and cytotoxic effects on aerobic and anaerobic faecal flora.

Animals↗
PubMed1997

Low- or high-vacuum drains in hip arthroplasty? A randomized study of 73 patients.

We compared the effect of low-vacuum and high-vacuum drains on blood loss and blood transfusions in a randomized study of 73 patients undergoing primary hip arthroplasties. During the first postoperative hour, the high-vacuum drains evacuated more blood than the low-vacuum ones, median 135 and 35 mL (p < 0.001). After that, the rate of blood loss into the drains was approximately the same. Median blood losses into the drains after 24 hours were 570 mL in the high-vacuum group and 480 mL in the low-vacuum group (p = 0.03). Corresponding values after 48 hours were 785 mL and 585 mL (p = 0.002). The hemoglobin concentration in the drain fluid during the second postoperative day was lower in the high-vacuum group, indicating a more serous discharge. Our findings indicate that drains should be removed within 24 hours. High-vacuum drains evacuate more blood initially but may cause more damage to the tissues, especially if they are left for more than 24 hours. We found no significant difference in postoperative hemoglobin decrease or in the number of blood transfusions and wound complications in the 2 groups.

Aged↗
PubMed1997

The post-discharge prophylactic management of the orthopedic patient with low-molecular-weight heparin: enoxaparin.

This prospective, double-blind trial was performed to determine whether 4 weeks' prophylaxis with enoxaparin after total hip replacement (THR) is more effective in protecting against deep vein thrombosis (DVT) than prophylaxis during hospitalization. Two hundred sixty-two patients undergoing THR were given enoxaparin 40 mg once daily during hospitalization (9 +/- 2 days) before being randomized at discharge to continue enoxaparin (N = 131) or receive placebo (N = 131) for a total of 1 month (30 +/- 4 days). According to intention-to-treat analysis, 43 DVT and 2 pulmonary emboli (PE) occurred in the placebo group (34.4%) versus 21 DVT and no PE in the enoxaparin group (P < 0.001). The reduction in proximal DVT was also significant (21.4 vs 6.1%; P < 0.001). No major bleeding complications developed. Prophylaxis with enoxaparin for one month significantly reduces venous thromboembolic disease in patients undergoing THR compared to conventional prophylaxis during hospitalization.

Adult↗
PubMed1997

Female gender and resistance to activated protein C (FV:Q506) as potential risk factors for thrombosis after elective hip arthroplasty.

Resistance to activated protein C (APC) caused by the R506Q mutation in factor V is the most common inherited risk factor for venous thrombosis. To elucidate whether APC-resistance is a risk factor for venous thrombosis after elective total hip replacement, the association between APC-resistance (presence of FV:Q506 allele) and postoperative thrombosis was investigated in patients (n = 198) randomised to received short (during hospitalisation, n = 100) or prolonged prophylaxis (three weeks after hospitalisation, n = 98) with low molecular weight heparin (LMWH). Among APC-resistant individuals receiving short prophylaxis, 7/10 developed thrombosis as compared to 2/12 receiving long prophylaxis (p <0.0179). Odds ratio for association between APC-resistance and thrombosis in the short prophylaxis group was 4.2 (CI 95% 1.02-17.5) (p <0.0465). Among those receiving prolonged prophylaxis, there was no increased incidence of thrombosis associated with APC-resistance. Two unexpected observations were made. One was that APC-resistance was much more common in women (19/109) than in men (3/89) (p <0.001). The other was that even women without APC-resistance were much more thrombosis-prone than men. Thus, 24/48 of women with normal FV genotype and short prophylaxis developed thrombosis vs 8/42 among men, p = 0.002. The increased risk of thrombosis associated with female gender and APC-resistance was neutralised by the prolonged treatment. In conclusion, among patients receiving short prophylaxis, female gender was found to be a strong risk factor for venous thrombosis. Even though APC-resistance appeared to be a risk factor for postoperative thrombosis, the uneven distribution of APC-resistance between men and women, taken together with the increased risk of thrombosis among women, precluded valid conclusions to be drawn about the association between APC-resistance and an increased risk of thrombosis. Our results suggest that prolonged prophylaxis with LMWH after hip surgery is more important for women than for men.

Adult↗
PubMed1996

Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement.

BACKGROUND: The risk of venous thromboembolism in patients undergoing total hip replacement is known to be high. However, the optimal duration of prophylaxis with anticoagulant agents after this procedure is unknown. We sought to determine whether one month of anticoagulant therapy with the low-molecular-weight heparin enoxaparin is more effective than enoxaparin therapy given only during the hospitalization for surgery. METHODS: Two hundred sixty-two patients undergoing total hip replacement received enoxaparin during their hospitalizations (average stay, 10 to 11 days). They were then randomly assigned to receive enoxaparin or placebo (131 patients each). Blinded outpatient therapy (or placebo) was continued long enough that the total treatment period, inpatient plus outpatient, was one month for each patient. Bilateral ascending phlebography was performed 19 to 23 days after discharge, with deep-vein thrombosis as the primary end point. Distal and proximal thrombosis, pulmonary embolism, and hemorrhage were also recorded, as were deaths. RESULTS: Venography was adequate in 116 patients in the placebo group and 117 in the enoxaparin group. We observed 43 episodes of deep-vein thrombosis and 2 episodes of pulmonary embolism in the placebo group, but only 21 episodes of deep-vein thrombosis and no episodes of pulmonary embolism in the enoxaparin group (incidence of thromboembolism, 39 percent and 18 percent, respectively; P<0.001). The difference in the incidence of proximal deep-vein thrombosis was also significant (24 percent and 7 percent in the placebo and enoxaparin groups, respectively; P<0.001). Six enoxaparin groups, respectively; P<0.001). Six patients in the enoxaparin group and one patient in the placebo group had hematomas at their injection sites. No patients died or had major complications. CONCLUSIONS: There were significantly fewer venous thromboembolic complications in patients undergoing elective hip replacement when prophylaxis with enoxaparin was given for a total of one month, rather than only during the hospitalization.

Adult↗
PubMed1996

Effect of single and repeated doses of a new nitroderivative of acetylsalicylic acid on platelet TXA2 production in rats.

The effects of a new ASA-nitroderivative compound, NCX 4016 (ASA-NO2), on platelet TXA2 synthesis after single and repeated doses in the rat were investigated. Compared to ASA, cumulative doses of ASA-NO2 showed similar inhibitory effects on platelet TXA2 synthesis and significant increases in nitrite/nitrate plasma concentrations 1 h after the last drug administration: 24 h later nitrite/nitrate plasma levels returned to the control values, while serum TXA2 concentrations did not change. A time-course study after a single dose of ASA-NO2 showed a significant inhibition of platelet TXA2 production also 24 h after drug administration and a significant increase in nitrite/nitrate plasma levels until 10 h.

Animals↗
PubMed1996

Fibrinolytic inhibition with tranexamic acid reduces blood loss and blood transfusion after knee arthroplasty: a prospective, randomised, double-blind study of 86 patients.

We investigated the effect of a fibrinolytic inhibitor, tranexamic acid, on blood loss and blood transfusion in knee arthroplasty by a randomised, double-blind study of 86 patients. A dose of 10 mg/kg body-weight of either tranexamic acid or placebo was given intravenously shortly before the release of the tourniquet, and repeated three hours later. The mean total blood loss was 730 +/- 280 ml in the tranexamic acid group as against 1410 +/- 480 ml in the placebo group (p < 0.001). Both the number of patients receiving blood transfusion and the number of blood units transfused were reduced to one-third in the treated group, and mean postoperative Hb concentrations were significantly higher after prophylaxis. The number of thromboembolic complications was the same in both groups. Tranexamic acid should be given prophylactically in order to be effective.

Aged↗
PubMed1996

The antiplatelet effects of a new nitroderivative of acetylsalicylic acid--an in vitro study of inhibition on the early phase of platelet activation and on TXA2 production.

We studied in vitro the antiplatelet activity of a new nitroderivative chemically related to acetylsalicylic acid: 2 acetoxybenzoate 2-[1-nitroxy-methyl]-phenyl ester (NCX 4016), in order to identify any effects due to the release of nitric oxide and the blockade of cyclo-oxygenase. The effects of scalar doses of NCX 4016 on the early phase of platelet activation, platelet aggregation and thromboxane A2 production were investigated. We observed inhibitory effects of NCX 4016 on platelet adhesion (IC50 = 7.3 x 10(-5) M), platelet cytosolic calcium concentration, assayed by fluorescent probe Fura 2, and the expression of glycoprotein IIb/IIIa (CD41/alpha IIb beta 3) (IC50 = 3.4 x 10(-5) M) and P-selectin (CD62/GMP-140) (IC50 = 4.9 x 10(-5) M) measured by flow cytometry. NCX 4016 also prevented thrombin-induced platelet aggregation (IC50 = 3.9 x 10(-5) M). None of these parameters were affected by acetylsalicylic acid. These inhibitory activities of NCX 4016 were abolished by oxyhaemoglobin and methylene blue. Intracellular cyclic GMP observed during thrombin-induced aggregation was increased by incubation with NCX 4016. These results appear to be attributable to the release of nitric oxide, which activates soluble platelet guanylylcyclase and promotes intracellular cyclic GMP increase. NCX 4016 almost completely inhibited platelet thromboxane A2 production and arachidonic acid-induced platelet aggregation. This also occurred in the presence of oxyhaemoglobin and methylene blue, indicating that its antiplatelet activity can be attributed not only to nitric oxide release but also to cyclo-oxygenase inhibition.

Adult↗
PubMed1995

Antiaggregating and vasodilatory effects of a new nitroderivative of acetylsalicylic acid.

We studied in vitro the effects on platelet aggregation and vascular tone of a new nitrocompound (nitroxy-butyl-acetylsalicylate: NO-ASA). In order to elucidate any possible activity due to the release of nitric oxide or the inhibition of platelet cyclo-oxygenase we compared NO-ASA to acetylsalicylic acid. NO-ASA 1 mM inhibited arachidonic acid-induced platelet aggregation (basal 75.4 +/- 2.35%; NO-ASA 22 +/- 3.46%; M +/- SEM; P < 0.001; n = 6), but proved less active than acetylsalicylic acid (complete inhibition at 2 x 10(-5) M). NO-ASA also significantly reduced thrombin-induced (0.04-0.08 U/ml) platelet aggregation in acetylsalicylic acid-treated platelets (basal 70.5 +/- 1.7%; NO-ASA 35.4 +/- 2.2%; P < 0.001; n = 10; IC50 7 x 10(-5) M). Methylene blue reduced the effects of NO-ASA on thrombin-induced (NO-ASA 46.7 +/- 5.25%; NO-ASA+MB 59.1 +/- 4.3%; P < 0.01; n = 8), but not arachidonic acid-induced platelet aggregation. The inhibitory effects of NO-ASA on platelet aggregation were partially removed by oxyhaemoglobin. Platelet thromboxane A2 production (TXB2 concentration in the supernatant of the aggregate 35.38 +/- 7.81 ng/ml; n = 8), was totally abolished by acetylsalicylic acid (0.17 +/- 0.04 ng/ml; P < 0.001; n = 8) and reduced by NO-ASA (8.3 +/- 4.05 ng/ml; P < 0.01; n = 8). In vitro studies on isolated rat aortic rings showed NO-ASA 10(-3) M, but not ASA up to 10(-3) M, induce a dose dependent vasorelaxation (100% of epinephrine-induced contraction) both in intact and endothelium denuded arteries (IC50 5 x 10(-5) M). Addition of methylene blue reversed this relaxation. In conclusion these data demonstrate that NO-ASA acts through a double mechanism: a) by inhibiting cyclo-oxygenase and b) by releasing NO active on guanylyn cyclase both in platelets and in vascular smooth muscle cells.

Adult↗
PubMed1995

Plasma concentrations and pharmacokinetic parameters of nitrofenac using a simple and sensitive HPLC method.

An accurate and sensitive HPLC method has been developed for the determination of nitrofenac, a new, original diclofenac derivate showing a good tolerability and a wide anti-inflammatory profile, diclofenac, and its metabolites in plasma. This method has been applied to evaluate the pharmacokinetic parameters of the drugs, using a noncompartmental model, after the oral administration of 5 mg/kg nitrofenac to rats. Nitrofenac and the internal standard flufenamic acid were dissolved in acetonitrile, and diclofenac was dissolved in methanol. The drugs were eluted from a 5 microns LC-8 column with a mobile phase consisting of acetonitrile/water (50/50 v/v) adjusted to pH 3.3 with glacial acetic acid, at a flow rate of 2 mL/min with UV detection at 280 nm for diclofenac and 275 nm for nitrofenac. The detection limit for the drugs in plasma was 25 ng/mL. The peak concentration of nitrofenac was reached 7 h after drug administration, while with diclofenac we observed three peaks at 2, 5, and 10 h; the mean residence time and the elimination rate constant for nitrofenac were 6.18 +/- 0.09 h and 0.37 +/- 0.03 h-1 respectively, while those for diclofenac were 12.24 +/- 0.11 h and 0.11 +/- 0.04 h-1. Under our conditions, the metabolism of nitrofenac produced 23% diclofenac and other metabolites: the plasma concentrations and kinetic characteristics of diclofenac are enough to induce an anti-inflammatory activity, while the clinical importance of the other metabolites remains to be elucidated.

Animals↗
PubMed1995

Effect of acute exercise on some haematological parameters and neutrophil functions in active and inactive subjects.

In this work we studied the possible effects of acute exercise on some haematological parameters and on some functions of neutrophils in seven active and six inactive subjects. Physical exercise (10 min on a cycle ergometer at a heart rate of 150 beats.min-1) induced a significant increase in total leucocyte, lymphocyte and neutrophil concentrations in active subjects; serum iron and ferritin concentrations were lower in active compared to inactive subjects. Cellular adhesion, bactericidal activity and superoxide anion production did not change after exercise, while we also observed some differences between active and inactive subjects before exercise. In particular, the neutrophils from active subjects showed a significantly higher percentage of adhesion, higher bactericidal activity and lower superoxide anion production. In conclusion, the training induced changes in some neutrophil functions, while acute exercise influenced, overall, leucocyte concentrations.

Adult↗
PubMed1995

Anti-inflammatory potency and gastrointestinal toxicity of a new compound, nitronaproxen.

Naproxen and its derivative nitronaproxen at the doses of 5 and 10 mg kg-1 were compared for their acute anti-inflammatory efficacy in a carrageenan oedema model and gastrointestinal toxicity in rats. Moreover, the effects of the two drugs were evaluated in the adjuvant arthritis, after chronic doses of 4 and 8 mg kg-1 administered orally for 18 days. The oedema reduction was maintained much longer (until 5 h) with nitronaproxen; the inhibition of arthritis was 50% or more with both doses of the examined drugs. From the histological examination of the stomachs, an extensive mucosal vasocongestion and haemorrhagic lesions have been observed in some rats treated with naproxen. The percentages of animals with ulcers were 50, 100 and 10 with naproxen 6 and 18 mg kg-1 and nitronaproxen 54 mg kg-1 respectively. A better gastrointestinal tolerability has been observed in arthritic and oedemic rats treated with nitronaproxen compared to naproxen: this could be due to the presence of nitric oxide that acts in maintaining the tissue perfusion and integrity.

Animals↗
PubMed1995

Changes in several neutrophil functions in basketball players before, during and after the sports season.

Neutrophils play an important role in the immune system, forming the "first line of defence" against invading microorganisms and there are few data available concerning neutrophil functions in relation to exercise. We investigated in 7 basketball professional players possible changes before, during and after the sports season, in some haematological parameters and in several aspects of the phagocytic process of neutrophils, such as adhesion, superoxide anion release and bactericidal activity. Training and competitions produced a significant rise in the number of total leukocytes and differential counts, but the values returned to the pre-start levels 3 weeks after the end of the championship. The bactericidal activity and the superoxide anion released were significantly greater during the sports season, while the percentage of cellular adhesion significantly decreased during the championship; after the sports season the values returned to the control levels. As in the literature data concerning neutrophil functions in relation to exercise are non-convergent, it is important in our opinion, to understand whether the alterations induced by exercise can persist after repeated stimuli.

Adult↗
PubMed1995

Inhibition by sodium nitroprusside of the expression of inducible nitric oxide synthase in rat neutrophils.

A well-known nitric oxide (NO)-releasing compound, sodium nitroprusside (SNP), decreases in a dose-dependent manner NO synthase (NOS) activity induced in rat neutrophils by treatment with lipopolysaccharide (LPS). This inhibitory action of SNP seems not to be due to its direct effect on the enzyme activity. The strong nitrosonium ion (NO+) character of SNP could be responsible for its inhibition of NOS induction in neutrophils.

Amino Acid Oxidoreductases↗
PubMed1995

Effect of a new non-steroidal anti-inflammatory drug, nitroflurbiprofen, on the expression of inducible nitric oxide synthase in rat neutrophils.

The effects of a non-steroidal anti-inflammatory drug, flurbiprofen, and its nitro-derivative, nitroflurbiprofen, on inducible nitric oxide synthase in rat neutrophils were examined. Nitroflurbiprofen was shown to inhibit nitric oxide synthase induction caused by lipopolysaccharide administration, while flurbiprofen had no effect on nitric oxide synthase induction. This inhibitory action may be ascribed to nitric oxide released from nitroflurbiprofen.

Administration, Oral↗
PubMed1995

Protective effect of NO on gastric lesions and inhibition of expression of gastric inducible NOS by flurbiprofen and its nitro-derivative, nitroflurbiprofen.

Nitroflurbiprofen (NFP) causes significantly less gastric lesions than flurbiprofen (FP), probably because of its capacity to release nitric oxide (NO) in the stomach. Lipopolysaccharide (LPS), which induces the expression of an inducible type of NO synthase (iNOS) in rat stomach, also reduces gastric mucosal damage elicited by FP. Furthermore, both FP and NFP decrease significantly the amount of mRNA encoding iNOS induced by LPS in the stomach. The inhibitory effect of NFP seems to be due at least in part to its ability to release NO.

Animals↗