PubMed Health⌕ Search

Biomedical subjects

G Leoncini

Publications and source records attributed to G Leoncini.

At least 37 records · Page 2Linked to original sources
PubMed1999

Discrepant expression of neprilysin on fibroblasts in diffuse systemic sclerosis.

OBJECTIVE: Neprilysin (NEP; EC3.4.24.11) is an ectopeptidase mainly produced by fibroblasts and cleaving a large number of neuropeptides. We previously found increased plasma circulating levels of NEP in patients with systemic sclerosis (SSc), but in SSc fibroblasts derived from the diffuse subset NEP was present in lower concentration. We evaluate in vitro fibroblasts of both subsets of the disease, diffuse and limited, the intracellular levels of NEP, and its expression as CD10 on the cellular surface. METHODS: Fibroblasts, derived from biopsies taken from affected skin of 8 patients with the limited subset and 5 with the diffuse subset, were grown in vitro and intracellular levels of NEP activity were measured with a fluorometric method, while CD10 surface expression was evaluated by FACS analysis. Cell proliferation was assessed by 3HThymidine incorporation. RESULTS: Intracellular NEP activity was significantly increased in diffuse (7.02+/-4.8 pg/ml/min 10(6) cells) compared to limited SSc (1.11+/-2.0) and control fibroblasts (1.41+/-0.9). CD10 expression was significantly impaired on diffuse SSc fibroblasts (47.3+/-15%) compared to controls (74.6+/-11%) and the limited subset (82.7+/-11%). Cell proliferation of diffuse SSc fibroblasts was strikingly higher than controls and limited SSc fibroblasts. CONCLUSION: These results confirm that NEP is produced by fibroblasts and indicate that in diffuse SSc fibroblasts NEP is produced in higher quantities, while the expression of the enzyme on the cell surface is significantly reduced. This condition may affect the proliferation rate of fibroblasts as well as the metabolism of various peptides.

Cell Division↗
PubMed1998

Hydrogen peroxide formation in platelets of patients with non-insulin-dependent diabetes mellitus.

A group of 29 patients with non-insulin-dependent diabetes mellitus (NIDDM) was compared with a group of 19 patients who had good glycemic control for platelet activity and hydrogen peroxide formation. NIDDM patients showed platelet hyperactivity in response to low ADP concentrations. In addition, stimulated platelets from untreated NIDDM patients produced more hydrogen peroxide than platelets of treated and normal subjects. Hydrogen peroxide accumulation was not related to modification of the enzymatic systems involved in its synthesis and break-down. The specific activities of NAD(P)H cytochrome C reductase, catalase, glutathione peroxidase and glutathione reductase were not different between patients and healthy subjects. It is likely that the platelet intracellular elevation of reactive oxygen free-radicals could play an important role in the vascular complications and thrombotic risk that is often present in NIDDM patients.

Journal Article↗
PubMed1998

[Intrathoracic perforation of the gastric fundus as a late complication of an unknown post-traumatic rupture of the diaphragm].

The Authors report a case of gastric perforation into the left pleural cavity due to the herniation of the gastric fundus into the thorax in a patient who suffered from a thoraco-abdominal trauma four months before. A few physiopathological aspects of post-traumatic rupture of the diaphragm with a delayed presentation are discussed. Clinical and radiological typical elements of the chronic undiscovered diaphragmatic herniation are underlined and the events related to the complications (strangulation, perforation) are described. Finally, a few therapeutical principles are discussed.

Adult↗
PubMed1997

Mechanism of action of two new pyrimidoquinoline and isoquinoline derivatives in human platelets.

In the present study the "in vitro" influence of 3-(1-piperazinyl)-1H-pyrimido[1,2-a]quinolin-1-one (AQ11) and 2-(piperazinyl)-4H-pyrimido[2,1-a]isoquinolin-4-one (IQ3b) on human platelet aggregation, cAMP elevation, cytosolic calcium and fibrinogen binding has been investigated. Both drugs inhibited platelet aggregation in a concentration-dependent manner. In PRP AQ11 was slightly more active than IQ3b when aggregation was induced by ADP, collagen, A23187 or PMA, whereas in washed platelets challenged by thrombin, IQ3b was more effective than AQ11. Both compounds produced increase in cAMP intracellular level being the effect potentiated by the adenylate cyclase activator iloprost and IQ3b was more powerful than AQ11. Moreover IQ3b was more effective in inhibiting cAMP in high affinity phosphodiesterase (IC50 values: IQ3b 11 +/- 5 microM; AQ11 43 +/- 8 microM) and calcium elevation (IC50 values: IQ3b 9 +/- 4 microM; AQ11 32 +/- 6 microM). These compounds also inhibited fibrinogen binding in platelets challenged by ADP or thrombin. The results suggest that these new potent agents inhibit platelet phosphodiesterase activity causing an elevation in cAMP levels sufficient to inhibit calcium rise and fibrinogen binding. This mechanism can be responsible for the ability of the compounds to prevent platelet aggregation.

Adenosine Diphosphate↗
PubMed1997

Effect of 2-(1-piperazinyl)-4H-pyrido[1,2-a]pyrimidin-4-one (AP155) on human platelets in vitro.

The effect on human platelets of 2-(1-piperazinyl)-4H-pyrido[1,2-a]pyrimi din-4-one (AP155) was tested in vitro by measuring cyclic adenosine monophosphate (cAMP) level, cytosolic Ca++, [(125I)]fibrinogen binding as well as aggregation induced by several agonists. AP155 dose-dependently inhibited aggregation both in platelet rich plasma (PRP) and in washed platelets (WP), exerting its maximal power in the presence of collagen, ADP and platelet activating factor (PAF). It specifically inhibited the activity of cAMP high affinity phosphodiesterase (PDE), resulting in a sufficient increase in cAMP levels to activate cAMP-dependent protein kinase. AP155 was able to inhibit aggregation, the increase in cytosolic Ca++ induced by thrombin, and fibrinogen binding to ADP or thrombin-stimulated platelets. Thus, this new pyridopyrimidine derivative exerts its antiplatelet activity by increasing cAMP intracellular concentration.

Blood Platelets↗
PubMed1997

Hyperactivity and increased hydrogen peroxide formation in platelets of NIDDM patients.

Free radical activity may contribute to atherosclerotic lesions which in diabetic subjects may frequently lead to vascular complications. It is known that oxidative stress is associated to diabetes. Protein glycation and glucose oxidation could be possible source of free radicals. 28 non insulin dependent diabetic subjects (NIDDM) were examined. 20 healthy subjects matched for age, sex and for the presence of hypertension and hyperlipidemia were also studied. Hydrogen peroxide, measured by intracellular levels of the fluorescent 2,7-dichloro-fluorescein (DCF), was considered as indicative parameter of free radical production. The results showed that in resting platelets the basal level of hydrogen peroxide was significantly higher in diabetic subjects than in controls. Moreover, after stimulation with thrombin, collagen, phorbol myristate acetate (PMA) and platelet activating factor (PAF), platelets of diabetic subjects generated significantly higher amounts of hydrogen peroxide than controls. Moreover, platelet aggregation induced by adenosine 5'-diphosphate (ADP) and plasma beta TG levels were higher in diabetics than in controls. In diabetic patients platelet free radical production and functional activity are increased and therefore could play a role in the elevated thrombotic risk described in diabetes.

Adenosine Diphosphate↗
PubMed1996

Effects of methylglyoxal on platelet hydrogen peroxide accumulation, aggregation and release reaction.

Methylglyoxal generates a slight increase in the basal level of hydrogen peroxide in platelets. The oxidation effect of methylglyoxal significantly potentiated by thrombin, depends on both the ketoaldehyde and the agonist concentrations. A further significant increase in hydrogen peroxide accumulation was obtained in platelets pretreated with the alkylating agent N-ethylmaleimide which depletes GSH and blocks glutathione peroxidase. Resting platelets completely transform the ketoaldehyde into D(-)lactate, whereas stimulated platelets transform about 10-15 per cent of the metabolized methylglyoxal into D(-)lactate. The metabolic modifications generated by methylglyoxal such as the GSH depletion and hydrogen peroxide accumulation induce modifications in platelet function. Methylglyoxal inhibits platelet aggregation induced by several agonists and ATP release induced by thrombin.

Blood Platelets↗
PubMed1996

Painful vein overdistension in migraine patients: no relationship with serotoninergic parameters.

Overdistension of the hand-forearm veins after a period of ischaemia-induced stasis causes local pain in a high percentage of migraineurs, but never in healthy subjects. To investigate the mechanism of such pain, we compared 5-hydroxytryptamine (5HT) whole blood levels and hand vein 5HT reactivity of migraine subjects who did experience pain during venous overdistension to those who did not. No differences were found in whole blood 5HT levels or in the venoconstrictor activity of 5HT between subjects experiencing pain and those who did not. No correlation was found between whole blood 5HT levels and the degree of 5HT-induced venoconstriction. Our results suggest that, if platelets are considered as a model of central antinociceptive 5HT neurons, pain appearance is not due to reduced 5HT at a central level and, therefore, to increased perception of peripheral nociceptive stimuli. Moreover, the similar 5HT venoconstrictive effect (indirect marker of venous tone and, therefore, of venous distensibility) seems to indicate that a mechanical factor is not involved in pain appearance during the HAVD test.

Adult↗
PubMed1996

Nerve growth factor circulating levels are increased in Kawasaki disease: correlation with disease activity and reduced angiotensin converting enzyme levels.

OBJECTIVE: To investigate the serum levels of nerve growth factor (NGF) and their possible relationship with disease activity in Kawasaki disease. METHODS: Twelve children with Kawasaki disease, 12 healthy children (afebrile controls), and 12 children with high fever related to upper respiratory tract viral infections (URTVI) were enrolled in the study. Serum NGF levels were measured by an ELISA method before and after therapy. In addition, angiotensin converting enzyme (ACE), and erythrocyte sedimentation rate (ESR), complete hemochrome, and C-reactive protein were tested as indicators of endothelial injury and disease activity, respectively. RESULTS: NGF levels were strikingly increased in the acute phase of Kawasaki disease (1219.54 +/- 1660.29 pg/ml) and decreased in the inactive phase of the disease (277.08 +/- 245.64 pg/ml), while remaining significantly higher than controls (6.5 +/- 2.03 pg/ml). In febrile patients with URTVI, NGF levels (30.18 +/- 44.70 pg/ml) were moderately but significantly increased compared to afebrile controls, but remarkably lower in respect to active and inactive Kawasaki disease. In active Kawasaki disease, ACE values were significantly lower than in healthy children (2.8 +/- 1.7 vs 10.1 +/- 4.2 pmol/ml/min; p < 0.001) and increased during the inactive phase, but remaining lower than in controls (4.8 +/- 2.7 pmol/ml/min); ESR, hemoglobin level, and platelet count showed significant correlation with NGF, while ACE levels showed a significant inverse correlation with ESR and NGF. CONCLUSION: In Kawasaki disease, NGF increased together with decreased ACE may be linked to a diffuse vascular inflammatory process. NGF and ACE levels remained abnormal even when there was no clinical sign of disease activity. This may indicate that the disease process is not in complete remission and suggests careful and prolonged cardiac followup until their normalization.

Child, Preschool↗
PubMed1995

Segmental organization of the pig liver: anatomical basis of controlled partition for experimental grafting.

Segmental anatomy has been investigated on 54 pig livers by bench-top radiology and ultrasonography of hepatic and portal vessels and bile ducts and dissection of suprahepatic veins. Eight segments were recognized, homologous to those of the human liver. Major variations were found only of arterial distribution. The inferior vena cava invariably ran within the parenchyma of the right lobe and close to the liver hilum; suprahepatic veins were also entirely intraparenchymal. Therefore, the pig liver can easily be divided into two halves, but only the right one can be used for reduced-size grafting into a recipient.

Animals↗
PubMed1995

Synthesis and inhibitory activities on platelet aggregation of some flavonoid analogues.

A series of 26 benzodioxan and benzodioxol derivatives of flavone have been prepared. The activity of the compounds on washed human platelet aggregation induced by adenosine diphosphate (ADP, 5 mumol/l), collagen (10 micrograms/ml) and calcimycin (20 mumol/l) was evaluated. The alkoxycarbonyl side chain derivatives inhibited all three types of aggregation inducers. Among the tested compounds Ia is the most potent inhibitor of collagen-induced aggregation but possesses a weak activity against the other two used inducers. The esters IIIb and in particular, IIIc are active against all the three used inducers. These results suggest that ethoxycarbonyl group is a potent substituent to provide the antiplatelet action in this series of flavonoids.

Flavonoids↗
PubMed1995

Pyran derivatives XIX. (Dialkylamino) substituted 1-benzopyranones and naphthopyranones with platelet antiaggregating activity.

2-(Dialkylamino)chromones 4 and 4-(1-piperazinyl)coumarins 11, as well as their angular benzo-fused derivatives 1, 2 and 12, 13, respectively, were synthesized and tested in vitro for their inhibitory activity on human platelet aggregation induced in platelet-rich plasma by ADP (5.0 microM), collagen (10.0 micrograms/ml), and A 23187 (calcimycin) (20.0 microM). Among the dialkylamino substituents used, and the ring systems examined, 1-piperazinyl and 1-benzopyran or naphtho[2,1-b]pyran, respectively, resulted the most effective ones for antiplatelet activity, both in the chromone and coumarin fields. 7-Ethoxy-4-(1-piperazinyl)coumarin 11b showed the highest activity, and higher than those of all reference compounds (ASA, trifluoperazine, propranolol, and dipyridamole) towards all platelet aggregation inducers.

Coumarins↗
PubMed1994

Thrombin induces S-D-lactoylglutathione accumulation by enhancing platelet glycolytic pathway.

1. Thrombin addition to human platelets stimulates L(+)lactate formation and S-D-lactoylglutathione (SDL) accumulation. 2. Monoiodoacetamide decreases lactate formation and potentiates SDL accumulation through a significant increase of dihydroxyacetone phosphate and fructose1,6bisphosphate intracellular levels both in resting and in activated platelets. 3. A similar effect is produced by exogenous methylglyoxal on L(+)lactate formation and SDL accumulation. 4. Resting platelets completely transform (1 hr at 37 degrees C) the ketoaldehyde into D(-)lactate: 5. When platelets are incubated in the presence of thrombin only 60% of the ketoaldehyde is found as D(-)lactate and the accumulated S-D-lactoylglutathione represents about the 0.7% of the initial substrate. 6. During platelet stimulation with thrombin the hemithioacetal adduct, formed as a by-product of glycolytic pathway, can be rapidly removed for important steps of cellular activation.

Alkylation↗
PubMed1994

N-ethylmaleimide inhibits platelet aggregation and potentiates hydrogen peroxide formation induced by thrombin.

The effect of NEM pretreatment on hydrogen peroxide accumulation and aggregation in non stimulated and activated human platelets was studied. It was shown that low concentrations of NEM potentiate hydrogen peroxide formation induced specifically by thrombin. The cooperative effect of NEM with thrombin is dose-dependent and reaches the maximum at 5 microM NEM. Thrombin is particularly effective at low concentrations (0.02-0.1 U). Extracellular Ca2+ significantly increases the NEM effect. Moreover NEM inhibits aggregation both in PRP and in washed platelets, exhibiting the greatest activity in washed platelets stimulated by thrombin.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Neutral endopeptidase (3.4.24.11) in plasma and synovial fluid of patients with rheumatoid arthritis. A marker of disease activity or a regulator of pain and inflammation?

In recent years the role of the peripheral nervous system has been focused on the pathogenesis of rheumatoid arthritis (RA). In particular, substance P (SP), released by the sensory terminals, has been demonstrated to be involved in cartilage breakdown [13]. The aim of our work was to study the levels of SP and its peptidases, neutral endopeptidase (3.4.24.11) (NEP) and angiotensin-converting enzyme (ACE), in the synovial fluid and plasma of 30 patients with RA and 14 patients with osteoarthritis (OA). ACE and NEP were determined with a fluorimetric assay and SP with a radioimmunoassay (RIA) method. ACE levels were normal in the plasma of patients with RA and OA (6.1 +/- 1.9 and 6.7 +/- 1.4 pmol/ml/min, respectively); we found no differences in the values, of ACE between RA and OA synovial fluid (5.7 +/- 4.2 and 5.5 +/- 4.1 pmol/ml/min, respectively). NEP levels were significantly increased in plasma (139.3 +/- 36 pmol/ml/min) and synovial fluid (133.8 +/- 32 pmol/ml/min) of patients with RA when compared to patients with OA (73.4 +/- 22 in plasma and 15.2 +/- 10.8 pmol/ml/min in synovial fluid) and healthy controls (89.7 +/- 14 pmol/ml/min in plasma). In synovial fluid, SP was significantly higher in RA patients (43.1 +/- 16.6 pg/ml) than in OA patients (12 +/- 13.1 pg/ml), while plasma levels did not show any difference (RA: 14.4 +/- 10.2; OA: 13.6 +/- 10.6; healthy subjects: 11.3 +/- 3.9 pg/ml). The only relationship detected in controls and in OA was among plasma NEP and ESR (P < 0.05) and synovial fluid NEP (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

S-D-lactoylglutathione accumulation in activated human platelets.

1. S-D-Lactoylglutathione accumulates in human platelets activated by agonists. Among the tested inducers thrombin is the most active. 2. The effect is dose and time-dependent. S-D-Lactoylglutathione, corresponding to depleted pool of reduced glutathione, can also be detected in platelets incubated with exogenous methylglyoxal. 3. A further significant increase was observed in platelets stimulated with thrombin in the presence of methylglyoxal. 4. No change in glyoxalase activities upon platelet stimulation with thrombin was shown.

Blood Platelets↗
PubMed1993

1,2-fused pyrimidines. VI. Substituted 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones with antiplatelet activity.

The N-substituted 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 2 d,g-i,l-p,r,s and derivatives 4,5 b,6 a,b, 7 a,b were prepared. Both these novel compounds (except the insoluble 7a) and compounds 2 a-c,e,f,j,k,q, 5a, previously prepared by us, were tested in vitro for their inhibitory activity on human platelet aggregation induced by ADP, collagen, or A23187. On the whole, the compounds tested proved to be more active towards collagen than towards ADP and A23187. The 2-(4-methyl-1-piperazinyl)derivative 2 g was the most active compound both towards ADP and collagen, whereas the 2-(diethylamino)derivative 2 b proved to be the most active one towards A23187.

Adenosine Diphosphate↗