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Biomedical subjects

L Mattiello

Publications and source records attributed to L Mattiello.

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

Insulin increases cyclic nucleotide content in human vascular smooth muscle cells: a mechanism potentially involved in insulin-induced modulation of vascular tone.

It has been suggested that insulin exerts a vasodilating effect, but the mechanisms involved are not completely understood. Since cyclic nucleotides mediate the vasodilation induced by endogenous substances, such as prostacyclin and nitric oxide, we aimed to investigate the influence of insulin (concentration range 240-960 pmol/l) on both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) content in human vascular smooth muscle cells. Insulin dose-dependently increased both nucleotides (cAMP: from 0.7 +/- 0.1 to 2.6 +/- 0.4 pmol/10(6) cells, p = 0.0001; cGMP: from 1.3 +/- 0.2 to 3.4 +/- 0.7 pmol/10(6) cells, p = 0.033). This increase is receptor-mediated, since it was blunted when cells were preincubated with the tyrosine kinase inhibitor genistein. The effect of insulin remained significant (p = 0.0001) when preincubation with the phosphodiesterase inhibitor theophylline prevented cyclic nucleotide catabolism. The increase of cGMP was blunted when the cells were preincubated with the guanylate cyclase inhibitor methylene blue, and with the nitric oxide-synthase inhibitor NG-monomethyl-L-arginine. At all the concentrations tested, insulin potentiated the increase of cAMP induced by the stable prostacyclin analogue Iloprost (p = 0.0001), whereas only at 1920 pmol/l did it potentiate the cGMP increase induced by glyceryltrinitrate (p = 0.05). This study demonstrates that the vasodilating effects exerted by insulin may at least in part be attributable to an increase of both cGMP and cAMP via a receptor-mediated activation of adenylate and guanylate cyclases in human vascular smooth muscle cells and that the insulin effect on cGMP is mediated by nitric oxide.

Arterioles↗
PubMed1995

Glyceryl trinitrate enhances the adenosine-induced inhibition of platelet responses: a mechanism potentially involved in the in vivo anti-aggregating effects of organic nitrates.

1. The present study investigated the influence of the organic nitrate glyceryl trinitrate (GTN) on the anti-aggregating effects of adenosine. We determined the effects of adenosine, GTN and their combination on platelet responses in platelet-rich plasma and whole blood, and on intracellular levels of 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP). 2. Adenosine inhibited the in vitro platelet aggregation in response to different agonists in a dose-dependent way through an elevation of intraplatelet cAMP levels. Effective adenosine concentrations were higher than those detectable under physiological conditions, but very close to levels achieved during myocardial ischaemia or haemorrhagic shock. 3. GTN was able to decrease platelet responses influencing intraplatelet cGMP levels. Furthermore, the drug increased the inhibitory effects of adenosine and enhanced its effects on intraplatelet cAMP levels. 4. The present data provides further evidence that compounds that increase intraplatelet levels of cGMP and cAMP act synergistically on the inhibition of platelet aggregability through the influence of increased cGMP levels on cAMP accumulation. The interplay between GTN and adenosine in the inhibition of platelet function could be effective during nitrate administration in the treatment of acute myocardial ischaemia when blood adenosine levels are significantly increased.

Adenosine↗
PubMed1995

Impaired insulin-induced platelet antiaggregating effect in obesity and in obese NIDDM patients.

To investigate the effects of insulin on platelets in obesity and in non-insulin-dependent diabetes mellitus (NIDDM)--classic insulin-resistant states--we determined ADP-induced platelet aggregation and platelet cGMP (guanosine 3',5'-cyclic monophosphate) content in platelet-rich plasma obtained from nine obese subjects and nine age-matched healthy volunteers and from eight NIDDM obese patients and nine age-matched healthy volunteers after a 3-min incubation with human recombinant insulin (0, 240, 480, 960, and 1,920 pmol/l). Platelet aggregation was evaluated using different ADP doses to measure the ADP concentration determined on the basis of a dose-response curve necessary to elicit a maximal aggregation of 50% (ED50). Insulin induced a dose-dependent decrease of platelet aggregation to ADP (P = 0.0001) in healthy subjects. A significant effect was evident starting from an insulin concentration of 240 pmol/l. On the contrary, in insulin-resistant subjects, insulin reduced platelet sensitivity to ADP only at a concentration of 1,920 pmol/l. When ADP ED50 values obtained in platelet-rich plasma incubated with insulin were expressed in percentage of the ADP ED50 values obtained in platelet-rich plasma without insulin, considered as 100%, we observed that ADP ED50 with 1,920 pmol/l insulin was 153.6 +/- 13.2% in the younger healthy subject group (P = 0.004), 150.0 +/- 3.8% in the older healthy subject group (P = 0.0001), 116.1 +/- 6.1% in obese subjects (P = 0.031), and 120.0 +/- 8.6% in NIDDM patients (P = 0.05). In healthy subjects, insulin induced a dose-dependent increase of platelet cGMP (P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1994

Effects of forskolin and organic nitrate on aggregation and intracellular cyclic nucleotide content in human platelets.

1. The present study investigated the effect of a combination between forskolin, a naturally occurring diterpene which directly activates adenylyl cyclase, and glyceryl trinitrate (GTN), which enhances intraplatelet cyclic guanosine monophosphate levels, on human platelet aggregation and intracellular content of cyclic nucleotides 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP). 2. Forskolin inhibited, in a dose-dependent way, platelet aggregation in response to collagen and adrenaline in platelet-rich plasma. In whole blood samples, forskolin inhibited collagen-stimulated aggregation. In presence of forskolin the intraplatelet cAMP levels were significantly increased. 3. GTN directly decreased the platelet response to collagen in whole blood samples (IC50 = 122 mumol/l) and it increased the intraplatelet levels of both cGMP and cAMP. 4. GTN at 20 and 40 mumol potentiated the inhibitory effects of forskolin on platelet aggregation in both platelet-rich plasma and whole blood. 5. Our results suggest a synergistic effect of the simultaneous increase of both cAMP and cGMP on the biochemical steps involved in the inhibition of the platelet response.

Adult↗
PubMed1994

Insulin increases guanosine-3',5'-cyclic monophosphate in human platelets. A mechanism involved in the insulin anti-aggregating effect.

To investigate whether insulin reduces platelet aggregability through a modulation of the guanosine-3',5'-cyclic monophosphate (cGMP) concentrations, we determined by a radioimmunoassay the cGMP values in the platelet-rich plasma (PRP) obtained from 17 healthy volunteers and incubated for 3 min with different concentrations of human recombinant insulin (0, 240, 480, 720, 960, and 1,920 pM). Insulin induced a dose-dependent cGMP increase, from 18.5 +/- 3.3 to 42.0 +/- 6.4 pmol/10(9) platelets (P = 0.0001). This increase was completely blunted when PRP was preincubated for 20 min with the tyrosine kinase inhibitor genistein (10 microM) or with the guanylate cyclase inhibitor methylene blue (10 microM), but the increase remained highly significant (P = 0.003 and 0.009) when PRP was preincubated for 20 min with the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX, 500 microM) or with the nitric oxide synthase inhibitor NG-mono-methyl-L-arginine (L-NMMA, 30 microM). Finally, the insulin-induced decrease of platelet aggregability to collagen and ADP was completely blunted when PRP was preincubated with 10 microM of the guanylate cyclase inhibitor methylene blue. This study demonstrates that the platelet anti-aggregatory effect exerted by insulin is attributable to the insulin-induced increase of cGMP that is due to a direct receptor-mediated platelet guanylate cyclase activation.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Insulin influences immunoreactive endothelin release by human vascular smooth muscle cells.

This study sought to investigate whether insulin influences immunoreactive endothelin release from cultured human vascular smooth muscle cells. For this purpose, we incubated cultured vascular smooth muscle cells (VSMC) obtained from human microvessels with 0, 80, and 320 microU/mL insulin with or without arginine vasopressin (10 nmol/L) and angiotensin II (10 nmol/L). After 6 hours, the culture supernatant was collected and immunoreactive endothelin was determined by radioimmunoassay. Insulin at a concentration of 320 microU/mL induced a significant increase of immunoreactive endothelin levels in medium (from 15.2 +/- 0.8 to 20.6 +/- 0.8 pg/200 microL, P < .01) and potentiated arginine vasopressin- and angiotensin II-induced immunoreactive endothelin release (P < .0001 and P < .04, respectively). Insulin at a concentration of 80 microU/mL did not induce a significant increase of spontaneous immunoreactive endothelin release, but significantly increased the effects of arginine vasopressin (P < .05). In conclusion, insulin influences immunoreactive endothelin release from human VSMC in culture.

Angiotensin II↗
PubMed1993

Effect of dopamine on adenosine 3',5'-cyclic monophosphate levels in human platelets.

1. The dopamine effect on intraplatelet adenosine 3',5'-cyclic monophosphate (cAMP) levels was evaluated in healthy subjects. 2. Dopamine levels over 30 nmol/l increased cAMP concentration in a concentration-dependent way. 3. The platelet preincubation with propranolol (beta-adrenoceptor antagonist) prevented the dopamine effect, whereas phentolamine (alpha-adrenoceptor antagonist) failed to modify the platelet response to this catecholamine. Dopamine receptor antagonist domperidone directly increased cAMP levels and it enhanced the dopamine effects. 4. Our results indicate that dopamine effect is mainly mediated by beta-adrenoceptor stimulation.

Adult↗
PubMed1993

Organic nitrates and compounds that increase intraplatelet cyclic guanosine monophosphate (cGMP) levels enhance the antiaggregating effects of the stable prostacyclin analogue iloprost.

The present study investigated the effect of a combination between the stable prostacyclin (PGI2) analogue iloprost and compounds, glyceryl trinitrate (GTN) and L-arginine-, which enhance the intraplatelet cyclic guanosine monophosphate (cGMP) levels on platelet aggregation, release reaction and cyclic nucleotide content: in particular cyclic adenosine monophosphate (cAMP) and cGMP. Iloprost inhibited in a dose-dependent way the platelet aggregation in response to collagen, adenosine diphosphate (ADP) and adrenaline and it increased the intraplatelet cAMP concentrations. GTN directly decreased the platelet responses and increased the intraplatelet levels of both cGMP and cAMP. GTN (20 x 10(-6) mol/l) and L-arginine (0.2 x 10(-3) mol/l) potentiated the inhibitory effects of iloprost on platelet aggregation and release reaction. Our results suggest: 1. A synergistic effect of the simultaneous increase of both cAMP and cGMP on the biochemical steps involved in the inhibition of the platelet response; 2. An influence of cGMP on cAMP accumulation.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Insulin, at physiological concentrations, enhances the polymorphonuclear leukocyte chemotactic properties.

We investigated the influence of insulin on human polymorphonuclear leukocyte (PMN) chemotaxis induced by mediators in a microchamber assay. Insulin increased, with a dose-response relationship, chemotaxis induced by formyl-methionyl-leucyl-phenylalanine, calcium ionophore and phorbol-miristyl acetate (p = 0.0057, p = 0.0001 and p = 0.0215, respectively). The hormone effect was present also at the physiological concentration of 40 microU/ml. Our data show that insulin affects PMN activity in normal subjects and therefore support the hypothesis that insulin deficiency may be responsible for the impaired PMN function observed in diabetic patients in poor metabolic control.

Adult↗
PubMed1992

Studies on the effect of dopamine on the human platelet response.

1. The present study investigated the in vitro effect of dopamine on platelet responses in healthy subjects. 2. Dopamine concentrations over 5 mumol/L induced a primary aggregating response and a slight release of alpha-granule proteins, beta-thromboglobulin and platelet factor-4 in all subjects. In 25% of investigated subjects a delayed secondary aggregation was observed with dopamine concentrations over 100 mumol/L. 3. Low dopamine concentrations (5-7.5 nmol/L) increased the platelet sensitivity to other aggregating agents (adenosine diphosphate, collagen and sodium arachidonate). The effect of subaggregating concentrations of serotonin was potentiated by dopamine. 4. The effect of dopamine on platelet responses was prevented by low concentrations of alpha-adrenoceptor antagonists (phentolamine and yohimbine); antagonists of dopamine receptors (haloperidol and domperidone) were able to decrease the extent of the dopamine-induced secondary aggregating wave in the responders, but they failed to prevent the primary aggregation and the effects on platelet response to other aggregating agents. 5. The present data demonstrated that the effects of dopamine on human platelets are mainly mediated by interactions with alpha-adrenoceptors.

Adenosine Diphosphate↗
PubMed1992

A comparison of the predictive power for overall blood glucose control of a 'good' fasting level in type 2 diabetic patients on diet alone or with oral agents.

The European NIDDM Policy Group classifies both fasting and post-prandial blood glucose concentrations into 'good', 'acceptable', and 'poor' categories. The aim of the present study was to evaluate whether a 'good' fasting blood glucose concentration in Type 2 diabetic patients on diet or diet + oral hypoglycaemic agents is able to predict 'good' blood glucose values throughout the day, and therefore to discover whether or not it is necessary to perform blood glucose profiles in Type 2 diabetic patients when their fasting value is 'good'. Capillary blood glucose profiles (n = 417) were measured in 287 Type 2 diabetic patients, on diet alone (279 profiles), or on diet + tablets (138 profiles). We observed that 66% of profiles on diet and 44% of profiles on diet + tablets had only 'good' blood glucose concentrations (p less than 0.001). Eleven percent of profiles on diet and 30% of profiles on diet + tablets included 'poor' blood glucose concentrations (p less than 0.001). Despite matched fasting blood glucose concentrations (diet 5.69 +/- 0.04 (+/- SE) vs tablets 5.75 +/- 0.05 mmol l-1), levels were higher in the diet + tablet treated patients at all later time-points (p less than 0.01-0.001). HbA1c was significantly higher in tablet-treated patients than in patients on diet alone (6.6 +/- 0.1 vs 5.9 +/- 0.1%, p less than 0.001), and correlated with the mean blood glucose concentration (r = 0.43, p less than 0.001) but not with the fasting glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1992

Moderate exercise increases platelet function in type I diabetic patients without severe angiopathy and in good control.

OBJECTIVE: The aim of this study was to investigate whether a 45-min moderate exercise, performed postprandially with a timing that partially prevented the risk of hypoglycemia, was able to modify platelet function in patients affected by insulin-dependent (type I) diabetes mellitus without severe late complications and in a good metabolic control. RESEARCH DESIGN AND METHODS: We submitted 6 male type I diabetic patients (27.2 +/- 3.4 yr; body mass index, 21.4 +/- 0.6 kg/m2; HbA1c, 7.6 +/- 0.9%) on a daily three-insulin injection regimen, without severe late complications of diabetes, to a 45-min moderate exercise (about 50% of maximal oxygen consumption) with a cycle ergometer, beginning 180 min after breakfast and 195 min after a subcutaneous shot of regular insulin. Serial venous blood samples were conducted to measure plasma glucose, free insulin, counterregulatory hormones (glucagon, growth hormone, cortisol, and catecholamines), platelet sensitivity to ADP, platelet activating factor and collagen, and plasma concentrations of the platelet-specific protein beta-thromboglobulin (a marker of the platelet release reaction in vivo). RESULTS: Exercise was accompanied by a decrease of plasma glucose (from 5.9 +/- 1.2 to 4.6 +/- 1 mmol/L, P = 0.067) and free insulin (from 180 +/- 36 to 114 +/- 30 pmol/L, P = 0.003), and by a significant increase of growth hormone (from 5 +/- 1 to 15 +/- 4 micrograms/L, P = 0.045), cortisol (from 240 +/- 30 to 406 +/- 69 nmol/L, P = 0.018), epinephrine (from 1005 +/- 240 to 5143 +/- 1753 pmol/L, P = 0.077), and norepinephrine (from 5.04 +/- 1.08 to 13.48 +/- 2.98 nmol/L, P = 0.009). Platelet sensitivity to the agonists and plasma concentrations of beta-thromboglobulin increased during the exercise period. In particular, ADP ED50 reached during exercise 61 +/- 16% of basal values (P = 0.048), platelet activating factor ED50 reached 73 +/- 11% (P = 0.043), and collagen ED50 reached 68 +/- 9% (P = 0.008). beta-Thromboglobulin rose from 24 +/- 2 to 32 +/- 3 micrograms/L (P = 0.007). CONCLUSIONS: Moderate exercise enhances platelet function in type I diabetic patients without severe angiopathy and in a good metabolic control.

Adenosine Diphosphate↗
PubMed1991

Occurrence of low blood glucose concentrations during the afternoon in type 2 (non-insulin-dependent) diabetic patients on oral hypoglycaemic agents: importance of blood glucose monitoring.

The European NIDDM Policy Group states that the lowest target for good control of Type 2 (non-insulin-dependent) diabetic patients is a blood glucose level 4.4 mmol/l, both fasting and postprandially. The aim of this study is to evaluate the occurrence and temporal distribution of values under this target in the clinical records of 463 Type 2 diabetic patients, treated by diet or diet and oral hypoglycaemic agents, monitored for at least 2 years. The protocol includes blood glucose measurements after overnight fasting (08.00 hours), 120-150 min after breakfast (11.00 hours) and 120 and 240 min after lunch (14.00 and 16.00 hours). At least one blood glucose concentration of less than 4.4 mmol/l was presented by 42% of the patients. The only difference between patients showing and not showing glycaemic levels under this target was the higher percentage on oral hypoglycaemic agents in the first group (68.4% vs 56.9%, p = 0.016). We considered 299 blood glucose profiles containing at least one value of less than 4.4 mmol/l, observing that a) 46.9% of profiles from patients treated by diet alone and 68.7% of profiles from patients treated both by diet and oral hypoglycaemic agents presented the lowest blood glucose concentration at 16.00 hours (p = 0.002). b) No correlation existed between fasting blood glucose and values at 16.00 hours in profiles from diet-treated patients, whereas a negative correlation was present in patients on diet and oral hypoglycaemic agents, indicating that an excess of oral agents, administered to correct fasting hyperglycaemia, was the cause of the low glycaemic values in the afternoon.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Phenothiazines inhibit collagen-induced thromboxane B2 synthesis and increase forskolin anti-aggregating effects in human platelets.

1. The aim of the present study was to investigate the effects of phenothiazine compounds chlorpromazine and trifluoperazine on human platelet response to collagen and sodium arachidonate. 2. The results demonstrated that phenothiazines inhibit collagen-induced platelet aggregation and thromboxane B2 synthesis in a dose-dependent way and increase the antiaggregating properties of forskolin. 3. Phenothiazines at high concentrations decreased the platelet aggregation in response to arachidonate, without a significant reduction of thromboxane B2 production. 4. The data provides evidence that phenothiazine effects could involve calmodulin-dependent enzymatic activities.

Adult↗
PubMed1991

Effects of diltiazem on thromboxane B2 production from platelet-rich plasma and whole blood.

The present study evaluated the effects of the calcium-channel blocking agent diltiazem on platelet aggregation and on synthesis of thromboxane B2 (the stable metabolite of thromboxane A2) from platelet-rich plasma (PRP) and whole blood samples. Our results showed that diltiazem inhibits collagen- and thrombin-induced platelet aggregation and TXB2 production from PRP. Since no significant interference with conversion of arachidonate to thromboxane A2 was demonstrated, inhibition of phospholipase A2 activity may be the prevailing mechanism of the diltiazem effect. The drug demonstrated a dose-related inhibitory activity on TXB2 synthesis from whole blood samples during spontaneous clotting or following stimulation with collagen or thrombin. The present results give further evidences for an antiplatelet activity of diltiazem and support the hypothesis that inhibition of platelet function contributes to the therapeutic efficacy of this drug in the treatment of cardiovascular diseases.

Adult↗
PubMed1991

Calcium-channel blocking agents verapamil and diltiazem are inhibitors of vasopressin-induced human platelet activation.

1. This study investigated the influences of calcium-channel blocking agents verapamil and diltiazem on platelet responses induced by arginine vasopressin (AVP) and lysine vasopressin (LVP). 2. The substances inhibited platelet aggregation induced by both low and high AVP concentrations, LVP and adrenaline plus AVP. IC50 values of each drug are lower than those determined for ADP- and collagen-elicited aggregation. Verapamil and diltiazem also decreased AVP-induced thromboxane B2 synthesis. 3. Other series of experiments showed that the addition of ethyleneglycol-bis-(beta-amino-ethyl ether) N, N'-tetra-acetic acid to platelet-rich plasma samples also prevented the platelet response to vasopressin polypeptides. 4. Our data provide evidence that the effects of verapamil and diltiazem on vasopressin-induced platelet responses may be directly related to inhibition of extracellular calcium entry.

Adult↗
PubMed1990

Studies on inhibition of human platelet response by diltiazem.

1. Aim of the present investigation was to investigate the effects of calcium blocking agent diltiazem on human platelet response to aggregating agents. 2. Results showed that diltiazem inhibits platelet aggregation induced by ADP, arginine vasopressin, adrenaline, collagen, Na arachidonate, thrombin and phorbol ester PMA in a dose-dependent way. 3. Diltiazem decreased also beta-thromboglobulin release and Thromboxane B2 production from stimulated platelets. 4. Intraplatelet cyclic AMP levels were not modified by the substance. 5. Data provide evidence that the modulation of human platelet function by diltiazem could be also related to inhibition of protein kinase C.

Adult↗