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Biomedical subjects

R Paniccia

Publications and source records attributed to R Paniccia.

At least 19 recordsLinked to original sources
PubMed2001

S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery: preliminary observation of a 6-month follow-up study.

Cerebral damage remains one of the hazards related to cardiac surgery with cardiopulmonary bypass. The use of biochemical markers of cerebral injury may be of practical value. We investigated the plasma release patterns of S-100 protein and neuron-specific enolase (NSE) during the intervention and their relationship with the development of neuropsychological deficits assessed 6 months after the intervention in 16 patients undergoing elective cardiac surgery with cardiopulmonary bypass. Both S-100 and NSE significantly increased peri- and postoperatively. Significant correlations were found between values measured at several time points and impaired performance in a few tests at the 6-month follow-up. A stratification into two age subgroups led to the hypothesis that age might have a confounding or a modifying effect on the association between S-100 and NSE levels, and cognitive impairment.

Aged↗
PubMed2000

Selective upregulation of cardiac endothelin system in patients with ischemic but not idiopathic dilated cardiomyopathy: endothelin-1 system in the human failing heart.

Only scarce information is available on the activity and modifications of the cardiac endothelin (ET)-1 system in heart failure due to ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy. The activity of the ET-1 system was investigated by measuring cardiac ET-1 and big ET-1 formation and quantifying cardiac mRNA for prepro-ET-1 (ppET-1), ET-converting enzyme-1, and ET(A) and ET(B) receptors both in myocardium and in isolated myocytes using Northern blot, reverse transcription-polymerase chain reaction, and in situ hybridization in 22 patients with DCM and 20 with ICM who underwent cardiac transplantation and in 7 potential heart transplant donors (nonfailing hearts). Notwithstanding a similar increase of plasma ET-1 in the 2 groups, cardiac ET formation, mRNA levels for ppET-1, and ET(A) and ET(B) receptors were higher on both the myocardium and isolated myocytes from ICM than on those from DCM hearts (P<0.001 for all). ppET-1 and ET-converting enzyme-1 mRNAs were expressed on myocytes and endothelial and interstitial cells in ICM, whereas in DCM and nonfailing hearts they were mainly expressed on nonmyocyte cells. In both ICM and DCM, the ET(A) mRNA signal was expressed on both myocytes and nonmyocyte cells, whereas ET(B) mRNA was almost exclusively localized on nonmyocyte cells. ET(A)- and ET(B)-specific receptor binding was increased on both myocytes and cardiac membranes, showing a positive correlation with left ventricular ejection fraction in ICM (r=0.78 and 0.70) but not in DCM patients. The present results show that human ventricular myocytes express all of the components of the ET-1 system, which is selectively upregulated in ICM patients and appears to be functionally important in the maintenance of cardiac function.

Adult↗
PubMed2000

Early sequence of cardiac adaptations and growth factor formation in pressure- and volume-overload hypertrophy.

To investigate the time sequence of cardiac growth factor formation, echocardiographic and hemodynamic measurements were performed at scheduled times, and mRNAs for angiotensinogen, prepro-endothelin-1 (ppET-1), and insulin-like growth factor I (IGF-I) were quantified with RT-PCR and localized with in situ hybridization in pigs (fluothane anesthesia) by use of pressure or volume overload (aortic banding and aorta-cava fistula, respectively). Relative peptide formation was also measured by radioimmunoassay. In pressure overload, angiotensinogen and ppET-1 mRNA overexpression on myocytes (13 times vs. sham at 3 h and 112 times at 6 h, respectively) was followed by recovery (12 h) of initially decreased (0.5-6 h) myocardial contractility. In volume overload, contractility was not decreased, the angiotensinogen gene was slightly upregulated at 6 h (6.7 times), and ppET-1 was not overexpressed. IGF-I mRNA was overexpressed on myocytes (at 24 h) in both volume and pressure overload (14 times and 37 times, respectively). In the latter setting, a second ppET-1 overexpression was detectable on myocytes at 7 days. In conclusion, acute cardiac adaptation responses involve different growth factor activation over time in pressure versus volume overload; growth factors initially support myocardial contractility and thereafter induce myocardial hypertrophy.

Adaptation, Physiological↗
PubMed1999

Endothelin receptors in adult human and swine isolated ventricular cardiomyocytes.

The present study aimed to investigate endothelin-1 (ET-1) receptors in human and swine cardiomyocytes with binding studies using ET(A) and ET(B) selective receptor antagonists (BMS-182874 and BQ-788, respectively). Cell distribution of mRNA expression for ET(A) and ET(B) subtypes was investigated by in situ hybridization using specific cDNA probes. The 1251-ET-1 binding, which reached equilibrium in about 120 min (Kobs = 0.051+/-0.003 min(-1)), was only partially displaceable by the addition of a large excess of ET-1 (about 15% with a half-life of 20 min). In equilibrium binding studies, 125I-ET-1 had a Kd of 0.43+/-0.08 nM and a maximum binding (Bmax) of 42.8+/-6.6 fmol/mg protein. ET(A) and ET(B) receptors are represented in human and swine cardiomyocytes with an 85:15 ratio as indicated by the biphasic pattern of competition of both BMS-182874 and BQ-788. In situ hybridization studies confirmed that myocytes mainly expressed mRNA for ET(A), whereas expression of mRNA for the ET(B) subtype was documented in non-myocyte cells. These results showed that ET-1 binds with high affinity and poor reversibility to specific receptors, in both human and swine isolated ventricular cardiomyocytes, without significant species differences.

Adult↗
PubMed1999

Cardiac growth factors in human hypertrophy. Relations with myocardial contractility and wall stress.

The aim of the present study was to investigate whether and which cardiac growth factors are involved in human hypertrophy, whether growth factor synthesis is influenced by overload type and/or by the adequacy of the hypertrophy, and the relationships between cardiac growth factor formation and ventricular function. Cardiac growth factor formation was assessed by measuring aorta-coronary sinus concentration gradient in patients with isolated aortic stenosis (n=26) or regurgitation (n=15) and controls (n=12). Gene expression and cellular localization was investigated in ventricular biopsies using reverse transcriptase-polymerase chain reaction and in situ hybridization. Cardiac hypertrophy with end-systolic wall stress <90 kdyne/cm2 was associated with a selective increased formation of insulin-like growth factor (IGF)-I in aortic regurgitation and of IGF-I and endothelin (ET)-1 in aortic stenosis. mRNA levels for IGF-I and preproET-1 were elevated and mainly expressed in cardiomyocytes. At stepwise analysis, IGF-I formation was correlated to the mean velocity of circumferential fiber shortening (r=0.86, P<0.001) and ET-1 formation to relative wall thickness (r=0.82, P<0. 001). When end-systolic wall stress was >90 kdyne/cm2, IGF-I and ET-1 synthesis by cardiomyocytes was no longer detectable, and only angiotensin (Ang) II was generated, regardless of the type of overload. The mRNA level for angiotensinogen was high, and the mRNA was exclusively expressed in the interstitial cells. Ang II formation was positively correlated to end-systolic stress (r=0.89, P<0.001) and end-diastolic stress (r=0.84, P<0.001). Multivariate stepwise analysis selected end-systolic stress as the most predictive variable and left ventricular end-diastolic pressure as the independent variable for Ang II formation (r=0.93, P<0.001). In conclusion, the present results indicate that the course of human left ventricular hypertrophy is characterized by the participation of different cardiac growth factors that are selectively related both to the type of hemodynamic overload and to ventricular function.

Aged↗
PubMed1999

Characterization of endothelin-1 receptor subtypes in isolated human cardiomyocytes.

On cardiac membranes and isolated cardiomyocytes from the human heart, cell-type distribution and functional activities of endothelin-1 (ET-1) receptor subtypes were investigated by using binding methods and messenger RNA (mRNA) in situ hybridization. The ET-receptor antagonist BMS-182874 selectively and competitively inhibits ET(A) receptors both on isolated myocytes and ventricular membranes with approximately 1,300 times greater affinity for ET(A) than ET(B) subtypes. The [125I]-ET-1 specific binding revealed 42.851+/-2,546 receptors/myocyte with a prevalent proportion of ET(A)-receptor subtypes on both myocytes (84+/-2%) and ventricular membranes (66+/-3%). In situ hybridization studies revealed that mRNA for ET(A) receptors was expressed on both myocytes and nonmyocyte cells, whereas mRNA for ET(B) receptors was almost exclusively expressed on fibroblasts and endothelial cells. Specific binding of [125I]-ET-1 to both myocytes and ventricular membranes in the presence of specific ET(A) (BMS-182874) and ET(B) (BQ-788)-receptor antagonists showed a displacement of [125I]-ET-1 by unlabeled ET-1, which were significantly faster from ET(B) than from ET(A). This suggests a clearance function of ventricular ET(B) receptors.

Antihypertensive Agents↗
PubMed1998

Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients.

Several studies have shown that n-3 polyunsaturated fatty acids (n-3 PUFA) are able to lower blood pressure (BP) in humans, but large doses of fish oils have been often used. Moreover, most of the studies available in the literature were not able to evaluate the specific effects of n-3 PUFA because they employed fish oils which contain, together with n-3 PUFA, many other different components. The aim of this preliminary study was to evaluate if medium-term supplementation with a moderate dose of highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl esters is able to reduce BP in mild hypertensive patients. Sixteen mild essential hypertensive (diastolic BP: 95-104 mm Hg), non-diabetic, normolipidemic male outpatients and 16 normotensive male controls were recruited to participate in the study. Both hypertensive and control subjects were randomly assigned to receive either EPA and DHA ethyl esters (2.04 g EPA and 1.4 g DHA) as active treatment or olive oil (4 g/day) as a placebo for a period of 4 months. These subjects were followed up with 24-hour ambulatory BP monitoring and blood chemistry analyses at 2 and 4 months of treatment and 2 months after its discontinuation. The intake of n-3 PUFA was checked by red blood cell (RBC) phosphatidylcholine (PC) fatty acid composition. The effect of n-3 PUFA on BP in the active group was maximum after 2 months. Both systolic (-6 mm Hg, p<0.05) and diastolic (-5 mm Hg, p<0.05) BP significantly decreased during the n-3 PUFA ethyl ester supplementation. No further effect was observed at 4 months with a return to baseline values during the recovery period. These data indicate that 4 g/day of highly purified EPA + DHA ethyl esters are able to favorably affect BP in mild hypertensives.

Adult↗
PubMed1998

Evaluation of clotting and fibrinolytic activation after protracted physical exercise.

The behavior of hemostatic system activation during protracted physical exercise is well known, but the duration of its modification is not yet defined. In order to evaluate the time of hemostatic system activation after prolonged strenuous endurance physical exercise (typical marathon race: 42.195 km, v=15.35 km/h; mean length of time run 2.45+/-0.15 hours) 12 well-trained long-distance male runners (mean age: 35+/-7, range 25-47 years) were investigated. Blood samples were drawn in the morning on the day before the performance, immediately after the race, and 24 hours and 48 hours after the end of run. With respect of baseline, immediately after the race, a significant decrease of fibrinogen (-25%) and significant increases of prothrombin fragment 1+2 (+633%) and thrombin-antithrombin complex (+848%) were observed. A significant acceleration of euglobulin lysis time (-41%), and rises of plasma levels of tissue plasminogen activator antigen (+361%), plasminogen activator inhibitor type 1 antigen (+235%), d-dimer (+215%), and plasma fibrinogen degradation products (+1200%) were also found. Only a slight, yet not significant, decrease in plasminogen activator inhibitor type 1 activity was observed. One day after the end of marathon different parameters were still unchanged. Forty-eight hours after the competition all parameters investigated returned to baseline values. These results indicate a persistence of clotting as well as fibrinolysis activation up to 24 hours after the end of the race.

Adult↗
PubMed1998

Effect of low-dose heparin on fibrinogen levels in patients with chronic ischemic heart disease.

Several prospective studies have demonstrated that high plasma fibrinogen levels are associated with an increased risk of ischemic heart disease. Since in most patients an increased thrombin generation has been reported, we investigated whether the control of thrombin generation could affect plasma fibrinogen levels. Forty male outpatients (20 asymptomatic with previous myocardial infarction and 20 with stable effort angina) were enrolled in a randomized medium-term (6 months) cross-over study. Clottable fibrinogen, according to Clauss, prothrombin fragment 1 + 2, thrombin-antithrombin complex, and fibrinopeptide A were evaluated in relation to treatment with low-dose heparin. After a 15-day wash-out period, during which patients had been treated only with nitrates if needed, patients were allocated to two sequential periods of treatment with standard heparin (12,500 U, subcutaneously daily) plus antianginal treatment or antianginal treatment alone, separated by a second 15-day wash-out period. At the end of the treatment period with low-dose heparin significant decreases in the plasma fibrinogen (2.5 +/- 0.6 g/l vs. 3.3 +/- 0.5 g/l, P < 0.001), prothrombin fragment 1 + 2 (1.4 +/- 0.5 nmol/l vs. 1.9 +/- 0.7 nmol/l, P < 0.001), thrombinantithrombin (4.5 +/- 2.4 ng/ml vs. 9.7 +/- 3.6 ng/ml, P < 0.001), and fibrinopeptide A (2.1 +/- 1.1 ng/ml vs. 3.5 +/- 2.1 ng/ml, P < 0.001) were observed compared with the period without heparin. The present results indicate that low-dose heparin can effectively control the increased abnormal thrombin generation and elevated fibrinogen levels in patients with ischemic heart disease, possibly decreasing the risk of cardiovascular death.

Aged↗
PubMed1997

Increased renal formation of thromboxane A2 and prostaglandin F2 alpha in heart failure.

Renal formation of the vasoconstrictor prostaglandins thromboxane A2 (TXA2) and prostaglandin F2 alpha (PGF2 alpha) was investigated in 25 patients with cardiac failure, divided into New York Heart Association functional classes I to IV, and in eight healthy control subjects. Plasma renin activity (PRA) and hemodynamic parameters were also investigated. Renal vasoconstrictor eicosanoid formation, measured in urinary daily excretion, was not different between patients in class I and control subjects. Class II to IV patients showed progressively increasing production of PGF2 alpha (F = 49.8, p < 0.001, analysis of variance) and TXA2 (F = 37.8, p < 0.002). PGF2 alpha excretion peaked in class IV (+ 1266% vs class I, p < 0.001). Compared with class I, urinary excretion of thromboxane B2 was + 816% in class III and + 1561% in class IV (both p < 0.001). PRA was significantly increased only in class IV (+ 1558%, p < 0.001). The current results indicate a progressive increase in renal production of vasoconstrictor eicosanoids directly related to New York Heart Association class and suggest that these prostanoids may have a role in deterioration of renal function.

Adolescent↗
PubMed1997

Cyclooxygenase and lipoxygenase metabolite generation in nasal polyps.

A role of prostaglandins (PGs) and leukotrienes (LTs) in the pathogenesis of nasal polyps has been recently suggested. Cyclooxygenase (CO) products (thromboxane B2, PGE2 and 6-keto PGF1 alpha) and lipoxygenase (LO) products (LTB4 and LTC4) were investigated by radioimmunoassay in polyps, hypertrophic turbinates and nasal mucosa from 14 patients with non-allergic (n = 6), allergic chronic rhinitis (n = 6) and aspirin-sensitive asthma (ASA) (n = 2), who underwent polypectomy. In all tissues CO metabolite levels were found higher than LO products (P < 0.01). Nasal polyps showed a significantly lower (P < 0.05) arachidonic acid (AA) metabolism in comparison to nasal mucosa. In polyps of allergic patients significantly higher LTB4 levels (P < 0.001) and a tendency to produce higher amounts of CO products in comparison to non-allergic subjects were observed, whereas in turbinates of non-allergic patients LT levels were significantly higher in comparison to those of allergic ones (P < 0.01). In ASA patients a decreased CO/LO ratio was found supporting the hypothesis of an imbalance of AA metabolism in this syndrome. These findings seem to indicate that the occurrence of nasal polyps may represent the result of different chronic inflammatory stimuli, regulated in part by AA metabolites.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

n-3 PUFA supplementation, monocyte PCA expression and interleukin-6 production.

n-3 polyunsaturated fatty acids (PUFA) can affect several monocyte functions and the biochemistry of blood cells, thus possibly influencing the initiation of thrombosis, inflammatory disease and atherosclerosis. In this study, we have investigated the effect of dietary supplementation with n-3 PUFA ethyl esters on procoagulant activity (PCA) and interleukin-6 (IL-6) production by human mononuclear cells. Nine healthy volunteers received 4 g/d of n-3 PUFA ethyl esters (4 x 1 g capsules with at least 85% eicosapentaenoic + docosahexaenoic acid ethyl esters) for 18 weeks. Before and at the end of the treatment, mononuclear cells were obtained from peripheral citrated blood by Ficoll-Hypaque density gradient centrifugation. Cellular suspensions (10(7) cells/ml) were incubated at 37 degrees C for 4 h in the absence and presence of lipopolysaccharide (10 micrograms/ml); PCA was determined by one-stage clotting assay and IL-6 concentrations were assayed in supernatants by specific ELISA. After 18-week treatment, both unstimulated and stimulated monocyte PCA were significantly reduced by 66% and 63%, respectively (P < 0.01). Similarly, a significant inhibitory effect by n-3 PUFA treatment on basal and LPS-stimulated IL-6 monocyte production was observed (50% and 46%, respectively, P < 0.05). These data indicate that 18-week n-3 PUFA supplementation may influence monocyte activities, which play a specific role in atherosclerosis and its thrombotic complications.

Adult↗
PubMed1996

Effect of n-3 polyunsaturated fatty acid intake on phospholipid fatty acid composition in plasma and erythrocytes.

To characterize the time course of plasma and red blood cell (RBC) changes after n-3 polyunsaturated fatty acid (PUFA) supplementation, 20 healthy male volunteers were randomly assigned to receive either four 1-g capsules of n-3 PUFA ethyl esters or four 1-g capsules of olive oil (as placebo) for a period of 4 mo, followed by a 3-mo washout period. Fatty acids of plasma and RBC phospholipid fractions were analyzed at 0, 2, and 4 mo of treatment and at 1, 2, and 3 mo of washout. During n-3 PUFA supplementation, accumulations of eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA) acids were marked after 2 mo with differences among different fractions of plasma and RBCs in further accumulation up to 4 mo. During the first and second months of the washout, slight differences were observed in changes of various fatty acids among different phospholipid fractions, but after 3 mo of washout, only minor alterations were still detectable with respect to pretreatment values. These data confirm the complex relations among different fatty acid pools after n-3 PUFA supplementation.

Administration, Oral↗
PubMed1996

pH dependence of neutrophil-endothelial cell adhesion and adhesion molecule expression.

Neutrophil adhesion to the vascular endothelium is enhanced during tissue ischemia and/or inflammation, conditions that are associated with tissue acidosis. This study examined the effects of hypercarbic acidosis (10 or 20% CO2) and of hypocarbic alkalosis (0% CO2) on human neutrophil CD18 and human aortic endothelial cell intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin expression quantified by flow cytometry. Acidosis with 20% CO2 for 4 h decreased ICAM-1 to 60.6 +/- 9.7% of control. In contrast, alkalosis with 0% CO2 for 4 h enhanced ICAM-1 expression to 143.8 +/- 10.1% of control. There was no pH dependence of VCAM-1 or E-selectin expression. Tumor necrosis factor-alpha (TNF-alpha; 10 ng/ml) increased endothelial ICAM-1, E-selectin, and VCAM-1; under these conditions, acidosis with 20% CO2 blunted both ICAM-1 and E-selectin surface expression compared with 5% CO2-, TNF-alpha-treated cells. Hypercarbic acidosis with 20% CO2 increased neutrophil CD18 expression and enhanced neutrophil adhesion. This latter effect was inhibited by neutrophil pretreatment with an anti-CD18 monoclonal antibody. In contrast, when only endothelial cells were preincubated with the hypercarbic buffer, neutrophil adhesion diminished to 55.6 +/- 7.8% of control. The results suggest that acidosis generated during tissue ischemia/inflammation may induce CD18-mediated neutrophil adhesion despite a decrease in ICAM-1 expression.

Cell Adhesion↗
PubMed1995

Calcitonin increases cytosolic free calcium concentration via capacitative calcium influx.

The calcitonin receptor has been proposed to function as an extracellular Ca2+ concentration ([Ca2+]o) sensor (Stroop, S. D., Thompson, D. L., Kuestner, R. E., and Moore, E. E. (1993) J. Biol. Chem. 268, 19927-19930). To test this hypothesis we studied the LLC-PK1 renal tubular cells and the PC1 cells, a cell line stably transfected with the cloned porcine calcitonin receptor. [Ca2+]i was measured by fura-2 single cell microfluorometry. Addition to the cells equilibrated in 1.25 mM Ca(2+)-containing media of 1-10 mM extracellular Ca2+ did not result in a significant increase of [Ca2+]i. Treatment with 10(-7) M salmon calcitonin (sCT) elicited a rapid, persistent elevation of [Ca2+]i. Addition of 1-10 mM extracellular Ca2+ in the presence of sCT induced a significant [Ca2+]i elevation, about 10-fold that observed in the absence of the hormone. Ca2+ influx was inhibited by lanthanum. The rise of [Ca2+]i at elevated [Ca2+]o was not due to a Ca2+ sensing mechanism with release of Ca2+ from intracellular stores, since it was prolonged, and was not abolished by prior depletion of Ca2+ stores with 10(-6)M thapsigargin. On the contrary, this agent potentiated Ca2+ influx after addition of 1-10 mM Ca2+ by 13-fold versus control. Prior stimulation of [Ca2+]i with 10(-7) M arginine-vasopressin had similar effects, enhancing the subsequent Ca2+ influx. Enhancement of Ca2+ influx by sCT was confirmed by increased Mn2+ quenching of fura-2 fluorescence. In conclusion, arginine-vasopressin or calcitonin enhance Ca2+ influx in LLC-PK1 cells via a Ca2+ release-activated conductance, probably dependent upon capacitative Ca2+ entry. Thus, these effects are not unique to the calcitonin receptor and argue against the receptor functioning as a [Ca2+]o sensor.

Animals↗
PubMed1995

Fibrin generation and digestion in patients with angina pectoris.

Fibrin generation and lysis were studied in 28 patients with angina pectoris (14 with active disease and 14 with inactive disease) and in 14 normal controls. The fibrinolytic response was evaluated by comparing the ratio between the plasma levels of fibrinopeptide A and fibrin degradation products. Levels of both were higher in patients than in controls (P < 0.001), with higher levels in active than in inactive disease (P < 0.001). The fibrinopeptide A/fibrin degradation products ratio was much higher (P < 0.001) in the active group than in other groups. Thus, in patients with angina pectoris, especially in the active state, the increased thrombin generation is not paralleled by an equivalent increase in fibrinolytic activity.

Adult↗
PubMed1995

Effect of n-3 fatty acid ethyl ester supplementation on fatty acid composition of the single platelet phospholipids and on platelet functions.

Twenty healthy male volunteers were randomly assigned to receive either four 1-g capsules of n-3 polyunsaturated fatty acids (PUFA) ethyl esters or four 1-g capsules of olive oil (as placebo) for a period of 4 months, followed by a 3-month wash-out period. Fatty acids of platelet phospholipid fractions, platelet aggregation, and thromboxane B2 (TXB2) formation were analyzed at 0, 2, and 4 months of treatment and at 1, 2, and 3 months of wash-out. During n-3 PUFA supplementation, accumulations of eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA) acids were markedly increased after 2 months, with slight differences in further accumulation up to 4 months among the various phospholipid fractions. Significant decreases in platelet sensitivity to collagen, serum TXB2 levels, and urinary TXB2 metabolites were also observed following n-3 PUFA treatment. During the first and second month of wash-out, slight differences were observed in changes of various fatty acids among different phospholipid fractions, but after 3 months of wash-out, alterations were no longer detectable with respect to pretreatment values. After 3 months of wash-out, platelet function parameters also were returned to baseline. Thus, both platelet lipids and function are influenced by n-3 PUFA ethyl ester supplementation, and significant alterations are still detectable after 2 months of wash-out.

Adult↗