Soluble antiapoptotic molecules and immune activation in chronic heart failure and unstable angina pectoris.

Programmed myocyte cell death and activation of the immune system have been shown to occur in patients with congestive heart failure. Besides, unstable angina episodes are likely to be associated with immune activation. Our aim was to evaluate the role of changes in circulating levels of soluble Fas (sFas), suggestive of an enhanced inhibitory response to ongoing apoptosis, and soluble IL2 receptor (sIL2-R), indicative of T-lymphocyte activation, in chronic heart failure and unstable angina pectoris. Thirty patients affected by chronic heart failure (20 idiopathic and 10 ischemic cardiomyopathy) and 13 patients with unstable angina were evaluated. Twenty healthy individuals matched for age and gender were used as controls. A complete biochemical determination of indexes of myocardial damage including cardiac troponin I (cTnI) and creatine kinase (MB/CK) was performed. The results demonstrated that mean levels of sFas and sIL2-R were significantly increased in patients affected by chronic heart failure and unstable angina and were not associated with changes in renal function or with serum levels of cTnI. Highest values of sFas were found in NYHA class IV patients (IV NYHA class = 7.39 +/- 0.52 vs. controls = 1.34 +/- 0.12 ng/ml; P < 0.01) and more elevated in idiopathic than in ischemic cardiomyopathy (3.64 +/- 0.40 vs. 1.82 +/- 0.37 ng/ml; P < 0.01). Moreover, in chronic heart failure patients sFas and ejection fraction were negatively correlated (P = 0.01), whereas sFas and sIL2-R were positively correlated (P < 0.01). In unstable angina patients too, sFas and sIL2-R appeared to be correlated (P = 0.03); whereas sFas (angina group = 3.18 +/- 0.39 vs. controls = 1.34 +/- 0.12 ng/ml; P < 0.01) and sIL2-R (angina group = 0.46 +/- 0.11 vs. controls = 0.00 UI/ml; P < 0.01) were higher in angina group than in controls. In most of the cases, the increase of sFas was associated with comparable changes in sIL2-R serum levels, indicating that the activation of Fas system is strictly associated with autoimmune-inflammatory reactions. This phenomenon, both in chronic heart failure and in unstable angina, occurs in the absence of biochemical evidences of myocardial damage and seems to parallel the activation of T cell. Soluble Fas could have a role in sustaining inflammatory response and in prolonging the detrimental effects correlated with it in chronic heart failure and angina pectoris.

Plasma homocysteine and folate are related to arterial blood pressure in type 2 diabetes mellitus.

The aim of this study was to assess the relationship between homocysteine (tHcy), folate and vitamin B12 levels, urinary albumin excretion, and arterial blood pressure in patients with non-insulin-dependent diabetes mellitus (NIDDM). Our study was carried out in 33 NIDDM patients (16 men, 17 women) and 16 healthy volunteers as controls (seven men, nine women). Fasting and postmethionine load plasma tHcy levels were assessed, together with folate, vitamin B12, and urinary albumin excretion levels. In NIDDM patients, there were correlations between folate and mean arterial pressure (r = -0.352, P = .046), folate and systolic blood pressure (r = -0.437, P = .013), folate and vitamin B12 (r = 0.499, P = .004), tHcy and vitamin B12 (r = -0.348, P = .04), ln tHcy and ln folate (r = -0.404, P = .01), and, lastly, between tHcy, either fasting or postload, and urinary albumin excretion. Patients with elevated tHcy levels had significantly higher diastolic blood pressure (P = .04) and mean arterial pressure (P = .03). Otherwise, higher folate values were associated with lower systolic blood pressure (P = .004) and mean arterial pressure (P = .02). In addition, NIDDM patients with complications presented higher tHcy basal values than the group without complications (P = .003). A particular propensity of such patients towards endothelial dysfunction could explain the presence of correlations between these metabolic parameters and arterial blood pressure.

Fasting and post-methionine load homocyst(e)ine values are correlated with microalbuminuria and could contribute to worsening vascular damage in non-insulin-dependent diabetes mellitus patients.

The study aim was to assess the relationship between homocyst(e)inemia and microalbuminuria in non-insulin-dependent diabetes mellitus (NIDDM) patients. The study was performed on 33 NIDDM patients (16 males and 17 females), and 16 healthy control subjects (seven males and nine females). Plasma fasting and post-methionine load homocyst(e)ine (tHcy), together with other parameters that could modify tHcy levels, were assessed. There were no significant differences between NIDDM patients and controls for fasting tHcy (8.12 +/- 3.17 v 7.19 +/- 2.40 micromol/L) and post-methionine load tHcy (26.51 +/- 11.50 v 25.06 +/- 10.76 micromol/L). Moreover, there was a significant correlation between urinary albumin excretion (UAE) and fasting tHcy (r = .340, P = .05) and post-methionine load tHcy (r = .502, P = .004) in NIDDM patients. Fasting tHcy was correlated both with post-methionine load tHcy (r = .429, P = .01) and with vitamin B12 (r = -.349, P = .04) in NIDDM patients. Microalbuminuric NIDDM patients had higher fasting tHcy (9.05 +/- 3.83 micromol/L) than normoalbuminurics (7.12 +/- 1.95 micromol/L). In addition, NIDDM patients with complications presented higher fasting tHcy values than the group without complications (9.61 +/- 3.34 v 6.53 +/- 2.09 micromol/L, Kolmogorov-Smirnov two-sample test for nonparametric data [KS] = 1.794, P = .003), without any other significant differences in the parameters considered. tHcy could be an important risk factor worsening the prognosis in NIDDM patients, especially microalbuminuric patients. Microalbuminuric NIDDM patients could be particularly prone to hyperhomocyst(e)inemia, probably due to endothelial or renal dysfunction with a reduction in the scavenging of tHcy.

Anthropometric or ultrasonic measurements in assessment of visceral fat? A comparative study.

The main aim of the study (study 1) was to compare the accuracy of anthropometric and ultrasonic measurements in assessing the amount of visceral adipose tissue. An additional aim (study 2) was to verify ultrasound technique precision. Study 1: using computed tomography (CT) L4-L5 adipose tissue area as a gold standard we compared the accuracy of waist/hip circumference ratio, sagittal diameter and ultrasonic measurements of intra-abdominal depth in assessing the amount of visceral adipose tissue. Study 2: ultrasonic measurements of the intra-abdominal muscle-vertebra distance were made in triplicate by three different operators. In study 1, 24 volunteers were used; body mass index (BMI): 19-43. In study 2, 22 volunteers were used; BMI 20-42. In study 1, ultrasonic measurements of the abdominal depth correlated best with CT visceral adipose tissue area (r = 0.89 - 0.91). In study 2, inter-operator and intra-operator mean variation coefficients were about 7% and 5% respectively. We concluded that using a well standardized technique and properly trained operators, ultrasonic measurement of intra-abdominal depth is a valid method in assessing the amount of visceral adipose tissue.

[Changes in lipid status during pravastatin treatment]. / Modificazioni del quadro lipidico durante trattamento con pravastatina.

Reduced cholesterolemia lowers the risk of ischemic cardiopathy, especially if LDL cholesterol levels are reduced. Today this effect can be achieved using drugs following the discovery of a new class of molecules: statins are specific inhibitors of HMG-CoA-reductase, a key enzyme in cholesterol biosynthesis. These molecules act by modifying the intracellular quota of cholesterol, especially at a hepatocytic level, thus enabling an enhanced expression of those genes responsible for forming receptors for membrane LDL with an increased number of receptors. This leads to a modulation of receptor activity which interferes with LDL uptake, promoting more rapid clearance. The aim of this study was to confirm the efficacy and tolerability of pravastatin when used for long periods in patients with high cholesterol levels, and to compare its activity to that of gemfibrozil.

Plasma alanine and lactate concentrations following glucose ingestion in normal and NIDDM subjects.

Conflicting evidence has been reported on the metabolic fate of glucose following oral ingestion. We measured the metabolic pattern of gluconeogenic substrates as alanine, predominantly produced by muscle, and lactate after an oral glucose load in ten normal subjects and in eighteen non-insulin dependent diabetes mellitus (NIDDM) subjects. Neither in normal or NIDDM subjects were significant increases in plasma alanine observed, whereas a significant increase in plasma lactate was observed at 60, 90 and 120 min after a glucose load. Although a similar behaviour in plasma alanine and lactate between normal and NIDDM subjects was found, in NIDDM significantly higher levels of plasma alanine and lactate were found at each time. From these observations we conclude: 1) when glucose is ingested under post-absorptive conditions, since plasma alanine levels do not change concurrently with lactate increase, muscle tissue does not play a predominant role in glucose disposal 2) after an oral glucose load, the pattern of gluconeogenic precursors (alanine and lactate) is similar in normal and NIDDM subjects 3) the main cause of fasting and post-prandial hyperglycemia in NIDDM subjects may be due to an overproduction of alanine as well as lactate.

[Changes in morning platelet aggregation in patients with peripheral obliterating arteriopathy after evening administration of picotamide]. / Modificazioni dell'aggregazione piastrinica mattutina in soggetti affetti da arteriopatia obliterante periferica dopo somministrazione serale di picotamide.

Platelets are involved in the progressive pathogenesis of atherosclerosis. It has been shown that there is usually an increase in platelet aggregation between 6 and 9 a.m.; in the present study. in 10 patients suffering from chronic occlusive arterial disease, the impedancemetric method was used to evaluate, in whole blood, platelet aggregation induced by ADP and collagen the day prior to and the day following the evening administration of 300 mg picotamide. Analysis of the data obtained shows, in accordance with the findings of other authors, in increase of platelet aggregation from 6 a.m. to 9 a.m. This increase is suppressed by the evening administration of the anti-aggregant.

Effects of defibrotide after oral and parenteral administration in patients with peripheral obliterative arterial disease (POAD).

Defibrotide (D) a polidesoxyribonucleotidic derivative provided with fibrinolytic and antithrombotic activity has already proven effective when administered by parenteral route in patients with peripheral obliterative arterial disease (POAD). Bioavailability studies gave evidence that the drug is absorbed by 50-70% when administered orally. Thus, aim of this trial was to evaluate whether the drug might exert similar clinical and biological effects after oral/parenteral dosing in a 2:1 ratio. This was a randomized cross-over study including 17 out patients with POAD (Leriche stage II). D was administered by oral (400 mg b.i.d.) and intramuscular route (200 mg b.i.d.), both treatments lasting 15 days. In basal conditions and at the end of both treatments the following evaluations were made: (1) absolute walking distance (tread mill); (2) Doppler ultrasonographic examination (Winsor index); (3) strain-gauge plethysmography (rest flow and peak flow). In addition in the same occasions plasma samples were collected for the assessment of plasminogen (chromogenic assay) and fibrinolytic activity (fibrin plates). Defibrotide administration was followed by a significant increase in walking distance both after oral and parenteral administration [basal conditions (IRL): 232.7 +/- 23.0 meters; oral: 273.1 +/- 28.1 m; i.m.: 277.9 +/- 26.8 m, p less than 0.01 - (IRA) basal conditions: 380.1 +/- 25.6; oral: 437.1 +/- 31.5 m; i.m.: 442.5 +/- 34.0 m, p less than 0.01] and by a significant increase in peak flow (basal conditions: 9.66 +/- 1.04; oral: 10.90 +/- 0.90; i.m.: 11.12 +/- 0.98, p less than 0.05), while Winsor index and rest flow were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of the efficacy and safety of pravastatin in primary hypercholesterolemia]. / Valutazione dell'efficacia e della sicurezza della pravastatina nelle ipercolesterolemie primitive.

Hypercholesterolemia can be a risk factor which engenders coronary heart disease. Today, it seems certain that lowering the cholesterolemia reduces this risk, especially if this reduction is referred to the cholesterol which is linked to the low density lipoprotein, called LDL. It has been demonstrated that the principle way to remove the LDL is by getting it into the hepatocyte through a specific membrane receptor, the research, therefore, has been developed with the aim of pharmacologically modifying the quota of intercellular cholesterol and consequently, in the modulation of the receptivity function by the interference of the LDL uptake, assisting a faster clearance. We can identify a new class of pharmacological drugs, that are the specific inhibitors of the HMGCoA reductase, fundamental enzime in the biosynthesis of cholesterol. This group of inhibitors has recently been enriched by the addition of a new molecule pravastatin. Our task has been to confirm the effectiveness and tolerability of pravastatin, administered for a prolonged period to patients with high levels of cholesterolemia; we have compared it with gemfibrozil, a well-known medicine which has hypocholesterolemic effects. In conclusion, our work, whilst emphasising the expediency of ipolipidic treatment, has undoubtedly proved, that 40 mg of pravastatin in a single evening dose, shows a high degree of efficiency, without side effects. Due to these factors, we can also say that pravastatin prevents, or really induces the regression, of atheroscherotic disease.

[Factor VII and cardiovascular risk in obese subjects]. / Fattore VII e rischio cardiovascolare negli obesi.

We investigated whether or not obesity is related to increased factor VII activity. We studied 70 obese subjects (aged 25 to 50 years, 25 males and 45 females, body mass index (BMI): mean +/- SD = 32.44 +/- 5.44) and 33 non-obese subjects (aged 25 to 50 years, 12 males and 21 females, BMI: mean +/- SD = 21.80 +/- 1.70). None of them were smokers or affected by hyperlipidemia, diabetes mellitus, impaired glucose tolerance or arterial hypertension. Factor VII activity was measured by the coagulometric method. We found higher factor VII activity in obese subjects (115.74 +/- 26.10%) than in healthy subjects (98.55 +/- 23.49%, p less than 0.005). Increased factor VII levels could determine a thrombophilic state involved in the genesis of cardiovascular accidents in obesity.

[Relations between overweight, thrombophilia and cardiovascular risk]. / Relazione tra sovrappeso corporeo, trombofilia e rischio cardiovascolare.

Seventy-one healthy subjects, aged 20 to 60, 19 males and 52 females, body mass index (BMI) 19 to 40, were enrolled in the study. None of them were smokers, or affected by hyperlipidemia, arterial hypertension or impaired glucose tolerance. We measured plasminogen activators inhibitor (PAI) activity, C-peptide levels, plasma fibrinolytic activity. We found a correlation between BMI and plasma fibrinolytic activity (r = -0.382, p less than 0.005), between BMI and PAI (r = 0.353, p less than 0.005), between BMI and C-peptide (r = 0.694, p less than 0.001) and between PAI and C-peptide (r = 0.404, p less than 0.02). Our data show a correlation between obesity and low fibrinolytic activity, probably due to high PAI levels. In obesity impaired fibrinolytic activity, maybe linked to hyperinsulinemia, could induce thrombophilic state.

Effect of indobufen on whole blood platelet aggregation recorded in the morning in patients with ischaemic heart disease.

Platelets are involved in the progression of coronary atherosclerosis as well as in the development of the acute precipitating event. Recently, it has been shown that normal subjects present increased platelet aggregation between 6.00 a.m. and 9.00 a.m.; epidemiological studies have shown a higher incidence of myocardial infarction between these times. This study evaluated, by an impedence method using whole blood, platelet aggregation induced by ADP (3 microM) and collagen (2 microM/ml). Measurements were made at 6.00 a.m., 9.00 a.m. and 12.00 noon, the day before and the day after evening administration of 200 mg indobufen, a platelet aggregation inhibitor, in 12 patients with ischaemic heart disease. Patients showed a significant increase of platelet aggregation between 6.00 a.m. and 9.00 a.m. which was inhibited by the prior evening administration of indobufen.

[Platelet aggregation in whole blood with the impedance method in subjects with non-complicated essential arterial hypertension]. / L'aggregazione piastrinica su sangue intero con metodo impedenzometrico nei soggetti portatori di ipertensione arteriosa essenziale non complicata.

Arterial hypertension is considered a major risk factor in atherosclerosis in the pathogenesis of which platelet activity plays a fundamental role. However the data in the literature on platelet function in arterial hypertension do not always agree. The present study was conducted on whole blood, using the impedance metering technique to assess platelet aggregation induced by ADP (10 pg) and collagen (2 mg/ml) in 15 patients with uncomplicated essential hypertension and 25 healthy controls. Analysis of the data shows a statistically significant difference between the aggregation curves of the hypertensive and the healthy subjects with excessive platelet aggregation in those suffering from uncomplicated arterial hypertension.