Giandomenico Bompiani

Coagulation, fibrinolysis and haemorheology in premenopausal obese women with different body fat distribution.

Recently waist/hip ratio (WHR), a marker of body fat distribution, has been described as a risk factor for cardiovascular disease (CVD). The aim of the present study was to evaluate the influence of body fat distribution on metabolic, haemostatic and haemorheological pattern in premenopausal obese women with different WHR. Fourty premenopausal obese women were subdivided into two groups, matched for age and body mass index (BMI): 20 women with abdominal obesity (WHR = 0.94 +/- 0.02) and 20 women with peripheral obesity (WHR = 0.77 +/- 0.03). Twenty nonobese women were recruited as control group. The abdominal obesity group had significantly higher blood glucose, triglycerides, total cholesterol, Apolipoprotein B and plasma insulin levels and lower high density lipoprotein (HDL) cholesterol and Apolipoprotein A1 levels than the control group. All the haemostatic (figrinogen, Factor VII, plasminogen activator inhibitor (PAI) activity and tissue plasminogen activator (t-PA) antigen (Ag) pre venous occlusion (VO)) and haemorheological parameters (haematocrit, whole blood filterability, blood and plasma viscosity) were significantly higher in the abdominal obesity group as compared to the control group. In contrast, mean values of t-PA (Ag) post VO were significantly lower in abdominal obese women. Moreover positive correlations between WHR and plasma insulin (r = 0.68, p < 0.05), between WHR and fibrinogen (r = 0.63, p < 0.05) and between WHR and PAI pre VO (r = 0.71, p < 0.05) and a negative correlation between WHR and t-PA (Ag) post VO (r = -0.55, p < 0.05) were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes induced by pravastatin treatment on hemostatic and fibrinolytic patterns in patients with type IIb hyperlipoproteinemia

Abstract A randomized, double-blind, parallel-group study of pravastatin versus placebo was carried out for 24 weeks in 20 patients with type IIb primary hyperlipoproteinemia. Total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, blood glucose, apolipoproteins (apo) A1 and B, and lipoprotein (a) (Lp[a]) levels were determined. A venous occlusion test was also performed in all patients. Pre- and postvenous occlusion tests were determined: tissue plasminogen activator antigen (t-PA[Ag]), plasminogen activator inhibitor (PAI) activity, factor VII, fibrinogen, plasminogen, and hematocrit. Compared with placebo, pravastatin significantly reduced total cholesterol, LDL cholesterol, apo B, and triglyceride levels, as well as significantly increased HDL cholesterol and apo A1 levels. A mild, statistically nonsignificant reduction in Lp(a) was observed in the patients treated with pravastatin. Compared with placebo, pravastatin significantly reduced factor VII, fibrinogen, plasminogen, and PAI activity levels before and after venous occlusion. A significant reduction of t-PA(Ag) at rest was found in patients treated with pravastatin, whereas there was no significant difference in t-PA(Ag) levels after venous occlusion. Our data confirm the well-known lipid-regulating effect of pravastatin and suggest a positive effect of pravastatin on the regulation of hemostatic and fibrinolytic systems in patients with type IIb hyperlipoproteinemia.

Immunoregulatory T-lymphocyte subset deficiency in newly diagnosed Type 1 (insulin-dependent) diabetes mellitus

SummaryHumoral and cell-mediated disorders in Type 1 (insulin-dependent) diabetes suggest that an imbalance of immunoregulatory T-cell subsets exists. In 23 newly diagnosed (onset < 3 months) and 21 long-standing Type 1 diabetic patients, T lymphocyte subsets were analyzed using monoclonal antibodies (OKT3, OKT4, OKT8, OKM1). The newly diagnosed patients showed a reduction with a significant difference from healthy controls in total T cells (OKT3+: 58.1 ±8.5% versus 70.7±8.0%), helper/inducer cells (OKT4+: 33.8 ±7.0% versus 47.1 ±8.3%), suppressor/cytotoxic cells (OKT8+: 18.5±7.3% versus 32 ± 6.8%) and monocytes (OKM1+: 11.5±3.8% versus 19.9±5.2%) (p< 0.001). The long-standing diabetic patients also revealed a low number of immunoregulatory T cells compared with control subjects, although to a lesser extent (p< 0.01–0.05). The helper/suppressor ratio (OKT4+/OKT8+) was higher in newly diagnosed patients than in control subjects (2.2±1.3 versus 1.5±0.3; p< 0.02). When compared with 95% tolerance limits in the control subjects, the reduction of OKT8+ cells in the newly diagnosed diabetic patients appeared more marked: the mean (18.5%) coincided with the lower limit of normal subjects (18.3%). Ten of the newly diagnosed Type 1 diabetic patients had a value below the normal lower limit. Our data point to the occurrence of different immunoregulatory abnormalities in newly diagnosed Type 1 diabetic patients, especially in OKT8+ and OKT4+ cells. The imbalance in T lymphocyte subsets is further proof of the role of cellular autoimmunity in the pathogenesis of the early phases of Type 1 diabetes.

Fibrinolysis in hypertriglyceridaemic subjects in response to venous occlusion.

We have measured various fibrinolytic and coagulation parameters (t-PA antigen, PAI, fibrinogen, plasminogen and factor VII) before and after 10 min of venous occlusion in 20 hypertryglyceridaemic subjects (twelve males and eight females, age 38 ± 4 years, body mass index 23 ± 1.5) and 20 healthy normal subjects, matched for sex (twelve males and eight females), age (37 ± 3.5 years) and body mass index (22.8 ± 1.4). At rest, t-PA:Ag, PAI, fibrinogen, plasminogen and factor VII were significantly (P < 0.005) higher in hypertriglyceridaemic subjects than in normal controls. After venous occlusion, the increase in all parameters except t-PA:Ag was more marked in the patient group than in the controls. Only the percentage increase in t-PA:Ag was higher in normal controls (358.8%) than in hypertriglyceridaemic subjects (91.9%). There was a positive correlation between serum triglycerides levels and PAI at rest (r = 0.72, P < 0.01) and a negative correlation between serum triglycerides levels and t-PA antigen after venous occlusion (r = −0.45, P < 0.05) suggesting an impairment of fibrinolysis in hypertriglyceridaemia.

Improvement of fibrinolysis and plasma lipoprotein levels induced by gemfibrozil in hypertriglyceridemia

A randomized double-blind study was carried out with gemfibrozil (600 mg b.i.d.) vs placebo in 20 patients (twelve males and eight females, age 52 +/- 3 years, BMI 24.2 +/- 0.4) suffering from primary hypertriglyceridemia (Fredricksons type IV). Each group was treated for a 12 week period with gemfibrozil (n = 10) or placebo (n = 10) patients) in a double-blind fashion. Total cholesterol, HDL-cholesterol (HDL-C) and its subfractions (HDL2-C and HDL3-C), blood glucose, Apolipoproteins A1 and B, fibrinogen, plasminogen, factor VII, t-PA:Ag and PAI activity pre- and post-venous occlusion (VO) were determined. In the gemfibrozil-treated group a significant decrease of total cholesterol and triglycerides and a significant increase of HDL-C and HDL2-C were found. During gemfibrozil treatment a significant reduction of factor VII, fibrinogen and plasminogen levels was also observed. After 12 weeks of treatment in the gemfibrozil group the release of t-PA:Ag in response to venous occlusion was significantly higher and plasma PAI activity was significantly lower than in placebo group. Moreover positive correlations between HDL cholesterol and t-PA:Ag post-VO (r = 0.56, P < 0.01) and between HDL2-C cholesterol and t-PA:Ag post-VO (r = 0.59, P < 0.01) and a negative correlation between triglycerides and t-PA:Ag post-VO (r = -0.65, P < 0.01) were found. The data obtained suggest that gemfibrozil, in addition to the well established lipid-regulating effect, appears to have a positive role in the regulation of reverse cholesterol transport and fibrinolytic system.

Effect of gemfibrozil treatment on fibrinolysis system in patients with hypertriglyceridemia

Abstract The effect of gemfibrozil on lipidic, coagulative, and fibrinolytic pattern was studied in 20 patients with primary type IV hyperlipoproteinemia. After a 4-week stabilization period during which administration of lipid-lowering drugs was stopped and an isocaloric diet (20% protein, 30% fat, and 50% carbohydrates) was prescribed, 20 patients (12 men and 8 women; mean age, 38 ± 4 years; body mass index, 23.4 ± 1.5) suffering from primary hypertriglyceridemia were included in this study and treated for a 12-week period with gemfibrozil (600 mg BID). Every 4 weeks the following parameters were checked: glycemia, triglycerides, total cholesterol, high density lipoprotein-cholesterol, total cholesterol/HDL-cholesterol ratio, apolipoproteins A–I and B, tissue plasminogen activator antigen, plasminogen activator inhibitor activity, fibrinogen, plasminogen, antithrombin III, protein C, factor VII, and inopeptide A. The data obtained suggest that gemfibrozil, in addition to the well established lipid-regulating effect, appears to have a positive role in the regulation of hemostasis and fibrinolytic system.

Fibrinolytic effect of gemfibrozil versus placebo administration in response to venous occlusion

Abstract Impact of hypertriglyceridemia on atherosclerotic vascular disease and thromboembolic events is recently emphasized by primary prevention studies on the development of coronary artery disease. A randomized double-blind study was carried out with gemfibrozil (600 mg b.i.d.) versus placebo in 20 patients (12 males and 8 females, age 52±3 years, BMI 24.2±0.4) suffering from primary hypertriglyceridemia (Fredricksons type IV). After a 4-week stabilization period in which administration of lipid-lowering drugs was stopped and an isocaloric diet was prescribed, patients were randomized into two groups. Each group was treated for a 12 week period with gemfibrozil (10 patients) or placebo (10 patients) in a double-blind fashion. Every 4 weeks triglycerides, total cholesterol, HDL-cholesterol, blood glucose and Apolipoproteins A1 and B were determined. At baseline and at the end of the treatment period a venous occlusion test was performed in all subjects. Before and after 10 min venous stasis were measured: t-PA antigen, PAI activity, fibrinogen, plasminogen, Factor VII and haematocrit. In the gemfibrozil-treated group a significant decrease of triglycerides and a significant increase of HDL-C was found. During gemfibrozil treatment a significant reduction of Factor VII, fibrinogen and plasminogen levels either before or after venous occlusion was also observed. After 12 weeks of treatment in the gemfibrozil group the release of t-PA in response to venous occlusion was significantly higher and plasma PAI activity was significantly lower than in placebo group, suggesting a profibrinolytic effect of the drug.

Placental lactogen, progesterone, total estriol and prolactin plasma levels in pregnant women with insulin-dependent diabetes mellitus

Fifteen insulin-dependent diabetic (Whites class B-C) and 10 healthy pregnant women were examined from the 12th to the 36th wk. Every 4 wk, a blood sample was drawn to determine total estriol, progesterone, placental lactogen and prolactin. Throughout the pregnancy, total estriol and progesterone in diabetic and non-diabetic women are very similar. On the contrary, the PRL levels are constantly lower in diabetic pregnant women, even though the difference is statistically significant only for the 24th wk determination. The hPL level is instead significantly lower in diabetic pregnant women at the 12th, 20th, 24th, 32nd and 36th wk. A negative correlation exists between the hPL value and the mean blood glucose level, performed the same day as the hormonal test. This correlation is statistically significant at the 12th, 16th, 20th, 28th and 36th wk. No significant difference is found between the two groups examined for the delivery week, the placental weight, the birth weight and the fetal body weight index. To conclude, while estriol and progesterone are not affected by the higher variability of glucose levels during pregnancy in diabetics, compared to normals, hPL and perhaps also PRL may be influenced by the mild hyperglycemia consequent to diabetes.

Insulin resistance and endogenous digoxin-like factor in obese hypertensive patients with glucose intolerance.

Hypertensive obese subjects with glucose intolerance have hyperinsulinaemia, insulin resistance and intracellular cation imbalance resulting in increased sodium content. The aim of our study was to assess in these patients plasma levels of endogenous digoxin-like factor (EDLF), an inhibitor of the sodium-pump mechanism. We studied 14 hypertensive and 12 normotensive subjects with obesity and glucose intolerance for fasting blood glucose, and plasma insulin, C-peptide and EDLF levels: the two groups were matched for age and BMI and were studied after a 2-week wash-out period from hypotensive drugs. Compared with normotensives, hypertensive subjects had higher plasma insulin levels, a greater immunoreactive insulin/C-peptide ratio, a lower glucose/insulin ratio and higher plasma EDLF levels. Our results confirm that among obese people with glucose intolerance, hypertensives are more hyperinsulinaemic and insulin-resistant than normotensives and indicate that the intracellular cation imbalance in these patients may be attributable, at least in part, to EDLF.

Study on maternal, fetal and amniotic prolactin in gestational diabetic women, at term

SummaryIn order to determine whether prolactin secretion was affected in diabetic pregnancy, maternal, fetal and amniotic fluid prolactin (PRL) concentrations were measured in gestational non treated diabetic women at parturition. Amniotic fluid PRL levels, though higher than those in maternal and fetal serum, were significantly lower than those of the controls (p<0.005); no case of respiratory distress syndrome or congenital malformation was found at birth.