Long-term anti-tumour necrosis factor therapy reverses the progression of carotid intima-media thickness in female patients with active rheumatoid arthritis.

The objective of the study is to evaluate the effect of TNF inhibition on carotid thickness over a 2-year period. 144 women with RA diagnosed according to ACR criteria, without clinical evidence of cardiac and/or vascular disease were enrolled and compared with 78 matched controls. All patients received methotrexate (15­20 mg weekly) for 3 months. Responders (n = 79) continued to be treated with methotrexate, non-responders (n = 40) moved to methotrexate plus a TNF alpha antagonist. Echosonographic studies of carotids were obtained before and after 2-year follow-up. A significant decrease of ca-IMT was observed in anti-TNF-treated patients (P < 0.001); on the other hand, no significant variation of ca-IMT was observed after 2 years in MTX-treated patients. Our study indicates that anti-TNF blocking agents, but not methotrexate, are capable of reducing IMT of carotid arteries in female RA patients in a 2-year follow-up.

Effect of dual blockade of renin-angiotensin system on TGFbeta1 and left ventricular structure and function in hypertensive patients.

The effects of 24 weeks losartan and ramipril treatment, both alone and in combination, on left ventricular mass (LVM), circulating transforming growth factor beta1 (TGFbeta1), procollagen type I (PIP) and III (PIIIP), have been evaluated in hypertensive (HT) patients. A total of 57 HT with stage 1 and 2 essential hypertension were included. After 4 weeks run in, a randomized double-blind, three arms, double dummy, independent trial was used. All HT patients were randomly allocated to three treatment arms consisting of losartan (50 mg/daily), ramipril (5 mg/ daily) and combined (losartan 50 mg/daily + ramipril 5 mg/daily) for 24 weeks. TGFbeta1, PIP and PIIIP, LVM, LVM/h(2.7) and other echocardiographic measurements, blood urea nitrogen, creatinine and clearance and potassium were determined after run in and after 24 weeks. All groups were comparable for gender, age, body mass index, blood pressure and LVM. The prevalence of baseline left ventricular hypertrophy (LVH) was not significantly different among three groups. At the end of treatment, a significant (P<0.05) reduction in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), TGFbeta1, PIP, PIIIP, LVM and LVM/h(2.7) was observed in all groups. The absolute and percent reduction in TGFbeta1 and LVM/h(2.7) were significantly higher in combined than losartan or ramipril groups and also in HT patients with LVH. No significant change in absolute and percent reduction of SBP, DBP and MBP were found. Our data indicate an additional cardioprotective effect of dual blockade of renin-angiotensin in HT patients.

Immunoinflammatory activation during the acute phase of lacunar and non-lacunar ischemic stroke: association with time of onset and diabetic state.

Several studies have stressed the involvement of inflammation in the pathophysiology of acute brain ischemia, but the role of immunoinflammatory activation in diabetic stroke patients has not yet been fully evaluated. The aim of our study was to evaluate immunoinflammatory activation of acute phase of stroke in relation to time of symptoms onset, diabetic state and diagnostic subtype. We enrolled 60 patients (32 diabetics; 28 non- diabetics) with acute ischemic stroke and 123 subjects without acute ischemic stroke, and measured levels of IL-1beta, TNF-alpha IL-6, IL-10, E-selectin, P-selectin, sICAM-1, sVCAM-1, VWF, 24-72 h and 7-10 days after stroke onset; TPA, PAI-1 plasma levels at 24-72h. Our stroke patients exhibited significantly higher plasma levels of cytokines, selectins, adhesion molecules and PAI-1, and diabetic stroke patients exhibited higher plasma levels of PAI-1 in comparison with non-diabetic ones. Lacunar strokes in comparison with those non-lacunar exhibited significantly lower levels of TNF-alpha and IL1-beta P-selectin and ICAM-1. Moreover, diabetic patients with lacunar strokes exhibited a minor grade of immunoinflammatory activation of the acute phase at 24-72h and 7-10 days after stroke onset. The minor grade of immunoinflammatory activation of patients with lacunar strokes, particularly diabetic ones, could be related to the minor extension of the infarct size, owing to the typical microvascular disease of diabetic subjects which could also explain the reported better outcome of this subtype of ischemic stroke.

Effects of moderate Sicilian red wine consumption on inflammatory biomarkers of atherosclerosis.

OBJECTIVE: The aim of the study is to evaluate the effect of moderate Sicilian red wine consumption on cardiovascular risk factors and, in particular, on some inflammatory biomarkers. METHODS: A total of 48 subjects of both sexes who were nondrinkers or rare drinkers of moderate red wine were selected and randomly subdivided into two groups assigned to receive with a crossover design a Sicilian red wine (Nero d'Avola or Etna Torrepalino) during meals: Group A (n = 24), in whom the diet was supplemented for 4 weeks with 250 ml/day of red wine, followed by 4 weeks when they returned to their usual wine intake; and Group B (n = 24), in whom the usual wine intake was maintained for 4 weeks, followed by 4 weeks when the diet was supplemented with 250 ml/day of red wine. The following were values measured in all tests: blood glucose, total and HDL-cholesterol and triglycerides, LDL-cholesterol, LDL/HDL ratio, apolipoproteins A1 and B, Lp(a), plasma C-reactive protein, TGFbeta1, D-Dimer, Factor VII , PAl Ag, t-PA Ag, fibrinogen, oxidized LDL Ab, total plasma antioxidant capacity. RESULTS: At the end of the red wine intake period, LDL/HDL, fibrinogen, factor VII, plasma C-reactive protein and oxidized LDL Ab were significantly decreased, while HDL-C, Apo A1,TGFbeta1, t-PA, PAI and total plasma antioxidant capacity were significantly increased. CONCLUSIONS: Our results show a positive effect of two Sicilian red wines on many risk factors and on some inflammatory biomarkers, suggesting that a moderate consumption of red wine in the adult population is a positive component of the Mediterranean diet.

One-year atorvastatin treatment in hypercholesterolemic patients with or without carotid artery disease.

AIM: Statins are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of premature cardiovascular events including myocardial infarction, stroke, and surgical revascularization. METHODS: A 1-year open-label study was conducted to test the efficacy and tolerability of Atorvastatin titrated to the target, in proven FH patients and to evaluate certain inflammatory parameters. One hundred and two FH patients (44 men and 58 women; mean age 58.7+/-3.6 years) were included in the study. After evaluation using the B-mode duplex scanning system of extracranial carotid arteries, the patients were divided into two groups: Group 1 (15 men, 25 women) with carotid plaques or intima-media thickness (IMT) greater than 0.95 mm and Group 2 (30 men, 32 women) without carotid plaques or IMT less than 0.95 mm. After a 6-week hypolipemic diet phase all the patients were treated with atorvastatin titrated to achieve a low density lipoprotein (LDL-C) <100 mg/dL. Patients with carotid lesions were also submitted to an oral fixed dose of aspirin 100 mg/day. RESULTS: In patients without and with carotid lesions, atorvastatin treatment (mean dosage: 23.5 mg/day) reduced triglycerides by 8.7% (P<0.005) and 10.6% (P<0.005), total cholesterol by 41.5% (P<0.005) and 42.6% (P<0.005), LDL-C by 55.8% (P<0.005) and 57.3% (P<0.005) and apolipoprotein B by 38.3% (P<0.005) and 37.2% (P<0.005) respectively, and increased the mean levels of high density lipoprotein cholesterol (HDL-C) by 8.7% (P<0.005) and 11% (P<0.005), and apolipoprotein A-I by 3.2% (P<0.05) and 3.3%, respectively. In both groups of patients the mean decrease (52 weeks) of fibrinogen was 19.8% (P<0.005) and 10.4% (P<0.005), respectively and of high sensitivity C-reactive protein (hs-CRP), 36.2% (P<0.005) and 38.2% (P<0.005), respectively. No variation of the parameters of safety and clinical tolerability of the drugs administered was observed. No variation in hematocrit in the patients taking ASA treatment was observed. CONCLUSIONS: In FH patients, 1-year atorvastatin treatment titrated to the target (LDL-C <100 mg/dL) was well tolerated and improved serum lipid levels and inflammatory parameters.

Inhibition of thromboxane biosynthesis by triflusal in type 2 diabetes mellitus.

Triflusal is an antiplatelet drug related to aspirin, with different pharmacological properties and a lower haemorrhagic risk. We aimed at comparing their effects on platelet and endothelial activation in type 2 diabetes mellitus (T2DM). In a randomized, double-blind, parallel group study, we compared the effects of three daily regimens (300, 600, and 900 mg) of triflusal, and aspirin (100mg/day) on urinary 11-dehydro-thromboxane (TX)B(2), index of in vivo platelet activation, ex vivo platelet function using the analyzer PFA-100, plasma von Willebrand factor (vWF), P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and serum nitrite and nitrate (NO(2)(-)+NO(3)(-)) in 60 T2DM patients. Triflusal induced a dose-dependent reduction in 11-dehydro-TXB(2) and a prolongation of closure time in the presence of collagen plus epinephrine (Coll/Epi-CT). The effects of the highest triflusal dose were not different from those of aspirin. The closure time in the presence of collagen plus ADP (Coll/ADP-CT), ICAM-1, VCAM-1, and NO(2)(-)+NO(3)(-) were not modified either by triflusal or aspirin. Plasma P-selectin and vWF were reduced by triflusal but not by aspirin. In T2DM triflusal causes a profound inhibition of platelet TXA(2) biosynthesis in vivo, acting on different targets involved in the platelet-endothelial cell interactions.

Left ventricular filling abnormalities and obesity-associated hypertension: relationship with overproduction of circulating transforming growth factor beta1.

This study has been designed to evaluate the relationship among transforming growth factor beta1 (TGFbeta1) and some measurements of diastolic function in a population of hypertensive subjects with normal left ventricular ejection fraction. We studied 67 hypertensive outpatients who according to their BMI levels were subdivided into three groups: lean (L), overweight (OW) and obese (OB) hypertensives (HT). Circulating TGFbeta1 and M- and B-mode echocardiography was determined. All hypertensives were further subgrouped, according to European Society of Cardiology Guidelines, into two subsets of patients with normal diastolic function or with diastolic dysfunction. Prevalence of left ventricular hypertrophy (LVH) was determined in all the groups. TGFbeta1, left ventricular mass (LVM), LVM/h(2.7), E-wave deceleration time and isovolumic relaxation time (IVRT) were significantly (P < 0.005) higher and E/A velocity ratio was significantly (P < 0.05) lower in OW-HT and OB-HT than in L-HT. Prevalence of LVH was significantly higher (P < 0.03) in group OB-HT than in L-HT. TGFbeta1 (P < 0.004), LVM/h(2.7) (P < 0.001) and prevalence of LVH were (P < 0.01) significantly higher in hypertensives with diastolic dysfunction than hypertensives with normal diastolic function. TGFbeta1 levels were positively correlated with BMI (r = 0.60; P < 0.0001), LVM/h(2.7) (r = 0.28; P < 0.03), IVRT (r = 0.30; P < 0.02) and negatively with E/A ratio (r = -0.38; P < 0.002) in all HT. Multiple regression analysis indicated that TGFbeta1, BMI and IVRT were independently related to E/A ratio explaining 71% of its variability (r = 0.84; P < 0.0001). This relationship was independent of LVH, age and HR suggesting that TGFbeta1 overproduction may be considered a pathophysiological mechanism in the development of left ventricular filling abnormalities in obesity-associated hypertension.

Pravastatin vs gemfibrozil in the treatment of primary hypercholesterolemia. The Italian Multicenter Pravastatin Study I.

This study compared the efficacy and safety of pravastatin and gemfibrozil in the treatment of primary hypercholesterolemia. Three hundred eighty-five outpatients from 13 lipid clinics in Italy participated in this randomized double-blind study. Patients were assigned to receive either 40 mg once daily of pravastatin or 600 mg of gemfibrozil twice daily after an initial diet lead-in period. After 24 weeks, mean reductions from baseline values of plasma total and low-density lipoprotein cholesterol were, respectively, 23% and 30% with pravastatin and 14% and 17% with gemfibrozil. Significant lipid-lowering effects were noted within 4 weeks. Apolipoprotein B decrease was 21% with pravastatin and 13% with gemfibrozil. A statistically significant increase of high-density lipoprotein cholesterol of 5% was achieved with pravastatin compared with a 13% increase for gemfibrozil. Serum triglyceride values decreased 5% with pravastatin and 37% with gemfibrozil. Familial and polygenic hypercholesterolemic patients were also examined separately. Pravastatin effectiveness in reducing low-density lipoprotein cholesterol was greater by 6% in polygenic than in familial hypercholesterolemic patients. Treatment for 25 patients (eight treated with pravastatin and 17 treated with gemfibrozil) was discontinued during the study. The incidence of clinical symptoms and laboratory alterations was low for both treatment groups. Pravastatin and gemfibrozil were well tolerated, but pravastatin was significantly more effective in reducing total and low-density lipoprotein cholesterol levels in primary (either familial or polygenic) hypercholesterolemias than gemfibrozil.

Effects of heparin treatment on hemostatic abnormalities in obese non-insulin-dependent diabetic patients.

This study was conducted to identify the mechanisms responsible for coagulative and fibrinolytic alterations and to study the effects of a short-term treatment with low-dose heparin on hemostatic abnormalities in obese non-insulin-dependent diabetes mellitus (NIDDM) patients. Four groups of age- and sex-matched patients were studied: (1) lean nondiabetic subjects (n = 30) with a body mass index (BMI) less than 25 kg/m2 (lean control subjects), (2) obese nondiabetic subjects (n = 30) with a BMI greater than 30 kg/m2 (obese control subjects), (3) lean NIDDM patients (n = 30), and (4) obese NIDDM patients (n = 30). All subjects were tested on the following parameters: fibrinogen, factor VII, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT), tissue plasminogen activator (t-PA) antigen (Ag) before and after venous occlusion (VO), and plasminogen activator inhibitor type-1 (PAI-1) activity pre- and post-VO. In addition, all these parameters were evaluated in obese NIDDM patients after 10 days of treatment with a single dose of 12,500-U/d subcutaneous calcium heparin and after a 10-day washout period. At baseline, obese nondiabetic subjects, lean NIDDM patients, and especially obese NIDDM patients displayed significantly (P < .01) higher levels of fibrinogen, factor VII, F1 + 2, TAT, t-PA(Ag) pre-VO, and PAI-1 pre- and post-VO and significantly (P < .01) lower levels of t-PA(Ag) post-VO. In obese NIDDM patients treated with heparin fibrinogen, factor VII, F1 + 2, TAT, t-PA(Ag) pre-VO, and PAI-1 pre- and post-VO levels significantly (P < .01) decreased and t-PA(Ag) post-VO levels significantly (P < .01) increased at the end of treatment. Our findings demonstrate in obese nondiabetic subjects, lean NIDDM patients, and especially obese NIDDM patients the hemostatic abnormalities contributing to an enhanced risk of thrombotic complications. We conclude that in obese NIDDM patients, short-term treatment with heparin may reduce this thrombophilic state and have a potential benefit in the progression of diabetic microvascular and macrovascular disease and needs further investigation.

Hemostatic function in young subjects with central obesity: relationship with left ventricular function.

This study was designed to evaluate coagulation and fibrinolysis activity and their relationship with left ventricular function in young obese subjects with central fat distribution. We assessed coagulation and fibrinolysis activity by evaluation of factor VII activity, fibrinogen and plasminogen, plasminogen activator inhibitor (PAI), and tissue plasminogen activator antigen basally (tPA1) and after venous occlusion (tPA2). These measures were evaluated in young (< 40 years) obese subjects with central fat distribution (n = 19) and in comparable lean subjects (n = 20). Blood glucose, triglycerides, total and high-density lipoprotein (HDL) cholesterol, apolipoprotein (apo) A1 and apo B, fasting immunoreactive insulin, and lipoprotein(a) levels were also measured by current methods. Left ventricular ejection fraction (LVEF) and peak filling rate (PFR) determined by radionuclide angiocardiography and left ventricular mass (LVM) and LVM indexed for body height (LVM/H) determined by echocardiographic study were calculated. Central obesity was evaluated by the waist to hip ratio (WHR) according to the criteria of the Italian Consensus Conference of Obesity. Factor VII (P < .001), fibrinogen (P < .001), plasminogen (P < .001), PAI activity (P < .001), tPA1 (P < .02), fasting blood glucose (P < .01), apo B (P < .02), and immunoreactive insulin (P < .01) were significantly higher in obese than in lean subjects. In contrast, HDL cholesterol (P < .01), tPA2 (P < .01), LVEF (P < .001), and PFR (P < .02) were significantly lower in obese than in lean subjects. In all subjects, WHR correlated directly with fibrinogen and inversely with tPA2; LVEF correlated inversely with tPA1, PAI, and fibrinogen; and PFR correlated inversely with factor VII activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Oxidation of melatonin by oxoferryl hemoglobin: a mechanistic study.

Reaction of melatonin with the hypervalent iron centre of oxoferryl hemoglobin, produced in aqueous solution from methemoglobin and H2O2, has been investigated at 37 degrees C and pH 7.4, by absorption spectroscopy. The reaction results in reduction of the oxoferryl moiety with formation of a heme-ferric containing hemoprotein. Stopped-flow spectrophotometric measurements provide evidence that the reduction of oxoferryl-Hb by melatonin is first-order in oxoferryl-Hb and first-order in melatonin. The bimolecular reaction constant at pH 7.4 and 37 degrees C is 112 +/- 1.0 M(-1) s(-1). Two major oxidation products from melatonin have been found by gas chromatography-mass spectroscopy: the cyclic compound 1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-3a-hydroxypyrrolo[2,3-b]indole (cyclic 3-hydroxy-melatonin), and N-acetyl-N'-formyl 5-methoxykynuramine (AFMK). The percentage yield of the two major products appears dependent on the ratio [oxoferryl-Hb]:[melatonin]--the higher the ratio the higher the yield of AFMK. The observed stoichiometry oxoferryl-Hb(reduced):melatonin(consumed) is 2, when the ratio [oxoferryl-Hb]:[melatonin] is 1:1, but appears >2 at higher molar ratios. The reduction of the hypervalent iron of the oxoferryl moiety may be consistent with an oxidation of melatonin by two one-electron steps.

Studies in organic mass spectrometry. Part 24dagger electron ionization mass spectra of some aryl(2-nitrobenzo

The main fragmentation routes of eighteen title compounds and of three 5-chloro derivatives have been investigated with the aid of linked scan (B/E = constant) spectrometry, accurate mass measurements and deuterium labelling. Copyright 1999 John Wiley & Sons, Ltd.

Relationship between transforming growth factor beta1 and progression of hypertensive renal disease.

In this study the role of circulating transforming growth factor beta1 (TGFbeta1) on progression of renal hypertensive disease has been investigated. Fifty consecutive outpatients with essential hypertension were enrolled and divided into three groups, according to their urinary albumin excretion (UAE). Group A comprised 10 hypertensives with UAE 20 < 300 mg/24 h (microalbuminuric group); Group C encompassed 19 hypertensives with UAE >or= 300 mg/24 h (proteinuric group). In all patients UAE by immunonephelometric assay, circulating TGFbeta1 by a solid phase specific sandwich ELISA technique, BUN and creatinine by routine laboratory methods were determined. In addition, left ventricular telediastolic internal diameter, interventricular septum diastolic (IVSTd), posterior wall thickness, total and normalised to height(2.7) left ventricular mass, relative wall thickness and left ventricular ejection fraction by M-B Mode echocardiography were calculated. Our results indicated that TGFbeta1 levels were significantly (P < 0.05) higher in Group B and C than Group A and in Group C than Group B. In addition IVSTd values were significantly (P < 0.05) higher in both Group B and C than Group A. An evident, but not significant, higher prevalence of subjects with left ventricular hypertrophy were observed in Group C as compared with other groups. In all hypertensive subjects TGFbeta1 correlated directly with UAE (P < 0.0001) but not with BMI, LVM/h(2.7) and mean blood pressure. Our data indicated that TGFbeta1 might be considered a useful marker to evaluate the severity and progression of hypertensive renal disease. Additional long-term clinical data are needed to evaluate whether inhibition of TGFbeta1 system may prolong the time to the ESRD in hypertensive patients.

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.

Elevated levels of lipoprotein (a) in patients suffering from myocardial infarction with carotid atherosclerotic lesions.

The aim of the present study was to evaluate metabolic, coagulation and fibrinolytic parameters in 45 patients [31 men, 14 women, aged 56.5 +/- 3.5 years (mean +/- SD)] who had suffered myocardial infarction more than 6 months earlier, with or without carotid atherosclerotic lesions. After the extracranial carotid arteries had been evaluated using a B-mode Duplex scanning system, patients were subdivided into two groups: group 1 (n = 20) with carotid plaques or measurable intima-media thickness; and group 2 (n = 25) without carotid plaques or measurable intima-media thickness. Twenty-two age- and sex-matched subjects were recruited as controls (group 3). Groups 1 and 2 displayed significantly higher levels of total cholesterol, apolipoprotein B, human autoantibodies against oxidised low-density lipoprotein and the c fraction of the third component system, and significantly lower levels of high-density lipoprotein cholesterol and apolipoprotein A1 than group 3. However, serum levels of triglyceride and lipoprotein (a) were significantly higher in group 1 than in the control group. Moreover, groups 1 and 2 displayed significantly higher levels of factor VII, fibrinogen, fragment 1+2, thrombin-antithrombin complex and plasminogen activator inhibitor after venous occlusion, and significantly lower levels of tissue-type plasminogen activator after venous occlusion than group 3. Significantly higher levels of tissue-type plasminogen activator and plasminogen activator inhibitor before venous occlusion were observed in groups 1 and 2 and significantly lower levels of antithrombin III, protein C and protein S were observed in group 1 compared with the controls. Patients were also analysed according to levels of lipoprotein (a). The lowest levels of tissue-type plasminogen activator after venous occlusion and the highest levels fragment 1 + 2, the c fraction of the third component system, and plasminogen activator inhibitor after venous occlusion were observed in patients with the highest levels of lipoprotein (a). Our data demonstrate an activation of coagulation and deficient fibrinolysis in survivors of myocardial infarction, particularly in those with associated carotid atherosclerotic lesions. We speculate that this thrombophilic state may play a key role in the pathogenesis of atherosclerotic vascular disease and thromboembolic complications.

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 (Fredrickson's 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.

Spectrophotometric investigation of the binding of vitamin E to water-containing reversed micelles.

The distribution constants of vitamin E partitioned between apolar organic phase and water-containing reversed micelles of sodium bis (2-ethylhexyl) sulfosuccinate (AOT), didodecyldimethylammonium bromide (DDAB), soybean phosphatidylcholine (lecithin) and tetraethylene glycol monododecyl ether (C12E4) have been evaluated by a spectrophotometric method. The results suggest that in the presence of domains from apolar organic solvent to surfactant and to water, vitamin E is partitioned between the micellar palisade layer and the organic solvent and also that its binding strength to reversed micelles depends mainly by specific interactions between the head group of vitamin E and that of the surfactant. Moreover, in addition to the advantageous interactions between vitamin E and water, the dependence of the distribution constants upon the molar ratio R (R=[water]/[surfactant]) indicates a competition between water and vitamin E for the binding sites at the water/surfactant interface. The biological implications of the preferential location and confinement of vitamin E in water-containing reversed micelles are discussed.

Evaluation of cardiovascular risk factors in overweight and obese subjects.

Twenty obese subjects (Males = 8, Females = 12; average age = 39.5 +/- 2.5 years; B.M.I. = 36.2 +/- 2.5), 20 overweight subjects (Males = 8, Females = 12; average age = 38.5 +/- 2 years; B.M.I. = 28.8 +/- 0.4) and 20 non obese healthy subjects as controls, matched for sex and age (Males = 8, Females = 12; average age = 37.5 +/- 2 years; B.M.I. = 22.4 +/- 0.8) were selected. We determined: blood glucose, triglycerides, total cholesterol, HDL-cholesterol, Apolipoproteins A1 and B, Factor VII, fibrinogen and plasminogen. Before and after a venous occlusion test were also measured: t-PA Antigen, PAI activity and haematocrit. Metabolic, coagulative and fibrinolytic pathological changes were observed in overweight and obese subjects and the interaction of these risk factors may contribute to the pathogenesis of atherosclerosis vascular disease and to the high rate of thromboembolic events reported in obesity.

Changes induced by gemfibrozil on lipidic, coagulative and fibrinolytic pattern in patients with type IV hyperlipoproteinemia.

A short term open study (90 days) was carried out with Gemfibrozil in patients (n = 10) suffering from type IV hyperlipoproteinemia. For the whole observation period (120 days) the patients followed a standard diet. Every 30 days the following parameters were checked: total cholesterol, serum triglycerides, HDL-C and its fractions (HDL2-C and HDL3-C), apolipoprotein A1 and B, glucose, fibrinogen, plasminogen, euglobulin lysis time, antithrombin III, alpha-2-antiplasmin and PTT. The administration of the drug caused a reduction of serum triglycerides by 39.5%, an increase of HDL-C by 16.2% together with a significant increase of cholesterol bound to HDL2 (+27.6%). A significant increase was also noticed for the mean levels of apolipoprotein A1 (+19.8%), confirming thus the antidislipidemic effect of the drug. Significant reductions were also found in the mean levels of fibrinogen and alpha-2-antiplasmin together with a return to normality of mean values of antithrombin III and of the euglobulin lysis time. The effect on the lipid, haemocoagulative and fibrinolytic parameters shows that the administration of Gemfibrozil causes favourable changes both on the hyperlipoproteinemic pattern and on the thrombophilic state present in these patients.