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Background: Findings from epidemiologic and autopsy studies suggest that the offspring of patients with premature coronary disease may be at increased risk for atherosclerosis. We undertook a study to determine whether changes in brachial-artery reactivity and thickness of the carotid intima and media, two markers of early atherosclerosis, are present in adolescents and young adults with a parental history of premature myocardial infarction., Methods: We enrolled 40 healthy young people whose parents had had premature myocardial infarction (48 percent male; mean [+/-SD] age, 19.0+/-5.2 years) and 40 control subjects who were matched with the first group according to age and sex. All the subjects underwent high-resolution B-mode ultrasound examinations for the measurement of the brachial-artery vasodilatory response after arterial occlusion (i.e., reactive hyperemia) and the intima-media thickness of the distal common carotid arteries. Lipid profiles, blood pressure while at rest, body-mass index, and smoking status were also determined., Results: As compared with the control subjects, the offspring of patients with premature myocardial infarction had lower flow-mediated reactivity of the brachial arteries (5.7+/-5.0 percent, vs. 10.2+/-6.6 percent in the control subjects; P=0.001) and greater mean intima-media thickness of the common carotid artery (0.49+/-0.08 mm, vs. 0.44+/-0.07 mm in the control subjects, P=0.004). In the subjects with a parental history of premature myocardial infarction, an inverse association was found between brachial-artery reactivity and carotid intima-media thickness (r=-0.46, P=0.003). In a conditional logistic-regression analysis, both brachial-artery reactivity and carotid intima-media thickness were significantly and independently correlated with a parental history of premature myocardial infarction., Conclusions: Structural and functional changes are present at an early age in the arteries of persons with a parental history of premature myocardial infarction.

To investigate the possible regulating role of omega-6 and of omega-3 fatty acids on platelet adhesiveness, we randomised 60 volunteers into three groups to take 20 ml (equivalent to 0.3 g omega-6, 3.6 g omega-3; omega-6/omega-3 ratio 0.1) per day of a fish oil supplement, or to take 25 g (equivalent to 1.5 g omega-6, 0.5 g omega-3; omega-6/omega-3 ratio 3) per day of a soy lecithin supplement, or to continue on their usual diet without any supplement (control group) for a period of 15 days. Platelet adhesion on fibrinogen-coated 96-well microtitre plates was evaluated in the resting condition and after stimulation with 2 microM ADP or 0.02 U/ml thrombin. Compared to the values before the experimental period, the fish oil group showed a significant reduction in stimulated adhesion (with ADP: from 18.8% to 15.6%, p<0.01; with thrombin: from 24.4% to 20.8%, p<0.005), whereas no difference was noted in the resting condition (from 3.6% to 3.5%, NS). In the soy lecithin group, platelet adhesion was increased in all test conditions (with ADP: from 18.7% to 23.2%, p<0.001; with thrombin: from 24.0% to 29.9% p<0.001; resting: from 3.5% to 6.6%, p<0.001). No significant changes were observed in the control group. A good correlation was found between platelet adhesion data and the changes in the platelet fatty acid omega-6/omega-3 ratio caused by the different supplementations. Our results indicate an inhibitory effect of fish oil rich in omega-3 fatty acids on stimulated human platelet adhesiveness and a stimulatory effect of soy lecithin rich in omega-6 fatty acids on resting and stimulated adhesion. They suggest moreover that the omega-6/omega-3 ratio is a determinant of platelet adhesion.

Background and Purpose: Arterial hypertension is associated with structural changes in the cardiovascular system. In hypertensives, a relationship has been found between left ventricular hypertrophy and carotid wall thickness, whereas the association with atherosclerotic plaque is less defined. The aim of this study was to evaluate the occurrence and severity of carotid atherosclerosis in hypertensive patients with or without left ventricular hypertrophy (LVH)., Materials and Methods: We studied 122 hypertensive subjects (62 men and 60 women), aged 60.1 +/- 12.1. Subjects were considered to have left ventricular hypertrophy if their left ventricular mass index (LVMI) at echocardiography exceeded 110 g/m2 in women and 135 g/m2 in men. Carotid intima-media thickness (IMT), external diameter and atherosclerotic plaques were evaluated by high resolution echo-color Doppler., Results: IMT in both common carotid and bifurcation was significantly greater in hypertensives with LVH (p < 0.01), whereas external diameter did not differ significantly in the two groups. Increased presence (73.4 vs 32.8%) and severity (18.7 vs 5.2% for stenosis > 40%) of atherosclerotic plaque were found in the hypertrophic group. A weak but significant association was present among left ventricular mass index, ventricular wall thicknesses and carotid intima-media thickness, and plaque., Conclusions: In asymptomatic hypertensive subjects, LVH is associated with an increased risk of plaque formation and progression. Vascular hypertrophy may represent a distinct prognostic factor in hypertension and the association of cardiac and vascular hypertrophy may identify a group at high risk of future cardiovascular events.

Fifty-seven healthy volunteers matched for sex and age were subdivided in 3 groups and their usual Western diets were supplemented according to three different protocols: group 1, fish oil supplement (20 ml/day); group 2, soybean phosphatidylcholine (PC) (25 g/day) and group 3, no supplementation (control group). After 2 weeks several important modifications of neutrophil fatty acid composition were observed: fish oil induced a significant decrease of linoleic (LA) and arachidonic acid (AA) and a significant increase of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), while soy PC induced significant increases of LA, total polyunsaturated fatty acid (PUFA) and PUFA/SFA ratio. Neutrophil superoxide generation and adhesion were not modified by fish oil diet, on the contrary a slight but significant increase of O2.- production in response to fMLP was measured after soy PC diet. Our study confirms the possibility of changing neutrophil fatty acid composition in vivo by dietary means, but also suggests that the manipulation of cell functions, like superoxide anion generation and adhesion, is not easily and directly achieved by controlling membrane lipid environment.

Background: We recently demonstrated that arachidonic:linoleic acid ratio of erythrocytes of essential hypertension patients is greater than normal., Objective: To investigate fatty acid composition, capability for adhesion to biological substrate and expression of beta2 integrins of leucocytes obtained from peripheral blood and skin window exudate of essential hypertension patients., Design: Neutrophil activation state was evaluated by reproducing the various conditions occurring in vivo during the life of the cell (i.e. under the 'resting' condition, such as in peripheral blood, and 'primed' condition, such as after transmigration through the endothelium and after administration of specific chemo-attractants). Because both peripheral blood and skin window leucocytes of the subjects were obtained on the same day, we could be sure that there had been no dietary influences on changes in levels of fatty acid. Thus, the observed changes should reliably reflect the metabolic rate of utilization of fatty acids coupled to the activation and migration of cells., Results: Leucocytes from essential hypertension patients were richer in arachidonic acid than were the corresponding cells from normotensive subjects; this difference was also evident for functionally activated skin window leucocytes, in spite of there having been a greater loss of poly-unsaturated fatty acids and arachidonic acid after migration. Moreover, a greater than normal arachidonic acid:linoleic acid ratio was shown for the first time to apply for leucocytes of essential hypertension patients, so extending our previous findings on the erythrocytes. Leucocytes from essential hypertension patients, collected both from peripheral blood and from skin window exudate, proved far more adhesive than the corresponding cells from age-matched and sex-matched controls, but this was not associated with a quantitative hyperexpression of beta2 integrins., Conclusions: The results suggest that an increase in availability of arachidonic acid in leucocytes could be a further expression of the generalized disturbance of fatty acid levels associated with essential hypertension and that a condition of hyperadhesion of neutrophils could occur spontaneously in vivo during the course of hypertension.

Background and Objective: Chorea-acanthocytosis is a disorder characterized by neuronal degeneration and the presence of acanthocytic erythrocytes on blood smear. The abnormal function and structure of the membrane protein band 3 are considered to be of pathogenetic relevance in determining the erythrocyte defect., Methods: In a clinically evident case of chorea-acanthocytosis, the following parameters were investigated: membrane cholesterol and fatty acid composition, sulphate influx (as a measure of the anion transport activity), membrane protein phosphorylation, membrane casein and tyrosin-kinase activities; moreover, the promoter and all exons of the EPB3 gene were screened for possible mutations by single strand conformational polymorphism (SSCP) study., Results: The sulphate influx, the Ser/Thr phosphorylation level, and the membrane casein-kinase activity were increased in chorea-acanthocytosis compared with normal controls. In the intact vanadate-treated 32P-labelled erythrocytes, Tyr-phosphorylation of the cytoplasmic domain of band 3, as well as the poly(Glu, Tyr) kinase activity in the membranes, were enhanced in the patient's sample. Apparent molecular weight and concentration of band 3 on SDS/PAGE analysis, membrane fatty acid composition and cholesterol/phospholipid molar ratio were normal and the SSCP study of EPB3 exons did not show any abnormal polymorphisms., Interpretations and Conclusions: An abnormal degree of phosphorylation of membrane proteins, in particular of band 2 (beta-subunit) and band 3, may contribute in determining both change of cell shape and increased anion transport in chorea-acanthocytosis.

Desaturase enzymes are responsible for the conversion of essential fatty acids to the longer-chain eicosanoid precursors. These enzymes require zinc as an essential cofactor, and the following ratios-C20:4/C18:2, C20:5/C18:3, and C22:6/C20:5-are considered indexes of their activity. We analyzed these parameters in plasma and erythrocyte membranes of 105 essential hypertensive patients, 20 white coat hypertensive patients, and 100 age-matched normotensive control subjects. Dietary analysis excluded significant quantitative and qualitative differences in fatty acid dietary intake between essential hypertensive patients and normotensive control subjects. Zinc levels and C20:4/C18:2, C20:5/C18:3, and C22:6/ C20:5 ratios were significantly higher in essential hypertensive patients than control subjects, whereas white coat hypertensive patients showed intermediate values for all these parameters. These data provide evidence for an alteration in fatty acid metabolism of essential hypertensive patients, consistent with increased activity of desaturase enzymes. The consequent greater bioavailability of eicosanoid precursors, and in particular of arachidonic acid, could affect several vascular functions and have a bearing on the pathogenesis or complications of hypertension.

Background: Raised serum uric acid (SUA) levels are associated with conditions at high risk for coronary heart disease. SUA levels can be partly modified by the diet, but little is known about the association of SUA with several dietary factors, particularly the quality of ingested lipids., Methods: The associations between SUA levels and biological and dietary factors were investigated in a sample of 90 healthy subjects (45 males and 45 females; ages 55.6 +/- 18 years) living in Nove, a village near Vicenza (Veneto Region, northern Italy). A careful selection of subjects to exclude those with chronic or acute disease (influencing SUA directly or indirectly through their pharmacological treatments) was obtained with the collaboration of three general practitioners operating in Nove., Results: SUA was higher among men than among women and higher among postmenopausal women than among women of child-bearing age (P < 0.01). Stepwise multiple linear regression analysis of the population as a whole showed that serum triglycerides and total RBC omega-6 PUFA were significant and independent predictors of a consistent proportion of serum uric acid variability (R = 0.59; R2 = 0.332; P < 0.001). Taking men and postmenopausal women together, the result was the same., Conclusions: Triglycerides and SUA are related even in the normal population and not only in "Syndrome X." Dietary enrichment with omega-6 PUFA might be useful for the negative modulation of SUA.

The peripheral blood neutrophils and the neutrophils accumulated into a skin-window experimental exudate were compared for their ability to release superoxide anion (O2-) and for their fatty acid composition, determined by capillary gaschromatography. The basal O2- release and the phorbol myristate acetate (PMA)-induced O2- release were not significantly different in the two neutrophil populations, while in response to formyl-methionyl-leucyl-phenylalanine (fMLP) the exudate cells showed an activity that was two fold higher than that of blood cells. The most significant changes of fatty acid composition of exudate versus blood cells were the following: i) increase of C16:0 (palmitic acid) from 21.3 +/- 1.2% to 23.5 +/- 1.3% (+ 10.2%) of total fatty acids (p < 0.001),ii) increase of C18:2 (linoleic acid) from 9.3 +/- 1.7% to 11.0 +/- 2.1% (+ 18.3%) (p = 0.005), iii) decrease of C20:4 (arachidonic acid) from 12.8 +/- 1.6% to 10.6 +/- 1.2% (-17.3%) (p < 0.001), whereas C18:1 (oleic acid) did not change. The total content of saturated or unsaturated fatty acids did not change. In exudate cells, a strong negative correlation was found between palmitic acid content and O2- release in response to both fMLP and PMA (r = -0.52, p < 0.02 and r = -0.49, p < 0.05, respectively) whereas arachidonic acid correlated positively, but weakly, with O2- (r = 0.40, p = 0.07 and r = 0.47, p = 0.05, with fMLP and PMA as stimulants respectively). A positive correlation was also found between the arachidonic acid content of blood cells and the number of cells that migrated into the inflammatory exudate. These results indicate that the process of extravasation from blood into the exudate causes specific and consistent modifications of the fatty acid composition of neutrophils and suggest that these modifications have a role in the activation and the regulation of the O2- forming system.

Community-based studies have suggested that the dietary intake of total fat influences factor VII coagulant activity (FVIIc), a predictor of fatal events from coronary heart disease (CHD). Nevertheless, the question whether the quality of dietary fats, with special reference to fatty acids (FAs), influences FVIIc is unsolved. The authors investigated in 90 healthy volunteers living in Nove, a village near Vicenza (northern Italy), the relationships between FVIIc and the plasma concentration of individual FAs. Several indices of other nutritional factors that have recently received increasing attention as determinants of CHD risk (antioxidant vitamins A and E, oligoelements) were also included in the multivariate analysis. The stepwise multiple linear regression analysis revealed body mass index (BMI), and the concentrations of plasma stearic acid (C18:0) and serum copper as significant independent predictors of a substantial proportion of FVIIc variability (R = 0 center dot 52; R2 = 0 center dot 27; P < 0 center dot 001). This study substantially supports the role of the plasma concentration of stearic acid as an important factor in modulating FVIIc.

Objective: To evaluate the effects of low doses of omega-3 polyunsaturated fatty acids on ambulatory blood pressure monitoring parameters in a group of mild essential hypertensives., Patients: We studied 24 consecutive essential hypertensive patients from our outpatient clinic with mild hypertension (diastolic blood pressure < or = 105 mmHg), no previous treatment for 4 weeks at least and no other disease., Methods: After a 3-month run-in period, the patients entered an intervention phase and were given 3 g omega-3 polyunsaturated fatty acids (85% eicosapentaenoic and docosahexaenoic acid concentrate) daily for 4 months; this phase was followed by a 4-month washout period. Ambulatory blood pressure monitoring was performed at the end of each phase; erythrocyte membrane fatty acids were assessed to check compliance., Results: After 4 months of treatment, erythrocyte omega-3 polyunsaturated fatty acids significantly increased but average systolic and diastolic blood pressure and the heart rate did not significantly change; no significant variations were recorded in blood pressure or heart rate variability (assessed as blood pressure and heart rate SD) nor in the diurnal blood pressure rhythm. After washout, a significant decrease was observed in erythrocyte omega-3 polyunsaturated fatty acids but the ambulatory blood pressure monitoring parameters were not substantially modified., Conclusions: The present data show that low doses of omega-3 polyunsaturated fatty acids as a single treatment are not effective in lowering blood pressure or the heart rate in mild essential hypertensive patients, despite a significant change in fatty acid cell membrane composition. Nor does this treatment seem likely to affect blood pressure variability or the diurnal rhythm.

We report two cases of atrial septal aneurysm, one associated with paroxysmal supraventricular tachycardia, the second with atrial septal defect. In both cases there were verified some transitory ischemic attacks. Carotid ultrasonography excluded atherosclerosis lesions. Two-dimensional transthoracic echocardiography showed an atrial septal aneurysm which, in the second case, was associated with atrial septal defect as demonstrated by color Doppler. The therapy is discussed in the case of septal atrial aneurysm associated with transitory ischemic attack, anticoagulant therapy is indicated; in the other, surgical correction of the defect is necessary.

Objective: Red blood cell (RBC) fatty acid composition and micronutrient status were investigated in patients with psoriatic arthritis (PsA), with special regard to their relationship to clinical variables., Methods: RBC fatty acid composition, selenium status--serum selenium and RBC glutathione-peroxidase activity (GSH-Px)--plasma copper, plasma and RBC zinc, plasma vitamins A and E, and RBC thiobarbiturate reactive substances (TBARS) after H2O2 exposure as an index of susceptibility to lipoperoxidation were measured in 25 patients with PsA and in 25 sex and age matched controls., Results: A significant increase in C16:0 (p < 0.01) and in total saturated fatty acids (SFA) (p < 0.05), a significant decrease in C18:2 (p < 0.05), C20:4 (p < 0.001) and omega-6 polyunsaturated fatty acids (PUFA) (p < 0.001), a lower level of serum selenium (p < 0.01) and an increased level of plasma copper (p < 0.05) were observed in patients with PsA in comparison with controls. Significant direct correlations were observed between RBC SFA and erythrocyte sedimentation rate (ESR) (r = 0.445), duration of disease (r = 0.403) and morning stiffness (r = 0.434)., Conclusion: As in other reports for rheumatoid arthritis (RA), our results support the view that an abnormal fatty acid pattern might be a particular metabolic modification involved or associated with the pathogenesis of rheumatic diseases.

Endothelial dysfunction may be present years before the clinical manifestations of atherosclerosis, which is particularly frequent in the late decades of life. Therefore, we have evaluated the presence of endothelial dysfunction in the elderly by measuring, by echo-Doppler technique, the vasodilatation of brachial artery in response to the hyperemia following forearm occlusion and decompression, a response that is dependent on endothelial function. We studied 10 subjects > 65 years (mean 72 +/- 8) and 10 subjects < 65 years (mean 40 +/- 6) all without clinical signs and without risk factors for atherosclerosis. The increase in brachial arterial flow during reactive hyperemia was similar in the young and elderly subjects (152 +/- 74% vs 129 +/- 63%, NS). While in the young at peak hyperemia we found a significant increase in brachial artery diameter from 3.4 +/- 0.9 to 4.1 +/- 1.0 mm (p < 0.005), there was no significant change in the elderly (from 3.0 +/- 0.7 to 3.1 +/- 0.7 mm, NS). In both groups sublingual glyceryl trinitrate produced a significant increase in brachial artery diameter (from 3.0 +/- 0.7 to 3.5 +/- 0.8 mm in the elderly, p < 0.01, and from 3.4 +/- 0.9 to 3.9 +/- 0.9 mm in the young subjects, p < 0.01, NS among groups), showing the absence in the elderly of structural vascular changes potentially responsible for absence of dilatation. In conclusion, elderly subjects without clinical signs or risk factors for atherosclerosis have a vascular endothelial dysfunction that may play an important role in pathologic processes of the cardiovascular system in the late decades of life.

The aim of the study was to evaluate arterial distensibility, intimal-medial thickening of the common carotid artery, left ventricular mass and the eventual correlations among these parameters in the hypertensive state. Our study population consisted of 89 hypertensive patients aged 35 to 80 years (mean age 60.8 +/- 10.6 years), and 76 normotensive subjects aged 45 to 85 years (mean age 61.2 +/- 11.1 years). Those patients constantly presenting systolic blood pressure values > or = 160 mmHg or diastolic blood pressure > 90 mmHg were diagnosed as hypertensive. Each patient underwent a B-mode echotomographic examination of the extracranial carotid tract performed with a Vingmed CFM 750 echotomographer with a 7.5 MHz probe and M-mode echocardiography with a Vingmed CFM 750 device equipped with a 3.0 MHz transducer. The results show the intimal-media thickness value in hypertensive patients (0.90 +/- 0.22 mm on the right and 0.92 +/- 0.22 mm on the left), was significantly greater than that in normotensive subjects (0.64 +/- 0.13 mm on the right and 0.64 +/- 0.13 mm on the left, p < 0.001); in hypertensive subjects, interventricular septum thickness (12.1 +/- 1.25 mm) was significantly greater than that in normotensive patients (9.1 +/- 0.77 mm, p < 0.001). In conclusion, we can say that hypertensive subjects have higher values of common carotid artery intimal-medial thickness than normotensives and that this finding is associated with the presence of left ventricular hypertrophy and with a reduction in arterial compliance. Vascular ultrasonography, as well as echocardiography and arterial mechanography can show, in hypertensive subjects, cardiac and vascular abnormalities in a non invasive way.

Background: The aim of this study was to evaluate the effects of nicardipine, at the dosage of 80 mg/day in two administrations, on blood pressure, intimal-media thickness of the common carotid artery and on arterial distensibility after 6 months of therapy. The study population consisted of 23 patients, 13 male and 10 female, mean age 61.7 +/- 10.1 years, with systolic blood pressure 170.4 +/- 14.5 mmHg and diastolic blood pressure 98.3 +/- 5.7 mmHg, affected by essential arterial hypertension of slight to moderate degree. Twenty-three subjects underwent high resolution B-mode echotomography of the common carotid artery, performed twice by the same operator within a one-week period. Treatment for 6 months with slow release Nicardipine at a dosage of 80 mg in two daily administrations was seen to be efficient in reducing systolic and diastolic blood pressure values. It also reduced the carotid-femoral pulse wave velocity. The results of our study show that 6 month's treatment with slow-release Nicardipine at 80 mg in two daily administrations, in effective reducing systolic and diastolic blood pressure values, and, to a slightly significant degree, in reducing the value of the intimal-medial thickness of the common carotid. Naturally the data which emerge from our study are preliminary and require a definitive analysis at the end the study, which is foreseen after a two year period from the enrolment of at least one hundred patients.

Arterial hypertension is considered an independent atherosclerotic risk factor. In hypertensive patients it increases cardiovascular morbidity and mortality risk. The aim of the study was to emphasize the presence of atherosclerotic lesions at the level of extracranial carotid tree in patients with essential arterial hypertension. In 110 hypertensive patients (63 males, 47 females) mean age 66 +/- 16 years, and in 100 normotensive patients (66 males, 34 females) mean age 65 +/- 15 years, high-resolution B-mode pulsed wave Doppler echotomography of internal, external and common carotid artery of both sides was performed. The value of the intimal-medial complex thickness of common carotid was measured, and the stenosis percentage evaluated by B-mode pulsed wave Doppler echotomography. Atherosclerotic plaques were classified according to their echogenic characteristic and surface; their localization was then evaluated. In hypertensive patients we observed the presence of common carotid intimal-medial thickening in 75.4%, atherosclerotic plaques in 60.9% and stenosis in 17.9%; 58.3% of these ones were localized at internal carotid, 33.3% at common carotid and 8.3% at external carotid. We observed that 36% of the 100 normotensive patients presented common carotid intimal-medial thickening (p < 0.001 versus hypertensives), 25% atherosclerotic plaques (p < 0.001 versus hypertensives) and 8% stenoses; 50% of these stenosis were localized at internal carotid, the second half at external carotid. In conclusion, high-resolution B-mode echotomography study with pulsed wave Doppler spectral analysis represents a necessary method to evaluate the condition of the extracranial carotid tree in patients with hypertension.

Since we have observed that monounsaturated fatty acids (MUFA) enriched diet modifies red cell membrane lipids and cation transport systems in normotensive subjects, we similarly evaluated a group of hypertensive patients undergoing an analogous dietary modification. In a group of 18 moderately hypertensive women, the diet was supplemented for two months with olive oil (about 45 g/day), which replaced an equal amount of seasoning fats. Before and after this period, red cell fatty acid composition was evaluated by gas-chromatography in order to verify diet compliance: a significant increase in oleic acid was observed, while the content of saturated and polyunsaturated fatty acids remained unchanged. After olive oil, maximal rates of Na-K pump (5580 +/- 329 vs 6995 +/- 390, p less than 0.001) and Na-K cotransport (Na-COT 544 +/- 52 vs 877 +/- 46, p less than 0.001: K-COT 790 +/- 76 vs 1176 +/- 66, p less than 0.001), cell Na content (9.58 +/- 0.4 vs 10.61 +/- 0.6, p less than 0.03) and passive permeability for Na (936 +/- 74 vs 1836 +/- 102, p less than 0.001) rose significantly. Although the reduction in maximal rate of the Li-Na CT after olive oil was not significant, it was the only cation transport parameter being correlated with the variations of membrane lipids, namely negatively with UFA (r = -0.528, p less than 0.05) and positively with SFA (r = 0.482, p less than 0.005). The change in maximal rate of Li-Na CT was also correlated with the variation of systolic and diastolic BP (r = 0.50, p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

In 25 patients (19 males and 6 females) suffering from chronic arteriopathy of lower extremities at Fontaine stage II, the clinical efficacy of picotamide was investigated in double blind, cross over placebo-controlled study. Patients were assigned randomly to the treatment with placebo or picotamide (900 mg/die) for three months and, after 15 days of wash-out, to the treatment with picotamide or placebo for the same period. Painfree walking distance and ankle/arm systolic pressure ratio improved significantly only during picotamide treatment. Laboratory monitoring revealed a significant decrease in platelet aggregation and an increase of fibrinogen degradation products only during picotamide treatment. Three patients during picotamide treatment referred transient gastrointestinal discomfort (nausea, vomiting and diarrhoea); however in no case the treatment was suspended because of the appearance of these symptoms. These results indicate that picotamide is an effective drug in the management of chronic arteriopathy of lower extremities.

We studied 40 subjects, 20 under 60 yrs old (10 normotensive and 10 hypertensive) and 20 over 60 yrs old (10 normotensive and 10 hypertensive). Each patient underwent a 24-hour ambulatory blood pressure monitoring (8:00 a.m. to 8:00 a.m.), by a noninvasive method using an ICR 5300 apparatus. Systolic blood pressure was significantly higher on random measurement and during the daytime in the older patients. Although comparison of the other parameters did not reveal significant differences, we noted a tendency to higher systolic values among the older group, and higher diastolic values in the younger one. The variability of the values was slightly higher, although not significantly, among the older patients. In both groups random systolic measurements, and in the younger group diastolic values as well, were significantly higher than mean 24 hour values. The incidence of abnormal systolic BP values ranged from 18.8% to 100% (mean 60.2% +/- 28.9) in younger hypertensives, and from 54% to 100% (mean 76.5% +/- 14.4) in older patients. The incidence of abnormal diastolic BP values ranged from 64.5% to 100% (mean 80.4% +/- 15.6) in younger patients and from 47.2% to 96% (mean 67.8% +/- 15.8) in older patients. The correlation between mean systolic and diastolic values recorded from 8:00 to 10:00 a.m., and mean 24-hour values was significant in young hypertensives, while in the older group there was a significant correlation only for diastolic BP. The lack of significance for systolic values is probably due to a greater variability in systolic pressure in elderly subjects during the morning.(ABSTRACT TRUNCATED AT 250 WORDS)

In a case of 'spur cell anaemia' (SCA) a reduced esterified/free cholesterol ratio was found in plasma, in LDL and HDL fractions and an increased cholesterol/phospholipid (C/PL) molar ratio in erythrocyte membrane. Cation transport was normal with the exception of Li-Na counter-transport was decreased. An increased intrinsic membrane proteolytic activity (IMPA) was demonstrated by the generalized reduction or, sometimes, disappearance of protein bands on SDS-PAGE in patient ghosts when the proteolysis was allowed. This characteristic was found to be transferable to normal cells by incubation in SCA-plasma; moreover membrane C/PL molar ratio was augmented after incubation. Normal plasma was not able to normalize IMPA of SCA cells 'in vitro', even if it induced a remarkable decrease of membrane C/PL molar ratio. Nevertheless IMPA normalization did occur 'in vivo', when the SCA cells were exposed to therapeutic 'plasma exchange' (3.3 litre/week). The results suggest the following conclusions: (a) in our SCA patient there is an increased IMPA; (b) this feature, as well as membrane lipid alteration, is transferable to normal erythrocytes; (c) this case seems to demonstrate, for the first time in our knowledge, a modulating effect of plasma on IMPA in erythrocytes.

Forty-one diabetic patients (21 males and 20 females) were divided into two groups according to treatment. One group (n = 22) was treated with insulin and the other with oral therapy (tolbutamide) (n = 19). The two groups of patients were in a good metabolic control in that the glucose loss in the urine was less than 10 g/24 h. In these two groups we have evaluated total serum cholesterol (TC), triglycerides (TG), VLDL TC/TG ratio and prevalence of 'double pre-beta lipoproteinemia'. For these parameters no significant differences have been found between the two groups. The results of our study suggest that, provided metabolic control is good, the VLDL metabolism does not seem to be affected by the type of treatment.

In 20 adult patients suffering from hyperlipidaemia we measured the lipid composition of erythrocyte membrane, the glutathione peroxidase activity in both erythrocytes and platelets, the production of malondialdehyde by platelets stimulated with thrombin, as well as the level of plasma selenium, retinol and alpha-tocopherol, before and after 8 weeks of fish oil supplementation (20 ml daily). We noted a remarkable reduction in plasma triglycerides which was associated with a significant decrease in blood pressure; moreover, we noted a reduction in the amount of arachidonic acid compensated by an increment of omega-3-fatty acid (particularly eicosapentaenoic and docosahexaenoic acids). The dietary supplementation with fish oil was associated with a significant increase in glutathione peroxidase activity in both erythrocytes and platelets. On the contrary, the production of malondialdehyde, which was originally higher than normal in hyperlipidaemics, was inhibited significantly after fish oil (p less than 0.001). Whereas no changes were observed in the concentration of plasma selenium and alpha-tocopherol, an increment of plasma retinol occurred. These data indicate that in hyperlipidaemics there is a proaggregant status; this situation may be normalized by using a dietary supplementation of fish oil; the increase of polyunsaturated fatty acids on the cell membrane, with a possible increment of the formation of lipoperoxides, induced by fish oil, is compensated by an increased activity of the scavenger enzyme glutathione peroxidase.

The fatty acid composition of erythrocyte membrane, the glutathione-peroxidase activity of erythrocytes and platelets, the production of malondialdehyde by platelets and the activity of the main systems of transmembrane cation transport have been studied in 5 members of a family, 2 of whom affected by Laurence-Moon-Barter-Biedl Syndrome. A remarkable increase of polyunsaturated fatty acids (particularly arachidonic acid) and of cholesterol/phospholipid molar ratio has been noted. This pattern of membrane lipids was associated to an increment of malondialdehyde production and an increase activity of glutathione-peroxidase. Serum retinol and a-tocopherol were in the normal range, whereas serum selenium was low in 3 out of 5 members. Moreover, the alteration of membrane lipids was associated to a decrease of the maximal velocity of Li-Na countertransport. We speculate that the enrichment of polyunsaturated fatty acids on the cell membranes may represent a condition favoring the lipoperoxidation and therefore the development of the retinitis pigmentosa characteristic feature of Laurence-Moon-Barter-Biedl Syndrome.

Erythrocytes from psoriatic patients have a significant increase in polyunsaturated fatty acids (p less than 0.001) especially in arachidonic acid (p less than 0.001). Glutathione peroxidase activity, in both erythrocytes and platelets, was stimulated when compared with normal cells (p less than 0.001, less than 0.02, respectively) and the production of malondialdehyde was also increased in psoriasis (p less than 0.01). The level of plasma selenium was significantly reduced (52.80 vs 72.49 ng/ml; p less than 0.001). alpha-Tocopherol and retinol were both normal in plasma of psoriatics. After two months of fish oil supplementation, the erythrocyte lipid pattern was changed, eicosapentaenoic and dochesaenoic acids substituting the arachidonate in the membrane. A reduction in malondialdehyde (p less than 0.01), a prolongation of bleeding time (p less than 0.05) and a further stimulation of glutathione-peroxidase (p less than 0.001) in both erythrocytes and platelets was also found.

Cholesterol/phospholipids molar ratio and fatty acid composition have been estimated in erythrocyte membrane of 12 patients suffering from nephrotic syndrome and compared to values obtained in 23 normal subjects matched for sex and age. The membrane lipid composition has been correlated with the activity of erythrocyte Li-Na countertransport of the same subjects. The results show a significant increase in cholesterol/phospholipids ratio and total saturated fatty acids when erythrocytes of nephrotic patients are compared to normal erythrocytes, whereas total unsaturated fatty acids were lower in nephrotics (p less than 0.002). Li-Na countertransport was higher in nephrotics (p less than 0.001) and it was positively correlated with the total amount of saturated fatty acids of the erythrocyte membrane (r = +0.451; p less than 0.01). On the contrary, Li-Na countertransport was negatively correlated with the total amount of unsaturated fatty acids (r = -0.468; p less than 0.01).

In some tissues such as liver and kidney, beta-glucuronidase is present not only in the lysosomes but also in the microsomes. Both enzymes are coded by the same structural gene. The function of the microsomal enzyme is still unclear. We have observed in primary cultures of mouse hepatocytes that the microsomal enzyme disappeared to a trace within 5 days after plating cells. This change of intracellular localization coincided with a change of the isoelectric focusing pattern of the lysosomal beta-glucuronidase. Within the multiple banding pattern of the lysosomal enzyme, a faintly staining group of bands in the more acidic range (mean pI 5.4) became more pronounced while a major group (mean pI 5.9) faded slightly. The correlation between the presence or absence of the microsomal beta-glucuronidase and distinct proportions of the two lysosomal enzyme forms was confirmed in vivo. The less acidic form (pI 5.9) prevailed in the presence (kidney, liver), the more acidic form (pI 5.4) in the absence of the microsomal enzyme (spleen). The two lysosomal forms differed also in their apparent molecular weight by approx. 1500 (Mr 71 500 versus 73 000). In order to elucidate the biosynthetic relationship between the microsomal enzyme and the two lysosomal enzyme forms we interfered with their processing in cultured hepatocytes. The addition of the protease/esterase inhibitor phenyl-methyl-sulfonyl-fluoride caused the disappearance of the microsomal and the appearance of the acidic pI 5.4 lysosomal enzyme within 24 h; with chloroquine, the microsomal enzyme remained nd no lysosomal pI 5.4 enzyme appeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Two groups of individuals, 26 normotensive normolipemic and 37 normotensive hyperlipemic, all without family history of hypertension have been selected in attempt to demonstrate whether Li-Na countertransport of erythrocytes is influenced by plasma and membrane lipid composition. The maximal rate of Li-Na countertransport was elevated in hyperlipemics (0.344 +/- 0.168 vs 0.220 +/- 0.074 mmol/l erythrocytes/h). This difference is highly significant. Hyperlipemics had different composition of membrane lipids than normals. The most important variations were: increase of palmitic, palmitoleic and total saturated fatty acids (SFA) as well as increase of cholesterol/phospholipids ratio (C/PL); in contrast, hyperlipemics had a reduced amount of linoleic acid and total unsaturated fatty acids (UFA) as well as total polyunsaturated fatty acids (PUFA). Consequently, UFA/SFA and PUFA/SFA ratios were lower than in normals. Li-Na countertransport was negatively correlated with the amount of PUFA (P less than 0.02), whereas it was positively correlated with the following parameters: oleic/linoleic ratio (p less than 0.02), monounsaturated fatty acids/polyunsaturated fatty acids ratio (p less than 0.03) as well as with the SFA + monounsaturated fatty acid/PUFA ratio (p less than 0.03). These findings suggest that the V max of Li-Na countertransport in erythrocytes is influenced by the lipid composition of the membrane.

After a 4-week wash-out period, picotamide was administered to 25 patients affected by chronic arteriopathy of the lower limbs (scale 2 according to Fontaine) at a dose of 900 mg/die for 90 days, and then at a dose of 600 mg/die for a further 90 days, in order to assess its efficacy according to the following parameters: duration of gait, residual pressure index (RPI) resting the ankles, hematochemicals, electrocardiogram. At the end of the study a statistically significant increase was observed in the duration of gait and RPI at the ankles and, of the hematochemical parameters, in an increase in fibrogenic degradation products. Adverse reactions were only observed in 3 patients and regressed spontaneously. In conclusion, picotamide was found to be efficacious in patients affected by chronic obliterating arteriopathy of the lower limbs with the possibility of reducing the dose after 3 months of therapy.