Effects of PGE-1 in patients suffering from peripheral arterial occlusive disease.

BACKGROUND: The purpose of the research is to determine the effects of PGE-1 in patients with chronic obliterans arteriopathy of the lower extremities and to investigate the possibility of its having an influence on local hemodynamics. METHODS: The study comprises 123 patients aged between 39 and 75 years, suffering from Fontaine's Stage Two peripheral arteriopathy randomised into 2 therapeutic groups: the patients of Group 1 were treated with PGE-1, those of Group 2 with the association pentoxyfillin-buflomedil by venous infusion. The following were evaluated: the free walking distance on a treadmill; Rest Flow, Peak Flow and basal and minimum vascular resistance by means of strain gauge plethysmography; RF, PF, tPF and tRF by means of laserdoppler. RESULTS: After 4 weeks of treatment an increase of 370% was observed in the absolute free walking distance and of 260% in that relative to patients treated with PGE-1, while the increase in the same parameters in Group 2 patients was considerably lower. Further, in Group 1 patients there was a significant increase in Peak Flow and an improvement in laserdoppler parameters markedly greater than those measured in the control group. CONCLUSIONS: In conclusion, the data obtained point to the effectiveness of PGE-1 in patients suffering from Fontaine's Stage 2 obliterans arteriopathy: this substance in fact improves the microcirculation and leads to the development of collateral circuits with a consequent improvement in local hemodynamics and an increase in walking distance.

[Hypertension and peripheral arterial hemodynamics]. / Ipertensione ed emodinamica arteriosa periferica.

Sixty uncomplicated hypertensive patients (40 stable and 20 borderline) were studied, by strain gauge plethysmography, in comparison with 25 normotensive subjects, in order to evaluate the arterial hemodynamics of the lower limbs in essential hypertension and to verify the different pattern in borderline and in stable hypertensives. Resting blood flow, even if lightly decreased in hypertensive groups, didn't show significant differences in its mean values; Peak Flow, instead, was reduced proportionally to the severity of hypertension in all the hypertensive patients, but only in the stable hypertensives did it prove statistically significant. Minimal Vascular Resistances showed a similar behaviour; they were significantly increased only in the stable hypertensives, whereas Basal Vascular Resistances, were raised in all hypertensive patients, in the borderline group too. Finally, half time and total hyperemic time, which indicate vascular reactivity, were significantly decreased in all hypertensives. These results suggest that the stable hypertensive patients principally develop arterial structural changes, while the borderline hypertensive patients have only functional modifications, such as a reduced compliance and a hyperdynamic condition.

Hypertension and peripheral arterial disease: a plethysmographic study.

Sixty patients suffering from arterial hypertension and/or obliterative arteriopathy of the lower limbs (20 hypertensive uncomplicated [H group], 20 normotensive affected by obliterative arteriopathy [A group], 20 suffering from both hypertension and peripheral arterial disease [HA group]) were studied, by strain gauge plethysmography, in comparison with 20 healthy subjects (N group). The aims were to evaluate the arterial and venous hemodynamics of the lower limbs in such conditions and also to determine whether the vascular damage is primary or represents a consequence of the hypertensive pathology in the patients affected by both hypertension and peripheral arterial disease. The resting blood flow did not show significant differences in the mean values, even if lightly decreased in hypertensive patients (with or without peripheral arteriopathy). The peak flow was reduced significantly both in the H group and in the A and HA groups. The half-time (t1/2) and total time (tT), which indicate vascular reactivity, were significantly decreased in the H group, but they were increased in the A and HA groups. Finally, the venous compliance was decreased in the H group, did not vary significantly in the A group, and showed an intermediate behavior in the HA group. These results suggest that hypertensive and arteriopathic patients develop similar arterial structural changes. However, they show a different behavior with regard to vascular reactivity and venous hemodynamics, as demonstrated by venous plethysmography.

Leukocyte flow properties, polymorphonuclear membrane fluidity and cytosolic Ca2+ content in subjects with vascular atherosclerotic disease.

In a group of subjects with monovascular atherosclerotic disease (MVAD) and in a group of subjects with polyvascular atherosclerotic disease (PVAD) we evaluated white blood cell (WBC) filtration (unfractionated, mononuclear -MN-, polymorphonuclear -PMN- cells), using the St. George Filtrometer and considering respectively the initial relative flow rate (IRFR) and the clogging rate (CR), the polymorphonuclear leukocyte membrane fluidity, employing the fluorescent probe 1.4-(trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH) and calculating the fluorescence polarization degree, and the polymorphonuclear leukocyte cytosolic Ca2+ content, adopting the fluorescent probe Fura 2-AM. Only the filtration parameters (IRFR, CR) of unfractionated WBCs discriminate normals from MVAD and PVAD subjects, and also monovascular and polyvascular VAD subjects between them. The filtration parameters of mononuclear and polymorphonuclear leukocytes do not distinguish normals from MVAD and PVAD subjects. PMN membrane fluidity does not differentiate normals from MVAD and PVAD subjects, while PMN cytosolic Ca2+ content discriminates normals from MVAD and PVAD subjects, but does not distinguish the two groups of VAD subjects. In conclusion, in subjects with vascular atherosclerotic disease we noted an alteration of the unfractionated leukocyte flow properties, more evident in PVAD subjects, and an increase of the PMN cytosolic Ca2+ content.

Hypertension and peripheral arterial hemodynamics.

Sixty uncomplicated hypertensive patients (30 stable and 30 borderline) were studied, by strain gauge plethysmography, in comparison with 25 normotensive subjects, in order to evaluate the arterial hemodynamics of the lower limbs in essential hypertension and to verify the different pattern in borderline and in stable hypertensives. Resting blood flow, even if slightly decreased in hypertensive groups, did not show significant differences in its mean values; peak flow, instead, was reduced proportionally to the severity of hypertension in all the hypertensive patients, but only in the stable hypertensives was it statistically significant. Minimal vascular resistance showed a similar behavior: it was significantly increased only in the stable hypertensives, whereas basal vascular resistance was raised in all hypertensive patients and also in the borderline group. Finally, the half-time and the total hyperemic response time, which indicate vascular reactivity, were significantly decreased in all the hypertensives. These results suggest that the stable hypertensive patients develop principally arterial structural changes, while the borderline hypertensive patients have only functional modifications, such as a reduced compliance and a hyperdynamic condition.

The free testosterone to dehydroepiandrosterone sulphate molar ratio as a marker of visceral fat accumulation in premenopausal obese women.

The aim of this paper was to investigate the relationship between sex hormones and fat distribution in premenopausal obese women. Serum concentrations of sex hormones, glucose tolerance and fat distribution were determined in a population of non-diabetic obese women, in the outpatient clinic of University Hospital, Bari, Italy. The subjects were 40 consecutive premenopausal obese women (BMI > 25). The amounts of visceral, abdominal subcutaneous, and femoral subcutaneous fat, and the visceral to abdominal subcutaneous fat ratio were measured by ultrasound techniques. Serum concentrations of total testosterone (T), free testosterone (FT), dehydroepiandrosterone sulphate (DHEAS), delta 4-androstenedione (A), 17-beta-estradiol (E2), sex hormone binding globulin (SHBG), and the FT to DHEAS molar ratio were measured during the follicular phase. Plasma glucose and insulin concentrations were evaluated during an oral glucose tolerance test. Of all sex hormones, the FT/DHEAS molar ratio was the parameter that most closely related to the amount of visceral fat (r: 0.544, P < 0.001), and this positive association was maintained (P < 0.01) after adjustment for age, BMI and insulin levels (fitted model: R2 adjusted: 0.504; F ratio: 14.73; P-value: < 0.0001). DHEAS was inversely correlated with the amount of visceral fat (r: -0.324, P < 0.05). T was inversely correlated with the amounts of both abdominal subcutaneous (r: -0.409, P < 0.01) and visceral fat (r: -0.324, P < 0.05). The FT to DHEAS molar ratio is the androgenic parameter that most closely relates to the accumulation of visceral fat in premenopausal obese women.

Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids.

One hundred patients with a history of hemorrhoidal disease and suffering from an acute hemorrhoidal attack were randomized into two parallel groups and treated with Daflon 500 mg* (D500) or placebo (PL) under double-blind conditions. Daflon 500 mg was administered at the dosage of three tablets bid the first four days and two tablets bid the following three days. Overall improvement of symptoms was greater in the D500 group than in the PL group, from D2 up to D7. The clinical severity of proctorrhagia, anal discomfort, pain, and anal discharge diminished in both groups but to a greater extent in the D500 group (P < 0.001 for all parameters except protorrhagia, P = 0.006). Inflammation, congestion, edema, and prolapse were more markedly improved in the D500 group than in the PL group. Duration and severity of the current hemorrhoidal episode, as assessed by patient self-evaluation, were less important in the D500 group as compared with previous episodes. Use of analgesics and topical medications diminished in both groups, with a major reduction in the D500 group from D4 (P < 0.001). Acceptability was good in both groups: no patient experienced major side effects. In summary, treatment with D500 resulted in a quicker and more pronounced relief of signs and symptoms of acute hemorrhoids than with the placebo.

Reduced effectiveness of atrial natriuretic factor in pre-menopausal obese women.

It is well-known that the prevalence of hypertension progressively increases with body weight. Since the major physiological activities of atrial natriuretic factor (ANF) are its natriuretic, diuretic and vasodilatory effects, the aim of the present study was to investigate the ANF basal plasma levels and platelet receptor number in 15 young normotensive obese (O) and 12 age-matched normal weight healthy (C) women. ANF effectiveness was also studied in eight of the obese and seven of the control women, after an intravenous bolus of the hormone (human ANF (99-126): 0.5 mg/kg body weight). Results are expressed as means+s.d. Basal ANF plasma levels were similar between obese (18.2 +/- 9.7 pg/ml) and control women (12.3 +/- 7.7 pg/ml), whereas obese patients showed an increase density of platelet ANF-binding sites (clearance receptors) (C: 28.7 +/- 33.5 fmol/10(9) cells; O: 39.6 +/- 4.6 fmol/10(9) cells; P < 0.001), without apparent differences in receptor affinity (Kd) (C: 6.0 +/- 3.0 pM; O: 7.0 +/- 2.0 pM). The biological response to ANF, evaluated by changes of mean blood pressure levels (C: 5 +/- 1 mmHg; O: 1 +/- 1 mmHg; P < 0.001) and the percentage increase of diuresis (C: 159 +/- 52%; O: 81 +/- 62%; P < 0.01) and natriuresis (C: 205 +/- 129%; O: 99 +/- 41%; P < 0.05) was significantly reduced in obese patients. The percentage increase in sodium excretion was inversely related to the basal insulin concentrations in the obese group (r = 0.64, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor-1 (IGF-1) and dehydroepiandrosterone sulphate in obese women.

Severe obesity is known to reduce either dehydroepiandrosterone circulating levels or growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion. The present study was undertaken to evaluate the possibility of a relationship between the circulating levels of IGF-1 and those of dehydroepiandrosterone sulphate (DHEAS) in 25 fertile obese women. A logarithmic transformation of the values of non-normally distributed variables was performed before statistical analysis. We found a significant positive correlation between DHEAS and IGF-1 (r = 0.615, P < 0.01). In addition, stepwise multiple regression analysis showed that IGF-1 maintained a strong positive relationship with DHEAS (P < 0.01) when adjusted for other variables such as age, body mass index (BMI), waist:hip ratio (WHR) and insulin levels (adjusted R2 = 0.373; P < 0.01). These findings suggest that IGF-1 may independently influence the DHEAS circulating levels. ADG (5 alpha-androstan-3 alpha, 17 beta-diol-glucuronide) was also positively correlated to IGF-1 (r = 0.436, P < 0.05). However, when ADG concentrations were adjusted for DHEAS levels, this metabolite was not significantly correlated with IGF-1, thus excluding a direct influence of IGF-1 on the 5-alpha-reductase activity. Therefore, although our data represent only a preliminary study, they seem to suggest a possible influence of IGF-1 on circulating levels of DHEAS in obese women.

Relation between sex hormones and serum lipoprotein and lipoprotein(a) concentrations in premenopausal obese women.

Lipoprotein(a) (Lp[a]) is generally considered to be a risk factor for the development of cardiovascular disease, but little is known about the possible influence of obesity on the circulating levels of this lipoprotein. The present study was undertaken to examine this aspect in 136 menstrually active women by comparing the serum concentrations of Lp(a) between 72 obese and 64 age-matched nonobese women. Since an adverse effect of androgens and a protective effect of estrogens have been described for plasma lipoprotein profiles in obese women, the relation between the circulating levels of Lp(a) and those of these other hormones was also investigated in obese patients. In addition, other lipoproteins, anthropometric parameters (body mass index and waist-to-hip ratio), and insulin were evaluated. The levels of Lp(a) were not significantly different (Mann-Whitney U test chi 2, 3.59; p = 0.0582 [NS]) between obese (rank sum, 5,367) and control (rank sum, 3,949) women; in addition, the percentage of patients with high Lp(a) levels (cutoff defined at 30 mg/dL) did not differ between the two groups (obese women, 30%; control, 21.8%; chi 2, 0.90; two-sided p = 0.341 [NS]). Moreover, no correlation was found between Lp(a) and body mass index. Lastly, when the Lp(a) prevalence odds ratio for obesity was examined by adjusting the levels of this lipoprotein for age, triglycerides, total cholesterol, and high density lipoprotein cholesterol, the probability value (0.88) was far from significant. In obese women, no correlation was found between the logarithmically transformed Lp(a) concentrations and all the other variables evaluated in the study. In conclusion, the present study shows that the circulating levels of Lp(a) are not influenced by body weight and cardiovascular risk factors commonly associated with obesity, such as enhanced androgenic activity, hyperinsulinemia, adverse lipoprotein profile, and abdominal fat accumulation.

Sulodexide and the microcirculatory component in microphlebopathies.

A double-blind, placebo-controlled study was carried out in 36 patients, aged 30 to 50 years, to evaluate the effectiveness of oral sulodexide in the treatment of chronic venous insufficiency due to idiopathic varices. Patients were allocated at random to receive either oral sulodexide as 2 capsules (each containing 250 lipoproteinolipase releasing units) twice daily or 2 identical placebo capsules twice daily over a period of 45 days. Using strain gauge plethysmographic data, assessments were made of the microcirculatory effects of treatment by calculating the coefficient of capillary filtration from measurements made on both legs of each patient on entry and after 30 and 45 days of treatment. The coefficient is derived from the transmembranous flow values at the occlusive pressures of 60 and 40 mmHg, the difference between the two occlusive pressures examined and a corrective factor to calculate the capillary pressure based on the pressure in the venous circulation. Statistical analysis of the results showed that sulodexide produced a significant mean reduction from baseline values of the coefficient at both the 30 and 45 day examinations whereas the coefficient increased in the placebo group. The difference between the two groups was also statistically significant. These findings suggest that sulodexide has a positive influence on capillary permeability.

Low dehydroepiandrosterone circulating levels in premenopausal obese women with very high body mass index.

Dehydroepiandrosterone (DHEA) has an anti-obesity effect in rodents and reduces body fat in normal men. Therefore, the plasma levels of DHEA were evaluated in nine premenopausal healthy women and in 13 menstrually active nondiabetic obese women, including patients (n = 6) with body mass index (BMI) over 40. In the obese group, a significant inverse correlation between DHEA levels and BMI was found. These results suggest that patients with severe obesity are unable to increase the DHEA adrenal production rate in order to parallel the increase in the hormone metabolic clearance rate (due to enlargement of body fat mass per se). The deficiency of this mechanism might itself contribute to the progressive fat accumulation in severe obesity.

Changes in overall plasma norepinephrine turnover and lymphomonocyte beta-adrenoceptor number during combined caloric and sodium restriction in normotensive obese subjects.

The aim of the study was to evaluate in eight normotensive obese patients the influence of low sodium intake (9 mEq/day) on the sympathetic activity modifications induced by caloric restriction (2511 kJ/day). As compared to the isocaloric salt balanced diet, 7 days of normosodic underfeeding induced a decrease in the overall norepinephrine turnover (clearance and appearance rate) and 24 hours urinary output, whereas the combined caloric and salt restriction significantly increased the norepinephrine appearance rate and even more the norepinephrine clearance but, on the other hand, decreased the beta-adrenergic receptor number on the lymphomonocyte surface, suggesting a reduced peripheral sensitivity to catecholamines. Therefore, the utility of the combined sodium and caloric restriction in the treatment of the normotensive obese patients remains still questionable.

Beta-adrenoceptors desensitization may modulate catecholamine induced insulin resistance in human pheochromocytoma.

Catecholamines acutely exert a pronounced insulin-antagonistic effect, which is mediated by beta-adrenergic receptors stimulation. Nevertheless, several patients with pheochromocytoma fail to exhibit an overt diabetic syndrome, in spite of steadily elevated plasma levels of catecholamines. This prompted us to investigate a 16 years old male patient, bearing an extra-adrenal pheochromocytoma, who displayed a slightly impaired glucose tolerance to oral glucose tolerance test, whereas fasting and post-prandial blood glucose, as well as glycaemic response to intravenous glucagon, were in the normal range. Peripheral insulin sensitivity, as evaluated by intravenous insulin tolerance test, was slightly decreased. Supine norepinephrine plasma levels were steadily upon 9 ng/ml; plasma insulin, both fasting and post-prandial, was within the normal range. beta-adrenergic receptors density of peripheral mononuclear cells was strongly reduced when compared to controls (0.97 +/- 0.08 vs 2.82 +/- 0.37 fmol/10(6) cells), without any concomitant change of affinity. Insulin binding to circulating monocytes was reduced as well (2.38 +/- 0.27 vs 5.1 +/- 0.4%/10(7) monocytes); insulin receptor affinity was quite normal (1.7 ng/ml) and total receptor number was 9,200 sites/cell. In desensitization experiments, 1 microM isoproterenol caused only a 20% decrease of beta-adrenergic receptors density in the patient's cells (70% decrease in controls). Six months after surgery, all the above modifications of receptor binding, as well as the mild glucose intolerance, were almost completely reversed. Thus, high levels of norepinephrine were able to induce a decrease of both beta-adrenoceptor and insulin receptor binding, together with a marked reduction of in vitro agonist-induced redistribution of beta-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Double blind study of the pharmacodynamic and clinical activities of 5682 SE in venous insufficiency. Advantages of the new micronized form.

A randomized double blind multicenter trial was performed to study the pharmacodynamic and clinical activities of 5682 SE, in comparison with diosmin (active principle) well recognised for many years. 5682 SE is a purified micronized flavonoid fraction containing 450 mg of diosmin and 50 mg of hesperidin per tablet. 90 patients with chronic venous insufficiency of the lower limbs stabilized for one year entered the study. They received either 2 tablets of 5682 SE or 900 mg of diosmin a day during two months. The following parameters were studied: functional clinical symptoms in the legs, ankle and calf circumferences measurements, strain-gauge plethysmographic parameters with 20, 40 and 60 mmHg venous occlusion, clinical and biochemical acceptabilities. In both groups of patients, the data showed statistically significant changes. But the improvement in the clinical symptoms and the decreases in the venous outflow parameters were more substantial with 5682 SE than with diosmin. The clinical and laboratory acceptabilities were equal in both groups. Due to its pharmacodynamic and clinical activities which are more considerable than those of non-micronized diosmin, the results of this study show the therapeutic advantage of 5682 SE in chronic venous insufficiency.

Biophysical and endocrine-metabolic changes during menopausal hot flashes: increase in plasma free fatty acid and norepinephrine levels.

Thermocutaneous, vascular, metabolic and hormonal changes were investigated during 11 hot flashes from 6 postmenopausal women. The first detectable change was an increase in finger blood flow with a concomitant enhancement of skin conductance. The increase in skin conductance was followed rapidly by a sharp rise in finger temperature. The main endocrine-metabolic changes associated with the above phenomena were a sharp increase in plasma free fatty acids (approximately 65%), norepinephrine (approximately 100%) and LH (approximately 20%) levels. Plasma glucose and cortisol tended to be increased but did not reach statistical significance; on the other hand, plasma insulin, glucagon, growth hormone, epinephrine and dopamine remained unchanged.