Silvia Severgnini

Retrospective analysis of long-term hemorheologic effects of pentoxifylline in diabetic patients with angiopathic complications

Abstract Blood rheology alterations have often been reported in diabetic patients and may be associated with an increased risk for diabetic vascular disease. In this light a hemorheologic approach with pentoxifylline has been suggested in diabetic patients with hemorheological changes in order to improve the hemorheology approach and to evaluate the long-term effects of this treatment on the other clinical and metabolic variables. The study concerned a 10-year retrospective analysis of diabetic patients with hemorheologic alterations and angiopathic complications. Pentoxifylline (Trental 400) significantly reduced blood and plasma viscosity (at high and low shear-rates), fibrinogen and erythrocyte aggregation, and increased erythrocyte filterability throughout the study. The improvement of the hemorheologic pattern was obtained independently of the variation in glycometabolic control and body weight changes, whereas concomitant reductions of arterial blood pressure levels and of urinary excretion of albumin and total proteins was observed during the treatment. Pentoxifylline might therefore be successfully employed for long-term periods in the treatment of hemorheologic disorders in diabetic patients without effects on the metabolic pattern.

Excitatory pattern of gamma-interferon on natural killer cell activity in senile dementia of the Alzheimer type

Spontaneous natural killer (NK) cell activity and NK-induced cytotoxicity after interferon-gamma (IFN-gamma) were measured in healthy elderly subjects and in patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID). Normal basal and IFN-gamma-stimulated NK cytotoxicity were found in healthy old subjects and in patients with MID. On the contrary higher NK cytotoxicity after IFN-gamma (650 IU) was demonstrated in SDAT patients than in MID and healthy subjects (p < 0.001). A significant inverse correlation between the percent increase of NK cytotoxicity after IFN-gamma and the Mini Mental State Examination score (p < 0.001) was also demonstrated in patients with SDAT. Our data might suggest a cytokine-dependent mechanism of NK activation in SDAT associated with the neuroimmune hypothesis of the disease.

Enhanced cytotoxic response of natural killer cells to interleukin-2 in Alzheimer's disease.

Experimental data suggest an involvement of immune cellular components in the development of Alzheimers disease (AD). Against this background, the spontaneous natural killer (NK) cell activity and the NK-induced cytotoxicity after interleukin-2 (IL-2) were studied in healthy elderly subjects and in patients with dementia of Alzheimer type (SDAT) and multi-infarct type (MID). Higher NK cytotoxicity (expressed as total lysis and percent increase) at different IL-2 concentrations (50 and 100 IU/ml/cells) was demonstrated in patients with SDAT than in healthy elderly subjects (p < 0.001) and MID patients (p < 0.001). NK cell activity of MID patients was similar to that of healthy elderly and healthy young subjects. A negative correlation between the percent increase in NK cytotoxicity after IL-2 and the Mini Mental State Examination Score was also found in SDAT patients (p < 0.01). Alterations of IL-2-mediated NK cytotoxicity may therefore support the neuroimmune hypothesis of AD.

Decreased Immunosuppressive Effect of Cortisol on Natural Killer Cytotoxic Activity in Senile Dementia of the Alzheimer Type

Former studies have indicated alterations of the cytotoxic activity of natural killer (NK) cells in senile dementia of the Alzheimer type (SDAT). These changes may be related to the increased reactivity of NK cells with cytokines, even if an impairment of the immunosuppressive effect of glucocorticoids cannot be excluded. In the present study we have demonstrated a lower immunosuppressive effect of cortisol on NK cytolytic function in patients with SDAT than in healthy elders and in patients with dementia of multi-infarct origin (MID). This suppression is completely lacking when cortisol is employed at low concentrations (10–7 M) and is significantly reduced after incubation at physiological (10–6 M; p < 0.001) and supraphysiological concentrations (10–5 M; p < 0.001). The addition of IL-2 (50 and 100 IU/ml/cells) significantly antagonizes the effects of cortisol in SDAT, whereas the cortisol-dependent immunosuppression is partially maintained in healthy elders and in patients with MID. Our data indicate that the defect of the immunosuppressive effect of cortisol may play a role in NK dysregulation in SDAT, contributing to the cytokine-mediated NK overactivity in this disease.

Circadian neuroendocrine functions in disorders of eating behavior

Eating behavior is a complex function determined by regulatory mechanisms characterized by bioperiodic fluctuations. It involves the hypothalamus as well as the related higher centers in the central nervous system (CNS). Many hormones, neurotransmitters and neuropeptides play an important role in the synchronization of food intake. Our study therefore sets out to evaluate the circadian rhythms of several endocrine functions in women with eating disorders, to clarify the pathophysiology of the limbic-hypothalamic system. We measured the circadian rhythms of plasma melatonin, serum cortisol, growth hormone (GH) and prolactin (PRL) in 26 patients with anorexia nervosa (AN), 27 with primary obesity (OB) and 7 with bulim ia nervosa (BN). Simultaneous evaluation of different neuroendocrine rhythms in these three groups revealed similar circadian abnormalities, (namely daytime persistence of melatonin secretion in AN and OB, and similar cortisol profile changes in AN and BN), together with evi dence of internal desynchronization among the different bioperiodic functions. These findings suggest that some changes of the central pathways involved in the control of eating, mood and endocrine functions are common to dissimilar kinds of eating disorders.

A long-term study of the hematological and metabolic effects of a low-dose monophasic oral contraceptive containing gestodene

This long-term metabolic and hemorheological study investigated the effects of monophasic contraceptive treatment with 30 μgethinylestradiol/75 m`g gestodene in 20 healthy young women. No modifications of arterial blood pressure levels, blood/plasma serum viscosity and erythrocyte deformability were demonstrated during the study. Likewise, α2-macroglobulin serum concentrations and hemostatic parameters (fibrinogen, fibronectin, antithrom-biti III, Von Willebrand factor antigen) remained unchanged in the 2-year follow-up period. Concerning the metabolic action of oral contraception on lipid, lipoprotein and apolipoprotein patterns, no significant variations of high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)-, very low density lipoprotein (VLDL)-cholesterol, triglyceride, non-esterified fatty acids (NEFA), LDL-, HDL-, VLDL-lipoprotein and apolipoprotein A-I, A and B levels werefound throughout the 24 months of treatment with the monophasic pill. No differences for each parameter studied were ...