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Biomedical subjects

E Ferrari

Publications and source records attributed to E Ferrari.

At least 379 records · Page 21Linked to original sources
PubMedDate not supplied

Hypoglycemic therapy and hemostasis in maturity- onset diabetes mellitus: existence of an early prethrombotic state.

We studied 115 patients with uncomplicated maturity-onset diabetes mellitus, 55 males and 60 females; patients were divided into 7 groups according to the hypoglycemic therapy (diet alone, tolbutamide, glibenclamide, phenformin, combination of the last two drugs, insulin, combination of insulin and phenformin). All patients were tested for a prethrombotic state by the simultaneous determination of the following parameters: ADP-induced platelet aggregation, Factor VIII as antigen and procoagulant activity and the plasma levels of fibrinogen and antithrobin III. Our results show that these parameters were markedly altered in diabetic patients when compared to apparently normal subjects of the same age; on the contrary, differences between groups of diabetic patients were very slight and hardly ever statistically significant. These results suggest that the prethrombotic alterations of hemostatic system are very similar in all groups of diabetic patients; this is true also for patients submitted to diet alone, i.e. with slight and usually recent-onset diabetes mellitus. In conclusion, our study suggests the opportunity, at least from the theoretical point of view, of systematic antiaggregant and/or anticoagulant treatment(s) in maturity-onset diabetes mellitus, whose severe and precocious prethrombotic alterations seem to be independent of the hypoglycemic treatment applied.

Adenosine Diphosphate↗
PubMedDate not supplied

Plasma fibronectin, von Willebrand factor antigen, and blood rheology. Association with diabetic microvascular disease.

Plasma fibronectin might play a role in the pathogenesis and progression of diabetic microvascular disease. To test this hypothesis we measured plasma fibronectin, von Willebrand factor antigen, fibrinogen, erythrocyte filtrability, whole-blood viscosity, proteinuria and albuminuria in 25 control subjects and 29 diabetic patients with and without microvascular complications. Plasma fibronectin was significantly higher in the diabetic patients, especially in those with retinopathy and nephropathy. A significant correlation between fibronectin and von Willebrand factor antigen was found in both patients with and without microangiopathy (p less than 0.001). In diabetic patients with and without microvascular complications, several significant correlations were found between increased fibronectin levels and reduced erythrocyte filtrability (p less than 0.001) and between the increase of fibronectin and whole-blood viscosity (p less than 0.001). Furthermore, a significant correlation was found between plasma fibronectin levels, proteinuria (p less than 0.001) and albuminuria (p less than 0.001). The relationship between plasma fibronectin and changes of blood rheology may be important for the occurrence and progression of diabetic microangiopathy.

Aged↗
PubMedDate not supplied

Pentoxifylline, albumin excretion rate and proteinuria in type I and type II diabetic patients with microproteinuria. Results of a short-term randomized study.

An association between renal microvascular complications and hemorheological alterations has been suggested in diabetes mellitus. Therefore, a hemorheologic approach in the treatment of diabetic microproteinuria has been proposed. Eighty-two type I and type II diabetic patients with microproteinuria were randomized and assigned to two different protocols: protocol A, patients treated with pentoxifylline (Trental 400); protocol B, patients without hemorheologic treatment, in whom hypoglycemic therapy was just more strictly enforced. A significant improvement of the hemorheologic pattern and a significant marked reduction of albumin excretion rate and proteinuria was found in diabetic patients treated with pentoxifylline, independently of the degree of metabolic control. These results were readily achieved and were confirmed throughout the study. Moreover, these results were comparable to those obtained in diabetic patients of protocol B. Pentoxifylline might therefore be considered as the first useful therapeutic agent in the treatment of diabetic microproteinuria.

Adult↗
PubMedDate not supplied

Hemorheologic and hemostatic changes in long-standing insulin-dependent (type I) diabetic patients with peripheral and autonomic cardiovascular neuropathy.

Diabetic microangiopathy may be associated with the pathogenesis and progression of autonomic and peripheral neuropathy. In 17 long-standing type I diabetic patients with peripheral and autonomic cardiovascular neuropathy, several hemorheological and hemostatic alterations were found compared to 13 matched type I patients without neuropathy. In particular, increased plasma von Willebrand factor antigen (p less than 0.001), fibronectin (p less than 0.001) and fibrinogen (p less than 0.001) levels were demonstrated in neuropathic in comparison with non-neuropathic diabetic patients. Moreover negative correlations between these parameters and both motor and sensitive conduction velocity of median, sural and peroneal nerves were observed in diabetic patients with neuropathy. Higher blood viscosity (p less than 0.05 at shear-rate of 450 and 225 s-1; p less than 0.01 at 90 s-1; p less than 0.001 at 4.5 and 2.25 s-1), plasma viscosity (p less than 0.001) and lower erythrocyte filtrability (p less than 0.001) were also found in neuropathic compared to non-neuropathic diabetics. Increased prevalence of retinopathy (p less than 0.01) and nephropathy (p less than 0.001) was finally reported in patients with autonomic and peripheral neuropathy. Microvascular disease may be involved in the development of neuropathy in long-term type I diabetes mellitus.

Blood Pressure↗
PubMedDate not supplied

Hypoglycemic treatments and the fibrinolytic system in maturity-onset diabetes mellitus without thromboembolic manifestations.

The fibrinolytic system was investigated in 115 patients with maturity-onset diabetes mellitus in good metabolic control and without thromboembolic manifestations. The patients were divided into 7 groups according to the hypoglycemic therapy: diet alone, tolbutamide, glibenclamide, phenformin, combination of the last two drugs, insulin, combination of insulin and phenformin. Our results indicate that in maturity-onset diabetes both fibrinolytic activity and inhibitors of fibrinolysis are increased. The enhanced fibrinolytic activity was not affected by different hypoglycemic drugs, whereas the main antiplasmins showed wide variations in the different treatment groups. In particular, a significant reduction of alpha 2M was observed in patients on glibenclamide therapy. In conclusion, our study showed that the high fibrinolytic state seems to be a constant element in diabetes, and that the different behaviors of the fibrinolytic system, reported by various authors in patients taking different hypoglycemic drugs, could be explained by the wide range of plasmin inhibitor levels observed in these conditions.

Aged↗
PubMedDate not supplied

Pentoxifylline, total urinary protein excretion rate and arterial blood pressure in long-term insulin-dependent diabetic patients with overt nephropathy.

A specific hemorheologic treatment might reduce urinary protein excretion and the decline in kidney function in diabetic patients with overt clinical nephropathy. Twenty-one insulin dependent (type I) diabetic patients were randomized and assigned to a treatment with conventional antihypertensive therapy (protocol I) or with pentoxifylline (Trental 400) (protocol II). A marked improvement of blood rheology pattern, together with a reduction of urinary albumin excretion rate and total urinary protein excretion rate, was demonstrated throughout a 1-year follow-up study with pentoxifylline. Furthermore a decrease of systolic and diastolic blood pressure levels was found during the treatment. The modification of these parameters was followed by a significant increase of creatinine clearance in each of the patients studied. The results obtained during pentoxifylline therapy were comparable to those obtained in patients treated with conventional antihypertensive drugs. Pentoxifylline may therefore be used in the treatment of advanced nephropathy in diabetic patients.

Adult↗
PubMedDate not supplied

Increased plasma apolipoprotein B levels and blood hyperviscosity in non-insulin-dependent diabetic patients: role in the occurrence of arterial hypertension.

An association between arterial blood pressure and blood viscosity has been suggested in healthy and in diabetic subjects, and that the hemorheological pattern may be influenced by blood lipid alterations. In diabetic patients a relationship between arterial hypertension and blood lipid changes may therefore be suggested. This study concerns 19 type II diabetics with hyperlipidemia (triglycerides = 3.2 +/- 1 mmol/l; total cholesterol = 6.1 +/- 1.2 mmol/l; HDL-cholesterol = 0.92 +/- 0.27 mmol/l; VLDL = 29 +/- 5%) (group A), and 19 normolipidemic type II diabetics (triglycerides = 1.15 +/- 0.5 mmol/l; total cholesterol = 5.1 +/- 1 mmol/l; HDL-cholesterol = 1.25 +/- 0.38 mmol/l; VLDL = 20 +/- 5%) (group B). No differences concerning age, body weight, duration of diabetes and glycemic control were found in hyperlipidemic compared to normolipidemic diabetics. On the contrary, higher systolic and diastolic blood pressure levels were demonstrated in group A (167 +/- 14 mmHg and 101 +/- 5.2 mmHg, respectively) than in group B (144 +/- 15 mmHg, p less than 0.001 and 87 +/- 6.9 mmHg, p less than 0.001, respectively). An increase of plasma apolipoprotein B level (163 +/- 27 mg/dl vs 102 +/- 21 mg/dl, p less than 0.001), of plasma viscosity (1.81 +/- 0.08 mPas vs 1.51 +/- 0.07 mPas, p less than 0.001) and of blood viscosity (5.37 +/- 0.33 mPas vs 5.07 +/- 0.04 mPas, p less than 0.01, at shear-rate of 90 s-1; 18.4 +/- 1 mPas vs 14.1 +/- 0.9 mPas, p less than 0.001 at shear-rate of 2.25 s-1) was found in group A, compared to group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Determination of albuminuria in type 1 and type 2 diabetic patients with microproteinuria and overt nephropathy. Comparative evaluation between a radial immunodiffusion procedure and a highly sensitive radioimmunoassay.

We have studied the correlation between urinary albumin excretion rate evaluated by a radial immunodiffusion technique and a highly sensitive radioimmunoassay in type 1 and type 2 diabetic patients with microproteinuria and overt clinical nephropathy. Several statistically significant correlations were found between urinary albumin excretion rate measured by radial immunodiffusion and by radioimmunoassay, both in patients with microproteinuria and overt nephropathy. Moreover, statistically significant correlations between urinary albumin excretion rate, albumin clearance and total urinary protein excretion rate were observed in each of the groups studied. The radial immunodiffusion procedure can therefore be considered a useful and sensitive method for the evaluation of urinary albumin excretion rate both in diabetic patients with microproteinuria and in patients with overt clinical nephropathy.

Albuminuria↗
PubMedDate not supplied

Plasma fibronectin as an indicator of microvascular damage in diabetic patients. Rapid and sensitive evaluation by a radial immunodiffusion technique.

Plasma fibronectin might be considered as an indicator of early and advanced microvascular damage in diabetic patients. We have therefore studied plasma fibronectin, using a radial immunodiffusion technique (LC-Partigen Fibronectin), in insulin-dependent and non-insulin-dependent diabetic patients with and without microangiopathic and neurological complications, i.e. retinopathy, nephropathy and autonomic and peripheral neuropathy. Steady and progressive increases of plasma fibronectin levels in association with the worsening of both diabetic retinopathy and nephropathy have been observed. However, significant variations of plasma fibronectin levels were already found in diabetic patients without microangiopathy when compared with healthy control subjects. Fibronectin levels were also higher in diabetic patients with autonomic and peripheral neuropathy than in control subjects and diabetic patients without neurological changes. The evaluation of plasma fibronectin by a specific radial immunodiffusion procedure might represent an important approach in the study and prevention of diabetic microcirculatory disorders.

Diabetes Mellitus↗
PubMedDate not supplied

Hemorheological changes and overproduction of cytokines from immune cells in mild to moderate dementia of the Alzheimer's type: adverse effects on cerebromicrovascular system.

An association between hemorheological alterations (i.e., whole-blood and plasma hyperviscosity, reduced erythrocyte deformability, increased red cell aggregation, hyperfibrinogenemia and increased acute-phase protein levels) and the mild stage of senile dementia of the Alzheimer's type (DAT) was suggested in the present study. In particular, hyperfibrinogenemia and the increase of erytrhocyte aggregation were correlated with the increased generation and release of TNF-alpha and IFN-gamma (spontaneous release and IL-2-modulated release) from natural killer (NK) lymphocytes (CD16+, CD56+, CD3- cells) of patients with DAT; whereas a normal cytokine release from NK cells was found in healthy old subjects and in patients with vascular dementia (VaD). The in vitro and in vivo administration of the hemorheologic drug pentoxifylline (PTX) significantly reduced spontaneous and IL-2-modulated cytokine overproduction from NK cells (in vitro effects with 500 U/ml and 1000 U/ml/NK cells) and improved all the hemorheological parameters. Taken together, these data suggest that disturbances of cerebrovascular flow and of hemorheology could be considered a negative component related to the pathogenesis and progression of DAT neurodegeneration. The association between hemorheological changes and alterations of TNF-alpha and IFN-gamma release from NK may indicate a potential immunorheologic mechanism associated with cerebrovascular damage in DAT and could suggest the use of vascular protective drugs as support of the main pharmacological and non-pharmacological therapy of AD.

Aged↗
PubMedDate not supplied

Increased natural killer cell cytotoxicity in Alzheimer's disease may involve protein kinase C dysregulation.

Increased cytokine-mediated cytotoxic natural killer (NK) cell activity has recently been demonstrated in patients with senile dementia of the Alzheimer's type (SDAT). In the present study, we evaluated whether protein-kinase C (PKC), a main regulatory enzyme involved in the mechanism of exocytosis by NK cells, has a role in the cytotoxic response of NK cells (during IL-2 and IFN-beta exposure) from SDAT patients. Our data demonstrate the presence of an increased cytotoxic response by NK cells to IL-2 (mean increase +102%) and IFN-beta (mean increase +132%) in SDAT patients in comparison with healthy elderly subjects (+75% and +88% for IL-2 and IFN-beta, respectively). A smaller suppression of NK cytotoxicity after cortisol was also observed in SDAT (mean decrease -24%) than in the control group (-44%). The NK cell activity of SDAT patients was inversely correlated with the cognitive status as evaluated by the analysis of MMSE (Mini Mental State Examination) score. A comparison of young and elderly healthy subjects revealed no variations in NK cell activity. A physiological decrease in cytosolic PKC activity was demonstrated in healthy old subjects after IL-2 and IFN-beta incubation, but not in SDAT patients, while no variations in kinase activity were observed after cortisol incubation. The decreased activity with cytokines was associated with reduced levels of PKC alpha and betaII isoforms. An alteration in cytokine-mediated NK cell activity associated with PKC dysregulation is therefore suggested to occur in patients with SDAT. These changes may indicate the existence of an immunological component to the pathogenesis and progression of the disease.

Adult↗
PubMedDate not supplied

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.

Aged↗
PubMedDate not supplied

Dehydroepiandrosterone sulfate decreases the interleukin-2-mediated overactivity of the natural killer cell compartment in senile dementia of the Alzheimer type.

Since dehydroepiandrosterone sulfate (DHEAS) has been involved in the regulation of cellular immunity, the aim of the presence study was to evaluate whether the age-dependent reduction of DHEAS was associated with changes of natural killer (NK) immune function in healthy elderly subjects and in patients with senile dementia of the Alzheimer type (SDAT). Circulating DHEAS was determined throughout 24 h (circadian profile). NK cytotoxic activity was measured as spontaneous and induced cytotoxicity during exposure with DHEAS (10(-7) M), interleukin-2 (IL-2; 100 IU) and IL-2 (100 IU) coincubated with DHEAS (10(-7) M). DHEAS was significantly reduced in healthy elderly subjects (mesor M +/- SD = 2.3 +/- 0.5 micromol/l) and SDAT (1.6 +/- 0.4 micromol/l) patients compared to healthy young subjects (6.7 +/- 0.9 micromol/l; p < 0.001); significant differences were also found when healthy elderly subjects and SDAT patients were compared (p < 0.01). A significant inverse correlation between age and DHEAS levels was demonstrated in SDAT and healthy elderly subjects (p < 0.05). The decrease in 24-hour DHEAS secretion was associated with a higher NK cytotoxic response to DHEAS in the healthy elderly subject group than in healthy subjects of young age (p < 0.01). Increased NK cell activity during IL-2 incubation was found in patients with SDAT in comparison with the healthy elderly subject (p < 0.001). On the contrary, NK cell cytotoxic response of SDAT patients was less pronounced during DHEAS exposure and when DHEAS was coincubated with IL-2 (p < 0.001). These data suggest an immunomodulatory role of DHEAS on NK functional activity in physiological aging and SDAT. The antagonizing effect of DHEAS on NK overactivity during exposure with cytokines might counteract some neuroimmune components related to the pathogenesis and progression of the disease.

Adult↗
PubMedDate not supplied

Association between changes in adrenal secretion and cerebral morphometric correlates in normal aging and senile dementia.

The circadian organization of adrenal secretion was studied in 23 healthy elderly subjects, 23 elderly demented patients and 10 healthy young subjects, in order to investigate the relationships between the hypothalamic-pituitary-adrenal axis and some cerebral morphometric parameters. The cerebral morphometric analysis was performed in some subjects of the three groups by MRI. A significant increase in cortisol levels during evening and nighttime was found in both groups of the aged subjects. In elderly subjects, particularly if demented, the mean serum dehydroepiandrosterone sulfate (DHEAs) levels throughout the 24-hour cycle were significantly lower than in young controls. A significant reduction of the hippocampal and temporal volume and an enlargement of the lateral ventricles were found in aged subjects, these changes being significantly related to subjects' age. Moreover, the hippocampal volume was positively correlated with the circadian mesor of DHEAs (i.e., the circadian rhythm adjusted mean) and with the cortisol nocturnal increase. Our data may suggest the existence of a link between the selective impairment of cortisol secretion and DHEAs levels, and the progression of hippocampal degeneration.

Adrenal Glands↗