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Biomedical subjects

A Trifiletti

Publications and source records attributed to A Trifiletti.

At least 19 recordsLinked to original sources

Hepatic osteodystrophy: does the osteoprotegerin/receptor activator of nuclear factor-kB ligand system play a role?

Multiple factors can contribute to the development of osteodystrophy in patients with chronic liver disease (CLD). Recently, two new cytokines, osteoprotegerin (OPG) and the receptor activator of nuclear factor-kB ligand (RANKL), have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Therefore, the aim of our study was to evaluate bone metabolism, bone mineral density (BMD) and OPG/RANKL system in 65 male patients with CLD and in 65 healthy controls. Our patients showed lower BMD values than controls both at lumbar and femoral levels. Moreover, they had an unbalanced bone turnover with an increased resorption phase, as shown by high levels of urinary deoxypyridinoline and a decreased formation phase, as shown by the slightly, but significant, low levels of bone-alkaline phosphatase. Patients showed lower plasma levels of free-testosterone than controls and higher - although not significantly so - plasma levels of 17 beta-estradiol. Furthermore, patients with CLD had higher levels of sex hormone-binding globulin and OPG, and lower levels of 25-hydroxyvitamin D (25-HOD) and IGF-I than the control group, while RANKL levels were similar in the two groups. In conclusion, our data do not confirm the hypothesis that the OPG/RANKL system could exert a key role in the pathogenesis of hepatic osteodystrophy, but rather that the observed increase in OPG levels may represent either the result of the inflammatory process per se or a compensation for the observed enhanced bone resorption.

Absorptiometry, Photon↗

Three-year effectiveness of intravenous pamidronate versus pamidronate plus slow-release sodium fluoride for postmenopausal osteoporosis.

All currently available and approved therapies for osteoporosis inhibit bone resorption. But, despite their great value, antiresorptive agents are generally not associated with dramatic increases in bone mass. In light of these data, the aim of our prospective, placebo-controlled, randomized clinical trial, with a 3-year follow up, was to examine the effects of cyclic intravenous pamidronate and fluoride in combination, versus pamidronate alone, on bone mineral density (BMD) at vertebral and femoral levels, biochemical markers of bone turnover, IGF-1 serum levels, and safety and tolerability in 40 postmenopausal women with osteoporosis. During the treatment period, pamidronate alone reduced both markers of bone formation and bone resorption, resulting in an increase of BMD, after 3 years, of 7.07% at the lumbar level and of 6.76% at the femoral level. In the group treated with pamidronate and fluoride, markers of bone turnover had a different trend: after 3 years, there was a lower reduction of bone resorption and an increase of bone formation markers, with a concomitant increase in IGF-1 levels. This resulted, after 3 years of treatment, in a marked variation of BMD at the lumbar level (+12.74%) and a reduced, but still significant, increase at the femoral level (3.89%). Spine radiography and clinical evaluation did not reveal any vertebral fractures in either treatment group. In conclusion, the combined use of pamidronate and fluoride produced somewhat larger, continuous increases in BMD, at the lumbar level, than pamidronate alone.

Alkaline Phosphatase↗

Metabolic effects of dehydroepiandrosterone replacement therapy in postmenopausal women.

OBJECTIVE: To investigate whether long-term treatment with dehydroepiandrosterone (DHEA) in postmenopausal women can modify insulin sensitivity and plasma lipid profile. DESIGN AND METHODS: Twenty healthy postmenopausal women with serum dehydroepiandrosterone sulfate (DHEA-S) concentrations <2.5 micromol/l were enrolled and randomly assigned to two different treatment groups: group 1 were treated with micronized DHEA, 25 mg/day at 0800 h for 12 months; group 2 were treated with an identical placebo tablet. At the beginning and at the end of the study, plasma lipid profile, glucose tolerance (oral glucose tolerance test) and insulin sensitivity (euglycemic hyperinsulinemic clamp: M index) were assessed. RESULTS: After 12 months, the group treated with DHEA showed a considerable improvement of insulin sensitivity (M index +29.55%, P=0.01) and lipid pattern (high-density lipoprotein cholesterol +11.61%, P=0.03; low-density lipoprotein cholesterol -11.07%, P=0.04; triglycerides -19.60%, P=0.03), but glucose tolerance did not change. No modifications were observed in the placebo group. CONCLUSIONS: Long-term treatment with DHEA ameliorates some metabolic parameters that are linked to increased cardiovascular risk and, consequently, this seems to be an interesting therapeutic tool in the management of the postmenopausal syndrome.

Dehydroepiandrosterone↗

Correlation between family history of hypertension and haemostatic disorders.

BACKGROUND: The aim of this study was to evaluate whether a family history of hypertension is associated with haemostatic disorders. METHODS: In 38 normotensive subjects with a family history of hypertension (relatives) and in 46 sex, age and body mass index matched controls with no family history of hypertension, tissue-type plasminogen activator (t-PA), plasminogen activator-inhibitor (PAI-1), D-dimer (DD) and prothrombin fragment 1+2 (F1+2) were evaluated. RESULTS: The t-PA and PAI-1 observed values were significantly higher than the values detected in the controls. CONCLUSIONS: These data seem to suggest a correlation between family history of hypertension and haemostatic disorders.

Adult↗

Evaluation of haemostatic parameters and circadian variations of the haemostatic system in patients with systemic sclerosis and Raynaud's phenomenon.

BACKGROUND: Systemic sclerosis (SSc) is a multisystemic disease characterized by proliferation and swelling of endothelial cells and other disorders. Raynaud's phenomenon (RP) is a disturbance, with unknown pathogenesis, that may be a precursor to SSc. The aim of this study was to investigate possible alterations in the haemostatic system and to examine whether there is a circadian variation in haemostatic variables at the initial stage of SSc. METHODS: In 20 patients with RP (in all patients secondary to SSc) and in 10 controls the levels of thrombomodulin (TM), beta-thromboglobulin (beta-TG), D-dimer (DD), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor (PAI-1) were measured in venous plasma samples taken at 9.00 and 14.00. RESULTS: Only TM levels were found to be higher in patients than in controls. Moreover the PAI-I levels, in the patient group, showed a significant circadian rhythm (with peak values at 9.00). No significant circadian variations for the other parameters were detected. CONCLUSIONS: These data seem to indicate that in patients with RP there is an endothelial damage reflected by a significant elevation of the TM plasma level and a circadian variation in plasma PAI-1, which was higher in the morning. This observation may be an area worth exploring for its importance potential in the knowledge of Raynaud's phenomenon.

Aged↗

Clinical and haemostatic effects of intravenous prostaglandin E1 therapy in patients with peripheral arterial occlusive disease.

BACKGROUND: In this study the action of an antiaggregatory prostaglandin, PGE1, was studied in a group of patients with peripheral arterial occlusive disease (PAOD). METHODS: In 16 patients with PAOD Fontaine stage IIb and III the clinical and haemostatic effects of the endovenous administration of 60 micrograms/die of alprostadil-PGE1 for four weeks, were evaluated. Before and after pharmacological treatment, were evaluated the clinical symptoms (claudicatio intermittens and rest pain) and the following haemostatic parameters: plasma thrombomodulin (TM), beta-thromboglobulin (beta-TG), D-dimer (DD), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor (PAI-1). RESULTS: No significant difference in plasma TM, t-PA and PAI-1 levels was observed after the treatment. On the other hand the patients showed plasma levels of beta-TG and DD significantly decreased at the end of the treatment. From the clinical point of view both claudicatio intermittens and rest pain satisfactorily improved in all patients. CONCLUSIONS: This data confirmed the therapeutic efficacy of PGE1 in the treatment of PAOD patients.

Aged↗

Study of thrombinic activation indexes, in patients with lower limb critic ischaemia, before and after prostaglandin E1 therapy.

BACKGROUND: In this study the action of a prostaglandin, PGE1, was studied in a group of patients with peripheral arterial occlusive disease (PAOD). METHODS: In 16 patients (14 men and 2 women, aged 47-70 years, mean 57 +/- 7) with PAOD, Fontaine stage IIb and III in critical ischemia, the effects on two indexes of thrombin generation and action of the endovenous administration (2 hours) of 60 micrograms of Alprostadil-PGE1 for four weeks were evaluated. In all artheriopathic patients, before and after pharmacological treatment, the following haemostatic parameters were evaluated: the prothrombin fragment 1 + 2 (F1 + 2) and the fibrinopeptide A(FPA). RESULTS: The patients showed plasma levels of FPA significantly decreased at the end of the treatment. On the other hand, no significant difference in plasma F1 + 2 levels was observed after treatment. CONCLUSIONS: These results seem to indicate that plasma F1 + 2 levels are significantly elevated, as a marker of thrombosis status, in patients with PAOD before and after treatment with PGE1.

Aged↗

Efficacy evaluation of prostaglandin E1 against placebo in patients with progressive systemic sclerosis and significant Raynaud's phenomenon.

BACKGROUND: Raynaud's phenomenon, due to connective tissue diseases, is difficult to treat successfully. Symptomatic improvement has been reported using nifedipine or iloprost, but adverse side effects may limit their use. The purpose of this study was to examine the effects of PGE1 (Alprostadil) in patients with scleroderma and severe Raynaud's disease. METHODS: Twelve females, aged 50-67 years, were included in the study with six of them receiving a 3-hour infusion of alprostadil at the standard dosage of 60 micrograms in 250 cc of physiological infusion for six consecutive days and the remaining six receiving placebo (250 cc of physiological infusion administered in the same manner). RESULTS: After infusion, blood flow, digitally measured by telethermography was increased only in patients treated with alprostadil. The number, frequency and severity of attacks recorded were reduced only in patients treated with alprostadil. No side effects were recorded during and after the infusion. CONCLUSION: In conclusion, alprostadil is effective in the management of Raynaud's phenomenon, due to scleroderma.

Alprostadil↗

Haemostatic changes in patients with deep vein thrombosis.

Thrombomodulin (TM), beta-thromboglobulin (beta-TG), D-dimer (DD), tissue-type plasminogen-activator (t-PA), plasminogen activator-inhibitor (PAI-1) and quantitative determination of functional protein S (PS) were measured using ELISA procedures in the plasma of 16 untreated patients with newly-diagnosed deep vein thrombosis in the leg and in 10 healthy volunteers. No significant difference in plasma TM, t-PA and PS levels was observed among the controls and patients with deep vein thrombosis. These patients, on the other hand, showed plasma DD, beta-TG and PAI-1 levels significantly higher than the control subjects. These data show that in patients with deep vein thrombosis a hypercoagulable state is a common occurrence.

Adult↗

Haemostatic parameters in patients with primitive venous hypertension.

In twenty patients with primitive venous hypertension and in ten healthy subjects we have determined the plasmatic levels of: Thrombomodulin (TM), beta-Thromboglobulin (beta-TG), D-Dimer (DD), the tissue activator of the plasminogen (t-PA) and the inhibitor of the activator of the plasminogen (PAI-1). The levels of the parameter we studied have shown in the patients a significant difference of beta-TG (p < 0.01) and PAI-1 (p < 0.01) compared to the controls, whereas there was no significant difference in the other parameters we studied. Our data underline, in patients with primitive venous hypertension, the importance that the activation of the platelets and the reduction of the potential fibrinolytic can assume, together with the stasis, regarding the onset of thrombotic complications.

Adult↗

Haemostatic effects of iloprost in patients with lower limb ischemia.

The aim of this study was to investigate the haemostatic effects of iloprost, a stable analogue of prostacyclin, in patients with peripheral arterial disease. In a group of 13 patients with obliterative arteriopathies of the lower limbs the plasma levels of thrombomodulin (TM), betathromboglobulin (beta-TG), D-dimer (DD) and plasminogen activator-inhibitor (pAI-1) were measured, and compared to the values obtained from 10 healthy volunteers. All the parameters were found to be significantly higher in vasculopathic patients. These haemostatic evaluations were carried out after 4 weeks of treatment with iloprost up to 2 ng/kg/min, 6 hours infusion per day. During and at the end of treatment a clinical improvement was recorded. The patients also showed a significant decrease in plasma beta-TG and DD at the end of treatment. These data suggest that iloprost exerts clinical improvement, in who may have a part the decrease of platelet activation and of fibrin turnover.

Adult↗

Protein S in normal subjects and patients with peripheral arterial disease.

The aim of the present study was to investigate if alterations in protein S levels occur in peripheral arterial disease. In a group of 33 patients with peripheral arterial disease and in a group of 10 healthy volunteers we have the quantitative determination of functional protein S. The observer values show non significant difference in protein S levels among vasculopathic patients and controls (only five out of 33 patients showed low protein S levels). These data seem to suggest that low protein S levels do not play an important role in the development of peripheral arterial disease.

Aged↗

No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide.

The aim of this study was to investigate the relationship between plasma insulin levels, peripheral insulin sensitivity and androgen secretion in ten patients with polycystic ovary syndrome and in six obese women as compared with six normal-weight control subjects. During a euglycemic-hyper-insulinemic clamp no significant change of testosterone, androstenedione or dehydroepiandrosterone sulfate plasma levels was observed in the two groups of patients or in the control subjects; insulin sensitivity was clearly reduced and was similar in polycystic ovary patients and in obese women, in spite of the different plasma androgen levels. A long-term (5 months) androgen suppression with the gonadotropin-releasing hormone agonist leuprolide was not able to improve significantly the insulin sensitivity. These results demonstrate that the short-term hyperinsulinemia achieved with the clamp technique does not affect androgen secretion and that insulin resistance, measured with the same technique, is not influenced by long-term suppression of plasma androgen levels in polycystic ovary syndrome.

Adult↗

Hemostatic disorders associated with arterial hypertension and peripheral arterial disease.

To study a possible hypercoagulability in vascular disease, in 22 patients with essential hypertension and in 13 patients with obliterative arteriopathies of the lower limbs we measured the levels of plasma thrombomodulin (TM), plasma and urine beta-thromboglobulin (beta-TG), plasma D-dimer (DD) and plasminogen activator-inhibitor (PAI-1) and compared to the values obtained from 10 healthy volunteers. The values observed in hypertensive patients show only PAI-1 levels significantly higher. All the parameters were found to be significantly increased in vasculopathic patients. These data confirm that in vasculopathic patients endothelium damage, platelet activation, impaired fibrinolytic potential and increase of fibrin turnover, occur. On the other hand, in the hypertensive patients, at first stages of the disease, we have found only an increase of PAI-1 plasma levels documenting impaired fibrinolytic potential.

Adult↗

[Hypertriglyceridemia, IRI and platelet aggregation].

The Authors have studied in 13 patients with type IV hyperlipoproteinemie the behaviour of platelet aggregation and the response of IRI and blood nefa to an oral glucose load. Only two, in whom it has been possible to evidence a basal hypernefemia and a net hyperinsulinism in response to glucose oral load, showed platelet hyperaggregation to all inducers. These findings suggest that type IV hyperlipoproteinemia does not significantly influence platelet aggregation, in which IRI may have a possible role.

Adult↗

[Platelet aggregation in normal and hypertensive subjects during cold pressor test].

The Authors have studied, in 5 normal subjects and in 10 with essential arterial hypertension, the behaviour of platelet aggregation before, during and after cold pressor test. It has been possible to evidence, in hypertensive subjects, a greater responsiveness of platelets to adrenaline induced aggregation. The Authors think that such effects may be due to hyperexcitability of sympathetic nervous system, which can regulate the functional behaviour of platelets in response to cold pressor test.

Adenosine Diphosphate↗