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Biomedical subjects

G Ferretti

Publications and source records attributed to G Ferretti.

At least 37 records · Page 2Linked to original sources

Intracellular oxidative activity and respiratory burst of leukocytes isolated from multiple sclerosis patients.

Oxidative damage induced by free radicals and reactive oxygen species (ROS) have been suggested to play an important role in the development of autoimmune diseases such as multiple sclerosis (MS) disease and it has been hypothesised that oxidative injury could mediate demyelination and axonal injury in MS subjects. In our study, we compared intracellular oxidative activity and the respiratory burst activity in MS patients (n=20) and healthy controls (n=15) using leukocytes as cellular model. At this purpose, intracellular ROS levels were evaluated by fluorometric assay using the 2'-7'-dichlorodihydrofluorescin diacetate probe (H(2)DCFDA) in untreated or in leukocytes stimulated with phorbol-12-myristate-13-acetate (PMA). Our results demonstrate that the intracellular spontaneous ROS production in leukocytes from MS patients was higher with respect to cells from control subjects (p<0.001). PMA addition induced a higher formation of ROS both in leukocytes from MS patients and controls (p<0.001). The PMA-induced production of ROS was significantly higher in leukocytes from MS with respect to controls (p<0.001). Significant positive correlations were established between intracellular spontaneous or PMA-induced production of ROS in leukocytes isolated from MS patients and the clinical parameters used to evaluate disease disability such as expanded disability status scale (EDSS), brain lesions evaluated by MRI and visual evoked potential (VEP) (p<0.001). In conclusion, our results demonstrate higher levels of intracellular ROS in untreated or in PMA-treated leukocytes isolated from MS patients with respect to healthy subjects confirming the role of oxidative stress in multiple sclerosis.

Adult↗

Renal artery entrapment by the diaphragmatic crus.

The aim of this study is to describe renal artery entrapment (RAE) by the diaphragmatic crus and to elucidate the diagnostic and therapeutic approach to this entity. From 1995 to 2002, 15 patients (mean age 65) were found to have a RAE. They were investigated by CT scan (n=14) and/or MRA (n=2) for hypertension (n=7), chronic renal insufficiency (n=4) or aneurysms (n=4). The right (n=11) or the left (n=4) renal artery (RA) was involved. The compression was ostial (n=8) or truncal (n=7), and was > or = 50% in eight cases. The course of the RA along the aorta on angiographic views (n=8) or a concentric ostial stenosis in a patient free of atheromatous lesions (n=7) were two findings suggestive of an RAE. Seven RAEs were indicated for treatment but only three were treated, by mean of stenting. Among the latter, two stents were patent at 6-month follow-up and one evolved to restenosis because of a stent fracture. RAEs may be suspected on angiographic views and proved by cross-sectional imaging because of specific imaging features. It is of importance to detect this etiology of RA stenosis because angioplasty with stenting is probably not always advisable.

Adult↗

Influence of 90-day simulated microgravity on human tendon mechanical properties and the effect of resistive countermeasures.

While microgravity exposure is known to cause deterioration of skeletal muscle performance, little is known regarding its effect on tendon structure and function. Hence, the aims of this study were to investigate the effects of simulated microgravity on the mechanical properties of human tendon and to assess the effectiveness of resistive countermeasures in preventing any detrimental effects. Eighteen men (aged 25-45 yr) underwent 90 days of bed rest: nine performed resistive exercise during this period (BREx group), and nine underwent bed rest only (BR group). Calf-raise and leg-press exercises were performed every third day using a gravity-independent flywheel device. Isometric plantar flexion contractions were performed by using a custom-built dynamometer, and ultrasound imaging was used to determine the tensile deformation of the gastrocnemius tendon during contraction. In the BR group, tendon stiffness estimated from the gradient of the tendon force-deformation relation decreased by 58% (preintervention: 124 +/- 67 N/mm; postintervention: 52 +/- 28 N/mm; P < 0.01), and the tendon Young's modulus decreased by 57% postintervention (P < 0.01). In the BREx group, tendon stiffness decreased by 37% (preintervention: 136 +/- 66 N/mm; postintervention: 86 +/- 47 N/mm; P < 0.01), and the tendon Young's modulus decreased by 38% postintervention (P < 0.01). The relative decline in tendon stiffness and Young's modulus was significantly (P < 0.01) greater in the BR group compared with the BREx group. Unloading decreased gastrocnemius tendon stiffness due to a change in tendon material properties, and, although the exercise countermeasures did attenuate these effects, they did not completely prevent them. It is suggested that the total loading volume was not sufficient to completely prevent alterations in tendon mechanical properties.

Adaptation, Physiological↗

Midazolam for acute emesis refractory to dexamethasone and granisetron after highly emetogenic chemotherapy: a phase II study.

GOALS OF THE WORK: To assess whether the addition of midazolam to dexamethasone and granisetron could ameliorate the refractory acute nausea and/or vomiting caused by a highly emetogenic platinum-based chemotherapy. PATIENTS AND METHODS: Enrolled in the study were 30 consecutive adult patients with refractory acute emesis. Nausea and vomiting were assessed by physicians and graded according to the NCI common toxicity criteria. Nausea was further self-assessed by patients using a visual analogue scale. Statistical analysis was performed by nonparametric tests. RESULTS: With the introduction of midazolam, 73% of patients had a reduction of at least one grade in nausea and vomiting intensity in comparison with the previous cycle of chemotherapy. From the second cycle, six patients (23%) had complete control of acute vomiting, a benefit that usually persisted in the subsequent cycles. Five more patients achieved complete control of acute vomiting during the third course; this effect persisted in the subsequent courses as well. The average relative reduction in acute nausea and vomiting grade from the first to the second course was 48% (95% CI 34-62%) and 48% (95% CI 31-65%), respectively. A significant difference in acute nausea and vomiting over all the six courses of chemotherapy administered was recorded (Friedman ANOVA, P <0.0001). Comparing each course with any subsequent course, a significant reduction in acute nausea and vomiting was observed between the first and second course, the first and third course, and the first and fourth course. CONCLUSIONS: Our results suggest that midazolam may be a useful adjunct to standard antiemetic drugs for patients receiving highly emetogenic cisplatin-based chemotherapy. A randomized trial is warranted to confirm these results.

Adult↗

[Imaging of adrenal ganglioneuroma: a case report].

The authors report a case of adrenal ganglioneuroma diagnosed in a young woman with melanoma. This benign hormone silent tumor arises from neural crest tissue. The imaging features at US, CT and MRI are described. Diagnosis was confirmed at CT guided biopsy.

Adrenal Gland Neoplasms↗

Atypical language lateralization and early linguistic development in children with focal brain lesions.

The effects of congenital, unilateral, focal brain lesions on early linguistic development and hemispheric lateralization for language were investigated longitudinally in 24 preschool children with hemiplegia (14 males, 10 females), 12 with left hemisphere damage (LHD) and 12 with right hemisphere damage (RHD). A comprehensive linguistic assessment was performed at 2 and 3 years of life; cerebral lateralization for language was measured by the Fused Dichotic Words Listening Test. An early left-side specificity for language was indicated by the presence of lexical and grammatical delay in most children with LHD. In the dichotic listening test all 12 children with LHD showed a shift of language lateralization from the left to the right hemisphere. Atypical lateralization coefficients (lambda), i.e. values falling more than two standard deviations from the mean of a normative sample, were associated with a delay in lexical and grammatical development, especially after LHD. In addition, cortical-subcortical-periventricular lesions rather than solely periventricular damage, and larger lesions rather than small, were associated with the most atypical lateralization coefficients, irrespective of lesion side. Results of this study suggest that language and lateralization data are closely related and that reallocation of language functions in alternative regions of the brain has a cost in terms of a slow rate of language acquisition.

Brain Diseases↗

Persistent aura without infarction: decription of the first case studied with both brain SPECT and perfusion MRI.

To the best of our knowledge, persistent visual symptoms, lasting months or years without evidence of infarction, a rare complication of migraine with aura, has been reported in only 20 patients. We report the case of a 43-year-old woman with a 31-year history of migraine with typical visual aura. At presentation, she experienced a visual aura in her right hemifield followed by a pulsating headache. The visual symptoms persisted. There were no abnormal findings on neurological and ophthalmological examinations, EEG, visual evoked potentials (VEPs), brain computed tomography and magnetic resonance imaging (MRI). Both brain single photon emission computed tomography (SPECT) and brain perfusion MRI revealed decreased left fronto-parieto-occipital and right occipital blood perfusion. A perfusion MRI, performed 7 months after symptom onset and almost complete extinction of symptoms, was normal. As previously reported, we demonstrated a cortical hypoperfusion by SPECT in a case of persistent visual aura. For the first time this finding was confirmed by perfusion MRI.

Adult↗

Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity.

Paraoxonase, an enzyme associated with high density lipoproteins (HDL), plays an important role in the anti-oxidant and anti-inflammatory properties exerted by HDL. Increasing evidence supports a role of free radicals and oxidative stress in the inflammatory processes and in the pathogenesis of multiple sclerosis (MS). The aim of this study was to further investigate the relationship between oxidative damage and MS; therefore we compared the paraoxonase activity and levels of cholesteryl ester hydroperoxides (CE-OOH), as marker of lipid peroxidation, in plasma isolated from healthy subjects (n = 89) and from MS patients (n = 24) in the early stage disability (EDSS<3.5). Our results demonstrated for the first time that the activity of paraoxonase in the plasma of MS subjects was significantly lower with respect to controls (P <0.001). Moreover, our results showed a significant increase in the levels of CE-OOH in plasma from MS subjects (P<0.001). CE-OOH are biologically active substances derived from the oxidation of cholesteryl ester localized in the hydrophobic core of plasma lipoproteins (HDL, LDL). Therefore, our study demonstrates alterations of lipoprotein peroxidation in MS and provides further evidence that oxidative stress and impairment of the anti-oxidant system may play a role in MS.

Adult↗

Prostate cancer: the role of hormonal therapy.

Prostate cancer is the cause of more than 1% of all deaths in men. Its incidence is increasing by 2-3% per year. The general prognosis for diagnosed prostate cancer remains poor, with 70% survival at 10 years compared to the general population. About 50% of the cases are diagnosed at a locally advanced stage, and about 30% have bone metastases at the time of diagnosis. Adjuvant systemic treatments (hormones or chemotherapy), which are effective for advanced-stage disease, might have a greater role in early-stage disease. Advanced prostate cancer is an incurable disease. Treatment objective is palliation only. Here, we review the major controversies concerning hormonal therapy, and provide a general approach to management of patients with early-stage and advanced prostate cancer.

Androgen Antagonists↗

Paraoxonase activity in high-density lipoproteins: a comparison between healthy and obese females.

Paraoxonase, an enzyme associated with high-density lipoprotein (HDL-PON), exerts a protective effect against oxidative damage of circulating cells and lipoproteins, modulates the susceptibility of HDL to atherogenic modifications such as glycation and homocysteinylation, and even exerts an antiinflammatory role. The aim of the present study was to investigate the relationship between lipoprotein oxidative stress and the activity of HDL-PON in healthy and obese subjects. Therefore, the activity of HDL-PON and the levels of lipid hydroperoxides in HDL and low-density lipoprotein (LDL) isolated from plasma of obese females (n = 12) and age-sex-matched controls (n = 31) were compared. Our results demonstrated for the first time that the activity of HDL-PON in obese subjects was significantly lower compared with that in controls (P < 0.001). Moreover, our results showed a significant increase in the levels of lipid hydroperoxides in HDL and LDL isolated from obese subjects (P < 0.001). The negative correlations established between HDL-PON activity and the levels of lipid hydroperoxides associated with HDL and LDL confirm the relationship between paraoxonase activity and lipid peroxidation of lipoproteins. Plasma levels of leptin correlated negatively with HDL-PON activity and positively with levels of lipid hydroperoxides in HDL and LDL of obese subjects, suggesting a relationship between leptin and oxidative damage of lipoproteins. In conclusion, our study demonstrated that the increase in oxidative stress in LDL and HDL of obese subjects is associated with a decrease in HDL-PON activity. The lower paraoxonase activity and the compositional changes in HDL and LDL could contribute to the greater risk of cardiovascular disease associated with obesity.

Adult↗

Effect of genistein against copper-induced lipid peroxidation of human high density lipoproteins (HDL).

Several studies have demonstrated that the isoflavone genistein exerts a protective effect against lipid peroxidation of low density lipoproteins (LDL). Aim of our study was to investigate whether genistein protects high density lipoproteins (HDL), isolated from normolipemic subjects, against Cu(++)-induced lipid peroxidation. Our results demonstrated that genistein exerts an inhibitory effect against Cu(++)-induced lipid peroxidation of HDL, as shown by the lower increase in the levels of conjugated dienes in lipoproteins oxidized after preincubation with different concentrations of genistein (0.5-2.5microM). Moreover the analysis of fluorescence emission spectra of tryptophan (Trp) and Laurdan (6-dodecanoyl-2-dimethyl-aminonaphthalene) demonstrated that genistein prevents the alterations of apoprotein structure and physico-chemical properties, associated with Cu(++)-triggered lipid peroxidation of lipoproteins. The protective effect exerted by genistein against oxidative damage of lipoproteins was realized at concentrations similar to those observed in plasma of human subjects consuming a traditional soy diet or receiving a soy supplement. Therefore, we suggested that antioxidant activity exerted by genistein against lipid peroxidation of HDL in vitro could be of physiological relevance.

2-Naphthylamine↗