A5086407745- Bone health and osteoporosis research
- Muscle Physiology and Disorders
- Bone health and treatments
- Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Bone Metabolism and Diseases
- Histone Deacetylase Inhibitors Research
- Neuropeptides and Animal Physiology
- Neurogenetic and Muscular Disorders Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Stress Responses and Cortisol
- Acute Myeloid Leukemia Research
- Pain Mechanisms and Treatments
- Receptor Mechanisms and Signaling
- Sleep and related disorders
- Pain Management and Placebo Effect
- Parathyroid Disorders and Treatments
- Sleep and Wakefulness Research
- Diet and metabolism studies
- Mental Health Research Topics
- Sexual function and dysfunction studies
- Growth Hormone and Insulin-like Growth Factors
- Genetic Neurodegenerative Diseases
- Statistical Methods in Clinical Trials
- Circadian rhythm and melatonin
- Treatment of Major Depression
Italfarmaco (Italy)
2016-2025
Ibero American University
2019
GlaxoSmithKline (Italy)
2008-2016
GlaxoSmithKline (United States)
2011
Procter & Gamble (United Kingdom)
2001-2002
Luigi Sacco Hospital
1997-2000
University of Trieste
1993-1997
Loma Linda University
1993-1996
Loma Linda University Medical Center
1996
Loma Linda Veterans Association for Research and Education
1994
Abstract Objective Several studies have suggested that increased subchondral bone turnover is a determinant of progression osteoarthritis (OA). To test this hypothesis, the level urinary N‐terminal type I collagen telopeptides (NTx) and C‐terminal (CTx), which are validated markers resorption, was measured at 3 different time points in subset patients from Chingford study. Methods The original study population comprised 1,003 women. From group, postmenopausal women not receiving any...
Placebo may yield beneficial effects that are indistinguishable from those of active medication, but the factors underlying proneness to respond placebo widely unknown. Here, we used functional neuroimaging examine neural correlates anxiety reduction resulting sustained treatment under randomized double-blind conditions, in patients with social disorder. Brain activity was assessed during a stressful public speaking task by means positron emission tomography before and after an 8 week...
We determined the skeletal content of insulin-like growth factor-I (IGF-I) and transforming factor-beta (TGF beta) in human bone as a function age, using 66 samples femoral cortical obtained from 46 men 20 women between ages 20-64 yr. found linear decline IGF-I (nanograms per mg protein) with donor age (r = -0.43; P < 0.001) total population. The TGF beta also decreased (i.e. 1/TGF vs. age; r 0.28; 0.02) for did not observe any difference factor male female donors. content, when analyzed by...
The aims of this study were to assess bone metabolism in inflammatory bowel disease (IBD) patients and evaluate potential differences between Crohn's (CD) ulcerative colitis (UC) with respect the mechanisms underlying loss group diseases.This was a cross-sectional which started 1992. Patients randomly selected for invitation participate examined during years 1992-95 one research clinic Milan.Fifty-one suffering from CD (30 women 21 men, mean age 38.7 +/- 13.2 years) 40 UC (15 25 34.4. 12.5...
Duchenne Muscular Dystrophy (DMD) is caused by mutations in the dystrophin gene leading to deficiency, muscle fiber degeneration and progressive fibrotic replacement of muscles. Givinostat, a histone deacetylase (HDAC) inhibitor, significantly reduced fibrosis promoted compensatory regeneration mdx mice. This study was conducted evaluate whether beneficial histological effects Givinostat could be extended DMD boys. Twenty ambulant boys aged 7 <11 years on stable corticosteroid treatment were...
Abstract Previous work has established the existence of dystrophin-nitric oxide (NO) signaling to histone deacetylases (HDACs) that is deregulated in dystrophic muscles. As such, pharmacological interventions target HDACs (that is, HDAC inhibitors) are potential therapeutic interest for treatment muscular dystrophies. In this study, we explored effectiveness long-term with different doses inhibitor givinostat mdx mice—the mouse model Duchenne dystrophy (DMD). This study identified an...
Objective To compare the effect of riluzole on median survival in population studies patients with amyotrophic lateral sclerosis (ALS) that observed clinical trials. Methods: Two independent PubMed searches were conducted, to identify reported for ALS who either treated or remained riluzole-free. Results: We identified 14 met inclusion criteria reporting and an additional study mean both riluzole-free patients. Analysis 15 found a majority increased vs. In 8 studies, was 6–19 months longer...
To assess the acute effects of SB-649868 in male subjects with Primary Insomnia regard to (1) objective and subjective sleep parameters, (2) safety tolerability, (3) next-day residual effects.
We compared the clinical performances of four bone-resorption (BR) assays (hydroxyproline, HYP; galactosyl hydroxylysine, GHYL; deoxypyridinoline, DPD; and pyridinoline, PYD) in subjects with different BR rates: normal (adult men premenopausal women), mildly increased (postmenopausal osteoporotic high (Paget disease patients), very (children). The discrimination power (Z score) accuracy (estimated by receiver-operating characteristic analysis) for GHYL, DPD, PYD were those HYP....
Full, persistent blockade of central neurokinin-1 (NK1) receptors may be a potential antidepressant mechanism. The selective NK1 antagonist orvepitant (GW823296) was used to test this hypothesis. A preliminary positron emission tomography study in eight male volunteers drove dose selection for two randomized six week studies patients with major depressive disorder (MDD). Displacement [ 11 C]GR205171 binding indicated that oral doses 30–60 mg/day provided >99% receptor occupancy ≥24 h....
Clinical study results for neurokinin (NK) receptor antagonists in the treatment of depression have been mixed, with Phase III studies failing to fulfill early promise demonstrated II studies. Casopitant, a selective NK1 antagonist that achieves nearly complete occupancy was studied 2 randomized, placebo-controlled, double-blind, trials depressed outpatients test hypothesis is required achieve antidepressant efficacy. Study 092 used an interactive voice response system recruit patients...
Abstract Polycythemia vera (PV) is a BCR-ABL1 -negative myeloproliferative neoplasm (MPN) characterized by excessive proliferation of erythroid, myeloid, and megakaryocytic components in the bone marrow, mainly due to Janus kinase 2 gene mutation ( JAK2 V617F ). Givinostat, histone-deacetylase inhibitor that selectively targets cell growth, has demonstrated good efficacy safety three phase 1/2 studies patients with PV. This manuscript focuses on 4-year mean (2.8 year median) follow-up an...
Abstract Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by excessive levels of platelets (PLT), white blood cells (WBC), and hematocrit (HCT). Givinostat (ITF2357) potent histone‐deacetylase inhibitor that showed good safety/efficacy profile in PV patients during phase I/II studies. A III clinical trial had been planned an adaptive dosing protocol proposed where givinostat dose iteratively adjusted every 28 days (one cycle) based on PLT, WBC, HCT. As support,...
The orexin system plays a major role in the integration of metabolic and circadian influences that drive wakefulness. This paper describes initial Phase I trials novel dual receptor antagonist SB-649868 has demonstrated preclinical potential for treatment sleep disorders. trial designs included single ascending dose escalation study (dose range: 10–80 mg fed fasted states) multiple repeat 5–30 state) enrolling total 103 male volunteer subjects. was well tolerated at all doses this...
Abstract Becker muscular dystrophy (BMD) is a severe X-linked muscle disease. Age of onset, clinical variability, speed progression and affected tissues display wide making trial design for drug development very complex. The histopathological changes in skeletal tissue are central to the pathogenesis, but they have not been thoroughly elucidated yet. Here we analysed biopsies from large cohort BMD patients, focusing our attention on parameters, as fibrosis, fatty replacement, fibre cross...
In patients with social anxiety disorder (SAD) it has been reported that selective serotonin reuptake inhibitors (SSRIs) and placebo induce anxiolytic effects by attenuating neural activity in overlapping amygdala subregions, i.e. left basolateral right ventrolateral amygdala. However, is not known whether these treatments inhibit subregions via similar or distinct brain pathways. As may alter amygdala-frontal couplings we investigated differences similarities functional co-activation...
No treatments are approved for Becker muscular dystrophy (BMD). This study investigated the efficacy and safety of givinostat, a histone deacetylase pan-inhibitor, in adults with BMD.Males aged 18-65 years diagnosis BMD confirmed by genetic testing were randomized 2:1 to 12 months treatment givinostat or placebo. The primary objective was demonstrate statistical superiority over placebo mean change from baseline total fibrosis after months. Secondary endpoints included other histological...