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Biomedical subjects

E Scarpini

Publications and source records attributed to E Scarpini.

At least 19 recordsLinked to original sources
PubMed2006

The leukocyte expression of CD36 is low in patients with Alzheimer's disease and mild cognitive impairment.

CD36, a scavenger receptor of class B (SR-B), helps mediate microglial and macrophage response to beta-amyloid fibrils (betaA), and seems to play a key role in the proinflammatory events associated with Alzheimer disease (AD) in many tissues. Peripheral leukocytes express many molecules and multiple receptors which undergo the same regulatory mechanisms as those operative in the brain. Thus, these cells, easily obtainable through peripheral blood sampling, may be used as a tool to investigate changes occurring in inaccessible brain areas. Based on these premises, we investigated the leukocyte expression of CD36 in 70 AD patients and in 30 subjects with mild cognitive impairment (MCI). Results were compared to those of 20 young and 40 age-matched control subjects. Leukocyte expression of CD36 was significantly reduced versus controls in both AD and MCI patients, while in young and old controls there were no age-related changes. Although preliminary, these data indicate that the reduction of CD36 expression in leukocytes is a disease-related phenomenon, occurring since the early stages of AD (MCI). Irrespective of the mechanism(s) underlying such changes, assessment of leukocyte CD36 expression might represent an useful tool to support the diagnosis of AD and to screen MCI patients candidates to develop the disease.

Adult↗
PubMed2006

Genetics and neurobiology of frontotemporal lobar degeneration.

Frontotemporal dementia (FTD) is characterised by brain intracellular deposition of abnormally phosphorylated tau protein, considered responsible for neuronal death. Several familial cases with different mutations in the tau encoding gene (MAPT), located on chromosome 17, have been described. Besides, in a Danish family, the genetic defect has been associated to chromosome 3. Although many FTD families exhibit known mutations, in some cases none of them occur. Recent findings demonstrate an increased intrathecal production of both pro- and anti-inflammatory cytokines in sporadic FTD patients. Besides, increased cerebrospinal fluid monocyte chemotactic protein-1 and interleukin-8 levels have been observed in FTD, whereas interferon-gamma-inducible protein-10 levels were similar to controls.

Dementia↗
PubMed2004

Behavioral symptoms in mild cognitive impairment.

The authors investigated neuropsychiatric symptoms in mild cognitive impairment (MCI) from baseline data of the Investigation in the Delay to Diagnosis of AD with Exelon (InDDEx) study (n = 1,010). Neuropsychiatric symptoms were reported in 59% of subjects (Neuropsychiatric Inventory [NPI]). NPI+ subjects had significantly greater impairment on global, cognitive, and functional scores than NPI- subjects. The presence of neuropsychiatric symptoms appears to be a marker of MCI severity.

Aged↗
PubMed2002

Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients.

Ghrelin, a novel endogenous ligand for the GH secretagogue receptor, has been reported to stimulate GH secretion and food intake in both humans and other animals. Interestingly, recent data indicate that ghrelin is up- and down-regulated in anorexia nervosa (AN) and obesity, which are also known to be accompanied by increased and reduced GH levels respectively. Ageing is associated with a gradual but progressive reduction in GH secretion, and by alterations in appetite and food intake. The role of ghrelin in the decline of somatotroph function and the anorexia of ageing is unknown. To investigate the influence of age on circulating levels of ghrelin, a total of 19 young and old normal weight subjects (Y-NW, n=12; O-NW, n=7), six patients with active AN (A-AN), and seven patients with morbid obesity (OB) were studied. In addition to fasting plasma ghrelin concentrations, baseline serum TSH, IGF-I and insulin levels were measured. Mean plasma ghrelin concentrations in A-AN or OB were higher and lower respectively than those present in Y-NW. Interestingly, mean plasma ghrelin concentrations in O-NW were significantly lower than those present in Y-NW and superimposable on those of OB. The mean fasting plasma ghrelin concentrations in all groups of subjects were negatively correlated with body mass index and serum insulin levels, but not with TSH and IGF-I levels. This study provides evidence of an age-related decline of plasma ghrelin concentrations, which might explain, at least partially, the somatotroph dysregulation and the anorexia of the elderly subject.

Adolescent↗
PubMed2001

Production of IL-6 by human myoblasts stimulated with Abeta: relevance in the pathogenesis of IBM.

OBJECTIVE: To determine whether amyloid-beta protein (Abeta) can induce the production of proinflammatory cytokines by cultured normal muscle cells. BACKGROUND: Sporadic inclusion body myositis (IBM) is characterized by the presence of rimmed vacuoles and fibrillary inclusions of Abeta in muscle fibers, and often inflammatory cells. Endomysial expression of proinflammatory molecules has suggested an ongoing immune process, but the site of sensitization and the mechanisms that trigger an inflammatory reaction is unknown. METHOD: The authors used Northern blot analysis and specific immunoassays to study the expression and secretion in cell-free supernatants of tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) by purified human myoblasts and C2C12 mouse skeletal muscle cells incubated with Abeta[1-42] or Abeta[25-35] peptides. RESULTS: Nonstimulated muscle cells produced detectable IL-6, whereas secretion of IL-1beta and TNFalpha was absent. Incubation with Abeta peptides increased IL-6 production, whereas TNFalpha and IL-1beta levels remained undetectable. Northern blot analysis of Abeta-stimulated human myoblasts revealed an increase in IL-6 mRNA expression. CONCLUSIONS: Cultured muscle cells increase the constitutive production of IL-6 in response to local deposition of Abeta in sporadic IBM. IL-6 could be a CD8(+) proliferation and differentiation agent, an autocrine proteolysis-inducing factor of damaged myotubes, and a proliferation-stimulating agent for satellite cells to replace the destroyed myofibers in IBM.

Adult↗
PubMed2000

The human astrocytoma cell line U373MG produces monocyte chemotactic protein (MCP)-1 upon stimulation with beta-amyloid protein.

Astrocytes associated with beta-amyloid (Abeta) accumulate in senile plaques of Alzheimer's disease (AD). To investigate the biological effects of Abeta/astrocyte interaction, we examined chemokine production by the human astrocytoma cell line U373MG stimulated with Abeta peptides. Northern blot analysis and specific immunoassays demonstrate that Abeta [1-42] and Abeta [25-35] induce mRNA expression and release of monocyte chemotactic protein (MCP)-1 but not of gamma-interferon inducible protein (IP)-10 by U373MG cells. The observation that Abeta induces astrocyte production of the potent microglia chemoattractant MCP-1 contributes to understanding mechanism of damage exerted by Abeta in AD senile plaques.

Amyloid beta-Peptides↗
PubMed2000

Severe polyneuropathy in a patient with Churg-Strauss syndrome.

We describe the clinicopathologic features of a 56-year-old woman affected with Churg-Strauss syndrome with major peripheral nerve involvement. The patient presented with a 1-month history of mainly distal upper-limb symmetrical paresthesias and hypostenia (bilateral "wrist drop"), palpable purpura and eosinophilia. Multiple pulmonary infiltrates and asthma had been present since the age of 52. Skin biopsy demonstrated an eosinophilic necrotizing vasculitis. During the hospitalization she was submitted to cardiac, bronchopulmonary, renal, and gastrointestinal evaluation and EMG. Peripheral nerve and skeletal muscle biopsies were performed. Sural nerve biopsy showed a marked degree of demyelination. A perivascular cellular infiltrate within the epineurium was immunoreactive for T lymphocytes and macrophages. Strong HLA-DR immunostaining was present in the endoneurium. IgM, IgE and fibrinogen deposition was found in some epi- and endoneurial vessels. Muscle biopsy showed neurogenic changes and 1 thrombosed vessel surrounded by mononuclear cells. Membrane attack complex (MAC) deposition was present in a few capillaries and major histocompatibility complex products I (MHCP I) was expressed at the subsarcolemmal level in a few isolated perivascular muscle fibers. After immunosuppressive therapy, the patient showed progressive improvement of both clinical symptoms and neurophysiological parameters.

Biopsy↗
PubMed2000

Synergistic effect of beta-amyloid protein and interferon gamma on nitric oxide production by C2C12 muscle cells.

Nitric oxide (NO) is an important mediator of diverse physiological and pathological responses. NO-induced oxidative stress has been proposed in the pathogenesis of muscle tissue damage in inclusion-body myositis (IBM), which is characterized by deposition of beta-amyloid protein (Abeta) in vacuolated muscle fibres. To determine whether Abeta can induce NO production in skeletal muscle, we stimulated C2C12 mouse skeletal muscle cells in vitro with Abeta[1-42] or Abeta[25-35] peptides in the presence or absence of interferon gamma (IFN-gamma). Neither Abeta peptides nor IFN-gamma were able to stimulate nitrite (NO(2)(-)) production by C2C12 cells when given alone. However, combination of IFN-gamma with either Abeta[1-42] or Abeta[25-35] resulted in significant NO(2)(-) release into cell-free supernatants. Northern blot analysis of RNA obtained from Abeta/IFN-gamma-stimulated C2C12 cells revealed increased mRNA accumulation of inducible nitric oxide synthase (iNOS). Moreover, approximately 4% of muscle cells incubated with Abeta peptides and IFN-gamma showed ultrastructural features of DNA fragmentation. These findings, taken together, indicate that the association of Abeta with IFN-gamma stimulates NO(2)(-) production via induction of iNOS gene expression in skeletal muscle cells, with occasional evidence for nuclear changes suggesting apoptotic morphology. These data further support a role for Abeta deposition in the pathogenesis of postulated oxidative damage in IBM.

Amyloid beta-Peptides↗
PubMed1999

Induction of adhesion molecules on human schwann cells by proinflammatory cytokines, an immunofluorescence study.

The presence of cytokines in the peripheral nerve was positively correlated to the induction and progression of inflammation during experimental allergic neuritis (EAN) and Guillain Barré syndrome (GBS). We investigated the induction of adhesion molecules such as L-selectin, E-selectin, ICAM-1, VCAM-1 and Mac-1 on Schwann cells by proinflammatory cytokines. Cultured human Schwann cells from normal adult, fetal and diabetic nerves were studied by immunofluorescence at basal condition and after stimulation with cytokines for 6, 24, 48 and 96 h. Incubation of human Schwann cells with TNFalpha, IFNgamma and IL-1beta induces the expression of ICAM-1 starting at 6 h and reaching a peak at 24 h on more than 90% of cells. VCAM-1 expression was induced after 6 h of treatment with TNFalpha and IL-1beta on almost 100% of Schwann cells. Surprisingly, stimulation with TNFalpha, IFNgamma and IL-1beta also induced the expression of L-selectin on fetal and diabetic Schwann cells, but not on normal adult cells. E-selectin, an adhesion molecule classically upregulated during inflammation, as well as Mac-1, a ligand for ICAM-1, were not expressed on human Schwann cells at basal condition or after treatment with cytokines. No ICAM-1, VCAM-1 and L-selectin expression was found on unstimulated Schwann cells. Our results suggest that upregulation of adhesion molecules on Schwann cells may have a role in the pathogenesis of inflammation in the peripheral nerve.

Adult↗
PubMed1999

Alpha-MSH peptides inhibit production of nitric oxide and tumor necrosis factor-alpha by microglial cells activated with beta-amyloid and interferon gamma.

Alpha-melanocyte stimulating hormone (alpha-MSH) is an ancient tridecapeptide with potent inhibitory activity in all major forms of inflammation. The anti-inflammatory message sequence of alpha-MSH resides in the COOH-terminal tripeptide alpha-MSH[11-13]. We tested the influence of alpha-MSH[1-13] and of alpha-MSH[11-13] in a cultured murine microglia cell line known to produce nitric oxide (NO(-)(2)) and tumor necrosis factor (TNFalpha) when stimulated with beta-amyloid protein (Abeta). Melanocortin peptides significantly inhibited release of both NO(-)(2) and TNFalpha into cell-free supernatants from microglia stimulated with Abeta[1-42] or Abeta[25-35] peptides and interferon gamma (IFNgamma). Northern blot analysis demonstrated that alpha-MSH[1-13] and alpha-MSH[11-13] inhibited accumulation of inducible nitric oxide synthase (iNOS) and TNFalpha mRNA was triggered by Abeta stimulation. Abeta/microglial interaction is believed to promote the progression of inflammatory and neurodegenerative changes in senile plaques in Alzheimer's disease. Our data indicate that alpha-MSH peptides might be used to modulate the local response of the brain to Abeta deposition in this neurodegenerative disease.

Amyloid beta-Peptides↗
PubMed1999

The expression of CD59 in experimental allergic neuritis.

Complement is implicated as an effector in inflammatory demyelination occurring in Guillain-Barré syndrome (GBS) and in experimental allergic neuritis (EAN). CD59, a potent complement regulatory protein that inhibits the formation of the terminal cytolytic membrane attack complex (MAC), is expressed on human and rat Schwann cells. In EAN the expression of CD59 was increased on Schwann cells during demyelination and axonal degeneration, evaluated by immunostaining of nerve sections and teased fibres. Mac-1 (CD11b) positive leukocytes were localized close to the Schwann cells showing enhanced CD59 staining. The increased CD59 expression in EAN could therefore be due to the release of cytokines or other immunoregulatory molecules from the inflammatory cells. However, interferon gamma (IFN-gamma) or tumor necrosis factor alfa (TNF-alpha) did not upregulate the expression of CD59 on rat Schwann cells in culture. The increased expression of CD59 in EAN is likely to be important in the protection of Schwann cells from MAC.

Animals↗
PubMed1999

Anti-GM2 IgM antibodies: clinical correlates and reactivity with a human neuroblastoma cell line.

Anti-GM2 IgM antibodies have been reported in some patients with dysimmune neuropathy or lower motor neuron syndrome, in whom they were often associated with a concomitant reactivity with GM1. To investigate the possible clinical and pathogenetic relevance of these antibodies we measured serum anti-GM2 IgM titers by ELISA in 224 patients with different neuropathies and motor neuron disease and examined their binding to SK-N-SH neuroblastoma cells by indirect immunofluorescence (IIF). High titers of anti-GM2 IgM antibodies were found in eight patients with dysimmune neuropathies including two with multifocal motor neuropathy (MMN), two with purely motor demyelinating neuropathy without conduction block (MN) and four with Guillain-Barré syndrome (GBS). In two MMN patients reactivity with GM2 was associated with anti-GM1 reactivity and in one MN patient with anti-GM1, -GD1a and -GD1b reactivity. All but one patient had a concomitant reactivity with GalNAc-GD1a. Serum IgM from all positive patients intensely stained by IIF the surface of SK-N-SH neuroblastoma cells. This reactivity was blocked by serum pre-incubation with GM2, was not observed with sera from patients without anti-GM2 antibodies including those with high anti-GM1 or other anti-glycolipid antibodies, and correlated with the presence of GM2 in the SK-N-SH neuroblastoma cells. These findings indicate that anti-GM2 antibodies, though infrequent, are strictly associated with dysimmune neuropathies and suggest that SK-N-SH neuroblastoma cells can be a suitable in vitro model to study the functional and biological effects of these antibodies.

Adolescent↗
PubMed1999

Proinflammatory profile of cytokine production by human monocytes and murine microglia stimulated with beta-amyloid[25-35].

Growing evidence indicates that amyloid (A beta) deposition and phagocyte activation participate in inflammatory reactions in the brain during the course of Alzheimer's disease. To further investigate the effects of A beta-phagocyte interaction, we examined the production of proinflammatory (IL-1beta, IL-6), chemotactic (MIP-1alpha, IP-10) and inhibitory (IL-1Ra, IL-10 and TGFbeta1) cytokines by cultured human monocytes and mouse microglial cells upon stimulation with A beta[25-35]. Northern blot analysis and specific immunoassays demonstrated that A beta[25-35] triggers mRNA expression and release of IL-1beta, IL-1Ra and MIP-1alpha but not of IL-6, IL-10, TGFbeta1 and IP-10 from human monocytes. Similar results were obtained by examining the production of IL-1beta, IL-6 and IL-10 from mouse microglial cells in the same experimental conditions. Taken together, these data indicate that A beta-phagocyte interaction can drive a different response towards cytokine production by monocytes and microglia, with a particular proinflammatory trend, and further support a role for A beta deposition as a triggering factor of inflammatory events in Alzheimer's disease.

Alzheimer Disease↗
PubMed1998

Schwann cell undergoes apoptosis during experimental allergic neuritis (EAN).

Schwann cell apoptosis is not detectable in the normal mature mammalian peripheral nervous system (PNS). However, during PNS cell-mediated demyelination, apoptosis contributes to the elimination of endoneurial T-lymphocytes. We report here that approximately 10% of Schwann cells die by apoptosis during the early phases of recovery from experimental autoimmune neuritis (EAN) in the adult rat, a model for the Guillain-Barrè syndrome. Schwann cell apoptosis, follows endoneurial T-cell clearance, and is prominent in the nerve roots, the site of most severe segmental demyelination, but is rare in the more distal regions of the PNS, where Wallerian degeneration predominates. Further immunological analysis showed that the p75 neurotrophin receptor (p75NTR) is expressed in 2% of both apoptotic and non apoptotic Schwann cells, while Ki-67, a marker of cell proliferation, is expressed in 20% of apoptotic and in 1% of non apoptotic Schwann cells. Our new observations indicate that apoptosis during cell-mediated demyelination can be a phenomenon related either to the development or the recovery of autoimmune cell mediated inflammation.

Animals↗