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E Corsini

Publications and source records attributed to E Corsini.

At least 37 records · Page 2Linked to original sources
PubMed2000

Organotins induce apoptosis by disturbance of [Ca(2+)](i) and mitochondrial activity, causing oxidative stress and activation of caspases in rat thymocytes.

Di-n-butyltin dichloride (DBTC) and tri-n-butyltin chloride (TBTC) cause thymus atrophy in rodents. At low doses, antiproliferative modes of action have been shown to be involved, whereas at higher doses apoptosis seems to be the mechanism of thymotoxicity by these chemicals. In vitro, a similar concentration-dependency has been observed. The purpose of the present research was to investigate the mechanisms underlying DNA fragmentation induced by these organotin compounds in freshly isolated rat thymocytes. As previously shown for TBTC, DBTC is also able to significantly increase intracellular Ca(2+) level ([Ca(2+)](i)). The rise in [Ca(2+)](i), already evident 5 min after treatment, was followed by a dose- and time-dependent generation of reactive oxygen species (ROS) at the mitochondrial level. Simultaneously, organotins induced the release of cytochrome c from the mitochondrial membrane into the cytosol. ROS production and the release of cytochrome c were reduced by BAPTA, an intracellular Ca(2+) chelator, or rotenone, an inhibitor of the electron entry from complex I to ubiquinone, indicating the important role of Ca(2+) and mitochondria during these early intracellular events. Furthermore, we demonstrated that rotenone prevents apoptosis induced by 3 microM DBTC or TBTC and, in addition, that both BAPTA and Z-DEVD FMK (mainly a caspase-3 inhibitor) decreased apoptosis by DBTC (already shown for TBTC). Taken together these data show the apoptotic pathway followed by organotin compounds starts with an increase of [Ca(2+)](i), then continues with release of ROS and cytochrome c from mitochondria, activation of caspases, and finally results in DNA fragmentation.

Animals↗
PubMed2000

Epidermal cytokines in experimental contact dermatitis.

Topical exposure to a variety of xenobiotics may result in irritant as well as allergic contact dermatitis both in rodents and in humans. Despite their induction by different mechanisms, they cannot be differentiated by macroscopic appearance and, by histological examination they are both generally characterized by a perivascular mononuclear cell infiltrate and capillary hyperpermeability. Recently, cytokines, a family of inducible glycoproteins that play a pivotal role in immune and inflammatory reactions, have been identified as useful tools for differentiation of irritant and allergic contact dermatitis. In this article the role of cytokines in the development and differentiation of irritant and allergic contact dermatitis is discussed.

Animals↗
PubMed2000

Dying neural cells activate glia through the release of a protease product.

The close relationship between neurodegeneration and gliosis could play a relevant role in propagating the degenerative event in the brain. Although there is evidence of the neurotoxicity of activated glia, the ability of damaged neurons to modulate glial response remains unexplored. Exposure of primary glial cells to damaged or dead hippocampal neurons was followed by glial release of tumor necrosis factor-alpha (TNF-alpha). This release was reduced by a partial prevention of neural death. By contrast, no TNF-alpha was released when glial cells were exposed to damaged murine fibroblasts. Exposure of glial cells to the cerebrospinal fluid (CSF) of patients with Alzheimer's disease was also followed by TNF-alpha release, while the CSF of subjects with nondegenerative brain disorders evoked no response. These data suggest that damaged neurons both in vitro and in vivo release factor(s) that activate glial response. Heat treatment of sonicated neurons or use of a mixture of protease inhibitors, among them the caspase inhibitors Z-DEVD-FMK and Z-YVAD-FMK, prevented TNF-alpha release from glial cells. We conclude that a primary neurodegenerative event may induce glial response by releasing a neurospecific protein factor via activation of a caspase.

Alzheimer Disease↗
PubMed2000

Long-term immunological changes in azathioprine-treated MS patients.

The long-term immunological effects of azathioprine treatment have been investigated in 8 multiple sclerosis patients with different course of disease, chronic progressive (CP) or relapsing progressive (RP). We studied fluctuations in peripheral blood mononuclear cell subsets, IgG, IgM and soluble vascular cell adhesion molecule-1 (sVCAM-1), before and after 2 (T24) and 3 (T36) years of therapy. We observed a significant decrease in CD8+ cells over time and a trend to lower percentage of CD3-CD56+ cells at T24 and T36. CD4+CD45RA+ cells in MS patients were lower than in healthy controls before therapy and reached values similar to those of healthy controls at T24 and T36. The remaining immunological parameters did not show any significant fluctuations.

Adult↗
PubMed2000

High-dose methylprednisolone reduces cytokine-induced adhesion molecules on human brain endothelium.

OBJECTIVE: We investigated the in vitro effects of low- and high-dose methylprednisolone (MP) on the cytokine-induced expression of HLA-DR, ICAM-1 and VCAM-1 on human brain microvessel endothelial cells (HBMECs). METHODS: Brain endothelium was obtained from microvessels included in the apparently normal white matter of surgical specimens of nine patients. Cells were stained with monoclonal antibodies anti-HLA-DR, anti-ICAM-1 and anti-VCAM-1 and analysed by flow cytometry as fluorescence histograms. The mean fluorescence intensity (MFI) of HBMECs treated with different stimuli was calculated. RESULTS: gamma-IFN-induced HLA-DR was down-regulated in a dose-dependent manner by MP. High-dose MP reduced the TNF-alpha-induced ICAM-1 and VCAM-1 expression. CONCLUSIONS: The down-regulation of adhesion molecules on cerebral endothelial cells could decrease mononuclear cell transmigration through the blood brain barrier and consequently the perivascular infiltrates. The results add support to the rationale for high-dose MP treatment in multiple sclerosis relapses.

Adult↗
PubMed1999

A defective protein kinase C anchoring system underlying age-associated impairment in TNF-alpha production in rat macrophages.

The ability of macrophages to secrete cytokines is important in host responses to infections inflammatory stimuli, both of which are altered with aging. In this study, age-associated changes in the release of TNF-alpha from LPS-stimulated rat alveolar macrophages were determined and correlated with a decrease in the level of RACK1, the anchoring protein involved in protein kinase C translocation and activation. Macrophages from aged rats produced approximately 50% less TNF-alpha than those from young rats. This effect was observed independently from the concentration of LPS used and the time considered. The decrease observed was associated with a defective PKC translocation, due to a reduction in the expression of RACK1, whereas no differences were detected in the expression of LPS receptor (CD14) or total PKC isoforms (alpha and betaIotaIota) in old and young rats. Use of RACK1 antisense oligonucleotide reduced the ability of young macrophages to respond to LPS, further supporting the idea that a deficit in RACK1 contributes to the functional impairment in aged macrophages and that age-induced macrophage immunodeficiencies are associated with alteration in signal transduction pathways.

Aging↗
PubMed1999

Immune parameters in biological monitoring of pesticide exposure: current knowledge and perspectives.

Exposure to pesticides can cause a number of effects on the immune system, varying from a slight modulation of immune functions to the development of clinical immune diseases. The aim of this study has been reviewing published data on immune effects of pesticides in humans, with particular attention for effects observed in absence of any other change, and to the possibility of identifying a dose effect relationship. Some evidence of immunotoxic effects in man involve organophosphorus compounds, some organochlorine insecticides (OC), some carbamates, some phenoxy herbicides, dithiocarbamates, and pentachlorophenol (PCP). The alterations are usually observed in absence of any other change; in some cases, data suggest the presence of a dose effect relationship. The prognostic significance of the observed changes is still unclear. The Authors propose a tier approach to assess immune effects in humans.

Antibodies↗
PubMed1999

Immunological effects of in vivo interferon-beta1b treatment in ten patients with multiple sclerosis: a 1-year follow-up.

Ten patients with multiple sclerosis and treated with interferon-beta1b (IFN-beta1b) were followed-up for 1 year with quantitation of serum VCAM-1 and ICAM-1 levels, mean fluorescence intensity of HLA-DR, VLA-4, CD11a, and CD18 on peripheral blood monocytes and lymphocytes, and adhesion of peripheral blood monocytes and CD45+ cells on endothelial cell monolayers. Adhesion molecule expression and adhesion of peripheral blood monocytes to endothelium were also monitored in healthy controls. No differences in adhesion were detected between MS patients before treatment and healthy controls, while after 1 year a marked decrease in the number of monocytes and mononuclear cells adhering to human umbilical vein endothelial cell monolayers was observed in patients treated with IFN-beta1b. After 1 year of treatment a significant increase in HLA-DR on peripheral blood monocytes was also detected. Our findings regarding lowered adhesion add information to available evidence of the mechanisms of action of IFN-beta1b in MS.

Adjuvants, Immunologic↗
PubMed1999

Sodium arsenate induces overproduction of interleukin-1alpha in murine keratinocytes: role of mitochondria.

It has recently been demonstrated that arsenic induces overexpression of keratinocyte-derived growth factors, which are likely to have a significant role in arsenic-induced skin hyperkeratoses and cancer. The mechanism(s) involved in this induction are, however, still elusive. The purpose of this study was to investigate the early intracellular events that follow in vitro treatment with sodium arsenate in a murine keratinocyte cell line (HEL30), which leads to cytokine overproduction. First, we observed that sodium arsenate induced a concentration-dependent production of interleukin-1alpha and a significant increase in cell proliferation, that could be suppressed by the addition of a neutralizing antibody against murine interleukin-1alpha, confirming the ability of arsenic to induce keratinocyte growth-promoting cytokines. Electron microscopic analysis revealed that arsenate induced a dramatic alteration in keratinocyte mitochondria. This effect could be prevented by rotenone pretreatment, which suggests the possible involvement of mitochondria-derived reactive oxygen species. Arsenic induced a concentration- and time-dependent increase in cellular oxidative activity, which was followed by activation of redox-sensitive transcription factors such as nuclear factor-kappaB and activator protein-1, that are essential for interleukin-1alpha synthesis. Prior treatment with rotenone or prolonged treatment with ethidium bromide, an inhibitor of mitochondrial DNA and RNA synthesis, to deplete cells of functional mitochondria, completely prevented sodium arsenate-induced interleukin-1alpha production, this indicates the pivotal role of these organelles in sodium arsenate-induced keratinocyte growth factors.

Animals↗
PubMed1998

Cytokines and irritant contact dermatitis.

Skin irritation is a complex phenomenon that involves resident epidermal cells, fibroblasts of dermis, and endothelial cells as well as invading leukocytes interacting with each other under the control of a network of cytokines and lipid mediators. Keratinocytes play an important role in the initiation and perpetuation of skin inflammatory reactions through the release of, and responses to cytokines. While resting keratinocytes produce some cytokines constitutively, a variety of environmental stimuli, such as tumor promoters, ultraviolet light and chemical agents, can induce epidermal keratinocytes to release inflammatory cytokines (IL-1, TNF-alpha), chemotactic cytokines (IL-8, IP-10), growth promoting cytokines (IL-6, IL-7, IL-15, GM-CSF, TGF-alpha) and cytokines regulating humoral vs. cellular immunity (IL-10, IL-12, IL-18). The role of cytokines in xenobiotics-induced skin irritation and the early molecular events that follow the treatment with irritant compounds will be discussed.

Calcium↗
PubMed1998

Selective induction of cell-associated interleukin-1alpha in murine keratinocytes by chemical allergens.

Cytokines may be useful tools to discriminate between irritant and allergic contact dermatitis. In the mouse only, it has been demonstrated by other, that contact sensitizers up-regulated keratinocytes-derived interleukin-1alpha (IL-1), macrophage inflammatory protein-2 and interferon induced protein 10 mRNAs. The purpose of this study was to investigate the possibility to use in vitro IL-1 production by a murine keratinocyte cell line for preliminary screening of chemicals for their irritant and/or allergic potential. We investigated the effects of five relevant skin allergens (dinitrochlorobenzene, oxazolone, nickel sulfate, penicillin G and eugenol), two skin irritants (benzalkonium chloride, and methylsalicilate) and two compounds with no sensitizing activity (glycerol and ethanol) on IL-1 production in HEL30 cells. Twenty four hours following treatment, both IL-1 release in conditioned media and cell-associated IL-1 were measured by a specific sandwich ELISA. Under our experimental conditions, only contact sensitizers were able to increase in a dose dependent fashion cell-associated IL-1, confirming the in vivo findings. Both skin irritants and allergens induced the release of IL-1, because of the irritative properties of both chemicals, while ethanol and glycerol failed to induce changes in IL-1 production, confirming the specificity of the proposed test. Taken together, these data indicate that it may be realistic to consider potential skin allergens those chemicals which are able to increase cell-associated IL-1, to consider skin irritants those chemicals which induce only IL-1 release, and to exclude as potential allergens or irritants those chemicals which fail to induce changes in IL-1 production.

Allergens↗
PubMed1998

Modulation of ICAM-1, VCAM-1 and HLA-DR by cytokines and steroids on HUVECs and human brain endothelial cells.

The in vitro effects of dexamethasone (Dx) and low and high-dose 6-methylprednisolone (MP) on the expression of adhesion molecules ICAM-1,VCAM-1 and class II antigen HLA-DR on human brain endothelial cells (HBECs) was studied. HBECs were obtained from the surgical specimen of a multiple sclerosis patient undergoing brain surgery for vascular aneurysm. HBECs obtained from apparently normal brain capillaries of surgical specimens of two patients undergoing brain surgery for a meningioma and a low-grade glioma, respectively, were used as controls. The effect of steroids was studied both in the basal condition and after stimulation with proinflammatory cytokines (gamma-IFN and TNF-alpha). In order to detect possible endothelium local tissue specific differences, the experiment was repeated using human umbilical vein endothelial cells (HUVECs). Only high-dose MP was able to down-regulate TNF-alpha-induced VCAM-1 expression on endothelial cells.

Adult↗
PubMed1998

Glia increase degeneration of hippocampal neurons through release of tumor necrosis factor-alpha.

This study characterizes the role of glial cells in chemically induced neurodegeneration. We evaluated the effect of trimethyltin, a trisubstituted organotin compound that elicits distinct lesions in the central nervous system in vivo, on a sandwich co-culture of neurons and glia. Exposure of a 98% pure culture of rat hippocampal neurons to 0.1-1 microM trimethyltin for 24 h caused neural cell death and nuclear changes typical of apoptosis; at these doses glial cells viability was not affected but the cells released significant amounts of tumor necrosis factor-alpha (TNF-alpha). Neuronal apoptosis and TNF-alpha release from glial cells both increased when the two cell types were exposed together to trimethyltin, which indicates synergy. Treatment of a neuron-glia co-culture with TNF-alpha antibody prevented the increase in neuronal apoptosis, and TNF-alpha administration induced apoptosis in hippocampal cells. We conclude that glial cells and TNF-alpha both modulate trimethyltin-induced neurodegeneration.

Animals↗
PubMed1998

Immunocompetence of human microvascular brain endothelial cells: cytokine regulation of IL-1beta, MCP-1, IL-10, sICAM-1 and sVCAM-1.

Endothelia from the brains of four patients undergoing neurosurgery, including one multiple sclerosis (MS) patient, were studied in vitro to determine cytokine and chemokine production; the release of soluble adhesion molecules was also investigated. The same procedure was repeated on human umbilical vein endothelial cells (HUVECs) in order to detect possible district-specific differences. After isolation, the endothelium was cultured and stimulated with gamma-interferon (IFN), tumour necrosis factor alpha (TNF-alpha) and LPS. The results showed that brain endothelium, in our experimental conditions, does not produce interleukin (IL)-10 and produces lower amounts of IL-1beta and soluble intercellular adhesion molecule-(sICAM-1) than HUVECs do; no differences were detected in soluble vascular cell adhesion molecule-(sVCAM-1) production. MCP-1 mRNA was detected both without and after stimulation with TNF-alpha and gamma-IFN in HUVECs and MS human brain endothelial cells (HBECs), while in non-MS-HBECs it was found only after gamma-IFN stimulation.

Adult↗
PubMed1998

Adolescent issues in renal treatment.

Everyone who helps to care for a growing and developing child has the potential to impact the future. Families provide the greatest influence and bear the major responsibility, but physicians, nurses, dietitians, social workers, teachers, camp counselors, and others who work with children make a direct contribution toward the development of the child's self image and image of the world around them. At no other time in an individual's life do other people have such awesome power and responsibility. Families and caregivers working together on behalf of a child may be likened to an extended family; their combined efforts are needed to help promote the resilience that children need to cope with serious chronic illness.

Adolescent↗