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Biomedical subjects

F Aloisi

Publications and source records attributed to F Aloisi.

60 records · Page 4Linked to original sources

Evaluation of the analgesic activity of morphine, enkephalins and their synthetic analogues.

In the rabbit, a morphine-like analgesic activity of natural and synthetic enkephalins has been demonstrated using the method of the return of corneal anesthesia due to conjunctival instillation of procaine. FK 33824 is the most effective drug in producing analgesia when administered intracerebroventricularly, whereas morphine is much more active when injected i.v. The effect of morphine and enkephalins is readily reversed by nalorphine (10 mg/kg, i.v.) indicating an involvement of opiate receptors in the CNS.

Analgesics↗

Establishment, characterization, and evolution of cultures enriched in type-2 astrocytes.

The aim of the present study was to prepare cultures enriched in type-2 astrocytes (AS) and to analyze some of the properties of these cells over relatively long culture periods. Cultures enriched in type-2 AS were obtained by subculturing, at low cell density and in the presence of fetal calf serum, a cell population containing numerous bipotential glial precursors. This cell population was detached mechanically from 2- to 3-week primary mixed glial cultures prepared from 1-day postnatal rat cerebral cortex. The cellular composition of the subcultures was analyzed immunocytochemically over a period of 3 weeks using various combinations of antibodies, recognizing a set of differentiated and a set of undifferentiated glial antigens (glial fibrillary acidic protein [GFAP], galactocerebroside, sulfatide, gangliosides binding the monoclonal antibodies A2B5 and LB1, fibronectin). Most LB1+, A2B5+ glial precursors differentiated into type-2 AS within a week. At this stage, type-2 AS accounted for more than 70% of cells in the cultures and exhibited the characteristic features previously described for these cells (stellate shape, GFAP, LB1 and A2B5 positivity, ability to accumulate [3H]GABA and to synthesize chondroitin sulfate, low proliferative activity). About one third of the type-2 AS also were recognized by O4 (antisulfatide) antibodies. The major contaminants were macrophages (10-15%) and fibroblastic cells (5-10%). In longer term cultures, type-2 AS tended to lose several of these features. Many acquired a flat, polygonal shape and lost LB1 positivity. The ability to accumulate [3H]GABA progressively decreased, as did the expression of chondroitin sulfate, although to a lesser degree. Although losing several of their properties, type-2 AS did not appear to acquire the properties of type-1 AS: their proliferative activity remained very low, and they did not express class II antigens of the major histocompatibility complex upon stimulation with gamma-interferon. Some became positive for fibronectin.

Animals↗

Cytokine regulation of astrocyte function: in-vitro studies using cells from the human brain.

Participation of astrocytes in central nervous system pathophysiology is likely to involve cytokines, both as stimulators and mediators of astrocyte function. We have used highly enriched human astrocyte cultures as an experimental tool to investigate the influence of cytokines on adhesion molecule expression and synthesis of mediators that are probably important in immune and inflammatory reactions involving the nervous system and in cerebral tissue repair. The response of astrocytes to interferon-gamma mainly resulted in increased expression of major histocompatibility complex antigens and co-stimulatory molecules (intercellular adhesion molecule-1, LFA-1 alpha) which mediate astrocyte-T-cell interactions. Another co-stimulatory molecule, B7, was neither expressed nor inducible by IFN-gamma and other cytokines. TNF-alpha and IL-1 beta were more efficient in stimulating synthesis of immunoregulatory and proinflammatory cytokines (IL-6, IL-8 and colony-stimulating factors), cytokine antagonists (TNF-alpha soluble receptors), or cytokines with a possible neuroprotective role (leukemia inhibitory factor); they also increased expression of some co-stimulatory molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1). Transforming growth factor-beta 1 was a strong inducer of leukemia inhibitory factor, but did not affect either major histocompatibility complex/co-stimulatory molecule expression or cytokine synthesis. Thus, different cytokines activate distinct functional programs in astrocytes, which may play a specific role in different brain diseases or at different stages of the same disease. It was additionally observed that the response of human astrocytes to cytokines (in particular the inducible synthesis of certain cytokines) varied greatly depending on the presence or absence of neurons in the culture system. This finding suggests that neuronal-glial interactions may be implicated in determining the activation threshold of astrocytes to inflammatory cytokines.

Antigen-Presenting Cells↗