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Biomedical subjects

F Antonetti

Publications and source records attributed to F Antonetti.

9 recordsLinked to original sources
PubMed1996

A highly precise reporter gene bioassay for type I interferon.

We describe the setting up and validation of a reporter gene assay for type I IFN based on monkey Vero cells transfected with pMx-Luc, a plasmid carrying the luciferase gene under the control of the type I IFN inducible mouse Mx1 promoter. Vero cells were stably transfected with pMx-Luc and clone 3-143/5 was selected on the basis of luciferase inducibility by IFN-beta. A linear dose-response relationship was found between 1 and 16 IU/ml IFN-beta. The assay was shown to be specific for IFN-alpha and -beta as no effect by a number of other cytokines including IFN-gamma could be detected. In order to render the IFN-beta reporter gene assay protocol more suitable for routine assays, a 3 x 3 balanced parallel line assay design was applied using a 96-well luminometer for luminescence measurement. The assay was shown to be precise with a coefficient of variation of less than 9%. This assay is characterized by high precision coupled to high efficiency, as reflected by a very short assay duration (1 day), when compared to the classical cytopathic effect assays for IFNs and the previously published IFN reporter gene assay based on growth hormone measurement (Lleonart, R., Näf, D., Browning, H. and Weissmann, C. (1990) A novel, quantitative bioassay for type 1 interferon using a recombinant indicator cell line. Biotechnology 8, 1263-1267).

Animals↗
PubMed1996

In vitro comparison of inhibiting ability of soluble TNF receptor p75 (TBP II) vs. soluble TNF receptor p55 (TBP I) against TNF-alpha and TNF-beta.

Tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin (LT, TNF-beta) are pleiotropic cytokines involved in diverse biologic processes, including immune and inflammatory reactions. The biologic responses to TNF are mediated through two forms of cell surface receptors, p55R and p75R. Both receptors exist in a soluble form (p55-sR or TBP I and p75-sR or TBP II), generated by the proteolytic cleavage of the extracellular regions of the molecule. These soluble forms may act by binding and, hence, neutralizing circulating TNF. In the present study, the murine A9 cell line in vitro bioassay was used to test TBP I and TBP II for their neutralizing activity against recombinant human TNF-alpha (rHu-TNF-alpha), and TNF-beta (rHu-TNF-beta) and recombinant murine TNF-alpha (rMu-TNF-alpha). Moreover, TBP I and TBP II were tested for their ability to displace TBP I in the TNF-TBP receptor binding assay (RIBA) against human and murine TNF-alpha as well as TNF-beta. TBP I, from either recombinant (from CHO and Escherichia coli) or urinary origin, was the most effective inhibitor with respect to rHu-TBP II (from CHO) against either human or murine TNF-alpha both in the A9 cells bioassay and in the RIBA assay. Both TBP I and TBP II preparations were less effective in protecting the A9 cells from the toxic effects of rMu-TNF-alpha than from those of rHu-TNF-alpha. The rHu-TBP II preparation was the most effective in inhibiting the cytocidal effect of rHu-TNF-beta on A9 cells and as active as TBP I in the RIBA assay. This result seems to indicate rHu-TBP II as the better soluble TNF receptor able to reverse the rHu-TNF-beta-induced toxicity, at least on A9 cells, leading to consideration of its therapeutic use in those diseases, such as multiple sclerosis, where a role for TNF-beta is indicated.

Animals↗
PubMed1987

Effect of thymostimulin in models of cell-mediated and humoral autoreactivity and on T-dependent suppression.

To explore the therapeutic potential of the thymic hormone preparation thymostimulin (TS) in animal models of cell-mediated and humoral autoimmunity, its effects were investigated on experimental allergic encephalomyelitis in guinea pigs and on anti-erythrocytic autoantibody production in C57B1/6 mice. In both autoimmunity models, TS produced significant therapeutic effects in terms of proportion of diseased animals, disease severity and/or disease duration; however, both the TS dose and the time of treatment start relative to the disease-inducing stimulus critically influenced results. TS effects on the generation and expression of suppressive activity induced in C57B1/6 mice by a supraoptimal immunization with 10(10) SRBC were also examined. TS given after 10(10) SRBC did not influence the level of suppression, and the activity of effectors of suppression was not modified by this agent. Conversely, using a treatment protocol analogous to that effective in reducing murine autoantibody production, TS administration prior to 10(10) SRBC was associated with a significant increase in the subsequent generation of T-dependent, antigen-specific suppressive activity. These findings suggest that effects of TS on the development of suppressor cells may be involved in the activity of this agent in animal models of autoaggression.

Animals↗
PubMed1986

The co-operative action of hyaluronidase and urokinase on the isoproterenol-induced myocardial infarction in rats.

The effects of the intravenous administration of hyaluronidase (HY; 2,500 IU/kg) and urokinase (UK; 20,000 and 40,000 IU/kg), alone or in combination, on the isoproterenol (ISP) induced myocardial infarction (MI) in rats, were studied. The severity of infarction was determined by measuring the levels of serum enzymes (CPK, GOT, LDH) and by evaluating the extent of the injured areas and the incidence of mortality. Plasma thromboxane B2 (TXB2) levels were also determined. All the treatments reduced the infarction area and the enzyme levels (increased by ISP) to a varying degree. However, a definite potentiating activity was obtained when HY was combined with the highest dose of UK. This combination was also capable of reducing the mortality rate. Finally, both HY and UK or the combined preparation brought the plasma TXB2 levels back to normal. These findings suggest the possibility of complementary activities of HY and UK in the treatment of experimental MI.

Animals↗
PubMed1983

The vascular protection of ditazole and its effect on arachidonic acid metabolism.

Ditazole (4,5-diphenyl-2-bis-(2-hydroxyethyl)-aminoxazol) is a weak anti-inflammatory drug and has been shown to inhibit thrombus formation following electrically stimulated vascular damage in the microcirculation of the hamster cheek pouch. The drug was found to inhibit thromboxane A2 (TXA2) production ex vivo as determined by radioimmunoassay (RIA) and to reversibly antagonise the effect of TXA2 on smooth vascular tissue. However, in contrast to acetylsalicylic acid (ASA), it does not inhibit vessel cyclooxygenase. The apparent vascular protective effect of ditazole could not be ascribed to an enhanced production of vascular prostacyclin (PGI2) since the latter, when estimated ex vivo by RIA, was not enhanced following oral treatment with the drug. It is suggested that the mode-of-action of ditazole may be different from the cyclo-oxygenase/PG synthetase blocking action of most other non-steroidal anti-inflammatory drugs.

Animals↗
PubMed1983

Sex-related toxicity of somatostatin and its interaction with pentobarbital and strychnine.

The intravenous LD50 of the hypothalamic tetradecapeptide somatostatin was determined in mice and rats of both sexes. It was found that somatostatin has a sex-related toxicity both in mice and rats. The interaction of low and high doses of peptide with the LD50s of two central nervous system (CNS) drugs, namely pentobarbital and strychnine, was also studied in male and female mice. Differential effects were observed as follows: a very low dose (0.1 mg/kg) of somatostatin does not affect the toxicity of these compounds, whereas the injection of 1 mg/kg of peptide increased pentobarbital toxicity and decreased the toxicity of strychnine. However, an increase in the toxicity of both substances was obtained with very high non-lethal doses of peptide (20 and 30 mg/kg, in female and male mice, respectively).

Animals↗
PubMed1982

"In vitro" activity of urokinase on platelet function and on ADP degradation by vascular tissue.

The effects of urokinase on ADP breakdown by vessel-wall, platelet aggregation and the related prostaglandin system "in vitro" were investigated. It is confirmed that urokinase does not induce platelet aggregation both in humans and rabbits "in vitro". Conversely, in high concentrations, urokinase inhibits ADP-induced platelet aggregation in human and rabbit platelet-rich plasma. No effects were observed on rabbit platelet thromboxane A2 release and on rat vascular prostacyclin production, both measured by radioimmunoassay of thromboxane B2 and 6-keto-F1 alpha prostaglandin, respectively. Moreover, the incubation of urokinase with vascular endothelium resulted in an increased disappearance rate.

Adenosine Diphosphate↗
PubMed1980

Activity ratio between antiprostacyclin and antiaggregating effects of acetylsalicylic acid, indometacin and ditazole.

The effects of acetylsalicylic acid (ASA) indometacin and ditazole on prostacyclin production from rabbit aortic rings were studied in comparison to their inhibiting activity on platelet aggregation. The result were expressed as the ratio between the drug dose inhibiting by 50% prostacycline production and the minimum oral antiaggregating dose. The following ratios were found: 2.4 for ASA, 7.3 for indometacin and 20.4 for ditazole.

Animals↗