Inflammatory molecule release by beta-amyloid-treated T98G astrocytoma cells: role of prostaglandins and modulation by paracetamol.

Deposition of beta-amyloid in the brain triggers an inflammatory response which accompanies the neuropathologic events of Alzheimer's disease and contributes to the destruction of brain tissue. The present study shows that beta-amyloid can stimulate human astrocytoma cells (T98G) to secrete the proinflammatory factors interleukin-6 and prostaglandins. Furthermore, prostaglandins can stimulate T98G to secrete interleukin-6, which in turn triggers the formation of additional prostaglandins. Prostaglandins are, therefore, a key element in the induction and maintenance of a state of chronic inflammation in the brain which may exacerbate the fundamental pathology in Alzheimer patients. Paracetamol (0.01-1000 microM), an unusual analgesic/antipyretic drug which acts preferentially by reducing prostaglandin production within the central nervous system, and indomethacin (0.001-10 microM) caused a clear dose-dependent reduction of prostaglandin E2 production by stimulated T98G cells whereas interleukin-6 release was not affected. These data provide further evidence of the involvement of non-steroidal anti-inflammatory drugs in the inflammatory processes that can be generated by glial cells in intact brain.

A flow-cytometric method to evaluate drug antiaggregating effect on rat neutrophils.

Neutrophils are one of the first cellular populations to become involved in inflammatory processes and some features of the response to inflammatory stimuli can be partially reproduced in vitro by treatment with chemotactic peptides such as N-formyl-methionyl-leucyl-phenylalanine (FMLP). Nonsteroidal antiinflammatory drugs (NSAIDs), such as indomethacin, are known to interfere in vitro with human and rat neutrophil functions and to inhibit FMLP-induced aggregation. In this article we define the scatter parameters of rat neutrophils and demonstrate that flow-cytometric analysis of these cells can be used to analyze the inhibiting action of drugs in an in vitro model of aggregation. We show, in fact, that indomethacin at 100 microM (p < 0.05) and 200 microM (p < 0.01) is able to significantly reduce rat neutrophil aggregation. These results confirm the data obtained by light transmittance aggregometry and indicate that cytometric analysis of aggregation phenomena is a technique suitable for the screening of antiaggregating drugs.

Radical scavenger activity of bendazac, an anticataract non-steroidal anti-inflammatory agent.

Oxidative damage to lens components is associated with cataract formation and reactive oxygen species (ROS) overproduction at inflammation sites is thought to lead to the development of inflammatory disorders. Bendazac is a non-steroidal anti-inflammatory drug able to delay the cataractogenic process. Aim of the present study is to characterize, both chemically and biologically, the activity of this anticataract agent as a radical scavenger. Bendazac has been shown to be a strong reacting substrate in a chemical oxidizing system, which mimics a physiological pathway of hydroxy radical generation. In the Fenton-Cier reaction the drug rapidly forms a mixture of hydroxylated derivatives, among which 5-hydroxybendazac, bendazac's main metabolite, being a hydroxy radical scavenger itself. Moreover, by means of a rapid and sensitive flow cytometric method able to determine reactive oxygen intermediate production, bendazac and its 5-hydroxy derivative were shown to inhibit oxidative burst activation in polymorphonuclear neutrophil leukocytes (PMNLs).

A total body hyperthermia animal model for pharmacological studies.

Toxic side effects are the main drawback in localized and total body hyperthermia for the treatment of tumours. This paper reports a total body hyperthermia animal model which may be used as an experimental tool in the search for conditions or drugs capable of inhibiting the toxic effects of hyperthermia.

Chemotherapeutic agents with an imidazole moiety. II. Synthesis and biological activities of new 1,4-diarylimidazoles.

The synthesis, antifungal and pharmacological activities of new 1,4-diarylimidazoles are reported. Antimicrobial data in comparison with antifungal antibiotic pyrrolnitrin pointed out that the 1,4-diaryl-2-mercaptoimidazole derivatives were inactive and all 1,4-diarylimidazoles exhibited a weak antifungal activity. Some compounds showed a selective activity against strains of Candida sp. Instead pharmacological data did not evidence any significant antiinflammatory activity. The tested compounds were prepared by reacting appropriate phenacylanilines with potassium thiocyanate in acidic medium to afford 1,4-diaryl-2-mercapto imidazoles which were then transformed into title compounds by treatment with nitric acid.