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Biomedical subjects

A Cifarelli

Publications and source records attributed to A Cifarelli.

23 records · Page 2Linked to original sources

Studies on the safety of a new non-steroidal anti-inflammatory drug: protacine (CR 604).

The effects of 3'-(4-[2-(1-p-chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazinyl-1-yl)propyl-4-benzamido-N,N-dipropyl-glutaramate(+/-)dimaleate(protacine, CR 604) on gastrointestinal physiology and tolerance were investigated. The anti-inflammatory activities and the effects on the gastrointestinal tract showed a very good separation. Protacine showed a smaller influence on gastric prostaglandins and did not stimulate both basal and cAMP enhanced gastric acid output as did other antiinflammatory drugs. This may explain, at least in part, its gastrointestinal safety. Articular cartilage metabolism showed to remain practically unchanged by protacine both in in vitro and ex vivo experiments. All these results show that protacine has very good gastrointestinal safety indexes, that effects on articular cartilage metabolism are very low and that, from these points of view, it is superior to other non-steroidal anti-inflammatory drugs of similar potency.

Animals↗

Uptake of fluorochrome-labelled exotoxins by different cell types in culture.

The uptake of diphtheria toxin and of Staphylococcus alpha-toxin by two different human cell types cultured in vitro (the HEp-2 continuous cell line and human adult hepatocytes) was studied by fluorescence microscopy and phase-contrast microscopy. The behavior of these two bacterial exotoxins was quite different. Diphtheria toxin was incorporated into cells by pinocytosis, whereas alpha-hemolysin penetrated into the cytoplasm probably through lesions in the cell membrane. In addition, the penetration of diphtheria toxin into the cells was not inhibited by specific antiserum, whereas anti-alpha-haemolysin inhibited the penetration of alpha-tpxin through the cell membrane. The significance of these findings is discussed.

Animals↗

Ultrastructural changes in HEp-2 cells treated with staphylococcal alpha-toxin.

The effect of highly purified staphylococcal alpha-toxin on HEp-2 neoplastic cells growing in culture was studied by electron microscopy. In addition to some nuclear modifications, the most significant morphological changes were in mitochondrial structure, alpha-toxin seems to induce a defined sequence of changes in mitochondrial configuration which can be summarized as an earlier phase of 'condensation' of mitochondrial structure and a later phase of mitochondrial swelling with an intermediate 'transitional' configuration. The significance of these findings is discussed in the light of the present state of knowledge of the biological characteristics of staphylococcal alpha-toxin.

Bacterial Toxins↗

Phagocytosis and cellular metabolism (a study on mouse and human macrophages in culture).

The uptake of foreign particles by mouse and human macrophages influenced by various metabolic inhibitors was examined in order to obtain further informations about the energy-dependent mechanisms which are involved in the phagocytic process. The inhibitors employed were iodoacetate, fluoroacetate, fluoride, malonate, sodium azide, 2-4-dinitrophenol, cycloheximide and ouabain. These substances were tested on monolayer cultures and the phagocytosis assay was performed by using zymosan suspension in the nutrient media. The quantitation of phagocytosis was obtained by the direct count of intracellular zymosan particles (immersion microscopy, 100x) and the results were evaluated and compared by biometrical analysis. The effects of these inhibitors on phagocytosis and their relation with the metabolic intracellular pathways are discussed.

Animals↗