@article {1758,
	title = {Control of inflammatory processes by cell-impermeable inhibitors of phospholipase A2},
	journal = {Agents Actions},
	volume = {46},
	year = {1995},
	pages = {77-84},
	abstract = {Cell-impermeable inhibitors of phospholipase A2 were prepared by linking inhibiting molecules to macromolecular carriers which prevent the inhibitor{\textquoteright}s internalization. These preparations inhibit the release of oxygen reactive species from neutrophils and cell death induced by inflammatory agents, as well as bleomycin-induced lung injury.},
	author = {S. Yedgar and P. Dan and A. Dagan and Isaac Ginsburg and IS Lossos and R. Breuer}
}
@article {1757,
	title = {Antioxidants inhibit ethanol-induced gastric injury in the rat. Role of manganese, glycine, and carotene},
	journal = {Scandinavian Journal of Gastroenterology},
	volume = {30},
	number = {9},
	year = {1995},
	pages = {854-860},
	abstract = {BACKGROUND:

Oxygen-derived radicals are implicated in the pathogenesis of tissue damage and ulcerogenesis. This study aimed to examine the effect of manganese, glycine, and carotene, oxygen radical scavengers, on ethanol-induced gastric lesions in the rat and on ethanol cytotoxicity in epithelial cell culture.
METHODS:

MnCl2 + glycine (12.5-50 mg/rat) were injected subcutaneously up to 6 h before oral administration of 1 ml of 96\% ethanol, and 0.5 ml carrot juice or beta-carotene was given orally 30 min before the ethanol. Mucosal injury was evaluated 1 h later by gross and microscopic scoring. The effect of Mn2+ and carrot juice was also tested in monolayers of radiolabeled epithelial cells exposed to H2O2 + ethanol injury as expressed by the extent of the isotope leakage.
RESULTS:

Mn2+ and glycine pretreatment dose-dependently reduced ethanol-induced gastric lesion formation. Protection was maximal when treatment was applied 4 h before the insult. Gross damage was also markedly prevented by pretreatment with carotenes and dimethylthiourea (DMTU, 75 mg/kg intraperitoneally) but not by allopurinol. Mixtures of subtoxic concentrations of ethanol and H2O2 were highly lethal for epithelial cell monolayers. In this model, cell death was markedly attenuated by catalase, DMTU, Mn2+, and carrot juice.
CONCLUSIONS:

Ethanol-induced gastric mucosal damage may involve generation of oxygen-derived radicals, independent of the xanthine oxidase system. By acting as oxygen radical scavengers, Mn2+, glycine, and carotenes, like catalase and DMTU, provide significant gastroprotection.},
	author = {M.  Ligumsky and M. Sestieri and E. Okon and Isaac Ginsburg}
}
@article {1712,
	title = {Synergistic effects among oxidants, membrane-damaging agents, fatty acids, proteinases, and xenobiotics: killing of epithelial cells and release of arachidonic acid},
	journal = {Inflammation},
	volume = {19},
	number = {1},
	year = {1995},
	pages = {101-118},
	abstract = {The assumption that cellular injury induced in infectious and in inflammatory sites might be the result of a well-orchestrated, synergistic "cross-talk" among oxidants, membrane-damaging agents, proteinases, and xenobiotics was further investigated in a tissue culture model employing monkey kidney epithelial cells (BGM) labeled either with 51 chromium or [3H]arachidonate. The cells could be killed in a synergistic manner following exposure to combinations among H2O2 and the following membrane-damaging agents: streptolysins S (SLS) and O (SLO), poly-D-lysine, arachidonic acid, eicosapentanoic acid, arachidic acid, lysophosphatidylcholine, lysophosphatidylinositol, lysophosphatidylglycerol, ethanol, and sodium taurocholate. Peroxyl radical (ROO) generated by azobisdiamidinopropane dihydrochloride (AAPH) further enhanced cell killing induced by SLS, SLO, and nitroprusside when combined with H2O2 and trypsin. BGM cells labeled either with chromium or with tritiated arachidonate, which had been treated with increasing concentrations of sodium nitroprusside (a donor of NO) and with subtoxic amounts of SLS and H2O2, were also killed in a synergistic manner and also lost a substantial amounts of their arachidonate label. Both cell killing and the release of membrane lipids were totally inhibited by hemoglobin (an NO scavenger) but not by methylene blue, an antagonist of NO2-BGM cells that had been treated with increasing concentrations of taurocholic acid were killed in a synergistic manner by a mixture of subtoxic amounts of ethanol, H2O2, and crystalline trypsin (quadruple synergism). Normal human serum possessing IgM complement-dependent cytotoxic antibodies against Ehrlich ascites tumor cells were killed in a dose-dependent fashion. Cell killing was doubled by the addition of H2O2. Cell killing and the release of membrane lipids by all the mixture of agonists tested were both strongly inhibited by the antioxidants catalase, Mn2+, vitamin A, and by fresh carrot juice. It appears that in order to overcome the antioxidant capacities of the epithelial cells, a variety of membrane-damaging agents had to be present in the reaction mixtures. Taken together, it might be speculated that the killing of mammalian cells in infectious and in inflammatory sites is a synergistic phenomenon that might be inhibited by antagonizing the cross-talk among the various proinflammatory agonists generated by microorganisms by activated phagocytes or by combinations among these agents. Our studies might also open up new approaches to the assessment of the toxicity of xenobiotics and of safe drugs to mammalian cells by employing tissue culture techniques.},
	author = {Isaac Ginsburg and Ron Kohen}
}
@booklet {1673,
	title = {Inflammation: more than one explanation},
	journal = {Environmental Health Perspectives},
	volume = {103},
	number = {11},
	year = {1995},
	pages = {985},
	abstract = {I read with interest the EHP supplement
on oxygen radicals and lung injury (vol.
102, supplement 10). I would like to
take this opportunity to comment about
this supplement and raise a key issue
concerning the major concepts regarding
the mechanisms of cellular injury in
inflammatory diseases.
As an active investigator in this field
of research, I cannot fully understand
why there was no mention in the supplement
about the basic understanding that
cellular damage in inflammation is multifactorial.
The nonexpert reader of this
supplement might receive an erroneous
impression that oxygen radicals, per se,
are the exclusive toxic agonists that
induce cellular injury. Many in this field
share the view that cellular damage in
inflammatory diseases might be caused
by a "coordinated cross-talk" among oxidants,
membrane-damaging agents, proteinases,
arachidonic acid metabolites,
phospholipases, cationic proteins, and
cytokines. All these agents are likely to be
present in sites of infection and inflammation.
But sadly, none of the publications
elaborating on this multifactorial
view are quoted in modern textbooks or
in symposia on inflammation and
inflammatory diseases. Instead, the literature
is filled with publications that insist
on a single agonist, be it an oxidant, a
protease, a cytokine, etc., in experimental
models. No attempt to integrate the various
agonists into the full picture is made.
Several of our publications (1-7) deal
with synergistic interactions among multiple
proinflammatory agonists in cellular
injury during inflammation. I believe
that this issue is important, timely, and
might contribute to an understanding of
how drugs, chemicals, and xenobiotics
function in vivo.
Isaac Ginsburg
Hadassah School of Dental Medicine
Hebrew University
Jerusalem},
	author = {Isaac Ginsburg}
}
@article {1644,
	title = {Invited Review: Cell Damage in Inflammatory and Infectious Sites Might Involve A Coordinated {\textquotedblleft}Cross-Talk{\textquotedblright} Among Oxidants, Microbial Haemolysins and Ampiphiles, Cationic Proteins, Phospholipases, Fatty Acids, Proteinases and Cytokines (An Overview)},
	journal = {Free Radical Research},
	volume = {22},
	number = {6},
	year = {1995},
	pages = {489-517},
	author = {Isaac Ginsburg and Ron Kohen}
}
