@article {2141,
	title = {Measurement of croton oil induced rabbit ear swelling and evaluation of anti-inflammatory agents with a standard low pressure caliper},
	journal = {Skin Research and Technology},
	volume = {2},
	number = {3},
	year = {1996},
	pages = {142-145},
	abstract = {Background/airns: Carbobenzoxy-phenylalanyl-methionine (CBZ-Phe-Met), a known inhibitor of the chemotactic peptide N- formyl-methionyl-leucyl-phenylalanine (fMLP)  in vitro,  has  not been evaluated as a topical anti-inflammatory agent in vivo.  In order to measure the effect of CBZ-phe-met, one needs a repeat- able,  quantitative,  easily  obtainable  standard  measurement  of the  edema  formation.  In  this  study,  a  caliper  designed  for measuring soft materials was  used to evaluate the edema,  in- duced by croton oil on rabbit ears, as well as the effects of CBZ- phe-met. Methods: The model used in this study was croton-induced in- flammation on rabbit ears. A caliper for measuring soft materials ( European standard  DIN 863 part 3, manufactured  by  TESA Ltd.,  Renens,  Switzerland) was  used to  evaluate  the  edema, which is part of the inflammatory effect . The action of CBZ-phe- met and two other anti-inflammatory agents; hydrocortisone and Na-ibuprofen, were compared. 
Results: CBZ-phe-met 1-5\% was found to reduce the  edema on rabbit ears induced by croton oil by 15 to 93\%. 5\% CBZ-phe- met was found to be as effective as 5\% Na-ibuprofen and 0.1\% hydrocortisone. Conclusion: The caliper for soft materials was found to be suit- able for measuring the edema induced by croton-oil, as well as the  reducing edema due to anti-inflammatory treatment. It was also found that CBZ-phe-met is a potent topical anti-inflamma- tory  agent  in  the  croton-oil-induced  inflammatory  model.  This may indicate a new approach in the treatment of inflammation. Key words: Soft material caliper - inflammation - N-formyl-me- thionyl-leucyl-phenylalanine (fMLP) - carbobenzoxy-phenylala- nyl-methionyl (CBZ-phe-met).},
	author = {V. Manny-Aframian and A. Shafran and A. Zlotogorski and Isaac Ginsburg and S. Dikstein}
}
@patent {1793,
	title = {Thionophosphate derivatives, process for their preparation and pharmaceutical compositions containing them},
	volume = {WO 1996016663 A1},
	year = {1996},
	edition = {United States of America},
	chapter = {US},
	abstract = {The invention relates to a compound of formula (I) in which X1 and X2 each independently represents an oxygen or nitrogen atom; p, m and n are each independently an integer of at least 2; R, R1 and R2 each independently represents a hydrogen atom; a halogen atom; an optionally substituted straight-chained or branched alkyl, alkenyl or alkynyl radical; a group R3O in which R3 is hydrogen atom, an optionally substituted straight-chained or branched alkyl, alkenyl or alkynyl radical; optionally substituted acyl or optionally substituted aryl or heteroaryl; a group R4O(O)C in which R4 is a hydrogen atom or an optionally substituted straight-chained or branched alkyl, alkenyl or alkynyl radical; a group -SR5 in which R5 is a hydrogen atom or an optionally substituted straight-chained or branched alkyl, alkenyl or alkynyl radical; a group -NR6R7 in which R6 and R7 each independently represents a hydrogen atom, an optionally substituted straight-chained or branched alkyl, alkenyl or alkynyl radical; optionally substituted acyl; or an optionally substituted phosphate ester group. The invention also relates to processes for the preparation of compounds of the formula and to pharmaceutical compositions containing the same.},
	author = {Y. Barenholz and Isaac Ginsburg and J. Katzhendler and Ron Kohen and O. Tirosh}
}
@article {1788,
	title = {Prevention of oxidative damage in fibroblast cell cultures and rat skin by positively-charged submicron emulsion of alpha-tocopherol},
	journal = {European Journal of Pharmaceutics and Biopharmaceutics},
	volume = {42},
	number = {4},
	year = {1996},
	pages = {291-298},
	abstract = {An attempt was made to incorporate alpha-tocopherol in negatively and positively-charged submicron emulsions, with the aim of providing an effective topical preparation against skin oxidative damage. In cell culture toxicity experiments using human fibroblast it was shown that the positively-charged alpha-tocopherol emulsion did not exhibit any toxic effect despite the low dilution and respective high concentration used. Negatively and positively-charged submicron emulsions of alpha-tocopherol and their respective blank emulsions were topically applied to rats that were subjected to UVA irradiation under different experimental conditions. No difference was observed between the negatively and positively-charged alpha-tocopherol submicron emulsions regarding the rate of oxidation and peroxyl radical scavenging ability of skin homogenates and both were able to protect rat skin against oxidative stress. However, in a non-invasive evaluation of the lipid hydroperoxidation process in rat skin following exposure to UVA irradiation, the positively-charged alpha-tocopherol submicron emulsion elicited a significantly better protective effect than the corresponding negatively-charged emulsion. These results suggest that the positively-charged emulsion exhibits a more prolonged residence time in the uppermost layers of the skin than the negatively-charged emulsion.},
	author = {Revital Ezra and Shimon Benita and Isaac Ginsburg and Ron Kohen}
}
@article {1756,
	title = {Antioxidant properties of amidothionophosphates: novel antioxidant molecules},
	journal = {Free Radical Biology and Medicine},
	volume = {20},
	number = {3},
	year = {1996},
	pages = {421-432},
	abstract = {This work describes the synthesis and characterization of a new family of antioxidants. The molecules have the same active group, but different oil-to-water and octanol-to-water partition coefficients due to different substituents. Three new molecules were synthesized based on the chemical structure of the primary amide attached to a thiophosphate group forming an amidothionophosphate. The amidothionophosphate molecules were exposed to the oxidative stress of hydrogen peroxide and sodium hypochlorite, and the chemical changes following the exposure were monitored by 31P NMR. The reaction constants with the reactive oxygen species hydroxyl radical and superoxide radical were also calculated and found to be 1.5 x 10(9) M-1s-1 and 8.1 x 10(2) M-1s-1, respectively. To elucidate the ability of amidothionophosphates to act as antioxidants in protecting lipids and proteins, we examined damage prevention in bovine serum albumin, egg phosphatidylcholine liposomes, and lipid emulsions following oxidative stress. Amidothionophosphate showed unique protection properties in these models. In contrast to other antioxidant molecules (ascorbic acid, cysteine, and alpha-tocopherol) the new group did not have any pro-oxidative effects as measured by oxygen consumption from buffer solutions containing amidothionophosphates and cupric sulfate as a source of redox-active metal ions. Amidothionophosphates reduced significantly and in a dose-dependent manner the oxidative burst in human neutrophils as measured by luminol-dependent chemiluminescence, and they also markedly depressed the killing of human fibroblasts by mixtures of glucose oxidase and streptolysin S. The toxicity of these molecules was tested by IP injection of doses up to 1000 mg/kg to white Sabra mice. No mortality was observed 30 d after administration of up to 500 mg/kg.},
	author = {O. Tirosh and Y. Katzhendler and Y. Barenholz and Isaac Ginsburg and Ron Kohen}
}
@article {1719,
	title = {H2O2 renders cells accessible to lysis by exogenous phospholipase A2: a novel mechanism for cell damage in inflammatory processes.},
	journal = {FEBS Letters},
	volume = {383},
	number = {1-2},
	year = {1996},
	pages = {75-8},
	abstract = {Phospholipase A2 (PLA2) and H2O2, secreted from activated inflammatory cells, play a central role in the tissue damage occurring in inflammatory processes. However, while exogenous PLA2 alone does not cause cell lysis, it readily does so when acting with H2O2. We have found that H2O2 degrades cell surface proteoglycans, thus rendering the membrane PL accessible to hydrolysis by exogenous PLA2. This novel mechanism introduces a role for cell surface proteoglycans in protection of cells from damage by pro-inflammatory agents, and may assign a central role for the combined action of H2O2 and PLA2 in inflammatory and bacteriocidal processes.},
	author = {P. Dan and D.W.  Nitzan and A. Dagan and Isaac Ginsburg and S. Yedgar}
}
@article {1577,
	title = {A novel approach to the assessment of toxicity of hexachlorocyclohexane (Lindane) and of certain organic solvents: Killing of cells in culture and the release of arachidonate by synergism among H2O2 membranedamaging agents histone and trypsin},
	journal = {Journal of Basic and Applied Research},
	volume = {9},
	number = {3},
	year = {1996},
	pages = {305-313},
	abstract = {A novel approach to the assessment of the toxicity of the chlorinated pesticide hexachlorocyclohexane (lindane) and the organic solvents methanol and w-butanol, employing endothelial cells in culture, is presented. This highly reproducible system involves the simultaneous treatment of [51Cr]. and [3H]arachidonic acid-labeled rat pulmonary endothelial cells with xenobiotics combined with glucose oxidase-generated H2O2, phospholipase c, streptolysin S, diethyldithiocarbamate (DDC), sodium nitroprusside (NP), histone, and trypsin. Such treatment leads to synergistic cell killing and the release of arachidonic acid (Ginsburg and Kohen, 1995b). Thus, subtoxic amounts of xenobiotics that failed to kill the cells became highly cytolytic when combined with the various mixtures of agonists. Cytotoxicity and the release of membrane lipids are strongly inhibited by catalase, by Mn2+, and by soybean trypsin inhibitor. The "synergism" concept of cellular toxicity is relevant, in particular, in infectious and inflammatory sites where phagocyte- and tissue-derived proinflammatory agonists are generated in large amounts as a result of cellular damage induced either by pathogenic microorganisms, by activated phagocytes, or by xenobiotics. This simple and inexpensive in vitro model of cellular cytotoxicity might supplement and even replace the more costly animal experimentations involved in the assessment of the toxicity and safety of newly designed drugs.},
	author = {Isaac Ginsburg and Douglas F. Gibbs and Steven Tarapchak and James Varani}
}
