No abstract

Summary1. Local injection of carrageenin in the rat's paw produced oedema and leakage of dye which had been administered previously by the intravenous route. A net dissociation between both parameters was observed: while oedema developed slowly, maximal intensity being attained after 4-5 h, dye-leakage was maximum after 1 hour. 2. Anti-inflammatory drugs such as acetylsalicylic acid and indomethacin were effective in reducing oedema and dye-leakage when given before the injection of carrageenin, but much less effective when given 30 or 60 min after carrageenin. Hexadimethrine bromide was effective in reducing dye-leakage also when given 1 h after the injection of carrageenin. 3. Combined administration of benadryl and methysergide, before the injection of carrageenin caused only a slight reduction in oedema and dye-leakage.4. When the paws were heated (550 C for 30 s) as a noxious stimulus the dissociation between maximal oedema and maximal dye-leakage was not observed, both phenomena running parallel. Pre-treatment of the animals with indomethacin did not afford any protection. 5. These results suggest that the inflammatory reaction to mild stimuli (carrageenin in our experiments) develops through different phases: initially the increased vascular permeability involves extravasation of plasma proteins and that phase is followed by an increased permeability mainly to water. Stronger stimuli (heating in our experiments) produce an overlapping of both phases, probably by inflicting severe damage to the vascular bed of the affected area.6. The anti-inflammatory drugs employed affected chiefly the initial phase of the response. 1fitroductionDyes injected intravenously localize in areas of developing inflammatory reactions. Using xylene as an irritant applied to the skin of rabbits, Rigdon (1939Rigdon ( , 1940 was able to show that Trypan blue and Indian ink concentrate in the injured areas only when injected into the circulation immediately after or within a period of less than 3-5 h following the application of xylene, though after that time these skin areas exhibited all the macroscopic and microscopic alterations associated with the inflammatory response. Rigdon concluded that increased vascular permeability is of brief duration following injury where xylene is applied.

The colloidal carbon technique used in rats to study vascular permeability changes shows two main pictures: (1) Predominant capillary accumulation of carbon, observed in pulmonary edemas produced by many different methods.(2) Predominant venular and arteriolar labeling, as seen in alpha-naphtylthioureainduced pulmonary edema. The ultrastructural alterations of the lung blood vessels in acute immunological pulmonary edemas of rats, mice and guinea-pigs are characterized by vacuolization, swelling and sloughing of the endothelium and epithelium, by occlusion of small vessels by platelet thrombi, by opening of the endothelial and epithelial junctions and by interstitial edema. Separation of the endothelium from the epithelium, forming channels, may be observed in the alveolar vessels, suggesting drainage of fluids through these channels from the alveolar level to larger interstitial spaces.Because of biochemical importance of the neurotransmitters at the sinapses, the study of the enzymatic systems which interfere with their metabolism and function became relevant and two research groups have been working in this field, with the following results: (1) At the cholinergic level it could be observed (C. Baratti and J. Mifio) that eserine and oxotremorine, increasing acetylcholine content of the dorsal hippocampus of the rat, acts differently on the cholinacetilase (ChAc) and cholinesterase (ChE) activity eserine: + ChE; = ChAc, oxotremorine: = ChE; + ChAc. This latter effect could be due to the intraneuronal increase of acetylcholine. Eserine facilitates and oxotremorine does not modify discrimination unpublished data. (2) At the serotoninergic level, in mesencephalon, pons and medulla oblongata rat (J. A. Izquierdo, E. Chemerinski and M. Billiet) it was found that pregnenolone medroxy-progesterone and DOCA by inducing a liver enzyme with pyrrol oxygenase activity, decreased significantly serotonin content in those brain regions; 5-Hydroxyindoleacetic content is not modified.Swelling induced in the rat's paw by dextran, carrageenin and cellulose-sulfate is markedly reduced in alloxan-diabetic rats or in rats submitted to sub-total pancreatectomy. Render-ing diabetic animals normoglycemic through fasting, the swelling inhibition still persisted. Insulin reversed such inhibition. Diabetic animals presented decreased responses to intradermally