LUNDVALL, J., S. MELLANDER, H. WESTLING and T. WHITE. Fluid transfer between blood and tissues during exercise. Acta physiol. scand. 1972. 85. 258-269.

So far it has not been possible to assign with certainty a part for histamine in normal physiology. Considering its omnipresence and wide range of actions, when liberated or injected, this situation is envisaged 'not without an inner feeling of disappointment' (Rocha e Silva, 1955).There are no methods available for the accurate estimation of small changes in the histamine concentration of blood or plasma such as might possibly occur during increased activity of certain tissues, e.g. the parietal cells of the gastric mucosa. It has been suggested that the estimation of histamine in the urine is more likely to give information about the release of histamine in the body than investigations on venous blood (Adam, 1950;Gaddum, 1951). This promising approach is limited by the fact that the food commonly eaten by man and laboratory animals contains substantial amounts of histamine, part of which is excreted in the urine. Further, with such a diet intestinal bacteria decarboxylate histidine to histamine, constituting an additional source of exogenous histamine (Schayer, Wu & Smiley, 1954). Large amounts of urinary histamine derived from exogenous sources are likely to conceal increases in urinary histamine derived from increased production or release of endogenous histamine. Schayer, Davis & Smiley (1955) showed that in rats exogenous urinary histamine could be diminished by giving the animals a protein-free diet containing antibacteral agents. This procedure, however, seems hardly suitable for experiments over a long period of time.The complications due to exogenous histamine can now be overcome. It has been observed that in rats raised and maintained on a synthetic histamine-free diet the distribution and urinary excretion of histamine is the same as in germ-free-reared rats, accordingly devoid of intestinal bacteria, and fed on the same diet (Gustafsson, Kahlson & Rosengren, 1957). This similarity indicates that, even in normally kept rats fed as mentioned, histamine from exogenous sources does not contribute detectably to the urinary excretion.

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The carboxyhemoglobin (COHb) level was estimated in patients attending an anti-smoking clinic. A surprisingly large fraction of patients that reported "no smoking" were found to have abnormally high COHb. We believe that this discrepancy is due to the patients not reporting their smoking habits correctly. This phenomenon is further evidence that smoking should be regarded as a form of drug addiction in some persons. Some early relapses in stop-smoking programs can apparently be explained by the patient's admitting previously concealed smoking. For scientific purposes the results of stop-smoking cures should be evaluated by other means than the patient's own reports.

['4C]Histamine was injected subcutaneously in rats. The urine was collected for 24 hr. and analysed for ["4C]histamine and its various metabolites. It was found that male rats excreted less unchanged ['4C]histamine than female ones, the difference between the sexes existing also when the animals were treated with aminoguanidine. The cause of the sexual difference appeared to be that the male rats had a larger capacity to methylate histamine. Leitch, Debley, and Haley (1956) observed that male rats excreted about 10 times less histamine in the urine than female ones. Similar results were obtained by Gustafsson, Kahlson, and Rosengren (1957), who found that males excreted much less free histamine than females.The urinary excretion of histamine, particularly in rats, has been used as an indicator of liberation or production of histamine in the body (see, for example, Wilson, 1954;Schayer, Davis, and Smiley, 1955;Leitch et al., 1956). It appeared therefore of interest to study more closely the cause of the difference in histamine excretion between the sexes. The smaller urinary histamine excretion in male rats could be due to many causes. A priori, it seems most likely that it is due either to a lower rate of production or to a more efficient metabolic transformation of histamine. The latter possibility was examined in the experiments described below. METHODSWhite rats, 4 to 8 months old, were used. They were of the same inbred stock as the animals used by Gustafsson et al. (1957) and Kahlson, Rosengren, and Westling (1958). The rats were given a synthetic, histamine-free diet and were kept in metabolism cages as described by Kahlson et al. (1958) Table I gives the amount of [14C]histamine excreted, and it may be seen that the male rats excreted considerably less unmetabolized [14C] histamine than the females. If the rats were given aminoguanidine sulphate, in a dosage which inhibits the action of histaminase (diamine oxidase)