A report is given on the recent discovery of outstanding immunological properties in BA 1 [N-(2-cyanoethylene)-urea] having a (low) molecular mass M = 111.104. Experiments in 214 DS carcinosarcoma bearing Wistar rats have shown that BA 1, at a dosage of only about 12 percent LD50 (150 mg kg) and negligible lethality (1.7 percent), results in a recovery rate of 40 percent without hyperglycemia and, in one test, of 80 percent with hyperglycemia. Under otherwise unchanged conditions the reference substance ifosfamide (IF) -- a further development of cyclophosphamide -- applied without hyperglycemia in its most efficient dosage of 47 percent LD50 (150 mg kg) brought about a recovery rate of 25 percent at a lethality of 18 percent. (Contrary to BA 1, 250-min hyperglycemia caused no further improvement of the recovery rate.) However this comparison is characterized by the fact that both substances exhibit two quite different (complementary) mechanisms of action. Leucocyte counts made after application of the said cancerostatics and dosages have shown a pronounced stimulation with BA 1 and with ifosfamide, the known suppression in the post-therapeutic interval usually found with standard cancerostatics. In combination with the cited plaque test for BA 1, blood pictures then allow conclusions on the immunity status. Since IF can be taken as one of the most efficient cancerostatics--there is no other chemotherapeutic known up to now that has a more significant effect on the DS carcinosarcoma in rats -- these findings are of special importance. Finally, the total amount of leucocytes and lymphocytes as well as their time behaviour was determined from the blood picture of tumour-free rats after i.v. application of BA 1. The thus obtained numerical values clearly show that further research work on the prophylactic use of this substance seems to be necessary and very promising.

The dose dependence of the acute effects of ethanol upon liver intermediary metabolism in vivo has been demonstrated in rats. Ethanol was given i.p. in doses of 0.69, 1.7, and 3.0 g/kg in equal volumes (20 ml/kg). The liver was freeze-clamped 120 min after injection, and multiple metabolites were measured in the perchloric acid extract of the tissue. Each group showed a significantly different pattern of metabolites, redox states, and phosphorylation potentials although the rate of ethanol disappearance, at least between the two highest dose groups, was not significantly different. The mitochondrial free [NAD+]/[NADH] ratios and the cytoplasmic free [NADP+]/[NADPH] ratio were paradoxically most reduced with the lowest dose of ethanol and became progressively more oxidized with increasing dose. Once established, the differences in these ratios between the groups tended to persist with time, relatively independent of the concentration of ethanol. In a somewhat different pattern, the phosphorylation potential ([ATP]/[ADP][P1]) remained at the control level in the low-dose group but was significantly elevated in the two higher-dose groups. The results, therefore, show distinct and complicated dose-dependent patterns of intermediary metabolism that cannot be explained completely by any one hypothesis but that imply significant dose-dependent effects of ethanol upon intermediary metabolism not directly related to NADH production.

The influence of aging on the renin-angiotensin-aldosterone system was evaluated by comparing young (20 to 30 yr) with elderly (62 to 70 yr) healthy subjects. Despite comparable body sodium-fluid balance in the two age groups, serum renin concentration, plasma renin activity and aldosterone concentrations were lower in the elderly. The age-related decreases in circulating renin and aldosterone concentrations were slight while subjects were supine and receiving normal sodium intake; when upright and during sodium depletion, they were more pronounced. Inverse renin-blood pressure interrelations were noted during two of four study conditions involving normal sodium intake or mild sodium depletion (r = --0.44 and --0.47, respectively), but not during progressive sodium depletion. Plasma renin levels were decreased in the elderly regardless of the presence or absence of an inverse relationship with blood pressure. Aldosterone and cortisol responses to corticotropin infusion were unaltered in the elderly. It is concluded that aging may cause a decrease in circulating renin, with parallel lowering of plasma aldosterone concentrations.

(11 Cell extracts and extracellular culture fluids of species of the yeast genus Schizosaccharomyces exhibited exo-beta-(1 leads to 3)- and exo-beta-(1 leads to 6)-glucanase (EC 3.2.1.-) activities. (2) Using a combination of Sephadex G-100 and DEAE-cellulose chromatography, the exo-beta-(1 leads to 3)-glucanases from the cell extracts and culture fluid of Schizosaccharomyces japonicus var. versatilis were purified extensively. The enzymes from either location exhibited similar purification and other properties. (3) The purified enzymes hydrolysed the beta-(1 leads to 6)-glucosidic linkage in addition to the beta-(1 leads to 3) linkage. Heat denaturation, inhibition and electrophoretic studies indicated that both hydrolytic activities were properties of a single protein. Laminarin and pustulan hydrolysis followed Michaelis-Menten kinetics. The Km and V for laminarin hydrolysis were 6.25 mg/ml and 350 mumol of glucose released/min/mg protein, and for pustulan they were 166 mg/ml and 52 mumol of glucose released/min/mg protein. (4) The exo-beta-glucanase was assigned a molecular weight of 43 000. (5) the purified enzyme failed to hydrolyse isolated cell walls from either baker's yeast or Schizosaccharomyces pombe or to induce protoplast formation from intact cells of S. japonicus var. versatilis or Saccharomyces cerevisiae.

The virostatic compound N,N-diethyl-4-[2-(2-oxo-3-tetradecyl-1-imidazolidinyl)-ethyl]-1-piperazinecarboxamide-hydrochloride (5531) was analyzed as to its effect on the induction of tryptophan-pyrrolase and tyrosineaminotransferase in rat liver. 1. The basic activity of the enzymes was not influenced by the substance either in normal or in adrenalectomized animals. 2. The induction of the enzymes by cortisone increased in the presence of the compound whereas the substrate induction remained unchanged. 3. The induction of tyrosine-aminotransferase by dexamethasonephosphate in tissue culture is inhibited if the dose of compound 5531 is higher than 5 mug/ml.

Five distinct ester hydrolases (EC 3-1) have been characterized in guinea-pig epidermis. These are carboxylic esterase, acid phosphatase, pyrophosphatase, and arylsulphatase A and B. Their properties are consistent with those of lysosomal enzymes.

RMI 61 140, RMI 61 144 and RMI 61 280 are newly synthetized N-[8-R-dibenzo(b,f)oxepin-10-yl]-N'-methyl-piperazine-maleates which show interesting psychopharmacologic effects. This work contains the results of a study performed with these three compounds, in order to demonstrate their neuropsycholeptic activity in comparison with chloropromazine (CPZ) and chlordiazepoxide (CPD). The inhibition of motility observed in mice shows that the compounds reduce the normal spontaneous motility as well as the muscle tone. The central-depressant activity is evidenced by increased barbiturate-induced sleep and a remarkable eyelid ptosis can also be observed. Our compounds do not show any activity on electroshock just as do CPZ and CPD. As to the antipsychotic outline, our compounds show strong reduction of lethality due to amphetamine in grouped mice and a strong antiapomorphine activity. They show also an antiaggressive effect and an inhibitory activity on avoidance behaviour much stronger than CPZ. We have also found extrapyramidal effects, as catalepsy, common to many tranquillizers of the kind of the standards used by us. As for vegetative phenomena, the compounds show hypotensive dose related action ranging from moderate to strong, probably due to an a-receptor inhibition. Adrenolytic activity against lethal doses of adrenaline, antiserotonin and antihistaminic effects, as well as other actions (hypothermia, analgesia, etc.) confirm that RMI 61 140, RMI 61 144 and RMI 61 280 are endowed with pharmacologic properties similar and more potent than those of CPZ. Studies on the metabolism of brain catecholamines show that they are similar to CPZ, although with less effect on dopamine level.

A phospholipase hydrolyzing cardiolipin to phosphatidic acid and phosphatidyl glycerol was characterized in gram-negative bacteria but was absent in preparations of gram-positive bacteria, Saccharomyces cerevisiae, and rat liver mitochondria. In cell-free extracts of Escherichia coli, Salmonella typhimurium, Proteus vulgaris, and Pseudomonase aeruginosa, this cardiolipin-hydrolyzing enzyme had similar pH and Mg2+ requirements and displayed a specificity which excluded phosphatidyl glycerol and phosphatidyl ethanolamine as substrates.

Many eyes donated for use in corneal grafting are rejected because of signs of autolysis in the donor material. The purpose of this experimental study was to determine whether hydrocortisone acting as a lysosome membrane stabilizer could prevent or retard autolysis of the corneas under storage, and if so, what was the most efficacious concentration. Different groups of rabbit corneas were placed in saline as controls or in varying concentrations of hydrocortisone (10(-10) M to 10(-4) M at pH 7.4) at 37 degrees C and 4 degrees C. Acid phosphatase released after six hours was measured biochemically. This enzyme was used as a marker enzyme reflecting lysosomal labilization. Results showed a significant stabilization of the lysosomal membrane at 4 degrees C as compared to 37 degrees C. A trend towards stabilization of the lysosomal membrane was seen when 10(-8) M concentration of hydrocortisone at 37 degrees C was used, there being no demonstrable stabilization at 4 degrees C.