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The purpose of the present study was to test Enterogenin for genotoxicity. The micronuclearic test of Schmid W. was used. Enterogenin was introduced intraperitoneally, once and/or twice in two doses on male and female mice of the BDF 1 hybrid line. The positive controls were injected with clastogenic agent. Bone marrow smear preparations were made, determining the ratio between the normochromic erythrocytes (NCE) and polychromic erythrocytes (PCE), and the number of micronuclearic erythrocytes (MNE). Enterogenin has no genotoxic effect on the hemopoietic tissue of bone marrow of mice the ratio NCE/PCE being within the reference values. The preparation showed no clastogenic effect (p > 0.05), compared to the controls, as the number of PCE with micronuclei did not change 24, 48 and 72 hours after treatment with the two studied doses.

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Inhibiting enterocytogenin (IEG), a 4.5 kDa nucleopeptide isolated from pig intestinal mucosa induced dose-dependent alterations in the spontaneous contractile and bioelectric activities of rat gastric smooth muscle when applied at 10(-8) to 10(-4) M. Two separate phases were apparent in the effects observed, an initial contractile phase followed by a relaxation phase. The depolarization and the related contraction were reduced by amiloride and to a lesser extent by nifedipine. This reduction resulted in a corresponding decrease in the magnitude of the subsequent relaxation phase. Charybdotoxin and apamin caused a statistically significant decrease in the hyperpolarization and the magnitude of the relaxation phase and increased the duration of the contractile phase. On a caffeine or noradrenaline background the effects induced by IEG were diminished, suggesting that they are mediated through Ca2+ release from the intracellular Ca2+ stores. We hypothesize that the depolarization induced by IEG involves activation of the voltage-dependent Ca2+ channels with subsequent stimulation of the Ca(2+)-dependent K+ channels and late development of hyperpolarization.

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The effects of a new intestinal peptide, inhibiting enterocytogenin (IEG) derived from pig intestinal mucosa were studied in vitro on 3T3 mouse fibroblasts and L5178Y mouse lymphoma cell line. IEG caused considerable growth inhibition together with specific morphological changes, necrotic effects as well as formation of monolayers at the highest concentration applied (1000 micrograms/ml). A biologically active fraction (IEG-BAF) derived by further purification of IEG by gel-filtration, proved to possess most of the described activity. The concentrations of IEG and IEG-BAF inhibiting the growth of L5178Y lymphoma cells by 50% (IC50 values) were calculated to be 759 micrograms/ml and 192 micrograms/ml, respectively. IEG-BAF has a molecular mass of 4450 +/- 180 Da and is most probably a peptidylnucleotidate as revealed by spectral analysis.

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Rat liver cells were homogenized and subsequently fractionated by a simplified method based on microfiltration, which proved to give a high recovery of membrane-bound phosphatidylinositol phospholipase C (PI-PLC) activity. The effects of insulin, acetylcholine (AC), epinephrine (EN) and bacterial phospholipase C (bPLC) on the PI-PLC activity were studied after in vitro treatment of isolated membranes or after in situ application in rat liver. A dose-dependent increase of membranous PI-PLC (up to 3-fold) and corresponding 36 to 72% decline of the cytosolic activity were established upon treatment with supraphysiological doses of insulin or with bPLC, respectively. AC induced a biphasic response with a maximal stimulation in the micromolar range. On the other hand EN promoted a slight but significant dose-dependent inhibition of PI-PLC in both cytosol and membranes. Sodium fluoride was also a potent inhibitor of the membrane-associated PI-PLC with an EC50 value of about 5 mM. The combined assay with NaF and EN revealed no additivity between their inhibitory effects, suggesting a common step in the mechanism(s) of inhibition caused by the two agents. The stimulatory effects of insulin and AC were partially reduced by soluble cytosolic factors, which still remain to be identified. When insulin and AC were applied in combination in the presence of cytosol, this resulted in a 56% inhibition of PI-PLC below the control level.

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Phosphatidylinositol-specific phospholipase C (PIPLC) from Bacillus thuringiensis (0.11 units per ml) inhibited growth of IC-Sofia carcinoma cell line in culture by 64%. The growth of transplanted carcinoma in hamsters was also inhibited by 29% at a dose of 4.9 units of PIPLC/kg animal/day. In addition, degeneration processes and a significant fibrosis of the tumour occurred. The functional, clinical, biochemical and haematological parameters studied were consistent with the established antitumour effect in vivo.

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The authors describe a system for preventing the initial forms of mental disorders, introduced at a large industrial enterprise. The system comprises 6 stages: psychohygiemic, psychoprophylactic, psychocorrection, ambulatory psychotherapeutic, inpatient, and maintenance psychotherapy. The principles of the structure of the system, the results of its functioning for 3 years are outlined in accordance with the data of the medical hygiene division.

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Follow-up investigation of the blood sera from preparturient women and women with habitual abortions showed the presence of a factor which has an activating effect on smooth muscle preparations because it causes the release of prostaglandins. Gel-chromatographic counter flow separation and microelectrophoresis of the blood sera have shown that the isolated serum factor is a water soluble glycopeptide with a molecular weight of about 2000.

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