Polyamine levels in sarcoma-bearing rats in relation to growth and necrosis of the tumour cells.

Putrescine (PU), spermidine (SPD) and spermine (SPM) levels in blood serum of MC Sa 1828 P-bearing rats have been studied in relation to tumour weight and the histological picture. A statistically significant increase of PU and SPD was found in the course of tumour development. Decrease in the level of polyamines in the necrosis stage was also found. Only increased SPD level appeared in the period of intensified necrosis, accompanied by lymphocyte infiltration.

The histamine-induced skin reaction in schizophrenic and normal subjects.

Most published data on histamine skin tests on schizophrenic patients show them to be insensitive relative to normals or other psychotic patients. However, experimental conditions have varied and in most cases only a single dose of histamine was used. We have compared 13 volunteer controls and 16 paranoid schizophrenics; each subject was injected intradermally with histamine, 10, 20, and 50 microgram, doses predetermined in volunteers to give a dose-response curve. Wheal and flare were measured at 10 and 20 minutes, intervals near the time of maximum flare. We found no statistically significant differences between normal controls and schizophrenic patients.

An interaction of histamine H2-receptor antagonists with the noradrenergic system in rat brain.

Intraventricular administration of 50 microgram of burimamide or 250 microgram of either metiamide or cimetidine decreased the NA concentration in rat hypothalamus by nearly 30%. Cimetidine did not significantly influence either DA or DOPAC levels in striatum. Cimetidine and metiamide significantly potentiated locomotor activity of tranylcypromine-treated rats and this effect was antagonized by phentolamine. It is concluded that the three histamine H2-receptor antagonists released NA in rat brain.

The FAD dependent amine oxidases in relation to developmental state of enterocyte.

Epithelial cells from bovine and guinea pig small intestines contain monoamine and polyamine oxidases with MAO-A preponderance at any maturational stage. For either species, Km values for 5HT and N1acetylspermine remain throughout cellular maturation on the same levels, whereas the Vmax values do not. For serotonin, the dividing crypt cells showed in cow lower and in guinea pig higher Vmax than the mature cells; for N1acetylspermine, mature cells, independently of species, showed lower Vmax.

Keyhole limpet hemocyanin (KLH)--a potent antigen in reaginic sensitization of mice and rats; a comparison with egg albumin (EA)-induced reaction.

Two distinct antigenic functions of KLH and EA were tested in four inbred strains of mice (BALB/c, 129, C3H/A, C57BL/6J:a) stimulation of reaginic antibody production after subcutaneous introduction of antigen in alum-precipitated form, and b) ability to elicit an anaphylactic reaction in vitro on pre-sensitized peritoneal mast cells. KLH was found to be more effective than EA in both functions tested, inducing higher titres of IgE and IgG1 antibody levels in the sera as well as higher percentage of histamine release from actively and passively sensitized peritoneal mast cells. Two different forms of KLH (associated and dissociated) were tested for potency in stimulating an anaphylactic sensitization of mice and rats and capacity to elicit an anaphylactic reaction on their peritoneal mast cells in vitro. In all rats as well as in BALB/c, 129 and C3H/A mice sensitization with dissociated KLH resulted in higher percentage of antigen-induced histamine release from peritoneal mast cells (an exception: mast cells of C57CL/6J mice released a little more histamine on the challenge with associated KLH). The PCA tests show, that the dissociated KLH does not act through greater stimulation of antibody formation.

Passive sensitization of mice and rats with IgE antibodies.

The strain-dependent variation in susceptibility to passive sensitization of the skin and peritoneal mast cells with homologous IgE antibodies was observed in inbred strains of mice. Strain 129 showed low susceptibility to passive sensitization and high efficiency of normal serum in blocking mouse reagin-induced PCA in rats. Balb/c and C3H/A strains showed higher susceptibility to passive sensitization and the efficiency of normal serum in blocking rat PCA lower than strain 129. The serum factor responsible for rat PCA inhibiting effect was heat-labile. The anaphylactic response of peritoneal mast cells of inbred strains to the challenge with anti-mouse IgE and anti-rat IgE in vitro was low in Balb/c mice, as compared with the response of C57BL/6J and 129 mice. The results suggest, that non-specific IgE present in the serum or bound to the mast cells may be one of the factors determining the susceptibility of mouse strains to reagin-induced passive sensitization. However, the results obtained with C57BL/6J strain suggest the existence of other factors effecting this susceptibility.

Effect of complexes of lidocaine with transient metals on histamine release from rat mast cells.

The effect of complexes of lidocaine with zinc, copper and cobalt on histamine release from peritoneal rat mast cells induced by various secretagogues was investigated. The complexes of lidocaine with metal ions inhibited histamine release induced by compound 48/80 and ionophoreous antibiotics: A23187 and X537A. The ionic complex of lidocaine with zinc was found to be the most potent against 48/80--induced histamine release and exerted the significant inhibition in the concentration of 10(-5) M. The action of coordination complex of lidocaine with zinc was somewhat weaker. The significant inhibitory effect on 48/80-induced histamine release of the copper and cobalt lidocaine complexes was observed in concentration of 10(-4) M. Histamine release by ionophores A23187 and X537A was also affected by zinc lidocaine complexes. However, coordination complex had more potent action on histamine release than the ionic one.

Reaginic sensitization of mice and rats.

The reagin response to hemocyanin (KLH) and egg albumin (EA) was studied in inbred strains (Balb/c, 129, C3H/A, C57BL/6J) and Swiss-Copacabana mice. Both antigens induced apparent and in certain experimental conditions, persistent reagin production, KLH being more effective. Al(OH)3 gel as an adjuvant was more suitable for IgE antibody production, while the Freund's complete adjuvant appeared more appropriate for IgG1 antibody response. The reaginic response to EA and Al(OH)3 in rats Wistar, Sprague-Dawley and F1 hybrids (Wistar x August) was weak and transient. The best sensitization, though relatively low as compared with mouse sensitization, was obtained in Sprague-Dawley and F1 hybrids. The results suggest, that a mouse model of sensitization is quite suitable for studying the persistent reagin response, while a rat model may be useful for investigating the early suppression of reagin response.

The relationship between specific IgE antibody and non-specific IgE in anaphylactic sensitization of mice and rats.

The mice from inbred strains BALB/c, 129, C3H/A, C57BL/6J and outbred Wistar rats were tested for their capacity for reaginic sensitization on the response to antigenic stimuli. The total serum IgE level measured before immunization was highest in 129 mice and increased (2.5-3-fold) after immunization. BALB/c mice also showed an increase of the total serum IgE after immunization, whereas in two other strains such effect was not observed. All mouse strains tested produced IgE antibodies after immunization and the results suggest, that these IgE antibodies form only minor part of the total IgE content during immunization; in 129 and BALB/c mice beside IgE antibody response the production of non-specific IgE may be potentiated and these IgE may interfere in passive sensitization of mast cells with IgE antibodies. The examination of rats also showed, that mast cells with lower concentration of non-specific IgE are better acceptors for sensitization with IgE antibodies.

Reversed anaphylaxis with anti-IgE on mouse and rat mast cells.

Peritoneal mast cells of four inbred strains of mice (BABL/c, 129, C3H/A, C57BL/6J) and F1 hybrids of August and Wistar rats were studied for their sensitivity to the action of anti-IgE antibody for histamine release. The mast cells of normal mice from four mouse strains tested showed different abiltiy to release histamine after challenge with several dilutions of anti-IgE; mast cells of BALB/c mice showed the lowest reaction to anti-IgE. After active sensitization of mice and rats their mast cells release histamine after challenge with specific antigen, however, the detectable changes in their sensitivity to anti-IgE were not observed. After passive sensitization of mice the mast cells of three out of four strains tested show slightly enhanced sensitivity to anti-IgE for histamine release. Thus, the sensitization of mast cells not always stimulates their sensitivity to anti-IgE in reversed anaphylaxis.

The immunomodulating preparation Ukrain does not induce anaphylactic sensitization in mice and guinea pigs.

The ability of Chelidonium majus L. alkaloids derivative Ukrain to induce an anaphylactic sensitization was tested on mice and guinea pigs. The levels of IgE antibody in the mouse sera, and IgG1a, IgG1b as well as IgE antibody levels in guinea pig sera, were evaluated by passive cutaneous anaphylaxis (PCA) tests. Ukrain alone or adsorbed on aluminium hydroxide gel (alum) introduced into BALB/c mice in several subcutaneous injections was unable to stimulate measurable anti-Ukrain IgE antibody response. Moreover, Ukrain introduced together with ovalbumin (OA) into mice in the course of immunization with OA induced lower anti-OA antibody response as compared to the response induced by OA alone. Ukrain adsorbed on alum and injected subcutaneously into guinea pigs did not induce measurable IgG1a, IgG1b and IgE antibody response. The present results suggest that the immunomodulating preparation Ukrain could be therapeutically safe at least as far its inability to induce anaphylaxis is concerned.

Neurotransmitters in hepatic encephalopathy.

The pathogenesis of hepatic encephalopathy (HE), a neuropsychiatric disorder resulting from liver failure, is still a matter of debate. Recently attention has been focused on brain neurotransmitters. The accumulating evidence indicates that the imbalanced metabolism and turnover as well as the altered functions of neurotransmitters (dopamine, noradrenaline, serotonin, GABA) and false neurotransmitters (phenylethanolamine, octopamine, synephrine) may be of high importance in the pathomechanism of HE. Our data permit adding histamine (HA) to the multifactorial pathogenesis of HE. The enhanced rate of histidine influx into the brain following portocaval anastomosis and a dramatic increase in the HA content in the hypothalamus may suggest the involvement of HA in the symptomatology of hepatic encephalopathy.

The influence of Tolpa Peat Preparation (TPP) on rat liver regeneration.

The effect of Tolpa peat preparation (TPP) on the regenerative response has been examined in rats submitted to two thirds hepatectomy. The ornithine decarboxylase activity, spermidine and histamine levels, DNA and RNA content, RNA/DNA ratio and the mass of restituted liver were used to test the intensity of the regenerative processes. The action of TPP is dual: a short-term application of TPP at a dose of 20 mg/kg/day causes an inhibition of the ornithine decarboxylase activity, the decrease in spermidine formation, the levels of DNA and RNA, and liver restitution. The multiple application of TPP, on the other hand, results in a stimulation of ornithine decarboxylase, the increase in spermidine and histamine as well as RNA and DNA levels in regenerating liver; concomitantly, the liver mass tends to increase in TPP treated groups. TPP might exert its effects, at least partially, by interfering with polyamine biosynthesis.

Investigations on allergogenic properties of Tolpa Peat Preparation.

The ability of Tolpa Peat Preparation (TPP) to induce or enhance an allergic sensitization was tested on mice and guinea pigs. The levels of IgE antibody in the mouse sera and IgG1 as well as IgE antibody levels in guinea pig sera were evaluated by PCA (Passive Cutaneous Anaphylaxis) tests. TPP adsorbed on aluminium hydroxide gel (alum) and introduced into BALB/c mice by several subcutaneous injections was unable to stimulate the noticeable anti-TPP IgE antibody response. TPP introduced together with ovalbumin (OA) into the mice in the course of immunization with OA did not enhance anti-OA IgE antibody response. TPP adsorbed on alum and injected subcutaneously into guinea pigs was unable to induce noticeable IgG1a, IgG1b and IgE antibody response, and mast cells obtained from lung and mesentery of these animals did not release histamine when challenged with TPP in vitro at 37 degrees C. In conclusion, our results show that under the experimental conditions used in the present experiments TPP was unable to induce or enhance an allergic sensitization of mice and guinea pigs.

Influence of Tolpa Peat Preparation on the IgE-induced anaphylactic reactions in mice.

The ability of Tolpa Peat Preparation (TPP) to affect anaphylactic sensitization and mast cell secretory function was tested in BALB/c mice treated with TPP orally for 12 days. TPP in the doses of 20 and 50 mg/kg/day reduced histamine release from mouse peritoneal mast cells challenged with anti-IgE or concanavalin A in vitro. The treatment of mice with TPP from day 1 to day 12 of immunization with Ovalbumin (OA) absorbed on aluminium hydroxide gel resulted in a decrease of antigen-induced histamine release from mast cells of these mice in vitro and in decreased IgE antibody level in their sera. TPP introduced into OA-immunized mice showing developed IgE antibody response was less effective in decreasing anaphylactic histamine release from mast cells of these mice. In all experiments low doses of TPP used for oral treatment were more effective than high doses in inhibiting anaphylactic events in the mice.