Ampullosporin A, a peptaibol from Sepedonium ampullosporum HKI-0053 with neuroleptic-like activity.

The potential neuroleptic-like effect of ampullosporin A, a new peptaibol, isolated from the fungus Sepedonium ampullosporum HKI-0053, was characterized using specific behavioural models and methods. Ampullosporin A (amp) disrupted the retrieval of a well-trained conditioned reaction and normalized the behavioural effects of subchronic ketamine treatment in the social interaction test in a dose which showed only inconsiderable side effects. The experiments demonstrated that the substance did not antagonize the apomorphine (apo) induced hyperactivity. On the other hand, the locomotor stimulation induced by the NMDA receptor antagonist MK-801 was nearly completely suppressed by ampullosporin A, supposing interactions with the glutamatergic system. Binding studies demonstrated no interaction with dopaminergic D(1) and D(2) receptors. However, amp can alter the activity of glutamate receptors. The results resemble characteristics of an atypical neuroleptic drug. But further experiments are necessary to validate the suggested neuroleptic-like activity.

[Prion dementias: nosology and diagnostic difficulties in the spectrum of Creutzfeld-Jakob encephalopathy]. / Prion dementiák: A Creutzfeldt-Jakob-encephalopathia spektrum nozológiája és diagnosztikus nehézségei.

Creutzfeldt-Jakob disease (CJD) is one form of subacute prion diseases with spongiform encephalopathy. Hereditary, infectious and sporadic types of the disorder can be distinguished. The abnormal transformation of the prion protein, relevant in the normal synaptic transmission is considered as an important factor in the development of this disease. Gerstmann-Sträussler-Scheinker syndrome (GSS) and familial fatal insomnia (FFI) are the other diseases belonging to the same disease spectrum. The common feature of these disorders is that the different mutation of the same prion protein could result in different phenotypes and symptoms. CJD is considered as a neurologic disorder but the clinical symptoms and differential diagnosis of the disease are also relevant problems in psychiatry. Because of the early onset of dementia and the psychotic and delusive symptoms, the patients with CJD are frequently admitted to psychiatric wards. Recently worldwide public interest has been focused on prion dementias because of the possible human transmission of bovine spongiform encephalopathy in the UK. The diagnostic problems of our seven CJD patients diagnosed since 1991 in the catchment area of Szeged city are discussed in the view of recent findings of molecular biology, nosology, diagnostic and therapeutic problems of this devastating disease.

Immunomodulating activities on cellular cytotoxicity and the blast transformation of human lymphocytes by 10-[n-(phthalimido)alkyl-2-substituted-10H-phenothiazines and 1-(2-chloroethyl)-3-(2-substituted-10 H-phenothiazin-10-yl)alkyl-1-ureas.

Phenothiazines, 10-[n-(phthalimido)alkyl-2-substituted-10H- phenothiazines, and 1-(2-chloroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alkyl-1- ureas were investigated for their effects on antibody-dependent cellular cytotoxicity (ADCC), natural killer (NK) cells and the blast transformation of human peripheral blood mononuclear cells. All of the compounds dose-dependently suppressed mitogen-stimulated T cell proliferation. In contrast, a strong enhancing effect on NK cell activity was detected mostly in the case of 1-(2-choroethyl)-3-(2-substituted-10H-phenothiazin-10-yl)alk yl-1-ureas and their related compounds. The stimulating effect directly influenced the NK cells and was demonstrated at all tested concentrations.

Immunomodulating effect of acridine tautomers on eukaryotic cells.

The immunomodulating effect of some new amino- and imino-acridine derivatives, were investigated on antibody dependent cellular cytotoxicity (ADCC) and induced-blast transformation of lymphocytes. In different concentrations (2.0 x 10(-6) M, 4.0 x 10(-8) M and 2.0 x 10(-5) M) the drugs produced a suppression of PHA and ConA induced cell proliferative response except in the case of 2b, 2d and 2g amino-acridines. The suppressive effects were dose dependent and exhibited a higher inhibitory level in the case of imino-acridines. Some drugs at low concentration exerted a little enhancing effect on ADCC reaction.

Effect of benzo[a]phenothiazines on natural killer cell activity of human peripheral blood mononuclear cells.

Four benzo[a]phenothiazines were investigated for their effects on antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) cell and blast transformation of human peripheral blood mononuclear cells (PBM). Benzo[a]phenothiazines dose-dependently suppressed the nitrogen-stimulated T cell proliferation. The suppressive effect of non differentiation-inducing benzo[a]phenothiazines was higher than that of differentiation-inducing benzo[a]phenothiazines. The stimulation effect of differentiation-inducing compounds on the NK activity was reduced by removal of monocytes from the PBM. The results suggest the direct activation of monocytes (Mo) by differentiation-inducing benzo[a]phenothiazines.

The effects of cannabinoids and cannabispiro compounds on Escherichia coli adhesion to tissue culture cells and on leukocyte functions in vitro.

delta 9-Tetrahydrocannabinol, cannabidiol, cannabidiolic acid, tetrahydrocannabidiolic acid, cannabispirol, acetylcannabispirol, cannabispirone, and cannabispirenone in a low concentration did not affect the adhesion of Escherichia coli on cultured HEp-2 cells. Cannabinoids at 10(-6) M increased the chemiluminescence of human polymorphonuclear leukocytes, while the cannabispiro compounds failed to enhance the oxidative burst of leukocytes. In lymphocyte and granulocyte function tests (E- and EA-rosette formation, blast transformation of T-lymphocytes in the presence of phytohaemagglutinin and concanavalin-A, ADCC and phagocytosis) all compounds displayed immunosuppressive effect at 1.5 X 10(-5) M. Tetrahydrocannabidiolic acid exerted the weakest immunosuppression on human leukocyte functions.

Further investigation of nonspecific biological substance in anti-Rh(D) preparations.

Fc receptor-blocking activity, based on the EA rosetting inhibition of anti-Rh(D) gamma-globulin preparations, was determined during biological analyses. After sample purification by means of precipitation with a low concentration of ammonium sulphate, fractions were obtained containing anti-D activity and Fc receptor-blocking activity separately. Fc receptor-blocking antibodies inhibited both the formation of EA rosettes and the antibody-dependent cellular cytotoxicity activity. It is suggested that Fc receptor-blocking antibodies obtained during hyperimmunization probably result in the immunosuppressive effect of Rh immune globulin (via the blocking of Fc receptors of activated lymphocytes) that decreases in turn the progress of Rh immunization.

Mapping the uroporphyrinogen III cosynthase locus in Bacillus subtilis.

The gene hemD taking part in the formation of uroporphyrinogen III from porphobilinogen was mapped by two- and three-factor transduction crosses in Bacillus subtilis. This gene codes uroporphyrinogen III cosynthase. The gene hemD is linked to the hemA locus and is located between the hemA and pheA loci.

Mapping the uroporphyrinogen decarboxylase, coproporphyrinogen oxidase and ferrochelatase loci in Bacillus subtilis.

Three genes hemE, hemF, hemG taking part in the porphyrin biosynthesis of Baccillus subtilis were mapped by two- and three-factor transduction crosses. The gene hemE determines uroporphyrinogen decarboxylase (EC 4.1.1.37) the gene hemF coproporphyrinogen oxidase (EC 1.3.3.3) and the gene hemG ferrochelatase (EC 4.99.1.1) enzymes. The loci hemE, hemF, hemG, are not linked to hemA locus and located near the argC and metD loci.

Effects of kryptopyrrole on porphyrin synthesis in Bacillus subtilis 168.

We investigated the effects of exogenous 5-aminolaevulinate and kryptopyrrole, separately and together, on the porphyrin synthesis of Bacillus subtilis 168. It was confirmed that 5-aminolaevulinate increases the porphyrin content of the culture fluid in the way previously described. In comparison with the basic activity of the bacteria, kryptopyrrole enhances the amount of extracellular copro III, uro III and 5-carboxyl porphyrins. The combination of 5-aminolaevulinate and kryptopyrrole enhances the porphyrin synthesis; moreover, a more pronounced increased in porphyrin synthesis occurs if the kryptopyrrole solution used is rich in its oxidation products. In this latter case, the amount of 5,6,7-carboxylic porphyrins increases markedly along with uro III and particularly copro III, while suburoporphyrins also makes their appearance. An hypothesis is advanced to explain tentatively the increase in the porphyrin synthesis provoked by kryptopyrrole.

Genetic and biochemical analysis of haemin dependent mutants of Bacillus subtilis.

Numerous porphyrin auxotrophic mutants have been isolated from the 168 trpC2 strain of Bacillus subtilis by selection with streptomycin. Some of them could be supplemented with ALA while the majority grew only in the presence of haemin. Among the latter strains, the syntropism test allowed to distinguish two groups different in phenotype, viz., feeders accumulating ALA and non-feeders accumulating instead of ALA other porphyrin intermediates. On the basis of transductional studies, feeders and non-feeders could be divided into two and four groups, respectively. Biochemical investigation revealed that, with one exception, one enzyme of the porphyrin biosynthesis was coordinated to each hem locus. The following genes were identified:hemB yields ALA-dehydrase;hemC yields PBG-deaminase; hemE yields uroporphyrinogen decarboxylases; hemF yields coproporphyrinogen oxidase; hemG yields protoporphyrin-iron-chelatase.