[Affective mentalizing in Addictive Borderline Personality: A literature review].

This literature review concerns affective mentalizing in borderline addictive personality. This concept postulates the group between addictions and borderline personalities may correspond to Personality Disorders (PDs). First, we will present conceptualizations and evaluations of affective mentalizing.

Cytochrome P-450-mediated O-demethylation of two ellipticine derivatives. Differential effect of the murine Ah locus phenotype.

The O-demethylation of two antitumor drugs (9-methoxyellipticine and a 1-polyalkylamino-substituted analog) was studied by incubation with liver microsomes from rats and mice. The former drug underwent a cytochrome P1-450-independent biotransformation in mice, as shown by an indiscriminate response from individuals genetically responsive or nonresponsive to induction by 3-methylcholanthrene. On the other hand, the second drug was O-demethylated only by genetically responsive mice after pretreatment by 3-methylcholanthrene.

A dual assay for the specific screening of 3-methylcholanthrene- and phenobarbital-like chemical inducers of cytochrome P-450 monooxygenases.

We present and evaluate a dual assay, the CYPIA (Cytochrome P-450 induction assay) for the detection and the simultaneous identification of chemicals belonging either to the 3-methylcholanthrene or phenobarbital classes of cytochrome P-450 monooxygenase inducers. These inducers play an important role in the mutagenic activation of chemical compounds as well as in many pharmacological and toxicological events and therefore should be screened by drug and chemical designers. After treatment of male rats or mice by chemicals, the liver preparations (S9) have been used in the Salmonella typhimurium test, to activate either ethidium bromide or cyclophosphamide into mutagenic metabolites.

Mutagenicity and cytotoxicity of five antitumor ellipticines in mammalian cells and their structure-activity relationships in Salmonella.

The mutagenicity and cytotoxicity of five antitumor compounds (ellipticines) were investigated in the Chinese hamster ovary cell hypoxanthine-guanine phosphoribosyltransferase assay and in six strains of Salmonella. All five compounds (ellipticine, 9-methoxyellipticine, 9-hydroxyellipticine, 9-aminoellipticine, and 2-methyl-9-hydroxyellipticinium) were cytotoxic and mutagenic in the Chinese hamster ovary cell hypoxanthine-guanine phosphoribosyltransferase assay in the presence or absence of Aroclor 1254-induced rat liver S9, and all except the last compound were mutagenic in Salmonella. Based on the reversion pattern obtained in various frame-shift and DNA repair-proficient (uvrB+) or -deficient (uvrB) strains of Salmonella in the presence or absence of S9, the first three compounds appear to cause frame-shift mutations by both intercalation and covalent bonding with DNA; thus, these are classified as reactive intercalators.

[Metabolism and pharmacokinetics of methoxy-9-ellipticine and its principal metabolite, hydroxy-9-ellipticine].

The biliary and urinary excretion of 9-methoxyellipticine in Rats yield the 0-demethylated metabolite 9-hydroxyellipticine, partly present as the glucuronide. Whole blood kinetics of 9-methoxyellipticine in Rabbits following a single i.v.

Metabolism of ethidium bromide in rats.

The biliary excretion products recovered after iv administration of ethidium bromide to rats were found to consist of: unchanged drug, 8-acetylethidium, and an 8-acetylated hydroxylated metabolite. Proofs of structure were obtained by field desorption mass spectroscopy and 1H NMR, which indicated that the latter metabolite is probably substituted at position 2-. The yield of these various metabolites was critically influenced by pretreatment of the animals with inducers of the hepatic mixed function oxidases.

Ellipticines as potent inhibitors of microsomes-dependent chemical mutagenesis.

9-Hydroxyellipticine (9-OHE), an inhibitor of microsomal monooxygenase activities has been shown to exert a large or even complete decrease of the mutagenicity, on the Salmonella strains of a great number of compounds (aromatic amines, polycyclic aromatic hydrocarbons, fungal toxins, azo compounds, tobacco smoke condensate). 9-OHE and 9-fluoroellipticine are more potent inhibitors than ellipticine itself. The inhibitions exerted by 9-OHE are not even equalled by 10-fold higher doses of 7,8-benzoflavone (7,8-BF).

Comparative cytotoxic and antitumoral effects of ellipticine derivatives on mouse L 1210 leukemia.

Twelve derivatives of the antitumoral alkaloid ellipticine (E) and ellipticinium were assayed in vitro on cultured L 1210 cells. These drugs possess varying abilities to decrease the cell growth rate in a 1--1000-fold range. Some of them have a highly cytotoxic effect in the 10(-8)--10(-6) M range.

A class of strong inhibitors of microsomal monooxygenases: the ellipticines.

Ellipticine (E) and its 9-hydroxy derivative inhibit strongly various liver monooxygenase activities mediated by microsomes from control and phenobarbital (PB), benzo[alpha]pyrene (BP) or Aroclor 1254 (Aroclor)-pretreated rats. The inhibition constants, Ki, are remarkably low, and often smaller than 1 micron, particularly in the case of microsomes containing cytochrome P-448. The inhibitory potency (I50) of 9-hydroxyellipticine (9-OHE) is larger (about ten-fold) than the one of classical inhibitors (metyrapone or 7,8-benzoflavone (7,8-BF)), whatever the activities studied and the induction of microsomes.

Some antitumor derivatives of ellipticine deprived of mutagenic properties.

Seven derivatives of the antitumor alkaloid ellipticine were assayed for activity against murine leukaemia L1210 and for mutagenicity in Ames' Salmonella-microsomes test. Not only did the results show a complete lack of correlation between these two properties, but it was possible to choose a highly efficient analog which was completely devoid of mutagenic and hence, probably, carcinogenic effect. The lack of interaction of this product (2-methyl-9-hydroxyellipticinium acetate) with Cytochrome P-450 of hepatic monooxygenases prevents the formation of reactive intermediates and their subsequent binding to DNA.

Synthesis of a 125I-labelled derivative of the antibiotic griseofulvin.

A derivative of griseofulvin has been synthesised, in which the 2'-O-methyl group is replaced by a 2'-(2-iodoethoxy), 125I-labelled group. This derivative is at least as potent as griseofulvin itself, when assayed for inhibition of growth on the Myxomycete Physarum polycephalum.

Relative efficiencies of a series of square-planar plantinum(II) compounds on Salmonella mutagenesis.

Twelve Pt(II) compounds have been tested for mutagenicity on Salmonella typhimurium (strain TA 100). Very high mutagenic activities were found for the cis derivatives. A correlation is suggested between these results and a formerly described model of chemical reactivity towards DNA, according to which cis derivatives from intra-strand chelates with guanine.

[Induction of rat hepatic mono-oxygenases by ellipticine: formation of cytochrome p448. Hydroxylating activity].

Ellipticine is able to induce cytochrome P448 synthesis in Rat liver microsomes which converts the drug into 9-hydroxy derivative, with a higher rate than microsomal cytochrome P450 of non-treated or phenobarbital induced Rats. In vivo, ellipticine is also transformed into a second hydroxylated product on the indole aromatic ring.