New technique for managing second trimester intrauterine fetal death.

In this study, a new method for terminating second trimester pregnancies complicated by intrauterine fetal death is analysed. The technique consisted of a combination of extraamniotic ethacridine lactate with intramuscular sulprostone (16-phenoxy-omega-17,18,19,20 tetranor PGE2 methyl sulfonylamide). Objective documentation of the efficacy of this method was obtained by continuous monitoring of intrauterine pressure in two patients. The method was found to be simple, safe, cheap and effective and deserves increased acceptance.

Second trimester abortion with ethacridine lactate plus carboprost--which is the best time to administer the carboprost?

Extra-amniotic ethacridine lactate plus intramuscular prostaglandin has become a popular method for terminating second trimester pregnancies. In this study, intrauterine pressure was continuously monitored in order to objectively compare the efficacy of 3 different times of administration of Carboprost (15-methyl PGF2 alpha) - at 2 hours, 4 hours and 8 hours after the instillation of ethacridine lactate. The best results were obtained with the administration of Carboprost 8 hours after the instillation of the extra-amniotic ethacridine lactate. The synergistic effect of ethacridine lactate and Carboprost is optimal after this time. This is probably because the ethacridine lactate will have produced sufficient cervical ripening to ensure optimal efficacy of the prostaglandin-induced uterine contractions in expelling the products of conception.

Use of Ames test in evaluation of shale oil fractions.

Conditions that affect the sensitivity of the Ames assay of complex hydrocarbon mixtures derived from shale oil were studied. Two fractions, one enriched in polynuclear aromatic compounds (PNA fraction), and a second fraction enriched in aromatic and heterocyclic amines (basic fraction), were selected for most of this work because of their comparatively high mutagenicity (i.e., compared with raw shale oil). The crude shale oil, as well as the basic, PNA, and tar fractions were mutagenic against the Salmonella typhimurium test strains, TA98 and TA100. Mutation was dependent on metabolic activation by microsomal (S9) enzymes. Both test strains responded equally well to the crude product and to the basic fraction; however, strain TA100 was more effective than TA198 in demonstrating the mutagenicity of the PNA fraction. The mutagenicity of the tar fraction could be most easily detected after metabolic activation in a liquid medium, as opposed to S9 activation in the top agar of the standard Ames assay. The mutagenicity of the basic fraction or 2-aminoanthracene was also demonstrated by metabolic activation in a liquid medium. In other set of experiments, the effect of chemical composition on the expression of mutagenicity in the standard Ames assay was estimated. Premutagens requiring metabolic activation were added to the basic and PNA fractions, and the numbers of revertants obtained in the presence of the fractions were compared with mutation induced by the compounds alone. The basic fraction did not interfere with the mutagenicity of 2-aminoanthracene and 7,9 dimethylbenz[c]acridine. Moreover, in certain experiments, the mutagenicity of the complex fraction plus the added compound was higher than expected on the basis of assays performed on these materials separately. Conversely, the PNA fraction prevented or strongly inhibited mutation by several polynuclear aroumatic compounds, and an acridine. However, the PNA fraction did not inhibit mutation induced by 2-aminoanthracene. The effect of the basic fraction on stability of the S9 enzymes in the standard Ames test was also determined.

Dimethyl-10,12-benz(a)acridine; evidence for differential effects on the synthesis of RNA of mammalian or avian fibroblasts and some RNA viruses.

We have studied the differential effect of dimethyl-10,12-benz(a)acridine (DBMAcr) on the synthesis of RNA of chicken or mouse fibroblasts in culture and that of some RNA-containing viruses such as Rous sarcoma virus and Mengovirus. DMBAcr at low concentrations blocks the cell multiplication of both normal and Rous sarcoma virus-transformed chicken fibroblasts in culture; it affects transformed cells more than normal ones. The cell growth inhibiting effect of DMBAcr is reversible after short periods of incubation. DMBAcr depresses the synthesis of cellular DNA and RNA in parallel. Concurrently the synthesis of protein proceedes at a relatively high rate in DMBAcr-treated cultures. Its inhibitory effect on cellular RNA synthesis is mostly due to a block in the formation of 28 S and 18 S ribosomal RNA species; in contrast, the synthesis of 45 S ribosomal RNA precursor is proceeding at almost control rate. Also, the synthesis of heterogeneous nuclear RNA is not blocked by DMBAcr. The production of Rous sarcoma virus in transformed fibroblasts is not affected by DMBAcr. Since this is correlated with persisting high rates of protein and heterogenous nuclear RNA synthesis, the effects of DMBAcr suggest that the synthesis of Rous sarcoma virus-RNA shares the specificity of messenger and heterogeneous nuclear RNA. DMBAcr inhibits the synthesis of viral RNA of Mengovirus under conditions where the synthesis of total cellular RNA is not appreciably depressed, suggesting its differential effect on the DNA-directed and the RNA-directed RNA synthesis.

Fractionation of of proteolytic enzymes by affinity chromatography on sepharose aminocaproyl proflavin.

The serine proteinases trypsin, chymotrypsin, elastase, and acrosin bind to the proflavin resin, the sulfhydryl proteinases ficin, bromelain, and papain are retarded by the resin, whereas most proteins and enzymes tested are not bound. Elution of the bound activities is accomplished NaCl or by variation from the pH optimum of the enzyme. Commercially available enzymes that are bound or retarded are easily further purified by the column. The acrosin activity of sperm acrosomal extracts is separated into bound and unbound activities. Acrosin is purified 120-fold from sperm acrosomal extracts in a single step, yielding a specific activity of 96.

Interactions of heteroaromatic compounds with nucleic acids. 1. The influence of heteroatoms and polarizability on the base specificity of intercalating ligands.

We have examined the origins of base specificity in intercalating ligands by studying the interaction with DNA of a series of proflavine and acridine orange analogs differing in the heteroatoms present in the chromophore. Base specificity was determined by differential dialysis of the dye against DNA samples of differing G-C content. We find that G-C specificity increases as the visible absorbance band of the chromophore moves to longer wavelength, implying a relation between specificity and polarizability of the chromophore. This can be rationalized by recognizing that the G-C pair is more polar than A-T, and should therefore interact more favorably with an easily polarized ring system. We find in addition that dimethylation of the chromophore amino groups increases specificity which we discuss in terms of steric and coupled steric-electronic contributions. Our results also bear on the origin of G-C specificity in binding actinomycin to DNA. Some of the compounds studied are as G-C specific as actinomycin, yet they lack hydrogen-bonding functions as plausible determinants of specificity. This observation gives new life to the hypothesis that the specificity of actinomycin is determined primarily by preferential interaction of the chromophore with a G-C pair.

[Uptake of methyl-12-benzo (a) and methyl-7-benzo (c) acridines by target organs of the female rat studied by fluorescence microscopy (author's transl)]. / Etude en microscopie de fluorescence de la fixation des méthyl-12-benzo (a) et méthyl-7-benzo (c) acridines sur les organes cibles du rat femelle

The diffusion and uptake of two benzacridines with very similar chemical structures, but with different carcinogenic powers were investigated at the level of various organs and at the cellular level in the female rat. The chronology of the processes and lesions observed was different according to the respective carcinogenic power of the two benzacridines. On account of the small doses used, only necrotic lesions were observed, mainly in the liver and adrenal glands, but no tumorous lesions were observed. Uptake of fluorescent substance at the level of the nuclei of certain cells (submaxillaris, liver, pancreas, adrenal glands) was noticed as in previous experiments; this transient process appeared about the 100th day and lasted fairly long according to the form of benzacridine and the organ.