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Vasospams is a major cause of morbidity and mortality after cerebral aneurysm rupture. This article outlines the results of transcranial Doppler and cerebral angiography and discusses the pathophysiology of delayed cerebral infarct. According to our data, cerebral infarct is mainly the result of stenoses of large proximal arteries, which supports the use of balloon angioplasty in symptomatic vasospasm.

Ellipticines are aromatic compounds that intercalate between DNA base pairs and display significant antitumor activity. The cytotoxicity of these compounds is mediated by DNA topoisomerase II, and the presence of a hydroxy group at position 9 of the pyridocarbazole ring system of ellipticines has been found to be essential for high levels of cytotoxicity. The ability of 13 ellipticine derivatives to stabilize the topoisomerase II-DNA covalent complex in vitro was studied, and the data obtained with five pairs of hydroxylated and nonhydroxylated analogues indicate that the hydroxy group at position 9 plays a crucial role in the stabilization of the complex. The influence, upon the complex stabilization, of various substituents at positions 1, 2, 5, and 6 of the pyridocarbazole ring system was investigated. The interaction with DNA of four ellipticine derivatives was studied in the topoisomerase II standard medium. Results suggest that the degree of unwinding might be a determinant of topoisomerase II-DNA-drug complex stability. In addition, the 5-ethyl derivative was observed to induce covalent complex stabilization by a cooperative mechanism.

The transformation of the antitumor drug N2-methyl-9-hydroxy-ellipticinium by a peroxidase-hydrogen peroxide system, which has been shown to occur in vivo, leads to an electrophilic quinone-imine derivative. This unstable molecule arylates in vitro purine nucleosides and nucleotides, leading to regioselective adducts substituted only at the 2'-O position of the ribose, as shown by mass spectrometry and NMR. It is likely that an important preliminary step in this reaction is a stacking process between the ellipticinium ion and the purine rings, which might explain this regioselectivity.

We have studied the kinetics of breakage of apurinic (AP) sites by the intercalating agent 9-aminoellipticine using fluorimetric methods with single (ss)- and double (ds)-stranded apurinic DNA. In order to understand the chemical process, high performance liquid chromatography was used to follow the reaction kinetics with the apurinic oligonucleotide model T(AP)T. The unstable intermediate, which is responsible for the β-elimination step, is a Schiff base resulting from the interaction of the amino group of the aromatic amine with the aldehyde function of the deoxyribose moiety (AP site). Fluorescence occurs simultaneously with the breakage of both ss and ds DNA and of the oligonucleotide and arises from the formation of a conjugated double bond on the Schiff base through the β-elimination reaction. In optimal conditions, the second order rate constant for the fluorescence build up is 15 × 103min−1M−1for ds DNA and 0.105 × 103min−1M−1for T(AP)T. The ability of 9-aminoellipticine to induce fluorescence and breakage of ss DNA and T(AP)T shows that intercalation is not essential for this reaction to occur. Nevertheless, the greater rate constant with DNA suggests that stacking is an important parameter for the reaction of the aromatic amine with the AP site.

The basal level of recA protein in Escherichia coli K-12 was estimated by an immunoradiometric assay; it is approximately equal to 1,200 molecules per wild-type bacteria in midexponential phase of growth, slightly more in an excision-deficient (uvrA) strain, and markedly more in recF mutants. Kinetics of induction after UV irradiation showed a rapid increase of recA protein content, which reached a peak level after 60-90 min (20- to 55-fold amplification) and then decreased by dilution of the protein in the growing population. In order to obtain an identical extent of induction of recA protein, a 10-fold higher UV dose was necessary in a wild-type strain compared to the uvrA mutant strain. In the uvrA strain, the presence of one or only very few pyrimidine dimers on DNA was accompanied by a measurable increase of the constitutive level of recA protein; however, the unexcised dimers were unable to permanently induce the formation of recA protein. The derepressed promoter of recA gene is one of the strongest in E. coli. Its sequence displays many similarities with that of the strongest early promoters of T5 phage. Mutants (umuC uvrB and recF uvrB) unable to carry out W-reactivation produced high levels of recA protein after UV irradiation. The data suggested that the recF and umuC genes negatively control the regulation of recA protein level.

recA protein was purified to homogeneity from Salmonella typhimurium TA98 strain after induction of the cells by nalidixic acid. The purification was monitored with a radioimmune assay and involved a specific elution of the protein by ATP from a single-stranded DNA-cellulose column. From 240 liters of cell culture we obtained 40 mg of recA protein which was more than 98% pure. This protein exhibited the same molecular weight as measured on sodium dodecyl sulfate-polyacrylamide gel and the same isoelectric point as the Escherichia coli recA protein purified by a similar procedure. In addition, the S. typhimurium recA protein is endowed with a single-stranded DNA-dependent ATPase activity and cleaves the phage lambda repressor in vitro at the same rate as E. coli recA protein and with the same qualitative requirements. However, peptide mapping with the Staphylococcus aureus V8 protease and cross-reaction with heterologous antibodies show that these two proteins are slightly different.

The creep response of a Ti-6Al-4V alloy produced by additive manufacturing was investigated at 500, 600, and 650 °C using constant load experiments. A collection of recent data from the literature on Ti-6Al-4V produced by conventional technologies and heat treated to produce different microstructures was analysed to determine the effect of the microstructure on the creep behaviour of this material. A unique constitutive equation derived from a model developed for face-centred cubic (fcc) metals was successfully used to describe the creep response, irrespective of the different microstructures. The same constitutive model was able to provide an excellent description of the minimum creep rate dependence on the applied stress for the alloy produced by additive manufacturing, notwithstanding the obvious differences in the microstructures. These observations led to the reconsideration of some consolidated opinions on the behaviour of Ti-6Al-4V, shedding light on the substantial similarities in the creep responses when the microstructure has different morphologies. The initial microstructural features, which have traditionally been thought to greatly influence the creep response, indeed played an important role because they determined the magnitude of the ultimate tensile strength, but this effect gradually disappeared at high temperatures and low stresses.