Scanning force microscopy studies of X-ray-induced double-strand breaks in plasmid DNA.

We present an analysis of X-ray-induced damage in PhiX174 plasmid DNA, applying doses between D = 250 and 1,500 Gy. To analyse this damage in detail, the distribution of plasmid fragments after irradiation have been determined by scanning force microscopy. The results show that even for the lowest dose of D = 250 Gy, a significant amount of double-strand breaks are observed. For increasing dose, the percentage of small fragments increases and is accompanied by a shortening of the average fragment length from < L > = 1,400 nm for a dose of D = 250 Gy to < L > = 1,080 nm after irradiation with D = 1,500 Gy. The most crucial parameter, the average number of double-strand breaks per broken plasmid ( ) has been determined for the first time for the applied doses. The results show that the average number of DSBs per broken plasmid increases almost linearly from a value of = 1.3 after irradiation with D = 250 Gy to = 1.7 after exposure to D = 1,500 Gy. The presented results show that the amount of DSBs induced by X-ray radiation in plasmid DNA can be calculated with high accuracy by means of scanning force microscopy, providing relevant information regarding the interaction of X-rays with DNA molecules.

Hypersensitivity reactions to neuromuscular blocking agents.

Neuromuscular blocking agents are the leading drugs responsible for immediate hypersensitivity reactions during anaesthesia. Most hypersensitivity reactions represent IgE-mediated allergic reactions. Their incidence is estimated to be between 1 in 3,000 to 1 in 110,000 general anaesthetics. However striking variations have been reported among countries. The mechanism of sensitisation seems to implicate the presence of a substituted ammonium ion in the molecule. Due to lack of exposure prior to the reaction in a large number of reactors, it has been hypothesised that sensitisation may involve other, as yet undefined, substituted (quaternary and tertiary) ammonium ion containing compounds such as pholcodine, present in the environment of the patient. This hypothesis is still under investigation. The mechanism of non-IgE mediated hypersensitivity reactions is less well known. Identified mechanisms correspond to direct histamine release or interactions with muscarinic and nicotinic receptors. Allergic reactions cannot be clinically distinguished from non-IgE-mediated reactions. Therefore, any suspected hypersensitivity reaction must be investigated using combined pre and postoperative testing. Because of the frequent but not systematic cross-reactivity observed with muscle relaxants, every available neuromuscular blocking agent should be tested, using intradermal tests to confirm the responsibility of the suspected drug which should be definitely excluded. Cross-sensitivity investigation will also try to identify the safety of drugs that can be potentially used in future anaesthesia. The determination of basophil activation investigations using direct leukocyte histamine release test or flow cytometry would be of particular interest to investigate cross sensitisation in complement to skin tests. There is no demonstrated evidence supporting systematic pre-operative screening in the general population at this time. However, since no specific treatment has been shown to reliably prevent anaphylaxis, allergy assessment must be performed in all high-risk patients. In view of the relative complexity of allergy investigation, and of the differences between countries, an active policy to identify patients at risk and to provide any necessary support from expert advice to anaesthetists and allergologists through the constitution of allergo-anaesthesia centres in every country should be promoted.

Synthesis and Crystal Structure of Diaqua(1,10-Phenanthroline-N,N')(Thiosulfato-O,S)Manganese(II). Biological Properties.

The synthesis of diaqua(1,10-phenanthroline-N,N')(thiosulfato-O,S)manganese(ll) [Mn(phen)(S(2)O(3))(H(2)O)(2)] was investigated. Its structure was determined by single crystal X-ray diffraction from 2418 reflections (I > 3 sigma(I)) to a final value of R = 0.047 and Rw = 0.054. Crystal data are as follows : space group P(2) (1); a = 10.356(3), b = 7.097(3), c = 20.316(2) A, beta = 94.29(2) degrees , V = 1489.1(8) , A(3), Z = 2. There are two independent title compounds in the asymetric unit. Each manganese atom has a distorted octahedral Mn(SO)N(2)O(2) geometry with the S and O atoms (from two neighbouring thiosulfate ligands) mutually trans, two N atoms from the 1,10-phenanthroline ligand and two water oxygen. The thiosulfate group behaves as a bridging ligand, connecting, through sulfur and oxygen, Mn atoms related by the binary b translation, thus forming infinite chains running parallel to this axis. Infrared and electronic spectra are reported.