DNA binding, solubility, and partitioning characteristics of extended lexitropsins.

Four new ligands that bind to the minor groove of DNA have been designed, synthesized, and evaluated by DNA footprinting. Two of the ligands are polyamides containing central regions with five or six N-methylpyrrole units, conferring hydrophobicity and good binding affinity but without retaining the correct spacing for hydrogen bonding in the base of the minor groove. The two remaining ligands have central regions which are head-to-head-linked polyamides, in which the linker is designed to improve the phasing of hydrogen bonding of the ligand with the floor of the minor groove. The highest affinity was obtained with the two polypyrroles without headgroup spacers, indicating that H-bond phasing is secondary in determining affinity compared to the major hydrophobic driving force. With a dimethylaminoalkyl group, representing a moiety with modest base strength, at both ends, water solubility is good and pH-partition theory predicts that penetration through lipid membranes will be enhanced, compared to strongly basic amidine analogues of the alkaloid precursors. All four compounds bind to DNA, with strong selectivity for AT sequences but some tolerance of GC base pairs and subtle individual preferences. The data show that very high affinities can be anticipated for future compounds in this series, but drug design must take account of overall physicochemical properties as well as the details of hydrogen bonding between ligands and the floor of the minor groove.

Writing the changes for nurses.

Prescribing powers for family planning nurses has been a heated and topical issue for decades and progress has been impossibly slow. Jane Urwin wonders if this extended role for nurses will ever materialise.

Current issues in contraception.

This article discusses the currently available methods of contraception and their advantages and disadvantages. It relates to UKCC Professional Development categories Care enhancement and Reducing risk.

Contraception. Choice advice.

PIP: The nurses' main purpose when discussing family planning with clients is to provide them with complete information about all available contraceptive methods so clients can choose the method best suited to them. Nurses should not use age or social factors to assume the client's contraceptive needs. They should not allow their perception of client's contraceptive needs to influence the information they provide to clients. Nurses need to consider the client's and family's medical history to identify and discuss contraindications. Contraindications for oral contraceptives (OCs) include deep vein thrombosis, smoking, past clotting problems, and an immediate family history of cardiovascular disease at a young age. IUD contraindications are past pelvic inflammatory disease or ectopic pregnancy. Nurses must monitor any changes in the health of their contraceptive clients and record their health status. They may need to advise a client to change their contraceptive method. Women considering OCs have 30 brands from which to choose. They may need to try several formulations to identify one that is best for them. There are also a variety of types and sizes of barrier methods. Nurses must be familiar with the primary and secondary mode of actions of each contraceptive method since women often choose a method based on how it works. In addition to effectiveness, women also consider perceived risk and religious and cultural values. Nurses should be able to discuss the client's needs and expectations openly and honestly. They must maintain confidentiality. Life events (e.g., childbirth and change in financial status) effect changes in contraceptive needs. During follow-up visits, nurses need to determine whether the chosen method is still the best option and to encourage the client to ask questions. The UK's Family Planning Association publishes leaflets and operates a helpline to provide family planning information to the public.^ieng

Particle size stability of intralipid and mixed total parenteral nutrition mixtures.

The determination of the particle size of Intralipid fat emulsions by the non-perturbing method of photon correlation spectroscopy has been extended to include particle size determination using the Coulter counter and optical microscopy. Although little increase in particle size in 3-litre bags containing total parenteral nutrition mixtures was observed with the methods involving large dilutions, creaming was observed and optical microscopy showed aggregation and some coalescence to have taken place. The problem of re-dispersion upon dilution of aggregated (but not coalesced) fat emulsions makes direct optical observation essential in assessing the stability and safety of such fat emulsion mixtures. The effect of electrolytes (NaCl and CaCl2) on creaming, particle size and electrophoretic mobility showed both minimum stability and minimum zeta potential at 3 X 10(-3) mol dm-3 CaCl2 and at 2.5 X 10(-1) mol dm-3 NaCl. Thus, these maximum levels for electrolytes in total parenteral mixtures are indicated.

Atracurium: conception and inception.

The rationale underlying the design of atracurium, a bis-quaternary ammonium neuromuscular blocking agent which incorporates the Hofmann elimination as a novel biodegradation pathway, is described. Destruction in vivo, of the bis-quaternary structure essential for neuromuscular blocking activity, by the combination of Hofmann elimination and a parallel ester hydrolysis leads to innocuous breakdown products that are without neuromuscular or cardiovascular effects and to a time-course of action which is unaffected by the level of plasma esterase activity, renal or hepatic function.