SUMMARY Because severe constipation is a disorder largely confined to young women, the possibility that menstrually related factors contribute to disturbed gastrointestinal motor function has been raised. It has also been reported that normal menstruating women show changes in upper gut transit between the follicular and luteal phases of the menstrual cycle and that patients with constipation show prolonged transit. We therefore studied relationships between symptom severity and orocaecal transit during the menstrual cycle in a group of 14 constipated women and a series of control groups comprising seven normal menstruating women, five postmenopausal women, and eight normal men, to determine whether phases of the menstrual cycle were associated with alteration in symptoms or transit. A regular menstrual cycle was reported by 13 of the 14 patients (range 26-30 days) and by all the menstruating female volunteers. Seven patients noted variation in constipation during the menstrual cycle, in all cases this comprised an improvement in symptoms just before or during menstruation. No consistent relationship between symptom severity and follicular or luteal phase was noted. Repeated orocaecal transit measurements in the four study groups showed no consistent differences (>0 05) between groups or during the menstrual cycle (mean change weeks 1-4, -10±20 min). These findings are inconsistent with the hypothesis of a progesterone related effect upon orocaecal transit in either normal or constipated women.Severe constipation is a major clinical problem; it is distinguishable from the minor degrees of defecatory disability which are part of Western culture, by its severity, its chronicity and by its strong female preponderance.' 2 Because it is largely a disorder of women, the possibility that sex hormones are contributory is often raised. This view has been strengthened by the observations that many patients report menstrual cycle disorders,3 that progesterone can inhibit intestinal smooth muscle in vitro,4 and that constipation often occurs during normal pregnancy when circulating progesterone concentrations show a marked increase.56In addition, a recent survey of defecatory patterns in a normal population has suggested that women may pass harder stools in the luteal phase and have more prolonged gut transit.7 Further suggestive evidence is provided by an apparent relationship between upper gut transit as measured by the exhaled breath hydrogen sampling technique and menstrual

The 1,2-addition of formaldehyde N,N-dialkylhydrazones to simple aldehydes takes place in the presence of ZnCl 2 or Et 2 AlCl to afford the corresponding a-hydroxyhydrazones. More reactive aldehydes undergo addition of these reagents in the absence of promoters. Use of (S)-1-methyleneamino-2-(diphenylmethoxymethyl) pyrrolidine as the reagent afforded separable mixtures of diastereoisomers, thereby allowing for the isolation of optically pure adducts in a single step.

The crystal structures of a biologically and therapeutically active recombinant homotrimeric fragment of human lung surfactant protein D with a series of bound ligands have been determined. While the structures reveal various different binding modes, all utilise a similarly positioned pair of mannose-type O3′ and O4′ hydroxyls with no direct interaction between any non-terminal sugar and protein. The orientation, position, and interactions of the bound terminal sugar depend on the sugar itself, the presence and form of glycosidic linkage, and the environment in the crystal, which, via Asp325, places stereochemical and electronic constraints, different for the three different subunits in the homotrimer, on the ligand-binding site. As a direct consequence of this influence, the other binding-pocket flanking residue, Arg343, exhibits variable conformation and variable interactions with bound ligand and leaves open to question which orientation of terminal mannobiose, and of other terminal disaccharides, may be present in extended physiological ligands. The combined structural evidence shows that there is significant flexibility in recognition; that Asp325, in addition to Arg343, is an important determinant of ligand selectivity, recognition, and binding; and that differences in crystal contact interfaces exert, through Asp325, significant influence on preferred binding modes.

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