Central nervous system drugs: Low temperature X-ray structures of (I) the base 5-(2,3-dichlorophenyl)-2,4-diamino-6-fluoromethyl-pyrimidine (4030W92) and (II) 5-(2,6-dichlorophenyl)-1-H-2,4-diamino-6-methyl-pyrimidine methanesulphonic acid salt (227C89)

The X-ray crystal structures of (I), the base 4030W92, 5-(2,3-dichlorophenyl)-2,4-diamino-6-fluoromethyl-pyrimidine, C11H9Cl2FN4, and (II) 227C89, the methanesulphonic acid salt of 5-(2,6-dichlorophenyl)-1-H-2,4-diamino-6-methyl-pyrimidine, C11H11Cl2N4 center dot CH3O3S, have been carried out at low temperature. A detailed comparison of the two structures is given. Structure (I) is non-centrosymmetric, crystallizing in space group P2(1) with unit cell a = 10.821(3), b = 8.290(3), c = 13.819(4) angstrom, beta = 105.980(6)degrees, V = 1191.8(6) angstrom(3), Z = 4 (two molecules per asymmetric unit) and density (calculated) = 1.600 mg/m(3). Structure (II) crystallizes in the triclinic space group P (1) over bar with unit cell a = 7.686(2), b = 8.233(2), c = 12.234(2) angstrom, alpha = 78.379(4), beta = 87.195(4), gamma = 86.811(4)degrees, V = 756.6(2) angstrom(3), Z = 2, density (calculated) = 1.603 mg/m(3). Final R indices [I > 2sigma(I)] are R1 = 0.0572, wR2 = 0.1003 for (I) and R1 = 0.0558, wR2 = 0.0982 for (II). R indices (all data) are R1 = 0.0983, wR2 = 0.1116 for (I) and R1 = 0.1009, wR2 = 0.1117 for (II). 5- Phenyl-2,4 diaminopyrimidine and 6-phenyl-1,2,4 triazine derivatives, which include lamotrigine (3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine), have been investigated for some time for their effects on the central nervous system. The three dimensional structures reported here form part of a newly developed data base for the detailed investigation of members of this structural series and their biological activities.

Effects of exercise intensity on salivary antimicrobial proteins and markers of stress in active men

In the present study, we assessed the effects of exercise intensity on salivary immunoglobulin A (s-IgA) and salivary lysozyme (s-Lys) and examined how these responses were associated with salivary markers of adrenal activation. Using a randomized design, 10 healthy active men participated in three experimental cycling trials: 50% maximal oxygen uptake (VO2max), 75%VO2max, and an incremental test to exhaustion. The durations of the trials were the same as for a preliminary incremental test to exhaustion (22.3 min, sx = 0.8). Timed, unstimulated saliva samples were collected before exercise, immediately after exercise, and 1 h after exercise. In the incremental exhaustion trial, the secretion rates of both s-IgA and s-Lys were increased. An increase in s-Lys secretion rate was also observed at 75%VO2max. No significant changes in saliva flow rate were observed in any trial. Cycling at 75%VOmax and to exhaustion increased the secretion of alpha-amylase and chromogranin A immediately after exercise; higher cortisol values at 75%VO2max and in the incremental exhaustion trial compared with 50%VO2max were observed 1 h immediately after exercise only. These findings suggest that short-duration, high-intensity exercise increases the secretion rate of s-IgA and s-Lys despite no change in the saliva flow rate. These effects appear to be associated with changes in sympathetic activity and not the hypothalamic - pituitary - adrenal axis.

Sediment transfer and accumulation in two contrasting salt marsh/mudflat systems: the Seine estuary (France) and the Medway estuary (UK)

Understanding the dynamics of fine sediment transport across the upper intertidal zone is critical in managing the erosion and accretion of intertidal areas, and in managed realignment/estuarine habitat recreation strategies. This paper examines the transfer of sediments between salt marsh and mudflat environments in two contrasting macrotidal estuaries: the Seine (France) and the Medway (UK), using data collected during two joint field seasons undertaken by the Anglo-French RIMEW project (Rives-Manche Estuary Watch). High-resolution ADCP, Altimeter, OBS and ASM measurements from mudflat and marsh surface environments have been combined with sediment trap data to examine short-term sediment transport processes under spring tide and storm flow conditions. In addition, the longer-term accumulation of sediment in each salt marsh system has been examined via radiometric dating of sediment cores. In the Seine, rapid sediment accumulation and expansion of salt marsh areas, and subsequent loss of open intertidal mudflats, is a major problem, and the data collected here indicate a distinct net landward flux of sediments into the marsh interior. Suspended sediment fluxes are much higher than in the Medway estuary (averaging 0.09 g/m(3)/s), and vertical accumulation rates at the salt marsh/mudflat boundary exceed 3 cm/y. Suspended sediment data collected during storm surge conditions indicate that significant in-wash of fine sediments into the marsh interior can occur during (and following) these high-magnitude events. In contrast to the Seine, the Medway is undergoing erosion and general loss of salt marsh areas. Suspended sediment fluxes are of the order of 0.03 g/m(3)/s, and the marsh system here has much lower rates of vertical accretion (sediment accumulation rates are ca. 4 mm/y). Current velocity data for the Medway site indicate higher velocities on the ebb tide than occur on the flood tide, which may be sufficient to remobilise sediments deposited on the previous tide and so force net removal of material from the marsh.

X-ray crystallographic structures of neuroprotective pyrimidine derivatives: (I) the mesylate salt of BW1003C87 and (II) sipatrigine base

Drugs based on 5-phenyl-2,4 diamino pyrimidine and 6-phenyl-1,2,4 triazine derivatives are well known for their effects on the central nervous system. The study presented here provides detailed crystal structures of two pyrimidine derivatives which have neuroprotective properties in models of both grey and white matter ischemia. Recently published studies suggest that the compounds lamotrigine (a triazine derivative), and the two pyrimidines BW1003C87 (I) and sipatrigine (II) mediate their primary in vivo mode of action by inhibiting voltage-gated Na+ channels. The X-ray crystal structures will contribute valuable data for applications involving binding and modelling studies of the biological actions of these drugs.