Structure–activity relationship studies on 1-heteroaryl-3-phenoxypropan-2-ones acting as inhibitors of cytosolic phospholipase A2α and fatty acid amide hydrolase: replacement of the activated ketone group by other serine traps

Cytosolic phospholipase A₂α (cPLA₂α) and fatty acid amide hydrolase (FAAH) are serine hydrolases. cPLA₂α is involved in the generation of pro-inflammatory lipid mediators, FAAH terminates the anti-inflammatory effects of endocannabinoids. Therefore, inhibitors of these enzymes may represent new drug candidates for the treatment of inflammation. We have reported that certain 1-heteroarylpropan-2-ones are potent inhibitors of cPLA₂α and FAAH. The serine reactive ketone group of these compounds, which is crucial for enzyme inhibition, is readily metabolized resulting in inactive alcohol derivatives. In order to obtain metabolically more stable inhibitors, we replaced this moiety by α-ketoheterocyle, cyanamide and nitrile serine traps. Investigations on activity and metabolic stability of these substances revealed that in all cases an increased metabolic stability was accompanied by a loss of inhibitory potency against cPLA₂α and FAAH, respectively.     

Population genetic structure and the effect of founder events on the genetic variability of introduced sika deer, Cervus nippon, in Germany and Austria

The relationships among 214 wild-living sika deer from five locations in Germany and two in Lower Austria were examined using mitochondrial DNA (mtDNA) control region sequence. A total of 18 haplotypes are grouped consistently into two major divergent clades, A and B, which differ by a mean of 8.4% sequence divergence. Recently introduced sika deer showed a complex pattern of population structuring, which probably results from historical vicariance in at least two unknown source populations from southeastern Asia (as previously described by morphological and mtDNA findings), and subsequent population admixture as a result of human-mediated restocking. A strong genetic differentiation among populations was indicated by a global _ST value of 0.78 reflecting mainly the differential distribution of clades A and B haplotypes. There was no association between related haplotypes and their distribution among local populations. These indicate that genealogy is a better predictor of the genetic affinity among most sika deer populations than their present-day locations. The abundant mitochondrial divergence we observed, may reflect a subspecies differentiation and could be associated with phenotypic differences among the introduced sika deer.An erratum to this article can be found at     

Absence of antibodies to foot-and-mouth disease virus in free-ranging roe deer from selected areas of Germany (2001-2002)

Blood samples (n = 223) of free-ranging roe deer (Capreolus capreolus) were collected from selected hunting grounds in Germany between October 2001 and October 2002. Samples originated from Lower Saxony (n = 43) and North-Rhine Westphalia (n = 108) within a 20-km area ("cordon") cordoned off along the border of The Netherlands. This is adjacent to the area of a foot-and-mouth disease outbreak that occurred between 21 March and 22 April 2001 in The Netherlands. Negative control samples were taken from northern Germany (Schleswig-Holstein, n = 72). Two different enzyme-linked immunosorbent assays (ELISAs) were used for the detection of antibodies against foot-and-mouth disease virus (FMDV) serotype O strain Manisa. To confirm ELISA-positive results, a virus neutralization test was performed. All samples tested negative for antibodies against FMDV. These results suggest that FMDV was not transmitted to free-ranging roe deer living in parts of Germany adjacent to the area affected by the 2001 foot-and-mouth disease outbreak in The Netherlands.