A rare case of Salmonella Paratyphi C osteomyelitis: A genetic analysis and review of Salmonella osteomyelitis in England.

Salmonella osteomyelitis is rare in patients without sickling hemoglobinopathies. Invasive disease caused by Salmonella Paratyphi C is rarer still with only one case reported in the United Kingdom in the last 15 years. We report a case of relapsing S. Paratyphi C osteomyelitis in a newly diagnosed diabetic patient from Ghana. Our patient was initially treated successfully with surgical debridement followed by 6 weeks of IV ceftriaxone before recrudescence 9 months later. Due to the rarity of S. Paratyphi C and the lack of recent travel, genomic analysis was undertaken to assess possible sources with the closest related strain being from Cote d'Ivoire. The patient had likley picked up the strain several years before presentation. We review current Salmonella osteomyelitis literature and audit all cases referred to the England and Wales Salmonella national reference laboratory over the last 15 years.

The discovery of potent and selective kynurenine 3-monooxygenase inhibitors for the treatment of acute pancreatitis.

A series of potent, competitive and highly selective kynurenine monooxygenase inhibitors have been discovered via a substrate-based approach for the treatment of acute pancreatitis. The lead compound demonstrated good cellular potency and clear pharmacodynamic activity in vivo.

Molecular interactions between desmosomal cadherins.

Desmocollins (Dscs) and desmogleins (Dsgs) are cell-adhesion molecules involved in the formation of desmosome cell-cell junctions and share structural similarities to classical cadherins such as E-cadherin. In order to identify and provide quantitative information on the types of protein-protein interactions displayed by the type 2 isoforms and investigate the role of Ca(2+) in this process, we have developed an Escherichia coli expression system to generate recombinant proteins containing the first two extracellular domains, namely Dsg2(1-2) and Dsc2(1-2). Analytical ultracentrifugation, chemical cross-linking, CD, fluorescence and BIAcore have been used to provide the first direct evidence of Ca(2+) binding to desmosomal cadherins. These studies suggest that Dsc2(1-2) not only exhibits homophilic interactions in solution, but can also form heterophilic interactions with Dsg2(1-2). The latter, on the other hand, shows much weaker homophilic association. Our results further demonstrate that heterophilic interactions are Ca(2+)-dependent, whereas the Ca(2+)-dependence of homophilic association is less clear. Our data indicate that the functional properties of Dsc2(1-2) are more similar to those of classical cadherins, consistent with the observation that Dsc shares a higher level of sequence homology with classical cadherins than does Dsg. In addition to corroborating the conclusions of previously reported transfection studies which suggest the formation of lateral heterodimers and homodimers, our results also provide direct quantitative information on the strength of these interactions which are essential for understanding the adhesion mechanism.