Discitis

Discitis is an inflammatory condition of the intervertebral disc or disc space. It is an uncommon condition which occurs mostly in young children or as a post-operative complication, such as following an epidural. It is extremely rare in the elderly as disc size and sponginess decreases with age and consequently the risk of infection decreases. In this case, discitis occurred spontaneously in an elderly patient and was complicated by a psoas abscess. The patient also suffers from acute renal failure, chronic heart failure, left sided pneumonia and shingles (Herpes Zoster) in dermatome S3. A trapped spinal nerve occurring at the intervertebral foramen is a common complication in fact, the subject did suffer from sciatica for the past 30 years.peer-reviewe

Liver abscess following ingestion of a foreign object

A 31 year old, previously healthy female presented to A&E on 24/07/2012 with a 2 day history of colicky epigastric pain and spiking fever; however on investigation no pathology was found except for an ovarian cyst of 4cm. It was concluded that it was unlikely that the cyst was causing pain and fever and the patient was discharged. She was given proton pump inhibitors for 2 weeks and pain improved, however on stopping therapy, the pain became much more severe, with radiation to the back. She presented to A&E again on 05/08/2012. A more detailed history elicited the fact that she had ingested half a toothpick by mistake 3 weeks previously. Imaging showed the formation of an abscess between the stomach and liver; which needed drainage.peer-reviewe

Evaluation and optimization of in silico designed β-Secretase modulators for the treatment of "Alzheimer's Disease"

Alzheimer's disease affects cognitive function through formation of ß- secretase mediated extracellular cerebral protein plaques and intracellular neurofibrillary tangles, thus its antagonism could mitigate disease progression. This project aims to identify newly obtained and optimized molecules which decrease the formation of ß -amyloid plaques through inhibition of the ß- secretase enzyme. Protein databank (PDB) depositions describing the bound coordinates of 6 lead structures complexed with ß- secretase were identified (PDB ID- 2VKM, 4B05, 4IVS, 3U6A, 3IGB, 2Q11) as leads for in silico ligand based and de novo design of novel antagonist molecules. For the first part of this study, ligands extracted from the protein were used as templates for screening ViCi Hamburg‟s database. Protomols were generated for each of the ligands using the Surflex Dock suite in SYBYL-X. The molecules received through ViCi were then used as ligand sources. For the second part of the study the ligand binding affinity (LBA) of each small molecule for its cognate receptor was calculated in X-Score for baseline affinity establishment. 2D topology maps highlighting the important interactions between ligand and receptor were generated using Poseview, and noncritical moieties were computationally removed in the process of creating seed structures (n=3, 2, 3,2,2,2 respectively) on to which novel moieties were computationally introduced using the GROW module of LigBuilder. Protomol and Keysite volumes were then compared using UCSF Chimera. 1636 novel structures were generated with 253 structures being Lipinski Rule compliant. The highest ranking molecules from each pharmacophoric family were identified for optimization and in vitro validation.peer-reviewe