Preoperative low albumin level, steroid use, and the presence of abscess or fistula at the time of laparotomy significantly increased the risk of septic complications after surgery in Crohn's disease.

Neurofibrillary tangles in Alzheimer disease (AD) brains are composed of the microtubule-associated protein tau. Noninvasive monitoring of tau protein aggregates in the living brain will provide useful information regarding tau pathophysiology in AD. However, no PET probes are currently available for selective detection of tau pathology in AD. We have previously reported 18 F-labeled THK-523 ( 18 F-6-(2-fluoroethoxy)-2-(4-aminophenyl)quinoline) as a tau imaging radiotracer candidate for PET. After compound optimization, we developed novel 18 F-labeled arylquinoline derivatives, 18 F-THK-5105 and 18 F-THK-5117, for use as tau imaging PET tracers. Methods: 18 F-labeled compounds were prepared from the corresponding tosylated precursors. The binding affinity of compounds to synthetic tau aggregates and tau-rich AD brain homogenates was determined by saturation and competition binding assays. The binding selectivity of compounds to tau pathology was evaluated by autoradiography of AD brain sections. The pharmacokinetics of compounds were assessed in biodistribution studies in normal mice. A 14-d toxicity study with intravenous administration of compounds was performed using rats and mice. Results: In vitro binding assays demonstrated higher binding affinity of THK-5105 and THK-5117 than THK-523 to tau protein aggregates and tau-rich AD brain homogenates. Autoradiographic analyses of AD brain sections showed that these radiotracers preferentially bound to neurofibrillary tangles and neuropil threads, which colocalized with Gallyas-positive and immunoreactive tau protein deposits. The distribution of this radiotracer binding in AD brain sections was completely different from that of 11 C-Pittsburgh compound B, showing preferential binding to amyloid plaques. Furthermore, these derivatives demonstrated abundant initial brain uptake and faster clearance in normal mice than 18 F-THK-523 and other reported 18 F-labeled radiotracers. THK-5105 and THK-5117 showed no toxic effects related to the administration of these compounds in mice and rats and no significant binding for various neuroreceptors, ion channels, and transporters at 1-mM concentrations. Conclusion: 18 Flabeled THK-5105 and THK-5117 are promising candidates as PET tau imaging radiotracers.

Although in Crohn's disease post-operative recurrence is common, the determinants of disease recurrence remain speculative. The aim of this study was to examine factors affecting post-operative recurrence of Crohn's disease. A Medline-based literature review was carried out. The following factors were investigated: age at onset of disease, sex, family history of Crohn's disease, smoking, duration of Crohn's disease before surgery, prophylactic medical treatment (corticosteroids, 5-amino salicylic acid (5-ASA) and immunosuppressants), anatomical site of involvement, indication for surgery (perforating or non-perforating disease), length of resected bowel, anastomotic technique, presence of granuloma in the specimen, involvement of disease at the resection margin, blood transfusions and post-operative complications. Smoking significantly increases the risk of recurrence (risk is approximately twice as high), especially in women and heavy smokers. Quitting smoking reduces the post-operative recurrence rate. A number of studies have shown a higher risk when the duration of the disease before surgery was short. There were, however, different definitions of 'short' among the studies. Prophylactic corticosteroids therapy is not effective in reducing the post-operative recurrence. A number of randomized controlled trials offered evidence of the efficacy of 5-ASA (mesalazine) in reducing post-operative recurrence. Recently, the therapeutic efficacy of immunosuppressive drugs (azathioprine and 6-mercaptopurine) in the prevention of post-operative recurrence has been investigated and several studies have reported that these drugs might help prevent the recurrence. Further clinical trials would be necessary to evaluate the prophylactic efficacy of immunosuppressants. Several studies showed a higher recurrence rate in patients with perforating disease than in those with non-perforating disease. However, evidence for differing recurrence rates in perforating and non-perforating diseases is inconclusive. A number of retrospective studies reported that a stapled functional end-to-end anastomosis was associated with a lower recurrence rate compared with other types of anastomosis. However, prospective randomized studies would be necessary to draw a definite conclusion. Many studies found no difference in the recurrence rates between patients with radical resection and non-radical resection. Therefore, minimal surgery including strictureplasty has been justified in the management of Crohn's disease. In this review, the following factors do not seem to be predictive of post-operative recurrence: age at onset of disease, sex, family history of Crohn's disease, anatomical site of disease, length of resected bowel, presence of granuloma in the specimen, blood transfusions and post-operative complications. The most significant factor affecting post-operative recurrence of Crohn's disease is smoking. Smoking significantly increases the risk of recurrence. A short disease duration before surgery seems, albeit to a very minor degree, to b...

The abnormal deposition of the amyloid ␤-protein (A␤) in the brain appears crucial to the pathogenesis of Alzheimer's disease (AD). Recent studies have suggested that highly amyloidogenic A␤ 1-42 is a cause of neuronal damage leading to AD pathogenesis and that monomeric A␤ 1-40 has less neurotoxicity than A␤ 1-42 . We found that mouse and human brain homogenates exhibit an enzyme activity converting A␤ 1-42 to A␤ 1-40 and that the major part of this converting activity is mediated by the angiotensin-converting enzyme (ACE).