Chronic treatment with anesthetic propofol attenuates β-amyloid protein levels in brain tissues of aged mice

Alzheimer’s disease (AD) is the most common form of dementia. At the present time, however, AD still lacks effective treatments. Our recent studies showed that chronic treatment with anesthetic propofol attenuated brain caspase-3 activation and improved cognitive function in aged mice. Accumulation of β-amyloid protein (Aβ) is a major component of the neuropathogenesis of AD dementia and cognitive impairment. We therefore set out to determine the effects of chronic treatment with propofol on Aβ levels in brain tissues of aged mice. Propofol (50 mg/kg) was administrated to aged (18 month-old) wild-type mice once a week for 8 weeks. The brain tissues of mice were harvested one day after the final propofol treatment. The harvested brain tissues were then subjected to enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Here we report that the propofol treatment reduced Aβ (Aβ40 and Aβ42) levels in the brain tissues of the aged mice. Moreover, the propofol treatment decreased the levels of β-site amyloid precursor protein cleaving enzyme (the enzyme for Aβ generation), and increased the levels of neprilysin (the enzyme for Aβ degradation) in the brain tissues of the aged mice. These results suggested that the chronic treatment with propofol might reduce brain Aβ levels potentially via decreasing brain levels of β-site amyloid precursor protein cleaving enzyme, thus decreasing Aβ generation; and via increasing brain neprilysin levels, thus increasing Aβ degradation. These preliminary findings from our pilot studies have established a system and postulated a new hypothesis for future research

A conscious mouse model of gastric ileus using clinically relevant endpoints

BACKGROUND: Gastric ileus is an unsolved clinical problem and current treatment is limited to supportive measures. Models of ileus using anesthetized animals, muscle strips or isolated smooth muscle cells do not adequately reproduce the clinical situation. Thus, previous studies using these techniques have not led to a clear understanding of the pathophysiology of ileus. The feasibility of using food intake and fecal output as simple, clinically relevant endpoints for monitoring ileus in a conscious mouse model was evaluated by assessing the severity and time course of various insults known to cause ileus. METHODS: Delayed food intake and fecal output associated with ileus was monitored after intraperitoneal injection of endotoxin, laparotomy with bowel manipulation, thermal injury or cerulein induced acute pancreatitis. The correlation of decreased food intake after endotoxin injection with gastric ileus was validated by measuring gastric emptying. The effect of endotoxin on general activity level and feeding behavior was also determined. Small bowel transit was measured using a phenol red marker. RESULTS: Each insult resulted in a transient and comparable decrease in food intake and fecal output consistent with the clinical picture of ileus. The endpoints were highly sensitive to small changes in low doses of endotoxin, the extent of bowel manipulation, and cerulein dose. The delay in food intake directly correlated with delayed gastric emptying. Changes in general activity and feeding behavior were insufficient to explain decreased food intake. Intestinal transit remained unchanged at the times measured. CONCLUSION: Food intake and fecal output are sensitive markers of gastric dysfunction in four experimental models of ileus. In the mouse, delayed gastric emptying appears to be the major cause of the anorexic effect associated with ileus. Gastric dysfunction is more important than small bowel dysfunction in this model. Recovery of stomach function appears to be simultaneous to colonic recovery

An Online Logic Programming Development Environment

Recent progress in logic programming, particularly answer set programming, has enabled us to teach it to undergraduate and high school students. We developed an online answer set programming environment with simple interface and self contained file system. It is expected to make the teaching of answer set programming more effective and help us to reach more students

Preparation of Stable Wetting Surface by Hyperthermal Hydrogen Induced Cross-Linking of Poly(acrylic acid) on Poly(chloro‑<i>p</i>‑xylylene) Film

Enhancing surface wetting is very critical for various applications of polymer films. Although existing modification methods (e.g., UV radiation and plasma treatments) can improve the wetting of polymer films by inserting hydrophilic groups, the resultant polymer surface is unstable and shows strong hydrophobic recovery in a short time (less than 1 day) due to the rearrangement of the polymer chains. Herein, we report a new approach to prepare stable wetting surface by cross-linking hydrophilic poly­(acrylic acid) (PAA) molecules on poly­(chloro-<i>p</i>-xylylene) (PPXC) films via hyperthermal hydrogen induced cross-linking (HHIC) treatment. With the HHIC treatment, the polar functionalities of PAA (e.g., −COOH) can be preserved through selective cleavage of C–H bonds and subsequent cross-linking of resulting carbon radicals generated on PAA and PPXC chains. HHIC-treated PAA–PPXC film shows an excellent wetting stability, of which WCA and surface energy stay almost the same over 40 days. The improved wetting stability of PPXC film is attributed to the controllable HHIC reaction without undesirable side reaction (e.g., the scission of polymer chain backbone), which effectively restricts the rearrangement of PAA chains on the surface. Besides, the improved wetting stability by our approach results in reliable adhesion between silver ink and polymer films. Thus, fixing hydrophilic molecules on hydrophobic polymer surface by HHIC treatment could be an alternative approach to conventional surface treatments for preparation of stable wetting surface on polymer films