East meets West in the search for Alzheimer's therapeutics - novel dimeric inhibitors from tacrine and huperzine A.

Alzheimer's disease (AD) is linked to cholinergic deficiency and the overactivation of glutamate receptors. The acetylcholinesterase (AChE) inhibition treatment approach has produced the most encouraging results in clinical practice, and memantine, a moderate antagonist of N-methyl-D-aspartate (NMDA) receptors, has been approved for treating AD. However, AChE inhibitors have limited success as they only improve memory in mild dementia but cannot stop the process of neurodegeneration; while memantine possesses neuroprotective effects only with a little ability in memory enhancement. There has been a major rush among neuroscience research institutions and pharmaceutical firms worldwide to search for safer and more effective therapeutic agents for AD. The novel dimers, derived from tacrine and the fragment of huperzine A (HA'), have been demonstrated to be potent and selective reversible inhibitors of AChE. Bis(7)-tacrine, bis(12)-hupyridone (E12E) and HA'(10)-tacrine, are representatives of three series of novel dimers. According to the preclinical studies, these compounds have been shown to have low toxicity and high efficacy for improving cognitive deficits in several animal models. More interestingly, bis(7)-tacrine, similar to memantine, prevents glutamate-induced neurotoxicity by moderately blocking glutamate receptor NMDA subtype. Furthermore, bis(7)-tacrine, as well as E12E, possesses multiple neuroprotective effects in vitro and in vivo. Taking together, these dimeric AChE inhibitors, especially bis(7)-tacrine, E12E and HA'(10)-tacrine, may provide beneficial effects in AD and other neurodegenerative diseases.

Evaluation of impulse noise criteria using human volunteer data.

Four impulse noise auditory injury criteria adopted by NATO countries, namely, the MIL-STD-1474D (USA), Pfander (Germany), Smoorenburg (Netherlands), and L(Aeq8) (France), are evaluated against human volunteer data. Data from subjects wearing single-hearing protection exposed to increasing blast overpressure effects were obtained from tests sponsored by the US Army Medical Research and Material Command. Using logistic regression, the four criteria were each correlated with the test data. The analysis shows that all four criteria are overly conservative by 9.6-21.2 dB for the subjects as tested. The MIL-STD-1474D for single-hearing protection is 9.6 dB lower than the observed injury threshold for 95% protection with 95% confidence for this particular group of subjects as tested. Similar conclusions can be drawn for the other three criteria.

Chemical composition of winged bean (Psophocarpus tetragonolobus) varieties.

The chemical composition of dry seeds of four varieties, pods, stalks and leaves of winged beans (Psophocarpus tetragonolobus) was determined. The seeds had a high range of protein (27.8-36.6%) and fat (14.8-17.9%), which were similar to soybeans. the seeds contained high phosphorus, calcium and magnesium. The leaf was highest in protein content (33.7%) of all the parts studied except for the seeds. The protein and fat content of pods decreased as pods ripened. the calcium content in the leaf was much higher than in the other parts. Protein was extracted sequentially with 2% NaCl, 30% isopropyl alcohol, 4% lactic acid and 0.5% KOH from dry seeds of four varieties of winged beans. The NaCl extract showed the highest range of protein concentration (60.2-77.6%). The NaCl extract was separated into two fractions based on solubility in water. the amino acid composition of the flour from the seeds and of the two fractions from the NaCl extract were determined. Contents of lysine, aspartic acid, glutamic acid and leucine were large, while the sulfur-amino acid content was small. Trypsin and chymotrypsin inhibitory activities of 2% NaCl extract from the seeds were determined, and chymotrypsin inhibitory activity was higher than the trypsin.