Anti-amyloidogenic therapies: strategies for prevention and treatment of Alzheimer’s disease

Deposition of amyloid β-protein (Aβ) in the brain is an early and invariant neuropathological feature of Alzheimer’s disease (AD). The current search for anti-AD drugs is mainly focused on modification of the process of accumulation of Aβ in the brain. Here, we review four anti-amyloidogenic strategies: (i) reduction of Aβ production, which has mainly been approached with secretase inhibition, (ii) promotion of the Aβ degrading catabolic pathway, including an Aβ degrading enzyme, neprilysin, (iii) immunotherapy for Aβ and (iv) inhibition of Aβ aggregation. We have reported that AD patients have a favorable molecular environment for Aβ aggregation and that various compounds, such as polyphenols, interfere with Aβ aggregation and destabilize preformed Aβ fibrils. Received 21 December 2005; received after revision 14 February 2006; accepted 29 March 2006     

Effect of physical exercise on the specific activity of carbonic anhydrase isozyme in human erythrocytes

Summary Significant decreases in the levels of both carbonic anhydrase type B and total esterase activity of human erythrocytes were observed after physical exercise (bicycle ergometer, 150 W for 30 min). Since carbonic anhydrase B-dependent esterase activity likewise decreased, the decrease in the total esterase activity would be caused by the decrease of carbonic anhydrase B activity. The specific activity of carbonic anhydrase B tended to decrease after the exercise. On the other hand no such effects were noted for carbonic anhydrase type C.     

The influence of prostacyclin (PGI2) on contractile properties of isolated right ventricle of rat heart

The mechanism of the positive inotropic effect of prostacyclin (PGI₂) (2.6×10^?6 mol/l) on the isolated right ventricle of rat heart was studied. Our results show that the positive inotropic effect of prostacyclin is produced indirectly through beta adrenoceptors and slow Ca²⁺ channels, because blockade of slow Ca²⁺ channels with verapamil (10^?6 mol/l) and beta adrenoceptors with propranolol (10^?6 mol/l) abolishes this effect. Alpha adrenoceptors do not mediate the action of PGI₂.     

Generalized invexity-type conditions in constrained optimization

This paper defines a new class of generalized type I functions, and obtains Kuhn-Tucker necessary and sufficient conditions and duality results for constrained optimization problems in the presence of the aforesaid weaker assumptions on the objective and constraint functions involved in the problem.     

Schistosoma mansoni: onset of chemoattraction in developing worms

Heterosexual chemoattraction studies on juvenile worms showed that 20- and 21-day-old worms do not attract each other, whereas 23- and 28-day-old worms are attracted to each other and pair with worms of the opposite sex. This onset of chemoattraction in vitro corresponds to the time when worms begin pairing in vivo. The ability of single worms to locate each other and mate is presumably mediated by chemoreceptors.