Dual-Acting Cholinesterase-Human Cannabinoid Receptor 2 Ligands Show Pronounced Neuroprotection in Vitro and Overadditive and Disease-Modifying Neuroprotective Effects in Vivo

We have designed and synthesized a series of 14 hybrid molecules out of the cholinesterase (ChE) inhibitor tacrine and a benzimidazole-based human cannabinoid receptor subtype 2 (hCB2R) agonist and investigated them in vitro and in vivo. The compounds are potent ChE inhibitors, and for the most promising hybrids, the mechanism of human acetylcholinesterase (hAChE) inhibition as well as their ability to interfere with AChE-induced aggregation of \u3b2-amyloid (A\u3b2), and A\u3b2 self-aggregation was assessed. All hybrids were evaluated for affinity and selectivity for hCB1R and hCB2R. To ensure that the hybrids retained their agonist character, the expression of cAMP-regulated genes was quantified, and potency and efficacy were determined. Additionally, the effects of the hybrids on microglia activation and neuroprotection on HT-22 cells were investigated. The most promising in vitro hybrids showed pronounced neuroprotection in an Alzheimer's mouse model at low dosage (0.1 mg/kg, i.p.), lacking hepatotoxicity even at high dose (3 mg/kg, i.p.)

The plaque and gingivitis reducing effect of a chlorhexidine and aluminium lactate containing dentifrice (Lacalut aktiv) over a period of 6 months.

Item does not contain fulltextAIM: The aim of the study was to determine the plaque and gingivitis reducing effect of a dentifrice containing chlorhexidine and aluminium lactate compared with a control toothpaste during the course of 6 months. MATERIAL AND METHODS: This randomized, double-blind study looked prospectively at participants over a 6-month period. Plaque, gingivitis, calculus formation and tooth staining were assessed in 59 participants, who were divided into parallel groups. The participants used either a chlorhexidine and aluminium lactate-containing toothpaste (test group) or a minus active control toothpaste (control group). Parameters were assessed at baseline and again after 1, 3 and 6 months. RESULTS: After 6 months of product use, both groups had less gingivitis compared with the baseline evaluation (p<0.001). At this time point, the test group showed a statistically significant lower gingival index values compared with the control group (p=0.001). No statistically significant differences between either the groups or time points were detected with regard to plaque index and the development of calculus and staining. CONCLUSION: Although there was a statistically significant difference at 6 months between test and control groups, this difference was too small to be considered clinically meaningful