Recent epidemiological evidence suggests that some antihypertensive medications may reduce the risk for Alzheimer disease (AD). We screened 55 clinically prescribed antihypertensive medications for AD-modifying activity using primary cortico-hippocampal neuron cultures generated from the Tg2576 AD mouse model. These agents represent all drug classes used for hypertension pharmacotherapy. We identified 7 candidate antihypertensive agents that significantly reduced AD-type β-amyloid protein (Aβ) accumulation. Through in vitro studies, we found that only 1 of the candidate drugs, valsartan, was capable of attenuating oligomerization of Aβ peptides into high-molecular-weight (HMW) oligomeric peptides, known to be involved in cognitive deterioration. We found that preventive treatment of Tg2576 mice with valsartan significantly reduced AD-type neuropathology and the content of soluble HMW extracellular oligomeric Aβ peptides in the brain. Most importantly, valsartan administration also attenuated the development of Aβ-mediated cognitive deterioration, even when delivered at a dose about 2-fold lower than that used for hypertension treatment in humans. These preclinical studies suggest that certain antihypertensive drugs may have AD-modifying activity and may protect against progressive Aβ-related memory deficits in subjects with AD or in those at high risk of developing AD.

No abstract

The solubility of Ls‐54 surfactant in supercritical CO2 was determined. It was found that the surfactant was highly soluble in SC CO2 and the water‐in‐CO2 microemulsions could be formed, despite it being a non‐fluorous and non‐siloxane nonionic surfactant. The main reasons for the high solubility and formation of the microemulsions may be that the surfactant has four CO2‐philic groups (propylene oxide) and five hydrophilic groups (ethylene oxide) and its molecular weight are relatively low. The results of this work provide useful information for designing CO2‐soluble non‐fluorous and non‐siloxane surfactants. The phase behavior of the CO2/Ls‐54/H2O system, solvatochromic probe study, and the UV spectrum of lysozyme proved the existence of water domains in the SC CO2 microemulsions. The method of synchrotron radiation small‐angle X‐ray scattering was used to obtain the structural information on the Ls‐54 based water‐in‐CO2 reverse micelles. By using the Guinier plot (ln I(q) versus q 2) on the data sets in a defined small q range (0.022–0.040 Å−1), the radii of the reverse micelles were obtained at different pressures and molar ratio of water to surfactant, W0, which were in the range of 20.4–25.2 Å.

A liquid paraffin-water emulsion was investigated using layered double hydroxide (LDH) particles and sodium dodecyl sulfate (SDS) as emulsifiers. Both emulsifiers are well-known to stabilize oil-in-water (o/w) emulsions. Surprisingly, a double phase inversion of the emulsion containing LDH particles is induced by the adsorption of SDS. At a constant LDH concentration, the emulsion is o/w type when SDS concentrations are low. At intermediate SDS concentrations, the first emulsion inversion from o/w to w/o occurs, which is attributed to the enhanced hydrophobicity of LDH particles caused by the desorption of the second layer of surfactant, leaving a densely packed SDS monolayer on the LDH exterior surfaces. The second inversion from water-in-oil (w/o) to o/w occurs at higher SDS concentrations, which may be due to the competitive adsorption at the oil/water interfaces between the LDH particles modified by the SDS bilayers and the free SDS molecules in the bulk solution, but the free SDS molecules dominate and determine the emulsion type. Laser-induced fluorescent confocal micrographs clearly confirm the adsorption of LDH particles on the surfaces of the initial o/w and intermediate w/o emulsion droplets, whereas no LDH particles were adsorbed on the final o/w emulsion droplet surfaces. Also, transmission electron microscopy (TEM) observations indicate that the shape of the final o/w emulsions is similar to that of the monomeric SDS-stabilized emulsion but different from that of the initial o/w emulsions. The adsorption behavior of SDS on LDH particles in water was investigated to offer an explanation for the emulsion double phase inversion. The zeta potential results show that the particles will flocculate first and then redisperse following surfactant addition. Also, X-ray diffraction (XRD) measurements indicate that SDS adsorption on the LDH interior surfaces will be complete at intermediate concentrations.