Age, Sex, Hypertension and HDL-C Alter Serum BACE1 Activity in Cognitively Normal Subjects: Implications for Alzheimer's Disease.

BACKGROUND: Increasing evidence indicates that ß-secretase 1 (BACE1) activity and concentration in blood are candidate biomarkers for Alzheimer's disease (AD). Investigating potential demographic, biological, and clinical determinants of BACE1 in the blood matrix is the critical step to validate and qualify BACE1 bio-indicators for different contexts-of-use (CoU), such as risk assessment, early detection, diagnosis, prognosis, management of AD, and outcome of amyloid pathway targeted drugs. OBJECTIVES: To evaluate the influence of age, sex, HDL-cholesterol and comorbidities (cardiovascular diseases, hypertension, diabetes) on circulating BACE-1 activity. DESIGN: prospective analysis of serum samples, clinical, biological, and demographic variables. SETTING: Three cohorts: 1) Memory Clinic of the Department of Internal Medicine, S. Anna University Hospital, Ferrara (Italy); 2) outpatients attending the Menopause and Osteoporosis Centre (MOC) of the University of Ferrara (Ferrara, Italy); 3) Prevention Center of the University of Ferrara. PARTICIPANTS: 504 cognitively healthy individuals (median age: 62 years, interquartile range: 51-73) and 175 patients with AD (78 years, 74-82). MEASUREMENTS: serum BACE1 (sBACE1), age, sex, HDL-cholesterol, major comorbidities. RESULTS: Age was the strongest independent predictor of sBACE1 variance (ß=0.425, p<0.0001), followed by sex (ß=0.180, p<0.0001), high density lipoprotein-cholesterol (HDL-C) (ß=-0.168, p<0.0001) and hypertension (ß=0.111, p<0.05) (overall model, R2: 0.232). The probability of having elevated sBACE1 activity increased after 70 years of age, with women being more susceptible to higher sBACE1 activity than men. CONCLUSIONS: We provide evidence about potential clinical and biological determinants of sBACE1 activity with a strong association among biomarker, female sex, and older age.

Influence of the polymer amount on bioactivity and biocompatibility of SiO2/PEG hybrid materials synthesized by sol-gel technique.

SiO2/PEG organic-inorganic hybrid materials, which differ in polyethylene glycol (PEG) content, were synthesized by sol-gel technique and the characterization of their structure and biological properties was carried out in order to evaluate the possible use in biomedical field. FT-IR spectroscopy detected that the two components of the hybrids (SiO2 and PEG) are linked by hydrogen bonds between the Si-OH groups of the inorganic phase and the terminal alcoholic groups and/or the ethereal oxygen atoms in the repeating units of polymer. X-ray diffraction analysis ascertained the amorphous nature of the gels and the observation of their morphology by SEM microscopy confirmed that the interpenetration of the two phases (organic and inorganic) occurs on nanometric scale. The biological characterization was carried out as a function of the polymer amount to study its influence on material behavior. The results showed that the synthesized materials were bioactive and biocompatible. The formation of a hydroxyapatite layer, indeed, was observed on their surface by SEM/EDX analysis after soaking in simulated body fluid. Moreover, the biocompatibility of SiO2/PEG hybrids was assessed performing MTT and SRB cytotoxicity tests on fibroblast cell NIH 3T3 after 24 and 48h of exposure, as well as Trypan Blue dye exclusion test. The response to the presence of the investigated materials was positive. The cell growth and proliferation showed dependence on polymer amount and time of exposure to the material extracts. Therefore, the obtained results are encouraging for the use of the obtained hybrids in dental or orthopedic applications.

TiO2/PCL hybrid materials synthesized via sol-gel technique for biomedical applications.

The aim of the present work has been the synthesis of organic/inorganic hybrid materials based on titanium dioxide and poly(ε-caprolactone) (PCL) to be used in the biomedical field. Several materials have been synthesized using sol-gel methods by adding different amounts of polymer to the inorganic sol. The obtained gels have been characterized using Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and atomic force microscopy (AFM). The FT-IR data allowed us to hypothesize that the structure formed was that of an interpenetrating network, realized by hydrogen bonds between TiOH groups in the sol-gel intermediate species and carbonyl groups in the polymer repeating units. SEM and AFM analyses highlighted that the obtained materials were nanostructurated hybrids. To evaluate the biological properties of the hybrids, their bioactivity and cytotoxicity were investigated as a function of the PCL amount. The bioactivity of the synthesized systems was proven by the formation of a hydroxyapatite layer on the surface of samples soaked in a fluid simulating human blood plasma (SBF). MTT cytotoxicity tests and Trypan Blue dye exclusion tests were carried out exposing NIH-3T3 mouse embryonic fibroblasts for 24 and 48h to extracts from the investigated hybrid materials. The results showed that all the hybrids had a non-cytotoxic effect on target cells.

Biological evaluation of zirconia/PEG hybrid materials synthesized via sol-gel technique.

The objective of the following study has been the synthesis via sol-gel and the characterization of novel organic-inorganic hybrid materials to be used in biomedical field. The prepared materials consist of an inorganic zirconia matrix containing as organic component the polyethylene glycol (PEG), a water-soluble polymer used in medical and pharmaceutical fields. Various hybrids have been synthesized changing the molar ratio between the organic and inorganic parts. Fourier transform spectroscopy suggests that the structure of the interpenetrating network is realized by hydrogen bonds between the Zr-OH group in the sol-gel intermediate species and both the terminal alcoholic group and ethereal oxygen atoms in the repeating units of polymer The amorphous nature of the gels has been ascertained by X-ray diffraction analysis. The morphology observation has been carried out by using the Scanning Electron Microscope and has confirmed that the obtained materials are nanostructurated hybrids. The bioactivity of the synthesized system has been shown by the formation of a hydroxyapatite layer on the surface of samples soaked in a fluid simulating the human blood plasma. The potential biocompatibility of hybrids has been assessed as performing indirect MTT cytotoxicity assay towards 3T3 cell line at 24, 48, and 72 h exposure times.

Synthesis of zirconia/polyethylene glycol hybrid materials by sol-gel processing and connections between structure and release kinetic of indomethacin.

Controlled and local drug delivery systems of anti-inflammatory agents are attracting an increasing attention because of their extended therapeutic effect and reduced side effects. In this work, the sol-gel process was used to synthesize zirconia/polyethylene glycol (ZrO2/PEG) hybrid materials containing indomethacin for controlled drug delivery. Different percentages of PEG were introduced in the synthesis to modulate the release kinetic and an exhaustive chemical characterization of all samples was performed to detect the relationship between their structure and release ability. Fourier transform spectroscopy and solid-state NMR show that the Zr-OH groups of the inorganic matrix bond both the ethereal oxygen atoms of the polymer and the carboxylic groups of the drug. X-ray diffraction analysis ascertains the amorphous nature of those materials. Scanning electron microscopy detects the nanostructure and the homogeneous morphology of the synthesized materials. The bioactivity was demonstrated by the formation of a hydroxyapatite layer on the surface of the samples, after soaking in a simulated body fluid. The release kinetics study, performed by HPLC UV-Vis spectroscopy, proves that the release ability depends on PEG and the drug amount and also demonstrates the indomethacin integrity after the synthetic treatment.

French marine bark extract pycnogenol as a possible enrichment ingredient for yogurt.

The influence of Pycnogenol, French marine bark extract, added to yogurt preparation on the viability of Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus and on pH, titratable acidity, macro-nutrients, and folate content were evaluated throughout the shelf life of products. At all concentrations studied, Pycnogenol additions neither significantly affected the growth of microorganisms nor caused any modification of nutritional parameters during storage in yogurt. To highlight any possible degradation of Pycnogenol components by yogurt flora, an estimation of total polyphenol contents and an evaluation of some phenolic compounds in yogurt at the greatest concentration of Pycnogenol were carried out at the beginning and at the end of the study. Our data indicates that neither total polyphenol content nor selected phenolic substances (cathechin, epicatechins, chlorogenic acid, and caffeic acid) was affected during the shelf life. In conclusion, these results suggest Pycnogenol as a valuable ingredient to enrich yogurt preparation.

Bile salt and acid tolerance of Lactobacillus rhamnosus strains isolated from Parmigiano Reggiano cheese.

This study aimed to compare phenotypic and genetic characteristics of Lactobacillus rhamnosus strains isolated at the end of the ripening of Parmigiano Reggiano cheese and to investigate an important prerequisite of probiotic interest, such as the capability to survive at low pH and in presence of bile salts. The use of API 50 CH, RAPD-PCR analysis and species-specific PCR allowed to ascertain the identity of 63 L. rhamnosus strains. Three L. rhamnosus strains isolated from Parmigiano Reggiano cheese, L. rhamnosus ATCC 7469T and the commercial strain L. GG were assayed to estimate the resistance to various stress factors reproducing in vitro some conditions of the gastro-intestinal environment such as low pH and different amounts of bile salts and acids. The behaviour of almost all the tested strains isolated from Parmigiano Reggiano cheese resulted analogous to that showed by L. GG.