Supplementary cementitious materials

The use of silica rich SCMs influences the amount and kind of hydrates formed and thus the volume, the porosity and finally the durability of these materials. At the levels of substitution normally used, major changes are the lower Ca/Si ratio in the C–S–H phase and consumption of portlandite. Alumina-rich SCMs increase the Al-uptake in C–S–H and the amounts of aluminate containing hydrates. In general the changes in phase assemblages are well captured by thermodynamic modelling, although better knowledge of the C–S–H is needed.At early ages, “filler” effects lead to an increased reaction of the clinker phases. Reaction of SCMs starts later and is enhanced with pH and temperature. Composition, fineness and the amount of glassy phase play also an important role. Due to the diverse range of SCM used, generic relations between composition, particle size, exposure conditions as temperature or relative humidity become increasingly crucial.     

Formation of mesoglobules in aqueous media from thermo-sensitive poly(ethoxytriethyleneglycol acrylate)

A series of six poly(ethoxytriethyleneglycol acrylate) (PETEGA) homopolymers were synthesized by atom transfer radical polymerization, reversible addition-fragmentation transfer polymerization, and anionic polymerization in order to cover a molecular weight range from 7,000 to 40,000 Da. The polymers exhibited a lower critical solution temperature (LCST) behavior in water, which was observed by the occurrence of a cloud point (CP) at around 35 °C. The transmittance of visible light versus temperature dependence overlapped during the cooling and the heating cycles, showing almost a complete lack of hysteresis. Moreover, instead of the occurrence of an uncontrolled macroscopic phase separation, stable colloidal aggregates (mesoglobules) of narrow distribution in particle size were formed in water at temperatures above the LCST of PETEGA at 1 g L⁻¹ solutions. The dimensions of the mesoglobules ranged from 91 to 235 nm, and particle size was not influenced by the molecular weight of PETEGA. Temperature changes caused considerable variations of the mesoglobules dimensions, which were smaller at higher temperatures. The addition of an anionic surfactant simultaneously increased the CP values by 4–6 °C and lowered the dimensions of the mesoglobules.     

Beyond platinum: synthesis,characterization, and in vitro toxicity of Cu(II)-releasing polymer nanoparticles for potential use as a drug delivery vector

The field of drug delivery focuses primarily on delivering small organic molecules or DNA/RNA as therapeutics and has largely ignored the potential for delivering catalytically active transition metal ions and complexes. The delivery of a variety of transition metals has potential for inducing apoptosis in targeted cells. The chief aims of this work were the development of a suitable delivery vector for a prototypical transition metal, Cu²⁺, and demonstration of the ability to impact cancer cell viability via exposure to such a Cu-loaded vector. Carboxylate-functionalized nanoparticles were synthesized by free radical polymerization and were subsequently loaded with Cu²⁺ via binding to particle-bound carboxylate functional groups. Cu loading and release were characterized via ICP MS, EDX, XPS, and elemental analysis. Results demonstrated that Cu could be loaded in high weight percent (up to 16 wt.%) and that Cu was released from the particles in a pH-dependent manner. Metal release was a function of both pH and the presence of competing ligands. The toxicity of the particles was measured in HeLa cells where reductions in cell viability greater than 95% were observed at high Cu loading. The combined pH sensitivity and significant toxicity make this copper delivery vector an excellent candidate for the targeted killing of disease cells when combined with an effective cellular targeting strategy.     

Interplay between Endothelin and Erythropoietin in Astroglia: The Role in Protection against Hypoxia

We show that, under in vitro conditions, the vulnerability of astroglia to hypoxia is reflected by alterations in endothelin (ET)-1 release and capacity of erythropoietin (EPO) to regulate ET-1 levels. Exposure of cells to 24 h hypoxia did not induce changes in ET-1 release, while 48–72 h hypoxia resulted in increase of ET-1 release from astrocytes that could be abolished by EPO. The endothelin receptor type A (ETA) antagonist BQ123 increased extracellular levels of ET-1 in human fetal astroglial cell line (SV-FHAS). The survival and proliferation of rat primary astrocytes, neural precursors, and neurons upon hypoxic conditions were increased upon administration of BQ123. Hypoxic injury and aging affected the interaction between the EPO and ET systems. Under hypoxia EPO decreased ET-1 release from astrocytes, while ETA receptor blockade enhanced the expression of EPO mRNA and EPO receptor in culture-aged rat astroglia. The blockade of ETA receptor can increase the availability of ET-1 to the ETB receptor and can potentiate the neuroprotective effects of EPO. Thus, the new therapeutic use of combined administration of EPO and ETA receptor antagonists during hypoxia-associated neurodegenerative disorders of the central nervous system (CNS) can be suggested.     

Angiopoietin-like Proteins in Colorectal Cancer—A Literature Review

Colorectal cancer (CRC) is one of the most common types of malignancy, with an annual incidence of about 10% of the total number of new cases. Despite well-developed screening tests, mortality from this type of cancer remains unchanged. Therefore, it is important to search for more accurate markers that are useful in the detection of colorectal cancer (especially in its early stages), and treatment. Angiopoietin-like proteins (ANGPTLs) are a family of eight proteins with a diversity of applications, including pro- and anti-angiogenic properties. Consequently, we performed an extensive search of the literature, pertaining to our investigation, via the MEDLINE/PubMed database. Based on the available literature, we summarize that some of those proteins are characterized by increased or decreased concentrations during the course of CRC. We can also assume that some ANGPTLs can inhibit the development of CRC, while others induce its progress. Moreover, some factors are dependent on the stage or histological type of the tumor, the presence of hypoxia, or metastases. Most importantly, some ANGPTLs can be useful in anti-cancer therapy. Therefore, further studies on ANGPTLs as potential markers of CRC should be continued.     

Xenobiotic Metabolism: The Effect of Acute Kidney Injury on Non-Renal Drug Clearance and Hepatic Drug Metabolism

Acute kidney injury (AKI) is a common complication of critical illness, and evidence is emerging that suggests AKI disrupts the function of other organs. It is a recognized phenomenon that patients with chronic kidney disease (CKD) have reduced hepatic metabolism of drugs, via the cytochrome P450 (CYP) enzyme group, and drug dosing guidelines in AKI are often extrapolated from data obtained from patients with CKD. This approach, however, is flawed because several confounding factors exist in AKI. The data from animal studies investigating the effects of AKI on CYP activity are conflicting, although the results of the majority do suggest that AKI impairs hepatic CYP activity. More recently, human study data have also demonstrated decreased CYP activity associated with AKI, in particular the CYP3A subtypes. Furthermore, preliminary data suggest that patients expressing the functional allele variant CYP3A5*1 may be protected from the deleterious effects of AKI when compared with patients homozygous for the variant CYP3A5*3, which codes for a non-functional protein. In conclusion, there is a need to individualize drug prescribing, particularly for the more sick and vulnerable patients, but this needs to be explored in greater depth.     

Simultaneous Enhancement of Fracture Toughness and Unipolar Strain in Pb(Zr,Ti)O3‐ZrO2 Composites Through Composition Adjustment

The influence of second phase zirconia particles on the electrical properties and fracture behavior of various polycrystalline soft Pb(Zr_1?xTi_x)O₃ (PZT) compositions was investigated. PZT composites with yttria‐stabilized tetragonal zirconia particles exhibited enhanced crack resistance in comparison to monolithic compositions, regardless of the PZT composition. The addition of zirconia, however, was found to change the PZT composition through the diffusion of zirconium, resulting in variations in the observed piezoelectric and ferroelectric responses. Through the tailoring of the PZT matrix composition, the large electromechanical response and enhanced fracture toughness could be retained. The variation in both small and large signal properties is contrasted to fracture results and crystal structure changes, as determined by X‐ray diffraction.     

Novel Tacrine‐Grafted Ugi Adducts as Multipotent Anti‐Alzheimer Drugs: A Synthetic Renewal in Tacrine–Ferulic Acid Hybrids

Herein we describe the design, multicomponent synthesis, and biological, molecular modeling and ADMET studies, as well as in vitro PAMPA‐blood–brain barrier (BBB) analysis of new tacrine–ferulic acid hybrids (TFAHs). We identified (E)‐3‐(hydroxy‐3‐methoxyphenyl)‐N‐{8[(7‐methoxy‐1,2,3,4‐tetrahydroacridin‐9‐yl)amino]octyl}‐N‐[2‐(naphthalen‐2‐ylamino)2‐oxoethyl]acrylamide (TFAH 10 n ) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC₅₀=68.2 nM ), strong antioxidant activity (4.29 equiv trolox in an oxygen radical absorbance capacity (ORAC) assay), and good β‐amyloid (Aβ) anti‐aggregation properties (65.6 % at 1:1 ratio); moreover, it is able to permeate central nervous system (CNS) tissues, as determined by PAMPA‐BBB assay. Notably, even when tested at very high concentrations, TFAH 10 n easily surpasses the other TFAHs in hepatotoxicity profiling (59.4 % cell viability at 1000 μM ), affording good neuroprotection against toxic insults such as Aβ_1–40, Aβ_1–42, H₂O₂, and oligomycin A/rotenone on SH‐SY5Y cells, at 1 μM . The results reported herein support the development of new multipotent TFAH derivatives as potential drugs for the treatment of Alzheimer′s disease.