Flubendazole carbonyl reduction in drug-susceptible and drug-resistant strains of the parasitic nematode Haemonchus contortus: changes during the life cycle and possible inhibition.

Carbonyl-reducing enzymes (CREs) catalyse the reduction of carbonyl groups in many eobiotic and xenobiotic compounds in all organisms, including helminths. Previous studies have shown the important roles of CREs in the deactivation of several anthelmintic drugs (e.g., flubendazole and mebendazole) in adults infected with the parasitic nematode Haemonchus contortus, in which the activity of a CRE is increased in drug-resistant strains. The aim of the present study was to compare the abilities of nematodes of both a drug-susceptible strain (ISE) and a drug-resistant strain (IRE) to reduce the carbonyl group of flubendazole (FLU) in different developmental stages (eggs, L1/2 larvae, L3 larvae, and adults). In addition, the effects of selected CRE inhibitors (e.g., glycyrrhetinic acid, naringenin, silybin, luteolin, glyceraldehyde, and menadione) on the reduction of FLU were evaluated in vitro and ex vivo in H. contortus adults. The results showed that FLU was reduced by H. contortus in all developmental stages, with adult IRE females being the most metabolically active. Larvae (L1/2 and L3) and adult females of the IRE strain reduced FLU more effectively than those of the ISE strain. Data from the in vitro inhibition study (performed with cytosolic-like fractions of H. contortus adult homogenate) revealed that glycyrrhetinic acid, naringenin, mebendazole and menadione are effective inhibitors of FLU reduction. Ex vivo study data showed that menadione inhibited FLU reduction and also decreased the viability of H. contortus adults to a similar extent. Naringenin and mebendazole were not toxic at the concentrations tested, but they did not inhibit the reduction of FLU in adult worms ex vivo.

Effect of Aluminosilicates' Particle Size Distribution on the Microstructural and Mechanical Properties of Metakaolinite-Based Geopolymers.

The present study focused on investigating the differences in properties between calcined and milled aluminosilicates with different particle size distributions. Two types of clay, i.e., kaolin and kaolinitic claystone, were subjected to calcination at 750 °C, and subsequent milling to obtain different fractions with distinct particle size distributions. These fractions were then combined with a potassium alkaline activator and quartz sand in a 50:50 weight ratio to form a geopolymer composite. The geopolymer binders were then characterized using a mercury intrusion porosimeter (MIP), scanning electron microscopy (SEM), and a rotary rheometer. Mechanical tests were conducted on the geopolymer composites prepared from aluminosilicates with varying particle size distributions. The findings indicated that aluminosilicates with a finer particle size distribution exhibited higher levels of dissolved aluminum (10,000 mg/kg) compared to samples with coarser particle size distributions (1000 mg/kg). Additionally, as the particle size distribution decreased, the dynamic viscosity of the geopolymer binders increased, while the average pore size decreased. Finally, the mechanical properties of the geopolymer composites derived from both tested aluminosilicates demonstrated a decline in performance as the mean particle size increased beyond 10 µm.

Effect of Different Types of Aluminosilicates on the Thermo-Mechanical Properties of Metakaolinite-Based Geopolymer Composites.

In this study, the effect of different types of aluminosilicates on the thermo-mechanical properties of metakaolinite-based geopolymer binders and composites was examined. The metakaolinite-based geopolymer binders and composites were produced from three different types of aluminosilicates (one metakaolin and two calcined claystones) and a potassium alkaline activator. Chamotte was added as a filler, amounting to 65% by volume, to create geopolymer composites. Geopolymer binders were characterized by X-ray diffraction, rotary rheometer and scanning electron microscopy. The mechanical properties, thermal dilatation and thermal conductivity were investigated on geopolymer composites with three different aluminosilicates before and after exposure to high temperatures (up to 1200 °C). The results showed that the geopolymer binders prepared from calcined claystones had a lower dynamic viscosity (787 and 588 mPa·s) compared to the geopolymer binders prepared from metakaolin (1090 mPa·s). Geopolymer composites based on metakaolin had lower shrinkage (0.6%) and higher refractoriness (1520 °C) than geopolymers from calcined claystones (0.9% and 1.5%, 1500 °C and 1470 °C). Geopolymers based on calcined kaolinitic claystones are a promising material with higher compressive (95.2 and 71.5 MPa) and flexural strength (12.4 and 10.7 MPa) compared to geopolymers based on metakaolin (compressive strength 57.7 MPa).

Effect of K/Al Molar Ratio on the Thermo-Mechanical Properties of Metakaolinite-Based Geopolymer Composites.

A metakaolinite-based geopolymer binder was prepared by using calcined claystone as the main raw material and potassium as the alkaline activator. Chamotte was added (65 vol%) to form geopolymer composites. Potassium hydroxide (KOH) was used to adjust the molar ratio of K/Al and the effect of K/Al on thermo-mechanical properties of geopolymer composites was investigated. This study aimed to analyze the effect of K/Al ratio and exposure to high temperatures (up to 1200 °C) on the compressive and flexural strengths, phase composition, pore size distribution, and thermal dilatation. With an increasing K/Al ratio, the crystallization temperature of the new phases (leucite and kalsilite) decreased. Increasing content of K/Al led to a decline in the onset temperature of the major shrinkage. The average pore size slightly increased with increasing K/Al ratio at laboratory temperature. Mechanical properties of geopolymer composites showed degradation with the increase of the K/Al ratio. The exception was the local maximum at a K/Al ratio equal to one. The results showed that the compressive strength decreases with increasing temperature. For thermal applications above 600 °C, it is better to use samples with lower K/Al ratios (0.55 or 0.70).

Effect of Potassium Phosphate Content in Aluminosilicate Matrix on Mechanical Properties of Carbon Prepreg Composites.

Six matrices based on alkali-activated aluminosilicate with different amounts of potassium phosphate were prepared for the production of six-layer composite plates. The addition of potassium phosphate in the matrix was 2 wt%, 4 wt%, 6 wt%, 8 wt% and 10 wt% of its total weight. The matrix without the potassium phosphate was also prepared. The aim of this study was to determine whether this addition has an effect on the tensile strength or Young's modulus of composites at temperatures up to 800 °C. Changes in the thickness and weight of the samples after this temperature were also monitored. Carbon plain weave fabric was chosen for the preparation of the composites. The results show that under normal conditions, the addition of potassium phosphate has no significant effect on the mechanical properties; the highest measured tensile strengths were around 350 MPa. However, at temperatures of 600 °C and 800 °C the addition of potassium phosphate had a positive effect, with the tensile strength of the composites being up to 300% higher than the composites without the addition. The highest measured values of composites after one hour at 600 °C were higher than 100 MPa and after 1 h at 800 °C higher than 85 MPa.