Relative pharmacokinetics of three amikacin brands in onco-hemotologic pediatric patients experiencing febrile neutropeina.

Three commercially available brands of amikacin were investigated in a parallel study design for the assessment of comparative pharmacokinetics in pediatric oncology patients with chemotherapy-induced neutropenic febrile episode. Amikacin concentration in serum samples was determined by fluorescence polarization immunoassay method using Abbott TDx system. Computer software, PK II was used for computation of pharmacokinetic parameters of amikacin. The serum concentration of all brands nonsignificantly (p > 0.05) varied at all time points, except at 1 and 2 hrs post dosing. At 1 hr post dosing, the serum concentration of brand II varied from rest of two brands. Whereas at 2 hr following I/V infusion, brands II and I were statistically different. Highest serum concentration of 38.69 +/- 1.45 microg/ml was observed in case of brand III while brands I and II showed lower but not significantly different serum concentration values, i.e., 36.30 +/- 1.65 and 37.89 +/- 1.32 microg/ml, respectively when compared with brand I. The other pharmacokinetic parameters of 3 brands found to have non-significant difference (P < 0.05) except, t(1/2)alpha and Cl of brands I and II that deviated statistically significant (p < 0.01). The relative bioavailability of brand II and III as compared with brand I, considered as standard 86.17 and 96.86%, respectively falls within the accepted limits of +/- 20% required for the bioequivalence of any two brands. Based upon findings of the present study, all these brands may be used interchangeably in oncology patients. Further studies, however are needed to determine whether the statistically elevated Cl value in brand II is of any clinical significance.     

Quercetin alters the DNA damage response in human hematopoietic stem and progenitor cells via TopoII‐ and PI3K‐dependent mechanisms synergizing in leukemogenic rearrangements

Quercetin (Que) is an abundant flavonoid in the human diet and high‐concentration food supplement with reported pro‐ and anti‐carcinogenic activities. Topoisomerase II (TopoII) inhibition and subsequent DNA damage induction by Que was implicated in the mixed lineage leukemia gene (MLL) rearrangements that can induce infant and adult leukemias. This notion raised concerns regarding possible genotoxicities of Que in hematopoietic stem and progenitor cells (HSPCs). However, molecular targets mediating Que effects on DNA repair relevant to MLL translocations have not been defined. In this study we describe novel and potentially genotoxic Que activities in suppressing non‐homologous end joining and homologous recombination pathways downstream of MLL cleavage. Using pharmacological dissection of DNA‐PK, ATM and PI3K signalling we defined PI3K inhibition by Que with a concomitant decrease in the abundance of key DNA repair genes to be responsible for DNA repair inhibition. Evidence for the downstream TopoII‐independent mutagenic potential of Que was obtained by documenting further increased frequencies of MLL rearrangements in human HSPCs concomitantly treated with Etoposide and Que versus single treatments. Importantly, by engaging a tissue engineered placental barrier, we have established the extent of Que transplacental transfer and hence provided the evidence for Que reaching fetal HSPCs. Thus, Que exhibits genotoxic effects in human HSPCs via different mechanisms when applied continuously and at high concentrations. In light of the demonstrated Que transfer to the fetal compartment our findings are key to understanding the mechanisms underlying infant leukemia and provide molecular markers for the development of safety values.     

Phase I trial of fludarabine and paclitaxel in non-Hodgkin's lymphoma

Fludarabine is an active agent in low-grade non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Paclitaxel is also active in patients with refractory lymphoma, and preclinical data suggest an additive effect with fludarabine in vitro. We performed a phase I trial of fludarabine (25 mg/m² d 1–3) plus a 3-h infusion of paclitaxel (125, 150, or 175 mg/m²) on d 3 every 28 d in 13 patients with non-Hodgkin’s lymphoma. The paclitaxel dose was escalated in cohorts of 3–4 patients using standard phase I design schema. Dose-limiting toxicity was defined as febrile neutropenia, platelet nadir less than 50,000/μL, or grade 3–4 nonhematologic toxicity. Thirteen patients were accrued to the study, 8 of these 13 patients (62%) had received prior chemotherapy. At the 125-, 150-, and 175-mg/m² dose levels of paclitaxel, dose-limiting toxicity occurred in 1/4, 0/4, and 0/4 patients, respectively. The single patient with dose-limiting toxicity had febrile neutropenia. Partial response occurred in two of eight patients with low-grade lymphoma and none of five patients with other types of lymphoma. A paclitaxel dose of 175 mg/m² given as a 3-h infusion on d 3 in conjunction with fludarabine (25 mg/m² d 1–3 every 4 wk) is a well-tolerated regimen for non-Hodgkin’s lymphoma. Further study will be required in order to determine whether the fludarabine-paclitaxel is more active than fludarabine alone in patients with low-grade lymphoma and chronic lymphocytic leukemia.     

Synthesis of Geopolymer from a Novel Aluminosilicate-Based Natural Soil Precursor Using Electric Oven Curing for Improved Mechanical Strength

Natural soil (NS)-based geopolymers (GPs) have shown promise as environmentally friendly construction materials. The production of ordinary Portland cement is known to release significant amounts of greenhouse gas (CO₂) into the atmosphere. The main objective of this work is to synthesize a geopolymer (GP) from an uncommon aluminosilicate-based NS and a sodium silicate (SS) activating solution that would not only minimize the emission of harmful gases, but also offer improved mechanical strength. Samples of different compositions were produced by varying the wt.% of NS from 50% to 80% and adding a balancing amount of SS solution. The drying and curing of the samples were carried out in an electric oven at specific temperatures. The degree of geopolymerization in the samples was measured by Fourier transform infrared spectroscopy, and microstructural analysis was performed using a scanning electron microscope. Mechanical tests were conducted to evaluate the range of compressive strength values of the prepared GP samples. A minimum compressive strength of 10.93 MPa at a maximum porosity of 37.56% was observed in a sample with an NS to SS ratio of 1:1; while a ratio of 3:1 led to the maximum compressive strength of 26.39 MPa and the minimum porosity of 24.60%. The maximum strength (26.39 MPa) was found to be more than the reported strength values for similar systems. Moreover, an improvement in strength by a factor of three has been observed relative to previously developed NS-based GPs. It may be inferred from the findings that for the given NS, with almost 90% aluminosilicate content, the extent of geopolymerization increases significantly with its increasing proportions, yielding better mechanical strength.     

Study of the Magnetized Hybrid Nanofluid Flow through a Flat Elastic Surface with Applications in Solar Energy

The main theme of the present study is to analyze numerically the effects of the magnetic field on the hybrid nanofluid flow over a flat elastic surface. The effects of the thermal and velocity slips are also analyzed in view of the hybrid nanofluid flow. It is considered a combination of titanium oxide (TiO₂) and copper oxide (CuO) nanoparticles that are suspended in the incompressible and electrically conducting fluid (water). The behavior of the Brownian motion of the nanoparticles and the thermophoretic forces are contemplated in the physical and mathematical formulations. Moreover, the impact of the Joule heating and viscous dissipation are also discussed using the energy equation. The mathematical modeling is simulated with the help of similarity variables. The resulting equations are solved using the Keller–Box method with a combination of finite difference schemes (FDSs). Hybrid nanofluids provide significant advantages over the usual heat transfer fluids. Therefore, the use of nanofluids is beneficial to improve the thermophysical properties of the working fluid. All of the results are discussed for the various physical parameters involved in governing the flow. From the graphical results, it is found that the hybrid nanoparticles improve the concentration, temperature, and velocity profiles, as well as the thickness of the relevant boundary layer. The conjunction of a magnetic field and the velocity slip, strongly opposes the fluid motion. The boundary layer thickness and concentration profile are significantly reduced with the higher levels of the Schmidt number.     

A Study on Sustainable Concrete with Partial Substitution of Cement with Red Mud: A Review

Every year, millions of tons of red mud (RDM) are created across the globe. Its storage is a major environmental issue due to its high basicity and tendency for leaching. This material is often kept in dams, necessitating previous attention to the disposal location, as well as monitoring and maintenance during its useful life. As a result, it is critical to develop an industrial solution capable of consuming large quantities of this substance. Many academics have worked for decades to create different cost-effective methods for using RMD. One of the most cost-effective methods is to use RMD in cement manufacture, which is also an effective approach for large-scale RMD recycling. This article gives an overview of the use of RMD in concrete manufacturing. Other researchers’ backgrounds were considered and examined based on fresh characteristics, mechanical properties, durability, microstructure analysis, and environmental impact analysis. The results show that RMD enhanced the mechanical properties and durability of concrete while reducing its fluidity. Furthermore, by integrating 25% of RDM, the environmental consequences of cumulative energy demand (CED), global warming potential (GWP), and major criteria air pollutants (CO, NO_X, Pb, and SO₂) were minimized. In addition, the review assesses future researcher guidelines for concrete with RDM to improve performance.     

Mechanical and Durability Evaluation of Metakaolin as Cement Replacement Material in Concrete

Due to the increasing prices of cement and its harmful effect on the environment, the use of cement has become highly unsustainable in concrete. There is a considerable need for promoting the use of cement replacement materials. This study investigates the effect of variable percentages of metakaolin (MK) on the mechanical and durability performance of concrete. Kaolin clay (KC) was used in the current research to prepare the MK by the calcination process; it was ground in a ball mill to its maximum achievable fineness value of 2550 m²/Kg. Four replacement levels of MK, i.e., 5%, 10%, 15%, and 20% by weight of cement, in addition to control samples, at a constant water-to-cement (w/c) ratio of 0.55 were used. For evaluating the mechanical and durability performance, 27 cubes (6 in. × 6 in. × 6 in.) and 6 cylinders (3.875 in. diameter, 2 in. height) were cast for each mix. These samples were tested for compressive strength under standard conditions and in an acidic environment, in addition to being subjected to water permeability, sorptivity, and water absorption tests. Chemical analysis revealed that MK could be used as pozzolana as per the American Society for Testing and Materials (ASTM C 618:2003). The results demonstrated an increased compressive strength of concrete owing to an increased percentage of MK in the mix with aging. In particular, the concrete having 20% MK after curing under standard conditions exhibited 33.43% higher compressive strength at 90 days as compared to similarly aged control concrete. However, with increasing MK, the workability of concrete decreased drastically. After being subjected to an acid attack (immersing concrete cubes in 2% sulfuric acid solution), the samples exhibited a significant decrease in compressive strength at 90 days in comparison to those without acid attack at the same age. The density of acid attack increased with increasing MK with a maximum corresponding to 5% MK concrete. The current findings suggest that the local MK has the potential to produce good-quality concrete in a normal environment.     

Improvements in the Engineering Properties of Cementitious Composites Using Nano-Sized Cement and Nano-Sized Additives

The findings of an extensive experimental research study on the usage of nano-sized cement powder and other additives combined to form cement–fine-aggregate matrices are discussed in this work. In the laboratory, dry and wet methods were used to create nano-sized cements. The influence of these nano-sized cements, nano-silica fumes, and nano-fly ash in different proportions was studied to the evaluate the engineering properties of the cement–fine-aggregate matrices concerning normal-sized, commercially available cement. The composites produced with modified cement–fine-aggregate matrices were subjected to microscopic-scale analyses using a petrographic microscope, a Scanning Electron Microscope (SEM), and a Transmission Electron Microscope (TEM). These studies unravelled the placement and behaviour of additives in controlling the engineering properties of the mix. The test results indicated that nano-cement and nano-sized particles improved the engineering properties of the hardened cement matrix. The wet-ground nano-cement showed the best result, 40 MPa 28th-day compressive strength, without mixing any additive compared with ordinary and dry-ground cements. The mix containing 50:50 normal and wet-ground cement exhibited 37.20 MPa 28th-day compressive strength. All other mixes with nano-sized dry cement, silica fume, and fly ash with different permutations and combinations gave better results than the normal-cement–fine-aggregate mix. The petrographic studies and the Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) analyses further validated the above findings. Statistical analyses and techniques such as correlation and stepwise multiple regression analysis were conducted to compose a predictive equation to calculate the 28th-day compressive strength. In addition to these methods, a repeated measures Analysis of Variance (ANOVA) was also implemented to analyse the statistically significant differences among three differently timed strength readings.