Comparison of Repeated Doses of C-kit-Positive Cardiac Cells versus a Single Equivalent Combined Dose in a Murine Model of Chronic Ischemic Cardiomyopathy

Using a murine model of chronic ischemic cardiomyopathy caused by an old myocardial infarction (MI), we have previously found that three doses of 1 × 10⁶ c-kit positive cardiac cells (CPCs) are more effective than a single dose of 1 × 10⁶ cells. The goal of this study was to determine whether the beneficial effects of three doses of CPCs (1 × 10⁶ cells each) can be fully replicated by a single combined dose of 3 × 10⁶ CPCs. Mice underwent a 60-min coronary occlusion; after 90 days of reperfusion, they received three echo-guided intraventricular infusions at 5-week intervals: (1) vehicle × 3; (2) one combined dose of CPCs (3 × 10⁶) and vehicle × 2; or (3) three doses of CPCs (1 × 10⁶ each). In the combined-dose group, left ventricular ejection fraction (LVEF) improved after the 1st CPC infusion, but not after the 2nd and 3rd (vehicle) infusions. In contrast, in the multiple-dose group, LVEF increased after each CPC infusion; at the final echo, LVEF averaged 35.2 ± 0.6% (p < 0.001 vs. the vehicle group, 27.3 ± 0.2%). At the end of the study, the total cumulative change in EF from pretreatment values was numerically greater in the multiple-dose group (6.6 ± 0.6%) than in the combined-dose group (4.8 ± 0.8%), although the difference was not statistically significant (p = 0.08). Hemodynamic studies showed that several parameters of LV function in the multiple-dose group were numerically greater than in the combined-dose group (p = 0.08 for the difference in LVEF). Compared with vehicle, cardiomyocyte cross-sectional area was reduced only in the multiple-dose group (−32.7%, 182.6 ± 15.1 µm² vs. 271.5 ± 27.2 µm², p < 0.05, in the risk region and −28.5%, 148.5 ± 12.1 µm² vs. 207.6 ± 20.5 µm², p < 0.05, in the noninfarcted region). LV weight/body weight ratio and LV weight/tibia length ratios were significantly reduced in both cell treated groups vs. the vehicle group, indicating the attenuation of LV hypertrophy; however, the lung weight/body weight ratio was significantly reduced only in the multiple-dose group, suggesting decreased pulmonary congestion. Taken together, these results indicate that in mice with chronic ischemic cardiomyopathy, the beneficial effects of three doses of CPCs on LV function and hypertrophy cannot be fully replicated with a single dose, notwithstanding the fact that the total number of cells delivered with one or three doses is the same. Thus, it is the multiplicity of doses, and not the total number of cells, that accounts for the superiority of the repeated-dose paradigm. This study supports the idea that the efficacy of cell therapy in heart failure can be augmented by repeated administrations.     

pH Responsive Abelmoschus esculentus Mucilage and Administration of Methotrexate: In-Vitro Antitumor and In-Vivo Toxicity Evaluation

The rapid progression in biomaterial nanotechnology apprehends the potential of non-toxic and potent polysaccharide delivery modules to overcome oral chemotherapeutic challenges. The present study is aimed to design, fabricate and characterize polysaccharide nanoparticles for methotrexate (MTX) delivery. The nanoparticles (NPs) were prepared by Abelmoschus esculentus mucilage (AEM) and chitosan (CS) by the modified coacervation method, followed by ultra-sonification. The NPs showed much better pharmaceutical properties with a spherical shape and smooth surface of 213.4–254.2 nm with PDI ranging between 0.279–0.485 size with entrapment efficiency varying from 42.08 ± 1.2 to 72.23 ± 2.0. The results revealed NPs to possess positive zeta potential and a low polydispersity index (PDI). The in-vitro drug release showed a sustained release of the drug up to 32 h with pH-dependence. Blank AEM -CS NPs showed no in-vivo toxicity for a time duration of 14 days, accompanied by high cytotoxic effects of optimized MTX loaded NPs against MCF-7 and MD-MBA231 cells by MTT assay. In conclusion, the findings advocated the therapeutic potential of AEM/CS NPs as an efficacious tool, offering a new perspective for pH-responsive routing of anticancer drugs with tumor cells as a target.     

Analysis of a novel metal hydride cycle for simultaneous heating and cooling

Out of the many promising applications of metal hydrides, refrigeration, heat pumping and heat transformation are important. In order to achieve improved performance, a novel three-alloy cycle is proposed in which, for heat input at an intermediate temperature, heat outputs at high temperature and also at warm temperature are obtained in addition to refrigeration. The performance of this cycle using the alloys LaNi_4.6Sn_0.4, LaNi_4.7Al_0.3 and MmNi_4.5Al_0.5 is studied based on thermodynamics and reaction kinetics. Coefficients of performance, half-cycle times and specific alloy outputs are evaluated.     

Thermal Annealing of Gold Thin Films on the Structure and Surface Morphology Using RF Magnetron Sputtering

Gold(Au)thin films were deposited on SiO2 substrate under argon(Ar)gas environment using RF(radio frequency)magnetron sputtering at room temperature for various...     

A scalable sparse Cholesky based approach for learning high-dimensional covariance matrices in ordered data

Machine Learning - Covariance estimation for high-dimensional datasets is a fundamental problem in machine learning, and has numerous applications. In these high-dimensional settings the number of...     

An optimized skin texture model using gray-level co-occurrence matrix

Neural Computing and Applications - Texture analysis is devised to address the weakness of color-based image segmentation models by considering the statistical and spatial relations among the group...     

DOE applied to multi-response optimisation study on performance,combustion and emission characteristics of a VCR diesel engine

There are various parameters which may influence the IC engine performance. The trial and error method is a technique used to identify the best parameters. However, this method demands extensive experimental work and results in a great waste of time and resources. Thus, the design of experiments (DOEs) developed by Taguchi is employed. The multi-responses which need to be maximised are brake thermal efficiency, mechanical efficiency, cylinder pressure and cumulative heat release rate, whereas the responses which are to be minimised are specific fuel consumption, oxides of nitrogen and carbon monoxide. In the present study, an optimised DOE(L9) orthogonal array based on the Taguchi statistical method was formulated and a series of experiments were conducted under controlled supervision by considering three different injection operating pressures (IOPs) (200, 220 and 240 bar) and three different compression ratios (CRs) (16.5, 17.5 and 18.5). The main objective of this paper is to find the best suited IOP and CR values which obtain higher performance, better combustion and lower emissions.