Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue

Introduction

Left ventricular dysfunction is a frequent and potentially severe side effect of many tyrosine kinase inhibitors (TKI). The mode of toxicity is not identified, but may include impairment of mitochondrial or sarcomeric function, autophagy or angiogenesis, either as an on-target or off-target mechanism.

Methods and Results

We studied concentration-response curves and time courses for nine TKIs in three-dimensional, force generating engineered heart tissue (EHT) from neonatal rat heart cells. We detected a concentration- and time-dependent decline in contractile force for gefitinib, lapatinib, sunitinib, imatinib, sorafenib, vandetanib and lestaurtinib and no decline in contractile force for erlotinib and dasatinib after 96 hours of incubation. The decline in contractile force was associated with an impairment of autophagy (LC3 Western blot) and appearance of autophagolysosomes (transmission electron microscopy).

Conclusion

This study demonstrates the feasibility to study TKI-mediated force effects in EHTs and identifies an association between a decline in contractility and inhibition of autophagic flux.     

Bacillusstearothermophilus from Saudi Arabian soils

Ten thermophilic Gram-positive bacteria were isolated from various soils of Saudi Arabia. The strains are spore-forming rods belonging to the speciesBacillus stearothermophilus. The cells are motile, strictly aerobic, catalase and oxidase positive. The sporangia appear to be swollen and their position varies from terminal in some to sub-terminal in others. The thermal stability of some enzymes of these bacteria was investigated; extracellular α-amylase appears to be very sensitive to pH and temperature. The ultrastructure of these bacteria shows specific changes in the cell wall when grown at the maximum, minimum and optimum growth temperatures, respectively.     

Guaianolides from the leaves of Centaurea incana

Six guaianolides have been isolated from the aerial parts of Centaurea incana from Algeria. They were identified as desoxyrepin, repin or subluteolide, repin monochlorhydrin, acroptilin, janerin and repdiolide triol.     

Complex permittivity of representative biological solutions in the 2–67 GHz range

The main purpose of this study is to provide experimental data on the complex permittivity of some biological solutions in the 2–67 GHz range at room and human body temperatures. The permittivity measurements are performed using an open‐ended coaxial probe. Permittivity spectra of several representative monomolecular solutions of proteins, amino acids, nucleic acids, and carbohydrates are analyzed and compared. Furthermore, measurements have also been performed for complex biomolecular solutions, including bovine serum albumin (BSA)–DNA–glucose mixture, culture medium, and yeast extract solution. The results demonstrate that for concentrations below 1%, the permittivity spectra of the solutions do not substantially differ from that of distilled water. Measurements carried out for 4% and 20% BSA solutions show that the presence of proteins results in a decrease in permittivity. For highly concentrated RNA solutions (3%), a slight increase in the imaginary part of the permittivity is observed below 10 GHz. Experimental data show that free water permittivity can be used for modeling of the culture medium above 10 GHz. However, at lower frequencies a substantial increase in the imaginary part of the permittivity due to ionic conductivity should be carefully taken into account. A similar increase has also been observed for the yeast extract solution in the lower frequency region of the considered spectrum. Above 10 GHz, the high concentration of proteins and other low‐permittivity components of the yeast extract solution results in a decrease in the complex permittivity compared to that of water. Obtained data are of utmost importance for millimeter‐wave dosimetry studies. Bioelectromagnetics 33:346–355, 2012. © 2011 Wiley Periodicals, Inc.