Ultrastructural detection in vitro of WGA-, RCAI-, and Con A-binding sites involved in the invasion of heart muscle cells byTrypanosoma cruzi

1992 ◽  
Vol 78 (5) ◽  
pp. 404-409 ◽  
Author(s):  
Helene S. Barbosa ◽  
Maria de Nazareth ◽  
S. L. de Meirelles
2020 ◽  
Vol 122 (4) ◽  
pp. 209-257 ◽  
Author(s):  
Philipp Kügler

Abstract As a potentially life threatening side effect, pharmaceutical compounds may trigger cardiac arrhythmias by impeding the heart’s electrical and mechanical function. For this reason, any new compound needs to be tested since 2005 for its proarrhythmic risk both during the preclinical and the clinical phase of the drug development process. While intensive monitoring of cardiac activity during clinical tests with human volunteers constitutes a major cost factor, preclinical in vitro tests with non cardiac cells and in vivo tests with animals are currently under serious debate because of their poor extrapolation to drug cardiotoxicity in humans. For about five years now, regulatory agencies, industry and academia are working on an overhaul of the cardiac drug safety paradigm that is built a) on human heart muscle cells, that can be abundantly bioengineered from donor stem cells without ethical concerns (human induced pluripotent stem cell derived cardiomyocytes, hiPSC-CMs), and b) on computational models of human cardiac electrophysiology both at the cellular and the organ level. The combined use of such human in vitro and human in silico models during the preclinical phase is expected to improve proarrhythmia test specificity (i.e. to lower the false-positive rate), to better inform about the need of thorough heart monitoring in the clinic, and to reduce or even replace animal experiments. This review article starts by concisely informing about the electrical activity of the human heart, about its possible impairment due to drug side effects, and about hiPSC-CM assays for cardiac drug safety testing. It then summarizes the mathematical description of human cardiac electrophysiology in terms of mechanistic ODE and PDE models, and illustrates how their numerical analysis may provide insight into the genesis of drug induced arrhythmias. Finally, this paper surveys proarrhythmic risk estimation methods, that involve the simulation of human heart muscle cells, and addresses opportunities and challenges for future interdisciplinary research.


Author(s):  
K. Werdan ◽  
B. Zwißler ◽  
B. Wagenknecht ◽  
W. Krawietz ◽  
E. Erdmann

2019 ◽  
Vol 279 (3) ◽  
pp. 189-196 ◽  
Author(s):  
B. VANSLEMBROUCK ◽  
A. KREMER ◽  
F. VAN ROY ◽  
S. LIPPENS ◽  
J. VAN HENGEL

1984 ◽  
Vol 98 (2) ◽  
pp. 1088-1091
Author(s):  
N. V. Dmitrieva ◽  
E. I. Shtresgeim ◽  
N. A. Burnashev ◽  
V. V. Chernokhvostov

1979 ◽  
Vol 236 (2) ◽  
pp. H189-H199 ◽  
Author(s):  
H. G. Glitsch

An active Na transport maintains the Na and K concentration gradients across the cell membrane of many cells and restores them following excitation. Heart muscle cells display frequent electrical discharges and thus the cardiac Na pump is of fundamental functional significance. Some methods for studying active Na transport are described. The active Na efflux from heart muscle cells is activated by an increase in the intracellular Na and the extracellular K concentration. The linkage between active Na efflux and active K influx varies widely according to the experimental conditions. The cardiac Na pump is electrogenic and can contribute directly to the membrane potential of the cells. The effects of active Na transport on contraction and intercellular coupling in myocardium are discussed.


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