Considerations in Modeling Cell Death Processes

Author(s):  
John A. Pearce

Traditional single-reaction Arrhenius models have been successfully used for many years in burn studies[1–3] and have been adapted and used to predict quantitative histologic results in laser, RF and microwave heating at high temperatures.[4–6] The single reaction kinetics model also forms the basis for the time scaling ratio as is currently used in calculating the cumulative equivalent minutes (CEM) assessment of tumor hyperthermia treatments.[7] Recently, it has been clearly demonstrated that these models are not acceptably accurate predictors of the early stages of cell death processes in hyperthermic heating — moderate temperature rises (< ∼15 C) for times from several minutes to hours.[8, 9] A typical ensemble of cell survival curves has an initial slowly-developing shoulder region, a constant-rate region and, often, a “foot’, as it were, which has a much slower death rate. Simple first-order Arrhenius predictions are constant-rate models, only, and substantially over-estimate population cell death in the early stages of heating.

2015 ◽  
Vol 137 (12) ◽  
Author(s):  
John A. Pearce

The Arrhenius formulation for single-step irreversible unimolecular reactions has been used for many decades to describe the thermal damage and cell death processes. Arrhenius predictions are acceptably accurate for structural proteins, for some cell death assays, and for cell death at higher temperatures in most cell lines, above about 55 °C. However, in many cases—and particularly at hyperthermic temperatures, between about 43 and 55 °C—the particular intrinsic cell death or damage process under study exhibits a significant “shoulder” region that constant-rate Arrhenius models are unable to represent with acceptable accuracy. The primary limitation is that Arrhenius calculations always overestimate the cell death fraction, which leads to severely overoptimistic predictions of heating effectiveness in tumor treatment. Several more sophisticated mathematical model approaches have been suggested and show much-improved performance. But simpler models that have adequate accuracy would provide useful and practical alternatives to intricate biochemical analyses. Typical transient intrinsic cell death processes at hyperthermic temperatures consist of a slowly developing shoulder region followed by an essentially constant-rate region. The shoulder regions have been demonstrated to arise chiefly from complex functional protein signaling cascades that generate delays in the onset of the constant-rate region, but may involve heat shock protein activity as well. This paper shows that acceptably accurate and much-improved predictions in the simpler Arrhenius models can be obtained by adding a temperature-dependent time delay. Kinetic coefficients and the appropriate time delay are obtained from the constant-rate regions of the measured survival curves. The resulting predictions are seen to provide acceptably accurate results while not overestimating cell death. The method can be relatively easily incorporated into numerical models. Additionally, evidence is presented to support the application of compensation law behavior to the cell death processes—that is, the strong correlation between the kinetic coefficients, ln{A} and Ea, is confirmed.


2016 ◽  
Vol 81 (6) ◽  
pp. 697-705 ◽  
Author(s):  
Xuepeng Yang ◽  
Yan Ji ◽  
Fangfang Wang ◽  
Jia Xu ◽  
Xiangzhen Liu ◽  
...  

Vibrio fischeri bioluminescence inhibition has been widely used to test acute toxicities of metals and organics contaminants. However, the differences of metals and organics acute toxicities to V. fischeri have not been compared. Here, four heavy metals (Zn2+, Cu2+, Cd2+, Cr6+) and five organics (phenol, benzoic acid, p-hydroxy benzoic acid, nitro-benzene and benzene) acute toxicities to V. fischeri were investigated. Heavy metals toxicities to V. fischeri were increased along with the reaction time, while the organics toxicities kept the same level in different reaction times. In order to explain the difference, the relative cell death rate of V. fischeri was detected. In metals toxicities tests, the bioluminescence inhibition rate of V. fischeri was found to be significantly higher than the relative cell death rate (P<0.05), while for the organics toxicities tests, the cell death rate was similar to the bioluminescence inhibition rate. These results indicated that organics acute toxicities to V. fischeri could reflect the death of cell, but metals acute toxicities to V. fischeri may not lead to the death of cell, just represent the bioluminescence inhibition.


1989 ◽  
Vol 37 (1) ◽  
pp. 47-60
Author(s):  
S.E.A.T.M. van der Zee ◽  
W.H. van Riemsdijk ◽  
J.J.M. van Grinsven

The interpolation or extrapolation in time of physicochemical processes from experimental data is often difficult. A theoretically derived time-scaling procedure using an exposure variable of the concentration integrated in time, with at most one adjustable parameter was applied successfully to three systems taken from metallurgical, agricultural and environmental engineering. This scaling rule is potentially useful as a research or management tool for systems that are too complex for mechanistic modelling. (Abstract retrieved from CAB Abstracts by CABI’s permission)


2005 ◽  
Vol 96 (2) ◽  
pp. 337-342 ◽  
Author(s):  
KEIKO YOSHINAGA ◽  
SHIN-ICHI ARIMURA ◽  
YASUO NIWA ◽  
NOBUHIRO TSUTSUMI ◽  
HIROFUMI UCHIMIYA ◽  
...  

1982 ◽  
Vol 49 (2) ◽  
pp. 329-336 ◽  
Author(s):  
Richard J. Marshall

SummaryIn this method, the curd, formed in a beaker, was retained after cutting by means of a wire grid placed on top of it. This enabled the whey to be poured off easily at timed intervals for measurement of its volume. The method gave results reproducible within 1·5%. Increasing the amount of rennet added to the milk increased the rate of syneresis of the curd slightly. Adding CaCl2 to the milk, raising the temperature and decreasing the pH, all increased the rate of syneresis. Addition of fat, as cream, to skim-milk decreased the rate of syneresis proportionally. The rate of syneresis was decreased if the milk was concentrated by ultrafiltration and increased if the milk was diluted with permeate. In all instances the early stages of syneresis followed first-order kinetics, the rate depending on the amount of whey remaining within the curd. The later stages of syneresis appeared to depend on hydrophobic forces. Probably, the increasing aggregation of the casein within the curd caused the whey to be squeezed out.


2012 ◽  
Vol 38 (3) ◽  
pp. 419-425 ◽  
Author(s):  
Guilherme Fartes ◽  
Fábio Lorenzetti ◽  
Larissa Beloti Salvador ◽  
Valdemar Ortiz ◽  
Miriam Dambros

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