On the dynamics of the adenylate energy system: homeorhesis vs homeostasis.

Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life

CT/SPECT image fusion in patients treated with iodine-131

Computer tomography gives visualization of anatomical structures and abnormalities, but it lacks of functional information. On the other hand, single photon emission tomography provides the missing information about the tumour function, but it has relative low resolution and the localization of the visible focus may be difficult, especially when iodine ¹³¹I is used. Thus, several methods of image fusion are applied. We present an algorithm of image fusion based on affine transformation. On the base of a phantom study, we showed that the created program can be a useful tool to fuse CT and SPECT images and then applied to patients' datasets. External marker method was used to align patient functional and anatomical data. Image alignment quality depends on appropriate marker placement and acquisition protocol. The program estimates maximal misalignment in a volume between the markers. Created acquisition protocol minimizes misalignment of patient placement on both CT and gamma camera, however misalignment derived from respiratory movements cannot be avoided. The proposed technique is simple, low-cost and can be easily adopted in any hospital or diagnostic centre equipped with gamma camera and CT. Fusion of morphology and function can improve diagnostic accuracy in many clinical circumstances