Theoretical Biology and Medical Modelling

A novel approach to the analysis of human growth.

Publication Date: 2012 May 17 PMID: 22594680
Authors: Gliozzi, A. S. - Guiot, C. - Delsanto, P. P. - Iordache, D. A.
Journal: Theor Biol Med Model

ABSTRACT: Objectives: Several formulations have been proposed in order to model human growth from birth to maturity. They are usually based on "ad hoc" heuristic assumptions. In the present contribution we adopt, as an alternative, a completely general (interdisciplinary) approach, based on the formalism of the Phenomenological Universalities (PUN). METHODS: The main PUN class investigated to date, i.e. UN, can only account for the overall growth pattern. For a realistic description it is necessary to add to it one or more "spurts", as expected on biological grounds, due to the stimulation of growth and sex hormones. RESULTS: A new PUN class (UN+FM ) is generated and shown to be able to provide excellent agreement with standard auxological datasets. The accuracy of the fitting and reliability of the model suggest applications both at the diagnostic and therapeutic level. CONCLUSIONS: The developed formalism can be suitably related to the biological description of bone plate growth under selective hormonal stimulation on the bone epiphysis; i.e., the additional increase of stature is the "macroscopic" response to a well defined biological signal.

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Bariatric surgery and T2DM improvement mechanisms: a mathematical model.

Publication Date: 2012 May 15 PMID: 22587410
Authors: Toghaw, P. - Matone, A. - Lenbury, Y. - De Gaetano, A.
Journal: Theor Biol Med Model

ABSTRACT: BACKGROUND: Consensus exists that several bariatric surgery procedures produce a rapid improvement of glucose homeostasis in obese diabetic patients, improvement apparently uncorrelated with the degree of eventual weight loss after surgery. Several hypotheses have been suggested to account for these results: among these, the anti-incretin, the ghrelin and the lower-intestinal dumping hypotheses have been discussed in the literature. Since no clear-cut experimental results are so far available to confirm or disprove any of these hypotheses, in the present work a mathematical model of the glucose-insulin-incretin system has been built, capable of expressing these three postulated mechanisms. The model has been populated with critically evaluated parameter values from the literature, and simulations under the three scenarios have been compared. RESULTS: The modeling results seem to indicate that the suppression of ghrelin release is unlikely to determine major changes in short-term glucose control. The possible existence of an anti-incretin hormone would be supported if an experimental increase of GIP concentrations were evident post-surgery. Given that, on the contrary, collected evidence suggests that GIP concentrations decrease postsurgery, the lower-intestinal dumping hypothesis would seem to describe the mechanism most likely to produce the observed normalization of Type 2 Diabetes Mellitus (T2DM) after bariatric surgery. CONCLUSIONS: The proposed model can help discriminate among competing hypotheses in a context where definitive data are not available and mechanisms are still not clear.

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The allometric model in chronic myocardial infarction.

Publication Date: 2012 May 11 PMID: 22578057
Authors: Bonomini, M. P. - Valentinuzzi, M. E. - Arini, P. D. - Gonzalez, G. E. - Buchholz, B.
Journal: Theor Biol Med Model

ABSTRACT: BACKGROUND: An allometric relationship between different electrocardiogram (ECG) parameters and infarcted ventricular mass was assessed in ten New Zealand rabbits. METHODS: Animals underwent left anterior descending coronary artery ligation to provoke infarction (7-35% area). Myocardial infarction (MI) evolved and stabilized during a three month-period, after which, rabbits were sacrificed and the injured area was histologically confirmed. Right before sacrifice, ECGs were obtained to correlate several of its parameters to the infarcted mass. The latter was normalized after combining data from planimetry measurements and heart weight. The following ECG parameters were studied: RR (RR) and PR intervals (PR), P-wave duration (PD), QRS complex duration (QRSD) and amplitude (QRSA), Q-wave (QA), R-wave (RA) and S-wave (SA) amplitudes, T-wave peak amplitude (TA), the interval from the peak to the end of the T-wave (TPE), ST segment deviation (STA), QT interval (QT), corrected QT and JT (JT) intervals. Corrected QT was analyzed with different QT correction formulae (Bazett (QTB), Framingham (QTFRA), Fridericia (QTFRI), Hodge (QTHO) and Matsunaga (QTMA)) and compared thereafter. The former variables and infarcted ventricular mass were also fitted to the allometric equation. RESULTS: Six variables (JT, QTB, QA, SA, TA and STA) presented statistical differences among leads. QA showed the best allometric fit (r=0.83), followed by the STA (r=0.73), SA (r=0.71) and TPE (r=0.68). Corrected QT's and the uncorrected counterpart performed alike (QT, QTFRA and QTFRI), scaling allometrically with similar goodness of fits. CONCLUSIONS: QA could possibly be used to assess infarction extent in an old MI event as a first approach.

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Numerical test concerning bone mass apposition under electrical and mechanical stimulus.

Publication Date: 2012 May 11 PMID: 22578031
Authors: Garzon Alvarado, D. A. - Ramirez-Martinez, A. M. - Cardozo de Martinez, C. A.
Journal: Theor Biol Med Model

ABSTRACT: This article proposes a model of bone remodeling that encompasses mechanical and electrical stimuli. The remodeling formulation proposed by Weinans and collaborators was used as the basis of this research, with a literature review allowing a constitutive model evaluating the permittivity of bone tissue to be developed. This allowed the mass distribution that depends on mechanical and electrical stimuli to be obtained. The remaining constants were established through numerical experimentation. The results demonstrate that mass distribution is altered under electrical stimulation, generally resulting in a greater deposition of mass. In addition, the frequency of application of an electric field can affect the distribution of mass; at a lower frequency there is more mass in the domain. These numerical experiments open up discussion concerning the importance of the electric field in the remodeling process and propose the quantification of their effects.

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