Environmental health & biomedicine

Selected conference papers.(AU)

Neurochemical bases of visceral nociception: mathematical model.

A mathematical model of visceral perception was constructed, comprising primary sensory, motor, intestinofugal and principal neurons, interstitial cells of Cajal and smooth muscle elements that are arranged in a functional circuit through chemical synapses. The mathematical description of constructive elements was based on detailed morphological, anatomical, electrophysiological and neuropharmacological characteristics of cells and chemical processes of electrochemical coupling. Emphasis was given to signal transduction mechanisms that involved multiple neurotransmitters and receptor polymodality. The role of co-transmission by acetylcholine (ACh), serotonin (5-HT), noradrenalin (NA), N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and their corresponding receptors-muscarinic and nicotinic type ACh receptors, beta-adrenoceptors, 5-HT(3/4) type serotonergic receptors, NMDA and AMPA receptors in pathogenesis of nociception was studied numerically. Results of computer simulations reproduced patterns of electrical activity of neurons and mechanical responses of the smooth muscle similar to those observed in in vivo and in vitro experiments when ACh, 5-HT, NA, NMDA and AMPA were acting either alone or co-jointly. The results provide neurochemical bases for explanation of pathophysiological mechanisms of visceral nociception, which cannot be elucidated by existing experimental methods. Care should be taken though when extrapolating the numerical results onto the actual system because of limiting assumptions of the model.

Dynamics of intestinal propulsion.

A biomechanical model and mathematical formulation of the problem of propulsion of a solid non-deformable pellet by an isolated segment of the gut are presented. The organ is modeled as a soft orthotropic cylindrical biological shell. Its wall is reinforced by transversely isotropic muscle fibers of orthogonal type of weaving embedded in a connective tissue stroma. The mechanical properties of the wall are assumed to be nonlinear, deformations are finite. The longitudinal smooth muscle syncitium possesses anisotropic and the circular muscle syncytium has anisotropic electrical properties. Their electromechanical activity is under control of a pacemaker, which is represented by interstitial cells of Cajal. The model describes the dynamics of the generation and propagation of mechanical waves of contraction-relaxation along the surface of the bioshell and propulsion of the pellet. The governing system of equations was solved numerically. The combined finite-difference and finite-element method was used. The results demonstrate that pendular movements alone provide an aboral transit, without mixing though, of the bolus. Non-propagating segmental contractions show small amplitude librations of the pellet without its visible propulsion. Only the coordinated activity of both smooth muscle layers in a form of the peristaltic reflex provides physiologically significant simultaneous propulsion and mixing of the intraluminal content (pellet).

Intestinal propulsion of a solid non-deformable bolus.

A mathematical model of a segment of the gut with an enclosed pellet is constructed. The gut is represented as a thin deformable soft biological shell with the pellet modeled as a non-deformable solid. Mechanical properties of the gut wall were represented as longitudinal and circular smooth muscle layers embedded in stroma that satisfies the general type of nonlinear orthotropy. Deformations of the wall are finite. Bolus propulsion is numerically simulated by generation and propagation of an electromechanical wave along the syncytia. Pharmacological manipulation is applied to model 5-HT type 3 antagonist (Lotronex, GlaxoSmithKline) and 5-HT type 4 agonist (Zelnorm, Novartis, AB) drugs on the dynamics of bolus progression. The results lead to new quantitative insights into the complex spatio-temporal patterns of gastrointestinal transit. It is demonstrated that the reciprocal relationship in contraction of the longitudinal and circular smooth muscle syncytia is necessary to provide the "mixing" type of movements during the preparatory phase of propulsion. Strong simultaneous contractions of the both smooth muscle layers are required to expel the "mixed" pellet from the segment. The model is implemented as an interactive software system, Gut Discovery(www.aincompany.com), and accurately predicts the effects of drugs on gut motility.