Computational model for the analysis of cartilage and cartilage tissue constructs.

We propose a new non-linear poroelastic model that is suited to the analysis of soft tissues. In this paper the model is tailored to the analysis of cartilage and the engineering design of cartilage constructs. The proposed continuum formulation of the governing equations enables the strain of the individual material components within the extracellular matrix (ECM) to be followed over time, as the individual material components are synthesized, assembled and incorporated within the ECM or lost through passive transport or degradation. The material component analysis developed here naturally captures the effect of time-dependent changes of ECM composition on the deformation and internal stress states of the ECM. For example, it is shown that increased synthesis of aggrecan by chondrocytes embedded within a decellularized cartilage matrix initially devoid of aggrecan results in osmotic expansion of the newly synthesized proteoglycan matrix and tension within the structural collagen network. Specifically, we predict that the collagen network experiences a tensile strain, with a maximum of ~2% at the fixed base of the cartilage. The analysis of an example problem demonstrates the temporal and spatial evolution of the stresses and strains in each component of a self-equilibrating composite tissue construct, and the role played by the flux of water through the tissue.

Multiscale modeling of gastrointestinal electrophysiology and experimental validation.

Normal gastrointestinal (GI) motility results from the coordinated interplay of multiple cooperating mechanisms, both intrinsic and extrinsic to the GI tract. A fundamental component of this activity is an omnipresent electrical activity termed slow waves, which is generated and propagated by the interstitial cells of Cajal (ICCs). The role of ICC loss and network degradation in GI motility disorders is a significant area of ongoing research. This review examines recent progress in the multiscale modeling framework for effectively integrating a vast range of experimental data in GI electrophysiology, and outlines the prospect of how modeling can provide new insights into GI function in health and disease. The review begins with an overview of the GI tract and its electrophysiology, and then focuses on recent work on modeling GI electrical activity, spanning from cell to body biophysical scales. Mathematical cell models of the ICCs and smooth muscle cell are presented. The continuum framework of monodomain and bidomain models for tissue and organ models are then considered, and the forward techniques used to model the resultant body surface potential and magnetic field are discussed. The review then outlines recent progress in experimental support and validation of modeling, and concludes with a discussion on potential future research directions in this field.

A mathematical model of fatigue in skeletal muscle force contraction.

The ability for muscle to repeatedly generate force is limited by fatigue. The cellular mechanisms behind muscle fatigue are complex and potentially include breakdown at many points along the excitation-contraction pathway. In this paper we construct a mathematical model of the skeletal muscle excitation-contraction pathway based on the cellular biochemical events that link excitation to contraction. The model includes descriptions of membrane voltage, calcium cycling and crossbridge dynamics and was parameterised and validated using the response characteristics of mouse skeletal muscle to a range of electrical stimuli. This model was used to uncover the complexities of skeletal muscle fatigue. We also parameterised our model to describe force kinetics in fast and slow twitch fibre types, which have a number of biochemical and biophysical differences. How these differences interact to generate different force/fatigue responses in fast- and slow- twitch fibres is not well understood and we used our modelling approach to bring new insights to this relationship.

Anatomically based lower limb nerve model for electrical stimulation.

BACKGROUND: Functional Electrical Stimulation (FES) is a technique that aims to rehabilitate or restore functionality of skeletal muscles using external electrical stimulation. Despite the success achieved within the field of FES, there are still a number of questions that remain unanswered. One way of providing input to the answers is through the use of computational models. METHODS: This paper describes the development of an anatomically based computer model of the motor neurons in the lower limb of the human leg and shows how it can be used to simulate electrical signal propagation from the beginning of the sciatic nerve to a skeletal muscle. One-dimensional cubic Hermite finite elements were used to represent the major portions of the lower limb nerves. These elements were fit to data that had been digitised using images from the Visible Man project. Nerves smaller than approximately 1 mm could not be seen in the images, and thus a tree-branching algorithm was used to connect the ends of the fitted nerve model to the respective skeletal muscle. To simulate electrical propagation, a previously published mammalian nerve model was implemented and solved on the anatomically based nerve mesh using a finite difference method. The grid points for the finite difference method were derived from the fitted finite element mesh. By adjusting the tree-branching algorithm, it is possible to represent different levels of motor-unit recruitment. RESULTS: To illustrate the process of a propagating nerve stimulus to a muscle in detail, the above method was applied to the nerve tree that connects to the human semitendinosus muscle. A conduction velocity of 89.8 m/s was obtained for a 15 mum diameter nerve fibre. This signal was successfully propagated down the motor neurons to a selected group of motor units in the muscle. CONCLUSION: An anatomically and physiologically based model of the posterior motor neurons in the human lower limb was developed. This model can be used to examine the effect of external stimulation on nerve and muscle activity, as may occur, for example, in the field of FES.

Stimulation of insulin secretion by extracts of piper tuberculatum - abstract

Piper tuberculatum, locally known as candle-bush, is widely used in folk medicine in Trinidad and Tobago in the control of diabetes mellitus. It is commonly administered as a tea prepared from the leaves of the plant. This study was undertaken to investigate the hypoglycaemic activity (if any) of the plant, to identify and partially purify the active component and to obtain some information on the mechanism(s) of action. A methanol extract of leaves of the plant was screened for hypoglycaemic activity. The chloroform phase obtained from a chloroform form/H[2]O partition of the extract contained the active component which was further partially purified by column and thin-layer chromatography. Based on the chromatographic behaviour and HNMR spectroscopy, the active component was indentified as an amide alkaloid, most likely piplartine or a closely related derivative. The hypoglycaemic activity of the component, as tested on streptozotocin-diabetic rats, was found to be similar to that of an authentic sample of piplartine. The partially purified active component produced an increase in phospholipase C activity of the plasma membrane of pancreatic islet cells and induced insulin secretion in diabetic rats. The exact mechanism of the stimulation of insulin release requires further investigation but may be similar to that of sulphonylureas (AU)

Effect of alcohol on serum lipids in diabetes

This report emanated from a three-year study conducted at the Diabetic Outpatient Clinics convened at the Port-of-Spain and Sangre-Grande Hospitals in Trinidad. The diabetic population which participated consisted of 132 men and 245 women of African descent; and 99 men and 163 women of East Indian origin. The mean age was 50 years (ñ13). The effect of alcohol on lipid fractions varied in the two races. A lower incidence of ischaemic heart disease was observed among the alcohol consumers when compared to those who abstained (AU)

The effect of demographic factors on serum lipids in diabetics of Trinidad and Tobago: possible association with ischaemic heart disease

This study was undertaken in order to investigate the effect of race, sex, weight, activity level and residential area on serum lipoprotein patterns, and to determine how this could possibly relate to the incidence ofischaemic heart disease (IHD). Seven hundred (700) diabetics attending outpatient clinics at Sangre-Grande and Port-of-Spain hospitals were screened. There were 132 males and 249 females of African descent; 99 males and 163 females of East Indian extract, and 19 males and 38 females of other ethnic origins. The average age of the population studied was 50 years (+/-15). The results obtained from this study indicate that diabetes mellitus is apparently more common in women than in men, particularly in those women who have borne children, and the incidence rises markedly after menopause. East Indians have higher triglyceride (TG), very low density lipoprotein cholesterol (VLDL-C) and low density lipoprotein cholesterol (LDL-C), but lower high density lipoprotein cholesterol (HDL-C) concentrations than their counterparts of African origin. TG, LDL-C and total serum cholesterol (TC) concentrations are highest in overweight-obese patients while HDL-C concentrations are highest in the lower weight division. The domestic working class, as well as those who were in retirement, have higher TG, LDL-C and TC than members of other occupational status. The fractions mainly affected by a residential area are TG, HDL-C and LDL-C. Moreover, diabetes mellitus and its consequent impact on lipoprotein homeostasis imposes a greater predilection to IHD, especially among members of the East Indian community.

The effect of blood sugar, therapy and blood pressure on lipoprotein profiles of diabetics in Trinidad and Tobago: possible association with ischaemic heart disease

The aim of this investigation was to examine the effects of fasting blood sugar, the type of therapy and blood pressure levels on lipoprotein profiles of diabetics in Trinidad and Tobago, and to determine how these biochemical and physiological risk factors may influence the development of ischaemic heart disease. Seven hundred (700) diabetic patients attending outpatient clinics at Sangre Grande and Port-of-Spain General Hospitals were surveyed. The data obtained in this study on the relationship of serum lipids to diabetic control support the hypothesis that poor control of blood sugar is conducive to accelerated atherosclerosis. Hypertensive patients and those maintained on insulin showed a greater disposition to ischaemic heart disease (IHD) than did non-hypertensives and patients maintained on oral hypoglycaemic agents, respectively. (AU)