A physiologically based, multi-scale model of skeletal muscle structure and function.

Models of skeletal muscle can be classified as phenomenological or biophysical. Phenomenological models predict the muscle's response to a specified input based on experimental measurements. Prominent phenomenological models are the Hill-type muscle models, which have been incorporated into rigid-body modeling frameworks, and three-dimensional continuum-mechanical models. Biophysically based models attempt to predict the muscle's response as emerging from the underlying physiology of the system. In this contribution, the conventional biophysically based modeling methodology is extended to include several structural and functional characteristics of skeletal muscle. The result is a physiologically based, multi-scale skeletal muscle finite element model that is capable of representing detailed, geometrical descriptions of skeletal muscle fibers and their grouping. Together with a well-established model of motor-unit recruitment, the electro-physiological behavior of single muscle fibers within motor units is computed and linked to a continuum-mechanical constitutive law. The bridging between the cellular level and the organ level has been achieved via a multi-scale constitutive law and homogenization. The effect of homogenization has been investigated by varying the number of embedded skeletal muscle fibers and/or motor units and computing the resulting exerted muscle forces while applying the same excitatory input. All simulations were conducted using an anatomically realistic finite element model of the tibialis anterior muscle. Given the fact that the underlying electro-physiological cellular muscle model is capable of modeling metabolic fatigue effects such as potassium accumulation in the T-tubular space and inorganic phosphate build-up, the proposed framework provides a novel simulation-based way to investigate muscle behavior ranging from motor-unit recruitment to force generation and fatigue.

Pancolonic motor response to subsensory and suprasensory sacral nerve stimulation in patients with slow-transit constipation.

BACKGROUND: Sacral nerve stimulation (SNS) is emerging as a potential treatment for patients with constipation. Although SNS can elicit an increase in colonic propagating sequences (PSs), the optimal stimulus parameters for this response remain unknown. This study evaluated the colonic motor response to subsensory and suprasensory SNS in patients with slow-transit constipation. METHODS: Patients with confirmed slow-transit constipation were studied. Either a water-perfused manometry catheter or a high-resolution fibre-optic manometry catheter was positioned colonoscopically to the caecum. A temporary electrode was implanted transcutaneously in the S3 sacral nerve foramen. In the fasted state, three conditions were evaluated in a double-blind randomized fashion: sham, subsensory and suprasensory stimulation. Each 2-h treatment period was preceded by a 2-h basal period. The delta (Δ) value was calculated as the frequency of the event during stimulation minus that during the basal period. RESULTS: Nine patients had readings taken with a water-perfused catheter and six with a fibre-optic catheter. Compared with sham stimulation, suprasensory stimulation caused a significant increase in the frequency of PSs (mean(s.d.) Δ value - 1·1(7·2) versus 6·1(4·0) PSs per 2 h; P = 0·004). No motor response was recorded in response to subsensory stimulation compared with sham stimulation. Compared with subsensory stimulation, stimulation at suprasensory levels caused a significant increase in the frequency of PSs (P = 0·006). CONCLUSION: In patients with slow-transit constipation, suprasensory SNS increased the frequency of colonic PSs, whereas subsensory SNS stimulation did not. This has implications for the design of therapeutic trials and the clinical application of the device.

Anatomical registration and three-dimensional visualization of low and high-resolution pan-colonic manometry recordings.

BACKGROUND: Colonic propagating sequences (PS) are important for the movement of colonic content and defecation, and aberrant PS patterning has been associated with slow transit constipation. However, because these motor patterns are typically recorded over long periods (24 h +), the visualization of PS spatiotemporal patterning is difficult. Here, we develop a novel method for displaying pan-colonic motility patterns. METHODS: A 3D mesh representing the geometry of the human colon was created as follows: (i) Human colon images from the Visible Human Dataset were digitized to create a 3D data cloud, and (ii) A surface mesh was fitted to the cloud using a least-squares minimization technique. Colonic manometry catheters were placed in the ascending colon of healthy controls and patients with slow transit constipation (STC), with the aid of a colonoscope. The colonic manometry data were interpolated and mapped to the model according to the following anatomical landmarks: cecum, hepatic flexure, splenic flexure, sigmoid-descending junction, and anus. KEY RESULTS: These 3D images clearly and intuitively communicate characteristics of normal and abnormal colonic motility. Specifically we have shown the reduced amplitude of the antegrade propagating pressure waves (PPW) throughout the colon and reduced frequency of PPWs at the mid-colon in patients with STC. CONCLUSIONS AND INFERENCES: A novel method for the 3D visualization of PS is presented, providing an intuitive method for representing a large volume of physiological data. These techniques can be used to display frequency, amplitude or velocity data, and will help to convey regions of abnormally in patient populations.

Mathematically modeling the effects of electrically stimulating skeletal muscle.

A framework for modeling the activation of skeletal muscle is presented for studying functional electrical stimulation. A mathematical model of the cellular responses of skeletal muscle, created at AgResearch (Ruakura, New Zealand www.agresearch.co.nz), has been integrated with an anatomical, finite element model of the semitendinosus muscle, which was constructed from CT scans of the hind limb of a sheep. The tibial nerve was also constructed from digitized CT scans, and has been modeled using the Hodgkin Huxley neural model. The relevant cellular equations have been solved over these geometries. The results obtained, i.e speed of action potential propagation through the nerve and muscle, and the duration of twitch force, agree with published values.

Modulation of integrin function inhibits HIV transmission to epithelial cells and fertilization.

Integrin-mediated adhesive interactions are viewed in the context of HIV transmission to susceptible cells and fertilization. The ability of a low-molecular-weight non-peptide integrin modulator to inhibit HIV infection (virus-to-cell and cell-to-cell) and sperm-egg fusion is demonstrated. It is concluded that integrin-modulating substances offer significant promise as female-controlled means for preventing sexual transmission of HIV (whatever entity acts as HIV vector in semen and other penile secretions) and as female-controlled contraceptives.

Effect of alcohol on serum lipids in diabetics.

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 (+/- 13). 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.

Effect of alcohol on serum lipids in diabetics

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 races. A lower incidence of ischaemic heart disease was observed among the alcohol consumers when compared to those who abstained

The effect of blood sugar, therapy and blood pressure on lipoprotein profiles of diabetics in Trinidad & 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 predisposition to ischaemic heart disease (IHD) than did non-hypertensives and patients maintained on oral hypoglycaemic agents, respectively.

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 of ischaemic 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 that 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 & 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 predisposition to ischaemic heart disease (IHD) that did non-hypertensives and patients maintained on oral hypoglycaemic agents, respectively

The effect of demographic factors on serum lipids in diabetics of Trinida & Tobago: possible association with ischaemic ischamic heart disease

This study was undertaken in order to investigate the effect of race, sex, weight, activity level and to determine how this could possibly relate to the incidence of ischaemic 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 (ñ 15). The results obtained from this study indicate that diabetes mellitus is apparently more common in women that 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 lipprotein cholesterol (LDL-C), but lower high density liprotein 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 highester in the lower weight division. The domestic working class, as well as those who were in retirement, have higher TG, LDL-C than members of ther occupational status. The fractions mainly affected by a residental area are TG, HDL-C. Moreover, diabetes mellitus and its consequent impact on lipoprotein homeostasis a greater predilection to IHD, especially among members of the East Indian community

Rapid electronic autofluorography of labeled macromolecules on two-dimensional gels.

The feasibility of electronically locating and measuring tritium-labeled macromolecules directly on dried electrophoretic gels has been demonstrated. This new procedure eliminates the usual long film exposure in autofluorography and the attendant delay in processing and data reduction. An image intensifier and electronic camera tube are used to integrate the light produced by the tritium interaction with a scintillator incorporated in the gel. Preliminary results show that, compared to film, the exposure is reduced 100 to 1000 times. The response to low activity levels is improved, and spatial resolution is maintained. A proposed instrument could be used for measuring other isotopes as well as fluorescent and visible stains.