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A theoretical model for treatment of soft tissue injuries: treatment of an ankle sprain in a college tennis player.

OBJECTIVE: To present theories of manual treatment approaches to soft tissue injuries using an example case report. CLINICAL FEATURES: A college tennis player with an ankle sprain for 6 weeks, not responding to standard treatment, was unable to play tennis or compete in tournaments. INTERVENTION AND OUTCOME: Soft tissue treatment was applied to the ankle for 2 visits. The patient experienced complete resolution of the problem and returned to play without relapse during a 9-month follow-up period. Theories of myofascial distortion treatment are discussed. CONCLUSION: This treatment approach may have potential for soft tissue problems that are not amenable to current therapy approaches.

Adult↗

An experimental and theoretical model for solar UVA-irradiation of soluble eumelanin: towards modelling UVA-photoreactions in the melanosome?

A model is developed for the UVA-irradiation of soluble eumelanin exposed to levels of irradiation comparable to sunlight. Radical production was determined in soluble dl- and l-dopa melanins exposed to solar levels of UVA, using electron spin resonance spectroscopy and the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Steady-state concentrations of DMPO-O(2)H(.-), which increased up to 0.3 mg/ml melanin, and then declined above 0.3 mg/ml, were detected at pH 4.5. The kinetic model incorporated the photosensitizing and radical-scavenging reactions of eumelanin, and assumed semiquinone radical reduction of oxygen to be fast compared to disproportionation. The model is consistent with experimental data for melanin concentrations <0.1 mg/ml; but >0.1 mg/ml melanin is consistent only with data at raised oxygen tension. The rate-constant for reaction of the melanin semiquinone-radical and oxygen is estimated to be 10(3) mol(-1)dm(3)s(-1). In this model, where DMPO competes with melanin for HO(2)(.-), at ambient oxygen levels, eumelanin exposed to solar levels of UVA photosensitizes superoxide at concentrations <0.3 mg/ml melanin, and is increasingly stable towards oxidation when >0.3 mg/ml concentration. Eumelanin could have a negligible screening effect <0.1 mg/ml and very strong screening >1 mg/ml. This model would be biologically relevant if soluble forms of eumelanin were shown to exist in vivo, and is potentially useful for studies of the photochemistry and photophysics of eumelanin and phaeomelanin and to explore the effects of metal-ions, proteins and lipids in a model system.

Cyclic N-Oxides↗

Malaria transmission intensity and the rate of spread of chloroquine resistant Plasmodium falciparum: Why have theoretical models generated conflicting results?

The rate at which falciparum resistant malaria spreads in different transmission settings is still a controversial subject. We have assessed the spread of mutant Plasmodium falciparum parasites in six Ugandan populations with varying prevalence of chloroquine resistance (CQR), malaria transmission intensity, multiplicity of parasite clones and prevalence of CQ use. For each population, we have determined the wild and mutant allele frequency at codons 76 and 86 of the pfcrt and pfmdr1 genes, respectively. The highest frequency (median = 16.3%, range: 0.0-70.4%) of infections with two pure mutants (no wild genotype in either gene), adjusted for clone multiplicity, was observed at the extremes of malaria transmission intensity. The wild/mutant (W/M) allele ratio (an index for tracking the progression of CQR) was less than one in all sites (median = 0.51, range: 0.09-0.98) for the pfcrt-76 gene, while it was greater than one in two of six sites (median = 0.75, range: 0.4-1.6) for the pfmdr1-86 gene, suggesting that the pfcrt-76 mutants were the predominant parasites at all sites. Furthermore, the pfmdr1-86 W/M allele ratio was consistently higher than that of the pfcrt-76. The spread of mutations linked to CQR in P. falciparum commences with the pfcrt-76 gene mutations, followed later by the pfmdr1-86 gene mutations that modulate higher CQR. Such spread occurs faster at the extremes of the transmission spectrum and could explain why mathematical models have previously generated conflicting results with respect to malaria transmission intensity and spread of CQR.

Alleles↗

Theories and theoretical models for percolation and permeability in multiphase systems: comparative analysis.

The terminology and the physical sense of percolation and permeability were analyzed. Existing theories of percolation and permeability were analytically compared with respect to their applicability and effectiveness. It is concluded that the main tendency in the development of the concept of percolation/permeability consists in the fundamental investigation of the relationship between the preparation conditions of the solid, its structural characteristics and measured properties - not only percolation/permeability but also adsorption, Hg-intrusion, etc.

Models, Theoretical↗

A theoretical model of slow wave regulation using voltage-dependent synthesis of inositol 1,4,5-trisphosphate.

A qualitative mathematical model is presented that examines membrane potential feedback on synthesis of inositol 1,4,5-trisphosphate (IP(3)), and its role in generation and modulation of slow waves. Previous experimental studies indicate that slow waves show voltage dependence, and this is likely to result through membrane potential modulation of IP(3). It is proposed that the observed response of the tissue to current pulse, pulse train, and maintained current injection can be explained by changes in IP(3), modulated through a voltage-IP(3) feedback loop. Differences underlying the tissue responses to current injections of opposite polarities are shown to be due to the sequence of events following such currents. Results from this model are consistent with experimental findings and provide further understanding of these experimental observations. Specifically, we find that membrane potential can induce, abolish, and modulate slow wave frequency by altering the excitability of the tissue through the voltage-IP(3) feedback loop.

Animals↗

Binding of small basic peptides to membranes containing acidic lipids: theoretical models and experimental results.

We measured directly the binding of Lys3, Lys5, and Lys7 to vesicles containing acidic phospholipids. When the vesicles contain 33% acidic lipids and the aqueous solution contains 100 mM monovalent salt, the standard Gibbs free energy for the binding of these peptides is 3, 5, and 7 kcal/mol, respectively. The binding energies decrease as the mol% of acidic lipids in the membrane decreases and/or as the salt concentration increases. Several lines of evidence suggest that these hydrophilic peptides do not penetrate the polar headgroup region of the membrane and that the binding is mainly due to electrostatic interactions. To calculate the binding energies from classical electrostatics, we applied the nonlinear Poisson-Boltzmann equation to atomic models of the phospholipid bilayers and the basic peptides in aqueous solution. The electrostatic free energy of interaction, which arises from both a long-range coulombic attraction between the positively charged peptide and the negatively charged lipid bilayer, and a short-range Born or image charge repulsion, is a minimum when approximately 2.5 A (i.e., one layer of water) exists between the van der Waals surfaces of the peptide and the lipid bilayer. The calculated molar association constants, K, agree well with the measured values: K is typically about 10-fold smaller than the experimental value (i.e., a difference of about 1.5 kcal/mol in the free energy of binding). The predicted dependence of K (or the binding free energies) on the ionic strength of the solution, the mol% of acidic lipids in the membrane, and the number of basic residues in the peptide agree very well with the experimental measurements. These calculations are relevant to the membrane binding of a number of important proteins that contain clusters of basic residues.

Amino Acid Sequence↗

A theoretical model study of the influence of fluid stresses on a cell adhering to a microchannel wall.

We predict the amplification of mechanical stress, force, and torque on an adherent cell due to flow within a narrow microchannel. We model this system as a semicircular bulge on a microchannel wall, with pressure-driven flow. This two-dimensional model is solved computationally by the boundary element method. Algebraic expressions are developed by using forms suggested by lubrication theory that can be used simply and accurately to predict the fluid stress, force, and torque based upon the fluid viscosity, muoffhannel height, H, cell size, R, and flow rate per unit width, Q2-d. This study shows that even for the smallest cells (gamma = R/H << 1), the stress, force, and torque can be significantly greater than that predicted based on flow in a cell-free system. Increased flow resistance and fluid stress amplification occur with bigger cells (gamma > 0.25), because of constraints by the channel wall. In these cases we find that the shear stress amplification is proportional to Q2-d(1-gamma)-2, and the force and torque are proportional to Q2-d(1-gamma2)-5/2. Finally, we predict the fluid mechanical influence on three-dimensional immersed objects. These algebraic expressions have an accuracy of approximately 10% for flow in channels and thus are useful for the analysis of cells in flow chambers. For cell adhesion in tubes, the approximations are accurate to approximately 25% when gamma > 0.5. These calculations may thus be used to simply predict fluid mechanical interactions with cells in these constrained settings. Furthermore, the modeling approach may be useful in understanding more complex systems that include cell deformability and cell-cell interactions.

Animals↗

Comparison of cost-effectiveness of preventive and reactive mass immunization campaigns against meningococcal meningitis in West Africa: a theoretical modeling analysis.

For epidemic meningitis control in sub-Saharan Africa, the World Health Organization recommends a strategy of emergency vaccination with meningococcal A + C polysaccharide vaccine when epidemic thresholds are exceeded. An alternative strategy for areas without effective surveillance systems is mass preventive campaigns before outbreaks occur. A model was formulated to simulate epidemics and to compare the cost-effectiveness of these two strategies for the district of Matam, Senegal, where an actual preventive campaign was performed during 1997. The preventive strategy prevented 59% of the cases compared to 49% for the emergency strategy. The cost per case prevented was US$59 for the preventive strategy and US$133 for the reactive strategy, and the preventive strategy saved US$0.20 per habitant. Preventive meningococcal vaccination through mass campaigns prevented more outcomes at a lower cost, provided that the occurrence of an epidemic could be predicted within 3 years and that the vaccination coverage rates for the preventive and standard strategies were > 70% and < 94%, respectively. Sub-Saharan African countries without effective surveillance systems should consider mass preventive campaigns while awaiting an affordable conjugate vaccine.

Adolescent↗

The intra-spine electric force can drive vesicles for fusion: a theoretical model for long-term potentiation.

We have estimated the intensity of intra-spine electric fields triggered by stimulation of excitatory spine synapses. We show that this electric force can cause fast electrophoretic movement of negatively charged vesicles which bring new postsynaptic receptors and membrane for insertion during the induction of long-term potentiation (LTP). Due to the direction of an intra-spine electric field, movement of vesicles is electrophoretically directed along the longitudinal spine axis towards the spine head. Thus, the number of fused vesicles may be proportional not only to the increased calcium concentration within the spine head during the induction of LTP but also to the magnitude of electric force which drives vesicles towards the postsynaptic membrane.

Animals↗

A new theoretical model to characterize the densification behavior of tableting materials.

The purpose of the study was to develop a new three-dimensional model using force, time and displacement to characterize the densification behavior of tableting materials. Normalized time (x), displacement converted to ln(1/1 - D(rel)) according to Heckel (y) and force presented as pressure (z) were used to plot a graph. A twisted plane was fitted to this three-dimensional plot. This plane was characterized by three parameters d, the slope over time called 'time plasticity', e, the slope over pressure called 'pressure plasticity' and omega, the angle of rotation called 'fast elastic decompression'. These parameters were used to characterize the densification behavior of the well-known materials microcrystalline cellulose, dicalcium phosphate dihydrate, theophylline monohydrate, cellulose acetate and hydroxypropyl methylcellulose at different rho(rel, max). It could be shown that brittle, elastic and plastic compression properties could be very well distinguished and differentiated. Further on, it could be shown whether these properties were due to pressure or time. Thus this model has the prevailing advantage to characterize tableting materials in one step according to time and pressure and it is a useful tool to develop tablet formulations or new excipients.

Algorithms↗

A theoretical model using mechanical principles to quantify the physical principles of balloon dilatation.

RATIONALE AND OBJECTIVES: Balloon dilatation is a mechanical form of controlled injury used to alleviate vascular stenoses. Several factors influence successful angioplasty. Few mechanical models exist to illustrate the physical principles of balloon dilatation. METHODS: We used mechanical analysis of membrane stresses, along with Laplace's law, to determine a relation between balloon inflation and dilating pressures exerted by balloons in stenoses of varying severity, length, and eccentricity. The balloons were assumed to be perfectly inelastic and flexible. We also examined the resultant stresses in the lesion wall of concentric and eccentric stenoses from exertion of dilating pressures. RESULTS: Dilating pressures depend directly on maximal balloon inflation pressure and balloon diameter. Short, focal stenoses experience greater dilating pressures, which often are several multiples of the inflation pressure, than similarly narrowed longer lesions. CONCLUSION: Dilating pressures depend on inflation pressure, balloon diameter, and lesion severity.

Angioplasty, Balloon↗

Alterations in proteolytic activity at low pH and its association with invasion: a theoretical model.

The extracellular pH (pHe) of solid tumours is often lower than in normal tissues, with median pH values of about 7.0 in tumours and 7.5 in normal tissue. Despite this more acidic tumour microenvironment, non-invasive measurements of intracellular pH (pHi) have shown that the pHi of solid tumours is neutral or slightly alkaline compared to normal tissue (pHi 7.0-7.4). This gives rise to a reversed cellular pH gradient between tumours and normal tissue, which has been implicated in many aspects of tumour progression. One such area is tumour invasion: the incubation of tumour cells at low pH has been shown to induce more aggressive invasive behaviour in vitro. In this paper the authors use mathematical models to investigate whether altered proteolytic activity at low pH is responsible for the stimulation of a more metastatic phenotype. The authors examined the effect of culture pH on the secretion and activity of two different classes of proteinases: the metalloproteinases (MMPs), and the cysteine proteinases (such as cathepsin B). The modelling suggests that changes in MMP activity at low pH do not have significant effects on invasive behaviour. However, the model predicts that the levels of active-cathepsin B are significantly altered by acidic pH. This result suggests a critical role for the cysteine proteinases in tumour progression.

Cell Movement↗