Muscle models and

Description of muscle contraction has essentially evolved into two separate approaches — lumped whole muscle models and specialized crossbridge models of the sarcomere. The former seek to interpret muscle s complex mechanical properties with a single set of model elements. Muscle experiments measure muscle force and length subjected to isometric (fixed length) conditions, isotonic (fixed load) conditions, and transient analysis where either length or load is rapidly changed. 

Theoretical models available in the literature consider the electron loss, the counter-ion diffusion, or the nucleation process as the rate-limiting steps they follow traditional electrochemical models and avoid any structural treatment of the electrode. Our approach relies on the electro-chemically stimulated conformational relaxation control of the process. Although these conformational movements179 are present at any moment of the oxidation process (as proved by the experimental determination of the volume change or the continuous movements of artificial muscles), in order to be able to quantify them, we need to isolate them from either the electrons transfers, the counter-ion diffusion, or the solvent interchange we need electrochemical experiments in which the kinetics are under conformational relaxation control. Once the electrochemistry of these structural effects is quantified, we can again include the other components of the electrochemical reaction to obtain a complete description of electrochemical oxidation. 

PBPK models have also been used to explain the rate of excretion of inhaled trichloroethylene and its major metabolites (Bogen 1988 Fisher et al. 1989, 1990, 1991 Ikeda et al. 1972 Ramsey and Anderson 1984 Sato et al. 1977). One model was based on the results of trichloroethylene inhalation studies using volunteers who inhaled 100 ppm trichloroethylene for 4 horns (Sato et al. 1977). The model used first-order kinetics to describe the major metabolic pathways for trichloroethylene in vessel-rich tissues (brain, liver, kidney), low perfused muscle tissue, and poorly perfused fat tissue and assumed that the compartments were at equilibrium. A value of 104 L/hour for whole-body metabolic clearance of trichloroethylene was predicted. Another PBPK model was developed to fit human metabolism data to urinary metabolites measured in chronically exposed workers (Bogen 1988). This model assumed that pulmonary uptake is continuous, so that the alveolar concentration is in equilibrium with that in the blood and all tissue compartments, and was an expansion of a model developed to predict the behavior of styrene (another volatile organic compound) in four tissue groups (Ramsey and Andersen 1984). 

Fig. 4.1. Cellular model illustrating cell types in vascular wall involved in vasorelaxation induced by SERMs. Putative targets of SERMs are indicated within cyan tags. SERMs directly affect L-type VDCC, BK fil subunit in smooth muscle cells, and ER in endothelial cells. L-type VDCC L-type voltage-dependent calcium channel BK calcium-activated large conductance K+ channel PKG protein kinase G eNOS endothelial nitric oxide synthase GC soluble guanylate cyclase cGMP cyclic GM P V electrochemical membrane potential ER estrogen receptor. See text for further details...

Nelson We have the phospholamban knockout mouse model, and John Lederer was able to peel out a component of the decay that was due to reuptake. We didn t see any difference between the control and the knockouts. Presumably it is happening, but we couldn t see any difference in the decay in the phospholamban knockouts, as was seen in heart muscle, nor could we see any effect of lanthanum or zero Na+. Examining the decay of the spark would be a good indicator of local Ca2+ removal, though. It would also be worth examining the decay of the BK current. 

Table V contains data for two model substances, p-aminohippurate (PAH) and phenol red. Consideration of the highest values in this table tells you where the major portions of the substances appear. For example, urine and bile show the largest concentrations of PAH and phenol red. Both compounds appear in significant concentrations in the kidney while the values in muscle, brain and cerebrospinal fluid (CSF) are invariably lower than the values seen in plasma. The values in parentheses (Table V) are percent of the administered dose in a given tissue or fluid compartment. They add to the previous information by revealing the overall importance of a particular compartment in the disposition of a substance. For example, while the hepatic concentrations of PAH and phenol red at 4 hrs. are only about 2-fold those of plasma, the large size of the shark liver relative to its body weight, typically about 10%, leads to the appearance of 30-40% of these substances in the liver. The relative handling of these compounds by the urinary and biliary system is obvious from considering the percentage figures. Thus in 24 hours phenol red is about equally distributed in the bile and urine (38 vs 31%) the urinary route is the dominant route of excretion of PAH, i.e., 56 vs 2%.

The anxiolytic properties of 5-HT3 receptor antagonists have been demonstrated in several animal models of anxiety. In these models, the 5-HT3 antagonists mimic the anxiolytic effects of the benzodiazepines but differ from the latter in their lack of sedative, muscle relaxant and anticonvulsant action. These compounds appear to be extremely potent... 

Resident CSCs were first isolated in murine hearts. Characterization of these cells was based on the expression of the stem cell-related surface antigens c-Kit and Sea-1. In the first study, freshly isolated c-Kit /Lin cells were shown to be clono-genic and to differentiate into myocytes, smooth muscle cells, and endothelial lineage cells [35]. Those cells generated functional myocardium when injected into ischemic areas of the heart. The second study characterized CSCs as Sca-l/c-Kit. When treated in culture with 5-azacytidine, those cells differentiated into a myogenic lineage. Subsequently, intravenous injection of the cells in an ischemia/reperfusion model resulted in infarct healing with cardiomyocyte transdifferentiation... 

Warren GL, Summan M, Gao X, Chapman R, Hulderman T, Simeonova PP (2007) Mechanisms of skeletal muscle injury and repair revealed by gene expression studies in mouse models. J Physiol 582 825-41... 

The use of needle-free jet devices for the delivery of nucleic acids has been described for various disease models, and has been found to generally enhance DNA uptake in various tissues and to increase DNA vaccine efficacy. Jet injection has been found to be an efficient method to induce papillomas in rabbits by inoculation with cottontail rabbit papillomavirus DNA (Brandsma et al., 1991). Jet injection has been used to introduce DNA through the skin surface, effectively transfecting skin, muscle, fat and mammary tumor tissue (Furth et al., 1992). 

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