Physiological flow measurements

Stopped-flow measurements with superoxide in aqueous solution at physiological pH are not possible due to its fast self-dismutation under these conditions. Therefore, the indirect assays such as McCord-Fridovich, adrenalin and nitroblue tetrazolium (NET) assays are widely used in the literature, not only for qualitative but also for quantitative detection of SOD activity of small molecular weight mimetics 52). Not going into details, we just want to stress that the indirect assays have very poor even qualitative reliability, since they can demonstrate the SOD activity of the complexes which does not react with superoxide at all. It has been reported in the literature that this is caused by the interference of hydrogen peroxide 29). We have observed that the direct reaction between complexes and indicator... 

An attractive feature of fiber sensors is the possibility of performing in vivo tests and monitoring. Numerous fiber-optic sensors have already been described that measure physical parameters of the human body [41]. Pressure, temperature, physiological flow, strain, motion, displacement, or flow velocity can be monitored by optical methods such as variable reflection, laser Doppler velocimetry, optical holography, or diffraction. In this section the application of optosensing methods to the determination of molecular species encountered in clinical and biomedical analysis is described. 

The measurement of the flow velocity by introduction of radioactive substance or electrolyte into a cross section, followed by measurement of the radioactivity or electric conductivity in cross sections further downstream, has gained wide acceptance in different branches of engineering and, in particular, in physiology (the measurement of flow velocity of blood in arteries). The main difficulty associated... 

Skin conductivity (also called electrodermal response or Galvanic Skin Response, GSR) is thought to be an indicator of psychological, emotional or physiological arousal. Measurement of skin conductivity is typically performed by an ohmmeter in which a constant 0.5 V is applied between the electrodes and the resulting current flow is measured by amplifying the voltage across a resistor in series with the skin [5]. 

A final, highly specialized procedure for monitoring carbon flow in plants involves the use of "CO . The use of this positron gamma-emitting isotope of C, with a half-life of 20.3 min, allowed several physiological parameters of my-corrhizal and non-mycorrhizal plants of Panicum coloratum to be measured simultaneously in real time (82). However, the technical problems associated with using "COi, particularly the ability to produce i.sotopes of carbon, and with handling this short half-life are likely to limit this approach to specialised facilities. 

Dissolution test data will be required in all cases (and for all strengths of product) for development and routine control and should be based on the most suitable discriminatory conditions. The method should discriminate between acceptable and unacceptable batches based on in vivo performance. Wherever possible Ph Eur test methods should be used (or alternatives justified). Test media and other conditions (e.g., flow through rate or rate of rotation) should be stated and justified. Aqueous media should be used where possible and sink conditions should be maintained. A small amount of surfactant may be added where necessary to control surface tension or for active ingredients of very low solubility. Buffer solutions should be used to span the physiologically relevant range—the current advice is over pH 1 6.8 or perhaps up to pH 8 if necessary. Ionic strength of media should be reported. The test procedure should employ six dosage forms (individually) with the mean data and a measure of variability reported. 

FIGURE 1.10 Laser-doppler flowmetry (a) and NO measurement (b) from one subject. Upon heating the subject to 39°C, at 10 min, NO production and skin blood flow increased, which instantly returned to normal upon cooling the subject at 45 min. After heat stress and cooling, ACh was administered by intra-dermal microdialysis to confirm the ability of the microelectrode to measure NO concentrations. (Reprinted with permission from the American Physiological Society [125].)... 

Because PB-PK models are based on physiological and anatomical measurements and all mammals are inherently similar, they provide a rational basis for relating data obtained from animals to humans. Estimates of predicted disposition patterns for test substances in humans may be obtained by adjusting biochemical parameters in models validated for animals adjustments are based on experimental results of animal and human in vitro tests and by substituting appropriate human tissue sizes and blood flows. Development of these models requires special software capable of simultaneously solving multiple (often very complex) differential equations, some of which were mentioned in this chapter. Several detailed descriptions of data analysis have been reported. 

The problem has now been solved, and it is possible to measure the phase angle of the probe as the cells pass through the laser beam.09,40) While these measurements have not yet been applied to Ca2+, the method has been validated with standard beads and stained cells. In our opinion, this new flow cytometry parameter, and our increasing knowledge of lifetimes of probes, will result in the increased use of flow cytometry for studies of intracellular physiology, in addition to the current emphasis in immunology, cell activation, and ploidy. 

Yokoi F, Komiyama T, Ito T, Flayashi T, Lio M, Flara T. (1993). Application of carbon-11 labelled nicotine in the measurement of human cerebral blood flow and other physiological parameters. EurJ NucI Med. 20(1) 46-52. 

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