1" sensitivity Plasmas

The use of potent combination antiretroviral therapy to suppress HIV replication to below the levels of detection of sensitive plasma HIV RNA assays limits the potential for selection of antiretroviral-resistant HIV variants, the major factor limiting the ability of antiretroviral drugs to inhibit virus replication and delay disease progression. 

Greeb, J., Shull, G.E., 1989, Molecular cloning of a third isoform of the calmodulin-sensitive plasma membrane Ca2+-transporting ATPase that is expressed predominantly in brain and skeletal muscle. J Biol Chem 264, 18569-18576. 

Engstrom G, Lind P, Hedblad B, Stavenow L, Janzon L, Lindgarde F. Effects of cholesterol and inflammation-sensitive plasma proteins on incidence of myocardial infarction and stroke in men. Circulation 2002 105 2632-2637. 

This obvious dependence on extracellular calcium is somewhat unexpected because (1) the sustained enhancement of calcium influx rate is adequately balanced by an increase in calcium efflux rate so that (2) the calcium concentration in the bulk cytosol is maintained near the basal value. This apparent paradox may be resolved by a model [54] which postulates that during the sustained phase of cellular response the high rate of calcium cycling across the plasma membrane raises the calcium concentration in a region just below the plasma membrane, often called the submembrane domain (see Rasmussen and Barrett, Chapter 4). Because the elevated calcium level in this domain is not conducted into the bulk cytosol, it cannot activate calcium-dependent response elements in the cytosol. Rather it regulates the activity of calcium-sensitive, plasma membrane-associated enzymes such as the calcium pump and PKC, the previously described phospholipid-dependent, calcium-activated protein kinase. 

Persons with acute primary HTV infections should be treated with combination antiretroviral therapy to suppress virus replication to levels below the limit of detection of sensitive plasma HTV RNA assays. 

An example may illustrate how sensitive plasma BuChE is to inhibition. Rats dosed orally with bromophos needed only 10.1 mg/kg of body weight for the enzyme activity to be reduced to half, whereas the erythrocyte AChE I50 was 1938 mg/kg and the brain AChE I50 was 576 mg/kg. The plasma 150 dose did not give any symptoms of poisoning (oral LD50 for rats = 3750 to 7700 mg/kg). It is very clear that plasma enzymes may be inhibited at much lower concentrations than needed to give the more severe symptoms associated with AChE inhibition in the nervous system, and they can be used in early-warning monitoring (Shivanandappa et al., 1988). 

The choice between X-ray fluorescence and the two other methods will be guided by the concentration levels and by the duration of the analytical procedure X-ray fluorescence is usually less sensitive than atomic absorption, but, at least for petroleum products, it requires less preparation after obtaining the calibration curve. Table 2.4 shows the detectable limits and accuracies of the three methods given above for the most commonly analyzed metals in petroleum products. For atomic absorption and plasma, the figures are given for analysis in an organic medium without mineralization. 

On leaving the column, the components enter a plasma functioning in identical manner to that described in article 2.2.6.3. All the atoms present emit their own specific emission spectra and can be detected and quantified. The sensitivity is excellent for carbon, hydrogen, and sulfur and average for nitrogen and oxygen. 

Ionization of Metals in a Plasma. A loss in spectrochemical sensitivity results when a free metal atom is split into a positive ion and an electron ... 

Sensitivity Sensitivity in flame atomic emission is strongly influenced by the temperature of the excitation source and the composition of the sample matrix. Normally, sensitivity is optimized by aspirating a standard solution and adjusting the flame s composition and the height from which emission is monitored until the emission intensity is maximized. Chemical interferences, when present, decrease the sensitivity of the analysis. With plasma emission, sensitivity is less influenced by the sample matrix. In some cases, for example, a plasma calibration curve prepared using standards in a matrix of distilled water can be used for samples with more complex matrices. 

A major advantage of this hydride approach lies in the separation of the remaining elements of the analyte solution from the element to be determined. Because the volatile hydrides are swept out of the analyte solution, the latter can be simply diverted to waste and not sent through the plasma flame Itself. Consequently potential interference from. sample-preparation constituents and by-products is reduced to very low levels. For example, a major interference for arsenic analysis arises from ions ArCE having m/z 75,77, which have the same integral m/z value as that of As+ ions themselves. Thus, any chlorides in the analyte solution (for example, from sea water) could produce serious interference in the accurate analysis of arsenic. The option of diverting the used analyte solution away from the plasma flame facilitates accurate, sensitive analysis of isotope concentrations. Inlet systems for generation of volatile hydrides can operate continuously or batchwise. 

The nebulization concept has been known for many years and is commonly used in hair and paint spays and similar devices. Greater control is needed to introduce a sample to an ICP instrument. For example, if the highest sensitivities of detection are to be maintained, most of the sample solution should enter the flame and not be lost beforehand. The range of droplet sizes should be as small as possible, preferably on the order of a few micrometers in diameter. Large droplets contain a lot of solvent that, if evaporated inside the plasma itself, leads to instability in the flame, with concomitant variations in instrument sensitivity. Sometimes the flame can even be snuffed out by the amount of solvent present because of interference with the basic mechanism of flame propagation. For these reasons, nebulizers for use in ICP mass spectrometry usually combine a means of desolvating the initial spray of droplets so that they shrink to a smaller, more uniform size or sometimes even into small particles of solid matter (particulates). 

In principle, DSI is the simplest method for sample introduction into a plasma torch since the sample is placed into the base of the flame, which then heats, evaporates, and ionizes the sample, all in one small region. Inherent sensitivity is high because the sample components are already in the flame. A diagrammatic representation of a DSI assembly is shown in Figure 17.4. 

Thermospray nebulizers are somewhat expensive but can be used on-line to a liquid chromatographic column. About 10% of sample solution is transferred to the plasma flame. The overall performance of the thermospray device compares well with pneumatic and ultrasonic sprays. When used with microbore liquid chromatographic columns, which produce only about 100 pl/min of eluant, the need for spray and desolvation chambers is reduced, and detection sensitivities similar to those of the ultrasonic devices can be attained both are some 20 times better than the sensitivities routinely found in pneumatic nebulizers. 

Greater sensitivity is attained if an additional ionization mode is included. This can be in the form of a radioactive source, a heated filament, or a plasma or glow discharge. 

To increase the number of ions, a plasma or corona discharge is produced in the mist issuing from the capillary. The electrical discharge induces more ionization in the neutrals accompanying the few thermospray ions. This enhancement increases the ionization of sample molecules and makes the technique much more sensitive to distinguish it from simple thermospray, it is called plasmaspray. 

Gold is a useflil caUbration standard for this method (see Radioactive tracers). Whereas similar sensitivities can be achieved by inductively coupled plasma mass spectrometry (qv), the latter requires more extensive sample preparation to overcome interference by other metals such as copper (64). 

Aluminum is best detected quaUtatively by optical emission spectroscopy. SoHds can be vaporized direcdy in a d-c arc and solutions can be dried on a carbon electrode. Alternatively, aluminum can be detected by plasma emission spectroscopy using an inductively coupled argon plasma or a d-c plasma. Atomic absorption using an aluminum hoUow cathode lamp is also an unambiguous and sensitive quaUtative method for determining alurninum. 

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