Pressure, selective

Aquatic organisms, such as fish and invertebrates, can excrete compounds via passive diffusion across membranes into the surrounding medium and so have a much reduced need for specialised pathways for steroid excretion. It may be that this lack of selective pressure, together with prey-predator co-evolution, has resulted in restricted biotransformation ability within these animals and their associated predators. The resultant limitations in metabolic and excretory competence makes it more likely that they will bioacciimiilate EDs, and hence they may be at greater risk of adverse effects following exposure to such chemicals. 

Fig. 1.1. The pressure range over which shock-compression events are of interest is very broad. Quite different and distinctive behaviors are to be expected at the various pressures. The figure shows pressures produced by impact and detonation as well as physical (p), mechanical (m), and chemical (c) events at selected pressures. The indicated impact pressures are those for impactor and target materials which are the same.

A single rupture disk can be used as the only overpressure protection on a vessel or system (Figure 7-10). The disk must be stamped by the manufacturer with the guaranteed bursting pressure at a specific temperature. The disk must rupture within +5% of its stampied bursting pressure at its specified burst temperature of operation. The expected burst temperature may need to be determined by calculation or extrapolation to be consistent with the selected pressure. 

This is greater than the selected pressure of 110 psia, therefore, for a binary the results will work out without a trial-and-error solution. But, for the case of other mixtures of 3 or more components, the trial-and-error assumption of the temperature for the vapor pressure will require a new temperature, redetermination of the component s vapor pressure, and repetition of the process until a closer match with the pressure is obtained. 

Atmospheric or pressure distillation, select pressure drop of 0.50-1.0 in. water/ft. 

The class A enzymes have Mx values around 30,000. Their substrate specificities are quite variable and a large number of enzymes have emerged in response to the selective pressure exerted by the sometimes abusive utilization of antibiotics. Some of these new enzymes are variants of previously known enzymes, with only a limited number of mutations (1 4) but a significantly broadened substrate spectrum while others exhibit significantly different sequences. The first category is exemplified by the numerous TEM variants whose activity can be extended to third and fourth generation cephalosporins and the second by the NMCA and SME enzymes which, in contrast to all other SXXK (3-lactamases, hydrolyse carbapenems with high efficiency. Despite these specificity differences, the tertiary structures of all class A (3-lactamases are nearly superimposable. 

Matagne A et al (1999) The p-lactamase cycle a tale of selective pressure and bacterial ingenuity. Nat Prod Rep 16 1-19... 

Substances that do not target the active site but display inhibition by allosteric mechanisms are associated with a lower risk of unwanted interference with related cellular enzymes. Allosteric inhibition of the viral polymerase is employed in the case of HIV-1 nonnucleosidic RT inhibitors (NNRTl, see chapter by Zimmermann et al., this volume) bind outside the RT active site and act by blocking a conformational change of the enzyme essential for catalysis. A potential disadvantage of targeting regions distant from the active site is that these may be subject to a lower selective pressure for sequence conservation than the active site itself, which can lower the threshold for escape of the virus by mutation. 

Short replication cycles that may be completed within a few hours, a large amount of viral progeny from one infected host-cell, as well as the general inaccuracy of viral nucleic acid polymerases result in an evolution occurring in fast motion, allowing rapid adaptation of viruses to selective pressures (see chapter by Boucher and Nijhius, this volume). Generalizing, it can be stated that any effective antiviral therapy will lead to the occurrence of resistance mutations. A well studied example... 

Kleim JP, ROsner M, Winkler I, Paessens A, Kirsch R, Hsiou Y, Arnolds E, Riess G (1996) Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74 -> Val or He and Val-75 - > Leu or He) HIV-1 mutants, Proc Natl Acad Sci USA 93 34-38... 

As explained in Chapter 1, the toxicity of natural xenobiotics has exerted a selection pressure upon living organisms since very early in evolutionary history. There is abundant evidence of compounds produced by plants and animals that are toxic to species other than their own and which are nsed as chemical warfare agents (Chapter 1). Also, as we have seen, wild animals can develop resistance mechanisms to the toxic componnds prodnced by plants. In Anstralia, for example, some marsupials have developed resistance to natnrally occnrring toxins produced by the plants upon which they feed (see Chapter 1, Section 1.2.2). 

It is only very recently that organic componnds synthesized by humans have begun to exert a selection pressure upon natural populations, with the consequent emergence of resistant strains. Pesticides are a prime example and will be the principal subject of the present section. It should be mentioned, however, that other types of biocides (e.g., antibiotics and disinfectants) can produce a similar response in microbial populations that are exposed to them. 

Interestingly, it appears that earlier selective pressure by dichlorodiphenyl trichloroethene (DDT) raised the frequency of kdr genes in the population before pyrethroids came to be used. Thus, some pyrethroid resistance already existed before these insecticides were applied in the field. 

Bacterial resistance to antibiotics has been recognized since the first drugs were introduced for clinical use. The sulphonamides were introduced in 1935 and approximately 10 years later 20% of clinical isolates of Neisseria gonorrhoeae had become resistant. Similar increases in sulphonamide resistance were found in streptococci, coliforms and other bacteria. Penicillin was first used in 1941, when less than 1 % of Staphylococcus aureus strains were resistant to its action. By 1947,3 8% of hospital strains had acquired resistance and currently over 90% of Staph, aureus isolates are resistant to penicillin. Increasing resistance to antibiotics is a consequence of selective pressure, but the actual incidence of resistance varies between different bacterial species. For example, ampicillin resistance inEscherichia coli, presumably under similar selective pressure as Staph, aureus with penicillin, has remained at a level of 30-40% for mai years with a slow rate of increase. Streptococcus pyogenes, another major pathogen, has remained susceptible to penicillin since its introduction, with no reports of resistance in the scientific literature. Equally, it is well recognized that certain bacteria are unaffected by specific antibiotics. In other words, these bacteria have always been antibiotic-resistant. 

Resistance to quinolones by efflux has been described in Staph, aureus and Proteus mirabilis. This gene has been designated nor A in Staph, aureus and is homologous to membrane transport proteins coupled to the electromotive force. These proteins have the ability to remove small amounts of quinolone from cells normally and nor A may have arisen as a result of mutations under selective pressure from quinolone use, resulting in a transport protein with increased affinity for these agents. 

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