Resistance evolution

In this chapter we describe the current insights into the evolution of viruses under pressure of antiviral therapy and the potential impact on viral fimess. As most recent work in this field has been done in the field of human immunodeficiency virus (HIV), we use the evolution of this virus as the basis for the chapter. Subsequently, we describe resistance evolution for Hepatitis B virus (HBV), where large progress has been made in recent years. Furthermore, we describe the resistance development for Hepatitis C virus (HCV), for which a very active drug development program is undertaken by several pharmaceutical companies. Finally, we discuss resistance evolution for Influenza. 

The dramatic increase of severe or lethal infections caused by antibiotic-resistant bacteria triggered numerous studies on antibiotic resistance, not only from clinical but also from environmental sources. Nowadays it is clear that environment, and water in particular, plays a central role on antibiotic resistance dispersion to and from clinical settings. However, the current state of the art clearly suggests that only a small fraction of the environmental resistome is known. The modes and mechanisms of emergence, evolution and transmission of resistance determinants are still not very well understood. Although environmental pollution is recognized to play an important role on antibiotic resistance evolution and spreading, it is still very difficult to draw cause-effect relationships, which sometimes seems to be strain/species dependent. 

One elegant approach to reducing the rate of resistance evolution could be to apply herbicides as mixtures of active partners which cannot be rendered inactive by the same resistance mechanism. This is analogous to the use of drug combinations to ensure broad-sectrum control of susceptible and potentially resistant pathogoi strains. In such a... 

Many different bioassays and biochemical or genetic tests have been developed to identify resistant weeds. However, these are normally conducted after the suspected development of resistance, not in a proactive or preventive manner. The potential for evolution of resistance to a new herbicide can be examined in several ways wild-type populations can be screened for resistant individuals, model plant populations can be muta-genized and screened for resistance, resistant cells can be selected in culture, with or without prior exposure to the herbicide, or biochemical or genetic assays can be used to identify known resistance mechanisms. However, more complex or obscure resistance mechanisms may exist, and certain mechanisms may only be expressed in whole plants, not in cell cultures. More recent techniques focused on rapid genetic evolution can also provide a clue to the relative ease with which resistance can be generated, but still require a large investment. However, as in many predictive studies, it is often difficult to relate the results of such experiments to resistance evolution in the field. 

The major difference between OPs and carbamates is in their metabolic fate. This strongly indicates that metabolism and detoxification are the most important factors in resistance evolution. The current emphasis on target site interactions and their associated resistance mechanisms reflects their perceived practical importance, the importance of their study for the development of new insecticidal molecules, and the fundability of such research. But detailed studies of the biochemical characteristics and physiological behavior of the enzymes involved in insecticide metabolism and detoxification are still very important. 

Richter, R 1992. Possible genetic start points and end points of insecticide resistance evolution. In Mechanism of Action and Resistance, Otto, D. and Weber, B., Eds. Intercept Ltd., Andover, U.K. pp. 355-363. 

The electrical potential distribution is a function of the electrical resistance of the soil and therefore depends on the instantaneous local concentration and mobility of all ions existing in the pore water of the soil, which ultimately determine the electrical resistance evolution. Therefore, a set of conservation equation, one for each ion, has to be simultaneously integrated, with the difficulty that aU these differential equations are strongly coupled through the electrical potential distribution. Therefore, an analytical solution would be very difficult to obtain, if at all possible. So, a numerical solution must be used instead. 

The classification of fungicides according to their mode of action and cross resistance pattern became necessary to facilitate resistance management at the field level under practical agronomic conditions. If fungicides are recommended to be used in alternation or mixtures to achieve robust disease control and delaying resistance evolution, clear information on the cross-resistance behavior for each... 

Therefore, the level and extent of resistance evolution is estimated as moderate (see FRAC classification). However, the mode of action of AP fungicides remains speculative. 

Fie. 8 Test results for ACA flip-chip joints, (a) Typical resistance evolution of a single ACA joint subjected to the temperature cycling test and (b) cumulative failures of ACA A joints during the test. Data were in situ measured up to 3000 cycles. 

Table 2 Parameters used for calculation of the resistance evolution of an adhesive joint at 85 °C (185 °F) and 85% RH...

Figure 2.60 Friction coefficient and electrical contact resistance evolutions (P = 0.83 GPa, v 2.5 mm/s, T = 20 °C, 1000 cycles), with the triboscopic image of the electrical contact resistance...

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