Folds resistivity

Class of drug/compound Mutation Fold-resistance Cross-resistance Comments Reference... 

Indeed, the resistance problem has sometimes been severe enough to threaten a loss of control over the pest. A study of a number of resistant strains from the field has revealed two major types of resistance mechanism. Some individuals possess aberrant forms of the target site, the Na" channel. At least two forms are known that confer either kdr (<100-fold) or super kdr (>100-fold) resistance, which is the consequence of the presence of insensitive forms of the Na+ channel protein (McCaffery 1998, and Chapter 4, Section 4.4 of this book). 

Fig. 2.3 Therapeutic effect of dEpoB and padi- on days 6, 8,10,12 and 14. o, control with taxel (Taxol ) in nude mice bearing CCRF- vehicle only co, paclitaxel 20 mg/kg and X, CEM/paclitaxel xenografts (57-fold resistant to dEpoB 30 mg/kg. The average tumor volume of paclitaxel) following Q2D x 5, i.v. 6 h infusion. the control group on days 12,14,16,18, and 24...

Vogler M, Butterworth M, Majid A et al (2009) Concurrent up-regulation of BCL-XL and BCL2A1 induces approximately 1000-fold resistance to ABT-737 in chronic lymphocytic leukemia. Blood 113 4403-4413... 

As the NNRTIs are structurally diverse and yet bind to RT at a common site, the similar occurrence of resistance-conferring mutations is not surprising. As a consequence, the effectiveness of other NNRTIs may be compromised by the emergence of HIV-1 variants caused by a previous NNRTI therapy (Sardana et ah, 1992). Experiments were performed in which HIV-1 strains (JR-CSF or ME) are cultured in human lymphocytes in the presence of partially inhibitory concentrations of delavirdine (Dueweke et al., 1993b). These conditions yield mutants that are 100-fold resistant. In order to determine what mutation(s) occurs, PCR (polymerase chain reaction) amplification and DNA sequence analysis of the RT coding region were applied and indicated that mutation P236L had occurred. Mutations at amino acids 181 or 183, which have been associated with resistance to other NNRTIs, are not detected. 

These cross-resistance patterns were studied by J. R. Busvine at the London School of Hygiene. His partly dieldrin resistant strain of M. domestica vicina from the Sudan became 1000-fold resistant when subjected to intense pressure with dieldrin at Slough. 4... 

Hence, in simple cases each bulk layer, each grain boundary plane, and both electrodes of the brick layer model sample, can be represented by separate RC elements (Fig. 7b). The RC elements of the n bulk layers can be combined to a single RC element with the -fold resistance and the 1 / -fold capacitance of a single layer. The n — 1 grain boundary impedances can also be summed, as can the two electrode impedances, and hence the model sample corresponds to a series connection of three RC elements (Fig. 7c) with... 

A single gene may be responsible for the resistance, and in these cases the level of resistance can be quite high. Well-known examples are the 2000-fold resistance to organophosphates in spider mites, spinosad resistance in western flower thrips, DDT resistance in houseflies, and dieldrin resistance in several Diptera. In other cases, multiple genes are clearly involved in the resistance. Examples are carbaryl resistance in houseflies (Georghiou, 1972), carbaryl resistance in fall army worms (Yu et al., 2003), and malathion resistance in oriental houseflies (Yeoh et al., 1981). 

Yu and Nguyen (1996) showed that selection of a strain of diamondback moth (Plu-tella xylostella) with permethrin for 21 generations resulted in over 600-fold resistance to permethrin in this strain. The resistant strain was also cross-resistant to all pyrethroids tested, including bifenthrin, fenvalerate, esfenvalerate, A.-cyhalothrin, fluvalinate, and tral-omethrin. However, it remained susceptible to organophosphate, carbamate, cyclodiene, neonicotinoid, avermectin, and microbial insecticides tested. Biochemical studies indicated that pyrethroid resistance observed in this strain was most likely due to decreased target site sensitivity. 

An example taken from the work of Georghiou (1972) on the housefly is illustrated in Figure 10.5. In this case, the combination of chromosome 2, which confers a 3.2-fold resistance to carbaryl because of enhanced detoxification (P450s) (strain R-2), and chromosome 3, which confers a 1.7-fold resistance because of reduced penetration (strain R-3), increases resistance 50-fold. The addition of chromosome 5 to the combination (strain R-235) increases resistance further, to nearly the original level of the parental R strain. 

The combination of various resistance factors can act multiplicatively. For example, Yeoh et al. (1981) showed that a 519-fold resistance to malathion was observed in oriental houseflies having a 5-fold increase in carboxylesterase activity, a 10-fold increase in GST activity, and a 10-fold increase in AChE insensitivity (i.e., 5 x 10 x 10 = 500). Similarly, a 238-fold resistance to fenitrothion was found to have a 10-fold increase in GST activity and a 25- to 30-fold increase in AChE insensitivity (i.e., 10 x 25 = 250). 

The nature of enzyme inhibition by profenofos and PRO was further studied in the GO-fold resistant strain and enzyme, examining enzyme kinetic activity toward 12.5, 25, 50, 100 and 200 mmol L concentrations of I-naphthyl acetate. 

Bioassay data for the H. armi era strains arc shown in Tabic 13.1. Strains were 1U-, 30- and 60-fold resistant to fen valerate. Profenofos was ineffective as a pyrethroid synergist, but PBO rendered the 10-fold-resistant strain almost completely susceptible to fen valerate, In the more highly resistant populations (30-and 60-fold), PBO was much less effective. 

Thomas et al. (1991) induced 1449- fold resistance to deltaniethriii t[trough con tin nous larval selections of Quito quinqueftiM-iaiuji for 40 generations. When the larvae were subjected to selection pressure using deltamethrin and PBO (1 5) the speed of selection for del tame thrin resistance in the larvae slowed down considerably by 17 to 6195-. 

Genetic analysis and biochemical studies have shown that kdr resistance is linked to one of the building blocks of the sodium channels in the axon (the gene for the so-called a-subunit). The gene has been sequenced in R-and S-flies. The substitution of a leucine residue with a phenylalanine residue makes the difference. Equivalent mutations have been found in pyre-throid-resistant strains of several other insect species. Two point mutations in the a-subunit of the sodium channels are associated with super-kdr resistance. Such mutations have been detected in the housefly, horn fly, diamond moth, and body louse. It may cause several hundred-fold resistance. It is interesting to note that if knockdown, and not death, is used as the endpoint, the resistance level is much higher. 

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