Metabolic inactivation, tolerance

The daily dose of allopurinol is 300-600 mg. In combination with benzbromarone, the daily allopurinol dose is reduced to 100 mg. In general, allopurinol is well tolerated. The incidence of side effects is 2-3%. Exanthems, pruritus, gastrointestinal problems, and dty mouth have been observed. In rare cases, hair loss, fever, leukopenia, toxic epidermolysis (Lyell syndrome), and hqDatic dysfunction have been reported. Allopurinol inhibits the metabolic inactivation of the cytostatic dtugs azathioprine and 6-mercaptopurine. Accordingly, the administered doses of azathioprine and 6-mercaptopurine must be reduced if allopurinol is given simultaneously. 

The dally pattern of mydriasis noted after each Injection suggested metabolic Inactivation of BZ by rats within 24 h. No tolerance to the mydriatic response was, however, apparent during the course of the study. At the high dose there appeared to be a progressive... 

Work has also been done on the absorption and inactivation of organomercurials by micro-organisms that tolerate and even thrive on mercurials [26, 27]. It has been postulated that inactivation occurred by the uptake of fungicide by micro-organisms, followed by metabolic breakdown and by possible utilization of portions of the byproducts. However, whether or not biological inactivation and mercury evolution occur together has not been determined. 

Most of the antibiotics commercially available nowadays are derivatives of natural compounds produced by bacteria or fungi. It is widely accepted that in nature these secondary metabolites can act as weapons for microbial cell defence, inhibiting the growth of competitors. However, it seems that antibiotics have, in nature, more sophisticated and complex functions [1-3]. Many environmental bacteria can not only cope with natural antimicrobial substances but also benefit from their presence. For instance, the use of antibiotics by bacteria as biochemical signals, modulators of metabolic activity or even carbon sources has been demonstrated [1, 2, 4]. In other cases, antibiotics can be tolerated because they have structures similar to the natural substrates of bacterial housekeeping enzymes and thus are inactivated, leading to a natural form of resistance [2]. These are just some... 

Adaptability of Shewanella oneidensis MRl and Escherichia coli in these experiments indicates that microorganisms can continue to metabolize substrate at pressures far beyond those previously reported [34, 35,41], Although an evolutionary component to the adaptation of microbial communities to temperature and salinity is well known [71], whether there might be any evolutionary component for pressure adaptation is still in question. Shewanella MRl belongs to a genus that contains a number of piezophiles however, E. coli clearly does not. Despite this, there is evidence that exposure of E. coli to pressures up to 800 MPa selects a population of cells less sensitive to pressure inactivation [71]. Furthermore, it is well known that the increase in pressure tolerance is also associated with heat tolerance [71]. 

Shimabukuro et al. (1971), investigating the metabolism of atrazine in maize, found that the tolerance of maize is not brought about by the above nonenzymatic inactivation alone, but that the primary factor is an enzyme, which conjugates triazine with glutathione, which is then converted to the glutamyl-S-cysteine derivative ... 

Since erythromycin complexes and inactivates drug oxidizing systems such as cytochrome P-450, it has the potential to alter the metabolism of other drugs. The metabolism and excretion of theophylline, warfarin, carbamaz-epine, and methylprednisolone are inhibited by erythromycin [283-286]. As a potent antibiotic, it can also affect metabolism by gut micro-organisms of drugs such as digoxin. At least some of the newer derivatives may cause fewer drug interactions and thus may be better tolerated if co-administered with medications for other illnesses [287-289]. 

Potentially, a safener could increase the tolerance of the crop by reduction of herbicide uptake and translocation, or by enhancement of metabolic herbicide inactivation in the crop tissue. Furthermore, a safener could counteract the effect of a herbicide at its biochemical target site, with a resultant reduction of crop susceptibility. Evidence for and against these potential modes of action is presented in the following sub-sections. In addition, aspects of safener specificity (crop versus weed) are covered for situations where the safener is applied in tank mix with the herbicide. 

Just as wheat appeared to be tolerant toward diclofop at the whole-plant but not the enzyme level, because of selective inactivation, so various fescue grasses have been shown to be tolerant. At the chloroplast level, the sensitivity of Festuca ovina and F. rubra toward diclofop was comparable to that of the sensitive P. arundinacea The resistance to diclofop in vivo appears to be due to metabolism of the herbicide to less active compounds, as in wheat. By contrast, F. ovina and F. rubra are also resistant to cycloxydim, but, in that case, fatty acid synthesis by isolated chloroplasts is also relatively unaffected (I50 about 100 pM). There may be some differences in the acetyl-CoA carboxylase protein structure in these species that renders cycloxydim binding less effective than usual. 

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