Decreased uptake

Some of the previous sections have described the acquisition of low-level resistance to various antibiotics by alterations in the cell membrane causing decreased uptake of the drugs. These have normally have characterized as changes in components such as porins which result in a decrease of penetration by antibiotics. 

Amendation of soil with lime and organic matter decreases uptake (Adriano 1979 Hoyt and Adriano 1979). This is thought to reduce the solubility or increase americium binding, thereby reducing its availability. 

In principle, any kind of limitation of the medium (e.g. due to some kind of clustering in a zone) tends to diminish the individual uptake rate [31]. From the point of view of modelling, the breaking of the symmetry rapidly complicates the problem (see Chapter 3 in this volume). As an exception to the general rule of decreased uptake due to inter-cell competition, it has been shown [49] that biouptake through siderophore excretion is only viable for nonisolated cells. 

Extracellular chelators are not only known for decreasing uptake fluxes. Under iron-limiting conditions, many organisms are known to release side-rophores that strongly complex and solubilise iron (see Chapter 6 of this... 

The test is based on an in vitro assay of the uptake of the dye, neutral red (NR), in Balb/c 3T3 fibroblasts. It was developed to detect the phototoxicity induced by the combined interaction of the test substance and light of the wavelength range from 315 to 400 nm, the so-called UVA. The cytotoxicity is evaluated in the presence (+UVA) or absence (-UVA) of UVA light exposure, after application of a nontoxic dose of the compound. The cytotoxicological impact is assessed via the inhibition of the fibroblasts to take up the vital dye NR (NR is a weak cationic dye, penetrating easily into the cell membrane by a nonionic diffusion and accumulates in the lysosomes) one day after the initial treatment. Normally, healthy cells may incorporate and bind NR. Alterations of the cell surface or the lysosomal membranes, however, lead to a decreased uptake and binding of the dye. 

Lee, J., Bae, H., Jeong, J., Lee, J.-Y., Yang, Y.-Y., Hwang, L, Martinoia, E., and Lee, Y., 2003a, Functional expression of a bacterial heavy metal transporter in Arabidopsis enhances resistance to and decreases uptake of heavy metals. Plant Physiol. 133 589-596. 

Increased density of 5-HT2a receptors on the platelet membrane Decreased uptake of 3H-5-HT into platelet Increased beta adrenoceptor density on lymphocyte membrane Increased density of alpha-2 adrenoceptors on platelet membranes ) Blrmted growth hormone response to a clonidine challenge Blrmted prolactin response to a fenfluramine challenge... 

Thyroid 1 uptake may be decreased. False-negative results with the nitroblue-tetrazolium test for bacterial infection. Dexamethasone, given for cerebral edema, may alter the results of a brain scan (decreased uptake of radioactive material). 

Decreased uptake Methotrexate, melphalan, nitrogen mustards, cisplatin... 

Failure of Insulin to suppress gluconeogenesis in liver leads to overproduction of new glucose, which exacerbates the elevation of blood glucose due to decreased uptake of dietary glucose by muscle and adipose. 

Tuomisto J, Tukiainen E. Decreased uptake of 5-hydroxytryptamine in blood platelets from depressed patients. Nature 1976 262 596-598. 

Guanadrel [P] Decreased uptake of guanadrel into sites of action. 

The aminoglycosides interfere with bacterial protein synthesis by binding irreversibly to ribosome and could cause cell membrane damage. They may be inactivated by bacterial resistant enzymes but bacteria could also display resistance through ribosomal modifications or by decreased uptake of antibiotic into the bacterial cell. 

Decreased uptake of fatty acids In fasting, lipoprotein lipase activity of adipose tissue is low. Consequently, circulating triacyl-glycerol of lipoproteins is not available for triacylglycerol synthesis in adipose tissue. 

The mechanism by which the more recently used WR-2721 (Fig. 8) reduces nephrotoxicity is not very well understood. WR-2721 protects against nephrotoxicity when administered just prior to cis-Pt (144,145) and it is known that WR-2721 is preferentially taken up by normal cells and not by tumor cells (146). Recently, it was concluded that the uncharged form of the dephosphorylated WR-2721 (known as WE-1065) is the actual species taken up by both normal and tumor cells (147). It has been proposed that the conversion of WR-2721 to WR-1065 is slower in tumors, compared with normal tissues (147), possibly because tumors generally have lower levels of alkaline phosphatase (148). Furthermore, it has been proposed (147) that once formed, WR-1065 will have a decreased uptake rate in tumors, probably as a consequence of their lower pH (149) as compared with normal tissues i.e., the neutral form of WR-1065 will only constitute 0.1% of the total drug present at pH 7 and 1% of the total at pH 8. The reactive WR-1065 is likely to bind directly to cis-Pt, thereby preventing side reactions of cis-Pt. 

Many water-insoluble drugs are either weak bases or weak acids. There exists an equilibrium of ionized and unionized species for a weak base or a weak acid in an aqueous solution. The pH car affect the equilibrium between ionized and nonionized solute species, and consequently can have an effect on the capacity of micellar solubility. An example of this is the decreased uptake of 4-chlorobenzoic acid by polysorbate 80 micelles observed when the pH is changed from 3 to 4.4 (Collette and Koo, 1975). Another example regarding the effect of SDS micelles orKthefp atenolol, nadolol, midazolam, and nitrazepam is provided by Castro et al. (1998). Apparent acidity constants (p of the drugs were determined potentiometrically or spectrophotometrically in... 

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