Intracellular penetration

Avrameas, S., and Ternynck, T. (1971) Peroxidase labelled antibody and Fab conjugates with enhanced intracellular penetration. Immunochemistry 8, 1175. 

Antibiotics that block bacterial protein biosynthesis. Macrolides Target the 508 ribosome subunit. Tylosin, which is widely used in the livestock Clarithromycin (biaxin) Semisynthetic and has better intracellular penetration compared to earlier... 

Oral bioavailability of telithromycin is 57%, and tissue and intracellular penetration is generally good. Telithromycin is metabolized in the liver and eliminated by a combination of biliary and urinary routes of excretion. It is administered as a once-daily dose of 800 mg, which results in peak serum concentrations of approximately 2 mcg/mL. Telithromycin is indicated... 

The component(s) of the mycobacterial cell wall responsible for conferring intrinsic resistance to antibiotics are not yet known with any certainty. However, it has been shown [91-93] that inhibitors of arabinogalactan synthesis increase mycobacterial sensitivity to antibiotics. When M. avium is treated with inhibitors of mycolic acid biosynthesis there are significant alterations in outer cell wall layers and the cells show an increased antibiotic susceptibility [93], Thus, arabinogalactan and mycolic acids are components of the wall associated with intrinsic resistance of mycobacteria to chemotherapeutic drugs and alteration of these structural building blocks leads to increased intracellular penetration of antibiotics [88,94,95],... 

Garcia I, Pascual A, Ballesta S, Joyanes P, Perea EJ. Intracellular penetration and activity of gemifloxacin in human polymorphonuclear leukocytes. Antimicrob Agents Chemother 2000 44(ll) 3193-5. 

Monoterpenes are most fi-equently applied as promotors of sorption. The growth of intracellular penetration of a drug in the presence of terpenes is probably connected with an increase of solubility of this drug in the corny stratum of the skin. Monoterpenes can also disturb the regular order of lipids in the intracellular spaces. Monoterpenes as promoters increase the division coefficient of corny stratum/matrix for lipophilic drugs. The penetration speed of lipophilic compounds increases together with their solubility in the promoter (monoterpenes). On the other hand, however, the increase of the penetration speed for hydrophilic compoxmds increases together with the diffusion coefficient [62-68]. 

Modified short DNA and RNA molecules with novel bond linkages between the bases have been designed with the aim to use the antisense approach by binding to the RNA template in the hTR subunit(s) to prevent or halt transcription and thereby act as competitive inhibitors of telomerase activity. Hence, the hTR RNA template is unavailable to hTERT for reverse transcription (52). The various types of sugar phosphodiester backbone modifications in these molecules are intended to confer certain desirable characteristics or properties, such as intracellular penetration, superior binding affinity, and therefore specificity, to the hTR RNA template and in order to enable intact delivery to their target. 

Compound 23 also interfered with the settling behavior of the aphid M. persicae an efficient plant virus transmitter. Choice assays showed that this compound had antifeedant potencies slightly lower than the positive control famesol (table 7). Furthermore, the electronic monitorization of the aphid s probing behavior (EPG) showed that 23 reduced the number of intracellular penetrations (table 8) [34], This is an important parameter when considering the transmission of non-persistent plant viruses by this insect [35],... 

The in vitro vasodilating potencies of several S-nitrosothiols with varying oil/water partition coefficient (and therefore cellular permeability) were found to be essentially identical (Kowaluk and Fung, 1990), indicating that intracellular penetration of intact S-nitrosothiols may not he required for vasodilating activity. Bovine vascular smooth muscle cells were found to... 

DNA polyplexes have been encapsulated and released from polymer microspheres, which may enable these microspheres to be fabricated into matrices using an approach such as the gas-foaming procedure. PLL/DNA complexes have been incorporated into PLG microspheres using a double emulsion process. DNA is incorporated with efficiencies ranging from 30% to 45%, is released over approximately 35 days, and retains its integrity [207, 208]. Alternatively ONs complexed with PEI have been incorporated and released from PLG microspheres. The release profile of the ON/PEI complexes depended on the size, loading, and pore structure of the microspheres. The sustained release of ON/PEI complexes resulted in improved intracellular penetration of the delivered vector as compared with uncom-plexed DNA [209, 210]. PLG/DNA scaffolds have successfully been used in vivo to enhance matrix deposition [113], angiogenesis [112, 113, 115], and bone formation [114]. 

De Rosa G, et al. (2003). Long-term release and improved intracellular penetration of oligonucleotide-polyethylenimine complexes entrapped in biodegradable microspheres. Biomacromol. 4 529-536. 

Another approach to demonstrating intracellular penetration is to examine nuclear uptake in the cells. After incubation of neuroblast monolayers with T3 or T, the cells are disrupted and the nuclei are isolated and their hormone content measured. We have shown that the accumulation of labeled hormone in nuclei is strongly diminished in the presence of antimycin or MDC. These agents, however, do not inhibit uptake by isolated nuclei. Further evidence is presented in Fig. 5, based on the apparent affinity of nuclear receptors after whole cell incubations compared to the affinity determined with previously isolated nuclei. It can be seen that the receptor affinity for L-T3 and L-T measured in intact cells is more than 3 times that in isolated nuclei. This can be attributed to a step-up in the concentration of free hormone in the cytoplasm over the concentration in the medium, the latter value being used in the calculation of Ka in intact cells. 

Strontium is transferred from blood to the interstitial fluid to the same extent as calcium, but intracellular penetration appears to be limited [68,69]. In biological membranes, it has the unique capacity that it can replace calcium even at sites highly specific for calcium [70]. Inside the cell, strontium accumulates, among others, in the mitochondria to levels of 2.5 p,mol strontium/mg mitochondrial protein [71]. 

Although cortisone interferes with protein synthesis in peripheral tissue, the hormone stimulates protein synthesis in liver. The increased rate of protein synthesis results from an effect of the hormone on the penetration of the amino acid through the cell membrane. The effects of the steroid hormones on the amino acid penetration were demonstrated with the aid of a-aminoisobutyric acid, a nonmetabolizable amino acid the intracellular penetration of which is regulated by mechanisms similar to those controlling glycine penetration. The penetration of a-aminoisobu-tyric acid is competitively inhibited by valine. Two hours after the injection of cortisol, the aminoisobu-tyric acid content of the liver is increased 70%. The increase in amino acid uptake may explain the increase of protein synthesis in liver observed early after cortisone injection. In that connection, it is of interest that an accelerated turnover of serum albumin has been reported early after the injection of cortisone. Since the concentrations in the levels of the blood protein are not changed, it seems that increased synthesis only compensates for increased catabolism. 

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