Tissue penetration

Most ACE inhibitors are prodrugs, with the exceptions of captopril, lisinopril, and ceranapril. Prodrugs exert improved oral bioavailability, but need to be converted to active compounds in the liver, kidney, and/or intestinal tract. In effect, converting enzyme inhibitors have quite different kinetic profiles with regard to half time, onset and duration of action, or tissue penetration. 

TCA is a chemical cauterant the application of which to the skin causes protein denaturation, so called keratocoagulation, resulting in a readily observed white frost. The degree of tissue penetration and ensuing injury by a TCA solution is dependent on several factors, including strength of TCA used, skin preparation and anatomic site. 

This is important when considering your subsequent period of fixation. For example, suspended cells in fixative for 24h are not being subjected to the same effects as a 5-mm biopsy for the same period. The formalin penetration and fixation effects are greater across a 50-100p cell versus a 5-mm piece of tissue. Penetration and the actual fixation of the tissue, cells, and protein are two different things. 

In addition to key factors that have guided improvements in our design of drugs, such as stability in the dark and controlled photoactivation, efforts are aimed particularly at shifting the absorption band relevant for photoactivation towards higher wavelengths for better tissue penetration, while maintaining the... 

The importance of tissue penetration varies with the site of infection. The CNS is one body site where the importance of antimicrobial penetration is relatively well defined and correlations with clinical outcomes are established. Drugs that do not reach significant concentrations in cerebrospinal fluid should either be avoided or instilled directly when treating meningitis. 

Protein block Incubate slides in nonimmune serum (e.g., 10% normal horse serum in phosphate buffered saline [PBS]), for 20-30 min to prevent nonspecific binding. An appropriate concentration (e.g., 0.1%-1.0%) of detergent like triton X-100 may be used during this step to increase tissue penetration. Shake off rather than rinse off blocking serum. 

The general immunocytochemical principles as applied to whole-mounts do not differ substantially from those applied to cells (see Chapters 16 and 17). However, several additional factors must be taken into account. Foremost is the problem of tissue penetration by reagents. Unlike sectioned material where intracellular components are directly exposed to the reagents, in whole-mount... 

Delayed mortality after bromine exposure has been associated with peribronchiolar abscesses and is thought to be due to deep tissue penetration and damage caused by the relatively soluble bromine. ... 

Increase the depth of tissue penetration. This could be achieved by moving to... 

Nitrofurantoin is administered orally and is rapidly and almost completely absorbed from the small intestine only low levels of activity are achieved in serum because the drug is rapidly metabolized. Relatively high protein binding (about 70%) also affects serum levels, reducing potential for systemic toxicity and alteration of intestinal flora. Relative tissue penetration is much lower than other antimicrobials for UTIs, and therefore, nitrofurantoin is not indicated in the therapy of infections such as pyelonephritis and renal cortical or perinephric abscesses. Nitrofurantoin is rapidly excreted by glomerular filtration and tubular secretion to yield effective urinary levels. In moderate to severe renal dysfunction, toxic blood levels may occur while urinary levels may be inadequate. The drug is inactivated in the liver. 

D) He has cumulative CNS toxicity of ciprofloxacin secondary to poor urinary and prostatic tissue penetration. 

Tissue penetration of endotamponade media should be avoided because of non-calculable side effects. One way to reduce the penetration rate is the use of branched species. In a similar experiment as described above, small pieces of fatty tissue and muscle tissue from pig were immersed in the test liquids for 15 min and then rinsed with PFD to clean the surfaces. Table 13 shows the reduced ratio of penetration of branched perfluorobutyl-butane in comparison to the linear form (044 perfluorobutyl-n-butane and 044v 1-perfluorbutyl-2-methyl-propane, own unpublished results). The relative penetration ratio was determined on the basis of the concentration of the two types of perfluorobutyl-butane indicated by GC/MS measurements. 

But it has to be taken into consideration that a complete suppression of tissue penetration may have not only surgical advantages. 

Table 13. Difference in tissue penetration of branched and unbranched species...

All these parameters are very close to the requirements which a long-term ocular endotamponade has to fulfil. Also the in vivo tests in a rabbit eye model were extremely promising no emulsification, no changes in the vascular structure of the retina and no increase of the intra-ocular pressures. All negative side effects, seen with the monomeric FCLs, seemed to be eliminated. In addition, some additional advantages could be claimed reduced tissue penetration and the potential to dissolve drugs [44,45]. 

Tetracycline of choice due to broad spectrum, long t>/2, superior tissue penetration, and excellent oral absorption... 

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