Target site

W. Knller, ed.. Target Sites of Fungicide Mction, CRC Press, Boca Raton, Fla., 1992. 

Insulin is a peptide hormone, secreted by the pancreas, that regulates glucose metabolism in the body. Insufficient production of insulin or failure of insulin to stimulate target sites in liver, muscle, and adipose tissue leads to the serious metabolic disorder known as diabetes mellitus. Diabetes afflicts millions of people worldwide. Diabetic individuals typically exhibit high levels of glucose in the blood, but insulin injection therapy allows diabetic individuals to maintain normal levels of blood glucose. 

Gene in pla.smid with mutation target. site X... 

Drugs can only be effective if enough is present at the target site and they can be harmful if too much is present so as to produce toxic side effects. Any attempt to draw conclusions about the clinical efficacy of a drug in a clinical trial without knowledge of the concentration at the target site is premature. The science of pharmacokinetics basically... 

From the mechanistic point of view three basic principles of microbial resistance to drugs are known inactivation of the drug, alteration of the target, and reduced drug accumulation at the target site. However, several variations on these themes are known. 

Two mechanisms are operating alone or in concert to minimize the antibiotic concentration at the intracellular target site Downregulation of the expression of the pore proteins, also called porins, and upregulation of one or a set of several unspecific efflux pumps. However, the impact of these mechanisms on the resistance is low, since due to the essential function of porins for uptake of nutrients their reduction is limited and to avoid disturbances of membrane integrity due to extensive oveiproduction of mdr efflux pumps these are subjected a strict regulation. 

Finally, it has to be mentioned that LPA also has an intracellular target site, which is the nuclear transcription factor, peroxisome proliferator-activated receptor-y (PPARy). LPA competes for thiazolidinedione binding and activates PPARy-dependent gene transcription. Thereby, LPA induced neointima formation in a rat carotid artery model. 

A common means that causes resistance is the inactivation of the antibiotic before it reaches the target site. Antibiotics can be either enzymatically cleaved or modified. In both cases the antibiotic loses its capacity to bind to its target. 

The second general mechanism to cause resistance to antibacterial agents is to prevent the drug from reaching its target site. This is either achieved by altered rates of entry (reduced uptake) or by the active removal of the dtug (active efflux) [4]. 

Bacterial resistance can be caused by actively pumping antibiotics out of the cell and therefore decreasing the concentration at the target site. Drug efflux systems in bacteria are classified into four major groups based on their sequence homologies and functional similarities (Table 3). 

Lambert PA (2005) Bacterial resistance to antibiotics modified target sites. Adv Drug Deliv Rev 29 1471-1485... 

From these studies it is clear that the progression of PAR-based therapy relies upon the future development of new specific agonists and antagonists for PARs 2-4 with much higher potencies than those currently available, with an efficient mode of delivery to target sites. However despite these problems the PARs still rqiresent one of the most attractive therapeutic targets for a number of disease states. 

Most dragp have an affinity for certain organs or tissues and exert their greatest action at the cellular level on those specific areas, which are called target sites. There are two main mechanisms of action ... 

The pilosebaceous follicles are the target sites for acne. The pathophysiology of acne centers on interplay of follicular hyperkeratinization, increased sebum production, action of Propi-onibacterium acnes (P. acnes) within the follicle, and production of inflammation (Table 11.1). 

Resistance to DDT has been developed in many insect species. Although there are some cases of metabolic resistance (e.g., strains high in DDT dehydrochlorinase activity), particular interest has been focused on kdr and super kdr mechanisms based upon aberrant forms of the sodium channel—the principal target for DDT. There are many examples of insects developing resistance to dieldrin. The best-known mechanism is the production of mutant forms of the target site (GABA receptor), which are insensitive to the insecticide. 

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