Human therapeutic strategies

Other major early contributions of biochemical engineering have been in the development of the artificial kidney and physiologically based pharmacokinetic models. The artificial kidney has been literally a lifesaver. Pharmacokinetic models divide the body of an animal or human into various compartments that act as bioreactors. These mathematical models have been used very successfully in developing therapeutic strategies for the optimal delivery of chemotherapeutic drugs and in assessing risk from exposure to toxins. 

In summary, these varied therapeutic strategies for using NO and fatty acids have potential for usefulness in human disease. The examples given are for cancer, but the potential extends to a variety of other human disorders. 

It has been postulated that ACE prevents ABP accumulation in the brain (634), and that treatment with ACE N-terminal domain-related peptides might be a potential therapeutic strategy in AD (641). Eckman et al. (642) analyzed ABP accnmulation in brains from ACE-deficient mice and in mice treated with ACE inhibitors and found that ACE deficiency did not alter steady-state ABP concentration in contrast, ABP levels were significantly elevated in ACE and NEP knockout mice, and inhibitors of these enzymes cause a rapid increase in ABP concentration in the brain (642). In contrast. Hemming and Selkoe (643) reported that ABP is degraded by ACE and elevated by ACE inhibitors, such as captopril, raising the question of whether currently prescribed ACE inhibitors could elevate brain ABP levels in humans. 

To explore the utility of this approach, plasma samples obtained after injection of TACA into the posterior segment of the eye in pigs were analyzed [8], The objective of this therapeutic strategy was to achieve a local, sustained, pharmacologically active concentration in the eye, with minimal systemic concentrations. In this application, the low water solubility of TACA contributes to its prolonged duration of action at the injection site a previous human study showed that intraocular TACA maintained concentrations >100 ng/mL in the eye for at least 700 h after a single 4-mg intravitreal TACA treatment [9], However, TACA concentrations in plasma... 

K. Sakamoto. Ubiquitin-dependent proteolysis its role in human diseases and the design of therapeutic strategies. Mol. Genet. Metab., 77 44—56, 2002. 

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