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A number of laboratories have been working oncombinatorial therapy with the MDM2 antagonists as shown in Table 16.2.Combinatorial therapy in a systematic manner seems more effective than empiri-cally determined combination regimens, as p53 mutations confer absolute resistanceor de novo p53-mutated multi-drug resistance emerges to MDM2 antagonists [135,136], and more than 50 % of human cancers carry p53 mutants . Peri-implantitishas been characterized by some as an inflammatory process around an implant,which includes both soft tissue inflammation and progressive loss of supportingbone beyond biological bone remodeling  Peri-implantitishas been characterized by some as an inflammatory process around an implant,which includes both soft tissue inflammation and progressive loss of supportingbone beyond biological bone remodeling . Fogal V, Hsieh JK, Royer C, Zhong S, Lu X (2005) Cell cycle-dependent nuclear retention ofp53 by E2F1 requires phosphorylation of p53 at Ser315. If a significantamount of albumin leaks out of the blood vessels into theloose connective tissue or is lost from the blood to urine inthe kidneys, then the colloid osmotic pressure of the blooddecreases, and fluid accumulates in the tissues.
This disparity is likelyto continue to grow as medical technologies advance giving us the ability to prolonglife further. Butethical standards and norms cannot be written in stone and applied uniformlyeverywhere Butethical standards and norms cannot be written in stone and applied uniformlyeverywhere.
However, aging also is associated withreduced ability to tolerate sleep deprivation.
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Figure 22.1 provides a generic template forunderstanding a general process for completing each ofthese tasks, illustrating the interrelatedness of the healthparadigm.
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