Half-life mechanism

The principal organs involved in the peripheral clearance of hGH from the plasma are the kidney and fiver. hGH is cleared via glomerular filtration at the kidney and by a receptor-mediated mechanism at the fiver (58,59). In animal models, derivatives of hGH such as the 20,000 mol wt variant, oligomeric forms, and hGH complexed with GH-binding protein have been shown to be cleared from the semm at significandy lower rates than 22,000 mol wt hGH (60—62). The prolonged plasma half-life of these derivatives probably reflects a combination of decreased receptor affinity and size constraints on glomerular filtration. 

Calcitonin is secreted when abnormally high calcium levels occur in plasma. Although plasma concentrations are normally minute (<100 pg/mL), they increase two- to threefold after calcium infusion. Calcitonin has a short plasma half-life (ca 10 min). Certain thyroid tumors are the result of CT concentrations 50—500 times normal. The mechanism of action is a direct inhibition of bone resorption. Calcitonin is used clinically in various diseases in which hypercalcemia is present, eg, Paget s disease (46). 

Because bretylium is poody absorbed from the GI tract (- 10%), it is adrninistered iv or im. Very litde dmg is protein bound in plasma. Bretylium is taken up by an active transport mechanism into and concentrated in postganglionic nerve terminals of adrenergicahy innervated organs. Peak plasma concentrations after im injections occur in about 30 min. Therapeutic plasma concentrations are 0.5—1.0 p.g/mL. Bretylium is not metabolized and >90% of the dose is excreted by the kidneys as unchanged dmg. The plasma half-life is 4—17 h (1,2). 

The mechanisms by which a jurisdiction develops its air pollution control strategies and episode control tactics are outlined in Fig. 5-1. Most of the boxes in the figure have already been discussed—sources, pollutant emitted, transport and diffusion, atmospheric chemistry, pollutant half-life, air quality, and air pollution effects. To complete an analysis of the elements of the air pollution system, it is necessary to explain the several boxes not vet discussed. 

In the field of nuclear energy, titanium has been used for processing of fuel elements, where this demands use of nitric acid or aqua regia ", and for control-rod mechanism, in which the short half-life of irradiated titanium is of advantage. 

The regulation of receptor synthesis is a second component of receptor downregulation. It involves processes that reduce gene transcription, mRNA stability, and receptor half-life time. It should be noted that mechanisms in addition to the regulation of the receptor number may account for tolerance development. Second messenger levels and enzyme activities that participate in the signaling of a given receptor are... 

The triazolinyl radical 116 is thermally unstable with a half-life of -20 min at 95 °C. The compound 117 is stable under similar conditions. The decomposition mechanism involves loss of a phenyl radical and formation of a stable aromatic triazene (Scheme 9.26).24 This provides a mechanism for self regulation of the stable radical concentration during polymerization and a supplemental source of initiating radicals. 

Bunnett (1991) expresses doubts that the aryldiazene can be formed at all under these strongly basic conditions, after Huang and Kosower (1968) showed that phenyldiazene is destroyed in water at pH 13.8 (25 °C) with a half-life of <10s, doubtless via C6H5-N2. In addition, Broxton s proposal (Scheme 8-53) does not provide a satisfying explanation of why the ortho halogen has such a strong effect in favor of the carbanion mechanism. 

ALASl. This repression-derepression mechanism is depicted diagrammatically in Figure 32-9. Thus, the rate of synthesis of ALASl increases greatly in the absence of heme and is diminished in its ptesence. The turnover rate of ALASl in rat liver is normally rapid (half-life about 1 hour), a common feature of an enzyme catalyzing a rate-limiting reaction. Heme also affects translation of the enzyme and its transfer from the cytosol to the mitochondrion. 

Toremifene also undergoes oxidative metabolism to form a QM.59 The 4-hydro-xytoremifene QM has a half-life of lh at physiological pH and temperature (Table 10.2), while its half-life in the presence of GSH is approximately 6 min.59 The 4-hydroxytoremifene QM reacts with two molecules of GSH and loses chlorine to yield the corresponding di-GSH conjugate (Scheme 10.9). This reaction mechanism likely involves an electrophilic episulfonium ion intermediate, which could contribute to the potential cytotoxicity of toremifene. 

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