Multiple mechanisms

These unpredicted Avrami exponents may be indications that multiple mechanisms are operative and/or that f and/or N is itself a function of d. 

Mechanisms of Leukocyte Adsorption. The exact mechanism of leukocyte adhesion to filter media is not yet fuUy understood. Multiple mechanisms simultaneously contribute to the adhesion of cells to biomaterials, however, physical and biological mechanisms have been distinguished. Physical mechanisms include barrier phenomenon, surface tension, and electrostatic charge biological mechanisms include cell activation and cell to cell binding. 

Research and clinical experience on dmg resistance suggests that tumor cells are particularly adept at genetic selections leading to alterations in the stmcture, function, or synthesis of proteins involved in the antitumor dmg action and detoxification. Multiple mechanisms of resistance have been shown to account for the resistance seen in the clinic (46). 

There are multiple mechanisms known to underlie the neuronal cell damage associated with injury or disease that at least theoretically could be targeted for pharmaceutical intervention. Currently however, there is no clinically available therapeutic agent that can reliably protect the brain from progressive neurodegenerative processes for sustained periods. Due to the extensive amount of preclinical research that has been conducted in recent years, there is a basis for optimism, however, it appears likely that some of these approaches will result in clinically effective therapeutic modalities in the near future. A short overview of some of the investigational approaches to combat neurodegeneration appears below. 

ENZYMES EMPLOY MULTIPLE MECHANISMS TO FACILITATE CATALYSIS... 

Figure 46-5. Variations in the way in which proteins are inserted into membranes. This schematic representation, which illustrates a number of possible orientations, shows the segments of the proteins within the membrane as a-helicesand the other segments as lines. The LDL receptor, which crosses the membrane once and has its amino terminal on the exterior, is called a type I transmembrane protein. The asialoglycoprotein receptor, which also crosses the membrane once but has its carboxyl terminal on the exterior, is called a type II transmembrane protein. The various transporters indicated (eg, glucose) cross the membrane a number of times and are called type III transmembrane proteins they are also referred to as polytopic membrane proteins. (N, amino terminal C, carboxyl terminal.) (Adapted, with permission, from Wickner WT, Lodish HF Multiple mechanisms of protein insertion into and across membranes. Science 1985 230 400. Copyright 1985 by the American Association for the Advancement of Science.)...

The mechanisms of HIV-associated DSP are incompletely understood. Over the years, various hypotheses have been put forward, but recent data suggest that multiple mechanisms are likely to play a role in neuronal or axonal injury in DSP. These processes may be mediated by direct neurotoxicity of HIV or secreted viral proteins such as the envelope glycoprotein gpl20, or by indirect mechanisms... 

Non-selective P-blockers are first-line treatment for preventing variceal bleeding they vasoconstrict the splanchnic bed through multiple mechanisms. 

Each antidepressant has a response rate of approximately 60% to 80%, and no antidepressant medication or class has been reliably shown to be more efficacious than another 22 MAOIs may be the most effective therapy for atypical depression, but MAOI use continues to wane because of problematic adverse effects, dietary restrictions, and possibility of fatal drug interactions.22,28 There is some evidence that dual-action antidepressants, such as TCAs and SNRIs, may be more effective for inpatients with severe depression than are the single-action drugs such as SSRIs,22,28 but the more general assertion that multiple mechanisms of action confer efficacy advantages is quite controversial.33... 

Treatment of ocular allergy is aimed at slowing or stopping these processes. Antihistamines block the histamine receptors and some prevent histamine production and/or inhibit mediator release from the mast cells.15 Mast cell stabilizers inhibit the degranulation of mast cells, preventing mediator release. Some topical agents have multiple mechanisms of action, combining antihistaminic, mast cell stabilization, and antiinflammatory properties (Tables 60-3 and 60-4).16... 

Because of the multiple degradation pathways that may take place at elevated temperature, protein stability monitoring data may not conform to the Arrhenius relationship, and the maximum temperature selected for accelerated stability studies must be carefully selected. Gu et al. [32] described the different mechanisms of inactivation of interleukin-1 (3 (IL-1 (3) in solution above and below 39°C. In this example, the multiple mechanisms precluded the prediction of formulation shelf life from accelerated temperature data. In contrast, by working at 40° C and lower, Perlman and Nguyen [33] were able to successfully extrapolate data from stability studies of tissue plasminogen activator down to 5°C. 

Regulation of volume and water balance is of critical importance to survival in sepsis therefore it is not surprising that multiple mechanisms exist to maintain normovolemia and adequate blood pressure. 

These results indicate that multiple mechanisms account for the resistance of post-MBT embryos to ionizing radiation (Fig. 3). The relative importance of these mechanisms for resistance is not yet fully clear. However, over-expression of x-Bcl2 in pre-MBT embryos is sufficient to completely block apoptosis, and as indicated above, over-expression of constitutively active Akt reduces or delays the... 

FIG. 3. Apoptosis regulation at the MBT. The figure denotes the relative resistance of the embryo after the MBT to apoptosis induced by ionizing radiation (IR, X-rays) and the multiple mechanisms implicated in this resistance. 

Parathyroid hormone carries out these effects through multiple mechanisms of action ... 

Facilitation of dopaminergic activity by A9-THC may result from multiple mechanisms. A9-THC increases DA synthesis149 and release150 in synaptosomal preparations. In addition, using in vivo... 

Sweetnam P., Lancaster J., Snowman A. et al. Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine s putative anti-addictive activity. Psychopharmacology. 118 369, 1995. 

Among the multiple mechanisms that microorganisms have invented to acquire iron, some may lend themselves to preventive medicine by vaccination. Two such microbial strategies, manipulated to the benefit of the host, are briefly discussed here. 

The molecular details by which NAMI-A exerts antimetastatic effects in vivo have not been definitely determined, and may occur by multiple mechanisms. The solution chemistry of NAMI-A involves both loss of Cl and DMSO. Interestingly, the antimetastatic activity is retained under a wide variety of experimental conditions producing solvolyzed intermediates.192 The exact nature of the active species may be difficult to resolve. 

Kahvejian, A., Svitkin, Y. V., Sukarieh, R., M Boutchou, M. N., and Sonenberg, N. (2005). Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms. Genes Dev. 19, 104—113. 

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