Dual effects

Two compressors (one dual-effect type) Individual expansion valves 47.3 10.2... 

Thus inhibitive anions can retard the dissolution of both the T-FejO, and the magnetite layers of the passivating oxide layer on iron. This has the dual effect of preventing breakdown of an existing oxide film and also of facilitating the formation of a passivating oxide film on an active iron surface, as discussed in the previous section. 

PTH has a dual effect on bone cells, depending on the temporal mode of administration given intermittently, PTH stimulates osteoblast activity and leads to substantial increases in bone density. In contrast, when given (or secreted) continuously, PTH stimulates osteoclast-mediated bone resorption and suppresses osteoblast activity. Further to its direct effects on bone cells, PTH also enhances renal calcium re-absorption and phosphate clearance, as well as renal synthesis of 1,25-dihydroxy vitamin D. Both PTH and 1,25-dihydroxyvitamin D act synergistically on bone to increase serum calcium levels and are closely involved in the regulation of the calcium/phosphate balance. The anabolic effects of PTH on osteoblasts are probably both direct and indirect via growth factors such as IGF-1 and TGF 3. The multiple signal transduction... 

Badr AE, Yin W, Mychaskiw G, Zhang JH. Dual effect of hbo on cerebral infarction in mcao rats. Am J Physiol Regul Integr Comp Physiol 2001 280 R766-R770. 

It has been known for some time that the Cl -conductance of epithelial cells can, in addition to its regulation via cAMP, be enhanced by increases in cytosolic Ca " (cf. Fig. 3). This has been shown with Ca -ionophores [120,121] or with hormones increasing cytosolic Ca such as carbachol, neurotensin, ATP, etc. [50,103,104]. Usually these agonists have dual effects. They increase the Cl - as well as the K" -conductance [104]. Stubs et al. [122] have shown that CF cells still increase their Cl -conductance in response to ATP. Another mechanism of Cl -channel activation has been described in whole-cell patches of colonic carcinoma and RE cells [123,124] when the cells are exposed to hypotonic media they swell and increase their Cl -conductance. This is a rather general phenomenon which is present in a lot of cells [11]. In their effort to reduce cell volume in hypotonic media (regulatory... 

Sun, H. Liu, X. Xiong, Q. Shikano, S. Li, M. Chronic inhibition of cardiac Kir2.1 and hERG potassium channel by celastrol with dual effects on both ion conductivity and protein trafficking. J. Biol. Chem. 2006, 281, 5877-5884. 

Oyajobi BO, Franchin G, Williams PJ, et al. Dual effects of macrophage inflammatory protein-lalpha on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease. Blood 2003 102(1) 311—319. 

Evidently, the activation energy for a thermally neutral reaction with participation of a hydrogen atom or a radical (alkyl, alkoxyl, etc.) is higher in these cases where there is a iT-bond or an aromatic ring adjacent to the attacked C—H bond. This effect is a property of the structures themselves, and the n-bond exerts a dual effect on the reaction center. On the one hand, by weakening the C—H bond the ir-bond in the a-position lowers the enthalpy... 

In animal studies, mirex (a nonmutagenic hepatocarcinogen) promoted mouse skin squamous carcinomas and papillomas after initiation with 7,12-dimethyl-benz[a]anthracene (DMBA) for 1 week. Mirex, also, potentiated the promotional potency of the phorbol ester tumor promoter, 12-0 -tetradecanoylphorbol-13-acetate (TPA). There was a 90% incidence (activation) of the c-Ha-ras tumor gene in these co-promoted tumors. When both mirex and TPA gave a similar tumor yield, only the TPA response was associated with biochemical markers of enhanced cell proliferation, induction of epidermal ornithine decarboxylase activity and increased DNA synthesis, and hyperplasia. Thus, there is evidence for a dual effect of mirex during co-promotion first, as an independent tumor promoter with a mechanism different than that of phorbol esters and second, as a compound that also potentiates skin tumor promotion by TPA (Meyer et al. 1993, 1994 Moser et al. 1992, 1993). 

Bupropion is another alternative pharmacological approach to tobacco abstinence. It is an antidepressant drug that blocks reuptake of norepinephrine and dopamine, and also blocks nicotinic receptors in the low to intermediate micromolar range (Fryer and Lukas 1999). Thus, the effects of bupropion on nicotine addiction may be through dual effects on dopaminergic and nicotinic systems. Further, it has been an effective treatment in controlled studies, both alone and in combination with the nicotine patch. Bupropion alone or in combination with a nicotine patch was more effective than placebo or the nicotine patch alone. 

Anandamide has dual effects on NMDA receptor function. It reduces NMDA Ca2-i- currents, which is mediated by cannabinoid receptors and G-protein mechanisms (Hampson et al. 1998). However, anandamide potentiates NMDA currents due to a direct effect on the NMDA receptor itself. THC did not have the same effect. So anandamide appears to have at least one other CNS effect that is not through the cannabinoid receptors. THC also reduces AMPA/kainate activity, which is mediated by CBl receptors (Shen and Thayer 1999) (table 10.5). THC may in-... 

Hampson AJ, Bornheim LM, Scanziani M, Yost CS, Gray AT, Hansen BM, Leonoudakis DJ, Bickler PE. (1998). Dual effects of anandamide on NMDA receptor-mediated responses and neurotransmission. J Neurochem. 70(2) 671-6. 

Peyrin, E. et ah. Interactions between d,L dansyl amino acids and immobilized teicoplanin study of the dual effect of sodium citrate on chiral recognition, Chromatographia, 53, 645, 2001. 

Some agents are bifunctional, causing the release of histamine and recruiting leukocytes. Bifunctional mediators include bacterial peptides, endotoxins, DNA, C3a, C5a and bradykinin. Each of these substances can exert dual effects. This may either occur directly, as in the case of bacterial peptides and bradykinin causing chemotaxis and bronchial smooth muscle contraction, or indirectly, as endotoxin and DNA conversion of complement. C3a and C5a act indirectly as complement fragments to effect histamine release, which in turn contracts bronchial smooth muscle. However, both appear to act directly to effect chemotaxis with C5a, the more potent fragment. 

Figure 7.15 Inhibition of acetyl-CoA carboxylase by cyclic AMP dependent protein kinase and AMP dependent protein kinase the dual effect of glucagon. Phosphorylation of acetyl-CoA carboxylase by either or both enzymes inactivates the enzyme which leads to a decrease in concentration of malonyl-CoA, and hence an increase in activity of carnitine palmitoyltransferase-I and hence an increase in fatty acid oxidation. Insulin decreases the cyclic AMP concentration maintaining an active carboxylase and a high level of malonyl-CoA to inhibit fatty acid oxidation.

Treatment with a diuretic and an ACE inhibitor is usually very effective. ACE inhibition may be preferable to the use of a receptor antagonist since the inhibition has a dual effect on vasodilation it decreases the concentration of angiotensin II, which is a vasoconstrictor, but increases that of bradykiitin, which is a vasodilator (see Eigure 22.16). 

Simons V et al (2006) Dual effects of plant steroidal alkaloids on Saccharomyces cerevisiae. Antimicrob Agents and Chemother 50 2732... 

Castilla, R. et al. (2004) Dual effect of ethanol on cell death in primary culture of human and rat hepatocytes. Alcohol and Alcoholism (Oxford, Oxfordshire), 39 (4), 290-296. 

With this caveat in mind, each side of the debate has evidence to support its position. The evidence is first summarized supporting the position that SSRIs are less effective than are some other antidepressants (particularly those with dual effects on both serotonin and NE CNS systems) in patients with more severe depression or who are hospitalized. Danish investigators in two double-blind, active-controlled studies found that clomipramine produced a superior response with either paroxetine or citalopram in the treatment of patients hospitalized for major depression (116, 117). Two double-blind studies also have shown that venlafaxine and mirtazapine were more effective than fluoxetine in patients hospitalized with depression ( 114,118). Finally, there are studies showing that the addition of desipramine (one of the most selective NE reuptake inhibitors) to an SSRI can convert nonresponders or pamal responders to full response ( 119, 119a, 120). 

Cunningham MO et al Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro. Euro 3 Neurosci 2004 20 1566. 

The effectiveness of ketoprofen at dosages of 100-300 mg/d is equivalent to that of other NSAIDs. In spite of its dual effect on prostaglandins and leukotrienes, ketoprofen is not superior to other NSAIDs in clinical efficacy. Its major adverse effects are on the gastrointestinal tract and the central nervous system (see common adverse effects above). 

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