IV aminophylline and IV caffeine provide rapid, safe reversal of regadenoson-induced adverse effects during SPECT MPI. Oral caffeine appeared similarly effective for CR but not for the combined CR + PRE. Our results suggest PO caffeine may be an effective initial strategy for reversal of regadenoson, but IV aminophylline or IV caffeine should be available to optimize symptom reversal as needed.

We have previously demonstrated that both isoprenylcysteine carboxylmethyltransferase (ICMT) and one of its substrates, the RhoGTPase Rac1, are critical for the tumor necrosis factor ␣ (TNF␣) stimulation of vascular cell adhesion molecule-1 expression in endothelial cells (EC). Here, we have shown that ICMT regulates TNF␣ stimulation of Rac1 activity. TNF␣ stimulation of EC increased the membrane association of Rac1, an event that is essential for Rac1 activity. ICMT inhibitor Nacetyl-S-farnesyl-L-cysteine (AFC) blocked the accumulation of Rac1 into the membrane both in resting and TNF␣-stimulated conditions. Similarly, the membraneassociated Rac1 was lower in Icmt-deficient versus wildtype mouse embryonic fibroblasts (MEFs). TNF␣ also increased the level of GTP-Rac1, the active form of Rac1, in EC. AFC completely suppressed the TNF␣ stimulation of increase in GTP-Rac1 levels. Confocal microscopy revealed resting EC Rac1 was present in the plasma membrane and also in the perinuclear region. AFC mislocalized Rac1, both from the plasma membrane and the perinuclear region. Mislocalization of Rac1 was also observed in Icmt-deficient versus wild-type MEFs. To determine the consequences of ICMT inhibition, we investigated the effect of AFC on p38 mitogen-activated protein (MAP) kinase phosphorylation, which is downstream of Rac1. AFC inhibited the TNF␣ stimulation of p38 MAP kinase phosphorylation in EC. TNF␣ stimulation of p38 MAP kinase phosphorylation was also significantly attenuated in Icmt-deficient versus wild-type MEFs. To understand the mechanism of inhibition of Rac1 activity, we examined the effect of ICMT inhibition on the interaction of Rac1 with its inhibitor, Rho guanine nucleotide dissociation inhibitor (RhoGDI). The association of Rac1 with its inhibitor RhoGDI was dramatically increased in the Icmt-deficient versus wild-type MEFs both in resting as well as in TNF␣-stimulated conditions, suggesting that RhoGDI was involved in inhibiting Rac1 activity under the conditions of ICMT inhibition. These results suggest that ICMT regulates Rac1 activity by controlling the interaction of Rac1 with RhoGDI. We hypothesize that ICMT regulates the release of Rac1 from RhoGDI.Some signaling proteins, such as small GTPases and the ␥ subunits of heterotrimeric G proteins, end with a CAAX (C for cysteine, A for aliphatic amino acids, and X for almost any other amino acid) sequence, which is post-translationally modified in three ways (1). Isoprenylation (farnesylation or geranylgeranylation) at cysteine is followed by cleavage of the last three amino acids (AAX) (1-3). Finally, the isoprenylated cysteine is carboxyl methylated by an endoplasmic reticulum resident enzyme (4, 5) isoprenylcysteine carboxylmethyltransferase (ICMT) 1 (5). This carboxyl methylation provides additional hydrophobicity to the isoprenylated proteins. Carboxyl methylation is dependent on the first two modifications and is potentially reversible.We demonstrated that ICMT and one of its substrates, the RhoGTPase Rac1, regulate in endothelial cells...

Importance of addressing dissatisfied consumers has increased very much these days because of intense competition due to establishment of new kind of stores and offering many kinds of customer services by service providers. This study focuses on effects of attitudinal and perceptional variables (attitude toward complaining, prior complaint experience, perceived possibility of success and customer"s loyalty) on Consumer Complaining Behavior (CCB). Model of this research is to complete the attitudinal or behavioral perspective and consumer complaining behavior literature in the frame work. A total of 232 people were asked to become the part of this study through a self administered questionnaire from Bahawalpur City. ISSN 2164-4063 2013 www.macrothink.org/ijld 122 This study uses a non-probability sampling technique that is convenience sampling. Regression results shown that attitude toward complaining, perceived possibility of success and customer loyalty had significant positive impact on consumer complaining behavior but relation between prior complaint experience and CCB was not proved to be significant. Careful studies have been carried out in order to validate conceptual frame-work that can be taken as an initial point to understand the concepts of Consumer Complaining Behavior (CCB). International Journal of Learning & Development

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