Neuromarketing is an emerging field that bridges the study of consumer behavior with neuroscience. Controversial when it first emerged in 2002, the field is gaining rapid credibility and adoption among advertising and marketing professionals. Each year, over 400 billion dollars is invested in advertising campaigns. Yet, conventional methods for testing and predicting the effectiveness of those investments have generally failed because they depend on consumers' willingness and competency to describe how they feel when they are exposed to an advertisement. Neuromarketing offers cutting edge methods for directly probing minds without requiring demanding cognitive or conscious participation. This paper discusses the promise of the burgeoning field of neuromarketing and suggests it has the potential to significantly improve the effectiveness of both commercial and cause-related advertising messages around the world.
A new bisboronic acid based glucose sensor 7 was synthesized from 9,10-bis(chloromethyl)anthracene
and 2,2-dimethyl-1,3-propanediol protected 3-pyridineboronic acid. Due to its ionic structure 7 was
found sufficiently water soluble for carbohydrate binding studies at neutral pH by means of NMR
spectroscopy, fluorometry, and potentiometry. The pK
a's of 7 have been determined to 3.7 and 4.7
by potentiometric titration. From a solution of 7 and glucose (1:1) in water (pH 7.4) we observed
the formation of a bisdentate boronic acid complex 7·Glu which has been assigned to a 1,2:3,5
bound α-d-glucofuranose complex. The evidence for this furanose structure comprises 1H and 13C
NMR data with emphasis on the information from 1
J
C
-
C coupling constants. Complex 7·Glu shows
an increased fluorescence compared to 7. The stability constant for the 1:1 complex (log K = 3.4)
was determined from fluorometric titration, potentiometry, and NMR spectroscopy. Boronic acid 7
shows good selectivity for glucose compared to fructose and galactose.
Chemotherapy of malaria parasites is limited by established drug resistance and lack of novel targets. Intraerythrocytic stages of Plasmodium falciparum are wholly dependent on host glucose for energy. Glucose uptake is mediated by a parasite-encoded facilitative hexose transporter (PfHT). We report that O-3 hexose derivatives inhibit uptake of glucose and fructose by PfHT when expressed in Xenopus oocytes. Selectivity of these derivatives for PfHT is confirmed by lack of inhibition of hexose transport by the major mammalian glucose and fructose transporters (Gluts) 1 and 5. A long chain O-3 hexose derivative is the most effective inhibitor of PfHT and also kills P. falciparum when it is cultured in medium containing either glucose or fructose as a carbon source. To extend our observations to the second most important human malarial pathogen, we have cloned and expressed the Plasmodium vivax orthologue of PfHT, and demonstrate inhibition of glucose uptake by the long chain O-3 hexose derivative. Furthermore, multiplication of Plasmodium berghei in a mouse model is significantly reduced by the O-3 derivative. Our robust expression system conclusively validates PfHT as a novel drug target and is an important step in the development of novel antimalarials directed against membrane transport proteins.Xenopus oocyte ͉ malaria ͉ antimalarial ͉ glucose analogues ͉ transport
The ionization and lipophilicity behavior of the antihistamine (H1-receptor antagonist) cetirizine was investigated, showing the drug to exist almost exclusively as a zwitterion in the pH region 3.5-7.5. In this pH range, its octanol/water lipophilicity is constant and low compared to cationic antihistamines (log D = log PZ = 1.5), whereas its H-bonding capacity is relatively large (delta log PZ > or = 3.1). Conformational, electronic, and lipophilicity potential calculations revealed that zwitterionic cetirizine experiences partial intramolecular charge neutralization in folded conformers of lower polarity. Pharmacokinetic investigations have shown the drug to be highly bound to blood proteins, mainly serum albumin, and to have a low brain uptake, explaining its lack of sedative effects. As such, cetirizine does not differ from "second-generation" antihistamines. In contrast, its very low apparent volume of distribution in humans (0.4 L kg-1, smaller than that of exchangeable water) implies a low affinity for lean tissues such as the myocardium and is compatible with the absence of cardiotoxicity of the drug. The zwitterionic nature and modest lipophilicity of cetirizine may account for this pharmacokinetic behavior. The suggestion is offered that cetirizine and analogous zwitterions, whose physicochemical, pharmacokinetic, and pharmacodynamic properties differ from those of "first-" and "second-generation" drugs in this class, could be considered as "third-generation" antihistamines.
A Plasmodium falciparumhexose transporter (PfHT) has previously been shown to be a facilitative glucose and fructose transporter. Its expression in Xenopus laevisoocytes and the use of a glucose analogue inhibitor permitted chemical validation of PfHT as a novel drug target. Following recent re-annotations of the P. falciparum genome, other putative sugar transporters have been identified. To investigate further if PfHT is the key supplier of hexose to P. falciparum and to extend studies to different stages of Plasmodium spp., we functionally analysed the hexose transporters of both the human parasite P. falciparum and the rodent parasite Plasmodium berghei using gene targeting strategies. We show here the essential function of pfht for the erythrocytic parasite growth as it was not possible to knockout pfht unless the gene was complemented by an episomal construct. Also, we show that parasites are rescued from the toxic effect of a glucose analogue inhibitor when pfht is overexpressed in these transfectants. We found that the rodent malaria parasite orthologue, P. berghei hexose transporter (PbHT) gene, was similarly refractory to knockout attempts. However, using a single cross-over transfection strategy, we generated transgenic P. berghei parasites expressing a PbHT–GFP fusion protein suggesting that locus is amenable for gene targeting. Analysis of pbht-gfp transgenic parasites showed that PbHT is constitutively expressed through all the stages in the mosquito host in addition to asexual stages. These results provide genetic support for prioritizing PfHT as a target for novel antimalarials that can inhibit glucose uptake and kill parasites, as well as unveiling the expression of this hexose transporter in mosquito stages of the parasite, where it is also likely to be critical for survival.
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