Nicotine Deprivation Influences P300 Markers of Cognitive Control

Studies suggest that reduced cognitive control due to nicotine withdrawal may have a critical role in promoting tobacco use. The P3 family of event-related brain potential (ERP) components is thought to serve as markers of cognitive control processes. Unfortunately, existing research that examines the effects of nicotine deprivation on P3 amplitude has been marred by small sample sizes and other design limitations. The present study sought to determine the effects of nicotine deprivation on P3b and P3a amplitudes, which index task relevant target detection and orienting responses to novelty, respectively. A secondary aim was to examine self-reported trait cognitive control as a moderator of nicotine deprivation-induced reductions in P3b and P3a amplitudes. In all, 121 nicotine-dependent smokers attended two experimental sessions following 12-h smoking/nicotine deprivation. In a counterbalanced manner, participants smoked nicotine cigarettes during one session and placebo cigarettes during the other session. Findings indicated that nicotine deprivation reduced P3b amplitude (p<0.00001) during a three-stimulus oddball task independent of trait cognitive control. In contrast, nicotine deprivation reduced P3a only among participants who scored lower on measures of trait cognitive control. Implications for conceptualizing risk for nicotine dependence, and its treatment, are discussed.     

International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations

Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for HIV-1 and other pathogens have been shown to be limited by high titers of Ad5 neutralizing antibodies (NAbs) in the developing world. Alternative serotype rAd vectors have therefore been constructed. Here we report Ad5, Ad26, Ad35, and Ad48 NAb titers in 4381 individuals from North America, South America, sub-Saharan Africa, and Southeast Asia. As expected, Ad5 NAb titers were both frequent and high magnitude in sub-Saharan Africa and Southeast Asia. In contrast, Ad35 NAb titers proved infrequent and low in all regions studied, and Ad48 NAbs were rare in all regions except East Africa. Ad26 NAbs were moderately common in adults in sub-Saharan Africa and Southeast Asia, but Ad26 NAb titers proved markedly lower than Ad5 NAb titers in all regions, and these relatively low Ad26 NAb titers did not detectably suppress the immunogenicity of 4 × 10¹⁰ vp of a rAd26-Gag/Pol/Env/Nef vaccine in rhesus monkeys. These data inform the clinical development of alternative serotype rAd vaccine vectors in the developing world.     

Globalization and Food Prestige among Indian Adolescents

This study provides a foundation for understanding how globalization and changing food environments are linked to cultural models of food prestige in adolescents. We used methods from cognitive anthropology, including free lists, pile sorts, and consensus modeling, to explore the meanings that Indian adolescents attribute to foods. Adolescents (n = 29) were asked to free list foods eaten outside and inside the home. Different adolescents (n = 65) were asked to pile sort and rank 30 foods identified during the free lists according to which foods are the most prestigious, traditional, routine, and advertised on television. We found that adolescents overwhelmingly believed nontraditional foods to be the most prestigious. Nonlocal foods, both from foreign countries and other regions of India, as well as foods eaten outside the home, were also considered prestigious.     

Cyclized dipeptide model for a beta-bend.

A cyclic dipeptide in which L-Ala-Gly was cyclized with epsilon-aminocaproic acid has been synthesized as a model for a beta-bend. Its conformational properties have been examined by means of conformational energy calculations and nuclear magnetic resonance, infrared, Raman, and circular dichroism spectroscopy in various solvents. These calculations and experiments suggest that a type II beta-bend exists in the Ala-Glymoiety, with an NH...O = C hydrogen bond in the epsilon-aminocaproic acid portion of the molecule, and that the molecule adopts a unique conformation in solution. In contrast, an open-chain analog of this compound exists in solution as an ensemble of conformations but with a significant amount of a type II beta-bend structure in the ensemble.     

Pharmacological profile of non-hydroxylated and ether derivatives of the potent D2-selective agonist N-0437

Summary Derivatives of the potent dopamine D2-selective agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) were designed, aimed at producing drugs with less sensitivity towards metabolic inactivation (in particular glucuronidation at the 5-OH position). Since aminotetralins with a 5-methoxy substituent or lacking the 5-hydroxy group have been reported to retain dopaminergic activity, the non-5-hydroxylated N-0437 (N-0918) and two ethers of N-0437 [5-methoxyN-0437 (N-0724) and 5-cyclopentoxy-N-0437 (N-0953)] have been prepared and tested. Three indices for activity at central dopamine receptors are considered: (1) the displacement of (3 H)-SCH-23390 and (³H)-spiperone from calf caudate membranes, (2) the effects on dopamine release and metabolism in the striatum of freely moving rats after systemic and intrastriatal administration as assessed by brain microdialysis, and (3) the ability to elicit contralateral turning in rats with a unilateral 6-OH-dopamine lesion of the nigrostriatal pathway. In order to differentiate between direct dopaminergic activity and metabolic activation, brain and plasma levels of N-0437 after administration of N-0724 and N-0953 were measured.The results show the necessity of the 5-OH group for direct dopaminergic activity: N-0918, N-0724 and N-0953 are all inactive after intrastriatal administration in the microdialysis model and all three drugs show a weak in vitro affinity for both D1 and D2 receptors.Although N-0918 is also inactive after systemic administration in the microdialysis and turning model, N-0724 and N-0953 do exhibit dopaminergic activity after systemic administration in these models. Because of the in vivo formation of N-0437 after N-0724 and N-0953 administration, it is hypothesized that this dopaminergic activity is the result of metabolic activation. The cyclopentoxy group (present in N-0953) then appears to be an interesting prodrug moiety because it seems to give rise to small (but sufficient) and constant N-0437 levels in the brain.Deceased January 2, 1990Send offprint requests to J. M. Jansen at the above addressPart of this work was presented at a satellite meeting of the XIth international congress of pharmacology: Dopamine '90 in Como, Italy (July 1990).     

Rate of tension development in isometric contractions of a human hand muscle

The amplitude and rate of tension development during both electrical stimulation and voluntary activation of a human hand muscle were compared. The contractile responses from the first dorsal interosseous muscle of 14 normal human subjects were studied to provide the experimental data. At different forces less than 400g, under conditions of both electrical stimulation and voluntary contraction, force was directly proportional to speed of contraction. This linear relationship between the speed and force of contraction, as the proportion of active motor units varied, implies that these two parameters are similarly related in motor units of various sizes. In fast voluntary contractions, the rate of rise of tension at any given force level was greater than that observed in response to repetitive stimuli delivered to the motor nerve. Even at 200 and 500 impulses per second at maximal intensity, the speed of tension development was less than that found in fast voluntary contractions. The importance of asynchronous impulses and optimum discharge sequencing in generating a faster speed of tension development in fast voluntary contractions is underscored by these findings.