Behavioral effects of plasma tryptophan depletion in aggressive and nonaggressive men

Serotonin (5-HT) neurotransmission deficits have been implicated in impulsive aggression. A Trp-free beverage of amino acids competitively inhibits Trp uptake into the brain for 5-HT synthesis and also lowers endogenous plasma Trp for several hours. This has worsened mood and/or increased aggressive behavior, especially in hostile persons or those with histories of depression. In 24 community-recruited men (12 each with and without significant aggression histories), aggressive and impulsive behavior in the laboratory was assessed before and after plasma Trp depletion and Trp loading. In the aggression model, subjects were provoked by periodic subtractions of participation earnings, and these subtractions were blamed on a ficitious other participant. Aggression was measured as the responses the subject made to subtract money from his antagonist. Impulsiveness was operationalized as: (1) the choice of smaller reward after a shorter delay over having to wait longer to receive a larger reward, and (2) “false alarm” commission errors in a modified Continuous Performance Task, which represent a failure to inhibit responding to stimuli similar (but not identical) to target stimuli. Finally, plasma cortisol and Trp were measured under each condition immediately following a aggression testing session when subjects were highly provoked. I hypothesized that 5-HT may tonically modulate (inhibit) the hypothalmnic-pituitary-adrenal stress response, such that Trp depletion may enhance the cortisol response to high provocation in aggressive men. ^ Trp depletion had no effect in the laboratory tasks purported to measure impulsive behavior, and failed to cause increases in aggressive behavior under low provocation conditions. Under higher provocation, however, aggressive responses we re elevated under Trp-depleted conditions relative to Trp-loaded conditions in aggressive men, whereas the reverse was true in nonaggressive men. Cortisol levels nonsignificantly paralled the group differences in aggression under Trp-depleted and Trp-loaded conditions. Aggressive men achieved lower plasma Trp levels after Trp loading than did nonaggressive men, possibly due to heavy alcohol use histories. The high post-loading plasma Trp levels in nonaggressive men tended also to correlate with their aggressive responding rates, due perhaps to increases in other psychoactive Trp metabolites. ^

Sugar sweetened beverage consumption and behavioral correlates in a pilot study of high school students in Austin, Texas

Habitual consumption of sugar-sweetened beverages (SSB) has been reliably linked to obesity in adolescents. A wide variety of beverages sweetened with sugar are available to this population. The objective of this secondary data analysis was to assess the consumption of SSB by category and to identify behaviors that occur concurrently with the consumption of soda, sport drinks and fruit-flavored drinks in high school students. The analysis used self-reported survey data from 97 adolescents ages 14 to 18. SSB categories considered in the consumption analysis included regular soda, sports drinks, fruit-flavored drinks (FFD), iced tea, coffee drinks and energy drinks. The mean weekly sweetened beverage load in this population, calculated from the frequency and amount of consumption, was 145 ounces when all categories were considered. When SSB categories were considered independently, sports drinks (45 oz.) had the highest contribution to the mean sweetened beverage load followed by FFD (41 oz.), iced tea (27 oz.), soda (26 oz.) coffee drinks (15 oz.) and energy drinks (2 oz.). Sweetened beverage load was higher in boys (151 oz.) than girls (138 oz.) and was highest in Hispanics (159 oz.) followed by whites (152 oz.), blacks (137 oz.) and others (104 oz.). Behaviors that occurred on a usual basis during SSB consumption included watching TV, eating a family meal, eating salty and fried foods, being on the computer and hanging out with friends. Activities concurrent with sports drink consumption included physical activity behaviors whereas soda and FFD did not. Sports drink and FFD consumption commonly co-occurred with fruit consumption. Multiple SSB categories contribute to the total SSB consumption and the common dietary and activity behaviors are distinct between categories. Several of the concurrent behaviors point to the importance of home beverage availability, and to the influence that parents and peers have on SSB consumption. Identifying and assessing intervention strategies targeted to specific beverage categories could be an important step in behavioral intervention research aimed at reducing added sugar consumption, and ultimately, promote a healthy weight in adolescents. ^

Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP) in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP) is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP) while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP) in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP) is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP) while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

Energy beverages: content and safety.

Exercise is making a resurgence in many countries, given its benefits for fitness as well as prevention of obesity. This trend has spawned many supplements that purport to aid performance, muscle growth, and recovery. Initially, sports drinks were developed to provide electrolyte and carbohydrate replacement. Subsequently, energy beverages (EBs) containing stimulants and additives have appeared in most gyms and grocery stores and are being used increasingly by "weekend warriors" and those seeking an edge in an endurance event. Long-term exposure to the various components of EBs may result in significant alterations in the cardiovascular system, and the safety of EBs has not been fully established. For this review, we searched the MEDLINE and EMBASE databases from 1976 through May 2010, using the following keywords: energy beverage, energy drink, power drink, exercise, caffeine, red bull, bitter orange, glucose, ginseng, guarana, and taurine. Evidence regarding the effects of EBs is summarized, and practical recommendations are made to help in answering the patient who asks, "Is it safe for me to drink an energy beverage when I exercise?"

Cytochrome P450 2D18 in the mammalian brain: Recombinant expression, purification, and characterization of xenobiotic and endobiotic metabolism

The cytochromes P450 (P450) comprise a superfamily of hemoproteins that function in concert with NADPH-cytochrome P450 reductase (P450-reductase) to metabolize both endogenous and exogenous compounds. Many pharmacological agents undergo phase I metabolism by this P450 and P450-reductase monooxygenase system. Phase I metabolism ensures that these highly hydrophobic xenobiotics are made more hydrophilic, and hence easier to extrude from the body. While the majority of phase I metabolism occurs in the liver, metabolism in extrahepatic organ-systems like the intestine, kidney, and brain can have important roles in drug metabolism and/or efficacy. ^ While P450-mediated phase I metabolism has been well studied, investigators have only recently begun to elucidate what physiological roles P450 may have. One way to approach this question is to study P450s that are highly or specifically expressed in extrahepatic tissues. In this project I have studied the role of a recently cloned P450 family member, P450 2D18, that was previously shown to be expressed in the rat brain and kidney, but not in the liver. To this end, I have used the baculovirus expression system to over-express recombinant P450 2D18 and purified the functional enzyme using nickel and hydroxylapatite chromatography. SDS-PAGE analysis indicated that the enzyme was purified to electrophoretic homogeneity and Western analysis showed cross-reactivity with rabbit anti-human P450 2D6. Carbon monoxide difference spectra indicated that the purified protein contained no denatured P450 enzyme; this allowed for further characterization of the substrates and metabolites formed by P450 2D18-mediated metabolism. ^ Because P450 2D18 is expressed in brain, we characterized the activity toward several psychoactive drugs including the antidepressants imipramine and desipramine, and the anti-psychotic drugs chlorpromazine and haloperidol. P450 2D18 preferentially catalyzed the N-demethylation of imipramine, desipramine, and chlorpromazine. This is interesting given the fact that other P450 isoforms form multiple metabolites from such compounds. This limited metabolic profile might suggest that P450 2D18 has some unique function, or perhaps a role in endobiotic metabolism. ^ Further analysis of possible endogenous substrates for P450 2D18 led to the identification of dopamine and arachidonic acid as substrates. It was shown that P450 2D18 catalyzes the oxidation of dopamine to aminochrome, and that the enzyme binds dopamine with an apparent KS value of 678 μM, a value well within reported dopamine concentration in brain dopaminergic systems. Further, it was shown that P450 2D18 binds arachidonic acid with an apparent KS value of 148 μM, and catalyzes both the ω-hydroxylation and epoxygenation of arachidonic acid to metabolites that have been shown to have vasoactive properties in brain, kidney, and heart tissues. These data provide clues for endogenous roles of P450 within the brain, and possible involvement in the pathogenesis of Parkinson's disease. ^

Knowledge of exercise recommendations and energy intake from foods and beverages in relation to exercise behaviors within two Hispanic border communities

This research is a secondary analysis of the Qué Sabrosa Vida population-based cross-sectional study of two predominately Mexican American communities located along the Texas-Mexico border in 2000. There were two aims for this research. The first was to determine the relationship between knowledge of exercise and water recommendations, and exercise behavior and water consumption. The second was to determine the relationship between exercise behavior and percentage of energy consumption from beverages. Chi-square analysis revealed the majority of both populations had adequate knowledge about water and exercise recommendations, although significant percentages of the populations (>40%) did not consume water or exercise in adequate amounts. Knowledge was found to be a component of both behaviors, as it was more prevalent in the adults who exercised and consumed water in adequate amounts. Analysis of variance revealed no significant difference between overall beverage calorie percentage and exercise level (all p-values > 0.05); both regions and genders reported ∼18% of total caloric intake from beverages. There was no disproportionate influence of beverage calories on total caloric intake, after controlling for water consumption and independent of exercise behavior. These findings suggest that overall caloric intake, from both foods and beverages, may be the most influential factor to the energy imbalance contributing to the obesity crisis in these Hispanic border populations. ^

Validity and reliability of a measure of Latina mother's nutritional self-efficacy

Background. Not only has obesity played a role in Texas adults but it is also becoming a large issue among low-income Latino children. In Latino children between 2-5 years of age, the Pediatric Nutrition Surveillance data in 1997 found the prevalence of obesity was 12 percent, highest among all ethnic groups. Children learn what and how to eat from their environment. Despite many mothers being working mothers they are still the principal caregivers and source of influence on their toddler's diet. Self-efficacy, a concept created by Albert Bandura, one's belief that one is capable of performing a behavior needed to reach an intended goal, is increasingly becoming important in nutrition and health education. This study is important to understand the degree of impact that a mother's self-efficacy will have on a child's diet. This is useful knowing if influencing a mother's self-efficacy could improve a child's diet to prevent certain public health issues such as obesity and diabetes. The purpose of this study was to examine nutrition self-efficacy of Latina mothers, focusing on sweets and beverage and if their self-efficacy impacted their child's diet. Methods. The data was collected during July-September 2008. Mothers were recruited from two federally qualified San Antonio health centers. In order to qualify, participants had to be Hispanic with children of toddler age. Mothers were informed of incentives available upon completion. The interview consisted of demographic info, a set of five self-efficacy questions repeated at completion, testing reliability and a 24-hour food recall diary asked of the participant's child's diet. Results. There were 225 mothers who participated between both clinics. The Crohnbach alpha scores for the two different times the self-efficacy questions were asked were .44 corresponding to the first time and .49 for the second time. The three most common beverages reported were milk, juice, and water. The mothers who met or gave their child more milk than recommended by the scientific community, 800mg of calcium/3 cups (24oz) set, had a higher self-efficacy score than those who did not meet the standard at all. Mothers who gave their children more juice than the standard recommends, 4-6oz for children 1-6 years of age, had slightly higher self-efficacy scores than mother's who simply met the standard. In general, the lower the mother's self-efficacy, the more sweets they gave their child and vice versa. Conclusion. This study's Kappa values were adequate and this research showed that Latina mothers did in fact have high self-efficacy. In general some of the children's diets did not reflect the current scientific nutrition recommendations. In order to improve self-efficacy and have an impact on children's diets, the scientific community has a responsibility to make recommendations that are easily understood and can be put into practice. The public health community needs to ensure that we encourage those we serve to be more active in their health and educate them about what constitutes good health and nutrition for both themselves and their children.^

Crack and powder cocaine federal legislation: A sentencing disparity and potential for policy improvement

Since its introduction into the United States in the 1980s, crack cocaine has been a harsh epidemic that has taken its toll on a countless number of people. This highly addictive, cheap and readily available drug of abuse has permeated many demographic sectors, mostly in low income, lesser educated, and urban communities. This epidemic of crack cocaine use in inner city areas across the Unites States has been described as an expression of economic marginality and “social suffering” coupled with the local and international forces of drug market economies (Agar 2003). As crack cocaine is a derivative of cocaine, it utilizes the psychoactive component of the drug, but delivers it in a much stronger, quicker, and more addictive fashion. This, coupled with its ready availability and cheap price has allowed for users to not only become very addicted very quickly, but to be subject to the stringent and sometimes unequal or inconsistent punishments for possession and distribution of crack-cocaine. ^ There are many public health and social ramifications from the abuse of crack-cocaine, and these epidemics appear to target low income and minority groups. Public health issues relating to the physical, mental, and economic strain will be addressed, as well as the direct and indirect effects of the punishments that come as a result of the disparity in penalties for cocaine and crack-cocaine possession and distribution. ^ Three new policies have recently been introduced into the United Stated Congress that actively address the disparity in sentencing for drug and criminal activities. They are, (1) Powder-Crack Cocaine Penalty Equalization Act of 2009, (HR 18, 111th Cong. 2009), (2) The Drug Sentencing Reform and Cocaine Kingpin Trafficking Act of 2009, (HR 265, 111th Cong. 2009) and (3) The Justice Integrity Act of 2009, (111th Cong. 2009). ^ Although they have only been initiated, if passed, they have potential to not only eliminate the crack-cocaine disparity, but to enact laws that help those affected by this epidemic. The final and overarching goal of this paper is to analyze and ultimately choose the ideal policy that would not only eliminate the cocaine and crack disparity regardless of current or future state statutes, but will provide the best method of rehabilitation, prevention, and justice. ^

Effects of a health advocacy program to promote physical activity and nutrition behaviors among adolescents: An evaluation of the Young Leaders for Healthy Change program

Background. This study was designed to evaluate the effects of the Young Leaders for Healthy Change program, an internet-delivered program in the school setting that emphasized health advocacy skills-development, on nutrition and physical activity behaviors among older adolescents (13–18 years). The program consisted of online curricular modules, training modules, social media, peer and parental support, and a community service project. Module content was developed based on Social Cognitive Theory and known determinants of behavior for older adolescents. ^ Methods. Of the 283 students who participated in the fall 2011 YL program, 38 students participated in at least ten of the 12 weeks and were eligible for this study. This study used a single group-only pretest/posttest evaluation design. Participants were 68% female, 58% white/Caucasian, 74% 10th or 11th graders, and 89% mostly A and/or B students. The primary behavioral outcomes for this analysis were participation in 60-minutes of physical activity per day, 20-minutes of vigorous- or moderate- intensity physical activity (MVPA) participation per day, television and computer time, fruit and vegetable (FV) intake, sugar-sweetened beverage intake, and consumption of breakfast, home-cooked meals, and fast food. Other outcomes included knowledge, beliefs, and attitudes related to healthy eating, physical activity, and advocacy skills. ^ Findings. Among the 38 participants, no significant changes in any variables were observed. However, among those who did not previously meet behavioral goals there was an 89% increase in students who participated in more than 20 minutes of MVPA per day and a 58% increase in students who ate home-cooked meals 5–7 days per week. The majority of participants met program goals related to knowledge, beliefs, and attitudes prior to the start of the program. Participants reported either maintaining or improving to the goal at posttest for all items except FV intake knowledge, taste and affordability of healthy foods, interest in teaching others about being healthy, and ease of finding ways to advocate in the community. ^ Conclusions. The results of this evaluation indicated that promoting healthy behaviors requires different strategies than maintaining healthy behaviors among high school students. In the school setting, programs need to target the promotion and maintenance of health behaviors to engage all students who participate in the program as part of a class or club activity. Tailoring the program using screening and modifying strategies to meet the needs of all students may increase the potential reach of the program. The Transtheoretical Model may provide information on how to develop a tailored program. Additional research on how to utilize the constructs of TTM effectively among high school students needs to be conducted. Further evaluation studies should employ a more expansive evaluation to assess the long-term effectiveness of health advocacy programming.^

Association between sugar-sweetened beverages and both gestational weight gain and gestational diabetes

This cross-sectional study aimed at evaluating the association between sugar sweetened beverage (SSB) consumption and both excessive gestational weight gain (EGWG) and gestational diabetes mellitus (GDM). The study was conducted in the postpartum units of Memorial Hermann Hospital, Lyndon Baines Johnson General Hospital, the University of Texas Medical Branch at Galveston General Hospital, and the University of Texas at Brownsville Hospital. Between June 2009 and September 2010, women between the ages of 18 and 49 years with singleton pregnancies who delivered an infant born at 37 weeks of gestation or later were approached. Descriptive, univariate and multivariate analysis were employed in our study using the Statistical Analysis System (SAS) software version 9.1 (SAS Institute Inc. Cary, North Carolina). Our investigation did not find statistically significant associations between SSBs and EGWG. Our study reported no evidence of an association between SSBs and GDM except for sports drinks. However, the estimate of this association was deemed very imprecise. In conclusion, our study did not find strong provide strong support for the hypothesis that high consumption of SSBs increases the risk of EGWG or GDM. ^