Reduced learning ability as a consequence of evolutionary adaptation to nutritional stress in Drosophila melanogaster

1. Dietary conditions affect cognitive abilities of many species, but it is unclear to what extent this physiological effect translates into an evolutionary relationship. 2. A reduction of competitive ability under nutritional stress has been reported as a correlated response to selection for learning ability in Drosophila melanogaster. Here we test whether the reverse holds as well, i.e. whether an evolutionary adaptation to poor food conditions leads to a decrease in learning capacities. 3. Populations of D. melanogaster were: (i) not subject to selection (control), (ii) selected for improved learning ability, (iii) selected for survival and fast development on poor food, or (iv) subject to both selection regimes. 4. There was no detectable response to selection for learning ability. 5. Selection on poor food led to higher survival, faster development and smaller adult size as a direct response, and to reduced learning ability as a correlated response. This study supports the hypothesis that adaptation to poor nutrition is likely to trade off with the evolution of improved learning ability.

The effect of exercise, alcohol or both combined on health and physical performance.

Alcohol (ethanol) is consumed on a daily basis by a large fraction of the population, and in many countries, light-to-moderate alcohol consumption is considered as an integral part of the diet. Although the relationship between alcohol intake and obesity is controversial, regular consumption of alcohol, through its effects in suppressing fat oxidation, is regarded as a risk factor for weight gain, increased abdominal obesity and hypertriglyceridemia. Indeed, alcohol taken with a meal leads to an increase in postprandial lipemia-an effect on postprandial metabolism that is opposite to that observed with exercise. Furthermore, although regular exercise training and/or a preprandial exercise session reduce postprandial lipemia independently of alcohol ingestion, the exercise-induced reduction in postprandial lipemia is nonetheless less pronounced when alcohol is also consumed with the meal. Whether or not alcohol influences exercise and sport performance remains contradictory. It is believed that alcohol has deleterious effects on the performance, although it may contribute to reduce pain and anxiety. The alcohol effects on sports performance depend on the type and dosage of alcohol, acute vs chronic administration, the alcohol elimination rate as well as the type of exercise.

Effect of a small dose of alcohol on the endurance performance of trained cyclists.

AIM: The aim of this study was to investigate the effect of an acute small ethanol (EtOH) dose (0.5 ml EtOH/kg fat-free mass, combined with carbohydrate) in a drink on endurance performance of trained cyclists. METHODS: Thirteen well-trained male cyclists took part in this study. A 60-min cycling endurance performance test (time trial) was performed in a calorimetric chamber after drinking an EtOH (30 +/- 1.8 ml) or a non-EtOH control (C) drink. RESULTS: Overall, EtOH induced a significant decrease in the average cycling power output (PO) (EtOH: 233 +/- 23 W versus C: 243 +/- 24 W, P < 0.01). The time course of mechanical PO showed an early decrease during the EtOH trial as compared to C (P < 0.01). Due to the lower PO, oxygen consumption, carbon dioxide production and glucose oxidation were significantly lower (P < 0.05) as compared to C. Relative to PO, heart rate response and ratings of perceived exertion (RPE) were increased by EtOH as compared to C (P < 0.05). In contrast, EtOH did not influence gross work efficiency, glycaemia and blood lactate concentration. CONCLUSIONS: These results show that the acute low dose of EtOH decreased endurance performance. An increase of cardio-vascular strain and psychobiological mechanisms may explain this decrease of endurance performance.

Screening of the inhibitory effect of xenobiotics on alcohol metabolism using S9 rat liver fractions.

The purpose of this work was to develop and optimize a simple and suitable method to detect the potential inhibitory effect of drugs and medicines on alcohol dehydrogenase (ADH) activity in order to evaluate the possible interactions between medicines and alcohol metabolism. Commonly used medicines that are often involved in court litigations related with driving under the influence of alcohol were selected. Alprazolam, flunitrazepam and tramadol were tested as drugs with no known effect on ADH activity. Cimetidine, reported previously as having inhibitory effect on ADH, and 4-methylpyrazole (4-MP), a well known ADH inhibitor, were tested as positive controls. Apart from 4-MP, tramadol was identified as having the higher inhibitory effect with an IC50 of 44.7×10(-3)mM, followed by cimetidine (IC50 of 122.9×10(-3)mM). Alprazolam and flunitrazepam also reduced liver ADH activity but to a smaller extent (inhibition of 11.8±5.0% for alprazolam 1.0mM and 34.5±7.1% for flunitrazepam 0.04mM). Apart from cimetidine, this is the first report describing the inhibitory effect of these drugs on ethanol metabolism. The results also show the suitability of the method to screen for inhibitory effect of drugs on ethanol metabolism helping to identify drugs for which further study is justified.

Combined effect of tobacco and alcohol on laryngeal cancer risk : a case-control study

OBJECTIVE: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites. METHODS: This was a case-control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. RESULTS: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for > or = 25 cigarettes/day) and for duration of smoking (OR = 37.2 for > or = 40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for > or = 56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9). CONCLUSIONS: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.

Alcohol and relatively pure cannabis use, but not schizotypy, are associated with cognitive attenuations

Elevated schizotypy relates to similar cognitive attenuations as seen in psychosis and cannabis/polydrug use. Also, in schizotypal populations cannabis and polydrug (including licit drug) use are enhanced.These cognitive attenuations may therefore either be a behavioral marker of psychotic (-like) symptoms or the consequence of enhanced drug use in schizotypal populations.To elucidate this, we investigated the link between cognitive attenuation and cannabis use in largely pure cannabis users (35) and non-using controls (48), accounting for the potential additional influence of both schizotypy and licit drug use (alcohol, nicotine). Cognitive attenuations commonly seen in psychosis were associated with cannabis and alcohol use, but not schizotypy. Future studies should therefore consider (i) non-excessive licit substance use (e.g., alcohol) in studies investigating the effect of cannabis use on cognition and (ii) both enhanced illicit and licit substance use in studies investigating cognition in schizotypal populations.

A follow-up study on the quality of alcohol dependence-related information on the web.

ABSTRACT: In order to evaluate the one-year evolution of web-based information on alcohol dependence, we re-assessed alcohol-related sites in July 2007 with the same evaluating tool that had been used to assess these sites in June 2006. Websites were assessed with a standardized form designed to rate sites on the basis of accountability, presentation, interactivity, readability, and content quality. The DISCERN scale was also used, which aimed to assist persons without content expertise in assessing the quality of written health publications. Scores were highly stable for all components of the form one year later (r = .77 to .95, p &lt; .01). Analysis of variance for repeated measures showed no time effect, no interaction between time and scale, no interaction between time and group (affiliation categories), and no interaction between time, group, and scale. The study highlights lack of change of alcohol-dependence-related web pages across one year.

Associations between alcohol consumption and selected cytokines in a Swiss population-based sample (CoLaus study).

To assess the associations between alcohol consumption and cytokine levels (interleukin-1beta - IL-1β; interleukin-6 - IL-6 and tumor necrosis factor-α - TNF-α) in a Caucasian population. Population sample of 2884 men and 3201 women aged 35-75. Alcohol consumption was categorized as nondrinkers, low (1-6 drinks/week), moderate (7-13/week) and high (14+/week). No difference in IL-1β levels was found between alcohol consumption categories. Low and moderate alcohol consumption led to lower IL-6 levels: median (interquartile range) 1.47 (0.70-3.51), 1.41 (0.70-3.32), 1.42 (0.66-3.19) and 1.70 (0.83-4.39) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.01, but this association was no longer significant after multivariate adjustment. Compared to nondrinkers, moderate drinkers had the lowest odds (Odds ratio=0.86 (0.71-1.03)) of being in the highest quartile of IL-6, with a significant (p<0.05) quadratic trend. Low and moderate alcohol consumption led to lower TNF-α levels: 2.92 (1.79-4.63), 2.83 (1.84-4.48), 2.82 (1.76-4.34) and 3.15 (1.91-4.73) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.02, and this difference remained borderline significant (p=0.06) after multivariate adjustment. Moderate drinkers had a lower odds (0.81 [0.68-0.98]) of being in the highest quartile of TNF-α. No specific alcoholic beverage (wine, beer or spirits) effect was found. Moderate alcohol consumption is associated with lower levels of IL-6 and (to a lesser degree) of TNF-α, irrespective of the type of alcohol consumed. No association was found between IL-1β levels and alcohol consumption.

Effect of rufinamide on gating properties of voltage-gated sodium channel Na(v)1.7

Background: Voltage-gated sodium channels (Nav1.x) are important players in chronic pain. A particular interest has grown in Nav1.7, expressed in nociceptors, since mutations in its gene are associated to two inherited pain syndromes or insensitivity to pain. Rufinamide, a drug used to treat refractory epilepsy such as the Lennox-Gastaut syndrome, has been shown to reduce the number of action potentials in cortical neurons without completely blocking Na channels. Aim: The goal of this study was to investigate the effect of rufinamide on Nav1.7 current. Methods and results: Whole-cell patch clamp experiments were performed using HEK293 cells stably expressing Nav1.7. Rufinamide significantly decreased peak sodium current by 28.3, 21.2 and 12.5% at concentrations of 500, 100 and 50μM respectively (precise EC50 could not be calculated since higher rufinamide concentrations could not be achieved in physiological buffer solution). No significant difference on the V1/2 of voltage-dependence of activation was seen; however a shift in the steady-state inactivation curve was observed (-82.6 mV to -88.8 mV and -81.8 to -87.6 mV for 50 and 100 μM rufinamide respectively, p <0.005). Frequency-dependent inhibition of Nav1.7 was also influenced by the drug. One hundred μM rufinamide reduced the peak sodium current (in % of the peak current taken at the first sweep of a train of 50) from 90.8 to 80.8% (5Hz), 88.7 to 71.8% (10 Hz), 69.1 to 49.2% (25 Hz) and 22.3 to 9.8% (50 Hz) (all p <0.05). Onset of fast inactivation was not influenced by the drug since no difference in the time constant of current decay was observed. Conclusion: In the concentration range of plasma level in human treated for epilepsy, 15 μM, rufinamide only minimally blocks Nav1.7. However, it stabilizes the inactivated state and exerts frequencydependent inhibition of Nav1.7. These pharmacological properties may be of use in reducing ectopic discharges as a causal and symptom related contributor of neuropathic pain syndrome.

Alcohol Brief Intervention in Primary Care: A Systematic Review

BACKGROUND: The purpose of the present review was to evaluate the evidence of the effectiveness of brief interventions aimed at reducing chronic alcohol use and harm related to alcohol consumption, conducted among individuals actively attending primary care but who were not seeking help for alcohol problems. METHODS: Randomised trials reporting at-least one outcome related to alcohol consumption and conducted in outpatients who were actively attending primary care centre or provider were selected using Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, ISI Web of Science, ETOH database, and bibliographies of the retrieved references and previous reviews. Selection and data abstraction were performed independently and in duplicate. We assessed validity of the studies and performed a meta-analysis for studies reporting alcohol consumption at 6 or 12 months follow up. RESULTS: We included 24 reports, reporting results of 19 trials and including 5,639 individuals. Seventeen trials reported a measure of alcohol consumption, eight reporting a significant effect of intervention. The meta-analysis showed a mean pooled difference of -41 (95% CI: −54; −28) g of pure ethanol per week in favour of brief intervention group. Evidences for other outcomes (laboratory values, health related quality of life, morbidity and mortality, health care utilisation) were inconclusive. CONCLUSION: Our systematic review indicated that brief intervention might be effective for both men and women in reducing alcohol consumption compared to a controlled intervention, in a primary health care population. The meta-analysis confirmed the reduction in alcohol consumption at 6 and 12 month. Further research should precise the components of effectiveness of brief intervention and the evidence of effects on morbidity, mortality, and quality of life related outcomes.

No interaction between alcohol consumption and HDL-related genes on HDL cholesterol levels.

OBJECTIVE: To assess the relationships and possible interactions between polymorphisms related to HDL levels and alcohol consumption. METHODS: Cross-sectional population-based study including 2863 women and 2546 men aged 35-75 years (CoLaus study). Alcohol intake was assessed by the reported alcohol consumption of the last 7 days. Nineteen candidate genes known to influence HDL levels were studied. RESULTS: Alcohol consumption increased HDL cholesterol levels in both genders. After multivariate adjustment for gender, age, body mass index, smoking, hypolipidaemic drug treatment, physical activity and alcohol consumption, APOA5, CETP, LIPC and LPL gene polymorphisms were significantly (10(-5) threshold) related with HDL cholesterol levels, while no genexalcohol intake interaction was found for all SNPs studied. ABCA1 polymorphisms were related to HDL cholesterol levels on bivariate analysis but the relationship was no longer significant after multivariate analysis. CONCLUSION: Our data confirm the association of alcohol consumption and of APOA5, CETP, LIPC and LPL gene polymorphisms with HDL cholesterol levels. Conversely, no genexalcohol consumption interactions were found, suggesting that the effect of alcohol consumption on HDL cholesterol levels is not mediated via a modulation of HDL related genes.

The effectiveness of brief alcohol interventions in primary care settings: a systematic review.

Issues. Numerous studies have reported that brief interventions delivered in primary care are effective in reducing excessive drinking. However, much of this work has been criticised for being clinically unrepresentative. This review aimed to assess the effectiveness of brief interventions in primary care and determine if outcomes differ between efficacy and effectiveness trials. Approach. A pre-specified search strategy was used to search all relevant electronic databases up to 2006. We also hand-searched the reference lists of key articles and reviews. We included randomised controlled trials (RCT) involving patients in primary care who were not seeking alcohol treatment and who received brief intervention. Two authors independently abstracted data and assessed trial quality. Random effects meta-analyses, subgroup and sensitivity analyses and meta-regression were conducted. Key Findings. The primary meta-analysis included 22 RCT and evaluated outcomes in over 5800 patients. At 1 year follow up, patients receiving brief intervention had a significant reduction in alcohol consumption compared with controls [mean difference: -38 g week(-1), 95%CI (confidence interval): -54 to -23], although there was substantial heterogeneity between trials (I(2) = 57%). Subgroup analysis confirmed the benefit of brief intervention in men but not in women. Extended intervention was associated with a non-significantly increased reduction in alcohol consumption compared with brief intervention. There was no significant difference in effect sizes for efficacy and effectiveness trials. Conclusions. Brief interventions can reduce alcohol consumption in men, with benefit at a year after intervention, but they are unproven in women for whom there is insufficient research data. Longer counselling has little additional effect over brief intervention. The lack of differences in outcomes between efficacy and effectiveness trials suggests that the current literature is relevant to routine primary care.

Quality of life depends on the drinking pattern in alcohol-dependent patients.

AIMS: In patients with alcohol dependence, health-related quality of life (QOL) is reduced compared with that of a normal healthy population. The objective of the current analysis was to describe the evolution of health-related QOL in adults with alcohol dependence during a 24-month period after initial assessment for alcohol-related treatment in a routine practice setting, and its relation to drinking pattern which was evaluated across clusters based on the predominant pattern of alcohol use, set against the influence of baseline variables METHODS: The Medical Outcomes Study 36-Item Short-Form Survey (MOS-SF-36) was used to measure QOL at baseline and quarterly for 2 years among participants in CONTROL, a prospective observational study of patients initiating treatment for alcohol dependence. The sample consisted of 160 adults with alcohol dependence (65.6% males) with a mean (SD) age of 45.6 (12.0) years. Alcohol use data were collected using TimeLine Follow-Back. Based on the participant's reported alcohol use, three clusters were identified: 52 (32.5%) mostly abstainers, 64 (40.0%) mostly moderate drinkers and 44 (27.5%) mostly heavy drinkers. Mixed-effect linear regression analysis was used to identify factors that were potentially associated with the mental and physical summary MOS-SF-36 scores at each time point. RESULTS: The mean (SD) MOS-SF-36 mental component summary score (range 0-100, norm 50) was 35.7 (13.6) at baseline [mostly abstainers: 40.4 (14.6); mostly moderate drinkers 35.6 (12.4); mostly heavy drinkers 30.1 (12.1)]. The score improved to 43.1 (13.4) at 3 months [mostly abstainers: 47.4 (12.3); mostly moderate drinkers 44.2 (12.7); mostly heavy drinkers 35.1 (12.9)], to 47.3 (11.4) at 12 months [mostly abstainers: 51.7 (9.7); mostly moderate drinkers 44.8 (11.9); mostly heavy drinkers 44.1 (11.3)], and to 46.6 (11.1) at 24 months [mostly abstainers: 49.2 (11.6); mostly moderate drinkers 45.7 (11.9); mostly heavy drinkers 43.7 (8.8)]. Mixed-effect linear regression multivariate analyses indicated that there was a significant association between a lower 2-year follow-up MOS-SF-36 mental score and being a mostly heavy drinker (-6.97, P < 0.001) or mostly moderate drinker (-3.34 points, P = 0.018) [compared to mostly abstainers], being female (-3.73, P = 0.004), and having a Beck Inventory scale score ≥8 (-6.54, P < 0.001), at baseline. The mean (SD) MOS-SF-36 physical component summary score was 48.8 (10.6) at baseline, remained stable over the follow-up and did not differ across the three clusters. Mixed-effect linear regression univariate analyses found that the average 2-year follow-up MOS-SF-36 physical score was increased (compared with mostly abstainers) in mostly heavy drinkers (+4.44, P = 0.007); no other variables tested influenced the MOS-SF-36 physical score. CONCLUSION: Among individuals with alcohol dependence, a rapid improvement was seen in the mental dimension of QOL following treatment initiation, which was maintained during 24 months. Improvement was associated with the pattern of alcohol use, becoming close to the general population norm in patients classified as mostly abstainers, improving substantially in mostly moderate drinkers and improving only slightly in mostly heavy drinkers. The physical dimension of QOL was generally in the normal range but was not associated with drinking patterns.

Physiological differences between cycling and running: lessons from triathletes

The purpose of this review was to provide a synopsis of the literature concerning the physiological differences between cycling and running. By comparing physiological variables such as maximal oxygen consumption (V O(2max)), anaerobic threshold (AT), heart rate, economy or delta efficiency measured in cycling and running in triathletes, runners or cyclists, this review aims to identify the effects of exercise modality on the underlying mechanisms (ventilatory responses, blood flow, muscle oxidative capacity, peripheral innervation and neuromuscular fatigue) of adaptation. The majority of studies indicate that runners achieve a higher V O(2max) on treadmill whereas cyclists can achieve a V O(2max) value in cycle ergometry similar to that in treadmill running. Hence, V O(2max) is specific to the exercise modality. In addition, the muscles adapt specifically to a given exercise task over a period of time, resulting in an improvement in submaximal physiological variables such as the ventilatory threshold, in some cases without a change in V O(2max). However, this effect is probably larger in cycling than in running. At the same time, skill influencing motor unit recruitment patterns is an important influence on the anaerobic threshold in cycling. Furthermore, it is likely that there is more physiological training transfer from running to cycling than vice versa. In triathletes, there is generally no difference in V O(2max) measured in cycle ergometry and treadmill running. The data concerning the anaerobic threshold in cycling and running in triathletes are conflicting. This is likely to be due to a combination of actual training load and prior training history in each discipline. The mechanisms surrounding the differences in the AT together with V O(2max) in cycling and running are not largely understood but are probably due to the relative adaptation of cardiac output influencing V O(2max) and also the recruitment of muscle mass in combination with the oxidative capacity of this mass influencing the AT. Several other physiological differences between cycling and running are addressed: heart rate is different between the two activities both for maximal and submaximal intensities. The delta efficiency is higher in running. Ventilation is more impaired in cycling than in running. It has also been shown that pedalling cadence affects the metabolic responses during cycling but also during a subsequent running bout. However, the optimal cadence is still debated. Central fatigue and decrease in maximal strength are more important after prolonged exercise in running than in cycling.

Pro-opiomelanocortin gene and melanin-based colour polymorphism in a reptile

Colour polymorphism is widespread among vertebrates and plays important roles in prey-predator interactions, thermoregulation, social competition, and sexual selection. However, the genetic mechanisms involved in colour variation have been studied mainly in domestic mammals and birds, whereas information on wild animals remains scarce. Interestingly, the pro-opiomelanocortin gene (POMC) gives rise to melanocortin hormones that trigger melanogenesis (by binding the melanocortin-1-receptor; Mc1r) and other physiological and behavioural functions (by binding the melanocortin receptors Mc1-5rs). Owing to its pleiotropic effect, the POMC gene could therefore account for the numerous covariations between pigmentation and other phenotypic traits. We screened the POMC and Mc1r genes in 107 wild asp vipers (Vipera aspis) that can exhibit four discrete colour morphs (two unpatterned morphs: concolor or melanistic; two patterned morphs: blotched or lined) in a single population. Our study revealed a correlation between a single nucleotide polymorphism situated within the 3-untranslated region of the POMC gene and colour variation, whereas Mc1r was not found to be polymorphic. To the best of our knowledge, we disclose for the first time a relationship between a mutation at the POMC gene and coloration in a wild animal, as well as a correlation between a genetic marker and coloration in a snake species. Interestingly, similar mutations within the POMC 3-untranslated region are linked to human obesity and alcohol and drug dependence. Combined with our results, this suggests that the 3-untranslated region of the POMC gene may play a role in its regulation in distant vertebrates.