Renske Penning

Drugs of Abuse, Driving and Traffic Safety

Roadside studies indicate that 1-15% of drivers drive under the influence of one or more drugs of abuse. After drug use, drivers are more often culpable for an accident than non-users. Information on drugs and traffic safety comes from roadside studies, epidemiological research, experimental studies on driving-related skills, and on-the-road driving tests. Road-side studies show that drivers most frequently test positive for the use of alcohol and/or cannabis. These two drugs affect driving ability in a dose-dependent matter and result in poor vehicle control, especially when used in combination. Drivers on cocaine, ecstasy and amphetamine show no impairment on basic driving skills, but often overestimate their driving skills. In combination with impaired decision making, this increases risk taking during driving. Only few studies looked at the effects on driving of other drugs of abuse, such as ketamine, inhalants and anabolic steroids, but suggest a negative effect on driving performance. In conclusion, most drugs of abuse negatively affect driving ability, especially when used in combination with alcohol or another drug. It is of concern that a substantial number of drug users are not aware that their driving is impaired.

The Alcohol Hangover Research Group Consensus Statement on Best Practice in Alcohol Hangover Research

Alcohol-induced hangover, defined by a series of symptoms, is the most commonly reported consequence of excessive alcohol consumption. Alcohol hangovers contribute to workplace absenteeism, impaired job performance, reduced productivity, poor academic achievement, and may compromise potentially dangerous daily activities such as driving a car or operating heavy machinery. These socioeconomic consequences and health risks of alcohol hangover are much higher when compared to various common diseases and other health risk factors. Nevertheless, unlike alcohol intoxication the hangover has received very little scientific attention and studies have often yielded inconclusive results. Systematic research is important to increase our knowledge on alcohol hangover and its consequences. This consensus paper of the Alcohol Hangover Research Group discusses methodological issues that should be taken into account when performing future alcohol hangover research. Future research should aim to (1) further determine the pathology of alcohol hangover, (2) examine the role of genetics, (3) determine the economic costs of alcohol hangover, (4) examine sex and age differences, (5) develop common research tools and methodologies to study hangover effects, (6) focus on factor that aggravate hangover severity (e.g., congeners), and (7) develop effective hangover remedies.

The Pathology of Alcohol Hangover

Research on human subjects analyzing blood and urine samples determined biological correlates that may explain the pathology of alcohol hangover. These analyses showed that concentrations of various hormones, electrolytes, free fatty acids, triglycerides, lactate, ketone bodies, cortisol, and glucose were not significantly correlated with reported alcohol hangover severity. Also, markers of dehydration (e.g., vasopressin) were not significantly related to hangover severity. Some studies report a significant correlation between blood acetaldehyde concentration and hangover severity, but most convincing is the significant relationship between immune factors and hangover severity. The latter is supported by studies showing that hangover severity may be reduced by inhibitors of prostaglandin synthesis. Several factors do not cause alcohol hangover but can aggravate its severity. These include sleep deprivation, smoking, congeners, health status, genetics and individual differences. Future studies should more rigorously study these factors as well as biological correlates to further elucidate the pathology of alcohol hangover.

The effect of stress on core and peripheral body temperature in humans

Abstract Even though there are indications that stress influences body temperature in humans, no study has systematically investigated the effects of stress on core and peripheral body temperature. The present study therefore aimed to investigate the effects of acute psychosocial stress on body temperature using different readout measurements. In two independent studies, male and female participants were exposed to a standardized laboratory stress task (the Trier Social Stress Test, TSST) or a non-stressful control task. Core temperature (intestinal and temporal artery) and peripheral temperature (facial and body skin temperature) were measured. Compared to the control condition, stress exposure decreased intestinal temperature but did not affect temporal artery temperature. Stress exposure resulted in changes in skin temperature that followed a gradient-like pattern, with decreases at distal skin locations such as the fingertip and finger base and unchanged skin temperature at proximal regions such as the infra-clavicular area. Stress-induced effects on facial temperature displayed a sex-specific pattern, with decreased nasal skin temperature in females and increased cheek temperature in males. In conclusion, the amplitude and direction of stress-induced temperature changes depend on the site of temperature measurement in humans. This precludes a direct translation of the preclinical stress-induced hyperthermia paradigm, in which core temperature uniformly rises in response to stress to the human situation. Nevertheless, the effects of stress result in consistent temperature changes. Therefore, the present study supports the inclusion of body temperature as a physiological readout parameter of stress in future studies.

Treatment and prevention of alcohol hangover.

The search for alcohol hangover cures is as old as alcohol itself. Many cures and prophylactic agents are available, but scientific evidence for their effectiveness is generally lacking. This review summarizes and discusses the limited number of studies that examined the effectiveness of alcohol hangover treatments. From these studies it must be concluded that most remedies do not significantly reduce overall hangover severity. Some compounds reduce specific symptoms such as vomiting and headache, but are not effective in reducing other common hangover symptoms such as drowsiness and fatigue. Hangover cures that showed positive effects were those inhibiting prostaglandin synthesis or accelerating alcohol metabolism. Future studies should elucidate the pathology of alcohol hangover. Until then, it is unlikely that an effective hangover cure will be developed.

Caffeinated Drinks, Alcohol Consumption, and Hangover Severity

This study examined the relationship between consumption of caffeinated beverages and alcohol, and effects on next day hangover severity. In 2010, a survey funded by Utrecht University was conducted among N=549 Dutch students. Beverages consumed on their latest drinking session that produced a hangover were recorded. Hangover severity was scored using the Acute Hangover Scale. No significant correlation between caffeine use and hangover severity was found. Subjects who mixed alcohol with colas consumed significantly more alcohol than those who drank alcohol alone (p=0.001), or mixed alcohol with energy drinks (p=0.001). Future studies with larger sample sizes should confirm these findings.

Next day effects of naturalistic alcohol consumption on tasks of attention

The aim of this study was to examine the next day effects of alcohol consumption on a range of attention tasks.

Stress-induced hyperthermia in translational stress research

The stress-induced hyperthermia (SIH) response is the transient change in body temperature in response to acute stress. This body temperature response is part of the autonomic stress response which also results in tachycardia and an increased blood pressure. So far, a SIH response has been found in a variety of species (including rodents, baboons, turtles, pigs, impalas and chimpanzees), and there are indications that stress exposure alters body temperature in humans. This review aims to assess the translational potential and the different aspects of the body temperature reaction in response to stress. If stress-induced temperature changes are consistent across species, the SIH paradigm may be employed in preclinical and clinical setups and provide a tool to examine the pharmacological, genetic and mechanistic background of stress at both the preclinical and the clinical level.

Robust, Sensitive, and Automated Phosphopeptide Enrichment Optimized for Low Sample Amounts Applied to Primary Hippocampal Neurons

Because of the low stoichiometry of protein phosphorylation, targeted enrichment prior to LC-MS/MS analysis is still essential. The trend in phosphoproteome analysis is shifting toward an increasing number of biological replicates per experiment, ideally starting from very low sample amounts, placing new demands on enrichment protocols to make them less labor-intensive, more sensitive, and less prone to variability. Here we assessed an automated enrichment protocol using Fe(III)-IMAC cartridges on an AssayMAP Bravo platform to meet these demands. The automated Fe(III)-IMAC-based enrichment workflow proved to be more effective when compared to a TiO2-based enrichment using the same platform and a manual Ti(IV)-IMAC-based enrichment workflow. As initial samples, a dilution series of both human HeLa cell and primary rat hippocampal neuron lysates was used, going down to 0.1 μg of peptide starting material. The optimized workflow proved to be efficient, sensitive, and reproducible, identifying, localizing, and quantifying thousands of phosphosites from just micrograms of starting material. To further test the automated workflow in genuine biological applications, we monitored EGF-induced signaling in hippocampal neurons, starting with only 200 000 primary cells, resulting in ∼50 μg of protein material. This revealed a comprehensive phosphoproteome, showing regulation of multiple members of the MAPK pathway and reduced phosphorylation status of two glutamate receptors involved in synaptic plasticity.

Monitoring light/dark association dynamics of multi-protein complexes in cyanobacteria using size exclusion chromatography-based proteomics

UNLABELLED Diurnal rhythms are recurring 24h patterns such as light/dark cycles that affect many natural environmental and biological processes. The cyanobacterium Synechococcus elongatus PCC 7942 (S. elongatus) produces its energy through photosynthesis and therefore its internal molecular machinery is strongly influenced by these diurnal rhythms. Moreover, it has one of the simplest, self-sustained, circadian rhythms, extensively studied functionally and structurally. These characteristics together with the relatively small genome of S. elongatus, make it an ideal model system for the study of diurnal and circadian rhythms. Although expression of many gene transcripts has been shown to fluctuate in phase with the circadian rhythm, fluctuations at the protein level were less pronounced. This led us to hypothesize that the diurnal adaptation occurs at the level of higher organization of protein complexes. Therefore, we probed the abundance and constituency of S. elongatus protein complexes during the day and night. Following several well-known complexes such as the RNA polymerase, the ribosome and photosynthetic protein complexes, we observe for the first time that these complexes change not only in abundance but also in constituency. Therefore, we conclude that the dynamic assembly of protein complexes is indeed also a key-player in the processes governing the diurnal rhythm. SIGNIFICANCE The succession of day and night periods imposes drastic changes in all living organisms. Cyanobacteria produce their energy through photosynthesis and are therefore strongly influenced by diurnal rhythms. The cyanobacteria, Synechococcus elongatus PCC 7942 (S. elongatus), also exhibit a self-sustained biological clock. The connection between the central circadian oscillator and its output to the rest of the cell is not completely known. It has been shown that the expression of many gene transcripts heavily fluctuates in phase with the circadian rhythm; however, our recent global proteomics investigation revealed that the diurnal fluctuations seemed to be less pronounced at the protein level. As many known regulatory functions depend on protein-protein interactions (PPIs) and/or protein assemblies and the fact that so few fluctuations in protein abundances were observed earlier, here we investigated the diurnal adaptation at the level of dynamic changes in protein assembly. The paper demonstrates that the combination of native protein complex fractionation and high-resolution proteomics provides insight in the regulation of megadalton protein assemblies in cyanobacteria, including the ribosomal and photosynthetic complexes. The differences observed between the light and dark conditions in these complexes indicate a cyclic regulation of essential cellular processes.