Secretin—a new stress hormone?

The plasma concentration of secretin was measured during a 5-day military training course comprising prolonged physical exercise (35% of max O₂ uptake), severe caloric deficiency (approx. 35700 kJ/24 h) and sleep deprivation (only 2 h of sleep as a total during 5 days). 24 subjects were divided into 3 groups, one group was compensated for the caloric deficiency and another group was partly compensated for the sleep deprivation. The results showed that the fasting plasma secretin increased 3–6-fold (from 1.8–3.7 to 13.3–19.1 pmol/l) during the course with small differences in increase between the groups. Ingestion of a mixed meal reduced the fasting plasma secretin by about 40% during the course, while oral glucose reduced the plasma secretin to the concentrations found in the control experiment.The study shows that plasma secretin is increased when man is exposed to prolonged multifactorial stress. Additional food or sleep appears to have small influence on the fasting plasma secretin, but after giving a meal or oral glucose solution the plasma secretin decreases rapidly.     

Oxidative stress: a theoretical model or a biological reality?

Although oxidative stress has been extensively studied the last fifteen years, many physicians and biologists are still sceptical concerning its interest in biology and medicine. This is probably due, in part, to the fact that this subject is a matter of biophysics, and the first studies reported were written using a physical language that inspired these people used to a more concrete problematic very little. Another problem is the difficulty to detect the species mediating oxidative stress, and to determine their role in biological processes. This review is aimed at presenting oxidative stress, as well as reactive oxygen species and free radicals--the molecules that mediate it--in a clear form able to convince all researchers involved in life sciences that these short-lived intermediates are indissociable from any aerobic organism. Moreover, if reactive oxygen species and free radicals are undoubtedly involved in many pathologies, they have physiological functions too.     

When does stress end? Evidence of a prolonged stress reaction in shiftworking truck drivers

This study aimed to analyze individual cortisol levels in relation to work conditions, sleep, and health parameters among truck drivers working day shifts (n = 21) compared to those working irregular shifts (n = 21). A total of 42 male truck drivers (39.8 (+/-) 6.2 yrs) completed questionnaires about sociodemographics, job content, work environment, health, and lifestyle. Rest-activity profiles were measured using actigraphy, and cardiovascular blood parameters were collected. Salivary cortisol samples were obtained: (i) at waking time, (ii) 30?min after waking, and (iii) at bedtime, during both one workday and one day off from work. Irregular-shift workers, compared to day-shift workers, showed significantly higher waist-hip ratio, very-low-density lipoprotein (VLDL) cholesterol, tiredness after work, years working as a driver, truck vibration, and less job demand (p < .05). High cortisol levels in irregular-shift workers were correlated with certain stressors, such as short sleep duration and low job satisfaction, and to metabolic parameters, such as total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), VLDL, and triglycerides. Day-shift workers had higher cortisol levels collected 30?min after waking (p = .03) and a higher cortisol awakening response (CAR; p = .02) during workdays compared to off days. Irregular-shift workers had higher cortisol levels on their off days compared to day-shift workers (p = .03). In conclusion, for the day-shift workers, a higher cortisol response was observed on workdays compared to off days. Although no direct comparisons could be made between groups for work days, on off days the irregular-shift workers had higher cortisol levels compared to day-shift workers, suggesting a prolonged stress response in the irregular-shift group. In addition, cortisol levels were correlated with stressors and metabolic parameters. Future studies are warranted to investigate further stress responses in the context of irregular work hours.     

Is stress-induced analgesia a measure of stress severity?

When comparing magnitudes of "behavioural despair" (duration of immobility) and stress-induced analgesia in the tail suspension test and cold water swim test with SHR and NMRI male mice. The results might depend on saline injection prior the test and on the fact that exposure to cold water in swim test was sufficient to alter the response patterns. The findings show that the main parameters are closely related to each other. Stress-induced analgesia seems to be a measure of stress as the stress becomes stronger analgesia changes in linear dependence, whereas duration of immobility has an invert U-shaped function.     

Enteric bacteria and osmotic stress: intracellular potassium glutamate as a secondary signal of osmotic stress?

Enteric bacteria have evolved an impressive array of mechanisms that allow the cell to grow at widely different external osmotic pressures. These serve two linked functions; firstly, they allow the cell to maintain a relatively constant turgor pressure which is essential for cell growth; and secondly they permit changes in cytoplasmic composition such that the accumulation of intracellular osmolytes required to restore turgor pressure does not impair enzyme function. The primary event in turgor regulation is the controlled accumulation of potassium and its counterion glutamate. At high external osmolarities the cytoplasmic levels of potassium glutamate can impair enzyme function. Rapid growth is therefore dependent upon secondary responses, principally the accumulation of compatible solutes, betaine (N-trimethylglycine), proline and trehalose. The accumulation of these solutes is achieved by the controlled activity of transport systems and enzymes in response to changes in external osmotic pressure. It has been proposed that the accumulation of potassium glutamate during turgor regulation acts as a signal for the activation of these systems [1,2]. This brief review will examine the evidence that control over the balance of cytoplasmic osmolytes is achieved by sensing of the intracellular potassium (and glutamate) concentration.     

Do the serum oxidative stress biomarkers provide a reasonable index of the general oxidative stress status?

The oxidant status of an individual is assessed by determining a group of markers in noninvasive samples. One limitation when measuring these biomarkers is that they do not give information about tissue localization of oxidative stress. The present study was undertaken to establish whether the serum oxidative stress biomarkers are indicative of oxidative stress in tissues of an individual. To accomplish this, we determined a few generic markers of oxidation in serum and tissues of six groups of rats treated experimentally, to modulate their oxidative stress status. The correlation between serum and tissue levels was calculated for each marker. Also, for each tissue, the correlation between the values of these oxidative stress biomarkers was analysed. Our results show that only lipid peroxides in serum could be useful to predict the oxidative stress in tissues. No correlation was found between any of the oxidative stress markers in serum.     

The effects of mechanically-induced stress in plants — a review

Mechanically-induced stress (MIS) occurs naturally in plants as the aerial parts are moved, usually by wind, but also by such agents as rain and animals. It can be induced indoors by various actions such as rubbing or bending the stem or shaking or brushing the entire shoot. The most noticeable effect of MIS is a reduction in stem, leaf or petiole length invariably resulting in plants which are smaller and more compact than unstressed controls. However, the response of other variables can often differ between species and there may be either increases or decreases in stem or petiole diameter, root: shoot weight ratio, chlorophyll content or drought resistance. Why species should differ in this way, and what is the endogenous control mechanism for MIS responses, are inanswered questions. Ethylene, which increases as a result of MIS in several species may cause some MIS responses such as increased stem diameter, epinasty or a change in sex expression. However, evidence suggests that MIS retardation of extension growth may equally be due to lower or supraoptimal auxin levels or lower gibberellin levels.The uses in the field of the growth promoter gibberellin or the growth retardant chlormequat chloride (CCC) appear to be examples of respectively reversing or stimulating MIS growth response. MIS may be applied indoors if short compact plants are needed, either for aesthetic purposes as with floral crops, or if hardier and more manageable plants are needed, such as seedlings for transplanting in the field. Much more research is needed to estimate the importance of MIS in the field and to assess how such knowledge may be used to improve crop yield.     

Could oxidative stress be a factor in neurodevelopmental disorders?

There is evidence of co-morbidity in the neurodevelopmental disorders and they display depletion of polyunsaturated fatty acids (PUFAs) in their plasma and red cell membranes. This suggests an abnormal fatty acid metabolism, which may affect cell signalling and synthesis of eicosanoids. This common feature in the neurodevelopmental disorders may be genetic in origin: however, oxidative stress may also contribute to decreased PUFAs found in these disorders.     

Is serum gamma glutamyltransferase a marker of oxidative stress?

The primary role of cellular gamma glutamyltransferase (GGT) is to metabolize extracellular reduced glutathione (GSH), allowing for precursor amino acids to be assimilated and reutilized for intracellular GSH synthesis. Paradoxically, recent experimental studies indicate that cellular GGT may also be involved in the generation of reactive oxygen species in the presence of iron or other transition metals. Although the relationship between cellular GGT and serum GGT is not known and serum GGT activity has been commonly used as a marker for excessive alcohol consumption or liver diseases, our series of epidemiological studies consistently suggest that serum GGT within its normal range might be an early and sensitive enzyme related to oxidative stress. For example, serum and dietary antioxidant vitamins had inverse, dose-response relations to serum GGT level within its normal range, whereas dietary heme iron was positively related to serum GGT level. More importantly, serum GGT level within its normal range positively predicted F2-isoprostanes, an oxidative damage product of arachidonic acid, and fibrinogen and C-reactive protein, markers of inflammation, which were measured 5 or 15 years later, in dose-response manners. These findings suggest that strong associations of serum GGT with many cardiovascular risk factors and/or events might be explained by a mechanism related to oxidative stress. Even though studies on serum and/or cellular GGT is at a beginning stage, our epidemiological findings suggest that serum GGT might be useful in studying oxidative stress-related issues in both epidemiological and clinical settings.     

Can stress act as a sleep inertia countermeasure when on-call?

The nature of on-call work is such that workers can be called and required to respond immediately after being woken. However, due to sleep inertia, impaired performance immediately upon waking is typical. We investigated the impact of a preceding stressor (an alarm/mobilisation procedure) on sleepiness and performance upon waking. Healthy, adult males (n = 16) attended the sleep laboratory for four consecutive nights which included two, counterbalanced on-call sleeps where participants were woken at 04:00 h by (a) an alarm/mobilisation procedure (Alarm) or (b) gently by a researcher (Control). Following waking was a 2-h testing session comprising the repeated administration of the Karolinska Sleepiness Scale (KSS) and 5-min Psychomotor Vigilance Task (PVT). Results from within-subjects analysis of variance in both the Control and Alarm conditions showed that for subjective sleepiness (KSS) there was a significant fixed effect of time (p = 0.012), with participants becoming less sleepy as time post-wake increased. In terms of PVT performance outcomes, in neither the Alarm or Control conditions were there measurable signs of sleep inertia with performance remaining stable across the 2-h testing period. Based on previous research measuring impact of sleep inertia when woken near the circadian nadir, performance findings in particular were unexpected. We propose that stress caused by study procedures (i.e. finger pricks using lancets) unrelated to the simulated wake-up protocols may have countered any impact of sleep inertia on performance.     

Is cancer a disease set up by cellular stress responses?

For several decades, the somatic mutation theory (SMT) has been the dominant paradigm on cancer research, leading to the textbook notion that cancer is fundamentally a genetic disease. However, recent discoveries indicate that mutations, including “oncogenic” ones, are widespread in normal somatic cells, suggesting that mutations may be necessary but not sufficient for cancer to develop. Indeed, a fundamental but as yet unanswered question is whether or not the first step in oncogenesis corresponds to a mutational event. On the other hand, for some time, it has been acknowledged the important role in cancer progression of molecular processes that participate in buffering cellular stress. However, their role is considered secondary or complementary to that of putative oncogenic mutations. Here we present and discuss evidence that cancer may have its origin in epigenetic processes associated with cellular adaptation to stressful conditions, and so it could be a direct consequence of stress-buffering mechanisms that allow cells with aberrant phenotypes (not necessarily associated with genetic mutations) to survive and propagate within the organism. We put forward the hypothesis that there would be an inverse correlation between the activation threshold of the cellular stress responses (CSRs) and the risk of cancer, so that species or individuals with low-threshold CSRs will display a higher incidence or risk of cancer.     

Cumulative stress in research animals: Telomere attrition as a biomarker in a welfare context?

Progress in improving animal welfare is currently limited by the lack of objective methods for assessing lifetime experience. I propose that telomere attrition, a cellular biomarker of biological age, provides a molecular measure of cumulative experience that could be used to assess the welfare impact of husbandry regimes and/or experimental procedures on non‐human animals. I review evidence from humans that telomere attrition is accelerated by negative experiences in a cumulative and dose‐dependent manner, but that this attrition can be mitigated or even reversed by positive life‐style interventions. Evidence from non‐human animals suggests that despite some specific differences in telomere biology, stress‐induced telomere attrition is a robust phenomenon, occurring in a range of species including mice and chickens. I conclude that telomere attrition apparently integrates positive and negative experience in an accessible common currency that translates readily to novel species – the Holy Grail of a cumulative welfare indicator.     

Oxidative stress impairs HIF1α activation: a novel mechanism for increased vulnerability of steatotic hepatocytes to hypoxic stress

Steatosis increases the sensitivity of hepatocytes to hypoxic injury. Thus, this study was designed to elucidate the role of hypoxia-inducible factor-1α (HIF1α) in steatotic hepatocytes during hypoxia. AML12 hepatocytes and isolated rat hepatocytes were treated with a free fatty acid mixture of oleate and palmitate (2:1, 1 mM) for 18 h, which generated intrahepatocyte fat accumulation. The cells were then exposed to hypoxia (1% oxygen, 6-24 h). After hypoxia, a further increase in cellular fat accumulation was seen. In steatotic hepatocytes, a decreased HIF1α activation by hypoxia was observed. The capacity of these cells to express HIF1α-dependent genes responsible for the utilization of nutrients for energy was also impaired. This resulted in significantly lower intracellular ATP levels and greater cell death in steatotic hepatocytes compared with control hepatocytes. In contrast, overexpression of constitutively active HIF1α significantly increased cell viability as well as ATP and GLUT1 mRNA levels in steatotic hepatocytes under hypoxia. Hypoxia significantly enhanced HIF1α mRNA levels in control but not in steatotic hepatocytes. Concomitantly, an increase in oxidative stress was found in steatotic hepatocytes under hypoxic conditions compared with control cells. This included higher reactive oxygen species generation, lower cellular and nuclear GSH levels, and higher accumulation of 4-hydroxynonenal protein adducts. Hypoxia-mediated oxidative stress was accompanied by inactivation of basal nuclear factor-κB (NF-κB) DNA binding. Treatment with N-acetyl-l-cysteine, a reducing agent, improved NF-κB DNA-binding capacity and restored HIF1α induction. Conversely, overexpression of an NF-κB super-suppressor in control hepatocytes (IκBαΔN-transfected cells) resulted in complete inhibition of HIF1α expression, confirming that indeed NF-κB regulates HIF1α expression in hypoxic hepatocytes. In conclusion, hypoxia in combination with hepatic steatosis was shown to promote augmented oxidative stress, leading to NF-κB inactivation and impaired HIF1α induction and thereby increased susceptibility to hypoxic injury.