Antagonistic and synergistic effects of glucocorticoids and IL-7 on CD4+ T cell activation

Glucocorticoids (GCs) are steroidal compounds widely used to treat chronic and acute inflammatory diseases. In particular, GCs at pharmacological doses induce apoptosis of activated and naïve T cells, inhibit their proliferation and block pro-inflammatory cytokine secretion. At physiological concentrations, the effect of these steroids on T cell immunity are not yet fully understood, and various studies reported paradoxical roles exerted by GCs on T cell immunity. Here, we show that GCs surprisingly induce proliferation of activated CD4(+) T cells in the presence of IL-7, a cytokine secreted in the thymus and at mucosal sites. Increased proliferation is dependent on a GC-mediated survival of mitotic cells. Moreover, we observe a downmodulation of Th1 cytokine secretion in cells treated with GCs, an outcome which is not affected by the presence of IL-7. GCs exert thus a positive role in the presence of IL-7 by enhancing proliferation of CD4(+) T cells and simultaneously a negative role by suppressing pro-inflammatory cytokine production.

Arteriolar vasoconstrictive response: comparing the effects of arginine vasopressin and norepinephrine

INTRODUCTION: This study was designed to examine differences in the arteriolar vasoconstrictive response between arginine vasopressin (AVP) and norepinephrine (NE) on the microcirculatory level in the hamster window chamber model in unanesthetized, normotonic hamsters using intravital microscopy. It is known from patients with advanced vasodilatory shock that AVP exerts strong additional vasoconstriction when incremental dosage increases of NE have no further effect on mean arterial blood pressure (MAP). METHODS: In a prospective controlled experimental study, eleven awake, male golden Syrian hamsters were instrumented with a viewing window inserted into the dorsal skinfold. NE (2 microg/kg/minute) and AVP (0.0001 IU/kg/minute, equivalent to 4 IU/h in a 70 kg patient) were continuously infused to achieve a similar increase in MAP. According to their position within the arteriolar network, arterioles were grouped into five types: A0 (branch off small artery) to A4 (branch off A3 arteriole). RESULTS: Reduction of arteriolar diameter (NE, -31 +/- 12% versus AVP, -49 +/- 7%; p = 0.002), cross sectional area (NE, -49 +/- 17% versus AVP, -73 +/- 7%; p = 0.002), and arteriolar blood flow (NE, -62 +/- 13% versus AVP, -80 +/- 6%; p = 0.004) in A0 arterioles was significantly more pronounced in AVP animals. There was no difference in red blood cell velocities in A0 arterioles between groups. The reduction of diameter, cross sectional area, red blood cell velocity, and arteriolar blood flow in A1 to A4 arterioles was comparable in AVP and NE animals. CONCLUSION: Within the microvascular network, AVP exerted significantly stronger vasoconstriction on large A0 arterioles than NE under physiological conditions. This observation may partly explain why AVP is such a potent vasopressor hormone and can increase systemic vascular resistance even in advanced vasodilatory shock unresponsive to increases in standard catecholamine therapy.

Effects of an aging vascular model on healthy and diseased hearts

The vitamin D(3) and nicotine (VDN) model is a model of isolated systolic hypertension (ISH) due to arterial calcification raising arterial stiffness and vascular impedance similar to an aged and stiffened arterial tree. We therefore analyzed the impact of this aging model on normal and diseased hearts with myocardial infarction (MI). Wistar rats were treated with VDN (n = 9), subjected to MI by coronary ligation (n = 10), or subjected to a combination of both MI and VDN treatment (VDN/MI, n = 14). A sham-treated group served as control (Ctrl, n = 10). Transthoracic echocardiography was performed every 2 wk, whereas invasive indexes were obtained at week 8 before death. Calcium, collagen, and protein contents were measured in the heart and the aorta. Systolic blood pressure, pulse pressure, thoracic aortic calcium, and end-systolic elastance as an index of myocardial contractility were highest in the aging model group compared with MI and Ctrl groups (P(VDN) < 0.05, 2-way ANOVA). Left ventricular wall stress and brain natriuretic peptide (P(VDNxMI) = not significant) were highest, while ejection fraction, stroke volume, and cardiac output were lowest in the combined group versus all other groups (P(VDNxMI) < 0.05). The combination of ISH due to this aging model and MI demonstrates significant alterations in cardiac function. This model mimics several clinical phenomena of cardiovascular aging and may thus serve to further study novel therapies.

Drug-induced respiratory depression: an integrated model of drug effects on the hypercapnic and hypoxic drive

Drug-induced respiratory depression is a common side effect of the agents used in anesthesia practice to provide analgesia and sedation. Depression of the ventilatory drive in the spontaneously breathing patient can lead to severe cardiorespiratory events and it is considered a primary cause of morbidity. Reliable predictions of respiratory inhibition in the clinical setting would therefore provide a valuable means to improve the safety of drug delivery. Although multiple studies investigated the regulation of breathing in man both in the presence and absence of ventilatory depressant drugs, a unified description of respiratory pharmacodynamics is not available. This study proposes a mathematical model of human metabolism and cardiorespiratory regulation integrating several isolated physiological and pharmacological aspects of acute drug-induced ventilatory depression into a single theoretical framework. The description of respiratory regulation has a parsimonious yet comprehensive structure with substantial predictive capability. Simulations relative to the synergistic interaction of the hypercarbic and hypoxic respiratory drive and the global effect of drugs on the control of breathing are in good agreement with published experimental data. Besides providing clinically relevant predictions of respiratory depression, the model can also serve as a test bed to investigate issues of drug tolerability and dose finding/control under non-steady-state conditions.

The role of purinergic signaling in the liver and in transplantation: effects of extracellular nucleotides on hepatic graft vascular injury, rejection and metabolism

Extracellular nucleotides (e.g. ATP, UTP, ADP) are released by activated endothelium, leukocytes and platelets within the injured vasculature and bind specific cell-surface type-2 purinergic (P2) receptors. This process drives vascular inflammation and thrombosis within grafted organs. Importantly, there are also vascular ectonucleotidases i.e. ectoenzymes that hydrolyze extracellular nucleotides in the blood to generate nucleosides (viz. adenosine). Endothelial cell NTPDase1/CD39 has been shown to critically modulate levels of circulating nucleotides. This process tends to limit the activation of platelet and leukocyte expressed P2 receptors and also generates adenosine to reverse inflammatory events. This vascular protective CD39 activity is rapidly inhibited by oxidative reactions, such as is observed with liver ischemia reperfusion injury. In this review, we chiefly address the impact of these signaling cascades following liver transplantation. Interestingly, the hepatic vasculature, hepatocytes and all non-parenchymal cell types express several components co-ordinating the purinergic signaling response. With hepatic and vascular dysfunction, we note heightened P2- expression and alterations in ectonucleotidase expression and function that may predispose to progression of disease. In addition to documented impacts upon the vasculature during engraftment, extracellular nucleotides also have direct influences upon liver function and bile flow (both under physiological and pathological states). We have recently shown that alterations in purinergic signaling mediated by altered CD39 expression have major impacts upon hepatic metabolism, repair mechanisms, regeneration and associated immune responses. Future clinical applications in transplantation might involve new therapeutic modalities using soluble recombinant forms of CD39, altering expression of this ectonucleotidase by drugs and/or using small molecules to inhibit deleterious P2-mediated signaling while augmenting beneficial adenosine-mediated effects within the transplanted liver.

Reading on LCD vs e-Ink displays: effects on fatigue and visual strain

Purpose:  Most recently light and mobile reading devices with high display resolutions have become popular and they may open new possibilities for reading applications in education, business and the private sector. The ability to adapt font size may also open new reading opportunities for people with impaired or low vision. Based on their display technology two major groups of reading devices can be distinguished. One type, predominantly found in dedicated e-book readers, uses electronic paper also known as e-Ink. Other devices, mostly multifunction tablet-PCs, are equipped with backlit LCD displays. While it has long been accepted that reading on electronic displays is slow and associated with visual fatigue, this new generation is explicitly promoted for reading. Since research has shown that, compared to reading on electronic displays, reading on paper is faster and requires fewer fixations per line, one would expect differential effects when comparing reading behaviour on e-Ink and LCD. In the present study we therefore compared experimentally how these two display types are suited for reading over an extended period of time. Methods:  Participants read for several hours on either e-Ink or LCD, and different measures of reading behaviour and visual strain were regularly recorded. These dependent measures included subjective (visual) fatigue, a letter search task, reading speed, oculomotor behaviour and the pupillary light reflex. Results:  Results suggested that reading on the two display types is very similar in terms of both subjective and objective measures. Conclusions:  It is not the technology itself, but rather the image quality that seems crucial for reading. Compared to the visual display units used in the previous few decades, these more recent electronic displays allow for good and comfortable reading, even for extended periods of time.

Acute effects of stochastic resonance whole body vibration

AIM: To investigate the acute effects of stochastic resonance whole body vibration (SR-WBV) training to identify possible explanations for preventive effects against musculoskeletal disorders. METHODS: Twenty-three healthy, female students participated in this quasi-experimental pilot study. Acute physiological and psychological effects of SR-WBV training were examined using electromyography of descending trapezius (TD) muscle, heart rate variability (HRV), different skin parameters (temperature, redness and blood flow) and self-report questionnaires. All subjects conducted a sham SR-WBV training at a low intensity (2 Hz with noise level 0) and a verum SR-WBV training at a higher intensity (6 Hz with noise level 4). They were tested before, during and after the training. Conclusions were drawn on the basis of analysis of variance. RESULTS: Twenty-three healthy, female students participated in this study (age = 22.4 ± 2.1 years; body mass index = 21.6 ± 2.2 kg/m2). Muscular activity of the TD and energy expenditure rose during verum SR-WBV compared to baseline and sham SR-WBV (all P < 0.05). Muscular relaxation after verum SR-WBV was higher than at baseline and after sham SR-WBV (all P < 0.05). During verum SR-WBV the levels of HRV were similar to those observed during sham SR-WBV. The same applies for most of the skin characteristics, while microcirculation of the skin of the middle back was higher during verum compared to sham SR-WBV (P < 0.001). Skin redness showed significant changes over the three measurement points only in the middle back area (P = 0.022). There was a significant rise from baseline to verum SR-WBV (0.86 ± 0.25 perfusion units; P = 0.008). The self-reported chronic pain grade indicators of pain, stiffness, well-being, and muscle relaxation showed a mixed pattern across conditions. Muscle and joint stiffness (P = 0.018) and muscular relaxation did significantly change from baseline to different conditions of SR-WBV (P < 0.001). Moreover, muscle relaxation after verum SR-WBV was higher than after sham SR-WBV (P < 0.05). CONCLUSION: Verum SR-WBV stimulated musculoskeletal activity in young healthy individuals while cardiovascular activation was low. Training of musculoskeletal capacity and immediate increase in musculoskeletal relaxation are potential mediators of pain reduction in preventive trials.

Effects of weight on blood pressure at rest and during exercise.

Body weight (BW) and blood pressure (BP) have a close relationship, which has been accounted for by hormonal changes. No previous study has evaluated the effect of wearing an external weight vest on BP to determine whether there is a simple mechanism between BW and BP. Seventeen healthy volunteers underwent weight reduction (WR) through caloric restriction. Before and after WR, BW, body fat percentage and BP at rest and during exercise were measured. Before and after WR, exercise testing was performed twice with the random allocation of a weight vest (10 kg) during one of the tests. Linear regression was used to detect independent associations between BP and the weight vest, BW and body fat percentage. BW decreased from 89.4 ± 15.4 kg to 79.1 ± 14.0 kg following WR (P<0.001). WR led to significant decreases in BP at rest (from 130.0/85.9 mm Hg to 112.5/77.8 mm Hg, P<0.001 for systolic and diastolic BPs) and during exercise. The weight vest significantly increased BP at rest (to 136.1/90.7 mm Hg before and 125.8/84.6 mm Hg after WR) and during exercise. Linear regression analysis identified an independent association between the weight vest and BP (P=0.006 for systolic BP and P=0.009 for diastolic BP at rest). This study demonstrates that wearing an external weight vest has immediate effects on BP at rest and during exercise independent of BW or body fat. More research is needed to understand the physiological mechanisms between weight and BP.

Reproducibility of effects of homeopathically potentised gibberellic acid on the growth of Lemna gibba L. in a randomised and blinded bioassay

BACKGROUND: Reproducibility of basic research investigations in homeopathy is challenging. This study investigated if formerly observed effects of homeopathically potentised gibberellic acid (GA3) on growth of duckweed (Lemna gibba L.) were reproducible. METHODS: Duckweed was grown in potencies (14x-30x) of GA3 and one time succussed and unsuccussed water controls. Outcome parameter area-related growth rate was determined by a computerised image analysis system. Three series including five independent blinded and randomised potency experiments (PE) each were carried out. System stability was controlled by three series of five systematic negative control (SNC) experiments. Gibbosity (a specific growth state of L. gibba) was investigated as possibly essential factor for reactivity of L. gibba towards potentised GA3 in one series of potency and SNC experiments, respectively. RESULTS: Only in the third series with gibbous L. gibba L. we observed a significant effect (p = 0.009, F-test) of the homeopathic treatment. However, growth rate increased in contrast to the former study, and most biologically active potency levels differed. Variability in PE was lower than in SNC experiments. The stability of the experimental system was verified by the SNC experiments. CONCLUSIONS: Gibbosity seems to be a necessary condition for reactivity of L. gibba to potentised GA3. Further still unknown conditions seem to govern effect direction and the pattern of active and inactive potency levels. When designing new reproducibility studies, the physiological state of the test organism must be considered. Variability might be an interesting parameter to investigate effects of homeopathic remedies in basic research.

Effects of Passive Hydrotherapy WATSU (WaterShiatsu) in the Third Trimester of Pregnancy: Results of a Controlled Pilot Study

Background. WATSU (WaterShiatsu) is a complementary therapeutic treatment method comprising passive stretches and massage techniques administered in 35°C warm water. Pregnant women claim safe methods to reduce pain, stress, and fatigue. Therefore, we conducted a pilot study evaluating the effects of WATSU on pregnancy-related complaints in third trimester pregnant women. Methods. Nine healthy pregnant women at gestational week ≥34 were included in an intervention group (receiving WATSU) and compared to eight women in a passive control group (receiving no treatment). WATSU was performed on days 1 and 4 of the study, accompanied by ultrasound examinations. Outcomes include physiological and psychometric as well as qualitative data. Participants in the control group completed questionnaires only. Results. WATSU was found to significantly lower participants’ levels of stress and pain and to improve their mental health-related quality of life and mood. In comparison to the passive control group, participants in the intervention group reported reduction in perceived stress from day 1 to day 8 (p = 0.036, Cohen’s f = 0.57). Qualitative data indicate that WATSU was appreciated as enjoyable and deeply relaxing. No negative side effects were reported. Conclusion. Our findings support the notion that WATSU yields therapeutic benefits for pregnant women and warrant further research. This study has been registered at ClinicalTrials.gov: NCT01708018.

Manipulations to reduce simulator-related transient adverse health effects during simulated driving

User comfort during simulated driving is of key importance, since reduced comfort can confound the experiment and increase dropout rates. A common comfort-affecting factor is simulator-related transient adverse health effect (SHE). In this study, we propose and evaluate methods to adapt a virtual driving scene to reduce SHEs. In contrast to the manufacturer-provided high-sensory conflict scene (high-SCS), we developed a low-sensory conflict scene (low-SCS). Twenty young, healthy participants drove in both the high-SCS and the low-SCS scene for 10 min on two different days (same time of day, randomized order). Before and after driving, participants rated SHEs by completing the Simulator Sickness Questionnaire (SSQ). During driving, several physiological parameters were recorded. After driving in the high-SCS, the SSQ score increased in average by 129.4 (122.9 %, p = 0.002) compared to an increase of 5.0 (3.4 %, p = 0.878) after driving in the low-SCS. In the low-SCS, skin conductance decreased by 13.8 % (p < 0.01) and saccade amplitudes increased by 16.1 % (p < 0.01). Results show that the investigated methods reduce SHEs in a younger population, and the low-SCS is well accepted by the users. We expect that these measures will improve user comfort.

Parasite- and predator-induced maternal effects in the great tit (Parus major)

Both predators and parasites can elicit behavioral and physiological responses in prey and hosts, respectively. These responses may involve the reallocation of resources and may thus limit each other. We investigated the effects of concurrent pre-laying exposure of great tit females (Parus major) to both a simulated predation risk and a nest-based ectoparasite, the hen flea (Ceratophyllus gallinae), on nestling growth and development. We manipulated perceived predation risk using models and vocalizations of sparrowhawks (Accipiter nisus). At the start of incubation, we swapped whole clutches between treated and untreated nests to separate pre-laying maternal effects from posthatching effects. Since costs and benefits of maternal responses to parasites need to be assessed under parasite pressure, we infested half of the rearing nests with hen fleas. Parasites had negative effects on mass gain and wing growth, both via maternal effects and via direct exposure of nestlings, whereas maternal predation risk had no significant effect. The interaction between predator and parasite treatments was not significant and, thus, suggests the absence of a trade-off between the 2 stressors operating at the level of maternal effects. Alternatively, the complexity of the design, despite a relatively large sample size, may have limited the power for detection of this expected trade-off.

Effects of Thoratec pulsatile ventricular assist device (PVAD) timing on the abdominal aortic wave intensity pattern

Arterial waves are seen as possible independent mediators of cardiovascular risks, and the wave intensity analysis (WIA) has therefore been proposed as a method for patient selection for ventricular assist device (VAD) implantation. Interpreting measured wave intensity (WI) is challenging and complexity is increased by the implantation of a VAD. The waves generated by the VAD interact with the waves generated by the native heart, and this interaction varies with changing VAD settings. Eight sheep were implanted with a pulsatile VAD (PVAD) through ventriculo-aortic cannulation. The start of PVAD ejection was synchronized to the native R-wave and delayed between 0 % - 90 % of the cardiac cycle in 10 % steps or phase shifts (PS). Pressure and velocity signals were registered, using a combined Doppler and pressure wire positioned in the abdominal aorta, and used to calculate the WI. Depending on the PS, different wave interference phenomena occurred. Maximum unloading of the left ventricle (LV) coincided with constructive interference and maximum blood flow pulsatility, and maximum loading of the LV coincided with destructive interference and minimum blood flow pulsatility. We believe, that non-invasive WIA could potentially be used clinically to assess the mechanical load of the LV, and to monitor the peripheral hemodynamics such as blood flow pulsatility and risk of intestinal bleeding.

Extreme climatic events: impacts of drought and high temperature on physiological processes in agronomically important plants

Climate models predict more frequent and more severe extreme events (e.g., heat waves, extended drought periods, flooding) in many regions for the next decades. The impact of adverse environmental conditions on crop plants is ecologically and economically relevant. This review is focused on drought and heat effects on physiological status and productivity of agronomically important plants. Stomatal opening represents an important regulatory mechanism during drought and heat stress since it influences simultaneously water loss via transpiration and CO2 diffusion into the leaf apoplast which further is utilized in photosynthesis. Along with the reversible short-term control of stomatal opening, stomata and leaf epidermis may produce waxy deposits and irreversibly down-regulate the stomatal conductance and non-stomatal transpiration. As a consequence photosynthesis will be negatively affected. Rubisco activase—a key enzyme in keeping the Calvin cycle functional—is heat-sensitive and may become a limiting factor at elevated temperature. The accumulated reactive oxygen species (ROS) during stress represent an additional challenge under unfavorable conditions. Drought and heat cause accumulation of free amino acids which are partially converted into compatible solutes such as proline. This is accompanied by lower rates of both nitrate reduction and de novo amino acid biosynthesis. Protective proteins (e.g., dehydrins, chaperones, antioxidant enzymes or the key enzyme for proline biosynthesis) play an important role in leaves and may be present at higher levels under water deprivation or high temperatures. On the whole plant level, effects on long-distance translocation of solutes via xylem and phloem and on leaf senescence (e.g., anticipated, accelerated or delayed senescence) are important. The factors mentioned above are relevant for the overall performance of crops under drought and heat and must be considered for genotype selection and breeding programs.