Stress In Healthy Volunteers Research Articles

Evaluation of pain and stress in healthy volunteers undergoing research lumbar punctures.

The use of lumbar punctures (LPs) in clinical research is increasing as emerging data demonstrate that CSF biomarkers can provide useful information about neurophysiology and the pathogenesis of diseases such as Alzheimer disease, amyotrophic lateral sclerosis, and Parkinson disease. Given the invasive nature of LPs, we sought to prospectively evaluate pain and hormonal indices of stress in participants undergoing research LPs in order to improve the quality of informed consent. Acknowledgment: The authors are grateful to the study participants for their involvement and to Shveta Dighe for help with recruitment and administration.

A single blueberry (Vaccinium corymbosum) portion does not affect markers of antioxidant defence and oxidative stress in healthy volunteers following cigarette smoking.

We previously reported that a portion of blueberries reversed endothelial dysfunction induced by acute cigarette smoking. Since smoking-induced endothelial dysfunction is associated with a condition of oxidative stress, we evaluated whether the observed effect was mediated by modulation of markers of oxidative stress and antioxidant defence. Fourteen out of 16 male healthy smokers previously enrolled, participated in a three-armed randomized controlled study with the following experimental conditions: smoking treatment (one cigarette); blueberry treatment (300g of blueberries) + smoking (one cigarette); control treatment (300ml of water with sugar) + smoking (one cigarette). The cigarette was smoked 100min after blueberry/control/water consumption. Each treatment was separated by 1 week of washout period. Plasma vitamin (C, B12 and folate) and aminothiol concentrations, endogenous [formamidopyrimidine-DNA glycosylase (FPG)-sensitive sites] and oxidatively induced DNA damage (resistance to H2O2-induced DNA damage) in peripheral blood mononuclear cells (PBMCs) were measured at baseline and 20, 60, 90, 120min and 24h after smoking. On the whole, analysis of variance did not show a significant effect of treatment on the modulation of markers of oxidative stress and antioxidant defence but revealed an effect of time for plasma concentrations of vitamin C (P = 0.003), B12 (P < 0.001), folate (P < 0.001), total cysteine (P = 0.007) and cysteine-glycine (P = 0.010) that increased following the three treatments after smoking. No significant effect of treatment was observed for the levels of FPG-sensitive sites (P > 0.05) and H2O2-induced DNA damage (P > 0.05) in PBMCs. In conclusion, the consumption of a single blueberry portion failed to modulate markers of oxidative stress and antioxidant defence investigated in our experimental conditions. Further studies are necessary to elucidate this finding and help clarifying the mechanisms of protection of blueberries against smoking-induced endothelial dysfunction.

Psychosocial Stress Increases Salivary Alpha-Amylase Activity Independently from Plasma Noradrenaline Levels.

Salivary alpha-amylase activity (sAA) and plasma noradrenaline (NA) concentrations are often considered to be surrogate markers of sympathetic activation in response to stress. However, despite accumulating evidence for a close association between sAA and noradrenaline and other indicators of sympathetic activity, reliability and generality of this relation remains unclear. We employed the Trier Social Stress Test (TSST) in order to directly compare the responses in sAA and NA to psychological stress in healthy volunteers (n = 23). The TSST significantly increased sAA and NA plasma levels with no significant differences in females and males. However, when subjects were divided according to their NA responses into low versus high responders, both groups did not significantly differ in their sAA before, during or after stress exposure. These data suggest that in response to acute psychological stress both plasma NA levels and sAA reflect sympathetic activity, however seemed to increase independently from each other.

The impact of stress on financial decision-making varies as a function of depression and anxiety symptoms.

Stress can precipitate the onset of mood and anxiety disorders. This may occur, at least in part, via a modulatory effect of stress on decision-making. Some individuals are, however, more resilient to the effects of stress than others. The mechanisms underlying such vulnerability differences are nevertheless unknown. In this study we attempted to begin quantifying individual differences in vulnerability by exploring the effect of experimentally induced stress on decision-making. The threat of unpredictable shock was used to induce stress in healthy volunteers (N = 47) using a within-subjects, within-session design, and its impact on a financial decision-making task (the Iowa Gambling Task) was assessed alongside anxious and depressive symptomatology. As expected, participants learned to select advantageous decks and avoid disadvantageous decks. Importantly, we found that stress provoked a pattern of harm-avoidant behaviour (decreased selection of disadvantageous decks) in individuals with low levels of trait anxiety. By contrast, individuals with high trait anxiety demonstrated the opposite pattern: stress-induced risk-seeking (increased selection of disadvantageous decks). These contrasting influences of stress depending on mood and anxiety symptoms might provide insight into vulnerability to common mental illness. In particular, we speculate that those who adopt a more harm-avoidant strategy may be better able to regulate their exposure to further environmental stress, reducing their susceptibility to mood and anxiety disorders.

Evaluation of antioxidant potential of Rasayana drugs in healthy human volunteers.

Background:It is increasingly being realized that many of today's diseases are due to “oxidative stress” that results from an imbalance between formation and neutralization of free radicals. Rasayana Chikitsa is a unique branch of Ayurveda. The word Rasayana means the way for attaining excellent Rasadi Dhatus. Several medicinal plants have been described as Rasayanas in Ayurveda. Ashwagandha and Guduchi are the best among the Rasayanas described by Charaka.Aim:To study the efficacy of Ashwagandha and Guduchi in oxidative stress in healthy volunteers.Materials and Methods:The study was carried out on 30 healthy volunteers after obtaining written informed consent. They were randomly distributed in three groups. Each group was treated with three different colored capsules containing Ashwagandha, Guduchi and placebo in the dose of 1 capsule (500 mg) twice a day for 6 months. The parameters such as hemoglobin%, Erythorcyte Sedimentation Rate (ESR), Malondialdehyde (MDA), Super-Oxide Dismutase (SOD) level, etc., were assessed before and after treatment. The Student's t-test was applied to assess significant variations in all of the studied parameters.Results:In this study, there was a significant increase in SOD level and decrease in MDA level in Ashwagandha and Guduchi groups.Conclusion:Ashwagandha and Guduchi may be helpful in preventing the oxidative stress and premature aging.

Cardiovascular magnetic resonance myocardial feature tracking for the measurement of myocardial twist and untwist at rest and during dobutamine stress in healthy volunteers

Background CMR feature tracking (CMR-FT) is a method of assessing strain from routinely acquired steady- state free precession (SSFP) cine images similar to echocardiographic speckle tracking. However, its application to determine myocardial twist and untwist has never previously been explored. We sought to determine the feasibility of measuring twist and untwist from routine cine images in healthy volunteers at rest and during inotropic stimulation.

Increased cerebral oxygen delivery during sodium nitroprusside administration despite reduced blood flow velocity in the middle cerebral artery

We investigated whether the nitric oxide donor sodium nitroprusside (SNP) dilates and phenylephrine constricts the MCA in 10 supine young healthy volunteers. We combined transcranial Doppler (TCD) measurements of the MCA with near infrared spectroscopy (NIRS) over the frontal cortex. Cerebral oxyhemoglobin and total hemoglobin increased by 14±1 and 15±1 μM/L with 100μg SNP despite hypotension, and were reduced by 6±1 and 7±1 μM/L with 150μg phenylephrine despite hypertension. SNP increased NIRS derived cerebral blood flow estimates by approximately 40±8% from baseline, while TCD derived CBFv decreased by 15±3%. Phenylephrine decreased NIRS derived cerebral blood flow estimates by approximately 11±5% from baseline, while TCD derived CBFv increased by 5±3%. Studies using upright tilt and lower body negative pressure were consistent with the literature and demonstrated similar relative changes in cerebral blood flow and CBFv as orthostatic stress progressed. We concluded that the MCA dilates to SNP and constricts to phenylephrine, but does not dilate during orthostatic stress in healthy volunteers. Supported by NIH (HL‐074873) and (HL‐087803).

Impact of Ramadan Intermittent Fasting on Oxidative Stress Measured by Urinary 15-F2t-Isoprostane

Fasting and caloric restriction have been associated with reduced incidence of chronic diseases and cancers. These effects have been attributed to reduced oxidative stress. Since Ramadan intermittent fasting (RIF) has been associated with reduced caloric intake, it was hypothesized that RIF would alleviate oxidative stress in healthy volunteers. The study was designed to elucidate the impact of RIF on oxidative stress measured by 15-F2t-Isoprostane (15FIP). Fifty healthy subjects (23 men and 27 women) who intended to fast Ramadan were recruited. Urine and serum sampling and anthropometric and dietary assessments were conducted one week before Ramadan (T0), at the end of the third week of Ramadan (T1), and one month after Ramadan (T2). Biochemical measurements included urinary 15FIP, creatinine, and hematological indices. Results revealed that the urinary level of 15FIP measured at T0 was normal, while they showed a significantly (P < 0.05) higher level when measured at T1 concomitant with a significant (P < 0.05) increase in the body weight and total body fat percent. In conclusion, results suggest that increased body weight is associated with increased lipid peroxidation and oxidative stress, and the impact of RIF on oxidative stress is mediated by the changes in body weight at the end of the month.

Effects of acetylsalicylic acid on serum paraoxonase activity, Ox-LDL, coenzyme Q 10 and other oxidative stress markers in healthy volunteers

Objectives: The aim of the study was to examine the effects of acetylsalicylic acid (ASA) on oxidative stress in healthy volunteers. Design and Methods: 30 volunteers of which 17 received ASA as 100 mg/day (Group I) and 13 received ASA as 150 mg/day (Group II) for 2 months. Serum paraoxonase 1 (PON1), arylesterase, total antioxidant status (TAS), total oxidant status (TOS), oxidized LDL (Ox-LDL) and coenzyme Q 10 (CoQ 10) levels were measured before and 1 and 2 months after treatment. Results: There was no significant differences between the measured parameters of the groups. However, TOS and Ox-LDL levels of group II were significantly reduced after 2 months of treatment ( p < 0.05). Conclusions: Significantly inhibition of LDL oxidation and significantly reduction in TOS levels of group II after 2 months of ASA treatment shows that ASA treatment may contribute to the prevention of atherosclerosis, a beneficial effect which is dose and time dependent.

Acute Psychological Stress Reduces Working Memory-Related Activity in the Dorsolateral Prefrontal Cortex

Acute psychological stress impairs higher-order cognitive function such as working memory (WM). Similar impairments are seen in various psychiatric disorders that are associated with higher susceptibility to stress and with prefrontal cortical dysfunctions, suggesting that acute stress may play a potential role in such dysfunctions. However, it remains unknown whether acute stress has immediate effects on WM-related prefrontal activity. Using functional magnetic resonance imaging (fMRI), we investigated neural activity of 27 healthy female participants during a blocked WM task (numerical N-back) while moderate psychological stress was induced by viewing strongly aversive (vs. neutral) movie material together with a self-referencing instruction. To assess stress manipulation, autonomic and endocrine, as well as subjective, measurements were acquired throughout the experiment. Successfully induced acute stress resulted in significantly reduced WM-related activity in the dorsolateral prefrontal cortex (DLPFC), and was accompanied by less deactivation in brain regions that are jointly referred to as the default mode network. This study demonstrates that experimentally induced acute stress in healthy volunteers results in a reduction of WM-related DLPFC activity and reallocation of neural resources away from executive function networks. These effects may be explained by supraoptimal levels of catecholamines potentially in conjunction with elevated levels of cortisol. A similar mechanism involving acute stress as a mediating factor may play an important role in higher-order cognitive deficits and hypofrontality observed in various psychiatric disorders.

Working memory performance after acute exposure to the cold pressor stress in healthy volunteers

Effects of acute stress exposure on learning and memory have been frequently studied in both animals and humans. However, only a few studies have focused specifically on working memory performance and the available data are equivocal. The present study examined working memory performance during the Sternberg item recognition task after exposure to a predominantly adrenergic stressor. Twenty four healthy subjects were randomly assigned to a stress group or a control group. The stress group was exposed to the cold pressor stress test (CPS; i.e. insertion of the dominant hand into ice water for 60s), while 37 °C warm water was used with the control group. Twenty minutes after the stress exposure, working memory performance was tested with the Sternberg item recognition task with three levels of cognitive load. Sympathetic nervous system and hypothalamic pituitary adrenocortical (HPA) axis activation during CPS, were assessed by measuring heart rate and salivary cortisol before and during (heart rate) or 30 min after (cortisol) the stress procedure. Exposure to the CPS test was associated with a significant increase in heart rate but no increase in salivary cortisol. Participants exposed to the stress procedure showed significantly shorter reaction times during trials with higher cognitive load but tended to show higher false alarm rates than control subjects. The present results indicate that exposure to CPS can be associated with signs of both enhanced and impaired working memory performance. The observed behavioral pattern might represent a form of streamlined information processing advantageous in a threatening situation.

A Single High Dose of Ascorbic Acid and Iron Is Not Correlated with Oxidative Stress in Healthy Volunteers

Fe (II) is a potential prooxidant in vivo and can induce cellular oxidative stress. Ascorbic acid (AA) is a powerful physiological antioxidant and, in the presence of free Fe (II), can exhibit prooxidant effects in vitro. However, in vivo prooxidant effects of Fe (II) and AA have not yet been indisputably demonstrated. Here we evaluate the potential toxic effect of supplementation of Fe (II) associated with AA. Nine healthy, nonsmoking male volunteers (20–31 years old) participated in the crossover study design. The volunteers were supplemented with either a dose of 2 g of AA, 150 mg of iron carbonyl or 2 g of AA plus 150 mg of iron carbonyl with a washout period of 15 days between each treatment. AA, iron, ferritin, thiobarbituric acid-reactive substances, catalase, δ-aminolevulinic dehydratase and SH thiol groups were measured in the blood of the volunteers. Plasma AA levels were increased at 2, 5 and 24 h after AA or AA plus iron ingestion. Plasma Fe levels were increased at 2 and 5 h in the AA plus iron group. Erythrocyte malondialdehyde levels decreased at 5 and 24 h after AA and 5 h after AA plus iron ingestion. Catalase activity from erythrocytes was increased 5 h after supplementation with AA plus iron. There was no significant difference between groups in the other biochemical parameters evaluated. Thus, the present study does not support the hypothesis that the combination of high plasma concentrations of AA and iron, or iron alone, could cause in vivo oxidative damage after a single supplementation dose.

Effect of 4 days of intermittent hypoxia on oxidative stress in healthy men

Periodic occlusion of the upper airway in patients with obstructive sleep apnea (OSA) leads to intermittent hypoxia (IH). IH is characterized by repeated episodes of hypoxia/reoxygenation, which is known to increase the production of reactive oxygen species (ROS). Causal relationships between OSA, IH and oxidative stress have not been established because of confounding effects of medical co‐morbidities and obesity which are frequently associated with OSA. The aim of this study was to determine if IH changes oxidative stress in healthy volunteers. Nine men (29.3 ± 1.7 years; BMI, 25.0 ± 0.4 kg.m−2; mean±SD) were studied. Following baseline measurements breathing room air (day zero (D0)), all subjects were exposed to 4 days (D1 to D4) of IH while awake (2 min at PetO2 = 45 Torr and 2 min at PetO2 = 88 Torr) 6 hours.d−1. Lipid peroxidation (malondialdehides, MDA), DNA oxidation (8‐Hydroxy‐2′‐deoxyguanosine, 8‐OHdG) and oxidation protein products (AOPP) were assessed in plasma. MDA increased significantly between baseline (D0) and D1 (+39%: 3.48 ± 1.17 vs 4.85 ± 0.90 μmol.l−1) and then tended to return to baseline levels. 8‐OHdG increased significantly between D0 and D1 (+51%: 53.84 ± 54.63 vs 83.30 ± 45.49 μmol.l−1) and remained elevated until D4 (+67%: 53.84 ± 54.63 vs 89.71 ± 36.06 μmol.l−1). These findings demonstrate that IH increases oxidative stress and suggest that IH may contribute to ROS overproduction in OSA.Supported by the Alberta Heritage Foundation for Medical Research and the Heart &amp; Stroke Foundation of Canada.

Effect of hyperbaric oxygen and vitamin C and E supplementation on biomarkers of oxidative stress in healthy men

The objectives of the present study were to evaluate the effect of normobaric and hyperbaric O2 (HBO) on plasma antioxidants and biomarkers of oxidative stress in plasma and urine and to investigate the effect of a 4-week vitamin C plus E supplementation on HBO-induced oxidative stress. Nineteen healthy men were exposed to HBO (100 % O2; 240 kPa) before and after 4 weeks' supplementation with 500 mg vitamin C plus 165 mg alpha-tocopherol equivalents. Exposure to 21 % O2 at 100 kPa served as intra-individual controls (control). Samples for the analysis of plasma antioxidants and oxidative stress biomarkers were collected before and immediately after each treatment. The present results showed that when compared with 'control', a single exposure to HBO resulted in a decrease of plasma vitamin C (P = 0.027) and an increase of lipid peroxides (P = 0.0008) and urinary 8-oxo-deoxyguanosine (8-oxodG) excretion (P = 0.006). Oxidative stress was not prevented by a 4-week supplementation with vitamins C and E. HBO-induced changes in plasma parameters correlated with basal antioxidant levels. The increase of urinary 8-oxodG after HBO plus supplementation correlated negatively with vitamin E intake (P = 0.023). We concluded that in healthy men HBO caused oxidative stress, which could not be prevented by dietary vitamin C plus E supplementation. The present data support the idea that HBO is a suitable model for oxidative stress in healthy volunteers.

Effects of vitamin E depletion/repletion on vitamin E status and oxidative stress in healthy volunteers

Effects of vitamin E depletion/repletion on vitamin E status and oxidative stress in healthy volunteers

Effects of a high-fat meal on resistance vessel reactivity and on indicators of oxidative stress in healthy volunteers.

High fat meals postprandially impair macrovascular endothelial function and a link to increased oxidative stress is suggested. Few information, on the other hand, exists on the effect of postprandial hyperlipidaemia on resistance vessel function. Under normal circumstances this vascular bed regulates tissue perfusion and, by controlling flow, impacts on macrovascular nitric oxide formation. The impact of a high fat meal (1200 kcal, 90 g fat, 46 g protein and 47 g carbohydrates) on postprandial resistance vessel reactivity and on indicators of oxidative stress was studied in 11 healthy subjects by venous-occlusion plethysmography using another six subjects as time control group. Ingestion of the test meal resulted in a pronounced increase of serum triglycerides from 1.05 +/- 0.61 mmol l(-1) in the fasting state to peak postprandial values of 1.94 +/- 0.41 mmol l(-1) (P < 0.001) reached after 4 h and a return to baseline after 8 h. Fasting peak reactive hyperaemia (RH) was 19.6 +/- 2.4 ml min(-1) (100 ml)(-1). Two hours after ingestion of the test meal peak RH was transiently reduced to 16.8 +/- 2.2 ml min(-1) (100 ml)(-1) (P < 0.05). No alteration of resting forearm perfusion was observed. The time course of peak RH suggested a potential biphasic effect of the test meal with an early impairment and a late increase of RH. Ingestion of a lipid rich test meal did not exert any influence on either total plasma antioxidant capacity given in trolox equivalents (513 +/- 26 micromol l(-1) at baseline) or on plasma peroxides measured as H2O2 equivalents (469 +/- 117 micromol l(-1)). Our results suggest that ingestion of a meal containing 90 g of fat results in a transient impairment of reactive hyperaemia in healthy subjects but these vascular alterations are not accompanied by signs of systemically increased oxidative stress.

A multi-biomarker approach to study the effects of smoking on oxidative DNA damage and repair and antioxidative defense mechanisms.

We investigated the effects of smoking-induced oxidative stress in healthy volunteers (21 smokers versus 24 non-smokers) by quantifying various markers of oxidative DNA damage and repair, and antioxidative defense mechanisms. Lymphocytic 7-hydroxy-8-oxo-2'-deoxyguanosine (8-oxo-dG) levels measured by high performance liquid chromatography with electrochemical detection, were significantly lower in smokers as compared with non-smokers (38.6 +/- 5.2 versus 50.9 +/- 4.6/10(6) dG, P = 0.05). The levels of oxidized pyrimidine bases in lymphocytes of smokers quantified by the endonuclease III-modified comet assay were non-significantly lower than those of non-smokers (% DNA in tail: 13 +/- 3 versus 14 +/- 2; tail length: 69 +/- 13 versus 96 +/- 10; tail moment: 6416 +/- 1220 versus 7545 +/- 1234). Urinary excretion levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) assessed by enzyme-linked immunosorbent assay did not differ significantly between smokers and non-smokers (197 +/- 31 versus 240 +/- 33 ng/body mass index, P = 0.3). Overall DNA repair activity expressed as unscheduled DNA synthesis in blood leukocytes, was not significantly different between smokers and non-smokers (2.9 +/- 0.3 versus 3.3 +/- 0.3, P = 0.4). Plasma antioxidative capacity measured by the Trolox equivalent antioxidant capacity assay was slightly higher in smokers as compared with non-smokers (440 +/- 16 versus 400 +/- 15 microM Trolox equivalent, P = 0.09), and it was significantly related to lymphocytic 8-oxo-dG levels (r = 0.4, P = 0.001). Genotyping of human 8-OH-dG glycosylase/apurinic lyase and glutathione S-transferase M1 showed that a polymorphism in either or both of the two genes does not affect any of the quantified biomarkers. We conclude that oxidative stress imposed by cigarette smoking has a low impact upon certain pathways involved in DNA damage and the antioxidative defense system.

Does free fatty acid infusion impair insulin action also through an increase in oxidative stress?

In vitro studies have demonstrated that free fatty acids (FFA) may enhance oxidative stress. In contrast, no in vivo studies have addressed such a relationship. This four-part study aims at investigating the association between FFA and oxidative stress in healthy volunteers. The following experimental procedures were carried out: 1) determination and simple correlations among fasting plasma FFA, glucose, insulin, plasma thiobarbituric acid-reactive substance (TBARS), the ratio of reduced glutathione (GSH) to oxidized GSH, and lipid hydroperoxide (n = 30); 2) time-dependent effect of FFA on plasma TBARS concentrations and GSH/oxidized GSH ratio (n = 10); 3) dose-dependent effect of FFA on plasma TBARS concentrations (n = 9); and 4) relationship among plasma FFA concentrations, plasma TBARS concentrations, and insulin action (n = 11). The results demonstrate that fasting plasma FFA concentrations correlated with fasting plasma TBARS concentrations (r = 0.65; P < 0.001) and lipid hydroperoxide (r = 0.79; P < 0.001). The correlation between plasma FFA and TBARS remained significant even after adjustment for age, sex, body mass index, and fasting and 2-h plasma glucose concentrations (r = 0.43; P < 0.01). In the time-dependent study, plasma TBARS concentrations increased with the rise in plasma FFA concentrations. In the dose-response study, a progressive increase in fasting plasma FFA concentrations was achieved by varying the Intralipid infusion rate, which also caused plasma TBARS concentrations to increase progressively until they reached a plateau between the last two infusion rates (0.3 and 0.4 mL/min). A euglycemic hyperinsulinemic glucose clamp (insulin infusion rate, 10.2 pmol/kg min for 360 min) was also performed. Simultaneous 10% Intralipid (0.4 mL/min) infusion significantly enhanced plasma TBARS concentrations and inhibited insulin-stimulated whole body glucose disposal (WBGD). GSH infusion (15 mg/min for 360 min) had opposite effects on plasma TBARS concentrations and WBGD. A combined infusion of 10% Intralipid and GSH was associated with a stimulation of WBGD with a magnitude midway between that of 10% Intralipid and GSH infused separately. In conclusion, fasting plasma FFA seems to enhances oxidative stress, which might contribute to the disruptive effects of plasma FFA on insulin-mediated glucose uptake.

Does free fatty acid infusion impair insulin action also through an increase in oxidative stress?

In vitro studies have demonstrated that free fatty acids (FFA) may enhance oxidative stress. In contrast, no in vivo studies have addressed such a relationship. This four-part study aims at investigating the association between FFA and oxidative stress in healthy volunteers. The following experimental procedures were carried out: 1) determination and simple correlations among fasting plasma FFA, glucose, insulin, plasma thiobarbituric acid-reactive substance (TBARS), the ratio of reduced glutathione (GSH) to oxidized GSH, and lipid hydroperoxide (n = 30); 2) time-dependent effect of FFA on plasma TBARS concentrations and GSH/oxidized GSH ratio (n = 10); 3) dose-dependent effect of FFA on plasma TBARS concentrations (n = 9); and 4) relationship among plasma FFA concentrations, plasma TBARS concentrations, and insulin action (n = 11). The results demonstrate that fasting plasma FFA concentrations correlated with fasting plasma TBARS concentrations (r = 0.65; P < 0.001) and lipid hydroperoxide (r = 0.79; P < 0.001). The correlation between plasma FFA and TBARS remained significant even after adjustment for age, sex, body mass index, and fasting and 2-h plasma glucose concentrations (r = 0.43; P < 0.01). In the time-dependent study, plasma TBARS concentrations increased with the rise in plasma FFA concentrations. In the dose-response study, a progressive increase in fasting plasma FFA concentrations was achieved by varying the Intralipid infusion rate, which also caused plasma TBARS concentrations to increase progressively until they reached a plateau between the last two infusion rates (0.3 and 0.4 mL/min). A euglycemic hyperinsulinemic glucose clamp (insulin infusion rate, 10.2 pmol/kg min for 360 min) was also performed. Simultaneous 10% Intralipid (0.4 mL/min) infusion significantly enhanced plasma TBARS concentrations and inhibited insulin-stimulated whole body glucose disposal (WBGD). GSH infusion (15 mg/min for 360 min) had opposite effects on plasma TBARS concentrations and WBGD. A combined infusion of 10% Intralipid and GSH was associated with a stimulation of WBGD with a magnitude midway between that of 10% Intralipid and GSH infused separately. In conclusion, fasting plasma FFA seems to enhances oxidative stress, which might contribute to the disruptive effects of plasma FFA on insulin-mediated glucose uptake.

Effects of psychosocial stress on the fibrinolytic system in man

In our study exposure to standardized acute mental stress in healthy volunteers caused similar alterations in fibrinolysis, although less pronounced, as physical exercise and adrenaline infusion. Thus, tPA:Ag and activity were significantly increased and PAI-1 activity had a tendency to decrease in response to mental stress. However, the effects of long-term mental stress on fibrinolysis in healthy persons and patients are, so far, not known.