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Biomedical subjects

Ulrike Ehlert

Publications and source records attributed to Ulrike Ehlert.

34 records · Page 2Linked to original sources

Glucocorticoid sensitivity of circulating monocytes in essential hypertension.

BACKGROUND: Essential hypertension ranks among the strongest cardiovascular risk factors. Cytokine production by monocytes plays a key role in atherosclerosis development and acute coronary syndromes. We investigated whether stimulated monocyte cytokine release and its inhibition by glucocorticoids would differ between hypertensive and normotensive subjects. METHODS: Study participants were 222 middle-aged male employees with industrial jobs. Following the criteria of the World Health Organization/International Society for Hypertension, 76 subjects were classified as being hypertensive (systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg). In vitro monocyte tumor necrosis factor (TNF)-alpha release after lipopolysaccharide (LPS) stimulation was assessed with and without coincubation with incremental doses of dexamethasone. Monocyte glucocorticoid sensitivity was defined as the dexamethasone concentration inhibiting TNF-alpha release by 50%. RESULTS: Hypertensive subjects showed 11% higher LPS-stimulated TNF-alpha release than normotensive subjects (F(1,181)= 5.21, P =.024). In hypertensive subjects, monocyte glucocorticoid sensitivity was 21% lower than in normotensive subjects (F(1,178)= 4.94, P =.027), indicating that dexamethasone inhibited relatively less TNF-alpha release in hypertensive subjects. Results held significance when a set of classic cardiovascular risk factors was controlled for. CONCLUSION: The findings suggest that proinflammatory activity of circulating monocytes is higher in hypertensive than in normotensive men, providing one potential pathway to explain the increased atherosclerotic risk with essential hypertension.

Adult↗

Enhanced glucocorticoid sensitivity of cytokine release from circulating leukocytes stimulated with lipopolysaccharide in healthy male smokers.

Smoking is a strong cardiovascular risk factor that promotes inflammation. The source of elevated pro-inflammatory cytokines in the circulation of smokers is not fully understood. We investigated the release of pro-inflammatory cytokines from circulating leukocytes stimulated with lipopolysaccharide (LPS) and its inhibition by glucocorticoids in smokers and non-smokers. Ninety-three middle-aged apparently healthy men were categorized as smokers (> 10 cigarettes/day; n = 41) or life-long non-smokers (n = 52). Peripheral cortisol was assessed from overnight urine. C-reactive protein (CRP) and tumor necrosis factor (TNF)-alpha were measured in plasma. LPS-stimulated interleukin (IL)-6 and TNF-alpha release from harvested circulating leukocytes were assessed using an in vitro whole blood assay with and without co-incubation of increasing concentrations of either dexamethasone or hydrocortisone. Glucocorticoid sensitivity was defined as the concentration of glucocorticoids required that inhibits LPS-stimulated cytokine release by 50%. Smokers had higher CRP levels (p = .005) and a trend for higher basal TNF-alpha levels (p < .07), and they also showed lower IL-6 and TNF-alpha release after LPS-stimulation than non-smokers (p's < .001). While peripheral cortisol concentration showed no significant group difference, inhibition of LPS-stimulated leukocyte IL-6 and TNF-alpha release by either glucocorticoid was enhanced in smokers as compared to non-smokers (p's < .022). The finding suggests that, in spite of a low-grade systemic inflammation, smokers have decreased LPS-stimulated cytokine release from circulating leukocytes and greater glucocorticoid sensitivity of this cytokine release than non-smokers. Circulating leukocytes unlikely contribute to the elevated pro-inflammatory cytokine levels in the blood of smokers.

Adult↗

Adjustment to trauma exposure: prevalence and predictors of posttraumatic stress disorder symptoms in mountain guides.

OBJECTIVE: The present study was designed to assess the frequency of trauma exposure, the prevalence rates of posttraumatic stress disorder, comorbid symptoms, and sense of coherence (SOC) in Swiss mountain guides. METHOD: All mountain guides (n=1347) were surveyed using of the Posttraumatic Stress Diagnostic Scale (PDS), the General Health Questionnaire (GHQ-28), and the Sense of Coherence Self-Rating Scale (SOC-29). RESULTS: Although Swiss mountain guides are exposed to many traumatic situations, the prevalence rate of PTSD is very low (2.7%), and their SOC total scores are high (157.9+/-18.4). Subgroups differentiated by the extent of traumatic stress symptoms differ significantly in SOC and GHQ total scores. Regression analysis showed SOC total score to be a significant predictor, although it only accounted for 1% of the variance in the number of PTSD symptoms endorsed. CONCLUSION: The low prevalence rate of PTSD is not in line with findings in other high-risk populations for PTSD. SOC seems to be a marker for psychological health rather than a protective factor against PTSD.

Adaptation, Psychological↗

Associations between neuroendocrine responses to the Insulin Tolerance Test and patient characteristics in chronic fatigue syndrome.

OBJECTIVE: Subtle dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis have been proposed as an underlying pathophysiological mechanism in chronic fatigue syndrome (CFS). This study attempted to assess the relationship between patient characteristics and HPA axis functioning using a neuroendocrine challenge test. METHOD: A test battery designed to assess different dimensions of CFS was given to 18 CFS patients and 17 controls. To evaluate the integrity of the HPA axis, the Insulin Tolerance Test (ITT), a centrally acting neuroendocrine challenge test, was performed on patients and controls. ACTH, salivary free cortisol and total plasma cortisol levels were assessed as a measure of the HPA axis stress response. Correlations of patient characteristics were calculated with integrated responses for all endocrine parameters. RESULTS: CFS patients had a significantly reduced area under the ACTH response curve (AUC) in the ITT. The AUC was significantly associated with the duration of CFS symptoms (r = -.592, P = .005) and the severity of fatigue symptomatology (r = -.41, P = .045). In addition, duration of CFS was correlated with the severity of fatigue symptoms (r = .38, P = .045). Similar associations were not observed for cortisol parameters. CONCLUSION: It has been postulated that neuroendocrine dysregulations observed in CFS are of an acquired nature. The results of a strong association between the integrated ACTH response and the duration of CFS emphasizes the need to consider factors known to be risk factors for the chronicity of CFS symptoms, such as profound inactivity, deconditioning and sleep abnormalities, as possible candidates for secondary causes of neuroendocrine dysregulations in CFS.

Adrenocorticotropic Hormone↗

Psychosocial stress-induced activation of salivary alpha-amylase: an indicator of sympathetic activity?

Assessment of sympathoadrenal medullary system (SAM) activity is only possible to date via measurement of catecholamines in blood plasma or via electrophysiological methods. Both ways of measurement are restricted to endocrinological or psychophysiological laboratories, as both require either immediate freezing of blood samples or complex recording devices. Efforts have therefore been undertaken to find a method comparable to salivary cortisol measurements, in which noninvasive samples can be taken at any place and stored at room temperature for sufficient time before later analysis in the laboratory. Salivary alpha-amylase (sAA) is a candidate that may prove useful in this context. We show here that sAA activity is increased by acute psychosocial stress (Trier Social Stress Test) and that increases in sAA correlate with increases in norepinephrine. We further report that sAA exhibits a stable circadian pattern that mirrors that of salivary cortisol. In conclusion, the current data show that salivary alpha-amylase may serve as an easy-to-use index for SAM activity. However, some questions remain to be answered; for example, what impact does salivary flow rate exert on stress-induced sAA activity?

Adrenal Medulla↗

Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress.

BACKGROUND: The presence of social support has been associated with decreased stress responsiveness. Recent animal studies suggest that the neuropeptide oxytocin is implicated both in prosocial behavior and in the central nervous control of neuroendocrine responses to stress. This study was designed to determine the effects of social support and oxytocin on cortisol, mood, and anxiety responses to psychosocial stress in humans. METHODS: In a placebo-controlled, double-blind study, 37 healthy men were exposed to the Trier Social Stress Test. All participants were randomly assigned to receive intranasal oxytocin (24 IU) or placebo 50 min before stress, and either social support from their best friend during the preparation period or no social support. RESULTS: Salivary free cortisol levels were suppressed by social support in response to stress. Comparisons of pre- and poststress anxiety levels revealed an anxiolytic effect of oxytocin. More importantly, the combination of oxytocin and social support exhibited the lowest cortisol concentrations as well as increased calmness and decreased anxiety during stress. CONCLUSIONS: Oxytocin seems to enhance the buffering effect of social support on stress responsiveness. These results concur with data from animal research suggesting an important role of oxytocin as an underlying biological mechanism for stress-protective effects of positive social interactions.

Administration, Intranasal↗

Allostatic load and work conditions.

Adverse work characteristics and poor social support have been associated with an increased risk for cardiovascular disease and other adverse health outcomes in otherwise apparently healthy adults. We undertook a cross-sectional study to evaluate the relationship between objective health status and work characteristics in industrial workers in Germany. Volunteers (n=324) were recruited from a representative random sample (n=537) of employees of an airplane manufacturing plant. Psychosocial work characteristics were assessed by the 52-item, 13-subscale salutogenetic subjective work analysis (SALSA) questionnaire, which assesses potentially salutogenic and pathogenic conditions. Factor analysis revealed three factors: decision latitude, job demands and social support. Biological health status was determined by the revised allostatic load score with 14 components: body-mass index, waist-to-hip ratio; systolic and diastolic blood pressure; plasma levels of C-reactive protein (CRP), tumor-necrosis factor-alpha, HDL, cholesterol, dehydroepiandrosterone sulfate; glycosylated hemoglobin; urinary cortisol, epinephrine, norepinephrine, and albumin. Score points were given for values in the high-risk quartile (maximum=14). General linear models revealed that older individuals and men had significantly higher allostatic load scores than younger participants or women. Of the SALSA factors, only job demands related significantly to allostatic load. The effect of demands was stronger in older individuals. Post-hoc analysis showed possible positive associations between high job demands and blood pressure or CRP, and between low social support and nocturnal excretion of cortisol or plasma levels of CRP. We conclude that this cross-sectional study on industrial employees found a weak association between a health summary score based on objective medical data and self-reported adverse work characteristics.

Adult↗

Assessment of exhaustion and related risk factors in employees in the manufacturing industry--a cross-sectional study.

OBJECTIVES: Vital exhaustion, a construct overlapping with burnout, is an independent risk factor for adverse health outcomes, including cardiovascular disease. We aimed to assess vital exhaustion in employees in the manufacturing industry and identify work characteristics associated with exhaustion. METHODS: Cross-sectional study. A stratified, representative random sample of employees from a manufacturing plant for airplane parts and assemblies was invited ( n=647), of whom 537 employees (83% accrual) volunteered to participate. Scores obtained by the nine-item Shortened Maastricht Exhaustion Questionnaire were compared with the mental and physical summary scales of the SF-12 General Health Survey and to a list of 20 health complaints. Pathogenic and salutogenic work characteristics were assessed by the self-reported 52-item, 13-subscale SALSA questionnaire. RESULTS: Vital exhaustion correlated with the mental summary score of the SF-12 and the number of health complaints and was positively associated with age. Exhaustion was not associated with gender, position (socio-economic status) or being on a wage (paid per completed item up to a contracted amount) or salary (payment as fixed monthly income). The instrument identified departments with high levels of exhaustion. Of the observed variance in exhaustion, 29% was explained by age, department, and five work characteristics: High levels of exhaustion (score >10) were related to excessive workload or qualitative demands (scoring in the highest quartile; OR(adj) 7.5; 95% CI 2.4-23), to adverse physical work conditions (OR(adj) 6.9; 95% CI 2.2-21), to adverse co-worker behavior (OR(adj) 4.8; 95% CI 1.4-16), to qualification potential (OR(adj) 0.32; 95% CI 0.11-0.97), and to social support by co-workers (OR(adj) 0.34; 95% CI 0.13-0.99), respectively. CONCLUSIONS: The nine-item instrument allows rapid screening of employees for self-reported levels of exhaustion. Besides physical work conditions and workload, absence or presence of social support by co-workers is strongly associated with exhaustion.

Adult↗

Lactation and stress: protective effects of breast-feeding in humans.

Whilst most research on breast-feeding has been designed to assess its importance for infant health or to find a human nutrient replacement for infant formula, the effects of breast-feeding on maternal health have received little scientific attention. In several animal studies lactation has been shown to be associated with a marked blunting of physiological and behavioral responses to physical and psychological stress. However, the literature on the effects of lactation on stress in humans remains limited. This review focuses primarily on recent findings on the effects of breast-feeding on neuroendocrine and behavioral responses to acute stress exposure in lactating women. The available data suggest that breast-feeding suppresses the hypothalamic-pituitary-adrenal (HPA) axis response to physical and psychosocial stress. However, lactation in women, in contrast to lactating rats, does not seem to result in a general restraint of the endocrine stress response during the whole period of lactation. Recent data strongly suggest that the blunted HPA axis response to stress in women seems to be counterbalanced if the acute stressor, at least when of a psychosocial nature, occurs later than 1 h after suckling. Further elucidation of the underlying psychobiological mechanisms involved in suppressed stress responses during lactation will no doubt lead to new insights into improved health sequelae of breast-feeding in women and to a better understanding of the psychobiology of human stress protection in general.

Animals↗

[Psychotherapy service utilization and psychotherapy motivation in a representative community sample of the elderly -- results of the zurich older age study].

OBJECTIVE: To study the extent of real and potential psychotherapy service utilization in the older (65 - 96) population. METHOD: We used the Zurich Older Age Study on PTSD, complicated grief and depressive disorders which consists of a random sample of 712 older adults based on a two-stage screening design. Utilization of psychotherapy was assessed by a checklist on service utilization for psychological problems/disorders. Potential psychotherapy motivation was assessed by means of a validated Questionnaire on Psychotherapy Motivation (FPTM-23). RESULTS: Around 5 % indicated to have used psychotherapy since age 65 (either alone or in combination with pharmacological treatment) and 10 % of participants indicated use of any therapeutic treatment for psychological problems with women twice as frequent as men. Potential psychotherapy motivation was medium highly pronounced and varied only slightly between the sexes. Predictors of high psychotherapy motivation are the extent of suffering as well as the absence of rejection of psychological need for assistance. DISCUSSION: The frequency numbers of psychotherapy service utilization and motivation indicate their moderate extents in old age. Limitations of the study are discussed, e. g., the possibly higher density of service providers in an urban population like the city of Zurich.

Age Factors↗

Low-dose dexamethasone suppression test in chronic fatigue syndrome and health.

OBJECTIVE: Subtle dysregulations of the hypothalamus-pituitary-adrenal axis in chronic fatigue syndrome have been described. The aim of this study was to examine the negative feedback regulations of the hypothalamus-pituitary-adrenal axis in chronic fatigue syndrome. METHODS: In 21 patients with chronic fatigue syndrome and 21 healthy control subjects, awakening and circadian salivary free cortisol profiles were assessed over 2 consecutive days and compared with awakening and circadian salivary free cortisol profiles after administration of 0.5 mg of dexamethasone at 11:00 PM the previous day. RESULTS: Patients with chronic fatigue syndrome had normal salivary free cortisol profiles but showed enhanced and prolonged suppression of salivary free cortisol after the administration of 0.5 mg of dexamethasone in comparison to the control subjects. CONCLUSIONS: Enhanced negative feedback of the hypothalamus-pituitary-adrenal axis could be a plausible explanation for the previously described alterations in hypothalamus-pituitary-adrenal axis functioning in chronic fatigue syndrome. Because similar changes have been described in stress-related disorders, a putative role of stress in the pathogenesis of the enhanced feedback is possible.

Adult↗

Hypothalamic-pituitary-adrenal axis reactivity in chronic fatigue syndrome and health under psychological, physiological, and pharmacological stimulation.

OBJECTIVES: Subtle alterations of the hypothalamic-pituitary-adrenal (HPA) axis in chronic fatigue syndrome (CFS) have been proposed as a shared pathway linking numerous etiological and perpetuating processes with symptoms and observed physiological abnormalities. Because the HPA axis is involved in the adaptive responses to stress and CFS patients experience a worsening of symptoms after physical and psychological stress, we tested HPA axis functioning with three centrally acting stress tests. METHODS: We used two procedures mimicking real-life stressors and compared them with a standardized pharmacological neuroendocrine challenge test. CFS patients were compared with healthy control subjects regarding their cardiovascular and endocrine reactivity in a psychosocial stress test and a standardized exercise test, and their endocrine response in the insulin tolerance test (ITT). RESULTS: Controlling for possible confounding variables, we found significantly lower ACTH response levels in the psychosocial stress test and the exercise test, and significantly lower ACTH responses in the ITT, with no differences in plasma total cortisol responses. Also, salivary-free cortisol responses did not differ between the groups in the psychosocial stress test and the exercise test but were significantly higher for the CFS patients in the ITT. In all tests CFS patients had significantly reduced baseline ACTH levels. CONCLUSIONS: These results suggest that CFS patients are capable of mounting a sufficient cortisol response under different types of stress but that on a central level subtle dysregulations of the HPA axis exist.

Adult↗

Reduced glucocorticoid sensitivity of monocyte interleukin-6 production in male industrial employees who are vitally exhausted.

OBJECTIVE: Proinflammatory changes are thought to link vital exhaustion with adverse cardiovascular outcomes. Monocytes play a central role in the pathogenesis of atherosclerotic lesions and are a major source of circulating cytokines. We hypothesized that vital exhaustion may alter the regulation of monocyte activity, as measured by lipopolysaccharide (LPS)-stimulated and glucocorticoid inhibited release of the proinflammatory cytokine interleukin-6 (IL-6). METHODS: In 166 middle-aged apparently healthy men, vital exhaustion was measured by the Shortened Maastricht Exhaustion Questionnaire. Subjects in the highest quartile (highly exhausted, N= 38) were compared with those in the second and third quartiles (moderately exhausted N= 89) vs. those in the lowest quartile (nonexhausted, N= 39) in terms of plasma C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-alpha) levels, and as to IL-6 release after LPS stimulation in vitro. Inhibition of IL-6 release was determined by coincubation with increasing concentrations of dexamethasone. Monocyte glucocorticoid sensitivity was defined as the dexamethasone concentration inhibiting IL-6 release by 50%. RESULTS: Highly exhausted individuals had higher CRP levels than nonexhausted subjects (p=.008). LPS-stimulated IL-6 release was not significantly different between groups. However, in highly exhausted participants, dexamethasone was less able to inhibit IL-6 release (p=.010), and the glucocorticoid sensitivity was lower (p=.003) than in nonexhausted subjects. CONCLUSIONS: In highly exhausted individuals, glucocorticoids exert less suppressive action on monocyte IL-6 release than in nonexhausted subjects. This finding points to altered regulation of monocyte cytokine production as one possible pathway linking exhaustion with atherosclerosis.

Adult↗

Basal and stimulated hypothalamic-pituitary-adrenal axis activity in patients with functional gastrointestinal disorders and healthy controls.

OBJECTIVE: The aim of this study was to investigate alterations of pituitary-adrenal activity under both stimulated and unstimulated conditions in patients with functional gastrointestinal disorders. METHODS: Thirty subjects who fulfilled the Rome Diagnostic Criteria for either irritable bowel syndrome or nonulcer dyspepsia and 24 healthy controls took part in the study. Free salivary morning cortisol and diurnal cortisol profiles were obtained for all subjects. On a second day, a low-dose dexamethasone suppression test was applied. Additionally, in all subjects a corticotropin-releasing hormone (CRH) challenge test was performed. RESULTS: The results show attenuated unstimulated cortisol levels in patients compared with controls. After CRH challenge, blunted adrenocorticotropic hormone and cortisol responses were observed. These findings suggest lower pituitary and adrenocortical activity in patients with functional gastrointestinal disorders. CONCLUSION: The observed pituitary-adrenal reactivity in these patients is discussed as a possible consequence of lower adrenocortical activity, possibly resulting in a disinhibition of CRH in the brain.

Adult↗

Are stress-induced cortisol changes during pregnancy associated with postpartum depressive symptoms?

OBJECTIVE: The purpose of this study was to examine the association between psychobiological stress reactivity during healthy pregnancy and depressive symptoms in the early puerperium. METHODS: A sample of healthy nulliparous pregnant women (N = 57) between the ages of 21 and 35 years underwent a standardized psychosocial stress test during pregnancy. Within an average of 13 days after delivery, postpartum depressive symptoms were assessed using the German version of the Edinburgh postnatal depression scale (EPDS). The sample was divided into a group with probable cases (EPDS score >9, N = 16) and a group with probable noncases (EPDS score < or =9, N = 41). RESULTS: The probable case group showed significantly higher cortisol responses to the stress test compared with the probable noncase group, whereas baseline levels did not differ. Additionally, women in the probable case group showed significantly higher state anxiety and lower mood state throughout the experiment. Furthermore, the probable case group showed higher stress susceptibility, higher trait anxiety, and higher levels in the Symptom Checklist. No differences were found for prior episodes of psychiatric disorders, obstetrical complications, birth weight, or mode of delivery. CONCLUSIONS: Our data provide evidence that healthy pregnant women developing postpartum depressive symptoms might already be identified during pregnancy by means of their higher cortisol reactivity and their higher psychological reactivity in response to psychosocial stress. Further investigations are required to explore whether higher psychobiological stress responses not only precede depressive symptoms within 2 weeks after birth, but might also predict postpartum major depression.

Adult↗

Anticipatory cognitive stress appraisal and the acute procoagulant stress response in men.

OBJECTIVE: Acute mental stress elicits blood hypercoagulability. Following a transactional stress model, we investigated whether individuals who anticipate stress as more threatening, challenging, and as exceeding their coping skills show greater stress reactivity of the coagulation activation marker D-dimer, indicating fibrin generation in plasma. METHODS: Forty-seven men (mean age 44 +/- 14 years; mean blood pressure [MBP] 101 +/- 12 mm Hg; mean body mass index [BMI] 26 +/- 3 kg/m(2)) completed the Primary Appraisal Secondary Appraisal (PASA) scale before undergoing the Trier Social Stress Test (combination of mock job interview and mental arithmetic task). Heart rate, blood pressure, plasma catecholamines, and D-dimer levels were measured before and after stress, and during recovery up to 60 minutes poststress. RESULTS: Hemodynamic measures, catecholamines, and D-dimer changed across all time points (p values <.001). The PASA "Stress Index" (integrated measure of transactional stress perception) correlated with total D-dimer area under the curve (AUC) between rest and 60 minutes poststress (r = 0.30, p = .050) and with D-dimer change from rest to immediately poststress (r = 0.29, p = .046). Primary appraisal (combined "threat" and "challenge") correlated with total D-dimer AUC (r = 0.37, p = .017), D-dimer stress change (r = 0.41, p = .004), and D-dimer recovery (r = 0.32, p = .042). "Challenge" correlated more strongly with D-dimer stress change than "threat" (p = .020). Primary appraisal (DeltaR(2) = 0.098, beta = 0.37, p = .019), and particularly its subscale "challenge" (DeltaR(2) = 0.138, beta = 0.40, p = .005), predicted D-dimer stress change independently of age, BP, BMI, and catecholamine change. CONCLUSIONS: Anticipatory cognitive appraisal determined the extent of coagulation activation to and recovery from stress in men. Particularly individuals who anticipated the stressor as more challenging and also more threatening had a greater fibrin stress response.

Adaptation, Psychological↗