ABSTRACT
Oxidative stress is generated by a multitude of environmental and endogenous challenges such as radiation, inflammation, or psychoemotional stress. It also speeds the aging process. Graying ...is a prominent but little understood feature of aging. Intriguingly, the continuous melanin synthesis in the growing (anagen) hair follicle generates high oxidative stress. We therefore hypothesize that hair bulb melanocytes are especially susceptible to free radical‐induced aging. To test this hypothesis, we subjected human scalp skin anagen hair follicles from graying individuals to macroscopic and immunohistomorphometric analysis and organ culture. We found evidence of melanocyte apoptosis and increased oxidative stress in the pigmentary unit of graying hair follicles. The “common” deletion, a marker mitochondrial DNA‐deletion for accumulating oxidative stress damage, occurred most prominently in graying hair follicles. Cultured unpigmented hair follicles grew better than pigmented follicles of the same donors. Finally, cultured pigmented hair follicles exposed to exogenous oxidative stress (hydroquinone) showed increased melanocyte apoptosis in the hair bulb. We conclude that oxidative stress is high in hair follicle melanocytes and leads to their selective premature aging and apoptosis. The graying hair follicle, therefore, offers a unique model system to study oxidative stress and aging and to test antiaging therapeutics in their ability to slow down or even stop this process.—Arck, P. C., Overall, R., Spatz, K., Liezman, C., Handjiski, B., Klapp, B. F., Birch‐Machin, M. A., Peters, E. M. J. Towards a “free radical theory of graying”: melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage. FASEB J. 20, E908‐E920 (2006)
► GOAT was recently detected in the circulation of rodents. ► GOAT protein is also present in human plasma. ► GOAT levels are lower in anorexia and higher in obesity compared to normal weight. ► ...Plasma GOAT is positively correlated with BMI and negatively with ghrelin. ► The ghrelin activating enzyme GOAT may play a role in anorexia and obesity.
Ghrelin is the only known peripherally produced and centrally acting peptide hormone stimulating food intake. The acylation of ghrelin is essential for binding to its receptor. Recently, the ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) was identified in mice, rats and humans. In addition to gastric mucosal expression, GOAT was also detected in the circulation of rodents and its expression was dependent on metabolic status. We investigated whether GOAT is also present in human plasma and whether expression levels are affected under different conditions of body weight. Normal weight, anorexic and obese subjects with body mass index (BMI) 30–40, 40–50 and >50 were recruited (n=9/group). In overnight fasted subjects GOAT protein expression was assessed by Western blot and ghrelin measured by ELISA. GOAT protein was detectable in human plasma. Anorexic patients showed reduced GOAT protein levels (−42%, p<0.01) whereas obese patients with BMI>50 had increased concentrations (+34%) compared to normal weight controls. Ghrelin levels were higher in anorexic patients compared to all other groups (+62–78%, p<0.001). Plasma GOAT protein expression showed a positive correlation with BMI (r=0.71, p<0.001) and a negative correlation with ghrelin (r=−0.60, p<0.001). Summarized, GOAT is also present in human plasma and GOAT protein levels depend on the metabolic environment with decreased levels in anorexic and increased levels in morbidly obese patients. These data may indicate that GOAT counteracts the adaptive changes of ghrelin observed under these conditions and ultimately contributes to the development or maintenance of anorexia and obesity as it is the only enzyme acylating ghrelin.
•Dipeptidyl peptidase IV (DPPIV) is involved in various homeostatic processes.•Obese have higher DPPIV protein levels compared to normal weight controls.•DPPIV activity was similar while ...concentration/activity ratio was higher in obese.•Plasma pancreatic polypeptide negatively correlates with body mass index.•The increased ratio might contribute to reduced anorexigenic signaling.
Dipeptidyl peptidase IV (DPPIV) is a protease with broad distribution involved in various homeostatic processes such as immune defense, psychoneuroendocrine functions and nutrition. While DPPIV protein levels were investigated in patients with hyporectic disorders, less is known under conditions of obesity. Therefore, we investigated DPPIV across a broad range of body mass index (BMI). Blood samples from hospitalized patients with normal weight (BMI 18.5–25kg/m2), anorexia nervosa (BMI <17.5kg/m2) and obesity (BMI 30–40, 40–50 and >50kg/m2, n=15/group) were tested cross-sectionally and DPPIV concentration and total enzyme activity and the DPPIV targets, pancreatic polypeptide (PP) and glucagon-like peptide (GLP-1) were measured. DPPIV protein expression was detected in human plasma indicated by a strong band at the expected size of 110kDa and another major band at 50kDa, likely representing a fragment comprised of two heavy chains. Obese patients had higher DPPIV protein levels compared to normal weight and anorexics (+50%, p<0.05) resulting in a positive correlation with BMI (r=0.34, p=0.004). DPPIV serum activity was similar in all groups (p>0.05), while the concentration/activity ratio was higher in obese patients (p<0.05). Plasma PP levels were highest in anorexic patients (∼2-fold increase compared to other groups, p<0.05), whereas GLP-1 did not differ among groups (p<0.05). Taken together, circulating DPPIV protein levels depend on body weight with increased levels in obese resulting in an increased concentration/activity ratio. Since DPPIV deactivates food intake-inhibitory hormones like PP, an increased DPPIV concentration/activity ratio might contribute to reduced food intake-inhibitory signaling under conditions of obesity.
The present study was designed to gather preliminary information regarding the feasibility of implementing a psychosocial resilience program and to assess if the program would potentially promote ...protective factors (such as resiliency, self-efficacy) and job satisfaction as well as decreasing perceived stress among a sample of German junior physicians.
Eighty-two junior physicians in their first year after graduation took part in the project and were randomized in a controlled trial to either an intervention or a control group for 3 months. The intervention group was offered resilience training combined with cognitive behavioral and solution-focused counseling. Primary outcome measures included scales of the PSQ, BRCS, SWOPE, and COPSOQ. Two post-intervention follow-up measurements proved the effectiveness of the intervention.
There was a significant improvement between baseline and follow-up intervention scores on measures of resilience, self-efficacy, optimism, and perceived stress observed in the intervention group compared to the control group. Job satisfaction did not significantly differ between baseline and follow-ups.
These results indicate that the program to enhance resilience and decrease stress among physicians is feasible to implement as a group training program in a workplace setting. Further, the intervention provides statistically significant improvement in perceptions of distress and strengthens protective factors (such as resiliency).
Adjustment disorders are re-conceptualized in the DSM-5 as a stress-related disorder; however, besides the impact of an identifiable stressor, the specification of a stress concept, remains unclear. ...This study is the first to examine an existing stress-model from the general population, in patients diagnosed with adjustment disorders, using a longitudinal design.
The study sample consisted of 108 patients consecutively admitted for adjustment disorders. Associations of stress perception, emotional distress, resources, and mental health were measured at three time points: the outpatients' presentation, admission for inpatient treatment, and discharge from the hospital. To evaluate a longitudinal stress model of ADs, we examined whether stress at admission predicted mental health at each of the three time points using multiple linear regressions and structural equation modeling. A series of repeated-measures one-way analyses of variance (rANOVAs) was performed to assess change over time.
Significant within-participant changes from baseline were observed between hospital admission and discharge with regard to mental health, stress perception, and emotional distress (p<0.001). Stress perception explained nearly half of the total variance (44%) of mental health at baseline; the adjusted R2 increased (0.48), taking emotional distress (i.e., depressive symptoms) into account. The best predictor of mental health at discharge was the level of emotional distress (i.e., anxiety level) at baseline (β= -0.23, R2corr=0.56, p<0.001). With a CFI of 0.86 and an NFI of 0.86, the fit indices did not allow for acceptance of the stress-model (Cmin/df=15.26; RMSEA=0.21).
Stress perception is an important predictor in adjustment disorders, and mental health-related treatment goals are dependent on and significantly impacted by stress perception and emotional distress.
Abstract Background Computerized adaptive testing (CAT) based on Item Response Theory, (IRT) offers an efficient way for accurate measurement of patient reported outcomes. The efficiency lies within ...a minimal response burden and a high measurement precision over a broad measurement range. The objective of the study was to evaluate and compare the responsiveness of CATs measuring anxiety, depression, and stress reaction to standard static self-assessment tools. Methods Longitudinal data of n =595 psychosomatic inpatients were analyzed for evaluating retest-reliability and sensitivity to change of the CATs compared to static measures (GAD-7, PHQ-9, and PSQ) using correlational and ANOVA statistics. The study hypothesized that CATs are at least as retest-reliable and as sensitive to change as static tools. Results The three CATs show a low burden for patients, administering on average 5–7 (±2–6SD) items with similar retest-reliability compared to the static tools applied (A-CAT: r =.78 vs. GAD-7: r =.75, D-CAT: r =.71 vs. PHQ-9: r =.75, S-CAT: r =.80 vs. PSQworries scale: r =.80). The CATs were overall as sensitive to change as the static tools (Cohen׳s d ranged between .19 and .69). Limitations This is a monocenter, observational, longitudinal study without external clinical criteria; thus generalization to other settings may be limited. Conclusions The tested CATs belong to the first generation of CATs being used in daily routine for more than a decade. They are as retest reliable and sensitive to change as static tools. Newer CATs may provide further practical advantages.
During the process of tinnitus diagnostics, various psychometric instruments are used to measure tinnitus-related distress. The aim of present work was to explore whether candidates for biological ...correlates of the tinnitus-related distress could be found in peripheral blood of patients and if so, whether there was association between them and psychometric scores that reflect tinnitus-related distress. The concentrations of interleukin-1β (IL1β), interleukin-6 (IL6), tumor necrosis factor-α (TNFα) and a brain-derived neutrotrophic factor (BDNF) were measured in serum of 30 patients diagnosed with chronic tinnitus and tested for correlation with psychometric scores collected on the same day. Spearman's correlation analyses detected significant positive association between the concentrations of tumor necrosis factor α and tinnitus loudness, total perceived stress, tension and depression and a negative association between tumor necrosis factor α and a psychometric score “joy”. Concentrations of interleukin-1β correlated with the awareness grade of tinnitus. The correlation between visual analogue scale (VAS) “loudness” and tumor necrosis factor α as well as between “joy” and tumor necrosis factor α retained their significance (p < 0.00167) after the application of Bonferroni correction for multiple testing. Partial correlations removing the effects of age, hearing loss and the duration of tinnitus verified the results obtained using Spearman correlation. We conclude that measuring the concentrations of selected circulating cytokines could possibly become an additional objective element of tinnitus diagnostics in the future.
•Concentrations of TNF-alpha correlate with selected psychometric scores of tinnitus related distress.•Concentrations of IL1-beta correlate with tinnitus related awareness.•Data suggests that those cytokines may be biological markers for tinnitus related distress.
Purpose
Cancer patients frequently suffer from psychological comorbidities such as depression and elevated stress. Previous studies could demonstrate that cancer patients benefit from massage therapy ...on the physical and psychological level. This pilot study investigates the effects of massage on depression, mood, perceived stress, and the Th1/Th2 ratio in breast cancer patients.
Methods
Thirty-four breast cancer patients were randomly assigned to a massage group (
n
= 17) and a control group (
n
= 17). Patients of the massage group received two 30-min classical massages per week for 5 weeks. At baseline, at the end of the intervention period, and 6 weeks after the end of intervention, patients of both groups completed the Perceived Stress Questionnaire (PSQ), the Patient Health Questionnaire (PHQ), and the Berlin Mood Questionnaire (BFS) and blood was withdrawn for determining cytokine concentrations and the Th1/Th2 ratio.
Results
Twenty-nine patients were included in the statistical analysis. Depression (PHQ) and anxious depression (BSF) were significantly reduced immediately after massage compared to the control group. Stress (PSQ) and elevated mood (BSF) did not show significant alterations after massage therapy. Changes of cytokine concentrations and Th1/Th2 ratio were insignificant as well, although there was a slight shift towards Th1 in the massage group over time.
Conclusions
Massage therapy is an efficient treatment for reducing depression in breast cancer patients. Insignificant results concerning immunological parameters, stress, and mood indicate that further research is needed to determine psychological and immunological changes under massage therapy.
The aim was to translate, revise, and standardize the Perceived Stress Questionnaire (PSQ) by Levenstein et al. (1993) in German. The instrument assesses subjectively experienced stress independent ...of a specific and objective occasion.
Exploratory factor analyses and a revision of the scale content were carried out on a sample of 650 subjects (Psychosomatic Medicine patients, women after delivery, women after miscarriage, and students). Confirmatory analyses and examination of structural stability across subgroups were carried out on a second sample of 1,808 subjects (psychosomatic, tinnitus, inflammatory bowel disease patients, pregnant women, healthy adults) using linear structural equation modeling and multisample analyses. External validation included immunological measures in women who had suffered a miscarriage.
Four factors (worries, tension, joy, demands) emerged, with 5 items each, as compared with the 30 items of the original PSQ. The factor structure was confirmed on the second sample. Multisample analyses yielded a fair structural stability across groups. Reliability values were satisfactory. Findings suggest that three scales represent internal stress reactions, whereas the scale "demands" relates to perceived external stressors. Significant and meaningful differences between groups indicate differential validity. A higher degree of certain immunological imbalances after miscarriage (presumably linked to pregnancy loss) was found in those women who had a higher stress score. Sensitivity to change was demonstrated in two different treatment samples.
We propose the revised PSQ as a valid and economic tool for stress research. The overall score permits comparison with results from earlier studies using the original instrument.
The orexigenic peptide ghrelin and the anorexigenic peptide nesfatin-1 are expressed by the same endocrine cell of the rat stomach, the X/A-like cell. However, data in humans are lacking, especially ...under conditions of obesity. We collected gastric tissue of obese patients undergoing sleeve gastrectomy and investigated the expression of nesfatin-1 and ghrelin in the gastric oxyntic mucosa by immunofluorescence. Nesfatin-1 immunoreactivity was detected in the human oxyntic mucosa in cells with an endocrine phenotype. A major portion of nesfatin-1 immunoreactive cells (78 %) co-localized with ghrelin indicating the occurrence in human X/A-like cells. In patients with very high body mass index (BMI 55–65 kg/m
2
), the number of nesfatin-1 immunoreactive cells/low-power field was significantly higher than in obese patients with lower BMI (40–50 kg/m
2
, 118 ± 10 vs. 82 ± 11,
p
< 0.05). On the other hand, the number of ghrelin immunoreactive cells was significantly reduced in obese patients with higher compared to lower BMI (96 ± 12 vs. 204 ± 21,
p
< 0.01). Also the ghrelin-acylating enzyme ghrelin-
O
-acyltransferase decreased with increasing BMI. In conclusion, nesfatin-1 immunoreactivity is also co-localized with ghrelin in human gastric X/A-like cells giving rise to a dual role of this cell type with differential effects on stimulation and inhibition of appetite dependent on the peptide released. The expression of these two peptides is differentially regulated under obese conditions with an increase of nesfatin-1 and a decrease of ghrelin immunoreactivity with rising BMI pointing towards an adaptive change of expression that may counteract further body weight increase.
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