Long-term endurance training increases serum cathepsin S levels in healthy female subjects.

BACKGROUND: Circulating cathepsin S (CS) has been associated with a lower risk for breast cancer in a large Swedish cohort. Long-term physical activity has been shown to have beneficial effects on the development of various cancer subtypes, in particular breast and colorectal cancers. The aim of this study was to investigate the effect of long-term endurance sport on CS levels in females. MATERIAL AND METHODS: Thirty-six of 40 subjects completed the study. Subjects were told to increase their activity pensum for 8 months reaching 150 min/week moderate or 75 min/week intense exercise. Ergometries were performed at the beginning and the end of the study to prove/quantify the performance gain. Blood samples were drawn at baseline and every 2 months. Serum CS levels were measured by ELISA. To analyse the change and the progression of CS, Wilcoxon rank sum and Friedman tests were used. RESULTS: The sportive group (performance gain by > 4.9%) showed a significant increase of CS levels from 3.32/2.73/4.09 to 4.00/3.09/5.04 ng/ml (p = 0.008) corresponding to an increase of 20.5%. CONCLUSIONS: We could show a significant increase of circulating CS levels in healthy female subjects induced by long-term physical activity. CS, occurring in the tumour microenvironment, is well-known to promote tumour growth, e.g. by ameliorating angiogenesis. However, the role of circulating CS in cancer growth is not clear. As physical activity is known as preventive intervention, in particular concerning breast and colorectal cancers, and long-term physical activity leads to an increase of CS levels in female subjects, circulating CS might even be involved in this protective effect. TRIAL REGISTRATION: Clinical trial registration: NCT02097199.

Antithrombotic triple therapy and coagulation activation at the site of thrombus formation: a randomized trial in healthy subjects.

BACKGROUND: Patients with acute coronary syndrome and concomitant atrial fibrillation may require antithrombotic triple therapy but clinical evidence of safety and efficacy is poor. We have therefore studied the combination of different antithrombotic medicines for coagulation activation in an in vivo model in the skin microvasculature. METHODS AND RESULTS: Platelet activation (ß-thromboglobulin [ß-TG]) and thrombin generation (prothrombin fragment 1 + 2 [F1+2 ], thrombin-antithrombin complex [TAT]) were studied in an open-label, randomized, parallel group trial in 60 healthy male subjects (n = 20 per group) who received ticagrelor and acetylsalicylic acid (ASA) in combination with dabigatran (150 mg bid), rivaroxaban (20 mg od) or phenprocoumon (INR 2.0-3.0). Coagulation biomarkers in shed blood were assessed at 3 h after monotherapy with the medicines under study, at 3 h after triple therapy dosing and at steady state trough conditions. Single doses of ticagrelor, dabigatran or rivaroxaban caused comparable decreases in shed blood ß-TG and were more pronounced than phenprocoumon at an INR of 2.0-3.0. In contrast, thrombin generation was more affected by rivaroxaban and phenprocoumon than by dabigatran. During triple therapy a similarly sustained inhibition of platelet activation and thrombin generation with a maximum decrease of ß-TG, F1+2 and TAT at 3 h post-dosing was noted, which remained below pre-dose levels at trough steady state. CONCLUSION: A triple therapy at steady state with ticagrelor plus ASA in combination with dabigatran or rivaroxaban is as effective as a combination with phenprocoumon for platelet activation and thrombin generation in vivo.

Endostatin and physical exercise in young female and male athletes and controls.

It was suggested that endostatin, an angiogenic mediator, is influenced by physical exercise. We performed bicycle stress testing in 88 healthy non-smoking female and male individuals, divided into athlete and non-athlete groups. Serum endostatin and norepinephrine were measured at rest, after reaching maximum workload and after 20 min of recovery. At baseline, both female and male controls showed significant lower levels compared to female and male athletes (89.39±15.32 resp. 93.39±15.00 ng/ml; p<0.001 vs. 128.81±20.84 resp. 147.52±27.72; p<0.001). An increase in endostatin levels in both groups and sexes was associated with bicycle stress testing (p for all groups<0.001). The extent of endostatin increase was comparable in both groups and sexes and varied between 23-27%. Significance was obscured when the performance was entered as covariate. Acutely induced physical strain leads to an increase in endostatin levels in athletes and controls of both sexes, the extent of increase depending on the extent of workload. An athletic lifestyle with >3 h of endurance training/week seems to lead to higher long-term endostatin levels which might play a role in the connection between sports and cardiovascular prevention.

Cardiovascular, endocrine, and receptor measures as related to sex and menstrual cycle phase.

OBJECTIVE: The present study was undertaken to elucidate possible mechanisms underlying sex differences in cardiovascular measures or reactivity to challenge. Because there is vastly diverging literature on the issue, we tried to control for endocrine and psychological factors, which might contribute to some of the apparent discrepancies. METHODS: Blood pressure, heart rate, adrenaline, and noradrenaline in women (N = 24) and men (N = 14) were examined during baseline and challenge (Stroop Test and Cold Face Test). Adrenoceptor density on lymphocytes (beta 2) and platelets (alpha 2) were determined to examine possible sex differences in underlying cardiovascular mechanisms. Gender effects were controlled by assessing gender role orientation and task appraisal. Women were tested during either the follicular (N = 12) or the luteal (N = 12) phase of the menstrual cycle (verified by estradiol, progesterone, and luteinizing hormone). RESULTS: Follicular and luteal phase women did not differ in any parameter except progesterone. We observed sex-related differences in absolute levels of physiological parameters, the male group having higher systolic blood pressure levels, higher adrenaline plasma concentrations, and significantly more alpha 2-adrenergic receptors. Both challenges elicited pronounced cardiovascular and endocrine responses. Men and women did not differ in response magnitude, in task appraisal, or gender role orientation. CONCLUSIONS: The assumption that female sex hormones reduce reactivity to challenge is not supported by our data. The frequently reported male/female differences in reactivity may be caused by an interaction of gender and task characteristics.

Working with new technologies: hormone excretion as an indicator for sustained arousal. A pilot study.

Effects of working with new technologies (visual display units) on hormone levels were investigated in a pilot study. The relationship between subjective strain and hormone levels was also assessed. Twenty subjects participated in the study reported here, which is a part of a comprehensive longitudinal study, in which 279 employees participated. Measurements were taken two months before the new technology was installed (baseline: work with conventional technology), during the implementation phase of the new technology, and at a 12-month interval. Fourteen complete data sets were analysed. The introduction of new technologies was accompanied by enhanced levels of catecholamines (epinephrine and norepinephrine). Levels also remained high one year after the implementation. Similar values were found on work days and rest days. Cortisol changes were less evident; excretion tended to increase after the implementation had been completed. The relationship was weak between hormone levels and subjective strain measurements. The results indicate that working with new technologies was accompanied by enhanced physiological arousal of the employee. Reactivity was related more to a particular occupational setting than to scales of subjective assessment.

[Personal variables and their effects on physiologic stress reactions]. / Personale Variable in ihren Auswirkungen auf die physiologischen Beanspruchungsreaktionen.

In 24 male medical students hormonal, cardiovascular and state of mood data were collected on the day of an oral examination as compared to a control day. Analyses included 24-hour-noradrenaline-, adrenaline- and cortisol-excretion, blood levels of free testosterone, heart rate and blood pressure readings and state of mood ratings (Nitsch). Furthermore subdimensions of the type A construct, as included in the need-for-control questionnaire (Siegrist), were determined. Four subgroups were established according to total amount and stress reactivity of noradrenaline (NA) excretion. Further analysis showed that this line of separation held for the remaining hormones as well, thus revealing rather homogenous group- inherent hormonal patterns. However, in both groups with low hormonal stress reactivity cardiovascular reactivity was higher than in the groups with a pronounced hormonal stress response. Blood pressure rose highest and recovered slowest in the group, who had the highest NA and cortisol excretion on control day and highest allover cortisol excretion. This group rated high in the Siegrist subdimension "task-involvement" (inability to withdraw), the difference to the remaining groups being statistically significant. Neither the amount of hormonal nor that of cardiovascular reactivity were related to the state of mood ratings.

[Activation-induced changes in visual functions]. / Aktivierungsinduzierte Veränderungen visueller Funktionen.

Visual functions were tested in 18 healthy male medical students on a control day and on the day of an oral examination. Stress induced impairment was observed in binocular tests measuring accommodation, convergence or their mutual relationship (near points of accommodation and convergence, Maddox-wing). Results of tests in which fusion operates as stabilizing factor (slightly dissociating test: Polatest) or of tests designed for far distance vision (synoptophore, Maddox-cross, Pola-cross) did not show significant impairment under examination stress. In slightly dissociating tests an activity-dependent improvement in stereoscopic vision became evident. Flicker fusion frequency values increased under stress. Colour vision analysis by means of the Nagel anomaloscope revealed that the absolute matching range remained unchanged, whereas the relative matching range broadened on the day of examination. The results indicate activity-dependence of binocular vision, with an improvement in central nervous functions on the one hand and an impairment of peripheral accommodative components on the other hand. Furthermore, it may be concluded that binocular coordination is achieved independently from accommodation dependent focusing of the image and is apparently processed separately and parallel to monocular image components.