Executive control processes are associated with individual fitness outcomes following regular exercise training: blood lactate profile curves and neuroimaging findings.

Cardiovascular training has been associated with neuroimaging correlates of executive control functions (ECF) in seniors and children/adolescents, while complementary studies in middle-aged populations are lacking. Ascribing a prominent role to cardiorespiratory fitness improvements, most studies concentrated on training-induced gains in maximal oxygen uptake (VO2max), although other fitness indices may provide complementary information. Here, we investigated the impact of long-term sub-maximal exercise training on interference control, considering individual training-induced shifts in blood lactate profile curves (BLC) and VO2max. Twenty-three middle-aged sedentary males (M = 49 years) underwent a six-month exercise program (intervention group, IG). Additionally, 14 individuals without exercise training were recruited (control group, CG, M = 52 years). Interference control was assessed before and after the intervention, using a functional magnetic resonance imaging (fMRI) flanker paradigm. Task performance and brain activations showed no significant group-by-time interactions. However, regression analyses in the IG revealed significant associations between individual fitness gains and brain activation changes in frontal regions, which were not evident for VO2max, but for BLC. In conclusion, training-induced plasticity of ECF-related brain activity can be observed in late middle adulthood, but depends on individual fitness gains. For moderate training intensities, BLC shifts may provide sensitive markers for training-induced adaptations linked to ECF-related brain function.

Long-term endurance exercise decreases antiangiogenic endostatin signalling in overweight men aged 50-60 years.

BACKGROUND: Endurance training may decrease the risk of coronary artery disease. It has been speculated that these effects may be due to an exercise-induced stimulation of angiogenesis. The underlying mechanisms are not yet clear. Therefore, using ELISA, we investigated the plasma level of vascular endothelial growth factor (VEGF, angiogenic factor) and endostatin (antiangiogenic factor) in a group of untrained men aged 50-60 years with obesity. METHODS: All men were randomised into a "running" group (training 3 times/week, 60 min each, n = 7), a "cycling" group ( training 3 times/week, 90 min each, n = 7) and a sedentary control group ( n = 7). Both training groups worked at moderate intensity (2-4 mmol/l lactate). The intervention had a duration of 6 months. Before and after this period, blood samples were taken from the participants at rest and they underwent a medical investigation. RESULTS: Body mass index (BMI), systolic and diastolic blood pressure, and plasma levels of VEGF and endostatin were comparable in all three groups. Endurance training significantly reduced BMI in both exercise groups (mean (SEM) before v after 29.7 (0.7) v 29.1 (0.6) kg/m2 and 31.1 (0.7) v 30.1 (0.9) kg/m2 for the running and cycling groups respectively) but not in the control group (30.0 (1.0) v 30.2 (0.8) kg/m2). Endurance training did not influence VEGF plasma level (before v after 1.3 (0.4) v 1.5 (0.2) ng/ml for the running group; 1.6 (0.3) v 1.5 (0.2) ng/ml for the cycling group; and 2.5 (0.6) v 2.1 (0.7) ng/ml for the control group). Plasma level of endostatin was significantly reduced in both exercise groups (mean (SEM) before v after: 20.9 (1.6 v 17.5 (1.0) ng/ml and 21.3 (1.4 v 18.0 (1.6) ng/ml for the running and cycling groups respectively) but not in controls (19.7 (1.3 v 17.7 (1.1 ng/ml). CONCLUSIONS: Endurance training may reduce the antiangiogenic mechanisms in men aged 50-60 years by reducing endostatin plasma level and this may subsequently decrease the risk of cardiovascular disease.

Integrated effects of the vasodilating beta-blocker nebivolol on exercise performance, energy metabolism, cardiovascular and neurohormonal parameters in physically active patients with arterial hypertension.

OBJECTIVE: The present study was designed to investigate the integrated effects of the beta-1-selective blocker with vasodilator properties, nebivolol, on systemic haemodynamics, neurohormones and energy metabolism as well as oxygen uptake and exercise performance in physically active patients with moderate essential hypertension (EH). DESIGN AND METHODS: Eighteen physically active patients with moderate EH were included: age: 46.9 +/- 2.38 years, weight: 83.9 +/- 2.81 kg, blood pressure (BP): 155.8 +/- 3.90/102.5 +/- 1.86 mm Hg, heart rate: 73.6 +/- 2.98 min(-1). After a 14-day wash-out period a bicycle spiroergometry until exhaustion (WHO) was performed followed by a 45-min submaximal exercise test on the 2.5 mmol/l lactate-level 48 h later. Before, during and directly after exercise testing blood samples were taken. An identical protocol was repeated after a 6-week treatment period with 5 mg nebivolol/day. RESULTS: Nebivolol treatment resulted in a significant (P < 0.01) decrease in systolic and diastolic BP and heart rate at rest and during maximal and submaximal exercise. Maximal physical work performance, blood lactate and rel. oxygen uptake (rel. VO(2)) before and after nebivolol treatment at rest and during maximal and submaximal exercise remained unaltered. Free fatty acid, free glycerol, plasma catecholamines, beta-endorphines and atrial natriuretic peptide (ANP) increased before and after treatment during maximal and submaximal exercise but remained unaltered by nebivolol treatment. In contrast, plasma ANP levels at rest were significantly higher in the presence of nebivolol, endothelin-1 levels were unchanged. CONCLUSIONS: Nebivolol was effective in the control of BP at rest and during exercise in patients with EH. Furthermore, nebivolol did not negatively affect lipid and carbohydrate metabolism and substrate flow. The explanation for the effects on ANP at rest remain elusive. This pharmacodynamic profile of nebivolol is potentially suitable in physically active patients with EH.

G(-699)/C polymorphism in the bradykinin-1 receptor gene in patients with renal failure.

BACKGROUND: Bradykinin is thought to have protective effects on the progression of renal failure. Of particular interest, it has been reported that one polymorphism in the promoter region of the human kinin B1-receptor gene which is associated with higher activity, is less frequently found in patients with end-stage renal failure. The present study was performed to independently confirm these results. DESIGN: Cross-sectional study on 376 healthy controls, 262 non-diabetic dialysis patients and 175 patients with type 1 diabetes >/=10 years and microalbuminuria (of whom 21 were dialysis-dependent) and 334 patients with type 2 diabetes >/=10 years and nephropathy (of whom 61 were dialysis-dependent). METHODS: Genotyping was performed by polymerase chain reaction, followed by restriction enzyme analysis. RESULTS: All groups were in Hardy Weinberg equilibrium. The study showed no significant difference in the frequency of the C-allele between controls (0.093) and non-diabetic dialysis patients (0.095). No significant difference in C-allele frequency was observed between controls and patients with type 1 diabetes and microalbuminuria (0.092) or patients with type 2 diabetes and nephropathy (0.099). CONCLUSION: In large cohorts of patients with non-diabetic end-stage renal disease and diabetic renal disease with and without end-stage renal failure, no change in the frequency of the C-699 allele of the B-1-receptor gene was found.

Increased frequency of G-protein beta 3-subunit 825 T allele in dialyzed patients with type 2 diabetes.

BACKGROUND: A polymorphism (C825T) in exon 10 of the gene encoding the beta 3 subunit of heterotrimeric G proteins (GN beta 3) has recently been described, and the T allele was found to be associated with late-onset hypertension. Because hypertension is a known risk factor for the development of clinically manifest progressive renal disease, we examined the C825T polymorphism in older hemodialysis patients suffering from nondiabetic renal disease or type 2 diabetes with presumed diabetic nephropathy, respectively, and in older healthy controls. METHODS: Genotyping was performed by polymerase chain reaction, followed by restriction enzyme analysis. RESULTS: The study showed that the frequency of the T allele in the nondiabetic patients on dialysis (0.232) was significantly (P < 0.03) lower than in older healthy controls (0.293). In contrast, the frequency was significantly (P < 0.02) higher in older patients with type 2 diabetes on dialysis. No significant change in T-allele frequency was noted in older patients with type 2 diabetes without microangiopathy (0.286). The odds ratios for patients with type 2 diabetes on dialysis versus nondiabetic patients on dialysis were 3.24 (1.3 to 7.9, P < 0.00079) for TT/CC and 1.82 (1.07 to 3.09, P < 0.02) for CT/CC. The respective odds ratios for patients with type 2 diabetes on dialysis versus controls were 2.05 (1.07 to 3.9, P < 0.028) for CT/CC and 1.216 (0.79 to 1.87; P < 0.37) for CT/CC. CONCLUSION: The data do not support a role of the hypertension-associated T allele in the genesis of dialysis-dependent end-stage renal failure in general, but are compatible with a specific role of the T allele in the development or progression of diabetic nephropathy.

The outer surface lipoprotein OspA of Borrelia burgdorferi provides co-stimulatory signals to normal human peripheral CD4+ and CD8+ T lymphocytes.

Studies in man and mice have indicated that T cells induced during Borrelia burgdorferi infection are involved in the pathogenesis of the disease. We analyzed the ability of B. burgdorferi to provide co-stimulatory signals to highly enriched normal human CD2+ T lymphocytes in the presence of suboptimal concentrations of immobilized anti-CD3 antibodies. Here we show that the lipid-containing recombinant outer surface lipoprotein A (rlip-OspA) of B. burgdorferi but not its delipidated derivative rNS1-OspA augmented CD3-induced T cell proliferation in a dose-dependent manner and at levels similar to that obtained with anti-CD28 antibodies. Lipopolysaccharide had no effect in this system at any concentration tested, suggesting that the active principle of co-stimulation is associated with the lipid moiety of rlip-OspA and distinct from conventional lipid A. Furthermore, incubation of CD2+ T cells or selected CD4+ as well as CD8+ subpopulations with rlip-OspA, but not with rNS1-OspA led to the production of interferon (IFN)-gamma, interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, but not IL-4. In contrast, co-stimulation of the respective T cell populations with anti-CD28 antibodies resulted in the generation of IFN-gamma, IL-4 and TNF-alpha, but not IL-6. This indicated that the signal transduction pathway induced by rlip-OspA is distinct from that elicited via the CD28 receptor. Co-stimulation of T cells with rlip-OspA also resulted in the development of cytolytic effector cells. In light of the fact that inflamed tissues of B. burgdorferi-infected hosts contain blood leukocytes together with spirochetes, their degradation products, or both, these results suggest that infiltrating CD4+ and CD8+ T cells of any specificities, including spirochetes, autoantigens, or both, participate in the pathogenesis of Lyme disease.

The exercise-induced increase in plasma levels of endothelin-1 is enhanced in patients with atherosclerotic coronary artery disease. Modulation by pentaerithrityltetranitrat (PETN).

BACKGROUND AND OBJECTIVE: Previous studies have suggested that endothelin (ET)-1 with its marked vasoconstrictive potency may play a role in the induction of coronary artery spasms. Furthermore, it was demonstrated using in-vitro vessel preparations that the secretion of ET-1 by the vascular endothelium is enhanced in the presence of atherosclerotic alterations. The objective of the present study was to investigate a) the effects of ergometric exercise on ET-1 plasma concentrations in 10 patients with coronary artery disease (CAD) as compared to an age and sex matched control group and b) the modulatory role of the orally administered organic nitrate, pentaerithrityltetranitrat (PETN), in patients with CAD. PATIENTS AND METHODS: 10 male patients with CAD confirmed by coronarography and 10 male healthy controls underwent a bicycle ergometry according to the WHO-standards upt to 125 watts. Venous blood samples for determination of ANP and ET-1 plasma concentrations were drawn in supine position directly before and 5 min after ergometric exercise. Subsequently, patients were randomized and treated for 3 days in a crossover design either with placebo or PETN (150 mg b.i.d.). RESULTS: Basal plasma levels of ET-1 were 6.1 +/- 0.7 pg/ml (patients) and 5.5 +/- 0.6 pg/ml (controls), resp. (n.s.). After ergometric exercise ET-1 plasma concentrations rose significantly (7.3 +/- 0.9 pg/ml; p < 0.05) in the placebo-treated patient group, whereas they remained constant (5.5 +/- 0.7 pg/ml) in the PETN-treated patient group. Blood pressure and heart rate were not modified by the PETN-treatment. ET-1 plasma levels remained unaffected by ergometric exercise in controls. DISCUSSION: In contrast to healthy controls ergometric exercise induced an increase in ET-1 plasma concentrations in patients with CAD that may be potentially harmful by promoting coronary vasospasms. The almost complete blunting of the ET-1-increase in the presence of PETN-therapy may result from local-hemodynamic effects of the organic nitrate; it may be hypothesized that the nitrate-induced rise in local NO-concentrations counteracts ET-secretion. The findings of the present study are in accordance with the beneficial clinical effects of organic nitrates in patients with CAD.

Exercise increases endothelin-1 plasma concentrations in patients with coronary artery disease: modulatory role of LDL cholesterol and of pentaerithrityltetranitrate.

Previous studies suggest that ET-1 plays a role in induction of coronary artery disease (CAD). It was shown that secretion of endothelin-1 (ET-1) by the vascular endothelium is enhanced in atherosclerotic alterations and may be antagonized by EDRF. The objective of the present study was to investigate the effects of ergometric exercise on plasma ET-1 concentrations, and the potential modulatory role of LDL cholesterol, and the effects of an orally administered nitrate, PETN, in patients with CAD. Ten men with CAD and 10 healthy men underwent bicycle ergometry according to the WHO-standards. Venous blood samples for determination of ET-1 concentrations were drawn directly before and 5 min after ergometric exercise. Patients were randomized and treated for 72 h in a crossover design either with placebo or pentaerithrityltetranitrate (PETN). After 72 h the identical ergometric protocol was repeated. Basal plasma levels of ET-1 were 6.1 +/- 0.7 pg/ml (patients) and 5.5 +/- 0.6 pg/ml (controls) (n.s.). After ergometric exercise ET-1 plasma concentrations rose significantly (7.3 +/- 0.9 pg/ml; p < 0.05) in the patient group under placebo treatment, whereas they remained constant (5.5 +/- 0.7 pg/ml) with PETN treatment. ET-1 levels remained unaffected by ergometric exercise in healthy controls. Mean LDL cholesterol plasma levels in patients with CAD were 156 +/- 8 mg% and 152 +/- 7 mg% in healthy controls. In the patient group there was a significant (p < 0.002) positive correlation between the exercise-induced increase in ET-1 and the LDL cholesterol plasma concentrations (r = 0.85). Blood pressure and heart rate were not modified by PETN treatment. In patients with CAD bicycle ergometry induced an increase in ET-1 plasma concentrations. The positive correlation with the LDL cholesterol plasma levels indicates that LDL cholesterol is involved in regulation of ET-1 secretion in vivo. PETN therapy completely abolished the exercise-induced increase in ET-1 plasma levels. This may result from local hemodynamic effects of the nitrate; hypothetically a nitrate-induced rise in the local NO concentrations can be considered. The clinical implications of these findings remain elusive. However, the findings of the present study are in accordance with the beneficial clinical effects of nitrates in patients with CAD.

[Detection of retinal visual field defects by sectorial photic stimulation in scotopic luminance ERG]. / Nachweis retinaler Gesichtsfelddefekte durch sektorielle Lichtreizung im skotopischen H-ERG.

We developed an electroretinographic procedure to assess visual field defects due to dysfunction of the outer retinal layers. For this objective we determined the amplitude/intensity function of the scotopic b-wave to full field (100 degrees of visual angle), quadrant and hemifield stimulation in 14 healthy volunteers and in patients with visual field disturbances. To prevent stray light effects, we confined the test light illuminance to 10(1.3) of the extrapolated normal ERG threshold (about 10(4.2) the sensory dark threshold). Whereas patients with dysfunction of the proximal retinal layers or the optic nerve did not show any change when the corresponding visual field was stimulated, those suffering from disturbances of the distal retinal layers (e.g., amotio, chorioretinal diseases) showed a reduction in the amplitude/intensity function, which was related to the extension and the degree of the field losses. The method reveals visual field defects caused by disturbances in the outer retinal layers where one-fourth or more of the corresponding retinal quadrant exhibits a sensitivity loss of more than 15 dB.