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ABSTRACT: Objectives: A training intervention comparing resistance exercise with or without whole-body vibration (WBV) was conducted to compare acute and chronic effects on functional and molecular parameters. Methods: A six-week training intervention was performed including 26 healthy males (26 years, SD=4). Two groups were analyzed in a parallel design performing either resistive exercise (RE, n=13) or resistive vibration exercise (RVE, n=13) training with weekly increasing vibration frequencies (20-40Hz). Resting and exercising blood pressure and heart rate were measured before and after the 6-week intervention. Results: Both training interventions decreased resting systolic blood pressure (P=0.003). Resting diastolic blood pressure was significantly decreased only in the RVE group (P=0.01). Exercising diastolic blood pressure was significantly decreased during the final training (P<0.001) with no additional effect of superimposed vibrations. Resistance exercise with superimposed vibrations evoked back pain to a higher degree than resistance exercise alone when training at frequencies above 30Hz (P<0.01). Conclusions: These data suggest positive effects of resistance exercise upon cardiovascular health and vascular responsiveness and a further beneficial effect of superimposed vibrations in decreasing resting diastolic blood pressure. Finally, development of back pain may be fostered by superimposed vibrations to high training loads, particularly at higher frequencies.
Journal of musculoskeletal & neuronal interactions 06/2013; 13(2):147-156. · 2.00 Impact Factor
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ABSTRACT: Exposure of human oral mucosa to lead (Pb) and benzo[a]pyrene (BaP) by inhalation and ingestion can lead to pathological conditions via apoptosis and oxidative and nitrosative stress. However, few studies have investigated the the effects of Pb and BaP on oral mucosa cells. Furthermore, previous studies focused on chronic Pb and BaP exposure. Therefore, we evaluated important markers of apoptosis and oxidative and nitrosative stress in oral mucosa cells by incubating the cells with Pb and BaP for 5 to 360 min. Ex vivo samples of human oral mucosa were exposed to Pb or BaP, and immunohistochemical staining was performed to evaluate active caspase-3, 8-epi prostaglandin F2 alpha (8-epi-PGF2a), and 3-nitrotyrosine (3-NT). Pb and BaP treatments significantly increased active caspase-3 levels in a time-dependent manner. Furthermore, the treatments induced an early increase in 3-NT level, which ceased with longer incubation times. 8-epi-PGF2a level increased only after prolonged incubation with Pb, and this elevation was irrespective of BaP incubation duration. Smokers' samples had significantly lower levels of markers of oxidative and nitrosative stress than did nonsmokers' samples. Thus, single, short-term exposure to Pb or BaP increases the levels of apoptosis markers and markers of oxidative and nitrosative stress.
Toxicology in Vitro 01/2013; · 2.78 Impact Factor
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ABSTRACT: The purpose of the present study was to compare the acute hormonal response of angiogenic regulators to a short-term hypoxic exposure at different altitudes with and without exercise. 7 subjects participated in 5 experimental trials. 2 times subjects stayed in a sedentary position for 90 min at 2 000 m or 4 000 m, respectively. The same was carried out again in combination with exercise at the same relative intensity (2 mmol∙L - 1 of lactate). The fifth trial consisted of 90 min exercise at sea level. Venous blood samples were taken under resting conditions, 0 and 180 min after each condition to determine VEGF, EPO, IL-6, IL-8 and IGF-1 serum concentrations. EPO, VEGF, and IL-8 showed increases only, when hypoxia was combined with exercise. IL-6 was increased after exercise, independent of altitude. IGF-1 showed no changes in any intervention. The present study suggests that short term hypoxic exposure combined with low intensity exercise is able to up-regulate angiogenic regulators, which might be beneficial to induce angiogenesis and to improve endurance performance. However, in some cases high altitudes are needed, or it can be speculated that exercise intensity needs to be increased.
International Journal of Sports Medicine 08/2012; · 2.43 Impact Factor
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ABSTRACT: The description of mechanisms underlying exercise-induced heart and vascular bed adaptations reveals and highlights the significance of different mechanical and metabolic stimuli that possibly evoke various short-term and long-term regulations and adaptations of these tissues. In this brief review the molecular mechanisms mediated by free radicals and/or mechanical stimulation and, are therefore involved in the modulation of the extracellular matrix and epigenetics-based regulation of the functional genome will be discussed. In the heart and the vascular bed free radicals play important roles in physiological and pathophysiological processes. Exercise leads on the one hand to increased free radicals but on the other hand improves the antioxidative capacity. This phenomenon shifts the cellular oxidative stress balance and also a variety of signal cascades that mediate physiological and pathophysiological heart and vascular bed adaptations. A similar great significance can be attributed to mechanical stimulation which directly or indirectly influences a variety of signaling cascades. It was demonstrated that exercise alters the molecular composition and architecture of the extracellular matrix which in turn plays an important role in the regulation of different mechanical stimuli-mediating signaling cascades. These alterations in the molecular composition and architecture of the extracellular matrix are of high significance for cellular adaptation processes, possibly also in the sense of epigenetic modulations that are actually only indirectly linked to exercise in cardiovascular tissues. However, there is growing evidence that epigenetic modulations mediated by exercise and physical activity can provoke modifications of the functional genome in heart and vascular beds, comparable to already well-described phenomena, e.g. diet or inflammation.
Herz 06/2012; 37(5):508-15. · 0.92 Impact Factor
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ABSTRACT: Oxidative stress is thought to be an important factor in the onset, progression and recurrence of cancer. In order to investigate how it is influenced by physical activity, we measured oxidative stress and antioxidative capacity (aoC) in 12 women with breast cancer and 6 men with prostate cancer, before and after long hiking trips. Before the hike, the men had a ROS-concentration of 1.8±0.6 mM H2O2 and an aoC of 0.7±0.6 mM Trolox-equivalent (Tro), while the women had a ROS-concentration of 3.1±0.7 mM H2O2 and an aoC of 1.2±0.2 mM Tro. After the hike, women showed no significant change in ROS and a significant increase in aoC (1.3±0.2 mM Tro), while the ROS concentration in men increased significantly (2.1±0.3 mM H2O2) and their aoC decreased (0.25±0.1 mM Tro). After a regenerative phase, the ROS concentration of the men decreased to 1.7±0.4 mM H2O2 and their aoC recovered significantly (1.2±0.4 mM Tro), while the women presented no significant change in the concentration of H2O2 but showed an ulterior increase in antioxidant capacity (2.05±0.43 mM Tro). From this data we conclude that physical training programs as for example long distance hiking trips can improve the aoC in the blood of oncological patients.
International Journal of Sports Medicine 11/2011; 32(12):960-4. · 2.43 Impact Factor
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ABSTRACT: Oxidative stress plays a leading role in the progression of diabetic secondary complications, e.g., of cardio-vascular illnesses. Physical activity has been shown to delay and even prevent the progression of type 2 diabetes by improving the antioxidative capacity and thereby decreasing systemic oxidative stress. Peroxiredoxins (PRDX) are important antioxidative components that are highly abundant in erythrocytes. The present study examines the influence of glycemic control and physical fitness on oxidative stress and the peroxiredoxin system in the erythrocytes of non-insulin-dependent type 2 diabetic men ( N=22, years=61 ± 10) at rest. Oxidative stress was measured by immunohistochemical stainings for 8-iso-prostaglandin-F2α (8-Iso-PGF) and the overoxidized form of peroxiredoxins (PRDX-SO (2-3)). Peroxiredoxin isoforms PRDX1 and PRDX2 were also quantified immunohistochemically. Physical fitness was determined during the WHO-step test. Regression analyses showed a positive relationship between 8-Iso-PGF plotted against HbA (1c) (hyperbolic curve (y=a+b/x), R (2)=0.346, P=0.013), a positive relationship between 8-Iso-PGF plotted against fasting glucose (hyperbolic curve (y=a+b/x), R (2)=0.440, P=0.003), as well as positive relationships between PRDX2 plotted against VO (2 peak) (S-curve (y=e(a+b/x)), R(2)=0.259, P=0.018) and between PRDX2 plotted against the workload corresponding to the 4 mmol/l blood lactate concentration (hyperbolic curve (y=a+b/x), R(2)=0.203, P=0.041). Further significant relationships were not found. CONCLUSIONS: Poor glycemic control may increase oxidative stress in the erythrocytes of type 2 diabetic men. Good physical fitness seems to be associated with increased peroxiredoxin contents. Therefore, it can be speculated that physical training can contribute to the improvement of the erythrocyte peroxiredoxin system to counteract free radicals in type 2 diabetic patients.
Experimental and Clinical Endocrinology & Diabetes 06/2011; 119(9):559-64. · 1.69 Impact Factor
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C Brinkmann,
N Chung,
U Schmidt,
T Kreutz,
E Lenzen,
T Schiffer,
S Geisler,
C Graf,
G Montiel-Garcia,
R Renner, W Bloch,
K Brixius
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ABSTRACT: The present study analyzes the oxidative stress situation in the skeletal muscle of overweight/obese men suffering from non-insulin-dependent type 2 diabetes mellitus [T2DM, n=16, years=61±7, body mass index (BMI)=31±4 kg/m(2) ] and BMI-matched non-diabetic male control subjects (CON, n=7, years=53±6, BMI=30±4 kg/m(2) ). Furthermore, it investigates whether physical training can alter the skeletal muscle antioxidative capacity of T2DM patients at rest. Molecule content analyses (immunohistochemical stainings) of 8-iso-prostaglandin-F2α (8-Iso-PGF), superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (GPX1), peroxiredoxin isoforms (PRDX 1-6) and heat-shock-protein-70 (HSP70) were performed in biopsies taken from the vastus lateralis muscle. Under basal conditions, 8-Iso-PGF was significantly decreased in T2DM patients (-35.7%), whereas PRDX2 and PRDX6 were significantly increased relative to CON (+82.6%; +82.3%). Differences were neither observed in SOD2 nor in GPX1 or PRDX1, 3, 4, 5 density. Regular physical activity (moderate endurance or resistance training twice a week for 3 months) did not alter PRDX1, 2, 3, 4, 6 in the skeletal muscle of T2DM patients, but significantly increased SOD2 (+65.9%), GPX1 (+62.4%), PRDX5 (+37.5%), and HSP70 (+48.5%). Overweight/obese men with non-insulin-dependent T2DM exhibit up-regulated cytosolic peroxiredoxin contents relative to BMI-matched controls. Regular training further up-regulates cytosolic and mitochondrial antioxidative enzymes in T2DM patients and improves their cellular protection systems. This may contribute to a retardation of the disease's progression.
Scandinavian Journal of Medicine and Science in Sports 04/2011; 22(4):462-70. · 2.87 Impact Factor
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ABSTRACT: The nitric oxide (NO) receptor enzyme soluble guanylate cyclase (sGC) contains one prosthetic heme group as an αβ heterodimer, and two heterodimer isoforms (α(1)β(1), α(2)β(1)) were characterized to have enzyme activity. To test the irreversible inflammation-dependent regulation of sGC in odontoblasts, we incubated decalcified frozen sections of healthy and inflamed human third molars with antibodies against β-actin, nitrotyrosine, inducible nitric oxide synthase (iNOS), α(1)-, β(1)-, and α(2)-subunits of sGC and analyzed them at protein levels by quantitative immunohistochemistry. The irreversible inflammation induced an increase in the signal intensities for nitrotyrosine and iNOS and a decrease for the α(1)-, β(1)-, and α(2)-subunits of sGC in odontoblasts. Inflammatory mediators, reactive oxygen, and nitrogen species may impair the expression of the α(1)-, β(1)-, and α(2)-subunits in odontoblasts. The decrease of sGC at the protein level in inflamed odontoblasts is compatible with a critical role for sGC to mediate biological effects of NO in health.
Journal of dental research 01/2011; 90(4):517-22. · 3.46 Impact Factor
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ABSTRACT: Studies have shown that, depending on intensity, endurance exercise increases neurotrophins and thereby induces neuroplasticity. However, data on the effect of acute resistance exercise at different intensities on neurotrophins is not yet available. Thus, we conducted 2 trials to determine the serum concentrations of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF-1) before and after a low or high intensity resistance exercise in 11 healthy humans. Exercise load was related to 3 repetitions of maximal effort isokinetic work involving knee extension under alternating concentric and eccentric conditions for muscle work at a velocity of 60°s-1 registered during a familiarization session. The torque angle diagrams from these 3 repetitions were averaged and displayed as target curves in the test sessions, the intensity of resistance exercise was set at 40% (trial: R1) or 110% (trial: R2) of the averaged individual maximal effort curve, respectively. After resistance exercise, serum IGF-1 was increased significantly (p<0.01) by 28% in R1 and 16% in R2 compared to pre-exercise levels. Resistance exercise did not increase serum VEGF at any time point. Serum BDNF increased during exercise compared to post-exercise, but did not achieve significant difference from pre-exercise values. The present study shows that either low or high resistance exercise increases levels of IGF-1, but not of BDNF or VEGF. This finding is of importance for health promotion by means of resistance exercise because circulating serum IGF-1 has been demonstrated to mediate positive effects of exercise on brain functions.
Hormone and Metabolic Research 11/2010; 42(13):982-6. · 2.19 Impact Factor
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ABSTRACT: Both 19-norandrostenedione (estr-4-ene-3,17-dione, NOR) and desoxymethyltestosterone (17alpha-methyl-5alpha-androst-2-en-17beta-ol, DMT or "madol") are 'designer steroids' misused for doping purposes in the bodybuilding scene. We have previously characterized the pharmacological profile of madol and identified potential adverse side effects. The aim of this study was to investigate the anabolic potency of NOR, madol and the reference substance testosterone propionate (TP). Besides wet weight of the M.levator ani (LA), we examined the effects on muscle fiber type composition and myosin heavy chain (MHC) expression in the M.gastrocnemius (Gas) muscle as additional markers for anabolic potency. A Hershberger assay was performed, where orchiectomized (orchi) male Wistar rats were treated subcutaneously with NOR, madol, TP or vehicle control (all 1 mg/kg BW/day) for 12 days. Wet weights of the Gas, LA, prostate and seminal vesicle were examined to determine anabolic and androgenic effects. Fiber type composition of the Gas muscle was analyzed using ATPase staining, and MHC protein profiles were determined by silver stain and Western blot analysis. NOR and madol exhibited strong anabolic and weak androgenic potency by stimulating growth of the LA but not the prostate and seminal vesicle. Skeletal muscle fiber type composition characterized by ATPase staining was not significantly altered between the treatment groups, although there was a tendency toward lower levels of type IIB and increased type IIA fibers in all treatment groups relative to orchi. MHC protein expression determined by Western blot and silver stain analysis revealed that MHC IId/x was significantly up-regulated, while MHC IIb was significantly down-regulated in NOR, madol and TP groups relative to orchi. There were no significant differences for MHC IIa and MHC I expression between groups. Results suggest that the observed MHC expression shift could serve as a molecular marker to determine anabolic activity of anabolic steroids at least in skeletal muscle of orchi rats. The molecular mechanisms as well as the androgen-dependent regulation of MHC expression in intact skeletal muscle remain to be further investigated.
Archive für Toxikologie 10/2010; 85(6):635-43. · 4.67 Impact Factor
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ABSTRACT: This study investigated (cardiac) remodeling of the myocardial microvasculature in patients with terminal heart failure due to ischemic (ICM) and dilative (DCM) cardiomyopathy. Seventeen transmural left-ventricular (LV) biopsies (9 ICM and 8 DCM), taken from heart transplant recipients at transplantation (n=4) or during ventricular assist device implantation (n=13) were investigated by immunohistostaining for VEGFR-1 and VEGFR-2 as capillary markers and VEGFR-3, D2-40, PROX-1 and LYVE-1 as lymphatic markers. Results were compared to LV biopsies from 7 donor hearts (control). Compared to control, DCM hearts showed a significantly higher density of LYVE-1 positive lymphatics (p < 0.05), whereas no difference was seen for other markers. ICM hearts showed a significantly higher density of D2-40 positive lymphatics (p < 0.01) and a lower density of VEGFR-2 capillaries compared to control (p < 0.05). In comparison to normal donor hearts, ICM and DCM hearts showed a significantly different pattern of microvascular receptor expression. As distinct patterns were seen in ICM and DCM, the effect of microvascular remodeling may be substantially different between two clinically important causes of cardiomyopathy. Further research should be aimed at defining the impact of extracellular matrix composition and VEGF-related angiogenesis on the myocardial microvasculature at various stages of heart failure.
Lymphology 09/2010; 43(3):110-7. · 1.02 Impact Factor
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ABSTRACT: Little is known about sex-dependent physiological and pathophysiological differences in cardiac endothelial nitric oxide synthase (eNOS) expression and activation. Therefore, we investigated cardiac morphology and eNOS protein expression, including its translocation-dependent activation and phosphorylation, in cardiac tissue of male and female wild-type mice and transgenic heart-failure mice having a cardiac-specific, 5-fold overexpression of the Galphaq protein. In addition, we measured calcineurin protein expression. Heart-to-body weight ratio was increased in Galphaq mice. Female wild-type mice showed higher eNOS protein expression and activation (translocation and phosphorylation) than did wild-type males. In cardiac tissue of Galphaq mice, these sex-dependent differences remained or were enhanced. Protein expression of the catalytic subunit calcineurin A, which has been shown to dephosphorylate eNOS, was higher in wild-type males than in wild-type females. These differences were increased in the Galphaq mice model. We conclude that sex differences exist in cardiac eNOS protein expression and phosphorylation. Increased activation of the Galphaq protein appears to alter eNOS protein expression and phosphorylation only in males.
Canadian Journal of Physiology and Pharmacology 02/2010; 88(2):121-9. · 1.95 Impact Factor
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S Lee,
S Grafweg,
T Schneider,
M Jimenez,
J-P Giacobino,
A Ghanem,
K Tiemann, W Bloch,
J Müller-Ehmsen,
R H G Schwinger,
K Brixius
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ABSTRACT: The present study investigated cardiac function in hearts of mice with total deficiency of the beta1-, beta2- and beta3-adrenoceptors (TKO) in comparison to wildtype mice (WT). We investigated cardiac morphology and echocardiographic function, measured protein expression of Ca2+-regulatory proteins, SERCA 2a activity, myofibrillar function, and performed running wheel tests. Heart weight and heart-to-body weight ratio were significantly smaller in TKO as compared to WT. This was accompanied by a decrease in the size of the cardiomyocytes in TKO. Heart rate and ejection fraction were significantly diminished in TKO as compared to WT. Protein expressions of SERCA 2a, ryanodine receptor and Na+/Ca2)-exchanger were similar in TKO and WT mice, but phospholamban protein expression was increased. PKA-dependent phosphorylation of phospholamban at serine 16 was absent and CaMKII-dependent phosphorylation at threonine 17 was decreased in TKO. All alterations were paralleled by a decrease in SERCA 2a-activity. A similar maximal calcium-dependent tension but an increased myofibrillar calcium-sensitivity was measured in TKO as compared to WT. We did not observe relevant functional impairments of TKO in running wheel tests. In the absence of beta-agonistic stimulation, SERCA 2a activity is mainly regulated by alterations of phospholamban expression and phosphorylation. The decreased SERCA 2a activity following beta-adrenoceptor deficiency may be partly compensated by an increased myofibrillar calcium-sensitivity.
Physiological research / Academia Scientiarum Bohemoslovaca 01/2010; 59(5):679-89. · 1.55 Impact Factor
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ABSTRACT: Nitric oxide (NO) production by both coronary endothelial cells and cardiomyocytes is thought to play a significant role in myocardial pathophysiology following ischemia/reperfusion (I/R).
In thirteen pigs subjected to 1 hour cardioplegic arrest (CA) on CPB, left ventricular (LV) biopsies were collected prior to CPB (baseline), at 60 min CPA, at 15 and 30 min reperfusion on CPB, and at 120 min post CPB. LV specimens were immunocytochemically stained against phospho-eNOS (Ser1177), phospho-eNOS (Thr495), phosphorylated ERK1/2, and AKT/PKB. Four additional pigs without CA served as controls. Cardiomyocytes were quantitatively investigated using TV densitometry (gray units: U).
After 60 min CA phosphorylation of eNOS (Ser1177) increased significantly and remained elevated until 30 min of reperfusion. In contrast, eNOS (Thr495) phosphorylation remained unchanged during CA and throughout reperfusion. In control animals, eNOS phosphorylation remained unchanged. Akt/PKB activity significantly increased after 60 min CA and decreased thereafter. ERK1/2 activity remained unchanged during ischemia but increased during reperfusion.
ENOS activation during ischemia occurs through phosphorylation at Ser1177 mediated by Akt/PKB. ERK1/2 does not seem to be involved in myocardial eNOS regulation especially not via phosphorylation at eNOS (Thr495).
The Thoracic and Cardiovascular Surgeon 10/2009; 57(7):379-85. · 0.88 Impact Factor
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ABSTRACT: Exercise induces alterations of the extracellular matrix (ECM), e.g. by an increased release of endostatin or by regulation of matrix metalloproteases (MMP)-2/-9, and cathepsin L. To investigate the influence of training status on exercise-induced ECM-processing of angiogenic molecules, alterations of endostatin-, MMP-2, and MMP-9 plasma concentrations during incremental running step tests in male elite short-track (n=6) and male elite long-track runners (n=7) were studied. Three blood samples (pre-exercise, 0, and 1 h post-exercise) were taken from each subject at each running test. In both groups, the basal endostatin plasma concentration was significantly decreased at the second running test, i.e. after the training season. Exercise-related acute alterations of the parameters were also observed only during the second test. In the long-track group, there was a significant increase in endostatin at 0 h and of MMP-2 at 1 h post-exercise. In the short-track group, only MMP-9 was significantly increased at 0 h post-exercise. Cathepsin L was increased at 0 h post-exercise. In conclusion, regular exercise performance decreases the basal endostatin plasma concentration, facilitates ECM-processing of angiogenic molecules by regular performance, and seems to be dependent on the kind of training.
Scandinavian Journal of Medicine and Science in Sports 07/2009; 20(3):441-8. · 2.87 Impact Factor
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ABSTRACT: Sulphur mustard (SM) is a chemical warfare agent that causes erythema and blistering of the skin with a latency of several hours. Although SM is known for almost 200 years the cellular mechanisms involved in the damaging process are not fully understood. There is evidence that changes in nitric oxide (*NO), reactive oxygen species (ROS) and reactive nitrogen species (RNS) might be involved in the damaging process.
To find out more about the pathophysiology of SM, we investigated the initial formation of biochemical markers of nitrosative and oxidative stress as well as activation (translocation from plasma-membrane) and upregulation of eNOS and iNOS, respectively.
Human immortalized keratinocytes (HaCaT cell line) were exposed to SM (100 microM or 300 microM) for 30 min. Cells were fixed after 1h, 3h or 6h of incubation in SM-free medium and immunostained. Live cell experiments were performed using the NO-sensitive dye DAF2-DA. In order to assess cell viability after BH(4) supplementation, we analyzed apoptosis using CDD-ELISA.
SM significantly increased biochemical markers of nitrosative and oxidative stress already 1h after exposure. Moreover, the NO producing enzymes eNOS and iNOS showed concentration- and time-dependent changes in their activation or expression levels. Initially, live cell imaging experiments could not confirm NO production after SM exposure. Only when cells were supplemented with tetrahydrobiopterine, stable NO production was detectable. Apoptotic activity was increased due to SM exposure and could be reduced after BH(4) treatment.
Our data point towards concentration- and time-dependent formation of iNOS and activation of eNOS due to translocation from plasma-membrane. Live cell experiments yielded first indications of catalytic decoupling of NOS that could be reversed by supplementation with tetrahydrobiopterin (BH(4)). Addition of BH(4) 1h after SM exposure significantly decreased apoptosis compared to the unsupplemented control.
Toxicology Letters 05/2009; 188(3):263-9. · 3.23 Impact Factor
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ABSTRACT: The present study investigated the effects of the preferential β3-AR agonist BRL 37344 (BRL) on force of contraction (FOC), Ca2+-transient and eNOS-activity in human right atrial myocardium.BRL concentration-dependently caused an increase in FOC that was paralleled by an increase in Ca2+-transient and a shortening of time to half peak relaxation (T0.5T). These effects were abolished in the presence of propranolol (0.3 μM).BRL acted as a competitive antagonist towards isoprenaline and in binding experiments it was shown to have a distinct affinity towards β1/2-AR.In immunohistochemical experiments BRL (10 μM) increased detection of activated eNOS. This effect remained constant in the presence of propranolol (0.3 μM).BRL increased directly detected NO in DAF-staining experiments. This increase was significantly smaller in the presence of the NO-inhibitor L-NAME.The inotropic effects of BRL were not changed in the presence of L-NMA.These results suggest that the inotropic effects of BRL in human atrium are mediated via β1/2-AR, whereas the increase of atrial eNOS-activity is due to β3- adrenergic stimulation. This increase in eNOS-activity did not influence atrial myocardial contractility. In conclusion, this study shows that β3-adrenergic stimulation is present in human atrium, but may not be functionally as significant as in the left ventricle.British Journal of Pharmacology (2003) 138, 521–529. doi:10.1038/sj.bjp.0705065
British Journal of Pharmacology 01/2009; 138(3):521 - 529. · 4.41 Impact Factor
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ABSTRACT: The extracellular signal-regulated kinases 1 and 2 (ERK1/2) have been implicated in the inflammation-dependent sensitization of nociceptors, and the inflammatory mediator bradykinin (BK) led to a reduced threshold in the nociceptor terminals, activating intracellular signaling by phosphorylating receptors and ion channels. The effects of BK on the non-transcriptional modulation of the ERK1/2 in the peripheral nociceptor terminals, including in nerve endings of the dentin-pulp complex, are unknown. The time-dependent effects of BK (10(-7) M) on the ERK1/2 phosphorylation in nerve terminals of the dentin-pulp complex were investigated by quantitative and double immunolabeling with organ bath experiments. In nerve terminals, total and p-ERK1/2 were detected. In comparison with the controls, the numbers of p-ERK1/2-positive nerve endings increased after 1 and 3 min and decreased after 10 min of BK treatment. Analysis of the data indicates that BK induces phosphorylation-mediated local activation of ERK1/2 in nerve terminals modulating nociception in the dentin-pulp complex.
Journal of dental research 01/2009; 87(12):1149-54. · 3.46 Impact Factor
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ABSTRACT: Blood neurotrophins like insulin-like growth factor (IGF-1) and brain-derived neurotrophic factor (BDNF) are discussed to mediate health benefits of physical activity in humans. The aim of the study was to analyze the training effects of moderate endurance training (Em) and strength training with high loads (Sh) on blood plasma concentrations of IGF-1 and BDNF in humans. Venous blood samples were obtained from 27 healthy students, randomly assigned to an Em, Sh, and a control group, before and after a 12-week training intervention. Sh resulted in an increase in isometric (14.5%) and dynamic (8.3%) strength of the knee extensor muscles in the Sh group and Em led to a significant increase in the endurance performance in the Em group (p<0.05). IGF-1 basal plasma concentrations decreased (p<0.05) after the intervention in all groups. There were no significant changes for BDNF. Despite specific functional adaptations induced by Em and Sh there are no correspondingly different adaptations in the basal blood concentrations of the neurotrophins IGF-1 and BDNF. Additionally, exercise per se does not result in changes in basal plasma concentrations of BDNF, suggesting that the mode of the exercise programme is a decisive factor.
Hormone and Metabolic Research 10/2008; 41(3):250-4. · 2.19 Impact Factor
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ABSTRACT: The objective of this study was to evaluate the role of collagen membrane and Bio-Oss coverage in healing of an onlay graft to the mandible. Twelve adult sheep each received an onlay bone graft (experiment 1), bone graft+Bio-Gide (experiment 2), and bone graft+Bio-Oss/Bio-Gide (experiment 3) on the lateral surface of the mandible. The animals were euthanized at 4, 8, 12 or 16 weeks after surgery, and findings were analysed by routine microscopy and immunohistochemistry for proliferation (Ki67) and apoptotic (Caspase-3) markers. Grafts were fully incorporated in all specimens. Pronounced resorption was observed in experiment 1. Minimal loss of graft volume was seen in experiment 2 specimens without membrane displacement. A remarkable increase in the augmented region of the mandible was observed in experiment 3. A high number of osteoclasts were expressed within the grafts during the early healing period, and thereafter declined markedly. Osteoblasts within the grafts expressed a moderate level of Ki67 at 8 weeks, which thereafter declined markedly. The strongest expression of Caspase-3 on the bone surface was observed after 16 weeks. In conclusion, the effect of collagen membrane coverage on bone graft volume maintenance was dependent on membrane stability during healing. An autogenous bone graft covered with Bio-Oss particles resulted in a remarkable increase in augmented lateral surface of the mandible. The late stage of bone graft healing was associated with a high apoptotic induction pathway of osteoblasts lining the surfaces of the new bone, demonstrated by strong positive Caspase-3 immunoreactivity.
International Journal of Oral and Maxillofacial Surgery 08/2008; 37(7):651-9. · 1.51 Impact Factor
