Search PubMed⌕ Search

Biomedical subjects

S Bruhn

Publications and source records attributed to S Bruhn.

12 recordsLinked to original sources
PubMed2006

Cellular effects and metabolic stability of N1-cyclic inosine diphosphoribose and its derivatives.

BACKGROUND AND PURPOSE: Recently, a number of mimics of the second messenger cyclic ADP-ribose (cADPR) with replacement of adenosine by inosine were introduced. In addition, various alterations in the molecule ranging from substitutions at C8 of the base up to full replacement of the ribose moieties still retained biological activity. However, nothing is known about the metabolic stability and cellular effects of these novel analogues. EXPERIMENTAL APPROACH: cADPR and the inosine-based analogues were incubated with CD38, ADP-ribosyl cyclase and NAD-glycohydrolase and metabolism was analysed by RP-HPLC. Furthermore, the effect of the analogues on cytokine expression and proliferation was investigated in primary T-lymphocytes and T-lymphoma cells. KEY RESULTS: Incubation of cADPR with CD38 resulted in degradation to adenosine diphosphoribose. ADP-ribosyl cyclase weakly catabolised cADPR whereas NAD-glycohydrolase showed no such activity. In contrast, N1-cyclic inosine 5'-diphosphoribose (N1-cIDPR) was not hydrolyzed by CD38. Three additional N1-cIDPR analogues showed a similar stability. Proliferation of Jurkat T-lymphoma cells was inhibited by N1-cIDPR, N1-[(phosphoryl-O-ethoxy)-methyl]-N9-[(phosphoryl-O-ethoxy)-methyl]-hypoxanthine-cyclic pyrophosphate (N1-cIDP-DE) and N1-ethoxymethyl-cIDPR (N1-cIDPRE). In contrast, in primary T cells neither proliferation nor cytokine expression was affected by these compounds. CONCLUSIONS AND IMPLICATIONS: The metabolic stability of N1-cIDPR and its analogues provides an advantage for the development of novel pharmaceutical compounds interfering with cADPR mediated Ca2+ signalling pathways. The differential effects of N1-cIDPR and N1-cIDPRE on proliferation and cytokine expression in primary T cells versus T-lymphoma cells may constitute a starting point for novel anti-tumor drugs.

ADP-ribosyl Cyclase↗
PubMed2006

Combinatory effects of high-intensity-strength training and sensorimotor training on muscle strength.

It has been shown in classical strength training studies using high loads that improvements in rate of force development are mainly due to adaptations in the intramuscular coordination. Adaptations following sensorimotor training were also characterized by improvements in the rate of force development during maximum voluntary isometric contraction. The purpose of the present study was to investigate neuromuscular adaptations of combined sensorimotor and classical strength training. Eighteen subjects were randomly assigned to two groups. Group 1 (SMT-HST) had to perform a period of sensorimotor training at first and a high-intensity strength training afterwards. Group 2 (HST-SMT) performed the high intensity strength training at first and the sensorimotor training after. Maximum voluntary isometric contraction and neuromuscular activation were measured at three occasions: Before training, after the first, and after the second period. The results after the first period confirmed the positive effects of both training regimen on rate of force development (13 % [SMT-HST] and 27 % [HST-SMT], p < 0.05) and on maximum strength (9 % [HST-SMT] and 12 % [SMT-HST], p < 0.05) during maximum voluntary contraction. Improvements caused by sensorimotor training could only be achieved, when it was performed at first. It is supposed that classical strength training with high loads basically improves the mechanical efficiency of the effectors, whereas sensorimotor training alters the afferent input on the central nervous system. In combination, the sensorimotor training can have preconditioning effects on the strength training. A combination of both training methods can thus be recommended, if the sensorimotor training is performed at first.

Adaptation, Physiological↗
PubMed2006

Specific adaptations of neuromuscular control and knee joint stiffness following sensorimotor training.

The aim of this study was to examine how fixations of the ankle joint during sensorimotor training (SMT) influence adaptations in mechanical stiffness and neuromuscular control of the knee joint. Sixty-three healthy subjects were randomly assigned to three training groups that differed in their degree of ankle joint fixation, which was either barefooted, with an ankle brace or with a ski boot. Mechanical knee joint stiffness and reflex control of m. vastus medialis, m. vastus lateralis, m. biceps femoris, and m. semitendinosus were tested during force controlled anterior tibial displacements. This force was applied as both a fast and a slow stimulus. After the training period the group that trained barefooted showed an increase in mechanical stiffness of the knee joint from 79 +/- 21 (Mean +/- SD) N/mm to 110 +/- 38 N/mm (p < 0.05) in the fast stimulus. The training group that trained with ski boots was able to improve knee joint stiffness from 67 +/- 26 N/mm to 96 +/- 47 N/mm (p < 0.05) in the slow stimulus. These improvements correspond with an enhanced activity of the hamstring muscles (m. biceps femoris and m. semitendinosus). From a more functional point of view, specific adaptations due to the fixation of the ankle joint may be helpful in the prevention and rehabilitation of knee joint injuries.

Adaptation, Physiological↗
PubMed2004

The effects of a sensorimotor training and a strength training on postural stabilisation, maximum isometric contraction and jump performance.

Previous studies revealed that adaptations following sensorimotor training, performed to improve functional joint or postural stability, were characterized by improvements in the rate of force development during maximum voluntary isometric contraction. In classical strength training studies using intense loads it has been shown that improvements in rate of force development is mainly due to adaptations in the intramuscular coordination. The purpose of the present study was to compare possible neuromuscular adaptations in two training groups following either sensorimotor or classical strength training over a period of four weeks. Additionally a control group was investigated to contrast the adaptations seen after training. Postural stability, maximum voluntary isometric contraction and performance in squat-jump and in drop-jump were measured before and after training. The results confirmed the positive effects of both training regimen on rate of force development and on maximum strength during maximum voluntary contraction as well as on jump performance, while only the improvements after the strength training were significant. Strength training reduced iMEG, while it was enhanced after sensorimotor training in most testing situations. Strength training had positive effects also on concentric contractions like squat-jump. The sensorimotor training improved performance in reactive drop-jump by enhanced neuromuscular activity immediately after ground contact. It is concluded that classical strength training with high loads basically improves the mechanical efficiency of the efferent drive on the motoneurons, whereas sensorimotor training alters the afferent input on the central nervous system. Both adaptations yield to specific effects during force development.

Adult↗
PubMed2003

Inhaled nitric oxide induces cerebrovascular effects in anesthetized pigs.

Although inhaled nitric oxide (NO(i)) is considered to act selectively on pulmonary vessels, EEG abnormalities and even occasional neurotoxic effects of NO(i) have been proposed. Here, we investigated cerebrovascular effects of increasing concentrations of 5, 10 and 50 ppm NO(i) in seven anesthetized pigs. Cerebral hemodynamics were assessed non-invasively by use of near-infared spectroscopy and indicator dilution techniques. NO(i) increased cerebral blood volume significantly and reversibly. This effect was not attributable to changes of macrohemodynamic parameters or arterial blood gases. Simultaneously, cerebral transit time increased while cerebral blood flow remained unchanged. These data demonstrate a vasodilatory action of NO(i) in the cerebral vasculature, which may occur preferentially in the venous compartment.

Anesthetics↗
PubMed2002

[Evaluation of mechanical and neurophysiological effects of wearing bandages for the knee joint in functional testing situations].

The purpose of the study was to estimate the stabilising effects of two functional bandages for the knee joint. Two mechanisms typically leading to knee injuries were simulated. Three-dimensional recordings of knee joint angles and recordings of the tibial displacement in anterior-posterior direction were used to determine the destabilisation of the knee joint as a result of the applied mechanical stimuli, as well as the stabilising support of wearing the bandages. Reflex activations of the knee joint muscles and their modulation by the bandages were measured by EMG. To estimate limitations of the sports performance by the bandages, the subjects performed an additional test for postural stability. The testing performance, the three-dimensional knee joint angles and muscle activities were measured. While the FUTURO(R)-knee joint bandage (BDF AG) caused both mechanical and neurophysiological effects, the action of the KASSELER bandage (Sporlastic(R) GmbH) relied solely on the enhancement of muscular activities. The applied methods proved to be a very useful tool for the evaluation of stabilising effects of bandages in functional situations.

Adult↗
PubMed1990

Dominance of memory over naive T cells in contact dermatitis is due to differential tissue immigration.

CD4+ T cells include a naive (CD4-, CD45RO-, CD29-, CD45RA+) as well as a memory subpopulation (CD4+, CD45RO+, CD29+, CD45RA-). These subpopulations represent different stages in T-cell development and function. Recently, it has been shown that inflammatory and neoplastic CD4+ T-cell infiltrates are dominated by the memory subpopulation, whereas both subpopulations are about the same size in the peripheral blood. This was thought to be the result of in situ maturation of naive into memory T cells. We analysed early positive patch-test reactions 1-2 days after antigen challenge and found that most of the CD4+ T cells that had freshly immigrated into the tissue carried the memory phenotype. Their preferential migration may be mediated by at least five adhesion molecules expressed on their cell surface. This observation has important pathogenetic implications, since memory T cells can be rapidly activated by antigens and secrete a wide variety of pro-inflammatory cytokines.

Antigens, CD↗
PubMedDate not supplied

Improved ventricular function during inhalation of PGI(2) aerosol partly relies on enhanced myocardial contractility.

Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular (RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng.kg(-1).min(-1)) and, consecutively, ILO (60 ng.kg(-1).min(-1)) for 20 min each. We measured pulmonary artery pressure (PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E(es)). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E(es) was enhanced during all doses tested, which reached statistical significance during EPO(25 ng) and ILO, but not during EPO(50 ng). PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function.

Administration, Inhalation↗
PubMedDate not supplied

Cellular delivery of CNTF but not NT-4/5 prevents degeneration of striatal neurons in a rodent model of Huntington's disease.

The delivery of neurotrophic factors to the central nervous system (CNS) has gained considerable attention as a potential treatment strategy for neurodegenerative disorders such as Huntington's disease (HD). In the present study, we directly compared the ability of two neurotrophic factors, ciliary neurotrophic factor (CNTF), and neurotrophin-4/5 (NT-4/5), to prevent the degeneration of striatal neurons following intrastriatal injections of quinolinic acid (QA). Expression vectors containing either the human CNTF or NT-4/5 gene were transfected into a baby hamster kidney fibroblast cell line (BHK). Using a polymeric device, encapsulated BHK-control cells and those secreting either CNTF (BHK-CNTF) or NT-4/5 (BHK-NT-4/5) were transplanted unilaterally into the rat lateral ventricle. Seven days later, the same animals received unilateral injections of QA (225 nmol) into the ipsilateral striatum. Nissl-stained sections demonstrated that the BHK-CNTF cells significantly reduced the volume of striatal damage produced by QA. Quantitative analysis of striatal neurons further demonstrated that both choline acetyltransferase (ChAT)- and glutamic acid decarboxylase (GAD)-immunoreactive neurons were protected by CNTF implants. In contrast, the volume of striatal damage and loss of striatal ChAT and GAD-positive neurons in animals receiving BHK-NT-4/5 implants did not differ from control-implanted animals. These results help better define the scope of neuronal protection that can be afforded following cellular delivery of various neurotrophic factors. Moreover, these data further support the concept that implants of polymer-encapsulated CNTF-releasing cells can be used to protect striatal neurons from excitotoxic damage, and that this strategy may ultimately prove relevant for the treatment of HD.

Animals↗