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Biomedical subjects

B Frick

Publications and source records attributed to B Frick.

At least 19 recordsLinked to original sources
PubMed2006

Homocysteine but not neopterin declines in demented patients on B vitamins.

Inflammation and immune system activation seem to play an important role in the development and progression of dementia. Hyperhomocysteinemia is common in various forms of dementia, and a significant relationship was found between concentrations of homocysteine and immune activation marker neopterin. B vitamin supplementation is able to slow-down homocysteine formation in patients. In an open-label study, effects of B vitamin supplementation (Beneuran compositum ) on concentrations of homocysteine and neopterin were investigated in 58 patients with Alzheimer's disease (n=30), vascular dementia (n=12) and mild cognitive impairment (n=16). In all groups of patients, a significant percentage of patients presented with homocysteine concentrations >15 micromol/L and with elevated concentrations of immune activation marker neopterin. Decline of homocysteine concentrations was observed after one month of B vitamin supplementation (all p<0.01; paired Kruskal-Wallisn-test). By contrast, neopterin concentrations remained unchanged (all p>0.05). B vitamin supplementation in patients with various forms of dementia did not influence neopterin concentrations, which indicates that the degree of immune activation and inflammation remained unchanged. The question remains, if lowering of homocysteine by folate supplementation alone could have any beneficial effect to modulate the course of dementia development and if longer period of supplementation would also ameliorate immune system activation status.

Dementia↗
PubMed2006

ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology.

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where normal food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in cancer patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards, are based on all relevant publications since 1985 and were discussed and accepted in a consensus conference. Undernutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis. EN should be started if undernutrition already exists or if food intake is markedly reduced for more than 7-10 days. Standard formulae are recommended for EN. Nutritional needs generally are comparable to non-cancer subjects. In cachectic patients metabolic modulators such as progestins, steroids and possibly eicosapentaenoic acid may help to improve nutritional status. EN is indicated preoperatively for 5-7 days in cancer patients undergoing major abdominal surgery. During radiotherapy of head/neck and gastrointestinal regions dietary counselling and ONS prevent weight loss and interruption of radiotherapy. Routine EN is not indicated during (high-dose) chemotherapy.

Cachexia↗
PubMed2006

[Effectiveness of antiviral therapy in patients with chronic hepatitis C treated by private practice gastroenterologists].

The standard treatment for patients with chronic hepatitis C consists of pegylated interferon (PegIFN) alpha in combination with ribavirin. Information on treatment effectiveness outside clinical trials is sparse. To study community-based health care, a regional network supported by the German network of competence for hepatitis (Hep-Net) was created between gastroenterologists in private practice and a tertiary referral centre. A treatment register containing evidence-based guidelines was established and 212 consecutive patients who were treated with either PegIF Nalpha 2a/ribavirin (n = 126) or PegIFNalpha2b/ribavirin (n = 86) for 24 weeks (HCV genotype 2, 3) and 48 weeks (HCV genotype 1, 4, 5), respectively, were included and followed prospectively. Twenty-four weeks after cessation of antiviral treatment a sustained virological response was achieved in 54 % of the patients. By univariate analyses, infection with HCV genotypes 2 or 3 (p < 0.0001), younger age (p < 0.0001), normal gamma-glutamyltransferase levels before initiation of treatment (p = 0.003), and absence of language communication problems (p = 0.023) were associated with a sustained virological response. The presence of liver cirrhosis in patients with HCV genotype 1, 4, 5 infection was associated with lower sustained response rates (p = 0.025). Patients infected with HCV genotype 1 in whom the PegIFNalpha dose was reduced had higher virological relapse rates (p = 0.049). With regard to the treating physician, sustained virological response rates ranged from 26 - 67 % in patients infected with HCV genotype 1. Our study shows that virological response rates similar to those in international randomised clinical trials can be achieved by private practice gastroenterologists. The presented network allows characterization of the treatment outcome in chronic hepatitis C not only with regard to virus- and host-related factors but also on an individual physician basis.

Adult↗
PubMed2005

Sub-Tg dynamics in polycarbonate by neutron scattering and its relation with secondary gamma relaxation.

We have investigated the dynamics of phenylene rings in glassy bisphenol-A (BPA) polycarbonate (PC) by means of quasielastic neutron scattering. Taking advantage of selective deuteration of the samples, we have studied the incoherent scattering of hydrogens in phenylene rings on the one hand, and on the other hand the coherent quasielastic scattering of all the atoms in the sample. Two different types of neutron spectrometers, time of flight and backscattering, were used in order to cover a wide dynamic range, which extends from microscopic (approximately 10(-13) s) to mesoscopic (approximately 10(-9) s) times. Moreover, neutron-diffraction experiments with polarization analysis were carried out in order to characterize the structural features, and the relative coherent and incoherent contributions of the samples investigated. In contrast with previous studies of phenylene ring dynamics in BPA polysulfone performed by us also by neutron scattering, phenylene rings in BPA PC exhibit an "extra" motion in addition to those found for BPA polysulfone's phenylene rings. This extra motion of the rings in PC perfectly correlates with the main carbonate group motion followed by dielectric spectroscopy and allows us to (i) consistently interpret the PC's gamma relaxation in terms of two different motions; and (ii) experimentally confirm the relation between the motion of phenylene rings and carbonate groups within BPA PC formerly predicted by computational methods.

Journal Article↗
PubMed2005

Aspirin downregulates homocysteine formation in stimulated human peripheral blood mononuclear cells.

Moderate hyperhomocysteinaemia is established as an independent risk factor for atherosclerosis, thrombosis, stroke and dementia. Hyperhomocysteinaemia is mostly caused by the deficiency of B-vitamins folate and vitamin B12, which are essential cofactors in the remethylation of homocysteine to methionine. Interestingly, moderate hyperhomocysteinaemia is also often observed in chronic diseases, in which also elevated immune activation markers such as neopterin or sTNFR-II are found. In order to simulate immune activation in vitro, human peripheral blood mononuclear cells (PBMC) were stimulated with mitogens. Stimulation significantly increased homocysteine production in comparison with unstimulated PBMC; in parallel also neopterin formation was induced. Homocysteine formation was due to cell proliferation, proliferating T lymphocytes, and also the myelomonocytic cell line U-937 produced homocysteine. Treatment with the anti-inflammatory drug aspirin dose-dependently inhibited homocysteine production and also neopterin formation in human PBMC. Treatment with salicylic acid showed similar effects as aspirin; FACS analysis showed that both compounds inhibited cell proliferation by arresting cells in the G0/G1-phase. In U-937, both compounds also slightly induced apoptosis at 5 mm. Proliferation-induced homocysteine formation and in parallel also monocyte activation can be suppressed effectively by aspirin and salicylic acid in vitro, suggesting that also in vivo aspirin may downregulate not only inflammation but also formation of homocysteine.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Phenylene ring dynamics in bisphenol-A-polysulfone by neutron scattering.

We have investigated the dynamics of phenylene rings in a glassy polysulfone (bisphenol-A-polysulfone) by means of quasielastic neutron scattering. Nowadays it is well known that these molecular motions are directly connected with the mechanical properties of engineering thermoplastics in general. The particular system investigated by us has the advantage that by selective deuteration of the methyl groups, the neutron scattering measured is dominated by the incoherent contribution from the protons in the phenylene rings. In this way, the dynamics of such molecular groups can be experimentally isolated. Two different types of neutron spectrometers: time of flight and backscattering, were used in order to cover a wide dynamic range, which extends from microscopic (10(-13) s) to mesoscopic (10(-9) s) times. Moreover, neutron diffraction experiments with polarization analysis were also carried out in order to characterize the structural features of the sample investigated. Fast oscillations of increasing amplitude with temperature and pi-flips are identified for phenylene rings motions. Due to the structural disorder characteristic of the amorphous state, both molecular motions display a broad distribution of relaxation times, which spreads over several orders of magnitude. Based on the results obtained, we propose a model for phenylene rings dynamics, which combines the two kinds of molecular motions identified. This model nicely describes the neutron scattering results in the whole dynamic range investigated.

Journal Article↗
PubMed2004

Moderate hyperhomocysteinemia and immune activation.

Moderate hyperhomocysteinemia is associated with an increased risk of atherosclerosis, thrombosis and neurodegenerative diseases. Homocysteine accumulation in the blood can be due to many underlying causes, which may interact with each other, e.g. genetic disposition and B-vitamin status. The role of the sulfur-containing amino acid homocysteine in the pathogenesis of diseases remains unclear, even if many studies suggest a causal relationship between homocysteine-mediated processes like oxidative stress, NO-inactivation and endothelial deficiency and atherogenesis. Proposed mechanisms of action of homocysteine are discussed, and the question is addressed, whether effects that are attributed to homocysteine, are not rather the consequence of folate and vitamin B12-deficiency. Deficiency of these B-vitamins in parallel with moderate hyperhomocysteinemia is often found in patients with enhanced activation of the cellular immune system, like Alzheimer's disease, rheumatoid arthritis and also vascular diseases. In patients with these diseases an association between homocysteine metabolism, oxidative stress and immune activation exists. On the one hand proliferation of immunocompetent cells having an enhanced demand for B-vitamins leads to the accumulation of homocysteine. On the other hand macrophages stimulated by TH1-type cytokine interferon-gamma form reactive oxygen species (ROS), which oxidize antioxidants, lipoproteins and oxidation-sensitive B-vitamins. Thereby Th1-type immune response could contribute importantly to the development of hyperhomocysteinemia, and may also be a major determinant of disease progression.

Animals↗
PubMed2003

Methyl group dynamics in a confined glass.

We present a neutron scattering investigation on methyl group dynamics in glassy toluene confined in mesoporous silicates of different pore sizes. The experimental results have been analysed in terms of a barrier distribution model, such a distribution following from the structural disorder in the glassy state. Confinement results in a strong decreasing of the average rotational barrier in comparison to the bulk state. We have roughly separated the distribution for the confined state in a bulk-like and a surface-like contribution, corresponding to rotors at a distance from the pore wall respectively larger and smaller than the spatial range of the interactions which contribute to the rotational potential for the methyl groups. We have estimated a distance of 7 A as a lower limit of the interaction range, beyond the typical nearest-neighbour distance between centers-of-mass (4.7 A).

Journal Article↗
PubMed2003

First inelastic neutron scattering studies on thin free standing polymer films.

Glass transition studies in free standing polymer films have revealed values of the transition temperature, T(g), which were substantially reduced below the bulk for sufficiently thin films. Here we report on the preparation of two stacks of free standing polystyrene films: 70 films with a thickness of h approximately 107 nm and 140 films with h approximately 55 nm with equivalent total sample thicknesses of approximately 7.5 microm. We have performed the first measurements on such samples using inelastic neutron scattering, and demonstrate that inelastic neutron scattering experiments, performed on the time-of-flight spectrometer IN6 and the backscattering spectrometer IN16 at the Institut Laue-Langevin, are feasible.

Journal Article↗
PubMed2003

Influence of density and temperature on the microscopic structure and the segmental relaxation of polybutadiene.

We investigate the influence of temperature and density on the local structure and the dynamics of polybutadiene by controlling both hydrostatic pressure and temperature in polarized neutron diffraction experiments on deuterated polybutadiene and in inelastic incoherent scattering experiments on protonated polybutadiene. We observe that the static structure factor S(Q) does not change along macroscopic isochores. This behavior is contrary to the relaxations observed on the nanosecond and picosecond time scales and viewed by the dynamic incoherent scattering law S(Q,omega), which differ strongly along the same thermodynamic path. We conclude that the static behavior, i.e., S(Q), is dominated by macroscopic density changes, similar to the vibrational excitations in the meV range. However, the relaxation dynamics is more sensitive to thermal energy changes. This is confirmed by the finding that lines of identical relaxation behavior (in time, shape, and Q dependence), isochrones on the 10(-9) sec time scale, clearly cross the constant density lines in the (P,T) plane. Concerning S(Q), we can reasonably relate the variation of the main-peak position to the average neighbor chain distance and deduce crude microscopic thermal expansion and compressibility coefficients. In the low-Q regime, the observed pressure and temperature variation of S(Q) exceeds the compressibility contribution and suggests the existence of additional scattering, which might originate from structural correlations arising at higher temperature and low pressure.

Journal Article↗
PubMed2003

Experimental evidence by neutron scattering of a crossover from Gaussian to non-Gaussian behavior in the alpha relaxation of polyisoprene.

We report incoherent quasielastic neutron scattering experiments exploring the alpha-relaxation range in polyisoprene over an unprecedented range in momentum transfer Q. The data corroborate and validate earlier molecular dynamics simulations and reveal the existence of a crossover from Gaussian to non-Gaussian character of the main chain protons self-correlation function in the alpha-relaxation regime. The real challenge of the experiment was to push the neutron techniques to cover a Q range as wide as possible. By combining two neutron spin echo spectrometers and a backscattering instrument, we have been able to study the dynamics in a Q range of 0.1 < or = Q < or = 4.7 A(-1). In the low-Q regime the shape of the relaxation function was found to be related to the dispersion of the relaxation times as predicted by the Gaussian assumption. At short distances or large Q, this relationship is strongly violated indicating a non-Gaussian regime. We have performed a detailed comparison between the experiments and simulations at different temperatures and found, apart from a temperature shift, complete agreement. Combining experiments and simulations led to a consistent interpretation in terms of a distribution of jumps underlying the diffusive motion of protons in the alpha process. This model leads to a time-dependent non-Gaussianity parameter that agrees nearly quantitatively with the simulations and exhibits all features resolved so far from various simulations.

Journal Article↗
PubMed2003

Local structure and glass transition of polybutadiene up to 4 GPa.

This communication presents a determination of the glass transition of polybutadiene under very high pressure, and raises the problem of the determination of the relative effects of temperature and density on the glass transition, depending on the pressure and temperature conditions. Local structure and slow dynamics were studied, by neutron scattering and calorimetry. To the best of our knowledge in neutron diffraction on soft matter such a high pressure, up to 4 GPa, was achieved.

Journal Article↗
PubMed2003

Homocysteine accumulates in supernatants of stimulated human peripheral blood mononuclear cells.

Moderate hyperhomocysteinaemia is associated with atherosclerosis, thrombosis and also with stroke and dementia. Elevated homocysteine concentrations are related to deficiency of folate and also vitamin-B12, as these two vitamins are essential co-factors in the remethylation of homocysteine to methionine. A causal role of homocysteine in the pathogenesis of vascular disease has been discussed over years. Immune activation appears to be involved strongly in atherogenesis as well as in other diseases found to be associated with moderate hyperhomocysteinaemia. To study a possible influence of immune stimulation on homocysteine metabolism, in vitro experiments were performed using peripheral blood mononuclear cells upon stimulation with mitogens concanavalin A, phytohaemagglutinin and pokeweed mitogen. In stimulated cells a dose-dependent increase of homocysteine concentrations was found. When cells were kept in medium supplemented with methionine, homocysteine concentrations increased further, while supplementation with folate had only a slight effect. We conclude that in supernatants of stimulated peripheral blood mononuclear cells homocysteine is accumulating. T cell activation could be involved in the development of moderate hyperhomocysteinaemia.

Cells, Cultured↗
PubMed2003

Glassy dynamics of polymers confined to nanoporous glasses revealed by relaxational and scattering experiments.

The glassy dynamics of poly(propylene glycol) (PPG) and poly(dimethyl siloxane) (PDMS) confined to a nanoporous host system revealed by dielectric spectroscopy, temperature-modulated DSC and neutron scattering is compared. For both systems the relaxation rates estimated from dielectric spectroscopy and temperature-modulated DSC agree quantitatively indicating that both experiments sense the glass transition. For PPG the segmental dynamics is determined by a counterbalance of adsorption and confinement effect. The former results form an interaction of the confined macromolecules with the internal surfaces. A confinement effect originates from an inherent length scale on which the underlying molecular motions take place. The increment of the specific-heat capacity [Formula: see text] at the glass transition vanishes at a finite length scale of 1.8 nm. Both results support the conception that a characteristic length scale is relevant for glassy dynamics. For PDMS only a confinement effect is observed which is much stronger than that for PPG. Down to a pore size of 7.5 nm, the temperature dependence of the relaxation times follows the Vogel-Fulcher-Tammann dependence. At a pore size of 5 nm this changes to an Arrhenius-like behaviour with a low activation energy. At the same pore size [Formula: see text] vanishes for PDMS. Quasielastic neutron scattering experiments reveal that also the diffusive character of the relevant molecular motions --found to be characteristic above the glass transition-- seems to disappear at this length scale. These results gives further strong support that the glass transition has to be characterised by an inherent length scale of the relevant molecular motions.

Adsorption↗
PubMed2003

Confinement of molecular liquids: consequences on thermodynamic, static and dynamical properties of benzene and toluene.

We relate the dynamical behavior of molecular liquids confined in mesoscopic cylindrical pores to the thermodynamic properties, heat capacity and density and to the static structure by combining different experimental methods (H-NMR, calorimetry, elastic and inelastic neutron scattering, numerical simulations). The crystallization process is greatly reduced or avoided by confinement under standard cooling conditions, instead a glass transition temperature T(g) at the 1000s time scale can be observed. The pore averaged local structure of the confined liquid is not noticeably affected when "excluded-volume" corrections are carefully applied, but follows the density changes reflected by the Bragg peak intensities of the porous matrices. The pore size dependence of T(g) is dominated by two factors, surface interaction and finite-size effect. For the smallest pores ([Formula: see text], [Formula: see text] being the van der Waals radius of a molecule), one observes an increase of T(g) and a broadening of the transition region, related to the interaction with the surface that induces a slowing-down of the molecules close to the wall. This is confirmed by neutron scattering experiments and molecular-dynamics simulations at shorter time scales and higher temperatures, which indicate a remaining fraction of frozen molecules. For larger pore sizes, taking the decrease of density under confinement conditions into account, a decrease of T(g) is observed. This could be related to finite-size effects onto the putative cooperativity length that is often invoked to explain glass formation. However, no quantitative determination of this length (not to mention its T-dependence) can be extracted, since the interaction with the wall itself introduces an additional length that adds to the complexity of the problem.

Journal Article↗
PubMed2003

Interferon-gamma-induced conversion of tryptophan: immunologic and neuropsychiatric aspects.

Tryptophan is an essential amino acid and the least abundant constituent of proteins. In parallel it represents a source for two important biochemical pathways: the generation of neurotransmitter 5-hydroxytryptamine (serotonin) by the tetrahydrobiopterin-dependent tryptophan 5-hydroxylase, and the formation of kynurenine derivatives and nicotinamide adenine dinucleotides initiated by the enzymes tryptophan pyrrolase (tryptophan 2,3-dioxygenase, TDO) and indoleamine 2,3-dioxygenase (IDO). Whereas TDO is located in the liver cells, IDO is expressed in a large variety of cells and is inducible by the cytokine interferon-gamma. Therefore, accelerated tryptophan degradation is observed in diseases and disorders concomitant with cellular immune activation, e. g. infectious, autoimmune, and malignant diseases, as well as during pregnancy. According to the cytostatic and antiproliferative properties of tryptophan-depletion on T lymphocytes, activated T-helper type 1 (Th-1) cells may down-regulate immune response via degradation of tryptophan. Especially in states of persistent immune activation availability of free serum tryptophan is diminished and as a consequence of reduced serotonin production, serotonergic functions may as well be affected. Accumulation of neuroactive kynurenine metabolites such as quinolinic acid may contribute to the development of neurologic/psychiatric disorders. Thus, IDO seems to represent a link between the immunological network and neuroendocrine functions with far reaching consequences in regard to the psychological status of patients. These observations provide a basis for the better understanding of mood disorder and related symptoms in chronic diseases.

Animals↗
PubMed2002

Non-Gaussian nature of the alpha relaxation of glass-forming polyisoprene.

We report quasielastic neutron scattering experiments exploring the alpha relaxation in polyisoprene over an unprecedented range in momentum transfer. Corroborating and validating earlier molecular dynamics simulations, the measurements reveal a crossover from a Gaussian regime of sublinear diffusion to a strongly non-Gaussian regime at short distances. We show that a consistent interpretation in terms of a distribution of finite jumps underlying the alpha process is possible. This model leads to a time-dependent non-Gaussian parameter exhibiting all features revealed so far from various simulations.

Journal Article↗