[Aspects of prevention of obesity in children and adolescents - a European perspective]. / Aspekte der Prävention von Adipositas im Kindes- und Jugendalter - eine europäische Perspektive.

The prevalence of overweight in childhood and adolescence in Europe is still growing. This development could not yet be stopped despite numerous intervention and prevention measures. Due to the lack of longitudinal data, so far no reliable evaluation of incidence rates or long-term health effects of overweight and obesity can be made. Overweight and adiposity are caused by multiple factors. Beside genetic predisposition and individual lifestyle, effective prevention measures should e. g. also take account of psycho-social, context and environmental factors. The prevention of obesity is an issue that clinical medicine and public health should tackle together.

Neutron decoherence imaging for visualizing bulk magnetic domain structures.

Here we introduce a novel neutron imaging method, which is based on the effect that the spatial coherence of the neutron wave front can be changed through small-angle scattering of neutrons at magnetic domain walls in the specimen. We show that the technique can be used to visualize internal bulk magnetic domain structures that are difficult to access by other techniques. The method is transferable to a wide variety of specimens, extendable to three dimensions, and well suited for investigating materials under the influence of external parameters, as, e.g., external magnetic field, temperature, or pressure.

Creatine feeding does not enhance intramyocellular glycogen concentration during carbohydrate loading: an in vivo study by 31P- and 13C-MRS

The main aim of this study was to examine the hypothesis that creatine (Cr) feedingenhances myocellular glycogen storage in humans undergoing carbohydrateloading. Twenty trained male subjects were randomly assigned to have their dietssupplemented daily with 252 g of glucose polymer (GP) and either 21 g of Cr (CRGP,n=10) or placebo (PL-GP, n=10) for 5 days. Changes in resting myocellularglycogen and phosphocreatine (PCr) were determined with Magnetic ResonanceSpectroscopy (13C- and 31P-MRS, respectively). After CR-GP, the levels of intramyocellularglycogen increased from 147 ± 13 (standard error) mmol·(kg wet weight-1)to 172 ± 13 mmol·(kg wet weight)-1, while it increased from 134 ± 17 mmol·(kg wetweight)- to 182 ± 17 mmol·(kg wet weight)-1 after PL-GP; the increments in intramyocellularglycogen concentrations were not statistically different. The increment inthe PCr/ATP ratio after CR-GP (+ 0.20 ± 0.12) was significantly different comparedto PL-GP (- 0.34 ± 0.16) (p<0.05). The present results do not support the hypothesisthat Cr loading increases muscle glycogen storage (AU)

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Design, fabrication, and characterization of diffraction gratings for neutron phase contrast imaging.

We have developed a neutron phase contrast imaging method based on a grating interferometer setup. The principal constituents are two absorption gratings made of gadolinium and a phase modulating grating made of silicon. The design parameters of the setup, such as periodicity, structure heights of the gratings, and the distances between the gratings, are calculated. The fabrication of each grating is described in detail. The produced diffraction gratings were finally characterized within the setup, by locally evaluating the produced contrast (visibility) in each detector pixel, resulting in a visibility map over the whole grating size. An averaged value of 23% is achieved.

Creatine feeding does not enhance intramyocellular glycogen concentration during carbohydrate loading: an in vivo study by 31P- and 13C-MRS.

The main aim of this study was to examine the hypothesis that creatine (Cr) feeding enhances myocellular glycogen storage in humans undergoing carbohydrate loading. Twenty trained male subjects were randomly assigned to have their diets supplemented daily with 252 g of glucose polymer (GP) and either 21 g of Cr (CR-GP, n = 10) or placebo (PL-GP, n = 10) for 5 days. Changes in resting myocellular glycogen and phosphocreatine (PCr) were determined with Magnetic Resonance Spectroscopy (13C- and 31P-MRS, respectively). After CR-GP, the levels of intramyocellular glycogen increased from 147 +/- 13 (standard error) mmol x (kg wet weight(-1)) to 172 +/- 13 m mol x (kg wet weight)(-1), while it increased from 134 +/- 17 mmol x (kg wet weight)(-) to 182 +/- 17 mmol x (kg wet weight)(-1) after PL-GP; the increments in intramyocellular glycogen concentrations were not statistically different. The increment in the PCr/ATP ratio after CR-GP (+ 0.20 +/- 0.12) was significantly different compared to PL-GP (- 0.34 +/- 0.16) (p < 0.05). The present results do not support the hypothesis that Cr loading increases muscle glycogen storage.

Highly absorbing gadolinium test device to characterize the performance of neutron imaging detector systems.

We report on the fabrication and application of a novel neutron imaging test device made of gadolinium. It is designed for a real time evaluation of the spatial resolution, resolution direction, and distortions of a neutron imaging detector system. Measurements of the spatial resolution of (6)LiF doped ZnS scintillator screens with different thicknesses and of imaging plates were performed. The obtained results are in good agreement with comparison measurements using the standard knife edge detection method.

Application of boron-entrapped stealth liposomes to inhibition of growth of tumour cells in the in vivo boron neutron-capture therapy model.

Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons. It is necessary for effective BNCT therapy to accumulate (10)B atoms in the tumour cells. The delivery system consisted of polyethylene-glycol (PEG) binding liposomes (DPPC/cholesterol/DSPC-PEG2000) with an entrapped (10)B-compound and we evaluated the cytotoxic effects of intravenously injected (10)B-PEG-liposomes on human pancreatic carcinoma xenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with (10)B-PEG-liposomes, growth of AsPC-1 tumours was suppressed relative to controls. Injection of (10)B-PEG-liposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of (10)B-PEG-liposomes can increase the retention of (10)B atoms by tumour cells, causing suppression of tumour growth in vivo, after thermal neutron irradiation.

Measured total cross sections of slow neutrons scattered by solid deuterium and implications for ultracold neutron sources.

The total scattering cross sections for slow neutrons with energies in the range 100 neV to 3 meV for solid ortho-2H2 at 18 and 5 K, frozen from the liquid, have been measured. The 18 K cross sections are found to be in excellent agreement with theoretical expectations and for ultracold neutrons dominated by thermal up scattering. At 5 K the total scattering cross sections are found to be dominated by the crystal defects originating in temperature induced stress but not deteriorated by temperature cycles between 5 and 10 K.

Measured total cross sections of slow neutrons scattered by gaseous and liquid 2H(2).

The total scattering cross sections for slow neutrons with energies E in the range 300 neV to 3 meV for gaseous and liquid ortho-2H2 have been measured. The cross sections for 2H2 gas are found to be in excellent agreement with both the Hamermesh and Schwinger and the Young and Koppel models. For liquid 2H(2), we confirm the existing experimental data in the cold neutron range and the discrepancy with the gas models. We find a clear 1 / square root[E'] dependence at low energies for both states. A simple explanation for the liquid 2H2 cross section is offered.

Investigation of Solid D 2 for UCN Sources.

Solid deuterium (sD2) will be used for the production of ultra-cold neutrons (UCN) in a new generation of UCN sources. Scattering cross sections of UCN in sD2 determine the source yield but until now have not been investigated. We report first results from transmission and scattering experiments with cold, very cold and ultra-cold neutrons on sD2 along with light transmission and Raman scattering studies showing the influence of the sD2 crystal properties.

Neutron capture autoradiographic study of the biodistribution of 10B in tumor-bearing mice.

For the study on boron neutron capture therapy, the whole-body sections of tumor-bearing mice infused with 10B attached to CR-39 plastic track detectors were exposed to thermal and cold neutron beams. Neutron capture autoradiographic images obtained by the cold neutron irradiation were extremely superior in quality to those of the thermal neutron beams. From the autoradiographic images, the 10B reaction dose of the neutron-induced particles was estimated using the differential LET distribution.

Resynthesis of muscle glycogen after soccer specific performance examined by 13C-magnetic resonance spectroscopy in elite players.

The purpose of this study was to examine using 13C-magnetic resonance spectroscopy whether muscle glycogen (Gly) utilized during a simulation of a fatiguing soccer match followed by repeated sprints would be resynthesized during the next 24 h while players consumed their habitual diet. A group of 12 elite young players [mean age 17.5 (SD 0.8) years, mean body mass 68.9 (SD 6.6) kg, mean height 177.0 (SD 5.4) cm] participated in the study. Average muscle Gly content before the simulation was 134 (SD 16) mmol.(kg wet mass)-1 and decreased during the test (P < 0.001) to 80 (SD 29) mmol.(kg wet mass)-1. The value had increased (P < 0.01) to 122 (SD 33) mmol.(kg wet mass)-1 24 h later but it was not significantly different from the value obtained before the soccer test. Dietary analysis of the food intake during the 24 h after the running test revealed that players consumed an average of 2,681 (SD 970) kcal.day-1. Mean daily protein, fat, and carbohydrate (CHO) intakes were 85 (SD 29), 99 (SD 44), and 327 (SD 116) g, respectively. The mean amounts of CHO intake normalised to body mass were 4.8 (SD 1.8) g.(kg body mass)-1. In conclusion, the results of this study showed that despite a CHO intake of less than 5 g.(kg body mass)-1 the habitual diet of soccer players might be sufficient to replenish in 24 h the muscle Gly utilized during soccer specific performance. However, cumulative deficits of about 10% in Gly replenishment as found in the present study might provoke decrements in performance. Thus, players should pay attention to their habitual diets and add more carbohydrates to replenish their daily deficits and perhaps increase their basal levels of intake.

Noninvasive measurement of muscle high-energy phosphates and glycogen concentrations in elite soccer players by 31P- and 13C-MRS.

PURPOSE: The purpose of this study was to measure noninvasively the absolute concentrations of muscle adenosine triphosphate [ATP], phosphocreatine [PCr], inorganic phosphate (Pi), and glycogen [Gly] of elite soccer players. METHODS: Magnetic resonance spectroscopy (31P- and 13C-MRS) was used to measure the concentrations of metabolites in the calf muscles of 18 young male players [age = 17.5 +/- 1.0 (SD) yr]. RESULTS: Average muscle [PCr] and [ATP] were 17.8 +/- 3.3 and 6.0 +/- 1.2 mmol x (kg wet weight)(-1), respectively. The ratios of Pi/PCr and PCr/ATP were 0.15 +/- 0.05 and 3.00 +/- 0.26, respectively. The muscle [Gly] was 144 +/- 54 mmol x (kg wet weight)(-1). There was a high correlation (r = 0.93, P < 0.0001) between muscle ATP and PCr concentrations, but there was no correlation between [Gly] and [PCr] or [ATP]. The concentrations of the different metabolites determined in the present study with noninvasive MRS methods were within the ranges of values reported in human muscle from biochemical analysis of muscle biopsies. CONCLUSION: MRS methods can be utilized to assess noninvasively the muscle energetic status of elite soccer players during a soccer season. The high correlation between ATP and PCr might be indicative of fiber type differences in the content of these two metabolites.

Identification of the end stage of scrapie using infected neural grafts.

Although the formal pathogenesis of spongiform encephalopathies has been described in detail, it is not known whether the infectious agent targets primarily neurons, glial cells, or both. To address this question, we have transplanted transgenic embryonic neural tissue overexpressing PrP(c) into the forebrain of Prnp -knockout mice, and infected it with scrapie prions. After infection, grafts developed severe spongiform encephalopathy. As the infected hosts were not clinically affected, we were able to prolong the experiment and to assess changes in the graft over periods of time, which vastly exceeded the normal life span of scrapie-infected mice. Sequential contrast-enhanced magnetic resonance imaging (MRI) revealed progressive impairment of blood-brain barrier properties in infected grafts. However, loss of astrocytes was not observed. Subtotal neuronal loss occurred during the progression of the disease in the grafts, reactive astrocytes persisted until the terminal stage of disease. We conclude that scrapie encephalopathy primarily leads to neuronal death, while degeneration of astrocytes does not occur. Functional impairment of the blood-brain barrier suggests involvement of astrocytes and endothelial cells in the pathological process.

Development of a V79 cell line expressing human cytochrome P450 2D6 and its application as a metabolic screening tool.

Expression of human cytochrome P450 (CYP) in heterologous cells is a means of specifically studying the role of these enzymes in drug metabolism. The complete cDNA encoding CYP2D6-VAL(374) was inserted into an expression vector containing the strong mycloproliferative sarcoma virus promotor in combination with the enhancer of the cytomegalovirus and stably expressed in V79 Chinese hamster cells. The presence of genomically integrated CYP2D6 cDNA was confirmed by polymerase chain reaction analysis. The protein expression was shown by Western blotting. Functional expression could be demonstrated by O-demethylation of dextromethorphan to dextrorphan in live cells. The enzymatic activity of 154 ± 16 pmol min(-1) mg(-1) protein was comparable with dextromethorphan-O-demethylation activities of human liver. The metabolism of two dopaminergic ergoline derivatives was investigated in whole recombinant V19 cells. Both lisuride and terguride were monodeethylated; in case of lisuride a correlation to the in vivo situation was demonstrated comparing poor and extensive metabolizers.

Comparative in vivo and pathological analysis of the blood-brain barrier in mouse telencephalic transplants.

The post-transplantation status of the blood-brain barrier (BBB) is still a matter of debate. In an attempt to define BBB properties after neural transplantation in mice of a defined genetic background, we have used two exogenous markers (horseradish peroxidase and Evans blue), one endogenous marker (immunoglobulins), and in vivo contrast enhanced magnetic resonance imaging (MRI) and compared the results obtained with the different methods. With all four techniques employed, we found the BBB to be reconstituted in 67% of the grafts 3 weeks after grafting, and in more than 90% of all grafts 50 days after grafting. Horseradish peroxidase and contrast enhanced MRI were the most sensitive techniques, the latter offering the unique advantage of repetitive scanning of individual grafts. Our findings provide important information for transplantation studies in mouse models for neurodegenerative diseases.

In vivo evaluation of magnetite nanoparticles for use as a tumor contrast agent in MRI.

Magnetite nanoparticles, coated by three different artificial polypeptides, were conjugated to an antibody specific to the carcinoembryonic antigen (CEA). To protect the particles from fast blood elimination, the coats were modified by various sugars, polyethyleneglycol, albumin, and sialoproteins, respectively. The protective effect was determined by using a specific in vitro test and by analyzing the biodistribution of the nanoparticles in nude mice grafted with CEA-tumors. In particular, a prolongation of the blood circulation time has been expected, if a natural modifier is attached to the coated nanoparticles. Although the elimination rate could hardly be decreased by any modifiers, the tumor accumulation is slightly improved by using the specific sialoprotein glycophorin B. The usefulness of nanoparticles as image contrast agents is probably limited by their microdistribution within the tumor tissue. The requirements for a contrast agent to be highly tissue specific are discussed.

The AMOG/beta 2 subunit of Na,K-ATPase is not necessary for long-term survival of telencephalic grafts.

Adhesion molecule on glia (AMOG) represents the beta 2-subunit of murine Na,K-ATPase. Mice carrying a targeted deletion of the AMOG/beta 2 gene exhibit tremor and limb paralysis at postnatal day (P) 15 and die 2 days after the onset of symptoms. The brains of these mice show edema and swelling of astrocytic end feet. However, the cause of death has remained unclear. To identify long-term consequences of AMOG/beta 2 deficiency, we have grafted parts of the embryonic telencephalic anlage of AMOG/beta 2-deficient mice into the caudoputamen of wild-type mice and analyzed the grafts up to 500 days after transplantation. Histological, immunocytochemical, and in situ hybridization techniques were applied to examine histoarchitecture, proliferation, differentiation, and long-term survival of grafts. AMOG/beta 2-deficient telencephalic grafts develop normally and form solid neural tissue that cannot be distinguished from control grafts by morphological features or with immunocytochemical stains for neuronal and glial markers. No signs of degeneration can be found. Expression analysis, however, revealed that no AMOG/beta 2 protein of possible host origin can be detected in AMOG/beta 2-deficient grafts. Graft-borne astrocytes express neither the AMOG/beta 1 nor the AMOG/beta 2 subunit of Na,K-ATPase as examined with immunocytochemistry and in situ hybridization. These findings indicate that AMOG/beta 2 is not necessary for long-term survival of telencephalic graft tissue.

Circadian plasma level profile of lisuride in rats and mice after continuous administration via the diet.

Lisuride (Dopergin, CAS 18016-80-3), a dopamine D2 agonist, was administered to male and female rats and mice continuously via the diet for 14 days. The doses were 0.2 mg/kg/d in mice and 1 mg/kg/d in mice and rats. Plasma level profiles (0-22 or 24 h) were determined by measuring lisuride concentrations by radioimmunoassay. At all doses a plateau-like plasma level of lisuride was observed. A clear circadian rhythm of lisuride concentrations (highs during night, low levels during day) was found for male rats (1 mg/kg/d) and for male mice (0.2 mg/kg/d). Female animals did not show this phenomenon as pronounced. At the same dose of 1 mg/kg/d rats showed higher plasma levels than mice. For males the ratio of total AUCs was 1.9 and for female animals 8.6.

Anti-inflammatory activity of rolipram in a rat ear edema model.

In the present study the anti-inflammatory activity of the phosphodiesterase inhibitor rolipram (ZK 62,711, CAS 61413-54-5) was tested in a rat model where edema was induced in the ears of the animals by the epicutaneous application of croton oil in ethanol (5%, by volume). The administration of 0.015, 0.15 and 1.5 mg rolipram per ear dose-dependently inhibited the formation of edema. Concomitantly, the body temperature of the rats was decreased. 4-14% of rolipram was percutaneously absorbed within a 5-h interval. The absorbed proportion, represented by the area under the plasma level-time curve, correlated with the inhibition of edema formation and with the decrease in body temperature.