A simple and widely applicable method to 59Fe-radiolabel monodisperse superparamagnetic iron oxide nanoparticles for in vivo quantification studies.

A simple, fast, efficient, and widely applicable method to radiolabel the cores of monodisperse superparamagnetic iron oxide nanoparticles (SPIOs) with (59)Fe was developed. These cores can be used as precursors for a variety of functionalized nanodevices. A quality control using filtration techniques, size-exclusion chromatography, chemical degradation methods, transmission electron microscopy, and magnetic resonance imaging showed that the nanoparticles were stably labeled with (59)Fe. Furthermore, the particle structure and the magnetic properties of the SPIOs were unchanged. In a second approach, monodisperse SPIOs stabilized with (14)C-oleic acid were synthesized, and the stability of this shell labeling was studied. In proof of principle experiments, the (59)Fe-SPIOs coated with different shells to make them water-soluble were used to evaluate and compare in vivo pharmacokinetic parameters such as blood half-life. It could also be shown that our radiolabeled SPIOs embedded in recombinant lipoproteins can be used to quantify physiological processes in closer detail than hitherto possible. In vitro and in vivo experiments showed that the (59)Fe label is stable enough to be applied in vivo, whereas the (14)C label is rapidly removed from the iron core and is not adequate for in vivo studies. To obtain meaningful results in in vivo experiments, only (59)Fe-labeled SPIOs should be used.

[Familial transmission of depression: the importance of harm avoidance]. / Familiäre Transmission depressiver Störungen : Die Bedeutung von Schadensvermeidung.

BACKGROUND: Previous research about the aetiology of depression has analysed how depression-associated personality traits influence familial transmission. Using the community-based sample of the Greifswald Family Study, we investigated longitudinally to which extent the temperament factor harm avoidance influences the correlation between parent's depression and the depression of their offspring (with regard to possible sex differences). METHODS: To test this familial transmission a structural equation model was conducted with the data of 193 children (mean age 19.5, SD=2.41) and their biological parents. Depression was assessed with structured clinical interviews, and harm avoidance with Cloninger's Temperament and Character Inventory (TCI, JTCI). RESULTS: The harm avoidance scores of the mothers were significantly correlated with the harm avoidance scores of their children, but the correlation of the father's and children's scores did not reach significance. The extent of harm avoidance at the first assessment of the 14-year-old children predicted depression 5 years later. CONCLUSION: These results indicate the importance of personality as a vulnerability marker for developing affective disorders. The results are discussed with respect to prevention programmes for children and parents with depression, especially if they exhibit strongly avoidant or anxious behaviour.

Brown adipose tissue activity controls triglyceride clearance.

Brown adipose tissue (BAT) burns fatty acids for heat production to defend the body against cold and has recently been shown to be present in humans. Triglyceride-rich lipoproteins (TRLs) transport lipids in the bloodstream, where the fatty acid moieties are liberated by the action of lipoprotein lipase (LPL). Peripheral organs such as muscle and adipose tissue take up the fatty acids, whereas the remaining cholesterol-rich remnant particles are cleared by the liver. Elevated plasma triglyceride concentrations and prolonged circulation of cholesterol-rich remnants, especially in diabetic dyslipidemia, are risk factors for cardiovascular disease. However, the precise biological role of BAT for TRL clearance remains unclear. Here we show that increased BAT activity induced by short-term cold exposure controls TRL metabolism in mice. Cold exposure drastically accelerated plasma clearance of triglycerides as a result of increased uptake into BAT, a process crucially dependent on local LPL activity and transmembrane receptor CD36. In pathophysiological settings, cold exposure corrected hyperlipidemia and improved deleterious effects of insulin resistance. In conclusion, BAT activity controls vascular lipoprotein homeostasis by inducing a metabolic program that boosts TRL turnover and channels lipids into BAT. Activation of BAT might be a therapeutic approach to reduce elevated triglyceride concentrations and combat obesity in humans.

Microencapsulation of inorganic nanocrystals into PLGA microsphere vaccines enables their intracellular localization in dendritic cells by electron and fluorescence microscopy.

Biodegradable poly-(D,L-lactide-co-glycolide) microspheres (PLGA-MS) are approved as a drug delivery system in humans and represent a promising antigen delivery device for immunotherapy against cancer. Immune responses following PLGA-MS vaccination require cross-presentation of encapsulated antigen by professional antigen presenting cells (APCs). While the potential of PLGA-MS as vaccine formulations is well established, the intracellular pathway of cross-presentation following phagocytosis of PLGA-MS is still under debate. A part of the controversy stems from the difficulty in unambiguously identifying PLGA-MS within cells. Here we show a novel strategy for the efficient encapsulation of inorganic nanocrystals (NCs) into PLGA-MS as a tool to study their intracellular localization. We microencapsulated NCs as an electron dense marker to study the intracellular localization of PLGA-MS by transmission electron microscopy (TEM) and as fluorescent labels for confocal laser scanning microscopy. Using this method, we found PLGA-MS to be rapidly taken up by dendritic cells and macrophages. Co-localization with the lysosomal marker LAMP1 showed a lysosomal storage of PLGA-MS for over two days after uptake, long after the initiation of cross-presentation had occurred. Our data argue against an escape of PLGA-MS from the endosome as has previously been suggested as a mechanism to facilitate cross-presentation of PLGA-MS encapsulated antigen.

A highly effective, nontoxic T1 MR contrast agent based on ultrasmall PEGylated iron oxide nanoparticles.

In this study we systematically developed a potential MR T(1) contrast agent based on very small PEGylated iron oxide nanoparticles. We adjusted the size of the crystalline core providing suitable relaxometric properties. In addition, a dense and optimized PEG coating provides high stability under physiological conditions together with low cytotoxicity and low nonspecific phagocytosis into macrophage cells as a part of the reticulo endothelial system at biologically relevant concentrations. The as developed contrast agent has the lowest r(2)/r(1) ratio (2.4) at 1.41 T reported so far for PEGylated iron oxide nanoparticles as well as a r(1) relaxivity (7.3 mM(-1) s(-1)) that is two times higher compared to that of Magnevist as a typical T(1) contrast agent based on gadolinium as a clinical standard.

Real-time magnetic resonance imaging and quantification of lipoprotein metabolism in vivo using nanocrystals.

Semiconductor quantum dots and superparamagnetic iron oxide nanocrystals have physical properties that are well suited for biomedical imaging. Previously, we have shown that iron oxide nanocrystals embedded within the lipid core of micelles show optimized characteristics for quantitative imaging. Here, we embed quantum dots and superparamagnetic iron oxide nanocrystals in the core of lipoproteins--micelles that transport lipids and other hydrophobic substances in the blood--and show that it is possible to image and quantify the kinetics of lipoprotein metabolism in vivo using fluorescence and dynamic magnetic resonance imaging. The lipoproteins were taken up by liver cells in wild-type mice and displayed defective clearance in knock-out mice lacking a lipoprotein receptor or its ligand, indicating that the nanocrystals did not influence the specificity of the metabolic process. Using this strategy it is possible to study the clearance of lipoproteins in metabolic disorders and to improve the contrast in clinical imaging.

[At the border of social psychiatric care systems--a study of "high utilizers" in Mecklenburg-Vorpommern]. / Am Rande sozialpsychiatrischer Versorgungsstrukturen--eine Untersuchung zur "Systemsprengerproblematik" in Mecklenburg-Vorpommern.

Research in social psychiatry has partly neglected the problem of comparatively disturbed persons, who are characterized by a shift from the regular social psychiatric care system into homelessness, closed psychiatric treatment or other desintegrated areas. Against this background in Mecklenburg-Vorpommern, an evaluation of all clinical and complementary institutions engaged in psychiatry was realized. 83.5 % of the institutions took part in the study and 137 (5.21 %) persons were identified as critical. 59.4 % of the institutions, especially therapeutic living groups, remarked that they had treated critical persons during the last year. Sociodemographically, the critical persons could be characterized by comparatively limited interpersonal relationships und a high unemployed status. A factor analysis has resulted in 4 factors characterizing the problematical behaviour: (i) aggression, low social adjustment and impulsivity; (ii) suicidal behaviour; (iii) delinquency and substance use; (iv) manipulative behaviour and pestering. Defining a comparatively high of disturbed behaviour, 51 persons could be identified.

Size and surface effects on the MRI relaxivity of manganese ferrite nanoparticle contrast agents.

Superparamagnetic MnFe2O4 nanocrystals of different sizes were synthesized in high-boiling ether solvent and transferred into water using three different approaches. First, we applied a ligand exchange in order to form a water soluble polymer shell. Second, the particles were embedded into an amphiphilic polymer shell. Third, the nanoparticles were embedded into large micelles formed by lipids. Although all approaches lead to effective negative contrast enhancement, we observed significant differences concerning the magnitude of this effect. The transverse relaxivity, in particular r2*, is greatly higher for the micellar system compared to the polymer-coated particles using same-sized nanoparticles. We also observed an increase in transverse relaxivities with increasing particle size for the polymer-coated nanocrystals. The results are qualitatively compared with theoretical models describing the dependence of relaxivity on the size of magnetic spheres.

[Effect of temperament, effect of alcohol expectancies and peer group on amount of drinking and alcohol-related problems in adolescence]. / Der Einfluss von Temperament, Alkoholwirksamkeitserwartungen und Bezugsgruppe auf Trinkmenge und Alkoholprobleme im Jugendalter.

OBJECTIVE: The purpose of this longitudinal study was to investigate the relationship between temperament (novelty seeking, harm avoidance and reward dependence), alcohol expectancies, membership in a deviant/substance-using peergroup and drinking behaviour of adolescents drawn from a general population. METHODS: 147 adolescents about 15 years of age were interviewed and completed several self-rating questionnaires. We gathered additional information by interviewing their parents. One year after the initial assessment the adolescents only were interviewed and given questionnaires again. RESULTS: Adolescents with alcohol problems at the time of the second interview reported less harm avoidance, less reward dependence, and were more likely to be a member of a deviant/substance-using peergroup a year before, compared to offspring without alcohol problems. Furthermore, they held more positive alcohol expectancies than adolescents without alcohol problems. Taking into account the quantity of alcohol consumed per occasion, all results were confirmed, but temperament did not predict the extend of alcohol consumed after one year. CONCLUSIONS: Alcohol expectancies and peer group deviance/substance-use are strongly associated to alcohol problems and the amount of alcohol consumed. Therefore, they should be the focus of prevention and intervention in this age group.

[CT of Achilles tendons]. / CT af akillessener.

Until recently, direct imaging of the Achilles tendon has been proved difficult. CT scanning was performed in three patients with Achilles tendon pain. The authors find that CT scanning is of diagnostic value but further experience is required.

Eye movements in cocaine abusers.

Using electro-oculography, we quantitatively investigated eye movements in nine heavy cocaine abusers and three groups of controls. Plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of brain norepinephrine, in cocaine abusers were reduced to an average of 53% of normal. Cocaine abusers had normal smooth pursuit, optokinetic nystagmus, vestibulo-ocular reflex, visual suppression of the vestibulo-ocular reflex, and caloric nystagmus. Data were suggestive of a significant reduction in the degree of immediate enhancement of visual-vestibulo-ocular reflex gain by magnified vision in the cocaine abusers. However, adaptive plasticity of the vestibulo-ocular reflex was normal in the cocaine abusers. These results suggest that, despite animal data linking vestibulo-ocular reflex plasticity to central norepinephrine, this neurotransmitter may not be important to plasticity in human beings.

Predictors of functional success in telescopic spectacle use by low vision patients.

Telescopic spectacles can theoretically improve function of low vision patients by enlarging retinal images. However, unintended head movement may produce sufficient instability of enlarged retinal images to negate the visual benefit. We investigated this phenomenon as a cause of failure in 38 low vision patients who had previously attempted use of telescopic spectacles. Patients underwent evaluation of the vestibulo-ocular reflex, visual-vestibulo-ocular reflex, head stability in the pitch and yaw axes, and sensitivity of magnified visual acuity to head motion. Although it was impossible to distinguish successful from unsuccessful telescopic spectacle users by means of clinical or historical data, multiple logistic regression analysis was used to derive a useful predictive function based on measurements of sensitivity of magnified vision to head motion, and head instability in the pitch axis. Predictive performance was found to be superior to conventional clinical judgement. These findings support the hypothesis that retinal image stability is important to functional vision, and suggest that head-stabilizing strategies may improve function with telescopic spectacles in certain low vision patients.

[Results and complications of balloon dilatation of renal artery stenosis in patients with renovascular hypertension]. / Resultater og komplikationer ved ballondilatation af nyrearteriestenoser hos patienter med renovaskulaer hypertension.

During the years 1981 to 1987, 32 patients with renovascular hypertension due to renal artery stenosis were submitted to percutaneous transluminal renal angioplastic (PTRA) in four hospitals in Copenhagen. Nineteen of the interventions were technically successful and six of these patients (32%) no longer required medicine, eight (42%) were able to manage on reduced medication while the circumstances where five were concerned (26%) remained unchanged. Serious complications occurred in 16% and the mortality was 6%. The results of this treatment correspond to those reported elsewhere but the frequency of complications is high. It is concluded that the procedure should be centralized, possibly as a national function.

[Minimal brain dysfunction and social class (author's transl)]. / Frühkindliche Hirnschädigung und soziale Klasse

The dependence of early occuring minimal brain dysfunction on the standard of living was tested. 1355 6-15 year old patients with psychosomatic and psychiatric disorders were examined and divided into the 3 groups: "no brain dysfunction", "suspected brain dysfunction" and "brain dysfunction" (diagnosed medically). A highly significant correlation between brain dysfunction and a low socio-economic status--evaluated in terms of living conditions and the fathers occupation--was found. A similar dependence of both, early mortality and morbidity on the living standard of different groups of the population is described in the literature.