Quantitative Activity Measurements of Brown Adipose Tissue at 7 T Magnetic Resonance Imaging After Application of Triglyceride-Rich Lipoprotein 59Fe-Superparamagnetic Iron Oxide Nanoparticle: Intravenous Versus Intraperitoneal Approach.

Objectives: The aim of this study was to determine metabolic activity of brown adipose tissue (BAT) with in vivo magnetic resonance imaging (MRI) after intravenous (IV) and intraperitoneal (IP) injection of radioactively labeled superparamagnetic iron oxide nanoparticles (SPIOs) embedded into a lipoprotein layer.

Materials And Methods: Fe-labeled SPIOs were either polymer-coated or embedded into the lipid core of triglyceride-rich lipoproteins (TRL-Fe-SPIOs). First biodistribution and blood half time analysis in thermoneutral mice after IP injection of either TRL-Fe-SPIOs or polymer-coated Fe-SPIOs (n = 3) were performed.

The distribution and degradation of radiolabeled superparamagnetic iron oxide nanoparticles and quantum dots in mice.

(51)Cr-labeled, superparamagnetic, iron oxide nanoparticles ((51)Cr-SPIOs) and (65)Zn-labeled CdSe/CdS/ZnS-quantum dots ((65)Zn-Qdots) were prepared using an easy, on demand, exchange-labeling technique and their particokinetic parameters were studied in mice after intravenous injection. The results indicate that the application of these heterologous isotopes can be used to successfully mark the nanoparticles during initial distribution and organ uptake, although the (65)Zn-label appeared not to be fully stable. As the degradation of the nanoparticles takes place, the individual transport mechanisms for the different isotopes must be carefully taken into account.

Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice.

Background & Aims: It is well-known that the liver can induce immune tolerance, yet this knowledge could, thus far, not be translated into effective treatments for autoimmune diseases. We have previously shown that liver sinusoidal endothelial cells (LSECs) could substantially contribute to hepatic tolerance through their ability to induce CD4+ Foxp3+ regulatory T cells (Tregs). Here, we explored whether the Treg-inducing potential of LSECs could be harnessed for the treatment of autoimmune disease.

The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver.

Semiconductor quantum dots (QD) and superparamagnetic iron oxide nanocrystals (SPIO) have exceptional physical properties that are well suited for biomedical applications in vitro and in vivo. For future applications, the direct injection of nanocrystals for imaging and therapy represents an important entry route into the human body. Therefore, it is crucial to investigate biological responses of the body to nanocrystals to avoid harmful side effects.

Determination of liver-specific r2 * of a highly monodisperse USPIO by (59) Fe iron core-labeling in mice at 3 T MRI.

Accurate determination of tissue concentration of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) using T2 * MR relaxometry is still challenging. We present a reliable quantification method for local USPIO amount with the estimation of the liver specific relaxivity r2 * using monodisperse (59) Fe-core-labeled USPIO ((59) FeUSPIO). Dynamic and relaxometric in vivo characteristics of unlabeled monodisperse USPIO were determined in MRI at 3 T.

TGF-β-dependent induction of CD4⁺CD25⁺Foxp3⁺ Tregs by liver sinusoidal endothelial cells.

Background & Aims: CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) have a profound ability to control immune responses. We have previously shown that the liver is a major source of peripherally induced Tregs. Here, we investigate the liver cell types and molecular mechanisms responsible for hepatic Treg induction.

Intraperitoneal injection improves the uptake of nanoparticle-labeled high-density lipoprotein to atherosclerotic plaques compared with intravenous injection: a multimodal imaging study in ApoE knockout mice.

Background: The aim of this study was to assess whether high-density lipoprotein (HDL) labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and quantum dots was able to detect atherosclerotic lesions in mice after intravenous and intraperitoneal injection by multimodal imaging.

Methods And Results: Nanoparticle-labeled HDLs (NP-HDLs) were characterized in vitro by dynamic light scattering and size exclusion chromatography with subsequent cholesterol and fluorescence measurements. For biodistribution and blood clearance studies, NP-HDL(SPIOs) radiolabeled with (59)Fe (NP-HDL(59Fe-SPIOs)) were injected intravenously or intraperitoneally into ApoE knockout mice (n=6), and radioactivity was measured using a gamma counter.

Bioavailability of chromium(III)-supplements in rats and humans.

Chromium(III) is long regarded as essential trace element but the biochemical function and even basic transport ways in the body are still unclear. For a more rational discussion on beneficial as well as toxic effects of Cr(III), we re-investigated the bioavailability of the most important oral Cr supplements by using radiolabeled compounds and whole-body-counting in rats and in the first time also in humans. The apparent absorption of (51)Cr(III) from Cr-picolinate, Cr-nicotinate, Cr-phenylalaninate, Cr-proprionate, or Cr-chloride was generally low (0.

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.

High interstitial fluid pressure is associated with low tumour penetration of diagnostic monoclonal antibodies applied for molecular imaging purposes.

The human epithelial cell adhesion molecule (EpCAM) is highly expressed in a variety of clinical tumour entities. Although an antibody against EpCAM has successfully been used as an adjuvant therapy in colon cancer, this therapy has never gained wide-spread use. We have therefore investigated the possibilities and limitations for EpCAM as possible molecular imaging target using a panel of preclinical cancer models.

Investigations on the usefulness of CEACAMs as potential imaging targets for molecular imaging purposes.

Members of the carcinoembryonic antigen cell adhesion molecules (CEACAMs) family are the prototype of tumour markers. Classically they are used as serum markers, however, CEACAMs could serve as targets for molecular imaging as well.In order to test the anti CEACAM monoclonal antibody T84.

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.

Continued driving and time to transition to nondriver status through error-specific driving restrictions.

We developed driving restrictions that are linked to specific driving errors, allowing cognitively impaired individuals to continue to independently meet mobility needs while minimizing risk to themselves and others. The purpose of this project was to evaluate the efficacy and duration expectancy of these restrictions in promoting safe continued driving. We followed 47 drivers age 60 years and older for 18 months, evaluating driving performance at 6-month intervals.

In my car the brake is on the right: pedal errors among older drivers.

Purpose: To assess to what extent specific cognitive functions contribute to pedal errors among older drivers.

Methods: 180 subjects aged 65 and older completed a 30 min driving evaluation on a simulator as well as three cognitive tests, the Mini-Mental State Exam (MMSE), the Clock Drawing Test, and Trailmaking Part A and B. Analyses based on logistic regressions were performed using age, gender, MMSE, Trailmaking Part A and B, and Clock Drawing Test as independent variables.

Error specific restrictions for older drivers: promoting continued independence and public safety.

Objectives: To describe a population of older drivers with driving restrictions, their most common restrictions, and to compare restricted drivers to their safe and unsafe counterparts. Safe drivers are those who do not commit hazardous errors or traffic violations. Unsafe drivers are those who commit hazardous errors and/or traffic violations that place them in hazardous situations.

Self-rated driving performance among elderly drivers referred for driving evaluation.

Purpose: To explore whether elderly drivers of varying driving skill levels (1) differ in their perception of their driving evaluation performance and (2) determine if self-rated driving evaluation performance is related to cognitive ability.

Methods: One hundred and fifty-two drivers aged 65 years or older and referred for a driving evaluation were enrolled into the study. Subjects were asked the question, "how well do you think you will perform today on your driving evaluation compared to others your own age?" Subjects also completed the Mini-Mental State Exam and a 30-min drive on a STISIM Drivetrade mark simulation (Systems Technology, Inc.

Drawing clocks and driving cars.

Objective: The purpose of the study was to determine whether a new method of scoring the Clock Drawing Test (CDT) is a reliable and valid method for identifying older adults with declining driving competence.

Design: Prospective cohort study.

Setting: An outpatient driving evaluation clinic.

Effects of cognition on driving involvement among the oldest old: variations by gender and alternative transportation opportunities.

Purpose: This study explored the impact of cognition and the availability of other drivers on driving restriction and cessation among older adults.

Design And Methods: Survey data from the first wave of the Asset and Health Dynamics Among the Oldest Old data were analyzed, using multinomial logistic regressions.

Results: Cognitive impairment is associated with driving restriction and cessation, although a noteworthy minority of mildly and severely cognitively impaired individuals continue to drive.

Problems in transition following bone marrow transplantation: psychosocial aspects.

The number of patients achieving long-term survival following bone marrow transplantation is increasing. Psychosocial issues that may arise for the pediatric patient and for the family following discharge from the hospital are described. Implications for other situations in which there is a lengthy hospitalization for an organ transplant or life-threatening condition are highlighted.