Research plans in Europe for radiation health hazard assessment in exploratory space missions.

The European Space Agency (ESA) is currently expanding its efforts in identifying requirements and promoting research towards optimizing radiation protection of astronauts. Space agencies use common limits for tissue (deterministic) effects on the International Space Station. However, the agencies have in place different career radiation exposure limits (for stochastic effects) for astronauts in low-Earth orbit missions.

Adsorption properties of oligo(fluorooxetane)-b-poly(ethylene oxide)-b-oligo(fluorooxetane) triblock copolymers at the air-water interface: comparison of hydroxyl and acetate end groups.

ABA triblock copolymers, where A is an oligo(fluorooxetane) and B is poly(ethylene oxide) (PEO), are prepared easily using an alpha,omega-dihydroxy PEO initiator and cationic, ring-opening polymerization of a fluorinated oxetane monomer. Terminal hydroxyl groups can be converted readily and quantitatively to acetate groups using acetic anhydride. Both types of triblock copolymers are surface active in water.

Synthesis, characterization, adsorption, and interfacial rheological properties of four-arm anionic fluorosurfactants.

Four-arm oligo(fluorooxetane) tetraols containing -CF3 and -C2F5 groups were prepared in reasonable yields by cationic, ring-opening polymerization of fluorinated oxetane monomers using a tetrafunctional, alkoxylated polyol as initiator and BF3.THF as catalyst. The tetraols were then converted to ammonium sulfate salts using oleum followed by neutralization with ammonium hydroxide in excellent yields.

Effect of binding of an oligomeric cationic fluorosurfactant on the dilational rheological properties of gelatin adsorbed at the air-water interface.

The effect of binding of an oligomeric cationic fluorooxetane surfactant on the interfacial properties of adsorbed gelatin-fluorooxetane complexes has been studied using dynamic surface tension and dilational rheological measurements. Adsorption kinetics of gelatin-fluorooxetane complexes are reminiscent of a mixed (barrier/diffusion limited) process, while the dilational rheological properties of the interface exhibit a strong dependence on surfactant concentration. At low surfactant concentrations, dilational surface moduli as well as phase angles are relatively insensitive to the presence of the fluorooxetane.

Synthesis, characterization, and interfacial properties of an oligomeric, cationic fluorooxetane.

The synthesis and characterization of a cationic oligo(fluorooxetane) surfactant with pendant -C4F9 groups are reported. Molecular area demand at saturation was determined to be 55.6 +/- 0.

Met326Ile aminoacid polymorphism in the human p85 alpha gene has no major impact on early insulin signaling in type 2 diabetes.

Class I alpha phosphatidylinositol (PI) 3-kinase is an important enzyme in the early insulin signaling cascade, and plays a key role in insulin-mediated glucose transport. Despite extensive investigation, the genes responsible for the development of the common forms of type 2 diabetes remain unknown. This study was performed to identify variants in the coding region of p85 alpha, the regulatory subunit of PI 3-kinase.

Performance of electronic portal imaging devices (EPIDs) used in radiotherapy: image quality and dose measurements.

The aim of our study was to compare the image and dosimetric quality of two different imaging systems. The first one is a fluoroscopic electronic portal imaging device (first generation), while the second is based on an amorphous silicon flat-panel array (second generation). The parameters describing image quality include spatial resolution [modulation transfer function (MTF)], noise [noise power spectrum (NPS)], and signal-to-noise transfer [detective quantum efficiency (DQE)].

Palmitate, but not unsaturated fatty acids, induces the expression of interleukin-6 in human myotubes through proteasome-dependent activation of nuclear factor-kappaB.

Circulating interleukin-6 (IL-6), insulin, and free fatty acid (FFA) concentrations are associated with impaired insulin action in obese and type 2 diabetic individuals. However, a causal relationship between elevated plasma FFAs and IL-6 has not been shown. Because skeletal muscle represents a major target of impaired insulin action, we studied whether FFAs may affect IL-6 expression in human myotubes.

Skeletal muscle cells from insulin-resistant (non-diabetic) individuals are susceptible to insulin desensitization by palmitate.

We recently demonstrated that in vivo insulin resistance is not retained in cultured skeletal muscle cells. In the present study, we tested the hypothesis that treating cultured skeletal muscle cells with fatty acids has an effect on insulin action which differs between insulin-sensitive and insulin-resistant subjects. Insulin effects were examined in myotubes from 8 normoglycemic non-obese insulin-resistant and 8 carefully matched insulin-sensitive subjects after preincubation with or without palmitate, linoleate, and 2-bromo-palmitate.

Induction of adiponectin gene expression in human myotubes by an adiponectin-containing HEK293 cell culture supernatant.

Aims/hypothesis: Adiponectin, an adipocytokine known to be down-regulated in obesity-linked disorders, is considered to be a potential key mediator of insulin sensitivity. In this study, we asked whether adiponectin is able to regulate ten selected genes possibly associated with insulin sensitivity in human skeletal muscle cells.

Methods: To this end, we treated in vitro differentiated human myotubes with the culture supernatant of HEK293 cells stably transfected with human recombinant adiponectin and assessed gene expression by RT-PCR.

Palmitate-induced activation of the hexosamine pathway in human myotubes: increased expression of glutamine:fructose-6-phosphate aminotransferase.

The nutrient sensing capacity of the hexosamine biosynthetic pathway (HBP) has been implicated in the development of insulin resistance of skeletal muscle. To study the molecular mechanism of the free fatty acid (FFA)-induced activation of the HBP myotubes obtained from muscle biopsies of metabolically characterized, subjects were stimulated with different fatty acids for 20 h. Incubation with the saturated fatty acids palmitate and stearate (0.

Effect of glimepiride on insulin-stimulated glycogen synthesis in cultured human skeletal muscle cells: a comparison to glibenclamide.

Objective: To examine the effect of glimepiride on insulin-stimulated glycogen synthesis in cultured human skeletal muscle cells in comparison with glibenclamide.

Research Design And Methods: Myotubes derived from glucose-tolerant subjects were incubated with glimepiride or glibenclamide (0-100 micro mol/l) for 4 h and with or without insulin (100 nmol/l) for 2 h, and subsequently glycogen synthesis was determined.

Results: Glimepiride had no significant effect on basal glycogen synthesis; in contrast, glimepiride caused a dose-dependent increase of insulin-stimulated glycogen synthesis, with a maximal effect of 39.

Troglitazone downregulates delta-6 desaturase gene expression in human skeletal muscle cell cultures.

Delta-6 Desaturase, one of the rate-limiting enzymes, catalyzes the conversion of linoleic acid (C18:2 omega6) into gamma-linolenic acid (C18:3 omega6), arachidonic acid (C20:4 omega6), and further metabolites. Recently, it has been shown that human Delta-6 desaturase is expressed not only in liver but in a variety of human tissues, including muscle. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty acid composition of muscle lipids.

Effects of troglitazone on cellular differentiation, insulin signaling, and glucose metabolism in cultured human skeletal muscle cells.

To determine the immediate effect of thiazolidinediones on human skeletal muscle, differentiated human myotubes were acutely (1 day) and myoblasts chronically (during the differentiation process) treated with troglitazone (TGZ). Chronic TGZ treatment resulted in loss of the typical multinucleated phenotype. The increase of muscle markers typically observed during differentiation was suppressed, while adipocyte markers increased markedly.

Insulin signaling and action in cultured skeletal muscle cells from lean healthy humans with high and low insulin sensitivity.

The aim of these studies was to investigate whether insulin resistance is primary to skeletal muscle. Myoblasts were isolated from muscle biopsies of 8 lean insulin-resistant and 8 carefully matched insulin-sensitive subjects (metabolic clearance rates as determined by euglycemic-hyperinsulinemic clamp: 5.8 +/- 0.

Association of impaired phosphatidylinositol 3-kinase activity in GLUT1-containing vesicles with malinsertion of glucose transporters into the plasma membrane of fibroblasts from a patient with severe insulin resistance and clinical features of Werner syndrome.

The purpose of this study was to examine the molecular mechanism responsible for the defective insulin-stimulated glucose transport in cultured fibroblasts from a patient (VH) with clinical features of Werner syndrome and severe insulin resistance. Thus, in cells derived from VH, the subcellular distribution, structure, functional activity, as well as plasma membrane insertion of GLUT1 glucose transporters were analyzed. Furthermore, the insulin signal transduction pathway leading to activation of phosphatidylinositol (PI) 3-kinase as well as components of GLUT1-containing membrane vesicles were characterized.

Monte Carlo simulations of the imaging performance of metal plate/phosphor screens used in radiotherapy.

The imaging performance of metal plate/phosphor screens which are used for the creation of portal images in radiotherapy is investigated by using Monte Carlo simulations. To this end the modulation transfer function, the noise power spectrum and the detective quantum efficiency [DQE(f)] are calculated for different metals and phosphors and different thicknesses of metal and phosphor for a range of spatial resolutions. The interaction of x-rays with the metal plate/phosphor screen is modeled with the EGS4 electron gamma shower code.

Insulin-mediated pseudoacromegaly in a patient with severe insulin resistance: association of defective insulin-stimulated glucose transport with impaired phosphatidylinositol 3-kinase activity in fibroblasts.

The purpose of this study was to clinically and biochemically describe an insulin resistant patient with insulin-mediated pseudoacromegaly and in addition, to examine the molecular cause responsible for the defective insulin-stimulated glucose transport in cultured fibroblasts derived from the patient. The patient was a 64 year old female with severe insulin resistant diabetes mellitus, requiring up to 200 U insulin per day, associated with typical acromegaloid characteristics including increased hand and foot size, macroglossia and development of coarse facial features. Pituitary magnetic resonance imaging as well as multiple GH and IGF-1 measurements were normal.

Chronic leptin treatment does not prevent the development of obesity in transgenic mice with brown fat deficiency.

With the exception of ob/ob mice, circulating plasma leptin is elevated in all other obese rodents as well as in obese humans, suggesting that leptin resistance rather than leptin deficiency is a characteristic feature of obesity. The exact molecular mechanisms leading to leptin resistance and the applicability of exogenous leptin to overcome resistance to the anorectic effect of the hormone, are insufficiently characterized. The aim of this study was to investigate whether chronic leptin administration could prevent the development of obesity and its associated disorders in transgenic mice with toxigene mediated ablation of brown adipose tissue (BAT).

Effect of in vivo thyroid hormone status on insulin signalling and GLUT1 and GLUT4 glucose transport systems in rat adipocytes.

To examine the effect of thyroid hormone status on insulin action in isolated rat adipocytes, age- and weight-matched Sprague-Dawley rats were rendered hypothyroid (h) by i.p. injection of 2 mCi [131I]/kg.