Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain

The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT2A receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV), estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20%). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12% or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT2A receptors determined by postmortem autoradiographic studies (r2 = 0.95, P < 0.001 for the 4C model and r2 = 0.96, P < 0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood-brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT2A receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors.     

Cloning and tissue expression of the mouse ortholog of AIM1, a betagamma-crystallin superfamily member

Fast tissue regeneration after therapeutic manipulations is a central problem of periodontology, oral surgery and trauma of the periodontal tissues, including bone. Several products, which augment tissue regeneration, have been manufactured and assayed in clinical practice with positive results. Emdogain is a recent addition in this field, as a tissue-regenerating product. The substance is a derivative of amelogenin, obtained from porcine embryonic tissues. At the present time, it is not known whether the substance can induce a local (due to the uptake of the substance) or systemic immune response. The aim of the present study was to evaluate, in vitro, the ability of Emdogain to influence, in vitro, the immune system. Peripheral blood lymphocytes, isolated for 10 healthy donors, were cultured in the presence of various concentrations of the substance, in order to determine the rate of cell proliferation, the expression of surface antigens and the production of cytokines and immunoglobulins. Under our experimental conditions, Emdogain produced a slight increase of the proliferation of lymphocytes, restricted to the CD25 (IL-2 receptor) fraction of the CD4 positive T-lymphocytes, and a concomitant decrease of CD19 positive B-lymphocytes. Other cell fractions (CD8 positive T-cells, B-cells and NK-cells) were not affected. Under our conditions too, immunoglobulin and cytokin (IL-2 and IL-6) production was not modified, even after a 3-day application of concentrations much higher than those used in clinical practice. Our data suggest that Emdogain slightly induce an immune response, restricted to the activated fraction of CD4 T-lymphocytes in vitro.     

Fish liver and seagull eggs,vitamin D‐rich foods with a shadow: Results from the Norwegian Fish and Game Study

Scope Fish liver, fish liver oil, oily fish and seagull eggs have been major sources of vitamin D for the coastal population of Norway. They also provide dioxin and polychlorinated dioxin‐like compounds (dl‐compounds), which may interfere with vitamin D homeostasis. We investigated whether serum 25‐hydroxyvitamin D (25(OH)D) might be compromised by concomitant intake of dl‐compounds. Methods and results We studied 182 adults participating in the Norwegian Fish and Game Study. Participants who consumed fish liver and/or seagull eggs had higher dl‐compound intake and blood concentrations than non‐consumers (p < 0.001). Vitamin D intake was higher (p < 0.001), whereas serum 25(OH)D was lower (p = 0.029) in consumers than in non‐consumers. Among non‐consumers, vitamin D intake was associated with serum 25(OH)D (β=1.06; 95% CI: 0.48, 1.63). This association was weaker among consumers (β = 0.52; 95% CI: ?0.05, 1.08), but strengthened when adjusted for retinol intake (β = 0.66; 95% CI: 0.12, 1.21). The association between vitamin D intake and serum 25(OH)D did not seem to be compromised by intake of dl‐compounds. Conclusion To secure adequate vitamin D status while keeping the intake of dioxins and dl‐polychlorinated biphenyls low, a healthy diet should include both supplemental vitamin D and oily fish. Despite high nutrient content, dietary fish liver and seagull eggs should be restricted, due to dl‐compounds and possible vitamin A‐D antagonism.     

Plasmonics—A Route to Nanoscale Optical Devices

The further integration of optical devices will require the fabrication of waveguides for electromagnetic energy below the diffraction limit of light. We investigate the possibility of using arrays of closely spaced metal nanoparticles for this purpose. Coupling between adjacent particles sets up coupled plasmon modes that give rise to coherent propagation of energy along the array. A point dipole analysis predicts group velocities of energy transport that exceed 0.1c along straight arrays and shows that energy transmission and switching through chain networks such as corners (see Figure) and tee structures is possible at high efficiencies. Radiation losses into the far field are expected to be negligible due to the near‐field nature of the coupling, and resistive heating leads to transmission losses of about 6 dB/μm for gold and silver particles. We analyze macroscopic analogues operating in the microwave regime consisting of closely spaced metal rods by experiments and full field electrodynamic simulations. The guiding structures show a high confinement of the electromagnetic energy and allow for highly variable geometries and switching. Also, we have fabricated gold nanoparticle arrays using electron beam lithography and atomic force microscopy manipulation. These plasmon waveguides and switches could be the smallest devices with optical functionality.     

Ratings of journals by and for personality psychologists.

Rank ordered reference sources used by the authors selected by editors of the Annual Review of Psychology to cover the field of personality during 1970–1976 and found the assessment to be more reliable than D. Koulack and H. J. Keselman's (see record 1976-24649-001) ratings based on responses of American Psychological Association members. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Atopy and IgE in a pediatric allergy practice

In children under six years of age referred to a pediatric allergy practice the usefulness of serum IgE assay was evaluated in relation to age, symptoms, nasal eosinophilia, skin tests and family history. In more than 60% of the children the initial symptom, usually rhinorrhea, had occurred before one year of age. In infancy the diagnosis was more difficult, gastrointestinal complaints were more frequent and nasal eosinophilia less frequent than in the older children. Many infants had positive skin tests to foods and to environmental allergens. There was a significant correlation between elevated serum IgE level and age, nasaeosinophilia, the number of positive skin tests and the probability of immunotherapy being prescribed. Although no clear diagnostic level is seen, an IgE level above 100 micron/ml at any age and an IgE level above 20 micron/ml in infants strongly suggest the possibility of atopic disease. However, a low IgE level does not exclude atopic disease.     

Clinical and antiinflammatory effects of intranasal budesonide aqueous pump spray in the treatment of perennial allergic rhinitis

BACKGROUND: Neutrophils are of great importance for the host's defense against invading organisms. Granulocyte colony-stimulating factor (G-CSF) has been used to augment both the neutrophil number and function, and its prophylactic administration has proved beneficial in animal models of sepsis. However, pretreatment with G-CSF is not practical under clinical conditions. We therefore investigated the effect of recombinant human (rh)G-CSF, administered only after infection, on the survival rate as well as the hemodynamic and cytokine response of the animals. METHODS: Chronically catheterized conscious pigs were challenged with Pseudomonas aeruginosa (8 x 10(7) colony-forming units kg(-1) x h(-1) for 120 h (control group, n = 10). Animals in the G-CSF group (n = 7) also received rhG-CSF (5 microg kg(-1) x day(-1)), the first dose being given 3 h after beginning bacterial infusion. RESULTS: The mortality rate was 50% (5/10) and 29% (2/7) in the control and G-CSF groups, respectively (p = NS, control vs. G-CSF group). Fever, severe pulmonary hypertension, and a hyperdynamic response were recorded in all of the animals. In spite of a prompt and significant recovery from the initial leukopenia (p < .05 vs. control group), the animals of the G-CSF group showed no significant differences in the parameters investigated from those of the controls. Compared with the survivors, the interleukin-1 receptor antagonist was markedly elevated in all nonsurvivors after 6 h of sepsis (p < .05). CONCLUSIONS: These data suggest that treatment with rhG-CSF after the onset of bacterial sepsis might not significantly improve the chances of survival for non-neutropenic patients.