Deep brain stimulation of subthalamic neurons increases striatal dopamine metabolism and induces contralateral circling in freely moving 6-hydroxydopamine-lesioned rats

Recent studies have reported a genetic association between the -1438 G/A polymorphism within the promoter region of the 5-HT(2A) receptor gene and eating disorders (ED), with conflicting results. To clarify the role of the -1438 G/A polymorphism in different ED categories we have analyzed the genotype and allele frequency distribution in 54 Italian patients with Binge ED (BED) compared to 132 obese non-BED subjects. No significant differences were found between obese BED and obese non-BED individuals, suggesting that this polymorphism does not genetically distinguish these two phenotypes. Moreover, the evaluation of 148 patients with anorexia nervosa and 86 patients with bulimia nervosa revealed an association of the A allele with both these disorders.     

Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice

We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals.     

Voronoi Polyhedra Analysis of Optimized Arterial Tree Models

Topological and metric properties of Voronoi polyhedra (VP) generated by the distal end points of terminal segments in arterial tree models grown by the method of constrained constructive optimization (CCO) are analyzed with the aim to characterize the spatial distribution of their supply sites relative to randomly distributed points as a reference model. The distributions of the number N _f of Voronoi cell faces, cell volume V, surface area S, area A of individual cell faces, and asphericity parameter of the CCO models are all significantly different from the ones of random points, whereas the distributions of V, S, and are also significantly different among CCO models optimized for minimum intravascular volume and minimum segment length (p < 0.0001). The distributions of N _f , V, and S of the CCO models are reasonably well approximated by two-parameter gamma distributions. We study scaling of intravascular blood volume and arterial cross-sectional area with the volume of supplied tissue, the latter being represented by the VP of the respective terminal segments. We observe scaling exponents from 1.20 ± 0.007 to 1.08 ± 0.005 for intravascular blood volume and 0.77 ± 0.01 for arterial cross-sectional area. Setting terminal flows proportional to the associated VP volumes during tree construction yields a relative dispersion of terminal flows of 37% and a coefficient of skewness of 1.12. © 2003 Biomedical Engineering Society. PAC2003: 8719Uv, 8710+e, 4720Ky, 0260Pn, 0230Oz     

Diurnal changes of thermoregulatory functions in pigeons

In pigeons, we studied the diurnal variation of body temperatures and its dependence on the diurnal variations of shivering, vasomotor activity and panting in light-dark (LD) — conditions (1212 h, 1001 Lux) and in different, but for at least 24 h constant ambient temperatures.In low ambient temperatures (below thermoneutrality) shivering was reduced shortly after lights off (early dark phase), and it increased again some hours before lights on (late dark phase); the lower the ambient temperature, the larger the reduction of shivering and the shorter the time of reduction.Within thermoneutrality, the decrease ofT _b in the early dark phase was associated with an increase of foot skin temperature, probably due to vasodilatation. Later-on foot skin temperature decreased again (vasoconstriction). The feet remained constricted even in the late dark phase, whenT _b already increased.At higher ambient temperature (above thermoneutrality) vasodilatation persisted all over the 24 h, while in these conditions respiratory rate increased significantly after lights off.The described diurnal variations of thermoregulatory effector mechanisms are in agreement with the concept of an active adjustment of the body temperature rhythm.Supported by the Deutsche Forschungsgemeinschaft (SBF 114)     

Localization of corticotropin-releasing activity in the rat hypothalamus

Hypothalamic nuclei were removed from frozen sections of rat brain and examined for their corticotropin-releasing activity. The highest concentration was measured in the median eminence. In addition there was significantly more activity detected in the nuclei paraventricularis, supraopticus, suprachiasmaticus and arcuatus than in the other nuclei.     

Suggestions for the assessment of the allergenic potential of genetically modified organisms

The prevalence of allergic diseases has been increasing continuously and, accordingly, there is a great desire to evaluate the allergenic potential of components in our daily environment (e.g., food). Although there is almost no scientific evidence that genetically modified organisms (GMOs) exhibit increased allergenicity compared with the corresponding wild type significant concerns have been raised regarding this matter. In principle, it is possible that the allergenic potential of GMOs may be increased due to the introduction of potential foreign allergens, to potentially upregulated expression of allergenic components caused by the modification of the wild type organism or to different means of exposure. According to the current practice, the proteins to be introduced into a GMO are evaluated for their physiochemical properties, sequence homology with known allergens and occasionally regarding their allergenic activity. We discuss why these current rules and procedures cannot predict or exclude the allergenicity of a given GMO with certainty. As an alternative we suggest to improve the current evaluation by an experimental comparison of the wild-type organism with the whole GMO regarding their potential to elicit reactions in allergic individuals and to induce de novo sensitizations. We also recommend that the suggested assessment procedures be equally applied to GMOs as well as to natural cultivars in order to establish effective measures for allergy prevention.     

Recombinant allergens promote expression of CD203c on basophils in sensitized individuals

BACKGROUND: Traditionally, the diagnosis of type I allergies is based on clinical data, skin test results, and laboratory test results with allergen extracts. During the past few years, several attempts have been made to refine diagnostic assays in clinical allergy by introducing recombinant allergens and novel markers of IgE-dependent cell activation. OBJECTIVES: We have identified the ectoenzyme CD203c as a novel basophil antigen that is upregulated on IgE receptor cross-linkage. In this study we applied CD203c and a panel of recombinant allergens to establish a novel basophil test that allows for a reliable quantification of IgE-dependent responses at the effector cell level. METHODS: Patients allergic to birch (Bet v 1, n = 15; Bet v 2, n = 8) and grass (Phl p 1, n = 15; Phl p 2, n = 10; Phl p 5, n = 14) pollen allergens, as well as 10 nonallergic donors, were examined. Basophils were exposed to various concentrations of recombinant allergens for 15 minutes and then examined for expression of CD203c by means of flow cytometry. CD203c upregulation was correlated with the increase in CD63. RESULTS: Exposure to recombinant allergens resulted in a dose-dependent increase in expression of CD203c on peripheral blood basophils in sensitized individuals, whereas no increase was seen in healthy control subjects. The effects of the recombinant allergens on CD203c expression were also time dependent. There was a good correlation between allergen-induced upregulation of CD203c and upregulation of CD63 (R = 0.76). CONCLUSION: Flow cytometric quantitation of CD203c on blood basophils exposed to recombinant allergens is a useful approach to determine the allergic state in sensitized individuals and represents a basis for a sensitive novel allergy test.     

Effects of topography and composition of titanium surface oxides on osteoblast responses

To investigate the roles of composition and characteristics of titanium surface oxides in cellular behaviour of osteoblasts, the surface oxides of titanium were modified in composition and topography by anodic oxidation in two kinds of electrolytes, (a) 0.2 M H(3)PO(4), and (b) 0.03 M calcium glycerophosphate (Ca-GP) and 0.15 M calcium acetate (CA), respectively. Phosphorus (P: ca.10at%) or both calcium (Ca: 1-6at%) and phosphorus (P: 3-6at%) were incorporated into the anodized surfaces in the form of phosphate and calcium phosphate. Surface roughness was slightly decreased or enhanced (R(a) in the range of 0.1-0.5 microm) on the anodized surfaces. The geometry of the micro-pores in the anodized surfaces varied with diameters up to 0.5 microm in 0.2 M H(3)PO(4) and to 2 microm in 0.03 M Ca-GP and 0.15 M CA, depending on voltages and electrolyte. Contact angles of all the anodic oxides were in the range of 60-90 degrees. Cell culture experiments demonstrated absence of cytotoxicity and an increase of osteoblast adhesion and proliferation by the anodic oxides. Cells on the surfaces with micro-pores showed an irregular and polygonal growth and more lamellipodia, while osteoblasts on the titanium surface used as a control or on anodic oxides formed at low voltages showed many thick stress fibres and intense focal contacts. Alkaline phosphatase (ALP) activity of the cells did not show any correlation with surface characteristics of anodic oxides.