P2-purinoceptor-mediated inhibition of noradrenaline release in rat atria.

1. We looked for P2-purinoceptors modulating noradrenaline release in rat heart atria. Segments of the atria were preincubated with [3H]-noradrenaline and then superfused with medium containing desipramine (1 microM) and yohimbine (1 microM) and stimulated electrically, by 30 pulses/1 Hz unless stated otherwise. 2. The adenosine A1-receptor agonist, N6-cyclopentyl-adenosine (CPA; EC50 9.7 nM) and the nucleotides, ATP (EC50 6.6 microM) and adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S; EC50 4.8 microM), decreased the evoked overflow of tritium. The adenosine A2a-agonist, 2-p-(2-carbonylethyl)-phenethylamino-5'-N-ethylcarboxamido-a denosine (CGS-21680; 0.03-0.3 microM) and the P2x-purinoceptor agonist beta, gamma-methylene-L-ATP (30 microM) caused no change. 3. The concentration-response curve of CPA was shifted to the right by the adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropyl-xanthine (DPCPX; 3 nM; apparent pKB value 9.7) but hardly affected by the P2-purinoceptor antagonist, cibacron blue 3GA (30 microM). In contrast, the concentration-response curves of ATP and ATP gamma S were shifted to the right by DPCPX (3 nM; apparent pKB values 9.3 and 9.4, respectively) as well as by cibacron blue 3GA (30 microM; apparent pKB values 5.0 and 5.1, respectively). Combined administration of DPCPX and cibacron blue 3GA caused a much greater shift of the concentration-response curve of ATP than either antagonist alone. The concentration-response curve of ATP was not changed by indomethacin, atropine or the 5'-nucleotidase blocker alpha, beta-methylene-ADP. 4. Cibacron blue 3GA (30 microM) increased the evoked overflow of tritium by about 70%.(ABSTRACT TRUNCATED AT 250 WORDS)     

GIRK2 deficient mice. Evidence for hyperactivity and reduced anxiety

G-protein activated inwardly rectifying potassium channel (GIRK2)-deficient (null mutant) mice were examined in three tests for anxiety: the elevated plus-maze, light/dark box and "canopy" test. In the elevated plus-maze test, GIRK2 null mutant mice spent a higher percentage of time in the open arms and showed a higher number of total entries. A short (6 days) period of social isolation decreased anxiety and also increased the total activity in GIRK2 mutant mice. However, the increase of total activity in GIRK2 null mutant mice was mostly due to an increase in the number of entries into the open arms. The behavior of the wild-type animals was not substantially changed after social isolation. In the light/dark box, GIRK2 homozygous (-/-) mice demonstrated a higher level of locomotion and a higher number of rearings in the light area. In the "canopy" test, GIRK2 mutant mice displayed an increased locomotion in the exposed area and a strong trend to decrease in the number of stretched attend postures (SAP) in the most secure "canopy" area. GIRK2 heterozygous (+/-) animals showed behavioral changes intermediate between wild-type and null mutants only in the elevated plus-maze test after social isolation. In all other tests, GIRK2 heterozygous (+/-) animals did not differ from wild-type mice. Taken together, this data demonstrates that GIRK2 null mutant mice have reduced anxiety with signs of hyperactivity. We suggest that the functional block of dopamine D3 receptors may be a reason for this phenotype.     

Assessing the Effectiveness of Front of Pack Labels: Findings from an Online Randomised-Controlled Experiment in a Representative British Sample

Front of pack food labels (FOPLs) provide accessible nutritional information to guide consumer choice. Using an online experiment with a large representative British sample, we aimed to examine whether FOPLs improve participants’ ability to identify the healthiness of foods and drinks. The primary aim was to compare ability to rank between FOPL groups and a no label control. Adults (≥18 years), recruited from the NatCen panel, were randomised to one of five experimental groups (Multiple Traffic Light, MTL; Nutri-Score, N-S; Warning Label, WL; Positive Choice tick, PC; no label control). Stratification variables were year of recruitment to panel, sex, age, government office region, and household income. Packaging images were created for three versions, varying in healthiness, of six food and drink products (pizza, drinks, cakes, crisps, yoghurts, breakfast cereals). Participants were asked to rank the three product images in order of healthiness. Ranking was completed on a single occasion and comprised a baseline measure (with no FOPL), and a follow-up measure including the FOPL as per each participant’s experimental group. The primary outcome was the ability to accurately rank product healthiness (all products ranked correctly vs. any incorrect). In 2020, 4504 participants had complete data and were included in the analysis. The probability of correct ranking at follow-up, and improving between baseline and follow-up, was significantly greater across all products for the N-S, MTL and WL groups, compared to control. This was seen for only some of the products for the PC group. The largest effects were seen for N-S, followed by MTL. These analyses were adjusted for stratification variables, ethnicity, education, household composition, food shopping responsibility, and current FOPL use. Exploratory analyses showed a tendency for participants with higher compared to lower education to rank products more accurately. Conclusions: All FOPLs were effective at improving participants’ ability to correctly rank products according to healthiness in this large representative British sample, with the largest effects seen for N-S, followed by MTL.     

A novel technique for laser-assisted revascularization: an in vitro pilot study

Lasers in Medical Science - The common limitation of surgical revascularization procedures for severe tissue ischemia due to cardiovascular diseases is the need to interrupt blood flow during the...     

Einsatzgebiete der numerischen Simulation in der muskuloskelettalen Forschung und ihre Bedeutung für die Orthopädische Chirurgie

Finite element analyses (FEA) as well as multibody system dynamics (MSD) are the main tools used for numerical simulation in the field of musculoskeletal research. While FEA is utilized for field problems, such as calculation of stress and strain distribution, MSD is applied for solving kinematic analyses, such as calculation of muscle and joint forces. Depending on the focus of investigation, modelling of biological tissue may vary from simple homogeneous behavior to modelling biochemical processes on the microscale and nanoscale. An important milestone in biomechanical research was the analysis of stress shielding, which led to further research on bone remodelling. Various models of implant-bone fixation used for the prediction of micromotion have been published. New possibilities for biomechanical analyses are achieved by consideration of complex muscle forces which are generated by MSD simulation and imported into FEA models as limiting conditions. A numerical model always requires experimental validation. If the results are confirmed experimentally, various advantages of numerical simulation apply and problems can be analysed isolated from many influencing factors. Therefore, straightforward parameter variation is possible, enabling studies which would be impossible in an experimental or clinical setup.     

The pancreatic beta cell surface proteome

The pancreatic beta cell is responsible for maintaining normoglycaemia by secreting an appropriate amount of insulin according to blood glucose levels. The accurate sensing of the beta cell extracellular environment is therefore crucial to this endocrine function and is transmitted via its cell surface proteome. Various surface proteins that mediate or affect beta cell endocrine function have been identified, including growth factor and cytokine receptors, transporters, ion channels and proteases, attributing important roles to surface proteins in the adaptive behaviour of beta cells in response to acute and chronic environmental changes. However, the largely unknown composition of the beta cell surface proteome is likely to harbour yet more information about these mechanisms and provide novel points of therapeutic intervention and diagnostic tools. This article will provide an overview of the functional complexity of the beta cell surface proteome and selected surface proteins, outline the mechanisms by which their activity may be modulated, discuss the methods and challenges of comprehensively mapping and studying the beta cell surface proteome, and address the potential of this interesting subproteome for diagnostic and therapeutic applications in human disease.