[³H]Chiba-1001(methyl-SSR180711) has low in vitro binding affinity and poor in vivo selectivity to nicotinic alpha-7 receptor in rodent brain.

Neuronal nicotinic acetylcholine receptor (nAChR) agonists active at the alpha-7 (α-7) receptor subtype are potential therapeutics for cognitive deficits in schizophrenia, Alzheimer's disease, and other mental disorders. SSR180711, an α-7 selective partial agonist, has been shown to improve preclinical cognition. A novel positron emission tomography (PET) radioligand, ¹¹C-Chiba1001, is a close analog of SSR180711.

[Limitations of reconstruction - prostheses].

Fractures of the proximal humerus are common, particularly seen in elderly, female patients. Using open reduction and internal fixation good clinical results can be achieved in general. But even today not every problem has been solved in the treatment of proximal humeral fractures.

Drosophila G-protein-coupled receptor kinase 2 regulates cAMP-dependent Hedgehog signaling.

G-protein-coupled receptor kinases (GRKs) play a conserved role in Hedgehog (Hh) signaling. In several systems, GRKs are required for efficient Hh target gene expression. Their principal target appears to be Smoothened (Smo), the intracellular signal-generating component of the pathway and a member of the G-protein-coupled receptor (GPCR) protein family.

Optimizing parameters for clinical-scale production of high IL-12 secreting dendritic cells pulsed with oxidized whole tumor cell lysate.

Background: Dendritic cells (DCs) are the most potent antigen-presenting cell population for activating tumor-specific T cells. Due to the wide range of methods for generating DCs, there is no common protocol or defined set of criteria to validate the immunogenicity and function of DC vaccines.

Methods: Monocyte-derived DCs were generated during 4 days of culture with recombinant granulocyte-macrophage colony stimulating factor and interleukin-4, and pulsed with tumor lysate produced by hypochlorous acid oxidation of tumor cells.

In vivo analysis of coracoclavicular ligament kinematics during shoulder abduction.

Background: Anatomic reconstruction of the coracoclavicular ligaments for the treatment of acromioclavicular joint separations provides superior biomechanical stability compared with other procedures. Clavicular and coracoidal footprints of the conoid ligament (CL) and the trapezoid ligament (TL) are well described. So far, little is known about their kinematics and the changes of the coracoclavicular distance during shoulder abduction.

Fractures of the scapula.

The scapula connects the arm with the chest wall and is therefore of great importance for a free range of shoulder of motion. For a long-term scapular fractures had been treated predominantly conservative. However, clinical studies of the past decades revealed that some fracture patterns deserve operative treatment to prevent unfavorable functional outcome and chronic state of pain.

Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist.

The preclinical pharmacology and pharmacokinetic properties of (2R)-6-methoxy-8-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)chromane-2-carboxamide (AZD3783), a potent 5-hydroxytryptamine 1B (5-HT(1B)) receptor antagonist, were characterized as part of translational pharmacokinetic/pharmacodynamic hypothesis testing in human clinical trials. The affinity of AZD3783 to the 5-HT(1B) receptor was measured in vitro by using membrane preparations containing recombinant human or guinea pig 5-HT(1B) receptors and in native guinea pig brain tissue. In vivo antagonist potency of AZD3783 for the 5HT(1B) receptor was investigated by measuring the blockade of 5-HT(1B) agonist-induced guinea pig hypothermia.

[Traumatic injuries of the sternoclavicular joint].

Traumatic injuries of the sternoclavicular joint occur rarely and are mainly caused by an indirect trauma mechanism with high kinetic energy. Anterior dislocation is much more common than posterior dislocation, which may be associated with life-threatening injuries. The CT scan is the diagnostic tool of choice for accurate assessment of the injury and coexisting pathologies.

Structural and functional analysis of the repressor complex in the Notch signaling pathway of Drosophila melanogaster.

In metazoans, the highly conserved Notch pathway drives cellular specification. On receptor activation, the intracellular domain of Notch assembles a transcriptional activator complex that includes the DNA-binding protein CSL, a composite of human C-promoter binding factor 1, Suppressor of Hairless of Drosophila melanogaster [Su(H)], and lin-12 and Glp-1 phenotype of Caenorhabditis elegans. In the absence of ligand, CSL represses Notch target genes.

Development of a headspace trap HRGC/MS method for the assessment of the relevance of certain aroma compounds on the sensorial characteristics of commercial apple juice.

A reliable and simple method was developed for the completely automatised analysis of apple juice aroma compounds. In total 26 flavour compounds could be measured by headspace trap gas chromatography/mass spectrometry (GC/MS). We used the method to analyse 85 commercially available apple juices, of which 67 apple juices were not from concentrate.

Ultra-low exposure to α-7 nicotinic acetylcholine receptor partial agonists elicits an improvement in cognition that corresponds with an increase in α-7 receptor expression in rodents: implications for low dose clinical efficacy.

Αlpha-7 neuronal nicotinic receptors (NNRs) are considered targets for cognitive enhancement in schizophrenia and Alzheimer's disease. AZD0328 is an alpha-7 NNR partial agonist that enhances cognition in rodents and nonhuman primates at sub-microgram to microgram doses. We hypothesized that increased expression of the alpha-7 receptor contributes to this beneficial activity at low doses and tested this by examining the effect of AZD0328 using in vivo and ex vivo binding, RT-PCR and cognitive function in rodents.

Phosphorylation of Ser 402 impedes phosphatase activity of slingshot 1.

By using mass spectrometry, we have identified Ser 402 as a new phosphorylation site within the catalytic domain of human slingshot 1 (SSH1). Phosphorylation at this site inhibits substrate binding and, thus, phosphatase activity in vitro, resulting in enrichment of phosphorylated cofilin in monolayer cell culture. We further demonstrate that protein kinase D (PKD) is upstream from Ser 402 phosphorylation.

2,6-Disubstituted pyrazines and related analogs as NR2B site antagonists of the NMDA receptor with anti-depressant activity.

Herein we describe the discovery of compounds that are competitive antagonists of the CP101-606 binding site within the NR2B subtype of the NMDA receptor. The compounds identified do not possess phenolic functional groups such as those in ifenprodil and related analogs. Initial identification of hits in this series focused on a basic, secondary amine side chain which led to good potency, but also presented a hERG liability.

Pre-clinical validation of a novel alpha-7 nicotinic receptor radiotracer, [(3)H]AZ11637326: target localization, biodistribution and ligand occupancy in the rat brain.

The alpha-7 neuronal nicotinic receptor is a novel pharmacological target for psychiatric and cognitive disorders. Selective radiotracer tools for pre-clinical receptor occupancy can facilitate the interpretation of the biological actions of small molecules at a target receptor. We discovered a high affinity nicotinic alpha-7 subtype-selective ligand, AZ11637326, with physical-chemical and pharmacokinetic properties suitable for an in vivo radioligand tool.

Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders: a double-blind study.

Background: Recent data suggest a role for the intestinal microbiota in the pathogenesis of functional bowel disorders (FBDs). Probiotic studies in FBDs generated inconsistent results suggesting a strain-specific and product-specific effect.

Aim: To investigate the clinical efficacy of Lactobacillus acidophilus NCFM (L-NCFM) and Bifidobacterium lactis Bi-07 (B-LBi07) in nonconstipation FBDs.

Knowledge management for systems biology a general and visually driven framework applied to translational medicine.

Background: To enhance our understanding of complex biological systems like diseases we need to put all of the available data into context and use this to detect relations, pattern and rules which allow predictive hypotheses to be defined. Life science has become a data rich science with information about the behaviour of millions of entities like genes, chemical compounds, diseases, cell types and organs, which are organised in many different databases and/or spread throughout the literature. Existing knowledge such as genotype-phenotype relations or signal transduction pathways must be semantically integrated and dynamically organised into structured networks that are connected with clinical and experimental data.

Selection of first in vitro fertilization cycle stimulation protocol for good prognosis patients: gonadotropin releasing hormone antagonist versus agonist protocols.

Objective: The objective of this study was to compare outcome parameters in patients anticipated to have a good response to stimulation based upon baseline characteristics using either a gonadotropin releasing hormone (GnRH) agonist or antagonist protocol in their first in vitro fertilization (IVF) cycle.

Study Design: A retrospective chart review of all first-time IVF cycles performed during the time period 2005 through 2007 in an academic teaching center. Patients <40 years of age with a normal baseline follicle stimulating hormone (<10 mIU/mL) and normal antral follicle counts (> or = 3 in each ovary) were included.

MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.

The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy.

Economics of integrated insect management in stored corn.

Insects can cause substantial damage to stored grain. In addition, consumers and therefore food processors are increasingly interested in chemical-free products. Integrated pest management (IPM) may increase farmers' profits while reducing their use of pesticides.

Constitutively active protein kinase D acts as negative regulator of the Slingshot-phosphatase in Drosophila.

The mammalian protein kinase D family is involved in manifold cellular processes including cell migration and motility. Recently it was shown that human PKD1 and PKD2 phosphorylate and thereby inhibit Slingshot 1 Like (SSH1L), a phosphatase which is central to the regulation of actin cytoskeletal dynamics. We noted before that the overexpression of a constitutively active form of Drosophila PKD (PKD-SE) affects the fly retina and the resultant phenotypes suggest underlying defects in the actin cytoskeleton.

Imaging-based disease pattern in a consecutive series of cranial CTs and MRIs in a rural and an urban Tanzanian hospital: a comparative, retrospective, neuroradiological analysis.

The prevalence of neurological diseases and cranial pathologies in sub-Saharan Africa remains a very little investigated field. This study aims at providing an imaging-based overview of cranial pathologies in two Tanzanian hospitals and at identifying possible differences in the spectrum of diseases between rural and urban African populations. At rural Haydom Lutheran Hospital (Manyara region) the data of 726 patients were included in a retrospective survey.

Prevalence and pattern of spinal pathologies in a consecutive series of CTs/MRIs in an urban and rural Tanzanian hospital--a retrospective neuroradiological comparative analysis.

The prevalence of spinal pathologies in sub-saharan Africa has received little attention so far. The aim of the survey was to investigate and compare the prevalence pattern of spinal lesions in two different populations of Tanzania, one coming from the urban and semi-urban catchment area of Aga Khan Hospital in Dar es Salaam and the other coming from the rural catchment area of Haydom Lutheran Hospital in Mbulu, northern Tanzania. At the Aga Khan Hospital a total number of 1163 patients were included in the survey.

Titering replication-defective rSV40 vectors.

Recombinant simian virus 40 (rSV40)-derived vectors are particularly useful for gene delivery to bone marrow progenitor cells and their differentiated derivatives, certain types of epithelial cells (e.g., hepatocytes), and central nervous system neurons and microglia.

Production of SV40-derived vectors.

Recombinant simian virus 40 (rSV40)-derived vectors are particularly useful for gene delivery to bone marrow progenitor cells and their differentiated derivatives, certain types of epithelial cells (e.g., hepatocytes), and central nervous system neurons and microglia.