Aprotinin increases release of von Willebrand factor in cultured human umbilical vein endothelial cells.

Through the perioperative administration of the proteinase inhibitor aprotinin, hemostasis can be improved and postoperative bleeding reduced after cardiac operations. The mechanism of action has been only partially clarified. The goal of our study was to investigate the influence of aprotinin on the synthesis of von Willebrand factor (vWF) in human endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultivated in vitro and incubated with different aprotinin concentrations (55, 100, and 215 mol/L). With all investigated aprotinin concentrations, there was an increase in vWF synthesis compared with basal secretion (p less than 0.001). When the HUVEC were preincubated with aprotinin and stimulated with thrombin, there was a further significant increase in vWF synthesis. HUVEC that, were first incubated with aprotinin and then stimulated with thrombin demonstrated a significant increase in vWF synthesis compared with basal secretion in nonincubated cells (p less than 0.0001). Also, compared with the cells that had received thrombin stimulation alone, the combination of aprotinin incubation and thrombin stimulation led to a significantly higher vWF concentration (p less than 0.05). Because vWF is necessary for the interaction with platelet factor glycoprotein Ib and platelet adhesion, the demonstrated increase in vWF synthesis could be one of the mechanisms of action of aprotinin leading to its blood-sparing effect.     

Instrument development: cardiac diet and exercise self-efficacy.

Self-efficacy has been documented as a strong predictor of health behaviors. Unfortunately, availability of reliable and valid measures of self-efficacy for a range of health behaviors is still limited. This study validated two measures of cardiac risk factor self-efficacy: the Cardiac Diet Self-Efficacy Instrument (CDSEI) and the Cardiac Exercise Self-Efficacy Instrument (CESEI). A sample of 370 cardiac rehabilitation participants provided data for principal factor analyses showing the unidimensionality of each instrument. Known groups construct validity was supported by a comparison of CDSEI and CESEI scores for cardiac rehabilitation participants and marathon runners. The value of CDSEI and CESEI scores in predicting subsequent exercise and diet performance was demonstrated with a third group of cardiac rehabilitation participants. Stability and internal consistency estimates in the .80s and .90s, respectively, support the scales' reliabilities.     

DNA patterns of Helicobacter pylori isolated from gastric antrum, body, and duodenum.

Biopsy specimens for culture of Helicobacter pylori were obtained from two different sites in the antrum, gastric body, and duodenal cap in 20 patients during endoscopic investigation of dyspepsia. H. pylori was identified in 64 isolates obtained from 15 of the 20 patients. Analysis of chromosomal DNA from these isolates of H. pylori showed that 13 of 15 patients harbored a single strain of H. pylori throughout their stomach and duodenum. Two differing H. pylori types were found in two patients. Unique DNA patterns were shown in each of the 15 patients. The genetic heterogeneity of H. pylori is unexplained but it could be of considerable value for epidemiological studies.     

Discovery of potent and selective inhibitors of procollagen C-proteinase for the treatment of fibrotic disorders

Introduction   Fibrosis is a component of many tissue pathologies leading to loss of normal tissue function, primarily due to excessive collagen deposition. Collagen is deposited following cleavage of the C- and N- terminal peptides from the pro-collagen molecule. The cleavage of the globular C-peptide by PCP reduces solubility of the fibrillar collagen molecule, resulting in deposition of insoluble collagen. Increased insoluble collagen deposition is a feature of all organ fibroses, with inhibition of this process, a key potential anti-fibrotic mechanism. The aim of this work was to discover potent and selective PCP inhibitors as experimental, topically applied, anti-fibrotic drugs for clinical evaluation.
Materials and methods   PCP was cloned from human osteosarcoma cells and enzymatic activity demonstrated using a PCP-specific peptide cleavage assay. Activities were confirmed by measuring cleavage of [³H]C-peptide from type-I pro-collagen. A cell-based fibroplasias model was employed to demonstrate compound efficacy using collagen deposition, liberated C-peptide and histological endpoints. The activities of PCP inhibitors in fibroblast and epithelial in vitro cell proliferation and migration assays, and selectivity vs. a panel of MMPs were also determined.
Discussion   In summary, we have identified and characterized potent and selective inhibitors of PCP for progression to clinical studies for investigation as a treatment paradigm for fibrotic disease.  

  Results     

58.

Soundings: Saving lives on the Silk Road     

James Owen Drife 《British medical journal》2004,329(7460):299

     

59.

Saccadic trajectory in Huntington's disease.     

Joanne Fielding  Nellie Georgiou-Karistianis  Lynette Millist  Michael Fahey  Owen White 《Journal of the International Neuropsychological Society》2006,12(4):455-464

Trajectories of saccadic eye movements can be modulated by the presence of a competing visual distractor. It is proposed that the superior colliculus (SC) controls the initial deviation through competitive lateral interactions. Given the ramifications of connections between basal ganglia (BG) thalamo-cortical circuitry and the SC, it was anticipated that this modulation would be differentially effected in those with Huntington's disease, which in its early stages is primarily a disorder of the BG. Horizontal deviation was determined for exogenously driven and endogenously driven vertical saccades in the presence of peripheral distractors. For neurologically healthy participants, the initial trajectories of both saccade types curved away from distractor locations, as predicted. However, for HD participants exogenous saccades consistently deviated leftwards, irrespective of distractor location. Endogenous saccades also revealed anomalous horizontal deviation, with significant leftward deviation evident for saccades directed upward and significant rightward deviation for saccades directed downward. Further, both groups generated a comparable proportion of erroneous responses to distractor stimuli, but only neurologically healthy participants demonstrated a response time advantage for compatible target/distractor presentation. These results suggest anomalous regulation of distractor-related activity in HD.     

60.

GlaxoSmithKline to set up comprehensive online clinical trials register     

Owen Dyer 《British medical journal》2004,329(7466):590

     

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Saccadic trajectory in Huntington's disease.

Trajectories of saccadic eye movements can be modulated by the presence of a competing visual distractor. It is proposed that the superior colliculus (SC) controls the initial deviation through competitive lateral interactions. Given the ramifications of connections between basal ganglia (BG) thalamo-cortical circuitry and the SC, it was anticipated that this modulation would be differentially effected in those with Huntington's disease, which in its early stages is primarily a disorder of the BG. Horizontal deviation was determined for exogenously driven and endogenously driven vertical saccades in the presence of peripheral distractors. For neurologically healthy participants, the initial trajectories of both saccade types curved away from distractor locations, as predicted. However, for HD participants exogenous saccades consistently deviated leftwards, irrespective of distractor location. Endogenous saccades also revealed anomalous horizontal deviation, with significant leftward deviation evident for saccades directed upward and significant rightward deviation for saccades directed downward. Further, both groups generated a comparable proportion of erroneous responses to distractor stimuli, but only neurologically healthy participants demonstrated a response time advantage for compatible target/distractor presentation. These results suggest anomalous regulation of distractor-related activity in HD.