Prophylactic Glycine Administration Attenuates Pancreatic Damage and Inflammation in Experimental Acute Pancreatitis

Background/Aims: Acute pancreatitis (AP) is characterized by premature zymogen activation, systemic inflammatory response resulting in inflammatory infiltrates, sustained intracellular calcium, neurogenic inflammation and pain. The inhibitory neurotransmitter and cytoprotective amino acid glycine exerts a direct inhibitory effect on inflammatory cells, inhibits calcium influx and neuronal activation and therefore represents a putative therapeutic agent in AP. Methods: To explore the impact of glycine, mild AP was induced in rats by supramaximal cerulein stimulation (10 µg/kg BW/h) and severe AP by retrograde injection of sodium taurocholate solution (3%) into the common biliopancreatic duct. 100/300 mmol glycine was administered intravenously before induction of AP. To elucidate the effect of glycine on AP, we determined pathomorphology, pancreatic cytokines as well as proteases, serum lipase and amylase, pancreatic and lung MPO activity and pain sensation. Results: Glycine administration resulted in a noticeable improvement of pathomorphological alterations in AP, such as a reduction of necrosis, inflammatory infiltrates and cytoplasmic vacuoles in cerulein pancreatitis. In taurocholate pancreatitis, glycine additionally diminished pancreatic cytokines and MPO activity, as well as serum lipase and amylase levels. Conclusions: Glycine reduced the severity of mild and much more of severe AP by attenuating the intrapancreatic and systemic inflammatory response. Therefore, glycine seems to be a promising tool for prophylactic treatment of AP

Estimation of cooling rates during close-coupled gas atomization using secondary dendrite arm spacing measurement

Al-4 wt pct Cu alloy has been gas atomized using a commercial close-coupled gas-atomization system. The resulting metal powders have been sieved into six size fractions, and the SDAS has been determined using electron microscopy. Cooling rates for the powders have been estimated using a range of published conversion factors for Al-Cu alloy, with reasonable agreement being found between sources. We find that cooling rates are very low relative to those often quoted for gas-atomized powders, of the order of 10 K s for sub-38 μm powders. We believe that a number of numerical studies of gas atomization have overestimated the cooling rate during solidification, probably as a consequence of overestimating the differential velocity between the gas and the particles. From the cooling rates measured in the current study, we estimate that such velocities are unlikely to exceed 20 m s

Genome-wide Association Study of Change in Fasting Glucose over time in 13,807 non-diabetic European Ancestry Individuals

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 × 10−8) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these da

Quantification of collateral artery growth by automated fluorescent microsphere perfusion

Background: Since their introduction, genetically modified mice have become more and more important to examine molecular mechanisms involved in vascular growth. Today the gold standard for measuring vessel conductivity is to directly assess in vivo perfusion. However, this usually becomes more complicated the smaller the animal, especially due to the need for extensive instrumentation and requirement of maximal vasodilation. Methods: We developed an automated system that allows pressure-controlled in vivo perfusion of small animals with differently labeled fluorescent microspheres. Results: Besides precise operation of the system (mean pressures divergence 0.08%), automation of small animal microsphere perfusion is reliable and highly accurate in mice with and without femoral artery occlusion. In sham-operated control mice, which did not undergo femoral occlusion, highly reproducible measurements of hind limb perfusion (right vs. left=1.03 +/- 0.037) could be assessed. In mice after unilateral femoral artery occlusion, mean perfusion ratios of the automated method (ratio occluded vs. non-occluded hind limb=0.598 +/- 0.046) were comparable to the manual approach (0.561 +/- 0.062). However, inter-individual variances were significantly smaller with the automated system. Conclusion: We describe here a novel and innovative technical approach for pressure-controlled fluid handling specifically designed for microsphere perfusion measurements in small animals

Comparative evaluation of six ELISAs for the detection of antibodies to the non-structural proteins of foot-and-mouth disease virus

To validate the use of serology in substantiating freedom from infection after foot-and-mouth disease (FMD) outbreaks have been controlled by measures that include vaccination, 3551 sera were tested with six assays that detect antibodies to the non-structural proteins of FMD virus. The sera came from naïve, vaccinated, infected and vaccinated-and-infected animals; two-thirds from cattle, the remainder from sheep and pigs. The assays were covariant for sensitivity, but not necessarily for specificity. A commercial kit from Cedi-diagnostics and an in-house assay from IZS-Brescia were comparable to the NCPanaftosa-screening index method described in the Diagnostic Manual of the World Animal Health Organisation. Using these three tests the specificity and sensitivity for the detection of carriers in vaccinated cattle approaches or exceeds 99% and 90%, respectively