Vascular endothelial growth factor (VEGF) induces rapid prourokinase (pro-uPA) activation on the surface of endothelial cells

Vascular endothelial growth factor (VEGF) is the pivotal angiogenic growth factor activating endothelial cells to migrate, proliferate, and form capillary tubes. For an ordered endothelial cell migration, tissue invasion, and degradation of the extracellular matrix, proteolytic machinery is indispensable. Such machinery, suitable for localized proteolysis, is provided by the prourokinase-urokinase-plasmin system. Prourokinase (pro-uPA), the initial component of this system, is, however, synthesized in its inactive precursor form and as such bound to its cellular receptor uPAR. Here we identify a mechanism via which VEGF(165) interacting with its receptor VEGFR-2 rapidly induces prourokinase activation that is dependent on a change in integrin affinity, activation of matrix metalloproteinase 2 (MMP-2), and pro-uPA being bound to its surface receptor uPAR. This VEGF-induced pro-uPA activation on endothelial cells is responsible for VEGF-dependent local fibrinolytic activity and might be one of the initial steps in the angiogenic process.     

Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess

Excessive ingestion of licorice induces a syndrome of hypokalemia and hypertension that reflects increased activation of renal mineralocorticoid receptors by cortisol. A similar syndrome of cortisol-dependent mineralocorticoid excess occurs in congenital deficiency of the enzyme 11 beta-hydroxysteroid dehydrogenase, which normally inactivates cortisol to cortisone. It has been shown that licorice inhibits 11 beta-dehydrogenase, preventing local inactivation of cortisol and allowing cortisol inappropriate access to intrinsically nonspecific renal mineralocorticoid receptors. Further studies with licorice and its derivatives have revealed a widespread role for 11 beta-dehydrogenase in regulating tissue sensitivity to cortisol. Deficient 11 beta-dehydrogenase activity provides a novel pathogenetic mechanism for hypertension, and current research suggests that several common forms of hypertension can be explained by the mechanisms that operate in licorice-induced hypertension.     

A comparison of in vivo and in vitro methods for determining availability of iron from meals

A comparison is made between in vitro and human and rat in vivo methods for estimating food iron availability. Complex meals formulated to replicate meals used by Cook and Monsen (Am J Clin Nutr 1976;29:859) in human iron availability trials were used in the comparison. The meals were prepared by substituting pork, fish, cheese, egg, liver, or chicken for beef in two basic test meals and were evaluated for iron availability using in vitro and rat in vivo methods. When the criterion for comparison was the ability to show statistically significant differences between iron availability in the various meals, there was substantial agreement between the in vitro and human in vivo methods. There was less agreement between the human in vivo and the rat in vivo and between the in vivo and the rat in vivo and between the in vitro and the rat in vivo methods. Correlation analysis indicated significant agreement between in vitro and human in vivo methods. Correlation between the rat in vivo and human in vivo methods were also significant but correlations between the in vitro and rat in vivo methods were less significant and, in some cases, not significant. The comparison supports the contention that the in vitro method allows a rapid, inexpensive, and accurate estimation of nonheme iron availability in complex meals.     

A multi-year composite of GVI data as a clear reflectance database

A method is developed to generate a top of the atmosphere clear reflectance from the Global Vegetation Index (GVI) product. Our goal is to use this dataset as a threshold to be applied to the forthcoming POLDER observations, for operational cloud detection. The method is based on the hypothesis that clouds add a high frequency signal to the slow variations of the surface reflectance in clear conditions. The validity of our algorithm is verified through an analysis of the temporal profile of the reflectance that it generates. We show that these profiles are better than those resulting from the simpler Maximum Value Composite (MVC) method. The method is applied to five years of GVI products and the results are used to derive a reference database which accounts for the interannual variability of the surface reflectance.     

Investigation of the Gas‐Liquid Flow in a Stopper‐Rod Controlled SEN

The behaviour of two‐phase gas‐liquid flows in a stopper‐rod controlled submerged entry nozzle (SEN) is investigated in water model experiments. The observed two‐phase flow patterns can be classified into either bubble coring or bubbly slug. The scaling of the two‐phase flows by means of similarity parameters is discussed. In the experiments, it is found that the liquid flow rates depend strongly on the two‐phase flow patterns. Additionally, the influence of swirl on the flow patterns is investigated in detail. It is shown that swirl has a marked impact on the transition from bubble coring to bubbly slug. Finally, an estimation of the two‐phase argon‐steel flow patterns in industrialscale SEN flows is given.     

Intraoperative monitoring with stimulus-evoked electromyography during placement of iliosacral screws. An initial clinical study

Cells of the innate immune system secrete cytokines early in immune responses that guide maturing T helper (Th) cells along appropriate lineages. This study investigates the role of cytokine networks, bridging the innate and acquired immune systems, in the pathogenesis of an organ specific autoimmune disease. Experimental allergic encephalomyelitis (EAE), a demyelinating disease of the central nervous system, is widely used as an animal model for multiple sclerosis. We demonstrate that interleukin (IL)-12 is essential for the generation of the autoreactive Th1 cells that induce EAE, both in the presence and absence of interferon gamma. The disease-promoting effects of IL-12 are antagonized by IL-10 produced by an antigen nonspecific CD4+ T cell which, in turn, is regulated by the endogenous production of IL-12. This unique immunoregulatory circuit appears to play a critical role in controlling Th cell differentiation and provides a mechanism by which microbial triggers of the innate immune system can modulate autoimmune disease.     

Zoonoses and potential zoonoses transmitted by bats

PURPOSE: The purpose of this study was to develop an analytical method for the quantitative determination of the extent of neutralization of the carboxylic acid function in Carbopol 974P NF using Diffuse Reflectance Fourier Transform Infrared Spectroscopy (DRIFT) with Kubelka-Munk function analysis. METHODS: Carbopol 974P NF is a high molecular weight, chemically crosslinked polymer of acrylic acid, that has the C=O stretching band of the unionized carboxylic acid function at 1695 cm(-1). The quantitative determination of the extent of neutralization of the carboxylic acid function in Carbopol 974P NF is based upon the asymmetrical C=O stretching of the carboxylate anion at 1570 cm(-1) measured by DRIFT spectroscopy. RESULTS: To overcome spectral differences arising from sample preparation (powders, granules and tablets) and in an effort to increase the precision of the analytical method, the following approaches were used: (1) an internal standard, (2) first derivative of the spectrum to eliminate the effect of baseline drift and (3) the ratio of the first derivative of the C=O stretch of the carboxylate anion peak (1570 cm(-1)) in the neutralized Carbopol 974P NF to that of the peak of the internal standard (866 cm(-1)). The above data treatment techniques proved to be superior to the usual methods of peak height or peak area. The calibration curve of the ratio of the first derivative (1570 cm(-1)/866 cm(-1)) was a linear function of the mass of sodium carboxylate over the range from 0.0% to 100.0% neutralization of the carboxylic acid function in Carbopol 974P NF (Fig. 1a). No particle size or sample preparation effects were noted within the experimental error. CONCLUSIONS: DRIFT spectroscopy using the Kubelka-Munk function is a powerful tool for the routine determination of the extent of neutralization of the carboxylic acid function in Carbopol 974P NF in complex pharmaceutical formulations.