Effects of NO synthase inhibitors on the synovial microcirculation in the mouse knee joint

Production of nitric oxide by the inducible NO synthase (iNOS) is known to be enhanced in chronic joint inflammation and osteoarthritis as well as aseptic loosening of joint prostheses. Initial studies yielded promising results after inhibition of the nitric oxide synthase (NOS). However, the effect of NOS inhibition has not been studied at the site of the primary function of NO, the microcirculation of the synovium in vivo. Using our recently developed model for the in vivo study of synovial microcirculation in the mouse knee joint, the effects of selective versus nonselective inhibition of iNOS were investigated by means of intravital fluorescence microscopy. After resection of the patella tendon, the synovial fatty tissue was exposed for intravital microscopy. Diameter of arterioles, functional capillary density (FCD), diameter of venules, venular red blood cell velocity and leukocyte-endothelial cell interaction were quantitatively analyzed before, and 10 and 60 min after intravenous injection of NOS inhibitors {[}selective iNOS inhibitor N-iminoethyl-L-lysine (L-NIL), and nonselective NOS inhibitor N-G-nitro-L-arginine methyl ester (L-NAME)]. Our results demonstrate that L-NAME causes a significant decrease in the arteriolar diameter and FCD associated with an increase in the leukocyte accumulation in the synovium in vivo. In contrast, L-NIL neither altered the microhemodynamics nor the leukocyte-endothelial cell interaction in the synovium, indicating its potential use for selective inhibition of iNOS in joint inflammation. Using our method, further studies will provide new insights into the unknown effect of NOS inhibition on the synovial microvasculature in inflammatory joint disease in vivo. Copyright (C) 1999 S. Karger AG, Basel

Quantitative assessment of angiogenesis in murine antigen-induced arthritis by intravital fluorescence microscopy

Inhibition of angiogenesis might be a therapeutic approach to prevent joint destruction caused by the overgrowing synovial tissue during chronic joint inflammation. The aim of this study was to investigate angiogenesis in the knee joint of mice with antigen-induced arthritis (AIA) by means of intravital microscopy. In 14 mice (C57BL6/129Sv) intravital microscopic assessment was performed on day 8 after AIA induction in two groups (controls, AIA). Synovial tissue was investigated by intravital fluorescence microscopy using FITC-dextran (150 kD). Quantitative assessment of vessel density was performed according to the following categories: functional capillary density (FCD, vessels 10 mum) and FVD of vessels with angiogenic criteria (convoluted vessels, abrupt changes of diameter, vessels which are generated by sprouting and progressively pruned and remodelled). Microvessel count was performed using immunohistochemistry. There was no significant difference in FCD between the control group (337 +/- 9 cm/cm(2); mean +/-SEM) and the AIA group (359 +/- 13 cm/cm(2)). The density of vessels larger than 10 gm diameter was significantly increased in animals with AIA (135 +/- 10 vs. 61 +/- 5 cm/cm(2) in control). The density of blood vessels with angiogenic criteria was enhanced in arthritic animals (79 +/- 17 vs. 12 +/- 2 cm/cm(2) in control). There was a significant increase in the microvessel count in arthritic animals (297 +/- 25 vs. 133 +/- 16 mm(-2) in control). These findings demonstrate that angiogenesis in murine AIA can be assessed quantitatively using intravital microscopy. Further studies will address antiangiogenic strategies in AIA

Comparison of aerosol optical depths from the Ozone Monitoring Instrument (OMI) on Aura with results from airborne sunphotometry, other space and ground measurements during MILAGRO/INTEX-B

Airborne sunphotometer measurements are used to evaluate retrievals of extinction aerosol optical depth (AOD) from spatially coincident and temporally near-coincident measurements by the Ozone Monitoring Instrument (OMI) aboard the Aura satellite during the March 2006 Megacity Initiative-Local And Global Research Observations/Phase B of the Intercontinental Chemical Transport Experiment (MILAGRO/INTEX-B). The 14-channel NASA Ames Airborne Tracking Sunphotometer (AATS) flew on nine missions over the Gulf of Mexico and four in or near the Mexico City area. Retrievals of AOD from near-coincident AATS and OMI measurements are compared for three flights over the Gulf of Mexico for flight segments when the aircraft flew at altitudes 60–70 m above sea level, and for one flight over the Mexico City area where the aircraft was restricted to altitudes ~320–800 m above ground level over the rural area and ~550–750 m over the city. OMI-measured top of atmosphere (TOA) reflectances are routinely inverted to yield aerosol products such as AOD and aerosol absorption optical depth (AAOD) using two different retrieval algorithms: a near-UV (OMAERUV) and a multiwavelength (OMAERO) technique. This study uses the archived Collection 3 data products from both algorithms. In particular, AATS and OMI AOD comparisons are presented for AATS data acquired in 20 OMAERUV retrieval pixels (15 over water) and 19 OMAERO pixels (also 15 over water). At least four pixels for one of the over-water coincidences and all pixels for the over-land case were cloud-free. Coincident AOD retrievals from 17 pixels of the Moderate Resolution Imaging Spectroradiometer (MODIS) aboard Aqua are available for two of the over-water flights and are shown to agree with AATS AODs to within root mean square (RMS) differences of 0.00–0.06, depending on wavelength. Near-coincident ground-based AOD measurements from ground-based sun/sky radiometers operated as part of the Aerosol Robotic Network (AERONET) at three sites in and near Mexico City are also shown and are generally consistent with the AATS AODs (which exclude any AOD below the aircraft) both in magnitude and spectral dependence. The OMAERUV algorithm retrieves AODs corresponding to a non-absorbing aerosol model for all three over-water comparisons whereas the OMAERO algorithm retrieves best-fit AODs corresponding to an absorbing biomass-burning aerosol model for two of the three over-water cases. For the four cloud-free pixels in one over-water coincidence (10 March), the OMAERUV retrievals underestimate the AATS AODs by ~0.20, which exceeds the expected retrieval uncertainty, but retrieved AODs agree with AATS values within uncertainties for the other two over-water events. When OMAERO retrieves AODs corresponding to a biomass-burning aerosol over water, the values significantly overestimate the AATS AODs (by up to 0.55). For the Mexico City coincidence, comparisons are presented for a non-urban region ~50–70 km northeast of the city and for a site near the center of the city. OMAERUV retrievals are consistent with AERONET AOD magnitudes for the non-urban site, but are nearly double the AATS and AERONET AODs (with differences of up to 0.29) in the center of the city. Corresponding OMAERO retrievals exceed the AATS and/or AERONET AODs by factors of 3 to 10

Intercomparison of desert dust optical depth from satellite measurements

This work provides a comparison of satellite retrievalsof Saharan desert dust aerosol optical depth (AOD)during a strong dust event through March 2006. In this event,a large dust plume was transported over desert, vegetated,and ocean surfaces. The aim is to identify the differencesbetween current datasets. The satellite instruments consideredare AATSR, AIRS, MERIS, MISR, MODIS, OMI,POLDER, and SEVIRI. An interesting aspect is that the differentalgorithms make use of different instrument characteristicsto obtain retrievals over bright surfaces. These includemulti-angle approaches (MISR, AATSR), polarisationmeasurements (POLDER), single-view approaches using solarwavelengths (OMI, MODIS), and the thermal infraredspectral region (SEVIRI, AIRS). Differences between instruments,together with the comparison of different retrievalalgorithms applied to measurements from the same instrument,provide a unique insight into the performance andcharacteristics of the various techniques employed. As wellas the intercomparison between different satellite products,the AODs have also been compared to co-located AERONETdata. Despite the fact that the agreement between satellite andAERONET AODs is reasonably good for all of the datasets,there are significant differences between them when comparedto each other, especially over land. These differencesare partially due to differences in the algorithms, such as assumptionsabout aerosol model and surface properties. However,in this comparison of spatially and temporally averageddata, it is important to note that differences in sampling, relatedto the actual footprint of each instrument on the heterogeneousaerosol field, cloud identification and the qualitycontrol flags of each dataset can be an important issue

Leveraging Social Norms to Encourage Online Learning: Empirical Evidence from a Blended Learning Course

The growing role of digital learning environments in education poses new challenges to individuals’ self-regulated learning which may exacerbate self-control problems (i.e., procrastination) if not addressed. The present study explores the role of social norms in information systems to support university students by encouraging online learning. Based on a field experiment with 58 participants of an eighteen-week blended learning course, we investigate the impact of descriptive and injunctive normative feedback on participants’ online learning behavior. Specifically, we find that a small modification to the learning environment increases participants’ course-specific online learning time by 25.4%. The study provides additional evidence that this effect largely stems from a time segment in which the participants of the control group were disproportionately less active, potentially due to self-control problems. Ultimately, our findings have important implications for the design of digital learning environments to effectively support individuals in achieving their learning goals