50 Jahre GATT

Am 1. Januar 1948 trat das Allgemeine Zoll- und Handelsabkommen (GATT) in Kraft. Welche Liberalisierungsfortschritte beim Welthandel wurden in den vergangenen 50 Jahren gemacht? Welche Aufgaben stehen auf der Tagesordnung? --

Synergistic anti-inflammatory activity of ginger and turmeric extracts in inhibiting lipopolysaccharide and interferon-γ-induced proinflammatory mediators

This study aims to investigate the combined anti-inflammatory activity of ginger and turmeric extracts. By comparing the activities of individual and combined extracts in lipopolysaccharide and interferon-gamma-induced murine RAW 264.7 cells, we demonstrated that ginger-turmeric combination was optimal at a specific ratio (5:2, w/w) in inhibiting nitric oxide, tumour necrosis factor and interleukin 6 with synergistic interaction (combination index < 1). The synergistic inhibitory effect on TNF was confirmed in human monocyte THP-1 cells. Ginger-turmeric combination (5:2, w/w) also upregulated nuclear factor erythroid 2-related factor 2 activity and heme oxygenase-1 protein expression. Additionally, 6-shogaol, 8-shogaol, 10-shogaol and curcumin were the leading compounds in reducing major proinflammatory mediators and cytokines, and a simplified compound combination of 6-s, 10-s and curcumin showed the greatest potency in reducing LPS-induced NO production. Our study provides scientific evidence in support of the combined use of ginger and turmeric to alleviate inflammatory processes

The M81 Group Dwarf Irregular Galaxy DDO 165. II. Connecting Recent Star Formation with ISM Structures and Kinematics

We compare the stellar populations and complex neutral gas dynamics of the M81 group dIrr galaxy DDO 165 using data from the HST and the VLA. Paper I identified two kinematically distinct HI components, multiple localized high velocity gas features, and eight HI holes and shells (the largest of which spans ~2.2x1.1 kpc). Using the spatial and temporal information from the stellar populations in DDO 165, we compare the patterns of star formation over the past 500 Myr with the HI dynamics. We extract localized star formation histories within 6 of the 8 HI holes identified in Paper I, as well as 23 other regions that sample a range of stellar densities and neutral gas properties. From population synthesis modeling, we derive the energy outputs (from stellar winds and supernovae) of the stellar populations within these regions over the last 100 Myr, and compare with refined estimates of the energies required to create the HI holes. In all cases, we find that "feedback" is energetically capable of creating the observed structures in the ISM. Numerous regions with significant energy inputs from feedback lack coherent HI structures but show prominent localized high velocity gas features; this feedback signature is a natural product of temporally and spatially distributed star formation. In DDO 165, the extended period of heightened star formation activity (lasting more than 1 Gyr) is energetically capable of creating the observed holes and high velocity gas features in the neutral ISM.Comment: The Astrophysical Journal, in press. Full-resolution version available on request from the first autho

The M81 Group Dwarf Irregular Galaxy DDO 165. I. High Velocity Neutral Gas in a Post-Starburst System

We present new multi-configuration VLA HI spectral line observations of the M81 group dIrr post-starburst galaxy DDO 165. The HI morphology is complex, with multiple column density peaks surrounding a large region of very low HI surface density that is offset from the center of the stellar distribution. The bulk of the neutral gas is associated with the southern section of the galaxy; a secondary peak in the north contains ~15% of the total HI mass. These components appear to be kinematically distinct, suggesting that either tidal processes or large-scale blowout have recently shaped the ISM of DDO 165. Using spatially-resolved position-velocity maps, we find multiple localized high-velocity gas features. Cross-correlating with radius-velocity analyses, we identify eight shell/hole structures in the ISM with a range of sizes (~400-900 pc) and expansion velocities (~7-11 km/s). These structures are compared with narrow- and broad-band imaging from KPNO and HST. Using the latter data, recent works have shown that DDO 165's previous "burst" phase was extended temporally (>1 Gyr). We thus interpret the high-velocity gas features, HI holes, and kinematically distinct components of the galaxy in the context of the immediate effects of "feedback" from recent star formation. In addition to creating HI holes and shells, extended star formation events are capable of creating localized high velocity motion of the surrounding interstellar material. A companion paper connects the energetics from the HI and HST data.Comment: The Astrophysical Journal, in press. Full-resolution version available on request from the first autho

Synergistic inhibition of pro-inflammatory pathways by ginger and turmeric extracts in RAW 264.7 cells

Synergy plays a prominent role in herbal medicines to increase potency and widen the therapeutic windows. The mechanism of synergy in herbal medicines is often associated with multi-targeted behavior and complex signaling pathways which are challenging to elucidate. This study aims to investigate the synergistic mechanism of a combination (GT) of ginger (G) and turmeric (T) extracts by exploring the modulatory activity in lipopolysaccharides (LPS)-induced inflammatory pathways and key molecular targets. A Bioplex ProTM mouse cytokine 23-plex assay was utilized to assess the broad anti-cytokine activity of GT in LPS and interferon (IFN)-gamma (both at 50 ng/mL)-activated RAW 264.7 cells. The inhibitory effects of individual and combined G and T on major proinflammatory mediators including nitric oxide (NO), tumor necrosis factor (TNF) and interleukin (IL)-6 were tested using Griess reagents and ELISA assays, respectively. Immunofluorescent staining and Western blot were used to investigate the modulatory effect of GT on key proteins in the LPS/TLR4 signaling transduction. The regulation of murine microRNA miR-155-5p was tested using real-time PCR. The IC50 value and combination index (CI) values were used to demonstrate potency and synergistic interaction, respectively. GT synergistically attenuated a range of pro-inflammatory mediators including inducible NO, major cytokines (TNF and IL-6) and secondary inflammatory cytokines (GM-CSF and MCP-1). GT significantly inhibited LPS-induced NF-kB p65 translocation, the activation of TLR4, TRAF6, and phosphorylation of JNK and c-JUN. Moreover, the suppressive effect of GT on each of the protein targets in this axis was stronger than that of the individual components. Real-time PCR analysis showed that GT suppressed miR-155-5p to a greater extent than G or T alone in LPS-stimulated cells. Our study demonstrates the synergistic mechanism of GT in downregulating LPS-induced proinflammatory pathways at the miRNA and protein levels. Our results establish a scientific basis for the combined application of G and T as an advanced therapeutic candidate in inflammatory diseases with broad and synergistic anti-inflammatory activity and multi-targeted mechanisms

Efficacy and Safety of Antioxidant Treatment With α-Lipoic Acid Over 4 Years in Diabetic Polyneuropathy

Objective: To evaluate the efficacy and safety of α-lipoic acid (ALA) over 4 years in mild-to-moderate diabetic distal symmetric sensorimotor polyneuropathy (DSPN). Research Design and Methods: In a multicenter randomized double-blind parallel-group trial, 460 diabetic patients with mild-to-moderate DSPN were randomly assigned to oral treatment with 600 mg ALA once daily (n = 233) or placebo (n = 227) for 4 years. Primary end point was a composite score (Neuropathy Impairment Score [NIS]–Lower Limbs [NIS-LL] and seven neurophysiologic tests). Secondary outcome measures included NIS, NIS-LL, nerve conduction, and quantitative sensory tests (QSTs). Results: Change in primary end point from baseline to 4 years showed no significant difference between treatment groups (P = 0.105). Change from baseline was significantly better with ALA than placebo for NIS (P = 0.028), NIS-LL (P = 0.05), and NIS-LL muscular weakness subscore (P = 0.045). More patients showed a clinically meaningful improvement and fewer showed progression of NIS (P = 0.013) and NIS-LL (P = 0.025) with ALA than with placebo. Nerve conduction and QST results did not significantly worsen with placebo. Global assessment of treatment tolerability and discontinuations due to lack of tolerability did not differ between the groups. The rates of serious adverse events were higher on ALA (38.1%) than on placebo (28.0%). Conclusions: Four-year treatment with ALA in mild-to-moderate DSPN did not influence the primary composite end point but resulted in a clinically meaningful improvement and prevention of progression of neuropathic impairments and was well tolerated. Because the primary composite end point did not deteriorate significantly in placebo-treated subjects, secondary prevention of its progression by ALA according to the trial design was not feasible

Aortic dissection associated with cogans's syndrome: deleterious loss of vascular structural integrity is associated with GM-CSF overstimulation in macrophages and smooth muscle cells

<p>Abstract</p> <p>Background</p> <p>Cogan's syndrome is a rare disorder of unknown origin characterized by inflammatory ocular disease and vestibuloauditory symptoms. Systemic vasculitis is found in about 10% of cases.</p> <p>Case presentation</p> <p>A 46-year-old female with Cogans's syndrome and a history of arterial hypertension presented with severe chest pain caused by an aneurysm of the ascending aorta with a dissection membrane located a few centimeters distal from the aortic root. After surgery, histopathological analysis revealed that vascular matrix integrity and expression of the major matrix molecules was characterized by elastolysis and collagenolysis and thus a dramatic loss of structural integrity. Remarkably, exceeding matrix deterioration was associated with massively increased levels of granulocyte macrophage colony stimulating factor (GM-CSF).</p> <p>Conclusion</p> <p>Our data suggest that the persistently increased secretion of the inflammatory mediator GM-CSF by resident inflammatory cells but also by SMC may be the trigger of aortic wall structural deterioration.</p

Individual Trade-Offs Between Possible Benefits and Risks of Cancer Treatments:Results from a Stated Preference Study with Patients with Multiple Myeloma

BackgroundThe objectives of this study were to elicit the preferences of patients with multiple myeloma regarding the possible benefits and risks of cancer treatments and to illustrate how such data may be used to estimate patients' acceptance of new treatments. Patients and MethodsPatients with multiple myeloma from the cancer charity Myeloma UK were invited to participate in an online survey based on multicriteria decision analysis and swing weighting to elicit individual stated preferences for the following attributes: (a) 1-year progression-free survival (PFS, ranging from 50% to 90%), (b) mild or moderate toxicity for 2 months or longer (ranging from 85% to 45%), and (c) severe or life-threatening toxicity (ranging from 80% to 20%). ResultsA total of 560 participants completed the survey. The average weight given to PFS was 0.54, followed by 0.32 for severe or life-threatening toxicity and 0.14 for mild or moderate chronic toxicity. Participants who ranked severe or life-threatening toxicity above mild or moderate chronic toxicity (56%) were more frequently younger, working, and looking after dependent family members and had more frequently experienced severe or life-threatening side effects. The amount of weight given to PFS did not depend on any of the collected covariates. The feasibility of using the collected preference data to estimate the patients' acceptance of specific multiple myeloma treatments was demonstrated in a subsequent decision analysis example. ConclusionStated preference studies provide a systematic approach to gain knowledge about the distribution of preferences in the population and about what this implies for patients' acceptance of specific treatments. Implications for PracticeThis study demonstrated how quantitative preference statements from a large group of participants can be collected through an online survey and how such information may be used to explore the acceptability of specific treatments based on the attributes studied. Results from such studies have the potential to become an important new tool for gathering patient views and studying heterogeneity in preferences in a systematic way, along with other methods, such as focus groups and expert opinions. The objectives of this study were to ascertain the treatment preferences of patients with multiple myeloma, considering benefits and risks of particular cancer treatments, and to illustrate how such data may be used to estimate patients' acceptance of new treatments

Frequency and Nature of Incidental Extra-Enteric Lesions Found on Magnetic Resonance Enterography (MR-E) in Patients with Inflammatory Bowel Diseases (IBD)

The aim of this study was to determine the occurrence of extra-enteric findings in a large cohort of patients undergoing magnetic resonance enterography (MR-E) and to classify the clinical significance of these findings.We retrospectively analyzed 1154 MR-E performed in 1006 patients referred to our radiological department between 1999-2005. The reasons for referral were suspected or proven inflammatory bowel diseases (IBD) (n = 710), further diagnostic work-up for small bowel disease because of non-specific abdominal symptoms (SBD; n = 182) or suspected small bowel malignancies (SBM; n = 114). All extra-enteric findings were reviewed by a radiologist and a gastroenterologist and were classified as having high, moderate, or low significance for further diagnostic or therapeutic procedures.The average age of all patients was 40+/-16 (Mean+/-SD) years (y) (IBD 35+/-13 y; SBD 49+/-16 y; SBM 57+/-15 y). A total of 1113 extra-enteric findings were detected in 600 of 1006 patients (59.6%). Of these findings 180 (16.2%) were judged as having a high, 212 (19.0%) a moderate and 721 (64.8%) a low significance. On a per group basis in patients with IBD 12.0% of the findings were of major clinical significance compared to 13.7% and 33.3% in patients with SBD and SBM, respectively. The most common major findings were abscesses (69.9%) in the IBD group and extraintestinal tumors, metastases or masses in the SBD and SBM groups (41.9% and 74.2%, respectively).MR-E reveals a substantial number of extra-enteric findings, supporting the role of a cross-sectional imaging method for the evaluation of the small bowel