NCX-1000, a nitric oxide-releasing derivative of UDCA, does not decrease portal pressure in patients with cirrhosis: results of a randomized, double-blind, dose-escalating study

NCX-1000 (2(acetyloxy) benzoic acid-3(nitrooxymethyl)phenyl ester) is an nitric oxide (NO)-releasing derivative of ursodeoxycholic acid (UDCA), which showed selective vasodilatory effect on intrahepatic circulation in animal models of cirrhosis. This study was aimed at testing the efficacy and tolerability of this compound in patients with cirrhosis and portal hypertension.

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Germanic Mythology in Music: Cultural Memory and Conflict within the Framework of Modern Globalization

The multi-layered enactment of a national past in music has been strongly intertwined with the usage of mythological elements. Having often been compiled as a coherent narrative during the emergence of the European nation-states (like the Finnish Kalevala), the mythological material has often been perceived as a form of historical truth and national justification. This focal role is also apparent in various music genres ranging from folk revival to metal in post-1989 Europe. Within the globalized context, however, local-national interpretations can collide with earlier nationalist appropriations. This complex and sometimes politically conflicting situation becomes particularly evident with groups falling back on symbols and narrations that had previously been employed by Nazi-Germany. While Nazi-Germany had, among others, tried replace the Christmas tradition with elements and songs from Germanic (and other) mythological sources, modern Neo-Nazi music groups often employ central mythological names (like Odin or Tyr) and iconic elements (like Vikings and warriors) in song lyrics and CD cover designs. However, while many covers and lyrics are legally forbidden in Germany, Scandinavian and Baltic groups (like the Faroese Viking metal group Tyr and the Latvian pagan metal band Skyforger) employ similar elements of Norse mythology, which are often combined with traditional material. Discussing selected case studies, this paper highlights central discursive points of colliding historical-national associations and individual interpretations of the mythological elements in musical contexts. How far can the material be disassociated from the earlier historical political usage and instrumentalization? Is this necessary ? And how can the specific global-local conflict points be approached by a theoretical framework ?