Attenuated portal hypertension in germ-free mice: Function of bacterial flora on the development of mesenteric lymphatic and blood vessels

Intestinal bacterial flora may induce splanchnic hemodynamic and histological alterations that are associated with portal hypertension (PH). We hypothesized that experimental PH would be attenuated in the complete absence of intestinal bacteria. We induced prehepatic PH by partial portal vein ligation (PPVL) in germ-free (GF) or mice colonized with altered Schaedler's flora (ASF). After 2 or 7 days, we performed hemodynamic measurements, including portal pressure (PP) and portosystemic shunts (PSS), and collected tissues for histomorphology, microbiology, and gene expression studies. Mice colonized with intestinal microbiota presented significantly higher PP levels after PPVL, compared to GF, mice. Presence of bacterial flora was also associated with significantly increased PSS and spleen weight. However, there were no hemodynamic differences between sham-operated mice in the presence or absence of intestinal flora. Bacterial translocation to the spleen was demonstrated 2 days, but not 7 days, after PPVL. Intestinal lymphatic and blood vessels were more abundant in colonized and in portal hypertensive mice, as compared to GF and sham-operated mice. Expression of the intestinal antimicrobial peptide, angiogenin-4, was suppressed in GF mice, but increased significantly after PPVL, whereas other angiogenic factors remained unchanged. Moreover, colonization of GF mice with ASF 2 days after PPVL led to a significant increase in intestinal blood vessels, compared to controls. The relative increase in PP after PPVL in ASF and specific pathogen-free mice was not significantly different. CONCLUSION In the complete absence of gut microbial flora PP is normal, but experimental PH is significantly attenuated. Intestinal mucosal lymphatic and blood vessels induced by bacterial colonization may contribute to development of PH.

Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension

BACKGROUND The diagnostic performance of biochemical scores and artificial neural network models for portal hypertension and cirrhosis is not well established. AIMS To assess diagnostic accuracy of six serum scores, artificial neural networks and liver stiffness measured by transient elastography, for diagnosing cirrhosis, clinically significant portal hypertension and oesophageal varices. METHODS 202 consecutive compensated patients requiring liver biopsy and hepatic venous pressure gradient measurement were included. Several serum tests (alone and combined into scores) and liver stiffness were measured. Artificial neural networks containing or not liver stiffness as input variable were also created. RESULTS The best non-invasive method for diagnosing cirrhosis, portal hypertension and oesophageal varices was liver stiffness (C-statistics=0.93, 0.94, and 0.90, respectively). Among serum tests/scores the best for diagnosing cirrhosis and portal hypertension and oesophageal varices were, respectively, Fibrosis-4, and Lok score. Artificial neural networks including liver stiffness had high diagnostic performance for cirrhosis, portal hypertension and oesophageal varices (accuracy>80%), but were not statistically superior to liver stiffness alone. CONCLUSIONS Liver stiffness was the best non-invasive method to assess the presence of cirrhosis, portal hypertension and oesophageal varices. The use of artificial neural networks integrating different non-invasive tests did not increase the diagnostic accuracy of liver stiffness alone.

Neuropeptide Y restores non-receptor-mediated vasoconstrictive action in superior mesenteric arteries in portal hypertension

BACKGROUND & AIMS Vascular hyporeactivity to vasoconstrictors contributes to splanchnic arterial vasodilatation and hemodynamic dysregulation in portal hypertension. Neuropeptide Y (NPY), a sympathetic cotransmitter, has been shown to improve adrenergic vascular contractility in portal hypertensive rats and markedly attenuate hyperdynamic circulation. To further characterize the NPY-effects in portal hypertension, we investigated its role for non-receptor-mediated vasoconstriction in the superior mesenteric artery (SMA) of portal vein ligated (PVL) and sham-operated rats. METHODS Ex vivo SMA perfusion of PVL and sham rats was used to analyse the effects of NPY on pressure response to non-receptor-mediated vasoconstriction. Dose-response curves to KCl (30-300 mM) were used to bypass G protein-coupled receptor mechanisms. Potential involvement of the cyclooxygenase-pathway was tested by non-selective cyclooxygenase-inhibition using indomethacin. RESULTS KCl-induced vascular contractility but not vascular sensitivity was significantly attenuated in PVL rats as compared with sham rats. Administration of NPY resulted in an augmentation of KCl-evoked vascular sensitivity being not different between study groups. However, KCl-induced vascular contractility was markedly more enhanced in PVL rats, thus, vascular response was no more significantly different between PVL and sham rats after addition of NPY. Administration of indomethacin abolished the NPY-induced enhancement of vasoconstriction. CONCLUSIONS Receptor-independent vascular contractility is impaired in mesenteric arteries in portal hypertension. NPY improves non-receptor mediated mesenteric vasoconstriction more effective in portal hypertension than in healthy conditions correcting splanchnic vascular hyporesponsiveness. This beneficial vasoactive action of NPY adds to its well known more pronounced effects on adrenergic vasoconstriction in portal hypertension making it a promising therapeutic agent in portal hypertension.

Portal der Synagoge [Illustration] : (Fotografie)

Jacob S. Baars

Jakobs Traum und Ringen mit dem Engel [Illustration] : Trani, Kathedrale, Relief vom Portal, Romanisch, 13. Jahrhundert

Scan von Monochrom-Mikroform

Portal der Nibelungenhalle, Königswinter a. Rh., Drachenfels

Signatur des Originals: S 36/F08008

Analytical frame for public policy implementation

"I don't think we truly understand how to implement. What does it mean to truly implement? Not the command center type that our culture is very good at, but a thorough planned systematic approach" (HP, 9.28.2011). This important question is asked by a clinician who works in a health care setting and who has experienced the implementation of a public policy. This case study applied the lessons learned from three generations of public policy research to a health care setting. As a result of the study an analytical frame was created as a guide to assess an organization's readiness for the implementation of a public policy.^

A refined Pliocene to early Pleistocene chronostratigraphic frame at ODP Hole 653A (West Mediterranean)

Two planktonic foraminiferal oxygen isotope records of ODP Hole 653A (Tyrrhenian Sea) are presented for the time period extending from approximately 0.8 to 3.0 Ma. Six, generally accepted, synchronous bioevents were used to precise the oxygen isotope chronology and to identify the oxygen isotope stages 22 down to 114. Subsequently, this oxygen isotope chronology was used to determine the synchronism or diachronism of various other biostratigraphic events with those recorded in the Singa and Ficarazzi land sections (Italy) and those in other DSDP/ODP sites. New results concern the diachronity of the FOD of the planktonic foraminiferal species N. atlantica, G.truncatulinoides truncatulinoides and G. inflata between ODP Hole 653A and the Italian landsections. Because many species entered the Mediterranean in short term fluxes, strongly related to the southward migration of cool North Atlantic surface waters, their time distribution through the Pliocene-Pleistocene generally corresponds to alternated intervals of presence and absence. This should explain most of the apparently diachronous appearances and disappearances. Alternating presence-absence patterns are of less importance for the various nannofossil events. The LOD of D. surculus occurs during the transition of stage 100 to 101 in both ODP Hole 653A and the Singa section, which is in perfect agreement with the disappearance of this species from the open ocean. The LOD of D. pentaradiatus in the Mediterranean occurs in stages 100-99, which seems to be consistent with the extinction of this species in the southern Hemisphere. G. oceanica, which corresponds to the 4 µm < Gephyrocapsa spp <5.5 µm is recorded in stages 65 to 64 at ODP Hole 653A. The Gephyrocapsa spp. >5.5 µm first occurred in stage 51 at Hole 653A, which fits within the uncertainty interval for this event stretching from stage 51 to 47 in the open ocean and seems therefore a useful tool for conventional biostratigraphy in the Mediterranean.

SIRGAS reference frame realization SIR11P01

To estimate the kinematics of the SIRGAS reference frame, the Deutsches Geodätisches Forschungsinstitut (DGFI) as the IGS Regional Network Associate Analysis Centre for SIRGAS (IGS RNNAC SIR), yearly computes a cumulative (multi-year) solution containing all available weekly solutions delivered by the SIRGAS analysis centres. These cumulative solutions include those models, standards, and strategies widely applied at the time in which they were computed and cover different time spans depending on the availability of the weekly solutions. This data set corresponds to the multi-year solution SIR11P01. It is based on the combination of the weekly normal equations covering the time span from 2000-01-02 (GPS week 1043) to 2011-04-16 (GPS week 1631), when the IGS08 reference frame was introduced. It refers to ITRF2008, epoch 2005.0 and contains 230 stations with 269 occupations. Its precision was estimated to be ±1.0 mm (horizontal) and ±2.4 mm (vertical) for the station positions, and ±0.7 mm/a (horizontal) and ±1.1 mm/a (vertical) for the constant velocities. Computation strategy and results are in detail described in Sánchez and Seitz (2011). The IGS RNAAC SIR computation of the SIRGAS reference frame is possible thanks to the active participation of many Latin American and Caribbean colleagues, who not only make the measurements of the stations available, but also operate SIRGAS analysis centres processing the observational data on a routine basis (more details in http://www.sirgas.org). The achievements of SIRGAS are a consequence of a successful international geodetic cooperation not only following and meeting concrete objectives, but also becoming a permanent and self-sustaining geodetic community to guarantee quality, reliability, and long-term stability of the SIRGAS reference frame. The SIRGAS activities are strongly supported by the International Association of Geodesy (IAG) and the Pan-American Institute for Geography and History (PAIGH). The IGS RNAAC SIR highly appreciates all this support.

La Cordillera de los Andes : de muro a portal : visiones del otro a través del espacio

Nos hemos planteado los cambios de percepción de un accidente geográfico, como la cadena montañosa de los Andes, desde la Colonia hasta nuestros días, como un modo de comprender mejor nuestras maneras de ver el mundo. En efecto, la relación con el espacio avala universalmente la particularidad de las identidades, tal como ha sido estudiado por la antropología, entre otras disciplinas que se han ocupado de la problemática entre identidad y espacio. Nos interesa concentrarnos en las significaciones que le ha sido asignado al macizo andino en ciertas etapas, en uno y otro lado del mismo. La significación de muro que se le atribuye a la cordillera constituye una de las varias que existen y circulan en los textos literarios y no literarios. La relevancia que tiene ese punto de vista –el muro- se puede apreciar mejor en el campo de las relaciones internacionales entre ambos países. Sin embargo, existen otras relaciones espacio-representación que han alentado procesos integracionistas.