Hepatic-portal vein infusions of glucagon-like peptide-1 reduce meal size and increase c-Fos expression in the nucleus tractus solitarii, area postrema and central nucleus of the amygdala in rats

We recently reported that brief, remotely controlled intrameal hepatic-portal vein infusions of glucagon-like peptide-1 (GLP-1) reduced spontaneous meal size in rats. To investigate the neurobehavioural correlates of this effect, we equipped male Sprague-Dawley rats with hepatic-portal vein catheters and assessed (i) the effect on eating of remotely triggered infusions of GLP-1 (1 nmol/kg, 5 min) or vehicle during the first nocturnal meal after 3 h of food deprivation and (ii) the effect of identical infusions performed at dark onset on c-Fos expression in several brain areas involved in the control of eating. GLP-1 reduced (P < 0.05) the size of the first nocturnal meal and increased its satiety ratio. Also, GLP-1 increased (P < 0.05) the number of c-Fos-expressing cells in the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala, but not in the arcuate or paraventricular hypothalamic nuclei. These data suggest that the nucleus tractus solitarii, the area postrema and the central nucleus of the amygdala play a role in the eating-inhibitory actions of GLP-1 infused into the hepatic-portal vein; it remains to be established whether activation of these brain nuclei reflect satiation, aversion, or both.

The future treatment of portal hypertension

Increased understanding of the hyperdynamic circulation syndrome has resulted in novel therapeutic approaches, some of which have already reached clinical practice. Central to the hyperdynamic circulation syndrome is an imbalance between the increase in different vasodilators (foremost among which is nitric oxide) and the compensatory increase in vasoconstrictors--usually accompanied by a blunted response. This chapter discusses the role of endothelin in the pathogenesis of the syndrome and in future treatment approaches. A relatively new area of research in this field is the role of infection and inflammation in the initiation and maintenance of the hyperdynamic circulation syndrome. The use of antibiotics in the setting of acute variceal bleeding is standard practice. Studies have suggested that chronic manipulation of the intestinal flora could have beneficial effects in the treatment of portal hypertension. The bile salts are another novel and interesting target. Although their vasoactive properties have been known for some time, recent data demonstrate that their effects could be central in the pathogenesis of the hyperdynamic circulation syndrome, and that manipulation of the composition of the bile acid pool could be a therapeutic approach to portal hypertension. Finally, hypoxia and angiogenesis play a role in the development of portal hypertension and the formation of collaterals. This role needs to be further defined but it appears likely that this phenomenon is yet another target for therapeutic intervention.

Testing the GlaaS algorithm for dose measurements on low- and high-energy photon beams using an amorphous silicon portal imager

The GLAaS algorithm for pretreatment intensity modulation radiation therapy absolute dose verification based on the use of amorphous silicon detectors, as described in Nicolini et al. [G. Nicolini, A. Fogliata, E. Vanetti, A. Clivio, and L. Cozzi, Med. Phys. 33, 2839-2851 (2006)], was tested under a variety of experimental conditions to investigate its robustness, the possibility of using it in different clinics and its performance. GLAaS was therefore tested on a low-energy Varian Clinac (6 MV) equipped with an amorphous silicon Portal Vision PV-aS500 with electronic readout IAS2 and on a high-energy Clinac (6 and 15 MV) equipped with a PV-aS1000 and IAS3 electronics. Tests were performed for three calibration conditions: A: adding buildup on the top of the cassette such that SDD-SSD = d(max) and comparing measurements with corresponding doses computed at d(max), B: without adding any buildup on the top of the cassette and considering only the intrinsic water-equivalent thickness of the electronic portal imaging devices device (0.8 cm), and C: without adding any buildup on the top of the cassette but comparing measurements against doses computed at d(max). This procedure is similar to that usually applied when in vivo dosimetry is performed with solid state diodes without sufficient buildup material. Quantitatively, the gamma index (gamma), as described by Low et al. [D. A. Low, W. B. Harms, S. Mutic, and J. A. Purdy, Med. Phys. 25, 656-660 (1998)], was assessed. The gamma index was computed for a distance to agreement (DTA) of 3 mm. The dose difference deltaD was considered as 2%, 3%, and 4%. As a measure of the quality of results, the fraction of field area with gamma larger than 1 (%FA) was scored. Results over a set of 50 test samples (including fields from head and neck, breast, prostate, anal canal, and brain cases) and from the long-term routine usage, demonstrated the robustness and stability of GLAaS. In general, the mean values of %FA remain below 3% for deltaD equal or larger than 3%, while they are slightly larger for deltaD = 2% with %FA in the range from 3% to 8%. Since its introduction in routine practice, 1453 fields have been verified with GLAaS at the authors' institute (6 MV beam). Using a DTA of 3 mm and a deltaD of 4% the authors obtained %FA = 0.9 +/- 1.1 for the entire data set while, stratifying according to the dose calculation algorithm, they observed: %FA = 0.7 +/- 0.9 for fields computed with the analytical anisotropic algorithm and %FA = 2.4 +/- 1.3 for pencil-beam based fields with a statistically significant difference between the two groups. If data are stratified according to field splitting, they observed %FA = 0.8 +/- 1.0 for split fields and 1.0 +/- 1.2 for nonsplit fields without any significant difference.

Portal vein omentin is increased in patients with liver cirrhosis but is not associated with complications of portal hypertension

BACKGROUND: Omentin is a visceral fat-derived adipokine associated with endothelium-dependent vasodilation. Impaired endothelial function is a major cause of portal hypertension in liver cirrhosis. The aim was to assess associations of omentin with systemic markers of endothelial function, namely arginine and asymmetric dimethylarginine (ADMA) and complications of portal hypertension in liver cirrhosis. MATERIALS AND METHODS: Systemic omentin was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS) and hepatic venous serum (HVS) of 40 patients with liver cirrhosis and 10 liver-healthy controls. ADMA and arginine were determined in SVS of the patients by ELISA. RESULTS: Omentin is elevated in PVS and tends to be increased in SVS and HVS of patients with liver cirrhosis compared with controls. Omentin is principally expressed in visceral fat, and PVS omentin tends to be higher than SVS levels. Lower HVS than PVS omentin suggests that omentin may be partly removed from the circulation by the liver. Omentin in serum is not associated with stages of liver cirrhosis defined by CHILD-POUGH or MELD score and is not affected in patients with ascites. HVS omentin tends to be reduced in patients with large varices compared with patients without/with small varices. Arginine/ADMA ratio is reduced in patients with massive ascites but is not associated with variceal size. Further, Arginine/ADMA ratio does not correlate with omentin. CONCLUSION: Current data show that PVS omentin is increased in liver cirrhosis but is not associated with complications of portal hypertension