Intravenous omega-3 fatty acids are associated with better clinical outcome and less inflammation in patients with predicted severe acute pancreatitis: A randomised double blind controlled trial.

BACKGROUND AND AIMS: Omega-3 fatty acids (FA) can ameliorate the hyper-inflammatory response that occurs in conditions such as severe acute pancreatitis (SAP) and this may improve clinical outcome. We tested the hypothesis that parenteral omega-3 FA from a lipid emulsion that includes fish oil could be beneficial in patients with predicted SAP by reducing C-reactive protein (CRP) concentration (primary outcome), and modulating the inflammatory response and improving clinical outcome (secondary outcomes). METHODS: In a phase II randomized double-blind single-centre controlled trial, patients with predicted SAP were randomised to receive a daily infusion of fish oil containing lipid emulsion (Lipidem® 20%, BBraun) for 7 days (n = 23) or a daily infusion of a lipid emulsion without fish oil (Lipofundin® MCT 20%, BBraun) (n = 22). RESULTS: On admission, both groups had comparable pancreatitis predicted severity and APACHE II scores. Administration of fish oil resulted in lower total blood leukocyte number (P = 0.04), CRP (P = 0.013), interleukin-8 (P = 0.05) and intercellular adhesion molecule 1 (P = 0.01) concentrations, multiple organ dysfunction score, sequential organ failure assessment score (P = 0.004), early warning score (P = 0.01), and systemic inflammatory response syndrome (P = 0.03) compared to the control group. The fish oil group had fewer new organ failures (P = 0.07), lower critical care admission rate (P = 0.06), shorter critical care stay (P = 0.03) and shorter total hospital stay (P = 0.04). CONCLUSIONS: It is concluded that intravenous administration of a fish oil containing lipid emulsion, a source of omega-3 FA, improves clinical outcomes in patients with predicted SAP, benefits that may be linked to reduced inflammation. CLINICALTRIALS. GOV NUMBER: NCT01745861. EU CLINICAL TRIALS REGISTER: EudraCT (2010-018660-16).

Excitatory amino acid projections to the nucleus accumbens septi in the rat: a retrograde transport study utilizing D[3H]aspartate and [3H]GABA.

Afferents to the nucleus accumbens septi utilizing glutamate or aspartate have been investigated in the rat by autoradiography following injection and retrograde transport of D[3H]aspartate. Parallel experiments with the intra-accumbal injection of [3H]GABA were employed to establish the transmitter-selective nature of the retrograde labelling found with D[3H]aspartate. The topography of cortical and thalamic perikarya labelled by D[3H]aspartate was extremely precise. D[3H]Aspartate labelled perikarya were found in layer V of agranular insular cortex; bilaterally within prelimbic and infralimbic subareas perikarya, but predominantly ipsilaterally. Ipsilateral labelling was observed in dorsal, ventral and posterior agranular insular cortices, and in perirhinal cortex. Injections into ventral accumbens labelled perikarya in ipsilateral entorhinal cortex, while infusion of D[3H]aspartate into anterior caudate-putamen resulted in labelling of perikarya in ipsilateral cingulate and lateral precentral cortices. Following infusion of D[3H]aspartate, ipsilateral midline thalamic nuclei contained the highest density of labelled perikarya; infusions centred on nucleus accumbens resulted in heavy retrograde labelling of the parataenial nucleus, but labelling was sparse from a lateral site and not observed after injection into anterior caudate-putamen. Less prominent labelling of perikarya was seen in other thalamic nuclei (mediodorsal, central medial, rhomboid, reuniens and centrolateral), mostly near the midline. Perikaryal labelling was also found in the ipsilateral amygdaloid complex, particularly in basolateral and lateral nuclei. Only weak labelling resulted in ventral subiculum. Numerous labelled cells were present bilaterally in anterior olfactory nucleus, although perikarya were more prominent ipsilaterally. Labelled perikarya were not consistently observed in other regions (ventral tegmental area, medial substantia nigra, raphe nuclei and locus coeruleus) known to innervate nucleus accumbens. Presumptive anterograde labelling was detected in ventral pallidum/substantia innominata, ventral tegmental area and medial substantia nigra. [3H]GABA was generally not retrogradely transported to the same regions labelled by D[3H]aspartate; an exception being the anterior olfactory nucleus, where large numbers of labelled perikarya were found. [3H]GABA failed to label perikarya in thalamus and amygdala, and a topographic distribution of label was absent in neocortex.(ABSTRACT TRUNCATED AT 400 WORDS)