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Body composition and fractional rates of protein synthesis (percentage of the protein mass synthesized per day) were determined in female Atlantic salmon returning to the River Tay, Scotland in July and in October after a 95 day period without food, during which time the animals became sexually mature. During the 95 day period of starvation/sexual maturation the ventricle and red muscle remained as a constant proportion of fresh weight whereas the liver, gill and ovary increased and the stomach and white muscle decreased. Fractional rates of protein synthesis increased markedly in the liver, stomach and ovary during the period of starvation/sexual maturation. In the gill, ventricle and white muscle fractional protein synthesis rates increased slightly or remained constant. From the estimated rates of protein loss or gain in the various tissues it is concluded that there is considerable protein turnover and repartitioning of amino acids during the period of starvation and sexual maturation. The absolute rate of protein synthesis rates in the ovary indicates that this tissue made the largest contribution to the energy and amino acid demands of the fish, whilst most of the amino acids required for maturation of the ovary were derived from white muscle, principally as the result of increased muscle protein degradation.

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SummaryThe pro-inflammatory cytokine tumour necrosis factor-a (TNF-α) is able to alter the haemostatic balance of human umbilical vein endothelial cells (HUVECs) towards that of a procoagulant and anti-fibrinolytic state. Treatment of HUVECs in culture with human recombinant TNF-α (0.5-50 U/ml; 6 h) significantly increased total cell expression of tissue factor (TF) 10-fold from 40 mU/well to 400-500 mU/well. Levels of plasminogen activator inhibitor-1 (PAI-1) antigen secreted from HUVECs also increased up to 2-fold in concentration-dependent fashion following addition of TNF-α (10-100 U/ml; 24 h). TNF-α induced total and cell surface expression of TF on HUVECs was significantly inhibited when the cells were pre-incubated with interleukin-4 (IL-4; p <0.001). This effect was time and concentration dependent. Pretreatment of HUVECs with IL-4 for 4 h had no significant effect, but increasing inhibition of total TF expression occurred after 8 and 16 h pre-incubations. Treatment with IL-4 at 20 and 200 U/ml significantly inhibited cell surface TF responses induced by TNF-α, whereas a low concentration (0.2 U/ml) was without effect. In contrast, the production of PAI-1 from HUVECs stimulated by TNF-α (50 U/ml) was unaffected by the presence and/or prior incubation with 200 U/ml IL-4. Thus, IL-4 may regulate the pro-coagulant but not the antifibrinolytic effects of TNF-α at sites of vascular inflammation.

Quorum sensing (QS) antagonists have been proposed as novel therapeutic agents to combat bacterial infections. We previously reported that the secondary metabolite 3-methyl-N-(2′-phenylethyl)-butyramide, produced by a marine bacterium identified as Halobacillus salinus, inhibits QS controlled phenotypes in multiple Gram-negative reporter strains. Here we report that N-phenethyl hexanamide, a structurally-related compound produced by the marine bacterium Vibrio neptunius, similarly demonstrates QS inhibitory properties. To more fully explore structure–activity relationships within this new class of QS inhibitors, a panel of twenty analogs was synthesized and biologically evaluated. Several compounds were identified with increased attenuation of QS-regulated phenotypes, most notably N-(4-fluorophenyl)-3-phenylpropanamide against the marine pathogen Vibrio harveyi (IC50 = 1.1 µM). These findings support the opportunity to further develop substituted phenethylamides as QS inhibitors.