Succinate is an inflammatory signal that induces IL-1ß through HIF-1α.

Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1ß but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1ß as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1ß production during inflammation.

Comparative analyses of Pasteurella multocida strains associated with the ovine respiratory and vaginal tracts.

Thirty-five isolates of Pasteurella multocida from the vagina and respiratory tract of sheep were compared by analysing their capsular polysaccharide types and outer membrane protein profiles. The phylogenetic relationships of selected isolates with respect to reference strains of P. multocida were also determined by comparative 16S rRNA sequence analysis. Three capsular types, A, D and F, and three major outer membrane protein types were identified, and there were four different combinations of these characteristics which probably marked four individual clones of P. multocida. Strains representing three of these clones were recovered from cases of ovine pneumonia, whereas isolates of the fourth clone were associated exclusively with the vagina of healthy ewes and the liver of a dead septicaemic lamb on the same farm. Analysis of the 16S rRNA sequences showed that there was 100 per cent identity between representative pneumonic isolates and reference strains of P. multocida subspecies galliseptica and P. multocida subspecies multocida. The 16S rRNA genes of representative vaginal and liver isolates from the same farm were identical but differed from the other strains at one nucleotide position, providing strong evidence that the vaginal and liver isolates represent a distinct subpopulation of P. multocida.

Monovision.

Monovision has been a controversial contact lens correction modality for over 30 years. This paper addresses the major issues and concerns and considers them in the light of patient safety, visual efficiency and practitioner liability.

Influence of dietary fat upon rats during gestation and lactation.

A comparison was made between rats fed purified rations containing different fats during gestation and lactation and rats fed a commercial ration during similar periods. The purified ration containign 20% cocoa butter did not result in appreciable differences in the mothers (body weight, behavior, litter production, and brain chemistry) or in the 1-day-old neonates (brain chemistry). The purified ration containing 20% safflower oil resulted in fewer completed gestation, in poorer maternal behavior during lactation, and in neonates with small brains. A fat-free purified ration resulted in low brain concentrations of RNA and low RNA-DNA ratios in the mothers.

Influence of maternal dietary fat upon rat pups.

Mother rats were fed purified rations containing different fats during gestation and lactation and at 1 day after parturition. Litter sizes were reduced to 2 male and 2 female pups. The behavior and the brain chemical composition of these selected pups were compared with similarly selected pups from dams fed a commercial ration. All offspring were fed a commercial ration after weaning. Pups from dams fed 20% safflower oil were similar to controls. Feeding 20% cocoa butter to dams resulted in pups with reduced exploratory activity and with a rapid learning performance in a T-maze, employing the aversive stimulation of an electrical shock. Feeding dams a fat-free ration produced pups which had reduced rates of growth, small brains at 2 months of age, and low brain concentrations of cholesterol, DNA, and RNA.