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.

Routine use of total hepatic vascular exclusion in major hepatectomy is not necessary.

The prime concert of a hepato-biliary surgeon undertaking liver resection is to minimise blood loss and prevent air embolism through the control of the major vascular structures. Several methods to achieve this are now available and include in particular clamping of the hepatic pedicle and total vascular exclusion. Both techniques are detailed as well as their benefits and drawbacks. For conventional liver resections, total vascular exclusion has no advantage over clamping of the hepatic pedicle in preventing blood loss and is associated with additional morbidity. This technique should be selectively used in patients with tumours involving major hepatic veins or the inferior vena cava.

Ultraviolet-B damages corneal endothelium.

Direct in vivo observation of acute ultraviolet (UV)-induced corneal endothelial damage is not possible due to the more severe damage produced in the epithelium. In order to quantify damage and evaluate endothelial recovery an indirect method was used. Eyes of pigmented rabbits were irradiated with UV-B (290 to 320 nm) isolated from the output of a high-pressure 1000 W reflectorized Xenon arc lamp by a grating monochromator and appropriate filters. The peak wavelength of the radiation used was 305 nm, with a 18 nm bandwidth at half-maximum. Corneal thickness variations measured with a modified Zeiss (Oberkochen) pachometer were used to follow alterations in epithelial and endothelial function. Epithelial damage alone resulted in a maximum thickness increase of 13.5% within 24 hr with recovery within a further 24 hr. Greater increases in corneal thickness, in the absence of anterior uveal involvement, were taken to indicate endothelial damage, and reached maximum at 2 days, with recovery occurring in 7 days. The threshold for endothelial damage sufficient to disturb corneal deturgescence was 0.12 J X cm-2.