Metabolism at the centre of the host-microbe relationship.

Maintaining homoeostatic host-microbe interactions is vital for host immune function. The gut microbiota shapes the host immune system and the immune system reciprocally shapes and modifies the gut microbiota. However, our understanding of how these microbes are tolerated and how individual, or communities of, gut microbes influence host function is limited. This review will focus on metabolites as key mediators of this complex host-microbe relationship. It will look at the central role of epithelial metabolism in shaping the gut microbiota, how microbial metabolites influence the epithelium and the mucosal and peripheral immune system, and how the immune system shapes microbial composition and metabolism. Finally, this review will look at how metabolites are involved in cross-talk between different members of the microbiota and their role during infections.

Effect of single-dose dexamethasone on acute phase response following zoledronic acid: a randomized controlled trial.

Zoledronic acid provokes an inflammatory reaction, or acute phase response, in some individuals. We examined whether treatment with dexamethasone could prevent this response. A single dose of dexamethasone 4 mg, given at the time of zoledronic acid infusion, did not influence the incidence or severity of the acute phase response. INTRODUCTION: The potent bisphosphonate zoledronic acid (ZOL) is used to treat osteoporosis, Paget's disease, and hypercalcemia of malignancy. This medication can provoke an inflammatory reaction, known as the acute phase response (APR). We examined whether glucocorticoid treatment at the time of first exposure to ZOL prevents the development of APR. METHODS: This double-blind, randomized, controlled trial assessed 40 adults receiving ZOL 5 mg intravenously for the first time. Participants received oral dexamethasone 4 mg (n = 20) or placebo (n = 20) at the time of ZOL infusion. Oral temperature was measured at baseline and three times a day for 3 days following infusion. Symptoms of APR were assessed via questionnaire at baseline then daily for 3 days and again at day 15 post-infusion. Use of rescue medications (paracetamol or ibuprofen) in the 3 days following infusion was evaluated. Primary outcome was between-group difference in temperature change from baseline. RESULTS: There was no significant difference in temperature change (p = 0.95) or symptom score (p = 0.42) in the 3 days following ZOL between dexamethasone and placebo recipients. Eleven (55%) in the dexamethasone group and 10 (50%) placebo recipients experienced a temperature increase of ≥1 °C (p = 0.99). Seven (35%) in the dexamethasone group and 9 (45%) in the placebo group experienced an increase in symptom score of ≥3 points (p = 0.75). Thirteen (65%) dexamethasone recipients and 12 (60%) in the placebo group required rescue medications (p = 0.99). Dexamethasone was well-tolerated. CONCLUSIONS: A single dose of dexamethasone 4 mg does not influence the incidence or severity of APR following first exposure to ZOL. TRIAL REGISTRATION: ACTRN12615000794505.

[Carl von Reyher's studies of wound therapy]. / Carl von Reyhers Studien zur Wundtherapie.

Carl von Reyher (1846-1890), a young Russian army surgeon of the late nineteenth century, established the principle of repeated debridements on a scientific basis. After a visit to Lister's clinic, acquainting himself with antiseptic wound management, von Reyher was the first to present a controlled study of debridement in contaminated gunshot wounds. He was able to show that the combination of primary debridement and antiseptic treatment decreased the mortality rate of gunshot injuries from 66% to 23%. Although published in more than 16 papers and presented at international congresses, Reyher's contribution was completely negated. Finally more than 30 years later in World War I, the Inter-allied Surgical Conference officially endorsed primary excision with delayed wound closure as the rule for treatment of gunshot wounds.