Centrally administered hemokinin-1 (HK-1), a neurokinin NK1 receptor agonist, produces substance P-like behavioral effects in mice and gerbils.

Hemokinin-1 (HK-1) is a recently described mouse tachykinin peptide whose biological functions are not fully understood. To date, a unique receptor for HK-1 has not been identified. Recent studies suggest HK-1 may have a role in immunological functions, but there has been little characterization of HK-1's effects in the central nervous system (CNS). In the present studies, we confirm that HK-1 is an endogenous agonist at all of the known tachykinin receptors, and is selective for the NK1 receptor over the NK2 and NK3 subtypes. CHO cells transfected with the human NK1 receptor released intracellular calcium in response to HK-1. In addition, HK-1 competed with substance P (SP) for binding to mouse NK1 and human NK1 receptors. In vivo central administration of HK-1 to gerbils and mice induced foot-tapping and scratching behaviors, respectively, similar to those observed following central administration of SP or the NK1 receptor agonist, GR-73632. Furthermore, these behavioral effects were blocked by the selective NK1 receptor antagonist, MK-869. Finally, a comprehensive expression analysis of HK-1 demonstrated that HK-1 mRNA is much more broadly expressed than previously reported with expression observed in many brain regions. Together these data demonstrate that HK-1 is a functional agonist at NK1 receptors and suggest that HK-1 may function both centrally and peripherally.

Prevention and treatment of diarrhoea with Saccharomyces boulardii in children with acute lower respiratory tract infections.

The aim of this study was to determine whether Saccharomyces boulardii prevents and treats diarrhoea and antibiotic-associated diarrhoea (AAD) in children. A total of 333 hospitalised children with acute lower respiratory tract infection were enrolled in a 2-phase open randomised controlled trial. During the 1st phase, all children received intravenous antibiotics (AB). They were randomly allocated to group A (S. boulardii 500 mg/day + AB, n=167) or group B (AB alone, n=166) and followed for 2 weeks. Diarrhoea was defined as ≥3 loose/watery stools/day during at least 2 days, occurring during treatment and/or up to 2 weeks after AB therapy had stopped. AAD was considered when diarrhoea was caused by Clostridium difficile or when stool cultures remained negative. In the 2nd phase of the study, group B patients who developed diarrhoea were randomly allocated to two sub-groups: group B1 (S. boulardii + oral rehydration solution (ORS)) and group B2 (ORS alone). Data from 283 patients were available for analysis. Diarrhoea prevalence was lower in group A than in group B (11/139 (7.9%) vs. 42/144 (29.2%); relative risk (RR): 0.27, 95% confidence interval (CI): 0.1-0.5). S. boulardii reduced the risk of AAD (6/139 (4.3%) vs. 28/144 (19.4%); RR: 0.22; 95% CI: 0.1-0.5). When group B patients developed diarrhoea (n=42), S. boulardii treatment during 5 days (group B1) resulted in lower stool frequency (P<0.05) and higher recovery rate (91.3% in group B1 vs. 21.1% in B2; P<0.001). The mean duration of diarrhoea in group B1 was shorter (2.31±0.95 vs. 8.97±1.07 days; P<0.001). No adverse effects related to S. boulardii were observed. S. boulardii appeared to be effective in the prevention and treatment of diarrhoea and AAD in children treated with intravenous antibiotics.