A multicentre analysis of Clostridium difficile in persons with Cystic Fibrosis demonstrates that carriage may be transient and highly variable with respect to strain and level.

PURPOSE: Clostridium difficile has been reported to occur in the gastrointestinal tract of 50% of Cystic Fibrosis (CF) subjects, however, clinical C. difficile infection (CDI) is a rare occurrence in this cohort despite the presence of toxigenic and hypervirulent ribotypes. Here, we present the first longitudinal, multicentre analysis of C. difficile prevalence among adult CF subjects. METHODOLOGY: Faecal samples were collected from adults with CF (selected based on confirmed Pseudomonas aeruginosa pulmonary colonisation) from Ireland, UK and Belgium as part of the CFMATTERS clinical research trial (grant No. 603038) and from non-CF controls. Faecal samples were collected on enrolment, at three monthly intervals, during pulmonary exacerbation and three months post exacerbation. C. difficile was isolated from faecal samples by ethanol shocking followed by culturing on cycloserine cefoxitin egg yolk agar. Isolates were characterised in terms of ribotype, toxin type and antibiotic susceptibility to antibiotics routinely used in the treatment of CDI (metronidazole and vancomycin) and those implicated in induction of CDI (ciprofloxacin and moxifloxacin). RESULTS: Prevalence of C. difficile among CF subjects in the three sites was similar ranging from 47% to 50% at baseline, while the healthy control cohort had a carriage rate of 7.1%. Including subjects who were positive for C. difficile at any time point there was a higher carriage rate of 71.4%, 66.7% and 63.2% in Ireland, UK, and Belgium, respectively. Ribotyping of 80 isolates from 45 CF persons, over multiple time points revealed 23 distinct ribotypes with two ribotypes (046 and 078) shared by all centres. The proportion of toxigenic isolates varied across the sites, ranging from 66.7% in Ireland to 52.9% in Belgium and 100% in the UK. Antibiotic susceptibility rates to vancomycin, metronidazole, ciprofloxacin and moxifloxacin was 100%, 97.5%, 1.3% and 63.8%, respectively. CONCLUSIONS: This study demonstrates the highest carriage rate of C. difficile to date in a CF cohort. Longitudinal data show that C. difficile can be a transient inhabitant of the CF gut, changing both in terms of strain and excretion rates.

[Nle3,d-Phe6 ]-γ2 -melanocyte-stimulating hormone possesses the renal excretory but not the cardiovascular actions of the native γ2 -melanocyte-stimulating hormone in anaesthetized rats.

The present study compared the cardiovascular and renal actions of γ(2) -melanocyte-stimulating hormone (γ(2) MSH) with those of the synthetic analogue [Nle(3) ,d-Phe(6) ]-γ(2) MSH (NDP-γ(2) MSH) and explored the effects of high dietary salt intake on the renal actions of NDP-γ(2) MSH. Both peptides were infused systemically (3-1000 nmol/kg) and intrarenally (500 fmol/min) into innervated and renally denervated rats fed either a normal (0.4% NaCl) or high-salt (4% NaCl; HS) diet. Mean arterial pressure (MAP), glomerular filtration rate (GFR), urinary sodium excretion (U(N) (a) V), urinary output (UV) and fractional sodium excretion were determined, as was expression of the melanocortin MC(3) receptor in inner medullary collecting duct (IMCD) epithelial cells. Both renal and systemic infusion of γ(2) MSH increased MAP by 23 ± 2% and 54 ± 4%, respectively, but equivalent doses of NDP-γ(2) MSH had no significant pressor effects. Both peptides had similar natriuretic and diuretic effects in rats fed a normal salt diet. However, NDP-γ(2) MSH increased U(N) (a) V and UV by two- to threefold in rats fed the normal salt diet and by six- to sevenfold in rats fed the HS diet. Furthermore, NDP-γ(2) MSH induced a 3.5-fold increase in GFR only in rats fed the HS diet. These renal effects of NDP-γ(2) MSH were not abolished by prior renal denervation. Rats fed the HS diet also exhibited a 4.5-fold increase in MC(3) receptor expression in IMCD epithelial cells. Intrarenal infusion of NDP-γ(2) MSH induced the natriuretic but not the cardiovascular effects exhibited by γ(2) MSH. The renal activities may be attributed to a direct binding of NDP-γ(2) MSH to MC(3) receptors expressed in IMCD cells, leading to a potent natriuretic effect that is independent of renal innervation.

Impact of cardiac hypertrophy on arterial and cardiopulmonary baroreflex control of renal sympathetic nerve activity in anaesthetized rats.

This study aimed to quantify the effect of cardiac hypertrophy induced with isoprenaline and caffeine on reflex regulation of renal sympathetic nerve activity by the arterial and cardiopulmonary baroreceptors. Male Wistar rats, untreated or given water containing caffeine and subcutaneous (s.c.) isoprenaline every 72 h for 2 weeks or thyroxine s.c. for 7 days, were anaesthetized and prepared for measurement of renal sympathetic nerve activity or cardiac indices. Both isoprenaline-caffeine and thyroxine treatment blunted weight gain but increased heart weight and heart weight to body weight ratio by 40 and 14% (both P<0.01), respectively. In the isoprenaline-caffeine group, the maximal rate of change of left ventricular pressure and the contractility index were higher by 17 and 14% (both P<0.01), respectively, compared with untreated rats. In the isoprenaline-caffeine-treated rats, baroreflex gain curve sensitivity was depressed by approximately 30% (P<0/05), while the mid-point blood pressure was lower, by 15% (P<0/05), and the range of the curve was 60% (P<0.05) greater than in the untreated rats. An acute intravenous infusion of a saline load decreased renal sympathetic nerve activity by 42% (P<0.05) in the untreated rats but had no effect in the isoprenaline-caffeine- or the thyroxine-treated groups. The isoprenaline-caffeine treatment induced cardiac hypertrophy with raised cardiac performance and an associated depression in the reflex regulation of renal sympathetic nerve activity by both high- and low-pressure baroreceptors. The thyroxine-induced cardiac hypertrophy also blunted the low-pressure baroreceptor-mediated renal sympatho-inhibition. These findings demonstrate that in cardiac hypertrophy without impaired cardiac function, there is a blunted baroreceptor control of renal sympathetic outflow.