Clinical science
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Randomized Controlled Trial Clinical Trial
Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability.
Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics but cause gastrointestinal injury. Present prophylactic measures are suboptimal and novel therapies are required. Bovine colostrum is a cheap, readily available source of growth factors, which reduces gastrointestinal injury in rats and mice. ⋯ In volunteers, indomethacin caused a 3-fold increase in gut permeability in the control arm (lactulose/rhamnose ratio 0.36+/-0.07 prior to indomethacin and 1.17+/-0.25 on day 5, P<0.01), whereas no significant increase in permeability was seen when colostrum was co-administered. In patients taking long-term NSAID treatment, initial permeability ratios were low (0.13+/-0.02), despite continuing on the drug, and permeability was not influenced by co-administration of test solutions. These studies provide preliminary evidence that bovine colostrum, which is already currently available as an over-the-counter preparation, may provide a novel approach to the prevention of NSAID-induced gastrointestinal damage in humans.
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Randomized Controlled Trial Clinical Trial
Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations.
Soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin (termed sICAM-1, sVCAM-1 and sE-selectin respectively) are found in the plasma, and are elevated during inflammatory conditions in which there is increased expression of the cellular forms of the molecules on endothelial and other cells. sICAM-1, sVCAM-1 and sE-selectin concentrations were measured in the plasma of 140 healthy Caucasian subjects aged between 18 and 75 years (100 males/40 females). sICAM-1 concentrations varied between 59.9 and 299.7 ng/ml (median 150 ng/ml), sVCAM-1 concentrations varied between 222.8 and 1672.9 ng/ml (median 662 ng/ml) and sE-selectin concentrations varied between 12.4 and 90.3 ng/ml (median 45.5 ng/ml). There were significant positive linear correlations between age and the plasma concentrations of sICAM-1 (r=0.580; P<0.001) and sVCAM-1 (r=0.392; P<0.001), which were retained when the effects of gender, body mass index and fasting plasma triacylglycerol and total cholesterol concentrations were controlled for. The significant positive linear correlation between age and the plasma concentration of sE-selectin (r=0.234; P=0.027) was lost when other variables were controlled for. ⋯ The level of eicosapentaenoic acid in plasma phospholipids did not change with placebo supplementation, but was significantly increased with fish oil supplementation in both young male and elderly subjects (median increase 200%). sICAM-1, sVCAM-1 and sE-selectin concentrations were unaffected by supplementation with placebo in either young male or elderly subjects. sICAM-1 concentrations were unaffected by fish oil supplementation. sE-selectin concentrations were significantly increased by fish oil supplementation in young males (P=0.043; median increase 38%), but fish oil tended to decrease plasma sE-selectin concentrations in the elderly subjects (P=0.075), with a median decrease of 11%. sVCAM-1 concentrations were unaffected by fish oil supplementation in young males. Fish oil supplementation significantly decreased plasma sVCAM-1 concentrations in the elderly subjects (P=0.043), with a median decrease of 20% (range 16-60%). These observations suggest that fish oil decreases endothelial activation in elderly subjects.
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Randomized Controlled Trial Clinical Trial
Effects of pre- and post-absorptive factors on the lactulose/rhamnose gut permeability test.
It is assumed that the outcome of the lactulose/rhamnose gut permeability test is not influenced by pre- or post-absorptive factors. The aim of our study was to investigate the role of a pre-absorptive factor, i.e. small-intestinal transit, and a post-absorptive factor, i.e. renal clearance. Ten healthy male subjects were studied. ⋯ There was no significant difference in urinary rhamnose recovery (P=0.575) between the high and the regular doses. This resulted in a significantly lower lactulose/rhamnose ratio (P=0.021) after intravenous administration of a high dose, compared with a regular dose, of the sugars. In conclusion, the assumption that post-absorptive processes do not influence the outcome of the lactulose/rhamnose permeability test appears not to be valid.
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Randomized Controlled Trial Clinical Trial
Beta2-adrenoceptor polymorphism and bronchoprotective sensitivity with regular short- and long-acting beta2-agonist therapy.
The aim of the present study was to investigate bronchoprotective sensitivity in patients receiving regular treatment with short- and long-acting beta2-agonists and to evaluate any possible association with genetic polymorphism. Thirty-eight patients with stable mild to moderate asthma and receiving inhaled corticosteroids were randomized in a parallel group, double-blind, double-dummy fashion to receive 2 weeks of treatment with either formoterol (12 microg once daily, 6 microg twice daily or 24 microg twice daily) or terbutaline (500 microg four times daily). Bronchoprotection against methacholine challenge (as a provocative dose to produce a 20% fall in forced expiratory volume in 1.0 s: PD20) was measured at baseline (unprotected) after an initial 1 week run-in without beta2-agonist, and at 1 h after the first and last doses of each treatment. ⋯ M.) for percentage desensitization according to each genotype (pooled treatments): Gly-16, 66+/-11%; Het-16, 53+/-8%; Arg-16, 69+/-18%; Glu-27, 68+/-12%; Het-27, 58+/-8%; Gln-27, 52+/-12%. The results of this preliminary study showed that bronchoprotective desensitization occurred readily in response to short- or long-acting beta2-agonist exposure irrespective of beta2-adrenoceptor polymorphism at codon 16 or 27. Further studies with larger patient numbers are required to further evaluate the effects of polymorphisms with lower doses of regular formoterol.
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Randomized Controlled Trial Clinical Trial
Subcutaneous glucagon-like peptide-1 improves postprandial glycaemic control over a 3-week period in patients with early type 2 diabetes.
1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is released into the circulation after meals and is the most potent physiological insulinotropic hormone in man. GLP-1 has the advantages over other therapeutic agents for Type 2 diabetes of also suppressing glucagon secretion and delaying gastric emptying. ⋯ The beneficial effects of GLP-1 on plasma glucose, insulin and glucagon concentrations were fully maintained for the 3-week treatment period. 4. We have demonstrated a significant improvement in postprandial glycaemic control with subcutaneous GLP-1 treatment. GLP-1 improves glycaemic control partially by restoring the first-phase insulin response and suppressing glucagon and is a potential treatment for Type 2 diabetes.