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Insulin-like growth factor (IGF)-1 is a growth factor that can influence fibroblast functioning, with effects including the inhibition of collagenases and the induction of collagen expression.To assess whether serum IGF-1, IGF-binding protein (IGFBP)3 and the ratio between IGF-1 and IGFBP3, as a measure of IGF-1 bioavailability, are associated with facial ageing and skin wrinkling.From a random sample comprising 617 subjects from the Leiden Longevity Study, perceived age and skin wrinkling were assessed from facial photographs, and IGF-1 and IGFBP3 were measured in serum. The associations were assessed using linear regression models, adjusted for chronological age, sex, body mass index, smoking and sun exposure.Across tertiles of the ratio of IGF-1 to IGFBP3, and after adjusting for all potential confounding factors, the mean perceived age decreased from 60·6 years in the lowest tertile to 59·5 years in the highest (P = 0·045). Similarly, the mean skin wrinkling grade decreased from 4·8 in the lowest tertile to 4·5 in the highest (P = 0·011). Adding skin wrinkling as a covariate in the analysis between IGF-1 and perceived age diminished this association.This study demonstrates that a higher ratio of IGF-1 to IGFBP3 associates with a lower perceived age, via its association with reduced skin wrinkling. Whether high IGF-1 levels actually delay the accumulation of skin wrinkling now needs investigating.

To determine the effects of poorly absorbed solute on intestinal absorption, the urinary recovery of ingested lactulose, L-rhamnose, D-xylose, and 3-O-methyl-D-glucose was measured after simultaneous ingestion of various 'loads' of mannitol given in iso-osmolar solution. Mannitol reduced intestinal uptake of the poorly absorbed test sugars, lactulose and L-rhamnose; uptake of D-xylose and 3-O-methyl-D-glucose, which are absorbed by carrier-mediated transport largely from the jejunum, was less affected. The dose-response effect of mannitol on the absorption of L-rhamnose was approximately exponential; doses of 5, 10, and 20 g mannitol reduced the average urinary excretion of L-rhamnose by 34.7%, 51.7%, and 61.2%, respectively. In this respect, an osmotically equivalent load of lactulose, ingested as 'solute', was approximately twice as effective as mannitol in reducing L-rhamnose absorption, probably because lactulose is more poorly absorbed than mannitol (less than 1.0% versus 32-41%). Ingestion of other poorly absorbed solutes such as raffinose, sorbitol, xylitol, magnesium sulphate, and sodium sulphate also significantly depressed the absorption of L-rhamnose; in contrast, more efficiently absorbed solutes, such as sodium chloride, glucose, glycerol, and urea had little effect.

Investigation of intestinal disaccharide hydrolysis and permeability by means of a non-invasive differential sugar absorption test was performed in a family containing two siblings with primary sucrase-isomaltase deficiency. The procedure, which depends on measurement of urinary excretion ratios after the oral administration of lactose, sucrose, palatinose, lactulose and L-rhamnose, is capable of simultaneous determination of intestinal lactase, sucrase, and isomaltase activity and lactulose:rhamnose permeability. The results corresponded well with those of disaccharidase assay and histological findings in jejunal biopsy tissue obtained from the patients. Palatinose proved a satisfactory substrate for in vivo assessment of intestinal isomaltase activity. The method described provides a reliable and comprehensive assessment of intestinal disaccharide hydrolysis, and simultaneous estimation of permeability assists discrimination of primary from secondary disaccharidase deficiency. The ability to assess three different disaccharidase activities in addition to intestinal permeability by means of a single test, and the simplicity of preservation and transport of urine samples for sugar analysis, makes this a convenient, definitive method for the investigation of defective sugar absorption in both patients and population groups.

A patient with congenital asucrasia was investigated using in vivo differential urinary disaccharide excretion. Impaired hydrolysis of sucrose and isomaltose, but normal lactase activity, were demonstrated and confirmed by in vitro estimation. The technique of differential disaccharide excretion can now be used to assess three disaccharidases simultaneously, in vivo, including isomaltase.

The urinary excretion of lactulose, 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), L-rhamnose and polyethyleneglycol 400 (PEG-400) has been measured after intravenous and oral administration in healthy volunteers. Intestinal permeation of the probes was compared after their ingestion in iso-osmolar, hyperosmolar and cetrimide-containing test solutions. Urinary recovery of lactulose and 51Cr-EDTA after intravenous administration reached 75% by 5 h, and exceeded 90% at 24 h, and these values were 62 and 72%, respectively, for L-rhamnose. Recovery of PEG-400, however, varied with the relative molecular mass (Mr) of each polymer from 25.9 to 68.5% in 24 h. Intestinal permeation of ingested lactulose and 51Cr-EDTA was low, but that of L-rhamnose was 45-fold, and that of PEG-400 100-fold, greater. Permeation of lactulose and 51Cr-EDTA was markedly increased by cetrimide and hyperosmolar stress, whereas that of L-rhamnose showed little change. PEG-400 permeation was not affected by cetrimide, but was slightly increased by hyperosmolar stress. The 5 h permeation of lactulose, but not of L-rhamnose or PEG-400, correlated with that of 51Cr-EDTA (r = 0.98, P less than 0.001). These findings are compatible with three distinct pathways of unmediated mucosal permeation, L-rhamnose (radius less than 0.4 nm) passing mainly through small aqueous 'pores' of high incidence, lactulose and 51Cr-EDTA (radius greater than 0.5 nm) through larger aqueous 'channels' of low incidence susceptible to cetrimide and hyperosmolar stress, and PEG-400, which has appreciable lipid solubility, by partition through cell membrane lipid as well as the aqueous 'pores'.