91 research outputs found

    Sodium alginate decreases the permeability of intestinal mucus

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    In the small intestine the nature of the environment leads to a highly heterogeneous mucus layer primarily composed of the MUC2 mucin. We set out to investigate whether the soluble dietary fibre sodium alginate could alter the permeability of the mucus layer. The alginate was shown to freely diffuse into the mucus and to have minimal effect on the bulk rheology when added at concentrations below 0.1%. Despite this lack of interaction between the mucin and alginate, the addition of alginate had a marked effect on the diffusion of 500 nm probe particles, which decreased as a function of increasing alginate concentration. Finally, we passed a protein stabilised emulsion through a simulation of oral, gastric and small intestinal digestion. We subsequently showed that the addition of 0.1% alginate to porcine intestinal mucus decreased the diffusion of fluorescently labelled lipid present in the emulsion digesta. This reduction may be sufficient to reduce problems associated with high rates of lipid absorption such as hyperlipidaemia

    Tissue Glucocorticoid Metabolism in Adrenal Insufficiency:A Prospective Study of Dual-release Hydrocortisone Therapy

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    Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo.Study Design and Methods: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls.Results: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.Conclusion: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC

    The risk of metabolic syndrome as a result of lifestyle among Ellisras rural young adults

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    The study aimed to investigate the association between metabolic syndrome (MetS) and lifestyle risk factors among Ellisras adults. A cross-sectional study was conducted on 624 adults (306 males and 318 females). MetS was defined according to the criteria of the International Diabetes Federation. The prevalence of MetS was 23.1% (8.6% males and 36.8 % females). Females appeared to have higher mean values for waist circumference (WC), fasting blood glucose (FBG), total cholesterol (TCHOL) and low-density lipoprotein cholesterol (LDL-C), while males had high mean values for high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP). No significant age and gender differences were observed for dietary intake. Significantly more females (51.9%) presented with increased WC than males (4.6%). Participants who had a high dietary energy intake were significantly less likely to present with larger WC (OR: 0.250 95% CI [0.161; 0.389]), low HDL-C (OR: 0.306 95% CI [0.220; 0.425]) and high LDL-C (OR: 0.583 95% CI [0.418; 0.812]) but more likely to present with elevated FBG (OR: 1.01 95% CI [0.735; 1.386]), high TCHOL (OR: 1.039 95% CI [0.575; 1.337]), high TG (OR: 1.186 95% CI [0.695; 2.023]) and hypertension (OR: 5.205 95% CI [3.156; 8.585]). After adjusting for age, gender, smoking, and alcohol status, high energy intake was more than two times likely to predict MetS in adults with a large WC (OR: 2.766 95% CI [0.863; 3.477] and elevated FBG (OR: 2.227 95% CI [1.051; 3.328]). Therefore, identifying groups that are at an increased risk and those that are in their early stages of MetS will help improve and prevent the increase of the MetS in the future

    Impact of cell types and culture methods on the functionality of in vitro liver systems - A review of cell systems for hepatotoxicity assessment.

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    Xenobiotic safety assessment is an area that impacts a multitude of different industry sectors such as medicinal drugs, agrochemicals, industrial chemicals, cosmetics and environmental contaminants. As such there are a number of well-developed in vitro, in vivo and in silico approaches to evaluate their properties and potential impact on the environment and to humans. Additionally, there is the continual investment in multidisciplinary scientists to explore non-animal surrogate technologies to predict specific toxicological outcomes and to improve our understanding of the biological processes regarding the toxic potential of xenobiotics. Here we provide a concise, critical evaluation of a number of in vitro systems utilised to assess the hepatotoxic potential of xenobiotics
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