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BACKGROUND: An increase in gastrointestinal viscosity or colonic fermentation is suggested to improve appetite control and reduce food intake. It has been proposed that beta-glucan and fructooligosaccharide (FOS) are food ingredients that increase gastrointestinal viscosity and colonic fermentation, but the results are inconclusive. OBJECTIVE: The objective was to test the effect of FOS, beta-glucan, or a combination thereof on appetite ratings and food intake over 2 consecutive days. DESIGN: In a 4-way balanced-order, crossover, double-blind design, 21 healthy volunteers [mean body mass index (in kg/m(2)) 25.9] consumed a meal-replacement bar at 0900 and an ad libitum lunch at 1300 on 2 consecutive days. On day 1 only, the subjects consumed a second (identical) bar at 1700 and a fixed snack at 1900. The control bar contained 0.3 g beta-glucan from 6.8 g oats (control), and the 3 equicaloric test bars contained an additional 0.9 g beta-glucan (from 8.0 g barley), 8 g FOS, or 0.9 g beta-glucan + 8 g FOS. Appetite scores and subsequent ad libitum test meal intakes were measured. Viscosities in response to bar consumption were determined under simulated gastric conditions. The results were analyzed by analysis of covariance. RESULTS: The addition of beta-glucan, FOS, or a combination thereof did not affect appetite ratings or food intake, although the addition of beta-glucan to the bar doubled gastric viscosity (841 compared with 351 mPa . s). CONCLUSIONS: Consumption of beta-glucan, FOS, or a combination thereof in meal-replacement bars at the levels tested for 2 consecutive days does not improve appetite control. Efficacy may have improved if the consumption period was longer, if the content of beta-glucan was greater, or if a form of beta-glucan that generates even higher gastric viscosity was consumed. This trial was registered at (clinicaltrials.gov) as NCT00776256. Copyright © 2009 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Based on 21 individual case studies, this article inventories the ways journalism deals with scientific uncertainty. The study identifies the decisions that impact a journalist's perception of a truth claim as unambiguous or ambiguous and the strategies to deal with uncertainty that arise from this perception. Key for understanding journalistic action is the outcome of three evaluations: What is the story about? How shall the story be told? What type of story is it? We reconstructed the strategies to overcome journalistic decision-making uncertainty in those cases in which they perceived scientific contingency as a problem. Journalism deals with uncertainty by way of omission, by contrasting the conflicting messages or by acknowledging the problem via the structure or language. One finding deserves particular mention: The lack of focus on scientific uncertainty is not only a problem of how journalists perceive and communicate but also a problem of how science communicates., (© The Author(s) 2016.)

This introduction sets the stage for the special issue on the public communication of scientific uncertainty that follows by sketching the wider landscape of issues related to the communication of uncertainty and showing how the individual contributions fit into that landscape. The first part of the introduction discusses the creation of media content as a process involving journalists, scientific sources, stakeholders, and the responsive audience. The second part then provides an overview of the perception of scientific uncertainty presented by the media and the consequences for the recipients' own assessments of uncertainty. Finally, we briefly describe the six research articles included in this special issue., (© The Author(s) 2016.)

In order to map scientists' views on media channels and explore their experiences interacting with journalists, the authors conducted a survey of about 1,000 Brazilian scientists. Results indicate that scientists have clear and high expectations about how journalists should act in reporting scientific information in the media, but such expectations, in their opinion, do not always seem to be met. Nonetheless, the results show that surveyed scientists rate their relation with the media positively: 67% say that having their research covered by media has a positive impact on their colleagues. One quarter of the respondents expressed that talking to the media can facilitate acquisition of more funds for research. Moreover, 38% of the total respondents believe that writing about an interesting topic for release on media channels can also facilitate research publication in a scientific journal. However, 15% of the respondents outright agree that research reported in the media beforehand can threaten acceptance for publication by a scientific journal. We hope that these results can foster some initiatives for improving awareness of the two cultures, scientists and journalists; increasing the access of journalists to Brazilian scientific endeavors; stimulating scientists to communicate with the public via social networks.

Background: Urinary excretion of alpha-1-microglobulin and beta-2-microglobulin reflects tubular damage and predicts outcome in patients with idiopathic membranous nephropathy with reasonable accuracy. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are novel biomarkers of tubular damage. We investigated if these markers could improve prediction of outcome in idiopathic membranous nephropathy., Methods: We measured kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in urine samples from patients with idiopathic membranous nephropathy, who had nephrotic proteinuria and normal renal function. Excretion of alpha-1-microglobulin and beta-2-microglobulin had been measured previously. Progression was defined as a serum creatinine rise >30%, a rise in serum creatinine to an absolute value of ≥135 µmol/L, or a clinical decision to start immunosuppressive therapy. Remission was defined as proteinuria <3.5 g/day and >50% reduction from baseline., Results: Sixty-nine patients were included. Median follow-up was 35 months (interquartile range 18-63 months). Progression occurred in 30 patients (44%), and spontaneous remission in 36 (52%). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates were significantly correlated with each other, and with alpha-1-microglobulin and beta-2-microglobulin. The areas under the receiver operating characteristic curves for progression were 0.75 (0.62-0.87) for kidney injury molecule-1 and 0.74 (0.62-0.87) for neutrophil gelatinase-associated lipocalin. In multivariate analysis with either alpha-1-microglobulin and beta-2-microglobulin, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not independently predict outcome., Conclusion: Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates correlated with excretion rates of other tubular damage markers and predicted outcome in patients with idiopathic membranous nephropathy. They did not add prognostic value compared to measurement of either alpha-1-microglobulin or beta-2-microglobulin., (© The Author(s) 2015.)

Background: There is limited evidence to support cytotoxic therapy in patients with IgA nephropathy and renal insufficiency. We studied the effect of cytotoxic therapy in patients with IgA nephropathy and renal insufficiency, and evaluated possible predictors of response., Methods: Retrospective analysis of patients with IgA nephropathy who received immunosuppressive therapy. The primary outcome measure was progression of renal disease, defined as an increase in serum creatinine levels of ≥ 50% or development of end-stage renal disease., Results: From 1996 to 2008, 19 patients with biopsy-proven IgA nephropathy were treated with cytotoxic agents and prednisone because of renal insufficiency and÷ or severe proteinuria. Characteristics of patients at the start of therapy: age 42&plusmn;11 years, serum creatinine 208 (96-490) μmol÷l, estimated glomerular filtration rate (eGFR) 33 (12-65) ml÷min÷1.73 m2, and protein- creatinine ratio 3.8 (0.6-18.2) g÷10 mmol. Follow-up after initiation of therapy was 35 (7-133) months. Ten patients had progressive renal disease, whereas eGFR was stable in nine. Serum creatinine levels and proteinuria at the start of treatment were not significantly different between responders and non- responders. Proteinuria response at six months after start of therapy proved a good predictor: proteinuria decreased by ≥ 50% and÷or reached levels below 1 g÷day in 8÷9 responders. In contrast, proteinuria decreased by more than 50% and reached levels < 1 g÷day in only 3÷10 non-responders (p < 0.01)., Conclusion: Prolonged immunosuppressive therapy with cytotoxic agents and prednisone may benefit a subgroup of patients with progressive IgA nephropathy. A reduction of proteinuria ≥ 50% to levels below 1 g÷day within six months predicts a favourable long-term response.

Background: Intragastric creaming and droplet size of fat emulsions may affect intragastric behavior and gastrointestinal and satiety responses., Objectives: We tested the hypotheses that gastrointestinal physiologic responses and satiety will be increased by an increase in intragastric stability and by a decrease in fat droplet size of a fat emulsion., Methods: This was a double-blind, randomized crossover study in 11 healthy persons [8 men and 3 women, aged 24 ± 1 y; body mass index (in kg/m(2)): 24.4 ± 0.9] who consumed meals containing 300-g 20% oil and water emulsion (2220 kJ) with 1) larger, 6-μm mean droplet size (Coarse treatment) expected to cream in the stomach; 2) larger, 6-μm mean droplet size with 0.5% locust bean gum (LBG; Coarse+LBG treatment) to prevent creaming; or 3) smaller, 0.4-μm mean droplet size with LBG (Fine+LBG treatment). The participants were imaged hourly by using MRI and food intake was assessed by using a meal that participants consumed ad libitum., Results: The Coarse+LBG treatment (preventing creaming in the stomach) slowed gastric emptying, resulting in 12% higher gastric volume over time (P < 0.001), increased small bowel water content (SBWC) by 11% (P < 0.01), slowed appearance of the (13)C label in the breath by 17% (P < 0.01), and reduced food intake by 9% (P < 0.05) compared with the Coarse treatment. The Fine+LBG treatment (smaller droplet size) slowed gastric emptying, resulting in 18% higher gastric volume (P < 0.001), increased SBWC content by 15% (P < 0.01), and significantly reduced food intake by 11% (P < 0.05, equivalent to an average of 411 kJ less energy consumed) compared with the Coarse+LBG treatment. These high-fat meals stimulated substantial increases in SBWC, which increased to a peak at 4 h at 568 mL (range: 150-854 mL; P < 0.01) for the Fine+LBG treatment., Conclusion: Manipulating intragastric stability and fat emulsion droplet size can influence human gastrointestinal physiology and food intake.

Background/objectives: We have previously shown that 500 ml of a foamed drink ('foam') significantly improved appetite versus a non-foamed control. The objectives of this research were to assess the effect of smaller volumes of foams on appetite, and the potential benefits of foam ingestion and its timing on appetite measures in a reduced-energy context., Subjects/methods: Two randomized, parallel design studies (pre- and main study) were conducted using healthy adult subjects. Pre-study: 133 subjects (age 18-50 years, body mass index (BMI) 20-32 kg m(-2)) each consumed either 10, 25, 50, 100, 150 or 250 ml foamed meal replacer (~0.2 kcal ml(-1)), 150 min after a fixed breakfast. Main study: four groups of subjects (n=134; age 18-60 years, BMI 22.5-35.0 kg m(-2)) consumed 200 ml/22 kcal foam (based on pre-study results) immediately after main meals (M), after snacks (S), in-between snacks and main meals (I) or not at all (control, C) within 1 day of a reduced-energy meal plan consisting of three main meals and three snacks. Measurements included self-reported appetite (six scales, reported as area under the curve (AUC)) and (main study only) end-of-day appetite questionnaire., Results: Pre-study: the strongest effect on appetite was produced by 250 ml (consistent across scales), whereas 150 ml showed more pronounced effects than 100 and 50 ml in most scales. Volumes 10 and 25 ml had no effects on any scale. Main study: 200 ml foam reduced appetite AUC substantially in all treatments, particularly M (for example, hunger AUC reduced by 35% (P <0.001), 28% (P <0.05) and 20% (P=0.11) for M, S and I, respectively versus C). A strong reduction in 'appetite for a snack' was seen for all timings (all P <0.05). The end-of-day appetite ratings confirmed these findings., Conclusions: Modest amounts of a low-energy foam can reduce appetite measures during a 1-day reduced-energy meal plan.

Background: Compared with nonaerated, isocaloric controls, aerated foods can reduce appetite throughout an entire dieting day. Increased gastric volumes and delayed emptying are possible but unexplored mechanisms., Objective: We tested the hypothesis that aerated drinks (foams) of differing gastric stability would increase gastric distension and reduce appetite compared with a control drink., Design: In a randomized, balanced, crossover trial, 18 healthy male participants consumed the following 3 skimmed-milk-based test products (all 110 kcal): 2 drinks aerated to foams by whipping (to 490 mL), one drink that was stable in the stomach [stable foam (SF)], and one drink that was less stable in the stomach [less-stable foam (LSF)], and a nonaerated drink [liquid control (LC); 140 mL]. Over 4 h, stomach contents (foam, air, and liquid) were imaged using magnetic resonance imaging (MRI), and self-reported appetite ratings were collected and quantified by the area under the curve or time to return to baseline (TTRTB)., Results: Compared with the LC, both foams caused significantly increased gastric volumes and reduced hunger (all P < 0.001). Compared with the LSF, SF further produced a significantly slower decrease in the total gastric content (P < 0.05) and foam volume (P < 0.0001) and a longer TTRTB (197 compared with 248 min, respectively; P < 0.05), although the hunger AUC was not statistically different. Results for other appetite scales were similar., Conclusions: With this MRI trial, we provide novel insights on the gastrointestinal behavior of aerated drinks by measuring separate volumes of foam, liquid, and air layers in the stomach. Appetite suppression induced by foams could largely be explained by effects on gastric volumes and emptying, which may be further enhanced by foam stability. This trial was registered at clinicaltrials.gov as NCT01690182., (© 2015 American Society for Nutrition.)

The article presents results from surveys of life scientists in Taiwan (n=270) and in Germany (n=326). Fewer Taiwanese than German researchers have frequent contact with the media and they rate their experiences with journalists less positively. Furthermore, they are less prepared to adapt to journalistic expectations and to a greater extent than German researchers they expect journalists to consider scientific criteria in their reporting. These findings are interpreted in Weingart's "medialization of science" framework as indicators of lower medialization of science in Taiwan than in Germany. However, Taiwanese scientists are more willing than German scientists to accept journalistic simplification at the expense of accuracy. This is explained as an adaptation to the media system and to the perceived scientific literacy of the media audience. We hypothesize that cultural differences regarding the relative priority of relational vs. rational communication goals may also contribute to more tolerance of journalistic simplification in Taiwan., (© The Author(s) 2013.)

Objective: Simple aeration of food matrices with gas has previously been shown to generate immediate suppression of appetite, though duration of effects has not been shown. This research tested whether liquids aerated with nitrous oxide (N2 O) to achieve high in-body stability could produce enhanced and sustained effects on eating motivations., Methods: In two randomized cross-over studies, appetite ratings were collected for 240 min. In Study 1, 24 volunteers consumed a full portion liquid (325 ml, 190 kcal) or aerated (1,000 ml, 190 kcal) drink at 0 min, or half portions of liquid (162 ml, 95 kcal) or aerated (500 ml, 95 kcal) drink at 0 and 120 min. In Study 2, assessing the effect of N2 O itself, 23 volunteers consumed water saturated with N2 O or with CO2 10 min after a mini-drink (180 kcal). Appetite was quantified by area-under-the curve (AUC) and time-to-return-to-baseline (TTRTB)., Results: Full- and half-size aerated drinks decreased hunger AUC over 4 h by 26 and 50% (P < 0.0001) versus the respective liquid versions. Effects were also sustained significantly longer (TTRTB from 203 to 335 and from 173 to 286 min, respectively). In Study 2, N2 O and CO2 had similar effects on appetite ratings., Conclusions: Aeration of foods using appropriate microstructural design has a powerful effect on eating motivations., (Copyright © 2014 The Obesity Society.)

For several decades scholars have studied media reporting on scientific issues that involve controversy. Most studies so far have focused on the western world. This article tries to broaden the perspective by considering China and comparing it to a western country. A content analysis of newspaper coverage of vaccination issues in the UK and China shows, first, that the government-supported 'mainstream position' dominates the Chinese coverage while the British media frequently refer to criticism and controversy. Second, scientific expertise in the British coverage is represented by experts from the health and science sector but by experts from health agencies in the Chinese coverage. These results are discussed with respect to implications for risk communication and scientists' involvement in public communication.

Purpose: Small fat droplets infused into the gut reduce food intake and hunger more than bigger ones, at levels as low as 6 g, and these effects are hypothesized to occur via satiety hormones such as cholecystokinin. It is, however, unknown whether the effect of droplet size would persist after oral consumption. It is also unknown whether an even smaller droplet size can affect hunger and food intake and at what minimum amount of fat. Therefore, the aim of the study was to test the effect of very fine fat droplets on satiety and food intake in two different quantities., Methods: In a balanced-order 4-way crossover design, 24 volunteers consumed a fat-free meal replacement drink with either 5 or 9 g oil (rapeseed) and either 3 or 0.1 μm droplet size. Appetite scores and plasma cholecystokinin levels (in n = 12 subset) were measured for 180 min, when food intake was assessed during an ad libitum meal. Data were analyzed by ANCOVA, followed by Dunnett's test and paired t test. The behavior of the emulsions was also characterized in a simulated gastrointestinal model., Results: Despite faster in vitro lipolysis of the smallest droplets, neither droplet size nor fat amount affected satiety or food intake. From t = 45-150 min, cholecystokinin response was 50% higher (P < 0.05) after the 0.1 versus 3 μm, but only with 9 g fat., Conclusion: When this particular fat at these amounts is delivered in a meal replacement drink, droplet size does not influence appetite or food intake. This effect is independent of the amount of fat or plasma cholecystokinin changes.

The present article presents an up-to-date account of the current media relations of scientists, based on a comprehensive analysis of relevant surveys. The evidence suggests that most scientists consider visibility in the media important and responding to journalists a professional duty--an attitude that is reinforced by universities and other science organizations. Scientific communities continue to regulate media contacts with their members by certain norms that compete with the motivating and regulating influences of public information departments. Most scientists assume a two-arena model with a gap between the arenas of internal scientific and public communication. They want to meet the public in the public arena, not in the arena of internal scientific communication. Despite obvious changes in science and in the media system, the orientations of scientists toward the media, as well as the patterns of interaction with journalists, have their roots in the early 1980s. Although there is more influence on public communication from the science organizations and more emphasis on strategic considerations today, the available data do not indicate abrupt changes in communication practices or in the relevant beliefs and attitudes of scientists in the past 30 y. Changes in the science-media interface may be expected from the ongoing structural transformation of the public communication system. However, as yet, there is little evidence of an erosion of the dominant orientation toward the public and public communication within the younger generation of scientists.

This article presents the results of a survey carried out at two space outreach events in the UK aimed at characterising "the public for space exploration" and measuring public support for space exploration. Attitude towards space exploration and policy preferences were used as measures of public support. The sample involved 744 respondents and was mainly composed of adults between 25 and 45 years old, with men slightly over-represented compared with women. Findings revealed that males appeared to be stronger supporters than females - men had a more positive attitude towards space exploration and stronger space policy preferences. Because mixed groups tend to come together to such events we argue that male respondents would be more likely to be part of the "attentive" and "interested" public who come to outreach activities and bring a less interested public with them.

Background: Hepcidin is a central regulator of iron metabolism. Serum hepcidin levels are increased in patients with renal insufficiency, which may contribute to anemia. Urine hepcidin was found to be increased in some patients after cardiac surgery, and these patients were less likely to develop acute kidney injury. It has been suggested that urine hepcidin may protect by attenuating heme-mediated injury, but processes involved in urine hepcidin excretion are unknown., Methods: To assess the role of tubular reabsorption we compared fractional excretion (FE) of hepcidin-25 with FE of β2-microglobulin (β(2)m) in 30 patients with various degrees of tubular impairment due to chronic renal disease. To prove that hepcidin is reabsorbed by the tubules in a megalin-dependent manner, we measured urine hepcidin-1 in wild-type and kidney specific megalin-deficient mice. Lastly, we evaluated FE of hepcidin-25 and β(2)m in 19 patients who underwent cardiopulmonary bypass surgery. Hepcidin was measured by a mass spectrometry assay (MS), whereas β(2)m was measured by ELISA., Results: In patients with chronic renal disease, FE of hepcidin-25 was strongly correlated with FE of β(2)m (r = 0.93, P <0.01). In megalin-deficient mice, urine hepcidin-1 was 7-fold increased compared to wild-type mice (p < 0.01) indicating that proximal tubular reabsorption occurs in a megalin- dependent manner. Following cardiac surgery, FE of hepcidin-25 increased despite a decline in FE of β(2)m, potentially indicating local production at 12-24 hours., Conclusions: Hepcidin-25 is reabsorbed by the renal tubules and increased urine hepcidin-25 levels may reflect a reduction in tubular uptake. Uncoupling of FE of hepcidin-25 and β(2)m in cardiac surgery patients suggests local production.

Background: Measurement of serum hepcidin levels may provide a useful alternative to the current methods of determining iron status in chronic haemodialysis (HD) patients. However, the biological variability of this pivotal regulator of iron homeostasis is unclear, and the impact of inflammation, dialysis clearance and iron therapy on hepcidin variability has not been established., Methods: Two independent studies in chronic HD patients were conducted; serum hepcidin levels were measured at the start of dialysis sessions in 20 UK patients and in 43 Dutch patients by mass spectrometry (MS). Samples from UK patients were also analysed by a competitive enzyme-linked immunosorbent assay (cELISA). Coefficient of variance (CV(1)) was calculated and potential factors affecting CV(1) were also examined., Results: The median CV(1) (inter-quartile range) was 23% (17-28) for the UK MS, 26% (17-48) for the Dutch MS and 23% (17-39) for the UK cELISA. The CV(1) was similar in those patients receiving and those not receiving regular intravenous iron. The CV(1) was not associated with the degree of inflammation. Hepcidin levels were higher following an inter-dialytic period of 3 versus 2 days (P = 0.02)., Conclusions: These findings suggest considerable variability of serum hepcidin levels in HD patients. Inflammation and the use of iron did not impact on the degree of variability, and hepcidin levels were higher after an inter-dialytic period of 3 versus 2 days. These findings need to be taken into account in future studies assessing the utility of serum hepcidin as a guide to the use of iron or erythropoiesis-stimulating agents therapy.

Background & Aims: : Infusion of fat into the small intestine induces satiety. Reducing fat droplet size accelerates fat digestion, but the effect on satiety after ileal fat infusion is not known. The aim of the study was to compare the effects of fat emulsions differing in droplet size (fine, coarse) infused in either duodenum or ileum on satiety, gastric emptying and peptide secretion., Methods: In a randomized single-blind crossover study 15 healthy volunteers received, after intubation with a nasoileal tube, 4 different treatments on 4 consecutive days. After consumption of a liquid meal, 6 g of fine or coarse fat emulsion was infused into duodenum or ileum. Study parameters were satiety, gastric emptying and gut peptides. These parameters were statistically evaluated using ANCOVA., Results: In the duodenum, Fine emulsion significantly reduced hunger, increased fullness, delayed gastric emptying, but did not affect peptide secretion versus Coarse. In the ileum, Fine emulsion did not affect hunger, fullness, or gastric emptying, but significantly increased peptide secretion versus Coarse., Conclusions: Compared to larger fat droplets, smaller droplets significantly affect satiety, gastric emptying and gut peptide release, but with the effect being dependent on the intestinal location of fat delivery. DUTCH TRIALREGISTER: NTR1515., (Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Connective tissue growth factor (CTGF) has a key role in the pathogenesis of renal and cardiac fibrosis. Its amino-terminal fragment (N-CTGF), the predominant form of CTGF detected in plasma, has a molecular weight in the middle molecular range (18 kDa). However, it is unknown whether N-CTGF is a uremic retention solute that accumulates in chronic kidney disease (CKD) due to decreased renal clearance and whether it can be removed by hemodiafiltration., Study Design: 4 observational studies in patients and 2 pharmacokinetic studies in rodents., Setting & Participants: 4 single-center studies. First study (cross-sectional): 88 patients with CKD not receiving kidney replacement therapy. Second study (cross-sectional): 23 patients with end-stage kidney disease undergoing low-flux hemodialysis. Third study: 9 kidney transplant recipients before and 6 months after transplant. Fourth study: 11 low-flux hemodialysis patients and 12 hemodiafiltration patients before and after one dialysis session., Predictor: First, second, and third study: (residual) glomerular filtration rate (GFR). Fourth study: dialysis modality., Outcomes & Measurements: Plasma (N-)CTGF concentrations, measured by enzyme-linked immunosorbent assay., Results: In patients with CKD, we observed an independent association between plasma CTGF level and estimated GFR (β = -0.72; P < 0.001). In patients with end-stage kidney disease, plasma CTGF level correlated independently with residual kidney function (β = -0.55; P = 0.046). Successful kidney transplant resulted in a decrease in plasma CTGF level (P = 0.008) proportional to the increase in estimated GFR. Plasma CTGF was not removed by low-flux hemodialysis, whereas it was decreased by 68% by a single hemodiafiltration session (P < 0.001). Pharmacokinetic studies in nonuremic rodents confirmed that renal clearance is the major elimination route of N-CTGF., Limitations: Observational studies with limited number of patients. Fourth study: nonrandomized, evaluation of the effect of one session; randomized longitudinal study is warranted., Conclusion: Plasma (N-)CTGF is eliminated predominantly by the kidney, accumulates in CKD, and is decreased substantially by a single hemodiafiltration session., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Visual analogue scales (VAS) are a standard tool used to measure subjective appetite. To explore a potentially more intuitive and precise alternative, we developed a method based on pictures and assessed its performance characteristics vs. VAS. The objective was to compare the capacity of the two methods to discriminate appetite ratings between interventions. Both methods were applied within a previously published trial in which 16 healthy adults received standardised meals followed by three different ileal infusions in a balanced crossover design. At regular intervals volunteers indicated how many units of individually pictured food portions (for 10 different items) they would like to eat, and also scored six VAS. Methods were compared over different timeframes and assessed for their sensitivity to intervention effects. Pictures were more sensitive than VAS in differentiating intervention effects; however, further refinement and validation would be needed for pictures to become a standardised and accepted alternative to VAS for this type of research., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The site of intestinal fat delivery affects satiety and may affect food intake in humans. Animal data suggest that the length of the small intestine exposed to fat is also relevant. The aim of the present study was to investigate whether increasing the areas of intestinal fat exposure and the way it is exposed would affect satiety parameters and food intake. In the present single-blind, randomised, cross-over study, fifteen volunteers, each intubated with a naso-ileal tube, received four treatments on consecutive days. The oral control (control treatment) was a liquid meal (LM) containing 6 g fat ingested at t = 0 min, with saline infusion at t = 30-120 min. Experimental treatments were a fat-free LM at t = 0 min, with either 6 g oil delivered sequentially (2 g duodenal, t = 30-60 min; 2 g jejunal, t = 60-90 min; 2 g ileal, t = 90-120 min), simultaneously (2 g each to all sites, t = 30-120 min) or ileal only (6 g ileal, t = 30-120 min). Satiety parameters (hunger and fullness) and cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY) secretion were measured until t = 180 min, when ad libitum food intake was assessed. Only the ileum treatment reduced food intake significantly over the control treatment. The ileum and simultaneous treatments significantly reduced hunger compared with the control treatment. Compared with control, no differences were observed for PYY, CCK and GLP-1 with regard to 180 min integrated secretion. Ileal fat infusion had the most pronounced effect on food intake and satiety. Increasing the areas of intestinal fat exposure only affected hunger when fat was delivered simultaneously, not sequentially, to the exposed areas. These results demonstrate that ileal brake activation offers an interesting target for the regulation of ingestive behaviour.

Background: The variable course of immunoglobulin A nephropathy (IgAN) warrants accurate tools for the prediction of progression. Urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are markers for the detection of early tubular damage caused by various renal conditions. We evaluated the prognostic value of these markers in patients with IgAN., Methods: We included patients (n = 65, 72% male, age 43 ± 13 years) with biopsy-proven IgAN, who were evaluated for proteinuria. Urinary KIM-1 and NGAL were measured by enzyme-linked immunosorbent assay. We analysed data using Cox regression for the outcome end-stage renal disease (ESRD)., Results: Median serum creatinine was 142 μmol/L and proteinuria 2.2 g/day. During follow-up (median 75 months), 23 patients (35%) developed ESRD. In patients with IgAN median urinary KIM-1 excretion was 1.7 ng/min and NGAL excretion was 47 ng/min, both significantly higher than in healthy controls. KIM-1 and NGAL were correlated with proteinuria (r = 0.40 and 0.34, respectively, P < 0.01) and each other (r = 0.53, P < 0.01) but not with estimated glomerular filtration rate (eGFR). Interestingly, KIM-1 was not significantly correlated with the excretion of α(1)-microglobulin (α(1)m) and β(2)-microglobulin (β(2)m), known markers of tubular injury. Univariate analysis showed that baseline serum creatinine and urinary excretion of total protein, α(1)m, β(2)m, immunoglobulin G, KIM-1 and NGAL were significantly associated with ESRD. By multivariate analysis, serum creatinine and KIM-1 excretion proved to be significant independent predictors of ESRD., Conclusion: KIM-1 and NGAL excretion are increased in patients with IgAN and correlate with proteinuria but not with eGFR. Baseline serum creatinine and urinary KIM-1, but not proteinuria, are independent predictors of ESRD.

Addition of specific types of alginates to drinks can enhance postmeal suppression of hunger, by forming strong gastric gels in the presence of calcium. However, some recent studies have not demonstrated an effect of alginate/calcium on appetite, perhaps because the selected alginates do not produce sufficiently strong gels or because the alginates were not sufficiently hydrated when consumed. Therefore, the objective of the study was to test effects on appetite of a strongly gelling and fully hydrated alginate in an acceptable, low-viscosity drink formulation. In a balanced order crossover design, 23 volunteers consumed a meal replacement drink containing protein and calcium and either 0 (control), 0.6, or 0.8% of a specific high-guluronate alginate. Appetite (six self-report scales) was measured for 5 h postconsumption. Relevant physicochemical properties of the drinks were measured, i.e., product viscosity and strength of gel formed under simulated gastric conditions. Hunger was robustly reduced (20-30% lower area under the curve) with 0.8% alginate (P < 0.001, analysis of covariance), an effect consistent across all appetite scales. Most effects were also significant with 0.6% alginate, and a clear dose-response observed. Gastric gel strength was 1.8 and 3.8 N for the 0.6 and 0.8% alginate drinks, respectively, while product viscosity was acceptable (<0.5 Pa.s at 10 s(-1)). We conclude that strongly gastric-gelling alginates at relatively low concentrations in a low-viscosity drink formulation produced a robust reduction in hunger responses. This and other related studies indicate that the specific alginate source and product matrix critically impacts upon apparent efficacy.

Background: Protease inhibitor 2 derived from potato (PI2) is claimed to reduce appetite and food intake, stimulate the satiety hormone cholecystokinin (CCK) and lower postprandial glucose peaks when taken before a meal. However, current literature is inconclusive with regard to its efficacy and mechanism. Furthermore, the potential effect of PI2 on appetite motivational ratings without an immediately following meal has not previously been reported., Objective: To comprehensively test the effects of 30 mg PI2 in a minidrink on appetite ratings, subsequent food intake, and plasma CCK and glucose responses., Design: Minidrinks with or without 30 mg PI2 were compared in three separate substudies (A, B and C), each using a two-way, placebo-controlled, balanced-order, cross-over design and 23 or 24 subjects (mean over groups: body mass index 25.0 kg m(-2), range 22.5-30.7 kg m(-2); age 41.3, range 18-62 years). The minidrink was given (A) 120 or (B) 30 min before an ad libitum lunch or (C) 30 min before a fixed lunch. Study parameters were self-reported satiety (substudies A and C), ad libitum meal intake (substudies A and B), and (in an n=12 subset) plasma CCK and blood glucose in all substudies. All results were analyzed using analysis of covariance. Protease-inhibitory activity of the PI2-containing minidrinks was assessed under simulated gut conditions., Results: PI2 did not differ from control for any study parameters, in any substudy, despite confirmation of the inhibitory activity of PI2., Conclusions: In this study protease inhibition using PI2 in a minidrink at a dose of 30 mg, as commercially used, had no (functional) efficacy on a range of behavioral and physiological appetite and intake control measures.

Background/objectives: To investigate the feasibility of Fabuless (previously called Olibra and Reducal) as a food ingredient for food intake and appetite reduction, by assessing the effects of food processing on efficacy., Subjects/methods: In total, 24 healthy volunteers (16 female, 8 male; age: 18-43 years; body mass index: 18-37 kg/m(2)) took part in a randomized, placebo-controlled, double-blinded, cross-over trial. Yoghurt-based meal replacement drinks (containing processed or unprocessed Fabuless, or a control fat) were followed by an ad libitum lunch and evening meal (dinner). Key outcome measures were energy intake and self-reported appetite ratings., Results: Compared with control, only unprocessed Fabuless reduced subsequent energy intake, although only during dinner (P < 0.01; control, processed and unprocessed: 4.3, 3.9 and 4.2 MJ, respectively) and not during lunch (3.6, 3.7 and 3.6 MJ). Self-reported appetite scores did not differ between treatments., Conclusions: Although modest effects of unprocessed Fabuless were seen on food intake, but not on appetite, the ingredient was not robust to common food-manufacturing processes (thermal and shear processing). Claims on reduced food intake and appetite relating to this ingredient in food products are, therefore, only valid if functionality has been demonstrated after all relevant processing and storage steps.

Background/objectives: 'Slowly digestible' carbohydrates have been claimed to reduce appetite through their effects on postprandial glucose and insulin levels, but literature is inconsistent. The inconsistencies between studies might be explained by factors other than glycemic effects per se, for example, nutritional or physical properties. We tested this possibility by examining postprandial glucose, insulin and appetite responses to drinks differing only in rate and extent of digestibility of carbohydrates. This was accomplished by comparing different glucose polymers: maltodextrin (rapidly digestible) versus medium-chain pullulan (slowly but completely digestible) versus long-chain pullulan (indigestible)., Subjects/methods: In a randomized double-blind balanced crossover design, 35 subjects received drinks with 15 g test carbohydrate polymers. Key outcome measures were appetite scores, digestibility (in vitro test and breath hydrogen), and (in a subset) glucose and insulin levels., Results: Digestibility, glucose and insulin data confirmed the rapid, slow and nondigestible nature of the test carbohydrates. Despite its low digestibility, only long-chain pullulan reduced appetite compared with the maltodextrin control, whereas the medium-chain pullulan did not., Conclusions: We conclude that glycemic responses per se have minimal effects on appetite, when tested in products differing in only carbohydrate digestibility rate and extent.

Background: Hepcidin is an iron-regulatory peptide hormone that consists of 3 isoforms: bioactive hepcidin-25, and inactive hepcidin-22 and hepcidin-20. Hepcidin is instrumental in the diagnosis and monitoring of iron metabolism disorders, but reliable methods for its quantification in serum are sparse, as is knowledge of their relative analytical strengths and clinical utility., Methods: We developed a competitive (c)-ELISA and an immunocapture TOF mass-spectrometry (IC-TOF-MS) assay. Exploiting these 2 methods and our previously described weak cation exchange (WCX)-TOF-MS assay, we measured serum hepcidin concentrations in 186 patients with various disorders of iron metabolism and in 23 healthy controls., Results: We found that (a) the relative differences in median hepcidin concentrations in various diseases to be similar, although the absolute concentrations measured with c-ELISA and WCX-TOF-MS differed; (b) hepcidin isoforms contributed to differences in hepcidin concentrations between methods, which were most prominent in patients with chronic kidney disease; and (c) hepcidin concentrations measured by both the c-ELISA and IC-TOF-MS correlated with ferritin concentrations <60 μg/L, and were suitable for distinguishing between iron deficiency anemia (IDA) and the combination of IDA and anemia of chronic disease., Conclusions: c-ELISA is the method of choice for the large-scale quantification of serum hepcidin concentrations, because of its low limit of detection, low cost, and high-throughput. Because of its specificity for bioactive hepcidin-25, WCX-TOF-MS can be regarded as a valuable special-purpose assay for disorders with variable concentrations of hepcidin isoforms, such as chronic kidney disease.

Connective tissue growth factor (CTGF) plays a key role in renal fibrosis. Urinary CTGF is elevated in various renal diseases and may have biomarker potential. However, it is unknown which processes contribute to elevated urinary CTGF levels. Thus far, urinary CTGF was considered to reflect renal expression. We investigated how tubular dysfunction affects urinary CTGF levels. To study this, we administered recombinant CTGF intravenously to rodents. We used both full-length CTGF and the NH(2)-terminal fragment, since the NH(2)-fragment is the predominant form detected in urine. Renal CTGF extraction, determined by simultaneous arterial and renal vein sampling, was 18 +/- 3% for full-length CTGF and 21 +/- 1% for the NH(2)-fragment. Fractional excretion was very low for both CTGFs (0.02 +/- 0.006% and 0.10 +/- 0.02%, respectively), indicating that >99% of the extracted CTGF was metabolized by the kidney. Immunohistochemistry revealed extensive proximal tubular uptake of CTGF in apical endocytic vesicles and colocalization with megalin. Urinary CTGF was elevated in megalin- and cubilin-deficient mice but not in cubilin-deficient mice. Inhibition of tubular reabsorption by Gelofusine reduced renal uptake of CTGF and increased urinary CTGF. In healthy volunteers, Gelofusine also induced an increase of urinary CTGF excretion, comparable to the increase of beta(2)-microglobulin excretion (r = 0.99). Furthermore, urinary CTGF correlated with beta(2)-microglobulin (r = 0.85) in renal disease patients (n = 108), and only beta(2)-microglobulin emerged as an independent determinant of urinary CTGF. Thus filtered CTGF is normally reabsorbed almost completely in proximal tubules via megalin, and elevated urinary CTGF may largely reflect proximal tubular dysfunction.

Background: Hepcidin is a key regulator of iron homeostasis and levels are elevated in patients with chronic kidney disease (CKD). Hepcidin may explain the often observed imbalance in iron metabolism in patients with CKD. We evaluated the influence of estimated glomerular filtration rate (eGFR) on serum levels of hepcidin-25 and its isoforms in patients with renal dysfunction., Methods: Serum levels of the biologically active hepcidin-25 and its isoforms were determined in CKD and dialysis patients by a mass spectrometry-based assay., Results: In 83 patients with CKD not requiring dialysis, serum hepcidin-25 levels were not significantly increased (5.1 nM versus 4.2 nM, P = 0.30) and positively correlated with ferritin (r = 0.74, P < 0.01). Multiple regression analysis showed ferritin to be the only significant predictor of hepcidin-25 levels. Serum hepcidin-25 levels were not dependent on eGFR. In contrast, hepcidin-20 and total hepcidin levels showed an independent significant inverse correlation with eGFR. In 48 haemodialysis patients, median hepcidin-25 levels were significantly higher than in CKD patients (9.4 nM versus 5.1 nM, P < 0.001) and again strongly correlated with ferritin (r = 0.79, P < 0.001)., Conclusions: eGFR is not a major determinant of serum hepcidin-25 levels. In contrast, the hepcidin isoforms hepcidin-20 and hepcidin-22 accumulate in patients with renal impairment.

The aim of this paper is to describe and discuss relevant aspects of the assessment of physiological functions - and related biomarkers - implicated in the regulation of appetite in humans. A short introduction provides the background and the present state of biomarker research as related to satiety and appetite. The main focus of the paper is on the gastrointestinal tract and its functions and biomarkers related to appetite for which sufficient data are available in human studies. The first section describes how gastric emptying, stomach distension and gut motility influence appetite; the second part describes how selected gastrointestinal peptides are involved in the control of satiety and appetite (ghrelin, cholecystokinin, glucagon-like peptide, peptide tyrosin-tyrosin) and can be used as potential biomarkers. For both sections, methodological aspects (adequacy, accuracy and limitation of the methods) are described. The last section focuses on new developments in techniques and methods for the assessment of physiological targets involved in appetite regulation (including brain imaging, interesting new experimental approaches, targets and markers). The conclusion estimates the relevance of selected biomarkers as representative markers of appetite regulation, in view of the current state of the art.

Intestinal intubation studies have demonstrated that lipids induce satiety, but the contribution of lipid processing by the stomach on satiety remains poorly understood. In this explorative, randomized, placebo-controlled, crossover study we tested whether delayed lipid absorption, increased cholecystokinin (CCK), decelerated gastric emptying (GE), and increased satiety can be achieved by controlling lipid distribution in the stomach. Six healthy men were intubated nasogastrically. Two treatments were performed and repeated in duplicate. In the oil-on-top treatment (OT), subjects received a fat-free liquid meal (LM, 325 ml, 145 kcal) followed by intragastric infusion of 4 g of high-oleic-acid rapeseed oil (4.6 ml, 36 kcal) labeled with 77 mg glyceryl-[(13)C]trioleate. In the emulsion treatment (EM, control), 4 g of labeled rapeseed oil was incorporated into the LM (325 ml, 181 kcal); 4.6 ml of saline was infused as a control. In OT and EM a second LM was consumed at time t = 270 min. Plasma (13)C-C18:1, CCK and satiety were measured over 480 min. GE was determined by the paracetamol absorption test. OT delayed oleic acid absorption shown by an increased lag time of absorption (EM: 37 +/- 7 min; OT: 75 +/- 10 min; P < 0.01) and time at maximum concentration (EM: 162 +/- 18 min; OT: 280 +/- 33 min; P = 0.01). OT released more CCK than EM (P = 0.03), including increased CCK after the second meal. OT accelerated initial GE until 30 min postprandial. OT showed a tendency (P = 0.06) to suppress hunger and increase satiety and fullness 120-270 min postprandially. The results demonstrate that low amounts of lipids, when separated from the aqueous phase of a meal, delay lipid absorption and increase CCK. An escalating-dose study should determine whether this could have implications for the development of weight-control foods.

Background: Ileal delivery of fat reduces hunger and food intake through activation of the ileal brake. Physicochemical properties of fat have been shown to affect satiety and food intake., Objective: The objective of this study was to assess the effect of ileal fat emulsions with differing degrees of fatty acid saturation on satiety, food intake, and gut peptides (cholecystokinin and peptide YY). We hypothesized that long-chain triacylglycerols with diunsaturated fatty acids would increase satiety and reduce energy intake compared with long-chain triacylglycerols with monounsaturated or saturated fatty acids., Design: We performed a double-blind, randomized, crossover study in which 15 healthy subjects [mean age: 24 y; mean body mass index (in kg/m(2)): 22] were intubated with a naso-ileal catheter and participated in 4 experiments performed in random order on 4 consecutive days. After consumption of a liquid meal, subjects received a fat or control infusion in the ileum. Fat emulsions consisted of 6 g of 18:0 (shea oil; mainly 18:0), 18:1 (canola oil; mainly 18:1), or 18:2 (safflower oil; mainly 18:2) oils. Food intake was measured during an ad libitum lunch. Satiety questionnaires (visual analog scale) and blood samples were collected at regular intervals., Results: Compared with the control, only 18:2 and 18:1 significantly increased fullness and reduced hunger. No effect on food intake was observed. 18:1 and 18:2 increased cholecystokinin secretion significantly compared with the control. Fatty acid saturation did not affect peptide YY secretion., Conclusions: When infused into the ileum, triacylglycerols with unsaturated fatty acids increase satiety, whereas triacylglycerols with saturated fatty acids does not. This trial was registered with the Dutch Trial Register as: ISRCTN51742545.

Background: Immunoglobulin A nephropathy (IgAN) is characterised by high variability in clinical course and outcome. Accurate prediction of prognosis is needed to optimise treatment. Urinary alpha1-microglobulin and beta2-microglobulin are markers of tubulointerstitial injury and predict the risk of end-stage renal disease (ESRD) in idiopathic membranous nephropathy. We questioned the relevance of these markers in IgAN., Methods: We included patients with biopsy proven IgAN, who were evaluated for proteinuria in our centre between 1995 and 2007. Data were analysed using univariate and multivariate Cox regression for the outcome variables ESRD and progression (rise in serum creatinine of >50% or start of immunosuppressive therapy)., Results: Seventy patients (71% men) were selected. Median age was 39 years, median serum creatinine 140 micromol/l, and median proteinuria 2.4 g/day. Median urinary alpha1-microglobulin excretion was 23.5 microg/min (range 3.5-275.3) and median urinary beta2-microglobulin excretion was 0.4 microg/min (range 0.1-62.1). Both alpha1m and beta2m correlated significantly with serum creatinine (r = 0.65, p<0.01 and r = 0.62, p<0.01) and total proteinuria (r = 0.35, p<0.01 and r = 0.28, p<0.05). During follow-up (median 75 months) 25 patients (36%) developed ESRD , and 46 patients (66%) showed progression. 19 patients (27%) were treated with immunosuppressive agents. In univariate analysis urinary alpha1- and beta2-microglobulin predicted ESRD and progression. In multivariate analysis only serum creatinine and urinary protein were independent predictors of both outcomes., Conclusion: Urinary excretion of low molecular weight proteins did not offer an advantage over total proteinuria and serum creatinine in predicting prognosis in patients with IgAN.

Objective: The ileal brake is a feedback mechanism activated by nutrients, especially fat, with marked effects on satiety. The effects of low doses of ileal fat on satiety are largely unknown. We therefore studied the effect of ileal vs oral delivery of low doses of fat on satiety and gut peptide secretion., Design: Randomized, single-blind crossover design., Subjects: Sixteen healthy, normal-weight volunteers (6 male; mean age 26 years, mean body mass index 22.4)., Intervention: Participants were intubated with a 290-cm-long nasoileal tube and consumed, on 3 consecutive days, either a liquid breakfast with 3 g fat followed by an ileal placebo infusion at t=105-150 min (treatment C) or a fat-free liquid breakfast followed by an ileal infusion of either an emulsion of 3 g (treatment 13 g) or 9 g (treatment 19 g) fat (safflower oil)., Measurements: Satiety parameters by visual analog scales and plasma concentrations of CCK and PYY., Results: C significantly increased satiety and CCK secretion compared with the fat-free breakfast. Ileal fat perfusion of both 3 and 9 g 13 g and 19 g) significantly increased satiety during and after fat perfusion, without differences in satiety between 13 g and 19 g. During ileal fat infusion, CCK increased dose dependently, whereas PYY concentrations increased significantly only after 9 g of fat. Secretion of CCK but not of PYY correlated to satiety levels., Conclusion: Postprandial satiety following a liquid breakfast can be effectively and significantly increased by small amounts (as little as 3 g) of fat perfused into the ileum. Ileal fat dose-dependently increased CCK but not PYY secretion. The satiating effect of ileal fat may be partly mediated by CCK.

Minimal change nephropathy (MCNS) and focal segmental glomerulosclerosis (FSGS) are the main causes of the idiopathic nephrotic syndrome. MCNS usually responds to steroids and the long-term prognosis is generally good. However, some patients require prolonged treatment with immunosuppressive agents. FSGS generally follows a less favourable course: patients do not always respond to steroids and may progress to end-stage renal disease. Recurrence of FSGS after renal transplantation is frequently observed and may result in graft loss. Recently, anecdotal case reports have described long-term resolution of nephrotic syndrome due to MCNS or FSGS after treatment with rituximab. We present four patients with nephrotic syndrome due to MCNS, FSGS or recurrence of FS GS after kidney transplantation, who were treated with rituximab with variable success. A review of the recent literature suggests that anti-CD20 antibodies may be a promising therapy, especially for patients with MCNS or idiopathic FSGS. Controlled studies are required to determine the efficacy of rituximab and to define which patients will benefit.

With the rising prevalence of obesity and related health problems increases, there is increased interest in the gastrointestinal system as a possible target for pharmacological or food-based approaches to weight management. Recent studies have shown that under normal physiological situations undigested nutrients can reach the ileum, and induce activation of the so-called "ileal brake", a combination of effects influencing digestive process and ingestive behaviour. The relevance of the ileal brake as a potential target for weight management is based on several findings: First, activation of the ileal brake has been shown to reduce food intake and increase satiety levels. Second, surgical procedures that increase exposure of the ileum to nutrients produce weight loss and improved glycaemic control. Third, the appetite-reducing effect of chronic ileal brake activation appears to be maintained over time. Together, this evidence suggests that activation of the ileal brake is an excellent long-term target to achieve sustainable reductions in food intake. This review addresses the role of the ileal brake in gut function, and considers the possible involvement of several peptide hormone mediators. Attention is given to the ability of macronutrients to activate the ileal brake, and particularly variation attributable to the physicochemical properties of fats. The emphasis is on implications of ileal brake stimulation on food intake and satiety, accompanied by evidence of effects on glycaemic control and weight loss.

Background: The gastrointestinal tract elicits numerous signals regulating food intake and satiety, and recently many studies have been performed to elucidate the mechanisms regulating these signals., Aim: To describe the effects of the gastrointestinal tract on satiety, satiation and food intake., Methods: A PubMed search was performed to identify and select the relevant literature using search terms including 'gastric satiety, intestine + satiety, satiation, cholecystokinin, ghrelin, peptide YY, glucagon-like peptide-1 and ileal brake'., Results: Satiation, satiety and food intake result, among other factors, from signals originating in the stomach caused by distension and signals from the small intestine. These intestinal signals result from nutrient sensing in the gut and activate neural and humoral pathways. Activation of the distal part of the gut, the so called ileal brake, leads to reduction in hunger and food intake, and models of chronic ileal brake activation lead to massive weight loss., Conclusion: Gastrointestinal signals are crucial for the regulation of food intake, satiety and satiation. The ileal brake deserves special attention, as both ileal intubation studies and surgical studies demonstrate that activation of the ileal brake reduces food intake. In the surgical models, weight loss occurs without adaptation to the anorectic effects of ileal brake activation.

Vasopressin is a critical regulator of water homeostasis. There are two major receptors for vasopressin: V1 and V2 receptors. Disturbances in water balance are commonly encountered in clinical practice and can be divided into disorders of urinary dilution and concentration. The major representatives of such disorders are diabetes insipidus and the syndrome of inappropriate secretion of antidiuretic hormone (SI ADH). Recent studies show that genetic forms of nephrogenic diabetes insipidus are due to mutations in the genes coding for the vasopressin V2 receptor (V2R) or aquaporin-2 (AQP2). Identification of the genes involved and analysis of the cellular fate of the V2R and AQP2 mutants are relevant for understanding the functioning of the V2R and AQP2 protein. These developments also have implications for future therapeutic options. The development of nonpeptide vasopressin receptor antagonists (VRAs) offers prospects for the treatment of euvolaemic (SI ADH) or hypervolaemic hyponatraemia (congestive heart failure or cirrhosis). Several nonpeptide VRAs are now in various stages of clinical trials. At present, only conivaptan is registered by the FD A for intravenous treatment of euvolaemic and hypervolaemic hyponatremia. A recent long-term study comparing tolvaptan with placebo in patients with chronic heart failure showed no reduction in risk of death and hospitalisation.