The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome Klooker, T.K.; Braak, B.; Koopman, K.E.; Welting, O.; Wouters, M.M.; van der Heide, S.; Schemann, M.; Bischoff, S.C.; van den Wijngaard, R.M.; Boeckxstaens, G.E. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Download date: 10 May 2018The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome

American children consume up to 27% of calories from high-fat and high-sugar snacks. Both sugar and fat consumption have been implicated as a cause of hepatic steatosis and obesity but the effect of meal pattern is largely understudied. We hypothesized that a high meal frequency, compared to consuming large meals, is detrimental in the accumulation of intrahepatic and abdominal fat. To test this hypothesis, we randomized 36 lean, healthy men to a 40% hypercaloric diet for 6 weeks or a eucaloric control diet and measured intrahepatic triglyceride content (IHTG) using proton magnetic resonance spectroscopy (1H-MRS), abdominal fat using magnetic resonance imaging (MRI), and insulin sensitivity using a hyperinsulinemic euglycemic clamp with a glucose isotope tracer before and after the diet intervention. The caloric surplus consisted of fat and sugar (high-fat-high-sugar; HFHS) or sugar only (high-sugar; HS) and was consumed together with, or between, the three main meals, thereby increasing meal size or meal frequency. All hypercaloric diets similarly increased body mass index (BMI). Increasing meal frequency significantly increased IHTG (HFHS mean relative increase of 45%; P = 0.016 and HS mean relative increase of 110%; P = 0.047), whereas increasing meal size did not (2-way analysis of variance [ANOVA] size versus frequency P = 0.03). Abdominal fat increased in the HFHS-frequency group (+63.3 ± 42.8 mL; P = 0.004) and tended to increase in the HS-frequency group (+46.5 ± 50.7 mL; P = 0.08). Hepatic insulin sensitivity tended to decrease in the HFHS-frequency group while peripheral insulin sensitivity was not affected. Conclusion: A hypercaloric diet with high meal frequency increased IHTG and abdominal fat independent of caloric content and body weight gain, whereas increasing meal size did not. This study suggests that snacking, a common feature in the Western diet, independently contributes to hepatic steatosis and obesity. (Trial registration: http://www.forestplots.net; nr.NCT01297738.) (Hepatology 2014;60:545–553)

Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

123 I-N-v-fluoropropyl-2b-carboxymethoxy-3b-(4-iodophenyl) nortropane ( 123 I-FP-CIT) is commonly used to assess the dopamine transporter in the striatum. However, recent studies suggest that this tracer may be used also to assess binding to monoamine transporters in the midbrain or diencephalon, which may reflect predominantly serotonin transporter (SERT) binding. However, it is still unclear at what time point after injection SPECT should be performed for optimal assessment of SERT with 123 I-FP-CIT. Therefore, we examined the time course of extrastriatal 123 I-FP-CIT binding. Methods: Nineteen healthy, male subjects were included, and SPECT images were acquired up to 3 h after 123 I-FP-CIT injection. Region-of-interest analysis was performed, and specific-to-nonspecific binding ratios were calculated. Results: Specific-to-nonspecific 123 I-FP-CIT binding ratios in the midbrain and diencephalon were significantly higher 2 h after injection than 1 h after injection and remained stable between 2 and 3 h after injection. Conclusion: The optimal time frame for assessing 123 I-FP-CIT binding to extrastriatal SERT is between 2 and 3 h after injection of the tracer. In 2000, the radiotracer 123 I-N-v-fluoropropyl-2b-carboxymethoxy-3b-(4-iodophenyl)nortropane ( 123 I-FP-CIT) was registered in Europe to assess striatal dopamine transporter (DAT) binding, and it is now commonly used to study the integrity of nigrostriatal dopaminergic neurons in vivo (1). Recently, the same tracer was licensed in the United States. The optimal time point for measuring striatal DAT is between 3 and 6 h after bolus injection of 123 I-FP-CIT (2).In vitro studies showed a high affinity of 123 I-FP-CIT for the DAT. However, this tracer also has a moderate affinity for the serotonin transporter (SERT) (3). Indeed, in healthy controls we showed that, after administration of the selective serotonin reuptake inhibitor paroxetine, 123 I-FP-CIT binding was significantly blocked in the SERT-rich midbrain and diencephalon (4). Likewise, another recent study showed that thalamic binding of 123 I-FP-CIT could be blocked by the selective serotonin reuptake inhibitor citalopram (5). The relative anatomic segregation between striatal DAT and extrastriatal SERT binding sets the condition for 123 I-FP-CIT SPECT studies to examine also SERT in vivo. Interestingly, recent clinical FP-CIT SPECT studies showed not only loss of striatal DAT but also loss of midbrain SERT binding in dementia with Lewy bodies and in Parkinson patients with depression (6,7). In these 2 studies, 123 I-FP-CIT binding in SERT-rich areas was measured 3 h after injection, but it is not known whether this time point is optimal for assessing FP-CIT binding to SERT.Abi-Dargham et al. studied 4 healthy controls and showed that peak specific 123 I-FP-CIT binding in the midbrain occurred at 72 6 37 min after injection, followed by slow washout (3). In a previous study, we measured SERT binding in the midbrain and diencephalon only at 1 and 3 h after injection of 123 I-FP-CIT (4). These preli...