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Background/objectives:The physiological changes that occur during fasting are not completely understood, regardless of the cause for fasting (for example, medical, lifestyle, religious, political or famine). The purpose of this study was to examine the effects of a 48-h fast on heart rate variability (HRV) and cortisol levels in healthy young female volunteers.Subjects/methods:A total of 16 young healthy female volunteers underwent 48 h of total fasting under 24-h medical surveillance. Psychological (subjective feeling of hunger) as well as physiological data (HRV, diurnal cortisol profiles) were measured upon admission (Day 1), and after 24 (Day 2) and 48 h (Day 3) of fasting.Results:There was a measured weight loss from Day 1 to Day 3 that resulted in significant body mass index (BMI) reduction across all subjects (P<0.001). The slope of the diurnal cortisol profile significantly shifted towards lower values from baseline to the end of experiment (P=0.002). HRV during resting showed a significant (P<.001) decrease in standard deviation of the normal-to-normal interval (SDNN) and root mean square of successive differences (RMSSDs) from Day 1 to Day 3 of the experiment, with a small increase after 24 h that did not reach statistical significance. A 48 h of fasting also induced a significant (P<.001) decrease of mean interbeat intervals (IBIs), SDNN, RMSSD and log high-frequency (HF) power during head-up tilt testing.Conclusions:An acute (48 h) total fast induced parasympathetic withdrawal with simultaneous sympathetic activation. These changes appear to reflect stress. Further studies are needed to demonstrate the specificity of these changes to fasting. [ABSTRACT FROM AUTHOR]

Background Enterochromaffin cells and enteric neurons synthesize and release serotonin (5-HT). Reuptake, mediated by a plasmalemmal transporter (SERT) terminates the action of released 5-HT. Serotonin secretion and serotonin reuptake transporter (SERT) expression have been reported to be decreased in TNBS-induced experimental colitis and in patients with ulcerative colitis. The present study was designed to utilize the transgenic deletion of SERT as a gain-of-function model to test the hypothesis that 5-HT is a pro-inflammatory mediator in experimental colitis. Methods Colitis was compared in animals with IL10+/+SERT+/+ (wild-type), IL10−/−SERT+/+, IL10−/−SERT+/−, and IL10−/−/SERT−/− (double knockout) genotypes. Macroscopic and histological damage scores were evaluated after a time period of up to 15 weeks. Key Results Serotonin reuptake transporter expression was significantly increased in the inflamed colons of IL-10−/− mice, which displayed intestinal damage and a minor decrement in general health. General health was significantly worse and intestinal inflammation was more severe in IL-10−/−SERT+/−, and IL-10−/−SERT−/− mice than in IL-10−/−SERT+/+ or wild-type animals. Regardless of the associated SERT genotype, the number of 5-HT-immunoreactive cells was decreased by ∼55–65% in all mice lacking IL-10. Conclusions & Inferences Our observations indicate that colitis associated with IL-10 deficient mice is enhanced when the IL-10 deficiency is combined with a SERT deficiency. The data support the concept that 5-HT is a pro-inflammatory mediator in the gut. [ABSTRACT FROM AUTHOR]

Objective:Sugar consumption has increased markedly over the last few decades and parallels the dramatic increase in overweight and obesity. Data obtained from animal studies suggest that the intestinal serotonergic system and herein particularly the serotonin receptor 3 (5-HT3R) may be involved in sugar detection and short-term control of food intake. Using a mouse model, we tested the hypothesis that blocking 5-HT3R prevents the development of sugar-induced obesity.Design:For 8 weeks, C57BL/J6 mice were offered either water containing 30% glucose or plain water in addition to normal chow. The effect of oral treatment with the 5-HT3R antagonist, tropisetron (0.2 mg kg−1 body weight), on body weight and caloric intake was studied.Results:Total caloric intake and weight gain were significantly increased in mice fed glucose compared with the control group. Tropisetron treatment reduced intestinal motility and almost completely blocked weight gain associated with glucose feeding; however, total caloric intake was not affected. The effect of tropisetron was not associated with a decreased expression of the intestinal and hepatic glucose transporters, SGLT1 (sodium-dependent glucose cotransporter) and Glut2 (glucose transporter 2); instead, the expression of these transporters was slightly increased by the 5-HT3R antagonist. However, expressions of carbohydrate responsive element binding protein and fatty acid synthase, as well as triglyceride levels in the liver were only enhanced in mice fed glucose, but remained unchanged at the level of the control group when mice were treated concomitantly with tropisetron. At the same time, β-hydroxybutyrate dehydrogenase mRNA expression and plasma levels of ketone bodies were significantly increased.Conclusion:Our results suggest that 5-HT3R is a new target for the modulation of hepatic glucose metabolism and for the prevention of obesity. [ABSTRACT FROM AUTHOR]

Neurotrophins are potent regulators of neuronal cell survival and function. Nerve growth factor (NGF) was shown to reduce apoptosis in cord blood-derived mast cells. Here, we examined the effect of the neurotrophins NGF and neurotrophin (NT)-3 on survival and mediator release of human intestinal mast cells. Mast cells isolated from normal intestinal tissue were cultured in the presence of NGF, NT-3, or stem cell factor (SCF) alone or in the presence of SCF together with each neurotrophin. NGF or NT-3 alone did not promote mast cell survival. In contrast, mast cell recovery was increased twofold when mast cells were cultured with NT-3 in addition to SCF for 14 days compared with control. Mast cell recovery was further increased following a combined addition of NT-3, SCF and IL-4. NT-3 mediated mast cell growth was dependent on the primary receptor for NT-3 TrkC. NGF in combination with SCF or with SCF and IL-4 showed no effect on mast cell survival. Histamine release and histamine content per mast cell remained unchanged, whereas leukotriene C4 release decreased if mast cells were cultured with NGF or NT-3 in addition to SCF. In summary, NT-3 affects mature human mast cells by promoting mast cell survival, whereas NGF does not. [ABSTRACT FROM AUTHOR]

Background Until now, hydrophilic and lipophilic vitamin preparations had to be administered separately during total parenteral nutrition. By addition of glycocholic acid, a vitamin supplement (Cernevit, Baxter, Heidelberg, Germany) was developed that combines all vitamins into one vial. However, little information exists about possible consequences of bile acid administration such as glycocholic acid, especially if liver disease is pre-existing. Aim To evaluate the effects of total parenteral nutrition with a vitamin preparation containing high doses of glycocholic acid in patients with and without liver disease. Methods In a prospective, randomized-controlled trial, 74 patients, 36 of them with hepatobiliary disease, received total parenteral nutrition for 16 ± 11 days, either with Cernevit or control vitamin supplements. Patients were closely monitored for clinical and biochemical parameters including serum bile acid profiles measured by high-performance liquid chromatography. Results Serum glycocholic acid increased in patients with liver disease treated with Cernevit, whereas total bile acids did not significantly change. Other liver function tests remained stable during treatment. No adverse events during Cernevit administration were noted except for a reversible slight increase of transaminases in one patient. Conclusions Cernevit was well tolerated after repeated dosing, even in patients with severe liver disease. Apart from standard controls of liver biochemistry, no specific surveillance is necessary during treatment with Cernevit. [ABSTRACT FROM AUTHOR]

Background and aims: Histamine is known as a regulator of gastrointestinal functions, such as gastric acid production, intestinal motility, and mucosal ion secretion. Most of this knowledge has been obtained from animal studies. In contrast, in humans, expression and distribution of histamine receptors (HR) within the human gastrointestinal tract are unclear. Methods: We analysed HR expression in human gastrointestinal tissue specimens by quantitative reverse transcription-polymerase chain reaction and immunostaining. Results: We found that H1R, H2R, and H4R mRNA were expressed throughout the gastrointestinal tract, while H3R mRNA was absent. No significant differences in the distribution of HR were found between different anatomical sites (duodenum, ileum, colon, sigma, and rectum). Immunostaining of neurones and nerve fibres revealed that H3R was absent in the human enteric nervous system; however, H1R and H2R were found on ganglion cells of the myenteric plexus. Epithelial cells also expressed H1R, H2R and, to some extent, H4R. Intestinal fibroblasts exclusively expressed H1R while the muscular layers of human intestine stained positive for both H1R and H2R. Immune cells expressed mRNA and protein for H1R, H2R, and low levels of H4R. Analysis of endoscopic biopsies from patients with food allergy and irritable bowel syndrome revealed significantly elevated H1R and H2R mRNA levels compared with controls. Conclusions: We have demonstrated that H1R, H2R and, to some extent, H4R, are expressed in the human gastrointestinal tract, while H3R is absent, and we found that HR expression was altered in patients with gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

Background:Studies in animal models of inflammatory bowel disease (IBD) suggest that supplementation of total parenteral nutrition with glutamine (gln), a conditionally essential amino acid in catabolic conditions, increases gln plasma concentrations, reduces intestinal damage, improves nitrogen balance and may improve the course of the disease. However, human data supporting this assumption are missing.Methods:A total of 24 consecutive patients with an acute exacerbation of IBD (19 Crohn's disease; five ulcerative colitis) and scheduled for total parenteral nutrition (TPN) (>7 days) were randomised. Parallel to a standardised anti-inflammatory therapy, the patients received either a TPN with 1.5 g/kg body weight of a standard amino acid or an isonitrogenic, isocaloric TPN with 1.2 g/kg body weight of a standard amino acid and 0.3 g/kg L-alanine-L-glutamine. Primary end points were gln plasma concentrations and intestinal permeability assessed by urinary lactulose and D-xylose ratio.Results:Gln plasma levels did not differ significantly in either group throughout the study. Intestinal permeability did not change within 7 days either with or without gln supplementation (Δ-lactulose/xylose ratio: 0.01±0.05 (gln+) vs 0.02±0.1 (gln−)). The observed changes in inflammatory and nutritional parameters, and also disease activity, length of TPN and hospital stay, were independent of glutamine substitution. Five (41%) patients in the gln+ group and three (25%) patients in the gln− group needed surgical intervention.Conclusion:Although limited by the sample size, these results do not support the hypothesis that glutamine substitution has an obvious biochemical or clinical benefit in patients with active IBD scheduled for total parenteral nutrition.European Journal of Clinical Nutrition (2005) 59, 1302–1309. doi:10.1038/sj.ejcn.1602243; published online 3 August 2005 [ABSTRACT FROM AUTHOR]

Background and aims: Transforming growth factor β1 (TGF-β1) is expressed in the healthy human intestine and controls mucosal immune responses and inflammation by regulating the function of lymphocytes, macrophages, dendritic cells, and eosinophils. Here, we asked whether human intestinal mast cells (MC) might also be subject to immunoregulation by TGF-β1. Methods: MC were isolated from the intestinal mucosa, purified, and cultured in vitro in the presence of stem cell factor (SCF) with or without TGF-β1. Growth characteristics, phenotype, and immunological mediator release of MC were analysed by reverse transcription-polymerase chain reaction, flow cytometry, immunocytochemistry, western blot, and different immunoassays, respectively. Results: TGF-β1 dose dependently (ED50 ≈ 0.1 ng/ml) inhibited SCF dependent growth of human intestinal MC by both enhancing apoptosis and decreasing proliferation. In parallel, TGF-β1 increased the percentage of connective tissue-type MC expressing tryptase and chymase while downregulating expression of the receptors for IgE and SCF. Furthermore, TGF-β1 dramatically changed the profile of mediators released by MC following IgE receptor crosslinking. Release of histamine, cysteinyl-leukotrienes, and tumour necrosis factor α was strongly reduced whereas prostaglandin D2 generation and cyclooxygenase 1 and 2 expression were upregulated by TGF-β1. Conclusions: Our data indicate that TGF-β1 acts as a novel potent inhibitor and modulator of human intestinal MC effector functions. The change in MC mediator release profile and protease expression induced by TGF-β1 might be of relevance for the control of MC associated disorders of the intestine such as allergic reactions, Crohn's disease, irritable bowel syndrome, and parasitic infection. [ABSTRACT FROM AUTHOR]

IgE-dependent activation of mast cells (MCs) is a key pathomechanism of type I allergies. In contrast, allergen-specific IgG Abs are thought to attenuate immediate allergic reactions by blocking IgE binding and by cross-linking the inhibitory Fcγ receptor IIB on MCs. To establish a defined in vitro system using human MCs to study the biological activity of allergens and to investigate the role of allergen-specific IgE and IgG. Purified human intestinal MCs sensitized with different forms of specific IgE Abs were triggered by monomeric and oligomeric forms of recombinant Bet v 1, the major birch pollen allergen, in the presence or absence of allergen-specific IgG Abs. MCs sensitized with an anti-Bet v 1 IgE mAb or sera obtained from birch pollen allergic patients released histamine and sulphidoleukotrienes after exposure to oligomeric Bet v 1. Monomeric Bet v 1 provoked mediator release only in MCs sensitized with patients sera but not in MCs sensitized with anti-Bet v 1 IgE mAb. Interestingly, MC activation could be induced by supercross-linking of monomeric Bet v 1 bound to monovalent IgE on MCs with a secondary allergen-specific IgG pAb. By using IgG F(ab′)2 fragments we provide evidence that this effect is not a result of IgG binding to Fcγ receptors. This assay represents a new tool for the in vitro study of MC activation in response to natural and genetically modified allergens. Fcℇ receptor I supercross-linking by allergen-specific IgG Abs provides a possible new mechanism of IgG-dependent enhancement of type I allergic reactions. [ABSTRACT FROM AUTHOR]

The mechanisms of gastrointestinal (GI) food allergy (FA) are poorly understood. Immunoglobulin E (IgE) is increased in stools from patients with FA, as well as the number of cells carrying IgE in intestinal mucosa, but the origin of IgE production remains unknown. To investigate a local production of IgE in intestine, we analysed the levels of transcripts for epsilon germ-line (εGT), and potential regulators of IgE production, IL-4, IL-13, IFN-γ, IL-4Rα, STAT6 and FcεRIα in intestinal mucosa of adult patients with FA.Endoscopic biopsies were obtained from the caecum of 25 patients with FA and 14 control patients. The levels ofεGT, IL-4, IL-13, IFN-γ, IL-4Rα, STAT6 and FcεRIα mRNA were analysed by real-time RT-PCR and compared with unpaired nonparametric Mann–Whitney test.The meanεGT transcript level in caecum was increased in FA patients compared with control patients (P < 0.05). IL-4 mRNA expression was also increased in FA patients (P < 0.05), whereas mRNA expression for IL-13, IFN-γ, IL-4Rα, STAT6 and FcεRIα mRNA expression was not altered. However, the ratio of IL-4 mRNA/IFN-γ mRNA was significantly increased in FA patients (P < 0.05). No correlation was observed betweenεGT transcripts expression in intestinal mucosa and total IgE levels in serum.This study shows that (i)εGT transcripts are expressed in human intestinal mucosa; (ii)εGT and IL-4 transcripts are increased in caecal mucosa from patients with FA. These results suggest local production of IgE in intestine that might be of importance for inflammatory reactions in the GI tract. [ABSTRACT FROM AUTHOR]

Neuroimmune interactions are an integral part of gut physiology and involved in the pathogenesis of inflammatory and functional bowel disorders. Mast cells and their mediators are important conveyors in the communication from the innate enteric immune system to the enteric nervous system (ENS). However, it is not known whether a mediator cocktail released from activated human mast cells affects neural activity in the ENS. We used the Multi-Site Optical Recording Technique to image single cell activity in guinea-pig and human ENS after application of a mast cell mediator cocktail (MCMC) that was released from isolated human intestinal mucosa mast cells stimulated by IgE-receptor cross-linking. Local application of MCMC onto individual ganglia evoked an excitatory response consisting of action potential discharge. This excitatory response occurred in 31%, 38% or 11% neurons of guinea-pig submucous plexus, human submucous plexus, or guinea-pig myenteric plexus, respectively. Compound action potentials from nerve fibres or fast excitatory synaptic inputs were not affected by MCMC. This study demonstrates immunoneural signalling in the human gut and revealed for the first time that an MCMC released from stimulated human intestinal mast cells induces excitatory actions in the human and guinea-pig ENS. [ABSTRACT FROM AUTHOR]

Mast cells and eosinophils have an important role in allergic inflammation and probably also in chronic inflammatory diseases resulting in fibrosis, such as Crohn disease where fibrosis is present as strictures. The involvement of mast cells and eosinophils in Crohn disease fibrosis was investigated. Mast cells were present in all the biopsies and only faintly positive for extra cellular matrix (ECM) products. Pronounced eosinophilia was detected in only two cases. Mast cell sonicates increased both Crohn disease (α-SMA positive) and control fibroblast proliferation, decreased collagen production and increased collagen gel contraction. Eosinophil sonicates increased fibroblast proliferation, gel contraction and collagen production. TNF-α decreased collagen production. Histamine, tryptase and chymase had no influence. These in vitro data show that mast cells and eosinophils could be involved in modulating Crohn disease fibrosis by directly influencing intestinal fibroblast properties. [ABSTRACT FROM AUTHOR]

Background & Aims: Sarcopenia is a muscle disorder associated with loss of muscle mass, strength and function. Early screening, diagnosis and treatment may improve outcome in different disease conditions. A wide variety of tools for estimation of muscle mass is available and each tool has specific technical requirements. However, different investigational settings and lack of homogeneity of populations influence the definition of gold standards, proving it difficult to systematically adopt these tools. Recently, the European Working Group on Sarcopenia in Older People (EWGSOP) published a revised recommendation (EWGSOP-2) and algorithm for using tools for screening and diagnosing sarcopenia. However, agreement of the EWGSOP2 criteria with other classifications is poor and although an overview of available tools is valuable, for the purpose of clinical decision-making the reverse is useful; a given scenario asks for the most suitable tools., Results: Tools were identified for screening, diagnostics and longitudinal monitoring of muscle mass. For each of these clinical scenarios the most appropriate tools were listed and for each technique their usability is specified based on sensitivity and specificity. Based on this information a specific recommendation is made for each clinical scenario., Conclusion: This narrative review provides an overview of currently available tools and future developments for different clinical scenarios such as screening, diagnosis and longitudinal monitoring of alterations in muscle status. It supports clinical decision-making in choosing the right tools for muscle mass quantification depending on the need within a given clinical scenario as well as the local availability and expertise., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Physical activity (PA) helps prevention and aftercare of sporadic breast cancer (BC), cardiopulmonary fitness (CPF) being an age-independent predictor of tumor-specific mortality. Therefore, we wanted to identify predictors of CPF (represented by peak oxygen uptake: VO 2peak ) in BRCA1/2 mutation carriers whose risk of developing BC is high. We used cross-sectional data from 68 BRCA1/2 germline mutation carrying women participating in the randomized, prospective, controlled clinical study LIBRE-1. Assessments included cardiopulmonary exercise testing, medical and lifestyle history plus socioeconomic status. Additionally, the participants completed a psychological questionnaire regarding their attitude, subjective norms, perceived behavior control and intention towards PA. A multivariate logistic regression model was used to identify predictors for participants reaching their age- and sex-adjusted VO 2peak reference values. 22 participants (median age: 40 years, interquartile range (IQR) 33-46) were cancer-unaffected and 46 cancer-affected (median age: 44 years, IQR 35-50). The strongest predictor for reaching the reference VO 2peak value was attitude towards PA (Odds Ratio 3.0; 95% Confidence Interval 1.3-8.4; p = 0.021). None of the other predictors showed a significant association. A positive attitude towards PA seems to be associated with VO 2peak , which should be considered in developing therapeutic and preventive strategies.Trial registrations: NCT02087592; DRKS00005736., (© 2022. The Author(s).)

Competing Interests: Die Interessenkonflikte sämtlicher Autoren finden sich im Leitlinienreport, Anhang D (https://www.dgvs.de/wissen/leitlinien/leitlinien-dgvs/intestinale-motilitaetsstoerungen/)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

The scientific rationale for dietary fibre intake recommendations comes from the recognition of their benefits for health based on studies first published many years ago. It remains unclear which are the key physiological effects generated by dietary fibre in view of the diversity of the food components considered as dietary fibre, of the relevance of their classification (soluble and insoluble) and from the recent discoveries putting forward their interactions with the gut microbiota. The project FiberTAG ( Joint Programming Initiative 'A Healthy Diet for a Healthy Life' 2017-2020 https://www.fibertag.eu/) aims to establish a set of biomarkers (markers of gut barrier function and bacterial co-metabolites including volatile compounds and lipid derivatives), measured in different biological compartments (faeces, blood or breath) linking dietary fibre intake and gut microbiota-related health effects. The FiberTAG consortium brings together academic and industrial partners from Belgium, France, Germany and Canada to share data and samples obtained from existing as well as new intervention studies in order to evaluate the relevance of such biomarkers. The FiberTAG consortium is currently working on five existing cohorts (prospective observational or nutritional interventions in healthy or obese patients), and a number of new intervention studies to analyse the effect of insoluble dietary fibre (wheat bran and chitin-glucan, provided by the industrial partners) in healthy individuals or in obese patients at high cardiometabolic risk., Competing Interests: The authors declare that they have no competing interests., (© 2020 The Authors. Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

Background: The intestinal microbiome consists of about 10 million genes, many of which encode digestive enzymes. This explains why animal and human experiments revealed that the intestinal microbiome adapts to food intake and optimizes energy harvest from food. This function is considered beneficial in states of lack of food, but following overnutrition, it might support the development of obesity., Objectives: The relevance of the intestinal microbiome for the pathogenesis of obesity and associated metabolic diseases such as fatty liver disease and type 2 diabetes mellitus and for the clinical management of such diseases shall be discussed., Materials and Methods: Recent literature related to the topic has been selected, presented, and discussed with regard to the objectives., Results: The intestinal microbiome plays a role in the pathogenesis of both obesity (by increasing the energy absorption from food) and fatty liver disease as well as type 2 diabetes mellitus (via induction of low-grade inflammation following translocation of lipopolysaccharides from the gut and dysregulation of metabolic pathways)., Conclusions: The findings might have consequences for diagnosis (identification of risk groups) and therapy (usage of known and novel probiotics or bacterial metabolites) of metabolic diseases.

Background: A lack of agreement on definitions and terminology used for nutrition-related concepts and procedures limits the development of clinical nutrition practice and research., Objective: This initiative aimed to reach a consensus for terminology for core nutritional concepts and procedures., Methods: The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a consensus group of clinical scientists to perform a modified Delphi process that encompassed e-mail communication, face-to-face meetings, in-group ballots and an electronic ESPEN membership Delphi round., Results: Five key areas related to clinical nutrition were identified: concepts; procedures; organisation; delivery; and products. One core concept of clinical nutrition is malnutrition/undernutrition, which includes disease-related malnutrition (DRM) with (eq. cachexia) and without inflammation, and malnutrition/undernutrition without disease, e.g. hunger-related malnutrition. Over-nutrition (overweight and obesity) is another core concept. Sarcopenia and frailty were agreed to be separate conditions often associated with malnutrition. Examples of nutritional procedures identified include screening for subjects at nutritional risk followed by a complete nutritional assessment. Hospital and care facility catering are the basic organizational forms for providing nutrition. Oral nutritional supplementation is the preferred way of nutrition therapy but if inadequate then other forms of medical nutrition therapy, i.e. enteral tube feeding and parenteral (intravenous) nutrition, becomes the major way of nutrient delivery., Conclusion: An agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established. This terminology consensus may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease (ICD). The continuous growth of knowledge in all areas addressed in this statement will provide the foundation for future revisions., (Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd.. All rights reserved.)

Background: Gastrointestinal hormone release and the regulation of appetite and body weight are thought to be dysbalanced in obesity. However, human data investigating the expression of gastrointestinal hormones in the obese are rare. We studied the expression of ghrelin, leptin, and the serotonergic system in stomach tissue and serum of obese and non-obese individuals., Methods: Gastric tissue and serum were collected from 29 adult obese (BMI 48.7 ± 10.6 kg/m(2) ; mean ± SD) who underwent laparoscopic sleeve gastrectomy. Gastric biopsies, surgery specimen or serum was obtained from 35 adult non-obese humans (BMI 22.7 ± 1.9 kg/m(2) ). Ghrelin, ghrelin O-acyl transferase (GOAT), leptin, leptin receptor, and tryptophan hydroxylase 1 (TPH1) mRNA expression were measured by qRT-PCR. Serotonin (5HT) and leptin protein concentration were quantified in tissue extracts and serum; GOAT and ghrelin-positive cells were immunohistologically quantified in tissue. Additionally, 21 blood immune markers were analyzed., Key Results: In gastric tissue, GOAT-positive cells were reduced (p < 0.01), but ghrelin-positive cells and mRNA were increased (both p < 0.05) in obese compared with non-obese individuals. Gastric leptin (p < 0.001) and leptin receptor (p < 0.001) mRNA expression, as well as leptin concentrations in serum (p < 0.001), were increased in obese compared with non-obese individuals. Serum 5HT was reduced (p < 0.05), while tissue 5HT and TPH1 mRNA were reduced only by trend. Interleukin 1 receptor a (IL1Ra), IL-8, IL-12, and monocyte chemoattractant protein 1 (IL1Ra) were increased and IL1Ra correlated negatively with serum leptin., Conclusions & Inferences: Our data indicate that obesity causes a dysregulation of gastrointestinal hormones at the tissue level and serum, including a negative correlation with an increased marker of subclinical inflammation., (© 2016 John Wiley & Sons Ltd.)

Background: IL-33 enhances FcεRI-induced mediator release in human basophils without inducing degranulation itself. In contrast, studies in mice suggested that in the presence of high IgE levels, IL-33 triggers degranulation and anaphylaxis of similar severity as specific allergen. Consistent with this view, sera of atopic patients contain elevated levels of IL-33 after anaphylaxis. In this study, we determined whether IL-33 is potentially anaphylactogenic in humans with high IgE levels by regulating exocytosis independent of FcεRI cross-linking. Furthermore, we investigated whether IL-33 is released upon allergen provocation in vivo., Methods: In subjects with high serum IgE levels, we measured IL-33-induced histamine/LTC4 in vitro, CD63 translocation ex vivo, and responsiveness of mast cells in vivo by skin prick test (SPT). In asthma patients, release of IL-33 and its correlation with early (tryptase)- and late-phase markers (IL-13 levels, eosinophil numbers) of the allergic response were assessed in bronchoalveolar lavage fluids (BALFs) after allergen challenge., Results: IL-33 itself does not trigger basophil degranulation in vitro and ex vivo, even in subjects with high serum IgE levels, and negative SPTs demonstrate that skin mast cells do not degranulate in response to IL-33. However, in response to allergen challenge, IL-33 is rapidly released into BALFs at levels that do not correlate with other immediate- and late-phase parameters., Conclusion: IL-33 is unlikely an independent trigger of anaphylaxis even in subjects with high IgE levels. However, the rapid release of IL-33 upon allergen provocation in vivo supports its role as a mediator of immediate allergic responses., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterised by abdominal pain, associated with stool abnormalities and changes in stool consistency. Diagnosis of IBS is based on characteristic symptoms and exclusion of other gastrointestinal diseases. A number of questionnaires exist to assist diagnosis and assessment of severity of the disease. One of these is the irritable bowel syndrome - severity scoring system (IBS-SSS). The IBS-SSS was validated 1997 in its English version. In the present study, the IBS-SSS has been validated in German language. To do this, a cohort of 60 patients with IBS according to the Rome III criteria, was compared with a control group of healthy individuals (n = 38). We studied sensitivity and reproducibility of the score, as well as the sensitivity to detect changes of symptom severity. The results of the German validation largely reflect the results of the English validation. The German version of the IBS-SSS is also a valid, meaningful and reproducible questionnaire with a high sensitivity to assess changes in symptom severity, especially in IBS patients with moderate symptoms. It is unclear if the IBS-SSS is also a valid questionnaire in IBS patients with severe symptoms because this group of patients was not studied., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Mast cells (MC) are main effector cells of allergic and other inflammatory reactions; however, only a few anti-MC agents are available for therapy. It has been reported that cinnamon extract (CE) attenuates allergic symptoms by affecting immune cells; however, its influence on MC was not studied so far. Here, we analyzed the effects of CE on human and rodent MC in vitro and in vivo., Methods: Expression of MC-specific proteases was examined in vivo in duodenum of mice following oral administration of CE. Release of mediators and phosphorylation of signaling molecules were analyzed in vitro in human MC isolated from intestinal tissue (hiMC) or RBL-2H3 cells challenged with CE prior to stimulation by FcεRI cross-linking., Results: Following oral treatment with CE, expression of the mast cell proteases MCP6 and MC-CPA was significantly decreased in mice. In hiMC, CE also caused a reduced expression of tryptase. Moreover, in hiMC stimulated by IgE cross-linking, the release of β-hexosaminidase was reduced to about 20% by CE. The de novo synthesis of cysteinyl leukotrienes, TNFα, CXCL8, CCL2, CCL3, and CCL4, was almost completely inhibited by CE. The attenuation of mast cell mediators by CE seems to be related to particular signaling pathways, because we found that activation of the MAP kinases ERK, JNK, and p38 as well as of Akt was strongly reduced by CE., Conclusion: CE decreases expression of mast cell-specific mediators in vitro and in vivo and thus is a new plant-originated candidate for anti-allergic therapy., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Objectives: To determine the effectiveness of a structured multidisciplinary non-surgical obesity therapy program on the basis of a temporary low-calorie-diet for 12 weeks, and additional intervention modules to enhance nutritional education, to increase physical activity and to modify eating behavior., Design: Prospective multicenter observational study in obese individuals undergoing a medically supervised outpatient-based 52-week treatment in 37 centers in Germany., Subjects: A total of 8296 participants with a body mass index (BMI) of >30 kg m(-2) included within 8.5 years., Measurements: Main outcome measures were body weight loss, waist circumference (WC), blood pressure, quality of life and adverse events., Results: In females, initial body weight was reduced after the 1-year-intervention by 19.6 kg (95% confidence intervals 19.2-19.9 kg) and in males by 26.0 kg (25.2-26.8) according to per protocol analysis of 4850 individuals. Intention-to-treat (ITT) analysis revealed a weight reduction of 15.2 kg (14.9-15.6) in females and 19.4 kg (18.7-20.1) in males. Overall, the intervention resulted in mean reduction in WC of 11 cm; it reduced the prevalence of the metabolic syndrome by 50% and the frequency of hypertension from 47 to 29% of all participants (ITT, all P<0.001). The beneficial effects could be documented for up to 3 years and comprised significant improvement of health-related quality of life. The incidence of adverse effects was low; the only event repeatedly observed and possibly related to either the intervention or the underlying disease was biliary disorders., Conclusion: The present non-surgical intervention program is a highly effective treatment of obesity grades I-III and obesity-related diseases, and therefore, could be a valuable basis for future weight maintenance strategies required for sustained success.

In patients with Crohn's disease and ulcerative colitis parenteral nutrition (PN) is indicated when enteral nutrition is not possible or should be avoided for medical reasons. In Crohn's patients PN is indicated when there are signs/symptoms of ileus or subileus in the small intestine, scars or intestinal fistulae. PN requires no specific compounding for chronic inflammatory bowel diseases. In both diseases it should be composed of 55-60% carbohydrates, 25-30% lipids and 10-15% amino acids. PN helps in the correction of malnutrition, particularly the intake of energy, minerals, trace elements, deficiency of calcium, vitamin D, folic acid, vitamin B12, and zinc. Enteral nutrition is clearly superior to PN in severe, acute pancreatitis. An intolerance to enteral nutrition results in an indication for total PN in complications such as pseudocysts, intestinal and pancreatic fistulae, and pancreatic abscesses or pancreatic ascites. If enteral nutrition is not possible, PN is recommended, at the earliest, 5 days after admission to the hospital. TPN should not be routinely administered in mild acute pancreatitis or nil by moth status <7 days, due to high costs and an increased risk of infection. The energy requirements are between 25 and 35 kcal/kg body weight/day. A standard solution including lipids (monitoring triglyceride levels!) can be administered in acute pancreatitis. Glucose (max. 4-5 g/kg body weight/day) and amino acids (about 1.2-1.5 g/kg body weight/day) should be administered and the additional enrichment of TPN with glutamine should be considered in severe, progressive forms of pancreatitis.

PN (parenteral nutrition) should be standardised to ensure quality and to reduce complications, and it should be carried out in consultation with a specialised nutrition support team whenever possible. Interdisciplinary nutrition support teams should be established in all hospitals because effectiveness and efficiency in the implementation of PN are increased. The tasks of the team include improvements of quality of care as well as enhancing the benefit to cost ratio. Therapeutic decisions must be taken by attending physicians, who should collaborate with the nutrition support team. "All-in-One" bags are generally preferred for PN in hospitals and may be industrially manufactured, industrially manufactured with the necessity to add micronutrients, or be prepared "on-demand" within or outside the hospital according to a standardised or individual composition and under consideration of sterile and aseptic conditions. A standardised procedure should be established for introduction and advancement of enteral or oral nutrition. Home PN may be indicated if the expected duration of when PN exceeds 4 weeks. Home PN is a well established method for providing long-term PN, which should be indicated by the attending physician and be reviewed by the nutrition support team. The care of home PN patients should be standardised whenever possible. The indication for home PN should be regularly reviewed during the course of PN.

Catheter type, access technique, and the catheter position should be selected considering to the anticipated duration of PN aiming at the lowest complication risks (infectious and non-infectious). Long-term (>7-10 days) parenteral nutrition (PN) requires central venous access whereas for PN <3 weeks percutaneously inserted catheters and for PN >3 weeks subcutaneous tunnelled catheters or port systems are appropriate. CVC (central venous catheter) should be flushed with isotonic NaCl solution before and after PN application and during CVC occlusions. Strict indications are required for central venous access placement and the catheter should be removed as soon as possible if not required any more. Blood samples should not to be taken from the CVC. If catheter infection is suspected, peripheral blood-culture samples and culture samples from each catheter lumen should be taken simultaneously. Removal of the CVC should be carried out immediately if there are pronounced signs of local infection at the insertion site and/or clinical suspicion of catheter-induced sepsis. In case PN is indicated for a short period (max. 7-10 days), a peripheral venous access can be used if no hyperosmolar solutions (>800 mosm/L) or solutions with a high titration acidity or alkalinity are used. A peripheral venous catheter (PVC) can remain in situ for as long as it is clinically required unless there are signs of inflammation at the insertion site.

A close cooperation between medical teams is necessary when calculating the fluid intake of parenterally fed patients. Fluids supplied parenterally, orally and enterally, other infusions, and additional fluid losses (e.g. diarrhea) must be considered. Targeted diagnostic monitoring (volume status) is required in patients with disturbed water or electrolyte balance. Fluid requirements of adults with normal hydration status is approximately 30-40 ml/kg body weight/d, but fluid needs usually increase during fever. Serum electrolyte concentrations should be determined prior to PN, and patients with normal fluid and electrolyte balance should receive intakes follwing standard recommendations with PN. Additional requirements should usually be administered via separate infusion pumps. Concentrated potassium (1 mval/ml) or 20% NaCl solutions should be infused via a central venous catheter. Electrolyte intake should be adjusted according to the results of regular laboratory analyses. Individual determination of electrolyte intake is required when electrolyte balance is initially altered (e.g. due to chronic diarrhea, recurring vomiting, renal insufficiency etc.). Vitamins and trace elements should be generally substituted in PN, unless there are contraindications. The supplementation of vitamins and trace elements is obligatory after a PN of >1 week. A standard dosage of vitamins and trace elements based on current dietary reference intakes for oral feeding is generally recommended unless certain clinical situations require other intakes.

Adequate nutrition is a part of medical treatment and is influenced by ethical and legal considerations. Patients, who cannot be sufficiently fed via the gastrointestinal tract, have the fundamental right to receive PN (parenteral nutrition) even so patients who are unable to give their consent. General objectives in nutrition support are to supply adequate nutrition with regards to the prevention of malnutrition and its consequences (increased morbidity and mortality), and thereby promoting improved outcome and/or quality of life for the patient considering always the patient's needs and wishes. The requests of the patient to renounce PN should be respected where a signed living will is helpful. During the course of a terminal illness the nutrition has to be adapted individually according to the needs and wishes of a patient in the corresponding phase. Capability of consent should be checked in each individual case and for each measure on an individual basis. Consent should only be accepted if the patient is capable of recognizing the nature, meaning and importance of the intervention as well as the consequences of relinquishment of such an intervention, and is capable to make a self-determined decision. If the patient is not capable of consenting, the patient's living will is the most important document when determining their assumed will and legally binding. Otherwise a guardian appointed by the patient, or the representative appointed by the court (if the patient has made no provisions) can make the decision.