Wolfgang Scheppach

Publications of Wolfgang Scheppach

• A fibreoptic endoscopic study of upper gastrointestinal bleeding at bugando medical centre in northwestern Tanzania: A retrospective review of 240 cases.

  Authors: Hyasinta Jaka, Mheta Koy, Anthony Liwa, Rodrick Kabangila, Mariam Mirambo, Wolfgang Scheppach, Eliasa Mkongo, Mabula D McHembe, Phillipo L Chalya

  BMC research notes. 04/2012; 5(1):200.

  ABSTRACT: BACKGROUND: Upper gastrointestinal (GI) bleeding is recognized as a common and potentially life-threatening abdominal emergency that needs a prompt assessment and aggressive emergencyABSTRACT: BACKGROUND: Upper gastrointestinal (GI) bleeding is recognized as a common and potentially life-threatening abdominal emergency that needs a prompt assessment and aggressive emergency treatment. A retrospective study was undertaken at Bugando Medical Centre in northwestern Tanzania between March 2010 and September 2011 to describe our own experiences with fibreoptic upper GI endoscopy in the management of patients with upper gastrointestinal bleeding in our setting and compare our results with those from other centers in the world. FINDINGS: A total of 240 patients representing 18.7% of all patients (i.e. 1292) who had fibreoptic upper GI endoscopy during the study period were studied. Males outnumbered female by a ratio of 2.1:1. Their median age was 37 years and most of patients (60.0%) were aged 40 years and below. The vast majority of the patients (80.4%) presented with haematemesis alone followed by malaena alone in 9.2% of cases. The use of non-steroidal anti-inflammatory drugs, alcohol and smoking prior to the onset of bleeding was recorded in 7.9%, 51.7% and 38.3% of cases respectively. Previous history of peptic ulcer disease was reported in 22(9.2%) patients. Nine (3.8%) patients were HIV positive. The source of bleeding was accurately identified in 97.7% of patients. Diagnostic accuracy was greater within the first 24 h of the bleeding onset, and in the presence of haematemesis. Oesophageal varices were the most frequent cause of upper GI bleeding (51.3%) followed by peptic ulcers in 25.0% of cases. The majority of patients (60.8%) were treated conservatively. Endoscopic and surgical treatments were performed in 30.8% and 5.8% of cases respectively. 140 (58.3%) patients received blood transfusion. The median length of hospitalization was 8 days and it was significantly longer in patients who underwent surgical treatment and those with higher Rockall scores (P < 0.001). Rebleeding was reported in 3.3% of the patients. The overall mortality rate of 11.7% was significantly higher in patients with variceal bleeding, shock, hepatic decompensation, HIV infection, comorbidities, malignancy, age > 60 years and in patients with higher Rockall scores and those who underwent surgery (P < 0.001). CONCLUSION: Oesophageal varices are the commonest cause of upper gastrointestinal bleeding in our environment and it is associated with high morbidity and mortality. The diagnostic accuracy of fibreoptic endoscopy was related to the time interval between the onset of bleeding and endoscopy. Therefore, it is recommended that early endoscopy should be performed within 24 h of the onset of bleeding.

• Metabolic Effects of Replacing Sucrose by Isomaltulose in Subjects With Type 2 Diabetes: A randomized double-blind trial.

  Authors: Stefanie Brunner, Ines Holub, Stephan Theis, Andrea Gostner, Ralph Melcher, Petra Wolf, Ulrike Amann-Gassner, Wolfgang Scheppach, Hans Hauner

  Diabetes care. 04/2012;

  OBJECTIVETo test the hypothesis that replacement of sucrose with isomaltulose in sweet foods and beverages improves metabolic control in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSOneOBJECTIVETo test the hypothesis that replacement of sucrose with isomaltulose in sweet foods and beverages improves metabolic control in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSOne hundred ten patients with type 2 diabetes were randomized to receive sweet foods containing either 50 g/day isomaltulose or sucrose for 12 weeks as part of their habitual diet under free-living conditions. HbA(1c) at 12 weeks was the primary outcome parameter.RESULTSIn the final analysis comprising 101 patients, isomaltulose did not significantly affect HbA(1c) at 12 weeks (sucrose: 7.39 ± 0.78%, isomaltulose: 7.24 ± 0.76%; regression coefficient [b]: 0.02 [95% CI: -0.21 to 0.25], P = 0.844). Triglycerides at 12 weeks were significantly lower in the isomaltulose versus the sucrose group (b: 34.01 [6.59-61.44], P = 0.016). Other secondary parameters did not significantly differ between groups.CONCLUSIONSIsomaltulose did not influence glycemic control assessed as HbA(1c) in type 2 diabetes under free-living conditions but was associated with lower triglyceride levels.

• Program and abstracts for the 2011 Meeting of the Society for Glycobiology.

  Authors: M Tony Hollingsworth, Gerald W Hart, James C Paulson, Elizabeth Stansell, Kevin Canis, I-Cheuh Huang, Maria Panico, Howard Morris, Stuart Haslam, Michael Farzan [......] Kazunori Hamamura, Takenosuke Yoshida, Kaoru Akita, Tetsuya Okajima, Keiko Furukawa, Takeshi Urano, Koichi Furukawa, L Renee Ruhaak, Suzanne Miyamoto, Carlito B Lebrilla

  Glycobiology. 11/2011; 21(11):1454-531.

  Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cellCell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine kinases and other cell surface receptors, and engage in signal transduction in order to communicate information regarding conditions at the cell surface to the nucleus. In that context, the MUC1 cytoplasmic tail (MUC1CT) receives phosphorylation signals from receptor tyrosine kinases and serine/threonine kinases, which enables its association with different signaling complexes that conduct these signals to the nucleus and perhaps other subcellular organelles. We have detected the MUC1CT at promoters of over 500 genes, in association with several different transcription factors, and have shown that promoter occupancy can vary under different growth factor conditions. However, the full biochemical nature of the nuclear forms of MUC1 and its function at these promoter regions remain undefined. I will present evidence that nuclear forms of the MUC1CT include extracellular and cytoplasmic tail domains. In addition, I will discuss evidence for a hypothesis that the MUC1CT possesses a novel catalytic function that enables remodeling of the transcription factor occupancy of promoters, and thereby engages in regulation of gene expression.

• Aortobifemoral prosthesis penetrating into the duodenal lumen.

  Authors: Wolfgang Scheppach, Martina Polzien, Wolfgang Kuesters

  Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 08/2011; 9(12):A28.

• Differential cathelicidin expression in duodenal and gastric biopsies from Tanzanian and German patients.

  Authors: Dorothee Rogoll, Juergen Schauber, Koy K Mheta, August Stich, Wolfgang Scheppach

  PloS one. 01/2011; 6(7):e22049.

  Epithelial surfaces such as the gastrointestinal mucosa depend on expression of antimicrobial peptides like cathelicidin for immune defence against pathogens. The mechanisms behind mucosalEpithelial surfaces such as the gastrointestinal mucosa depend on expression of antimicrobial peptides like cathelicidin for immune defence against pathogens. The mechanisms behind mucosal cathelicidin regulation are incompletely understood. Cathelicidin expression was analysed in duodenal, antral and corpus/fundic mucosal biopsies from African and German patients. Additionally, cathelicidin expression was correlated with Helicobacter pylori (HP) infection and the inflammatory status of the mucosa. High cathelicidin transcript abundance was detected in duodenal biopsies from African subjects. On the contrary, cathelicidin mRNA expression was either undetectable or very low in tissue specimens from German patients. Also, in the antrum and corpus/fundus regions of the stomach significantly higher cathelicidin transcript levels were measured in Tanzanian compared to German patients. In gastric biopsies from African patients cathelicidin expression was increased in HP positive compared to HP negative subjects. Additionally, the inflammatory status measured by IL-8 expression correlated well with the HP infection status. A higher duodenal and gastric cathelicidin expression in African (compared with European) individuals may be due to upregulation by antigenic stimulation and may confer a higher resistance against enteric infections.

• Intestinal transit and systemic metabolism of apple polyphenols.

  Authors: Kathrin Kahle, Michael Kempf, Peter Schreier, Wolfgang Scheppach, Dieter Schrenk, Tanja Kautenburger, Dorothée Hecker, Wolfgang Huemmer, Matthias Ackermann, Elke Richling

  European journal of nutrition. 12/2010; 50(7):507-22.

  Apples are the most widely consumed fruits in Germany and various other countries. Positive health effects of apple-derived polyphenols in vivo depend on their absorption, metabolism, distribution,Apples are the most widely consumed fruits in Germany and various other countries. Positive health effects of apple-derived polyphenols in vivo depend on their absorption, metabolism, distribution, and elimination from the body after consumption. Data on the metabolism of these polyphenols in humans are scarce. In order to study the intestinal transit and metabolism of apple polyphenols in humans, a variety of experiments were carried out. Polyphenols were incubated with saliva (for 5 min), simulated gastric or duodenal juice (4 or 10 h, respectively), or rat hepatocytes (4 h) under aerobic conditions, and with ileostomy fluid under aerobic conditions for 10 h. The polyphenol profile in human serum (8 h later) and renal elimination in urine (24 h later) were also investigated after consumption of 1 L apple juice. Polyphenols and their metabolites were identified and quantified by high-performance liquid chromatography with diode array detection (HPLC-DAD), HPLC-electrospray ionization-tandem mass spectrometry (ESI-MS/MS), and gas chromatography (GC)-MS. In the presence of native saliva or ileostomy fluid, β-glycosides of phloretin and quercetin were hydrolyzed, to varying degrees depending on the sugar moiety, and to much lesser degrees in the presence of antibiotics. In the gastric milieu, almost complete degradation of procyanidin B(2) to (-)-epicatechin was observed. In the presence of artificial duodenal juice flavan-3-ol epimerization occurred. Quercetin was completely converted to phloroglucinol, 3,4-dihydroxybenzoic acid, and 2,4,6-trihydroxybenzoic acid. Formation of isomeric products of hydroxycinnamic acid esters and their corresponding methyl esters was also observed, and similar results were obtained after incubation with rat hepatocytes. Products of phase II metabolism, two phloretin O-glucuronides and eight (methyl) quercetin O-glucuronides, were identified in the hepatocyte samples. Following enzymatic hydrolysis, 5-caffeoylquinic acid, 4-p-coumaroylquinic acid, caffeic acid, (-)-epicatechin, phloretin, and quercetin were recovered in both serum and urine (5.3% and 3.5% of the amounts consumed, respectively). In addition, 19.5% of the polyphenols consumed were identified in the urine in the form of hydroxylated phenolic and hippuric acids. The findings relating to the absorption, metabolism, and systemic availability of polyphenols in vivo should contribute to our understanding of their biological effects, and the characterization of newly formed metabolites should facilitate further studies.

• The Ussing type chamber model to study the intestinal transport and modulation of specific tight-junction genes using a colonic cell line.

  Authors: Hannah Bergmann, Dorothee Rogoll, Wolfgang Scheppach, Ralph Melcher, Elke Richling

  Molecular nutrition & food research. 09/2009;

  Polyphenols in apples, such as various hydroxycinnamic acids and flavonoids, have positive health effects that strongly depend on their bioavailability. In order to show that the Ussing-type chamberPolyphenols in apples, such as various hydroxycinnamic acids and flavonoids, have positive health effects that strongly depend on their bioavailability. In order to show that the Ussing-type chamber is a useful model to study metabolism, transport, and tightness of cell monolayers in one experimental setup, monolayers of the T84 colon carcinoma cell line mounted in Ussing-type chambers were incubated in the presence of physiological concentrations of various hydroxycinnamic acids (including ferulic, isoferulic, cinnamic, and hydrocinnamic acids) and flavonoids for 4 h. Concentrations of each tested polyphenol in the apical chamber, basolateral chamber, and those associated with the cells were then determined using HPLC with DAD (HPLC-DAD). The transport studies showed that the amounts of the tested polyphenols that passed from the apical to the basolateral side of the T84 monolayers depended on their polarity. Metabolites, such as glucuronides and sulfates of ferulic acid, were also detected at measurable levels by HPLC-ESI-MS/MS in the model system, but only when they were supplied at supra-physiological concentrations (>100 muM). In addition, the transepithelial resistance (TER) of T84 monolayers was measured before and after the addition of polyphenols, with and without short-term exposure to apical sodium caprate (C10), a tight junction (TJ) modulator. Exposure to C10 induced a decrease in TER that was reversible by incubation with polyphenols. However, no increase in paracellular permeability of tested polyphenols was observed after apical C10 exposure, so C10 did not promote fluxes of hydroxycinnamic acids across the monolayers. Further, real-time PCR analysis of the T84 colon cell line showed that ferulic and isoferulic acids induced significant increases in expression of the TJ components zonula occludens-1 (ZO-1) and claudin-4 transcription, but reductions in occludin expression. In contrast, caffeic and p-coumaric acids had no significant effects on the transcription of either ZO-1 or occludin. Our results provide confirmation that T84 cells could be used as model system to simulate the intestinal mucosa, and that polyphenols are able to increase the TER of C10-treated and -untreated T84 monolayers.

• Abdominal compartment syndrome.

  Authors: Wolfgang Scheppach

  Best practice & research. Clinical gastroenterology. 01/2009; 23(1):25-33.

  Increased intra-abdominal pressure (IAP) has received growing attention in critically ill patients. Pathophysiologically, it deranges cardiovascular haemodynamics, respiratory and renal functions andIncreased intra-abdominal pressure (IAP) has received growing attention in critically ill patients. Pathophysiologically, it deranges cardiovascular haemodynamics, respiratory and renal functions and may eventually lead to multi-organ failure. It is primarily seen in surgical intensive care units and is frequently associated with abdominal trauma but also occurs after elective abdominal surgery. Non-surgical intensivists ought to be aware that the syndrome is also seen in a wide spectrum of medical conditions, e.g. acute pancreatitis. An expert panel has recently set up definitions of intra-abdominal hypertension (IAH, sustained or repeated pathological elevation in IAP > or = 12 mmHg) and abdominal compartment syndrome (ACS, sustained IAP > 20 mmHg associated with a new organ dysfunction or failure). As clinical signs of IAH are unreliable, IAP should be measured non-invasively by the 'bladder technique'. It is hoped that the consensus definitions will contribute to a broader recognition and effective treatment of this life-threatening syndrome.

• Cysto-biliary fistula in a septic patient with cystic echinococcosis.

  Authors: Dennis Tappe, Wolfgang Scheppach, August Stich

  The American journal of tropical medicine and hygiene. 09/2008; 79(2):147-8.

• Intervention with cloudy apple juice results in altered biological activities of ileostomy samples collected from individual volunteers.

  Authors: Selvaraju Veeriah, Kamal Kumar Balavenkatraman, Frank-D Böhmer, Kathrin Kahle, Michael Glei, Elke Richling, Wolfgang Scheppach, Beatrice L Pool-Zobel

  European journal of nutrition. 08/2008; 47(5):226-34.

  Apple juice is considered to be an important component of the healthy diet, with anticancer activities in colon cancer animal models and key ingredients have numerous chemoprotective activities inApple juice is considered to be an important component of the healthy diet, with anticancer activities in colon cancer animal models and key ingredients have numerous chemoprotective activities in human colon cells in vitro. Since only little is known on comparable activities in the human colon in vivo, here a pilot study was performed to assess related mechanisms caused by ileostomy samples from volunteers that had consumed apple juice. Ileostomy samples were collected after intervention (0-8 h) with cloudy apple juice (1 l). They were characterized analytically for major apple polyphenols and biologically in HT29 colon cells for their potential to cause genotoxic damage, protect from the genotoxic insult by hydrogen peroxide (H(2)O(2)) and modulate the expression of GSTT2, an enzyme related to antioxidative defence against different peroxides. The analytical determination of polyphenols in the ileostomy samples revealed that the majority of the compounds were recovered in the samples collected 2 h after intervention. The comparison of genotoxic effects of samples before intervention and 2 h after intervention revealed a considerable variation of genotoxic response, but there was a trend for reduced genotoxicity in three of eight persons (P) after intervention. Samples collected at 2 h protected HT29 cells from genotoxic damage by H(2)O(2) (for 4 of 8 persons), resulted in an increased GSTT2 expression (for 2 of 6 persons) and of GSTT2 promotor activity (2 of 6 persons). The intervention with apple juice results in bioavailable concentrations of related polyphenols in the gut lumen, which could contribute to reduced genotoxicity, enhanced antigenotoxicity and favorable modulation of GSTT2 gene expression in some individuals. The pilot study for the first time used this combination of faecal biomarkers which in larger cohorts may either reveal overall significant alterations of chemoprotection or may be used to identify individuals which could particularly benefit from a personalized nutrition.

• Polyphenols are intensively metabolized in the human gastrointestinal tract after apple juice consumption.

  Authors: Kathrin Kahle, Wolfgang Huemmer, Michael Kempf, Wolfgang Scheppach, Thomas Erk, Elke Richling

  Journal of agricultural and food chemistry. 01/2008; 55(26):10605-14.

  Polyphenols are secondary plant compounds showing anticarcinogenic effects both in vitro and in animal experiments and may thus reduce the risk of colorectal cancer in man. The identification ofPolyphenols are secondary plant compounds showing anticarcinogenic effects both in vitro and in animal experiments and may thus reduce the risk of colorectal cancer in man. The identification of polyphenol metabolites formed via their passage through the small intestine of healthy ileostomy subjects after apple juice consumption is presented. Identification and quantification of polyphenols and their metabolites were performed using HPLC-DAD as well as HPLC-ESI-MS/MS. Total procyanidin content (TPA) was measured, and additionally the mean degree of polymerization (DPm) of the procyanidins was determined in the apple juice and ileostomy effluents. As products of polyphenol metabolism, D-(-)-quinic acid and methyl esters of caffeic acid and p-coumaric acid are liberated from the corresponding hydroxycinnamic acid esters. 1-Caffeoylquinic acid and 3-caffeoylquinic acid were determined as products of isomerization. Phloretin 2'-O-glucoside (phloridzin) and phloretin 2'-O-xyloglucoside were metabolized into the corresponding aglycons phloretin and phloretin 2'-O-glucuronide and all were found in the ileostomy effluent. Ninety percent of the consumed procyanidins were recovered in the ileostomy effluent and therefore would reach the colon under physiologic circumstances. The DP m was reduced (DP m of apple juice=5.7) and varied depending on the time point of excretion. The gastrointestinal passage seems to play an important role in the colonic availability of apple polyphenols.

• Human intestinal hydrolysis of phenol glycosides - a study with quercetin and p-nitrophenol glycosides using ileostomy fluid.

  Authors: Bastian Knaup, Kathrin Kahle, Thomas Erk, Anagnostis Valotis, Wolfgang Scheppach, Peter Schreier, Elke Richling

  Molecular nutrition & food research. 12/2007; 51(11):1423-9.

  In order to study the influence of sugar moiety, aglycon structure and microflora concentration on the human ileal hydrolysis of phenol glycosides, various quercetin and p-nitrophenol glycosides wereIn order to study the influence of sugar moiety, aglycon structure and microflora concentration on the human ileal hydrolysis of phenol glycosides, various quercetin and p-nitrophenol glycosides were incubated under anaerobic conditions (37 degrees C for 0, 0.5, 1, 2, 4, 6, 8, 10 and 24 h) with ileostomy fluids from three different donors. The glycosides, i.e. beta-D-glucopyranosides, beta-D-galactopyranosides, alpha-L-arabinofuranosides, beta-D-xylopyranosides and alpha-L-rhamnopyranosides as well as the liberated aglycones were identified by HPLC-DAD and HPLC-ESI-MS/MS. Among the quercetin glycosides under study, the 3-O-beta-D-glucopyranoside showed with 0.22 micromol/h the highest hydrolysis rate, followed by the 3-O-beta-D-galactopyranoside, the 3-O-beta-D-xylopyranoside and the 3-O-alpha-L-arabinofuranoside (0.04 and each 0.03 micromol/h, respectively). Quercetin 3-O-alpha-L-rhamnopyranoside was found to be stable for the entire incubation period. Using quercetin 3-O-beta-D-glucopyranoside as a representative example, linear hydrolysis rate was observed from 75 to 2500 microL ileostomy fluid corresponding to its microflora content (log 0.68 up to 21.9 colony forming units). Studies performed in the presence of antibiotics did not reveal any hydrolysis. The p-nitrophenol glycosides were hydrolyzed faster than the corresponding quercetin glycosides. The hydrolysis rate decreased from the beta-D-glucopyranoside (0.41 micromol/h), to the beta-D-galactopyranoside (0.21 micromol/h), the beta-D-xylopyranoside (0.12 micromol/h), the alpha-L-arabinofuranoside (0.09 micromol/h) to the alpha-L-rhamnopyranoside (0.06 micromol/h). These results demonstrate that the human ileal hydrolysis of phenol glycosides depends on the sugar and the aglycon structure as well as the microflora.

• Human rectal mucosal gene expression after consumption of digestible and non-digestible carbohydrates.

  Authors: Jürgen Schauber, Frank Weiler, Andrea Gostner, Ralph Melcher, Theodor Kudlich, Hardi Lührs, Wolfgang Scheppach

  Molecular nutrition & food research. 12/2006; 50(11):1006-12.

  The effect of regular consumption of the low-digestible and prebiotic isomalt versus the digestible sucrose on gene expression in rectal mucosa was examined in a randomized double-blind crossoverThe effect of regular consumption of the low-digestible and prebiotic isomalt versus the digestible sucrose on gene expression in rectal mucosa was examined in a randomized double-blind crossover trial. Nineteen healthy volunteers received 30 g isomalt per day or 30 g sucrose as part of a controlled diet over two 4-week test periods with a 4-week washout period in between. At the end of each test phase rectal biopsies were obtained. After RNA extraction mucosal gene expression was assayed using GeneChip microarrays. In addition, expression of cathelicidin hCap18/LL37, cellular detoxification enzymes GSTpi, UGT1A1 and CYP3A4, cyclooxygenase 2 and barrier factors MUC2 and ZO-1 were determined by real-time RT-PCR. Microbiological analyses of fecal samples revealed a shift of the gut flora towards an increase of bifidobacteria following consumption of the diet containing isomalt. Isomalt consumption did not affect rectal mucosal gene expression in microarray analyses as compared to sucrose. In addition, the expression of cathelicidin LL37, GSTpi, UGT1A1, CYP3A4, COX-2, MUC2 and ZO-1 was not changed in rectal biopsies. We conclude that gene expression of the human rectal mucosa can reliably be measured in biopsy material taken at endoscopy. Dietary intervention with the low digestible isomalt compared with the digestible sucrose did not affect gene expression in the lining rectal mucosa.

• Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases.

  Authors: Jürgen Schauber, Daniel Rieger, Frank Weiler, Jan Wehkamp, Matthias Eck, Klaus Fellermann, Wolfgang Scheppach, Richard L Gallo, Eduard F Stange

  European journal of gastroenterology & hepatology. 07/2006; 18(6):615-21.

  BACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by a breakdown of colon epithelial barrier function. Antimicrobial peptides like cathelicidins are molecules of the innate immuneBACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by a breakdown of colon epithelial barrier function. Antimicrobial peptides like cathelicidins are molecules of the innate immune system located at epithelial surfaces. Cathelicidins influence microbial growth and inflammation and may play a role in IBD. In this study, the expression of human cathelicidin hCAP18/LL-37 was investigated in the intestinal mucosa from patients suffering from ulcerative colitis or Crohn's disease. METHODS: Biopsy material from colon and ileal mucosa of a total of 89 patients (34 with Crohn's disease, 27 with ulcerative colitis, 28 control patients) was evaluated for cathelicidin expression by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. Colon epithelial cells were stimulated in vitro with various cytokines to evaluate mechanisms that influence cathelicidin production. RESULTS: Cathelicidin expression was significantly increased in inflamed and non-inflamed colon mucosa from ulcerative colitis patients compared to non-inflamed control mucosa. In patients with Crohn's disease cathelicidin expression was not changed in inflamed or non-inflamed colon or ileal mucosa independent of NOD2 status. Biopsies evaluated by immunohistochemistry showed epithelial cathelicidin expression in the upper crypt that was diffuse in controls and only basal in IBD patients. Inflammation mediators, alone or in combination with the known cathelicidin inducer butyrate, had no effect on cathelicidin expression in cultured colon cells. CONCLUSIONS: In IBD the colonic expression of human cathelicidin is altered: cathelicidin expression is increased in inflamed and non-inflamed mucosa in patients suffering from ulcerative colitis but not in Crohn's disease. This deficiency may further compromise the antimicrobial barrier in Crohn's disease.

• Studies on apple and blueberry fruit constituents: do the polyphenols reach the colon after ingestion?

  Authors: Kathrin Kahle, Michael Kraus, Wolfgang Scheppach, Matthias Ackermann, Friederike Ridder, Elke Richling

  Molecular nutrition & food research. 05/2006; 50(4-5):418-23.

  The aim of our studies was to determine the amount of polyphenols reaching the colon after oral intake of apple juice and blueberries. After a polyphenol-free diet healthy ileostomy volunteersThe aim of our studies was to determine the amount of polyphenols reaching the colon after oral intake of apple juice and blueberries. After a polyphenol-free diet healthy ileostomy volunteers consumed a polyphenol-rich cloudy apple juice while others consumed anthocyanin-rich blueberries. Ileostomy effluent was collected and polyphenols were identified using HPLC-DAD as well as HPLC-ESI-MS/MS; quantification was performed with HPLC-DAD. Most of the orally administered apple polyphenols were absorbed from or metabolized in the small intestine. Between 0 and 33% of the oral dose was recovered in the ileostomy bags with a maximum of excretion after 2 h. A higher amount of the blueberry anthocyanins under study (up to 85%, depending on the sugar moiety) were determined in the ileostomy bags and therefore would reach the colon under physiological circumstances. Such structure-related availability has to be considered when polyphenols are used in model systems to study potential preventive effects in colorectal diseases.

• Colonic availability of apple polyphenols--a study in ileostomy subjects.

  Authors: Kathrin Kahle, Michael Kraus, Wolfgang Scheppach, Elke Richling

  Molecular nutrition & food research. 01/2006; 49(12):1143-50.

  Nutrition is thought to play an essential role in the pathogenesis of inflammatory and malignant gastrointestinal diseases. It is well known that plant ingredients such as polyphenols and flavonoidsNutrition is thought to play an essential role in the pathogenesis of inflammatory and malignant gastrointestinal diseases. It is well known that plant ingredients such as polyphenols and flavonoids show anticarcinogenic effects both in vitro and in animal experiments, and may thus reduce the risk of colorectal cancer in man. The aim of the study was to determine the amount of polyphenols reaching the colon after oral intake of apple juice. After consumption of a polyphenol-free diet 11 healthy ileostomy volunteers drank 1 L of a polyphenol-rich cloudy apple juice. Ileostomy effluent was collected immediately before and 1, 2, 4, 6, and 8 h after consumption of apple juice. A broad spectrum of polyphenols was identified using HPLC-diode array detection (HPLC-DAD) as well as HPLC-ESI-MS/MS; quantitation was performed with HPLC-DAD. Most of the orally administered apple polyphenols were absorbed from or metabolized in the small intestine. Between 0 and 33% of the oral dose was recovered in the ileostomy bags with a maximum of excretion after 2 h. Phloretin glucuronide as product of polyphenol metabolism was detected in the ileostomy effluent. The present results show that most of the apple juice polyphenols are absorbed in the small intestine. Minor amounts of unmetabolized polyphenols are recovered in the ileostomy effluent, which would reach the colon under physiologic circumstances. These data have to be considered when polyphenols are used in model systems to show preventive effects in colorectal carcinogenesis.

• Influence of protein kinase C on transcription of the tight junction elements ZO-1 and occludin.

  Authors: Frank Weiler, Theresa Marbe, Wolfgang Scheppach, Jürgen Schauber

  Journal of cellular physiology. 08/2005; 204(1):83-6.

  Tight junctions as an epithelial barrier against paracellular diffusion have mainly been investigated on the protein level with particular respect to subcellular localization. In this study,Tight junctions as an epithelial barrier against paracellular diffusion have mainly been investigated on the protein level with particular respect to subcellular localization. In this study, real-time PCR has been established to investigate the influence of protein kinase C (PKC) modulation on the transcription of tight junction elements occludin and ZO-1 in the cell line T84. Activation of PKC by the phorbol ester TPA induced ZO-1 and occludin transcription, whereas PKC inhibition lead to decreased expression levels. Activation of PKC exerted its effect on transcript level directly. PKC signal was partially transduced via MEK1/MEK2 but depended strongly on MAPK independent pathways probably involving nuclear localized PKC, whereas p38 signaling was not implicated. TPA induced loss of function concomitant with a dislocation of ZO-1 and occludin could be prevented by inhibition of MEK1 by PD98059. Overall ZO-1 and occludin seem to be identically regulated in colonic epithelium on the transcript level.

• SKY and genetic fingerprinting reveal a cross-contamination of the putative normal colon epithelial cell line NCOL-1.

  Authors: Ralph Melcher, Stefanie Maisch, Sigrid Koehler, Martin Bauer, Claus Steinlein, Michael Schmid, Theodor Kudlich, Jürgen Schauber, Hardi Luehrs, Thomas Menzel, Wolfgang Scheppach

  Cancer genetics and cytogenetics. 05/2005; 158(1):84-7.

  In vitro studies addressing the primary prevention of colon carcinoma are preferably conducted using normal colonic cells, because these cells are more likely to represent the potential target forIn vitro studies addressing the primary prevention of colon carcinoma are preferably conducted using normal colonic cells, because these cells are more likely to represent the potential target for prevention in vivo. Established cell lines of normal colonic origin are mostly lacking; however, this is probably due to the difficulties associated with establishment of such cell lines. Cross-contamination with malignant cells is a frequent event, and so any successfully established cell line of normal origin should be scrutinized prior to further investigation. We performed a cytogenetic (spectral karyotyping) and genetic fingerprint (Promega PowerPlex ES multiplex system and Applied Biosystems AmpFlSTR SGM Plus multiplex system) analysis of the putative normal colon epithelial cell line NCOL-1, derived from two different sources (NCOL-1a and 1b). We show that NCOL-1a and 1b are probably derived from the colon carcinoma cell line LoVo, with a matching probability of 99.9995, most probably through cross-contamination. Karyotypes of LoVo and NCOL-1a were identical; NCOL-1b displayed additional marker chromosomes. Our findings highlight the importance of molecular and cytogenetic characterization of established cell lines to avoid drawing misleading conclusions from the original findings.

• The butyrate story: old wine in new bottles?

  Authors: Wolfgang Scheppach, Frank Weiler

  Current opinion in clinical nutrition and metabolic care. 10/2004; 7(5):563-7.

  PURPOSE OF REVIEW: Short-chain fatty acids are important end products of bacterial carbohydrate fermentation in the colon. In particular, n-butyrate is thought to play a regulatory role in thePURPOSE OF REVIEW: Short-chain fatty acids are important end products of bacterial carbohydrate fermentation in the colon. In particular, n-butyrate is thought to play a regulatory role in the maintenance of a physiological environment. Disturbances in the interplay between the microflora and the lining epithelium may lead to mucosal inflammation and promote carcinogenesis. The purpose of this article is to review the literature between March 2003 and February 2004 and to determine if recent studies have improved the understanding of butyrate effects in health and disease. RECENT FINDINGS: Preclinical studies (cell culture experiments, animal studies) using modern molecular biological tools (including cDNA arrays) have provided new insights into the action of butyrate on colonic epithelial, vascular endothelial and extracolonic cell types. The new information adds pieces of evidence to the assumption that butyrate may ameliorate colonic inflammation and may be chemopreventive in carcinogenesis. In contrast, new data from clinical studies have been limited in the review period. SUMMARY: In the era of molecular biology our understanding of subcellular processes that ultimately lead to inflammatory bowel disease or colorectal cancer has widened considerably. The new powerful technology of genomics and proteomics, however, raises new questions without easy answers. With this new information in mind, we will have to go back to human intervention trials to test the hypotheses generated in vitro. The preclinical data from the review period justify the need for carefully designed clinical trials to test the benefits derived from butyrate production.

• Histone-deacetylase inhibitors induce the cathelicidin LL-37 in gastrointestinal cells.

  Authors: Jürgen Schauber, Konrad Iffland, Susanne Frisch, Theodor Kudlich, Bernd Schmausser, Matthias Eck, Thomas Menzel, Andrea Gostner, Hardi Lührs, Wolfgang Scheppach

  Molecular immunology. 08/2004; 41(9):847-54.

  Histone-deacetylase (HDAC) -inhibitors enhance acetylation of core proteins and this is linked to formation of transcriptionally active chromatin in various cells. In this study, the effect of HDACHistone-deacetylase (HDAC) -inhibitors enhance acetylation of core proteins and this is linked to formation of transcriptionally active chromatin in various cells. In this study, the effect of HDAC inhibitors (butyrate, trichostatin A (TSA)) on the expression of the cathelicidin LL-37 in colon, gastric and hepatocellular cells was investigated. METHODS: LL-37 expression was assessed in colon, gastric and hepatocellular cancer cells after treatment with HDAC-inhibitors. In parallel, histone H4 and HMGN2, a non-histone protein, acetylation was evaluated. In addition, the intracellular signalling pathway MEK-ERK was explored. RESULTS: In contrast to normal colon epithelial cells, gastrointestinal cancer cells lacked LL-37 expression. LL-37 was induced following treatment with HDAC-inhibitors in all investigated cell lines. This induction was time-dependent in butyrate-treated cells while TSA exerted a transient effect. Induction of LL-37 by butyrate was paralleled by acetylation of the histone H4 and the non-histone HMGN2. Again, TSA resulted in transient acetylation. Furthermore, inhibition of MEK-ERK blocked HDAC inhibitor-induced LL-37 expression in colonic and gastric cells. CONCLUSIONS: We have previously shown that butyrate induces LL-37 in colon epithelial cells. In the present study, we demonstrate that cathelicidin expression is modulated by HDAC-inhibitors in various gastrointestinal cells including gastric and hepatocellular cells. This is paralleled by changes in the acetylation of distinct core proteins suggesting a common regulatory mechanism of cathelicidin LL-37 regulation in these cells.