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Bile acids play important physiological role in the solubilisation and absorption of dietary lipids. However, under pathophysiological conditions, such as short bowel syndrome, they can reach the colon in high concentrations inducing diarrhoea. In this study, our aim was to characterise the cellular pathomechanism of bile-induced diarrhoea using human samples. Colonic crypts were isolated from biopsies of patients (controls with negative colonoscopic findings) and of cholecystectomised/ileum-resected patients with or without diarrhoea. In vitro measurement of the transporter activities revealed impaired Na⁺/H⁺ exchanger (NHE) and Cl⁻/HCO₃⁻ exchanger (CBE) activities in cholecystectomised/ileum-resected patients suffering from diarrhoea, compared to control patients. Acute treatment of colonic crypts with 0.3 mM chenodeoxycholate caused dose-dependent intracellular acidosis; moreover, the activities of acid/base transporters (NHE and CBE) were strongly impaired. This concentration of chenodeoxycholate did not cause morphological changes in colonic epithelial cells, although significantly reduced the intracellular ATP level, decreased mitochondrial transmembrane potential and caused sustained intracellular Ca²⁺ elevation. We also showed that chenodeoxycholate induced Ca²⁺ release from the endoplasmic reticulum and extracellular Ca²⁺ influx contributing to the Ca²⁺ elevation. Importantly, our results suggest that the chenodeoxycholate-induced inhibition of NHE activities was ATP-dependent, whereas the inhibition of CBE activity was mediated by the sustained Ca²⁺ elevation. We suggest that bile acids inhibit the function of ion transporters via cellular energy breakdown and Ca²⁺ overload in human colonic epithelial cells, which can reduce fluid and electrolyte absorption in the colon and promote the development of diarrhea.

Chymotrypsin from shrimp, Penaeus californiensis, was compared to Bos taurus chymotrypsin, and its structure-function relationship was studied. Catalytic efficiency toward synthetic substrate is lower, but it has a broad specificity and higher activity toward protein substrates, including collagen. It is active at pH 4-10 and fully active up to 50 °C for 2 h and at least nine days at room temperature. The activation peptide is twice as long as bovine chymotrypsinogen, has less disulfide bridges, and is a single polypeptide. Only one activation step is necessary from chymotrypsinogen to the mature enzyme. Postmortem implications in muscle softening and melanisation, resistance to temperature and pH and efficiency with proteinaceous substrates make chymotrypsin useful as a biotechnological tool in food processing. This makes shrimp processing wastes useful as a material for production of fine reagents., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: Laparoscopy is used more widely for the surgery of ulcerative colitis. The objective of this study was a comparison of the surgical and 3-year follow-up results of patients treated with conventional and minimally invasive methods., Materials and Methods: A total of 45 patients received surgery for ulcerative colitis, 16 as emergency and 29 as elective cases. Laparoscopy was used in 23 and a conventional method in 22 cases. No difference was found between the two groups from the aspects of American Society of Anesthesiologists physical status (ASA) class, mean body mass index (BMI) and age. There were 4 emergency cases in the laparoscopy group, and 12 in the open group. Nineteen elective surgeries were performed in the laparoscopy group, and 10 in the open group., Results: There was no significant difference between the groups as concerns the length of hospital or intensive care unit (ICU) stay, the time to bowel function recovery, but the duration of open surgery was significantly shorter. There was no difference between the groups in the rate of early postoperative complications, whereas among potential late complications, the rates of intestinal obstruction (8.7% vs. 45%) and a septic condition (0% vs. 27%) were significantly lower in the laparoscopy group. There was a significant improvement in the quality of life after surgery in both groups, and better cosmetic results were observed in the laparoscopy group., Conclusion: Laparoscopy can be used for ulcerative colitis both emergency and elective cases, it provides a good quality of life and the mid-term rate of complications is lower as compared with open surgery.

Background: Potential non-invasive markers of pouchitis would have a great deal of significance within clinical practice., Aim: This study is aimed at assessing the diagnostic accuracy of fecal calprotectin and matrix metalloprotease-9 as potential markers in patients both with and without pouchitis., Patients and Methods: Stool and blood samples were collected from 33 ileal pouch-anal anastomosis patients before a follow-up pouchoscopy. Biopsy samples were taken for histological purposes. The presence of cuffitis and stenosis was evaluated with an endoscopy. Calprotectin and matrix metalloprotease-9 were quantified with an enzyme-linked immunosorbent assay., Results: Pouchitis was detected in 30.3% of the patients. The levels of fecal calprotectin and matrix metalloprotease-9 increased significantly in patients with pouchitis. The sensitivity and specificity of matrix metalloprotease-9 was higher than that of fecal calprotectin. Only matrix metalloprotease-9 correlated significantly with the severity of pouchitis., Discussion: Fecal matrix metalloprotease-9 has a high specificity in the diagnosis of pouchitis.

Background: Only limited data are available regarding the diagnostic accuracy of fecal matrix metalloprotease-9 [MMP-9] for inflammatory bowel disease [IBD]. The aims of our study were to assess the diagnostic accuracy of fecal MMP-9 in patients with active Crohn's disease [CD], ulcerative colitis [UC], and pouchitis, and to compare the diagnostic accuracy of fecal MMP-9 and fecal calprotectin [CP] in IBD., Methods: Stool and blood samples were collected in 50 CD, 54 UC, and 34 ileal pouch-anal anastomosis patients before control endoscopies were performed. Biopsies were taken for histologic purposes. The activities of CD, UC, and pouchitis were defined with the use of clinical, endoscopic, and histologic activity scores. Fecal CP and MMP-9 levels were quantified by enzyme-linked immunosorbent assay., Results: Active CD, UC, and pouchitis were detected in 38%, 54%, and 29% of the patients, respectively. A significant correlation was revealed between fecal CP and the clinical activities of CD and UC, and between fecal CP and the endoscopic activity of UC and pouchitis. Fecal MMP-9 did not correlate with any of the activity indices of CD; however, strong associations were shown between fecal MMP-9 and clinical, endoscopic, and histologic activities of both UC and pouchitis., Conclusions: This is the first study assessing the diagnostic accuracy of MMP-9 in different types of IBD. Our results showed that fecal MMP-9 has high sensitivity in the detection of endoscopically active UC and pouchitis. These non-invasive methods help assess intestinal inflammation., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Influenza vaccination is recommended for inflammatory bowel disease (IBD) patients on immunosuppressive therapy. The objective was to evaluate the antibody and cell-mediated immune response to the split and whole virion influenza vaccine in patients with IBD treated with anti-TNF-α and immunosuppressive therapy., Patients and Methods: One hundred and fifty-six immunocompromised IBD patients were vaccinated. Fifty-three patients (control group) refused vaccination. Split virion vaccine and whole virion vaccine were used. Serum samples were obtained for pre- and postimmunization antibody titers to influenza vaccine (A/California/7/2009 [H1N1], A/Victoria/361/2011 [H3N2], B/Wisconsin/1/2010-like B/Hubei-Wujiagang/158/2009). Cell-mediated response was evaluated using an interferon (INF)-γ, interleukine (IL)-2 and tumor necrosis factor (TNF)-α ELISA., Results: Postimmunization titers of both influenza subtypes increased significantly after the administration of split virion vaccines compared to the controls and to those who received whole virion vaccine. The antibody titers of Influenza B also increased significantly in patients immunized with split vaccine and treated with anti-TNF-α therapy. After influenza vaccination, the level of serum IL-2 significantly decreased. No serious side effects developed occurred after influenza vaccination, and the influenza-like symptoms did not differ significantly between vaccinated versus control patients. The relapse of the disease was observed in only 10% of the patients and was more common in vaccinated than in control subjects., Conclusion: Split virion vaccines seem to be more effective than whole virion vaccines. Measuring the antibody responses is worthwhile in patients treated with immunosuppressants to determine the efficacy of influenza vaccination.

Background and Aims: Recently, anti-TNF-alpha therapy has increasingly been used in the treatment of perianal Crohn's disease (PCD), but there is only limited data regarding its short- and long-term efficacy., Material and Methods: The medical records of 68 patients treated with anti-TNF-alpha for PCD were assessed retrospectively. Rate of complex fistulas was 75%. Every patient received induction therapy, but in 20 cases the treatment was discontinued before week 52 due to funding regulations, an allergic reaction, or compliance problems. On week 12, the luminal activity decreased in more than 80% of the cases and the complete remission (CR) rate was about 60%; by the end of the first year, this ratio did not change substantially. Complete fistula closure was achieved in 26 cases (38.3%) and 53 patients (51.5%) showed a partial response during the 1-year period. Regarding both perianal and luminal activities, CR rate was achieved in 23 cases (33.8%). However, after the biological therapy was discontinued, recurrence of fistulas could be detected in every second patient. Additional surgical intervention was performed in 45% of patients during the 1-year period (seton drainage of fistulas and abscess drainage)., Conclusion: The anti-TNF-alpha therapy combined with surgery is an effective treatment of PCD. Approximately every third patient revealed complete fistula closure, while half of the other cases showed a partial response. Due to the high rate of fistula recurrence after stopping the biological therapy, more than 1 year of anti-TNF-α treatment may be beneficial.

Background: CT-P13 is the first biosimilar monoclonal antibody to infliximab (IFX); it has been approved for the same indications as its IFX counterpart in Hungary. The aim of this study was to assess the efficacy of CT-P13 induction therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC)., Methods: Patients diagnosed with CD and UC, who were administered CT-P13, were prospectively enrolled. Disease activity was estimated at the start and after the induction therapy. In patients with UC, sigmoideoscopy was also performed at the end of the induction therapy., Results: Eighteen CD and 21 UC patients were enrolled. Induction treatment was completed in 16 of the CD and 15 of the UC patients. In those with luminal CD, clinical response and remission was achieved in 6 (37.5%) and 8 (50%) of the patients at Week 8. In UC, clinical response and remission was achieved in 3 (20%) and 10 (66.7%) patients at Week 8. Mucosal healing was shown in 11 patients., Conclusions: This was the first study to prospectively evaluate the outcome of CT-P13 induction therapy in CD and UC. Our results confirm that induction with CT-P13 is safe and effective.

Serine proteases and their natural inhibitors have long been served as excellent models for studying (primary, secondary and tertiary) structure - activity relationships of biologically interacting proteins. As protein flexibility has been accepted as a "fourth dimension" of the protein structure, its contribution to the binding process has gained much interest. In this article we review extreme cases of serine protease interactions with canonical serine protease inhibitors that provide unique insights into the dynamics of protein- protein interactions. The major conclusions of our review article are: a) taxon-specific inhibitory effects of two highly homologous protease inhibitors from Schistocerca gregaria (SGCI and SGTI), as investigated by H/D exchange experiments and NMR spectroscopy, are due to their differential flexibilities, b) stabilities of some protease and inhibitor complexes, the wide-spread and increased flexibility of some segments in the protein-protein complexes, as studied by X-ray crystallography and NMR-spectroscopy, appear to be proportional to the physical stability of the complex.

By using affinity and reversed-phase HPLC (RP-HPLC) chromatographies two chymotrypsin-trypsin inhibitors were isolated from seeds of Acacia karroo, a legume of the subfamily Mimosoideae. The primary structure of one of these inhibitors, named AkCI/1, was determined. The inhibitor consists of two polypeptide chains, 139 and 44 residues respectively, which are linked by a single disulfide bridge. The amino acid sequence of AkCI/1 is homologous to and showed more than 60% sequence similarity with other protease inhibitors isolated earlier from the group of Mimosoideae. AkCI/1 inhibits both chymotrypsin (EC 3.4.21.1) and trypsin (EC 3.4.21.4) in a 1:1M ratio with Ki values of 2.8 × 10(-12)M and 1.87 × 10(-12)M, respectively. The P1-P1' residues for trypsin were identified as Arg68-Ile69 by selective hydrolysis of the inhibitor at this site, with bovine trypsin and human trypsin IV. The cleavage did not affect the inhibition of trypsin, but fully abolished the chymotrypsin inhibitory activity of AkCI/1. This finding together with our studies on competition of the two enzymes for the same combining loop suggests that the same loop has to contain the binding sites for both proteases. The most likely P1 residue of AkCI/1 for chymotrypsin is Tyr67., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Ulcerative colitis (UC) and Crohn's disease (CD) are chronic inflammatory disorders, which require long term treatment to achieve remission and to prevent relapses and cancer. While current therapies are effective in most cases, they can have rare but serious side effects and are often associated with high costs. On the other hand, early discontinuation of an effective treatment may lead to a quick relapse and to complications at the restart of therapy. Therefore it is essential to determine the optimal duration of maintenance therapy, but clear guidelines are missing. The most important questions when deciding whether to continue or withdraw therapy in quiescent UC and CD patients are the efficacy of the continuous treatment to maintain remission in the long term, the frequency and severity of side effects, and the chance of relapse after discontinuation of therapy. This review summarizes the current knowledge on these topics with respect to 5-aminosalicylates, thiopurines, methotrexate, and biological therapies and collects information regarding when and in which specific patient groups, in the absence of risk factors, can withdrawal of therapy be considered without a high risk of relapse. Additionally, the particular aspect of colorectal cancer prevention by current therapies will also be discussed.

Endoscopic ultrasound is the most accurate imaging modality for the diagnosis of pancreatic cancer, and endoscopic ultrasound-guided fine needle injection has already been used for palliative interventions. Surgical resection is currently the standard treatment for pancreatic insulinoma. Medical treatment may be necessary for symptomatic patients with unresectable disease. Case reports have been published about the success of endoscopic ultrasound-guided alcoholic ablation, but it has not been reported previously in Hungarian literature. The authors present the history of an 83-year-old woman who was evaluated because of repeated hypoglycemic coma occurring during the night. Endosonographic image and laboratory findings (elevated serum insulin and chromogranin A) revealed pancreatic insulinoma. Because of severe comorbidities and high risk of surgical resection, the decision was made to ablate the insulinoma by endoscopic ultrasound-guided alcohol injection. A total of 3 mL 95% ethanol was injected into the tumor. Despite the discontinuation of the diazoxide therapy the hypoglycemic episodes disappeared. This case history confirms that endoscopic ultrasound-guided alcoholic ablation is a novel, minimal invasive alternative treatment for patients with pancreatic neuroendocrine tumors in whom surgery is not feasible.

Introduction: The effects of short course of corticosteroids on the metabolic processes and bone formation has not been well studied. Our aim was to compare the efficacy, the side effects and the bone and lipid metabolisms in IBD patients using bolus or conventional tapering of methylprednisolone for 12 weeks., Patients and Methods: Nineteen IBD patients received intravenous methylprednisolone of 1mg/kg for 5 days tapered by 4 mg per week. Patients were prospectively randomized in two groups. In "conventional" group (I) steroids were given daily. In "pulse" group (II) weekly doses of steroids were given on special days of the week. The body mass index (BMI) was measured before and after the corticosteroid therapy. Blood samples were collected to assess glucose level, electrolytes, cholesterol and triglyceride levels, inflammatory parameters, cortisol, osteocalcin and crosslaps values. Total body composition analysis was performed at the beginning and at the end of the steroid therapy., Results: In Group I, BMI increased, total body bone density decreased significantly at the end of the steroid therapy. Body fat percent showed a tendency to be higher at the end of steroid therapy in Group I. Cholesterol level increased significantly in Group I patients. The decrease in serum cortisol level was more remarkable in Group I vs. Group II after steroid therapy. Less side-effect occurred in Group II vs. Group I., Discussion: Our results suggest that bolus tapering of corticosteroids may have more favorable short term outcome than conventional tapering that may revolutionize steroid therapy in IBD., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

To date, corticosteroids have been the primary therapies for acute, severe ulcerative colitis (UC). Patients not responding to intravenous steroids assessed at 3-5 days of the treatment are candidates for second-line rescue therapy. Cyclosporine (CsA), tacrolimus and infliximab (IFX) are also effective therapeutic options in acute, severe UC. In this review we summarized the results of the published studies examining and comparing the efficacy of CsA, tacrolimus and IFX as rescue therapies, and assessing the outcome of switching the drugs in case of therapeutic failure.

Pancreatic endocrine and/or exocrine functional disorders can be commonly detected in patients with inflammatory bowel diseases. Autoimmune pancreatitis is a rare disease and its co-existence with inflammatory bowel disease has been rarely reported. The diagnosis of autoimmune pancreatitis is difficult due to variable nonspecific symptoms, and the high rate of asymptomatic cases. The conventional imaging scans (ultrasonography, computed tomography, retrograde cholangiography) are usually not sensitive enough and they are frequently not able to differentiate between inflammatory and malignant tumorous diseases of the pancreas. The authors present the case history of a patient who developed both ulcerative colitis and autoimmune pancreatitis. The morphological changes of the pancreas detected by ultrasonography suggested the presence of pancreatic cancer, and this diagnosis was supported by the elevated level of serum CA19-9. Computed tomography failed to identify abnormalities in the pancreas and, finally, endoscopic ultrasound combined with fine needle aspiration cytology confirmed the diagnosis of autoimmune pancreatitis.

Aim: To assess tumor necrosis factor-α (TNF-α), infliximab (IFX) concentrations, and antibodies against IFX molecules in patients with inflammatory bowel disease (IBD) who develop loss of response, side effects, or allergic reaction during anti TNF-α therapy., Methods: Blood samples of 36 patients with response loss, side effects, or hypersensitivity to IFX therapy (Group I) and 31 patients in complete clinical remission (Group II) selected as a control group were collected to measure trough serum TNF-α level, IFX, and anti-IFX antibody (ATI) concentration. We examined the correlation between loss of response, the development of side effects or hypersensitivity, and serum TNF-α, IFX trough levels, and ATI concentrations., Results: The serum TNF-α level was shown to be correlated with the presence of ATI; ATI positivity was significantly correlated with low trough levels of IFX. ATIs were detected in 25% of IBD patients with loss of response, side effects, or hypersensitivity, however no association was revealed between these patients and antibody positivity or lower serum IFX levels. Previous use of IFX correlated with the development of ATI, although concomitant immunosuppression did not have any impact on them., Conclusion: On the basis of the present study, we suggest that the simultaneous measurement of serum TNF-α level, serum anti TNF-α concentration, and antibodies against anti TNF-α may further help to optimize the therapy in critical situations.

Background and Aims: To assess work disability (WD) rates in an inflammatory bowel disease (IBD) cohort involving patients with Crohn's disease (CD) or ulcerative colitis (UC) cohort and to identify possible clinical or demographic factors associated with WD. To our knowledge, this is the first study from Eastern Europe that has estimated indirect costs in IBD., Methods: Data from 443 (M/F: 202/241, CD/UC: 260/183, mean age: 35.5 (CD) and 40.5 (UC) years, biological drug exposure 31.2/11.5%) consecutive patients were included. WD data were collected by questionnaire and the work productivity and activity impairment instrument. Disability pension (DP) rates in the general population were retrieved from public databases., Results: The overall DP rate in this IBD population was 32.3%, with partial disability in 24.2%. Of all DP events, 88.8% were directly related to IBD. Overall, full DP was more prevalent in IBD (RR: 1.51, p < 0.001) and CD (RR: 1.74, p < 0.001) but not in UC compared to the general population and also in CD compared to UC (OR 1.57, p = 0.03). RR for full DP was increased only in young CD patients (RR<35 year olds: 9.4; RR36-40 year olds: 9.4 and 5.6, p < 0.01 for both). In CD, age group, previous surgery, disease duration, frequent relapses, and the presence of arthritis/arthralgia were associated with an increased risk for DP. Among employed patients, absenteeism and presenteeism was reported in of 25.9 and 60.3% patients, respectively, leading to a 28% loss of work productivity and a 32% activity loss, and was associated with disease activity and age group. Average cost of productivity loss due to disability and sick leave with a human capital approach was 1,450 and 430 €/patient/year in IBD, respectively (total productivity loss 1,880 €/patient/year), the costs of presenteeism were 2,605 (SD = 2,770) and 2,410 (SD = 2,970) €/patient/year in CD and UC, respectively., Conclusion: Risk of DP was highly increased in young CD patients (sixfold to ninefold). Previous surgery and presence of arthritis/arthralgia was identified as risk factors for DP. Work productivity is significantly impaired in IBD and is associated with high productivity loss.

Background: Although cyclosporin is effective in severe ulcerative colitis (UC), long-term colectomy rate varies between 60 and 88% among patients in whom cyclosporin initially induced remission. The aim of our study was to evaluate the long-term outcome and the optimal duration of cyclosporin therapy in acute, severe UC., Methods: A total of 73 patients underwent i.v. cyclosporin therapy for a steroid refractory flare up of UC between 1998 and 2009. All patients were treated with 1 mg/kg i.v. methylprednisolone for 3-7 days before the administration of cyclosporin. Patients received i.v. cyclosporin of 4-5 mg/kg for 5 days following oral treatment., Results: The mean follow up after the initiation of cyclosporin was 4.2 years. There were 20 patients who underwent early colectomy. Cyclosporin had to be discontinued due to side effects in 22 patients. Cyclosporin failed and late colectomy was performed in 14 of the 53 responders. Duration of cyclosporin treatment was significantly longer in those who avoided colectomy. The probability of avoiding colectomy proved to be 66% in case of 1-year treatment period with cyclosporin. The longer treatment period resulted in longer colectomy-free disease course., Conclusions: Cyclosporin is effective in acute, severe UC during long-term follow up. Our data suggest that the longer cyclosporin is used, the more it is possible to avoid colectomy in the future.

Blastocystis sp. is one of the most common parasites in the human intestinal tract. This infection commonly is accompanied by diarrhoea and abdominal pain, but extraintestinal symptoms, such as skin lesions, may also accompany the disease. In this study, our aim was to assess the frequency, clinical symptoms and skin manifestations of confirmed positive Blastocystis sp. infections. Data of 80 patients with confirmed positive Blastocystis sp. infections were assessed retrospectively. The average age of the patients was 46.3 years of age (with a range between 13 and 85 years of age). The number of female patients was higher than the number of males (48 vs. 32; 60 vs. 40%). Gastrointestinal and dermatological symptoms and the results of routine biochemical and haematological blood tests of enrolled patients were collected and analyzed. The skin manifestations were analyzed using the data available (including descriptions, photos and histologies). We discovered that 11.25% of our enrolled patients exhibited skin manifestations associated to Blastocystis sp., mainly on the females. The occurrence of Blastocystis sp. was 6% in symptomatic patients who required medical attendance in the time period between 2005 and 2013. Of the 80 patients, 73.75% indicated that they had gastrointestinal symptoms: 40 patients complained of abdominal pain and 17 with blood in their stool, while other symptoms, such as meteorism (15 subjects), weigh loss (8 subjects), perianal pain or itching (6 subjects), passing stool with mucus (5 subjects), vomiting (2 subjects) and fever (2 subjects) were less frequent. The prevalence of abdominal pain in the cohort without skin lesions was higher compared to those patients with skin problems (p = 0.007). The mean value of C-reactive protein showed elevated levels, but eosinophils were within a normal range. In addition, we did not find significant difference in eosinophilia between patients with vs. without skin manifestations. Thus, we suggest that eosinophilia is not an obligatory laboratory finding in protozoon infections, such as Blastocystis sp. In the light of our results, we suggest a stool parasite examination for patients with skin lesions of unknown origin.

Aim: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn's disease (CD) and ulcerative colitis (UC)., Methods: The data from 41 patients with CD and 22 patients with UC were assessed. Twenty-four CD patients received infliximab, and 17 received adalimumab. The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn's disease in CD and with the Mayo endoscopic subscore in UC., Results: Mucosal healing was achieved in 23 CD and 7 UC patients. Biological therapy had to be restarted in 78% of patients achieving complete mucosal healing with CD and in 100% of patients with UC. Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC., Conclusion: Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped.

Introduction: Budesonide , a synthetic, non-halogenated corticosteroid, has been introduced in the topical treatment of ulcerative colitis (UC). Budesonide MMX, a novel, once-daily oral formulation of budesonide that uses a multi-matrix system (MMX) technology to extend the release of budesonide throughout the colon proved to be effective for the treatment of active UC. The focus of this review is the current status of budesonide MMX in extensive and left-sided UC., Areas Covered: This paper covers the recent studies of budesonide MMX to describe its efficacy and safety in the treatment of mild-to-moderately active left-sided UC. A literature search and review of budesonide MMX were carried out using the PubMed database up to August 2013., Expert Opinion: Clinical studies of budesonide MMX in adults with mild-to-moderately active UC demonstrated its efficacy and tolerability in achieving clinical and endoscopic remission. Although one trial is still ongoing, budesonide MMX 9 mg tablets represented the first orally administered topical corticosteroid formulation targeting the entire colon for the management of patients with active, mild-to-moderate UC.

Introduction: Several serious side effects may limit the use of cyclosporine. Cyclosporine has been reported to increase the total cholesterol level; however, the change in serum cholesterol levels before and after cyclosporine therapy has not been examined in ulcerative colitis (UC) patients. The purpose of this article was to compare serum cholesterol levels before and after cyclosporine therapy in patients with refractory UC and to examine the relationship between serum cholesterol levels and other common side effects., Patients and Methods: We prospectively assessed serum cholesterol levels in UC patients who had been treated with cyclosporine. Data of 72 patients were analyzed and compared to a control group treated with Infliximab., Results: The average duration of cyclosporine therapy was 9.6 months, and side effects developed in 52 patients. Elevated cholesterol levels were detected in 47.2% of the patients. Serum cholesterol levels were significantly increased during and after discontinuation of cyclosporine therapy compared to the time before use of the drug. However, cholesterol levels measured during cyclosporine therapy were significantly higher compared to the time after its discontinuation (p < 0.001). Patients with drug-related side effects showed higher cholesterol levels after discontinuation of the therapy compared to those who did not experience any adverse events., Conclusions: Our findings suggest that cyclosporine therapy may result in increased serum cholesterol levels even in the long-term, after discontinuation of the therapy. Considering that significantly higher post-therapy cholesterol levels were more common in patients who developed drug-related complications, routine measurement of serum cholesterol may increase the safety of the drug.

Introduction: Tumor necrosis factor-alpha inhibitors are increasingly used in the treatment of severe Crohn's disease., Aim: The aim of the authors was to assess retrospectively the short and long term efficacy of tumor necrosis factor-alpha inhibitors in fistulising Crohn's disease., Method: Responses to therapy was determined using Crohn's Disease Activity Index, Perianal Disease Activity Index, the rate of complete fistula closure and the additional surgical procedures during biological therapy., Results: After 12 weeks the perianal activity was decreased in more than 80% of the cases, and the complete remission rate was about 60%. After one year of therapy about one third of the patients had fistula closure, but after cessation of the biological therapy recurrence of fistulas was detected in every second patient. In most cases additional immunosuppressive therapy was necessary during biological treatment. During the one-year therapy period additional surgical treatments were performed in 45% of patients; seton insertion and abscess drainage were the most frequent procedures., Conclusions: Tumor necrosis factor-alpha inhibitor therapy is effective in the treatment of perianal Crohn's disease, however, additional immunosuppressive drugs and rectum sparing surgical procedures were necessary during the one-year treatment period. Because of the high rate of fistula recurrence, long term tumor necrosis factor-alpha treatment may be useful.

BACKGROUND. Some of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy. The RASH study revealed that previous use of biological therapy and dose intensification are associated with restarting of biological therapy in Crohn's disease. The aim of the study was to assess the disease course and frequency of relapse of ulcerative colitis (UC) following discontinuation of infliximab in patients with remission and to determine predictive factors for relapse. PATIENTS AND METHODS. Fifty-one UC patients who had achieved clinical remission following 1 year of infliximab therapy and for whom infliximab was then discontinued participated in this prospective observational study. 15.7% of the patients received infliximab before the 1-year period of biological therapy analyzed in the study. Biological therapy was restarted in case of recurrent clinical activity. Data were collected from four Hungarian IBD centers. RESULTS. Thirty-five percent of the patients needed to be retreated with infliximab within 1 year after treatment cessation. Logistic regression analysis revealed that previous biological therapy (p = 0.021) was associated with the need of restarting infliximab. None of the data relating to patients' demographic and clinical characteristics, concomitant therapy and CRP level showed association with the need for restarting biological therapy. CONCLUSIONS. Biological therapy was restarted at a median of 4 months after discontinuation in more than every third UC patients who had been in clinical remission following 1 year of infliximab therapy. Response to retreatment with infliximab was favorable in the majority of the patients who relapsed.

This paper provides evidence for the extremely high resistance of a complex of crayfish trypsin (CFT) and bovine pancreatic trypsin inhibitor (BPTI) against heating and chemical denaturing agents such as sodium dodecyl sulfate (SDS) and urea. To dissociate this complex, 15 min boiling in SDS was necessary, compared to a complex of bovine trypsin (BT) (EC 3.4.21.4) and BPTI, which dissociates in SDS without boiling. The CFT-BPTI complex remained stable even in 9 m urea, while the BT-BPTI complex started to dissociate at concentrations of approximately 4 m urea. The melting temperatures of the BT-BPTI and CFT-BPTI complexes, as determined by differential scanning calorimetry, were found to be 79.6 and 100.1 °C, respectively. The behaviour of the apo-enzymes - CFT was found to have a less stable structure compared to BT - did not provide a definite indication regarding the differential effects on their stabilities. To explore the structural features responsible for this extreme stability, we crystallized CFT in complex with BPTI, and identified extended contacts compared to the BT-BPTI complex. Comparison of the B-factors of similar trypsin-trypsin inhibitor complexes suggests that molecular flexibility of the components is also required for the strong protein-protein interaction. Although the structural reason for the extreme stability of the CFT-BPTI complex is not yet fully understood, our study may be a starting point for the development of new protein complexes with enhanced stability., (© 2013 FEBS.)

Introduction: The exact extent of rectal cancer and regional lymph node involvement are essential for providing the optimal treatment., Aim: The aim of the authors was to evaluate the diagnostic accuracy of endoscopic ultrasonography in routine clinical staging of rectal cancer., Method: Outcomes of endoscopic ultrasonography performed between 2006 and 2012 for rectal cancer staging were retrospectively analyzed. The correlation between the endoscopic and pathological stages was evaluated., Results: In patients without neoadjuvant chemotherapy the sensitivity (75% and 73%) and specificity (74% and 80%) of endoscopic ultrasonography for differentiating T1 and T2 stages (respectively) were high, however, it was significantly decreased in differentiation of T3 stage (58%). A weak association was found in different N stages (45-62%). The diagnostic accuracy of endoscopic ultrasound was reduced significantly after the oncological treatment due to the overevaluation (27%) of the findings. After a relatively short learning curve (30 examinations) high correlation was detected between pT and uT stages., Conclusions: Endoscopic ultrasonography provides great help in staging early rectal cancers. Due to the lower sensitivity in patients receiving neoadjuvant therapy, it is not a useful tool after down-staging.

Objectives: Luminal serine-proteases lead to increased colonic paracellular permeability and visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Other proteases, namely cysteine-proteases (CPs), increase airway permeability by digesting epithelial tight junction proteins. In this study, we focused on constipation-predominant IBS (IBS-C) and we aimed to (i) evaluate CP levels in two cohorts of IBS patients, (ii) test if IBS-C fecal supernatant (FSN) affects permeability, and visceral sensitivity after repeated administrations in mice, and (iii) evaluate occludin expression in IBS-C colonic biopsies., Methods: Fecal CP activity was determined using selective substrate and inhibitor (E64). The effect of papain, as positive control, and IBS-C FSN administrations were evaluated on colonic paracellular permeability and mucosal occludin levels in mice and T84 monolayers. Occludin protein levels were evaluated in IBS-C colonic biopsies. Sensitivity to colorectal distension (CRD) was measured after repeated administrations of IBS-C FSN., Results: We found in a subset of IBS-C patients an enhanced fecal CP activity, in comparison with healthy controls and IBS-D patients. CP activity levels positively correlated with disease severity and abdominal pain scoring. This association was confirmed by receiver operating characteristic curve analysis. In mice, repeated application of IBS-C FSN into colon triggered increased permeability, linked to the enzymatic degradation of occludin, and was associated with enhanced visceral sensitivity to CRD. Finally, occludin levels were found decreased in colonic biopsies from IBS-C patients, and IBS-C FSNs were able to degrade recombinant human occludin in vitro. All these effects were abolished by preincubation of IBS-C FSN with a CP inhibitor, E64., Conclusions: These data suggest that luminal CPs may represent a new factor contributing to the genesis of symptoms in IBS.

Biological therapies are supposed to trigger the development of autoimmune diseases. We report a case of a 27-year old woman presenting with drug induced systemic lupus erythematosus (SLE) associated with infliximab therapy. The development of paradoxical inflammation in immune-mediated inflammatory diseases patients treated with anti TNF-α suggests that an unknown inflammatory pathway may be provoked by inhibiting TNF-α. We suppose that in our case a cross reactivity between anti-infliximab antibodies and autoantibodies may lead to the development of TNF-induced immune disease., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Ulcerative colitis (UC) is characterized by frequent relapses, with the presence of colorectal inflammation and mucosal lesions. Matrix-metalloprotease 9 (MMP-9) is elevated in colonic biopsies, urine, and blood plasma of UC patients. MMP-9 has been suggested as a predictor of UC in the urine of children; however, 20% of the controls tested positive. So far, fecal MMP-9 levels have never been measured. Our aims were: 1) to compare fecal MMP-9 levels in UC patients to control subjects and a functional gastrointestinal disorder characterized by diarrhea (IBS-D); 2) to test the correlation between UC disease activity and fecal levels of MMP-9; and 3) to correlate fecal MMP-9 levels with a known fecal marker of UC activity, calprotectin., Methods: UC (n = 47), IBS-D (n = 23) patients, and control subjects (n = 24) provided fecal samples for MMP-9 analysis. In UC patients, disease severity was evaluated by the Mayo score. Fecal MMP-9 and calprotectin levels were measured by enzyme-linked immunosorbent assay and lateral flow assay, respectively., Results: MMP-9 was undetectable or ≤0.22 ng/mL in the feces of all controls and IBS-D patients. In UC patients, fecal MMP-9 levels significantly correlated with the overall Mayo score (P < 0.001), the endoscopic score (P < 0.001), and the serum C-reactive protein levels (P = 0.002). Additionally, in UC patients fecal MMP-9 levels showed a significant correlation with a known disease activity marker, fecal calprotectin (P = 0.014)., Conclusions: These results highlight fecal MMP-9 as a useful tool in the differential diagnosis of diarrheic disorders and in the noninvasive evaluation of disease activity and mucosal healing in UC.

Conventional radiologic imaging (abdominal ultrasound, computer tomography) used in the differential diagnosis of post-hepatic jaundice can frequently provide inaccurate diagnosis. Inflammatory lesions may mimic neoplastic processes and malignancy may be accompanied by perifocal inflammation resulting in histological misdiagnosis. Furthermore, chronic and autoimmune pancreatitis are associated with an increased risk for pancreatic cancer. Radial endosonography has become a markedly important method in the imaging of the pancreas. It has a crucial role in the diagnosis and staging of pancreatic cancer. The authors present three cases where the diagnosis of pancreatic cancer determined by conventional imaging techniques (abdominal ultrasound, computer tomography, endoscopic retrograde cholangiopancreatography) was excluded or confirmed by the radial endosonography. The authors conclude that radial endosonography is an essential complementary method among imaging techniques of the pancreas and in tumor staging. Application of that may prevent unnecessary surgeries, which is obviously useful for patients and cost effective for health care providers.

Background: Some of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy., Aim: To assess the disease course and frequency of relapse of Crohn's disease (CD) following discontinuation of biological therapy, and to determine predictive factors for relapse., Methods: One hundred twenty-one CD patients who had achieved clinical remission following 1 year of biological therapy and for whom biological therapy was then discontinued participated in this prospective observational study. Eighty-seven CD patients had received infliximab and 34 adalimumab. The definition of relapse was an increase of >100 points in CDAI to at least a CDAI of 150 points., Results: Biological therapy was restarted within 1 year of treatment cessation in 45% of patients. Logistic regression analysis revealed that previous biological therapy (P = 0.011) and dose intensification during the 1-year course of biological therapy (P = 0.024) were associated with the need for and the time to the restarting of biological therapy. Smoking was observed to have an effect that was not statistically significant (P = 0.053)., Conclusions: Biological therapy was restarted a median of 6 months after discontinuation in almost half of Crohn's disease patients in who had been in clinical remission following 1 year of biological therapy. These results suggest that, in the event of the presence of certain predictive factors, biological therapy should probably be continued for more than 1 year by most patients., (© 2012 Blackwell Publishing Ltd.)

Kisspeptin (KP) neurones in the rostral periventricular area of the third ventricle (RP3V) and arcuate nucleus (Arc) are important elements in the neuronal circuitry regulating gonadotropin-releasing hormone (GnRH) secretion. KP and co-synthesised neuropeptides/neurotransmitters act directly on GnRH perikarya and processes. GnRH neurones not only form the final output pathway regulating the reproductive functions of the anterior pituitary gland, but also provide neuronal input to sites within the hypothalamus. The current double-label immunohistochemical studies investigated whether GnRH-immunoreactive (IR) projections to the RP3V and/or Arc establish morphological connections with KP-IR neurones at these sites. To optimise visualisation of KP immunoreactivity in, respectively, the RP3V and Arc, ovariectomised (OVX) oestrogen-treated and OVX oil-treated female mice were studied. Confocal laser microscopic analysis of immunofluorescent specimens revealed GnRH-IR axon varicosities in apposition to approximately 25% of the KP-IR neurones in the RP3V and 50% of the KP-IR neurones in the Arc. At the ultrastructural level, GnRH-IR neurones were seen to establish asymmetric synaptic contacts, which usually reflect excitatory neurotransmission, with KP-IR neurones in both the RP3V and Arc. Together with previous data, these findings indicate reciprocal connectivity between both of the KP cell populations and the GnRH neuronal system. The functional significance of the GnRH-IR input to the two separate KP cell populations requires electrophysiological investigation., (© 2013 S. Karger AG, Basel.)

Introduction: Inactivated influenza vaccination is recommended yearly for patients with inflammatory bowel disease on immunosuppressive therapy., Aim: The aim of our study was to evaluate the immune response to seasonal influenza vaccination in patients with inflammatory bowel disease treated with immunosuppressants., Patients and Methods: Thirty patients were enrolled in this prospective study. Each patient was diagnosed with inflammatory bowel disease and treated with immunosuppressants. Blood samples were obtained from patients before and one month after influenza vaccination (A/California/7/2009(H1N1), A/Perth/16/2009(H3N2) B/Brisbane/60/2008) to assess the pre-and postimmunization antibody titers. Virus-specific antibodies were measured by ELISA., Results: The vaccine acceptance rate was 53.3%. Local adverse effect occurred in 5 patients. Seven patients developed systemic adverse events. Influenza-like symptoms occurred in 2 patients, although their antibody titers failed to increase significantly. Antibodies to influenza viruses were detected in each patient before the vaccination., Conclusion: The results confirmed that each patient had appropriate antibody titer as correlation of protection even before the immunisation. Seroprotection rates were not influenced by the vaccination. The vaccine seemed to be safe.

Objectives: Inflammatory bowel diseases (IBD) have a huge impact on the patients' lives and require continuous medication and long-term medical follow-up. The Short Form Health Survey (SF-36) is a commonly used questionnaire measuring health-related quality of life (HRQOL). Our aim was to evaluate whether HRQOL influences medication adherence and vice versa in IBD patients, and to find relationships between demographic parameters, therapeutic modalities and non-adherence or HRQOL., Patients and Methods: Five hundred ninety-two IBD patients treated at six Hungarian tertiary centers were enrolled. Patients completed the SF-36 questionnaire and a medication adherence report scale during their visits. The associations between demographic parameters, HRQOL, different kinds of therapies and non-adherence were analyzed., Results: The most affected dimension was physical functioning and least affected were the social functions. About 42.7% of the patients revealed their HRQOL to be acceptable. About 74.6% of the patients believed that the prescribed medications actually improved their HRQOL. Diarrhea was the most common and most severe symptom during the course of the disease. Non-adherence was reported in 13.4% of the patients. 'Forgetting to take the medication' was the main reason for non-adherence in 67.6% of the cases. Medication adherence was significantly higher among nonsmoker patients, and also in the case of immunomodulator therapy. There was no association between the sum of HRQOL and different subscores and non-adherence., Conclusion: Inflammatory bowel disease is associated with low HRQOL, which is not affected by drug therapy. The impaired quality of life in IBD is mainly influenced by the disease itself.

BACKGROUND & AIMS. Secondary loss of response is a frequent event occurring during biological therapy. The aim of this study was to assess loss of efficacy in patients with Crohn's disease treated with infliximab or adalimumab for a year. The secondary goals were to identify clinical or laboratory predictors of loss of response. METHODS. Sixty-one Crohn's disease patients achieved remission after the induction therapy and received regular maintenance therapy: 35 of them were on infliximab, 26 on adalimumab therapy. None of the patients treated with infliximab had received previous biological therapy, and 10 of the adalimumab-treated patients were naïve to biological therapy. The data of patients who relapsed and who remained in remission and also the characteristics of infliximab-treated patients and adalimumab-naïve patients were compared. Data were analyzed statistically. RESULTS. Remission was achieved in 70.5%; response was achieved in 29.5% of the patients after induction. Loss of response occurred in 22 of 61 patients after a year of therapy. The proportion of remission after induction was significantly lower in patients who lost response vs. those who remained in remission. More patients with sustained remission received immunosuppressive therapy before and during the biological therapy vs. those with loss of response. Loss of response was significantly more frequent and occurred earlier in adalimumab-naïve patients vs. infliximab-treated patients. CONCLUSION. The need for dose escalation should be calculated in the budget in the majority of patients, especially in adalimumab-treated patients.

A 19-year-old man with a 1-year history of ulcerative colitis presented with fever, bloody diarrhea and severe dehidration. He was on po.48 mg methylprednisolon and 3 g mesalazine daily, and has recently finished taking chlarythromycin for Campylobacter jejuni infection. On physical examination, no abdominal tenderness was found, but surprisingly, extensive bilateral subcutaneous emphysema was detected in the supraclavicular regions. Laboratory tests proved anaemia, elevated white blood cell count, thrombocyte count and CRP levels. Stool culture was negative. Chest X-ray and CT scan revealed pneumomediastinum and subcutaneous air on the neck spreading to the scapular regions. Besides blood transfusion, iv. cyclosporin therapy was initiated (200 mg/day) along with iv. methylprednisolon (1mg/kg/day) and iv. ceftriaxon (2 g/day). Stool frequency and bloody stools decreased remarkably within one week, and subcutaneous emphysema has resolved. Colonoscopy one week later revealed deep, extensive ulcerations in the transverse and descending colon without any sign of previous perforation. Cyclosporin and methylprednisolon was continued orally. Pneumomediastinum and subcutaneous emphysema in ulcerative colitis are unusual complications, typically linked to retroperitoneal colonic perforation or toxic megacolon, and are extremely rare without preceding endoscopic procedures. Except from two cases in the literature, conservative treatment with iv. antibiotics and steroids failed to save from urgent surgical procedure, resulting in a partial or total colectomy. In our case we were able to avoid urgent surgery by the immediate use of iv. cyclosporin in combination with iv. steroids and antibiotics, while the outcome of the bowel remains questionable in the next few months., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

The present study aimed in vivo tracking of maturation of male eel by computed tomography (CT). Additionally, individually monitored testes sizes were correlated with the conventionally used external maturity indicators (i.e. eye and nose indexes) in order to test and improve their usefulness at individual level. Testes could be clearly identified with the CT from the end of the third week of hCG administration routinely used to induce maturation in fish. The volume of testes increased exponentially during hormone treatment, and by the end of the sixth week of maturation procedure all males produced motilable spermatozoa. Present results prove that testes size can noninvasively be monitored with CT from maturity level where testes size rich 3000 mm3 volume. Eye and nose indexes are in close correlation with testes volume and thus can also be effectively used to monitor maturity level of male eel, but preferably only at stock level. However, due to their high individual variability, these indexes can be applied only with caution at individual level and should be supplemented with other noninvasive techniques such as CT.

Background: Surgical Site Infection (SSI) is the third most frequent nosocomial infection, and accounts for 14-16% of all infections. While the treatment of SSI can be very costly, previous results indicated that triclosan may reduce SSI rate. Therefore, we carried out a prospective randomised trial to further evaluate the effect of triclosan after elective colorectal surgery., Methods: Seven surgical units in Hungary were involved in a prospective, randomised, multicentric clinical trial to compare triclosan coated (PDS plus®) and uncoated (PDS II®) sutures for abdominal wall closure in elective colorectal surgery. Pre- and perioperative variables were recorded in an online database. The primary aims of the study were to determine the incidence of SSI and the pathogens associated with it, as well as evaluation of additional cost of treatment., Results: 485 patients were randomised. SSI occurred in 47 cases (12.5%), of those 23 (12.23%) from the triclosan group (n = 188) and 24 (12.18%) from the uncoated group (n = 197, p = 0.982). In 13 (27.66%) cases late appearance of SSI was detected, of those 4 patients with triclosan coated suture (8.51%) and 9 patients with uncoated suture (19.15%, p = 0.041). There was no difference between the type of incisions or elective colon and rectal resections in terms of incidence of SSI., Conclusion: Beneficial effect of triclosan against Gram positive bacteria could not be confirmed in our study due to the relatively low number of patients with SSI. Furthermore, triclosan did not influence the incidence of SSI due to Gram negative bacteria. SSI rate decreased by 50% compared to our previous study, however, it was regardless of the use of coated or uncoated PDS loop. Finally, operative factors were more important than patient's risk factors in terms of incidence of SSI. In case SSI developed, delayed discharge from hospital as well as special wound care significantly increased overall cost of treatment.

Unlabelled: Prospective data collection seems to be essential in evidence-based medicine. Because of the new therapeutic options, the need for standard data collection and testing has significantly increased. In Hungary, a registry for patients with inflammatory bowel disease has already been set up, which makes it possible for clinicians to collect prospective data on their patients., Aim: Basic characteristics of the database of patients with ulcerative colitis are presented in this paper., Methods: The inflammatory bowel disease registry uses the programme of Microsoft Access database management system. Data are stored in a central server., Results: The incidence of inflammatory bowel diseases has been permanently increasing in Hungary; however, its overall prevalence is still low among the European countries. The frequent administration of immunosuppressive medications (azathioprine and corticosteroids) and their increased doses worsen the estimation of the activity., Conclusions: 1., It would be very useful to gain prospective data from all national centres. This kind of database would be able to give a complete picture regarding the Hungarian therapeutical practice. 2., Medications of patients may alter the clinical value of the laboratory findings in the process of determining the severity of the disease.

In a study of 44 canine patients suffering from histopathologically proven urinary bladder tumour with a high incidence of transitional cell carcinoma (TCC) (n = 35), a close relationship was found either between the disease-free period and the age (r = -0.40) of animals or between the survival times and the age (r = -0.62) of animals after treatment. In addition to the dog breeds known to be prone to have urinary bladder tumour, we found an additional potentially sensitive breed, the Hungarian Vizsla. The median survival times obtained by the applied treatment types were as follow: 'surgery and chemotherapy' (n = 8/44) 475 days, 'surgery alone' (n = 19/44) 240 days, 'chemotherapy alone' (n = 7/44) 31 days, and 'no treatment' (n = 10/44) 7 days (P < 0.001). According to the findings, chemotherapy combined with surgery completed in time is the most effective protocol in the treatment of urinary bladder tumour cases in dogs. A rational and more effective procedure for the assessment and treatment of urinary bladder tumour cases is presented.

Background/aims: Defective epithelial barrier has been implicated in the pathogenesis of irritable bowel syndrome (IBS) and inflammatory bowel diseases. The aim of this study was to investigate gut permeability in patients with inactive ulcerative colitis (UC) and in patients with IBS., Methods: IBS patients of the diarrhea-predominant (IBS-D) and of the constipation-predominant subgroup (IBS-C), patients with inactive UC and healthy subjects were enrolled. Gut permeability was evaluated by measuring 24-hour urine excretion of orally administered (51)Cr-EDTA. Clinical symptoms were evaluated in IBS-D patients and correlated to colonic permeability., Results: There was a significant decrease in the proximal small intestinal permeability in IBS-C patients compared to controls (0.26 ± 0.05 vs. 0.63 ± 0.1%; p < 0.05). Distal small intestinal permeability showed no significant difference in the studied group of patients compared to controls. Colonic permeability of IBS-D and inactive UC patients was significantly increased compared to controls (2.68 ± 0.35 and 3.74 ± 0.49 vs. 1.04 ± 0.18%; p < 0.05, p < 0.001). Colonic permeability of IBS-D patients correlated with stool frequency., Conclusions: Elevated gut permeability is localized to the colon both in IBS-D and in inactive UC patients., (Copyright © 2011 S. Karger AG, Basel.)

Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. Recently, astroglial Ca(2+) transients evoked by the major citric acid cycle metabolite succinate (SUC) and gamma-hydroxybutyrate (GHB) that enters the citric acid cycle via SUC have been described in the brain reward area, the nucleus accumbens (NAc). Cells responding to SUC by Ca(2+) transient constitute a subset of ATP-responsive astrocytes that are activated in a neuron-independent way. In this study we show that GHB-evoked Ca(2+) transients were also found to constitute a subset of ATP-responsive astrocytes in the NAc. Repetitive Ca(2+) dynamics evoked by GHB suggested that Ca(2+) was released from internal stores. Similarly to SUC, the GHB response was also characterized by an effective concentration of 50 μM. We observed that the number of ATP-responsive cells decreased with increasing concentration of either SUC or GHB. Moreover, the concentration dependence of the number of ATP-responsive cells were highly identical as a function of both [SUC] and [GHB], suggesting a mutual receptor for SUC and GHB, therefore implying the existence of a distinct GHB-recognizing astroglial SUC receptor in the brain. The SUC-evoked Ca(2+) signal remained in mice lacking GABA(B) receptor type 1 subunit in the presence and absence of the N-Methyl-d-Aspartate (NMDA) receptor antagonist (2R)-amino-5-phosphonovaleric acid (APV), indicating action mechanisms independent of the GABA(B) or NMDA receptor subtypes. By molecular docking calculations we found that residues R99, H103, R252, and R281 of the binding crevice of the kidney SUC-responsive membrane receptor SUCNR1 (GPCR91) also predict interaction with GHB, further implying similar GHB and SUC action mechanisms. We conclude that the astroglial action of SUC and GHB may represent a link between brain energy states and Ca(2+) signaling in astrocytic networks.