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The care for a patient with ulcerative colitis (UC) remains challenging despite the fact that morbidity and mortality rates have been considerably reduced during the last 30 years. The traditional management with intravenous corticosteroids was modified by the introduction of ciclosporin and infliximab. In this review, we focus on the treatment of patients with moderate to severe UC. Four typical clinical scenarios are defined and discussed in detail. The treatment recommendations are based on current literature, published guidelines and reviews, and were discussed at a consensus meeting of Swiss experts in the field. Comprehensive treatment algorithms were developed, aimed for daily clinical practice.

Yacon is a root crop which contains high amounts of fructooligosaccharides (FOS). The aim of this study was to investigate the effects of yacon syrup on colon transit time in healthy volunteers.

P-glycoprotein (P-gp) is an important efflux transporter that supports the barrier function of the gut against invading antigens and against administered drugs. Since glucocorticoids, such as budesonide, are frequently used during inflammatory bowel disease we investigated how budesonide influences P-gp expression in different intestinal cell lines.LS180 and Caco-2 cells were incubated with budesonide and changes in P-gp expression were determined on mRNA, protein and functional level. The mRNA expression levels of glucocorticoid receptor (GR) and pregnane X receptor (PXR) were determined in these cell lines. PXR receptor was transiently transfected into Caco-2 cells.Budesonide showed an induction of P-gp in LS180 cells and a down-regulation in Caco-2 cells. Expression levels of nuclear receptors revealed high expression of PXR only in LS180 cells and exclusive expression of GR in Caco-2 cells. Mifepristone, an anti-glucocorticoid, could not reverse the down-regulation of P-gp by budesonide in Caco-2 cells. In PXR-transfected Caco-2 cells the budesonide-mediated down-regulation of P-gp was abolished. Furthermore the expression of cytochrome P450 3A4 (CYP3A4), another PXR target gene, was induced in PXR-transfected Caco-2 cells after budesonide treatment.Budesonide has the potential to influence MDR1 expression in vitro. In LS180 cells, the induction of MDR1 by budesonide probably is mediated via PXR. The mechanism of the down-regulation in Caco-2 cells still remains unclear, but GR does not seem to be involved. Further studies are required to evaluate how budesonide alters P-gp expression in vivo.

Infliximab is a monoclonal chimeric antibody, with high affinity and specificity for tumour necrosis factor alpha (TNFalpha) that plays a central role in the pathogenesis of immune mediated inflammatory disorders including Crohn's disease and ulcerative colitis. Globally over 600000 patients have been treated with infliximab to date. This global experience led to a better definition of the overall safety and efficacy profile of this medication. The goal of the present recommendations is to provide practical information to physicians involved in the care of patients with inflammatory bowel disease.

Multidrug resistance-associated protein (MRP) is a transport system that is involved in the elimination of xenobiotics and biologically active endogenous substrates. Recently, the presence of MRP has been demonstrated in cultured brain capillary endothelial cells (BCECs). The time-dependent, functional expression of MRP in porcine BCECs was investigated to assess the value of this cell culture model for drug transport at the blood-brain barrier. Western blot analysis was used to investigate MRP expression in freshly isolated porcine BCECs and compared to MRP expression at days 8 and 10 in culture. Subcellular localization of MRP was investigated by immunocytochemistry with an MRP-specific monoclonal antibody, MRPr1. Functional activity of MRP was assessed by efflux studies with the fluorescent MRP substrate glutathione-methylfluorescein (GS-MF). No significant MRP expression was detected in freshly isolated endothelial cells. However, MRP expression is up-regulated in cell culture in a time-dependent manner. Immunostaining revealed predominantly perinuclear and, to a lesser degree, plasma membrane localization of MRP. At 10 degrees C GS-MF efflux was significantly decreased, indicating the involvement of an energy-dependent transport system. Efflux of GS-MF was apparently inhibited by MK571, a specific inhibitor for MRP. Porcine BCECs demonstrate up-regulation of functional MRP expression during culture, as observed in human tissue, and therefore might serve as a useful in vitro system for studying MRP-mediated blood-brain barrier transport.

complications following pancreatic surgery). Somatostatin analogues including octreotide have been shown to reduce pressure in the splanchnic circulation, an effect that was exploited in the management of variceal and nonvariceal hemorrhages. Despite a widespread therapeutic application, octreotide seems to be a safe drug free of major side effects. Somatostatin, a peptide hormone initially isolated from ovine hypothalami, has been documented to inhibit the release of growth hormone. It soon became evident that this peptide was not only present in the brain but was widely distributed in the stomach, the gastrointestinal tract and the pancreas. By 1980, the gene encoding for prosomatostatin had been identified and it became eviMost of the reported side effects are gastrointestinal in dent that different molecular forms are present in the nature and include steatorrhea, bloating, minor nausea, body. Later on, different receptors for somatostatin were gallstones and mild forms of glucose intolerance. Recently identified and it became clear that the different molecular a new formulation of octreotide, octreotide LAR (longforms and the different receptors are part of a complicated acting repeatable), was developed which enables once-acontrol system which regulate a variety of body functions. month administration. Octreotide LAR combines over a Somatostatin molecules exert profound inhibitory funcdecade of proven benefits of the subcutaneous octreotide tions, not only on growth hormone secretion but also on administration with a more convenient formulation for many gastrointestinal functions. These different effects long-term treatment of a variety of diseases. Onceform the basis for an enormous therapeutic potential of monthly administration should improve patient acceptasomatostatin in different diseases. The short half-life of bility and compliance; it represents a significant advance natural somatostatin which necessitates a continuous inin the management of a number of conditions associated travenous infusion has made it difficult to transform the with excessive peptide secretion (acromegaly, neuroendonatural peptide into a successful drug. It was therefore a crine tumors). There is no doubt that additional indicamajor step forward when a synthetic analogue of somatotions will emerge as investigations continue. Treatment of statin, octreotide, was synthesized and became available certain gastrointestinal cancers and prevention of variceal for clinical use in the mid-eighties. For over a decade, bleeding are two clinical areas which are currently under subcutaneous octreotide has proven effective in the treatinvestigation. A decade of octreotide has been beneficial ment of acromegaly and in several clinical areas relating for many patients; hopefully many more will be able to to gastroenterology and digestive surgery. The ability of take advantage of this fascinating peptide. octreotide to control symptoms such as diarrhea or flush caused by gut-neuroendocrine tumors soon became evident. Subsequently, octreotide was used in other forms of secretory diarrhea (AIDS-related diarrhea, idiopathic Bern and Basel Markus W. Buchler diarrhea, diabetic diarrhea) but also in the management January 1999 Christoph Beglinger of pancreatic disorders (pancreatic fistulae, prevention of

Die Refluxkrankheit ist Folge eines defekten Abschlusses des Osophagus zum Magen hin. Die konservativen Behandlungsmoglichkeiten greifen erst an den Folgen dieses Defektes an. Die Symptome erscheinen bei dieser chronischen Krankheit erneut nach Abbruch der konservativen Behandlung mit groser Regelmasigkeit. Nur eine operative Rekonstruktion des Verschlusmechanismus kann anhaltend pathologischen Reflux verhindern. Seit Einfuhrung der Fiberendoskopie, Osophagusmanometrie und Langzeit-pH-Metrie ist eine eindeutige Diagnostik und strenge Indikation moglich geworden. Die geringe Belastung, welche die laparoskopische Antirefluxchirurgie fur den Patienten bedeutet, darf nichts an einer strengen Indikation andern. Die moglichen Komplikationen sind zu ernst. Das neue Verfahren soll aber andererseits jahrelange konservative Behandlungen (und ihre Komplikationen wie Stenosen, Blutungen, Barrett-Osophagus) verschwinden lassen und eine zeitgerechte Fundoplicatio begunstigen, sofern die Langzeitergebnisse jene der offenen Methode bestatigen. Die laparoskopische Antirefluxchirurgie setzt viel Ubung im laparoskopischen Operieren ganz allgemein voraus. Andernfalls drohen schwerste fruhpostoperative Komplikationen.