Release of 5-aminosalicylate from an MMX mesalamine tablet during transit through a simulated gastrointestinal tract system

5-Aminosalicylate (5-ASA; mesalamine) is the current first-line treatment for mild to moderate ulcerative colitis, a chronic inflammatory condition that most commonly affects the distal part of the colon. MMX™ mesalamine (Lialda™ [US]; Mezavant™ XL [UK and Ireland]; Mezavant™ [elsewhere]; Shire Pharmaceuticals Inc., Wayne, Pa, under license from Giuliani SpA, Milan, Italy) was created to be a novel, once-daily 5-ASA formulation. MMX mesalamine in tablet form has a pH-dependent, gastroresistant coating and is designed to delay the release of 5-ASA during transit through the upper gastrointestinal tract; it consists of hydrophilic and lipophilic excipients that are designed to prolong the release of 5-ASA throughout the colon. The release kinetics of 5-ASA from an MMX mesalamine tablet were assessed with the use of a dynamic in vitro gastrointestinal tract system (TNO GastroIntestinalModel) that simulates physiologic conditions in the adult human gastrointestinal tract under standardized fed and fasted conditions. This system incorporates removal of released drug via dialysis and automated sampling taken at various sections of the system. Less than 1 % of 5-ASA was found to be released from the tablet in the simulated stomach and small intestine (before introduction into the simulated colon). Most of the 5-ASA within each tablet was released in the simulated colon (fasted state conditions: 78.0%; fed state conditions: 68.5%). Substantial quantities were released during the 8-to 18-hour sampling period (49.6 mg/h [fasted] and 40.7 mg/h [fed]). In conclusion, with the use of an in vitro system, the investigators showed that 5-ASA release from an MMX mesalamine tablet was delayed until the tablet reached the simulated colon. Throughout the simulated colon, release of 5-ASA from an MMX mesalamine tablet was prolonged     

LAPAROSCOPIC ANTI‐REFLUX SURGERY IN NEW ZEALAND: A TREND TOWARDS PARTIAL FUNDOPLICATION

Background : The advent of laparoscopic anti‐reflux surgery has generated considerable debate regarding the best technique. The present study was undertaken to determine the trends and current technique in laparoscopic anti‐reflux surgery in New Zealand. Methods : A confidential nationwide postal survey was sent to all general surgeons in New Zealand; it was repeated after a month, and followed up with a telephone prompt, if necessary. Results : Of the 146 questionnaires sent out, 126 were returned (response rate: 86%), and 104 were excluded (no anti‐reflux surgery performed (n = 96); surgeon retired (n = 5); paediatric surgeon (n = 3)). The number of operations performed by the 22 (16%) adult general surgeons who had performed laparoscopic anti‐reflux surgery increased 4.6 times from 1991 to 1997 (474 open and 1218 laparoscopic operations). The median number of cases per surgeon was 30 (range: 5–300). In 1997 there were 208 (60%) total fundoplications (TF) and 135 (40%) partial fundoplications (PF) performed. Variations in the technique of TF included the Nissen–DeMeester (10 surgeons), the Nissen–Rosetti (nine surgeons), division of short gastric vessels (10 surgeons), and routine cruroplasty (14 surgeons). A PF had never been perfomed by six surgeons, was preferred by six surgeons, and four other surgeons were performing it more often. Variations in the technique of PF included posterior (12 surgeons) and anterior (four surgeons) forms. Conclusion : There is significant variation in the technique of laparoscopic anti‐reflux surgery in New Zealand. A TF is preferred by 16 surgeons, but there appears to be a trend towards PF among the more experienced surgeons.     

Role of natural antibodies in immune homeostasis: IVIg perspective

Intravenous immunoglobulin (IVIg) has increasingly been used for the treatment of autoimmune and systemic inflammatory diseases in addition to supportive therapy of immunodeficient patients. Although a considerable progress has been made in understanding the mechanisms by which IVIg exerts immunomodulatory functions in these diseases, they remain not fully elucidated. The mode of action of IVIg is complex, involving interference with activation of complement and the cytokine network, modulation of: idiotype network, expression of Fc receptors, and activation, differentiation and effector functions of T and B cells and of antigen-presenting cells such as dendritic cells. The therapeutic effects of IVIg most likely reflect the functions of natural antibodies in maintaining immune homeostasis in healthy individuals.     

Comparative study of the anti-inflammatory effect of two intravenous immunoglobulin preparations manufactured by different processes

Intravenous immunoglobulin (IVIG) is increasingly used in the treatment of diverse immune-mediated disorders. Since several preparations of IVIG are available for therapy, it is possible that different manufacturing processes might influence clinical efficacy of IVIG. An insight into the mechanisms of action of such different IVIG preparations is therefore necessary that will provide further guidelines for the utility of IVIG preparations in autoimmune and inflammatory diseases. Since endothelial cells (EC) influence the inflammatory process via production of cytokines, chemokines and expression of adhesive molecules, we analyzed the anti-inflammatory effect on EC of two IVIG preparations: caprylated IVIG (IVIG-C) versus solvent/detergent-treated IVIG (IVIG-SD) preparation. We found that both IVIG preparations inhibit in an equivalent manner, the expression of different pro-inflammatory factors such as IL-6, IL-8, GM-CSF, IL-1beta and TNF-alpha and the adhesion molecules ICAM-1 and VCAM-1. Our results thus suggest that the caprylate while inactivating the virus and enhancing the yield of IgG during IVIG formulation, does not modulate the immunomodulatory properties of IVIG at EC level and that the two preparations show similar anti-inflammatory effects.