Biomedical subjects

Axel U Dignass

Publications and source records attributed to Axel U Dignass.

4 recordsLinked to original sources

PubMed2003

Rescue therapy with tacrolimus in a patient with toxic megacolon.

BACKGROUND: Toxic megacolon is a life-threatening complication most commonly observed in patients with ulcerative colitis or Crohn's disease that is characterized by total or segmental nonobstructive colonic dilatation of at least 6 cm on plain abdominal films associated with systemic toxicity. CASE REPORT: We report an unusual case of fulminant steroid-refractory ulcerative colitis complicated by toxic megacolon treated successfully with the immunosuppressant tacrolimus. CONCLUSION: Tacrolimus administration induced clinical remission and bridged the time interval, until the standard immunosuppressant azathioprine could maintain clinical remission, thereby avoiding eminent emergency colectomy.

Adult↗

PubMed2002

Modulation of gastrointestinal wound repair and inflammation by phospholipids.

The mucosal surface of the digestive tract is a critical barrier between a broad spectrum of noxious and immunogenic substances present in the gastrointestinal lumen and the underlying mucosal immune system. Its preservation following various forms of injury or physiological damage is essential to prevent the invasion of harmful luminal factors into the host, which subsequently may lead to inflammation, uncontrolled immune response, and a disequilibrium of the homeostasis of the host. The preservation of this barrier following injuries is regulated by a broad spectrum of structurally distinct regulatory molecules, including phospholipids. Phospholipids play a pivotal role in the modulation of intestinal inflammation. They have been demonstrated to both promote and inhibit inflammation, and their overall impact in an individual setting seems to be dependent on several factors, including the level of immune cell activation and the presence of other mediators. Modulation of lipid mediators through administration of lysophosphatidic acid (LPA) or lisofylline (LSF), inhibitors of phospholipase A2 (PLA2) biosynthesis or monoclonal antibodies against thromboxane (TBX) or platelet-activating factor (PAF) as a therapeutic approach have been used in several models of inflammation; however, beneficial effects were not always convincing and further studies are warranted.

Animals↗

PubMed2002

Intestinal barrier function.

Intestinal barrier function regulates transport and host defense mechanisms at the mucosal interface with the outside world. Transcellular and paracellular fluxes are tightly controlled by membrane pumps, ion channels and tight junctions, adapting permeability to physiological needs. Food and microbial antigens are under constant surveillance of the mucosal immune system. Tolerance against commensals and immunity against pathogens require intact antigen uptake, recognition, processing and response mechanisms. Disturbance at any level, but particularly bacterial translocation due to increased permeability and breakdown of oral tolerance due to compromised epithelial and T cell interaction, can result in inflammation and tissue damage. New therapeutic approaches including probiotics and peptides to restore disrupted barrier function are evolving.

Biological Transport↗

PubMed2002

Lisofylline and lysophospholipids ameliorate experimental colitis in rats.

BACKGROUND: Intestinal inflammatory processes initiate a chain reaction in which membrane-bound lipids generate eicosanoids and phospholipids. Bioactive lipid mediators play a pivotal role in the pathogenesis of intestinal inflammation and colonic mucosa from patients with inflammatory bowel disease contains high levels of phospholipids. Therefore, we investigated the effects of lysophosphatidic acid and lysophosphatidylethanolamine, two natural occurring phospholipids and lisofylline, which decreases lipid peroxidation, in an in-vivo model of intestinal inflammation. METHODS: Colitis was induced by rectal administration of ethanol and trinitrobenzene sulfonic acid in rats. Rats were treated once daily with either lysophosphatidic acid or lysophosphatidylethanolamine rectally or twice daily intraperitoneally with lisofylline following induction of colitis. Rats were sacrificed after 7 days and the effect of lysophosphatidic acid, lysophosphatidylethanolamine, and lisofylline on colonic damage and inflammation were assessed using standardized macroscopical and histological injury scores. RESULTS: Treatment with lysophosphatidic acid, lysophosphatidylethanolamine, and lisofylline significantly reduced the degree of inflammation and necrosis in the distal colon compared to control rats. In addition, the weight loss was significantly less in the treatment groups compared to controls. Histological studies revealed a significant reduction of epithelial damage and colonic inflammation. CONCLUSION: The administration of anti-inflammatory lysophospholipids and suppression of proinflammatory lipid metabolites by lisofylline may provide new approaches to ameliorate intestinal inflammation.

Administration, Topical↗