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Biomedical subjects

H Tilg

Publications and source records attributed to H Tilg.

At least 19 recordsLinked to original sources
PubMed2006

[Aminosalicylates and steroids in the treatment ot chronic inflammatory bowel diseases--consensus paper of the Working Group for Chronic Inflammatory Bowel Diseases of the OGGH].

5-aminosalicylates (5-ASA) and steroids constitute a cornerstone of medical therapy in patients with inflammatory bowel diseases (IBD). Whereas the efficacy of 5-ASA in Crohn's disease (CD) is equivocal, ulcerative colitis (UC) is the main indication for this drug. In UC, 5-ASA is effective in the treatment of mild to moderate acute disease and in maintenance of remission. Furthermore, 5-ASA topical therapy is an important treatment option in patients with mild to moderate proctitis and/or left-sided UC and shows additive efficacy to oral therapy. From retrospective data a chemo-preventative activity of long-term 5-ASA therapy in UC is delineated. Steroids are treatment of first choice for moderate to severe cases of CD and UC. Budesonide, a modified steroid with less side effects, plays a major role in the treatment of ileocolonic CD +/- involvement of the right colon and is used as treatment of choice in mild-to-moderate cases. In case of acute, severe disease conventional steroids are superior compared to budesonide and therefore budesonide should only be used after considerable improvement of disease activity. The necessity to apply steroids in a given patient represents a negative prognostic indicator for the course of disease and should incite the early introduction of immunosuppressive therapy in this case. Steroids are only effective as short term therapy of IBD and are to be avoided for maintenance treatment. In all cases of steroid therapy an osteoporosis prophylaxis with calcium and vitamin D is recommended. Topical steroid treatment is less effective in left-sided UC compared to 5-ASA.

Aminosalicylic Acids↗
PubMed2006

[Endoscopy in IBD. A Consensus Report of the IBD Working of the Austrian Association of Gastroenterology and Hepatology].

Ileocolonoscopy including biopsies is the first line investigation in suspected inflammatory bowel disease (IBD). In up to 90 % of the cases ulcerative colitis and Crohn's disease are differentiated on endoscopic presentation. Standardised reporting of endoscopic results increases the validity and comparability of IBD findings. When there is a firm diagnosis of IBD, colonoscopy should only be performed for specific questions. An upper gastrointestinal endoscopy is only indicated in patients with upper gastrointestinal symptoms. Push and capsule endoscopy should also be limited to specific questions and situations. IBD with extended colitis is associated with an increased risk for colorectal cancer. Endoscopic surveillance with accurate biopsy sampling is a valuable tool for the prevention of colorectal cancer.

Endoscopy, Gastrointestinal↗
PubMed2006

Bosentan treatment of portopulmonary hypertension related to liver cirrhosis owing to hepatitis C.

Pulmonary arterial hypertension (PAH) with coexisting portal hypertension has been defined as portopulmonary hypertension (PPHTN). It is often related to liver cirrhosis of various aetiologies and is associated with a high mortality rate. Endothelin-1 (ET) is supposed to play an important role in the pathogenesis of PAH as well as portal hypertension. Therefore, therapy with an ET(A)/ET(B) receptor antagonist might be of use in the treatment of PPHTN. We report the case of a 76-year-old male with liver cirrhosis owing to chronic hepatitis C virus infection and PPHTN who was treated with the dual ET(A)/ET(B) receptor antagonist bosentan. The patient showed remarkable improvement of 6-min walking distance from 300 to 480 m after 2 weeks and to 540 m after 14 weeks, respectively. In addition, a significant decline of N-terminal pro B-type natriuretic peptide fraction (NT-proBNP) from 4928 ng mL(-1) to 640 ng mL(-1) was observed. Bosentan might be a promising new therapeutical option for patients suffering from PPHTN.

Administration, Oral↗
PubMed2005

The impact of prolonged strenuous endurance exercise on interleukin 18 and interleukin 18 binding protein in recreational cyclists.

Interleukin 18 (IL-18) is an important pro-inflammatory cytokine in the early phase of human immune response to microbial infections. The influence of strenuous exercise on the intrinsic balance of IL-18 and its endogenous antagonist IL-18 binding protein (IL-18 BP) is unknown, but could be of major relevance for the athlete's immune function empirically and epidemiologically proven to be altered after exhaustive exertion. To study the effect of strenuous marathon cycling on the interaction of IL-18 and IL-18 BP we investigated 37 male, healthy, and well-trained amateur cyclists participating in the Otztaler Radmarathon in Tyrol (distance: 230 km; cumulative altitude difference: 5500 m). IL-18 was measured by a commercially available ELISA-Kit and IL-18 BP by a novel IL-18 BP ELISA method. Free, unbound IL-18 was calculated according to a standard equation. The mean plasma level of IL-18 was 142.27 +/- 21.85 pg/ml pre-race, remained nearly unchanged (124.35 +/- 13.16 pg/ml; p = 1.0) immediately after competition (mean race time 9 h 38 min), but declined significantly 24 h afterward (62.92 +/- 6.80 pg/ml; p = 0.002). The plasma levels of IL-18 BP increased considerably immediately after and kept on rising for the following 24 h (pre-race: 1.51 +/- 0.20 ng/ml; immediately post-race: 3.84 +/- 0.26 ng/ml, p < 0.001; 24 h post-race: 4.33 +/- 0.42 ng/ml, p < 0.001). Therefore, the calculated free IL-18 was 122.06 +/- 16.79 pg/ml pre-race, declined to 82.86 +/- 8.59 (p = 0.05) immediately post-race and to 39.17 +/- 3.76 pg/ml 24 h post-race (p < 0.001). The respective percentages of this post-exercise reduction in free IL-18 plasma levels were 32 % and 68 %. The present study reveals an exercise-induced significant decline in free IL-18 accompanied by an immediate up-regulation of IL-18 BP and decreased IL-18 in marathon cyclists. This down-regulation of free IL-18 may (i) limit the magnitude and duration of a too excessive inflammatory response to the exercise-induced tissue damage and (ii) on the other hand contribute to the elevated susceptibility to infection in athletes undergoing exhaustive exercise.

Adult↗
PubMed2005

Circulating adiponectin reflects severity of liver disease but not insulin sensitivity in liver cirrhosis.

BACKGROUND: The adipocytokine adiponectin has been proposed to play important roles in the regulation of energy homeostasis, insulin sensitivity and shows anti-inflammatory properties. AIM: In this study we investigated the role of circulating adiponectin in different chronic liver diseases, its regulation by systemic anti-tumour necrosis factor (TNF)-alpha treatment and its hepatic metabolism. PATIENTS AND METHODS: Plasma adiponectin levels were determined in 87 patients with liver cirrhosis of different aetiologies, seven patients with alcoholic steatohepatitis undergoing systemic anti-TNF-alpha treatment, in 11 patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt implantation and in 21 healthy controls. RESULTS: Adiponectin levels were significantly higher in all subjects with liver cirrhosis of different aetiologies when compared with healthy controls and increased dependent on Child-Pugh classification. In subjects with alcoholic steatohepatitis, systemic anti-TNF-alpha treatment caused a significant decrease in circulating adiponectin. Adiponectin concentrations were similar in portal, hepatic and peripheral veins. No correlation between adiponectin levels and insulin resistance was found in any patient group. CONCLUSIONS: Our data suggest that circulating adiponectin is increased in liver cirrhosis independent of the aetiology of liver disease. We suggest that high adiponectin levels in chronic liver disease might reflect one of the body's anti-inflammatory mechanisms in chronic liver diseases.

Adiponectin↗
PubMed2005

Adiponectin and its receptors in non-alcoholic steatohepatitis.

BACKGROUND: Adiponectin, an adipocyte derived polypeptide, has been shown to alleviate steatosis and inflammation in mice with non-alcoholic fatty liver disease. AIM: In the present study, we wished to define liver expression of adiponectin and its receptors in morbidly obese patients undergoing bariatric surgery. Patients with non-alcoholic steatohepatitis (NASH) or simple steatosis were investigated to test whether dysregulation of this system might be involved in these disorders. PATIENTS AND METHODS: Liver mRNA expression of adiponectin and its recently cloned receptors RI and RII (adipoRI and adipoRII) were analysed by fluorescence based real time polymerase chain reaction in 13 patients with NASH and nine with simple steatosis. Adiponectin and adipoRII protein expression were assessed by immunohistochemistry in a subgroup of patients. RESULTS: Adiponectin and adipoRII mRNA expression were significantly reduced in liver biopsies of patients with NASH compared with simple steatosis while no difference was found in adipoRI mRNA expression. In NASH, adipoRII mRNA expression was negatively correlated with serum aspartate aminotransferase levels, serum alanine aminotransferase levels, and grade of fibrosis. Liver adiponectin protein expression was mainly found in endothelial cells of portal vessels and liver sinusoids whereas adipoRII expression was seen in hepatocytes only. Adiponectin and adipoRII staining were lower in biopsies of subjects with NASH compared with simple steatosis. CONCLUSION: Reduced hepatic expression of adiponectin and adipoRII might be of pathophysiological relevance in non-alcoholic fatty liver diseases.

Adiponectin↗
PubMed2005

The RANKL/OPG system is activated in inflammatory bowel disease and relates to the state of bone loss.

BACKGROUND AND AIMS: A substantial proportion of patients with inflammatory bowel disease (IBD) develops osteopenia and osteoporosis in the course of disease. Recent data from a mouse model of colitis suggest that the receptor activator of nuclear factor kappa B (RANKL)/osteoprotegerin (OPG) system may be responsible for bone loss. METHODS: We investigated the activation state of the RANKL/OPG system and its association with bone loss in human IBD. Plasma levels of OPG and RANKL were correlated with bone mineral density and current IBD therapy. Colonic secretion of OPG and RANKL and cell types responsible for such secretion were determined. RESULTS: OPG plasma levels were elevated 2.4-fold in Crohn's disease (CD) and 1.9-fold in ulcerative colitis (UC) whereas soluble RANKL (sRANKL) levels were not significantly different in IBD patients compared with healthy controls. High levels of OPG were released from colonic explant cultures (CEC) derived from inflamed IBD specimens, and colonic macrophages and dendritic cells costained for OPG. sRANKL levels from CEC were low both in IBD patients and healthy controls. Interestingly, increased expression of RANKL was mainly confined to cells in the lamina muscularis. A significant negative correlation was found between OPG plasma levels and femoral neck/lumbar spine bone mineral density. CONCLUSIONS: We have demonstrated that IBD is associated with alterations in the RANKL/OPG system. Applying results from a murine model of colitis associated bone loss, the constellation of OPG and sRANKL regulation observed in our study raises the possibility that RANKL/OPG may contribute to the development of bone loss in IBD.

Adolescent↗
PubMed2004

[Immunosuppressive therapy for inflammatory bowel disease: consensus by the Austrian working group on IBD].

Azathioprine (AZA) or 6-mercaptopurine (6-MP) are the immunosuppressive drugs of choice in the treatment of inflammatory bowel disorders (IBD). Optimal dosage for AZA is around 2.5 mg/kg body weight and induction of remission by these drugs may take 6 - 7 months. Intramuscularly applied Methotrexate (MTX) is the second choice, while its efficacy starts earlier than that of AZA; studies assessing oral low-dose MTX treatment are lacking. Cyclosporin is the standard treatment in case of steroid-refractory severe ulcerative colitis. This drug may also be used in patients with severe extraintestinal manifestations of IBD. Regarding other immunosuppressive drugs such as mycophenolic acid or 6-thioguanine respective controlled clinical study data are not available. The risk of malignancy using immunosuppressive drugs such as AZA is low and furthermore, especially AZA and 6-MP can be used rather safely during pregnancy.

Administration, Oral↗
PubMed2004

Imbalance between interleukin-1 agonists and antagonists: relationship to severity of inflammatory bowel disease.

Interleukin (IL)-1 is a key mediator in the pathogenesis of inflammatory bowel disease (IBD). Naturally occurring IL-1 modulators include IL-1 receptor antagonist (IL-1Ra), IL-1 soluble receptor Type I (IL-1sRI), IL-1sRII and IL-1 receptor accessory protein (AcP). Systemic and mucosal levels of IL-1 soluble receptors remain unknown in IBD. Plasma or colonic tissues were obtained from 185 consecutive unselected patients with Crohn's disease (CD) or ulcerative colitis (UC) and from 52 control subjects. Plasma and colonic explant culture supernatants were assessed for IL-1alpha, IL-1beta, IL-1Ra, IL-1sRI and IL-1sRII. Plasma IL-1Ra levels were higher in UC (+93%) than in healthy subjects. IL-1alpha and IL-1beta were not detected. IL-1sRII levels were marginally lower in CD (-10%) and UC (-9%), whereas IL-1sRI levels were elevated in CD (+28%) only. Plasma IL-1sRI levels correlated positively (P < 0.01) with Crohn's disease activity index (r = 0.53), C-reactive protein (r = 0.46) and alpha1-acid glycoprotein (r = 0.42). In colonic explant cultures, IL-1alpha and IL-1Ra levels were elevated in non-lesional (+233% and +185% respectively) and lesional CD (+353% and +1069%), lesional UC (+604% and +1138%), but not in non-lesional UC. IL-1beta was elevated in lesional UC (+152%) and CD (+128%). In contrast, IL-1sRII levels were elevated in non-lesional CD (+65%), but remained unchanged in lesional CD, non-lesional and lesional UC. IL-1sRI levels did not differ between patient and control groups. These results indicate that (i) the proinflammatory moiety IL-1sRI is a systemic marker of inflammation and activity in CD and (ii) local shedding of the functional antagonist IL-1sRII may dampen colonic inflammation in CD, but not in UC.

Adolescent↗
PubMed2003

Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro.

Resistin is a recently discovered polypeptide that induces insulin resistance in rodents. While in rodents resistin is predominantly expressed in adipocytes, in humans peripheral blood mononuclear cells (PBMC) seem to a be a major source of resistin. In the present study, we show that in human PBMC resistin mRNA expression-determined by fluorescence-based real-time polymerase chain reaction-is strongly increased by the proinflammatory cytokines interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-alpha), and also by lipopolysaccharides (LPS), respectively, while no effect was found by interferon-gamma (IFN-gamma) or leptin. Our results suggest that in humans resistin may be a link in the well-known association between inflammation and insulin resistance.

Chemokines↗
PubMed2003

A randomised placebo controlled trial of pegylated interferon alpha in active ulcerative colitis.

BACKGROUND: Pilot studies of interferon alpha (IFN-alpha) suggest a high remission rate in the treatment of active ulcerative colitis. We evaluated the safety of pegylated interferon alpha (PegIFN) and its role in induction of remission in patients with active ulcerative colitis, in a multicentre placebo controlled trial. METHODS: Sixty patients with a clinical activity score (CAI) of >6 were randomised to receive placebo (n=20), PegIFN 0.5 microg/kg (n=19), or PegIFN 1.0 microg/kg body weight (n=21) once weekly (PegIntron; Schering-Plough, USA) over 12 weeks. Patients receiving 5-aminosalicylates, steroids, and/or azathioprine in stable dosages were included. RESULTS: Serious adverse events were seen in none of the placebo patients, in 3/19 patients in the PegIFN 0.5 microg/kg group (hospitalisation due to disease flare up n=3), and in 3/21 in the PegIFN 1.0 microg/kg group (hospitalisation due to disease flare up n=1; thrombosis n=1; grand mal seizure n=1). Otherwise, we observed only minor IFN-alpha side effects. Clinical remission rates at week 12 (CAI < or =4) were 7/20 (35%) in the placebo, 9/19 (47%) in the PegIFN 0.5 microg/kg group, and 7/21 (33%) in the PegIFN 1.0 microg/kg group (NS). Early withdrawal from the study was observed in 11/20 placebo patients, in 6/19 in the PegIFN 0.5 microg/kg group, and in 10/21 in the PegIFN 1.0 microg/kg group, mainly due to lack of efficacy. The higher PegIFN dose was associated with a significant decrease in levels of C reactive protein (p=0.003, day 0 v 85). CONCLUSIONS: PegIFN is safe but not effective, at the dosages used, in patients with ulcerative colitis.

Adolescent↗
PubMed2002

Plasma levels of soluble CD40 ligand are elevated in inflammatory bowel diseases.

BACKGROUND AND AIMS: CD40/CD40 ligand (CD40L) interaction is important for induction of T cell dependent antibody production and cell-mediated immune responses. Overexpression of CD40/CD40L in the intestinal mucosa is likely to be involved in the pathogenesis of inflammatory bowel disease (IBD). A soluble form of CD40L (sCD40L) exists in the circulation. This study investigated whether plasma levels of sCD40L are higher in patients with IBD than in healthy controls. PATIENTS AND METHODS: Plasma levels of sCD40L were measured in 89 patients with Crohn's disease (CD), 56 patients with ulcerative colitis (UC), 17 patients with infectious diarrhea, and 42 healthy controls, using a specific enzyme-linked immunosorbent assay. RESULTS: In CD patients plasma levels of sCD40L were significantly higher than in healthy controls. Patients with UC and infectious diarrhea had higher sCD40L levels than healthy controls, but the differences were not significant. CD patients with fistulas and/or abscesses (n=38) had significantly higher levels of sCD40L than patients with uncomplicated CD (n=51). Only in patients with uncomplicated CD plasma levels of sCD40L correlated significantly with C-reactive protein and alpha(1)-glycoprotein. In UC patients there was a significant correlation of sCD40L with C-reactive protein. However, there was no significant correlation between plasma sCD40L levels and Crohn's disease activity index or Rachmilewitz score. CONCLUSION: Elevated plasma levels of sCD40L in CD patients supposedly reflect activation of functional CD40L in the intestine and might be a marker of intestinal inflammation.

Adolescent↗
PubMed2002

Interferon-alpha induces interleukin-18 binding protein in chronic hepatitis C patients.

Interleukin-18 (IL-18), derived from macrophages and Kupffer cells, is the central pro-inflammatory cytokine leading to experimental liver failure. IL-18 binding protein (IL-18BP) is a circulating protein that binds IL-18 and neutralizes its activity. Since IL-18 production is increased in chronic HCV infection, we asked whether IFN-alpha might act on the IL-18/IL-18BP system in HCV patients. IL-18BP, total and free IL-18 plasma levels were determined in 13 HCV patients receiving 1 x 107 IU IFN-alpha subcutaneously daily for 28 days. The in vitro effects of IFN-alpha on macrophage IL-18BP and IL-18 were studied by enzyme-linked immunosorbent assays and Northern analysis. IFN-alpha administration increased IL-18BP plasma levels 3.24 fold 24 h after institution of therapy, resulting in a 67.4% reduction of free IL-18. Total IL-18 levels decreased from day +24 on. In vitro, IFN-alpha diminished IL-18 release from macrophages of healthy volunteers and chronic HCV patients. On top of its inhibitory effects on IL-1 and TNF-alpha release, IFN-alpha also exerts its anti-inflammatory action in vivo by induction of IL-18BP. These anti-inflammatory properties might account - together with its antiviral action - for its clinical efficacy in chronic hepatitis C.

Down-Regulation↗
PubMed2002

Treatment of Crohn's disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon gamma.

BACKGROUND: Interleukin 10 (IL-10) exerts anti-inflammatory actions by counteracting many biological effects of interferon gamma (IFN-gamma). AIMS: To investigate this in humans, we studied the effects of human recombinant IL-10 administration on IFN-gamma production by patient leucocytes. Furthermore, we assessed the IFN-gamma inducible molecule neopterin and nitrite/nitrate serum levels, which are indicative of endogenous nitric oxide formation. METHODS: As part of two placebo controlled double blind studies, we analysed patients with chronic active Crohn's disease (CACD) who received either subcutaneous recombinant human IL-10 (n=44) or placebo (n=10) daily for 28 days, and patients with mild to moderate Crohn's disease (MCD) treated with either subcutaneous IL-10 (n=52) or placebo (n=16) daily for 28 days. Neopterin and nitrite/nitrate concentrations were measured in serum, and ex vivo IFN-gamma formation by lipopolysaccharide or phytohaemagglutinin (PHA) stimulated whole blood cells were investigated before, during, and after IL-10 therapy. RESULTS: In patients with CACD, the highest dose of 20 microg/kg IL-10 caused a significant increase in serum neopterin on days +15 and +29 of therapy compared with pretreatment levels. No changes were observed for nitrite/nitrate levels under either condition. In MCD, treatment with 20 microg/kg IL-10 resulted in a significant increase in PHA induced IFN-gamma production. CONCLUSIONS: High doses of IL-10 upregulate the production of IFN-gamma and neopterin. This phenomenon may be responsible for the lack of efficacy of high doses of IL-10 in the treatment of CACD and MCD.

Administration, Cutaneous↗